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OBJECTIVE: This study evaluated the impact of the COVID-19 pandemic and vaccine perceptions on Human Papillomavirus (HPV) vaccine hesitancy. Secondary endpoints included comparing COVID-19 and HPV vaccination trends regarding time, community of residence, and unmet social needs. METHODS: This was a survey-based, cross-sectional study that included 101 participants who were recruited through the Wyandotte County Public Health Department. Participants were eligible for inclusion in this study if they were a parent/guardian of one or more children aged 13 to 17; English- or Spanish-speaking. This study took place in Wyandotte County, Kansas. Descriptive statistics and chi-square analyses were utilized. RESULTS: There was no difference in completion of COVID-19 and HPV vaccines (p = 0.0975). Significantly more individuals started and did not finish the HPV vaccine series compared to the COVID-19 vaccine series (p = 0.0004). Most participants indicated their opinion on the HPV vaccine had not changed due to the pandemic (71.3 %). Participants who felt familiar with HPV had higher rates of HPV vaccine completion. While 77 % of participants felt extremely or moderately familiar with HPV, 61.4 % were unaware of its association with oropharyngeal cancer. CONCLUSION: There was minimal change in parents' perception of the HPV vaccine due to the COVID-19 pandemic despite decreased rates of vaccination during this time. HPV vaccine series completion was significantly lower than COVID-19 vaccine series completion, highlighting a need to improve HPV vaccine completion counseling. Additionally, patient education should address the knowledge gap discovered regarding the link between HPV infection and oropharyngeal cancer.
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COVID-19 , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Niño , Humanos , Pandemias , Vacunas contra la COVID-19 , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Estudios Transversales , Vacilación a la Vacunación , COVID-19/epidemiología , COVID-19/prevención & control , Conocimientos, Actitudes y Práctica en SaludRESUMEN
BACKGROUND: High-intensity focused ultrasound (HIFU) is a less invasive option offered for the treatment of large, compressive, benign thyroid nodules. METHODS: Observational studies of more than five participants using HIFU in the management of benign thyroid nodules from 2000 to 2021 were identified using predefined inclusion criteria. The primary outcome was an estimate of the effectiveness of HIFU. RESULTS: Out of 158 studies reviewed, 8 articles were included with 297 patients and 300 nodules. HIFU significantly reduced nodule volume from 1 to 24 months following therapy (weighted mean difference [WMD], 47.68, 95 % confidence interval [CI], 34.13-59.66, p < 0.0001) and achieved favorable success rates (risk ratio [RR], 1.49, 95 % CI, 1.15-1.84, p < 0.001) for 50 % volume reduction. CONCLUSIONS: HIFU appears to be a feasible, safe, and effective treatment modality for patients with benign thyroid nodules. Future research, including randomized controlled trials, is needed to determine therapy optimization, and patient selection to identify the potential role of this new therapy.
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Ultrasonido Enfocado de Alta Intensidad de Ablación , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/cirugía , Resultado del Tratamiento , Selección de Paciente , Oportunidad Relativa , Estudios Observacionales como AsuntoRESUMEN
BACKGROUND: To determine the safety of Botox and its potential effect on alleviating radiation therapy (RT)-induced sialadenitis in head and neck cancer patients. METHODS: Twenty patients with stage III/IV head and neck cancer were randomized to receive Botox or saline injections into both submandibular glands (SMG). There were three visits: one before RT (V1); 1 week after RT (V2); and 6 weeks after RT (V3), each of which included saliva collection, a 24-h dietary recall, and a quality-of-life survey. RESULTS: No adverse events were observed. While the control group was much older, the Botox group more commonly underwent induction chemotherapy compared with controls. From V1 to V2, salivary flow decreased in both groups, but only in the control group from V1 to V3. CXCL-1 (GRO), a neutrophil chemoattractant, was lower in the Botox group compared with the control group at V3. CONCLUSION: Botox can be safely administered to the salivary glands prior to external beam radiation without observed complications or side-effects. After an initial reduction in salivary flow following RT, the Botox group showed lack of further flow reduction compared with controls. The inflammatory marker CXCL 1, which was reduced in the in Botox group at V3, may be a candidate for further studies of radiation-induced sialadenitis.
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Toxinas Botulínicas Tipo A , Neoplasias de Cabeza y Cuello , Sialadenitis , Xerostomía , Humanos , Toxinas Botulínicas Tipo A/uso terapéutico , Proyectos Piloto , Xerostomía/etiología , Xerostomía/prevención & control , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/complicaciones , Sialadenitis/etiología , Sialadenitis/prevención & controlRESUMEN
According to the National Resident Matching Program in 2022, 631 pathology positions were offered. In total, 248 senior applicants from United States (US) allopathic schools filled 36.6% of these positions. To bolster medical student understanding of pathology, a medical school pathology interest group organized a multi-day activity to introduce rising second-year medical students to pathology as a career. Five students completed both pre- and post-activity surveys assessing their knowledge of the specialty. All five students had a BA/BS degree as their highest level of education. Only one student indicated that he or she had previously shadowed a pathologist as a medical laboratory scientist for a duration of four years. Two students indicated that they were interested in internal medicine, one indicated radiology, one forensic pathology or radiology, and one was undecided. During the activity, students biopsied tissue from cadavers in the gross anatomy lab. Thereafter, students participated in the standard tissue processing by shadowing a histotechnologist. Under the guidance of a pathologist, students microscopically examined slides and discussed the clinical findings. Post-activity survey results indicated that participation increased their knowledge of pathology as a career with a median increase of 0.8 points (range: 0.2 to 1.6) on a 5-point Likert scale. Students also indicated that their participation increased their knowledge of pathology skills and techniques-median increase of 1.2 (range: 0.8 to 1.8). This activity can be implemented by medical educators to expose medical students to pathology as a career with the benefit of increasing student knowledge in the specialty.
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Many medical schools have undergone curricular reform recently. With these reforms, time spent teaching anatomy has been reduced, and there has been a general shift to a pass/fail grading system. At Indiana University School of Medicine (IUSM), a new curriculum was implemented in fall 2016. The year-long human gross anatomy course taught in 2015 was condensed into an integrated, semester-long course starting in 2016. Additionally, the grading scale shifted to pass/fail. This study examined first-year medical student performance on anatomy practical laboratory examinations-specifically, among lower-order (pure identification) questions and higher-order (function, innervation) questions. Participants included medical students from a pre-curricular reform cohort (year 2015, 34 students) and two post-curricular reform cohorts (years 2016, 30 students and 2017, 33 students). A Kruskal-Wallis ANOVA test was used to determine differences of these questions among the three cohorts. Additionally, 40 of the same lower-order questions that were asked on gross anatomy laboratory examinations from medical student cohort year 2015 and year 2016 were further analyzed using an independent samples t-test. Results demonstrated that the pre-curricular reform cohort scored significantly higher on both lower-order (median = 81, p < 0.001) and higher-order questions (median = 82.5, p < 0.05) than both post-curricular reform cohorts. Additionally, when reviewing the selected 40 similar questions, it was found that the pre-curricular reform cohort averaged significantly higher (82.1 ± 16.1) than the post-curricular reform cohort from 2016 (69.3 ± 21.8, p = 0.004). This study provides evidence about the impact of curricular reform on medical student anatomical knowledge.
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Anatomía , Educación de Pregrado en Medicina , Estudiantes de Medicina , Humanos , Anatomía/educación , Educación de Pregrado en Medicina/métodos , Curriculum , Laboratorios , Evaluación EducacionalRESUMEN
Establishing an airway in the operating room is an interdisciplinary activity that requires focus of all participants. An interprofessional simulation event was designed to reestablish the importance of this OR event for student registered nurse anesthetists and registered nurse first assists.
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Relaciones Interprofesionales , Estudiantes de Enfermería , Comunicación , Humanos , Enfermeras Anestesistas , QuirófanosRESUMEN
INTRODUCTION: Nutritional status can affect surgical patients in terms of stress response, healing time, and outcomes. Several abnormalities are known to have a high prevalence in the general population such as vitamin D deficiency (VDD) and subclinical hypothyroidism. We hypothesized that there will be elevated rates of nutritional deficiencies in preoperative patients which may adversely affect postoperative outcomes following pediatric otolaryngology surgery. METHODS: IRB approval was obtained for a cross-sectional cohort study. Consecutive patients underwent nutritional evaluation when being scheduled for surgery including TSH, albumin and vitamin D. Demographic data, supplementation, and early complication rates were collected. RESULTS: 125 patients were included in the final cohort with adequate demographic distribution. Based on anthropometric data, 12% of our cohort was found to be undernourished, and 40% of our cohort with elevated BMI. However, there was no relationship found between Z-scores and complications. VDD was noted in 83/125 (66.4%) patients. Our cohort had increased rates of VDD in patients with elevated BMI and African American ethnicity. Thyroid hormone abnormalities were present in 12 patients. Mean serum albumin level was 4.29 in our cohort all within normal range. We did find increased risk of postoperative complications in patients with previously diagnosed comorbidities. (p=0.006). CONCLUSION: There is no current recommendation or consensus for nutritional assessment in preoperative pediatric patients. Our study did not show statistically significant correlation with z-scores, low vitamin D levels with supplementation, albumin, or TSH to postoperative complications. However, our patient cohort had higher than average rates of VDD compared to the many studies of the general pediatric population and significant negative correlation between vitamin D levels and z-scores. By early preoperative identification of VDD and supplementation with calciferol, we found no significant difference in complication rates in patients based on their initial vitamin D status. We suggest screening preoperative patients using z-score calculations and vitamin D levels based on individual patient risk factors including atrisk patient populations such as African American children, and obese children.
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Otolaringología , Obesidad Infantil , Deficiencia de Vitamina D , Niño , Estudios Transversales , Humanos , Estado Nutricional , Vitamina D , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiologíaRESUMEN
OBJECTIVE: Neurosurgical residents receive exposure to the subspecialty of pediatric neurosurgery during training. The authors sought to determine resident operative experience in pediatric neurosurgery across Accreditation Council for Graduate Medical Education (ACGME)-accredited neurosurgical programs. METHODS: During 2018-2019, pediatric neurosurgical case logs for recent graduates or current residents who completed their primary pediatric exposure were collected from US continental ACGME training programs. Using individual resident reports and procedure designations, operative volumes and case diversity were analyzed collectively, according to training site characteristics, and also correlated with the recently described Resident Experience Score (RES). RESULTS: Of the 114 programs, a total of 316 resident case logs (range 1-19 residents per program) were received from 86 (75%) programs. The median cumulative pediatric case volume per resident was 109 (IQR 75-161). Residents at programs with a pediatric fellowship reported a higher median case volume (143, IQR 96-187) than residents at programs without (91, IQR 66-129; p < 0.0001). Residents at programs that outsource their pediatric rotation had a lower median case volume (84, IQR 52-114) compared with those at programs with an in-house experience (117, IQR 79-170; p < 0.0001). The case diversity index among all programs ranged from 0.61 to 0.80, with no statistically significant differences according to the Accreditation Council for Pediatric Neurosurgery Fellowships designation or pediatric experience site (p > 0.05). The RES correlated moderately (r = 0.44) with median operative volumes per program. A program's annual pediatric operative volume and duration of pediatric experience were identified as significant predictive factors for median resident operative volume. CONCLUSIONS: Resident experience in pediatric neurosurgery is variable within and between programs. Case volumes are generally higher for residents at programs with in-house exposure and an accredited fellowship, but case diversity is relatively uniform across all programs. RES provides some insight on anticipated case volume, but other unexplained factors remain.
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Educación de Postgrado en Medicina/estadística & datos numéricos , Internado y Residencia , Neurocirugia/educación , Pediatría/educación , Competencia Clínica/normas , Humanos , Estados UnidosRESUMEN
OBJECTIVE: A left-sided cervical approach to esophageal mobilization is considered safer given the perceived oblique path and more lateral orientation of the right recurrent laryngeal nerve (RLN) in the tracheoesophageal groove. Given the risk of recurrent laryngeal nerve, the current study investigated if there are differences in right and left RLN location in the tracheoesophageal groove. METHODS: Right and left RLNs were carefully exposed in human cadavers. Comparison of location was determined at tracheal rings 2, 4, and 6 using 3 parameters: depth of the RLN from the anterior margin of the tracheal ring, lateral distance of the RLN from the posterior margin of the tracheal ring, and distance of the RLN to the anterior midline trachea following the curvature of the trachea. Statistical analysis was used to determine differences between the right and left sides. RESULTS: Compared with the right RLN, the left RLN was slightly over 1 mm deeper at the second tracheal ring. Despite this trend, there was no significant difference in RLN location between individual sides or as an aggregate for any of the 3 parameters at tracheal rings 2, 4, or 6. CONCLUSIONS: Careful characterization of RLN location precludes avoiding hoarseness, aphonia, and vocal cord paralysis. Counter to common surgical perception and educational beliefs, this study demonstrated that right and left RLN anatomical courses do not significantly differ along the trachea. Therefore, ensnarement on either side during a blind mobilization of the cervical esophagus is equally likely to occur.
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Traumatismos del Nervio Laríngeo Recurrente , Nervio Laríngeo Recurrente , Cadáver , Humanos , Cuello , TráqueaRESUMEN
OBJECTIVE: Standards for treatment of laryngeal clefts remain poorly defined. There are no large case series that report the efficacy of injection laryngoplasty (IL) in the treatment of pediatric Type 1 laryngeal clefts (LC-1). The objective of this study is to measure the effect of IL in young children with LC-1. METHODS: A retrospective case series of 130 patients was completed over 3 years at a at a single institution included patients aged 1 month to 8 years, diagnosed with aspiration and penetration issues during swallowing based on a Videofluoroscopic Swallow Study (VFSS). Patients underwent surgical evaluation and intervention using carboxymethylcellulose gel injection. Collected data points included age in months at time of first injection, gender, race, pre- and post-operation VFSS scores, number of injections, co-morbidities and post-operative complications. VFSS scores were evaluated pre- and post-operatively to assess efficacy of intervention. A secondary outcome was efficacy in patients with aspiration compared to those with penetration alone. RESULTS: This study included 77 male and 53 female patients. Sixty-two patients (48%) demonstrated a significant post-operative improvement in their swallowing function (P < .05). There were no statistical differences in age, number of injections, or the volume of the first injection. Patients that showed a post-operative improvement in swallowing function were on average 5 months older and had more severe aspiration and penetration compared to those who did not demonstrate a post-operative benefit and underwent less injections. The volume of injection did not appear to play a role in the success rate. CONCLUSION: Injecting the inter-arytenoid area in patients with LC-1 appears to confer some benefit to close to half of our patient population. Successful procedures seemed to occur in patients with more severe aspiration and penetration and older age.
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Anomalías Congénitas/cirugía , Laringoplastia/métodos , Laringe/anomalías , Niño , Preescolar , Anomalías Congénitas/clasificación , Femenino , Humanos , Lactante , Inyecciones , Laringe/cirugía , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Simulation can be an effective tool for educating health profession students and can enhance interprofessional education by involving roles across multiple disciplines. Perioperative nurse educators at one institution used a five-part branching simulation of preoperative, intraoperative, and postoperative events for a single patient undergoing a procedure to introduce RN first assistant (RNFA) students to their role in the perioperative environment. The simulation participants included student RN anesthetists, a surgeon, an RN circulator (played by an actor), and a standardized patient. The objectives for this simulation were to assess the implementation of the didactic RNFA curriculum and to enhance the RNFA students' transition into their role in the perioperative setting. The simulation and multiple debriefings reinforced the concepts of role acquisition, surgical conscience, closed-loop communication, and interprofessional collaboration. Perioperative nurse educators can use this type of educational activity to teach these concepts to their students.
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Relaciones Interprofesionales , Estudiantes del Área de la Salud , Actitud del Personal de Salud , Simulación por Computador , Curriculum , HumanosRESUMEN
BACKGROUND: Erosion of a pacer lead into the chest wall may result in pericardial effusion with cardiac tamponade. Free rupture into the pleura or mediastinum can result in hypotension and cardiac arrest. CASE PRESENTATION: We report a unique case of a right ventricular pacer lead which eroded through the right ventricle into the left chest wall and penetrated a rib. The patient presented with a tender chest wall mass without pericardial or pleural effusion. The segment of rib which the pacing lead had penetrated was removed. CONCLUSIONS: The patient tolerated the procedure well and was discharged 1 week after the operation. This case adds to the current literature the justification of removal of temporary and non-functional pacing leads.
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BACKGROUND: Established by the Centers for Medicare and Medicaid Services (CMS), the Open Payments Database (OPD) has reported industry payments to physicians since August 2013. OBJECTIVE: To evaluate the frequency, type, and value of payments received by academic neurosurgeons in the United States over a 5-yr period (2014-2018). METHODS: The OPD was queried for attending neurosurgeons from all neurosurgical training programs in the United States (n = 116). Information from the OPD was analyzed for the entire cohort as well as for comparative subgroup analyses, such as career stage, subspecialty, and geographic location. RESULTS: Of all identified neurosurgeons, 1509 (95.0%) received some payment from industry between 2014 and 2018 for a total of 106 171 payments totaling $266 407 458.33. A bimodal distribution was observed for payment number and total value: 0 to 9 (n = 438) vs > 50 (n = 563) and 0-$1000 (n = 418) vs >$10 000 (n = 653), respectively. Royalty/License was the most common type of payment overall (59.6%; $158 723 550.57). The median number (40) and value ($8958.95) of payments were highest for mid-career surgeons. The South-Central region received the most money ($117 970 036.39) while New England received the greatest number of payments (29 423). Spine surgeons had the greatest median number (60) and dollar value ($20 551.27) of payments, while pediatric neurosurgeons received the least (8; $1108.29). Male neurosurgeons received a greater number (31) and value ($6395.80) of payments than their female counterparts (11, $1643.72). CONCLUSION: From 2014 to 2018, payments to academic neurosurgeons have increased in number and value. Dollars received were dependent on geography, career stage, subspecialty and gender.
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Neurocirugia , Cirujanos , Anciano , Niño , Bases de Datos Factuales , Femenino , Humanos , Masculino , Medicare , Neurocirujanos , Columna Vertebral , Estados UnidosRESUMEN
BACKGROUND: Medical school wellness programs are rapidly becoming a prevalent feature of medical education. The wellness component of medical education is addressed by a multitude of different approaches, but is often led by administrative faculty rather than students. APPROACH: The first-year medical student authors collectively established a medical school wellness committee that is entirely student-driven. The goal of the wellness committee was to organize and promote student ideas centered on six aspects of wellness. EVALUATION: The formation, initial successes, and hurdles to the inception and continuation of the committee are described in a repeatable way. REFLECTION: This perspective provides insight into a student-led innovation that was formally accepted by faculty and administration to serve as part of the university's overall wellness initiatives.
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Promoción de la Salud/métodos , Facultades de Medicina/tendencias , Estudiantes de Medicina/estadística & datos numéricos , Educación de Pregrado en Medicina/métodos , Educación de Pregrado en Medicina/tendencias , Promoción de la Salud/estadística & datos numéricos , Humanos , Facultades de Medicina/organización & administraciónRESUMEN
The use of tetraspanin CD9 as a biomarker for renal cell carcinomas (RCC) has been explored with minor conclusions. Identification of a biomarker that not only distinguishes between the different types of renal cell carcinomas, but also predicts the metastatic potential of these tumors would significantly advance diagnosis and prognosis of kidney cancers. We utilized established cell lines to better understand the contribution of CD9 to the metastatic potential of clear cell renal cell carcinomas, and then applied our findings to the TCGA database and immunohistochemical analysis of human samples based on tumor grading to determine the utility of CD9 as a biomarker for RCC. Clear cell renal cell carcinoma (ccRCC) cell expression of tetraspanin CD9 was compared to normal kidney cells and found to be elevated. Upon knockdown of CD9, ccRCC cells obtained a more metastatic phenotype. We found E-cadherin expression to be repressed and the endothelial to mesenchymal transition markers Snail, Twist1, and Zeb1 to be elevated upon CD9 knockdown. Upon observing these gene expression changes in the TCGA database and in 10 cases, we found that CD9 and E-cadherin expression was lowered in higher grade ccRCC tumors. There was a significant correlation between CD9 and either E-cadherin, Snail, or Zeb1 in these tumors. Collectively, using tetraspanin CD9 in tandem with E-cadherin as a biomarker in renal cell carcinoma will help to not only distinguish between types, but also predict the metastatic potential of RCC.
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Cadherinas/metabolismo , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/secundario , Línea Celular Tumoral/metabolismo , Neoplasias Renales/metabolismo , Tetraspanina 29/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/diagnóstico , Femenino , Humanos , Neoplasias Renales/diagnóstico , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
INTRODUCTION: Dual anti-platelet therapy (DAPT) with aspirin and a P2Y12 antagonist is standard of care to reduce risk of thrombosis, but does not directly target thrombin-dependent platelet activation. Therefore, PAR-1 antagonist addition to DAPT (i.e., triple anti-platelet therapy; TAPT) may improve the efficacy of treatment, though at the expense of an increase in bleeding risk. Using an in vitro transfusion model, we evaluated if platelet function loss associated with TAPT can be remedied by the addition of drug-naïve platelets. METHODS: To mimic TAPT, platelet-rich plasma (PRP) prepared from consented DAPT patients (DPRP) was incubated with a vorapaxar at therapeutic plasma levels (TPRP). To simulate platelet transfusions, TPRP was mixed with increasing proportions of drug-naïve PRP (NPRP). Platelet function recovery was assessed by light transmission aggregometry (LTA), aggregate morphology, and P-selectin expression. RESULTS: LTA results demonstrated that 20% NPRP was required to restore the ADP aggregation response in TPRP to the response observed in DPRP and 40% NPRP recovered aggregation to >65%. Higher NPRP fractions (60%) were required to restore the platelet reactivity using TRAP-6 (SFLLRN) or arachidonic acid (AA). PAR-4 aggregation was unaffected by platelet antagonists. A decrease in single, free platelets and incorporation of mepacrine-labeled naïve platelets into aggregates occurred with increasing NPRP portions. Upon agonist activation, the surface density and percent of P-selectin positive platelets increased linearly upon addition of NPRP. CONCLUSION: This in vitro model demonstrated that administration of drug-naïve platelets can be a useful strategy for reversing overall platelet inhibition observed with TAPT.
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Transfusión Sanguínea/métodos , Inhibidores de Agregación Plaquetaria/química , Agregación Plaquetaria/efectos de los fármacos , Pruebas de Función Plaquetaria , Proteínas Reguladoras de la Apoptosis/efectos de los fármacos , Ácido Araquidónico/metabolismo , Aspirina/uso terapéutico , Plaquetas/efectos de los fármacos , Clopidogrel , Citometría de Flujo , Hemorragia , Humanos , Lactonas/uso terapéutico , Selectina-P/metabolismo , Fragmentos de Péptidos/metabolismo , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Transfusión de Plaquetas , Antagonistas del Receptor Purinérgico P2Y/química , Piridinas/uso terapéutico , Receptores Proteinasa-Activados/antagonistas & inhibidores , Receptores Purinérgicos P2Y12/metabolismo , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéuticoRESUMEN
The most prevalent cardiovascular diseases arise from alterations in vascular smooth muscle cell (VSMC) morphology and function. Tetraspanin CD9 has been previously implicated in regulating vascular pathologies; however, insight into how CD9 may regulate adverse VSMC phenotypes has not been provided. We utilized a human model of aortic smooth muscle cells to understand the consequences of CD9 deficiency on VSMC phenotypes. Upon knocking down CD9, the cells developed an abnormally small and rounded morphology. We determined that this morphological change was due to a lack of typical parallel actin arrangement. We also found similar total RhoA but decreased GTP-bound (active) RhoA levels in CD9 deficient cells. As a result, cells lacking a full complement of CD9 were less contractile than their control treated counterparts. Upon restoration of RhoA activity in the CD9 deficient cells, the phenotype was reversed and cell contraction was restored. Conversely, inhibition of RhoA activity in the control cells mimicked the CD9-deficient cell phenotype. Thus, alteration in CD9 expression was sufficient to profoundly disrupt cellular actin arrangement and endogenous cell contraction by interfering with RhoA signaling. This study provides insight into how CD9 may regulate previously described vascular smooth muscle cell pathophysiology.
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Actinas/metabolismo , Contracción Muscular , Miocitos del Músculo Liso/metabolismo , Transducción de Señal , Tetraspanina 29/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Actinas/genética , Células Cultivadas , Humanos , Miocitos del Músculo Liso/patología , Tetraspanina 29/genética , Enfermedades Vasculares/genética , Enfermedades Vasculares/metabolismo , Enfermedades Vasculares/patología , Enfermedades Vasculares/fisiopatología , Proteína de Unión al GTP rhoA/genéticaRESUMEN
Non-Hodgkin Lymphoma (NHL) is a type of hematological malignancy that affects two percent of the overall population in the United States. Tetraspanin CD9 is a cell surface protein that has been thoroughly demonstrated to be a molecular facilitator of cellular phenotype. CD9 expression varies in two human lymphoma cell lines, Raji and BJAB. In this report, we investigated the functional relationship between CD9 and cell proliferation regulated by histone deacetylase (HDAC) activity in these two cell lines. Introduction of CD9 expression in Raji cells resulted in significantly increased cell proliferation and HDAC activity compared to Mock transfected Raji cells. The increase in CD9-Raji cell proliferation was significantly inhibited by HDAC inhibitor (HDACi) treatment. Pretreatment of BJAB cells with HDAC inhibitors resulted in a significant decrease in endogenous CD9 mRNA and cell surface expression. BJAB cells also displayed decreased cell proliferation after HDACi treatment. These results suggest a significant relationship between CD9 expression and cell proliferation in human lymphoma cells that may be modulated by HDAC activity.
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Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patología , Histona Desacetilasas/metabolismo , Tetraspanina 29/metabolismo , Linfoma de Burkitt/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Curcumina/farmacología , Epigénesis Genética , Expresión Génica/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Ácidos Hidroxámicos/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Tetraspanina 29/genética , TransfecciónRESUMEN
Degradation of the surrounding extracellular matrix (ECM) by matrix metalloproteinases (MMPs) drives invasion and metastasis of cancer cells. We previously demonstrated that tetraspanin CD9 expression upregulates pro-MMP-9 expression and release and promotes cellular invasion in a human fibrosarcoma cell line (HT1080). These events were dependent upon the highly functional second extracellular loop of CD9. We report here that the epidermal growth factor receptor (EGFR) tyrosine kinase expression and activity are involved in the CD9-mediated increase in pro-MMP-9 release and cellular invasion. Pro-MMP-9 expression was significantly decreased in a dose-dependent manner using first a broad spectrum receptor tyrosine kinase inhibitor and multiple specific EGFR inhibitors in CD9-HT1080 cells. Furthermore, gefitinib treatment of CD9-HT1080 cells reduced invasion through matrigel. EGFR knockdown using short interfering RNA resulted in decreased pro-MMP-9 expression and release into the media and subsequent cellular invasion without affecting CD9 expression or localization. Conclusively, this study points to EGFR as a key mediator between CD9-mediated pro-MMP-9 release and cellular invasion of HT1080 cells.