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1.
bioRxiv ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38798480

RESUMEN

Lymphocytes can circulate as well as take residence within tissues. While the mechanisms by which circulating populations are recruited to infection sites have been extensively characterized, the molecular basis for the recirculation of tissue-resident cells is less understood. Here, we show that helminth infection- or IL-25-induced redistribution of intestinal group 2 innate lymphoid cells (ILC2s) requires access to the lymphatic vessel network. Although the secondary lymphoid structure is an essential signal hub for adaptive lymphocyte differentiation and dispatch, it is redundant for ILC2 migration and effector function. Upon IL-25 stimulation, a dramatic change in epigenetic landscape occurs in intestinal ILC2s, leading to the expression of sphingosine-1-phosphate receptors (S1PRs). Among the various S1PRs, we found that S1PR5 is critical for ILC2 exit from intestinal tissue to lymph. By contrast, S1PR1 plays a dominant role in ILC2 egress from mesenteric lymph nodes to blood circulation and then to distal tissues including the lung where the redistributed ILC2s contribute to tissue repair. The requirement of two S1PRs for ILC2 migration is largely due to the dynamic expression of the tissue-retention marker CD69, which mediates S1PR1 internalization. Thus, our study demonstrates a stage-specific requirement of different S1P receptors for ILC2 redistribution during infection. We therefore propose a fundamental paradigm that innate and adaptive lymphocytes utilize a shared vascular network frame and specialized navigation cues for migration.

2.
Soc Netw Anal Min ; 12(1): 167, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36407555

RESUMEN

Social media platforms have been exploited to disseminate misinformation in recent years. The widespread online misinformation has been shown to affect users' beliefs and is connected to social impact such as polarization. In this work, we focus on misinformation's impact on specific user behavior and aim to understand whether general Twitter users changed their behavior after being exposed to misinformation. We compare the before- and after-exposure behaviors of Twitter users to determine whether they changed their tweeting frequency, tweets sentiment, usage of specific types of words, and the ratio of liberal/conservative media URLs they shared. Our results show that users overall exhibited statistically significant changes in behavior across some of these metrics. Through language distance analysis, we show that exposed users were already different from baseline users before the exposure. We also study the characteristics of several specific user groups, which include liberal/conservative leaning groups and multi-exposure groups. Furthermore, we study whether the users' behavior changes after exposure to misinformation tweets vary based on their follower count or the follower count of the tweet authors. Finally, we examine potential bots' behaviors and find they are similar to that of normal users.

3.
J Arthroplasty ; 37(7S): S546-S551, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35277310

RESUMEN

BACKGROUND: Previous studies have demonstrated that patients with abnormal spinopelvic motion are at increased risk of dislocation. However, little is known about the effect of hip offset on dislocation risk following total hip arthroplasty (THA) in patients with abnormal spinopelvic motion. The purpose of this study is to investigate the prevalence of under-restored hip offset and spinopelvic abnormalities in a series of THA patients treated for recurrent instability. METHODS: This is a retrospective review of consecutive patients treated for hip instability following primary THA (THA+I) from 2012 to 2020. Patient demographics, surgical variables, and radiographic parameters were recorded. THA+I patients were compared to an age-matched and gender-matched control THA population without hip instability (THA). Univariate analyses were performed to compare differences between groups. RESULTS: Thirty-three THA+I patients (44 hips) were compared to 44 THA patients (44 hips). THA+I patients had a higher prevalence of spinopelvic pathology (odds ratio [OR] 7.80, 95% confidence interval [CI] 2.59-23.50, P < .001). The majority of acetabular components were placed within the Lewinnek safe zone (86.4% THA+I vs 72.7% THA; P = .119). THA+I patients were at greater risk of markedly under-restored hip offset (Δoffset ≤ 3 mm; OR 6.34, 95% CI 2.20-18.30, P = .001) and small (<32 mm) femoral head diameter (OR 4.38, 95% CI 1.53-12.53, P = .006) compared to THA patients. CONCLUSION: Lumbar degenerative disease and under-restoration of hip offset were present in a high proportion of patients with hip instability. Although multiple factors may contribute to THA instability, these data suggest that restoration of offset is essential, particularly in patients with spinopelvic pathology, and may be more important than historically described acetabular targets. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Luxación de la Cadera , Prótesis de Cadera , Luxaciones Articulares , Acetábulo/cirugía , Artroplastia de Reemplazo de Cadera/efectos adversos , Luxación de la Cadera/complicaciones , Luxación de la Cadera/etiología , Prótesis de Cadera/efectos adversos , Humanos , Luxaciones Articulares/cirugía , Estudios Retrospectivos
4.
Heart Vessels ; 37(2): 347-358, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34727208

RESUMEN

Calcific aortic valve disease (CAVD) is the most common heart valve disease requiring intervention. Most research on CAVD has focused on inflammation, ossification, and cellular phenotype transformation. To gain a broader picture into the wide range of cellular and molecular mechanisms involved in this disease, we compared the total protein profiles between calcified and non-calcified areas from 5 human valves resected during surgery. The 1413 positively identified proteins were filtered down to 248 proteins present in both calcified and non-calcified segments of at least 3 of the 5 valves, which were then analyzed using Ingenuity Pathway Analysis. Concurrently, the top 40 differentially abundant proteins were grouped according to their biological functions and shown in interactive networks. Finally, the abundance of selected osteogenic proteins (osteopontin, osteonectin, osteocalcin, osteoprotegerin, and RANK) was quantified using ELISA and/or immunohistochemistry. The top pathways identified were complement system, acute phase response signaling, metabolism, LXR/RXR and FXR/RXR activation, actin cytoskeleton, mineral binding, nucleic acid interaction, structural extracellular matrix (ECM), and angiogenesis. There was a greater abundance of osteopontin, osteonectin, osteocalcin, osteoprotegerin, and RANK in the calcified regions than the non-calcified ones. The osteogenic proteins also formed key connections between the biological signaling pathways in the network model. In conclusion, this proteomic analysis demonstrated the involvement of multiple signaling pathways in CAVD. The interconnectedness of these pathways provides new insights for the treatment of this disease.


Asunto(s)
Estenosis de la Válvula Aórtica , Calcinosis , Válvula Aórtica/metabolismo , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/metabolismo , Estenosis de la Válvula Aórtica/cirugía , Calcinosis/metabolismo , Humanos , Osteogénesis/fisiología , Proteoma/metabolismo , Proteómica
5.
Pain Med ; 22(6): 1420-1425, 2021 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-33675230

RESUMEN

OBJECTIVE: Postdural puncture headache (PDPH) is a potential complication of certain neuraxial anesthesia and spinal procedures, and some risk factors for PDPH have been identified. However, there have been no detailed analyses of rates and risk factors of PDPH after various spinal and neuraxial anesthesia procedures. METHODS: Patient data from January 1, 2015, to December 31, 2017, were retrospectively analyzed. The patients underwent dural puncture procedures (spinal anesthesia, lumbar puncture [spinal tap], lumbar cerebrospinal fluid [CSF] drainage) or nondural puncture procedures (transforaminal epidural injection, interlaminar epidural injection, epidural catheterization with patient-controlled analgesia for delivery). PDPH incidence and risk factors were evaluated. RESULTS: For dural puncture procedures, PDPH incidence was 2.96%, and risk factors were younger age, female sex, and lumbar puncture. Larger needle gauge was a risk factor according to Student t-test but not during logistic regression analysis. PDPH incidence was higher after lumbar puncture using a 22 G Tuohy needle (4.63%) than after lumbar CSF drainage using an 18 G Tuohy needle (3.05%). For nondural puncture procedures, PDPH incidence was 0.53% and did not differ between procedure types; no risk factors were identified. CONCLUSIONS: PDPH incidence and risk factors depended on the type of neuraxial anesthesia and spinal procedures. PDPH incidence after lumbar puncture using a 22 G Tuohy needle was higher than that after lumbar CSF drainage using an 18 G Tuohy needle, suggesting that catheter insertion may reduce PDPH risk. In non-dural puncture procedures, PDPH risk did not differ according to type of procedure, and no risk factors were found.


Asunto(s)
Anestesia Raquidea , Cefalea Pospunción de la Duramadre , Anestesia Raquidea/efectos adversos , Femenino , Humanos , Incidencia , Agujas/efectos adversos , Cefalea Pospunción de la Duramadre/epidemiología , Cefalea Pospunción de la Duramadre/etiología , Estudios Retrospectivos , Factores de Riesgo , Punción Espinal/efectos adversos
6.
Mol Cell ; 78(3): 459-476.e13, 2020 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-32240602

RESUMEN

The cyclin-dependent kinase 1 (Cdk1) drives cell division. To uncover additional functions of Cdk1, we generated knockin mice expressing an analog-sensitive version of Cdk1 in place of wild-type Cdk1. In our study, we focused on embryonic stem cells (ESCs), because this cell type displays particularly high Cdk1 activity. We found that in ESCs, a large fraction of Cdk1 substrates is localized on chromatin. Cdk1 phosphorylates many proteins involved in epigenetic regulation, including writers and erasers of all major histone marks. Consistent with these findings, inhibition of Cdk1 altered histone-modification status of ESCs. High levels of Cdk1 in ESCs phosphorylate and partially inactivate Dot1l, the H3K79 methyltransferase responsible for placing activating marks on gene bodies. Decrease of Cdk1 activity during ESC differentiation de-represses Dot1l, thereby allowing coordinated expression of differentiation genes. These analyses indicate that Cdk1 functions to maintain the epigenetic identity of ESCs.


Asunto(s)
Proteína Quinasa CDC2/metabolismo , Células Madre Embrionarias/fisiología , Epigénesis Genética , Adenosina Trifosfato/análogos & derivados , Adenosina Trifosfato/metabolismo , Animales , Proteína Quinasa CDC2/genética , Diferenciación Celular , Células Cultivadas , Inmunoprecipitación de Cromatina/métodos , Femenino , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Células MCF-7 , Masculino , Ratones , Ratones Noqueados , Fosforilación , Proteínas de Saccharomyces cerevisiae/metabolismo
7.
Mini Rev Med Chem ; 20(9): 779-787, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31902358

RESUMEN

Chemotherapy employs anti-cancer drugs to stop the growth of cancerous cells, but one common obstacle to the success is the development of chemoresistance, which leads to failure of the previously effective anti-cancer drugs. Resistance arises from different mechanistic pathways, and in this critical review, we focus on the Fanconi Anemia (FA) pathway in chemoresistance. This pathway has yet to be intensively researched by mainstream cancer researchers. This review aims to inspire a new thrust toward the contribution of the FA pathway to drug resistance in cancer. We believe an indepth understanding of this pathway will open new frontiers to effectively treat drug-resistant cancer.


Asunto(s)
Reparación del ADN , Resistencia a Antineoplásicos , Proteínas del Grupo de Complementación de la Anemia de Fanconi/metabolismo , Antineoplásicos/uso terapéutico , Biomarcadores/metabolismo , Reparación del ADN/efectos de los fármacos , Proteínas del Grupo de Complementación de la Anemia de Fanconi/antagonistas & inhibidores , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Transducción de Señal/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/metabolismo , Bibliotecas de Moléculas Pequeñas/farmacología
8.
Korean J Pain ; 32(3): 187-195, 2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31257827

RESUMEN

BACKGROUND: Steroid injections are commonly used in pain clinics to relieve pain and treat inflammation. In Korea, these steroid injections are well known as 'ppyeojusa', which means to inject into the bone in Korean. Some patients often have a negative perception of this treatment method due to inaccurate information about the treatment and side effects of steroids. The purpose of this study is to investigate patients' perception and knowledge of ppyeojusa. METHODS: A questionnaire about ppyeojusa was completed by patients who visited one of the pain clinics in nine university hospitals, from August 1 to September 10, 2017. RESULTS: Three-hundred seventy-four patients completed the survey. Eighty-five percent of patients had had ppyeojusa, and 74% of the respondents had heard of ppyeojusa from the mass media, friends or relatives. Only 39% of the patients answered that this injection was safe without side effects if properly spaced. Of the patients surveyed, 21% responded that ppyeojusa are "injections into the bone"; while 15% responded that ppyeojusa are "terrible injections that melted 'the bone if used a lot'". Half of the patients did not know what the active constituent is in ppyeojusa. If steroid injections are advised by the pain specialists, 89% of the patients would consent. CONCLUSIONS: Most pain clinic patients have heard of ppyeojusa. Most patients obtained information about ppyeojusa from mass media, rather than their physicians. Therefore, it is likely that most patients have inaccurate knowledge.

9.
EMBO Rep ; 20(4)2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30833345

RESUMEN

Fusobacterium nucleatum, a Gram-negative oral anaerobe, is a significant contributor to colorectal cancer. Using an in vitro cancer progression model, we discover that F. nucleatum stimulates the growth of colorectal cancer cells without affecting the pre-cancerous adenoma cells. Annexin A1, a previously unrecognized modulator of Wnt/ß-catenin signaling, is a key component through which F. nucleatum exerts its stimulatory effect. Annexin A1 is specifically expressed in proliferating colorectal cancer cells and involved in activation of Cyclin D1. Its expression level in colon cancer is a predictor of poor prognosis independent of cancer stage, grade, age, and sex. The FadA adhesin from F. nucleatum up-regulates Annexin A1 expression through E-cadherin. A positive feedback loop between FadA and Annexin A1 is identified in the cancerous cells, absent in the non-cancerous cells. We therefore propose a "two-hit" model in colorectal carcinogenesis, with somatic mutation(s) serving as the first hit, and F. nucleatum as the second hit exacerbating cancer progression after benign cells become cancerous. This model extends the "adenoma-carcinoma" model and identifies microbes such as F. nucleatum as cancer "facilitators".


Asunto(s)
Anexina A1/metabolismo , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/metabolismo , Infecciones por Fusobacterium/complicaciones , Infecciones por Fusobacterium/microbiología , Fusobacterium nucleatum/fisiología , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animales , Proliferación Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Retroalimentación Fisiológica , Xenoinjertos , Interacciones Huésped-Patógeno , Humanos , Ratones , Modelos Biológicos , Pronóstico , Unión Proteica , Transducción de Señal
10.
J Pediatr Surg ; 54(1): 189-193, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30355460

RESUMEN

BACKGROUND/PURPOSE: We initiated a pediatric surgical program including a caregiver for the induction of anesthesia. We measured preoperative midazolam administration, preoperative time, induction time, and program satisfaction. METHODS: Families with children undergoing surgery during the study period were included. Preoperative midazolam administration, preoperative time, and induction time were compared between participants and controls. Satisfaction surveys were given to participating caregivers and staff. RESULTS: The rate of preoperative midazolam use decreased from 41% (392/964) to 13% (16/118) among participants vs controls (p < 0.0001). After linear regression analysis, this difference persisted as an adjusted odds ratio of 0.29 (95% CI = 0.16-0.52). Preoperative and induction times (minutes) were similar between groups (76.2 vs 82.2, 13.8 vs 16.2, p = nonsignificant). Based on 5-point Likert surveys, the program was rated as "beneficial" or "very beneficial" to the patient by caregivers (99.2%) and staff (77.5%). Caregivers stated it "reduced" or "greatly reduced" anxiety for them (87.1%) and their child (93.2%). CONCLUSIONS: Opponents of similar programs suggest familial presence slows care and is disruptive. Our program decreased utilization of preoperative anxiolytics with no effect on operating room efficiency. Both hospital staff and participants felt the program was beneficial to the patient. Perceived caregiver and child anxiety was reduced. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Adyuvantes Anestésicos/administración & dosificación , Anestesia/métodos , Midazolam/administración & dosificación , Atención Dirigida al Paciente/métodos , Actitud del Personal de Salud , Niño , Preescolar , Familia , Femenino , Humanos , Lactante , Masculino , Satisfacción del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Encuestas y Cuestionarios
11.
PLoS One ; 13(2): e0191853, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29408885

RESUMEN

Epigenetic predisposition is thought to critically contribute to adult-onset disorders, such as retinal neurodegeneration. The histone methyltransferase, enhancer of zeste homolog 2 (Ezh2), is transiently expressed in the perinatal retina, particularly enriched in retinal ganglion cells (RGCs). We previously showed that embryonic deletion of Ezh2 from retinal progenitors led to progressive photoreceptor degeneration throughout life, demonstrating a role for embryonic predisposition of Ezh2-mediated repressive mark in maintaining the survival and function of photoreceptors in the adult. Enrichment of Ezh2 in RGCs leads to the question if Ezh2 also mediates gene expression and function in postnatal RGCs, and if its deficiency changes RGC susceptibility to cell death under injury or disease in the adult. To test this, we generated mice carrying targeted deletion of Ezh2 from RGC progenitors driven by Math5-Cre (mKO). mKO mice showed no detectable defect in RGC development, survival, or cell homeostasis as determined by physiological analysis, live imaging, histology, and immunohistochemistry. Moreover, RGCs of Ezh2 deficient mice revealed similar susceptibility against glaucomatous and acute optic nerve trauma-induced neurodegeneration compared to littermate floxed or wild-type control mice. In agreement with the above findings, analysis of RNA sequencing of RGCs purified from Ezh2 deficient mice revealed few gene changes that were related to RGC development, survival and function. These results, together with our previous report, support a cell lineage-specific mechanism of Ezh2-mediated gene repression, especially those critically involved in cellular function and homeostasis.


Asunto(s)
Proteína Potenciadora del Homólogo Zeste 2/genética , Homeostasis , Células Ganglionares de la Retina/metabolismo , Animales , Electrorretinografía , Presión Intraocular , Ratones , Ratones Noqueados , Traumatismos del Nervio Óptico/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica
12.
Proc Natl Acad Sci U S A ; 115(5): 1015-1020, 2018 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-29339491

RESUMEN

E-type cyclins (cyclins E1 and E2) are components of the core cell cycle machinery and are overexpressed in many human tumor types. E cyclins are thought to drive tumor cell proliferation by activating the cyclin-dependent kinase 2 (CDK2). The cyclin E1 gene represents the site of recurrent integration of the hepatitis B virus in the pathogenesis of hepatocellular carcinoma, and this event is associated with strong up-regulation of cyclin E1 expression. Regardless of the underlying mechanism of tumorigenesis, the majority of liver cancers overexpress E-type cyclins. Here we used conditional cyclin E knockout mice and a liver cancer model to test the requirement for the function of E cyclins in liver tumorigenesis. We show that a ubiquitous, global shutdown of E cyclins did not visibly affect postnatal development or physiology of adult mice. However, an acute ablation of E cyclins halted liver cancer progression. We demonstrated that also human liver cancer cells critically depend on E cyclins for proliferation. In contrast, we found that the function of the cyclin E catalytic partner, CDK2, is dispensable in liver cancer cells. We observed that E cyclins drive proliferation of tumor cells in a CDK2- and kinase-independent mechanism. Our study suggests that compounds which degrade or inhibit cyclin E might represent a highly selective therapeutic strategy for patients with liver cancer, as these compounds would selectively cripple proliferation of tumor cells, while sparing normal tissues.


Asunto(s)
Ciclina E/metabolismo , Neoplasias Hepáticas/metabolismo , Animales , Carcinogénesis/genética , Carcinogénesis/metabolismo , Línea Celular Tumoral , Proliferación Celular , Ciclina E/deficiencia , Ciclina E/genética , Quinasa 2 Dependiente de la Ciclina/metabolismo , Ciclinas/deficiencia , Ciclinas/genética , Ciclinas/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas Experimentales/genética , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratones , Ratones Noqueados , Proteínas Oncogénicas/deficiencia , Proteínas Oncogénicas/genética , Proteínas Oncogénicas/metabolismo
13.
Proc Natl Acad Sci U S A ; 114(40): 10660-10665, 2017 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-28923932

RESUMEN

MicroRNAs (miRNAs) have been known to affect various biological processes by repressing expression of specific genes. Here we describe an essential function of the miR-34/449 family during differentiation of epithelial cells. We found that miR-34/449 suppresses the cell-cycle machinery in vivo and promotes cell-cycle exit, thereby allowing epithelial cell differentiation. Constitutive ablation of all six members of this miRNA family causes derepression of multiple cell cycle-promoting proteins, thereby preventing epithelial cells from exiting the cell cycle and entering a quiescent state. As a result, formation of motile multicilia is strongly inhibited in several tissues such as the respiratory epithelium and the fallopian tube. Consequently, mice lacking miR-34/449 display infertility as well as severe chronic airway disease leading to postnatal death. These results demonstrate that miRNA-mediated repression of the cell cycle is required to allow epithelial cell differentiation.


Asunto(s)
Proteínas de Ciclo Celular/biosíntesis , Ciclo Celular/fisiología , Diferenciación Celular/fisiología , MicroARNs/metabolismo , Células Madre Embrionarias de Ratones/metabolismo , Animales , Proteínas de Ciclo Celular/genética , Línea Celular , Cilios/genética , Cilios/metabolismo , Trompas Uterinas/citología , Trompas Uterinas/metabolismo , Femenino , Ratones , MicroARNs/genética , Células Madre Embrionarias de Ratones/citología , Mucosa Respiratoria/citología , Mucosa Respiratoria/metabolismo
14.
Sensors (Basel) ; 16(5)2016 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-27223292

RESUMEN

We demonstrate the feasibility of constructing a novel and practical real-world mobile cloud system, called myBlackBox, that efficiently fuses multimodal smartphone sensor data to identify and log unusual personal events in mobile users' daily lives. The system incorporates a hybrid architectural design that combines unsupervised classification of audio, accelerometer and location data with supervised joint fusion classification to achieve high accuracy, customization, convenience and scalability. We show the feasibility of myBlackBox by implementing and evaluating this end-to-end system that combines Android smartphones with cloud servers, deployed for 15 users over a one-month period.

15.
Comput Biol Med ; 70: 210-219, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26851729

RESUMEN

BACKGROUND: Advanced atherosclerotic lesions are commonly characterized by the presence of calcification. Several studies indicate that extensive calcification is associated with plaque stability, yet recent studies suggest that calcification morphology and location may adversely affect the mechanical stability of atherosclerotic plaques. The underlying cause of atherosclerotic calcification and the importance of intra-plaque calcium distribution remains poorly understood. METHOD: The goal of this study was the characterization of calcification morphology based on histological features in 20 human carotid endarterectomy (CEA) specimens. Representative frozen sections (10µm thick) were cut from the common, bulb, internal and external segments of CEA tissues and stained with von Kossa׳s reagent for calcium phosphate. The morphology of calcification (calcified patches) and fibrous layer thickness were quantified in 135 histological sections. RESULTS: Intra-plaque calcification was distributed heterogeneously (calcification %-area: bulb segment: 14.2±2.1%; internal segment: 12.9±2.8%; common segment: 4.6±1.1%; p=0.001). Calcified patches were found in 20 CEAs (patch size: <0.1mm(2) to >1.0mm(2)). Calcified patches were most abundant in the bulb and least in the common segment (bulb n=7.30±1.08; internal n=4.81±1.17; common n=2.56±0.56; p=0.0007). Calcified patch circularity decreased with increasing size (<0.1mm(2): 0.77±0.01, 0.1-1mm(2): 0.62±0.01, >1.0mm(2): 0.51±0.02; p=0.0001). A reduced fibrous layer thickness was associated with increased calcium patch size (p<0.0001). CONCLUSIONS: In advanced carotid atherosclerosis, calcification appears to be a heterogeneous and dynamic atherosclerotic plaque component, as indicated by the simultaneous presence of few large stabilizing calcified patches and numerous small calcific patches. Future studies are needed to elucidate the associations of intra-plaque calcification size and distribution with atherothrombotic events.


Asunto(s)
Enfermedades de las Arterias Carótidas , Endarterectomía Carotidea , Placa Aterosclerótica , Calcificación Vascular , Enfermedades de las Arterias Carótidas/metabolismo , Enfermedades de las Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/cirugía , Femenino , Humanos , Masculino , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Placa Aterosclerótica/cirugía , Calcificación Vascular/metabolismo , Calcificación Vascular/patología , Calcificación Vascular/cirugía
16.
J Shoulder Elbow Surg ; 25(2): 256-61, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26440695

RESUMEN

BACKGROUND: With an aging population, fragility fractures including injuries to the proximal humerus continue to rise in the United States. The purpose of this study was to investigate recent trends in the incidence and treatment of proximal humerus fractures (PHFs) in a cross-sectional elderly population. METHODS: Medicare data from 2005 to 2012 were queried to identify patients treated for PHF. Associated patient demographics, hospitalization data, treatment, and revision status were obtained. Statistical analyses were performed to identify significant trends in treatment. RESULTS: There were 259,506 PHFs recorded, with 79% occurring in female patients. In all age groups, nonoperative treatment of PHF was the most common method (67%). Within the surgical group, open reduction with internal fixation was most frequently used, and total shoulder arthroplasty (TSA) or reverse total shoulder arthroplasty (RTSA) was the least common (11%). However, although the overall rate of surgical intervention remained constant, there was a significant increase in treatment with TSA from 3% in 2005 to 17% in 2012. In particular, RTSA represented 89% of all TSAs for PHF in 2011. All surgical treatment options demonstrated high 2-year survival rates without revision surgery (97%). CONCLUSION: Recent trends show that in the elderly population, nonoperative management remains the most common treatment for PHFs. Within the surgically treated cohort, there has been an increase in treatment with arthroplasty including RTSA, with a low rate of early revisions. There are excellent survival rates in all surgically treated PHFs, but long-term data will be required to fully evaluate the viability of these surgical options.


Asunto(s)
Artroplastia de Reemplazo/tendencias , Fijación Interna de Fracturas/tendencias , Fracturas Osteoporóticas/terapia , Fracturas del Hombro/terapia , Distribución por Edad , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo/métodos , Artroplastia de Reemplazo/estadística & datos numéricos , Estudios Transversales , Femenino , Fijación Interna de Fracturas/estadística & datos numéricos , Hospitalización , Humanos , Incidencia , Masculino , Medicare/estadística & datos numéricos , Persona de Mediana Edad , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/cirugía , Reoperación/estadística & datos numéricos , Distribución por Sexo , Fracturas del Hombro/epidemiología , Fracturas del Hombro/cirugía , Resultado del Tratamiento , Estados Unidos/epidemiología
17.
J Shoulder Elbow Surg ; 25(5): 739-46, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26700553

RESUMEN

BACKGROUND: Recent studies report high hardware removal rates after plate fixation of midshaft clavicular fractures. Precontoured clavicle plates may decrease hardware-related complications while improving healing rates and patient-reported outcomes (PROs). METHODS: Using a private-payer national database, we identified 7826 patients who underwent clavicle open reduction and internal fixation (ORIF) in 2007 to 2011. Database patients were tracked for 2 years to assess hardware removal and revision fixation. In addition, we retrospectively identified 73 patients who underwent plate fixation of midshaft clavicular fractures at our institution. These patients completed the Disabilities of Arm, Shoulder and Hand (DASH) assessment, the EQ-5D (EuroQol, Rotterdam, The Netherlands) quality of life assessment, and a hardware-related outcomes survey. RESULTS: Among 7826 database patients, 994 (12.7%) underwent hardware removal and 78 (1%) required revision ORIF. The annual incidence of clavicle ORIF increased 61.5% between 2007 and 2011. In our institutional cohort, 56 patients (77%) were fixed with precontoured plates and 17 (23%) with standard plates. At a mean follow-up of 4.2 years, 11 patients (15%) underwent hardware removal and 1 patient (1.4%) experienced nonunion. Patients reported excellent outcomes, with average DASH of 4.0 ± 8.9 and EQ-5D of 0.89 ± 0.19. There were no differences in PROs, hardware removal, or union rate between plate types, although our study was underpowered for these outcomes. Patients who underwent hardware removal reported lower DASH, EQ-5D, satisfaction, and shoulder function compared with patients with hardware retained. Women were more likely to undergo hardware removal in the institutional (P = .009) and the database (P < .001) cohorts. CONCLUSION: Displaced midshaft clavicle fractures have high union rates with precontoured plate fixation. Women are 4 times more likely than men to have hardware removed. Patients undergoing clavicle hardware removal report worse long-term outcomes than patients with hardware retained.


Asunto(s)
Placas Óseas/efectos adversos , Clavícula/lesiones , Fijación Interna de Fracturas/instrumentación , Fracturas Óseas/cirugía , Adolescente , Adulto , Niño , Remoción de Dispositivos , Diáfisis/lesiones , Diáfisis/cirugía , Femenino , Estudios de Seguimiento , Fijación Interna de Fracturas/efectos adversos , Curación de Fractura , Fracturas no Consolidadas/etiología , Humanos , Masculino , Persona de Mediana Edad , Reducción Abierta , Medición de Resultados Informados por el Paciente , Diseño de Prótesis/efectos adversos , Calidad de Vida , Reoperación , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto Joven
18.
Cardiovasc Eng Technol ; 5(4): 371-383, 2014 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-25419248

RESUMEN

PURPOSE: Calcific aortic valve disease (CAVD) is a serious condition with vast uncertainty regarding the precise mechanism leading to valve calcification. This study was undertaken to examine the role of the lipid lysophosphatidylcholine (LPC) in a comparison of aortic and mitral valve cellular mineralization. METHODS: The proportion of LPC in differentially calcified regions of diseased aortic valves was determined using thin layer chromatography (TLC). Next, porcine valvular interstitial cells (pVICs) from the aortic (paVICs) and mitral valve (pmVICs) were cultured with LPC (10-1 - 105 nM) and analyzed for cellular mineralization, alkaline phosphatase activity (ALPa), proliferation, and apoptosis. RESULTS: TLC showed a higher percentage of LPC in calcified regions of tissue compared to non-calcified regions. In pVIC cultures, with the exception of 105 nM LPC, increasing concentrations of LPC led to an increase in phosphate mineralization. Increased levels of calcium content were exhibited at 104 nm LPC application compared to baseline controls. Compared to pmVIC cultures, paVIC cultures had greater total phosphate mineralization, ALPa, calcium content, and apoptosis, under both a baseline control and LPC-treated conditions. CONCLUSIONS: This study showed that LPC has the capacity to promote pVIC calcification. Also, paVICs have a greater propensity for mineralization than pmVICs. LPC may be a key factor in the transition of the aortic valve from a healthy to diseased state. In addition, there are intrinsic differences that exist between VICs from different valves that may play a key role in heart valve pathology.

19.
Vasc Med ; 19(5): 343-50, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25193489

RESUMEN

BACKGROUND: Calcification in atherosclerotic plaques has been viewed as a marker of plaque stability, but whether calcification accumulates in specific anatomic sites in the carotid artery is unknown. We determined the burden and distribution of calcified plaque in carotid endarterectomy (CEA) tissues. METHODS: A total of 22 CEA tissues were imaged with high-resolution micro-computed tomography (micro-CT). Total plaque burden and total calcium score using the Agatston method were quantified. The Agatston score (AS) was also normalized for tissue size. Plaque and calcium distribution were analyzed separately for three CEA regions: common segment (CS), bulb segment (BS), and internal/external segments (IES). RESULTS: The average CEA tissue length was 40.83 (interquartile range [IQR] 33.31-42.41) mm with total plaque burden of 103.45 (IQR: 78.84-156.81) mm(3) and total AS of 38.58 (IQR 11.59-89.97). Total plaque volume was 21.02 (IQR: 14.47-25.42) mm(3) in the CS, 37.89 (22.59-48.32) mm(3) in the BS, and 54.05 (36.87-74.52) mm(3) in the IES. Of the 22 tissues, 15 had no calcium in the CS compared with three in the bulb and two in the IES. Normalized calcified plaque was most prevalent in the BS, the IES and was least prevalent in the CS. The overall correlation of calcification between histology sections and matched micro-CT images was 0.86 (p<0.001). CONCLUSIONS: Calcified plaque is heterogeneously distributed in CEA tissues with most in the bulb and IES regions. The amount of calcification in micro-CT slices shows a high correlation with matched histology sections.


Asunto(s)
Calcinosis/diagnóstico por imagen , Calcinosis/patología , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/patología , Biopsia con Aguja , Estenosis Carotídea/cirugía , Estudios de Cohortes , Endarterectomía Carotidea/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Masculino , Variaciones Dependientes del Observador , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Técnicas de Cultivo de Tejidos , Microtomografía por Rayos X/métodos
20.
Int J Burns Trauma ; 2(2): 80-5, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23071905

RESUMEN

Securing the airway is a crucial aspect during reconstructive surgeries of patients with extensive post-burn mentosternal scar contractures; however, the American Society of Anesthesiologists Difficult Airway Management Algorithm recommendation of initial direct laryngoscopy may not be appropriate for these complicated patients. Consequently, there is a significant risk for failure of intubation and airway emergency. We suggest that initial attempts at securing the airway be made with indirect laryngoscopy. Many airway techniques have been effectively used in burn patients, but the role of awake blind or fiberoptic bronchoscopy, although well established in the non-burn population, has yet to be evaluated in burn patients. We report a case series of successful management of difficult airways with fiberoptic bronchoscopy in patients with varying degrees of post-burn head and neck scar contractures.

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