RESUMEN

OBJECTIVES: The purpose of this practice example from one clinical center is to illustrate the use of interdisciplinary mobility, nutrition, and quality-of-life tools to guide prognostication, which can facilitate discussion on further treatment and goals of care. METHODS: Peer-reviewed scientific publications, expert opinions, and a case study are used to illustrate the advantages of using interdisciplinary assessment tools to assist in prognostication, culminating in shared decision-making. RESULTS: This overview includes tools identified for use by interdisciplinary teams to identify high-risk patients appropriate for timely discussions regarding goals of care to maximize the probability that people receive care aligned with their goals and values that are informed by prognostic concordance. CONCLUSIONS: Tools assessing mobility, functional status, nutrition, and quality of life can assist the interdisciplinary team in providing whole-person care and in forecasting mortality, thus giving the team valid and reliable information to present to patients and families in the shared decision-making process. Further research is needed to synthesize findings from these tools and share information amongst team members in a cohesive and reliable manner. IMPLICATIONS FOR NURSING PRACTICE: Nurses spend more time at the bedside than any other discipline. Improved knowledge of tools to forecast patients at elevated risk for mortality will empower collaboration with other disciplines to improve prognostic concordance and enhance shared decision-making culminating in optimal patient-centered care.

Asunto(s)

Toma de Decisiones Conjunta , Humanos , Pronóstico , Calidad de Vida , Femenino , Masculino , Neoplasias/enfermería , Neoplasias/terapia , Planificación de Atención al Paciente , Grupo de Atención al Paciente/organización & administración

RESUMEN

STUDY OBJECTIVES: To identify children who respond to oral iron supplementation as evidenced by increased ferritin levels and to identify factors that correlate with improvement in ferritin levels in those who respond. METHODS: A retrospective chart review of the PLMS/RLS/RSD database at Seattle Children's Hospital was carried out. Data collected included nocturnal polysomnography parameters, age, sex, initial and follow-up ferritin level and date of collection, and presence of restless legs syndrome (RLS), periodic limb movements of sleep (PLMS)/PLM disorder (PLMD), restless sleep disorder (RSD), obstructive sleep apnea (OSA), neurologic, psychiatric, neurodevelopmental, or medical comorbidity. Oral iron therapy was evaluated by side effects (none; constipation; bad taste/nausea), subjective outcome in symptoms (resolved, improved, no change), and adherence to therapy (poor, fair, good). RESULTS: Seventy-seven children were included in this study of whom 42 were classified as responders (increase in ferritin of ≥10 µg/L) and 35 were nonresponders. Age and sex were not different between groups. Adherence was the only significant predictor of an increase in ferritin of ≥10 µg/L. Constipation was seen in 7.1% of responders vs. 45.8% of nonresponders. No change in symptoms was reported in 26.2% of responders vs. 71.4% in nonresponders. A significant correlation was found between treatment duration and ferritin level change in responders but not in nonresponders. CONCLUSIONS: Side effects hinders adherence to oral iron supplementation in children. Responders to oral iron show improvement in ferritin levels and symptoms, while nonresponders show no improvement in ferritin levels despite a long-lasting treatment, at least in part of them.

Asunto(s)

Trastornos del Movimiento , Síndrome de Mioclonía Nocturna , Síndrome de las Piernas Inquietas , Trastornos del Sueño-Vigilia , Niño , Suplementos Dietéticos , Ferritinas , Humanos , Hierro , Movimiento , Síndrome de Mioclonía Nocturna/tratamiento farmacológico , Síndrome de las Piernas Inquietas/tratamiento farmacológico , Estudios Retrospectivos , Sueño

RESUMEN

We conducted a critical review of human papillomavirus (HPV) integration into the host genome in oral/oropharyngeal cancer, reviewed the literature for HPV-induced cancers, and obtained current data for HPV-related oral and oropharyngeal cancers. In addition, we performed studies to identify HPV integration sites and the relationship of integration to viral-host fusion transcripts and whether integration is required for HPV-associated oncogenesis. Viral integration of HPV into the host genome is not required for the viral life cycle and might not be necessary for cellular transformation, yet HPV integration is frequently reported in cervical and head and neck cancer specimens. Studies of large numbers of early cervical lesions revealed frequent viral integration into gene-poor regions of the host genome with comparatively rare integration into cellular genes, suggesting that integration is a stochastic event and that site of integration may be largely a function of chance. However, more recent studies of head and neck squamous cell carcinomas (HNSCCs) suggest that integration may represent an additional oncogenic mechanism through direct effects on cancer-related gene expression and generation of hybrid viral-host fusion transcripts. In HNSCC cell lines as well as primary tumors, integration into cancer-related genes leading to gene disruption has been reported. The studies have shown that integration-induced altered gene expression may be associated with tumor recurrence. Evidence from several studies indicates that viral integration into genic regions is accompanied by local amplification, increased expression in some cases, interruption of gene expression, and likely additional oncogenic effects. Similarly, reported examples of viral integration near microRNAs suggest that altered expression of these regulatory molecules may also contribute to oncogenesis. Future work is indicated to identify the mechanisms of these events on cancer cell behavior.

Asunto(s)

Genoma Humano/genética , Genoma Viral/genética , Neoplasias de Cabeza y Cuello/virología , Papillomaviridae/genética , Integración Viral/genética , Neoplasias de Cabeza y Cuello/etiología , Neoplasias de Cabeza y Cuello/genética , Humanos , Neoplasias de la Boca/etiología , Neoplasias de la Boca/genética , Neoplasias de la Boca/virología , Neoplasias Orofaríngeas/etiología , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/complicaciones

RESUMEN

Background: Inverted sinonasal (Schneiderian) papilloma (ISP) is a locally aggressive neoplasm often associated with sinonasal squamous cell carcinoma (SNSCC). While the etiology of ISP is not well understood, human papillomavirus (HPV) has been detected in a subset of cases. Our group recently identified activating somatic EGFR mutations in the majority of ISP and ISP-associated SNSCC. However, the relationship between EGFR mutations and HPV infection has not been explored. Patients and methods: We evaluated 58 ISP and 22 ISP-associated SNSCC (including 13 patients with matched ISP/SNSCC samples), as well as 14 SNSCC without clinical or pathologic evidence of an associated ISP. Formalin-fixed, paraffin-embedded samples were evaluated for EGFR mutations using Sanger sequencing and for HPV infection using GP5+/GP6+ PCR. HPV subtyping based on the L1 sequence was done for HPV positive cases including temporally distinct tumors for four patients. Clinicopathologic data including progression free survival was also analyzed. Results: All ISP and ISP-associated SNSCC demonstrated either an EGFR mutation or HPV infection. HPV and EGFR mutation were mutually exclusive in all cases of ISP-associated SNSCC and all but one ISP; this case was only weakly HPV positive, and analysis of a prior temporally distinct ISP specimen from this patient failed to show HPV infection, suggesting transient infection/incidental colonization. HPV subtypes in ISP and ISP-associated SNSCC were predominantly low-risk, in contrast with SNSCC without ISP association, which showed frequent high-risk HPV. All paired ISP and associated SNSCC samples demonstrated concordant HPV status and EGFR genotypes. ISP progression to SNSCC was significantly associated with the presence of HPV infection and the absence of an EGFR mutation (log-rank = 9.620, P = 0.002). Conclusions: Collectively our data show that EGFR mutations and HPV infection represent essential, alternative oncogenic mechanisms in ISP and ISP-associated SNSCC.

Asunto(s)

Neoplasias Primarias Múltiples/etiología , Papiloma Invertido/etiología , Infecciones por Papillomavirus/complicaciones , Neoplasias de los Senos Paranasales/etiología , Carcinoma de Células Escamosas de Cabeza y Cuello/etiología , Adulto , Anciano , Anciano de 80 o más Años , Receptores ErbB/genética , Femenino , Genes erbB-1 , Humanos , Masculino , Persona de Mediana Edad , Mutación , Senos Paranasales , Estudios Retrospectivos

RESUMEN

Advanced head and neck squamous cell carcinoma (HNSCC) remains a therapeutic challenge due to the development of therapy resistance. Several studies have implicated the development of cancer stem cells as a possible mechanism for therapy resistance in HNSCC. Heat shock protein 90's (Hsp90's) molecular chaperone function is implicated in pathways of resistance in HNSCC. Therefore, in the present study, we investigated the efficacy of novel C-terminal Hsp90 inhibitors (KU711 and KU757) in targeting HNSCC cancer stem cells (CSCs). Treatment of HNSCC human cell lines MDA1986, UMSCC 22B, and UMSCC 22B cisplatin-resistant cells with the KU compounds indicated complete blockage of self-renewal for the resistant and parent cell lines starting from 20 µM KU711 and 1 µM KU757. Dose-dependent decrease in the cancer stem cell markers CD44, ALDH, and CD44/ALDH double-positive cells was observed for all cell lines after treatment with KU711 and KU757. When cells were treated with either drug, migration and invasion were downregulated greater than 90% even at the lowest concentrations of 20 µM KU711 and 1 µM KU757. Western blot showed >90% reduction in client protein "stemness" marker BMI-1 and mesenchymal marker vimentin, as well as increase in epithelial marker E-cadherin for both cell lines, indicating epithelial to mesenchymal transition quiescence. Several CSC-mediated miRNAs that play a critical role in HNSCC therapy resistance were also downregulated with KU treatment. In vivo, KU compounds were effective in decreasing tumor growth with no observed toxicity. Taken together, these results indicate that KU compounds are effective therapeutics for targeting HNSCC CSCs.

Asunto(s)

Antineoplásicos/farmacología , Carcinoma de Células Escamosas/metabolismo , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Neoplasias de Cabeza y Cuello/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Dominios y Motivos de Interacción de Proteínas/efectos de los fármacos , Animales , Biomarcadores , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Autorrenovación de las Células/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Proteínas HSP90 de Choque Térmico/química , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Humanos , Ratones , MicroARNs/genética , Transducción de Señal , Carcinoma de Células Escamosas de Cabeza y Cuello , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

Size-selective harvest of fish stocks can lead to maturation at smaller sizes and younger ages, which may depress stock productivity and recovery. Such changes in maturation may be very slow to reverse, even following complete fisheries closures. We evaluated temporal trends in maturation of five Great Lakes stocks of yellow perch (Perca flavescens Mitchill) using indices that attempt to disentangle plastic and evolutionary changes in maturation: age at 50% maturity and probabilistic maturation reaction norms (PMRNs). Four populations were fished commercially throughout the time series, while the Lake Michigan fishery was closed following a stock collapse. We documented rapid increases in PMRNs of the Lake Michigan stock coincident with the commercial fishery closure. Saginaw Bay and Lake Huron PMRNs also increased following reduced harvest, while Lake Erie populations were continuously fished and showed little change. The rapid response of maturation may have been enhanced by the short generation time of yellow perch and potential gene flow between northern and southern Lake Michigan, in addition to potential reverse adaptation following the fishing moratorium. These results suggest that some fish stocks may retain the ability to recover from fisheries-induced life history shifts following fishing moratoria.

RESUMEN

BACKGROUND: The 9-item STarT-Back screening tool was developed in primary care patients with low back pain (LBP) to identify those at greatest risk for chronic pain and requiring targeted treatment. We conducted a secondary data analysis study to examine the performance of comparable questionnaire items in a sample of primary care patients with well-defined acute LBP. METHODS: In a prospective cohort study, 605 primary care patients with LBP of less than 30 days answered a questionnaire with 6 items identical and 3 items analogous to the 9-item STarT-Back. Participants were followed up at 6 months and 2 years. STarT-Back rules were applied to classify participant's risk of chronic LBP, and the performance of the screening items in predicting outcomes was assessed using likelihood ratios. RESULTS: The proportion of patients with chronic pain at follow-up was considerably lower (6 months: 22%; 2 years: 25%) than in the STarT-Back validation cohort (40%) of patients with pain of any duration. The probability of developing chronic pain given a high-risk designation by items similar to the STarT-Back increased the pre-test probability to 31% and 35%. Likelihood ratios were close to 1. CONCLUSIONS: A risk classification schema using the recommended cut-off scores with items similar to the STarT-Back in a primary care population with strictly defined acute LBP had limited ability to identify persons who progressed to chronic pain. The results suggest caution when applying the STarT-Back in patients with acute LBP and a need to consider a modification of its cut-offs.

Asunto(s)

Dolor Agudo/diagnóstico , Dolor Crónico/diagnóstico , Dolor de la Región Lumbar/diagnóstico , Dimensión del Dolor/normas , Dolor Agudo/clasificación , Dolor Agudo/epidemiología , Adulto , Anciano , California/epidemiología , Dolor Crónico/clasificación , Dolor Crónico/epidemiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Dolor de la Región Lumbar/clasificación , Dolor de la Región Lumbar/epidemiología , Masculino , Persona de Mediana Edad , Dimensión del Dolor/instrumentación , Atención Primaria de Salud/métodos , Atención Primaria de Salud/estadística & datos numéricos , Medición de Riesgo

RESUMEN

Cancer stem cells possess the qualities of self-renewal, tumorigenesis and the ability to recapitulate a heterogeneous tumor. Our group was the first to isolate head and neck squamous cell carcinoma (HNSCC) stem cells using the cell surface marker CD44. CD44 is a trans-membrane glycoprotein with a multitude of key-functions that regulate cancer cell proliferation and metastasis. The variety of CD44 functions is due to tissue-specific patterns of glycosylation of the extracellular portion, and to the multiple protein isoforms (CD44 variants, CD44v) generated by alternative splicing. This study investigates the expression pattern of CD44 variants in HNSCC. Ten cell lines from the most common HNSCC locations and representative of various clinical outcomes were assayed by quantitative realtime PCR, flow cytometry and immunofluorescence comparatively with normal oral keratinocytes. The CD44 v4 and v6 were exclusively abundant in HNSCC while the isoform v1,2 was expressed in normal oral keratinocytes. Of interest, the highest level of CD44v6 expression was detected in advanced metastatic HNSCC, suggesting a link between CD44v6 expression and HNSCC metastasis, while the highest CD44v4 was detected in a stage IV HNSCC refractory to chemotherapy which developed recurrence. Oral-derived HNSCC expressed the highest CD44v4 and v6, and levels corresponded with staging, showing also an increasing tendency with recurrence and metastasis. CD44v were detected predominantly in smaller cells (a characteristic that has been associated with stem cell properties) or cells with mesenchymal morphology (a characteristic that has been associated with the migratory and invasive potential of epithelial tumor cells), suggesting that CD44v differential expression in HNSCC may be representative of the morphological changes inherent during tumor progression towards a more aggressive potential, and thus contributing to the individual tumor biology. The mechanism of CD44 variant involvement in HNSCC progression and metastasis is under investigation.

Asunto(s)

Carcinoma de Células Escamosas/inmunología , Neoplasias de Cabeza y Cuello/inmunología , Receptores de Hialuranos/análisis , Neoplasias de la Boca/inmunología , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Técnica del Anticuerpo Fluorescente , Neoplasias de Cabeza y Cuello/patología , Humanos , Receptores de Hialuranos/fisiología , Neoplasias de la Boca/patología , Isoformas de Proteínas , Carcinoma de Células Escamosas de Cabeza y Cuello

RESUMEN

BACKGROUND: Cisplatin and other anticancer drugs are important in the treatment of head and neck squamous cell carcinoma; however, some tumours develop drug resistance. If chemoresistance could be determined before treatment, unnecessary drug administration would be avoided. Here, we investigated chemoresistance factors by comprehensive analyses at the protein level. METHODS: Four human carcinoma cell lines were used: cisplatin-sensitive UM-SCC-23, UM-SCC-23-CDDPR with acquired cisplatin resistance, naturally cisplatin-resistant UM-SCC-81B, and UM-SCC-23/WR with acquired 5-fluorouracil resistance. Extracted proteins were labelled with iTRAQ and analysed by tandem mass spectrometry to identify resistance. Protein expression was confirmed by western blotting and functional analysis was carried out using siRNA. RESULTS: Thirteen multiple-drug resistance proteins were identified, as well as seven proteins with specific resistance to cisplatin, including α-enolase. Differential expression of these proteins in cisplatin-resistant and -sensitive cell lines was confirmed by western blotting. Functional analysis for α-enolase by siRNA showed that cisplatin sensitivity significantly was increased in UM-SCC-81B and slightly in UM-SCC-23-CDDPR but not in UM-SCC-23/WR cells. CONCLUSIONS: We identified proteins thought to mediate anticancer drug resistance using recent proteome technology and identified α-enolase as a true cisplatin chemoresistance factor. Such proteins could be used as biomarkers for anticancer agent resistance and as targets of cancer therapy.

Asunto(s)

Antineoplásicos/farmacología , Carcinoma de Células Escamosas/metabolismo , Cisplatino/farmacología , Resistencia a Antineoplásicos , Fluorouracilo/farmacología , Neoplasias de Cabeza y Cuello/metabolismo , Proteoma/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Fosfopiruvato Hidratasa/genética , Fosfopiruvato Hidratasa/metabolismo , ARN Interferente Pequeño/genética , Receptor Notch1/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Coloración y Etiquetado , Espectrometría de Masas en Tándem

RESUMEN

BACKGROUND: Irish search and recovery divers dive on a voluntary basis to recover missing persons. During these procedures, they encounter situations not typically part of ordinary human experience and might be expected to experience psychological effects as a result. AIMS: To investigate the association of post-traumatic stress disorder (PTSD) symptoms with previous experience of missing person recovery among divers, and to investigate the coping mechanisms used. METHODS: Self-administered questionnaires were distributed to all 206 active search divers in Ireland. A validated questionnaire, the Impact of Event Scale revised (IES-R), was used together with a coping questionnaire to compare the level of symptoms in divers with and without recovery experience, and to describe the main coping factors. RESULTS: One hundred and fifty-five questionnaires were returned, a response rate of 75%. Divers with prior missing person recovery experience scored lower on all three PTSD dimensions (avoidance, intrusion and hyper-arousal) with a significant difference for intrusion (P < 0.001). Coping mechanisms listed by the divers were search and recovery training, support from peers and search unit and sense of duty. CONCLUSIONS: The results do not support the hypothesis of an accumulation of traumatic experience in experienced divers but may indicate a survivor bias of the most resilient individuals, or a wearing off of vulnerability to traumatic events with experience.

Asunto(s)

Adaptación Psicológica , Buceo , Exposición Profesional , Trabajo de Rescate , Privación Sensorial , Trastornos por Estrés Postraumático , Cadáver , Estudios Transversales , Buceo/efectos adversos , Femenino , Humanos , Irlanda , Masculino , Estrés Psicológico , Encuestas y Cuestionarios

Asunto(s)

Pierna/patología , Necrobiosis Lipoidea/patología , Adolescente , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/patología , Humanos , Masculino

RESUMEN

BACKGROUND AND PURPOSE: Head and neck squamous cell carcinoma tumors positive for laboratory biomarkers hrHPV and p16 and negative for EGFR often respond better to nonsurgical organ-preservation therapy than hrHPV-negative, p16-negative, and EGFR overexpressing tumors. CTP has been shown to distinguish which locally advanced head and neck squamous cell carcinomas will respond to induction chemotherapy or chemoradiation. Our purpose was to determine whether a relationship exists between CTP measures and the expression of these laboratory biomarkers, because both appear to separate head and neck squamous cell carcinoma tumors into similar groups. MATERIALS AND METHODS: We conducted an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective review of head and neck CTP in 25 patients with locally advanced head and neck squamous cell carcinoma who had signed informed consent. Eight women and 17 men, 41-80 years of age, constituted a pretreatment group of 18 patients and a palliative group of 7 patients. Tumor biopsy samples were analyzed for overexpression of hrHPV, p16, and EGFR. The hrHPV, p16, and EGFR status of the tumors was correlated with CTP parameters (MTT, BV, BF, CP) by using the Wilcoxon evaluation and Fischer exact test. RESULTS: There were significantly lower CP values in pretreatment tumors overexpressing EGFR (P = .04). CP values ≤17.23 were significantly correlated with EGFR overexpression (P = .015). A trend toward higher CP values was present in hrHPV-positive and p16-overexpressing pretreatment tumors (P = .14). CONCLUSIONS: A significant correlation exists between CTP measures and EGFR overexpression in head and neck squamous cell carcinomas, suggesting an association between certain imaging findings and molecular biomarkers. These results may be related to a tumor cell survival mechanism linking perfusion and biomarker expression.

Asunto(s)

Alphapapillomavirus/aislamiento & purificación , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virología , Receptores ErbB/análisis , Neoplasias de Cabeza y Cuello/metabolismo , Proteínas de Neoplasias/análisis , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/diagnóstico , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Femenino , Neoplasias de Cabeza y Cuello/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Imagen de Perfusión/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodos

RESUMEN

Despite the dismal prognosis for patients with squamous cell carcinoma of the head and neck (SCCHN), there have been no novel treatments in over 40 years. Identification of novel tumor antigens in SCCHN will facilitate the identification of potential novel treatment targets. Tumor antigens are proteins selectively expressed by tumor cells and recognized by the host immune system. Phage-displayed tumor antigens were enriched by biopanning with normal and then SCCHN-specific serum. Ninety-six phage clones were sequenced for identification, and 21 clones were validated using Luminex. One of these proteins, L23, a novel tumor antigen in SCCHN, was validated as an oncogene. L23 is upregulated in SCCHN compared with normal keratinocytes. Knockdown of L23 inhibited proliferation, invasion and cell survival. Overexpression of L23 had the reverse effect. Overexpression of L23 in non malignant cells led to transformation. Injection of SCCHN cells with knockdown of L23 in mice, induced tumors that were significantly smaller than control tumors. In conclusion, the immunomic screen yielded a panel of antigens specific to SCCHN; one of these proteins, L23, is a novel oncogene in SCCHN.

Asunto(s)

Antígenos de Neoplasias/genética , Autoanticuerpos/inmunología , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/inmunología , Neoplasias de Cabeza y Cuello/inmunología , Proteínas Ribosómicas/genética , Animales , Apoptosis/genética , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/inmunología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Línea Celular Tumoral , Proliferación Celular , Técnicas de Visualización de Superficie Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Humanos , Queratinocitos/inmunología , Ratones , Ratones Desnudos , Células 3T3 NIH , Oncogenes , Valores de Referencia , Reproducibilidad de los Resultados , Proteínas Ribosómicas/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello

RESUMEN

OBJECTIVE: (1) To determine associations between radiographic features of lumbosacral (LS) spine disc space narrowing (DSN) and osteophytes (OST) and joint metabolism biomarkers (serum cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), collagen neoepitope (C2C), C-propeptide of type II procollagen (CP-II), urine C-terminal cross-linking telopeptide (CTX-II) and N-terminal telopeptide (NTX-I)). (2) To explore interactions with race, gender and low back symptoms. DESIGN: Cross-sectional analysis of 547 participants enrolled in the Johnston County (JoCo) Osteoarthritis Project from 2003 to 2004. Mean biomarker levels were estimated with linear regression. Proportional and partial-proportional odds models were used to estimate associations. Interactions were tested with likelihood ratio tests at a P-value < 0.10. Biomarkers were natural log (ln) transformed. RESULTS: Significant differences in mean biomarker levels were found across severity of DSN for lnHA and lnC2C and lnCTX-II across severity of both DSN and OST. Moderate-to-strong associations were found between biomarkers of type II collagen and DSN, whereas associations with OST were weak. An association between lnHA and DSN was seen in women (adjusted odds ratio [aOR] = 1.34 (95% confidence intervals (CI) 1.08, 1.65)) but no association among men (aOR = 0.90 (95% CI 0.63, 1.26)). In Caucasians there was a decreased association with NTX-I and OST (aOR = 0.67 (95% CI 0.49, 0.91)) and no association in African Americans (AAs) (aOR = 1.06 (95% CI 0.76, 1.47)). There was a positive association of lnCOMP with DSN among those with low back symptoms (aOR = 1.82 (95% CI 1.02, 3.27)), but no association in those without low back symptoms (aOR = 0.65 (95% CI 0.35, 1.20)). CONCLUSION: Joint metabolism biomarkers suggest biological differences in the pathologic process involved in DSN and OST that may be gender (HA) and ethnicity (NTX-I) specific.

Asunto(s)

Desplazamiento del Disco Intervertebral/patología , Disco Intervertebral/patología , Vértebras Lumbares/diagnóstico por imagen , Osteoartritis/diagnóstico , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Progresión de la Enfermedad , Femenino , Humanos , Desplazamiento del Disco Intervertebral/complicaciones , Desplazamiento del Disco Intervertebral/metabolismo , Región Lumbosacra , Masculino , Persona de Mediana Edad , Osteoartritis/complicaciones , Osteoartritis/metabolismo , Osteofito/metabolismo , Osteofito/patología , Radiografía

Asunto(s)

Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/patología , Platibasia/etiología , Adolescente , Femenino , Humanos , Imagen por Resonancia Magnética , Osteogénesis Imperfecta/fisiopatología , Platibasia/patología

RESUMEN

Rap1GAP is a critical tumor suppressor gene that is downregulated in multiple aggressive cancers, such as head and neck squamous cell carcinoma, melanoma and pancreatic cancer. However, the mechanistic basis of rap1GAP downregulation in cancers is poorly understood. By employing an integrative approach, we demonstrate polycomb-mediated repression of rap1GAP that involves Enhancer of Zeste Homolog 2 (EZH2), a histone methyltransferase in head and neck cancers. We further demonstrate that the loss of miR-101 expression correlates with EZH2 upregulation, and the concomitant downregulation of rap1GAP in head and neck cancers. EZH2 represses rap1GAP by facilitating the trimethylation of histone 3 at lysine 27, a mark of gene repression, and also hypermethylation of rap1GAP promoter. These results provide a conceptual framework involving a microRNA-oncogene-tumor suppressor axis to understand head and neck cancer progression.

Asunto(s)

Carcinoma de Células Escamosas/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Silenciador del Gen , Neoplasias de Cabeza y Cuello/metabolismo , MicroARNs/metabolismo , Factores de Transcripción/metabolismo , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Metilación de ADN , Proteína Potenciadora del Homólogo Zeste 2 , Proteínas Activadoras de GTPasa/genética , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Neoplasias de Cabeza y Cuello/genética , Histona Metiltransferasas , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/metabolismo , Humanos , Lisina/metabolismo , Complejo Represivo Polycomb 2 , Regiones Promotoras Genéticas

RESUMEN

Antibodies to the solute carrier protein, CTL2/SLC44A2, cause hearing loss in animals, are frequently found in autoimmune hearing loss patients, and are implicated in transfusion-related acute lung injury. We cloned a novel CTL2/SLC44A2 isoform (CTL2 P1) from inner ear and identified an alternate upstream promoter and exon 1a encoding a protein of 704 amino acids which differs in the first 10-12 amino acids from the known exon 1b isoform (CTL2 P2; 706 amino acids). The expression of these CTL2/SLC44A2 isoforms, their posttranslational modifications in tissues and their localization in HEK293 cells expressing rHuCTL2/SLC44A2 were assessed. P1 and P2 isoforms with differing glycosylation are variably expressed in cochlea, tongue, heart, colon, lung, kidney, liver and spleen suggesting tissue specific differences that may influence function in each tissue. Because antibodies to CTL2/SLC44A2 have serious pathologic consequences, it is important to understand its distribution and modifications. Heterologous expression in X. laevis oocytes shows that while human CTL2-P1 does not transport choline, human CTL2-P2 exhibits detectable choline transport activity.

Asunto(s)

Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Animales , Antígenos CD/biosíntesis , Antígenos CD/química , Antígenos CD/genética , Antígenos CD/metabolismo , Enfermedades Autoinmunes , Línea Celular , Simulación por Computador , Oído Interno/metabolismo , Glicosilación , Cobayas , Pérdida Auditiva , Humanos , Inmunohistoquímica , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/genética , Proteínas de Transporte de Membrana/biosíntesis , Proteínas de Transporte de Membrana/química , Proteínas de Transporte de Membrana/genética , Ratones , Microscopía Fluorescente , Proteínas de Transporte de Catión Orgánico/biosíntesis , Proteínas de Transporte de Catión Orgánico/química , Proteínas de Transporte de Catión Orgánico/genética , Proteínas de Transporte de Catión Orgánico/metabolismo , Isoformas de Proteínas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Distribución Tisular

RESUMEN

BACKGROUND: Legislation enacted in the US State of North Carolina in 2003 requires all licenced nursing homes to report all medication errors. In 2007, nursing homes were encouraged to voluntarily convert from aggregate reporting to a new online system where they reported each individual error. METHODS: A new optional web-based reporting tool was made available to all 393 North Carolina nursing homes to submit error reports for each distinct medication error as they occurred during the year. RESULTS: A total of 5823 medication error reports were submitted by 203 sites (52%) using the new system during the reporting year, a median of 18 error reports per site. Of the 5823 error reports, 612 (10.5%) were categorised as serious. Serious errors were more likely to be caused by drugs given to the wrong patient (RR 4.39, CI 3.7 to 5.2), lab-work error (RR 2.40, CI 1.4 to 4.0), wrong product given (RR 2.22, CI 1.8 to 2.8) and medication overdoses (RR 1.49, 1.2 to 1.8). Serious errors were more likely to occur on second shift (RR 1.32, 1.1 to 1.5). Common medications that are involved in the most serious errors include warfarin (RR 2.58, CI 2.09 to 3.18) and insulin (RR 2.35, CI 1.86 to 2.97), and oxycodone combinations (RR 1.48, CI 1.07 to 2.06). CONCLUSIONS: Data collected from a nursing home medication error system can provide helpful information on serious errors that can be used to focus patient safety efforts to reduce harm. This improved information will be useful in nursing homes for continuous quality improvement efforts.

Asunto(s)

Errores de Medicación/estadística & datos numéricos , Casas de Salud/estadística & datos numéricos , Casas de Salud/normas , Seguridad del Paciente/normas , Mejoramiento de la Calidad , Sistemas de Información en Farmacia Clínica/organización & administración , Humanos , Internet , Notificación Obligatoria , Errores de Medicación/legislación & jurisprudencia , North Carolina , Casas de Salud/legislación & jurisprudencia

RESUMEN

We report a measurement of the angular distributions of Drell-Yan dimuons produced using an 800 GeV/c proton beam on a hydrogen target. The polar and azimuthal angular distribution parameters have been extracted over the kinematic range 4.5

RESUMEN

We report a high statistics measurement of Upsilon production with an 800 GeV/c proton beam on hydrogen and deuterium targets. The dominance of the gluon-gluon fusion process for Upsilon production at this energy implies that the cross section ratio, sigma(p+d-->Upsilon)/2sigma(p+p-->Upsilon), is sensitive to the gluon content in the neutron relative to that in the proton. Over the kinematic region 0