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1.
Palliat Support Care ; : 1-14, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38766704

RESUMEN

OBJECTIVES: Existing systematic reviews related to advance care planning (ACP) largely focus on specific groups and intervention efficacy or are limited to contextual factors. This research aims to identify the modifiable factors perceived by different users of ACP in healthcare settings and inform healthcare professionals about the factors affecting ACP practice. METHODS: Five English-language databases (ProQuest, PubMed, CINAHL Plus, Scopus, and Medline) and two Chinese-language databases (CNKI and NCL) were searched up to November 2022. Empirical research identifying factors related to ACP in healthcare settings was included. ACP is defined as a discussion process on future end-of-life care. Thematic synthesis was performed on all included studies. RESULTS: A total of 1871 unique articles were screened; the full texts of 193 were assessed by 4 reviewers, and 45 articles were included for analysis. Twenty-two (54%) studies were qualitative, 15 (33%) were quantitative, and 6 (13%) used mixed methods. Foci varied from 28 (62%) studies on a single subject group (either patient, family, or physician), 11 (25%) on 2 subject groups (either patient and family or patient and healthcare professional), and 6 (13%) covered 3 subject groups (patient, family, and healthcare professional). Among the 17 studies involving more than 1 subject group, only 2 adopted a dyadic lens in analysis. Complex interwoven factors were categorized into (1) intrapersonal factors, (2) interpersonal factors, and (3) socio-environmental factors, with a total of 11 themes: personal belief, emotions, the burden on others, timing, responsiveness, relationship, family dynamics, experience, person taking the lead, culture, and support. SIGNIFICANCE OF RESULTS: Patients, families, and healthcare professionals are the essential stakeholders of ACP in healthcare settings. Factors are interweaved among the intrapersonal, interpersonal, and socio-environmental dimensions. Research is warranted to examine the dynamic interactions of the 3 essential stakeholders from a multidimensional perspective, and the mechanism of the interweaving of factors.

2.
Nanotechnology ; 35(8)2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-37963407

RESUMEN

Feroxyhite (δ-FeOOH) nanomaterials were successfully synthesized through the atmospheric AC microplasma method at room temperature from ferrous sulfate aqueous solutions. Various syntheses conditions, including electric voltage, electric field strength, ferrous concentration, hydrogen peroxide concentration, and reaction duration, were systematically investigated. The synthesized products were characterized through x-ray diffraction, UV-vis absorption spectroscopy, photoluminescence spectroscopy, infra-red spectroscopy, and electron microscopy. The bandgap of the produced materials were strongly dependent of the ferrous concentration while the product ratio was dependent on all experimental conditions. The synthesis mechanism was thoroughly discussed. The synthesized nanomaterials were amorphous nanospheres, showing superparamagnetic properties at room temperature. The synthesized oxyhydroxide is a potential photovoltaic material besides its reported applications in photocatalysts and supercapacitors. The application of this synthesis technique could be extended to synthesize other oxy-hydroxide nanomaterials for renewable energy applications facilely, scalablely, cost-effectively, and environmentally.

3.
Molecules ; 28(10)2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37241892

RESUMEN

Magnetic tunnel junctions (MTJs) have been widely utilized in sensitive sensors, magnetic memory, and logic gates due to their tunneling magnetoresistance. Moreover, these MTJ devices have promising potential for renewable energy generation and storage. Compared with Si-based devices, MTJs are more tolerant to electromagnetic radiation. In this review, we summarize the functionalities of MgO-based MTJ devices under different electromagnetic irradiation environments, with a focus on gamma-ray radiation. We explore the effects of these radiation exposures on the MgO tunnel barriers, magnetic layers, and interfaces to understand the origin of their tolerance. This review enhances our knowledge of the radiation tolerance of MgO-based MTJs, improves the design of these MgO-based MTJ devices with better tolerances, and provides information to minimize the risks of irradiation under various irradiation environments. This review starts with an introduction to MTJs and irradiation backgrounds, followed by the fundamental properties of MTJ materials, such as the MgO barrier and magnetic layers. Then, we review and discuss the MTJ materials and devices' radiation tolerances under different irradiation environments, including high-energy cosmic radiation, gamma-ray radiation, and lower-energy electromagnetic radiation (X-ray, UV-vis, infrared, microwave, and radiofrequency electromagnetic radiation). In conclusion, we summarize the radiation effects based on the published literature, which might benefit material design and protection.

4.
Nephrology (Carlton) ; 27(11): 869-876, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36054582

RESUMEN

AIM: Early symptoms of primary (AL) amyloidosis are non-specific. Any delay in diagnosis and treatment results in poor outcome despite increasing treatment options. We aimed to determine baseline risk factors that identify patients with poor kidney outcomes and overall survivals. METHODS: We recruited all patients aged 18 years or above with biopsy-proven renal amyloidosis between years 2000 and 2019 in three Hong Kong regional hospitals. Patients' clinical and pathological parameters, treatment response, kidney outcomes and overall survivals were recorded and analysed. RESULTS: Thirty-six cases of renal amyloidosis were recruited. Four cases were diagnosed to have multiple myeloma. Edema was the most common presenting symptom. The mean estimated glomerular filtration rate (eGFR) was 98.8 ml/min/1.73 m2 at presentation. Autologous stem cell transplant conferred the best renal outcomes as well as patients' survival. Twenty-two patients had 50% decrease in eGFR, 12 patients developed end-stage kidney disease (ESKD) and 22 patients died. Hypertension, diabetes mellitus, proteinuria and low eGFR were identified as independent baseline risk factors for ESKD. Proteinuria, hyperlipidemia, and cardiac involvement were independent baseline risk factors for death. CONCLUSION: Amyloidosis, a rare disease with poor prognosis without treatment. Hypertension, diabetes mellitus, heavy proteinuria and low eGFR at diagnosis were associated with poor kidney outcome.


Asunto(s)
Amiloidosis , Diabetes Mellitus , Hipertensión , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Fallo Renal Crónico , Amiloidosis/diagnóstico , Amiloidosis/terapia , Tasa de Filtración Glomerular , Hong Kong/epidemiología , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/diagnóstico , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/terapia , Riñón , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Proteinuria/etiología
5.
J Youth Adolesc ; 50(7): 1437-1449, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33765227

RESUMEN

Research has shown hope to be associated with a person's well-being, but how it is affected by family factors is unclear. This study investigates whether family socio-economic status (SES) affects young adults' hope, and to what extent and how different types of parental support mediate this social disparity. The data is collected from a sample of Hong Kong youth (N = 760; 54.6% girls) which participated in a 7-year longitudinal study during age 15-22. The results from multiple regression models indicate that family SES significantly predicts hope. However, cultural and academic communication and career encouragement from parents in early years, and current parental emotional support fully mediate the relationship between family SES and hope, with parental emotional support being the strongest mediator. Implications for hope theory, practices for nurturing hope and further research are discussed to suggest possible actions.


Asunto(s)
Esperanza , Apoyo Social , Adolescente , Adulto , Femenino , Hong Kong , Humanos , Estudios Longitudinales , Masculino , Padres , Clase Social , Adulto Joven
6.
Ren Fail ; 36(6): 865-9, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24655030

RESUMEN

Kidney transplant recipients have increased risk of cancers when compared with the general population. Hepatocellular carcinoma (HCC) is extremely important in Asia where hepatitis B virus (HBV) infection is endemic. The aim is to study the epidemiological and clinical aspects of all de novo HCC in our kidney transplant recipients. Moreover, various preventive strategies which may help to optimize the outcome will also be discussed. A retrospective review of all patients who developed HCC after kidney transplantation between May 1972 and December 2011 in Hong Kong, based on the data from Hong Kong Renal Registry. After a follow-up period of 40,246 person-years, 20 patients (males 15: females 5) developed HCC. The annual incidence was 49.7/100,000 persons per year. Among them, 16 were HBV carriers, 2 were hepatitis C (HCV) carriers and 2 had HBV and HCV co-infection. Presence of HBV infection was associated with 78-fold higher risk for HCC development. Majority (85%) were asymptomatic when HCC was diagnosed by ultrasound or alpha-fetoprotein surveillance. All patients diagnosed by surveillance received active treatment while 2/3 of symptomatic patients could only receive symptomatic care and died rapidly. In conclusion, HBV infection is the major etiological factor for HCC development in kidney transplant recipients in HBV endemic areas. Regular HCC surveillance appeared to be able to detect early stage cancers which are amenable to treatment and offer the best hope of cure.


Asunto(s)
Carcinoma Hepatocelular/epidemiología , Trasplante de Riñón , Neoplasias Hepáticas/epidemiología , Complicaciones Posoperatorias/epidemiología , Sistema de Registros , Adulto , Femenino , Hong Kong/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
7.
Front Public Health ; 11: 1136744, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37181693

RESUMEN

Background: Adolescents, especially the socioeconomically disadvantaged, are facing devastating psychosocial impact of the COVID-19 pandemic during their critical developmental period. This study aims to (i) examine the socioeconomic patterning of the worsening of psychosocial wellbeing, (ii) delineate the underlying mediating factors (i.e., overall worry about COVID-19, family's financial difficulty, learning problems, and loneliness), and (iii) explore the moderating effect of resilience in the inter-relationship among adolescents under COVID-19. Methods: Based on maximum variation sampling of 12 secondary schools of diverse socioeconomic background in Hong Kong, 1018 students aged 14-16 years were recruited and completed the online survey between September and October 2021. Multi-group structural equation modeling (SEM) by resilience levels was employed to delineate the pathways between socioeconomic position and the worsening of psychosocial wellbeing. Results: SEM analysis showed a significant total effect of socioeconomic ladder with the worsening of psychosocial wellbeing during the pandemic in the overall sample (ß = -0.149 [95% CI = -0.217 - -0.081], p < 0.001), which operated indirectly through learning problems and loneliness (both p < 0.001 for their indirect effects). Consistent pattern with stronger effect size was observed in the lower resilience group; nonetheless, the associations were substantially mitigated in the higher resilience group. Conclusion: In addition to facilitating self-directed learning and easing loneliness during the pandemic, evidence-based strategies to build up resilience among adolescents are critical to buffer against the adverse socioeconomic and psychosocial impacts of the pandemic or other potential catastrophic events in the future.


Asunto(s)
COVID-19 , Humanos , Adolescente , Hong Kong/epidemiología , Pandemias , Condiciones Sociales , Análisis de Clases Latentes
8.
Nephrol Dial Transplant ; 25(7): 2303-9, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20185409

RESUMEN

BACKGROUND: The response to recombinant hepatitis B vaccine remains suboptimal among the dialysis population. METHODS: In this multi-centre randomized controlled trial, we studied the factors that modify the response to intramuscular Engerix-B vaccination in patients on peritoneal dialysis. The primary aim was to study if a three-dose schedule of extra-high dose (80 microg) of Engerix-B would offer better primary seroconversion and more persistent serological protection than the conventional 40-microg dose. RESULTS: Forty-two peritoneal dialysis patients were randomized to receive the conventional 40-microg Engerix-B dose and 45 patients to 80-microg dose. Seroconversion [hepatitis B surface antibody (anti-HBs) level > or =10 IU/l 3 months after completion of the third dose] occurred in 78.6% of patients after 40-microg Engerix-B dosage treatment versus 62.2% for those receiving 80-microg Engerix-B treatment (P = 0.11). After 12 months, the persistence of protective anti-HBs also did not differ between 40- (45.2%) and 80-microg (51.1%) treatment groups (P = 0.67). In contrast, patients with seroconversion 3 months after the third dose of Engerix-B had a higher normalized protein nitrogen appearance (nPNA) than patients without seroconversion (1.16 +/- 0.25 versus 0.96 +/- 0.23 g/kg/day, P = 0.001). Conclusions. We found no evidence of a worthwhile clinical benefit from increasing the three-dose intramuscular Engerix-B vaccine from 40- to 80-microg dose. An unplanned analysis suggested a role of improved protein intake to improve the immune response to hepatitis B vaccine in peritoneal dialysis patients.


Asunto(s)
Vacunas contra Hepatitis B/uso terapéutico , Virus de la Hepatitis B/inmunología , Hepatitis B/prevención & control , Fallo Renal Crónico/terapia , Diálisis Peritoneal , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Vacunas contra Hepatitis B/inmunología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
9.
Biochem J ; 410(3): 575-83, 2008 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-18047469

RESUMEN

During spermatogenesis, extensive restructuring of blood-testis barrier takes place to facilitate the migration of preleptotene/leptotene spermatocytes from the basal to the adluminal compartment in the seminiferous epithelium. However, the biochemical mechanisms involved in this event remain elusive. Recent studies have shown that pro-inflammatory cytokine TNFalpha (tumour necrosis factor alpha) plays a crucial role in this event by inhibiting the expression of tight junction proteins in Sertoli cells. In the present study, we sought to examine the detailed mechanism on how TNFalpha affects the expression of CLMP (coxsackie- and adenovirus-receptor-like membrane protein), a newly identified tight junction transmembrane protein, in the testis. Addition of TNFalpha (10 ng/ml) to Sertoli cell culture (TM4 cells) significantly reduced the steady-state CLMP mRNA and protein levels. In an mRNA stability assay, it was shown that the rate of CLMP mRNA degradation was significantly increased when cells treated with TNFalpha were compared with vehicle. Blockage of the JNK (c-Jun N-terminal kinase) signalling pathway by SP600125 significantly abolished the TNFalpha-mediated destabilization of CLMP mRNA. Activation of the JNK signalling pathway by TNFalpha up-regulated the expression of an RNA-binding protein, TTP (tristetraprolin). TTP was present in the RNA-protein complex in the RNA EMSA (electrophoretic mobility shift assay) and decreased the CLMP 3'-UTR (untranslated region)-dependent luciferase activity. Taken together, these results suggest that the TNFalpha-mediated mRNA degradation of the CLMP gene is controlled by TTP through the JNK signalling cascade.


Asunto(s)
Proteínas de la Membrana/metabolismo , Procesamiento Postranscripcional del ARN , ARN Mensajero/genética , Transducción de Señal/efectos de los fármacos , Tristetraprolina/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Regiones no Traducidas 3' , Animales , Secuencia de Bases , Western Blotting , Proteína de la Membrana Similar al Receptor de Coxsackie y Adenovirus , Cartilla de ADN , Ensayo de Cambio de Movilidad Electroforética , Proteínas de la Membrana/genética , Ratones , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
10.
J Cell Physiol ; 214(2): 334-44, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17620326

RESUMEN

Regulation of tight junction protein expressions in Sertoli cells is important for germ cell translocation across the blood-testis-barrier (BTB) during spermatogenesis. In this study, a novel tight junction transmembrane protein, CLMP, found expressed in mouse testis was shown to localize at the BTB along with the tight junction marker ZO-1. By the use of transient transfection assay performed in a mouse Sertoli cell-cell line, TM4 cells, we showed that the minimal CLMP promoter was located between nucleotides -550 and -288 relative to the translation start site. Site-directed mutagenic studies showed that three motifs, namely GATA, KLF4, and SRY, within this region functionally co-operated with one another to regulate CLMP gene transcription. Using specific antibodies in EMSA analysis, a ternary protein complex GATA-1/GATA-6/KLF4 was detected at all the three motifs, suggesting that a looping mechanism might involve in regulating CLMP gene transcription. Interestingly, the ubiquitously expressed transcription factors, Sp1 and Sp3, were also found in this ternary complex over the KLF4 motif. Overexpression of KLF4 significantly increased the promoter activity whilst overexpression of Sp1 or Sp3 exerted an opposite effect. In particular, co-transfection studies showed that Sp1 could significantly abolish the KLF4-induced transactivation of the CLMP gene, suggesting that KLF4 and Sp1 might compete for the same binding site on the CLMP promoter. Taken together, this differential interaction of the transcription factors, GATA-1, GATA-6, KLF4, Sp1, and Sp3, in CLMP gene expression might provide a precise machinery in regulating Sertoli cell tight junction dynamics.


Asunto(s)
Factores de Transcripción GATA/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Proteínas de la Membrana/metabolismo , Células de Sertoli/metabolismo , Factor de Transcripción Sp1/metabolismo , Animales , Línea Celular , Inmunoprecipitación de Cromatina , Proteína de la Membrana Similar al Receptor de Coxsackie y Adenovirus , Ensayo de Cambio de Movilidad Electroforética , Fluoresceína-5-Isotiocianato , Técnica del Anticuerpo Fluorescente Indirecta , Colorantes Fluorescentes , Genes Reporteros , Indoles , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Luciferasas/análisis , Luciferasas/metabolismo , Masculino , Proteínas de la Membrana/genética , Ratones , Microscopía Fluorescente , Modelos Genéticos , Mutagénesis Sitio-Dirigida , Células 3T3 NIH , Factor de Transcripción Sp1/genética , Transfección , beta-Galactosidasa/análisis , beta-Galactosidasa/metabolismo
12.
Am J Hosp Palliat Care ; 33(10): 952-958, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26261374

RESUMEN

A retrospective study was conducted to evaluate the symptoms prevalence and interventions initiated in the last 2 weeks of life, health care service utilization, and causes of death of patients with end-stage renal disease (ESRD under a renal palliative care (RPC) program. A total of 335 RPC patients were included, of which 226 patients died during the study period. The 5 most prevalent symptoms were dyspnea (63.7%), fatigue (51.8%), edema (48.2%), pain (44.2%), and anorexia (38.1%); and the 5 most prevalent interventions initiated were oxygen (69.5%), parenteral infusion (67.3%), antibiotics (53.5%), bladder catheterization (44.7%), and analgesic (39.8%) in the last 2 weeks of life. Each patient received 3.5 ± 4.4 outpatient clinic visit, 3.4 ± 10.3 home care visits, and 3.1 ± 2.7 hospital admissions. Besides ESRD (51.8%), the most common causes of death were cardiovascular events (18.6%) and infection (17.2%).


Asunto(s)
Servicios de Salud/estadística & datos numéricos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Cuidados Paliativos/métodos , Cuidado Terminal/métodos , Anciano , Anciano de 80 o más Años , Anorexia/etiología , Anorexia/terapia , Causas de Muerte , Disnea/etiología , Disnea/terapia , Edema/etiología , Fatiga/etiología , Femenino , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Humanos , Fallo Renal Crónico/mortalidad , Masculino , Dolor/etiología , Manejo del Dolor/métodos , Cuidados Paliativos/estadística & datos numéricos , Calidad de Vida , Estudios Retrospectivos , Cuidado Terminal/estadística & datos numéricos
14.
Disabil Rehabil Assist Technol ; 10(2): 149-59, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24377757

RESUMEN

PURPOSE: An electromyography-driven robot system integrated with neuromuscular electrical stimulation (NMES) was developed to investigate its effectiveness on post-stroke rehabilitation. METHODS: The performance of this system in assisting finger flexion/extension with different assistance combinations was evaluated in five stroke subjects. Then, a pilot study with 20-sessions training was conducted to evaluate the training's effectiveness. RESULTS: The results showed that combined assistance from the NMES-robot could improve finger movement accuracy, encourage muscle activation of the finger muscles and suppress excessive muscular activities in the elbow joint. When assistances from both NMES and the robot were 50% of their maximum assistances, finger-tracking performance had the best results, with the lowest root mean square error, greater range of motion, higher voluntary muscle activations of the finger joints and lower muscle co-contraction in the finger and elbow joints. Upper limb function improved after the 20-session training, indicated by the increased clinical scores of Fugl-Meyer Assessment, Action Research Arm Test and Wolf Motor Function Test. Muscle co-contraction was reduced in the finger and elbow joints reflected by the Modified Ashworth Scale. CONCLUSIONS: The findings demonstrated that an electromyography-driven NMES-robot used for chronic stroke improved hand function and tracking performance. Further research is warranted to validate the method on a larger scale. Implications for Rehabilitation The hand robotics and neuromuscular electrical stimulation (NMES) techniques are still separate systems in current post-stroke hand rehabilitation. This is the first study to investigate the combined effects of the NMES and robot on hand rehabilitation. The finger tracking performance was improved with the combined assistance from the EMG-driven NMES-robot hand system. The assistance from the robot could improve the finger movement accuracy and the assistance from the NMES could reduce the muscle co-contraction on finger and elbow joints. The upper limb functions were improved on chronic stroke patients after the pilot study of 20-session hand training with the combined assistance from the EMG-driven NMES-robot. The muscle spasticity on finger and elbow joints was reduced after the training.


Asunto(s)
Terapia por Estimulación Eléctrica/instrumentación , Electromiografía/instrumentación , Dedos/fisiopatología , Robótica/instrumentación , Rehabilitación de Accidente Cerebrovascular , Adulto , Anciano , Enfermedad Crónica , Femenino , Mano/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiopatología , Modalidades de Fisioterapia , Proyectos Piloto , Rango del Movimiento Articular , Recuperación de la Función
15.
IEEE Int Conf Rehabil Robot ; 2013: 6650392, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24187211

RESUMEN

Background and Purpose. Stroke survivors often show a limited recovery in the hand function to perform delicate motions, such as full hand grasping, finger pinching and individual finger movement. The purpose of this study is to describe the implementation of an exoskeleton robotic hand together with fine finger motor skill training on 2 chronic stroke patients. Case Descriptions. Two post-stroke patients participated in a 20-session training program by integrating 10 minutes physical therapy, 20 minutes robotic hand training and 15 minutes functional training tasks with delicate objects(card, pen and coin). These two patients (A and B) had cerebrovascular accident at 6 months and 11 months respectively when enrolled in this study. Outcomes. The results showed that both patients had improvements in Fugl-Meyer assessment (FM), Action Research Arm Test (ARAT). Patients had better isolation of the individual finger flexion and extension based on the reduced muscle co-contraction from the electromyographic(EMG) signals and finger extension force after 20 sessions of training. Discussion. This preliminary study showed that by focusing on the fine finger motor skills together with the exoskeleton robotic hand, it could improve the motor recovery of the upper extremity in the fingers and hand function, which were showed in the ARAT. Future randomized controlled trials are needed to evaluate the clinical effectiveness.


Asunto(s)
Terapia por Ejercicio/métodos , Mano/fisiopatología , Destreza Motora/fisiología , Robótica/instrumentación , Rehabilitación de Accidente Cerebrovascular , Terapia por Ejercicio/instrumentación , Humanos , Masculino , Persona de Mediana Edad , Contracción Muscular/fisiología , Recuperación de la Función , Robótica/métodos , Resultado del Tratamiento
16.
Hum Pathol ; 44(12): 2782-91, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24139214

RESUMEN

Basal-like breast cancer (BLBC) is the breast cancer subtype defined by gene profiling and generates keen clinical interest. Immunohistochemical panels using basal cytokeratins and epidermal growth factor receptor are widely adopted for its identification. Nonetheless, there are concerns about the risk for missing some true BLBCs. Both P-cadherin and vimentin have been proposed as BLBC markers, but their usefulness for BLBC classification has not been well documented. In this study, we evaluated by immunohistochemistry their expression in a large cohort of breast carcinoma. Cancers expressing vimentin or P-cadherin showed BLBC-related morphological features (high grade, presence of necrosis, and lymphocytic infiltration; P < .001 for all except P = .006 for vimentin with lymphocytic infiltration) and immunohistochemical profile (P < .001 for all markers tested except P = .007 for vimentin with human epidermal growth factor receptor 2). Concordantly, they were significantly associated with BLBC (P < .001 for both). Nonetheless, they did not appear to be good stand-alone BLBC markers. Compared with the commonly used reference panel, the specificity (95.9%) and sensitivity (43.1%) of coexpression of vimentin and P-cadherin were better than most single markers or their combinations tested. Moreover, their coexpression was significantly associated with basal features in non-BLBCs and worse disease-free survival in triple-negative breast cancers (hazard ratio, 2.232; P = .027). This raised the possibility that the vimentin and P-cadherin combination can be used to identify BLBC especially those that were missed by the commonly used basal cytokeratins and epidermal growth factor receptor panel. Together, P-cadherin and vimentin could be adjunctive to the commonly used immunohistochemical surrogates for BLBC identification.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Cadherinas/metabolismo , Carcinoma Ductal de Mama/diagnóstico , Neoplasias de la Mama Triple Negativas/diagnóstico , Vimentina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Diagnóstico Diferencial , Supervivencia sin Enfermedad , Receptores ErbB/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Sensibilidad y Especificidad , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología
17.
J Clin Invest ; 123(11): 4909-17, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24216480

RESUMEN

Lumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown. Here we report the findings from linkage and association studies on a total of 32,642 subjects consisting of 4,043 LDD cases and 28,599 control subjects. We identified carbohydrate sulfotransferase 3 (CHST3), an enzyme that catalyzes proteoglycan sulfation, as a susceptibility gene for LDD. The strongest genome-wide linkage peak encompassed CHST3 from a Southern Chinese family­based data set, while a genome-wide association was observed at rs4148941 in the gene in a meta-analysis using multiethnic population cohorts. rs4148941 lies within a potential microRNA-513a-5p (miR-513a-5p) binding site. Interaction between miR-513a-5p and mRNA transcribed from the susceptibility allele (A allele) of rs4148941 was enhanced in vitro compared with transcripts from other alleles. Additionally, expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of human subjects carrying the A allele of rs4148941. Together, our data provide new insights into the etiology of LDD, implicating an interplay between genetic risk factors and miRNA.


Asunto(s)
Degeneración del Disco Intervertebral/enzimología , Degeneración del Disco Intervertebral/genética , Vértebras Lumbares , Polimorfismo de Nucleótido Simple , Sulfotransferasas/genética , Regiones no Traducidas 3' , Pueblo Asiatico/genética , Secuencia de Bases , Sitios de Unión/genética , Estudios de Casos y Controles , Cromosomas Humanos Par 10/genética , Estudios de Cohortes , Femenino , Finlandia , Ligamiento Genético , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Heterocigoto , Humanos , Degeneración del Disco Intervertebral/patología , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Mutación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Carbohidrato Sulfotransferasas
18.
Orthop Clin North Am ; 42(4): 447-64, vii, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21944583

RESUMEN

The intervertebral disks along the spine provide motion and protection against mechanical loading. The 3 structural components, nucleus pulposus, annulus fibrosus, and cartilage endplate, function as a synergistic unit, though each has its own role. The cells within each of these components have distinct origins in development and morphology, producing specific extracellular matrix proteins that are organized into unique architectures fit for intervertebral disk function. This article focuses on various aspects of intervertebral disk biology and disruptions that could lead to diseases such as intervertebral disk degeneration.


Asunto(s)
Degeneración del Disco Intervertebral/fisiopatología , Disco Intervertebral/anatomía & histología , Disco Intervertebral/fisiología , Vértebras Cervicales , Citocinas/metabolismo , Femenino , Humanos , Disco Intervertebral/embriología , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/fisiopatología , Vértebras Lumbares , Masculino , Metaloproteinasas de la Matriz/metabolismo , Vértebras Torácicas
19.
J Cell Physiol ; 207(1): 144-57, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16250013

RESUMEN

Nectin-2, a major protein component of the adherens junctions (AJs), is found between Sertoli cells and germ cells in the seminiferous epithelium. Recent studies have shown that the expression of nectin-2 gene in testis is crucial to maintain normal spermatogenesis since male knockout mice lacking nectin-2 gene are sterile and possess morphologically abnormal spermatozoa. However, the molecular mechanisms governing its basal transcription remain poorly understood. By the use of Sertoli and germ cell-lines (TM4 and GC-2spd(ts) cells, respectively) in transient transfection studies, we showed that the minimal mouse nectin-2 promoter was located between nucleotides -316 and -211 (relative to the translation start site). Two putative Sp1 motifs and one each of the CRE, AP1, and AP2 motifs were identified within this region. Mutational studies showed that these two Sp1 motifs cooperated synergistically with the CRE motif, but not the AP1 and AP2 motifs, to regulate nectin-2 gene transcription in both TM4 and GC-2spd(ts) cells. By EMSAs, we found that an AP-1 consensus sequence was able to inhibit DNA-protein complex formation with the CRE motif, suggesting an interaction between the AP-1 transcription factor (c-Jun) and CREB within the CRE motif. Overexpressions of CREB and c-Jun, but not c-Fos, also significantly increased the promoter activity, which suggests that CREB and c-Jun are the crucial transcription factors involved in regulating nectin-2 gene transcription. Chromatin immunoprecipitation assay has shown that, in vivo, CREB, c-Jun, and Sp1 family proteins are bound to the mouse nectin-2 promoter. Analysis of the staged tubules has confirmed that the cyclic expressions of CREB and nectin-2 coincide with the event of adherens junction restructuring between Sertoli cells and germ cells. The cross-talk between CREB, c-Jun, and Sp1 family protein is believed to be a major transcription machinery to drive nectin-2 expression in Sertoli cells.


Asunto(s)
Moléculas de Adhesión Celular/genética , Expresión Génica/genética , Células de Sertoli/metabolismo , Espermatogonias/metabolismo , Factores de Transcripción/genética , Animales , Moléculas de Adhesión Celular/metabolismo , Línea Celular , Inmunoprecipitación de Cromatina , Colforsina/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Proteínas Quinasas Dependientes de AMP Cíclico/genética , ADN/metabolismo , Análisis Mutacional de ADN , Ensayo de Cambio de Movilidad Electroforética , Eliminación de Gen , Masculino , Ratones , Mutagénesis Sitio-Dirigida , Mutación , Nectinas , Regiones Promotoras Genéticas/genética , Unión Proteica , Proteínas Proto-Oncogénicas c-jun/metabolismo , ARN Interferente Pequeño/genética , Epitelio Seminífero/metabolismo , Factor de Transcripción Sp1/genética , Factor de Transcripción Sp1/metabolismo , Factor de Transcripción Sp3/genética , Factor de Transcripción Sp3/metabolismo , Testículo/citología , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Factor de Transcripción AP-2/genética , Factores de Transcripción/metabolismo , Transfección
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