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1.
BMC Med Inform Decis Mak ; 24(1): 71, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38475812

RESUMEN

BACKGROUND: Wearable devices have the advantage of always being with individuals, enabling easy detection of their movements. Smart clothing can provide feedback to family caregivers of older adults with disabilities who require in-home care. METHODS: This study describes the process of setting up a smart technology-assisted (STA) home-nursing care program, the difficulties encountered, and strategies applied to improve the program. The STA program utilized a smart-vest, designed specifically for older persons with dementia or recovering from hip-fracture surgery. The smart-vest facilitated nurses' and family caregivers' detection of a care receiver's movements via a remote-monitoring system. Movements included getting up at night, time spent in the bathroom, duration of daytime immobility, leaving the house, and daily activity. Twelve caregivers of older adults and their care receiver participated; care receivers included persons recovering from hip fracture (n = 5) and persons living with dementia (n = 7). Data about installation of the individual STA in-home systems, monitoring, and technical difficulties encountered were obtained from researchers' reports. Qualitative data about the caregivers' and care receivers' use of the system were obtained from homecare nurses' reports, which were explored with thematic analysis. RESULTS: Compiled reports from the research team identified three areas of difficulty with the system: incompatibility with the home environment, which caused extra hours of manpower and added to the cost of set-up and maintenance; interruptions in data transmissions, due to system malfunctions; and inaccuracies in data transmissions, due to sensors on the smart-vest. These difficulties contributed to frustration experienced by caregivers and care receivers. CONCLUSIONS: The difficulties encountered impeded implementation of the STA home nursing care. Each of these difficulties had their own unique problems and strategies to resolve them. Our findings can provide a reference for future implementation of similar smart-home systems, which could facilitate ease-of-use for family caregivers.


Asunto(s)
Demencia , Fracturas de Cadera , Servicios de Atención de Salud a Domicilio , Humanos , Anciano , Anciano de 80 o más Años , Cuidadores , Atención Domiciliaria de Salud , Vestuario
2.
Cancers (Basel) ; 15(3)2023 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-36765770

RESUMEN

BACKGROUND: Urothelial carcinoma of the bladder (UCB) is the second most common genitourinary cancer. This study aims to assess the diagnostic accuracy of CA125 in advanced UCB. METHODS: We searched prevalent studies in PubMed, the Cochrane Library, Scopus, Embase, the Web of Science China National Knowledge Infrastructure database, and Wanfang data before October 2022. Pooled sensitivity, specificity, and summary receiver operating characteristics were used to assess the diagnostic value of CA125. RESULTS: One thousand six hundred forty-one patients from 14 studies were analyzed. UCB stage T3-4N1 was defined as advanced UCB in ten studies; T2-4 was used in three studies; and N1M1 in one study. Patients' age was between 21 to 92, and 21% to 48.6% of patients were female. The pooled sensitivity was 0.695 (95% confidence interval (CI): 0.426-0.875). The pooled specificity was 0.846 (95% CI: 0.713-0.924). The diagnostic odds ratio was 8.138 (95% CI: 4.559-14.526). The AUC was 0.797. CONCLUSION: CA125 may provide significant diagnostic accuracy in identifying muscle-invasive, lymph node-involved, and distant metastatic tumors in patients with urothelial carcinoma of the bladder. Limited studies have been conducted on the prognostic role of CA125. More studies are needed for a meta-analysis on the prognostic role of CA125 in UCB.

3.
BMC Med Educ ; 22(1): 397, 2022 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-35606757

RESUMEN

BACKGROUND: Given that the consequences of treatment decisions for end-stage renal disease (ESRD) patients are long-term and significant, good communication skills are indispensable for health care personnel (HCP) working in nephrology. However, HCP have busy schedules that make participation in face-to-face courses difficult. Thus, online curricula are a rising trend in medical education. This study aims to examine the effectiveness of online ESRD communication skills training (CST) concerning the truth-telling confidence and shared decision-making (SDM) ability of HCP. METHODS: For this single-center, single-blind study, 91 participants (nephrologists and nephrology nurses) were randomly assigned to two groups, the intervention group (IG) (n = 45) or the control group (CG) (n = 46), with the IG participating in ESRD CST and the CG receiving regular in-service training. Truth-telling confidence and SDM ability were measured before (T0), 2 weeks after (T1), and 4 weeks after (T2) the intervention. Group differences over the study period were analyzed by generalized estimating equations. RESULTS: IG participants exhibited significantly higher truth-telling confidence at T1 than did CG participants (t = 2.833, P = .006, Cohen's d = 0.59), while there were no significant intergroup differences in the confidence levels of participants in the two groups at T0 and T2. Concerning SDM ability, there were no significant intergroup differences at any of the three time points. However, IG participants had high levels of satisfaction (n = 43, 95%) and were willing to recommend ESRD CST to others (n = 41, 91.1%). CONCLUSIONS: ESRD CST enhanced short-term truth-telling confidence, though it is unclear whether this was due to CST content or the online delivery. However, during pandemics, when face-to-face training is unsuitable, online CST is an indispensable tool. Future CST intervention studies should carefully design interactive modules and control for method of instruction.


Asunto(s)
Fallo Renal Crónico , Neoplasias , Comunicación , Atención a la Salud , Humanos , Fallo Renal Crónico/terapia , Neoplasias/terapia , Método Simple Ciego
4.
BMC Geriatr ; 22(1): 104, 2022 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-35123399

RESUMEN

BACKGROUND: The purpose of this preliminary study was to explore whether a smart clothes-assisted home-nursing care program could benefit family caregivers and their care recipients. METHODS: Family caregivers in charge of a care recipient's living situation participated in this convergent parallel, mixed methods study. We recruited older persons with dementia (n = 7) and those discharged following hip-fracture surgery (n = 6) from neurological clinics and surgical wards of a medical center, respectively, along with their family caregivers: three spouses, eight sons, one daughter, and one daughter-in-law. Care recipients were asked to wear a smart vest at least 4 days/week for 6 months, which contained a coin-size monitor hidden in an inner pocket. Sensors installed in bedrooms and living areas received signals from the smart clothing, which were transmitted to a mobile phone app of homecare nurses, who provided caregivers with transmitted information regarding activities, emergency situations and suggestions for caregiving activities. Outcomes included changes from baseline in caregivers' preparedness and depressive symptoms collected at 1- and 3-months, which were analyzed with Friedman's non-parametric test of repeated measures with post-hoc analysis. Transcripts of face-to-face semi-structured interview data about caregivers' experiences were analyzed to identify descriptive, interpretative, and pattern codes. RESULTS: Preparedness did not change from baseline at either 1- or 3-months for family caregivers of persons with dementia. However, depressive symptoms decreased significantly at 1-month and 3-months compared with baseline, but not between 1-months and 3-months. Analysis of the interview data revealed the smart clothes program increased family caregivers' knowledge of the care recipient's situation and condition, informed healthcare providers of the care recipient's physical health and cognitive status, helped homecare nurses provide timely interventions, balanced the care recipient's exercise and safety, motivated recipients to exercise, helped family caregivers balance work and caregiving, and provided guidance for caregiving activities. CONCLUSIONS: Experiences with the smart clothes-assisted home-nursing care program directly benefited family caregivers, which provided indirect benefits to the care recipients due to the timely interventions and caregiving guidance from homecare nurses. These benefits suggest a smart-clothes-assisted program might be beneficial for all family caregivers.


Asunto(s)
Demencia , Servicios de Atención de Salud a Domicilio , Anciano , Anciano de 80 o más Años , Cuidadores/psicología , Vestuario , Familia/psicología , Humanos
5.
BMC Gastroenterol ; 21(1): 406, 2021 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-34706664

RESUMEN

BACKGROUND: Underwater polypectomy without the need for submucosal injection has been reported. A heat-sink effect by immersing the polyp in water was proposed but no such experiment has been performed to support the claim. We compared the temperature rise on the serosal side during polypectomy between air- and water-filled colon. METHOD: Freshly harvested porcine colons were placed in a metal tray with cautery electrode pad attached to its bottom. An upper endoscope was used with a cap and a rubber band mounted to the distal end. A mucosal site was randomly selected and identified on its serosal surface with a marker while suction was applied. Suction was applied again and a ligation band was applied to create a polyp. A cautery snare grasped the artificial polyp just below the band. An assistant placed the tip of a thermometer at the marked site on the serosal surface to record the baseline temperature before cautery and the highest temperature during polypectomy. Seven polypectomies in air and underwater were performed. RESULTS: Mean (standard deviation) baseline temperature were 23.3 (0.6) °C and 23.4 (0.6) °C in the air and water groups, respectively. The maximum rise in temperature during polypectomy was 6.1 (4.5) °C and 1.4 (1.0) °C in the air and water groups, respectively (P = 0.004). CONCLUSIONS: The maximum temperature rise during polypectomy was significantly less when polypectomy was performed underwater, supporting the hypothesis that a heat-sink effect does exist during underwater polypectomy.


Asunto(s)
Pólipos del Colon , Animales , Colon , Pólipos del Colon/cirugía , Colonoscopía , Electrocoagulación , Calor , Porcinos
6.
Hepatology ; 74(2): 641-655, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33675094

RESUMEN

BACKGROUND AND AIMS: PreS mutants of HBV have been reported to be associated with HCC. We conducted a longitudinal study of the role of HBV preS mutations in the development of HCC, particularly in patients with chronic hepatitis B (CHB) having low HBV DNA or alanine aminotransferase (ALT) levels, and investigated the effects of secretion-defective preS2 deletion mutant (preS2ΔMT) on hepatocyte damage in vitro and liver fibrosis in vivo. APPROACH AND RESULTS: Association of preS mutations with HCC in 343 patients with CHB was evaluated by a retrospective case-control follow-up study. Effects of preS2ΔMT on HBsAg retention, endoplasmic reticulum (ER) stress, calcium accumulation, mitochondrial dysfunction, and liver fibrosis were examined. Multivariate analysis revealed a significant association of preS mutations with HCC (HR, 3.210; 95% CI, 1.072-9.613; P = 0.037) including cases with low HBV DNA or ALT levels (HR, 2.790; 95% CI, 1.133-6.873; P = 0.026). Antiviral therapy reduced HCC risk, including cases with preS mutations. PreS2ΔMT expression promoted HBsAg retention in the ER and unfolded protein response (UPR). Transmission electron microscopic examination, MitoTracker staining, real-time ATP assay, and calcium staining of preS2ΔMT-expressing cells revealed aberrant ER and mitochondrial ultrastructure, reduction of mitochondrial membrane potential and ATP production, and calcium overload. Serum HBV secretion levels were ~100-fold lower in preS2ΔMT-infected humanized Fah-/-/ Rag2-/-/Il2rg-/- triple knockout mice than in wild-type HBV-infected mice. PreS2ΔMT-infected mice displayed up-regulation of UPR and caspase-3 and enhanced liver fibrosis. CONCLUSIONS: PreS mutations were significantly associated with HCC development in patients with CHB, including those with low HBV DNA or ALT levels. Antiviral therapy reduced HCC occurrence in patients with CHB, including those with preS mutations. Intracellular accumulation of mutated HBsAg induced or promoted ER stress, calcium overload, mitochondrial dysfunction, impaired energy metabolism, liver fibrosis, and HCC.


Asunto(s)
Carcinoma Hepatocelular/epidemiología , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/inmunología , Cirrosis Hepática/epidemiología , Neoplasias Hepáticas/epidemiología , Precursores de Proteínas/genética , Adulto , Animales , Antivirales/uso terapéutico , Carcinogénesis/inmunología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Femenino , Estudios de Seguimiento , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/patología , Hepatitis B Crónica/virología , Hepatocitos/trasplante , Interacciones Huésped-Patógeno/genética , Humanos , Cirrosis Hepática/inmunología , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Estudios Longitudinales , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Mitocondrias Hepáticas/patología , Mutación , Precursores de Proteínas/inmunología , Estudios Retrospectivos , Quimera por Trasplante
7.
Front Neurol ; 12: 789216, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35250792

RESUMEN

BACKGROUND: We aimed to estimate the risk of rerupture after first-time aneurysmal clipping surgery, explore the possible related factors, and assess long-term physical functionality. We hypothesized that the modified Rankin scale (mRS) could serve as an effective substitute for Hunter and Hess scale. METHODS: This retrospective study included 171 patients with cerebral aneurysmal rupture who had completed aneurysmal clipping treatment and collected their demographic data and medical records. The outcome assessments include neuroimaging records, Hunter and Hess scale, and the mRS scale during hospitalization and follow-up after discharge. The mean length of follow-up was 4.28 years. RESULTS: After aneurysmal clipping treatment, 83 patients (48.5%) had subsequently ruptured aneurysms. The scores of the reruptured group on the Hunt and Hess scale and mRS were significantly higher than those of the non-reruptured group. Multiple Cox proportional-hazards regression also showed that postoperative mRS >2, smoking, and two or more aneurysms were potentially important risk factors leading to aneurysm rupture again [the corresponding hazard ratios (HRs) were 5.209, 2.109, and 2.775, respectively] in patients. In addition, the location of an aneurysm on the anterior cerebral artery (ACA) or the posterior communicating (Pcom) artery had a higher risk of rerupture (the corresponding HRs were 1.996 and 2.934, respectively). CONCLUSIONS: Nearly half of the collected participants experienced the rerupture episode, who had undergone the second-time clipping surgery. Smoking and multiple aneurysms are potential risk factors for aneurysmal rerupture. Most aneurysms are located along the ICA, but aneurysms located at the ACA or Pcom site are most likely to rerupture. As compared with the Hunter and Hess scale, the mRS scale does not have inferior predicting power in following patients' long-term functionalities.

8.
Phytomedicine ; 59: 152756, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31004885

RESUMEN

BACKGROUND: According to Compendium of Materia Medica, Gastrodia elata (GE) Blume as a top grade and frequently prescribed herbal medicine has been used in treating dizziness, headaches, and epilepsy, indicating a neuroprotective effect. Because GE is capable of suppressing a hyperactive liver and thus calming endogenous wind, and because Huntington's disease (HD) can be classified as a phenomenon of disturbed liver wind, it is suggested that GE might be beneficial in treating HD. However, although current studies support GE for the prevention of diverse neurodegenerations such as HD, its detailed mechanisms remain elusive. PURPOSE: To investigate the molecular mechanism of GE in preventing HD by focusing on mitochondrial morphology, which is highly associated with HD etiology and thus proposed as a therapeutic target of neurodegenerations. STUDY DESIGN/METHODS: The overexpression of the mutant huntingtin (mHTT) gene in rat pheochromocytoma (PC12) cells was used as an in vitro cell model of HD. A filter retardation assay was applied to measure protein aggregations during HTT expression. Cotransfection with mitochondrial fusion and fission genes was used to test their relationships with HTT aggregates by monitoring with a confocal laser scanning microscope and filter retardation assay. Western blot analysis was used to estimate protein expression under different drug treatments or cotransfections with other related genes. RESULTS: The overexpression of mutant but not normal HTT genes significantly resulted in protein aggregations in PC12 cells. GE dose-dependently attenuated mHTT-induced protein aggregations and free radical formations. GE significantly reversed mHTT-induced mitochondrial fragmentation and dysregulation of mitochondrial fusion and fission molecules. The overexpression of mitochondrial fusion genes attenuated mHTT-induced protein aggregations. Further, Mdivi-1, a DRP1 fission molecule inhibitor, significantly reversed mHTT-induced protein aggregations and mitochondrial fragmentation. CONCLUSION: GE attenuated mHTT aggregations through the control of mitochondrial fusion and the fission pathway.


Asunto(s)
Gastrodia , Proteína Huntingtina/metabolismo , Enfermedad de Huntington/metabolismo , Mitocondrias/efectos de los fármacos , Extractos Vegetales/farmacología , Agregado de Proteínas/efectos de los fármacos , Animales , Proteína Huntingtina/genética , Enfermedad de Huntington/tratamiento farmacológico , Mitocondrias/metabolismo , Mutación , Células PC12 , Fitoterapia , Extractos Vegetales/uso terapéutico , Ratas
9.
J Cell Sci ; 131(23)2018 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-30404828

RESUMEN

α-Synuclein is associated with Parkinson's disease, and is mainly localized in presynaptic terminals and regulates exocytosis, but its physiological roles remain controversial. Here, we studied the effects of soluble and aggregated α-synuclein on exocytosis, and explored the molecular mechanism by which α-synuclein interacts with regulatory proteins, including Rab3A, Munc13-1 (also known as Unc13a) and Munc18-1 (also known as STXBP1), in order to regulate exocytosis. Through fluorescence recovery after photobleaching experiments, overexpressed α-synuclein in PC12 cells was found to be in a monomeric form, which promotes exocytosis. In contrast, aggregated α-synuclein induced by lactacystin treatment inhibits exocytosis. Our results show that α-synuclein is involved in vesicle priming and fusion. α-Synuclein and phorbol 12-myristate 13-acetate (PMA), which is known to enhance vesicle priming mediated by Rab3A, Munc13-1 and Munc18-1, act on the same population of vesicles, but regulate priming independently. Furthermore, the results show a novel effects of α-synuclein on mobilizing Ca2+ release from thapsigargin-sensitive Ca2+ pools to enhance the ATP-induced [Ca2+]i increase, which enhances vesicle fusion. Our results provide a detailed understanding of the action of α-synuclein during the final steps of exocytosis.


Asunto(s)
Calcio/metabolismo , Exocitosis/fisiología , Tapsigargina/farmacología , alfa-Sinucleína/metabolismo , Animales , Fusión de Membrana/fisiología , Células PC12 , Ratas , Tapsigargina/metabolismo , Transfección , Proteína de Unión al GTP rab3A/genética , Proteína de Unión al GTP rab3A/metabolismo
10.
Nephrology (Carlton) ; 23(6): 559-564, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28346975

RESUMEN

AIM: The prevalence of hypothyroidism is high in haemodialysis (HD) patients and hypothyroidism increases all-cause mortality in HD patients. Comorbidities are common in HD patients and are associated with both mortality and hypothyroidism. The aim of the study is to explore the effect of the interactions of comorbidities and hypothyroidism on all-cause mortality in HD patients. METHOD: Patients with hypothyroidism (ICD-9-CM 244.0, 244.1, and 244.9) and matched patients without hypothyroidism in the Registry for Catastrophic Illness Patient Database of Taiwan Health Insurance from 2000 to 2010 were analyzed. The association of hypothyroidism and risk of all-cause mortality was analyzed using Cox proportional hazard regression. RESULT: Nine hundred and eight HD patients with hypothyroidism and 3632 sex-, age-, gender- matched HD patients without hypothyroidism were analyzed. Hypothyroidism was associated with increased all-cause mortality with an adjusted hazard ratio of 1.22 [95% confidence interval (CI): 1.10-1.36, P < 0.001]. TRT may decrease mortality associated with hypothyroidism (P < 0.001). There was a significant interaction (P = 0.04) between diabetes and hypothyroidism. There was no significant interaction found in hypothyroidism and the following comorbidities: hyperlipidaemia, hypertension, chronic obstructive pulmonary disease, coronary artery disease, stroke, peripheral arterial disease, asthma, congestive heart failure and cancer. CONCLUSION: Hypothyroidism is associated with increased all-cause mortality in chronic HD patients. The interaction of hypothyroidism and diabetes, but not other common comorbidities in HD patients, has an effect on mortality risks.


Asunto(s)
Hipotiroidismo/mortalidad , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Diálisis Renal/mortalidad , Adulto , Anciano , Distribución de Chi-Cuadrado , Comorbilidad , Bases de Datos Factuales , Diabetes Mellitus/mortalidad , Femenino , Humanos , Hipotiroidismo/diagnóstico , Estimación de Kaplan-Meier , Fallo Renal Crónico/diagnóstico , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Sistema de Registros , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiología , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
11.
PLoS One ; 12(4): e0175475, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28403222

RESUMEN

BACKGROUND: Comorbid medical diseases are highly prevalent in the geriatric population, imposing hardship on healthcare services for demented individuals. Dementia also complicates clinical care for other co-existing medical conditions. This study investigated the comorbidities associated with dementia in the elderly population aged 65 years and over in Taiwan. METHODS: We conducted a nationwide, population-based, cross-sectional survey; participants were selected by computerized random sampling from all 19 Taiwan counties between December 2011 and March 2013. After exclusion of incomplete or erroneous data, 8,456 subjects were enrolled. Of them, 6,183 were cognitively normal (control group), 1,576 had mild cognitive impairment (MCI), and 697 had dementia. We collected information about types of comorbidities (i.e., vascular risk factors, lung diseases, liver diseases, gastrointestinal diseases, and cancers), Charlson comorbidity index score, and demographic variables to compare subjects with normal cognition, MCI, and dementia. RESULTS: Regardless of the cognitive condition, over 60% of the individuals in each group had at least one comorbid disease. The proportion of subjects possessing at least three comorbidities was higher in those with cognitive impairment (MCI 20.9%, dementia 27.3%) than in control group (15%). Hypertension and diabetes mellitus were the most common comorbidities. The mean number of comorbidities and Charlson comorbidity index score were greater in MCI and dementia groups than in control group. Logistic regression demonstrated that the comorbidities significantly associated with MCI and dementia were cerebrovascular disease (OR 3.35, CI 2.62-4.28), cirrhosis (OR 3.29, CI 1.29-8.41), asthma (OR 1.56, CI 1.07-2.27), and diabetes mellitus (OR 1.24, CI 1.07-1.44). CONCLUSION: Multiple medical comorbid diseases are common in older adults, especially in those with cognitive impairment. Cerebrovascular disease, cirrhosis, asthma, and diabetes mellitus are important contributors to cognitive deterioration in the elderly. Efforts to lower cumulative medical burden in the geriatric population may benefit cognitive function.


Asunto(s)
Demencia/epidemiología , Anciano , Anciano de 80 o más Años , Comorbilidad , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Análisis de Regresión , Taiwán/epidemiología
12.
Int J Med Robot ; 13(3)2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27910205

RESUMEN

BACKGROUND: The aim of this work was to develop a neurosurgical robotic arm drilling navigation system that provides assistance throughout the complete bone drilling process. METHODS: The system comprised neurosurgical robotic arm navigation combining robotic and surgical navigation, 3D medical imaging based surgical planning that could identify lesion location and plan the surgical path on 3D images, and automatic bone drilling control that would stop drilling when the bone was to be drilled-through. Three kinds of experiment were designed. RESULTS: The average positioning error deduced from 3D images of the robotic arm was 0.502 ± 0.069 mm. The correlation between automatically and manually planned paths was 0.975. The average distance error between automatically planned paths and risky zones was 0.279 ± 0.401 mm. The drilling auto-stopping algorithm had 0.00% unstopped cases (26.32% in control group 1) and 70.53% non-drilled-through cases (8.42% and 4.21% in control groups 1 and 2). CONCLUSIONS: The system may be useful for neurosurgical robotic arm drilling navigation.


Asunto(s)
Huesos/cirugía , Procedimientos Neuroquirúrgicos/instrumentación , Procedimientos Quirúrgicos Robotizados/instrumentación , Cirugía Asistida por Computador/instrumentación , Algoritmos , Animales , Fenómenos Biomecánicos , Diseño de Equipo , Humanos , Imagenología Tridimensional/estadística & datos numéricos , Modelos Anatómicos , Modelos Animales , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Fantasmas de Imagen , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Cráneo/cirugía , Cirugía Asistida por Computador/estadística & datos numéricos , Sus scrofa
13.
Oncotarget ; 6(30): 30017-34, 2015 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-26356820

RESUMEN

Intrinsic apoptosis eliminates cells with damaged DNA and cells with dysregulated expression of oncogene. PGAM5, a member of the phosphoglycerate mutase family, has two splicing variants: PGAM5L (the long form) and PGAM5S (the short form). It has been well established that PGAM5 is at the convergent point of multiple necrosis pathways. However, the role of PGAM5 in intrinsic apoptosis is still controversial. Here we report that the PGAM5L, but not PGAM5S is a prerequisite for the activation of Bax and dephosphorylation of Drp1 in arenobufagin and staurosporine induced intrinsic apoptosis. Knockdown of PGAM5L inhibits the translocation of Bax to the mitochondria and reduces mitochondrial fission. The interaction between PGAM5L and Drp1 was observed in both arenobufagin and staurosporine treated HCT116 cells, but not in HCT116 Bax(-/-) cells. Bax transfection rescues the formation of the triplex in both arenobufagin and staurosporine stimulated HCT116 Bax(-/-) cells. Arenobufagin shows remarkable anti-cancer effects both in orthotropic and heterotropic CRC models and demonstrates less toxic effects as compared with that of cisplatin. Bax-PGAM5L-Drp1 complex is detected in arenobufagin and staurosporine treated CRC cells in vitro and in arenobufagin and cisplatin treated tumor in vivo as well. In summary, our results demonstrate that Bax-PGAM5L-Drp1 complex is required for intrinsic apoptosis execution.


Asunto(s)
Apoptosis/fisiología , Proteínas Portadoras/metabolismo , GTP Fosfohidrolasas/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Mitocondriales/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/genética , Western Blotting , Bufanólidos/administración & dosificación , Bufanólidos/farmacología , Proteínas Portadoras/genética , Línea Celular Tumoral , Cisplatino/administración & dosificación , Cisplatino/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Dinaminas , GTP Fosfohidrolasas/genética , Células HCT116 , Células HeLa , Humanos , Células MCF-7 , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Confocal , Proteínas Asociadas a Microtúbulos/genética , Proteínas Mitocondriales/genética , Complejos Multiproteicos/genética , Complejos Multiproteicos/metabolismo , Fosfoproteínas Fosfatasas , Unión Proteica , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estaurosporina/administración & dosificación , Estaurosporina/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína X Asociada a bcl-2/genética
14.
Cancer Res ; 75(17): 3568-82, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26100670

RESUMEN

Mitochondria are the powerhouses of cells. Mitochondrial C-Raf is a potential cancer therapeutic target, as it regulates mitochondrial function and is localized to the mitochondria by its N-terminal domain. However, Raf inhibitor monotherapy can induce S338 phosphorylation of C-Raf (pC-Raf(S338)) and impede therapy. This study identified the interaction of C-Raf with S308 phosphorylated DAPK (pDAPK(S308)), which together became colocalized in the mitochondria to facilitate mitochondrial remodeling. Combined use of the Raf inhibitors sorafenib and GW5074 had synergistic anticancer effects in vitro and in vivo, but targeted mitochondrial function, rather than the canonical Raf signaling pathway. C-Raf depletion in knockout MEF(C-Raf-/-) or siRNA knockdown ACHN renal cancer cells abrogated the cytotoxicity of combination therapy. Crystal structure simulation showed that GW5074 bound to C-Raf and induced a C-Raf conformational change that enhanced sorafenib-binding affinity. In the presence of pDAPK(S308), this drug-target interaction compromised the mitochondrial targeting effect of the N-terminal domain of C-Raf, which induced two-hit damages to cancer cells. First, combination therapy facilitated pC-Raf(S338) and pDAPK(S308) translocation from mitochondria to cytoplasm, leading to mitochondrial dysfunction and reactive oxygen species (ROS) generation. Second, ROS facilitated PP2A-mediated dephosphorylation of pDAPK(S308) to DAPK. PP2A then dissociated from the C-Raf-DAPK complex and induced profound cancer cell death. Increased pDAPK(S308) modification was also observed in renal cancer tissues, which correlated with poor disease-free survival and poor overall survival in renal cancer patients. Besides mediating the anticancer effect, pDAPK(S308) may serve as a predictive biomarker for Raf inhibitors combination therapy, suggesting an ideal preclinical model that is worthy of clinical translation.


Asunto(s)
Proteínas Quinasas Asociadas a Muerte Celular/genética , Sinergismo Farmacológico , Neoplasias Renales/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-raf/genética , Anciano , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia sin Enfermedad , Femenino , Técnicas de Inactivación de Genes , Humanos , Indoles/administración & dosificación , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Ratones , Persona de Mediana Edad , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Fenoles/administración & dosificación , Compuestos de Fenilurea/administración & dosificación , Fosforilación/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Sorafenib , Ensayos Antitumor por Modelo de Xenoinjerto
15.
PLoS One ; 10(5): e0128011, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26017803

RESUMEN

Areca nut (AN) is a popular carcinogen used by about 0.6-1.2 billion people worldwide. Although AN contains apoptosis-inducing ingredients, we previously demonstrated that both AN extract (ANE) and its 30-100 kDa fraction (ANE 30-100K) predominantly induce autophagic cell death in both normal and malignant cells. In this study, we further explored the action mechanism of ANE 30-100K-induced autophagy (AIA) in Jurkat T lymphocytes and carcinoma cell lines including OECM-1 (mouth), CE81T/VGH (esophagus), SCC25 (tongue), and SCC-15 (tongue). The results showed that chemical- and small hairpin RNA (shRNA)-mediated inhibition of AMP-activated protein kinase (AMPK) resulted in the attenuation of AIA in Jurkat T but not in OECM-1 cells. Knockdown of Atg5 and Beclin 1 expressions ameliorated AIA in OECM-1/CE81T/VGH/Jurkat T and OECM-1/SCC25/SCC-15, respectively. Furthermore, ANE 30-100K could activate caspase-3 after inhibition of Beclin 1 expression in OECM-1/SCC25/SCC15 cells. Meanwhile, AMPK was demonstrated to be the upstream activator of the extracellular-regulated kinase (ERK) in Jurkat T cells, and inhibition of MEK attenuated AIA in Jurkat T/OECM-1/CE81T/VGH cells. Finally, we also found that multiple myeloma RPMI8226, lymphoma U937, and SCC15 cells survived from long-term non-cytotoxic ANE 30-100K treatment exhibited stronger resistance against serum deprivation through upregulated autophagy. Collectively, our studies indicate that Beclin-1 and Atg5 but not AMPK are commonly required for AIA, and MEK/ERK pathway is involved in AIA. Meanwhile, it is also suggested that long-term AN usage might increase the resistance of survived tumor cells against serum-limited conditions.


Asunto(s)
Areca/química , Autofagia/efectos de los fármacos , Neoplasias de la Boca/tratamiento farmacológico , Nueces/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteína 5 Relacionada con la Autofagia , Beclina-1 , Caspasa 3/metabolismo , Línea Celular Tumoral , Humanos , Células Jurkat , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Boca/efectos de los fármacos , Boca/metabolismo , Neoplasias de la Boca/metabolismo , Células U937 , Regulación hacia Arriba/efectos de los fármacos
16.
J Med Biol Eng ; 35(2): 178-187, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25960706

RESUMEN

Posterior acoustic shadowing (PAS) can bias breast tumor segmentation and classification in ultrasound images. In this paper, half-contour features are proposed to classify benign and malignant breast tumors with PAS, considering the fact that the upper half of the tumor contour is less affected by PAS. Adaptive thresholding and disk expansion are employed to detect tumor contours. Based on the detected full contour, the upper half contour is extracted. For breast tumor classification, six quantitative feature parameters are analyzed for both full contours and half contours, including standard deviation of degree (SDD), which is proposed to describe tumor irregularity. Fifty clinical cases (40 with PAS and 10 without PAS) were used. Tumor circularity (TC) and SDD were both effective full- and half-contour parameters in classifying images without PAS. Half-contour TC [74 % accuracy, 72 % sensitivity, 76 % specificity, 0.78 area under the receiver operating characteristic curve (AUC), p > 0.05] significantly improved the classification of breast tumors with PAS compared to that with full-contour TC (54 % accuracy, 56 % sensitivity, 52 % specificity, 0.52 AUC, p > 0.05). Half-contour SDD (72 % accuracy, 76 % sensitivity, 68 % specificity, 0.81 AUC, p < 0.05) improved the classification of breast tumors with PAS compared to that with full-contour SDD (62 % accuracy, 80 % sensitivity, 44 % specificity, 0.61 AUC, p > 0.05). The proposed half-contour TC and SDD may be useful in classifying benign and malignant breast tumors in ultrasound images affected by PAS.

17.
Proc Inst Mech Eng H ; 228(10): 1069-82, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25332155

RESUMEN

Percutaneous thermal ablation has been widely used as a minimally invasive treatment for tumors. Treatment monitoring is essential for preventing complications while ensuring treatment efficacy. Mechanical testing measurements on tissue reveal that tissue stiffness increases with temperature and ablation duration. Different types of imaging methods can be used to monitor ablation procedures, including temperature or thermal strain imaging, strain imaging, modulus imaging, and shear modulus imaging. Ultrasound elastography demonstrates the potential to become the primary imaging modality for monitoring percutaneous ablation. This review briefly presented the state-of-the-art ultrasound elastography approaches for monitoring radiofrequency ablation and microwave ablation. These techniques were divided into four groups: quasi-static elastography, acoustic radiation force elastography, sonoelastography, and applicator motion elastography. Their advantages and limitations were compared and discussed. Future developments were proposed with respect to heat-induced bubbles, tissue inhomogeneities, respiratory motion, three-dimensional monitoring, multi-parametric monitoring, real-time monitoring, experimental data center for percutaneous ablation, and microwave ablation monitoring.


Asunto(s)
Ablación por Catéter/métodos , Diagnóstico por Imagen de Elasticidad/métodos , Electrocoagulación/métodos , Microondas/uso terapéutico , Monitoreo Intraoperatorio/métodos , Cirugía Asistida por Computador/métodos , Humanos
18.
Ultrason Imaging ; 36(4): 256-76, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24759696

RESUMEN

Computerized tumor segmentation on breast ultrasound (BUS) images remains a challenging task. In this paper, we proposed a new method for semi-automatic tumor segmentation on BUS images using Gaussian filtering, histogram equalization, mean shift, and graph cuts. The only interaction required was to select two diagonal points to determine a region of interest (ROI) on an input image. The ROI image was shrunken by a factor of 2 using bicubic interpolation to reduce computation time. The shrunken image was smoothed by a Gaussian filter and then contrast-enhanced by histogram equalization. Next, the enhanced image was filtered by pyramid mean shift to improve homogeneity. The object and background seeds for graph cuts were automatically generated on the filtered image. Using these seeds, the filtered image was then segmented by graph cuts into a binary image containing the object and background. Finally, the binary image was expanded by a factor of 2 using bicubic interpolation, and the expanded image was processed by morphological opening and closing to refine the tumor contour. The method was implemented with OpenCV 2.4.3 and Visual Studio 2010 and tested for 38 BUS images with benign tumors and 31 BUS images with malignant tumors from different ultrasound scanners. Experimental results showed that our method had a true positive rate (TP) of 91.7%, a false positive (FP) rate of 11.9%, and a similarity (SI) rate of 85.6%. The mean run time on Intel Core 2.66 GHz CPU and 4 GB RAM was 0.49 ± 0.36 s. The experimental results indicate that the proposed method may be useful in BUS image segmentation.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador , Ultrasonografía Mamaria/métodos , Algoritmos , Neoplasias de la Mama/patología , China , Reacciones Falso Positivas , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos
19.
FEBS Lett ; 587(19): 3202-9, 2013 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-23954234

RESUMEN

Targeted inhibition of multidrug ABCG2 transporter is believed to improve cancer therapeutics. However, the consequences of ABCG2 inhibition have not been systematically evaluated since ABCG2 is expressed in several organs including the liver. Here, we demonstrate that ABCG2-deficient hepatocytes have increased amounts of fragmental mitochondria accompanied by disruption of mitochondrial dynamics and functions. This disruption was due to ABCG2 knockout elevating intracellular protoporphyrin IX, which led to upregulation of DRP-1-mediated mitochondrial fission. The finding that ABCG2 deficiency can generate dysfunctional mitochondria in hepatocytes raises concerns regarding the systematic use of ABCG2 inhibitor in cancer patients.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/fisiología , Hepatocitos/metabolismo , Mitocondrias Hepáticas/metabolismo , Dinámicas Mitocondriales , Protoporfirinas/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Animales , Células Cultivadas , Glucógeno/metabolismo , Ratones , Ratones Noqueados , Mitocondrias Hepáticas/fisiología
20.
Int J Med Inform ; 81(12): 834-41, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22999224

RESUMEN

OBJECTIVE: The aim of this study is to create a national database to record incidents that endanger patient safety. We try to identify systemic problems in hospitals in order to avoid safety incidents in the future and improve the quality of healthcare. METHOD: The Taiwan Patient Safety Reporting System employs a voluntary notification model. We define 13 types of patient safety incidents, and the reports of different types of incidents are recorded using common terminology. Statistical analysis is used to identify the incident type, time of occurrence, location, person who reported the incident, and possible reasons for frequently occurring incidents. RESULTS: There were 340 hospitals that joined this program from 2005 to 2010. Over 128,271 incident events were reported and analyzed. The three most common incidents were drug-related incidents, falls, and endo tube related incidents. By analyzing the time of occurrence of incidents, we found that drug-related incidents usually occurred between 8 and 10 am. Falls and endo tube incidents usually occurred between 4 and 6 am. The most common location was wards (57.6%), followed by intensive care areas (13.5%), and pharmacies (9.1%). Among hospital staff, nurses reported the highest number of incidents (68.9%), followed by pharmacists (14.5%) and administrative staff (5.5%). The number of incidents reported by doctors was much lower (1.2%). Most staff members who reported incidents had been working for less than five years (58.1%). CONCLUSION: The unified reporting system was found to improve the recording and analysis of patient safety incidents. To encourage hospital staff to report incidents, hospitals need to be assisted in establishing an internal report and management system for safety incidents. Hospitals also need a protection mechanism to allow staff members to report incidents without the fear of punishment. By identifying the root causes of safety incidents and sharing the lessons learned across hospitals is the only way such incidents can be stopped from happening again.


Asunto(s)
Errores Médicos/prevención & control , Calidad de la Atención de Salud , Gestión de Riesgos/organización & administración , Administración de la Seguridad/organización & administración , Gestión de la Calidad Total , Accidentes por Caídas , Hospitales , Humanos , Gestión de Riesgos/tendencias , Administración de la Seguridad/tendencias , Medicina Estatal , Taiwán
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