RESUMEN
Controversy exists regarding the influence of the graft placement site in the mandible on the success of non-vascularised bone grafts. In this study, we examine the association between the compartment of the mandibular defect and the bone graft failure rate. A systematic literature review and meta-analysis was performed using MEDLINE, Embase, and Cochrane databases. Failure rates according to the compartment of mandibular defect were extracted and analysed by meta-analysis. The Newcastle-Ottawa Scale was used to assess the quality of the studies, and publication bias was evaluated using funnel plots. The search strategy identified 27 publications. After screening, five were selected for review. Based on the result of comparison among these five, we found no significant statistical association between the bone graft failure rate and compartment of mandibular defect, although further investigation of prospective randomised cohort studies is required.
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Reconstrucción Mandibular , Trasplante Óseo , Humanos , Mandíbula/cirugía , Complicaciones Posoperatorias , Estudios ProspectivosRESUMEN
Endochondral ossification during long bone development and natural fracture healing initiates by mesenchymal cell condensation, directed by local morphogen signals and mechanical cues. Here, we aimed to mimic development for regeneration of large bone defects. We hypothesized that engineered human mesenchymal condensations presenting transforming growth factor-ß1 (TGF-ß1) and/or bone morphogenetic protein-2 (BMP-2) from encapsulated microparticles promotes endochondral defect regeneration contingent on in vivo mechanical cues. Mesenchymal condensations induced bone formation dependent on morphogen presentation, with BMP-2 + TGF-ß1 fully restoring mechanical function. Delayed in vivo ambulatory loading significantly enhanced the bone formation rate in the dual morphogen group. In vitro, BMP-2 or BMP-2 + TGF-ß1 initiated robust endochondral lineage commitment. In vivo, however, extensive cartilage formation was evident predominantly in the BMP-2 + TGF-ß1 group, enhanced by mechanical loading. Together, this study demonstrates a biomimetic template for recapitulating developmental morphogenic and mechanical cues in vivo for tissue engineering.
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Desarrollo Óseo/fisiología , Huesos/fisiología , Morfogénesis/fisiología , Osteogénesis/fisiología , Animales , Biomimética/métodos , Huesos/metabolismo , Células Cultivadas , Humanos , Masculino , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/fisiología , Ratas , Ingeniería de Tejidos , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Autologous fat has long been used as a filler in the face, and has recently gained popularity in plastic surgery with a wound infection rate of 1% - 5%. The incidence of mycobacterial infections has increased over recent decades, which is attributed in part to the increased popularity of these procedures.2 Infections by non-tuberculosis mycobacteria often cause chronic inflammation and progressive infection that may eventually manifest themselves as severe scars, fistulas, and hollows, and irregular facial contours. However, few cases of mycobacterial infection have been reported to have been caused by plastic surgery. We present a rare case of non-tuberculosis mycobacterial infection after transfer of autologous fat to the face.
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Infecciones por Mycobacterium no Tuberculosas , Cirugía Plástica , Cara , Humanos , Micobacterias no TuberculosasRESUMEN
BACKGROUND AND OBJECTIVES: Despite safety measures to minimize the risk of transfusion-transmitted infections, a residual risk remains. To trace and review some such cases, we ask donors to notify the blood centre if they are diagnosed with an infection after they donate blood. MATERIALS AND METHODS: We analysed all data on postdonation cases of hepatitis A reported between 2007 and 2012. Archived specimens from these donors were tested for hepatitis A virus (HAV) using anti-HAV IgM/IgG and HAV-PCR as markers. If any of the test results were positive, we reviewed the medical records of the recipients and, if necessary, tested them for hepatitis A. RESULTS: Fifteen blood donors notified the blood centres of having been diagnosed with hepatitis A after donation. All archived samples except for one were HAV-PCR-positive and anti-HAV IgM/IgG-negative. Of the donated components, four RBCs and 14 FFPs had not been transfused to patients and were recalled. Among 26 recipients of the implicated components, fourteen were still alive when they were notified. Two patients showed clinical symptoms of hepatitis A and had positive results with anti-HAV IgM. CONCLUSION: Transfusion-transmitted hepatitis A is rare but exists. To reduce the risk, donors should be told to notify the blood centre if they are diagnosed with blood-borne diseases after they donate blood. Physicians should consider the possibility of transfusion-transmitted hepatitis A if a transfused patient has hepatitis A but no history of travel or route of faecal-oral infection.
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The purpose of this study was to determine the influence of insurance status on treatment and outcomes in oral cavity cancer. Patients were identified in the National Cancer Database (NCDB). Data were collected and analyzed using χ2 tests, Kaplan-Meier methods, and multivariable Cox regression models. Those uninsured or on Medicaid were more likely to be younger (P<0.001), minority race (P<0.001), have a lower median household income (P<0.001), lower educational attainment (P<0.001), not undergo primary resection (P<0.001), present with higher T (P<0.001),N (P<0.001), and M (P<0.001) stage of disease, and have a higher tumor grade (P<0.001). On univariate analysis, those with private insurance had significantly better overall survival than those uninsured (hazard ratio (HR) 1.481), under Medicaid (HR 2.006), or on Medicare (HR 1.921). On multivariable Cox regression analysis, insurance status remained an independent prognosticator even after accounting for multiple demographic, socioeconomic, treatment, and clinicopathological factors. These data suggest that insurance status is associated with treatment and outcomes in patients with oral cavity cancer. Being uninsured or on Medicaid was found to be associated with a higher risk of a poorer prognosis when compared to private insurance, and the data suggest the need to expand comprehensive medical coverage and optimize access to adequate medical care in vulnerable patient populations.
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Carcinoma de Células Escamosas/terapia , Cobertura del Seguro , Neoplasias de la Boca/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Demografía , Femenino , Humanos , Masculino , Medicaid/estadística & datos numéricos , Pacientes no Asegurados/estadística & datos numéricos , Medicare/estadística & datos numéricos , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del Tratamiento , Estados UnidosRESUMEN
This study examined how patients with cancer estimate caregiver burden (CB) and the association between their underestimation of CB and their caregivers' self-ratings of their quality of life (CQOLC-K; Korean version of the Caregiver Quality of Life Index-Cancer), depression and anxiety (Korean version of the Hospital Anxiety and Depression Scale). Participants consisted of 990 patient-caregiver dyads recruited from a nationwide cross-sectional survey conducted in South Korea. Medical baseline data were retrieved from the hospital information systems of the participating centres. The patients with cancer who underestimated CB ranged from 18.62% (for physical CB) to 23.33% (for social CB). They had less advanced cancer, a lower income, were the caregiver's spouse, reported higher levels of family avoidance of communication about cancer, and had female caregivers. The patients' underestimation of CB was significantly related to lower CQoL and higher levels of caregiver depression and anxiety. The current study provides empirical evidence for the link between the underestimation of CB by patients with cancer and compromised caregiving experiences of cancer caregivers. Open family communication about cancer was discussed as one of several practical strategies for decreasing patients' underestimation of CB.
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Trastornos de Ansiedad/etiología , Cuidadores/psicología , Trastorno Depresivo/etiología , Neoplasias/psicología , Calidad de Vida , Actitud Frente a la Salud , Comunicación , Costo de Enfermedad , Estudios Transversales , Relaciones Familiares , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Ribavirin (RBV) is a synthetic guanosine analog that is used as a drug against various viral diseases in humans. The in vitro antiviral effects of ribavirin against porcine viruses were demonstrated in several studies. The purposes of this study were to evaluate the adverse effects and pharmacokinetics of ribavirin following its intramuscular (IM) injection in pigs. Ribavirin was formulated as a double-oil emulsion (RBV-DOE) and gel (RBV-Gel), which were injected into the pigs as single-dose IM injections. After injection of RBV, all of the pigs were monitored. The collected serum and whole blood samples were analyzed by liquid chromatography-tandem mass spectrometry and complete blood count analysis, respectively. All of the ribavirin-treated pigs showed significant decreases in body weight compared to the control groups. Severe clinical signs including dyspnea, anorexia, weakness, and depression were present in ribavirin-treated pigs until 5 days postinjection (dpi). The ribavirin-treated groups showed significant decrease in the number of red blood cells and hemoglobin concentration until 8 dpi. The mean half-life of the RBV-DOE and RBV-Gel was 27.949 ± 2.783 h and 37.374 ± 3.502 h, respectively. The mean peak serum concentration (Cmax ) and area under the serum concentration-time curve from time zero to infinity (AUCinf ) of RBV-DOE were 8340.000 ± 2562.577 ng/mL and 16 0095.430 ± 61 253.400 h·ng/mL, respectively. The Cmax and AUCinf of RBV-Gel were 15 300.000 ± 3764.306 ng/mL and 207526.260 ± 63656.390 h·ng/mL, respectively. The results of this study provided the index of side effect and pharmacokinetics of ribavirin in pigs, which should be considered before clinical application.
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Antivirales/farmacocinética , Ribavirina/farmacocinética , Porcinos/metabolismo , Animales , Antivirales/efectos adversos , Humanos , Inyecciones Intramusculares/veterinaria , Ribavirina/efectos adversosRESUMEN
OBJECTIVES: The aim of this study was to examine the impacts of a government-directed palliative care demonstration (PCD) project, Per-diem Payment System (PDPS), on length of stay (LOS), hospital costs, resource usage and healthcare quality during the searched period from January in 2009 to December in 2010. STUDY DESIGN: A retrospective claim data review. METHODS: Individuals who had been eligible for the palliative care payment policy, PDPS, during 2 years (from 2009 to 2010) were assigned to the case group including seven hospitals (n = 3117). Those (seven hospitals) who were not come eligible for the palliative care payment policy were assigned to the control group (n = 2347) with fee for service. The data used in this study were electronically submitted requests of payment to the Health Insurance Review Agency during the period January 2009 to December 2010. RESULTS: After the PCD project, the length of stay for palliative patients with cancer diseases decreased by 2.56% (ß = -0.026; p-value = 0.0001) among patients hospitalized in a PCD project compared with patients hospitalized in seven hospitals that was not designed as a PCD project. Compared with costs before the PCD project, costs decreased by 0.76% (ß = 0.013; p-value = 0.0001). CONCLUSIONS: We provided evidence regarding the change in the societal burden due to palliative care. Although there was a reduction of direct medical costs reported in limited number of hospitals, in the long term, we can anticipate an expanding impact on medical costs in all palliative hospitals. Copyright © 2016 John Wiley & Sons, Ltd.
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Gastos en Salud , Hospitalización/economía , Tiempo de Internación/economía , Cuidados Paliativos/economía , Mecanismo de Reembolso , Anciano , Anciano de 80 o más Años , Femenino , Política de Salud , Recursos en Salud/estadística & datos numéricos , Investigación sobre Servicios de Salud , Humanos , Masculino , Persona de Mediana Edad , Calidad de la Atención de Salud , República de Corea , Estudios RetrospectivosRESUMEN
BACKGROUND: There is a lack of information regarding the oncological safety of robotic intersphincteric resection (ISR) with coloanal anastomosis. The objective of this study was to compare the long-term feasibility of robotic compared with laparoscopic ISR. METHODS: Between January 2008 and May 2011, consecutive patients who underwent robotic or laparoscopic ISR with coloanal anastomosis from seven institutions were included. Propensity score analyses were performed to compare outcomes for groups in a 1 : 1 case-matched cohort. The primary endpoint was 3-year disease-free survival. RESULTS: A total of 334 patients underwent ISR with coloanal anastomosis, of whom 212 matched patients (106 in each group) formed the cohort for analysis. The overall rate of conversion to open surgery was 0.9 per cent in the robotic ISR group and 1.9 per cent in the laparoscopic ISR group. Nine patients (8.5 per cent) in the laparoscopic group and three (2.8 per cent) in the robotic ISR group still had a stoma at last follow-up (P = 0.075). Total mean hospital costs were significantly higher for robotic ISR ( 12,757 versus 9223 for laparoscopic ISR; P = 0.037). Overall 3-year local recurrence rates were similar in the two groups (6.7 per cent for robotic and 5.7 per cent for laparoscopic resection; P = 0.935). The combined 3-year disease-free survival rates were 89.6 (95 per cent c.i. 84.1 to 95.9) and 90.5 (85.4 to 96.6) per cent respectively (P = 0.298). CONCLUSION: Robotic ISR with coloanal anastomosis for rectal cancer has reasonable oncological outcomes, but is currently too expensive with no short-term advantages.
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Adenocarcinoma/cirugía , Canal Anal/cirugía , Colectomía/métodos , Laparoscopía/métodos , Complicaciones Posoperatorias/epidemiología , Neoplasias del Recto/cirugía , Robótica/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Anastomosis Quirúrgica/métodos , Conversión a Cirugía Abierta , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/mortalidad , República de Corea/epidemiología , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
BACKGROUND AND AIMS: Low bilirubin and high gamma-glutamyltransferase (GGT), which are endogenous markers of oxidative stress, confer a higher risk of cardiovascular disease (CVD). We investigated associations between serum concentrations of bilirubin, GGT and coronary atherosclerosis. METHODS AND RESULTS: A cross-sectional analysis was performed on 1520 subjects who underwent multidetector computed tomography scans. Coronary atherosclerosis was assessed by coronary artery calcium score (CACS) and obstructive coronary artery disease (OCAD), was defined as the presence of coronary artery stenosis of ≥50%. Total bilirubin (TB) level was negatively correlated with CACS and coronary stenosis whereas GGT level was positively correlated with CACS in men. However, there was no correlation between TB, GGT levels and either CACS or coronary artery stenosis in women. In a multivariate-adjusted model, TB level was inversely associated with a CACS > 100 [odds ratio (OR) per log standard deviation (SD), 0.67; 95% confidence interval (CI), 0.52-0.87], and OCAD (OR per log SD, 0.77; 95% CI, 0.62-0.95) in men. By contrast, GGT level was positively associated with a CACS > 100 (OR per log SD, 1.35; 95% CI, 1.05-1.73) but not with OCAD. Adding TB and GGT to the conventional risk factors increased predictive accuracy for CACS > 100 (net reclassification improvement index [NRI] = 13.1%, P = 0.026; integrated discrimination index [IDI] = 0.024, P = 0.001) and for OCAD (NRI = 12.6%, P = 0.026; IDI = 0.010, P = 0.013). CONCLUSIONS: Low TB and high GGT levels were concomitantly associated with coronary atherosclerosis in Korean men. Future studies are needed to elucidate the causal associations of TB and GGT with CVD.
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Bilirrubina/sangre , Enfermedad de la Arteria Coronaria/sangre , gamma-Glutamiltransferasa/sangre , Adulto , Estenosis Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Estudios Transversales , Hígado Graso/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , República de Corea , Estudios Retrospectivos , Factores de Riesgo , Caracteres Sexuales , Calcificación Vascular/sangre , Calcificación Vascular/patologíaRESUMEN
AIMS: We investigated the effect of ozone treatment of apple juice at different pH levels for inactivation of Escherichia coli O157:H7, Salmonella Typhimurium and Listeria monocytogenes. METHODS AND RESULTS: Apple juice (pH 3.0, 4.0 and 5.0) inoculated with the three pathogens were treated with gaseous ozone (3.0 l min(-1) flow rate and 2.0-3.0 g m(-3) ) for up to 4 min. Ozone treatment (4 min) of pH 3.0 apple juice resulted in >5.36 log CFU ml(-1) reduction of E. coli O157:H7. Ozone treatment of pH 4.0 and 5.0 apple juice for 4 min reduced this pathogen by 5.12 log CFU ml(-1) and 1.86 log CFU ml(-1) respectively. The combination of low pH and ozone showed a great antimicrobial effect in apple juice. Salm. Typhimurium and L. monocytogenes showed a reduction trend similar to E. coli O157:H7. There were no significant changes of colour values when apple juice was treated with ozone, except for b values. Among all ozone treated samples, the browning index was lower than that of nontreated samples and there were no significant differences in total phenolic contents. CONCLUSIONS: In conclusion, ozone treatment of low pH apple juice was significantly effective in inactivation of foodborne pathogens while maintaining acceptable apple juice quality. SIGNIFICANCE AND IMPACT OF THE STUDY: The antimicrobial effect of ozone treatment on foodborne pathogens in apple juice can be reinforced by lowering the pH of apple juice.
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Bebidas/microbiología , Escherichia coli O157/efectos de los fármacos , Conservación de Alimentos/métodos , Malus/microbiología , Ozono/farmacología , Bebidas/análisis , Escherichia coli O157/crecimiento & desarrollo , Concentración de Iones de Hidrógeno , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/crecimiento & desarrollo , Ozono/química , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/crecimiento & desarrolloRESUMEN
PURPOSE: To determine the preoperative anatomic factors in macular holes and their correlation to hole closure. METHODS: Forty-six eyes with consecutive unilateral macular hole who had undergone surgery and followed up for at least 6 months were enrolled. Optical coherence tomography images and best-corrected visual acuity (BCVA) within 2 weeks prior to operation and 6 months after surgery were analyzed. The maximal hole dimension, foveal degeneration factors (inner nuclear layer cysts, outer segment (OS) shortening) and the widest foveolar floor size of the fellow eyes were measured. For overcoming preoperative individual variability of foveal morphology, an 'adjusted' hole size parameter (the ratio between the hole size and the fellow eye foveolar floor size) was used based on the fact that both eyes were morphologically symmetrical. RESULTS: Mean preoperative BCVA (logMAR) was 1.03±0.43 and the mean postoperative BCVA was 0.50±0.38 at 6 months. Preoperative BCVA is significantly associated with postoperative BCVA (P=0.0002). The average hole diameter was 448.9±196.8 µm and the average fellow eye foveolar floor size was 461.3±128.4 µm. There was a correlation between hole diameter and the size of the fellow eye foveolar floor (Pearson's coefficient=0.608, P<0.0001). The adjusted hole size parameter was 0.979±0.358 (0.761-2.336), which was a strong predictor for both anatomic (P=0.0281) and visual (P=0.0016) outcome. CONCLUSION: When determining the extent of preoperative hole size, we have to take into consideration the foveal morphologic variations among individuals. Hole size may be related to the original foveal shape, especially in relation to the centrifugal retraction of the foveal tissues.
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Fóvea Central/patología , Perforaciones de la Retina/patología , Perforaciones de la Retina/cirugía , Vitrectomía , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Perforaciones de la Retina/fisiopatología , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Vitrectomía/métodosRESUMEN
Cigarette smoke (CS) is a major risk factor for emphysema, which causes cell death in structural cells of the lung by mechanisms that are still not completely understood. We demonstrated previously that CS extract (CSE) induces caspase activation in MRC-5 human lung fibroblasts, activated protein kinase C-η (PKC-η), and translocated PKC-η from the cytosol to the membrane. The objective of this study was to investigate the involvement of PKC-η activation in a CSE-induced extrinsic apoptotic pathway. We determined that CSE increases expression of caspase 3 and 8 cleavage in MRC-5 cells and overexpression of PKC-η significantly increased expression of caspase 3 and 8 cleavage compared with control LacZ-infected cells. In contrast, dominant negative (dn) PKC-η inhibited apoptosis in MRC-5 cells exposed to CSE and decreased expression of caspase 3 and 8 compared with control cells. Exposure to 10% CSE for >8 h significantly increased lactate dehydrogenase release in PKC-η-infected cells compared with LacZ-infected cells. Additionally, PKC-η-infected cells had an increased number of Hoechst 33342 stained nuclei compared with LacZ-infected cells, while dn PKC-η-infected cells exhibited fewer morphological changes than LacZ-infected cells under phase-contrast microscopy. In conclusion, PKC-η activation plays a pro-apoptotic role in CSE-induced extrinsic apoptotic pathway in MRC-5 cells. These results suggest that modulation of PKC-η may be a useful tool for regulating the extrinsic apoptosis of MRC-5 cells by CSE and may have therapeutic potential in the treatment of CS-induced lung injury.
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Apoptosis/efectos de los fármacos , Nicotiana/toxicidad , Proteína Quinasa C/efectos de los fármacos , Humo/efectos adversos , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Humanos , L-Lactato Deshidrogenasa/metabolismo , Operón Lac/efectos de los fármacos , Pulmón/patología , Enfermedad Pulmonar Obstructiva Crónica/patología , beta-Galactosidasa/metabolismoRESUMEN
Gene fusion is involved in the development of various types of malignancies. Recent advances in sequencing technology have facilitated identification of gene fusions and have stimulated the research of this field in cancer. In the present study, we performed next-generation transcriptome sequencing in order to discover novel gene fusions in gastric cancer. A total of 282 fusion transcript candidates were detected from 12 gastric cancer cell lines by bioinformatic filtering. Among the candidates, we have validated 19 fusion transcripts, which are 7 inter-chromosomal and 12 intra-chromosomal fusions. A novel DUS4L-BCAP29 fusion transcript was found in 2 out of 12 cell lines and 10 out of 13 gastric cancer tissues. Knockdown of DUS4L-BCAP29 transcript using siRNA inhibited cell proliferation. Soft agar assay further confirmed that this novel fusion transcript has tumorigenic potential. We also identified that microRNA-coding gene PVT1, which is amplified in double minute chromosomes in SNU-16 cells, is recurrently involved in gene fusion. PVT1 produced six different fusion transcripts involving four different genes as fusion partners. Our findings provide better insight into transcriptional and genetic alterations of gastric cancer: namely, the tumorigenic effects of transcriptional read-through and a candidate region for genetic instability.
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Fusión Génica , Línea Celular Tumoral , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Proteínas de la Membrana/genética , Oxidorreductasas/genética , ARN Largo no Codificante/genética , Reproducibilidad de los Resultados , Neoplasias Gástricas/genéticaRESUMEN
Whole-genome expression profiling in postmortem brain tissue has recently provided insight into the pathophysiology of schizophrenia. Previous microarray and RNA-Seq studies identified several biological processes including synaptic function, mitochondrial function and immune/inflammation response as altered in the cortex of subjects with schizophrenia. Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes in schizophrenia cases as compared with unaffected controls. Immune/inflammation response was the main biological process over-represented in these genes. The upregulation of several of these genes, IFITM1, IFITM2, IFITM3, APOL1 (Apolipoprotein L1), ADORA2A (adenosine receptor 2A), IGFBP4 and CD163 were validated in the schizophrenia subjects using data from the SNCID database and with quantitative RT-PCR. We identified a co-expression module associated with schizophrenia that includes the majority of differentially expressed genes related to immune/inflammation response as well as with the density of parvalbumin-containing neurons in the hippocampus. The results indicate that abnormal immune/inflammation response in the hippocampus may underlie the pathophysiology of schizophrenia and may be associated with abnormalities in the parvalbumin-containing neurons that lead to the cognitive deficits of the disease.
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Hipocampo/inmunología , ARN Mensajero/análisis , Esquizofrenia/inmunología , Adulto , Antígenos CD/genética , Antígenos CD/inmunología , Antígenos de Diferenciación/genética , Antígenos de Diferenciación/inmunología , Antígenos de Diferenciación Mielomonocítica/genética , Antígenos de Diferenciación Mielomonocítica/inmunología , Apolipoproteína L1 , Apolipoproteínas/genética , Apolipoproteínas/inmunología , Estudios de Casos y Controles , Femenino , Perfilación de la Expresión Génica , Hipocampo/metabolismo , Humanos , Inflamación/genética , Proteína 4 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 4 de Unión a Factor de Crecimiento Similar a la Insulina/inmunología , Lipoproteínas HDL/genética , Lipoproteínas HDL/inmunología , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/inmunología , Receptor de Adenosina A2A/genética , Receptor de Adenosina A2A/inmunología , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Esquizofrenia/genética , Regulación hacia ArribaRESUMEN
BACKGROUND: The mechanism of primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer (NSCLC) has not been clearly understood. PATIENTS AND METHODS: Eleven patients exhibiting primary resistance (disease progression <3 months) were identified among 197 consecutive NSCLC patients with TKI-sensitive EGFR mutations who received EGFR TKIs at Seoul National University Hospital. Treatment-naïve tumors were examined for concurrent genetic alterations using fluorescence in situ hybridization and targeted deep sequencing of cancer-related genes. Deletion polymorphism of Bcl-2-interacting mediator of cell death (BIM) gene was examined to validate its predictive role for TKI outcome. RESULTS: The median progression-free survival (PFS) for patients receiving EGFR TKIs was 11.9 months, and the response rate 78.8%. Among the 11 patients exhibiting primary resistance, a de novo T790M mutation was identified in one patient, and two exhibited mesenchymal-epithelial transition amplification and anaplastic lymphoma kinase fusion. Targeted deep sequencing identified no recurrent, coexistent drivers of NSCLC. Survival analysis revealed that patients with recurrent disease after surgery had a longer PFS than those with initial stage IV disease. However, BIM deletion polymorphism, line of treatment, EGFR genotype, and smoking were not predictive of PFS for EGFR TKIs. CONCLUSIONS: We identified coexistent genetic alterations of cancer-related genes that could explain primary resistance in a small proportion of patients. Our result suggests that the mechanism of primary resistance might be heterogeneous.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Reguladoras de la Apoptosis/genética , Secuencia de Bases , Proteína 11 Similar a Bcl2 , Carcinoma de Pulmón de Células no Pequeñas/genética , Transdiferenciación Celular/genética , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Clorhidrato de Erlotinib , Femenino , Gefitinib , Genotipo , Humanos , Neoplasias Pulmonares/genética , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Mutación , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Quinazolinas/uso terapéutico , Análisis de Secuencia de ADN , Eliminación de Secuencia/genéticaRESUMEN
As hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, development of novel therapeutic approaches for HCC is urgently needed. Two different genes, LETM1 and CTMP, which target mitochondrial functions, were chosen and linked using 2A-peptide sequence. Successful self-cleavage of 2A-peptide induced synergistic antitumor effect in the liver of H-ras12V, the HCC model mice, by simultaneous activation of LETM1 (Leucine zipper/EF hand-containing transmembrane-1) and CTMP (carboxyl-terminal modulator protein). Overexpression of LETM1 and CTMP significantly reduced the incidence of tumorigenesis, which were confirmed by gross and microscopic observations. Morphological changes in mitochondria, such as swelling and loss of cristae, were significant, and the prolonged activation of defects in mitochondrial function led to mitochondria-mediated apoptosis. Furthermore, with CTMP as a direct binding partner of Akt1, and LETM1 as a binding partner of CTMP, LETM1-2A-CTMP downregulated the Akt1 pathway at both Ser473 and Thr308 sites of phosphorylation. Proliferation and angiogenesis, which are important in cancer prognosis, were reduced in tumor sites after introduction of LETM1-2A-CTMP. Taken together, the results indicate that introduction of the mitochondria-targeting genes, LETM1 and CTMP, and self-processing capacity of 2A-peptide sequence exerts an antitumor effect in liver of H-ras12V mice, suggesting its potential as a tool for gene therapy.
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Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas de Unión al Calcio/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Proteínas de la Membrana/genética , Plásmidos/administración & dosificación , Tioléster Hidrolasas/genética , Animales , Apoptosis/genética , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Expresión Génica , Orden Génico , Humanos , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/metabolismo , Ratones , Mitocondrias/genética , Mitocondrias/metabolismo , Neovascularización Patológica/genética , Péptidos/genética , Polietileneimina/análogos & derivados , Polietileneimina/química , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Recombinantes de Fusión/genética , Carga Tumoral/genéticaRESUMEN
Deferral of blood donors taking teratogenic drugs is critical. From March 2008 to January 2009, we analysed stored blood specimens from donors who had taken teratogenic drugs and whose blood was transfused to women of childbearing age to determine the plasma concentration at the time of donation using high-performance liquid chromatography. In total, 167 specimens were examined. The numbers of specimens exceeding the quantification limit were 7, 39, 4, 2 and 1 for finasteride, isotretinoin, acitretin, etretinate and dutasteride, respectively. Finasteride was beyond the recommended drug deferral period in one specimen. These results may help create practical deferral policies.
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Donantes de Sangre , Teratógenos/análisis , Reacción a la Transfusión , Acitretina/sangre , Adulto , Etretinato/sangre , Femenino , Finasterida/sangre , Humanos , Adulto JovenRESUMEN
Persistent organic pollutants (POPs), xenobiotics that accumulate in fat tissue, may impair bone metabolism. We studied (1) the association of bone mineral density (BMD) with POPs and (2) whether associations of fat mass (FM) or lean mass (LM), two components of body composition, with BMD differed depending on levels of POPs. Participants aged ≥ 20 in the National Health and Nutrition Examination Survey 1999-2004 were included (n=2769). Eight POPs with detection rate ≥ 80% and three skeletal subregions (left arm, pelvis, and right leg) were selected. All analyses were stratified by gender and age (cutpoint 50 years or more). POPs at background concentrations were mostly unassociated with BMD. However, the associations of FM and LM with BMD depended on POPs concentrations, in particular with BMD of the left arm (usually not weight-bearing) in postmenopausal women. When POPs concentrations were low, FM showed inverse associations with BMD while LM showed positive associations. However, when POPs levels were high, FM showed positive associations with BMD while the positive associations between LM and BMD weakened. POPs may biologically modify the associations of FM and LM with BMD, especially among postmenopausal women, possibly explaining inconsistent associations between FM and BMD in previous epidemiological studies.
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Índice de Masa Corporal , Densidad Ósea/efectos de los fármacos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales/sangre , Compuestos Orgánicos/sangre , Tejido Adiposo/metabolismo , Adulto , Anciano , Composición Corporal , Dioxinas/sangre , Dioxinas/toxicidad , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/metabolismo , Contaminantes Ambientales/toxicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Compuestos Orgánicos/metabolismo , Compuestos Orgánicos/toxicidad , Plaguicidas/sangre , Plaguicidas/toxicidad , Bifenilos Policlorados/sangre , Bifenilos Policlorados/toxicidad , Estados UnidosRESUMEN
Heart sound occurs when the heart contracts and expands. It provides information on myocardial contractility and blood vessels, which is not obtainable from ECG. For this reason, stethoscopy of heart sound in anesthesiology is a very crucial means for acquiring cardiac information and preventing intraoperative medical accidents, and it requires a system for precise objective measurement and analysis of heart sound and murmur. Thus, this study purposed to develop portable digital esophageal stethoscope (PDES) that can objectify and quantify heart sound and murmur. In this study, we designed PDES for precise measurement and analysis of heart sound and murmur data. Heart sound information obtained by inserting the sensor of the PDES into the patient's esophagus can be transmitted to a terminal or a PC and displayed on the screen The amplitude and waveform of heart sound are displayed using self-developed software Heart Sound 1.0. The results of experiment with the developed PDES showed that data on the amplitude and waveform of heart sound and murmur were produced stably in real-time. In addition, when heart sound was heard using a headphone, the sound was clear without external murmur. The PDES developed in this study, which complements the disadvantages of traditional esophageal stethoscope while preserving its advantages, could not only examine heart sound and murmur using an esophageal catheter but also display the amplitude and waveform of heart sound and murmur and measure the patient's body temperature. Accordingly, the developed PDES is expected to be useful in the continuous stethoscopy of heart sound during operation and to contribute to research on heart sound by providing heart sound data.