RESUMO
The dynamics of constituents and the surface response of cellular membranes-also in connection to the binding of various particles and macromolecules to the membrane-are still a matter of controversy in the membrane biophysics community, particularly with respect to crowded membranes of living biological cells. We here put into perspective recent single particle tracking experiments in the plasma membranes of living cells and supercomputing studies of lipid bilayer model membranes with and without protein crowding. Special emphasis is put on the observation of anomalous, non-Brownian diffusion of both lipid molecules and proteins embedded in the lipid bilayer. While single component, pure lipid bilayers in simulations exhibit only transient anomalous diffusion of lipid molecules on nanosecond time scales, the persistence of anomalous diffusion becomes significantly longer ranged on the addition of disorder-through the addition of cholesterol or proteins-and on passing of the membrane lipids to the gel phase. Concurrently, experiments demonstrate the anomalous diffusion of membrane embedded proteins up to macroscopic time scales in the minute time range. Particular emphasis will be put on the physical character of the anomalous diffusion, in particular, the occurrence of ageing observed in the experiments-the effective diffusivity of the measured particles is a decreasing function of time. Moreover, we present results for the time dependent local scaling exponent of the mean squared displacement of the monitored particles. Recent results finding deviations from the commonly assumed Gaussian diffusion patterns in protein crowded membranes are reported. The properties of the displacement autocorrelation function of the lipid molecules are discussed in the light of their appropriate physical anomalous diffusion models, both for non-crowded and crowded membranes. In the last part of this review we address the upcoming field of membrane distortion by elongated membrane-binding particles. We discuss how membrane compartmentalisation and the particle-membrane binding energy may impact the dynamics and response of lipid membranes. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.
Assuntos
Bicamadas Lipídicas/química , Lipídeos de Membrana/química , Difusão , Géis , Proteínas de Membrana/química , Simulação de Dinâmica Molecular , Eletricidade EstáticaRESUMO
Esophageal squamous cell carcinoma (ESCC) is associated with a poor prognosis and high postoperative recurrence rate. Although postoperative opioid use has been associated with cancer recurrence, its relevance in ESCC has not been determined. Therefore, this study investigated whether high-dose postoperative opioid use was associated with recurrence risk in patients with ESCC. For this retrospective analysis, the medical records of patients who were diagnosed with ESCC and who underwent surgery between January 2006 and December 2010 in the National Cancer Center, Korea were evaluated. Total opioid administration over a 10-day period, from during surgery to postoperative day 9, was calculated. A cutoff value was determined using receiver operating characteristic curve analysis, and patients were classified into the high-use and low-use groups. The primary and secondary outcomes of the study were freedom from recurrence and overall survival, respectively. After propensity score matching, the effect of opioid use on freedom from recurrence and overall survival was evaluated using the Kaplan-Meier method. The final analysis set included 258 patients. The cumulative opioid dose cutoff point was 1783.5 mg of oral morphine. High-dose postoperative opioid use was a significant factor affecting recurrence (Hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.583-2.954; P < 0.0001). In contrast, postoperative opioid use was not associated with death (HR, 1.274; 95% CI, 0.922-1.761; P = 0.1422). In patients with ESCC, compared with low-dose opioid use, high-dose intraoperative and postoperative opioid use was significantly associated with an increased risk of recurrence. However, opioid dosage did not affect overall survival.
Assuntos
Analgésicos Opioides/administração & dosagem , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Morfina/administração & dosagem , Recidiva Local de Neoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos Clínicos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Thickened uterine endometrium with abnormal uterine bleeding highly suggests endometrial hyperplasia or endometrial carcinoma. A case of 35-year-old nulliparous woman came to our department with endometrial mass manifesting as endometrial cancer. Transrectal ultrasonography and magnetic resonance imaging (MRI) showed an 8x6 cm multicystic, ill-defined mass compacted at the uterine endometrium, the anterior wall of the uterus, and 3x3 cm heterogenous mass at the left adnexa. The edometrial mass showed multiple septations with enhancement and low-signal intensity on T2-weighted images. After endometrial biopsy was done and simple hyperplasia without atypia was observed at the histopathologic finding, the patient underwent robot-assisted laparoscopy and diagnosed as adenomyoma at the frozen pathology. After adenomyomectomy, permanent pathologic analysis revealed the same result and she recovered without any complications and responded well to gonadotropin-releasing hormone (GnRH) agonist therapy.
Assuntos
Adenomioma/diagnóstico , Adenomioma/cirurgia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Adulto , Feminino , HumanosRESUMO
Dendritic cells (DCs) are promising therapeutic agents in the field of cancer immunotherapy due to their intrinsic immune-priming capacity. The potency of DCs, however, is readily attenuated immediately after their administration in patients as tumours and various immune cells, including DCs, produce various immunosuppressive factors such as interleukin (IL)-10 and transforming growth factor (TGF)-ß that hamper the function of DCs. In this study, we used small interfering RNA (siRNA) to silence the expression of endogenous molecules in DCs, which can sense immunosuppressive factors. Among the siRNAs targeting various immunosuppressive molecules, we observed that DCs transfected with siRNA targeting IL-10 receptor alpha (siIL-10RA) initiated the strongest antigen-specific CD8(+) T cell immune responses. The potency of siIL-10RA was enhanced further by combining it with siRNA targeting TGF-ß receptor (siTGF-ßR), which was the next best option during the screening of this study, or the previously selected immunoadjuvant siRNA targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN) or Bcl-2-like protein 11 (BIM). In the midst of sorting out the siRNA cocktails, the cocktail of siIL-10RA and siTGF-ßR generated the strongest antigen-specific CD8(+) T cell immunity. Concordantly, the knock-down of both IL-10RA and TGF-ßR in DCs induced the strongest anti-tumour effects in the TC-1 P0 tumour model, a cervical cancer model expressing the human papillomavirus (HPV)-16 E7 antigen, and even in the immune-resistant TC-1 (P3) tumour model that secretes more IL-10 and TGF-ß than the parental tumour cells (TC-1 P0). These results provide the groundwork for future clinical development of the siRNA cocktail-mediated strategy by co-targeting immunosuppressive molecules to enhance the potency of DC-based vaccines.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , RNA Interferente Pequeno/farmacologia , Receptores de Interleucina-10/genética , Fator de Crescimento Transformador beta/genética , Animais , Antígenos de Neoplasias/imunologia , Proteínas Reguladoras de Apoptose/genética , Proteína 11 Semelhante a Bcl-2 , Linhagem Celular Tumoral , Feminino , Papillomavirus Humano 16 , Imunoterapia/métodos , Ativação Linfocitária/imunologia , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , PTEN Fosfo-Hidrolase/genética , Proteínas E7 de Papillomavirus/metabolismo , Proteínas Proto-Oncogênicas/genética , Interferência de RNA , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/virologiaRESUMO
Hepatic stellate cells (HSCs) are major players in liver fibrogenesis. Accumulating evidence shows that suppression of autophagy plays an important role in the development and progression of liver disease. Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine to yield phosphatidic acid (PA) and choline, was recently shown to modulate autophagy. However, little is known about the effects of PLD1 on the production of type I collagen that characterizes liver fibrosis. Here, we examined whether PLD1 regulates type I collagen levels in HSCs through induction of autophagy. Adenovirus-mediated overexpression of PLD-1 (Ad-PLD1) reduced type I collagen levels in the activated human HSC lines, hTERT and LX2. Overexpression of PLD1 in HSCs led to induction of autophagy as demonstrated by increased LC3-II conversion and formation of LC3 puncta, and decreased p62 abundance. Moreover, inhibiting the induction of autophagy by treating cells with bafilomycin or a small interfering (si)RNA for ATG7 rescued Ad-PLD1-induced suppression of type I collagen accumulation in HSCs. The effects of PLD on type I collagen levels were not related to TGF-ß/Smad signaling. Furthermore, treatment of cells with PA induced autophagy and inhibited type I collagen accumulation. The present study indicates that PLD1 plays a role in regulating type I collagen accumulation through induction of autophagy.
Assuntos
Autofagia/fisiologia , Colágeno Tipo I/metabolismo , Células Estreladas do Fígado/citologia , Células Estreladas do Fígado/metabolismo , Fosfolipase D/metabolismo , Linhagem Celular , Regulação Enzimológica da Expressão Gênica/fisiologia , HumanosRESUMO
BACKGROUND: Pathologically confirmed microscopic extrathyroidal extension (ETE) is often identified after hemithyroidectomy in patients with papillary thyroid microcarcinoma (PTMC). Without the presence of microscopic ETE, these patients would be optimal candidates for hemithyroidectomy. AIM: The present study aimed at evaluating the clinical impact of microscopic ETE on the recurrence of PTMC treated with hemithyroidectomy. SUBJECTS AND METHODS: We compared the clinicopathological characteristics and 5-year outcomes for 262 PTMC patients without ETE and 86 with microscopic ETE who were treated with hemithyroidectomy between January 2004 and December 2010. RESULTS: The mean tumour size was larger (0.67 vs. 0.54 cm, p < 0.001) and the proportion of tumours measuring ≥0.5 cm was higher (84.9 vs. 66.8 %, p = 0.001) in patients with microscopic ETE as compared with patients without ETE. Occult multifocal disease was more frequent in patients with microscopic ETE than in those without ETE (14.0 vs. 6.5 %, p = 0.030). However, the recurrence rate was not different between the two groups during the mean 55.8-month follow-up period. In addition, univariate and multivariate analyses revealed no meaningful association between recurrence and microscopic ETE in patients with PTMC treated with hemithyroidectomy. CONCLUSIONS: Although microscopic ETE was associated with large tumour size and multifocal disease, its clinical impact on disease recurrence was not significant in PTMC patients treated with hemithyroidectomy. Therefore, microscopic ETE identified after hemithyroidectomy would not be an absolute indication for completion thyroidectomy in patients with PTMC.
Assuntos
Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adulto , Carcinoma Papilar/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/epidemiologia , Resultado do Tratamento , Carga TumoralRESUMO
This retrospective study evaluated the 5-year cumulative survival rate and complication rates of a 4·0-mm internal connection implant (MicroThread™ Osseospeed™, Astra Tech) installed for single-tooth restoration. The patients who were treated at Asan Medical Center between 2006 and 2007 were included in this study. A life table analysis was used to calculate the 5-year cumulative survival rate. Comparisons of cumulative survival rates among implant position (anterior, premolar and molar), jawbone (maxilla, mandible), gender and prosthesis type (screw-retained, cement-retained) were performed using the log-rank test. Post-loading complications were analysed using Fisher's exact test. Twelve of 136 implants (anterior; 22, premolar; 25, molar; 89) were lost during the loading period, and 11 were removed due to coronal fracture of fixture. The 5-year cumulative survival rate of the whole arch was 91·9%, and that of the molar region was 87·6%. Statistically significant differences were observed in cumulative survival rates among implant position (P = 0·037), whereas no statistically significant differences were observed among gender, jawbone, prosthesis type. Forty-seven of 114 (41·2%) implants in the posterior region showed post-loading complications, including coronal fracture of fixture and abutment screw loosening.
Assuntos
Implantação Dentária Endóssea/efeitos adversos , Implantes Dentários para Um Único Dente/efeitos adversos , Planejamento de Prótese Dentária/efeitos adversos , Prótese Dentária Fixada por Implante/efeitos adversos , Falha de Restauração Dentária/estatística & dados numéricos , Arcada Parcialmente Edêntula/reabilitação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
This study aimed to compare the dynamics of air temperature and velocity under two different ventilation and housing systems during summer and winter in Korea. The NH3 concentration of both housing systems was also investigated in relation to the pig's growth. The ventilation systems used were; negative pressure type for the enclosed pig house (EPH) and natural airflow for the conventional pig house (CPH). Against a highly fluctuating outdoor temperature, the EPH was able to maintain a stable temperature at 24.8 to 29.1°C during summer and 17.9 to 23.1°C during winter whilst the CPH had a wider temperature variance during summer at 24.7 to 32.3°C. However, the temperature fluctuation of the CPH during winter was almost the same with that of EPH at 14.5 to 18.2°C. The NH3 levels in the CPH ranged from 9.31 to 16.9 mg/L during summer and 5.1 to 19.7 mg/L during winter whilst that of the EPH pig house was 7.9 to 16.1 mg/L and 3.7 to 9.6 mg/L during summer and winter, respectively. These values were less than the critical ammonia level for pigs with the EPH maintaining a lower level than the CPH in both winter and summer. The air velocity at pig nose level in the EPH during summer was 0.23 m/s, enough to provide comfort because of the unique design of the inlet feature. However, no air movement was observed in almost all the lower portions of the CPH during winter because of the absence of an inlet feature. There was a significant improvement in weight gain and feed intake of pigs reared in the EPH compared to the CPH (p<0.05). These findings proved that despite the difference in the housing systems, a stable indoor temperature was necessary to minimize the impact of an avoidable and highly fluctuating outdoor temperature. The EPH consistently maintained an effective indoor airspeed irrespective of season; however the CPH had defective and stagnant air at pig nose level during winter. Characteristics of airflow direction and pattern were consistent relative to housing system during both summer and winter but not of airspeed. The ideal air velocity measurement favored the EPH and therefore can be appropriate for the Korean environment. Further emphasis on its cost effectiveness will be the subject of future investigations.
RESUMO
An emerging strategy in biomanufacturing involves using transgenic plants to express recombinant pharmaceutical and industrial proteins in large quantities. ß-Site APP cleaving enzyme 1 (ß-secretase 1, BACE1) is an enzyme involved in the abnormal production of Aß42, the major component of senile plaques in Alzheimer's disease (AD). Thus, BACE1 represents a key target protein in the development of new potential drugs to treat Alzheimer's disease. We aimed to develop a tomato-derived recombinant BACE1 (rBACE1) protein to serve as a vaccine antigen that would promote an immune response. We utilized a plant expression cassette, pE8BACE, to optimize BACE1 expression in tomato fruits. Polyemerase chain reaction and Southern blot analyses verified integration of the BACE1 gene into the plant genome. Northern and Western blot analyses demonstrated successful mRNA and protein expression of rBACE1, respectively; the Sensizyme assay kit estimated the expression level of rBACE1 protein at 136 ± 7 ng mg⻹ total soluble protein. The tomato-derived rBACE1 retains its activity for a long storage period at cool or room temperature, and is highly resistant to degradation in conditions such as low acidity. Tomato-derived rBACE1 was severely degraded by heat or boiling. The proteolytic activity of tomato-derived rBACE1, confirmed by fluorescence resonance transfer assay, was similar to that of a commercial sample of Escherichia coli-derived BACE1.
Assuntos
Vacinas contra Alzheimer/genética , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Frutas/genética , Plantas Geneticamente Modificadas/genética , Solanum lycopersicum/genética , Doença de Alzheimer/enzimologia , Doença de Alzheimer/imunologia , Doença de Alzheimer/prevenção & controle , Secretases da Proteína Precursora do Amiloide/isolamento & purificação , Ácido Aspártico Endopeptidases/isolamento & purificação , Expressão Gênica , Vetores Genéticos , Humanos , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismoRESUMO
BACKGROUND: Extrapulmonary TB (EPTB) is more difficult to diagnose than pulmonary TB. The delayed management of EPTB can lead to complications and increase the socio-economic burden.METHODS: Patients newly diagnosed with EPTB were retrospectively enrolled from 11 general hospitals in South Korea from January 2017 to December 2018. The basic characteristics of patients were described. Univariable and multivariable analyses were performed between early and delayed diagnosis groups to identify risk factors for delayed diagnosis and treatment in EPTB.RESULTS: In total, 594 patients were enrolled. Lymph node TB (28.3%) was the predominant form, followed by abdominal (18.4%) and disseminated TB (14.5%). Concurrent lung involvement was 17.8%. The positivity of diagnostic tests showed no significant difference between the two groups. Acute clinical manifestations in disseminated, pericardial and meningeal TB, and immunosuppression were associated with early diagnosis. Delayed diagnosis was associated with outpatient clinic visits, delayed sample acquisition and diagnostic departments other than infection or pulmonology.CONCLUSION: The delay in diagnosis and treatment of EPTB was not related to differences in microbiological characteristics of Mycobacterium tuberculosis itself; rather, it was due to the indolent clinical manifestations that cause referral to non-TB-specialised departments in the outpatient clinic and delay the suspicion of TB and diagnostic testing.
Assuntos
Diagnóstico Tardio , Tuberculose Extrapulmonar , Humanos , Mycobacterium tuberculosis , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Tuberculose Extrapulmonar/diagnósticoRESUMO
OBJECTIVES: To evaluate the effect of timing and appropriateness of antibiotics administration on mortality in patients diagnosed with sepsis according to the Sepsis-3 definition. METHODS: This prospective cohort study was conducted in patients diagnosed with sepsis according to the Sepsis-3 definition at the emergency department of Korea University Ansan Hospital from January 2016 to January 2019. The time to antibiotics was defined as the time in hours from emergency department arrival to the first antibiotic administration. Cox proportional hazards regression analysis was used to estimate the association between time to antibiotics and 7-, 14- and 28-day mortality. RESULTS: Of 482 patients enrolled onto this study, 203 (42.1%) of 482 and 312 (64.7%) of 482 were diagnosed with septic shock and high-grade infection respectively. The median time to receipt of antibiotic therapy was 115 minutes. Antibiotics were administered within 3 and 6 hours in 340 (70.4%) of 482 and 450 (93.2%) of 482 patients respectively. Initial appropriate empirical antibiotics were administered in 375 (77.8%) of 482 patients. The time to and appropriateness of the initial antibiotics were not associated with 7-, 14- and 28-day mortality in multivariate analysis. The Sequential Organ Failure Assessment (SOFA) score (adjusted hazard ratio (aHR) 1.229, 95% confidence interval (CI) 1.093-1.381, p 0.001) and initial lactate levels (aHR 1.128, 95% CI 1.034-1.230, p 0.007), Charlson comorbidity index (aHR 1.115, 95% CI 1.027-1.210, p 0.014), 2-hour lactate level (aHR 1.115, 95% CI 1.027-1.210, p 0.009) and SOFA score (aHR 1.077, 95% CI 1.013-1.144, p 0.018) affected 7-, 14- and 28-day mortality respectively. Subgroup analysis with septic shock, bacteraemia and high-grade infection did not affect mortality rates. CONCLUSIONS: Time to receipt of antibiotics may not affect the prognosis of patients with sepsis if a rapid and well-trained resuscitation is combined with appropriate antibiotic administration within a reasonable time.
Assuntos
Antibacterianos/administração & dosagem , Bacteriemia/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/metabolismo , Feminino , Humanos , Ácido Láctico/análise , Masculino , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Escores de Disfunção Orgânica , Prognóstico , Estudos Prospectivos , Choque Séptico/metabolismo , Choque Séptico/mortalidade , Fatores de Tempo , Tempo para o TratamentoRESUMO
Vitamin D3 up-regulated protein 1 (VDUP1) is a tumor suppressor of which expression is reduced in a variety of cancer cells, and enforced expression inhibits the tumor cell proliferation. It inhibits the activity of thioredoxin, thus contributing cellular ROS generation. Since ROS is a critical factor for angiogenesis, we investigated the role of VDUP1 in angiogenesis and endothelial proliferation. The expression of VDUP1 was upregulated by overexpression of an oncogene, Ras. Enforced expression of VDUP1 increases ROS production and proliferation of Ras-overexpressing endothelial cells. Overexpression of VDUP1 increases the resistance to the anchorage-dependent cell death and tube formation of the Ras-overexpressing endothelial cell. In addition, the removal of ROS by ROS scavenger attenuates the effect of VDUP1 on tube formation. These results suggest that VDUP1 is involved in Ras-mediated angiogenesis via ROS generation in endothelial cells.
Assuntos
Proteínas de Transporte/metabolismo , Neovascularização Fisiológica , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas/metabolismo , Proteínas ras/metabolismo , Animais , Proteínas de Transporte/genética , Linhagem Celular , Células Endoteliais/metabolismo , Camundongos , Tiorredoxinas/genética , Regulação para CimaRESUMO
The acaricidal activities of compounds derived from the oil of Pelargonium graveolens leaves against the storage food mite, Tyrophagus putrescentiae, were compared with the activity of a commercial acaricide, benzyl benzoate, in an impregnated fabric disk bioassay. Purification of the active constituent from P. graveolens was accomplished by silica gel chromatography and high-performance liquid chromatography. Structural analysis of the active constituent by 1H nuclear magnetic resonance (NMR), 13C-NMR, 1H-13C shift correlated spectroscopy NMR, and distortionless enhancement by polarization transfer NMR identified trans-3,7-dimethyl-2,6-octadien-1-ol (geraniol). Based on the 50% lethal dose values, the most toxic compounds against T. putrescentiae were geraniol (1.95 microg/cm3), which was followed by nerol (2.21 microg/cm3), citral (9.65 microg/cm3), benzyl benzoate (11.27 microg/cm3), and beta-citronellol (15.86 microg/cm3). Our results suggest that geraniol is more effective in controlling T. putrescentiae than benzyl benzoate is. Furthermore, geraniol, which is used as a flavoring for beverages, candies, ice creams, and baked goods and congeners (citral and nerol), may be useful for managing populations of T. putrescentiae.
Assuntos
Acaridae/efeitos dos fármacos , Conservação de Alimentos/métodos , Inseticidas/farmacologia , Pelargonium/química , Extratos Vegetais/farmacologia , Terpenos/farmacologia , Acaridae/crescimento & desenvolvimento , Monoterpenos Acíclicos , Animais , Benzoatos , Bioensaio , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Dose Letal Mediana , Monoterpenos/farmacologia , Controle Biológico de Vetores/métodosRESUMO
OBJECTIVES: To assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment. METHODS: We prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group. RESULTS: Among 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00-2.83; p 0.05). CONCLUSIONS: Inappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.
Assuntos
Anti-Infecciosos/administração & dosagem , Bacteriemia/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Infecções Estafilocócicas/mortalidade , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The objective of these studies was to develop simple, implantable devices that intermittently release PTH(1-34) and thus could be used for locally stimulating bone formation. The formulations were based on the association polymer system of cellulose acetate phthalate and Pluronic F-127. Release profiles for intermittent devices showed five discrete peaks, whereas sustained devices exhibited zero-order kinetics. Osteoblastic activity was greater for cells intermittently treated with PTH(1-34) compared to sustained exposure. These controlled release devices delivering PTH(1-34) in an intermittent manner may be useful for affecting osteoblast activities in a localized area.
Assuntos
Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Disponibilidade Biológica , Linhagem Celular , Celulose/análogos & derivados , Celulose/química , AMP Cíclico/metabolismo , Preparações de Ação Retardada/química , Excipientes/química , Concentração de Íons de Hidrogênio , Camundongos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Hormônio Paratireóideo/química , Hormônio Paratireóideo/farmacocinética , Poloxâmero/químicaRESUMO
The Hydrological Simulation Program-FORTRAN (HSPF) is a comprehensive model that was developed to simulate many processes related to water flow and quality in watersheds of almost any size and complexity. Paddy rice fields often dominate extensive portions of the landscape in the Asian monsoon region. The hydrological and environmental conditions of paddy fields differ somewhat from those of other land uses, and HSPF may not adequately simulate watersheds in paddy farming regions. HSPF was previously modified to HSPF-Paddy; here, we examined the applicability of the modified model. The model was applied to simulate the water flow and quality of the Saemangeum watershed (2523 km2) in Korea, where paddy rice fields comprise about one-third of the total watershed area. Long-term monitoring data (5 years for water flow, 10 years for water quality) were used in the calibration and verification processes. Model performance was in the range of "very good" and "good" based on model efficiency (R2) and percent difference. The accuracy of the daily simulation was lower than that of monthly simulation for water flow. The water-quality simulation results were encouraging for this sizable watershed with mixed land uses; HSPF-Paddy proved adequate, and its application is recommended to simulate watershed processes in paddy farming regions.
Assuntos
Simulação por Computador , Rios , Movimentos da Água , Calibragem , Coreia (Geográfico) , Nitrogênio/química , Oxigênio/química , Fósforo/química , Software , Fatores de TempoRESUMO
A study was performed to examine the effects of reclaimed-water irrigation on microorganism concentration in the ponded-water of paddy rice plots. Several treatments were used and each one was triplicated to evaluate the change of indicator microorganisms (total coliforms (TC), faecal coliforms (FC), and E. coli) concentrations in 2003 and 2004 growing seasons. Their concentrations increased significantly after irrigation, but decreased by approximately 45% in 24 h. It implies that agricultural activities such as ploughing and fertilising need to be practiced one or two days after irrigation, considering health risks. Treatments with UV-disinfected water irrigation, demonstrated significantly lower concentrations than others, including control plots where natural water was irrigated. The monitoring result from actual paddy rice fields and experimental paddy plots showed that concentrations of indicator microorganisms ranged from 10(2) to 10(5) MPN/100 mL. The field scale water reuse research project is in progress and national guidelines for reclaimed-water irrigation are under preparation in Korea. A comprehensive assessment of existing agricultural practices and a thorough monitoring in the fields as well as treatment plots are recommended to make national guidelines more representative.
Assuntos
Agricultura , Eliminação de Resíduos Líquidos , Microbiologia da Água , Conservação dos Recursos Naturais , OryzaRESUMO
The performance of a constructed wetland (CW) and wastewater stabilisation pond (WSP) system for sewage reclamation and paddy rice irrigation in a decentralised rural area was examined using a feasibility study. The CW was satisfactory for sewage treatment, with good removal efficiency even in the winter period, but the effluent concentration was relatively high in the winter period owing to the high influent concentration. The CW effluent was further treated in a WSP and the WSP effluent was considered safe for crop irrigation with respect to sewage-borne pathogens. Reclaimed water irrigation did not adversely affect the yield of rice; on the contrary, it resulted in an approximately 50% greater yield than in controls. The chemical characteristics of the soil did not change significantly during the experimental period of irrigation with reclaimed water. In the winter, CW effluent could be stored and treated in a WSP until the spring; the water could then be discharged or reused for supplemental irrigation during the typical Korean spring drought. Overall, sewage treatment and agronomic reuse using a CW-WSP system could be a practical integrated sewage management measure for protecting receiving water bodies and overcoming water shortages in decentralised rural areas.
Assuntos
Agricultura , Esgotos , Eliminação de Resíduos Líquidos/métodos , Áreas Alagadas , Conservação dos Recursos Naturais , Ecossistema , População Rural , SoloRESUMO
In this retrospective chart review we compared the subjective and objective benefits of active middle ear implants (AMEIs) with conventional hearing aids (HAs) in patients with sloping high tone hearing loss. Thirty-four patients with sensorineural hearing loss were treated with AMEIs. Of these, six had sloping high tone hearing loss and had worn an HA for more than 6 months. Objective assessments, a pure-tone audiogram, as well as a word recognition test, and the Korean version of the Hearing in Noise Test (K-HINT), and a subjective assessment, the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire, were performed. Tests were conducted under three circumstances: 1) the unaided state before surgery; 2) the HA-aided state before surgery; and 3) the AMEI-aided state 3 months after surgery. The average high-frequency hearing gain (≥ 2 kHz) was significantly better with AMEIs than with HAs. Although the result had no statistical significance, AMEIs showed a superior word recognition score (WRS) compared to HAs. However, the most comfortable hearing level at which the WRS was tested was significantly decreased with an AMEI compared to an HA. In the K-HINT, patients with an AMEI showed greater recognition than those fitted with an HA under both quiet and noisy conditions. The APAHB scores revealed that patients were more satisfied with an AMEI rather than an HA on all subscales. The use of vibroplasty in patients with sloping high tone loss resulted in positive hearing outcomes when compared to conventional HAs. Based on the data from this study, AMEIs provided better objective and subjective results and could, therefore, be a better alternative for the treatment of sloping hearing loss.
Assuntos
Auxiliares de Audição , Perda Auditiva Neurossensorial/reabilitação , Prótese Ossicular , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: The purpose of this study was to analyze the risk factors of recurrence in patients with early stage esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively analyzed the medical records of 190 patients with confirmed T1N0M0 ESCC after curative esophagectomy. The following potential prognostic factors for recurrence were investigated: age, sex, pathologic T category, tumor location, differentiation grade, tumor size, venous invasion, angiolymphatic invasion, perineural invasion and the maximum standardized uptake value (SUVmax) of the primary tumor. RESULTS: There were 174 male and 16 female patients with a median age of 66.0 years (range, 42.0-79.0 years). The pathologic status of the surgically resected ESCCs was T1a in 93 patients (48.9%) and T1b in 97 patients (51.1%). The median number of dissected lymph nodes was 35 (range, 10 to 86), and all lymph nodes were negative for tumors. The multivariate analysis showed presence of venous invasion [HR (hazard ratio), 11.433; P < 0.001) and SUVmax ≥ 3.2 (HR, 2.830; P = 0.011) as independent risk factors for recurrence. The 5-year recurrence-free survival (RFS) was 25.0% for patients with venous invasion and 78.9% for those without (P < 0.001). The 5-year RFS was 67.1% for patients with an SUVmax ≥3.2 and 81.5% for those with an SUVmax <3.2 (P = 0.003). CONCLUSIONS: Venous invasion and high SUVmax could be important prognostic factors coupled with the TNM staging system, in patients with early stage ESCC.