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A high-peak-power sub-500-fs mode-locked optically pumped semiconductor laser is innovatively developed with only three components of a semiconductor gain chip, a semiconductor saturable absorber, and a focusing lens. The developed laser near the threshold pump power of 3.9 W can be operated with stable fundamental mode locking. The laser output can be naturally turned into the stable harmonic mode locking (HML) with the order gradually changing from 2nd to 8th by increasing the pump power from 4.0 W to 5.0 W. Due to the onset of the high-order transverse modes, the order of HML is fixed at 8th for a pump power greater than 5.0 W. For the HML with order less than 8th, the overall peak power and pulse width in the HML are approximately 0.36â kW and 550 fs, respectively. In the operation of 8th-order HML, the minimum pulse width and maximum peak power can reach 480 fs and 0.95â kW, respectively.
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OBJECTIVE: In the context of universal health insurance coverage, this study aimed to determine whether urban-rural inequality still exists in preventive health care (PHC) amongst children in Taiwan. STUDY DESIGN: Prospective cohort study. METHODS: A total of 184,117 mothers and their children born in 2009 were identified as the study cohort. The number of children born in urban, satellite and rural areas was 40,176, 57,565 and 86,805, respectively. All children were followed for 7 years, before which a total of seven times PHC were provided by Taiwan's National Health Insurance (NHI) programme. Ordinal logistic regression models were used to associate urbanisation level with the frequency of PHC utilisation. Stratified analyses were further performed in accordance with the children's birth weight and the mothers' birthplace. RESULTS: Children from satellite areas had higher utilisation for the first four scheduled PHC visits. Children living in urban areas received more PHC for the fifth and sixth scheduled visits. Compared with those from rural areas, children in satellite areas exhibited a small but significant increase in odds in PHC utilisation, with a covariate-adjusted odds ratio (aOR) of 1.04 and 95% confidence interval (CI) of 1.02-1.06. By contrast, no significant difference was observed between rural and urban areas (aOR = 1.01). Further stratified analyses suggest more evident urban-rural difference in PHC utilisation amongst children with low birth weight and foreign-born mothers. CONCLUSIONS: Given a universal health insurance coverage and embedded mechanisms in increasing the availability of healthcare resources in Taiwan, a slight urban-rural difference is observed in PHC utilisation amongst children. Hence, sociodemographic inequality in utilisation of PHC still exists. This issue should be addressed through policy intervention.
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Aceptación de la Atención de Salud/estadística & datos numéricos , Servicios Preventivos de Salud/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Cobertura Universal del Seguro de Salud/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Disparidades en Atención de Salud , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Programas Nacionales de Salud , Estudios Prospectivos , Factores Socioeconómicos , Taiwán , Adulto JovenRESUMEN
How has evolution led to the variation in behavioural phenotypes (personalities) in a population? Knowledge of whether personality is heritable, and to what degree it is influenced by the social environment, is crucial to understanding its evolutionary significance, yet few estimates are available from natural populations. We tracked three behavioural traits during different life-history stages in a pedigreed population of wild house sparrows. Using a quantitative genetic approach, we demonstrated heritability in adult exploration, and in nestling activity after accounting for fixed effects, but not in adult boldness. We did not detect maternal effects on any traits, but we did detect a social brood effect on nestling activity. Boldness, exploration and nestling activity in this population did not form a behavioural syndrome, suggesting that selection could act independently on these behavioural traits in this species, although we found no consistent support for phenotypic selection on these traits. Our work shows that repeatable behaviours can vary in their heritability and that social context influences personality traits. Future efforts could separate whether personality traits differ in heritability because they have served specific functional roles in the evolution of the phenotype or because our concept of personality and the stability of behaviour needs to be revised.
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Conducta Animal/fisiología , Gorriones/fisiología , Animales , Personalidad , Carácter Cuantitativo Heredable , Conducta Social , Gorriones/genéticaRESUMEN
Reproductive success is associated with age in many taxa, increasing in early life followed by reproductive senescence. In socially monogamous but genetically polygamous species, this generates the interesting possibility of differential trajectories of within-pair and extra-pair siring success with age in males. We investigate these relationships simultaneously using within-individual analyses with 13 years of data from an insular house sparrow (Passer domesticus) population. As expected, we found that both within- and extra-pair paternity success increased with age, followed by a senescence-like decline. However, the age trajectories of within- and extra-pair paternity successes differed significantly, with the extra-pair paternity success increasing faster, although not significantly, in early life, and showing a delayed decline by 1.5 years on average later in life compared to within-pair paternity success. These different trajectories indicate that the two alternative mating tactics should have age-dependent pay-offs. Males may partition their reproductive effort between within- and extra-pair matings depending on their current age to reap the maximal combined benefit from both strategies. The interplay between these mating strategies and age-specific mortality may explain the variation in rates of extra-pair paternity observed within and between species.
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Paternidad , Conducta Sexual Animal , Gorriones , Animales , Masculino , ReproducciónAsunto(s)
Cardiomiopatía Dilatada , Síndrome de Churg-Strauss , Granulomatosis con Poliangitis , Insuficiencia Cardíaca , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/etiología , Síndrome de Churg-Strauss/complicaciones , Síndrome de Churg-Strauss/diagnóstico , Eosinófilos , Insuficiencia Cardíaca/etiología , HumanosRESUMEN
AIM: To evaluate the comparative effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on risk of bone fracture in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were systematically searched from inception to 27 January 2016 to identify randomized controlled trials (RCTs) reporting the outcome of fracture in patients with T2DM treated with SGLT2 inhibitors. Pairwise and network meta-analyses, as well as a cumulative meta-analysis, were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 38 eligible RCTs (10 canagliflozin, 15 dapagliflozin and 13 empagliflozin) involving 30 384 patients, with follow-ups ranging from 24 to 160 weeks, were included. The fracture event rates were 1.59% in the SGLT2 inhibitor groups and 1.56% in the control groups. The incidence of fracture events was similar among these three SGLT2 inhibitor groups. Compared with placebo, canagliflozin (OR 1.15; 95% CI 0.71-1.88), dapagliflozin (OR 0.68; 95% CI 0.37-1.25) and empagliflozin (OR 0.93; 95% CI 0.74-1.18) were not significantly associated with an increased risk of fracture. Our cumulative meta-analysis indicated the robustness of the null findings with regard to SGLT2 inhibitors. CONCLUSIONS: Our meta-analysis based on available RCT data does not support the harmful effect of SGLT2 inhibitors on fractures, although future safety monitoring from RCTs and real-world data with detailed information on bone health is warranted.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fracturas Óseas/epidemiología , Hipoglucemiantes/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Compuestos de Bencidrilo/uso terapéutico , Canagliflozina/uso terapéutico , Glucósidos/uso terapéutico , Humanos , Incidencia , Metaanálisis en Red , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de RiesgoRESUMEN
AIMS: To investigate the temporal relationship between non-steroidal anti-inflammatory drug use and the development of chronic kidney disease in people with Type 2 diabetes mellitus. METHODS: We conducted a retrospective cohort study and followed up a population with Type 2 diabetes who were chronic kidney disease-free (n = 48,715) using national health insurance claims data in Taiwan. Exposure status to non-steroidal anti-inflammatory drugs in 2007 was measured. A total of 6406 subjects with incident chronic kidney disease were identified from the period 2008 to 2011. Multivariable proportional hazards models were applied to determine the temporal relationship between non-steroidal anti-inflammatory drug use and the development of chronic kidney disease. RESULTS: We observed a significant temporal relationship between non-steroidal anti-inflammatory drug use and the development of chronic kidney disease in people with Type 2 diabetes. Compared with people not taking any non-steroidal anti-inflammatory drug in 2007, those who were taking such drugs for at least 90 days in 2007 had a higher risk of chronic kidney disease development (adjusted hazard ratio 1.37, 95% CI 1.26-1.49). In subgroup analyses, those people (irrespective of age, sex, various comorbidities and use of anti-hypertensive drugs, aspirin or acetaminophen) who were taking non-steroidal anti-inflammatory drugs for at least 90 days were more likely to develop chronic kidney disease than people who were not taking any non-steroidal anti-inflammatory drug. CONCLUSIONS: The results suggest that there is a positive temporal relationship between non-steroidal anti-inflammatory drug use and increased risk of chronic kidney disease in people with Type 2 diabetes. The use of non-steroidal anti-inflammatory drugs should be based on clinical evaluations of benefits and risks, and should be prescribed with caution for people with Type 2 diabetes.
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Antiinflamatorios no Esteroideos/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Insuficiencia Renal Crónica/epidemiología , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
AIMS: Serum ferritin has been found closely related with diabetes and glucose metabolism, but its impact on diabetic nephropathy remains unknown. This study aimed to explore the association between serum ferritin and microalbuminuria in Type 2 diabetes. METHODS: Eight hundred and fifty-one subjects with Type 2 diabetes were selected from a cohort participating in a glycaemic control study in Taiwan in 2008. We used urine albumin:creatinine ratio to define microalbuminuria; serum ferritin was divided into quartiles for analysis. Logistic regression and trend tests were used to delineate the association between serum ferritin and microalbuminuria. RESULTS: Subjects with diabetes with higher ferritin tended to have more metabolic disorders, higher high-sensitivity C-reactive protein and higher prevalence of microalbuminuria. Compared with those in the lowest quartile, subjects with diabetes in the highest ferritin quartile were 55% (P = 0.029) more likely to have microalbuminuria. After controlling for demographics, metabolic profiles and other inflammatory markers, the association between serum ferritin levels and microalbuminuria remained significant (P for trend < 0.001). This independent relationship was not changed either for those who had better glycaemic control or those who had not used an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. CONCLUSIONS: The current study shows hyperferritinemia may be an independent risk factor of nephropathy in patients with Type 2 diabetes.
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Albuminuria/etiología , Diabetes Mellitus Tipo 2/etiología , Nefropatías Diabéticas/etiología , Ferritinas/sangre , Albuminuria/sangre , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de Riesgo , TaiwánRESUMEN
AIMS: This study aimed to characterize the impact of lytic and temperate bacteriophages on the genetic and phenotypic diversity of Mannheimia haemolytica from feedlot cattle. METHODS AND RESULTS: Strictly lytic phages were not detected from bovine nasopharyngeal (n = 689) or water trough (n = 30) samples, but Myoviridae- or Siphoviridae-like phages were induced from 54 of 72 M. haemolytica strains by mitomycin C, occasionally from the same strain. Phages with similar restriction fragment length polymorphism profiles (RFLP ≥70% relatedness) shared common host serotypes 1 or 2 (P < 0·0001). Likewise, phages with similar RFLP tended to occur in genetically related host bacteria (70-79% similarity). Host range assays showed that seven phages from host serotypes 1, 2 and 6 lysed representative strains of serotypes 1, 2 or 8. The genome of vB_MhM_1152AP from serotype 6 was found to be collinear with P2-like phage φMhaA1-PHL101. CONCLUSIONS: Prophages are a significant component of the genome of M. haemolytica and contribute significantly to host diversity. Further characterization of the role of prophage in virulence and persistence of M. haemolytica in cattle could provide insight into approaches to control this potential respiratory pathogen. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated that prophages are widespread within the genome of M. haemolytica isolates and emphasized the challenge of isolating lytic phage as a therapeutic against this pathogen.
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Bacteriófagos/aislamiento & purificación , Especificidad del Huésped , Mannheimia haemolytica/virología , Animales , Bacteriófagos/clasificación , Bacteriófagos/genética , Bovinos , Enrofloxacina , Fluoroquinolonas/farmacología , Variación Genética , Mannheimia haemolytica/clasificación , Mannheimia haemolytica/genética , Profagos/aislamiento & purificaciónRESUMEN
OBJECTIVES: This study aims to assess the effectiveness of a multidomain intervention program on the change in functional status of hospitalized older adults. DESIGN: This single-arm, prospective, non-randomized interventional study investigates the efficacy of a multidomain interventional program including cognitive stimulation activity, simple exercises, frailty education, and nutrition counseling. SETTING AND PARTICIPANTS: At a tertiary hospital in southern Taiwan, 352 eligible patients were sequentially enrolled. Included patients were aged ≥65 years (mean age, 79.6 ± 9.0 years; 62% male), scored 3-7 on the Clinical Frailty Scale (CFS), and were hospitalized in the geriatric acute ward. INTERVENTION: Those receiving standard care (physical rehabilitation and nutrition counseling) during January-July 2019 composed the historical control group. Those receiving the multidomain intervention during August-December 2019 composed the intervention group. MEASUREMENTS: The primary outcome was the change in activities of daily life (ADL) and frailty status, as assessed by Katz Index and Clinical Frailty Scale, with using the generalized estimating equation model. The length of hospital stay, medical costs, and re-admission rates were secondary outcomes. RESULTS: Participants undergoing intervention (n = 101; 27.9%) showed greater improvements in the ADL and CFS during hospitalization (ADL adjusted estimate, 0.61; 95% CI, 0.11-1.11; p = 0.02; CFS adjusted estimate, -1.11; 95% CI, -1.42- -0.80; p < 0.01), shorter length of hospital stay (adjusted estimate, -5.00; 95% CI, -7.99- -2.47; p < 0.01), lower medical costs (adjusted estimate, 0.58; 95% CI, 0.49-0.69; p < 0.01), and lower 30- and 90-day readmission rates (30-day adjusted OR [aOR], 0.12; 95% CI, 0.27-0.50; p < 0.01; 60-day aOR, 0.04; 95% CI, 0.01-0.33; p < 0.01) than did controls. CONCLUSIONS: Participation in the multidomain intervention program during hospitalization improved the functional status and decreased the hospital stay length, medical costs, and readmission rates of frail older people.
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Fragilidad , Humanos , Masculino , Anciano , Anciano de 80 o más Años , Femenino , Fragilidad/complicaciones , Estudios Prospectivos , Hospitalización , Tiempo de Internación , Pacientes , Evaluación Geriátrica , Anciano FrágilRESUMEN
OBJECTIVES: To evaluate the negative effect of physical restraint use on the hospital outcomes of older patients. DESIGN: A retrospective cohort study. SETTING: Internal medicine wards of a tertiary medical center in Taiwan. PARTICIPANTS: Subjects aged 65 years and over who were admitted during April to Dec 2017 were recruited for study. MEASUREMENTS: Demographic data, geriatric assessments (polypharmacy, visual impairment, hearing impairment, activities of daily living before and after admission, risk of pressure sores, change in consciousness level, mood condition, history of falls in the previous year, risk of malnutrition and pain) and hospital conditions (admission route, department of admission, length of hospital stay and mortality) were collected for analysis. RESULTS: Overall, 4,352 participants (mean age 78.7±8.7 years, 60.2% = male) were enrolled and 8.3% had physical restraint. Results of multivariate logistic regression showed that subjects with physical restraints were at greater risk of functional decline (adjusted odds ratio 2.136, 95% confidence interval 1.322-3.451, p=0.002), longer hospital stays (adjusted odds ratio 5.360, 95% confidence interval 3.627-7.923, p<0.001) and mortality (adjusted odds ratio 4.472, 95% confidence interval 2.794-7.160, p<0.001) after adjustment for covariates. CONCLUSION: The use of physical restraints during hospitalization increased the risk of adverse hospital outcomes, such as functional decline, longer length of hospital stay and mortality.
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Evaluación Geriátrica/métodos , Restricción Física/métodos , Anciano , Anciano de 80 o más Años , Femenino , Hospitalización , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Dissolution tests were carried out to compare the mechanical properties of calcium phosphate based bioceramics with different compositions, before and after ageing for various time periods in Ringer's solution (pH 7.2) or distilled water (pH 7.2 and 4.0) at 37 degrees C. The results indicate that the sample composition seems to have more of an effect on the mechanical properties than does the storage environment. No obvious decrease in mechanical properties was found after samples had been aged in the various solutions during the different time periods. This indicates that these samples could be of significant clinical interest as their good structural properties were retained.
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Fosfatos de Calcio/química , Cerámica , Concentración de Iones de Hidrógeno , Soluciones Isotónicas , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Solución de Ringer , Solubilidad , AguaRESUMEN
BACKGROUND: Delayed diagnosis of pyogenic liver abscess remains a challenging problem in the emergency department because of the associated high morbidity and mortality. OBJECTIVE: To evaluate the sensitivity of ultrasono-graphy in the diagnosis of pyogenic liver abscess in patients presenting to the emergency department and the factors that may influence this sensitivity. METHODS: A retrospective study was conducted in patients diagnosed with pyogenic liver abscess in the emergency department (ED) of a tertiary care teaching hospital for a period of 5 years. Between May 2001 and April 2006, 268 patients diagnosed with pyogenic liver abscess were evaluated by ultrasonography and/or CT scanning. The age, sex, clinical presentation, location and number of abscesses and the underlying disease of these two groups were compared. RESULTS: Of the 268 patients admitted via the ED who were discharged or died with a diagnosis of pyogenic liver abscess, there was a predominance of men (M/F 173/95) and the mean age was 57.6 years (range 17-90). 38 had false negative findings on ultrasonography (sensitivity 85.8%) and required abdominal CT scanning for definitive diagnosis. In the other 230 cases, ultrasonography alone was sufficient for diagnosis. Location of the abscess in segments 4 and 5 of the liver raised the sensitivity of ultrasound for diagnosis, while location in segment 8 was most associated with delayed diagnosis by ultrasonography. Right costal angle knocking pain was significant for pyogenic liver abscess even if ultrasound was negative. CONCLUSIONS: The size and location of the liver abscess and the underlying comorbid diseases may affect the diagnostic sensitivity of ultrasound for pyogenic liver abscess in clinical practice. A high index of suspicion should be maintained in patients with diabetes mellitus, previous biliary tract intervention or gastrointestinal malignancy. Follow-up CT scanning is recommended if right flank knocking pain is present, even if ultrasonography is non-revealing. A diagnostic protocol for liver abscess may be feasible in the future.
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Servicio de Urgencia en Hospital , Absceso Piógeno Hepático/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Precoz , Métodos Epidemiológicos , Reacciones Falso Negativas , Femenino , Humanos , Absceso Piógeno Hepático/patología , Masculino , Persona de Mediana Edad , Factores Sexuales , Taiwán , Tomografía Computarizada por Rayos X , Ultrasonografía , Adulto JovenRESUMEN
OBJECTIVES: To determine whether nutritional status can predict 3-year cognitive and functional decline, as well as 4-year all-cause mortality in older adults. DESIGN: Prospectively longitudinal cohort study. SETTING AND PARTICIPANTS: The study recruited 354 men aged 65 years and older in the veteran's retirement community. MEASURES: Baseline nutritional status was evaluated using the Mini-Nutritional Assessment-Short Form (MNA-SF). Cognitive function and Activities of Daily Living (ADL) function were determined by the Mini-Mental State Examination (MMSE) and the Barthel Index, respectively. Three-year cognitive and functional decline were respectively defined as a >3 point decrease in the MMSE scores and lower ADL scores than at baseline. Univariate and multivariable logistic regression analyses were conducted to identify nutritional status as a risk factor in poor outcome. The Kaplan-Meier method and Cox proportional regression models were used to estimate the effect of malnutrition risk on the mortality. RESULTS: According to MNS-SF, the prevalence of risk of malnutrition was 53.1% (188/354). Multivariate logistic regression found risk of malnutrition significantly associated with 3-year cognitive decline (Adjusted odds ratio [OR] 2.07, 95% Confidence Interval [CI] 1.05-4.08, P =0.036) and functional decline (Adjusted OR 1.83, 95% CI 1.01-3.34, P =0.047) compared with normal nutritional status. The hazard ratio (HR) for all-cause mortality was 1.8 times higher in residents at risk of malnutrition (Adjusted HR 1.82, 95% CI 1.19-2.79, P =0.006). CONCLUSIONS: Our results provide strong evidence that risk of malnutrition can predict not only cognitive and functional decline but also risk of all-cause mortality in older men living in a veteran retirement's community. Further longitudinal studies are needed to explore the causal relationship among nutrition, clinical outcomes, and the effect of an intervention for malnutrition.
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Evaluación Geriátrica/métodos , Desnutrición/epidemiología , Desnutrición/patología , Evaluación Nutricional , Estado Nutricional/fisiología , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Cognición/fisiología , Disfunción Cognitiva/fisiopatología , Estudios de Cohortes , Humanos , Modelos Logísticos , Estudios Longitudinales , Masculino , Oportunidad Relativa , Prevalencia , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Veteranos/estadística & datos numéricosRESUMEN
Acute renal failure is an abrupt decrease in renal function. Interleukin (IL)-10 inhibits ischemic and cisplatin-induced acute renal failure. We aimed to determine whether IL-20 affects renal tubular epithelial cells and is associated with acute renal failure. We analyzed the expression of IL-20 and its receptor (R) in the kidneys of rats with HgCl(2)-induced acute renal failure. Reverse transcription-PCR showed upregulated IL-20, and its receptors and immunohistochemical staining showed strongly expressed IL-20 protein in proximal tubular epithelial cells. We analyzed human proximal tubular epithelial (HK-2) cells, which expressed both IL-20 and its receptors. IL-20 specifically induced mitochondria-dependent apoptosis by activating caspase 9 in HK-2 cells. IL-20 also activated c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2, the downstream signals implicated in the apoptosis of HK-2 cells. Furthermore, IL-20 upregulated the transcripts of transforming growth factor (TGF)-beta1, a critical mediator of renal injury. In hypoxic HK-2 cells, IL-20 and IL-22R1 transcripts increased, and IL-20 upregulated IL-1 beta transcripts. In vivo study further demonstrated that anti-IL-20 antibody reduced the expression of TGF-beta1 and IL-1 beta and the number of damaged tubular cells in the kidneys of rats with acute renal failure. We concluded that IL-20 may be involved in the injury of renal epithelial cells in acute renal failure.
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Lesión Renal Aguda/tratamiento farmacológico , Anticuerpos Monoclonales , Interleucinas/fisiología , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/inmunología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Secuencia de Bases , Western Blotting , Muerte Celular , Línea Celular , Células Cultivadas , Humanos , Inmunohistoquímica , Interleucinas/genética , Interleucinas/inmunología , Túbulos Renales Proximales/efectos de los fármacos , Masculino , Cloruro de Mercurio/farmacología , Datos de Secuencia Molecular , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
To study the protective effect of prostacyclin (PGI2) we increased PGI2 production by infected NRK-52E cells with an adenovirus carrying cyclooxygenase-1 and prostacyclin synthase. PGI2 overexpression protected these cells from gentamicin-induced apoptosis by reducing cleaved caspase-3 and caspase-9, cytochrome c, and decreasing generation of reactive oxygen species. Expression of the nuclear receptor of PGI2, peroxisome proliferator-activated receptor-alpha (PPARalpha), was reduced during gentamicin treatment of the cells, while its overexpression significantly inhibited gentamicin-induced apoptosis and the amount of cleaved caspase-3. Transformation with PPARalpha short interfering RNA abolished the protective effect of PGI2 overproduction in gentamicin-treated cells. The PPARalpha activator docosahexaenoic acid given to gentamicin-treated mice significantly reduced the number of apoptotic cells in renal cortex, but this protective effect was not seen in PPARalpha knockout mice. Our study suggests that increased endogenous PGI2 production protects renal tubular cells from gentamicin-induced apoptosis through a PPARalpha-signaling pathway.
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Apoptosis , Epoprostenol/metabolismo , Gentamicinas/toxicidad , Túbulos Renales/metabolismo , PPAR alfa/metabolismo , Adenoviridae/genética , Animales , Transporte Biológico , Ciclooxigenasa 1/genética , Sistema Enzimático del Citocromo P-450/genética , Oxidorreductasas Intramoleculares/genética , Túbulos Renales/efectos de los fármacos , Ratones , Ratones Noqueados , PPAR alfa/antagonistas & inhibidores , PPAR alfa/genética , Interferencia de ARN , Ratas , TransfecciónRESUMEN
AIMS: To characterize the clinicopathological features of sporadic Burkitt lymphoma (BL). METHODS AND RESULTS: A retrospective study of 17 paediatric and 14 adult BLs with history and histopathology review, immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization (EBER) and fluorescence in situ hybridization. There was no statistically significant difference in gender, frequency of central nervous system (CNS) involvement and leukaemic change at presentation, or frequency of CD10+/Bcl-2-/Bcl-6+ (88% versus 86%), Ki67 labelling index, EBER (24% versus 21%), or C-MYC translocation (100% versus 92%) between paediatric and adult tumours. Correct pretreatment diagnoses were made in 13/17 (76%) paediatric and in 9/14 (64%) adult tumours. Twenty-eight patients received chemotherapy including 13/16 (81%) paediatric and 3/12 (25%) adult patients with appropriate regimens; 16 (57%) received CNS prophylaxis. The 1- and 5-year overall survival (OS) rates for paediatric patients were 80% and 50%, respectively, whereas 1-year OS for adults was 15%. CONCLUSIONS: Sporadic paediatric and adult BLs were phenotypically and genotypically similar. The significant prognosticators were age (P = 0.001), with or without CNS prophylaxis (P = 0.004), and CNS involvement (P = 0.008) and leukaemic change (P = 0.019) in disease course. The poor outcome in adult patients might be related to incorrect diagnosis and inappropriate treatment.
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Linfoma de Burkitt/patología , Neoplasias del Sistema Nervioso Central/patología , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/análisis , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/genética , Linfoma de Burkitt/mortalidad , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/mortalidad , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Femenino , Genotipo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Persona de Mediana Edad , Fenotipo , ARN Viral/análisis , Proteínas de Unión al ARN/análisis , Estudios Retrospectivos , Proteínas Ribosómicas/análisis , Tasa de Supervivencia , Taiwán/epidemiologíaRESUMEN
BACKGROUND: The prognostic factors of intracerebral haemorrhage (ICH) in haemodialysis (HD) patients are not fully clear and there is no standard clinical grading scale to predict 30-day mortality. Our aim was to develop such a scale. METHODS: Records of all HD patients with spontaneous ICH presenting to Chang Gung Memorial Hospital in Taiwan during 1994-2004 were reviewed. The study design was a retrospective analysis of data collected from one hospital. Prognostic factors were identified by Student's t-test and chi(2)-test. Independent predictors of 30-day mortality were determined by the logistic regression method. An outcome score based on a combination of these predictors was developed with weighting of independent predictors based on strength of association. RESULTS: The overall 30-day mortality rate was 67.3%. Prognostic factors independently associated with mortality were the Glasgow Coma Scale score (P < 0.001), age >/=70 years (P = 0.032), systolic blood pressure <130 mmHg or >/=200 mmHg (P = 0.016), ICH volume >/=30 mL (P = 0.012), presence of intraventricular haemorrhage (P = 0.004) and serum glucose >/=8.8 mmol/L (P = 0.023). The score was the sum of individual points assigned as follows: Glasgow Coma Scale score 12-15 (0 points), 9-11 (1), 3-8 (4); age <70 years, yes (0), no (2); and systolic blood pressure 130-199 mmHg, yes (0), no (1). The 30-day mortality rate increased steadily with score (P < 0.001). CONCLUSION: The outcome score is a simple clinical grading scale that allows risk stratification of HD patients presenting with ICH. This scale could be used to design treatment protocols and clinical research studies of ICH in HD patients.
Asunto(s)
Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/mortalidad , Mortalidad Hospitalaria/tendencias , Diálisis Renal/mortalidad , Diálisis Renal/tendencias , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
We investigated the relationship between CAG and GGC repeat polymorphism of the androgen receptor (AR) gene and rheumatoid arthritis (RA) in female patients with different disease subtypes. This case-control study enrolled 215 women in three groups: RA patients refractory to standardized therapy (n = 51); RA patients at complete remission phase (n = 60); and healthy controls (n = 104). CAG and GGC repeat lengths were determined by automated fluorescence-based DNA fragment-sizing method. Demographic data, allele lengths, allele distribution, and zygosity status of CAG/GGC repeats were assessed for the three groups. Refractory RA patients tend to have a significantly younger onset age of RA and more elevated erythrocyte sedimentation rates than do remission RA patients. Mean and median values of CAG and GGC repeat lengths are similar in both RA and control patients. However, RA patients harboring any long CAG alleles with more than 23 repeats had an increased risk of a refractory course, whereas differences in risk were not observed between these patients and RA subtypes harboring any long GGC alleles with more than 16 repeats. In addition, the homozygous frequency of CAG but not GGC alleles was lower in refractory RA than in remission RA patients or in controls (p = 0.042). Neither CAG nor GGC repeat lengths had a significant relationship with rheumatoid factor reactivity. Our observations indicate that short CAG repeats of the AR gene with higher transactivation activity may have protective effects against refractory course of RA development and that homozygous frequency of CAG alleles may be involved in the disease remission subtype. In contrast, lack of association of GGC polymorphism and RA was also observed. Together, these data imply that CAG but not GGC alleles in the AR polymorphism may play an important role in modulating the disease pattern of RA among Taiwanese women.