RESUMEN
The aim of this study was to examine the accuracy of three dimensionally (3D) printed models of the bony orbit derived from magnetic resonance imaging (MRI) for the purpose of preoperative plate bending in the setting of orbital blowout fracture. Retrospective computed tomography (CT) and MRI data from patients with suspected orbital fractures were used. Virtual models were manually generated and analysed for spatial accuracy of the fracture margins. 3D-printed models were produced and orbital fan plates bent by a single operator. The plates were then digitized and analysed for spatial discrepancy using reverse engineering software. Seven orbital blowout fractures were evident in six orbits. Analysis of the virtual models revealed high congruence between blowout fracture margins on CT and MRI (n=7, average deviation 0.85mm). Three zygomaticomaxillary complex fractures were seen, for which MRI did not demonstrate the same accuracy. For plates bent to the 3D-printed models of blowout fractures (n=6), no significant difference was found between those bent to CT versus those bent to MRI when compared for average surface and average border deviation (Wilcoxon signed rank test). Orbital blowout fractures can be defined on MRI with clinically acceptable accuracy. 3D printing of orbital biomodels from MRI for bending reconstructive plates is an acceptable and accurate technique.
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Órbita , Fracturas Orbitales , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Impresión Tridimensional , Estudios RetrospectivosRESUMEN
BACKGROUND: In comparison with foreign countries, living-organ transplantations (LOT) have been performed more frequently than dead organ transplants, including brain-dead organ transplantation (BOT) in Japan. This situation has given rise to organ transplantation tourism. Therefore, we clarify laypersons' preferences regarding organ transplantation that are producing the current situation in Japan, to suggest a possible framework for further efforts. METHODS: Voluntary completion of a quantitative and anonymous survey was promoted online (a sample size of 1030). The questionnaire had two types of variables concerning demographic characteristics and organ transplantation-related issues. RESULTS: LOT was favored over BOT. However, for willingness to donate to family members, the participants showed a significantly more positive attitude toward brain-dead organ donors (BODs) than living organ donors (LODs). In the evaluation of each transplantation technology, BOT and LOT were positioned in the middle, between transplantation that does not depend on others and the utilization of animal organs. CONCLUSIONS: Although LOT was favored over BOT, for participants hypothesized to be in a position to donate and receive organs, BODs received a conversely better reputation than LODs. Our survey and discussion suggest that the present conditions of organ transplantation in Japan might be because there is a lack of deliberation on transplantation tourism and LOT. Therefore, more surveys concerning LOT cases and the implications of avoidance of organs from brain-dead bodies, coupled with more discussions based on these surveys, are necessary to formulate a Japanese transplantation policy for the future.
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Actitud Frente a la Salud , Conocimientos, Actitudes y Práctica en Salud , Donadores Vivos/psicología , Trasplante de Órganos/psicología , Adulto , Actitud Frente a la Muerte , Muerte Encefálica , Familia/psicología , Femenino , Humanos , Japón , Masculino , Encuestas y Cuestionarios , Adulto JovenRESUMEN
To evaluate the effect of postoperative irrigation with chlorhexidine on inflammatory complications after the extraction of lower third molars under local anaesthesia, we recruited 100 patients to participate in a controlled, single-blind, randomised clinical trial. They were assigned to one of two groups: the intervention group (postoperative irrigation of the surgical site with chlorhexidine for seven days) or the control group (postoperative chlorhexidine mouth rinse for seven days). The primary outcome variables were pain, swelling, trismus, infection, and alveolar osteitis. The secondary outcome variables were wound dehiscence and food impaction. A total of 95 participants completed the study (47 in the irrigation group and 48 in the rinse group). In the irrigation group, alveolar osteitis and facial swelling had reduced significantly at seven days postoperatively (both p<0.01). Pain scores had also reduced significantly at seven days (p<0.01), but not at 48hours, and patients had lower levels of food impaction (p<0.01) and less severe symptoms (p=0.02). Routine irrigation with chlorhexidine after the extraction of third molars helps to reduce pain and lowers the incidence of alveolar osteitis.
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Clorhexidina/uso terapéutico , Mandíbula/cirugía , Tercer Molar/cirugía , Irrigación Terapéutica/métodos , Extracción Dental , Adolescente , Adulto , Anciano , Alveolo Seco/tratamiento farmacológico , Alveolo Seco/etiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Dolor/tratamiento farmacológico , Dolor/etiología , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Método Simple Ciego , Cirugía Bucal/métodos , Dehiscencia de la Herida Operatoria/tratamiento farmacológico , Dehiscencia de la Herida Operatoria/etiología , Resultado del Tratamiento , Trismo/tratamiento farmacológico , Trismo/etiología , Adulto JovenRESUMEN
In the phase 3 RESONATE study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%) and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared with patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations.
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Leucemia Linfocítica Crónica de Células B/patología , Mutación/genética , Adenina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antineoplásicos/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Mutación/efectos de los fármacos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Piperidinas , Pronóstico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Inflammatory complications such as pain, swelling, trismus, infection and alveolar osteitis have an adverse affect on the quality of life of patients after third molar removal. This review presents the current evidence on postoperative strategies to reduce these complications. A literature search was performed to identify articles published in English between 2000 to 2016 using the following keywords: third molar(s), wisdom tooth/teeth, pain, swelling, trismus, infection, alveolar osteitis and dry socket. In total, 221 papers were reviewed. Methods published included analgesics, antibiotics, corticosteroids, mouthwashes, topical gels, cryotherapy and ozone therapy. This review highlights the variability in evidence available and summarizes the findings from best-quality evidence. In conclusion, paracetamol and ibuprofen are efficacious in managing postoperative pain. Corticosteroids and antibiotics should only be used in selected cases. Chlorhexidine reduces alveolar osteitis. The benefits of cryotherapy, postoperative irrigation and ozone gel are yet to be established.
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Alveolo Seco/prevención & control , Inflamación/prevención & control , Tercer Molar/cirugía , Dolor Postoperatorio/prevención & control , Complicaciones Posoperatorias/prevención & control , Extracción Dental/efectos adversos , HumanosAsunto(s)
Anemia Hemolítica Autoinmune/etiología , Antineoplásicos/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/etiología , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Adenina/análogos & derivados , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Ensayos Clínicos Fase III como Asunto , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Piperidinas , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The Cancer Moonshot emphasizes the need to learn from the experiences of cancer patients to positively impact their outcomes, experiences, and qualities of life. To realize this vision, there has been a concerted effort to identify the fundamental building blocks required to establish a National Learning Healthcare System for Cancer, such that relevant data on all cancer patients is accessible, shareable, and contributing to the current state of knowledge of cancer care and outcomes.
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Atención a la Salud/organización & administración , Oncología Médica/tendencias , Neoplasias/tratamiento farmacológico , Biología Computacional , Interpretación Estadística de Datos , Bases de Datos Factuales , Atención a la Salud/tendencias , Humanos , National Cancer Institute (U.S.) , Estados UnidosRESUMEN
INTRODUCTION: A point prevalence study was conducted to study the epidemiology of common infections among residents in Residential Care Homes for the Elderly in Hong Kong and their associated factors. METHODS: Residential Care Homes for the Elderly in Hong Kong were selected by stratified single-stage cluster random sampling. All residents aged 65 years or above from the recruited homes were surveyed. Infections were identified using standardised definitions. Demographic and health information-including medical history, immunisation record, antibiotic use, and activities of daily living (as measured by Barthel Index)-was collected by a survey team to determine any associated factors. RESULTS: Data were collected from 3857 residents in 46 Residential Care Homes for the Elderly from February to May 2014. A total of 105 residents had at least one type of infection based on the survey definition. The overall prevalence of all infections was 2.7% (95% confidence interval, 2.2%-3.4%). The three most common infections were of the respiratory tract (1.3%; 95% confidence interval, 0.9%-1.9%), skin and soft tissue (0.7%; 95% confidence interval, 0.5%-1.0%), and urinary tract (0.5%; 95% confidence interval, 0.3%-0.9%). Total dependence in activities of daily living, as indicated by low Barthel Index score of 0 to 20 (odds ratio=3.0; 95% confidence interval, 1.4-6.2), and presence of a wound or stoma (odds ratio=2.7; 95% confidence interval, 1.4-4.9) were significantly associated with presence of infection. CONCLUSIONS: This survey provides information about infections among residents in Residential Care Homes for the Elderly in the territory. Local data enable us to understand the burden of infections and formulate targeted measures for prevention.
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Hogares para Ancianos , Infecciones/epidemiología , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Comorbilidad , Costo de Enfermedad , Femenino , Hong Kong/epidemiología , Humanos , Masculino , PrevalenciaRESUMEN
BACKGROUND: Urea cycle disorders (UCD) are caused by rare inherited defects in the urea cycle enzymes leading to diminished ability to convert ammonia to urea in the liver. The resulting excess of circulating ammonia can lead to central nervous system toxicity and irreversible neurologic damage. Most cases are identified in children. However, UCDs can also be diagnosed in adulthood, and liver transplant is occasionally required. METHODS: We examined the UNOS database to evaluate outcomes in adult and pediatric patients who underwent liver transplant as treatment for a UCD. We identified 265 pediatric and 13 adult patients who underwent liver transplant for a UCD between 1987 and 2010. RESULTS: The majority (68%) of these patients were transplanted before age 5 years. Ornithine transcarbamylase (OTC) deficiency was the most common UCD in both adults and children who underwent transplant. UCD patients who underwent liver transplant were younger, more likely to be male (67%), had lower pediatric end-stage liver disease/model for end-stage liver disease scores, and were more likely to be Caucasian or Asian compared with all other patients transplanted during the same time period. UCD patients did not have an increased utilization of living donor transplantation in this US cohort. Univariate and multivariate risk factor analyses were performed and did not reveal any significant factors that were predictive of post-transplant death or graft loss. CONCLUSIONS: Excellent outcomes were seen in both children and adults with UCDs who underwent transplant with overall 1-, 5-, and 10-year survivals of 93%, 89%, and 87%, respectively.
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Enfermedad Hepática en Estado Terminal/complicaciones , Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado , Trastornos Innatos del Ciclo de la Urea/complicaciones , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Estados Unidos , Trastornos Innatos del Ciclo de la Urea/cirugía , Adulto JovenRESUMEN
AIM: To determine whether the low C-peptide levels (< 50 pmol/l) produced by the pancreas for decades after onset of Type 1 diabetes have clinical significance. METHODS: We evaluated fasting C-peptide levels, duration of disease and age of onset in a large cross-sectional series (n = 1272) of people with Type 1 diabetes. We then expanded the scope of the study to include the relationship between C-peptide and HbA1c control (n = 1273), as well as diabetic complications (n = 324) and presence of hypoglycaemia (n = 323). The full range of C-peptide levels was also compared with 1,5-Anhydroglucitol, a glucose responsive marker. RESULTS: C-peptide levels declined for decades after diagnosis, and the rate of decline was significantly related to age of onset (P < 0.0001), after adjusting for disease duration. C-peptide levels > 10 pmol/l were associated with protection from complications (e.g. nephropathy, neuropathy, foot ulcers and retinopathy; P = 0.03). Low C-peptide levels were associated with poor metabolic control measured by HbA1c (P < 0.0001). Severe hypoglycaemia was associated with the lowest C-peptide levels compared with mild (P = 0.049) or moderate (P = 0.04) hypoglycaemia. All levels of measurable C-peptide were responsive to acute fluctuations in blood glucose levels as assessed by 1,5-Anhydroglucitol (P < 0.0001). CONCLUSIONS: Low C-peptide levels have clinical significance and appear helpful in characterizing groups at-risk for faster C-peptide decline, complications, poorer metabolic control and severe hypoglycaemia. Low C-peptide levels may be a biomarker for characterizing at-risk patients with Type 1 diabetes.
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Péptido C/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Niño , Estudios Transversales , Desoxiglucosa/sangre , Desoxiglucosa/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Hemoglobina Glucada/metabolismo , Humanos , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
Physicians apply for Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exception points on a case-by-case basis to improve an individual patient's chances of receiving a liver transplant. This retrospective cohort study describes trends in the use of exceptions among the pediatric liver waitlist population with chronic liver disease. The cohort (n = 3728) included all children with a diagnosis of chronic liver disease listed in the United Network for Organ Sharing transplant database for first isolated liver transplant between February 27, 2002 and March 31, 2013. Exception score requests were common (34%); 90% of requests were approved. The rate of exception score requests in 2013 was five times that of 2002 (incident rate ratios [IRR] 5.25, 95% confidence interval [CI] 3.19-8.63, p < 0.01). Patients of non-White race had exception score request rates 13% lower than patients of White race (IRR 0.87, 95% CI 0.77-0.98, p = 0.02). Older patients had lower rates of exception score requests than younger patients (p = 0.03). Request rates varied by region. Time spent at an active exception status nearly tripled the hazard rate for transplantation (hazard ratio = 2.90, 95% CI 2.62-3.21, p < 0.01). There is disparity in use of exceptions by race that is not explained by clinical disease severity, diagnosis, geography or other demographic factors.
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Técnicas de Apoyo para la Decisión , Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado , Selección de Paciente , Receptores de Trasplantes , Listas de Espera , Adolescente , Factores de Edad , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Evaluación de Resultado en la Atención de Salud , Grupos Raciales , Estudios Retrospectivos , Factores Sexuales , Factores SocioeconómicosRESUMEN
First described over 25 years ago, epidural lysis of adhesions (LOA) involves the mechanical dissolution of epidural scar tissue, which may directly alleviate pain and facilitate the spread of analgesic substances to area(s) of pain generation. Although it most commonly performed for lumbar failed back surgery syndrome, there is a growing body of evidence that suggests it may be effective for spinal stenosis and radicular pain stemming from a herniated disc. There is weak positive evidence that LOA is more effective than conventional caudal epidural steroid injections for failed back surgery syndrome and spinal stenosis, and that LOA is more effective than sham adhesiolysis and conservative management for lumbosacral radiculopathy. For cervical disc herniation and spinal stenosis, there is only anecdotal evidence suggesting effectiveness and safety. Factors that may contribute to the enhanced efficacy compared to traditional epidural steroid administration include the high volume administered, the use of hypertonic saline, and to a lesser extent the use of hyaluronidase and a navigable catheter to mechanically disrupt scar tissue and guide medication administration. Although LOA is widely considered a safe intervention, the complication rates are higher than for conventional epidural steroid injection.
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Cicatriz/tratamiento farmacológico , Espacio Epidural/efectos de los fármacos , Síndrome de Fracaso de la Cirugía Espinal Lumbar/tratamiento farmacológico , Hialuronoglucosaminidasa/uso terapéutico , Estenosis Espinal/tratamiento farmacológico , Adherencias Tisulares/tratamiento farmacológico , Cicatriz/patología , Espacio Epidural/patología , Medicina Basada en la Evidencia , Síndrome de Fracaso de la Cirugía Espinal Lumbar/patología , Humanos , Inyecciones Espinales , Radiculopatía/tratamiento farmacológico , Radiculopatía/patología , Estenosis Espinal/patología , Adherencias Tisulares/patologíaRESUMEN
BACKGROUND: Professional mixed martial arts (MMA) competition is a full-contact sport that has risen rapidly in popularity in recent years. However, there is limited information regarding the incidence of competition injuries after sanctioning by an athletic commission. METHODS: We conducted a retrospective cohort study to examine MMA injury patterns during a 5 year period after sanctioning in the state of Nevada. Data from all regulated MMA competitions during the study period from March 2002 to September 2007 (1270 fight exposures) was obtained. Injury odds ratios were calculated by conditional logistic regression on match outcome, age, weight, and fight experience, using a pair-matched case-control design (n = 464) and by multiple logistic regression on match outcome, age, fight experience, weight, combat minutes, and scheduled rounds. RESULTS: During the 635 professional MMA matches, 300 of the 1270 athletes sustained documented injuries with an injury rate of 23.6 per 100 fight participations. Most common reported injuries were lacerations and upper limb injuries. Severe concussion rate was 15.4 per 1000 athlete exposures, or 3% of all matches. No deaths or critical sports-related injuries resulted from any of the regulated matches during the study period. Age, weight and fight experience did not statistically increase the likelihood of injuries after controlling for other covariates. CONCLUSIONS: Injury rates in regulated professional MMA competition are similar to other combat sports; the overall risk of critical sports-related injury seems to be low. Additional study is warranted to achieve a better understanding of injury trends and ways to further lower injury risk in MMA.
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Conducta Competitiva/fisiología , Artes Marciales/lesiones , Traumatismos en Atletas/epidemiología , Traumatismos en Atletas/prevención & control , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Nevada/epidemiología , Factores de RiesgoRESUMEN
Coronary artery dissection is a rare life-threatening complication resulting from blunt traumatic injury. Most cases of coronary artery injury, including dissection, involve the left anterior descending artery given its anatomical location relative to the impact. Right coronary artery (RCA) dissection secondary to blunt trauma is a particularly unusual occurrence, and has not previously been reported in the emergency medicine literature. We present a case of RCA dissection following low impact sport-related blunt chest trauma and discuss the pathophysiology, risk factors, diagnosis and current treatment options.
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Disección Aórtica/etiología , Baloncesto/lesiones , Dolor en el Pecho/etiología , Aneurisma Coronario/etiología , Traumatismos Torácicos/complicaciones , Heridas no Penetrantes/complicaciones , Adulto , Cateterismo Cardíaco , Aneurisma Coronario/diagnóstico , Humanos , MasculinoRESUMEN
Obesity is typically associated with resistance to leptin, yet the mechanism by which leptin signaling becomes impaired is poorly understood. Here we sought to determine if the development of obesity and leptin resistance correlates with increased expression of protein tyrosine phosphatase 1B (PTP1B) in peripheral tissues and whether over-expression of this phosphatase, specifically in liver, could alter the leptin-mediated effects on feeding and glucose metabolism. Obesity was induced in mice through a high-fat diet that resulted in hyperglycemia, hyperinsulinemia and hyperleptinemia. Resistance to leptin was confirmed as exogenous leptin administration reduced food intake in animals on low-fat, but not high-fat diets. Diet-induced resistance to leptin and insulin was associated with increased hepatic levels of PTP1B. Intriguingly, hepatic adenoviral over-expression of PTP1B in ob/ob mice attenuated the ability of exogenous leptin to reduce both plasma glucose levels and food intake. These findings suggest that leptin reduces both plasma glucose and food intake in part through actions on the liver, and hepatic leptin resistance resulting from over-expression of PTP1B may contribute to the development of both diabetes and obesity.
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Leptina/fisiología , Hígado/enzimología , Proteínas Tirosina Fosfatasas/metabolismo , Adenoviridae/genética , Animales , Secuencia de Bases , Glucemia/análisis , Células CHO , Cricetinae , Cartilla de ADN , Grasas de la Dieta/administración & dosificación , Conducta Alimentaria , Vectores Genéticos , Hiperglucemia/etiología , Hiperinsulinismo/etiología , Leptina/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena de la Polimerasa , Proteína Tirosina Fosfatasa no Receptora Tipo 1RESUMEN
The objective of this study is to provide a calculation of recycling rates of waste home appliances in Taiwan, for the EPA to amend these rates in order to increase the recycling efficiency. The recycling rate is calculated by a formula according to the statistical results obtained through: (1) an estimation of domestic use of home appliances using time series analysis with multiplicative seasonal ARIMA model, (2) a further estimation of generated waste home appliances based upon the estimated domestic use and the corresponding distribution of lifetime span, and (3) a cost analysis of recycling home appliances based on a sampling survey with stratified systematic sampling conducted among collectors and a survey on five recycling plants of waste home appliances. The suggested recycling rates in this study finally used by the EPA show that all of the recycling rates have increased compared with the rates in previous years. This study also implies that amending the recycling rates may only solve some recycling problems temporarily; however, the recycling system of waste home appliances in Taiwan has to be reformed to increase the recycling efficiency for the long term.
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Conservación de los Recursos Naturales , Artículos Domésticos , Modelos Organizacionales , Administración de Residuos , Eficiencia Organizacional , Humanos , Análisis Multivariante , Estaciones del Año , TaiwánRESUMEN
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), a common autosomal recessive disease in Caucasians. The broad mutation spectrum varies among different patient groups. Current molecular diagnoses are designed to detect 80-97% of CF chromosomes in Caucasians and Ashkenazi Jews but have a much lower detection rate in Hispanic CF patients. Grebe et al. [1994] reported a 58% detection rate in Hispanic patients. Since then, there has been no large-scale, complete mutational analysis of Hispanic CF patients. In this study, the mutations in 62 Hispanic patients from southern California were investigated. The entire coding and flanking intronic regions of the CFTR gene were analyzed by temporal temperature gradient gel electrophoresis (TTGE) followed by sequencing to identify the mutations. Eleven novel mutations were discovered in this patient group: 3876delA, 406-1G>A, 935delA, 663delT, 3271delGG, 2105-2117del13insAGAAA, 3199del6, Q179K, 2108delA, 3171delC, and 3500-2A>T. Among the mutations, seven were out-of-frame insertions and deletions that result in truncated proteins, two were splice-site mutations, one was an in-frame 6 bp deletion, and one was a missense mutation that involved the non-conservative change of glutamine-179 to lysine. All patients presented severe classical clinical course with pancreatic insufficiency and poor growth, consistent with the nature of truncation mutation. The results indicate that TTGE screening following the analysis of recurrent mutations will substantially improve the mutation detection rate for Hispanic CF patients from southern California.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/genética , Pruebas Genéticas/métodos , Hispánicos o Latinos/genética , Mutación/genética , Alelos , Secuencia de Bases , California , Fibrosis Quística/diagnóstico , Fibrosis Quística/fisiopatología , Análisis Mutacional de ADN , Exones , Frecuencia de los Genes , Genotipo , Humanos , Intrones , Fenotipo , Polimorfismo Genético/genéticaRESUMEN
The effects of voltage-dependent calcium channel (VDCC) antagonists and the non-specific calcium channel antagonists on both juvenile hormone acids (JHA) release and cytosolic free calcium concentration ([Ca2+]i) are investigated in the corpora allata (CA) of the adult males loreyi leafworm Mythimna loreyi. The VDCC antagonists used in this study are: the L-type antagonists diltiazem, nifedipine, and verapamil, the N-type antagonist omega-Conotoxin (CgTx) GVIA, the N- and P/Q-type antagonist omega-CgTx MVIIC, and the T-type antagonist amiloride. The non-specific calcium channel antagonists used in this study were cadmium (Cd2+), cobalt (Co2+), nickle (Ni2+), and lanthanum (La3+). The results show that both the DHPs-sensitive L-type antagonist nifedipine and the N-type antagonist omega-CgTx GVIA were able to inhibit JHA release, but only omega-CgTx GVIA was able to reduce the [Ca2+]i. Among the non-specific calcium channel antagonists, Cd2+ is the most potent in reducing JHA release but without obvious effect on the [Ca2+]i, La3+ significantly increases the [Ca2+]i but without effect on JHA release.
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Bloqueadores de los Canales de Calcio/farmacología , Corpora Allata/efectos de los fármacos , Corpora Allata/fisiología , Lepidópteros/efectos de los fármacos , Lepidópteros/fisiología , Animales , Calcio/metabolismo , Canales de Calcio/efectos de los fármacos , Hormonas Juveniles/metabolismo , Masculino , Metales/farmacología , Nifedipino/farmacología , omega-Conotoxina GVIA/farmacologíaRESUMEN
Akt1/protein kinase B and the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase 1 (ERK1) and ERK2 have been shown to promote cell survival in a cell-specific manner. Since many receptors activate both pathways, inhibitors are commonly used to study the relative role of each pathway. In the present study, we examined the effects of PD098059 and U0126, two structurally dissimilar inhibitors of MAP kinase kinase (MEK1/2), on the activation of ERK and Akt stimulated by human 5-hydroxytryptamine(1B) (serotonin) (5-HT1B) receptors. Surprisingly, pathways for activation of both ERK and Akt were found to be sensitive to the two MEK inhibitors at concentrations commonly used to selectively inhibit the activation of ERK. Both compounds caused complete inhibition of phosphorylation of ERK and a maximal 60% inhibition of 5-HT1B receptor-mediated phosphorylation of Akt. Inhibition of Akt activation required almost complete inhibition of ERK. Transfection with cDNA for activated forms of MEK1/2 caused increased phosphorylation of ERK but not of Akt, demonstrating that independent activation of MEK/ERK was insufficient for activation of Akt. Therefore, it is not clear whether inhibition of activation of Akt resulted from selective inhibition of MEK or from additional actions on other unidentified common pathways. Nevertheless, our findings that PD098059 and U0126 inhibit activation of Akt at commonly used concentrations demonstrate that in at least some systems, these compounds inhibit activation of both ERK and Akt, and cannot be used to discern the relative roles of each pathway in mediating cellular responses.