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OBJECTIVES: This study aimed to establish an occupational disease surveillance system by identifying high-risk industries for silicosis in Taiwan using a national database linkage approach. METHODS: The study was based on a comprehensive analysis of benefit claims from the National Labor Insurance Research Database and medical records from the National Health Insurance Research Database between 2004 and 2020, providing coverage for more than 88.5% of the workforce and 99.9% of citizens. Silicosis was defined as having received compensation for labor insurance benefits or having received a diagnosis of silicosis (International Classification of Diseases, 10th Revision: J62 or International Classification of Diseases, Ninth Revision: 502). The study used the International Standard Industrial Classification of All Economic Activities for industry-specific classification. Cox proportional hazard models were used to compare the silicosis incidence and risk among each industry and identify high-risk industries for silicosis. RESULTS: This study analyzed 1466 cases of silicosis between 2004 and 2020 and found that 28 industries had incidence rates of over 40 cases per 100,000 workers, indicating more than double the risk of developing silicosis. Of these industries, 14 were considered high risk (relative risk of over four times). Among these, this study identified industries rarely mentioned in the past, such as wholesale of brick, sand, cement, and products, artistic creation, landscape construction, and materials recovery. Stratification by years of work experience reveals those industries such as quarrying of stone, sand, clay, and other mining, construction of buildings, landscape construction, site preparation, foundation and structure construction, building completion and finishing, manufacture of ships, boats, and floating structures, and plumbing, heat, and air conditioning installation display higher hazard ratios for individuals with <10 years of work experience. CONCLUSIONS: The current surveillance system has identified certain industries that are at a higher risk of developing silicosis, which could be used for future occupational epidemiological surveys and targeted preventive measures in these sectors.
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Enfermedades Profesionales , Exposición Profesional , Silicosis , Humanos , Incidencia , Arena , Taiwán/epidemiología , Silicosis/epidemiología , Silicosis/diagnóstico , Silicosis/prevención & control , Enfermedades Profesionales/epidemiología , Exposición Profesional/efectos adversosRESUMEN
Zoonotic tuberculosis caused by Mycobacterium bovis (M. bovis), a member of Mycobacterium tuberculosis complex (MTBC) has increasingly gathered attention as a public health risk, particularly in developing countries with higher disease prevalence. M. bovis is capable of infecting multiple hosts encompassing a number of domestic animals, in particular cattle as well as a broad range of wildlife reservoirs. Humans are the incidental hosts of M. bovis whereby its transmission to humans is primarily through the consumption of cattle products such as unpasteurized milk or raw meat products that have been contaminated with M. bovis or the transmission could be due to close contact with infected cattle. Also, the transmission could occur through aerosol inhalation of infective droplets or infected body fluids or tissues in the presence of wound from infected animals. The zoonotic risk of M. bovis in humans exemplified by miscellaneous studies across different countries suggested the risk of occupational exposure towards M. bovis infection, especially those animal handlers that have close and unreserved contact with cattle and wildlife populations These animal handlers comprising of livestock farmers, abattoir workers, veterinarians and their assistants, hunters, wildlife workers as well as other animal handlers are at different risk of contracting M. bovis infection, depending on the nature of their jobs and how close is their interaction with infected animals. It is crucial to identify the underlying transmission risk factors and probable transmission pathways involved in the zoonotic transmission of M. bovis from animals to humans for better designation and development of specific preventive measures and guidelines that could reduce the risk of transmission and to protect these different occupational-related/populations at risk. Effective control and disease management of zoonotic tuberculosis caused by M. bovis in humans are also hindered by various challenges and factors involved at animal-human interface. A closer look into factors affecting proper disease control and management of M. bovis are therefore warranted. Hence, in this narrative review, we have gathered a number of different studies to highlight the risk of occupational exposure to M. bovis infection and addressed the limitations and challenges underlying this context. This review also shed lights on various components and approaches in tackling M. bovis infection at animal-human interface.
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Mycobacterium bovis , Exposición Profesional , Tuberculosis/transmisión , Animales , HumanosRESUMEN
INTRODUCTION: Quantitative polymerase chain reaction (qPCR) is commonly used in the investigation of acute myeloid leukaemias (AML). Stable reference genes (RG) are essential for accurate and reliable reporting but no standard method for selection has been endorsed. MATERIALS AND METHODS: We evaluated simple statistics and published model-based approaches. Multiplex-qPCR was conducted to determine the expression of 24 candidate RG in AMLs (N=9). Singleplex-qPCR was carried out on selected RG (SRP14, B2M and ATP5B) and genes of interest in AML (N=15) and healthy controls, HC (N=12). RESULTS: RG expression levels in AML samples were highly variable and coefficient of variance (CV) ranged from 0.37% to 10.17%. Analysis using GeNorm and Normfinder listed different orders of most stable genes but the top seven (ACTB, UBE2D2, B2M, NF45, RPL37A, GK, QARS) were the same. In singleplex-qPCR, SRP14 maintained the lowest CV in AML samples. B2M, one of most stable reference genes in AML, was expressed near significantly different in AML and HC. GeNorm selected ATP5B+SRP14 while Normfinder chose SRP14+B2M as the best two RG in combination. The median expressions of combined RG genes in AML compared to HC were less significantly different than individually implying smaller expression variation after combination. Genes of interest normalised with RG in combination or individually, displayed significantly different expression patterns. CONCLUSIONS: The selection of best reference gene in qPCR must consider all sample sets. Model-based approaches are important in large candidate gene analysis. This study showed combination of RG SRP14+B2M was the most suitable normalisation factor for qPCR analysis of AML and healthy individuals.
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Expresión Génica/genética , Leucemia Mieloide Aguda/genética , ATPasas de Translocación de Protón Mitocondriales/genética , Adolescente , Adulto , Médula Ósea/metabolismo , Células de la Médula Ósea/citología , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adulto JovenRESUMEN
Dysregulation of microRNAs (miRNAs) plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL). The Eµ-TCL1 transgenic mouse develops a form of leukemia that is similar to the aggressive type of human B-CLL, and this valuable model has been widely used for testing novel therapeutic approaches. Here, we adopted this model to investigate the potential effects of miR-26a, miR-130an and antimiR-155 in CLL therapy. Improved delivery of miRNA molecules into CLL cells was obtained by developing a novel system based on lipid nanoparticles conjugated with an anti-CD38 monoclonal antibody. This methodology has proven to be highly effective in delivering miRNA molecules into leukemic cells. Short- and long-term experiments showed that miR-26a, miR-130a and anti-miR-155 increased apoptosis after in vitro and in vivo treatment. Of this miRNA panel, miR-26a was the most effective in reducing leukemic cell expansion. Following long-term treatment, apoptosis was readily detectable by analyzing cleavage of PARP and caspase-7. These effects could be directly attributed to miR-26a, as confirmed by significant downregulation of its proven targets, namely cyclin-dependent kinase 6 and Mcl1. The results of this study are relevant to two distinct areas. The first is related to the design of a technical strategy and to the selection of CD38 as a molecular target on CLL cells, both consenting efficient and specific intracellular transfer of miRNA. The original scientific finding inferred from the above approach is that miR-26a can elicit in vivo anti-leukemic activities mediated by increased apoptosis.
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ADP-Ribosil Ciclasa 1/antagonistas & inhibidores , Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Glicoproteínas de Membrana/antagonistas & inhibidores , MicroARNs/uso terapéutico , ADP-Ribosil Ciclasa 1/genética , Animales , Anticuerpos Monoclonales de Origen Murino/química , Caspasa 7/metabolismo , Línea Celular Tumoral , Quinasa 6 Dependiente de la Ciclina/genética , Regulación hacia Abajo , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/genética , Lípidos/química , Glicoproteínas de Membrana/genética , Ratones , Ratones Transgénicos , MicroARNs/administración & dosificación , MicroARNs/antagonistas & inhibidores , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , Nanopartículas/química , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/genética , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas/genéticaRESUMEN
Current treatments for acute myeloid leukemia (AML) are designed to target rapidly dividing blast populations with limited success in eradicating the functionally distinct leukemia stem cell (LSC) population, which is postulated to be responsible for disease resistance and relapse. We have previously reported high miR-126 expression levels to be associated with a LSC-gene expression profile. Therefore, we hypothesized that miR-126 contributes to 'stemness' and is a viable target for eliminating the LSC in AML. Here we first validate the clinical relevance of miR-126 expression in AML by showing that higher expression of this microRNA (miR) is associated with worse outcome in a large cohort of older (⩾60 years) cytogenetically normal AML patients treated with conventional chemotherapy. We then show that miR-126 overexpression characterizes AML LSC-enriched cell subpopulations and contributes to LSC long-term maintenance and self-renewal. Finally, we demonstrate the feasibility of therapeutic targeting of miR-126 in LSCs with novel targeting nanoparticles containing antagomiR-126 resulting in in vivo reduction of LSCs likely by depletion of the quiescent cell subpopulation. Our findings suggest that by targeting a single miR, that is, miR-126, it is possible to interfere with LSC activity, thereby opening potentially novel therapeutic approaches to treat AML patients.
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Leucemia Mieloide Aguda/terapia , MicroARNs/antagonistas & inhibidores , Nanopartículas/administración & dosificación , Células Madre Neoplásicas/fisiología , Animales , Metilación de ADN , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Antígenos Comunes de Leucocito/antagonistas & inhibidores , Ratones , Ratones Endogámicos C57BL , MicroARNs/fisiología , Células Madre Neoplásicas/efectos de los fármacosRESUMEN
High levels of microRNA-155 (miR-155) are associated with poor outcome in acute myeloid leukemia (AML). In AML, miR-155 is regulated by NF-κB, the activity of which is, in part, controlled by the NEDD8-dependent ubiquitin ligases. We demonstrate that MLN4924, an inhibitor of NEDD8-activating enzyme presently being evaluated in clinical trials, decreases binding of NF-κB to the miR-155 promoter and downregulates miR-155 in AML cells. This results in the upregulation of the miR-155 targets SHIP1, an inhibitor of the PI3K/Akt pathway, and PU.1, a transcription factor important for myeloid differentiation, leading to monocytic differentiation and apoptosis. Consistent with these results, overexpression of miR-155 diminishes MLN4924-induced antileukemic effects. In vivo, MLN4924 reduces miR-155 expression and prolongs the survival of mice engrafted with leukemic cells. Our study demonstrates the potential of miR-155 as a novel therapeutic target in AML via pharmacologic interference with NF-κB-dependent regulatory mechanisms. We show the targeting of this oncogenic microRNA with MLN4924, a compound presently being evaluated in clinical trials in AML. As high miR-155 levels have been consistently associated with aggressive clinical phenotypes, our work opens new avenues for microRNA-targeting therapeutic approaches to leukemia and cancer patients.
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Ciclopentanos/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , MicroARNs/genética , Pirimidinas/farmacología , Secuencias Repetidas en Tándem/genética , Ubiquitinas/antagonistas & inhibidores , Tirosina Quinasa 3 Similar a fms/genética , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Inmunoprecipitación de Cromatina , Resistencia a Antineoplásicos , Femenino , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Humanos , Leucemia Mieloide Aguda/patología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Monocitos/patología , Proteína NEDD8 , FN-kappa B/genética , FN-kappa B/metabolismo , Regiones Promotoras Genéticas , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Cyclic AMP signaling is critical for activity-dependent refinement of neuronal circuits. Global disruption of adenylyl cyclase 1 (AC1), the major calcium/calmodulin-stimulated adenylyl cyclase in the brain, impairs formation of whisker-related discrete neural modules (the barrels) in cortical layer 4 in mice. Since AC1 is expressed both in the thalamus and the neocortex, the question of whether pre- or postsynaptic (or both) AC1 plays a role in barrel formation has emerged. Previously, we generated cortex-specific AC1 knockout (Cx-AC1KO) mice and found that these animals develop histologically normal barrels, suggesting a potentially more prominent role for thalamic AC1 in barrel formation. To determine this, we generated three new lines of mice: one in which AC1 is disrupted in nearly half of the thalamic ventrobasal nucleus cells in addition to the cortical excitatory neurons (Cx/pTh-AC1KO mouse), and another in which AC1 is disrupted in the thalamus but not in the cortex or brainstem nuclei of the somatosensory system (Th-AC1KO mouse). Cx/pTh-AC1KO mice show severe deficits in barrel formation. Th-AC1KO mice show even more severe disruption in barrel patterning. In these two lines, single thalamocortical (TC) axon labeling revealed a larger lateral extent of TC axons in layer 4 compared to controls. In the third line, all calcium-stimulated adenylyl cyclases (both AC1 and AC8) are deleted in cortical excitatory neurons. These mice have normal barrels. Taken together, these results indicate that thalamic AC1 plays a major role in patterning and refinement of the mouse TC circuitry.
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Adenilil Ciclasas/metabolismo , Corteza Somatosensorial/crecimiento & desarrollo , Tálamo/fisiología , Adenilil Ciclasas/genética , Animales , Axones/fisiología , Inmunohistoquímica , Ratones Noqueados , Técnicas de Trazados de Vías Neuroanatómicas , Plasticidad Neuronal/fisiología , Corteza Somatosensorial/fisiología , Tálamo/crecimiento & desarrollo , Vibrisas/fisiologíaRESUMEN
Selective cytotoxicity to cancer cells without compromising their normal counterparts pose a huge challenge for traditional drug design. Here we developed a tumor antigen-targeted delivery of immunonanoparticle carrying a novel non-immunosuppressive FTY720 derivative OSU-2S with potent cytotoxicity against leukemic B cells. OSU-2S induces activation of protein phosphatase 2A (PP2A), phosphorylation and nuclear translocation of SHP1(S591) and deregulation of multiple cellular processes in chronic lymphocytic leukemia (CLL) resulting in potent cytotoxicity. To preclude OSU-2S-mediated effects on these ubiquitous phosphatases in unintended cells and avoid potential adverse effects, we developed an OSU-2S-targeted delivery of immunonanoparticles (2A2-OSU-2S-ILP), that mediated selective cytotoxicity of CLL but not normal B cells through targeting receptor tyrosine kinase ROR1 expressed in leukemic but not normal B cells. Developing a novel spontaneous CLL mouse model expressing human ROR1 (hROR1) in all leukemic B cells, we demonstrate the therapeutic benefit of enhanced survival with 2A2-OSU-2S-ILP in vivo. The newly developed non-immunosuppressive OSU-2S, its delivery using human CLL directed immunonanoparticles and the novel transgenic (Tg) mouse model of CLL that expresses hROR1 exclusively in leukemic B cell surface are highly innovative and can be applied to CLL and other ROR1+ malignancies including mantle cell lymphoma and acute lymphoblastic leukemia.
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Linfocitos B/citología , Sistemas de Liberación de Medicamentos , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/terapia , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Animales , Apoptosis , Linfocitos B/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular , Clorhidrato de Fingolimod , Humanos , Inmunosupresores/química , Liposomas/química , Linfoma de Células del Manto/metabolismo , Ratones , Ratones Transgénicos , Nanopartículas/química , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosforilación , Glicoles de Propileno/química , Proteína Quinasa C/metabolismo , Esfingosina/análogos & derivados , Esfingosina/química , Resultado del TratamientoRESUMEN
Investigation of single molecule DNA dynamics in confined environments has led to important applications in DNA analysis, separation, and sequencing. Here, we studied the electrophoretic transport of DNA molecules through nanochannels shorter than the DNA contour length and calculated the associated translocation time curves. We found that the longer T4 DNA molecules required a longer time to traverse a fixed length nanochannel than shorter λ DNA molecules and that the translocation time decreased with increasing electric field which agreed with theoretical predictions. We applied this knowledge to design an asymmetric electric pulse and demonstrate the different responses of λ and T4 DNA to the pulses. We used Brownian dynamics simulations to corroborate our experimental results on DNA translocation behaviour. This work contributes to the fundamental understanding of polymer transport through nanochannels and may help in designing better separation techniques in the future.
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This work obtains the first molecular imaging of wall slip in entangled solutions. Using a combination of confocal fluorescence microscopy and rheometry, molecular images were captured in the nonlinear response regime of entangled DNA solutions. Conformations of DNA molecules were imaged during shear to correlate with the magnitude of wall slip. Interfacial chain disentanglement results in wall slip beyond the stress overshoot. Sufficient disentanglement can produce tumbling of individual DNA in the entangled solutions.
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ADN/química , ADN/ultraestructura , Conformación de Ácido Nucleico , Aumento de la Imagen , Microfluídica , Microscopía Confocal , Microscopía Fluorescente , Resistencia al Corte/fisiología , Soluciones/químicaRESUMEN
Pregnancy-related pelvic girdle pain (PRPGP) has a prevalence of approximately 45% during pregnancy and 20-25% in the early postpartum period. Most women become pain free in the first 12 weeks after delivery, however, 5-7% do not. In a large postpartum study of prevalence for urinary incontinence (UI) [Wilson, P.D., Herbison, P., Glazener, C., McGee, M., MacArthur, C., 2002. Obstetric practice and urinary incontinence 5-7 years after delivery. ICS Proceedings of the Neurourology and Urodynamics, vol. 21(4), pp. 284-300] found that 45% of women experienced UI at 7 years postpartum and that 27% who were initially incontinent in the early postpartum period regained continence, while 31% who were continent became incontinent. It is apparent that for some women, something happens during pregnancy and delivery that impacts the function of the abdominal canister either immediately, or over time. Current evidence suggests that the muscles and fascia of the lumbopelvic region play a significant role in musculoskeletal function as well as continence and respiration. The combined prevalence of lumbopelvic pain, incontinence and breathing disorders is slowly being understood. It is also clear that synergistic function of all trunk muscles is required for loads to be transferred effectively through the lumbopelvic region during multiple tasks of varying load, predictability and perceived threat. Optimal strategies for transferring loads will balance control of movement while maintaining optimal joint axes, maintain sufficient intra-abdominal pressure without compromising the organs (preserve continence, prevent prolapse or herniation) and support efficient respiration. Non-optimal strategies for posture, movement and/or breathing create failed load transfer which can lead to pain, incontinence and/or breathing disorders. Individual or combined impairments in multiple systems including the articular, neural, myofascial and/or visceral can lead to non-optimal strategies during single or multiple tasks. Biomechanical aspects of the myofascial piece of the clinical puzzle as it pertains to the abdominal canister during pregnancy and delivery, in particular trauma to the linea alba and endopelvic fascia and/or the consequence of postpartum non-optimal strategies for load transfer, is the focus of the first two parts of this paper. A possible physiological explanation for fascial changes secondary to altered breathing behaviour during pregnancy is presented in the third part. A case study will be presented at the end of this paper to illustrate the clinical reasoning necessary to discern whether conservative treatment or surgery is necessary for restoration of function of the abdominal canister in a woman with postpartum diastasis rectus abdominis (DRA).
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Fascia/fisiología , Periodo Posparto/fisiología , Complicaciones del Embarazo/fisiopatología , Respiración , Incontinencia Urinaria/fisiopatología , Adulto , Femenino , Humanos , Dolor/fisiopatología , Parto/fisiología , Embarazo , Recto del Abdomen/fisiologíaRESUMEN
AIMS: We systematically analysed evidence from randomized controlled trials (RCTs) examining the safety and efficacy of neutral protamine Hagedorn (NPH) insulin and glargine in the management of adults with Type 2 diabetes. METHODS: Studies were identified by searching medline (1966-March 2007), embase (1974-2007), American Diabetes Association abstract database and the Cochrane Central Register of Controlled Trials using Medical Subject Headings (MeSH) diabetes mellitus, Type 2, insulin, insulin isophane, hypoglycaemic agents and the keywords glargine and NPH. Data on study design, participants, fasting plasma glucose (FPG), glycated haemoglobin (HbA(1c)), body weight and hypoglycaemia were independently abstracted by two investigators using a standardized protocol. RESULTS: Data from a total of 4385 participants in 12 RCTs were pooled using a random-effects model. The mean net change (95% confidence interval) for FPG, HbA(1c) and body weight for patients treated with NPH insulin as compared with glargine was 0.21 mmol/l (-0.02 to 0.45), 0.08% (-0.04 to 0.21) and -0.33 kg (-0.61 to -0.06), respectively, with negative values favouring NPH and positive values favouring glargine. More participants experienced symptomatic and nocturnal hypoglycaemia on NPH than glargine, but there was no significant difference in confirmed or severe episodes. CONCLUSIONS: We identified no difference in glucose-lowering between insulin glargine and NPH insulin, but less patient-reported hypoglycaemia with glargine and slightly less weight gain with NPH in adults with Type 2 diabetes.
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Glucemia/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Insulina Isófana/efectos adversos , Insulina/análogos & derivados , Diabetes Mellitus Tipo 2/sangre , Femenino , Humanos , Hipoglucemia/inducido químicamente , Insulina/efectos adversos , Insulina/uso terapéutico , Insulina Glargina , Insulina de Acción Prolongada , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Estadística como Asunto , Aumento de Peso/efectos de los fármacosRESUMEN
BACKGROUND AND AIMS: There are a range of rates and a number of prognostic factors associated with the local recurrence of colorectal cancer after curative resection. The aim of this study was to identify the potential prognostic factors of local recurrence in patients with colon and rectal cancers. MATERIALS AND METHODS: A retrospective review of 1,838 patients who underwent curative resection of non-metastatic colorectal cancer was conducted. The patients were treated between 1994 and 2004, and had a minimum follow-up of 3 years. RESULTS: There were 994 patients with colon cancer and 844 patients with rectal cancer. The median duration of follow-up was 60.9 +/- 24.5 months. With respect to colon cancer, the local recurrence rate was 6.1% (61 patients). With respect to rectal cancer, 95 patients had a local recurrence (11.3%), the rate of which was statistically greater than the local recurrence rate for colon cancer (p < 0.001). The overall recurrence rate was 16.4% (301 patients), and the local recurrence rate, with or without systemic metastases, was 8.5% (156 patients). Local recurrences occurred within 2 and 3 years in 59.9% and 82.4% of the patients, respectively. In patients with colon and rectal cancer, the pathologic T stage (p = 0.044 and p = 0.034, respectively), pathologic N stage (p = 0.001 and p < 0.001, respectively), and lymphovascular invasion (p = 0.013 and p = 0.004, respectively) were adverse risk factors for local recurrence. The level of the anastomosis from the anal verge was an additional prognostic factor (p = 0.007) in patients with rectal cancer. CONCLUSION: Compulsive follow-up care of patients with colon and rectal cancers is needed for 3 years after curative resection, especially in patients who have adverse risk factors for local recurrence.
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Colectomía/métodos , Neoplasias del Colon/cirugía , Recurrencia Local de Neoplasia/epidemiología , Neoplasias del Recto/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/patología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Adulto JovenRESUMEN
An electrokinetics-induced stagnation flow was created inside a microscale cross-channel. Compared to hydrodynamic-induced microfluidics, this flow system can be readily assembled and the operation is very simple due to a low pressure drop. Through image analysis, a fairly homogeneous, two-dimensional elongational flow was observed. The initial conformation of DNA molecules and residence time inside the flow field play important roles in determining the extent of DNA stretching. A coarse-grain molecular simulation agrees reasonably well with experimental observations.
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ADN/análisis , ADN/química , Electroquímica/métodos , Electroforesis por Microchip/métodos , Microfluídica/métodos , Micromanipulación/métodos , Modelos Químicos , Simulación por Computador , Elasticidad , Modelos Moleculares , Conformación de Ácido Nucleico , Estrés MecánicoRESUMEN
AIMS: To investigate the association between cancer mortality risk and exposure to chlorinated hydrocarbons in groundwater of a downstream community near a contaminated site. METHODS: Death certificates inclusive for the years 1966-97 were collected from two villages in the vicinity of an electronics factory operated between 1970 and 1992. These two villages were classified into the downstream (exposed) village and the upstream (unexposed) according to groundwater flow direction. Exposure classification was validated by the contaminant levels in 49 residential wells measured with gas chromatography/mass spectrometry. Mortality odds ratios (MORs) for cancer were calculated with cardiovascular-cerebrovascular diseases as the reference diseases. Multiple logistic regressions were performed to estimate the effects of exposure and period after adjustment for age. RESULTS: Increased MORs were observed among males for all cancer, and liver cancer for the periods after 10 years of latency, namely, 1980-89, and 1990-97. Adjusted MOR for male liver cancer was 2.57 (95% confidence interval 1.21 to 5.46) with a significant linear trend for the period effect. CONCLUSION: The results suggest a link between exposure to chlorinated hydrocarbons and male liver cancer risk. However, the conclusion is limited by lack of individual information on groundwater exposure and potential confounding factors.
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Hidrocarburos Clorados/efectos adversos , Neoplasias Hepáticas/mortalidad , Salud Pública , Contaminantes Químicos del Agua/efectos adversos , Adulto , Anciano , Causas de Muerte , Certificado de Defunción , Exposición a Riesgos Ambientales , Femenino , Humanos , Neoplasias Hepáticas/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Características de la Residencia , Factores de Riesgo , Abastecimiento de Agua/análisisRESUMEN
Conflicting data for the effects of colchicine on cholesterol transport and steroidogenesis raise the question of the role of microtubules in cholesterol transport from the lipid droplet to mitochondria in steroidogenic cells. In this study, using corticosterone radioimmunoassay and immunofluorescence microscopy, we re-evaluated the effects of colchicine on hormone production and morphological changes of lipid droplets' and studied the signaling pathway involved in colchicine-induced steroidogenesis. Colchicine stimulated steroid production in a dose- and time-dependent manner. The structural integrity of both the microtubules and the lipid droplet capsule was destroyed by colchicine treatment. Disruption of the lipid droplet capsule occurred later than microtubule depolymerization. After cessation of colchicine treatment and a 3 h recovery in fresh medium, capsular protein relocated to the droplet surface before the cytoplasmic microtubule network was re-established. beta-lumicolchicine, an inactive analogue of colchicine, disrupted the capsule and increased hormone production without affecting microtubular structure. Thus, microtubule depolymerization is not required for the increase in steroid production and capsular disruption. To explore the signaling pathway involved in colchicine-induced steroidogenesis, we measured intracellular cAMP levels. Unlike ACTH, colchicine did not increase cAMP levels, suggesting that the cAMP-PKA system is not involved. Colchicine and ACTH had additive effects on corticosterone production, whereas colchicine and PMA did not, implying that part of the PKC signaling mechanism may be involved in colchicine-induced steroidogenesis. Cycloheximide, a protein synthesis inhibitor, completely inhibited colchicine-induced steroidogenesis and capsular disruption. These results demonstrate that the steroid production and lipid droplet capsule detachment induced by colchicine are both protein neosynthesis-dependent and microtubule-independent.
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Corteza Suprarrenal/efectos de los fármacos , Colchicina/farmacología , Corticosterona/biosíntesis , Corteza Suprarrenal/citología , Corteza Suprarrenal/metabolismo , Animales , AMP Cíclico/metabolismo , Femenino , Técnica del Anticuerpo Fluorescente , Microtúbulos/metabolismo , Radioinmunoensayo , Ratas , Ratas WistarRESUMEN
Using data collected from nationwide surveys of drug-using offenders in the United States and Taiwan, this article compares offender differences with respect to socio-demographic characteristics, childhood experiences, drug use and treatment patterns, and criminal histories. The results suggest that the experiences of U.S. drug-using offenders are more complex, with multiple routes and consequences of drug use, while the social constructionist view is more appropriate to explain the experience of Taiwanese drug-using offenders. Overall, U.S. drug-using offenders reported earlier drug and criminal involvement, experienced more prior arrests, and committed more non-drug-related crimes. Family problems were more prevalent among U.S. drug-using offenders than Taiwanese drug-using offenders. Drug-using offenders in the U.S. also reported using a variety of different drugs and participating in multiple treatment programs. The major agents supplying illicit drugs were known dealers, and friends or acquaintances of U.S. and Taiwanese drug-using offenders, respectively. The article concludes that to effectively eliminate the problem of drug misuse, the Taiwanese government should focus on treatment instead of imprisonment, while the U.S. should target troubled teens and families.
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Crimen/psicología , Comparación Transcultural , Trastornos Relacionados con Sustancias/epidemiología , Adulto , Demografía , Femenino , Humanos , Drogas Ilícitas , Masculino , Vigilancia de la Población , Prisioneros/psicología , Centros de Tratamiento de Abuso de Sustancias , Trastornos Relacionados con Sustancias/etiología , Trastornos Relacionados con Sustancias/terapia , Taiwán/epidemiología , Estados Unidos/epidemiologíaRESUMEN
1. This study investigated the effect of magnolol, a compound purified from Magnolia officinalis, on glucocorticoid production by primary adrenal cell culture. 2. Magnolol increased corticosterone secretion in a dose-dependent manner, this effect being maximal at 40 microM. A similar effect was seen in a minced adrenal gland system. 3. In magnolol-treated cells, the number and total area of cytoplasmic lipid droplets were reduced, suggesting a high utilization rate of cholesterol esters stored in lipid droplets. In control cells, the capsule of the lipid droplet was clearly delineated by immunostaining with antibody A2, whereas capsular staining was discontinuous or undetectable following magnolol treatment. The percentage of decapsulated cells increased significantly from 20% in the control group to 80% in the magnolol-treated group. 4. Magnolol-induced steroidogenesis was not mediated either via the traditional ACTH-cyclic AMP-protein kinase A pathway or by protein kinase C, since the intracellular cyclic AMP level did not change and inhibition of protein kinase A or C did not block the action of magnolol. Furthermore, calcium/calmodulin-dependent protein kinase II was not involved in magnolol-induced steroidogenesis. 5. The stimulatory effect of magnolol on steroidogenesis apparently requires new protein synthesis, since cycloheximide inhibited magnolol-induced corticosterone production by 50%. 6. Although other studies have shown that high concentrations of magnolol inhibit acyl-CoA: cholesterol acyltransferase and 11 beta-hydroxysteroid dehydrogenase in a cell-free system, our data show that, in adrenal cell cultures, low concentrations of magnolol have a stimulatory effect on steroidogenesis, and the glucocorticoid produced may explain the effective control of asthma by Magnolia officinalis.