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This study described for the first time, the synthesis of a greener, safer, and more effective termiticide using a bio-based surfactant, N-acyl glycine derived from palm oil for the control of Microcerotermes diversus. Laboratory findings showed that the highest repellent activity was observed in N-acyl glycine surfactant (83.33%) at 50 ppm. In addition, N-acyl glycine surfactant also exhibited substantial time and concentration-dependent anti-termiticidal activity in which the highest termite mortality was observed after 3 days of exposure at 50 ppm of the surfactant (100%). Furthermore, 32.49 ppm concentration of N-acyl glycine surfactant (LC50 = 32.49 ppm) attained 50% of termite lethality. The current innovated termiticide with the use of N-acyl glycine surfactant offers a better efficacy, lower cost, and prevents the use of dangerous termiticides that are critical in creating a more sustainable environment, and controls Microcerotermes diversus at the same time.
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Isópteros , Animales , Excipientes , Glicina/farmacología , Aceite de Palma , Tensoactivos/farmacologíaRESUMEN
With the development and progress in the concepts and techniques of perioperative management, especially the latest reports of clinical trials, the prospect of prevention and treatment of postoperative ileus (POI) is promising. Proper nutritional support therapy, optimized surgical and anesthetic treatment, individualized fluid management, timely psychosocial intervention, and active anti-inflammation and traditional Chinese medicine treatment can effectively reduce occurrence of POI. Nevertheless, how to optimize and combine perioperative treatments to comprehensively prevent and treat POI still needs further study.
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Ileus/prevención & control , Atención Perioperativa/métodos , Procedimientos Quirúrgicos Operativos/efectos adversos , Humanos , Ileus/etiología , Ileus/terapia , Procedimientos Quirúrgicos Operativos/métodosRESUMEN
AIM: Peritoneal metastases from colorectal cancer confer the worst survival among all metastatic sites. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer selected patients with isolated colorectal peritoneal metastases (CRPM) a favourable long-term survival. There are numerous factors postulated to influence survival in patients undergoing CRS and HIPEC. The aim of this study was to identify the key perioperative prognostic factors that influence survival in patients undergoing CRS and HIPEC for isolated CRPM. METHOD: A systematic review and meta-analysis were conducted to evaluate prognostic factors influencing survival in patients undergoing CRS and HIPEC for isolated CRPM. RESULTS: Thirty-three studies fitted the inclusion criteria for the systematic review, with 25 studies included in the meta-analysis. On pooled analysis, incomplete cytoreduction, increasing peritoneal carcinoma index (PCI) and lymph node involvement were significantly associated with a worse survival. Additionally, a rectal primary [hazard ratio (HR) 1.93, 95% CI 1.10-3.37], adjuvant chemotherapy (HR 0.71, 95% CI 0.54-0.93) and perioperative grade III/IV morbidity (HR 1.59, 95% CI 1.17-2.16) were also found to significantly influence survival. Notably, tumour differentiation and signet ring cell histology did not influence survival on pooled analysis. CONCLUSION: This meta-analysis confirms that in patients undergoing CRS and HIPEC for isolated CRPM, incomplete cytoreduction, high PCI and lymph node involvement have a negative influence on survival. In addition, a rectal primary, adjuvant chemotherapy use and grade III/IV morbidity are important factors that also significantly influence survival.
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Neoplasias Colorrectales , Hipertermia Inducida , Neoplasias Peritoneales , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorrectales/tratamiento farmacológico , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales/tratamiento farmacológico , Pronóstico , Tasa de SupervivenciaRESUMEN
Cognitive disability is a common feature associated with a variety of neurological conditions including Alzheimer's Disease (AD), Parkinson's Disease (PD), brain injury, and stroke. Emerging evidence has demonstrated that neuroinflammation plays an important role in the development of cognitive impairment. Current available therapies are relatively ineffective in treating or preventing cognitive disabilities, thus representing an important, unfulfilled medical need. Hence, developing potential treatment is one of the major areas of research interest. Edible bird's nests (EBN) are nests formed by swiftlet's saliva containing sialic acid, which is believed to improve brain function. This present study was embarked upon to evaluate the learning and memory enhancing potential effect of EBN by using Morris water maze test in a Wistar rat model of LPS-induced neuroinflammation. LPS elicited cognitive impairment in the rats by significantly increasing the escape latency while decreasing the number of entries in the probe trial, which are coupled with increased production of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and oxidative markers (ROS and TBARS) in the hippocampus. Treatment with EBN (125 mg/kg, 250 mg/kg, and 500 mg/kg; p.o.) effectively reversed the effect of LPS on escape latency and probe trial and, in addition, inhibited the LPS-induced upregulation of proinflammatory cytokines and oxidative markers. These findings are suggestive that there is existence of neuroprotective effect contained inside the edible bird's nest.
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The purpose of this study was to investigate the functional connectivity (FC) of thalamic subdivisions in patients with juvenile myoclonic epilepsy (JME). Resting state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were acquired from 22 JME and 25 healthy controls. We first divided the thalamus into eight subdivisions by performing independent component analysis on tracking fibers and clustering thalamus-related FC maps. We then analyzed abnormal FC in each subdivision in JME compared with healthy controls, and we investigated their associations with clinical features. Eight thalamic sub-regions identified in the current study showed unbalanced thalamic FC in JME: decreased FC with the superior frontal gyrus and enhanced FC with the supplementary motor area in the posterior thalamus increased thalamic FC with the salience network (SN) and reduced FC with the default mode network (DMN). Abnormalities in thalamo-prefrontocortical networks might be related to the propagation of generalized spikes with frontocentral predominance in JME, and the network connectivity differences with the SN and DMN might be implicated in emotional and cognitive defects in JME. JME was also associated with enhanced FC among thalamic sub-regions and with the basal ganglia and cerebellum, suggesting the regulatory role of subcortical nuclei and the cerebellum on the thalamo-cortical circuit. Additionally, increased FC with the pallidum was positive related with the duration of disease. The present study provides emerging evidence of FC to understand that specific thalamic subdivisions contribute to the abnormalities of thalamic-cortical networks in JME. Moreover, the posterior thalamus could play a crucial role in generalized epileptic activity in JME.
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Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatología , Epilepsia Mioclónica Juvenil/diagnóstico por imagen , Epilepsia Mioclónica Juvenil/fisiopatología , Tálamo/diagnóstico por imagen , Tálamo/fisiopatología , Adolescente , Adulto , Mapeo Encefálico , Imagen de Difusión Tensora , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Descanso , Adulto JovenRESUMEN
Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.
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Salud Global , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/mortalidad , Modelos Estadísticos , Viremia/epidemiología , Viremia/mortalidad , Antivirales/uso terapéutico , Política de Salud , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Incidencia , Prevalencia , Viremia/tratamiento farmacológicoRESUMEN
PurposeTo investigate the frequencies, trends, and in vitro drug susceptibilities of the causative pathogens in microbial keratitis in Manchester Royal Eye Hospital.Patients and methodsCorneal scrape results recorded by the microbiology service between 2004 and 2015 were extracted from an established database. A total of 4229 corneal scrape specimens were identified from an established database. First-line antibiotic treatment in our centre during the study period was ofloxacin and second line was cefuroxime and gentamicin.ResultsMean age was 45.9±21.0. A total of 1379 samples (32.6%) were culture positive. One hundred forty-eight (10.7%) specimens cultured multiple organisms. Of the 1539 organisms identified, 63.3% were Gram-positive bacteria, 27.3% Gram-negative bacteria, 7.1% fungi, and 2.3% Acanthamoebae. A decreasing trend in Gram-positive isolates was found together with a stable trend in Gram negatives and an increasing trend in Acanthamoeba and fungi. There appeared to be a significant increasing trend of Moraxella infection (P=0.001). In all, 83.1 and 90.8% of Gram-positive and -negative isolates tested were susceptible to ofloxacin, respectively. Cefuroxime covered 86.6% of Gram-positive and 61.4% of Gram-negative isolates, whereas gentamicin covered 88.8 and 96.5% of Gram-positive and -negative isolates, respectively.ConclusionWe found a change in the type of Gram-negative organisms isolated over time, with the Moraxella species on the rise. Reassuringly, no significant increase in resistance was observed in vitro for any of the commonly used antibiotics. Ofloxacin remains a good first-line antibiotic treatment but duo-therapy does have broader coverage and should be considered in non-responsive cases.
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Antibacterianos/uso terapéutico , Infecciones Bacterianas del Ojo/microbiología , Queratitis/microbiología , Acanthamoeba/aislamiento & purificación , Adulto , Anciano , Antibacterianos/farmacología , Úlcera de la Córnea/microbiología , Farmacorresistencia Bacteriana/efectos de los fármacos , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Femenino , Hongos/aislamiento & purificación , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/aislamiento & purificación , Humanos , Queratitis/tratamiento farmacológico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Retrospectivos , Centros de Atención Terciaria/estadística & datos numéricos , Reino UnidoRESUMEN
BACKGROUND/OBJECTIVES: Iron and phosphate are both vital to many biological cellular processes with central roles in energy metabolism, cellular proliferation and nucleic acid synthesis. Regulatory pathways in some of these metabolic pathways may intersect at fibroblast growth factor 23 (FGF23), a major phosphate regulatory hormone. Iron is reported to induce hypophosphataemia in rare cases, and recent reports suggest that iron deficiency may upregulate FGF23 synthesis by mechanisms involving hypoxia-inducible factor 1α (HIF1α). Our objective was to evaluate the effect of administration of intravenous iron polymaltose on intact and c-terminal FGF23 (i:cFGF23) ratios in two independent cohorts of patients, iron-deficient but non-inflamed patients and haemodialysis (HD)-dependent patients, and to examine the balance of synthesis and degradation. SUBJECTS/METHODS: We studied biochemical effects of intravenous iron polymaltose on both iFGF23 and cFGF23 fragments and their ratios in two patient groups: iron-deficient patients with normal renal function (ID-norm) and HD patients receiving iron supplementation (HD-ESKD) at a single institution. Patients were tested at baseline, day 4 and day 12 post iron administration. RESULTS: Parenteral iron polymaltose resulted in increased i:cFGF23 ratios in ID-norm patients where circulating cFGF23 levels decreased with no appreciable effect on iFGF23, whereas no significant changes in i:cFGF23 ratios were observed in HD-ESKD patients following intravenous administration of 100mg iron polymaltose. CONCLUSIONS: Dysregulation of intracellular FGF23-processing mechanisms may be related to iron deficiency per se rather than iron repletion with iron polymaltose. In ID-norm, i:cFGF23 ratios altered with iron administration without significant clinical alterations in mineral parameters, implying that other regulatory mechanisms may be important. Finally, iron supplementation in HD-ESKD patients does not appear to significantly affect i:cFGF23 ratios already disturbed by a chronic inflammatory or functionally iron-deficient state.
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Anemia Ferropénica/terapia , Compuestos Férricos/farmacología , Factores de Crecimiento de Fibroblastos/efectos de los fármacos , Hematínicos/farmacología , Insuficiencia Renal Crónica/terapia , Administración Intravenosa , Anciano , Anemia Ferropénica/metabolismo , Suplementos Dietéticos , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/metabolismo , Humanos , Hierro/administración & dosificación , Masculino , Persona de Mediana Edad , Nutrición Parenteral/métodos , Diálisis Renal/métodos , Insuficiencia Renal Crónica/metabolismo , Resultado del TratamientoRESUMEN
Colorectal cancer (CRC), the second leading cause of cancer-related deaths in the US, has been treated with targeted therapies. However, the mechanisms of differential responses and resistance of CRCs to targeted therapies are not well understood. In this study, we found that genetic alterations of FBW7, an E3 ubiquitin ligase and a tumor suppressor frequently mutated in CRCs, contribute to resistance to targeted therapies. CRC cells containing FBW7-inactivating mutations are insensitive to clinically used multi-kinase inhibitors of RAS/RAF/MEK/ERK signaling, including regorafenib and sorafenib. In contrast, sensitivity to these agents is not affected by oncogenic mutations in KRAS, BRAF, PIK3CA or p53. These cells are defective in apoptosis owing to blocked degradation of Mcl-1, a pro-survival Bcl-2 family protein. Deleting FBW7 in FBW7-wild-type CRC cells abolishes Mcl-1 degradation and recapitulates the in vitro and in vivo drug-resistance phenotypes of FBW7-mutant cells. CRC cells selected for regorafenib resistance have progressive enrichment of pre-existing FBW7 hotspot mutations, and are cross-resistant to other targeted drugs that induce Mcl-1 degradation. Furthermore, a selective Mcl-1 inhibitor restores regorafenib sensitivity in CRC cells with intrinsic or acquired resistance. Together, our results demonstrate FBW7 mutational status as a key genetic determinant of CRC response to targeted therapies, and Mcl-1 as an attractive therapeutic target.
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Proteínas de Ciclo Celular/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Proteínas F-Box/genética , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Niacinamida/análogos & derivados , Compuestos de Fenilurea/farmacología , Piridinas/farmacología , Ubiquitina-Proteína Ligasas/genética , Animales , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos , Proteínas F-Box/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD , Femenino , Técnicas de Inactivación de Genes , Células HCT116 , Xenoinjertos , Humanos , Ratones , Ratones Desnudos , Terapia Molecular Dirigida , Mutación Missense , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , Niacinamida/farmacología , Sorafenib , Transfección , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Garcinia mangostana is a well-known tropical plant found mostly in South East Asia. The present study investigated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of G. mangostana extract and its chemical constituents using Ellman's colorimetric method. Cholinesterase inhibitory-guided approach led to identification of six bioactive prenylated xanthones showing moderate to potent cholinesterases inhibition with IC50 values of lower than 20.5 µM. The most potent inhibitor of AChE was garcinone C while γ-mangostin was the most potent inhibitor of BChE with IC50 values of 1.24 and 1.78 µM, respectively. Among the xanthones, mangostanol, 3-isomangostin, garcinone C and α-mangostin are AChE selective inhibitors, 8-deoxygartanin is a BChE selective inhibitor while γ-mangostin is a dual inhibitor. Preliminary structure-activity relationship suggests the importance of the C-8 prenyl and C-7 hydroxy groups for good AChE and BChE inhibitory activities. The enzyme kinetic studies indicate that both α-mangostin and garcinone C are mixed-mode inhibitors, while γ-mangostin is a non-competitive inhibitor of AChE. In contrast, both γ-mangostin and garcinone C are uncompetitive inhibitors, while α-mangostin is a mixed-mode inhibitor of BChE. Molecular docking studies revealed that α-mangostin, γ-mangostin and garcinone C interacts differently with the five important regions of AChE and BChE. The nature of protein-ligand interactions is mainly hydrophobic and hydrogen bonding. These bioactive prenylated xanthones are worthy for further investigations.
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Inhibidores de la Colinesterasa/farmacología , Garcinia mangostana/química , Xantonas/farmacología , Simulación del Acoplamiento Molecular , Estructura Molecular , Prenilación , Relación Estructura-ActividadRESUMEN
BACKGROUND/OBJECTIVES: Snacks contribute toward a significant proportion of human total daily energy intake. This study investigated the effects of almonds, a satiating and nutrient-rich, common snack, on postprandial glycemia, appetite, short-term body weight and fasting blood parameters when consumed with meals or alone as a snack. METHODS: This was a 4-week randomized, parallel-arm study that entailed consuming almonds (43 g/day) with breakfast (BF) or lunch (LN), alone as a morning (MS) or afternoon (AS) snack or no almonds (CL). Participants (N=137) with increased risk for type 2 diabetes completed an oral glucose tolerance test (OGTT) and acute-feeding session at baseline, followed by almond consumption for 4 weeks before repeating the OGTT and acute-feeding trials. Anthropometric, biochemical and appetite responses were assessed. RESULTS: Almonds lowered serum glucose responses postprandially. Effects were most prominent in the snack groups. Almonds, consumed as snacks, also reduced hunger and desire to eat during the acute-feeding session. After 4 weeks, anthropometric measurements and fasting blood biochemistries did not differ from the control group or across intervention groups. Without specific guidance, daily energy intake was reduced to compensate for energy from the provided almonds. Dietary monounsaturated fat and α-tocopherol intakes were significantly increased in all almond groups. CONCLUSION: Almonds provide post-ingestive metabolic and appetitive benefits and did not increase the risk for weight gain. This suggests that almonds may be a healthful snack option.
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Apetito/efectos de los fármacos , Glucemia/metabolismo , Dieta , Nueces , Preparaciones de Plantas/farmacología , Prunus/química , Bocadillos , Adulto , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/sangre , Grasas de la Dieta/farmacología , Ingestión de Energía/efectos de los fármacos , Ácidos Grasos Monoinsaturados/administración & dosificación , Ácidos Grasos Monoinsaturados/sangre , Ácidos Grasos Monoinsaturados/farmacología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Comidas , Periodo Posprandial , Saciedad/efectos de los fármacos , Adulto Joven , alfa-Tocoferol/administración & dosificación , alfa-Tocoferol/farmacologíaRESUMEN
The emergence of multidrug-resistant bacterial strains has prompted the reintroduction of maggot therapy in the treatment of chronic, infected wounds. Many previous studies have demonstrated the potent antibacterial activity of larval excretions/secretions of the blowfly Lucilia sericata (Meigen) (Diptera:Calliphoridae) against bacteria. However, the antibacterial activity of its sibling species, Lucilia cuprina (Wiedemann) (Diptera:Calliphoridae) against a wide range of pathogenic bacteria has never been determined. The aim of this study was to develop a new procedure to produce whole body extract of larvae of L. cuprina via methanol extraction as well as to demonstrate the in vitro antibacterial activity of this extract against seven selected wound pathogens (Staphylococcus aureus, methicillin-resistant S. aureus, S. epidermidis, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli). The turbidimetric assay demonstrated that L. cuprina larval extract was significantly potent against all bacteria tested (P < 0.001). Additionally, colony-forming unit (CFU), agar well diffusion and minimum inhibitory concentration assays have confirmed the apparent potency of larval extract against P. aeruginosa. The reconstituted larval extract was highly robust and thermally stable. These observations substantiated the feasibility of the methanol extraction method in the production of larval extract.
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Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Extractos Celulares/farmacología , Dípteros/química , Metanol/química , Animales , Antibacterianos/química , Bacterias/clasificación , Extractos Celulares/química , Larva/químicaRESUMEN
BACKGROUND: The purpose of the present study was to determine whether intrahepatic injection of (131)I-lipiodol (Lipiodol) is effective against recurrence of surgically resected hepatocellular carcinoma (HCC). METHODS: From June 2001 through March 2007, this nationwide multi-center prospective randomized controlled trial enrolled 103 patients 4-6 weeks after curative resection of HCC with complete recovery (52: Lipiodol, 51: Control). Follow-up was every 3 months for 1 year, then every 6 months. Primary and secondary endpoints were recurrence-free survival (RFS) and overall survival (OS), respectively, both of which were evaluated by the Kaplan-Meier technique and summarized by the hazard ratio (HR). The design was based on information obtained from a similar trial that had been conducted in Hong Kong. RESULTS: The Lipiodol group showed a small, and nonsignificant, improvement over control in RFS (HR = 0.75; 95 % confidence interval [95 % CI] 0.46-1.23; p = 0.25) and OS (HR = 0.88; 95 % CI 0.51-1.51; p = 0.64). Only two serious adverse events were reported, both with hypothyroidism caused by (131)I-lipiodol and hepatic artery dissection during angiography. CONCLUSIONS: The randomized trial provides insufficient evidence to recommend the routine use of (131)I-lipiodol in these patients.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Aceite Etiodizado/uso terapéutico , Radioisótopos de Yodo/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Anciano , Quimioterapia Adyuvante , Femenino , Humanos , Inyecciones Intraarteriales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The first objective of this study was to provide data of arsenic (As) levels in Peninsular Malaysia based on soil samples and accumulation of As in Centella asiatica collected from 12 sampling sites in Peninsular Malaysia. The second objective was to assess the accumulation of As in transplanted C. asiatica between control and semi-polluted or polluted sites. Four sites were selected which were UPM (clean site), Balakong (semi-polluted site), Seri Kembangan (semi-polluted site) and Juru (polluted site). The As concentrations of plant and soil samples were determined by Instrumental Neutron Activation Analysis. The As levels ranged from 9.38 to 57.05 µg/g dw in soils, 0.21 to 4.33 µg/g dw in leaves, 0.18 to 1.83 µg/g dw in stems and 1.32-20.76 µg/g dw in roots. All sampling sites had As levels exceeding the CCME guideline (12 µg/g dw) except for Kelantan, P. Pauh, and Senawang with P. Klang having the highest As in soil (57.05 µg/g dw). In C. asiatica, As accumulation was highest in roots followed by leaves and stems. When the As level in soils were higher, the uptake of As in plants would also be increased. After the transplantation of plants to semi-polluted and polluted sites for 3 weeks, all concentration factors were greater than 50 % of the initial As level. The elimination factor was around 39 % when the plants were transplanted back to the clean sites for 3 weeks. The findings of the present study indicated that the leaves, stems and roots of C. asiatica are ideal biomonitors of As contamination. The present data results the most comprehensive data obtained on As levels in Malaysia.
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Arsénico/análisis , Centella/química , Contaminantes del Suelo/análisis , Suelo/análisis , Monitoreo del Ambiente , Contaminación Ambiental/estadística & datos numéricos , MalasiaRESUMEN
BACKGROUND: Pharmacogenetics-based algorithms would be especially desirable for patients undergoing heart valve replacement (HVR), who are particularly sensitive to warfarin during the initial treatment phase following surgery. We aimed to derive a warfarin dosing algorithm from data of Chinese patients undergoing HVR, and to compare it with previously published dosing algorithms as applied to our HVR patients. METHODS: 641 Chinese HVR patients on stable maintenance dose of warfarin were enrolled from a single clinic site. Data of 321 patients were used to derive a warfarin dosing algorithm using stepwise multiple linear regression analysis. Previously published algorithms were selected from Pubmed database for comparison. The performance of all the algorithms was characterized according to mean absolute error (MAE) and percentage of predicted doses falling within +/- 20% of clinically observed doses (percentage of ideal prediction) in the other 320 patients. RESULTS: The newly developed algorithm included eight factors: VKORC1-1639G > A, CYP2C9*3, BSA, age, number of increasing INR drugs, smoking habit, preoperative stroke history and hypertension. Our algorithm accounted for 56.4% of variations in the inter-patient warfarin stable doses. All the algorithms showed better performance in a medium-dose (1.88-4.38 mg/day) and high-dose (> or = 4.38 mg/day) groupings than in a low-dose (< or = 1.88 mg/day) grouping. Compared with the 14 previously published algorithms, our algorithm had the lowest MAE (-0.07 mg/day) and the highest percentage of ideal prediction (62.8%) in the total validation cohort. CONCLUSIONS: Our warfarin dosing algorithm is potentially useful for patients whose population profiles are similar to those of our patients.
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Anticoagulantes/administración & dosificación , Hidrocarburo de Aril Hidroxilasas/genética , Implantación de Prótesis de Válvulas Cardíacas/métodos , Warfarina/administración & dosificación , Adolescente , Adulto , Anciano , Algoritmos , Pueblo Asiatico , Citocromo P-450 CYP2C9 , ADN/biosíntesis , ADN/genética , Femenino , Genotipo , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Medicina de Precisión , Análisis de Regresión , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
The most important risk factor in the development of skin cancer is exposure to ultraviolet (UV) radiation. Cumulative lifetime UV radiation exposure has been shown to be most important in the pathogenesis of squamous cell carcinoma, whereas intermittent high-dose UV radiation exposure in childhood and adolescence may be more important in the aetiology of basal cell carcinoma and cutaneous malignant melanoma. Using established methodology and best available estimates on UV-related mortality and morbidity, it has been estimated that annually around 1·5 million disability-adjusted life years are lost through excessive exposure to UV radiation. Skin cancer is a significant health problem and its burden is such that it causes the health system more to treat than any other forms of cancer. Prevention is the key action in managing skin cancer at a population level. Investment in prevention programmes such as SunSmart encourages protective behaviours that will reduce the human and financial costs of skin cancer.
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Actividades Recreativas , Neoplasias Inducidas por Radiación/prevención & control , Neoplasias Cutáneas/prevención & control , Rayos Ultravioleta/efectos adversos , Dispositivos de Protección de los Ojos , Conductas Relacionadas con la Salud , Humanos , Ropa de Protección , Servicios de Salud Escolar , Deportes , Baño de Sol , Protectores Solares/uso terapéutico , Deficiencia de Vitamina D/prevención & controlRESUMEN
BACKGROUND: Lymphomatoid papulosis (LyP) is a low-grade cutaneous lymphoma, which lies within the spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. Around 10-20% of LyP cases are associated with a second lymphoma. AIM: To analyse a cohort of Asian patients with LyP, diagnosed from 1987 to 2007 at the National Skin Centre (NSC), Singapore, in terms of epidemiology, treatment and association with a second lymphoma. METHODS: Patients were identified through the NSC clinical and histological databases. RESULTS: During this period, 13 patients were diagnosed with LyP based on clinicopathological criteria. The mean age at diagnosis was 41 years, the male : female ratio was 2.3 : 1, and 92% of the patients were Chinese. Recurrent papulonecrotic lesions were present for a mean of 3 years before diagnosis. Treatment of LyP comprised monotherapy (n = 4) or combination therapy (n = 9) using corticosteroids, oral antibiotics, methotrexate and/or phototherapy. Mean duration of follow-up was 6.4 years. Eight patients (61.5%) were diagnosed with a second lymphoma, either before (n = 2), concurrently with (n = 1) or after (n = 5) the diagnosis of LyP. Mycosis fungoides (MF) was the commonest lymphoma (78%, n = 7), followed by primary cutaneous anaplastic large-cell lymphoma (12%, n = 2). There was one death (mortality rate 7.7%), which occurred in a patient who had developed stage IIA MF after LyP, which subsequently progressed to systemic T-cell lymphoma. CONCLUSIONS: LyP is a chronic, relapsing disease with considerable morbidity, but an overall good prognosis. A strikingly large proportion of our Asian patients (61.5%) had a second lymphoma, compared with previous studies. This emphasizes the importance of regular lifetime surveillance for associated lymphomas in all patients with LyP.
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Pueblo Asiatico , Papulosis Linfomatoide/epidemiología , Neoplasias Cutáneas/epidemiología , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Linfoma/epidemiología , Linfoma/etnología , Papulosis Linfomatoide/etnología , Papulosis Linfomatoide/patología , Masculino , Persona de Mediana Edad , Singapur/epidemiología , Neoplasias Cutáneas/etnología , Neoplasias Cutáneas/patología , Adulto JovenAsunto(s)
Parto Domiciliario , Partería , Misoprostol , Oxitócicos , Hemorragia Posparto/prevención & control , Femenino , Humanos , EmbarazoRESUMEN
High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is an established neurosurgical therapy for movement disability in advanced Parkinson's disease (PD), but some patients experience psychiatric side-effects like depression. In a previous electrophysiological study, we observed that HFS of the STN inhibited a population of neurones in the rat dorsal raphe nucleus (DRN), with firing properties characteristic of 5-HT neurones. The present study extended these findings to a second population of neurones, and combined extracellular recording with juxtacellular-labelling to investigate the chemical identity of the neurones affected by HFS. Bilateral HFS (130 Hz, 100-200 µA, 5 min) of the STN inhibited (26.0±2.9%) the firing of 37/74 DRN neurones displaying a slow, regular firing pattern. Slower firing neurones were more strongly inhibited than those firing faster. Importantly, 10 inhibited DRN neurones were juxtacellular-labelled with neurobiotin, and all neurones contained 5-HT as shown by post-mortem 5-HT immunocytochemistry. A minority of slow firing DRN neurones (18/74) were activated by STN HFS (37.9±8.3%) which was not observed previously. Of these neurones, three were juxtacellular-labelled and one was 5-HT immunopositive. Also a small number of DRN neurones (19/74) did not respond to HFS, four of which were juxtacellular-labelled and all contained 5-HT. These data show that individual chemically-identified 5-HT-containing neurones in the DRN were modulated by STN HFS, and that the majority were inhibited but some were activated and some failed to respond. These data extend previous findings of modulation of the 5-HT system by STN HFS but suggest a destabilisation of the 5-HT system rather than simple inhibition as indicated previously. Although the mechanism is not yet known, such changes may contribute to the psychiatric side-effects of STN stimulation in some PD patients.