Determinants of delayed childhood cancer care in low- and middle-income countries: A systematic review

Early access to care is essential to improve survival rates for childhood cancer. This study evaluates the determinants of delays in childhood cancer care in low- and middle-income countries (LMICs) through a systematic review of the literature. We proposed a novel Three-Delay framework specific to childhood cancer in LMICs by summarizing 43 determinants and 24 risk factors of delayed cancer care from 95 studies. Traditional medicine, household income, lack of transportation, rural population, parental education, and travel distance influenced most domains of our framework. Our novel framework can be used as a policy tool toward improving cancer care and outcomes for children in LMICs.     

Effect of probenecid on cerebrospinal fluid methotrexate kinetics.

The effect of probenecid (PBC) on methotrexate (MTX) kinetics in the cerebrospinal fluid (CSF) and serum was studied in 4 patients on high-dose MTX with leucovorin rescue to determine whether addition of PBC could prolong effective CSF MTX levels. Each patient received 2 courses of MTX, 1 with and 1 without PBC. PBC caused a 2.8 to 4.2-fold increase in CSF MTX concentrations but failed to prolong the CSF half-life (1 1/2). PBC prolonged the initial MTX elimination t 1/2 in the blood from 2.7 to 4.1 hr, but had little effect on subsequent t 1/2s. No effect of MTX on PBC clearance was detected. Our data suggest that in man PBC in concentrations that were high enough to inhibit the renal clearance of MTX failed to alter the clearance of MTX from the CSF when both drugs were administered systemically.     

Barriers to Surgical Care Among Children in Somaliland: An Application of the Three Delays Framework

World Journal of Surgery - There are complex barriers that increase delays to surgical care in low- and middle-income countries, particularly among the vulnerable population of children....     

The Role of the Neurokinin-1 Receptor in Stress-Induced Reinstatement of Alcohol and Cocaine Seeking

Neurokinin-1 receptors (NK1Rs) have been shown to mediate alcohol and opiate, but not cocaine reward in rodents. We recently reported that NK1R antagonism also blocks stress-induced reinstatement of alcohol seeking in rats, but it is presently unknown whether these antirelapse properties extend to other drug classes. Although some work has suggested that intracranial substance P (SP) infusion reinstates cocaine seeking following extinction, no studies have indicated a direct role for the NK1R in reinstatement of cocaine seeking. Here, we explored the effect of the NK1R antagonist L822429 on yohimbine-induced reinstatement of alcohol or cocaine seeking in Long–Evans rats. Consistent with our previous findings with footshock-induced reinstatement of alcohol seeking in Wistar rats, we found that L822429 attenuates yohimbine-induced reinstatement of alcohol seeking, but does not affect baseline alcohol self-administration. We observed a similar suppression of yohimbine-induced reinstatement of cocaine seeking by L822429, and found that Long–Evans rats exhibit greater sensitivity to NK1R antagonism than Wistar rats. Accordingly, Long–Evans rats exhibit differences in the expression of NK1Rs in some subcortical brain regions. Combined, our findings suggest that while NK1R antagonism differentially influences alcohol- and cocaine-related behavior, this receptor mediates stress-induced seeking of both drugs.     

Discovery and Development of LX7101, a Dual LIM-Kinase and ROCK Inhibitor for the Treatment of Glaucoma

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Identification of the gene (lgtG) encoding the lipooligosaccharide β chain synthesizing glucosyl transferase from Neisseria gonorrhoeae

The lipooligosaccharide from Neisseria gonorrhoeae (GC), consists of lipid A, an oligosaccharide core and three branches, α, β, and γ. We report the cloning of the gene (lgtG, lipooligosaccharide glycosyl transferase G) encoding the glucosyl transferase of GC that initiates the β chain which consists of a lactosyl moiety. This gene contains a homopolymeric tract of cytidine [poly(C)] and we demonstrate that changes in the number of Cs in poly(C) account for the variation of β chain expression in different GC strains. Biochemical analyses and mass spectrometry clearly attribute the reactivity of mAb 2C7 to the presence of the lactosyl β chain. In addition, we demonstrate that in the absence of the lactosyl group, a phosphoethanolamine is added to generate a new antigenic epitope as evidenced by the gain of reactivity to mAb 2-L1–8. These results show that, like the α chain, the β chain of lipooligosaccharide is subject to antigenic variation.     

Factor relationships of metabolic syndrome and echocardiographic phenotypes in the HyperGEN study

BACKGROUND: Metabolic syndrome and its risk factors are predictors of cardiovascular events. Metabolic syndrome is also directly associated with echocardiographic phenotypes. METHODS: The current study is the first to investigate the factors associated with both metabolic syndrome risk factors and echocardiographic phenotypes and assess their heritability. Multivariate factor analysis was performed on 15 traits in 1393 African-Americans and 1133 whites, as well as stratified by type 2 diabetes mellitus status. RESULTS: Factor analysis with varimax rotation established four to five latent factors across ethnicities and diabetes mellitus stratifications. Among metabolic syndrome risk factors, blood pressure was the most highly correlated with cardiac traits. The factor domains, in the order of the proportion of variance explained, were 'left ventricle wall thickness', 'left ventricle geometry', 'blood pressure', 'BMI-insulin', and 'lipid-insulin'. Factor analysis without any rotation identified special (cross domain) metabolic syndrome-echocardiographic factors, 'blood pressure-left ventricle geometry' and 'blood pressure-left ventricle dimension-wall thickness' in whites. Fifty to 57% of the total original risk factor variance was explained by the latent factors. Heritability was highest for BMI-insulin (37-53%), lowest for 'blood pressure' factors (15-27%), and intermediate for metabolic syndrome-echocardiographic factors. CONCLUSION: These latent factors identified can be utilized as summary phenotypes in epidemiological, linkage, and association studies.