A scoping review of burden of disease studies estimating disability-adjusted life years due to Taenia solium

BackgroundTaenia solium is the most significant global foodborne parasite and the leading cause of preventable human epilepsy in low and middle-income countries in the form of neurocysticercosis.ObjectivesThis scoping review aimed to examine the methodology of peer-reviewed studies that estimate the burden of T. solium using disability-adjusted life years.Eligibility criteriaStudies must have calculated disability-adjusted life years relating to T. solium.Charting methodsThe review process was managed by a single reviewer using Rayyan. Published data relating to disease models, data sources, disability-adjusted life years, sensitivity, uncertainty, missing data, and key limitations were collected.Results15 studies were included for review, with seven global and eight national or sub-national estimates. Studies primarily employed attributional disease models that relied on measuring the occurrence of epilepsy before applying an attributable fraction to estimate the occurrence of neurocysticercosis-associated epilepsy. This method relies heavily on the extrapolation of observational studies across populations and time periods; however, it is currently required due to the difficulties in diagnosing neurocysticercosis. Studies discussed that a lack of data was a key limitation and their results likely underestimate the true burden of T. solium. Methods to calculate disability-adjusted life years varied across studies with differences in approaches to time discounting, age weighting, years of life lost, and years of life lived with disability. Such differences limit the ability to compare estimates between studies.ConclusionsThis review illustrates the complexities associated with T. solium burden of disease studies and highlights the potential need for a burden of disease reporting framework. The burden of T. solium is likely underestimated due to the challenges in diagnosing neurocysticercosis and a lack of available data. Advancement in diagnostics, further observational studies, and new approaches to parameterising disease models are required if estimates are to improve.     

Introns are essential for growth-regulated expression of the mouse thymidylate synthase gene.

The thymidylate synthase (TS) gene is expressed at much higher levels in proliferating cells than in quiescent cells. We have been studying the sequences that are important for regulating the mouse TS gene. We previously showed that DNA sequences upstream of the essential promoter elements as well as downstream of the ATG codon are both necessary (but neither is sufficient) for normal regulation in growth-stimulated cells. In the present study, we examined the possible roles of the coding region, polyadenylation signal, and introns as downstream regulatory elements. Minigenes consisting of 1 kb of the TS 5'-flanking region, the coding region (with or without various introns at their normal locations), and polyadenylation signals from the TS gene, the human beta-globin gene, and the bovine growth hormone gene were stably transfected into wild-type mouse 3T6 cells. Minigenes that contained introns 5 and 6, 1 and 2, or 1 alone were regulated regardless of which polyadenylation signal was included. A minigene that contained an internally deleted version of intron 1 was also regulated in response to growth stimulation. However, when all introns were omitted, there was little if any change in the level of minigene expression as cells progressed from G1 through S phase. These observations indicate that TS introns contain sequences that are necessary for normal growth-regulated expression of the mouse TS gene. These sequences appear to be associated with sequences that are important for splicing and to function in cooperation with upstream regulatory elements to bring about normal S-phase-specific expression.     

How season of grazing and herbivore selectivity influence monsoon tall-grass communities of northern Australia

Abstract. The hypothesis that season of defoliation and herbivore selectivity may be as important as level of use in determining plant community response to grazing was tested in a monsoon grassland in northern Australia. Plots, dominated by the tussock grasses Themeda triandra and Chrysopogon fallax, were grazed by cattle at low, medium and high rates of utilization in either the early wet, late wet or dry seasons. Effects of grazing on species composition were greatest in the early wet season when high rates of utilization significantly reduced the proportion and occurrence of Themeda and increased the proportion of forbs. Grazing in the dry season had no significant effect on composition. At medium and high levels of utilization in the early wet season, the pasture responded negatively to defoliation, only partially compensating for plant tissue lost to herbivory. The negative response to defoliation carried over to the next wet season when these same medium and high-grazing treatments produced only 80 % and 60 % growth, respectively, of that in treatments grazed at low levels of utilization or those grazed during the dry season. The frequency of Themeda was still lower, and that of annual grasses and non-leguminous forbs higher, in plots that had been grazed at a high rate of utilization for just eight weeks in the early wet season two years previously. Species richness and diversity were also significantly affected by this grazing disturbance. If species composition is to be maintained in these grasslands then stocking rates must be set at low levels to cope with the combined effect of undercompensation in response to defoliation in the wet season and strong dietary preferences for grazing sensitive species.     

Effect of microinjected amine and diamine oxidases on the ultrastructure of eukaryotic cultured cells

Diamine oxide and serum amine oxidase, which catalyse the oxidation of diamines and polyamines, respectively, were trapped within reconstituted Sendai virus envelopes. These loaded envelopes were incubated with cultured normal chick fibroblasts or with fibroblasts transformed by Rous sarcoma viruses. The binding of the reconstituted envelopes to the cultured cells was confirmed by scanning electron microscopy. It has been shown that the reconstituted envelopes (1-3 microns diameter) were attached to the eukaryotic cells. No significant changes in the morphology of the normal chick embryo fibroblasts were noted upon treatment with enzyme-loaded envelopes. On the other hand, chick embryo fibroblasts transformed by Rous sarcoma virus were affected by the microinjected amine oxidases. Scanning electron microscopy demonstrated the formation of holes in the microinjected cells. Similar morphological changes were also observed when diamine oxidase was microinjected into cultured glioma cells. These holes may be the result of the ejection of the nucleus. These findings are in line with the observed effect of the injected amine oxidases on macromolecular synthesis in normal and transformed chick embryo fibroblasts.     

From plant neighbourhood to landscape scales: how grazing modifies native and exotic plant species richness in grassland

The interactive effect of grazing and soil resources on plant species richness and coexistence has been predicted to vary across spatial scales. When resources are not limiting, grazing should reduce competitive effects and increase colonisation and richness at fine scales. However, at broad scales richness is predicted to decline due to loss of grazing intolerant species. We examined these hypotheses in grasslands of southern Australia that varied in resources and ungulate grazing intensity since farming commenced 170 years ago. Fine-scale species richness was slightly greater in more intensively grazed upper slope sites with high nutrients but low water supply compared to those that were moderately grazed, largely due to a greater abundance of exotic species. At broader scales, exotic species richness declined with increasing grazing intensity whether nutrients or water supply were low or high. Native species richness declined at all scales in response to increasing grazing intensity and greater resource supply. Grazing also reduced fine-scale heterogeneity in native species richness and although exotics were also characterised by greater heterogeneity at fine scales, grazing effects varied across scales. In these grasslands patterns of plant species richness did not match predictions at all scales and this is likely to be due to differing responses of native and exotic species and their relative abundance in the regional species pool. Over the past 170 years intolerant native species have been eliminated from areas that are continually and heavily grazed, whereas transient, light grazing increases richness of both exotics and natives. The results support the observation that the processes and scales at which they operate differ between coevolved ungulate—grassland systems and those in transition due to recent invasion of herbivores and associated plant species.     

Increased susceptibility to infection with Brugia pahangi in aged female jirds (Meriones unguiculatus)

Female Mongolian jirds, Meriones unguiculatus, from 5 age groups of 2, 12, 16, 21, and 28 months, were infected with Brugia pahangi. Infections were followed for 125 days by weekly bleedings beginning 55 days postinoculation. Jirds were then killed and adult parasites recovered. Results showed a significant shortening of the prepatent period in the 12-, 21-, and 28-month-old groups. The proportion of gravid female worms did not vary significantly among the 5 groups. Similarly, the ratio of females to male worms showed little variation from group to group. Microfilaremia data for the 5 infection groups show an age-associated increase in numbers of circulating microfilariae. Some individuals in the 28-month group demonstrated 1,500 to 3,000 microfilariae per 0.25 ml peripheral blood, a level that was not approached by young females.     

TNFR1 and the TNFα axis as a targetable mediator of liver injury from stereotactic body radiation therapy

IntroductionRadiation therapy for the management of intrahepatic malignancies can adversely affect liver function. Liver damage has been associated with increased levels of inflammatory cytokines, including tumor necrosis factor alpha (TNFα). We hypothesized that an inflammatory state, characterized by increased soluble TNFα receptor (sTNFR1), mediates sensitivity of the liver to radiation.Materials/MethodsPlasma samples collected during 3 trials of liver radiation for liver malignancies were assayed for sTNFR1 level via enzyme-linked immunosorbent assay (ELISA). Univariate and multivariate logistic regression and longitudinal models were used to characterize associations between liver toxicity (defined as a ≥2-point increase in Child-Pugh [CP] score within 6 months of radiation treatment) and sTNFR1 levels, ALBI score, biocorrected mean liver dose (MLD), age, and baseline laboratory values.ResultsSamples from 78 patients given liver stereotactic body radiation therapy [SBRT] (92%) or hypofractionated radiation were examined. There was a significant association between liver toxicity and sTNFR1 levels, and higher values were associated with increased toxicity over a range of mean liver doses. When ALBI score and biocorrected dose were included in the model with sTNFR1, baseline ALBI score and change in ALBI (ΔALBI) were significantly associated with toxicity, but sTNFR1 was not. Baseline aminotransferase levels also predicted toxicity but not independently of ALBI score.ConclusionsElevated plasma sTNFR1 levels are associated with liver injury after liver radiation, suggesting that elevated inflammatory cytokine activity is a predictor of radiation-induced liver dysfunction. Future studies should determine whether administration of agents that decrease inflammation prior to treatment is warranted.     

miR-192 Directly Binds and Regulates Dicer1 Expression in Neuroblastoma

Neuroblastoma (NB) arises from the embryonic neural crest and is the most common extracranial solid tumor in children under 5 years of age. Reduced expression of Dicer1 has recently been shown to be in correlation with poor prognosis in NB patients. This study aimed to investigate the mechanisms that could lead to the down-regulation of Dicer1 in neuroblastoma. We used computational prediction to identify potential miRs down-regulating Dicer1 in neuroblastoma. One of the miRs that were predicted to target Dicer1 was miR-192. We measured the levels of miR-192 in 43 primary tumors using real time PCR. Following the silencing of miR-192, the levels of dicer1 cell viability, cell proliferation and migration capability were analyzed. Multivariate analysis identified miR-192 as an independent prognostic marker for relapse in neuroblastoma patients (p=0.04). We were able to show through a dual luciferase assay and side-directed mutational analysis that miR-192 directly binds the 3'' UTR of Dicer1 on positions 1232-1238 and 2282-2288. An increase in cell viability, proliferation and migration rates were evident in NB cells transfected with miR-192-mimic. Yet, there was a significant decrease in proliferation when NB cells were transfected with an miR-192-inhibitor We suggest that miR-192 might be a key player in NB by regulating Dicer1 expression.