Reduction of Urogenital Schistosomiasis with an Integrated Control Project in Sudan

Purpose

Schistosomiasis remains a major public health concern in Sudan, particularly Schistosoma haematobium infection. This study presents the disease-reduction outcomes of an integrated control program for schistosomiasis in Al Jabalain locality of White Nile State, Sudan from 2009 through 2011.

Methods

The total population of the project sites was 482,902, and the major target group for intervention among them was 78,615 primary school students. For the cross-sectional study of the prevalence, urine and stool specimens were examined using the urine sedimentation method and the Kato cellophane thick smear method, respectively. To assess the impacts of health education for students and a drinking water supply facility at Al Hidaib village, questionnaire survey was done.

Results

The overall prevalence for S. haematobium and S. mansoni at baseline was 28.5% and 0.4%, respectively. At follow-up survey after 6–9 months post-treatment, the prevalence of S. haematobium infection was reduced to 13.5% (95% CI = 0.331–0.462). A higher reduction in prevalence was observed among girls, those with moderately infected status (around 20%), and residents in rural areas, than among boys, those with high prevalence (>40%), and residents in urban areas. After health education, increased awareness about schistosomiasis was checked by questionnaire survey. Also, a drinking water facility was constructed at Al Hidaib village, where infection rate was reduced more compared to that in a neighboring village within the same unit. However, we found no significant change in the prevalence of S. mansoni infection between baseline and follow-up survey (95% CI = 0.933–6.891).

Conclusions

At the end of the project, the prevalence of S. haematobium infection was reduced by more than 50% in comparison with the baseline rate. Approximately 200,000 subjects had received either praziquantel therapy, health education, or supply of clean water. To consolidate the achievements of this project, the integrated intervention should be adapted continuously.     

The Drosophila Insulin Receptor Independently Modulates Lifespan and Locomotor Senescence

The Insulin/IGF-like signalling (IIS) pathway plays an evolutionarily conserved role in ageing. In model organisms reduced IIS extends lifespan and ameliorates some forms of functional senescence. However, little is known about IIS in nervous system ageing and behavioural senescence. To investigate this role in Drosophila melanogaster, we measured the effect of reduced IIS on senescence of two locomotor behaviours, negative geotaxis and exploratory walking. Two long-lived fly models with systemic IIS reductions (daGAL4/UAS-InR^DN (ubiquitous expression of a dominant negative insulin receptor) and d2GAL/UAS-rpr (ablation of insulin-like peptide producing cells)) showed an amelioration of negative geotaxis senescence similar to that previously reported for the long-lived IIS mutant chico. In contrast, exploratory walking in daGAL4/UAS-InR^DN and d2GAL/UAS-rpr flies declined with age similarly to controls. To determine the contribution of IIS in the nervous system to these altered senescence patterns and lifespan, the InR^DN was targeted to neurons (elavGAL4/UAS-InR^DN), which resulted in extension of lifespan in females, normal negative geotaxis senescence in males and females, and detrimental effects on age-specific exploratory walking behaviour in males and females. These data indicate that the Drosophila insulin receptor independently modulates lifespan and age-specific function of different types of locomotor behaviour. The data suggest that ameliorated negative geotaxis senescence of long-lived flies with systemic IIS reductions is due to ageing related effects of reduced IIS outside the nervous system. The lifespan extension and coincident detrimental or neutral effects on locomotor function with a neuron specific reduction (elavGAL4/UAS-InR^DN) indicates that reduced IIS is not beneficial to the neural circuitry underlying the behaviours despite increasing lifespan.     

Comparative analysis of sequence characteristics of imprinted genes in human, mouse, and cattle

Genomic imprinting is an epigenetic mechanism that results in monoallelic expression of genes depending on parent-of-origin of the allele. Although the conservation of genomic imprinting among mammalian species has been widely reported for many genes, there is accumulating evidence that some genes escape this conservation. Most known imprinted genes have been identified in the mouse and human, with few imprinted genes reported in cattle. Comparative analysis of genomic imprinting across mammalian species would provide a powerful tool for elucidating the mechanisms regulating the unique expression of imprinted genes. In this study we analyzed the imprinting of 22 genes in human, mouse, and cattle and found that in only 11 was imprinting conserved across the three species. In addition, we analyzed the occurrence of the sequence elements CpG islands, C + G content, tandem repeats, and retrotransposable elements in imprinted and in nonimprinted (control) cattle genes. We found that imprinted genes have a higher G + C content and more CpG islands and tandem repeats. Short interspersed nuclear elements (SINEs) were notably fewer in number in imprinted cattle genes compared to control genes, which is in agreement with previous reports for human and mouse imprinted regions. Long interspersed nuclear elements (LINEs) and long terminal repeats (LTRs) were found to be significantly underrepresented in imprinted genes compared to control genes, contrary to reports on human and mouse. Of considerable significance was the finding of highly conserved tandem repeats in nine of the genes imprinted in all three species. Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.     

Excess boron reduces polyphenol oxidase activities in embryo and endosperm of maize seed during germination

The effects of increasing concentrations of boron (0, 0.1, 1, 10 and 20 mM) as boric acid on the rate of germination and polyphenol oxidase activities in embryo and endosperm tissues of maize seeds (Zea mays L. cv. Arifiye) were studied. The germination percentage of maize seeds was not affected by boron concentrations up to 10 mM, and decreased by 20 mM. Distilled water and lower boron concentrations (0.1 and 1 mM) increased polyphenol oxidase activities at the beginning of germination up to 12 h whereas its excess levels (10 and 20 mM) decreased polyphenol oxidase activities in embryos and endosperm during germination. Polyphenol oxidase activities with o-diphenolic substrates (caffeic acid, catechol and dopa) were found to be higher than with a monophenolic substrat (tyrosine) in both embryos and endosperms. Further, caffeic acid oxidizing polyphenol oxidase was found to show more activity in embryos of the seeds germinating in distilled water when compared to other substrates.     

Influence of a niosomal formulation on the oral bioavailability of acyclovir in rabbits

The purpose of this research was to prepare acyclovir niosomes in a trial to improve its poor and variable oral bioavailability. The nonionic surfactant vesicles were prepared by the conventional thin film hydration method. The lipid mixture consisted of cholesterol, span 60, and dicetyl phosphate in the molar ratio of 65:60:5, respectively. The percentage entrapment was approximately 11% of acyclovir used in the hydration process. The vesicles have an average size of 0.95 microm, a most probable size of 0.8 microm, and a size range of 0.4 to 2.2 microm. Most of the niosomes have unilamellar spherical shape. In vitro drug release profile was found to follow Higuchi's equation for free and niosomal drug. The niosomal formulation exhibited significantly retarded release compared with free drug. The in vivo study revealed that the niosomal dispersion significantly improved the oral bioavailability of acyclovir in rabbits after a single oral dose of 40 mg kg(-1). The average relative bioavailability of the drug from the niosomal dispersion in relation to the free solution was 2.55 indicating more than 2-fold increase in drug bioavailability. The niosomal dispersion showed significant increase in the mean residence time (MRT) of acyclovir reflecting sustained release characteristics. In conclusion, the niosomal formulation could be a promising delivery system for acyclovir with improved oral bioavailability and prolonged drug release profiles.     

SNP analyses of growth factor genes EGF, TGFbeta-1, and HGF reveal haplotypic association of EGF with autism

Autism is a pervasive neurodevelopmental disorder diagnosed in early childhood. Growth factors have been found to play a key role in the cellular differentiation and proliferation of the central and peripheral nervous systems. Epidermal growth factor (EGF) is detected in several regions of the developing and adult brain, where, it enhances the differentiation, maturation, and survival of a variety of neurons. Transforming growth factor-beta (TGFbeta) isoforms play an important role in neuronal survival, and the hepatocyte growth factor (HGF) has been shown to exhibit neurotrophic activity. We examined the association of EGF, TGFbeta1, and HGF genes with autism, in a trio association study, using DNA samples from families recruited to the Autism Genetic Resource Exchange; 252 trios with a male offspring scored for autism were selected for the study. Transmission disequilibrium test revealed significant haplotypic association of EGF with autism. No significant SNP or haplotypic associations were observed for TGFbeta1 or HGF. Given the role of EGF in brain and neuronal development, we suggest a possible role of EGF in the pathogenesis of autism.     

The relationship between psychosocial circumstances and injuries in adolescents: An analysis of 87,269 individuals from 26 countries using the Global School-based Student Health Survey

BackgroundOver a million adolescents die globally each year from preventable or treatable causes, with injuries (intentional and unintentional) being the leading cause of these deaths. To inform strategies to prevent these injuries, we aimed to assess psychosocial factors associated with serious injury occurrence, type, and mechanism in adolescents.Methods and findingsWe conducted a secondary analysis of cross-sectional survey data collected from the Global School-based Student Health Survey between 2009 and 2015. We used logistic regression to estimate associations between prevalence of serious injuries, injury type (effects of injury), and injury mechanism (cause of injury) and psychosocial factors (factors that relate to individuals socially, or their thoughts or behaviour, or the interrelation between these variables). Psychosocial factors were categorised, based on review of the literature, author knowledge, and discussion amongst authors. The categories were markers of risky behaviour (smoking, alcohol use, drug use, and physical activity), contextual factors (hunger, bullying, and loneliness), protective factors (number of friends and having a supportive family), and markers of poor mental health (planned or attempted suicide and being too worried to sleep). Models were adjusted for country factors (geographical area and income status, both using World Bank classification), demographic factors (age and sex), and factors to explain the survey design. A total of 87,269 adolescents living in 26 countries were included. The weighted majority were 14–15 years old (45.88%), male (50.70%), from a lower-middle-income country (81.93%), and from East Asia and the Pacific (66.83%). The weighted prevalence of a serious injury in the last 12 months was 36.33%, with the rate being higher in low-income countries compared to other countries (48.74% versus 36.14%) and amongst males compared to females (42.62% versus 29.87%). Psychosocial factors most strongly associated with serious injury were being bullied (odds ratio [OR] 2.45, 95% CI 1.93 to 3.13, p < 0.001), drug use (OR 2.08, 95% CI 1.73 to 2.49, p < 0.001), attempting suicide (OR 1.78, CI 1.55 to 2.04, p < 0.001), being too worried to sleep (OR 1.80, 95% CI 1.54 to 2.10, p < 0.001), feeling lonely (OR 1.61, 95% CI 1.37 to 1.89, p < 0.001), and going hungry (OR 1.61, 95% CI 1.30 to 2.01, p < 0.001). Factors hypothesised to be protective were not associated with reduced odds of serious injury: Number of close friends was associated with an increased odds of injury (OR 1.23, 95% CI 1.06 to 1.43, p = 0.007), as was having understanding parents or guardians (OR 1.13, 95% CI 1.01 to 1.26, p = 0.036). Being bullied, using drugs, and attempting suicide were associated with most types of injury, and being bullied or too worried to sleep were associated with most mechanisms of injury; other psychosocial factors were variably associated with injury type and mechanism. Limitations include the cross-sectional study design, making it not possible to determine the directionality of the associations found, and the survey not capturing children who did not go to school.ConclusionsWe observed strong associations between serious injury and psychosocial factors, but we note the relationships are likely to be complex and our findings do not inform causality. Nevertheless, our findings suggest that multifactorial programmes to target psychosocial factors might reduce the number of serious injuries in adolescents, in particular programmes concentrating on reducing bullying and drug use and improving mental health.

In an analysis of data from the Global Schools-Based Student Health Survey, Samiha Ismail, Maria Odland, and colleagues investigate the relationships between serious injuries and psychosocial factors among adolescents across 26 countries.     

Restarted replication forks are error-prone and cause CAG repeat expansions and contractions

Disease-associated trinucleotide repeats form secondary DNA structures that interfere with replication and repair. Replication has been implicated as a mechanism that can cause repeat expansions and contractions. However, because structure-forming repeats are also replication barriers, it has been unclear whether the instability occurs due to slippage during normal replication progression through the repeat, slippage or misalignment at a replication stall caused by the repeat, or during subsequent replication of the repeat by a restarted fork that has altered properties. In this study, we have specifically addressed the fidelity of a restarted fork as it replicates through a CAG/CTG repeat tract and its effect on repeat instability. To do this, we used a well-characterized site-specific replication fork barrier (RFB) system in fission yeast that creates an inducible and highly efficient stall that is known to restart by recombination-dependent replication (RDR), in combination with long CAG repeat tracts inserted at various distances and orientations with respect to the RFB. We find that replication by the restarted fork exhibits low fidelity through repeat sequences placed 2–7 kb from the RFB, exhibiting elevated levels of Rad52- and Rad8^{ScRad5/HsHLTF}-dependent instability. CAG expansions and contractions are not elevated to the same degree when the tract is just in front or behind the barrier, suggesting that the long-traveling Polδ-Polδ restarted fork, rather than fork reversal or initial D-loop synthesis through the repeat during stalling and restart, is the greatest source of repeat instability. The switch in replication direction that occurs due to replication from a converging fork while the stalled fork is held at the barrier is also a significant contributor to the repeat instability profile. Our results shed light on a long-standing question of how fork stalling and RDR contribute to expansions and contractions of structure-forming trinucleotide repeats, and reveal that tolerance to replication stress by fork restart comes at the cost of increased instability of repetitive sequences.     

Schistosome resistance to praziquantel: Fact or artifact?

Praziquantel is the current drug of choice for human schistosomiasis. Recent reports from laboratory and field studies concerning reduced praziquantel efficacy against Schistosoma mansoni have generated some controversy. The prevailing question is whether the emergence of strains of schistosome resistant to praziquantel is a fact, or an artifact resulting from erroneous field or laboratory experimentation. In this article, Padraic Fallon, Liang-feng Tao, Magdi Ismail and James Bennett examine the available evidence for schistosome resistance to praziquantel. Contributory factors to the schistosomicidal activity of praziquantel, which may interfere with evaluation of drug efficacy or resistance, are also considered.