CAL1 is the Drosophila CENP-A assembly factor

Centromeres are specified epigenetically by the incorporation of the histone H3 variant CENP-A. In humans, amphibians, and fungi, CENP-A is deposited at centromeres by the HJURP/Scm3 family of assembly factors, but homologues of these chaperones are absent from a number of major eukaryotic lineages such as insects, fish, nematodes, and plants. In Drosophila, centromeric deposition of CENP-A requires the fly-specific protein CAL1. Here, we show that targeting CAL1 to noncentromeric DNA in Drosophila cells is sufficient to heritably recruit CENP-A, kinetochore proteins, and microtubule attachments. CAL1 selectively interacts with CENP-A and is sufficient to assemble CENP-A nucleosomes that display properties consistent with left-handed octamers. The CENP-A assembly activity of CAL1 resides within an N-terminal domain, whereas the C terminus mediates centromere recognition through an interaction with CENP-C. Collectively, this work identifies the “missing” CENP-A chaperone in flies, revealing fundamental conservation between insect and vertebrate centromere-specification mechanisms.     

Spatial Distribution of Podoconiosis in Relation to Environmental Factors in Ethiopia: A Historical Review

Background

An up-to-date and reliable map of podoconiosis is needed to design geographically targeted and cost-effective intervention in Ethiopia. Identifying the ecological correlates of the distribution of podoconiosis is the first step for distribution and risk maps. The objective of this study was to investigate the spatial distribution and ecological correlates of podoconiosis using historical and contemporary survey data.

Methods

Data on the observed prevalence of podoconiosis were abstracted from published and unpublished literature into a standardized database, according to strict inclusion and exclusion criteria. In total, 10 studies conducted between 1969 and 2012 were included, and data were available for 401,674 individuals older than 15 years of age from 229 locations. A range of high resolution environmental factors were investigated to determine their association with podoconiosis prevalence, using logistic regression.

Results

The prevalence of podoconiosis in Ethiopia was estimated at 3.4% (95% CI 3.3%–3.4%) with marked regional variation. We identified significant associations between mean annual Land Surface Temperature (LST), mean annual precipitation, topography of the land and fine soil texture and high prevalence of podoconiosis. The derived maps indicate both widespread occurrence of podoconiosis and a marked variability in prevalence of podoconiosis, with prevalence typically highest at altitudes >1500 m above sea level (masl), with >1500 mm annual rainfall and mean annual LST of 19–21°C. No (or very little) podoconiosis occurred at altitudes <1225 masl, with annual rainfall <900 mm, and mean annual LST of >24°C.

Conclusion

Podoconiosis remains a public health problem in Ethiopia over considerable areas of the country, but exhibits marked geographical variation associated in part with key environmental factors. This is work in progress and the results presented here will be refined in future work.     

Health Benefits of Reducing Sugar-Sweetened Beverage Intake in High Risk Populations of California: Results from the Cardiovascular Disease (CVD) Policy Model

Background

Consumption of sugar-sweetened beverage (SSB) has risen over the past two decades, with over 10 million Californians drinking one or more SSB per day. High SSB intake is associated with risk of type 2 diabetes, obesity, hypertension, and coronary heart disease (CHD). Reduction of SSB intake and the potential impact on health outcomes in California and among racial, ethnic, and low-income sub-groups has not been quantified.

Methods

We projected the impact of reduced SSB consumption on health outcomes among all Californians and California subpopulations from 2013 to 2022. We used the CVD Policy Model – CA, an established computer simulation of diabetes and heart disease adapted to California. We modeled a reduction in SSB intake by 10–20% as has been projected to result from proposed penny-per-ounce excise tax on SSB and modeled varying effects of this reduction on health parameters including body mass index, blood pressure, and diabetes risk. We projected avoided cases of diabetes and CHD, and associated health care cost savings in 2012 US dollars.

Results

Over the next decade, a 10–20% SSB consumption reduction is projected to result in a 1.8–3.4% decline in the new cases of diabetes and an additional drop of 0.5–1% in incident CHD cases and 0.5–0.9% in total myocardial infarctions. The greatest reductions are expected in African Americans, Mexican Americans, and those with limited income regardless of race and ethnicity. This reduction in SSB consumption is projected to yield $320–620 million in medical cost savings associated with diabetes cases averted and an additional savings of $14–27 million in diabetes-related CHD costs avoided.

Conclusions

A reduction of SSB consumption could yield substantial population health benefits and cost savings for California. In particular, racial, ethnic, and low-income subgroups of California could reap the greatest health benefits.     

Field evaluation of aqueous extract of Melia azedarach Linn. seeds against cabbage aphid,Brevicoryne brassicae Linn. (Homoptera: Aphididae), and its predator Coccinella septempunctata Linn. (Coleoptera: Coccinellidae)

Aqueous extract of Melia azedarach seeds were tested against cabbage aphid, Brevicoryne brassicae, and its predator Coccinella septempunctata in a cabbage field. The field experiment was conducted at Bridge to Israel children village farm, around the vicinity of Tewodros campus, University of Gondar, where the cabbage was grown fully organically. A field experiment was started in the middle of April 2011 and completed at the end of May 2011. The experiment was conducted in a randomised block design (RBD). For the field trial, a total of 12 plots were prepared with 1 m² area for data collection. The powdered M. azedarach seeds were used to prepare 5% concentration of aqueous solution and sprayed. Before spraying, percentage of aphid infestation was recorded from the control plot and the experimental plot. The average percentage of cabbage infestation in the control plot was 72% and in the experimental plot before treatment was 80.85%. The percentage reduction of aphid population was 19.06% after the first spraying. However, maximum percentage reduction of 86.5% was recorded after the completion of six-week treatment. The overall percentage reduction increased proportionately from the first to sixth week. The number of predator population was reduced and the reduction was not statistically significant (p > 0.05). The present study proved that Melia seed extracts were effective against cabbage aphids under field condition. Further, it is evident that the beneficial interaction between botanical extracts and biological control organism in the field showed safety to natural enemies. In conclusion, Melia seed extract can be useful for small-scale farmers to protect their cabbage crop against cabbage aphid, B. brassicae.     

Estimating true prevalence of Schistosoma mansoni from population summary measures based on the Kato-Katz diagnostic technique

BackgroundThe prevalence of Schistosoma mansoni infection is usually assessed by the Kato-Katz diagnostic technique. However, Kato-Katz thick smears have low sensitivity, especially for light infections. Egg count models fitted on individual level data can adjust for the infection intensity-dependent sensitivity and estimate the ‘true’ prevalence in a population. However, application of these models is complex and there is a need for adjustments that can be done without modeling expertise. This study provides estimates of the ‘true’ S. mansoni prevalence from population summary measures of observed prevalence and infection intensity using extensive simulations parametrized with data from different settings in sub-Saharan Africa.MethodologyAn individual-level egg count model was applied to Kato-Katz data to determine the S. mansoni infection intensity-dependent sensitivity for various sampling schemes. Observations in populations with varying forces of transmission were simulated, using standard assumptions about the distribution of worms and their mating behavior. Summary measures such as the geometric mean infection, arithmetic mean infection, and the observed prevalence of the simulations were calculated, and parametric statistical models fitted to the summary measures for each sampling scheme. For validation, the simulation-based estimates are compared with an observational dataset not used to inform the simulation.Principal findingsOverall, the sensitivity of Kato-Katz in a population varies according to the mean infection intensity. Using a parametric model, which takes into account different sampling schemes varying from single Kato-Katz to triplicate slides over three days, both geometric and arithmetic mean infection intensities improve estimation of sensitivity. The relation between observed and ‘true’ prevalence is remarkably linear and triplicate slides per day on three consecutive days ensure close to perfect sensitivity.Conclusions/significanceEstimation of ‘true’ S. mansoni prevalence is improved when taking into account geometric or arithmetic mean infection intensity in a population. We supply parametric functions and corresponding estimates of their parameters to calculate the ‘true’ prevalence for sampling schemes up to 3 days with triplicate Kato-Katz thick smears per day that allow estimation of the ‘true’ prevalence.     

Quality of Medicines Commonly Used in the Treatment of Soil Transmitted Helminths and Giardia in Ethiopia: A Nationwide Survey

Background

The presence of poor quality medicines in the market is a global threat on public health, especially in developing countries. Therefore, we assessed the quality of two commonly used anthelminthic drugs [mebendazole (MEB) and albendazole (ALB)] and one antiprotozoal drug [tinidazole (TNZ)] in Ethiopia.

Methods/Principal Findings

A multilevel stratified random sampling, with as strata the different levels of supply chain system in Ethiopia, geographic areas and government/privately owned medicines outlets, was used to collect the drug samples using mystery shoppers. The three drugs (106 samples) were collected from 38 drug outlets (government/privately owned) in 7 major cities in Ethiopia between January and March 2012. All samples underwent visual and physical inspection for labeling and packaging before physico-chemical quality testing and evaluated based on individual monographs in Pharmacopoeias for identification, assay/content, dosage uniformity, dissolution, disintegration and friability. In addition, quality risk was analyzed using failure mode effect analysis (FMEA) and a risk priority number (RPN) was assigned to each quality attribute. A clinically rationalized desirability function was applied in quantification of the overall quality of each medicine. Overall, 45.3% (48/106) of the tested samples were substandard, i.e. not meeting the pharmacopoeial quality specifications claimed by their manufacturers. Assay was the quality attribute most often out-of-specification, with 29.2% (31/106) failure of the total samples. The highest failure was observed for MEB (19/42, 45.2%), followed by TNZ (10/39, 25.6%) and ALB (2/25, 8.0%). The risk analysis showed that assay (RPN = 512) is the most critical quality attribute, followed by dissolution (RPN = 336). Based on Derringer''s desirability function, samples were classified into excellent (14/106,13%), good (24/106, 23%), acceptable (38/106, 36%%), low (29/106, 27%) and bad (1/106,1%) quality.

Conclusions/Significance

This study evidenced that there is a relatively high prevalence of poor quality MEB, ALB and TNZ in Ethiopia: up to 45% if pharmacopoeial acceptance criteria are used in the traditional, dichotomous approach, and 28% if the new risk-based desirability approach was applied. The study identified assay as the most critical quality attributes. The country of origin was the most significant factor determining poor quality status of the investigated medicines in Ethiopia.     

Can Interferon-Gamma or Interferon-Gamma-Induced-Protein-10 Differentiate Tuberculosis Infection and Disease in Children of High Endemic Areas?

Background

Diagnosis of childhood tuberculosis (TB) is difficult in high TB burden settings. Interferon-gamma-induced protein 10 (IP10) has been suggested as a marker of TB infection and disease, but its ability to differentiate the two conditions remains uncertain.

Objectives

To describe Interferon-gamma (INFγ) and IP10 expression in children with TB infection and disease and controls to assess their potential to differentiate latent and active TB.

Methods

This was a cross sectional study of 322 1–15 years old children with symptoms of TB (28 confirmed, 136 probable and 131 unlikely TB), 335 children in contact with adults with pulmonary TB and 156 community controls in Southern Ethiopia. The Tuberculin Skin Test (TST) and Quantiferon-In-Tube (QFT-IT) were performed. INFγ and IP10 were measured in plasma supernatants.

Results and Interpretation

Children with confirmed and probable TB and contacts were more likely to have TST+ (78.6%, 59.3% and 54.1%, respectively) than children with unlikely TB (28.7%) and controls (12.8%) (p<0.001). Children with confirmed TB (59.3%) and contacts (44.7%) were more likely to have INFγ+ than children with probable (37.6%) or unlikely TB (28.1%) and controls (13.1%) (p<0.001). IP10 concentrations were higher in INFγ+ children independently of TST (p<0.001). There was no difference between IP10 concentrations of children with confirmed TB and contacts (p = 0.8) and children with and without HIV (p>0.1).INFγ and IP10 can identify children with TB infection and disease, but cannot differentiate between the two conditions. HIV status did not affect the expression of IP10.     

Factors associated with HIV/AIDS diagnostic disclosure to HIV infected children receiving HAART: a multi-center study in Addis Ababa, Ethiopia

Background

Diagnostic disclosure of HIV/AIDS to a child is becoming an increasingly common issue in clinical practice. Nevertheless, some parents and health care professionals are reluctant to inform children about their HIV infection status. The objective of this study was to identify the proportion of children who have knowledge of their serostatus and factors associated with disclosure in HIV-infected children receiving HAART in Addis Ababa, Ethiopia.

Methods

A cross-sectional study was conducted in five hospitals in Addis Ababa from February 18, 2008–April 28, 2008. The study populations were parents/caretakers and children living with HIV/AIDS who were receiving Highly Active Antiretroviral Therapy (HAART) in selected hospitals in Addis Ababa. Univariate and multivariate logistic regression analysis were carried out using SPSS 12.0.1 statistical software.

Results

A total of 390 children/caretaker pairs were included in the study. Two hundred forty three children (62.3%) were between 6–9 years of age. HIV/AIDS status was known by 68 (17.4%) children, 93 (29%) caretakers reported knowing the child''s serostatus two years prior to our survey, 180 (46.2%) respondents said that the child should be told about his/her HIV/AIDS status when he/she is older than 14 years of age. Children less than 9 years of age and those living with educated caregivers are less likely to know their results than their counterparts. Children referred from hospital''s in-patient ward before attending the HIV clinic and private clinic were more likely to know their results than those from community clinic.

Conclusion

The proportion of disclosure of HIV/AIDS diagnosis to HIV-infected children is low. Strengthening referral linkage and health education tailored to educated caregivers are recommended to increase the rate of disclosure.