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.     

A novel conserved targeting motif found in ABCA transporters mediates trafficking to early post-Golgi compartments

The ATP binding cassette, class A (ABCA) proteins are homologous polytopic transmembrane transporters that function as lipid pumps at distinct subcellular sites in a variety of cells. Located within the N terminus of these transporters, there exists a highly conserved xLxxKN motif of unknown function. To define its role, human ABCA3 was employed as a primary model representing ABCA transporters, while mouse ABCA1 was utilized to support major findings. Transfection studies showed colocalization of both transporters with surfactant protein C (SP-C), a marker peptide for successful protein targeting to lysosomal-like organelles. In contrast, alanine mutation of xLxxKN resulted in endoplasmic reticulum retention. As proof of principle, swapping xLxxKN for the known lysosomal targeting motif of SP-C resulted in post-Golgi targeting of the SP-C chimera. However, these products failed to reach their terminal processing compartments, suggesting that the xLxxKN motif only serves as a Golgi exit signal. We propose a model whereby an N-terminal signal sequence, xLxxKN, directs ABCA transporters to a post-Golgi vesicular sorting station where additional signals may be required for selective delivery of individual transporters to final subcellular destinations.     

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.     

Impact of Mental Health Visits on Healthcare Cost in Patients with Diabetes and Comorbid Mental Health Disorders

Purpose

To assess the impact of mental health visits (MHV) on the cost of care for Veterans with diabetes and comorbid mental health conditions.

Methods

A national cohort of 120,852 Veterans with diabetes and at least one mental health diagnosis (i.e., substance abuse, depression or psychoses) in 2002 was followed through 2006. Outcomes were pharmacy, inpatient and outpatient costs in 2012 dollars.

Results

Least-square covariate adjusted estimates from the joint model of total VA costs of the number of MHV using December 31, 2012 value dollars indicate that relative to those with fewer MHV, those with 3+ MHV had the lowest mean inpatient cost ($21,406), but the highest mean outpatient and pharmacy cost ($9,727 and $2,015, respectively). If all Veterans who received zero MHV actually received 3+ MHV, we estimate through simulated scenarios that between $32,272,329 and $181,460,247 in inpatient costs would be saved. However, these savings would be offset by additional expenditures of between $1,166,017,547 and $1,166,224,787 in outpatient costs and between $151,604,683 and $161,439,632 in pharmacy costs.

Conclusions

Among Veterans with diabetes and comorbid mental disorders having three or more mental health visits is associated with marginally decreased inpatient cost, but these potential savings seem to be offset by increased outpatient and pharmacy costs.     

A nonaggregating surfactant protein C mutant is misdirected to early endosomes and disrupts phospholipid recycling

Interstitial lung disease in both children and adults has been linked to mutations in the lung-specific surfactant protein C (SFTPC) gene. Among these, the missense mutation [isoleucine to threonine at codon 73 = human surfactant protein C (hSP-C(I73T) )] accounts for ～30% of all described SFTPC mutations. We reported previously that unlike the BRICHOS misfolding SFTPC mutants, expression of hSP-C(I73T) induces lung remodeling and alveolar lipoproteinosis without a substantial Endoplasmic Reticulum (ER) stress response or ER-mediated intrinsic apoptosis. We show here that, in contrast to its wild-type counterpart that is directly routed to lysosomal-like organelles for processing, SP-C(I73T) is misdirected to the plasma membrane and subsequently internalized to the endocytic pathway via early endosomes, leading to the accumulation of abnormally processed proSP-C isoforms. Functionally, cells expressing hSP-C(I73T) demonstrated both impaired uptake and degradation of surfactant phospholipid, thus providing a molecular mechanism for the observed lipid accumulation in patients expressing hSP-C(I73T) through the disruption of normal phospholipid recycling. Our data provide evidence for a novel cellular mechanism for conformational protein-associated diseases and suggest a paradigm for mistargeted proteins involved in the disruption of the endosomal/lysosomal sorting machinery.     

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.     

Highly efficient Staphylococcus carnosus mutant selection system based on suicidal bacteriocin activation

Strains from various staphylococcal species produce bacteriocin peptides, which are thought to play important roles in bacterial competition and offer interesting biotechnological avenues. Many bacteriocins are secreted as inactive prepeptides with subsequent activation by specific proteolytic cleavage. By deletion of the protease gene gdmP in Staphylococcus gallinarum Tü3928, which produces the highly active lanthionine-containing bacteriocin gallidermin (lantibiotic), a strain was created producing inactive pregallidermin. On this basis, a new suicidal mutant selection system in the food-grade bacterium Staphylococcus carnosus was developed. Whereas pregallidermin was inactive against S. carnosus, it exerted potent bactericidal activity toward GdmP-secreting S. carnosus strains. To take advantage of this effect, gdmP was cloned in plasmid vectors used for random transposon mutagenesis or targeted allelic replacement of chromosomal genes. Both mutagenesis strategies rely on rare recombination events, and it has remained difficult and laborious to identify mutants among a vast majority of bacterial clones that still contain the delivery vectors. The gdmP-expressing plasmids pGS1 and pGS2 enabled very fast, easy, and reliable identification of transposon and gene replacement mutants, respectively. Mutant selection in the presence of pregallidermin caused suicidal inactivation of all clones that had retained the plasmids and allowed growth of only plasmid-cured mutants. Efficiency of mutant identification was several magnitudes higher than standard screening for the absence of plasmid-encoded antibiotic resistance markers and reached 100% specificity. Thus, the new pregallidermin-based mutant selection system represents a substantial improvement of staphylococcal mutagenesis methodology.     

Therapeutic Efficacy of Artemether-Lumefantrine (Coartem?) in Treating Uncomplicated P. falciparum Malaria in Metehara,Eastern Ethiopia: Regulatory Clinical Study

BackgroundAs per the WHO recommendation, the development of resistance by P. falciparum to most artemisinin combination therapies (ACTs) triggered the need for routine monitoring of the efficacy of the drugs every two years in all malaria endemic countries. Hence, this study was carried out to assess the therapeutic efficacy of Artemether-Lumefantrine (Coartem®) in treating the uncomplicated falciparum malaria, after 9 years of its introduction in the Metehara, Eastern Ethiopia.MethodThis is part of the therapeutic efficacy studies by the Federal Ministry of Health Ethiopia, which were conducted in regionally representative sentinel sites in the country from October 2014 to January 2015. Based on the study criteria set by WHO, febrile and malaria suspected outpatients in the health center were consecutively recruited to study. A standard six-dose regimen of AL was administered over three days and followed up for measuring therapeutic responses over 28 days. Data entry and analysis was done by using the WHO designed Excel spreadsheet and SPSS version 20 for Windows. Statistical significant was considered for P-value less than 0.05.ResultOf the 91 patients enrolled, the day-28 analysis showed 83 adequate clinical and parasitological responses (ACPRs). Per protocol analysis, PCR-uncorrected & corrected cure rates of Coartem® among the study participants were 97.6% (95%CI: 93.6–99.5) and 98.8% (CI: 93.5–100%), respectively. No parasite detected on day 3 and onwards. Fever clearance was above 91% on day-3. Mean hemoglobin was significantly increased (P<0.000) from 12.39 g/dl at day 0 to 13.45 g/dl on day 28. No serious adverse drug reactions were observed among the study participants.ConclusionThis study showed high efficacy of AL in the study area, which suggests the continuation of AL as first line drug for the treatment of uncomplicated P. falciparum malaria in the study area. This study recommends further studies on drug toxicity, particularly on repeated cough and oral ulceration.