A Randomized Controlled Double Blind Trial of Ciclosporin versus Prednisolone in the Management of Leprosy Patients with New Type 1 Reaction, in Ethiopia.

BACKGROUND: Leprosy Type 1 (T1R) reactions are immune-mediated events leading to nerve damage and preventable disability affecting hands, feet and eyes. Type 1 Reactions are treated with oral corticosteroids. There is little evidence on alternative treatments for patients who do not respond to steroids or experience steroid adverse effects. We report the results of a randomized controlled trial testing the efficacy and adverse effect profile of ciclosporin and prednisolone (CnP) in comparison to prednisolone only (P) in patients with new T1R in Ethiopia. Ciclosporin is a potent immunosuppressant. Outcomes were measured using a clinical severity score, recurrence rate, adverse events and quality of life. RESULTS: Seventy three patients with new T1R were randomized to receive CnP or P for 20 weeks. Recovery rates in skin signs was similar in both groups (91% vs 88%). Improvements in nerve function both, new and old, sensory (66% vs 49%) and motor (75% vs 74%) loss were higher (but not significantly so) in the patients on CnP. Recurrences rates of T1R (85%) were high in both groups, and recurrences occurred significantly earlier (8 weeks) in patients CnP, who needed 10% more additional prednisolone. Serious major and minor adverse events rates were similar in patients in the two treatment arms of the study. Both groups had a significant improvement in their quality of life after the study, measured by the SF-36. CONCLUSIONS: This is the first double-blind RCT assessing ciclosporin, in the management of T1R in Africa. Ciclosporin could be a safe alternative second-line drug for patients with T1R who are not improving with prednisolone or are experiencing adverse events related to prednisolone. This study illustrates the difficulty in switching off leprosy inflammation. Better treatment agents for leprosy patients with reactions and nerve damage are needed

Genetic Variability for Resistance to Leaf Blight and Diversity among Selected Maize Inbred Lines

Maize (Zea mays L.) is an important staple food crop in sub-Saharan Africa (SSA). The productivity of the crop is limited partly by the leaf blight disease caused by Exserohilum turcicum. In breeding for resistance to leaf blight, the germplasm needs to be well-characterized in order to design efficient breeding programs. This study evaluated the (i) genetic variability among maize inbred lines and (ii) diversity of selected medium to late maturity tropical maize inbred lines for hybrid breeding. Plants of 50 maize inbred lines were artificially inoculated in the field during 2011 and 2012. Disease severity and incidence as well as grain yield were measured. A subset of 20 elite maize inbred lines was genotyped using 20 SSR markers. The germplasm showed significant differences in reaction to leaf blight and were classified as either resistant or intermediate or susceptible. Mean disease severity varied from 2.04 to 3.25. Seven inbred lines were identified as potential sources of resistance to leaf blight for the genetic improvement of maize. The genotyping detected 108 alleles and grouped the inbred lines into five clusters consistent with their pedigrees. The genetic grouping in the source population will be useful in the exploitation of tropical maize breeding programs

Assessment of Fusarium head blight resistance in newly developed recombinant inbred lines of wheat

Fusarium head blight (FHB) is an important disease of wheat causing significant yield and quality losses globally. Breeding for host plant resistance is an economic approach to FHB control and management. The aim of this study was to identify potential sources of resistance from newly developed recombinant inbred lines (RILs) of wheat. A total of 778 RILs were developed through a bi-parental mating design followed by continuous selfing and selection. The RILs along with their eight parental lines (Baviaans, Buffels, Duzi, #910, #936, #937, #942 and #1036) and FHB resistant check cultivar ‘Sumai 3’ and susceptible check ‘SST 806’ were field evaluated across four environments in South Africa. Fusarium graminearum isolates were artificially inoculated to initiate infection and disease development. The percentage of wheat spikes showing FHB symptoms were scored. The research identified six percent of the RILs with disease resistance. Heritability for FHB resistance was the highest (64%) indicating the possibility of achieving higher selection gains for FHB resistance across the selected environments. The following five RILs were identified as potential sources of resistance: 681 (Buffels/1036-71), 134 (Duzi/910-8), 22 (Baviaans/910-22), 717 (Baviaans/937-8) and 133 (Duzi/910-7) with mean FHB scores of 6.8%, 7.8%, 9.5%, 9.8% and 10%, respectively. The selected lines expressed comparatively similar levels of resistance compared with that of Sumai 3. The identified RILs are useful genetic resources for resistance breeding against FHB disease of wheat. Since the presence of the F. graminearum is associated with deoxynivalenol (DON) accumulation, the DON levels amongst the selected lines should be determined to ensure the release of improved wheat cultivars with reduced levels of DON accumulation

Potential of Improving Agronomic Attributes in Tropical Legumes Using Two Mutation Breeding Techniques in Southern Africa

Tropical legumes such as cowpea (Vigna unguiculata) and tepary bean (Phaseolus acutifolius) are important in traditional smallholder cropping systems, particularly in sub-Saharan Africa. Both legumes are adapted to harsh environments including extreme temperatures, drought and poor soil fertility. They provide affordable sources of protein for human consumption and are valuable for income generation. These crops contribute significantly to soil fertility improvement through biological nitrogen fixation. In many parts of Africa, the productivity of these legumes is generally low partly because farmers grow unimproved varieties that are often produced for subsistence purposes on poor soils in mixed cropping systems with limited production inputs. Therefore, this research was designed to evaluate the potential of two distinct mutation breeding approaches in creating useful genetic variation in the two legumes in order to improve the agronomic attributes of both crops. The variation was determined by measuring a range of agronomic traits at both the seedling and adult plant stages. The results showed significant genetic variation among cowpea mutants that were induced with various doses of gamma radiation as well as among tepary bean mutants that were induced with a chemical mutagenic agent, ethyl methanesulphonate (EMS). The optimum doses at LD50 for two cowpea genotypes (Nakare and Shindimba) were ≤200 Gy while the third genotype (Bira) tolerated a dose three-fold higher. In the EMS mutagenesis of tepary bean, the estimated LD50 was ≤2.4% EMS (v/v). In both approaches, percent seed germination decreased with increased dose and the coefficients of determination for the linear functions were high (>75%), suggesting that there were notable associations between the reduction in seed germination and the concentration of the mutagen. At the adult plant stage, tepary bean showed that the mutant generation significantly (P 10.0% increase in both seed size and grain yield potential of some mutant cowpea genotypes compared with the standard check. These findings provide reference doses for large-scale gamma irradiation of cowpea as well as chemical mutagenesis for tepary bean. In addition, the germplasm produced from these approaches has the potential for selection in a range of agro-ecological conditions across the region, thus creating alternative cropping systems for the smallholder growers

Schistosomiasis mansoni and soil-transmitted helminthiasis in Bushulo village, southern Ethiopia

Background: Schistosomiasis mansoni and soil-transmitted helminthiasis (STHs) are considerable medical and public health problems in Ethiopia. However, information is limited on the epidemiology of these infections in different localities even though it is needed to plan effective prevention and control measures. Objective: This study was designed to determine the prevalence of Schistosoma mansoni and soil-transmitted helminth infections in school children and residents in Bushulo village near Lake Awassa (Hawassa), southern Ethiopia. Methods: Cross-sectional epidemiological and parasitological studies were conducted on schistosomiasis mansoni and STHs in Bushulo village in May and June 2007. A total of 419 participants (353 school children and 66 other residents) were included in the study. The principal investigator interviewed the study subjects about demographic status using structured questionnaires. Moreover, experienced nurse took history and conducted physical examination to assess symptoms and signs related to chronic S. mansoni infection. A single stool sample was collected from each participant and processed using the Kato-Katz technique. Experienced laboratory technician read all slides at Bushulo Health Center. Results: The overall infection rates of schistosomiasis mansoni, trichuriasis, ascariasis and hookworm infection were 73.7%, 41.5%, 37.2% and 28.4%, respectively. Other parasitic infections observed were caused by Hymenolepis nana (1.7%), Taenia species (1.4%), and Enterobius vermicularis (1.4%). Children in the age range 10-14 years and those attending at St. Paul’s School had higher rates of T. trichiura and S. mansoni, respectively. Intensity of infection was higher for A. lumbricoides in the age range 5-9 years. The overall prevalence of any STHs was 67.3%. The rates of single, dual, triple and quadruple infections were 29.6%, 32%, 20.3% and 7.4%, respectively. Conclusion: The high prevalence and intensity of schistosomiasis mansoni and soil-transmitted helminthiasis makes periodic deworming programme urgent to reduce morbidity and transmission of helminthiasis in the area. Provisions of sanitary facilities and clean water supply as well as health education are also critically needed to sustain the impact of chemotherapy

Effect of processing method on the Proximate composition, mineral content and antinutritional factors of Taro (Colocasia esculenta, L.) growth in Ethiopia

Although taro is widely grown in Ethiopia, it is an underutilized crop and little is known about its proximate and micro-element composition and the antinutritional factors of the raw, boiled and fermented products. Boiling and fermentation processing techniques are widely used in the country, especially within the rural community of the Southern region where the crop grows widely. A cultivar of taro grown in the country was analyzed for proximate and mineral composition and antinutritional factors. An investigation was also made on the effects of boiling and fermentation on the nutritional contents. Protein, fat, fiber, total ash and utilizable carbohydrates, respectively were found to be 6.43, 0.47, 2.63, 4.82 and 85.65%, while the Gross Energy was 372.55 Kcal/100g. The contents of the micronutrients namely: Fe, Zn, Mg, Ca, Na, P and Mn were 5.86, 43.08, 7.24, 45.23, 13.81, 7.77 and 3.61 mg/100g, respectively. Phytate for the raw product was 115.43 while oxalate and tannin were 243.06 and 47.69 mg/100g, respectively. Cyanide was not detected in all the samples. There was a significant difference (p < 0.05) in the contents of the proximate and mineral composition and antinutritional factors during boiling and fermentation. The protein content was lower by 9.37% and 8.46%, respectively, in the boiled and fermented products, under the sampling and processing conditions used in the study. The crude fat content was significantly different (p < 0.05) from the crude fat content of the boiled product which was 0.87%. On the other hand, analysis of variance conducted showed that the fiber content of raw sample was significantly different from the fermented samples. Fermentation resulted in a lower level of fiber which was 6.44% and phytates of about 84.75%. Boiling of taro resulted in a higher value of oxalate (70.9%). The data presented in this paper provide an evidence of the potential of Boloso I (which is one variety of taro) to serve as a nutrient dense product for the Ethiopian population provided that the techniques of its processing are optimized.Keywords: Ethiopia, Taro, Oxalates, PhytatesAfrican Journal of Food, Agriculture, Nutrition and Development, Volume 13 No. 2 April 201

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

A bis-calixarene from olefin metathesis

A ring-closing olefin metathesis reaction of tetra­kis­(all­yl­oxy)calix[4]arene gave the bis­ calixarene, (15E,40E,60E)-65,74-bis­(prop-2-en-1-yl­oxy)-13,18,38,43,58,63-hexa­oxado­deca­cyclo­[28.26.8.720,36.111,45.151,55.05,57.07,12.019,24.026,64.032,37.044,49.168,72]tetra­hepta­conta-1,3,5(57),7,9,11,15,19(24),20,22,26,28,30(64),32,34,36,40,44(49),45,47,51,53,55(65),60,68,70,72(74)-hepta­cosa­ene, C74H68O8. It is a cage formed from two calix[4]arene units joined by butenyl groups at three of the O atoms on the narrow rim. The fourth O atom on each calixarene unit is joined with an allyl group. Each of the calix[4]arene units has a flattened cone conformation in which the all­yloxy-substituted aryl group and the opposite aryl group are close together and almost parallel [dihedral angle between planes = 1.09 (11)°], and the other two aryl groups are splayed outward [dihedral angle between planes = 79.53 (11)°]. No guest mol­ecule (e.g. solvent) was observed within the cage. The alkene C atoms of one of the links between the calixarene moieties are disordered over two orientations with occupancies of 0.533 (9) and 0.467 (9)

Comparison of Efficacy and Safety of Ciclosporin to Prednisolone in the Treatment of Erythema Nodosum Leprosum: Two Randomised, Double Blind, Controlled Pilot Studies in Ethiopia.

BACKGROUND: Erythema Nodosum Leprosum (ENL) is a serious complication of leprosy. It is normally treated with high dose steroids, but its recurrent nature leads to prolonged steroid usage and associated side effects. There is little evidence on the efficacy of alternative treatments for ENL, especially for patients who have become steroid resistant or have steroid side effects. These two pilot studies compare the efficacy and side effect profile of ciclosporin plus prednisolone against prednisolone alone in the treatment of patients with either new ENL or chronic and recurrent ENL. METHODS AND RESULTS: Thirteen patients with new ENL and twenty patients with chronic ENL were recruited into two double-blinded randomised controlled trials. Patients were randomised to receive ciclosporin and prednisolone or prednisolone treatment only. Patients with acute ENL had a delay of 16 weeks in the occurrence of ENL flare-up episode, with less severe flare-ups and decreased requirements for additional prednisolone. Patients with chronic ENL on ciclosporin had the first episode of ENL flare-up 4 weeks earlier than those on prednisolone, as well as more severe ENL flare-ups requiring 2.5 times more additional prednisolone. Adverse events attributable to prednisolone were more common that those attributable to ciclosporin. CONCLUSIONS: This is the first clinical trial on ENL management set in the African context, and also the first trial in leprosy to use patients' assessment of outcomes. Patients on ciclosporin showed promising results in the management of acute ENL in this small pilot study. But ciclosporin, did not appear to have a significant steroid-sparing effects in patients with chronic ENL, which may have been due to the prolonged use of steroids in these patients in combination with a too rapid decrease of steroids in patients given ciclosporin. Further research is needed to determine whether the promising results of ciclosporin in acute ENL can be reproduced on a larger scale