Immunoinformatics assisted design of a multi-epitope kit for detecting <i>Cronobacter sakazakii</i> in powdered infant formula

Objectives: Cronobacter sakazakii, formerly Enterobacter sakazakii, is an emerging ubiquitous and opportunistic foodborne pathogen with a high mortality rate. It has been implicated in cases of meningitis, septicaemia, and necrotizing enterocolitis among infants worldwide in association with powdered infant formula (PIF). This study was an insilico designed peptide base kit framework, using immunoinformatic techniques for quick detection of C. sakazakii in PIF. Materials and Methods: In the present study, a peptide-based kit was designed with a bioinformatic technique to rapidly identify C. sakazakii in PIF using flhE, secY, and bcsC, which are genes responsible for its biofilm formation, as target genes. The antigenicity, membrane topology, and the presence of signal peptides of the target genes were analysed using VaxiJen, DeepTMHMM, and SignalP servers. To provide stability and flexibility to the multiple-epitope construct, the linear B cells and helper T cells (IL-4 (interleukin 4) and IL-10 (interleukin 10) inducing epitopes) were linked with a GSGSG linker followed by the addition of protein disulphide bonds. To ascertain specificity, the multi-epitope construct was molecularly docked against genes from sources other than PIF, like alfalfa, and the environment, with PIF being the highest: –328.48. Finally, the codons were modified using the pET28a(+) vector, and the resultant multi-epitope construct was successfully cloned in silico. Results: The final construct had a length of 486 bp, an instability index of 23.26, a theoretical pI of 9.34, a molecular weight of 16.5 kDa, and a Z-score of –3.41. Conclusions: The multi-epitope peptide construct could be a conceptual framework for creating a C. sakazakii peptide-based detection kit, which has the potential to provide fast and efficient detection. However, there is a need for additional validation through the in vitro and in vivo techniques

Assessment of Climate Change Adaptive Strategies in Small Ruminant Production in Rural Nigeria

Animals are intrinsically dependent on the environment, and any fluctuations in weather and climate can affect them through water and land changes, such as desertification, feed and water availability. Climate change will not only impact the health and welfare of animals, but also the more than a billion people who depend on them. This study was therefore aimed at evaluating the adaptive measures used by rural farmers to alleviate the effect of climate change on small ruminant (sheep and goats) production in rural Nigeria. The target population for this study was all the small ruminant farmers in the five agro-ecological zones of Nigeria. A total of 300 respondents were interviewed using validated structured interview schedule. Data were analyzed using frequency counts, means and percentage. The result shows that most (71.9%) of the respondents were adults between 20 and 50 years of age. About 35% keep sheep and goats together while others keep either of the species. The most preferred management system is semi-extensive system (64%). Majority (93.2%) of small ruminant farmers in the rural Nigeria were aware of what climate change is all about and about 54% of them had observed changes in climage through personal experience.Majority of them had also observed and attributed changes to effect of climate change on their flock. Majority of them have also used various strategies to combat climate change. Traditional health care and irrigation of pasture during dry season were not effective adaptive strategies to combat climate change.There is need to educate the farmers more on the possible effect of climate change through the use of radio and other extension organizations (government and non-governmental) on the current situation and implication of climate change on themselves and their animals

Assessment of Climate Change Adaptive Strategies in Small Ruminant Production in Rural Nigeria

Animals are intrinsically dependent on the environment, and any fluctuations in weather and climate can affect them through water and land changes, such as desertification, feed and water availability. Climate change will not only impact the health and welfare of animals, but also the more than a billion people who depend on them. This study was therefore aimed at evaluating the adaptive measures used by rural farmers to alleviate the effect of climate change on small ruminant (sheep and goats) production in rural Nigeria. The target population for this study was all the small ruminant farmers in the five agro-ecological zones of Nigeria. A total of 300 respondents were interviewed using validated structured interview schedule. Data were analyzed using frequency counts, means and percentage. The result shows that most (71.9%) of the respondents were adults between 20 and 50 years of age. About 35% keep sheep and goats together while others keep either of the species. The most preferred management system is semi-extensive system (64%). Majority (93.2%) of small ruminant farmers in the rural Nigeria were aware of what climate change is all about and about 54% of them had observed changes in climage through personal experience.Majority of them had also observed and attributed changes to effect of climate change on their flock. Majority of them have also used various strategies to combat climate change. Traditional health care and irrigation of pasture during dry season were not effective adaptive strategies to combat climate change.There is need to educate the farmers more on the possible effect of climate change through the use of radio and other extension organizations (government and non-governmental) on the current situation and implication of climate change on themselves and their animals

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

Post-doctoral research fellowship as a health policy and systems research capacity development intervention: a case of the CHESAI initiative

BACKGROUND: Building capacity in health policy and systems research (HPSR), especially in low- and middle-income countries, remains a challenge. Various approaches have been suggested and implemented by scholars and institutions using various forms of capacity building to address challenges regarding HPSR development. The Collaboration for Health Systems Analysis and Innovation (CHESAI) – a collaborative effort between the Universities of Cape Town and the Western Cape Schools of Public Health – has employed a non-research based post-doctoral research fellowship (PDRF) as a way of building African capacity in the field of HPSR by recruiting four post-docs. In this paper, we (the four post-docs) explore whether a PDRF is a useful approach for capacity building for the field of HPSR using our CHESAI PDRF experiences. METHODS: We used personal reflections of our written narratives providing detailed information regarding our engagement with CHESAI. The narratives were based on a question guide around our experiences through various activities and their impacts on our professional development. The data analysis process was highly iterative in nature, involving repeated meetings among the four post-docs to reflect, discuss and create themes that evolved from the discussions. RESULTS: The CHESAI PDRF provided multiple spaces for our engagement and capacity development in the field of HPSR. These spaces provided us with a wide range of learning experiences, including teaching and research, policy networking, skills for academic writing, engaging practitioners, co-production and community dialogue. Our reflections suggest that institutions providing PDRF such as this are valuable if they provide environments endowed with adequate resources, good leadership and spaces for innovation. Further, the PDRFs need to be grounded in a community of HPSR practice, and provide opportunities for the post-docs to gain an in-depth understanding of the broader theoretical and methodological underpinnings of the field. CONCLUSION: The study concludes that PDRF is a useful approach to capacity building in HPSR, but it needs be embedded in a community of practice for fellows to benefit. More academic institutions in Africa need to adopt innovative and flexible support for emerging leaders, researchers and practitioners to strengthen our health systemsIS

A narrative review of health research capacity strengthening in low and middle-income countries: lessons for conflict-affected areas

Abstract Conducting health research in conflict-affected areas and other complex environments is difficult, yet vital. However, the capacity to undertake such research is often limited and with little translation into practice, particularly in poorer countries. There is therefore a need to strengthen health research capacity in conflict-affected countries and regions. In this narrative review, we draw together evidence from low and middle-income countries to highlight challenges to research capacity strengthening in conflict, as well as examples of good practice. We find that authorship trends in health research indicate global imbalances in research capacity, with implications for the type and priorities of research produced, equity within epistemic communities and the development of sustainable research capacity in low and middle-income countries. Yet, there is little evidence on what constitutes effective health research capacity strengthening in conflict-affected areas. There is more evidence on health research capacity strengthening in general, from which several key enablers emerge: adequate and sustained financing; effective stewardship and equitable research partnerships; mentorship of researchers of all levels; and effective linkages of research to policy and practice. Strengthening health research capacity in conflict-affected areas needs to occur at multiple levels to ensure sustainability and equity. Capacity strengthening interventions need to take into consideration the dynamics of conflict, power dynamics within research collaborations, the potential impact of technology, and the wider political environment in which they take place