Characterization and factors associated with diarrhoeal diseases caused by enteric bacterial pathogens among children aged five years and below attending Igembe District Hospital, Kenya

Introduction: Diarrhoea remains a major public health problem in East African nations such as Kenya. Surveillance for a broad range of entericpathogens is necessary to accurately predict the frequency of pathogens and potential changes in antibiotic resistance patterns.Methods: A cross sectional study was conducted in Igembe District Hospital in Meru County to determine the burden and factors associated enteric  bacterial infection among children aged five years and below. Stool  samples were collected between March and July 2012. Bacterial pathogens were identified and antibiotic susceptibility of bacterial isolates was  ascertained. Questionnaire was administered to the 308 study participants to identify the modifiable risk factors. Data was entered and analyzed  using Epi Info version 3.5.3.Results: The study recruited 308 children. The mean age was 27.25  months, median of 26.0 months and age range  between 2-60 months. The bacterial isolation rates were ETEC 9.1%, EPEC 6.8% and EAEC 12.3%, Salmonella paratyphoid (10.4%), Shigella flexineri (1.9%) and Shigella dysentriae (0.9%). Over 95 %, of the isolates were resistance to  amoxicillin, sulphinatozole, cotrimoxazole. Six factors were independently associated with diarrhoeal diseases, occupation of the parent/guardian (miraa business) (OR=1.8, CI:1.44-4.99),care taker not washing hands after changing napkins (OR= 1.6, CI:1.2-19.7), child drank untreated water from the river (OR= 2.7, CI:2.4-9.9) child not exclusively breastfed (OR= 2.4, CI:2.1-10.5),child did not Wash hands before eating (OR=2.2, CI:1.91-16.3) and after visiting toilet (OR=3.7,CI:2.8-39.4).Eating of mangoes was found to be protective against diarrhoea (OR=0.5, CI:0.03-0.89).Conclusion: The bacterial pathogens were found to be a significant cause of diarrhoea in the study participants. We established higher resistance to several commonly prescribed antibiotics.Several  factors were significantly association with diarrhoea illness. We recommend multifaceted approach that acknowledges the public health aspects that would reduce the  burdenof diarrhoea infectious as identified in this study

Factors Affecting Effective Succession Management in the Civil Service in Kenya: A Case of Ministry of Water and Irrigation

Effective succession management can play a very important role in ensuring positive growth in an organization. However, in Kenyan context especially in the civil service this issue has received less attention from past researchers hence the need to undertake this study. Organizations all over the world are faced with succession challenges prompted by, among other factors; demographic shifts, stagnation in one level in employment and effects of natural attrition. The affected institutions respond by instituting necessary succession management measures aimed at ensuring availability of capable human resources for consistent service delivery. The Kenya Civil Service faces career succession and stagnation management problems manifested by the ageing Civil Servants with an estimate of 58% of the total workforce aged thirty five years and above. The purpose of this study was to examine the factors affecting succession management in the civil service. This study was carried out in the Ministry of Water and Irrigation headquarters in Nairobi. The target population was 300 civil servants in the middle and senior management level (job groups K and above) in the ministry of water and irrigation headquarters. Seventeen percent (17%) of the target population were sampled for the purpose of this study. The data had been analyzed using quantitative methods that involve simple descriptive statistics based on frequency tables and percentages and SPSS package for data analysis. The study has revealed that there is lack of effective succession management in the ministry of water and irrigation. Succession management initiatives were reported to be inconspicuous and incongruous owing to the fact that majority of the human resource management functions are performed by external agencies namely the public service commission of Kenya and Directorate of personnel Management. The Ministry should explore the possibility of forming a succession management committee to streamline succession issues and make provisions for outgoing officers to pass-on special skills to the likely successors in programmes akin to apprenticeships. It is also recommended that human resources managers should be empowered to carry out comprehensive Human resource management functions in their respective ministries Keywords:Succession Management,Stagnation,Civil service,Apprenticeships,Human Resources,Keny

PROVISION OF IN-SERVICE TRAINING NEEDS FOR HEADS OF DEPARTMENT IN SECONDARY SCHOOLS IN KENYA: A STUDY OF MARAKWET WEST SUB COUNTY

Ministry of Education together with public secondary schools have initiated continuous in-service training for their heads of departments. This study assessed the influence of in-service training of Heads of department (HODs). The objectives of the study were to; determine the mode of in-service training provided to HODs and the content of in-service training. The study was conducted in 28 public secondary schools in Marakwet Sub County. The target respondents were 28 principals and 112 HODs. Data collected was analysed qualitatively and quantitatively. Statistical Package for Social Sciences (SPSS Version 22.0) aided in quantitative data coding, entry and analysis. Study findings revealed that HODs rarely attend in-service training. Majority of schools were found not to have a plan for HODs in-service training. It was also established that in-service training for HODs focused on curriculum implementation, supervision, teaching methods and evaluation of learners compared to teacher resource management, innovation and management. The study recommends that there is need for regular in-service training provision for teachers. Needs assessment also needs to be conducted to ensure that training content provided to HODs is relevant.  Article visualizations

Immune Modulation by Antigenic Peptides and Antigenic Peptide Conjugates for Treatment of Multiple Sclerosis

The immune system defends our body by fighting infection from pathogens utilizing both the innate and adaptive immune responses. The innate immune response is generated rapidly as the first line of defense. It is followed by the adaptive immune response that selectively targets infected cells. The adaptive immune response is generated more slowly, but selectively, by targeting a wide range of foreign particles (i.e., viruses or bacteria) or molecules that enter the body, known as antigens. Autoimmune diseases are the results of immune system glitches, where the body’s adaptive system recognizes self-antigens as foreign. Thus, the host immune system attacks the self-tissues or organs with a high level of inflammation and causes debilitation in patients. Many current treatments for autoimmune diseases (i.e., multiple sclerosis (MS), rheumatoid arthritis (RA)) have been effective but lead to adverse side effects due to general immune system suppression, which makes patients vulnerable to opportunistic infections. To counter these negative effects, many different avenues of antigen specific treatments are being developed to selectively target the autoreactive immune cells for a specific self-antigen or set of self-antigens while not compromising the general immune system. These approaches include soluble antigenic peptides, bifunctional peptide inhibitors (BPI) including IDAC and Fc-BPI, polymer conjugates, and peptide-drug conjugates. Here, various antigen-specific methods of potential treatments, their efficacy, and limitations will be discussed along with the potential mechanisms of action

Noninvasive Brain Delivery and Efficacy of BDNF to Stimulate Neuroregeneration and Suppression of Disease Relapse in EAE Mice

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © 2019 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.molpharmaceut.9b00644.The number of FDA-approved protein drugs (biologics), such as antibodies, antibody–drug conjugates, hormones, and enzymes, continues to grow at a rapid rate; most of these drugs are used to treat diseases of the peripheral body. Unfortunately, most of these biologics cannot be used to treat brain diseases such as Alzheimer’s disease (AD), multiple sclerosis (MS), and brain tumors in a noninvasive manner due to their inability to permeate the blood–brain barrier (BBB). Therefore, there is a need to develop an effective method to deliver protein drugs into the brain. Here, we report a proof of concept to deliver a recombinant brain-derived neurotrophic factor (BDNF) to the brains of healthy and experimental autoimmune encephalomyelitis (EAE) mice via intravenous (iv) injections by co-administering BDNF with a BBB modulator (BBBM) peptide ADTC5. Western blot evaluations indicated that ADTC5 enhanced the brain delivery of BDNF in healthy SJL/elite mice compared to BDNF alone and triggered the phosphorylation of TrkB receptors in the brain. The EAE mice treated with BDNF + ADTC5 suppressed EAE relapse compared to those treated with BDNF alone, ADTC5 alone, or vehicle. We further demonstrated that brain delivery of BDNF induced neuroregeneration via visible activation of oligodendrocytes, remyelination, and ARC and EGR1 mRNA transcript upregulation. In summary, we have demonstrated that ADTC5 peptide modulates the BBB to permit noninvasive delivery of BDNF to exert its neuroregeneration activity in the brains of EAE mice

Immune response to controlled release of immunomodulating peptides in a murine experimental autoimmune encephalomyelitis (EAE) model

The effects of controlled release on immune response to an immunomodulating peptide were evaluated in a murine experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). The peptide, Ac-PLP-BPI-NH2-2 (Ac-HSLGKWLGHPDKF-(AcpGAcpGAcp)2-ITDGEATDSG-NH2; Ac = acetyl, Acp = aminocaproic acid) was designed to suppress T-cell activation in response to PLP139–151, an antigenic peptide in MS. Poly-lactide-co-glycolide (PLGA) microparticles containing Ac-PLP-BPI-NH2-2 (8±4 μm, 1.4±0.2% (w/w)) were prepared by a powder-in oil-in water emulsion-solvent evaporation method, sterilized and administered subcutaneously (s.c.) to SJL/J (H-2s) mice in which EAE had been induced by immunization with PLP139–151. Treatment groups received Ac-PLP-BPI-NH2-2: (i) in solution by repeated i.v. or s.c. injection, (ii) in solution co-administered with blank PLGA microparticles, (iii) in solution co-administered with Ac-PLP-BPI-NH2-2 loaded microparticles, and (iv) as Ac-PLP-BPI-NH2-2 loaded microparticles. Administration of Ac-PLP-BPI-NH2-2 as an s.c. solution produced clinical scores and maintenance of body weight comparable to i.v. solution, but with reduced overall survival, presumably due to anaphylaxis. Administration as s.c. microparticles provided a somewhat less effective reduction in symptoms but with no toxicity during treatment. Thus, the results suggest that s.c. administration of Ac-PLP-BPI-NH2-2 microparticles can provide pharmacological efficacy and reduction in dosing frequency without increased toxicity

Improving Brain Delivery of Biomolecules via BBB Modulation in Mouse and Rat: Detection using MRI, NIRF, and Mass Spectrometry

There is an urgent need to develop new and alternative methods to deliver functional biomolecules to the brain for diagnosis and treatment of brain diseases. The goal of this study was to evaluate the activity of blood-brain barrier (BBB) modulators (i.e., HAV and ADT peptides) to deliver functional biomolecules (i.e., galbumin, IRdye800cw-cLABL, and cIBR7) to the brains of mice and rats. HAV6, cHAVc3, and ADTC5 peptides but not HAV4 peptide significantly enhanced the brain delivery of 65 kDa galbumin compared to control in Balb/c mice as quantified by magnetic resonance imaging (MRI). Ten-minute pretreatment with ADTC5 peptide still significantly increased brain delivery of galbumin; however, no enhancement was observed after 10-min pretreatment with HAV6. There was no enhancement of galbumin deposition following 40-min pretreatment with ADTC5 or HAV6, suggesting a short duration of the BBB opening for large molecules. ADTC5 peptide also improved the brain delivery of IRdye800cw-cLABL peptide about 3.5-fold compared to control in Balb/c mice as detected by near infrared fluorescence (NIRF). The BBB modulator activity of ADTC5 to deliver cIBR7 peptide was also evaluated in vivo using Sprague-Dawley rats. The amount of cIBR7 in the brain was detected by LC-MS/MS. ADTC5 peptide enhanced the delivery of cIBR7 peptide into rat brain about 4-fold compared to control and the intact cIBR7 can be efficiently extracted and detected in rat brain. In conclusion, HAV and ADT peptides enhance the brain delivery of functional peptides (e.g., cLABL and cIBR7) and protein (e.g., 65 kDa galbumin) in two animal models, and the duration of the BBB opening for a large molecule (e.g., galbumin) was short

Modulation of Intercellular Junctions by Cyclic-ADT Peptides as a Method to Reversibly Increase Blood-Brain Barrier Permeability

It is challenging to deliver molecules to the brain for diagnosis and treatment of brain diseases. This is primarily due to the presence of the blood-brain barrier (BBB), which restricts the entry of many molecules into the brain. In this study, cyclic ADT peptides (ADTC1, ADTC5, and ADTC6) have been shown to modify the BBB to enhance the delivery of marker molecules (e.g., 14C-mannitol, Gd-DTPA) to the brain via the paracellular pathways of the BBB. The hypothesis is that these peptides modulate cadherin interactions in the adherens junctions of the vascular endothelial cells forming the BBB to increase paracellular drug permeation. In vitro studies indicated that ADTC5 had the best profile to inhibit adherens junction resealing in MDCK cell monolayers in a concentration-dependent manner (IC50 = 0.3 mM) with a maximal response at 0.4 mM. Under the current experimental conditions, ADTC5 improved the delivery of 14C-mannitol to the brain about twofold compared to the negative control in the in situ rat brain perfusion model. Furthermore, ADTC5 peptide increased in vivo delivery of Gd-DTPA to the brain of Balb/c mice when administered intravenously (i.v.). In conclusion, ADTC5 has the potential to improve delivery of diagnostic and therapeutic agents to the brain