128 research outputs found

    ROLE OF PI3K-AKT PATHWAY IN THE AGE ASSOCIATED DECLINE IN TLR MEDIATED ACTIVATION OF INNATE AND ADAPTIVE IMMUNE RESPONSES

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    Immunosenescence results in reduced immune response to infections with Streptococcus pneumoniae as well as to pneumococcal polysaccharide vaccines. The antibody response to the capsular polysaccharide (CPS) provides protection against S. pneumoniae infection. CPS immunoresponse is T cell independent and needs the macrophage-derived cytokines such as IL-12, IL-6 and IL-1β to elicit an antibody response. We showed a cytokine dysregulation, i.e. a decrease in IL-12, IL-6 and TNF-α but an increase in IL-10, in the aged (18-24 months old comparable to \u3e65 years in human) compared to young adult mouse (8-12 weeks less than 65 years old) splenic macrophages (SM) or bone marrow derived macrophages (BMDM) activated via TLR4, TLR2 or TLR9 as well as heat killed Streptococcus pneumoniae (HKSP). There is also an age-associated defect in splenic B cells in the production of IgG3 upon stimulation with these ligands. A microarray analysis in SM followed by validation by both qt-RTPCR and western blots indicated that this age-associated defect in aged SM, BMDM and B cells was due to a heightened activity of the PI3K-Akt signaling pathway. We hypothesized that the senescence of immune responses in macrophages and B cells is due to an increase in activity of PI3K/Akt and decrease in the activity of GSK-3, the downstream kinase. Inhibition of the PI3-kinase with either LY294002 or Wortmannin restored the TLR2, 4, 9 and HKSP induced cytokine phenotype of the aged to that of the young adult in both the SM and BMDM and an enhanced IgG3 production in aged mice. We also showed that inhibition of glycogen synthase kinase-3 (GSK-3) the downstream target of the PI3K-Akt signaling pathway with SB216763 in SM, BMDM and B cells resulted in an enhancement in production of IL-10, IL-6 and IL-1β by macrophages and in B cell activation. Treatment of B cells with SB216763 in the presence of ligands for TLR-1/2, 4 or 9 as well as HKSP under in vitro conditions led to enhanced production of IgG3 and IgA, plasma cell formation and a slight increase in the proliferation of the B-cells with no adverse effects on the viability of the cells. Therefore, targeting the PI3K-AKT-GKS-3 signaling pathway could rescue the intrinsic signaling defect in the aged macrophages, increase IL-12 and IL-6, and enhance anti-CPS antibody responses

    Communication as the key to guide workforce development in the health sector in public stakeholder partnerships: a case study in Liberia

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    AbstractBackgroundTo improve the academic capacity of disciplines that contribute directly to the training of the health-care workforce in Liberia, the University of Liberia, in partnership with American counterparts at Indiana University and University of Massachusetts, launched the Center for Excellence in Health and Life Sciences, funded by USAID and Higher Education for Development.MethodsWith a participatory approach, academics, government representatives, and community constituents developed a Certificate in Public Health (CPH). Targeting midlevel governmental health workers, the programme model combined traditional coursework with intensive community-based practice experiences, allowing students and faculty to move outside traditional academic and technical disciplinary boundaries. With a participatory approach to define measurable outcomes that were relevant to health-care planning for the country, the programme continually aligned its content with stakeholder expectations.FindingsThe first cohort of ten students completed the core course curriculum plus 90 h of internship activity at five government facilities around Monrovia. Findings are the facilitating and challenging factors associated with the programme's development, implementation, and evaluation. Challenges include increased home-based delivery by semitrained traditional midwives and increase in malaria, diarrhoea, and acute respiratory infection in children younger than 5 years.InterpretationThe Ministry of Health and Social Welfare has already provided a framework to guide the rehabilitation of the health sector in a plan called Rebuilding Basic Health Services. To align public institution outcomes to workforce needs, communication, collaboration, and synergy between stakeholders is key. Tracking the improvement of data being reported and the health outcomes of communities served by the CPH graduates will be important. Further analysis needs to be done to ensure training fills health worker gaps.FundingUSAID

    The mediation role of work environment in the relationship between occupational hygiene practices and the health and safety of waste scavengers in emerging economies

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    Abstract Due to the high unemployment rate in Liberia, many individuals engage in waste scavenging as a means of survival. These scavengers are exposed to various hazards, including infections, respiratory illnesses, and accidents, often operating in unsafe environments without protective equipment. This study applied the Job Demands-Resources (JD-R) Theory to examine how the work environment mediates the relationship between occupational hygiene practices and health and safety among waste scavengers. The sample size was determined using Cochran’s formula for an unknown population, and data were collected from 384 waste scavengers in Liberia through snowball sampling. Partial Least Squares Structural Equation Modeling (PLS-SEM), specifically the bootstrapping method, was employed to analyze the data and evaluate both measurement and structural models. The results showed that occupational hygiene practices have a significant positive effect on both health and safety and the work environment. Additionally, the work environment was found to partially mediate the relationship between occupational hygiene practices and health and safety. The study recommends that the government implement regulations to ensure safe working conditions for waste scavengers. These policies should require waste management companies to adopt appropriate hygiene standards, safeguard the environment, and follow proper waste disposal protocols

    J Public Health Afr

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    Diethylene glycol (DEG) and ethylene glycol (EG) are organic compounds often found in various consumer products, including antifreeze and industrial solvents used in pharmaceutical preparations, as well as serving as raw materials for polymer manufacturing. Since September 2022, seven consecutive episodes of DEG and EG contamination have been reported across at least nine countries. A notable commonality among the affected products is that at least 14 of them are fixed-dose combinations (FDCs). However, the evidence supporting the efficacy of most of these combinations is insufficient, which renders their prescription, dispensing, and use irrational. Moreover, these products are not without risk, as they can cause adverse reactions. Several factors contribute to the prevalence of these irrational FDCs, including low production costs, consumer popularity, and a tendency to authorise locally manufactured products. As a result, many countries' pharmaceutical markets keep marketing authorisation for irrational FDCs. The persistent reports of DEG or EG contamination-especially those involving irrational fixed-dose combinations-present a crucial opportunity to enhance quality control measures. In addition, it is imperative to reevaluate the marketing authorisations of these products that lack evidence of safety and efficacy, adapting the national medicines lists and clinical guidelines to WHO recommendations. Strengthening regulatory frameworks and implementing stringent manufacturing and quality assurance standards are essential to prevent contamination incidents and ensure the safety of pharmaceutical products

    Role of Phosphoinositide 3-Kinase – Akt Signaling Pathway in the Age-Related Cytokine Dysregulation in Splenic Macrophages Stimulated via TLR-2 or TLR-4 Receptors

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    Age-associated defects in both B-lymphocytes and macrophages in elderly result in a reduction in the efficacy of vaccines to many Gram positive bacteria like Streptococcus pneumoniae. Splenic macrophages from aged mice have been shown to have a defect in production of pro-inflammatory cytokines (IL-6, IL-12, IL-1β, TNF-α) but exhibit increased production of IL-10 upon TLR4 ligation. Here we showed that aged macrophages demonstrate similar cytokine dysregulation phenotype upon stimulation with TLR2 ligands, or killed S. pneumoniae. We hypothesized that an age-associated increase in activity of phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway may be playing a causal role in the age-associated cytokine dysregulation. We found that gene expression of both the regulatory (p85β) and the catalytic (p110δ) subunits of Class IA PI3K is higher in aged than in young splenic macrophages. The age-associated increase in the activity of PI3K was also demonstrated by an upregulation of P-Akt and its downstream target, glycogen synthase kinase-3 (GSK-3). Inhibition of PI3K enhanced induction of pro-inflammatory cytokines, by TLR-2/TLR-1, TLR-2/TLR-6 and TLR-4 ligands as well as heat killed S. pneumoniae (HKSP). Therefore, targeting PI3-Kinase could rescue cytokine dysregulation in aged macrophages and enhance the relevant pro-inflammatory cytokines needed to support B-cell activation and differentiation

    Mpox in Africa: What we know and what is still lacking.

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    Emerging as a major global health threat, Mpox previously known as Monkeypox has drawn attention due to a worrying surge in cases. This zoonotic disease, native to Central and West Africa, is marked by fever, rash, and lymphadenopathy and is primarily spread through direct contact with infected animals or people and indirectly through contaminated objects. Recent studies have indicated possible sexual transmission, underscoring how human behavior and environmental changes are increasing its prevalence, even though human-to-human transmission is less efficient than that of smallpox. Mpox is endemic in several African countries, and currently, the infection has spread in non-endemic countries, including Rwanda, Uganda, and Kenya. Democratic Republic of Congo is the epicenter of the current Mpox outbreak. From January 1, 2022, to August 6, 2024, sixteen African countries reported Mpox outbreak. Several factors, including population immunity deficiencies and changes to the environment and ecology, have led to the widespread of Mpox in Africa. Challenges such as the fragile healthcare system, limited vaccine availability and access, weak surveillance, and low public awareness poses difficulty in containing the infection in affected countries. Given the potential of Mpox to disrupt several sectors including health systems, which may ultimately reverse progress in achieving the sustainable development goals by 2030. It is imperative for countries, both within and outside Africa, to extend financial aid and human resources to combat the infection effectively
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