Pharmacological justification for the ethnomedicinal use of Amblygonocarpus andongensis stem bark in pain relief

Amblygonocarpus andongensis (family: Mimosaceae) is ethnomedicinally used in Northern Nigeria for the relief of pain. The methanolic extract of the plant stem bark was evaluated for anti-nociceptive activity using acetic acid-induced writhing model and formalin test in mice. Anti-inflammatory property was tested on egg albumin-induced oedema in rats while agar dilution method was used for antimicrobial effect. The acute toxicity effect (LD50) was also determined via intraperitoneal route. The results showed the LD50 value to be 547.7 mg/kg i.p. There was a significant (P < 0.05) dose-dependent reduction of acetic acid-induced pain at 50, 100, 200 mg/kg i.p. The extract at the same doses significantly (P < 0.05) inhibited pains in both early and late phases of the formalin test. However, the extract showed neither anti-inflammatory nor anti-microbial effects. The results corroborate the folkloric use of the plant

Evaluation of the Anticancer Activity of Bioactive Fraction G Extracted from \u3cem\u3ePavetta crassipes\u3c/em\u3e in Malignant Brain Tumor Cell Lines

Objective: Natural products have served as sources of lead compounds that are commonly used in the treatment of human diseases including cancer. Pavetta crassipes has been widely demonstrated to have ethnopharmacological potential in the management of malaria, gastrointestinal conditions, central nervous system behavioral disorders, hypertension, and cancer. The goal of our study was to evaluate the biological and molecular effects of Fraction G, obtained from the plant Pavetta crassipes, on glioblastoma invasive growth and survival. Methodology: The antiproliferative effects of Fraction G, obtained from Pavetta crassipes, was evaluated using the trypan blue exclusion, (3-(4, 5-Dimethylthiazol- 2yl)-2, 5-Diphenyltetrazolium Bromide; MTT), and lactate dehydrogenase (LDH) assays. Flow cytometry and Western blotting analyses were carried out to examine the effects of Fraction G on cell cycle check-points and its effects on epidermal growth factor receptor-mediated signaling of AKT and MAPK pathways. Results: In this paper, we report that the Fraction G obtained from the plant Pavetta crassipes induced a reduction in glioma cell viability and proliferation as well as induced an increase in apoptosis as evidenced by cleaved PARP, increased caspase 3/7 activity, and cell cycle arrest in the G0/G1 check point. Furthermore, we report that Fraction G inhibited the phosphorylation of AKT and MAPK following EGF treatment. Conclusion: Taken together, our results demonstrate that Fraction G has potent inhibitory effects on pathways involved in glioblastoma proliferation and survival

a systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury

Funding Information: Countries provided feedback on the estimates through WHO's consultation of its 194 Member States. We specially acknowledge the ILO for its strategic contributions, as well as its sharing of data and contributions to the production of the estimates. Eurostat produced and shared the transition probabilities for exposure to UVR assigned via proxy of occupation for 27 countries in the European Region. Dr Yuka Ujita (ILO) and then Dr Halim Hamzaoui (ILO) were the ILO focal point for the WHO/ILO Joint Estimates. Marion McFeedy (consultant to the ILO) contributed to initial database development, and Dr Bochen Cao (WHO) shared WHO Global Health Estimates. Dr Claudine Backes (WHO) and Dr Emilie van Deventer (WHO) contributed to the early development of the estimation approach. Jessica CY Ho (WHO), Wahyu R Mahanani (WHO), Dr Bálint Náfrádi (ILO), Dr Annette M Prüss (WHO) and Dr Yuka Ujita provided feedback on an earlier version of the manuscript. Dr Ivan D Ivanov (WHO), Nancy Leppink (ILO), Franklin Muchiri (ILO), Dr Maria P Neira (WHO), Vera L Isaac Paquete-Perdigão (ILO) and Joaquim P Pintado Nunes (ILO) contributed to the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury. Dr Maria P Neira and Vera L Isaac Paquete-Perdigão provided overall guidance. Funding Information: This modelling study was prepared with financial support to WHO from: the National Institute for Occupational Safety and Health of the Centers for Disease Control and Prevention of the United States of America (Grant 1E11OH0010676-02, Grant 6NE11OH010461-02-01 and Grant 5NE11OH010461-03-00); the German Federal Ministry of Health (BMG Germany) under the BMG-WHO Collaboration Programme 2020–2023 (WHO specified award ref. 70672); and the Spanish Agency for International Cooperation (AECID) (WHO specified award ref. 71208). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Publisher Copyright: © 2023 International Labour Organization, World Health OrganizationBackground: A World Health Organization (WHO) and International Labour Organization (ILO) systematic review reported sufficient evidence for higher risk of non-melanoma skin cancer (NMSC) amongst people occupationally exposed to solar ultraviolet radiation (UVR). This article presents WHO/ILO Joint Estimates of global, regional, national and subnational occupational exposures to UVR for 195 countries/areas and the global, regional and national attributable burdens of NMSC for 183 countries, by sex and age group, for the years 2000, 2010 and 2019. Methods: We calculated population-attributable fractions (PAFs) from estimates of the population occupationally exposed to UVR and the risk ratio for NMSC from the WHO/ILO systematic review. Occupational exposure to UVR was modelled via proxy of occupation with outdoor work, using 166 million observations from 763 cross-sectional surveys for 96 countries/areas. Attributable NMSC burden was estimated by applying the PAFs to WHO's estimates of the total NMSC burden. Measures of inequality were calculated. Results: Globally in 2019, 1.6 billion workers (95 % uncertainty range [UR] 1.6–1.6) were occupationally exposed to UVR, or 28.4 % (UR 27.9–28.8) of the working-age population. The PAFs were 29.0 % (UR 24.7–35.0) for NMSC deaths and 30.4 % (UR 29.0–31.7) for disability-adjusted life years (DALYs). Attributable NMSC burdens were 18,960 deaths (UR 18,180–19,740) and 0.5 million DALYs (UR 0.4–0.5). Men and older age groups carried larger burden. Over 2000–2019, attributable deaths and DALYs almost doubled. Conclusions: WHO and the ILO estimate that occupational exposure to UVR is common and causes substantial, inequitable and growing attributable burden of NMSC. Governments must protect outdoor workers from hazardous exposure to UVR and attributable NMSC burden and inequalities.publishersversionpublishe

Implementing novel regimens for drug-resistant TB in South Africa : what can the world learn?

CITATION: Ndjeka, N. et al. 2020. Implementing novel regimens for drug-resistant TB in South Africa: what can the world learn?. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 24(10):1073–1080. doi:10.5588/ijtld.20.0174The original publication is available at https://www.ingentaconnect.com/content/iuatld/ijtldWorldwide uptake of new drugs in the treatment of rifampicin-resistant tuberculosis (RR-TB) has been extremely low. In June 2018, ahead of the release of the updated WHO guidelines for the management of RR-TB, South Africa announced that bedaquiline (BDQ) would be provided to virtually all RR-TB patients on shorter or longer regimens. South Africa has been the global leader in accessing BDQ for patients with RR-TB, who now represent 60% of the global BDQ cohort. The use of BDQ within a shorter modified regimen has generated the programmatic data underpinning the most recent change in WHO guidelines endorsing a shorter, injectable-free regimen. Progressive policies on access to new drugs have resulted in improved favourable outcomes and a reduction in mortality among RR-TB patients in South Africa. This supported global policy change. The strategies underpinning these bold actions include close collaboration between the South African National TB Programme and partners, introduction of new TB diagnostic tools in closely monitored conditions and the use of locally generated programmatic evidence to inform country policy changes. In this paper, we summarise a decade´s work that led to the bold decision to use a modified, short, injectable-free regimen with BDQ and linezolid under carefully monitored programmatic conditions.https://www.ingentaconnect.com/content/iuatld/ijtld/2020/00000024/00000010/art00016Publishers versio

Global, regional and national burdens of non-melanoma skin cancer attributable to occupational exposure to solar ultraviolet radiation for 183 countries, 2000–2019 : A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury

Background: A World Health Organization (WHO) and International Labour Organization (ILO) systematic review reported sufficient evidence for higher risk of non-melanoma skin cancer (NMSC) amongst people occupationally exposed to solar ultraviolet radiation (UVR). This article presents WHO/ILO Joint Estimates of global, regional, national and subnational occupational exposures to UVR for 195 countries/areas and the global, regional and national attributable burdens of NMSC for 183 countries, by sex and age group, for the years 2000, 2010 and 2019. Methods: We calculated population-attributable fractions (PAFs) from estimates of the population occupationally exposed to UVR and the risk ratio for NMSC from the WHO/ILO systematic review. Occupational exposure to UVR was modelled via proxy of occupation with outdoor work, using 166 million observations from 763 cross-sectional surveys for 96 countries/areas. Attributable NMSC burden was estimated by applying the PAFs to WHO's estimates of the total NMSC burden. Measures of inequality were calculated. Results: Globally in 2019, 1.6 billion workers (95 % uncertainty range [UR] 1.6–1.6) were occupationally exposed to UVR, or 28.4 % (UR 27.9–28.8) of the working-age population. The PAFs were 29.0 % (UR 24.7–35.0) for NMSC deaths and 30.4 % (UR 29.0–31.7) for disability-adjusted life years (DALYs). Attributable NMSC burdens were 18,960 deaths (UR 18,180–19,740) and 0.5 million DALYs (UR 0.4–0.5). Men and older age groups carried larger burden. Over 2000–2019, attributable deaths and DALYs almost doubled. Conclusions: WHO and the ILO estimate that occupational exposure to UVR is common and causes substantial, inequitable and growing attributable burden of NMSC. Governments must protect outdoor workers from hazardous exposure to UVR and attributable NMSC burden and inequalities.Peer reviewe

MDR/XDR-TB management of patients and contacts: Challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network.

The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities

DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function

Background: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. Results: We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E−03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang’s 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β = − 0.12, 95% CI = [− 0.16, − 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E−08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E−06). The “first-generation” clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. Conclusion: DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries