Background The presence of harmful environmental exposures, which disproportionately affects low-and-middle income countries (LMICs), contributes to >25% of deaths and diseases worldwide and detrimentally affects child neurodevelopment. Few resources succinctly summarize the existing literature on this topic. Our objective is to systematically review and characterize the evidence regarding the relationship between heavy metals and neurodevelopment of children in LMICs. Methods We conducted a medical librarian-curated search on multiple online databases to identify articles that included individuals <18 years living in a LMIC, quantitatively measured exposure to a heavy metal (either prenatal or postnatal), and used a standardized measurement of neurodevelopment (i.e. cognitive, language, motor, and behavior). Reviews, editorials, or case studies were excluded. Results were analyzed qualitatively, and quality was assessed. Results Of the 18,043 screened articles, 298 full-text articles were reviewed, and 100 articles met inclusion criteria. The included studies represented data from 19 LMICs, only one of which was classified as a low-income country. Ninety-four percent of postnatal lead and all postnatal manganese studies showed a negative association with metal exposure and neurodevelopment, which were the strongest relationships among the metals studied. Postnatal exposure of mercury was associated with poor neurodevelopment in only half of studies. Limited data on postnatal arsenic and cadmium suggests an association with worse neurodevelopment. Findings were mixed for prenatal arsenic and lead, although some evidence supports that the neurotoxicity of lead was amplified in the presence of manganese. Conclusions and potential impact We found that lead and manganese appear to consistently have a detrimental effect on the neurodevelopment of children, and more evidence is needed for mercury, arsenic, and cadmium. Better characterization of these effects can motivate and inform prioritization of much needed international policies and programs to reduce heavy metal exposures for young children within LMICs.

Background: The presence of harmful environmental exposures contributes to >25% of deaths and diseases worldwide. Child neurodevelopment is negatively impacted by environmental exposures, such as certain heavy metals. In low and middle-income countries, where numerous risk factors for poor neurodevelopment exist, it is unclear if this negative impact persists. Our objective with this systematic review is to evaluate the association between heavy metals and the neurodevelopment of children in low-and-middle income countries.     Methods: We conducted a search on PubMed MEDLINE, Embase, Cochrane Library, CINAHL, PsychInfo, Scopus, and Web of Science for articles that included individuals below the age of 18, quantitively measured exposure to a heavy metal and used a standardized measurement of neurodevelopment.      Results: Of the 15,250 screened articles, 292 full-text articles were reviewed, and 96 articles met inclusion criteria. These studies were conducted in 18 countries and included 46,080 participants ranging from birth – 18 years old. At least one domain of neurodevelopment was inversely correlated with 8/11 of arsenic studies, 3/3 of cadmium studies, 29/32 of lead studies, 11/11 of manganese studies, 9/18 of mercury studies, and 21/21 studies with multiple metals. There was no consistent evidence of arsenic affecting behavior; mercury negatively affected neurodevelopment in only half the studies, indicating that the benefits of consuming mercury-containing fish might outweigh the negative impact of mercury exposure; ethylmercury did not affect neurodevelopment; hair manganese was a much more consistent biomarker of manganese exposure than blood; and the neurotoxicity of lead was amplified in the presence of manganese.    Conclusions and potential impact: In low and middle-income countries, heavy metals have a significantly detrimental effect on the neurodevelopment of children, highlighting the need for more regulation.

Background and Aim: Qarahine, a polyherbal formulation consisting of natural active ingredients, is used to treat peptic ulcer. The aim of the present study was to investigate the protective effect of qarahine against aspirin (200 mg/kg) and ethanol (5 ml/kg) induced gastric ulcer rat models. Methodology: The pH of stomach contents, numbers of lesions in gastric mucosa, severity score, ulcer index and percentage protection were determined. The stomachs mucosa was also evaluated for morphological changes. Three doses of qarahine (250, 500 and 1000 mg/kg) were evaluated. Omeprazole (20 mg/kg) was used as a standard drug. Results: Different doses of qarahine significantly raised pH and reduced the ulcer index in both aspirin and ethanol induced ulcerative rats. Qarahine (500 mg/kg) provided 29.9% and 32.9% protection in aspirin and ethanol-induced ulcer models. Histopathological studies validated the biochemical outcomes. Conclusion: This study suggested gastroprotective effect of qarahine which might be due to increase in gastric mucus secretions and mucus protective mechanisms. However, further studies are necessary to clarify the mechanisms of action of qarahine.

Exploring host-HTLV-1 interactions and the molecular processes underpinning HTLV-1-mediated carcinogenesis is crucial for establishing effective treatments for viral infection and associated leukemia/lymphoma. Several HTLV-1 proteins have been shown to play important roles in the cellular transformation and immortalization of infected T cells. Through interactions with MAVS, STING, and RIP1, the HTLV-1 oncoprotein Tax suppresses the innate IFN response, resulting in the inhibition of TBK1-mediated phosphorylation of IRF3/IRF7. The HTLV-1 protein HBZ affects genomic integrity and inhibits target cell death and autophagy. Furthermore, it has been discovered that HBZ promotes the growth of ATL cells and aids in the evasion of infected cells from immunosurveillance. It currently appears that the efficacy of an individual's cytotoxic T cell (CTL) response to HTLV-1 is the most important single predictor of that person's provirus load, which can differ by more than 10,000-fold amongst HTLV-1-infected persons. We examine recent improvements in our knowledge of the pathophysiology, or underlying processes, of the illness produced by HTLV-1 infection in this article. Furthermore, we explore the future approach for targeting HTLV-1-associated malignancies and anti-HTLV-1 therapies. The pathogenic agent of adult T-cell leukemia/lymphoma (ATL) is human T-cell lymphotropic virus type 1 (HTLV-1). ATL is a fast-developing clonal tumour of CD4+ T cells which are cellular and viral protein interactions and pave the way for the discovery of new classes of cellular modulators, which may induce Tax oncogenesis and its impact on survival signalling pathways such as the NF-B and PI3K-Akt pathways, therapeutic target opportunities for ATL have been presented in two collaborative studies.