The effect of nutrition-specific and nutrition-sensitive interventions on the double burden of malnutrition in low-income and middle-income countries: a systematic review.

BACKGROUND: Low-income and middle-income countries (LMICs) experiencing nutrition transition face an increasing double burden of malnutrition (DBM). WHO has urged the identification of risks and opportunities in nutrition interventions to mitigate the DBM, but robust evidence is missing. This review summarises the effect of nutrition-specific and nutrition-sensitive interventions on undernutrition and overnutrition in LMICs. METHODS: We searched four major databases and grey literature for publications in English, French, Portuguese, and Spanish from Jan 1, 2000, to Aug 14, 2023. Eligible studies evaluated nutrition-specific or nutrition-sensitive interventions on both undernutrition and overnutrition, employing robust study designs (individually randomised, cluster randomised, and non-randomised trials; interrupted time series; controlled before-after; and prospective cohort studies). Studies were synthesised narratively, and classified as DBM-beneficial, potentially DBM-beneficial, DBM-neutral, potentially DBM-harmful, and DBM-harmful, using vote counting. This review is registered with PROSPERO (CRD42022320131). FINDINGS: We identified 26 studies evaluating 20 nutrition-specific (maternal and child health [MCH] and school-based programmes) and six nutrition-sensitive (conditional cash transfers and other social policies) interventions. Seven of eight MCH interventions providing food-based or nutritional supplements indicated possible DBM-harmful effects, associated with increased maternal or child overweight. Most school-based programmes and MCH interventions that target behavioural change were considered potentially DBM-beneficial. Two studies of conditional cash transfers suggested DBM-beneficial effects in children, whereas one indicated potentially harmful effects on maternal overweight. A study on a family planning service and one on an education reform revealed possible long-term harmful effects on obesity. INTERPRETATION: There is considerable scope to repurpose existing nutrition interventions to reduce the growing burden of the DBM in LMICs. In settings undergoing rapid nutrition transition, specific policy attention is required to ensure that food-based or supplement-based MCH programmes do not unintentionally increase maternal or child overweight. Consistent reporting of undernutrition and overnutrition outcomes in all nutrition interventions is essential to expand the evidence base to identify and promote interventions maximising benefits and minimising harms on the DBM. FUNDING: President's Scholarship (Imperial College London) and National Institute for Health and Care Research. TRANSLATIONS: For the Portuguese, Spanish and French translations of the abstract see Supplementary Materials section.

A combination of direct reversion and nucleotide excision repair counters the mutagenic effects of DNA carboxymethylation.

Distinct cellular DNA damage repair pathways maintain the structural integrity of DNA and protect it from the mutagenic effects of genotoxic exposures and processes. The occurrence of O6-carboxymethylguanine (O6-CMG) has been linked to meat consumption and hypothesized to contribute to the development of colorectal cancer. However, the cellular fate of O6-CMG is poorly characterized and there is contradictory data in the literature as to how repair pathways may protect cells from O6-CMG mutagenicity. To better address how cells detect and remove O6-CMG, we evaluated the role of two DNA repair pathways in counteracting the accumulation and toxic effects of O6-CMG. We found that cells deficient in either the direct repair protein O6-methylguanine-DNA methyltransferase (MGMT), or key components of the nucleotide excision repair (NER) pathway, accumulate higher levels O6-CMG DNA adducts than wild type cells. Furthermore, repair-deficient cells were more sensitive to carboxymethylating agents and displayed an increased mutation rate. These findings suggest that a combination of direct repair and NER circumvent the effects O6-CMG DNA damage.

Systematic review and meta-analysis of integrated studies on antimicrobial resistance genes in Africa-A One Health perspective.

BACKGROUND: Increasing antimicrobial resistance (AMR) raises serious health and financial concerns. However, the main drivers of the emergence, spread and subsequent colonisation of resistant bacterial strains between humans, animals and the environment are still poorly understood. OBJECTIVE: The aim of this review was to identify molecular studies on AMR in One Health settings in Africa and to determine the prevalence of antimicrobial resistance genes in humans, animals and the environment. Due to the very low number of studies including environmental samples, the meta-analysis only includes data obtained from animals and humans. METHODS: The PubMed, Web of Science and Scopus databases were searched, identifying 10 464 publications on AMR in Africa from January 1st, 2000 until June 1st, 2020. Inclusion criteria were: (i) Integrated studies assessing AMR simultaneously in an animal-human, animal-environment, human-environment or animal-human-environment context, (ii) Genotypic characterisation of AMR and (iii) temporal and spatial relationship between samples from humans and animals. Statistical random-effects model meta-analysis was performed. RESULTS: Overall, 18 studies met our eligibility criteria and were included in this review. Six studies investigated Escherichia coli and Salmonella spp. (N = 6). The most prevalent AMR genes in animals included sul1 (36.2%), sul2 (32.0%), tetA (31.5%), strB (30.8%) and blaTEM (30.0%), whereas sul2 (42.4%), tetA (42.0%), strB (34.9%), blaTEM (28.8%) and sul1 (27.8%) were most prevalent in humans. We observed no clear pattern for a higher prevalence in either the animal or the human reservoir. CONCLUSION: To date, data on AMR in a One Health perspective in Africa are scarce. Prospective and longitudinal studies using an integrated One Health approach assessing the environment, animals and humans at the same time are needed to better understand the main drivers of AMR sharing in Africa.

Direct Alkylation of Deoxyguanosine by Azaserine Leads to O6-Carboxymethyldeoxyguanosine.

The O6-alkylguanosine adduct O6-carboxymethyldeoxyguanosine (O6-CMdG) has been detected at elevated levels in blood and tissue samples from colorectal cancer patients and from healthy volunteers after consuming red meat. The diazo compound l-azaserine leads to the formation of O6-CMdG as well as the corresponding methyl adduct O6-methyldeoxyguanosine (O6-MedG) in cells and is therefore in wide use as a chemical probe in cellular studies concerning DNA damage and mutation. However, there remain knowledge gaps concerning the chemical basis of DNA adduct formation by l-azaserine. To characterize O6-CMdG formation by l-azaserine, we carried out a combination of chemical and enzymatic stability and reactivity studies supported by liquid chromatography tandem mass spectrometry for the simultaneous quantification of O6-CMdG and O6-MedG. We found that l-azaserine is stable under physiological and alkaline conditions as well as in active biological matrices but undergoes acid-catalyzed hydrolysis. We show, for the first time, that l-azaserine reacts directly with guanosine (dG) and oligonucleotides to form an O6-serine-CMdG (O6-Ser-CMdG) adduct. Moreover, by characterizing the reaction of dG with l-azaserine, we demonstrate that O6-Ser-CMdG forms as an intermediate that spontaneously decomposes to form O6-CMdG. Finally, we quantified levels of O6-CMdG and O6-MedG in a human cell line exposed to l-azaserine and found maximal adduct levels after 48 h. The findings of this work elucidate the chemical basis of how l-azaserine reacts with deoxyguanosine and support its use as a chemical probe for N-nitroso compound exposure in carcinogenesis research, particularly concerning the identification of pathways and factors that promote adduct formation.