FOXM1 is a transcription factor required for a wide spectrum of essential biological functions, including DNA damage repair, cell proliferation, cell cycle progression, cell renewal, cell differentiation and tissue homeostasis. Recent evidence suggests that FOXM1 also has a role in many aspects of the DNA damage response. Accordingly, FOXM1 drives the transcription of genes for DNA damage sensors, mediators, signal transducers and effectors. As a result of these functions, it plays an integral part in maintaining the integrity of the genome and so is key to the propagation of accurate genetic information to the next generation. Preserving the genetic code is a vital means of suppressing cancer and other genetic diseases. Conversely, FOXM1 is also a potent oncogenic factor that is essential for cancer initiation, progression and drug resistance. An enhanced FOXM1 DNA damage repair gene expression network can confer resistance to genotoxic agents. Developing a thorough understanding of the regulation and function of FOXM1 in DNA damage response will improve the diagnosis and treatment of diseases including cancer, neurodegenerative conditions and immunodeficiency disorders. It will also benefit cancer patients with acquired genotoxic agent resistance.

FOXO3a and FOXM1 are two forkhead transcription factors with antagonistic roles in cancer and DNA damage response. FOXO3a functions like a typical tumour suppressor, whereas FOXM1 is a potent oncogene aberrantly overexpressed in genotoxic resistant cancers. FOXO3a not only represses FOXM1 expression but also its transcriptional output. Recent research has provided novel insights into a central role for FOXO3a and FOXM1 in DNA damage response. The FOXO3a-FOXM1 axis plays a pivotal role in DNA damage repair and the accompanied cellular response through regulating the expression of genes essential for DNA damage sensing, mediating, signalling and repair as well as for senescence, cell cycle and cell death control. In this manner, the FOXO3a-FOXM1 axis also holds the key to cell fate decision in response to genotoxic therapeutic agents and controls the equilibrium between DNA repair and cell termination by cell death or senescence. As a consequence, inhibition of FOXM1 or reactivation of FOXO3a in cancer cells could enhance the efficacy of DNA damaging cancer therapies by decreasing the rate of DNA repair and cell survival while increasing senescence and cell death. Conceptually, targeting FOXO3a and FOXM1 may represent a promising molecular therapeutic option for improving the efficacy and selectivity of DNA damage agents, particularly in genotoxic agent resistant cancer. In addition, FOXO3a, FOXM1 and their downstream transcriptional targets may also be reliable diagnostic biomarkers for predicting outcome, for selecting therapeutic options, and for monitoring treatments in DNA-damaging agent therapy.

PurposeTo define the prevalence and risk factors for epilepsy in children in a rural district of Tanzania by conducting a community-based case–control study.MethodsChildren aged 6–14 years with active epilepsy (at least two unprovoked seizures in the last 5 years) were identified in a cross-sectional survey in Tanzania. Cases were compared with age-matched controls.Key FindingsOverall 112 children with epilepsy (CWE) were identified; the unadjusted prevalence of epilepsy was 2.91 per 1,000 (95% confidence interval [95% CI] 2.4–3.5). The main seizure types were focal motor with secondary generalization in 73 (65.2%) of 112 and generalized convulsive seizures in 19 (16.9%) of 112. Adverse perinatal events were present in 16 (14%) of 112 cases but in no controls. In multivariate analysis, epilepsy was associated with number of parents who were resident at home (odds ratio [OR] 6.2 for none vs. both resident, 95% CI 1.5–25.5), history of adverse perinatal events (OR 14.9, 95% CI 1.4–151.3), family history of afebrile seizures (OR 5.7, 95% CI 1.0–27.5), and poor scholastic attainment (OR 8.6, 95% CI 4.0–18.4). Electroencephalography (EEG) and computed tomography (CT) scans were abnormal in 44 (44%) of 101 and 26 (29%) of 90 cases, respectively. Overall, 98 (88%) of 112 cases had focal features on assessment.SignificanceIn this study from sub-Saharan Africa, CWE predominantly had focal features that support the suggestion that most epilepsy in this region has a symptomatic etiology. Adverse perinatal events were strongly associated with epilepsy. Genetic and social factors may also be important. Epilepsy may be preventable in a significant proportion of children with better antenatal and perinatal care.

The eye care sector is well positioned to contribute to the advancement of universal health coverage within countries. Given the large unmet need for care associated with cataract and refractive error, coupled with the fact that highly cost-effective interventions exist, we propose that effective cataract surgery coverage (eCSC) and effective refractive error coverage (eREC) serve as ideal indicators to track progress in the uptake and quality of eye care services at the global level, and to monitor progress towards universal health coverage in general. Global targets for 2030 for these two indicators were endorsed by WHO Member States at the 74th World Health Assembly in May, 2021. To develop consensus on the data requirements and methods of calculating eCSC and eREC, WHO convened a series of expert consultations to make recommendations for standardising the definitions and measurement approaches for eCSC and eREC and to identify areas in which future work is required.