This study intended to explore the neuropsychological ramifications in childhood acute lymphoblastic leukemia (ALL) survivors in Malaysia and to examine treatment-related sequelae. A case-control study was conducted over a 2-year period. Seventy-one survivors of childhood ALL who had completed treatment for a minimum of 1 year and were in remission, and 71 healthy volunteers were enlisted. To assess alertness (processing speed) and essential executive functioning skills such as working memory capacity, inhibition, cognitive flexibility, and sustained attention, seven measures from the Amsterdam Neuropsychological Tasks (ANT) program were chosen. Main outcome measures were speed, stability and accuracy of responses. Mean age at diagnosis was 4.50 years (SD ± 2.40) while mean age at study entry was 12.18 years (SD ± 3.14). Survivors of childhood ALL underperformed on 6 out of 7 ANT tasks, indicating poorer sustained attention, working memory capacity, executive visuomotor control, and cognitive flexibility. Duration of treatment, age at diagnosis, gender, and cumulative doses of chemotherapy were not found to correlate with any of the neuropsychological outcome measures. Childhood ALL survivors in our center demonstrated significantly poorer neuropsychological status compared to healthy controls.
There has been much evidence showing the repercussions of prenatal bisphenol A (BPA) exposure with a postnatal high fat-diet (HFD) on offspring's health. However, the information on how the interaction between these two variables affects the gut microbiome is rather limited. Hence, we investigated the impact of a postnatal trans fat diet (TFD) on the gut microbiome of offspring exposed to BPA during the prenatal period in an animal model. Pregnant rats were divided into 5 mg/kg/day BPA, vehicle Tween80 (P80) or control (CTL) drinking water until delivery (N = 6 per group). Then, weaned male pups were further subdivided into three normal diet (ND) groups (CTLND, P80ND, and BPAND) and three TFD groups (CTLTFD, P80TFD, and BPATFD) (n = 6 per group). 180-250 g of faecal samples were collected on days 50 and 100 to assess the composition of the offspring's intestinal flora using next-generation sequencing. The alpha diversity indices of TFD offspring with and without BPA were markedly lower than their ND counterparts (p<0.001-p<0.05). The beta diversity, hierarchical cluster and network analyses of the offspring's microbiome demonstrated that the microbiome species of the TFD group with and without BPA were distinctly different compared to the ND group. Consistently, TFD and ND offspring pairings exhibited a higher number of significantly different species (p<0.0001-p<0.05) compared to those exposed to prenatal BPA exposure and different life stages comparisons, as shown by the multivariate parametric analysis DESeq2. Predictive functional profiling of the offspring's intestinal flora demonstrated altered expressions of genes involved in metabolic pathways. In summary, the gut flora composition of the rat offspring may be influenced by postnatal diet instead of prenatal exposure to BPA. Our data indicate the possibility of perturbed metabolic functions and epigenetic modifications, in offspring that consumed TFD, which may theoretically lead to metabolic diseases in middle or late adulthood. Further investigation is necessary to fully understand these implications.