Copy number alteration (CNA) profiling of human tumors has revealed recurrent patterns of DNA amplifications and deletions across diverse cancer types. These patterns are suggestive of conserved selection pressures during tumor evolution but cannot be fully explained by known oncogenes and tumor suppressor genes. Using a pan‐cancer analysis of CNA data from patient tumors and experimental systems, here we show that principal component analysis‐defined CNA signatures are predictive of glycolytic phenotypes, including 18F‐fluorodeoxy‐glucose (FDG) avidity of patient tumors, and increased proliferation. The primary CNA signature is enriched for p53 mutations and is associated with glycolysis through coordinate amplification of glycolytic genes and other cancer‐linked metabolic enzymes. A pan‐cancer and cross‐species comparison of CNAs highlighted 26 consistently altered DNA regions, containing 11 enzymes in the glycolysis pathway in addition to known cancer‐driving genes. Furthermore, exogenous expression of hexokinase and enolase enzymes in an experimental immortalization system altered the subsequent copy number status of the corresponding endogenous loci, supporting the hypothesis that these metabolic genes act as drivers within the conserved CNA amplification regions. Taken together, these results demonstrate that metabolic stress acts as a selective pressure underlying the recurrent CNAs observed in human tumors, and further cast genomic instability as an enabling event in tumorigenesis and metabolic evolution.
Background Despite the body of literature that links anemia with poorer cognition in children and the evidence that the severity of the effects of anemia on children’s cognition vary in different populations, few studies have investigated the effects of anemia on the cognitive development of Chinese children. Study Design This longitudinal cohort includes 171 children from a developing region of China. Hemoglobin and iron levels were taken when the children were 4 years old. At age 6, the children’s cognition was tested with Chinese WPPSI. Psychosocial information was also used in analyses. Results Results showed that the children who had low Hb levels had significantly lower scores in PIQ, but not VIQ. Although blood Fe levels were not shown to moderate the link between hemoglobin levels and IQ, we found children who performed the best on IQ tests exhibited low iron levels concurrent with high hemoglobin levels, whereas the group who performed the worst exhibited high iron but low hemoglobin levels. We also found that psychosocial adversity did not differ significantly between children who had normal or low hemoglobin levels, although the effect of hemoglobin on PIQ became only suggestive after controlling for psychosocial adversity, therefore the relationship is not causal but only a suggestive association. Conclusion Our findings are in agreement with literature on the negative effects of anemia on children’s cognition and point to the possibility that the portions of the brain associated with PIQ components are particularly affected by low Hb during crucial periods of development.
Previous research supports the link among malnutrition, cognitive dysfunction, and behavioral outcomes; however, less research has focused on micronutrient deficiencies. This study investigates whether micronutrient deficiencies, specifically blood zinc and iron levels, will be associated with increased behavior problem scores, including internalizing and externalizing behaviors. 1314 Children (55% boys and 45% girls) from the Jintan Preschool Cohort in China participated in this study. Venous blood samples were collected and analyzed for zinc and iron when the children were 3–5 years old. Behavior problems were measured with the Child Behavior Checklist (CBCL), which was completed by the parents when children were in their last months of preschool (mean age 5.6 years). General linear multivariate modeling was used, with adjustment for important sociodemographic variables. The results indicate that low zinc levels alone (p = 0.024) and combined low zinc and iron levels (p = 0.022) are significantly associated with increased reports of total behavior problems. We did not find an association between low iron and behavior problems. With regards to sociodemographics, living in the suburbs is associated with increased internalizing problems, while higher mother’s education and being female were associated with decreased externalizing problems. This study suggests that micronutrient deficiencies and sociodemographic facts are associated with behavior problems in preschoolers.
Background: Still considered one of the most prevalent nutritional problems in the world, anemia has been shown in many studies to have deleterious effects on neurobehavioral development. While most research efforts have focused on investigating the effects of anemia on social and emotional development of infants by using a cross-sectional design, research is still needed to investigate whether early childhood anemia, beyond infantile years, is linked with behavioral problems. Objective: This study assessed whether (1) hemoglobin (Hb) levels in early childhood are associated with externalizing behavior; and (2) this relationship is confounded by social adversity. Methods: Hemoglobin levels were taken from children (N = 98) of the China Jintan Cohort Study at age 4 years, and externalizing behaviors (attention and aggression) were assessed with the Child Behavior Checklist (ASEBA-CBCL) at age 6 years (mean age 5.77 ± 0.39 years old). Results: Compared with other children in the sample, children with relatively lower Hb levels at age 4 had more behavioral problems in both attention and aggression at age 6, independent of social adversity. For boys, this association was significant for attention problems, which did not interact with social adversity. For girls, the association was significant for aggression, which interacted with social adversity. While girls on average exhibited higher social adversity than boys, the main effect of Hb was only significant in girls with low social adversity. Conclusions: These results indicate that there is an inverse association between hemoglobin levels and later behavioral problems. Findings of this study suggest that regular monitoring of children’s hemoglobin levels and appropriate intervention may help with early identification of behavioral problems.
In recent years, a role for epigenetic modifications in the pathophysiology of disease has received significant attention. Many studies are now beginning to explore the gene–environment interactions, which may mediate early-life exposure to risk factors, such as nutritional deficiencies and later development of behavioral problems in children and adults. In this paper, we review the current literature on the role of epigenetics in the development of psychopathology, with a specific focus on the potential for epigenetic modifications to link nutrition and brain development. We propose a conceptual framework whereby epigenetic modifications (e.g., DNA methylation) mediate the link between micro- and macro-nutrient deficiency early in life and brain dysfunction (e.g., structural aberration, neurotransmitter perturbation), which has been linked to development of behavior problems later on in life.
The importance of interprofessional training in healthcare to improve quality of care and health outcomes has been increasingly recognized. This pilot study used an interprofessional and interdisciplinary team of undergraduate health and pre-health students to establish a unique community partnership with a local elementary school in developing and implementing a nutrition/exercise educational intervention. Our results suggest that children as young as 8 years old are capable of learning new information related to the benefits of particular food groups, are capable of retaining this knowledge for 6 months, and that an intervention program as short as one hour every few months stand to make significant impact on children’s knowledge about proper nutrition and healthy lifestyles. Our results suggest the potential benefits of further expanding the short-term intervention into a longer-term community-based curriculum targeting a younger age group previously or currently practiced.. Furthermore, this pilot study suggests that undergraduate health and pre-health students can form an interprofessional and collaborative team to take an active role in the dissemination of nutrition knowledge in the community.
Objectives Antibiotics for acute respiratory illness (ARI) constitute most pediatric medication use and contribute to the emergence of antimicrobial resistance. We investigated antibiotic prescription risk factors for ARI in pediatric clinics and clinical follow-up in individuals prescribed and not prescribed antibiotics. Methods In this observational study, we enrolled children ages 2 to 17 years old presenting with ARI with fever to two academic pediatric primary care outpatient clinics during influenza season 2013–2014. We collected information on demographics, initial symptoms, medical conditions, laboratory tests, discharge diagnoses, treatments, and 30 days of follow-up medical encounters. Factors associated with antibiotic prescription receipt were evaluated using logistic regression. Results Of 206 consented and enrolled children, 59 (29%) were prescribed antibiotics, 51 of 59 (86%) for indicated diagnoses: 34 for streptococcal pharyngitis, 15 for acute otitis media (AOM), and 2 for pneumonia. Discharge diagnoses were the only factors independently associated with an antibiotic prescription. Of children prescribed/not prescribed an antibiotic, 17%/17% received follow-up telephone calls and 27%/17% had follow-up visits related to ARI within 30 days. Two children with AOM were prescribed a second antibiotic during follow-up, and one developed Clostridium difficile colitis. Eighteen of 206 (9%) additional children were prescribed antibiotics within 30 days for ARI symptoms, 17 for streptococcal pharyngitis, AOM, pneumonia, or sinusitis; one was prescribed antibiotics for influenza-like illness. Conclusions Among study children 2 to 17 years old with outpatient ARI, 29% were prescribed antibiotics at the initial visit and another 9% were prescribed antibiotics during the 30-day follow-up (most were for appropriate indications). Further decreasing antibiotic use in similar settings will likely require wider implementation of watchful waiting for AOM, a change in guidelines for pharyngitis management, and/or reductions in these diseases.
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