Feasibility and success of a non-sedated brain MRI training protocol in 7-year-old children from rural and semi-rural Colombia.

BACKGROUND: Brain magnetic resonance imaging (MRI) is a crucial tool for clinical evaluation of the brain and neuroscience research. Obtaining successful non-sedated MRI in children who live in resource-limited settings may be an additional challenge. OBJECTIVE: To present a feasibility study of a novel, low-cost MRI training protocol used in a clinical research study in a rural/semi-rural region of Colombia and to examine neurodevelopmental factors associated with successful scans. MATERIALS AND METHODS: Fifty-seven typically developing Colombian children underwent a training protocol and non-sedated brain MRI at age 7. Group training utilized a customized booklet, an MRI toy set, and a simple mock scanner. Children attended MRI visits in small groups of two to three. Resting-state functional and structural images were acquired on a 1.5-Tesla scanner with a protocol duration of 30-40 minutes. MRI success was defined as the completion of all sequences and no more than mild motion artifact. Associations between the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Movement Assessment Battery for Children (MABC), Behavioral Rating Inventory of Executive Function (BRIEF), Child Behavior Checklist (CBCL), and Adaptive Behavior Assessment System (ABAS) scores and MRI success were analyzed. RESULTS: Mean (SD) age at first MRI attempt was 7.2 (0.2) years (median 7.2 years, interquartile range 7.1-7.3 years). Twenty-six (45.6%) participants were male. Fifty-one (89.5%) children were successful across two attempts; 44 (77.2%) were successful on their first attempt. Six (10.5%) were unsuccessful due to refusal or excessive motion. Age, sex, and scores across all neurodevelopmental assessments (MABC, TVIP, ABAS, BRIEF, CBCL, NIH Toolbox Flanker, NIH Toolbox Pattern Comparison, WPPSI) were not associated with likelihood of MRI success (P=0.18, 0.19, 0.38, 0.92, 0.84, 0.80, 1.00, 0.16, 0.75, 0.86, respectively). CONCLUSION: This cohort of children from a rural/semi-rural region of Colombia demonstrated comparable MRI success rates to other published cohorts after completing a low-cost MRI familiarization training protocol suitable for low-resource settings. Achieving non-sedated MRI success in children in low-resource and international settings is important for the continuing diversification of pediatric research studies.

Neurodevelopmental Outcomes of Normocephalic Colombian Children with Antenatal Zika Virus Exposure at School Entry.

The long-term neurodevelopmental effects of antenatal Zika virus (ZIKV) exposure in children without congenital Zika syndrome (CZS) remain unclear, as few children have been examined to the age of school entry level. A total of 51 Colombian children with antenatal ZIKV exposure without CZS and 70 unexposed controls were evaluated at 4-5 years of age using the Behavior Rating Inventory of Executive Function (BRIEF), the Pediatric Evaluation of Disability Inventory (PEDI-CAT), the Bracken School Readiness Assessment (BSRA), and the Movement Assessment Battery for Children (MABC). The mean ages at evaluation were 5.3 and 5.2 years for cases and controls, respectively. Elevated BRIEF scores in Shift and Emotional Control may suggest lower emotional regulation in cases. A greater number of cases were reported by parents to have behavior and mood problems. BSRA and PEDI-CAT activity scores were unexpectedly higher in cases, most likely related to the COVID-19 pandemic and a delayed school entry among the controls. Although PEDI-CAT mobility scores were lower in cases, there were no differences in motor scores on the MABC. Of 40 cases with neonatal neuroimaging, neurodevelopment in 17 with mild non-specific findings was no different from 23 cases with normal neuroimaging. Normocephalic children with ZIKV exposure have positive developmental trajectories at 4-5 years of age but differ from controls in measures of emotional regulation and adaptive mobility, necessitating continued follow-up.

Neurodevelopmental assessments used to measure preschoolers' cognitive development in Latin America: a systematic review.

OBJECTIVE: The objective of this study was to systematically review the standardized neurodevelopmental assessments used to study preschool-aged children's cognitive development in Spanish-speaking Latin America. METHODS: The authors systematically searched PubMed, PsycINFO, and ERIC databases for peer-reviewed articles from Spanish-speaking Latin American countries. Articles were included if they measured cognitive development among children aged 2-6 years using at least one standardized assessment tool; 97 articles were included and reviewed in accordance with PRISMA guidelines to assess their use of these tools. RESULTS: Ninety-seven studies across 13 countries used a total of 41 assessments to measure cognitive development; most widely used were the Wechsler intelligence scales (n = 46/97), particularly the Wechsler Preschool and Primary Scale of Intelligence and Wechsler Intelligence Scale for Children (n = 23 and 29, respectively). Other common assessments included the McCarthy Scales of Children's Abilities (n = 9), Raven's Progressive Matrices (n = 9), Child Neuropsychological Assessment (n = 8), and Peabody Picture Vocabulary Test (n = 7). In regions where normative data for a given assessment were unpublished, authors commonly used norms from the United States, Mexico, or Spain or did not report standard scores in their analyses. CONCLUSIONS: The wide range of tools used in these studies presents a challenge for generalizing results when measuring the neurodevelopment of Latin American preschool-aged children. The low availability of normative data for specific regions reveals concerns if some tools are culturally and linguistically appropriate even when Spanish is a common language, particularly in low-resource settings. Future work to forge greater consistency in the use of validated measures, clarity in reporting research methods, and publication of regional normative data would benefit the field.

Positive and negative effects of the COVID-19 pandemic on families of young children in rural Colombia and implications for child outcome research.

BACKGROUND: The COVID-19 pandemic has impacted the lives of children and families worldwide. The objective of this study is to examine exposures and impact of the COVID-19 pandemic on preschool-aged children and caregivers in the Atlántico region of Colombia. METHODS: The COVID-19 Exposure and Family Impact Scales (CEFIS) questionnaire was administered in Fall 2021 to 63 caregivers of children in Sabanalarga, Colombia enrolled in a neurodevelopment study as healthy controls. The CEFIS assesses pandemic-related exposures/events and impact; higher scores indicate greater exposure and negative impact. Descriptive and correlation analyses among exposure and impact scores were conducted. RESULTS: Caregivers reported a mean (standard deviation[SD]) of 11.1 (3.2) among 25 COVID-19-related exposures/events; most common types included stay-at-home orders, school closures, disruptions to living conditions and income loss. Total number of events was correlated with higher caregiver (P < .001) and child distress (P = .002). However, the mean (SD) impact score of 2.0 (0.6) suggests a trend toward more positive impact than negative. Caregivers reported improvements to sleep, exercise and family interactions. Some caregivers (n = 21) qualitatively reported negative effects including unemployment, fear/anxiety and inability to visit family, and positive effects such as unification, family closeness and spending more time with children. CONCLUSIONS: This study highlights the importance of comprehensively exploring positive and negative impacts of COVID-19 and families' subsequent resilience and transformation. Using tools like the CEFIS, those seeking to mitigate negative impacts can contextualize data to better understand study outcomes and tailor services, resources and policy to families' unique needs. CEFIS data likely depend on timing, economic/public health resources and cultural values; future work should prioritize understanding the generalizability of CEFIS findings across samples.

Preschool neurodevelopment in Zika virus-exposed children without congenital Zika syndrome.

BACKGROUND: Children with in utero Zika virus (ZIKV) exposure without congenital Zika syndrome (CZS) are at risk for abnormal neurodevelopment. Preschool-age outcomes for children with antenatal ZIKV exposure have not yet been established. METHODS: Children with in utero ZIKV exposure and non-exposed controls had neurodevelopmental evaluations at age 3-5 years in Sabanalarga, Colombia. Cases did not have CZS and were previously evaluated prenatally through age 18 months. Controls were born before ZIKV arrival to Colombia. Neurodevelopmental assessments included Pediatric Evaluation of Disability Inventory (PEDI-CAT), Behavior Rating Inventory of Executive Function (BRIEF-P), Bracken School Readiness Assessment (BSRA), and Movement Assessment Battery for Children (MABC). Family demographics and child medical history were recorded. RESULTS: Fifty-five ZIKV-exposed children were evaluated at mean age 3.6 years and 70 controls were evaluated at 5.2 years. Family demographics were similar between groups. BRIEF-P t-scores were higher for cases than controls in shift and flexibility domains. Cases had lower PEDI-CAT mobility t-scores compared to controls. There was no difference in MABC between groups. In 11% of cases and 1% of controls, parents reported child mood problems. CONCLUSIONS: Children with in utero ZIKV exposure without CZS may demonstrate emerging differences in executive function, mood, and adaptive mobility that require continued evaluation. IMPACT: Preschool neurodevelopmental outcome in children with in utero Zika virus exposure is not yet known, since the Zika virus epidemic occurred in 2015-2017 and these children are only now entering school age. This study finds that Colombian children with in utero Zika virus exposure without congenital Zika syndrome are overall developing well but may have emerging differences in executive function, behavior and mood, and adaptive mobility compared to children without in utero Zika virus exposure. Children with in utero Zika virus exposure require continued multi-domain longitudinal neurodevelopmental evaluation through school age.

High-Throughput Analysis of Gene Function in the Bacterial Predator Bdellovibrio bacteriovorus.

Bdellovibrio bacteriovorus is a bacterial predator capable of killing and replicating inside most Gram-negative bacteria, including antibiotic-resistant pathogens. Despite growing interest in this organism as a potential therapeutic, many of its genes remain uncharacterized. Here, we perform a high-throughput genetic screen with B. bacteriovorus using transposon sequencing (Tn-seq) to explore the genetic requirements of predation. Two hundred one genes were deemed essential for growth in the absence of prey, whereas over 100 genes were found to be specifically required for predative growth on the human pathogens Vibrio cholerae and Escherichia coli in both planktonic and biofilm states. To further this work, we created an ordered-knockout library in B. bacteriovorus and developed new high-throughput techniques to characterize the mutants by their stage of deficiency in the predator life cycle. Using microscopy and flow cytometry, we confirmed 10 mutants defective in prey attachment and eight mutants defective in prey rounding. The majority of these genes are hypothetical and previously uncharacterized. Finally, we propose new nomenclature to group B. bacteriovorus mutants into classes based on their stage of predation defect. These results contribute to our basic understanding of bacterial predation and may be useful for harnessing B. bacteriovorus to kill harmful pathogens in the clinical setting.IMPORTANCEBdellovibrio bacteriovorus is a predatory bacterium that can kill a wide range of Gram-negative bacteria, including many human pathogens. Given the global rise of antibiotic resistance and dearth of new antibiotics discovered in the past 30 years, this predator has potential as an alternative to traditional antibiotics. For many years, B. bacteriovorus research was hampered by a lack of genetic tools, and the genetic mechanisms of predation have only recently begun to be established. Here, we comprehensively identify and characterize predator genes required for killing bacterial prey, as well as genes that interfere in this process, which may allow us to design better therapeutic predators. Based on our study, we and other researchers may ultimately be able to genetically engineer strains that have improved killing rates, target specific species of prey, or preferentially target prey in the planktonic or biofilm state.