Development of a chemical probe against NUDT15.

The NUDIX hydrolase NUDT15 was originally implicated in sanitizing oxidized nucleotides, but was later shown to hydrolyze the active thiopurine metabolites, 6-thio-(d)GTP, thereby dictating the clinical response of this standard-of-care treatment for leukemia and inflammatory diseases. Nonetheless, its physiological roles remain elusive. Here, we sought to develop small-molecule NUDT15 inhibitors to elucidate its biological functions and potentially to improve NUDT15-dependent chemotherapeutics. Lead compound TH1760 demonstrated low-nanomolar biochemical potency through direct and specific binding into the NUDT15 catalytic pocket and engaged cellular NUDT15 in the low-micromolar range. We also employed thiopurine potentiation as a proxy functional readout and demonstrated that TH1760 sensitized cells to 6-thioguanine through enhanced accumulation of 6-thio-(d)GTP in nucleic acids. A biochemically validated, inactive structural analog, TH7285, confirmed that increased thiopurine toxicity takes place via direct NUDT15 inhibition. In conclusion, TH1760 represents the first chemical probe for interrogating NUDT15 biology and potential therapeutic avenues.

Fetal alcohol spectrum disorders (FASD) and youth firesetting: A call on criminal justice, emergency responder, and fire prevention specialists to become informed.

Central nervous system damage resulting from prenatal exposure to alcohol, often referred to as fetal alcohol spectrum disorders (FASD), commonly manifests as lacking cognitive functioning, problem solving, impulsivity, memory, executive functioning, and social skill deficits. For individuals with FASD, these brain-based deficits translate into impulsive behaviors and poorly thought-out decision-making, coupled with an inability to anticipate and recognize the sometimes very severe consequences of their behaviors. Not unexpectedly, individuals with FASD frequently find themselves disproportionately involved in the criminal justice system and mental health services. For some individuals with FASD, these behaviors can also include firesetting. First responders, like other health and legal professionals, are often unable to recognize the behavioral indicators of FASD, primarily due to a lack of training. As a result, firesetting behaviors are often attributed to deliberate, willful acts of delinquency, a desire to damage property, thrill seeking, or as attempts for personal gain, rather than being viewed as maladaptive attempts to solve problems by individuals who lack the tools to do this in more appropriate ways. These same skill deficits also present when individuals with FASD are interviewed about their involvement in such behaviors, sometimes resulting in confabulation, suggestibility, and false confessions. Further education and training in FASD are vital for first responders if they are to better support individuals with FASD and minimize their chances of becoming involved in firesetting behaviors. Furthermore, this training and education will help ensure that first responders can intervene in more appropriately when crisis situations do occur. This article will outline key behavioral symptoms of FASD as well as provide first responders with suggestions as to how to best support individuals when FASD is suspected. The brief quote that follows highlights some of the key challenges facing individuals with FASD and how poor decision-making and impulsiveness can result in severe consequences for the individual and those around them.

Fetal alcohol spectrum disorder and confabulation in psycholegal settings: A beginner's guide for criminal justice, forensic mental health, and legal interviewers.

Fetal alcohol spectrum disorders (FASD) are neurodevelopmental/neurobehavioral conditions caused by prenatal alcohol exposure (PAE). Impairments caused by PAE contribute to the over-representation of individuals with FASD in the United States juvenile and adult criminal justice systems. These same impairments can equally impact on individuals with FASD who are witnesses to or victims of crime who also have to navigate the complexities of the criminal justice system. Difficulties include increased susceptibility to confabulation throughout the legal process that, in turn, can contribute to increased rates of poor outcomes including false confessions and wrongful convictions. Individuals with FASD are particularity at risk of confabulation when they are subjected to tactics, such as stressful and anxiety-provoking situations, threats, and leading, suggestive, or coercive questioning. Many professionals in the forensic context are unfamiliar with FASD or related confabulation risk and may unintentionally utilize tactics that intensify impacts of pre-existing impairment. This article serves as a beginner's guide for professionals working in criminal justice settings by (a) providing research-based overviews of FASD and confabulation, (b) describing how FASD may lead to confabulation, and (c) suggesting ways that professionals can modify protocols when interacting with individuals with FASD. Suggestions in this article hold the potential to decrease the risk of confabulation in the criminal justice system and decrease problematic outcomes, such as false confessions and wrongful convictions among individuals with FASD.

COVID-19 Vaccine Uptake in Southeastern Ontario, Canada: Monitoring and Addressing Health Inequities.

CONTEXT: Implementation of a population-based COVID-19 vaccine strategy, with a tailored approach to reduce inequities in 2-dose coverage, by a mid-sized local public health agency in southeastern Ontario, Canada. PROGRAM: Coverage maps and crude and age-standardized coverage rates by material and social deprivation, urban/rural status, and sex were calculated biweekly and reviewed by local public health planners. In collaboration with community partners, the results guided targeted strategies to enhance uptake for marginalized populations. EVALUATION: The largest gaps in vaccine coverage were for those living in more materially deprived areas and rural residents-coverage was lower by 10.9% (95% confidence interval: -11.8 to -10.0) and 9.3% (95% confidence interval: -10.4 to -8.1) for these groups compared with living in less deprived areas and urban residents, respectively. The gaps for all health equity indicators decreased statistically significantly over time. Targeted strategies included expanding clinic operating hours and availability of walk-in appointments, mobile clinics targeted to marginalized populations, leveraging primary care partners to provide pop-up clinics in rural and materially and socially deprived areas, and collaborating with multiple partners to coordinate communication efforts, especially in rural areas. DISCUSSION: The scale and scope of monitoring and improving local vaccine uptake are unprecedented. Regular review of health equity indicators provided critical situational awareness for decision makers, allowing partners to align and tailor strategies locally and in collaboration with one another. Health care providers and pharmacies/pharmacists are key partners who require innovative support to increase uptake in marginalized groups. Continued engagement of other community partners such as schools, municipalities, and local service groups is also crucial. A "hyper local" approach is needed along with commitment from partners in all sectors and at all levels to reduce barriers to vaccination that lie further upstream for marginalized groups.

Crystal Structure and Substrate Specificity of the 8-oxo-dGTP Hydrolase NUDT1 from Arabidopsis thaliana.

Arabidopsis thaliana NUDT1 (AtNUDT1) belongs to the Nudix family of proteins, which have a diverse range of substrates, including oxidized nucleotides such as 8-oxo-dGTP. The hydrolysis of oxidized dNTPs is highly important as it prevents their incorporation into DNA, thus preventing mutations and DNA damage. AtNUDT1 is the sole Nudix enzyme from A. thaliana shown to have activity against 8-oxo-dGTP. We present the structure of AtNUDT1 in complex with 8-oxo-dGTP. Structural comparison with bacterial and human homologues reveals a conserved overall fold. Analysis of the 8-oxo-dGTP binding mode shows that the residues Asn76 and Ser89 interact with the O8 atom of the substrate, a feature not observed in structures of protein homologues solved to date. Kinetic analysis of wild-type and mutant AtNUDT1 confirmed that these active site residues influence 8-oxo-dGTP hydrolysis. A recent study showed that AtNUDT1 is also able to hydrolyze terpene compounds. The diversity of reactions catalyzed by AtNUDT1 suggests that this Nudix enzyme from higher plants has evolved in a manner distinct to those from other organisms.

Considerations for incorporating real-time PCR assays into routine marine biosecurity surveillance programmes: a case study targeting the Mediterranean fanworm (Sabella spallanzanii) and club tunicate (Styela clava) 1.

Molecular techniques may provide effective tools to enhance marine biosecurity surveillance. Prior to routine implementation, evidence-based consideration of their benefits and limitations is needed. In this study, we assessed the efficiency and practicality of visual diver surveys and real-time PCR assays (targeting DNA and RNA) for detecting two marine invasive species whose infestation levels varied between species and location: Sabella spallanzanii and Styela clava. Filtered water samples (n = 171) were collected in parallel with dive surveys at two locations as part of the New Zealand Marine High Risk Site Surveillance programme: Nelson Harbour (27 sites) and Waitemata Harbour (30 sites). Diver surveys resulted in a greater number of detections compared to real-time PCR: S. clava - 21 versus 5 sites in Nelson, 6 versus 1 in Auckland; S. spallanzanii - 18 versus 10 in Auckland, no detections in Nelson. Occupancy modelling derived detection probabilities for the real-time PCR for S. clava were low (14%), compared to S. spallanzanii (66%). This could be related to abundances, or species-specific differences in DNA shedding. Only one RNA sample was positive, suggesting that most detections were from extracellular DNA or non-viable fragments. While molecular methods cannot yet replace visual observations, this study shows they provide useful complementary information.

Utilizing a Human Factors Nursing Worksystem Improvement Framework to Increase Nurses' Time at the Bedside and Enhance Safety.

OBJECTIVE: The aim of this study is to increase nurses' time for direct patient care and improve safety via a novel human factors framework for nursing worksystem improvement. BACKGROUND: Time available for direct patient care influences outcomes, yet worksystem barriers prevent nurses adequate time at the bedside. METHODS: A novel human factors framework was developed for worksystem improvement in 3 units at 2 facilities. Objectives included improving nurse efficiency as measured by time-and-motion studies, reducing missing medications and subsequent trips to medication rooms and improving medication safety. RESULTS: Worksystem improvement resulted in time savings of 16% to 32% per nurse per 12-hour shift. Requests for missing medications dropped from 3.2 to 1.3 per day. Nurse medication room trips were reduced by 30% and nurse-reported medication errors fell from a range of 1.2 to 0.8 and 6.3 to 4.0 per month. CONCLUSIONS: An innovative human factors framework for nursing worksystem improvement provided practical and high priority targets for interventions that significantly improved the nursing worksystem.

The Dietary Flavonoid Rhamnetin Inhibits Both Inflammation and Excitotoxicity During Ethanol Withdrawal in Rat Organotypic Hippocampal Slice Cultures.

BACKGROUND: Ethanol (EtOH) causes neurotoxicity via several mechanisms including neuroinflammation (during EtOH exposure), and excitotoxicity (during EtOH withdrawal [EWD]). Alpha7 nicotinic acetylcholine receptor (nAChR) selective agonists have the potential to reduce both. The aim of this study was to evaluate the anti-inflammatory and neuroprotective potential of rhamnetin, a dietary flavonoid with alpha7 nAChR selective activity, in an in vitro model of EtOH-induced neurotoxicity. METHODS: The anti-inflammatory and neuroprotective properties of rhamnetin were assessed in neonatal organotypic hippocampal slice cultures undergoing EWD (or not) and challenged with N-methyl-D-aspartate (NMDA) and/or lipopolysaccharide (LPS). Neurotoxicity was determined using propidium iodide uptake, and the inflammatory response was evaluated by measuring the release of tumor necrosis factor (TNF)-alpha (NO; quantified by ELISA) and nitric oxide (quantified by the Griess reaction) into culture media. RESULTS: As predicted, rhamnetin reduced LPS-induced release of TNF-alpha and NO both under control conditions and during EWD. Additionally, rhamnetin had no effect on NMDA-induced neurotoxicity under control conditions, but significantly reduced NMDA toxicity during EWD. In contrast, rhamnetin had no effect on neurotoxicity induced by NMDA and LPS combined despite reducing TNF-alpha and NO levels under these conditions. CONCLUSIONS: Rhamnetin is anti-inflammatory and neuroprotective during EWD and therefore has potential value in treating neurotoxicity caused by EtOH.

Altered relation between lipopolysaccharide-induced inflammatory response and excitotoxicity in rat organotypic hippocampal slice cultures during ethanol withdrawal.

BACKGROUND: Ethanol (EtOH) causes neurotoxicity by several mechanisms including excitotoxicity and neuroinflammation, but little is known about the interaction between these mechanisms. Because neuroinflammation is known to enhance excitotoxicity, we hypothesized that neuroinflammation contributes to the enhanced excitotoxicity, which is associated with EtOH withdrawal (EWD). The aim of this study was to evaluate the lipopolysaccharide (LPS)-induced inflammatory response of cultured hippocampal tissue during EWD and its effects on the enhanced N-methyl-d-aspartate (NMDA) receptor-mediated excitotoxicity, which occurs at this time. METHODS: Using a neonatal organotypic hippocampal slice culture (OHSC) model, we assessed the effects of NMDA and LPS (separately or combined) during EWD after 10 days of EtOH exposure. Neurotoxicity was assessed using propidium iodide uptake, and the inflammatory response was evaluated by measuring the release of tumor necrosis factor (TNF)-alpha (quantified by enzyme-linked immunosorbent assay) and nitric oxide (NO; quantified by the Griess reaction) into culture media. Furthermore, we explored the potential role of the microglial cell type using immortalized BV2 microglia treated with EtOH for 10 days and challenged with LPS during EWD. RESULTS: As predicted, NMDA-induced toxicity was potentiated by LPS under control conditions. However, during EWD, the reverse was observed and LPS inhibited peak NMDA-induced toxicity. Additionally, LPS-induced release of TNF-alpha and NO during EWD was reduced compared to control conditions. In BV2 microglia, following EtOH exposure, LPS-induced release of NO was reduced, whereas TNF-alpha release was potentiated. CONCLUSIONS: During EWD following chronic EtOH exposure, OHSC exhibited a desensitized inflammatory response to LPS and the effects of LPS on NMDA toxicity were reversed. This might be explained by a change in microglia to an anti-inflammatory and neuroprotective phenotype. In support, studies on BV2 microglia indicate that EtOH exposure and EWD do alter the response of these cells to LPS, but this cannot fully explain the changes observed in the OHSC. The data suggest that neuroinflammation and excitotoxicity do interact during EWD. However, the interaction is not as simple as we originally proposed. This in turn illustrates the need to assess the extent, importance, and relation of these mechanisms in models of EtOH exposure producing neurotoxicity.

Determining thermodynamic properties of molecular interactions from single crystal studies.

The concept of single crystals of macromolecules as thermodynamic systems is not a common one. However, it should be possible to derive thermodynamic properties from single crystal structures, if the process of crystallization follows thermodynamic rules. We review here an example of how the stabilizing potentials of molecular interactions can be measured from studying the properties of DNA crystals. In this example, we describe an assay based on the four-stranded DNA junction to determine the stabilizing potentials of halogen bonds, a class of electrostatic interactions, analogous to hydrogen bonds, that are becoming increasing recognized as important for conferring specificity in protein-ligand complexes. The system demonstrates how crystallographic studies, when coupled with calorimetric methods, allow the geometries at the atomic level to be directly correlated with the stabilizing energies of molecular interactions. The approach can be generally applied to study the effects of DNA sequence and modifications of the thermodynamic stability of the Holliday junction and, by inference, on recombination and recombination dependent processes.

Mapping and Expression of Candidate Genes for Development Rate in Rainbow Trout (Oncorhynchus mykiss).

Development rate has important implications for individual fitness and physiology. In salmonid fishes, development rate correlates with many traits later in life, including life-history diversity, growth, and age and size at sexual maturation. In rainbow trout (Oncorhynchus mykiss), a quantitative trait locus for embryonic development rate has been detected on chromosome 5 across populations. However, few candidate genes have been identified within this region. In this study, we use gene mapping, gene expression, and quantitative genetic methods to further identify the genetic basis of embryonic developmental rate in O. mykiss Among the genes located in the region of the major development rate quantitative trait locus (GHR1, Clock1a, Myd118-1, and their paralogs), all were expressed early in embryonic development (fertilization through hatch), but none were differentially expressed between individuals with the fast- or slow-developing alleles for a major embryonic development rate quantitative trait locus. In a follow-up study of migratory and resident rainbow trout from natural populations in Alaska, we found significant additive variation in development rate and, moreover, found associations between development rate and allelic variation in all 3 candidate genes within the quantitative trait locus for embryonic development. The mapping of these genes to this region and associations in multiple populations provide positional candidates for further study of their roles in growth, development, and life-history diversity in this model salmonid.

Place and food insecurity: a critical review and synthesis of the literature.

OBJECTIVE: In some high-income countries, a sizeable proportion of households are estimated to be food insecure. It is well known that food insecurity varies between countries and is strongly tied to household income level. The local environment may be another level of influence, which has been relatively understudied. The present review sought to synthesize and critically appraise the existing literature examining local environmental characteristics in relation to individual/household-level food insecurity in the general population. DESIGN: A systematic search strategy was used to search MEDLINE, MEDLINE In-process and Other Non-indexed, EMBASE, PsychINFO, Social Services Abstracts and Sociological Abstracts databases for studies examining local place characteristic(s) in relation to self-reported food insecurity. SETTING: Studies could be experimental or observational, but had to be published in a peer-reviewed journal in French or English, and involve individuals from developed countries. 'Place' was defined locally, as ranging from the street to the county level. SUBJECTS: The target population for the review included non-institutionalized individuals in the general population. RESULTS: After obtaining full-text articles, eighteen primary studies met the eligibility criteria. Most studies were conducted in the USA and all but one was cross-sectional. Seven of the eleven studies that examined location of residence found that rural living was inversely associated with food insecurity. Mixed results were seen for other place measures such as social capital and distance to food stores. CONCLUSIONS: Studies were heterogeneous and had various limitations that preclude definitive conclusions from being drawn. Recommendations for future research are provided.

Enthalpy-entropy compensation in biomolecular halogen bonds measured in DNA junctions.

Interest in noncovalent interactions involving halogens, particularly halogen bonds (X-bonds), has grown dramatically in the past decade, propelled by the use of X-bonding in molecular engineering and drug design. However, it is clear that a complete analysis of the structure-energy relationship must be established in biological systems to fully exploit X-bonds for biomolecular engineering. We present here the first comprehensive experimental study to correlate geometries with their stabilizing potentials for fluorine (F), chlorine (Cl), bromine (Br), or iodine (I) X-bonds in a biological context. For these studies, we determine the single-crystal structures of DNA Holliday junctions containing halogenated uracil bases that compete X-bonds against classic hydrogen bonds (H-bonds), estimate the enthalpic energies of the competing interactions in the crystal system through crystallographic titrations, and compare the enthalpic and entropic energies of bromine and iodine X-bonds in solution by differential scanning calorimetry. The culmination of these studies demonstrates that enthalpic stabilization of X-bonds increases with increasing polarizability from F to Cl to Br to I, which is consistent with the σ-hole theory of X-bonding. Furthermore, an increase in the X-bonding potential is seen to direct the interaction toward a more ideal geometry. However, the entropic contributions to the total free energies must also be considered to determine how each halogen potentially contributes to the overall stability of the interaction. We find that bromine has the optimal balance between enthalpic and entropic energy components, resulting in the lowest free energy for X-bonding in this DNA system. The X-bond formed by iodine is more enthalpically stable, but this comes with an entropic cost, which we attribute to crowding effects. Thus, the overall free energy of an X-bonding interaction balances the stabilizing electrostatic effects of the σ-hole against the competing effects on the local structural dynamics of the system.

The influence of place on weight gain during early childhood: a population-based, longitudinal study.

The objective of this paper was to determine the influence of place factors on weight gain in a contemporary cohort of children while also adjusting for early life and individual/family social factors. Participants from the Québec Longitudinal Study of Child Development comprised the sample for analysis (n = 1,580). A mixed-effects regression analysis was conducted to determine the longitudinal relationship between these place factors and standardized BMI, from age 4 to 10 years. The average relationship with time was found to be quadratic (rate of weight gain increased over time). Neighborhood material deprivation was found to be positively related to weight gain. Social deprivation, social disorder, and living in a medium density area were inversely related, while no association was found for social cohesion. Early life factors and genetic proxies appeared to be important in explaining weight gain in this sample. This study suggests that residential environments may play a role in childhood weight change; however, pathways are likely to be complex and interacting and perhaps not as important as early life factors and genetic proxies. Further work is required to clarify these relationships.

Utilization and barriers to eye care following school-wide pediatric vision screening.

OBJECTIVE: In August 2018, Ontario introduced the Child Visual Health and Vision Screening Protocol outlining school-based senior kindergarten (aged 4-6 years) vision screening. We determine the prevalence of children at risk based on screening in an Ontario community and follow up to determine resource utilization after screening. METHODS: Vision screening data (HOTV, Randot, Autorefractor) from 41 schools (1127 children) were collected for the 2018-2019 and 2019-2020 school years. Phone follow-up was conducted 1-1.5 years after screening to determine whether an optometry visit occurred, if glasses were prescribed, and potential barriers to accessing eye care. Independent t tests were used to compare time to follow-up between groups, and χ2 testing was used for associations between material and social deprivation. RESULTS: Overall screening resulted in a 32.2% referral rate within our region. Of the referred children who responded, the rate of seeking out eye care was 69.9% (n = 64), and 65.2% of these visits were prompted specifically by vision screening, and 34.4% of referred children respondents were prescribed glasses. There was a significant relationship between receiving a referral and living in a more materially deprived (p = 0.001) and a more socially deprived area (p = 0.006). The most frequently reported barriers were related to insufficient insurance coverage for eye care or glasses, COVID-19-related difficulties, and scheduling conflicts. CONCLUSION: Our vision screening program identified and referred more than one third of children screened for follow-up eye examinations, with children in more deprived neighbourhoods being more frequently referred. Around two thirds of referred children sought care, and one third were prescribed glasses in the follow-up sample.

Local social environmental factors are associated with household food insecurity in a longitudinal study of children.

BACKGROUND: Food insecurity is a significant public health problem in North America and elsewhere. The prevalence of food insecurity varies by country of residence; within countries, it is strongly associated with household socioeconomic status, but the local environment may also play an important role. In this study, we analyzed secondary data from a population-based survey conducted in Québec, Canada, to determine if five local environmental factors: material and social deprivation, social cohesion, disorder, and living location were associated with changes in household food insecurity over a period of 6 years, while adjusting for household socioeconomic status (SES) and other factors. METHODS: Data from the Québec Longitudinal Study of Child Development, following same-aged children from 4-10 y of age, were analyzed using generalized estimating equations, to determine the longitudinal association between these environmental factors and food insecurity over a period of 6 years. RESULTS: Of the 2120 children originally included in the cohort, 1746 (82%) were included in the present analysis. The prevalence of food insecurity was 9.2% when children were 4 y of age (95% CI: 7.8 - 10.6%) but no significant changes were observed over time. On average over the 6 year period, three environmental factors were positively related to food insecurity: high social deprivation (OR 1.62, 95%CI: 1.16 - 2.26), low social cohesion (OR 1.45 95%CI: 1.10 - 1.92), and high disorder (OR 1.76, 95%CI: 1.37 - 2.27), while living location and material deprivation were not related to food insecurity. These associations were independent of household SES and other social variables. CONCLUSION: These results highlight the potential role of the local social environment in preventing and ameliorating food insecurity at the household level. Stakeholders providing food security interventions at the community level should consider interactions with local social characteristics and perhaps changing the social environment itself. Further intervention research also examining interactions with household-level factors could lead to the development of interventions that increase both household and community-level food security.

Fetal alcohol spectrum disorder and Risk-Need-Responsivity Model: A guide for criminal justice and forensic mental health professionals.

Fetal alcohol spectrum disorder (FASD) is an umbrella term used to describe a range of significant neurodevelopmental, brain-based disorders and impairments that result from prenatal alcohol exposure. FASD is a high prevalence but underdiagnosed group of disorders affecting between 17 and 36% of individuals in criminal justice settings. Despite being a high-impact disorder associated with lifelong impairments with a significant need for services and interventions, little research has been completed on how to best support individuals with these conditions in criminal justice settings. This article proposes a renewed focus on applying and adapting the Risk-Need-Responsivity (RNR) approach to individuals with FASD in criminal justice settings. This will assist in better determining the needs and interventions likely to effect change and reduce recidivism for this prominent criminal justice-based population. The RNR approach has been used with multiple corrections populations to determine the need and most appropriate interventions, as well as how to best allocate scarce resources. As the prevalence of FASD becomes better understood and recognized, evidence-based approaches to addressing this specific sub-population are necessary to effect change and reduce recidivism and ongoing involvement in the criminal justice system.

Fetal alcohol spectrum disorder (FASD) and suggestibility: A survey of United States federal case law.

This article summarizes four federal criminal cases that illustrate how suggestibility can impact defendants with FASD in the criminal justice system. Four cases were identified via a Google Scholar search of "suggestibility" and "fetal alcohol" in the federal case law database. These cases are illustrative of how FASD can affect legal defendants, including vulnerability to peer pressure, being easily manipulated, insufficient comprehension of legal proceedings, difficulty in assisting legal counsel, learning impairment, acquiescence or higher levels of suggestibility, and difficulty understanding consequences. The cases presented here provided the most comprehensive discussion of FASD and suggestibility issues but are by no means an exhaustive review of case law. Because defendants with FASD are the focal point of this article, we intentionally excluded cases involving eyewitness suggestibility, the suggestibility of child witnesses, and the suggestibility of those under hypnosis. Therefore, this review has been developed to explicate and illustrate problems common to FASD defendants within legal settings, especially regarding risk for suggestibility. The information provided from this discussion may better guide legal professionals who regularly come into contact with persons affected by FASD on how to more readily detect this neurodevelopmental condition and mitigate the likelihood of injustice during criminal proceedings. Additionally, we include suggestions on how to attenuate miscarriages of justice as a result of faulty confessions, wrongful convictions, and vulnerability of suggestibility in persons affected by FASD.

Higher intakes of energy and grain products at 4 years of age are associated with being overweight at 6 years of age.

This study examined dietary factors associated with overweight in a population-based sample of 6-y-old children. Analyses of data from the Québec Longitudinal Study of Child Development (QLSCD) included a representative sample (n = 1014) of children born in 1998 in the province of Québec, Canada. Dietary intake was measured by using a 24-h dietary recall administered at 4 y of age. Weight and height were measured using a standard protocol at 6 y. Using logistic regression, higher daily energy intake at 4 y was significantly related to overweight at 6 y. After adjustment for confounding and overweight at 4 y, the relationship remained significant among girls (P = 0.04) but became marginally significant among boys (P = 0.07). Additionally, boys who consumed ≥5 servings of grain products/d at 4 y were more likely to be overweight at 6 y compared to those who did not [adjusted OR = 3.20 (95% CI): 1.72-5.97]. The association attenuated somewhat after adjustment for overweight at 4 y [OR = 1.82 (95% CI): 0.894-3.71; P = 0.09]. The findings provide support for the revisions made in the Canadian dietary guidelines for young children, which now recommend 4-7 servings of grain products daily for children aged 4-8 y rather than the excessive 5-12 servings of previous recommendations.