Social evaluative stress enhances central detail memory, reduces false memory, and results in intrusive memories that last for days.

Few studies have quantified what an individual remembers about a laboratory-controlled stressor. Here, we aimed to replicate previous work by using a modified version of the Trier Social Stress Test (TSST) to quantify participant memory for a stressful experience. We also aimed to extend this work by quantifying false and intrusive memories that ensued. One hundred and seven participants were exposed to the TSST (stress) or the friendly TSST (f-TSST; no stress). The TSST required participants to deliver a ten-minute speech in front of two laboratory panel members as part of a mock job interview; the f-TSST required participants to casually converse with the panel members about their interests. In both conditions, the panel members interacted with (central) or did not interact with (peripheral) several objects sitting on a desk in front of them. The next day, participants' memory for the objects was assessed with recall and recognition tests. We also quantified participants' intrusive memories on Days 2, 4, 6, and 8. Stressed participants recalled more central objects and exhibited greater recognition memory, particularly for central objects, than controls. Stress also led to less false recall and more intrusive memories on Days 2 and 4. Consistent with previous work, these findings suggest that participants exhibit enhanced memory for the central details of a stressful experience; they also extend prior work by showing that participants exposed to a stressor have less false memories and experience intrusive memories for several days following the event. The modified TSST paradigm used here may be useful for researchers studying not only what participants remember about a stressful event but also their susceptibility to intrusive memory formation.

Backside versus Frontside SN2 Reactions of Alkyl Triflates and Alcohols.

Nucleophilic substitution reactions are elementary reactions in organic chemistry that are used in many synthetic routes. By quantum chemical methods, we have investigated the intrinsic competition between the backside SN2 (SN2-b) and frontside SN2 (SN2-f) pathways using a set of simple alkyl triflates as the electrophile in combination with a systematic series of phenols and partially fluorinated ethanol nucleophiles. It is revealed how and why the well-established mechanistic preference for the SN2-b pathway slowly erodes and can even be overruled by the unusual SN2-f substitution mechanism going from strong to weak alcohol nucleophiles. Activation strain analyses disclose that the SN2-b pathway is favored for strong alcohol nucleophiles because of the well-known intrinsically more efficient approach to the electrophile resulting in a more stabilizing nucleophile-electrophile interaction. In contrast, the preference of weaker alcohol nucleophiles shifts to the SN2-f pathway, benefiting from a stabilizing hydrogen bond interaction between the incoming alcohol and the leaving group. This hydrogen bond interaction is strengthened by the increased acidity of the weaker alcohol nucleophiles, thereby steering the mechanistic preference toward the frontside SN2 pathway.

Formation of Glycosyl Trichloroacetamides from Trichloroacetimidate Donors Occurs through an Intermolecular Aglycon Transfer Reaction.

To probe the reaction mechanism, underlying the rearrangement of oft-used trichloroacetimidate glycosyl donors into the corresponding anomeric trichloroacetamides, we have used a combination of 13C- and 15N-labeled glycosyl trichloroacetimidate donors in a series of crossover experiments. These unambiguously show that trichloroacetamides are formed via an intermolecular aglycon transfer mechanism. This insight enables the design of more effective glycosylation protocols, preventing the formation of dead-end side products.

Polygenic risk associations with developmental and mental health outcomes in childhood and adolescence: A systematic review.

Background: Neurodevelopmental and mental health disorders in childhood constitute an emerging global concern, with adverse sequelae which span children's physical, psychological and social well-being. The aetiology of these disorders is likely complex, multifactorial and polygenic. Polygenic risk scores (PRS), an estimate of an individual's genetic liability toward a disorder, have been increasingly used in psychiatric research to explore genetic associations with disorders of interest. However, limited work delineates polygenic associations with development and mental health in childhood populations.We aimed to systematically review existing literature on associations between genetic risk (as measured by PRS) and neurodevelopmental and mental health outcomes in childhood and adolescence. Methods: Following the recommended Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines, databases were searched using key search terms. The search commenced in March 2021 and concluded in June 2021. The studies eligible for inclusion were full-text articles investigating polygenic risk associations with neurodevelopmental and/or mental health outcomes in childhood or adolescence. Results: Fourteen studies were eligible for inclusion in this systematic review. The association between higher PRS for attention-deficit/hyperactivity disorder (ADHD) and adverse developmental/mental health outcomes in childhood and adolescence was reported by five studies. Additionally, associations between PRS for bipolar disorder or major depressive disorder and adverse outcomes of interest were also described by two studies; and two studies highlighted associations between schizophrenia PRS and mental health disorders in childhood. The remaining studies highlighted shared polygenic contributions between and within NDDs and mental health disorders in children. Conclusion: The findings of this systematic review suggest that PRS for neurodevelopmental and mental health disorders may associate with adverse neurodevelopmental and mental health outcomes from early childhood to adolescence. In addition, these associations seemed not to be phenotype-specific, suggesting potential shared genetic variation across the phenotypes of interest.

Mapping the effect of configuration and protecting group pattern on glycosyl acceptor reactivity.

The reactivity of the acceptor alcohol can have a tremendous influence on the outcome of a glycosylation reaction, both in terms of yield and stereoselectivity. Through a systematic survey of 67 acceptor alcohols in glycosylation reactions with two glucosyl donors we here reveal how the reactivity of a carbohydrate acceptor depends on its configuration and substitution pattern. The study shows how the functional groups flanking the acceptor alcohol influence the reactivity of the alcohol and show that both the nature and relative orientation play an essential role. The empiric acceptor reactivity guidelines revealed here will aid in the rational optimization of glycosylation reactions and be an important tool in the assembly of oligosaccharides.

Palladium-Catalyzed Cascade to Benzoxepins by Using Vinyl-Substituted Donor-Acceptor Cyclopropanes.

A palladium-catalyzed intermolecular cascade (4+3) cyclocondensation of salicylaldehydes and vinylcyclopropanes is reported. A key feature of the reaction is the use of a phosphonate group as an acceptor moiety on the cyclopropane, exploiting its propensity to undergo olefination with aldehydes. Subsequent O-allylation enabled the formation of a range of substituted benzoxepinsWith a novel chiral ligand, the products were obtained in generally good yield and with reasonable enantioselectivity.

Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

Maternal and infant factors had a significant impact on birthweight and longitudinal growth in a South African birth cohort.

AIM: This birth cohort study investigated longitudinal infant growth and associated factors in a multiethnic population living in a low-resource district surrounding the town of Paarl in South Africa. METHODS: Between March 2012 and October 2014, all mothers attending their second trimester antenatal visit at Paarl Hospital were approached for enrolment. Mother-infant pairs were followed from birth until 12 months of age. Comprehensive socio-demographic, nutritional and psychosocial data were collected at birth, two, six and 12 months. Infant anthropometry was analysed as z-scores for weight and height. Linear regression was used to investigate predictors of birthweight, and linear mixed-effects models were used to investigate predictors of infant growth. RESULTS: Longitudinal anthropometric data from 792 infants were included: 53% were Black African, 47% were mixed race, and 15% were born preterm. Stunting occurred in 13% of infants at 12 months. Maternal height, antenatal alcohol and tobacco use, ethnicity and socioeconomic status were significant predictors of birthweight. In the adjusted mixed-effects model, birthweight was a significant predictor of growth during the first year of life. CONCLUSION: Birthweight was an important predictor of growth trajectory during infancy. Birthweight and growth were influenced by several important modifiable factors.

The barriers that women face when choosing food for their primary school children: A case study in the Western Cape Province, South Africa

Background. Unhealthy food choices made by mothers can impact negatively on child health and may lead to unhealthy eating behaviours that persist into adulthood. Choosing food is a complex process influenced by many factors. Objectives. To determine the factors that influence mothers' food choices and to investigate barriers to purchasing healthy food.Methods. A cross-sectional, descriptive study, with an analytical component, was conducted. Mothers (N=476) were recruited from three randomly selected primary schools, from a low, middle and high quintile. A self-administered questionnaire was used to collect data on demographics, knowledge, attitude and practices of mothers. Six focus groups (FG) (two per school) were conducted to investigate the factors that prevent mothers from making healthy dietary decisions.Results. The mean nutrition knowledge score for the group was 68.6%. Nutrition knowledge was significantly lower (p<0.01) in mothers from the lower quintile school (64.0%). Primary factors influencing food purchases were cost (60%), nutritional value (37%) and time constraints (29%). Primary sources of nutrition information included magazines and health professionals at 62% and 44%, respectively. Time constraints resulted in mothers purchasing convenience foods more often (p=0.001). The main barriers identified were mixed media messages, the school environments and supermarket layouts.Conclusion. Nutrition education campaigns should include practical advice, e.g. the preparation of economical, wholesome meals. Policymakers should monitor increasing prices of healthy foods. School and supermarket environments, as well as the food industry, can play a pivotal role in facilitating mothers to make healthy food choices

Antenatal and early life tobacco smoke exposure in an African birth cohort study.

BACKGROUND: Exposure to tobacco smoke in African infants has not been well studied, despite the high burden of childhood respiratory disease in these communities. OBJECTIVE: To investigate the prevalence of antenatal and early life tobacco smoke exposure and associations with infant birth outcomes in an African birth cohort, the Drakenstein Child Health Study. METHODS: Self-report questionnaires assessing maternal and household smoking were administered. Maternal and infant urine cotinine testing was conducted antenatally, at birth and at 6-10 weeks of life to measure tobacco smoke exposure. Multivariate regression models explored the associations between exposure to smoke and infant birth outcomes. RESULTS: Of 789 pregnant women included, 250 (32%) were active smokers on cotinine testing. At birth and at 6-10 weeks of life, respectively 135/241 (56%) and 154/291 (53%) infants had urine cotinine levels indicating tobacco smoke exposure. Household smoking was prevalent and was associated with positive infant cotinine test results. Antenatal maternal smoking was associated with decreased infant birthweight-for-age Z-score (0.3, 95%CI 0.1-0.5). CONCLUSION: Antenatal and early life tobacco smoke exposure is highly prevalent in this community, and may impact on birth outcomes and subsequent child health. Smoking cessation interventions are urgently needed to reduce tobacco smoke exposure in African communities.

Genome-wide gene-based analysis suggests an association between Neuroligin 1 (NLGN1) and post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) develops in only some people following trauma exposure, but the mechanisms differentially explaining risk versus resilience remain largely unknown. PTSD is heritable but candidate gene studies and genome-wide association studies (GWAS) have identified only a modest number of genes that reliably contribute to PTSD. New gene-based methods may help identify additional genes that increase risk for PTSD development or severity. We applied gene-based testing to GWAS data from the Grady Trauma Project (GTP), a primarily African American cohort, and identified two genes (NLGN1 and ZNRD1-AS1) that associate with PTSD after multiple test correction. Although the top SNP from NLGN1 did not replicate, we observed gene-based replication of NLGN1 with PTSD in the Drakenstein Child Health Study (DCHS) cohort from Cape Town. NLGN1 has previously been associated with autism, and it encodes neuroligin 1, a protein involved in synaptogenesis, learning, and memory. Within the GTP dataset, a single nucleotide polymorphism (SNP), rs6779753, underlying the gene-based association, associated with the intermediate phenotypes of higher startle response and greater functional magnetic resonance imaging activation of the amygdala, orbitofrontal cortex, right thalamus and right fusiform gyrus in response to fearful faces. These findings support a contribution of the NLGN1 gene pathway to the neurobiological underpinnings of PTSD.

Translational neuroscience of basolateral amygdala lesions: Studies of Urbach-Wiethe disease.

Urbach-Wiethe disease (UWD) is an extremely rare autosomal recessive disorder characterized by mutations in the extracellular matrix protein 1 gene on chromosome 1. Typical clinical manifestations include voice hoarseness in early infancy and neuropsychiatric, laryngeal, and dermatological pathologies later in life. Neuroimaging studies have revealed a pattern of brain calcification often but not exclusively leading to selective bilateral amygdala damage. A large body of work on amygdala lesions in rodents exists, generally employing a subregion model focused on the basolateral amygdala (BLA) and the central-medial amygdala. However, human work usually considers the amygdala as a unified structure, not only complicating the translation of animal findings to humans but also providing a unique opportunity for further research. To compare data from rodent models with human cases and to complement existing data from Europe and North America, a series of investigations was undertaken on UWD subjects with selective BLA damage in the Namaqualand region, South Africa. This review presents key findings from this work, including fear processing, social-economic behavior, and emotional conflict processing. Our findings are broadly consistent with and support rodent models of selective BLA lesions and show that the BLA is integral to processing sensory stimuli and exhibits inhibitory regulation of responses to unconditioned innate fear stimuli. Furthermore, our findings suggest that the human BLA mediates calculative-instrumental economic behaviors and may compromise working memory via competition for attentional resources between the BLA salience detection system and the dorsolateral prefrontal cortex working memory system.

Kinetic Monte Carlo simulation of the photodegradation process of polyester-urethane coatings.

A numerical method to simulate reactions in a cross-linked polymer is developed and applied to the photodegradation process of polyester-urethane clearcoats during artificial exposure in a Weather-Ometer. This coarse-grained simulation method, which is based on a kinetic Monte Carlo scheme, is verified with experimental data on the depth-resolved changes in optical properties and chemical composition that have been previously determined. By modelling the depth-dependency of physical processes that occur in the coating, such as the absorption of photons and the diffusion of oxygen, the experimentally observed evolution of depth gradients in chemical composition can be well described by the simulation. A sensitivity analysis of individual simulation input parameters with respect to a set of resulting observables is performed and the results provide insight into the influence of specific reaction mechanisms on the overall degradation process and help to distinguish essential from less important processes. The values of input parameters that result in the most accurate simulation of the experimental data are determined with an optimisation procedure. In this way, the numerical values of several kinetic and physical parameters that are difficult to determine directly in an experimental way, such as various reaction rate constants, can be obtained from the simulations.

Investigating the psychosocial determinants of child health in Africa: The Drakenstein Child Health Study.

BACKGROUND: Early life psychobiological and psychosocial factors play a key role in influencing child health outcomes. Longitudinal studies may help elucidate the relevant risk and resilience profiles, and the underlying mechanisms that impact on child health, but there is a paucity of birth cohort data from low and middle-income countries (LMIC). We describe the rationale for and present baseline findings from the psychosocial component of the Drakenstein Child Health Study (DCHS). METHODS: We review the psychosocial measures used in the DCHS, a multidisciplinary birth cohort study in a peri-urban area in South Africa, and provide initial data on psychological distress, depression, substance use, and exposure to traumatic stressors and intimate partner violence (IPV). These and other measures will be assessed longitudinally in mothers in order to investigate associations with child neurodevelopmental and health outcomes. RESULTS: Baseline psychosocial data is presented for mothers (n=634) and fathers (n=75) who have completed antenatal assessments to date. The sample of pregnant mothers is characterized by multiple psychosocial risk factors, including a high prevalence of psychological distress and depression, high levels of substance use, and high exposure to traumatic stressors and IPV. DISCUSSION: These data are consistent with prior South African studies which have documented a high prevalence of a multitude of risk factors during pregnancy. Further longitudinal assessment of mothers and children may clarify the underlying psychobiological and psychosocial mechanisms which impact on child health, and so inform clinical and public health interventions appropriate to the South African and other LMIC contexts.

Psychosocial predictors of fetoplacental blood flow during pregnancy.

BACKGROUND: Although a number of studies have found significant associations between maternal psychological distress, anxiety and changes in fetoplacental blood flow, findings remain inconsistent. A recent pilot study by our group highlighted some of these inconsistencies. In the current study, we expanded this pilot analysis to include psychological distress, anxiety and a range of antenatal variables, with the aim of identifying predictors of fetoplacental blood flow. METHODS: Healthy pregnant women (n=148) underwent Doppler flow studies on uterine, umbilical and fetal arteries; as well as assessments of distress, anxiety and other antenatal variables (e.g. perceived social support, resilience, nicotine and alcohol use) in each trimester. RESULTS: Stepwise regression analyses found that state anxiety was associated with lower mid-cerebral artery pulsatility index at trimester 3. LIMITATIONS: Subjects were recruited from selected midwife obstetric units in the same health district, so the generalizability of our results may be limited. While most subjects received Doppler assessment at trimesters 2 and 3, only approximately half of our sample was assessed at trimester 1. CONCLUSION: The finding that anxiety is associated with increased blood flow to the fetal brain during trimester 3 of pregnancy, coincide with previous work. The findings emphasize a growing appreciation of the potential importance of psychological well-being during pregnancy for infant development. However, as associations were small and variable, further research using multivariate models to determine the precise mechanisms underlying these associations would be warranted.

The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm infants to improve neurodevelopmental outcome: a randomized controlled trial--BARTrial.

BACKGROUND AND OBJECTIVE: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome. METHODS: In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death. RESULTS: Composite motor (100 ± 13 vs. 101 ± 12) and cognitive (101 ± 12 vs. 101 ± 11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤ 1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g. CONCLUSIONS: The additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74465643.

Assessing the Knowledge and Perceptions of Medical Students from the Western Cape; South Africa; Regarding the Millennium Development Goals

Background: Health science students are key players in implementing the Millennium Development Goals (MDG). Knowledge and understanding at university level is essential to achieve the goals by 2015. The primary objective of this study was to assess the knowledge and perceptions of fifth-year medical students at Stellenbosch University and the University of Cape Town regarding the MDG. The secondary objectives were to determine the degree to which students are involved in awareness campaigns and implementation of the MDG; and to assess students' perceptions regarding the need for the MDG in South Africa. Method: This observational; descriptive; cross-sectional study collected quantitative data. A census was carried out. All participants completed a self-administered questionnaire. Results: Of the 176 participants; 61.14 said they had previously heard or read about the MDG. Forty per cent had heard about the MDG through awareness campaigns. More than half (54.86) claimed to know what the MDG were; but could not name all of the goals. Participants identified a mean of three out of eight MDG correctly. The majority of students considered MDG implementation in South Africa important but ineffective (69.85); and 85.82 believed that the MDG would not be achieved on time.Conclusion: It was found that fifth-year medical students in the Western Cape were not adequately informed about the MDG and their importance in South Africa. However; their perceptions were positive; in that the majority agreed that the implementation of the MDG in South Africa is important and that more needs to be done in creating awareness about the goals