A multi-level developmental approach to exploring individual differences in Down syndrome: genes, brain, behaviour, and environment.

In this article, we focus on the causes of individual differences in Down syndrome (DS), exemplifying the multi-level, multi-method, lifespan developmental approach advocated by Karmiloff-Smith (1998, 2009, 2012, 2016). We evaluate the possibility of linking variations in infant and child development with variations in the (elevated) risk for Alzheimer's disease (AD) in adults with DS. We review the theoretical basis for this argument, considering genetics, epigenetics, brain, behaviour and environment. In studies 1 and 2, we focus on variation in language development. We utilise data from the MacArthur-Bates Communicative Development Inventories (CDI; Fenson et al., 2007), and Mullen Scales of Early Learning (MSEL) receptive and productive language subscales (Mullen, 1995) from 84 infants and children with DS (mean age 2;3, range 0;7 to 5;3). As expected, there was developmental delay in both receptive and expressive vocabulary and wide individual differences. Study 1 examined the influence of an environmental measure (socio-economic status as measured by parental occupation) on the observed variability. SES did not predict a reliable amount of the variation. Study 2 examined the predictive power of a specific genetic measure (apolipoprotein APOE genotype) which modulates risk for AD in adulthood. There was no reliable effect of APOE genotype, though weak evidence that development was faster for the genotype conferring greater AD risk (ε4 carriers), consistent with recent observations in infant attention (D'Souza, Mason et al., 2020). Study 3 considered the concerted effect of the DS genotype on early brain development. We describe new magnetic resonance imaging methods for measuring prenatal and neonatal brain structure in DS (e.g., volumes of supratentorial brain, cortex, cerebellar volume; Patkee et al., 2019). We establish the methodological viability of linking differences in early brain structure to measures of infant cognitive development, measured by the MSEL, as a potential early marker of clinical relevance. Five case studies are presented as proof of concept, but these are as yet too few to discern a pattern

Increased hemorrhagic transformation and altered infarct size and localization after experimental stroke in a rat model type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Interruption of flow through of cerebral blood vessels results in acute ischemic stroke. Subsequent breakdown of the blood brain barrier increases cerebral injury by the development of vasogenic edema and secondary hemorrhage known as hemorrhagic transformation (HT). Diabetes is a risk factor for stroke as well as poor outcome of stroke. The current study tested the hypothesis that diabetes-induced changes in the cerebral vasculature increase the risk of HT and augment ischemic injury.</p> <p>Methods</p> <p>Diabetic Goto-Kakizaki (GK) or control rats underwent 3 hours of middle cerebral artery occlusion and 21 h reperfusion followed by evaluation of infarct size, hemorrhage and neurological outcome.</p> <p>Results</p> <p>Infarct size was significantly smaller in GK rats (10 ± 2 vs 30 ± 4%, p < 0.001). There was significantly more frequent hematoma formation in the ischemic hemisphere in GK rats as opposed to controls. Cerebrovascular tortuosity index was increased in the GK model (1.13 ± 0.01 vs 1.34 ± 0.06, P < 0.001) indicative of changes in vessel architecture.</p> <p>Conclusion</p> <p>These findings provide evidence that there is cerebrovascular remodeling in diabetes. While diabetes-induced remodeling appears to prevent infarct expansion, these changes in blood vessels increase the risk for HT possibly exacerbating neurovascular damage due to cerebral ischemia/reperfusion in diabetes.</p

Healthcare providers' views on the acceptability of financial incentives for breastfeeding:a qualitative study

BACKGROUND: Despite a gradual increase in breastfeeding rates, overall in the UK there are wide variations, with a trend towards breastfeeding rates at 6–8 weeks remaining below 40% in less affluent areas. While financial incentives have been used with varying success to encourage positive health related behaviour change, there is little research on their use in encouraging breastfeeding. In this paper, we report on healthcare providers’ views around whether using financial incentives in areas with low breastfeeding rates would be acceptable in principle. This research was part of a larger project looking at the development and feasibility testing of a financial incentive scheme for breastfeeding in preparation for a cluster randomised controlled trial. METHODS: Fifty–three healthcare providers were interviewed about their views on financial incentives for breastfeeding. Participants were purposively sampled to include a wide range of experience and roles associated with supporting mothers with infant feeding. Semi-structured individual and group interviews were conducted. Data were analysed thematically drawing on the principles of Framework Analysis. RESULTS: The key theme emerging from healthcare providers’ views on the acceptability of financial incentives for breastfeeding was their possible impact on ‘facilitating or impeding relationships’. Within this theme several additional aspects were discussed: the mother’s relationship with her healthcare provider and services, with her baby and her family, and with the wider community. In addition, a key priority for healthcare providers was that an incentive scheme should not impact negatively on their professional integrity and responsibility towards women. CONCLUSION: Healthcare providers believe that financial incentives could have both positive and negative impacts on a mother’s relationship with her family, baby and healthcare provider. When designing a financial incentive scheme we must take care to minimise the potential negative impacts that have been highlighted, while at the same time recognising the potential positive impacts for women in areas where breastfeeding rates are low

The Influence of Trait Compulsivity and Impulsivity on Addictive and Compulsive Behaviors During COVID-19.

Background: The COVID-19 pandemic has resulted in high levels of psychological distress worldwide, with experts expressing concern that this could result in corresponding increases in addictive behaviors as individuals seek to cope with their distress. Further, some individuals may be at greater risk than others for developing problematic addictive behaviors during times of high stress, such as individuals with high trait impulsivity and compulsivity. Despite the potential of such knowledge to inform early detection of risk, no study to date has examined the influence of trait impulsivity and compulsivity on addictive behaviors during COVID-19. Toward this aim, the current study examined the association between impulsive and compulsive traits and problematic addictive and compulsive behaviors during the first COVID-19 lockdown in Australia. Methods: Eight hundred seventy-eight adults completed a cross-sectional online survey during the first lockdown, between late May to June 2020. Participants completed scales for addictive and compulsive behaviors for the period prior to and during lockdown for problematic eating, pornography, internet use, gambling, drinking, and obsessive-compulsive behaviors. Negative binomial regressions examined the associations between impulsivity, compulsivity, and their interaction with problematic behaviors during lockdown, controlling for age, gender, sample, psychological distress, exposure to COVID-related stressors, and pre-COVID problems. Results: Greater trait compulsivity was associated with more problematic obsessive-compulsive behaviors (p < 0.001) and less problematic drinking (p = 0.038) during lockdown. Further, trait compulsivity interacted with trait impulsivity in relation to problematic eating behaviors (p = 0.014) such that greater trait compulsivity was associated with more problems among individuals with low impulsivity only (p = 0.030). Finally, psychological distress and/or exposure to COVID-related stressors were associated with greater problems across all addictive and compulsive behaviors, as was severity of pre-COVID problems. Discussion: Trait compulsivity was associated with addictive and compulsive behaviors in different ways. Further, the finding that stress-related variables (psychological distress and COVID-related stressors) were associated with greater problems across all lockdown behaviors supports the idea that stress may facilitate, or otherwise be associated with, problematic behaviors. These findings highlight the need for interventions that enhance resilience to stress, which in turn may reduce risk for addictive and compulsive disorders

Molecular Analysis of Precursor Lesions in Familial Pancreatic Cancer

PMCID: PMC3553106This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Forward Genetic Analysis of Visual Behavior in Zebrafish

The visual system converts the distribution and wavelengths of photons entering the eye into patterns of neuronal activity, which then drive motor and endocrine behavioral responses. The gene products important for visual processing by a living and behaving vertebrate animal have not been identified in an unbiased fashion. Likewise, the genes that affect development of the nervous system to shape visual function later in life are largely unknown. Here we have set out to close this gap in our understanding by using a forward genetic approach in zebrafish. Moving stimuli evoke two innate reflexes in zebrafish larvae, the optomotor and the optokinetic response, providing two rapid and quantitative tests to assess visual function in wild-type (WT) and mutant animals. These behavioral assays were used in a high-throughput screen, encompassing over half a million fish. In almost 2,000 F2 families mutagenized with ethylnitrosourea, we discovered 53 recessive mutations in 41 genes. These new mutations have generated a broad spectrum of phenotypes, which vary in specificity and severity, but can be placed into only a handful of classes. Developmental phenotypes include complete absence or abnormal morphogenesis of photoreceptors, and deficits in ganglion cell differentiation or axon targeting. Other mutations evidently leave neuronal circuits intact, but disrupt phototransduction, light adaptation, or behavior-specific responses. Almost all of the mutants are morphologically indistinguishable from WT, and many survive to adulthood. Genetic linkage mapping and initial molecular analyses show that our approach was effective in identifying genes with functions specific to the visual system. This collection of zebrafish behavioral mutants provides a novel resource for the study of normal vision and its genetic disorders

Impact of five years of peer-mediated interventions on sexual behavior and sexually transmitted infections among female sex workers in Mombasa, Kenya

<p>Abstract</p> <p>Background</p> <p>Since 2000, peer-mediated interventions among female sex workers (FSW) in Mombasa Kenya have promoted behavioural change through improving knowledge, attitudes and awareness of HIV serostatus, and aimed to prevent HIV and other sexually transmitted infection (STI) by facilitating early STI treatment. Impact of these interventions was evaluated among those who attended peer education and at the FSW population level.</p> <p>Methods</p> <p>A pre-intervention survey in 2000, recruited 503 FSW using snowball sampling. Thereafter, peer educators provided STI/HIV education, condoms, and facilitated HIV testing, treatment and care services. In 2005, data were collected using identical survey methods, allowing comparison with historical controls, and between FSW who had or had not received peer interventions.</p> <p>Results</p> <p>Over five years, sex work became predominately a full-time activity, with increased mean sexual partners (2.8 versus 4.9/week; <it>P </it>< 0.001). Consistent condom use with clients increased from 28.8% (145/503) to 70.4% (356/506; <it>P </it>< 0.001) as well as the likelihood of refusing clients who were unwilling to use condoms (OR = 4.9, 95%CI = 3.7–6.6). In 2005, FSW who received peer interventions (28.7%, 145/506), had more consistent condom use with clients compared with unexposed FSW (86.2% versus 64.0%; AOR = 3.6, 95%CI = 2.1–6.1). These differences were larger among FSW with greater peer-intervention exposure. HIV prevalence was 25% (17/69) in FSW attending ≥ 4 peer-education sessions, compared with 34% (25/73) in those attending 1–3 sessions (P = 0.21). Overall HIV prevalence was 30.6 (151/493) in 2000 and 33.3% (166/498) in 2005 (<it>P </it>= 0.36).</p> <p>Conclusion</p> <p>Peer-mediated interventions were associated with an increase in protected sex. Though peer-mediated interventions remain important, higher coverage is needed and more efficacious interventions to reduce overall vulnerability and risk.</p