Explore the vast range of titles available.

An association of the dopamine receptor D4 (DRD4) gene located on chromosome 11p15.5 and attention deficit/hyperactivity disorder (ADHD) has been demonstrated and replicated by multiple investigators. A specific allele [the 7-repeat of a 48-bp variable number of tandem repeats (VNTR) in exon 3] has been proposed as an etiological factor in attentional deficits manifested in some children diagnosed with this disorder. In the current study, we evaluated ADHD subgroups defined by the presence or absence of the 7-repeat allele of the DRD4 gene, using neuropsychological tests with reaction time measures designed to probe attentional networks with neuroanatomical foci in D4-rich brain regions. Despite the same severity of symptoms on parent and teacher ratings for the ADHD subgroups, the average reaction times of the 7-present subgroup showed normal speed and variability of response whereas the average reaction times of the 7-absent subgroup showed the expected abnormalities (slow and variable responses). This was opposite the primary prediction of the study. The 7-present subgroup seemed to be free of some of the neuropsychological abnormalities thought to characterize ADHD.

This study examined the effects of reward and response cost on the performance and motivation of 40 children with ADHD and 40 controls. Participants completed an arithmetic task under one of three (reward, response cost, and no contingency) conditions. Dependent variables included pretest attributional measures, direct performance measures, self-rated performance and motivation, and a postcontingency \"free-choice\" behavioral motivation measure. Relative to controls, children with ADHD reported a less adaptive attributional style and differed in their attributions for predicted good and poor performance. For children with ADHD, response cost improved accuracy on the arithmetic task relative to reward and resulted in higher motivation in the second half of the behavioral motivation measure; however, reward had a relatively more salutory effect on self-rated motivation. No negative effects of either reward or response cost on perceived performance or willingness to do the task again, or the behavioral motivation measure, were found for either group.

Recent literature has documented an association between Attention Deficit Hyperactivity Disorder (ADHD) and an increased prevalence of the 7-repeat allele of the dopamine receptor 4 (D4 receptor), which occurs in several lengths due to a natural polymorphism. This finding has been of particular theoretical interest given the history of dopaminergic theories of ADHD, and the striking pattern of D4 localization to brain regions implicated in the pathology of ADHD, including the frontal cortex, hippocampus, and nucleus accumbens. The current study was the first ever to investigate the possibility of neuropsychological differences between ADHD children with and without the DRD4.7 variant, in an attempt to integrate existing knowledge of the DRD4 receptor, neurobiological abnormalities in ADHD, and executive dysfunction in ADHD. Furthermore, a specific theory was proposed, predicting differential functioning between the two ADHD types (with and without the DRD4.7 polymorphism), with regards to fronto-hippocampal circuitry. All hypotheses predicted poorer performance among ADHD children with the DRD4.7 polymorphism. The sample included 13 ADHD children with the DRD4.7 polymorphism, 19 ADHD children without it, and 21 control children. ADHD children met strict inclusion criteria (DSM-IV diagnostic criteria for ADHD, Combined Type) with parents, teachers, and clinicians as informants. All participants completed an intellectual (Wechsler Intelligence Scale for Children-III) and academic skills (Wechsler Individual Achievement Tests) screening, as well as a neuro-cognitive battery. This battery included measures of sensory perception, motor learning, visual perception (Motor Free Visual Perception Test), verbal fluency (Controlled Oral Word Association Test), visual memory (non-standardized task), complex verbal learning (California Verbal Learning Test for Children), working memory, and planning/problem solving (Tower of London). Data were subjected to analyses of variance. Patterns of group differences were surprising in that the DRD4.7 polymorphism was no unilaterally associated with more impairment. Preliminary support emerged for differential front-hippocampal functioning between the two types of ADHD. Findings also implied differential localization of DRD4 receptors in various frontal lobe regions.

Antigen-naive IgM-producing B cells are atheroprotective, whereas mature B cells producing class-switched antibodies promote atherosclerosis. Activation-induced cytidine deaminase (AID), which mediates class switch recombination (CSR), would thus be expected to foster atherosclerosis. Yet, AID also plays a major role in the establishment of B cell tolerance. We sought to define whether AID affects atherosclerotic plaque formation. We generated Ldlr -/- chimeras transplanted with bone marrow from Aicda -/- or wild-type (WT) mice, fed a HFD for 14 weeks. Decreased B cell maturation in Ldlr -/- Aicda -/- mice was demonstrated by 50% reduction in splenic and aortic BAFFR expression, a key signaling component of B2 cell maturation. This was associated with increased plasma IgM in Ldlr –/- Aicda -/- compared with Ldlr -/- WT animals. Importantly, Ldlr -/- Aicda -/- mice had reduced atherosclerotic lesion area (0.20 ± 0.03mm 2 ) compared with Ldlr -/- WT (0.30 ± 0.04mm 2 , P < 0.05), although no differences in plaque composition were noted between groups. In addition, immunofluorescence analysis revealed increased splenic B and T cell areas independent of cell number. AID depletion directly inhibits atherosclerotic plaque formation.

Local governments have an important role to play in creating healthy, equitable and environmentally sustainable food systems. This study aimed to develop and pilot a tool and process for local governments in Australia to benchmark their policies for creating healthy, equitable and environmentally sustainable food systems. The Healthy Food Environment Policy Index (Food-EPI), developed in 2013 for national governments, was tailored to develop the Local Food Systems Policy Index (Local Food-EPI+) tool for local governments. To incorporate environmental sustainability and the local government context, this process involved a literature review and collaboration with an international and domestic expert advisory committee ( 35) and local government officials. Local governments. The tool consists of sixty-one indicators across ten food policy domains (weighted based on relative importance): leadership; governance; funding and resources; monitoring and intelligence; food production and supply chain; food promotion; food provision and retail in public facilities and spaces; supermarkets and food sources in the community; food waste reuse, redistribution and reduction; and support for communities. Pilot implementation of the tool in one local government demonstrated that the assessment process was feasible and likely to be helpful in guiding policy implementation. The Local Food-EPI+ tool and assessment process offer a comprehensive mechanism to assist local governments in benchmarking their actions to improve the healthiness, equity and environmental sustainability of food systems and prioritise action areas. Broad use of this tool will identify and promote leading practices, increase accountability for action and build capacity and collaborations.

Oncogenic alterations to DNA are not transforming in all cellular contexts 1 , 2 . This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet or under the nails 3 . We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma and enrichment for CRKL amplifications in acral melanoma. We modelled these changes in transgenic zebrafish models and found that CRKL -driven tumours formed predominantly in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL . RNA profiling of these fin and limb melanocytes, when compared with body melanocytes, revealed a positional identity gene programme typified by posterior HOX13 genes. This positional gene programme synergized with CRKL to amplify insulin-like growth factor (IGF) signalling and drive tumours at acral sites. Abrogation of this CRKL -driven programme eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults. In a zebrafish model of human cutaneous and acral melanomas, CRKL amplification causes tumours to favour a fin location, indicating that tumour location is determined by both the driver oncogenes and the pre-existing positional identity gene program.

BackgroundThe low mammography rates at the authors’ safety-net hospital (SNH) are associated with higher rates of late-stage disease. Previously, they showed that a phone call-based intervention with reminder and scheduling components significantly increased mammography uptake by 12% in their population, but implementation was resource-heavy. This study analyzed whether a text-based intervention with reminder and scheduling components could increase mammography uptake at 3 months compared with usual care.MethodsThis randomized controlled study analyzed 1277 women ages 50 to 65 years who were overdue for a mammogram but had established care at a primary-care clinic within an urban SNH. The patients received intervention 1 (a text reminder with specific scheduling options), intervention 2 (a text reminder with open-ended scheduling options), or usual care (control). Differences in the percentage of mammography uptake at 3 months were compared between the intervention and control groups using a two-tailed chi-square test.ResultsThe patients receiving a text-based reminder and scheduling opportunity were significantly more likely to receive mammograms within 3 months than those in the usual-care control group (10.2% vs 6.2%; χ2 = 5.6279; p = 0.03). In the intervention group, 10.3% of the participants scheduled an appointment for a mammogram via text, and 63% of these participants received a mammogram. Finally, mammography compliance did not differ by the type of scheduling offered (specific vs general) or by primary care clinic.ConclusionsLeveraging technology for reminders and scheduling via two-way text messaging is effective in increasing mammography uptake in an urban safety-net setting and may be used as part of a multi-tiered intervention to increase breast cancer screening in a safety-net setting.

IntroductionOur community-based participatory research partnership aims to expand understanding of the social, ethical and behavioural implications of COVID-19 testing and vaccination to inform the development of an integrated intervention that harnesses community-based peer navigation and mHealth strategies to improve COVID-19 testing and vaccination; test the intervention; and develop and disseminate practice, research and policy recommendations to further increase COVID-19 testing and vaccination among Spanish-speaking Latine communities in the USA.Methods and analysisWe will conduct 50 individual in-depth interviews with health providers, who have conducted COVID-19 testing and/or vaccination activities within Spanish-speaking communities, and with representatives from Latine-serving community-based organisations. We will also conduct six focus groups with 8–12 Spanish-speaking Latine community member participants each for a total number of about 60 focus group participants. Next, we will develop the Nuestra Comunidad Saludable intervention based on findings from interviews and focus groups and use a longitudinal group-randomised trial design with two arms (intervention and delayed intervention) to evaluate the impact of the intervention. We will recruit, enrol and collect baseline data from 20 community-based peer navigators (Navegantes) and their social network members (n=8 unique social network members per Navegante). Navegantes (coupled with their social networks) will be randomised to intervention or delayed intervention groups (10 Navegantes and 80 social network members per group).Ethics and disseminationEthical approval for data collection was granted by the Wake Forest University School of Medicine Institutional Review Board. Following the description of study procedures, we will obtain consent from all study participants. Study findings will be disseminated through an empowerment theory-based community forum, peer-reviewed publications and presentations at scientific meetings, and reports and briefs for lay, community and practitioner audiences.Trial registration numberNCT05302908.

Understanding the diversity of cell types in the brain has been an enduring challenge and requires detailed characterization of individual neurons in multiple dimensions. To systematically profile morpho-electric properties of mammalian neurons, we established a single-cell characterization pipeline using standardized patch-clamp recordings in brain slices and biocytin-based neuronal reconstructions. We built a publicly accessible online database, the Allen Cell Types Database, to display these datasets. Intrinsic physiological properties were measured from 1,938 neurons from the adult laboratory mouse visual cortex, morphological properties were measured from 461 reconstructed neurons, and 452 neurons had both measurements available. Quantitative features were used to classify neurons into distinct types using unsupervised methods. We established a taxonomy of morphologically and electrophysiologically defined cell types for this region of the cortex, with 17 electrophysiological types, 38 morphological types and 46 morpho-electric types. There was good correspondence with previously defined transcriptomic cell types and subclasses using the same transgenic mouse lines.