Episodic memory formation depends on information about a stimulus being integrated within a precise spatial and temporal context, a process dependent on the hippocampus and prefrontal cortex. ...Investigations of putative functional interactions between these regions are complicated by multiple direct and indirect hippocampal-prefrontal connections. Here application of a pharmacogenetic deactivation technique enabled us to investigate the mnemonic contributions of two direct hippocampal-medial prefrontal cortex (mPFC) pathways, one arising in the dorsal CA1 (dCA1) and the other in the intermediate CA1 (iCA1). While deactivation of either pathway impaired episodic memory, the resulting pattern of mnemonic deficits was different: deactivation of the dCA1→mPFC pathway selectively disrupted temporal order judgments while iCA1→mPFC pathway deactivation disrupted spatial memory. These findings reveal a previously unsuspected division of function among CA1 neurons that project directly to the mPFC. Such subnetworks may enable the distinctiveness of contextual information to be maintained in an episodic memory circuit.
•SARS-CoV-2 spike reactive serum immunoglobulin G antibodies are present in prepandemic samples.•SARS-CoV-2 spike reactive mucosal immunoglobulin A antibodies are present in prepandemic ...samples.•SARS-CoV-2 spike reactive prepandemic antibodies neutralize pseudotyped SARS-CoV-2.•Prepandemic antibodies are also cross-reactive to human endemic coronaviruses.
Many regions of Africa have experienced lower COVID-19 morbidity and mortality than Europe. Pre-existing humoral responses to endemic human coronaviruses (HCoV) may cross-protect against SARS-CoV-2. We investigated the neutralizing capacity of SARS-CoV-2 spike reactive and nonreactive immunoglobulin (Ig)G and IgA antibodies in prepandemic samples.
To investigate the presence of pre-existing immunity, we performed enzyme-linked immunosorbent assay using spike antigens from reference SARS-CoV-2, HCoV HKU1, OC43, NL63, and 229E using prepandemic samples from Kilifi in coastal Kenya. In addition, we performed neutralization assays using pseudotyped reference SARS-CoV-2 to determine the functionality of the identified reactive antibodies.
We demonstrate the presence of HCoV serum IgG and mucosal IgA antibodies, which cross-react with the SARS-CoV-2 spike. We show pseudotyped reference SARS-CoV-2 neutralization by prepandemic serum, with a mean infective dose 50 of 1: 251, which is 10-fold less than that of the pooled convalescent sera from patients with COVID-19 but still within predicted protection levels. The prepandemic naso-oropharyngeal fluid neutralized pseudo-SARS-CoV-2 at a mean infective dose 50 of 1: 5.9 in the neutralization assay.
Our data provide evidence for pre-existing functional humoral responses to SARS-CoV-2 in Kilifi, coastal Kenya and adds to data showing pre-existing immunity for COVID-19 from other regions.
•Evidence on the effect of pre-eclampsia on offspring ADHD is not well established.•Offspring of mothers with pre-eclampsia are at increased risk of ADHD.•Early screening for ADHD is recommended in ...offspring of women with pre-eclampsia.
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent heterogeneous neurodevelopmental syndrome associated with various environmental factors. This study examined the association between maternal pre-eclampsia and offspring ADHD at 7- and 10-years. The study cohort consisted of more than 7200 children who participated in Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort study. ADHD was diagnosed using parent reported Development and Wellbeing Assessment (DAWBA). Log-binomial regression and Generalized Estimating Equation (GEE) models were used. The GEE analysis showed that pre-eclampsia was associated with increased risk of ADHD in offspring (adjusted risk ratio RR = 2.77; 95% confidence interval CI = 1.42–5.38). Similarly, the results of multivariable log-binomial regression analysis at each time point showed that pre-eclampsia was associated with an almost threefold increase risk of offspring ADHD. This study suggests that offspring of mothers with pre-eclampsia are at increased risk of ADHD, although residual and unmeasured confounding by environmental and genetic factors warrants further study. If our findings are replicated by others, early screening for ADHD and other developmental delays may be recommended in offspring of women with pre-eclampsia.
We use Lévy processes to generate joint prior distributions, and therefore penalty functions, for a location parameter β= (β₁ ,... , β p ) as p grows large. This generalizes the class of local—global ...shrinkage rules based on scale mixtures of normals, illuminates new connections between disparate methods and leads to new results for computing posterior means and modes under a wide class of priors. We extend this framework to large-scale regularized regression problems where p > n, and we provide comparisons with other methodologies.
Objective: Negative affect precedes binge eating and purging in bulimia nervosa (BN), but little is known about factors that precipitate negative affect in relation to these behaviors. We aimed to ...assess the temporal relation among stressful events, negative affect, and bulimic events in the natural environment using ecological momentary assessment. Method: A total of 133 women with current BN recorded their mood, eating behavior, and the occurrence of stressful events every day for 2 weeks. Multilevel structural equation mediation models evaluated the relations among Time 1 stress measures (i.e., interpersonal stressors, work/environment stressors, general daily hassles, and stress appraisal), Time 2 negative affect, and Time 2 binge eating and purging, controlling for Time 1 negative affect. Results: Increases in negative affect from Time 1 to Time 2 significantly mediated the relations between Time 1 interpersonal stressors, work/environment stressors, general daily hassles, and stress appraisal and Time 2 binge eating and purging. When modeled simultaneously, confidence intervals for interpersonal stressors, general daily hassles, and stress appraisal did not overlap, suggesting that each had a distinct impact on negative affect in relation to binge eating and purging. Conclusions: Our findings indicate that stress precedes the occurrence of bulimic behaviors and that increases in negative affect following stressful events mediate this relation. Results suggest that stress and subsequent negative affect may function as maintenance factors for bulimic behaviors and should be targeted in treatment.
Stimulator of interferon genes (STING) is a receptor in the endoplasmic reticulum that propagates innate immune sensing of cytosolic pathogen-derived and self DNA
. The development of compounds that ...modulate STING has recently been the focus of intense research for the treatment of cancer and infectious diseases and as vaccine adjuvants
. To our knowledge, current efforts are focused on the development of modified cyclic dinucleotides that mimic the endogenous STING ligand cGAMP; these have progressed into clinical trials in patients with solid accessible tumours amenable to intratumoral delivery
. Here we report the discovery of a small molecule STING agonist that is not a cyclic dinucleotide and is systemically efficacious for treating tumours in mice. We developed a linking strategy to synergize the effect of two symmetry-related amidobenzimidazole (ABZI)-based compounds to create linked ABZIs (diABZIs) with enhanced binding to STING and cellular function. Intravenous administration of a diABZI STING agonist to immunocompetent mice with established syngeneic colon tumours elicited strong anti-tumour activity, with complete and lasting regression of tumours. Our findings represent a milestone in the rapidly growing field of immune-modifying cancer therapies.
Psychotic experiences (PEs) are robustly associated with subsequent non-suicidal self-injury (NSSI) and suicide attempts, but questions remain as to the temporal relation and underlying cause of this ...association. Most investigations have incorporated only two waves of data, and no study has comprehensively investigated mediating pathways. This study aimed to investigate both the PE-NSSI and PE-suicide attempt association, and their relevant mediators, across three waves of prospective data. Participants were from an Australian prospective longitudinal cohort of 1100 adolescents (12–17 years); data were collected at three time points over 2 years. NSSI and suicide attempts were measured using the Self-Harm Behaviour Questionnaire. Items from the Diagnostic Interview Schedule for Children were used to assess four PE subtypes (auditory hallucinatory experiences HEs and three delusional experiences). Potential mediators of interest included: psychological distress, self-reported mental disorders, self-esteem, recent traumatic life events (e.g. bullying, sexual assault), emotion regulation, and impulsivity/other personality traits. Analyses were adjusted for sociodemographics and substance use. Auditory HEs were indirectly associated with future NSSI and suicide attempts via recent traumatic life events, high psychological distress, and low self-esteem, across three waves of data. Other PE subtypes were generally not associated with incident NSSI/suicide attempts at 1- and 2-year follow-up, either directly or indirectly. These findings highlight the importance of screening for auditory HEs when assessing a young person’s self-harm/suicide risk. Clinical assessment would be further enhanced by a comprehensive review of recent interpersonal traumatic events, as well as levels of self-esteem and distress.
Socioeconomic bias in influenza surveillance Scarpino, Samuel V; Scott, James G; Eggo, Rosalind M ...
PLOS computational biology/PLoS computational biology,
07/2020, Letnik:
16, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Individuals in low socioeconomic brackets are considered at-risk for developing influenza-related complications and often exhibit higher than average influenza-related hospitalization rates. This ...disparity has been attributed to various factors, including restricted access to preventative and therapeutic health care, limited sick leave, and household structure. Adequate influenza surveillance in these at-risk populations is a critical precursor to accurate risk assessments and effective intervention. However, the United States of America's primary national influenza surveillance system (ILINet) monitors outpatient healthcare providers, which may be largely inaccessible to lower socioeconomic populations. Recent initiatives to incorporate Internet-source and hospital electronic medical records data into surveillance systems seek to improve the timeliness, coverage, and accuracy of outbreak detection and situational awareness. Here, we use a flexible statistical framework for integrating multiple surveillance data sources to evaluate the adequacy of traditional (ILINet) and next generation (BioSense 2.0 and Google Flu Trends) data for situational awareness of influenza across poverty levels. We find that ZIP Codes in the highest poverty quartile are a critical vulnerability for ILINet that the integration of next generation data fails to ameliorate.
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