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BackgroundThere is no clear guidance on how to implement opportunistic atrial fibrillation (AF) screening in daily clinical practice.ObjectivesThis study evaluated the perception of general practitioners (GPs) about value and practicalities of implementing screening for AF, focusing on opportunistic single-time point screening with a single-lead electrocardiogram (ECG) device.MethodsA descriptive cross-sectional study was conducted with a survey developed to assess overall perception concerning AF screening, feasibility of opportunistic single-lead ECG screening and implementation requirements and barriers.ResultsA total of 659 responses were collected (36.1% Eastern, 33.4% Western, 12.1% Southern, 10.0% Northern Europe, 8.3% United Kingdom & Ireland). The perceived need for standardized AF screening was rated as 82.7 on a scale from 0 to 100. The vast majority (88.0%) indicated no AF screening program is established in their region. Three out of four GPs (72.1%, lowest in Eastern and Southern Europe) were equipped with a 12-lead ECG, while a single-lead ECG was less common (10.8%, highest in United Kingdom & Ireland). Three in five GPs (59.3%) feel confident ruling out AF on a single-lead ECG strip. Assistance through more education (28.7%) and a tele-healthcare service offering advice on ambiguous tracings (25.2%) would be helpful. Preferred strategies to overcome barriers like insufficient (qualified) staff, included integrating AF screening with other healthcare programs (24.9%) and algorithms to identify patients most suitable for AF screening (24.3%).ConclusionGPs perceive a strong need for a standardized AF screening approach. Additional resources may be required to have it widely adopted into clinical practice.

We previously demonstrated that brain-resident cells produce IFN-γ in response to reactivation of cerebral infection with Toxoplasma gondii. To obtain an overall landscape view of the effects of IFN-γ from brain-resident cells on the cerebral protective immunity, in the present study we employed NanoString nCounter assay and quantified mRNA levels for 734 genes in myeloid immunity in the brains of T and B cell-deficient, bone marrow chimeric mice with and without IFN-γ production by brain-resident cells in response to reactivation of cerebral T. gondii infection. Our study revealed that IFN-γ produced by brain-resident cells amplified mRNA expression for the molecules to activate the protective innate immunity including 1) chemokines for recruitment of microglia and macrophages (CCL8 and CXCL12) and 2) the molecules for activating those phagocytes (IL-18, TLRs, NOD1, and CD40) for killing tachyzoites. Importantly, IFN-γ produced by brain-resident cells also upregulated cerebral expression of molecules for facilitating the protective T cell immunity, which include the molecules for 1) recruiting effector T cells (CXCL9, CXCL10, and CXCL11), 2) antigen processing (PA28αβ, LMP2, and LMP7), transporting the processed peptides (TAP1 and TAP2), assembling the transported peptides to the MHC class I molecules (Tapasin), and the MHC class I (H2-K1 and H2-D1) and Ib molecules (H2-Q1, H-2Q2, and H2-M3) for presenting antigens to activate the recruited CD8+ T cells, 3) MHC class II molecules (H2-Aa, H2-Ab1, H2-Eb1, H2-Ea-ps, H2-DMa, H2-Ob, and CD74) to present antigens for CD4+ T cell activation, 4) co-stimulatory molecules (ICOSL) for T cell activation, and 5) cytokines (IL-12, IL-15, and IL-18) facilitating IFN-γ production by NK and T cells. Notably, the present study also revealed that IFN-γ production by brain-resident cells also upregulates cerebral expressions of mRNA for the downregulatory molecules (IL-10, STAT3, SOCS1, CD274 [PD-L1], IL-27, and CD36), which can prevent overly stimulated IFN-γ-mediated pro-inflammatory responses and tissue damages. Thus, the present study uncovered the previously unrecognized the capability of IFN-γ production by brain-resident cells to upregulate expressions of a wide spectrum of molecules for coordinating both innate and T cell-mediated protective immunity with a fine-tuning regulation system to effectively control cerebral infection with T. gondii.

Neuroinflammation and the tissue-resident innate immune cells, the microglia, respond and contribute to neurodegenerative pathology. Although microglia have been the focus of work linking neuroinflammation and associated dementias like Alzheimer’s Disease, the inflammatory milieu of brain is a conglomerate of cross-talk amongst microglia, systemic immune cells and soluble mediators like cytokines. Age-related changes in the inflammatory profile at the levels of both the brain and periphery are largely orchestrated by immune system cells. Strong evidence indicates that both innate and adaptive immune cells, the latter including T cells and B cells, contribute to chronic neuroinflammation and thus dementia. Neurodegenerative hallmarks coupled with more traditional immune system stimuli like infection or injury likely combine to trigger and maintain persistent microglial and thus brain inflammation. This review summarizes age-related changes in immune cell function, with special emphasis on lymphocytes as a source of inflammation, and discusses how such changes may potentiate both systemic and central nervous system inflammation to culminate in dementia. We recap the understudied area of AD-associated changes in systemic lymphocytes in greater detail to provide a unifying perspective of inflammation-fueled dementia, with an eye toward evidence of two-way communication between the brain parenchyma and blood immune cells. We focused our review on human subjects studies, adding key data from animal models as relevant.

Introduction: Previous research suggests children diagnosed with autism spectrum disorder (ASD or “autism”) born extremely and very preterm face substantially delayed development than their peers born full-term. Further, children born preterm are proposed to show a unique behavioral phenotype, which may overlap with characteristics of autism, making it difficult to disentangle their clinical presentation. To clarify the presentation of autism in children born preterm, this study examined differences in key indicators of child development (expressive language, receptive language, fine motor, and visual reception) and characteristics of autism (social affect and repetitive, restricted behaviors).Materials and Methods: One fifty-eight children (136 full-term, twenty-two preterm) diagnosed with autism, aged 22–34 months, were identified prospectively using the Social Attention and Communication Surveillance tools during community-based, developmental surveillance checks in the second year of life. Those identified at “high likelihood” of an autism diagnosis were administered the Mullen Scales of Early Learning and the Autism Diagnostic Observation Schedule.Results: The children born preterm and full-term did not differ significantly in their fine motor, visual reception, expressive language, or receptive language skills. No significant differences in social affect and repetitive and restrictive behavior traits were found.Discussion: The findings of this study differs from previous research where children diagnosed with autism born very or extremely preterm were developmentally delayed and had greater autistic traits than their term-born peers. These null findings may relate to the large proportion of children born moderate to late preterm in this sample. This study was unique in its use of a community-based, prospectively identified sample of children diagnosed with autism at an early age. It may be that children in these groups differ from clinic- and hospital-based samples, that potential differences emerge later in development, or that within the autism spectrum, children born preterm and full-term develop similarly. It was concluded that within the current sample, at 2 years of age, children diagnosed with autism born preterm are similar to their peers born full-term. Thus, when clinicians identify characteristics of autism in children born preterm, it is important to refer the child for a diagnostic assessment for autism.

Several studies have shown that a single exposure to stress may improve or impair learning and memory processes, depending on the timing in which the stress event occurs with relation to the acquisition phase. However, to date there is no information about the molecular changes that occur at the synapse during the stress-induced memory modification and after a recovery period. In particular, there are no studies that have evaluated—at the same time—the temporality of stress and stress recovery period in hippocampal short-term memory and the effects on dendritic spine morphology, along with variations in N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits. The aim of our study was to take a multidimensional approach to investigate concomitant behavioral, morphological and molecular changes induced by a single restraint stress exposure (2.5 h) and a recovery period of 6 and 24 h in rats. We found that acute stress elicited a reduced preference to explore an object placed in a novel position (a hippocampal-dependent task). These changes were accompanied by increased activity of LIM kinase I (LIMK; an actin-remodeling protein) and increased levels of NR2A subunits of NMDA receptors. After 6 h of recovery from stress, rats showed similar preference to explore an object placed in a novel or familiar position, but density of immature spines increased in secondary CA1 apical dendrites, along with a transient rise in GluA2 AMPA receptor subunits. After 24 h of recovery from stress, the animals showed a preference to explore an object placed in a novel position, which was accompanied by a normalization of NMDA and AMPA receptor subunits to control values. Our data suggest that acute stress produces reversible molecular and behavioral changes 24 h after stress, allowing a full reestablishment of hippocampal-related memory. Further studies need to be conducted to deepen our understanding of these changes and their reciprocal interactions.Adaptive stress responses are a promising avenue to develop interventions aiming at restoring hippocampal function impaired by repetitive stress exposure.

Serotonin (5-HT) is a neurotransmitter that plays an important role in neuronal plasticity. Variations in the levels of 5-HT at the synaptic cleft, expression or dysfunction of serotonin receptors may alter brain development and predispose to various mental diseases. Here, we review the transduction pathways described in various cell types transfected with recombinant 5-HT1A receptor (5-HT1AR), specially contrasting with those findings obtained in neuronal cells. The 5-HT1AR is detected in early stages of neural development and is located in the soma, dendrites and spines of hippocampal neurons. The 5-HT1AR differs from other serotonin receptors because it is coupled to different pathways, depending on the targeted cell. The signaling pathway associated with this receptor is determined by Gα isoforms and some cascades involve βγ signaling. The activity of 5-HT1AR usually promotes a reduction in neuronal excitability and firing, provokes a variation in cAMP and Ca2+, levels which may be linked to specific types of behavior and cognition. Furthermore, evidence indicates that 5-HT1AR induces neuritogesis and synapse formation, probably by modulation of the neuronal cytoskeleton through MAPK and PI3K-Akt signaling pathways. Advances in understanding the actions of 5-HT1AR and its association with different signaling pathways in the central nervous system will reveal their pivotal role in health and disease.