Cortical State Fluctuations during Sensory Decision Making

In many behavioral tasks, cortex enters a desynchronized state where low-frequency fluctuations in population activity are suppressed. The precise behavioral correlates of desynchronization and its global organization are unclear. One hypothesis holds that desynchronization enhances stimulus coding in the relevant sensory cortex. Another hypothesis holds that desynchronization reflects global arousal, such as task engagement. Here, we trained mice on tasks where task engagement could be distinguished from sensory accuracy. Using widefield calcium imaging, we found that performance-related desynchronization was global and correlated better with engagement than with accuracy. Consistent with this link between desynchronization and engagement, rewards had a long-lasting desynchronizing effect. To determine whether engagement-related state changes depended on the relevant sensory modality, we trained mice on visual and auditory tasks and found that in both cases desynchronization was global, including regions such as somatomotor cortex. We conclude that variations in low-frequency fluctuations are predominately global and related to task engagement

Combined DNA Methylation and Gastric Microbiome Marker Predicts Helicobacter pylori-Negative Gastric Cancer.

BACKGROUND/AIMS: While DNA methylation and gastric microbiome are each associated with gastric cancer (GC), their combined role in predicting GC remains unclear. This study investigated the potential of a combined DNA methylation and gastric microbiome signature to predict Helicobacter pylori-negative GC. METHODS: In this case-control study, we conducted quantitative methylation-specific polymerase chain reaction to measure the methylation levels of DKK3, SFRP1, EMX1, NKX6-1, MIR124-3, and TWIST1 in the gastric mucosa from 75 H. pylori-negative patients, including chronic gastritis (CG), intestinal metaplasia (IM), and GC. A combined analysis of DNA methylation and gastric microbiome, using 16S rRNA gene sequencing, was performed in 30 of 75 patients. RESULTS: The methylation levels of DKK3, SFRP1, EMX1, MIR124-3, and TWIST1 were significantly higher in patients with GC than in controls (all q<0.05). MIR124-3 and TWIST1 methylation levels were higher in patients with IM than those with CG and also in those with GC than in those with IM (all q<0.05). A higher methylation level of TWIST1 was an independent predictor for H. pylori-negative GC after adjusting for age, sex, and atrophy (odds ratio [OR], 15.15; 95% confidence interval [CI], 1.58 to 145.46; p=0.018). The combination of TWIST1 methylation and GC microbiome index (a microbiome marker) was significantly associated with H. pylori-negative GC after adjusting for age, sex, and atrophy (OR, 50.00; 95% CI, 1.69 to 1,476; p=0.024). CONCLUSIONS: The combination of TWIST1 methylation and GC microbiome index may offer potential as a biomarker for predicting H. pylori-negative GC

IL-1RI (interleukin-1 receptor type I) signalling is essential for host defence and hemichannel activity during acute central nervous system bacterial infection

Staphylococcus aureus is a common aetiological agent of bacterial brain abscesses. We have previously established that a considerable IL-1 (interleukin-1) response is elicited immediately following S. aureus infection, where the cytokine can exert pleiotropic effects on glial activation and blood–brain barrier permeability. To assess the combined actions of IL-1α and IL-1β during CNS (central nervous system) infection, host defence responses were evaluated in IL-1RI (IL-1 receptor type I) KO (knockout) animals. IL-1RI KO mice were exquisitely sensitive to intracerebral S. aureus infection, as demonstrated by enhanced mortality rates and bacterial burdens within the first 24 h following pathogen exposure compared with WT (wild-type) animals. Loss of IL-1RI signalling also dampened the expression of select cytokines and chemokines, concomitant with significant reductions in neutrophil and macrophage infiltrates into the brain. In addition, the opening of astrocyte hemichannels during acute infection was shown to be dependent on IL-1RI activity. Collectively, these results demonstrate that IL-1RI signalling plays a pivotal role in the genesis of immune responses during the acute stage of brain abscess development through S. aureus containment, inflammatory mediator production, peripheral immune cell recruitment, and regulation of astrocyte hemichannel activity. Taken in the context of previous studies with MyD88 (myeloid differentiation primary response gene 88) and TLR2 (Toll-like receptor 2) KO animals, the current report advances our understanding of MyD88-dependent cascades and implicates IL-1RI signalling as a major antimicrobial effector pathway during acute brain-abscess formation

High incidence of diabetes after stroke in young adults and risk of recurrent vascular events: the FUTURE study

BACKGROUND: Diabetes diagnosed prior to stroke in young adults is strongly associated with recurrent vascular events. The relevance of impaired fasting glucose (IFG) and incidence of diabetes after young stroke is unknown. We investigated the long-term incidence of diabetes after young stroke and evaluated the association of diabetes and impaired fasting glucose with recurrent vascular events. METHODS: This study was part of the FUTURE study. All consecutive patients between January 1, 1980, and November 1, 2010 with TIA or ischemic stroke, aged 18-50, were recruited. A follow-up assessment was performed in survivors between November 1, 2009 and January 1, 2012 and included an evaluation for diabetes, fasting venous plasma glucose and recurrent vascular events. The association of diabetes and IFG with recurrent vascular events was assessed by logistic regression analysis, adjusted for age, sex and follow-up duration. RESULTS: 427 survivors without a medical history of diabetes were included in the present analysis (mean follow-up of 10.1 (SD 8.4) years; age 40.3 (SD 7.9) years). The incidence rate of diabetes was 7.9 per 1000 person-years and the prevalence of IFG was 21.1%. Patients with diabetes and IFG were more likely to have experienced any vascular event than those with normal fasting glucose values (OR 3.5 (95%CI 1.5-8.4) for diabetes and OR 2.5 (95%CI 1.3-4.8) for IFG). CONCLUSIONS: Diabetes or IFG in young stroke survivors is frequent and is associated with recurrent vascular events. Regular screening for IFG and diabetes in this population, yields potential for secondary prevention

Pneumatization Pattern of the Frontal Recess: Relationship of the Anterior-to-Posterior Length of Frontal Isthmus and/or Frontal Recess with the Volume of Agger Nasi Cell

ObjectivesWe analyzed the pneumatization pattern of the frontal recess (FR) in a Korean population. We also determined the correlation between the volume of the agger nasi cell (ANC) and the anterior-to-posterior (A-P) length of the frontal isthmus (FI) and FR.MethodsMultiplanar paranasal sinus computed tomography (CT) images from 105 patients who underwent endoscopic sinus surgery were reviewed. The prevalence of frontal recess cells (FRCs), thickness of the frontal beak (FB), volume of the ANC, A-P length of the FI, and FR were evaluated.ResultsThe ANC was identified in 96% of the patients and frontal cells (FCs) in 32% (FC type 1, 24.2%; type 2, 4.2%; type 3, 3.1%; and type 4, 0%). The prevalences of frontal bullar, suprabullar, supraorbital ethmoidal, and interfrontal sinus septal cells were 10%, 7.8%, 3.6%, and 6.8%, respectively. The A-P lengths of the FR and FI were 10.1±3.1 and 8.4±2.9 mm, respectively. The thickness of the FB was 7.8±1.8 mm and the volume of the ANC averaged 394.1±240.5 mm3. The thickness of the FB did not correlate with the volume of the ANC. In contrast, the A-P length of the FI and FR were positively correlated with the volume of the ANC.ConclusionANCs and FCs were found in 96% and 32% of the cases in this series. FC type 4 was not seen. What appeared to be FC4 on conventional CT was identified as FBC from reconstructed parasagittal images. A large ANC increased the A-P length of the FI and FR, regardless of the thickness of the FB

Plasmodium sporozoite phospholipid scramblase interacts with mammalian carbamoyl-phosphate synthetase 1 to infect hepatocytes

After inoculation by the bite of an infected mosquito, Plasmodium sporozoites enter the blood stream and infect the liver, where each infected cell produces thousands of merozoites. These in turn, infect red blood cells and cause malaria symptoms. To initiate a productive infection, sporozoites must exit the circulation by traversing the blood lining of the liver vessels after which they infect hepatocytes with unique specificity. We screened a phage display library for peptides that structurally mimic (mimotope) a sporozoite ligand for hepatocyte recognition. We identified HP1 (hepatocyte-binding peptide 1) that mimics a ~50 kDa sporozoite ligand (identified as phospholipid scramblase). Further, we show that HP1 interacts with a ~160 kDa hepatocyte membrane putative receptor (identified as carbamoyl-phosphate synthetase 1). Importantly, immunization of mice with the HP1 peptide partially protects them from infection by the rodent parasite P. berghei. Moreover, an antibody to the HP1 mimotope inhibits human parasite P. falciparum infection of human hepatocytes in culture. The sporozoite ligand for hepatocyte invasion is a potential novel pre-erythrocytic vaccine candidate. © 2021, The Author(s).1

High-yield methods for accurate two-alternative visual psychophysics in head-fixed mice

Research in neuroscience relies increasingly on the mouse, a mammalian species that affords unparalleled genetic tractability and brain atlases. Here we introduce high-yield methods for probing mouse visual decisions. Mice are head-fixed, which facilitates repeatable visual stimulation, eye tracking, and brain access. They turn a steering wheel to make two-alternative choices, forced or unforced. Learning is rapid thanks to intuitive coupling of stimuli to wheel position. The mouse decisions deliver high-quality psychometric curves for detection and discrimination, and conform to the predictions of a simple probabilistic observer model. The task is readily paired with two-photon imaging of cortical activity. Optogenetic inactivation reveals that the task requires the visual cortex. Mice are motivated to perform the task by fluid reward or optogenetic stimulation of dopaminergic neurons. This stimulation elicits larger number of trials and faster learning. These methods provide a platform to accurately probe mouse vision and its neural basis

Primary Language and Receipt of Recommended Health Care Among Hispanics in the United States

BackgroundDisparities in health care services between Hispanics and whites in the United States are well documented.ObjectiveThe objective of the study was to determine whether language spoken at home identifies Hispanics at risk for not receiving recommended health care services.DesignThe design of the study was cross-sectional, nationally representative survey of households.PatientsThe patients were non-Hispanic white and Hispanic adults participating in the 2003 Medical Expenditure Panel Survey.MeasurementsWe compared receipt of ten recommended health care services by ethnicity and primary language adjusting for demographic and socioeconomic characteristics, health status, and access to care.ResultsThe sample included 12,706 whites and 5,500 Hispanics. In bivariate comparisons, 57.0% of whites received all eligible health care services compared to 53.6% for Hispanics who spoke English at home, 44.9% for Hispanics who did not speak English at home but who were comfortable speaking English, and 35.0% for Hispanics who did not speak English at home and were uncomfortable speaking English (p < .001). In multivariate logistic models, compared to non-Hispanic whites, Hispanics who did not speak English at home were less likely to receive all eligible health care services, whether they were comfortable speaking English (risk ratio [RR] 0.88, 95% confidence interval [CI] 0.74-0.97) or not (RR 0.84, 95% CI 0.68-0.95).ConclusionsSpeaking a language other than English at home identified Hispanics at risk for not receiving recommended health care services, whether they were comfortable in speaking English or not. Identifying the mechanism for disparities by language usage may lead to interventions to reduce ethnic disparities

American Academy of Optometry Microbial Keratitis Think Tank

SIGNIFICANCE Think Tank 2019 affirmed that the rate of infection associated with contact lenses has not changed in several decades. Also, there is a trend toward more serious infections associated with Acanthamoeba and fungi. The growing use of contact lenses in children demands our attention with surveillance and case-control studies. PURPOSE The American Academy of Optometry (AAO) gathered researchers and key opinion leaders from around the world to discuss contact lens-associated microbial keratitis at the 2019 AAO Annual Meeting. METHODS Experts presented within four sessions. Session 1 covered the epidemiology of microbial keratitis, pathogenesis of Pseudomonas aeruginosa, and the role of lens care systems and storage cases in corneal disease. Session 2 covered nonbacterial forms of keratitis in contact lens wearers. Session 3 covered future needs, challenges, and research questions in relation to microbial keratitis in youth and myopia control, microbiome, antimicrobial surfaces, and genetic susceptibility. Session 4 covered compliance and communication imperatives. RESULTS The absolute rate of microbial keratitis has remained very consistent for three decades despite new technologies, and extended wear significantly increases the risk. Improved oxygen delivery afforded by silicone hydrogel lenses has not impacted the rates, and although the introduction of daily disposable lenses has minimized the risk of severe disease, there is no consistent evidence that they have altered the overall rate of microbial keratitis. Overnight orthokeratology lenses may increase the risk of microbial keratitis, especially secondary to Acanthamoeba, in children. Compliance remains a concern and a significant risk factor for disease. New insights into host microbiome and genetic susceptibility may uncover new theories. More studies such as case-control designs suited for rare diseases and registries are needed. CONCLUSIONS The first annual AAO Think Tank acknowledged that the risk of microbial keratitis has not decreased over decades, despite innovation. Important questions and research directions remain