Apathy scores in Parkinson's disease relate to EEG components in an incentivized motor task.

Apathy is one of the most prevalent non-motor symptoms of Parkinson's disease and is characterized by decreased goal-directed behaviour due to a lack of motivation and/or impaired emotional reactivity. Despite its high prevalence, the neurophysiological mechanisms underlying apathy in Parkinson's disease, which may guide neuromodulation interventions, are poorly understood. Here, we investigated the neural oscillatory characteristics of apathy in Parkinson's disease using EEG data recorded during an incentivized motor task. Thirteen Parkinson's disease patients with apathy and 13 Parkinson's disease patients without apathy as well as 12 healthy controls were instructed to squeeze a hand grip device to earn a monetary reward proportional to the grip force they used. Event-related spectral perturbations during the presentation of a reward cue and squeezing were analysed using multiset canonical correlation analysis to detect different orthogonal components of temporally consistent event-related spectral perturbations across trials and participants. The first component, predominantly located over parietal regions, demonstrated suppression of low-beta (12-20 Hz) power (i.e. beta desynchronization) during reward cue presentation that was significantly smaller in Parkinson's disease patients with apathy compared with healthy controls. Unlike traditional event-related spectral perturbation analysis, the beta desynchronization in this component was significantly correlated with clinical apathy scores. Higher monetary rewards resulted in larger beta desynchronization in healthy controls but not Parkinson's disease patients. The second component contained gamma and theta frequencies and demonstrated exaggerated theta (4-8 Hz) power in Parkinson's disease patients with apathy during the reward cue and squeezing compared with healthy controls (HCs), and this was positively correlated with Montreal Cognitive Assessment scores. The third component, over central regions, demonstrated significantly different beta power across groups, with apathetic groups having the lowest beta power. Our results emphasize that altered low-beta and low-theta oscillations are critical for reward processing and motor planning in Parkinson's disease patients with apathy and these may provide a target for non-invasive neuromodulation.

Air Pollution Coverage, Anti-Chinese Sentiment, and Attitudes Towards Foreign Policy in South Korea.

Air pollutants allegedly originating from China have become a thorny issue in South Korea. Despite a neutral view of the topic on the part of the South Korean government, recent public polls show a high correlation between the air pollution issue and negative sentiment toward China. How has the media reported on China regarding air pollutants in South Korea? What is the effect of media reports on air pollution on anti-Chinese sentiment and foreign policy attitudes? By examining news headlines and Twitter data in 2015 and 2018, this work finds that media reports blaming China for air pollution doubled during the 2015-2018 period. Discourse surrounding air pollution also shifted: negative sentiment directed at both the Chinese government and the Chinese people increased in 2018 compared to 2015. In addition, an original online survey experiment shows that China-blaming articles have a causal effect on increasing related resentment, particularly toward Chinese people, and that this effect is moderated by age group. Such articles have also had negative effects on foreign policy attitudes via increased anti-Chinese sentiment; greater hostility toward the Chinese people is found to have a causal effect on reduced support for strengthening relations with their country. Supplementary Information: The online version contains supplementary material available at 10.1007/s11366-023-09849-z.

A scoping review of psychiatric conditions associated with chronic pain in the homeless and marginally housed population.

The present review sought to examine and summarise the unique experience of concurrent pain and psychiatric conditions, that is often neglected, within the population of homeless individuals. Furthermore, the review examined factors that work to aggravate pain and those that have been shown to improve pain management. Electronic databases (MEDLINE, EMBASE, psycINFO, and Web of Science) and the grey literature (Google Scholar) were searched. Two reviewers independently screened and assessed all literature. The PHO MetaQAT was used to appraise quality of all studies included. Fifty-seven studies were included in this scoping review, with most of the research being based in the United States of America. Several interacting factors were found to exacerbate reported pain, as well as severely affect other crucial aspects of life that correlate directly with health, within the homeless population. Notable factors included drug use as a coping mechanism for pain, as well as opioid use preceding pain; financial issues; transportation problems; stigma; and various psychiatric disorders, such as post-traumatic stress disorder, depression, and anxiety. Important pain management strategies included cannabis use, Accelerated Resolution Therapy for treating trauma, and acupuncture. The homeless population experiences multiple barriers which work to further impact their experience with pain and psychiatric conditions. Psychiatric conditions impact pain experience and can work to intensify already adverse health circumstances of homeless individuals.

HBV and HIV/HBV Infected Patients Have Distinct Immune Exhaustion and Apoptotic Serum Biomarker Profiles.

BACKGROUND: Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to their shared routes of transmission, approximately 10% of HIV-infected patients worldwide are chronically coinfected with HBV. Additionally, liver disease has become a major cause of morbidity and mortality in HBV/HIV coinfected patients due to prolonged survival with the success of antiretroviral therapy. The relationship between immune exhaustion markers (PD-1/PD-L1) and apoptotic markers such as Fas/FasL, TGFß1, TNF-α, and Th1/Th2 cytokines are not clearly delineated in HBV/HIV coinfection. METHODS: Levels of soluble Fas/FasL, TGFß1, TNF-α, and sPD-1/sPD-L1 as well as Th1 and Th2 cytokines were evaluated in the sera of HBV-monoinfected (n = 30) and HBV/HIV-coinfected (n = 15) patients and compared to levels in healthy controls (n = 20). RESULTS: HBV-monoinfected patients had significantly lower levels of the anti-inflammatory cytokine IL-4 (P < 0.05) and higher levels of apoptotic markers sFas, sFasL, and TGFß-1 (P < 0.001) compared to healthy controls. Coinfection with HIV was associated with higher levels of sFas, TNF-α, and sPD-L1 (P < 0.005), and higher levels of the pro-inflammatory cytokines IL-6, IL-8, and IL-12p70 (P < 0.05) compared to healthy controls. Patients with HBV infection had a unique biomarker clustering profile comprised of IFN-γ, IL12p70, IL-10, IL-6, and TNF-α that was distinct from the profile of the healthy controls, and the unique HIV/HBV profile comprised GM-CSF, IL-4, IL-2, IFN-γ, IL12p70, IL-7, IL-10, and IL-1ß. In HBV monoinfection a significant correlation between sFasL and PD1(r = 0.46, P = < 0.05) and between sFas and PDL1 (r = 0.48, P = <0.01) was observed. CONCLUSION: HBV-infected and HBV/HIV-coinfected patients have unique apoptosis and inflammatory biomarker profiles that distinguish them from each other and healthy controls. The utilization of those unique biomarker profiles for monitoring disease progression or identifying individuals who may benefit from novel immunotherapies such as anti-PD-L1 or anti-PD-1 checkpoint inhibitors appears promising and warrants further investigation.

Extra-coding RNAs regulate neuronal DNA methylation dynamics.

Epigenetic mechanisms such as DNA methylation are essential regulators of the function and information storage capacity of neurons. DNA methylation is highly dynamic in the developing and adult brain, and is actively regulated by neuronal activity and behavioural experiences. However, it is presently unclear how methylation status at individual genes is targeted for modification. Here, we report that extra-coding RNAs (ecRNAs) interact with DNA methyltransferases and regulate neuronal DNA methylation. Expression of ecRNA species is associated with gene promoter hypomethylation, is altered by neuronal activity, and is overrepresented at genes involved in neuronal function. Knockdown of the Fos ecRNA locus results in gene hypermethylation and mRNA silencing, and hippocampal expression of Fos ecRNA is required for long-term fear memory formation in rats. These results suggest that ecRNAs are fundamental regulators of DNA methylation patterns in neuronal systems, and reveal a promising avenue for therapeutic targeting in neuropsychiatric disease states.

Peripheral GABAA receptor activation modulates rat tongue afferent mechanical sensitivity.

OBJECTIVES: The expression of GABA(A) receptors and the effects of GABAA receptor agonists on the response properties of tongue afferent fibres were investigated in female rats to determine if peripheral GABA receptors might be a target of topical benzodiazepines when used for pain relief in burning mouth syndrome patients. DESIGN: Nerve fibres in tongue sections from six female rats were identified using protein gene product 9.5, and the co-expression of the γ subunit of GABAA receptor and substance P assessed in the nerve fibres. In vivo extracellular recordings of trigeminal ganglion neurons that innervate the tongue were undertaken in 27 anesthetised female rats and their responses to mechanical and thermal stimulation characterised before and after topical application of GABA, the GABA(A) receptor selective agonist muscimol or vehicle control. RESULTS: The vast majority of tongue nerve fibres examined (95%) expressed the γ subunit of GABA(A) receptor. Bath application of muscimol, but not GABA, significantly increased the mechanical thresholds of tongue afferent fibres compared to vehicle, but only after the tongue had been heated with 60°C water. CONCLUSIONS: GABA(A) receptors are present on tongue nerve fibres and their activation alters the mechanical sensitivity these fibres. These findings suggest that topical application of benzodiazepines to the oral mucosa may decrease pain in burning mouth syndrome through a local action on peripheral GABAA receptors.

DNA methylation regulates associative reward learning.

Reward-related memories are essential for adaptive behavior and evolutionary fitness, but they are also a core component of maladaptive brain diseases such as addiction. Reward learning requires dopamine neurons located in the ventral tegmental area (VTA), which encode relationships between predictive cues and future rewards. Recent evidence suggests that epigenetic mechanisms, including DNA methylation, are essential regulators of neuronal plasticity and experience-driven behavioral change. However, the role of epigenetic mechanisms in reward learning is poorly understood. Here we show that the formation of reward-related associative memories in rats upregulates key plasticity genes in the VTA, which are correlated with memory strength and associated with gene-specific changes in DNA methylation. Moreover, DNA methylation in the VTA is required for the formation of stimulus-reward associations. These results provide the first evidence that that activity-dependent methylation and demethylation of DNA is an essential substrate for the behavioral and neuronal plasticity driven by reward-related experiences.

Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotype-specific polysaccharides in human urine.

To improve the clinical diagnosis of pneumococcal infection in bacteremic and nonbacteremic community-acquired pneumonia (CAP), a Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and validated. The UAD assay can simultaneously detect 13 different serotypes of Streptococcus pneumoniae by capturing serotype-specific S. pneumoniae polysaccharides (PnPSs) secreted in human urine. Assay specificity is achieved by capturing the polysaccharides with serotype-specific monoclonal antibodies (MAbs) on spectrally unique microspheres. Positivity for each serotype was based on positivity cutoff values calculated from a standard curve run on each assay plate together with positive- and negative-control urine samples. The assay is highly specific, since significant signals are detected only when each PnPS was paired with its homologous MAb-coated microspheres. Validation experiments demonstrated excellent accuracy and precision. The UAD assay and corresponding positivity cutoff values were clinically validated by assessing 776 urine specimens obtained from patients with X-ray-confirmed CAP. The UAD assay demonstrated 97% sensitivity and 100% specificity using samples obtained from patients with bacteremic, blood culture-positive CAP. Importantly, the UAD assay identified Streptococcus pneumoniae (13 serotypes) in a proportion of individuals with nonbacteremic CAP, a patient population for which the pneumococcal etiology of CAP was previously difficult to assess. Therefore, the UAD assay provides a specific, noninvasive, sensitive, and reproducible tool to support vaccine efficacy as well as epidemiological evaluation of pneumococcal disease, including CAP, in adults.