The neural tides of sleep and consciousness revealed by single-pulse electrical brain stimulation

Wakefulness and sleep arise from global changes in brain physiology that may also govern the flow of neural activity between cortical regions responsible for perceptual processing vs planning and action. To test whether and how the sleep/wake cycle affects the overall propagation of neural activity in large-scale brain networks, we applied single-pulse electrical stimulation (SPES) in patients implanted with intracranial EEG electrodes for epilepsy surgery. SPES elicited cortico-cortical spectral responses at high-gamma frequencies (CCSRHG, 80-150 Hz), which indexes changes in neuronal population firing rates. Using event-related causality analysis (ERC), we found that the overall patterns of neural propagation among sites with CCSRHG were different during wakefulness and different sleep stages. For example, stimulation of frontal lobe elicited greater propagation toward parietal lobe during slow wave sleep than during wakefulness. During REM sleep, we observed a decrease in propagation within frontal lobe, and an increase in propagation within parietal lobe, elicited by frontal and parietal stimulation, respectively. These biases in the directionality of large-scale cortical network dynamics during REM sleep could potentially account for some of the unique experiential aspects of this sleep stage. Together these findings suggest that the regulation of conscious awareness and sleep is associated with differences in the balance of neural propagation across large-scale frontal-parietal networks

Pathway to psychiatric care in Japan: A multicenter observational study

<p>Abstract</p> <p>Background</p> <p>This study examines pathways to psychiatric care in Japan using the same method as the collaborative study carried out in 1991 under the auspices of the World Health Organization.</p> <p>Methods</p> <p>Thirteen psychiatric facilities in Japan were involved. Of the 228 patients who contacted psychiatric facilities with any psychiatric illness, eighty four visiting psychiatric facilities for the first time were enrolled. Pathways to psychiatric care, delays from the onset of illness to treatment prior to reaching psychiatrists were surveyed.</p> <p>Results</p> <p>Thirty three patients (39.4%) directly accessed mental health professionals, 32 patients (38.1%) reached them via general hospital, and 13 patients (15.5%) via private practitioners. The patients who consulted mental health professionals as their first carers took a longer time before consulting psychiatrists than the patients who consulted non-mental health professionals as their first carers. The patients who presented somatic symptoms as their main problem experienced longer delay from the onset of illness to psychiatric care than the patients who complained about depressive or anxiety symptoms. Prior to the visit to mental health professionals, patients were rarely informed about their diagnosis and did not receive appropriate treatments from their physicians. Private practitioners were more likely to prescribe psychotropics than physicians in general hospitals, but were less likely to inform their patients of their diagnosis.</p> <p>Conclusion</p> <p>This first pathway to psychiatric care study in Japan demonstrated that referral pathway in Japan heavily relies on medical resources. The study indicates possible fields and gives indications, underlining the importance of improving skills and knowledge that will facilitate the recognition of psychiatric disorders presenting with somatic and depressive symptoms in the general health care system and by private practitioners.</p

Effect of light intensity and powder/liquid ratio on bleaching efficiency of the Hi-Lite vital bleaching system

光強度および粉液比が生活歯漂白剤ハイライトの漂白効果に及ぼす影響を,ヘマトポルフィリン変色モデルを用いて検討した。0.1%濃度のヘマトポルフィリンエタノール水溶液を濾紙に染み込ませ変色モデルとし,この上に粉液比1:2および1:3で練和した松風ハイライトを填入し3分間放置し,光照射器にて光強度300,600mW/cm^2で3分間光照射を行った。対照群として,光照射を行わず3分間放置したもの用いた。漂白前後の変色モデルの色差ΔE(以下ΔE)を算出した。松風ハイライトの漂白効果は,より強い光強度,液量の増加,およびその両者の相乗効果によって増加することが明らかとなった。We evaluate the effect of the light intensity and powder/liquid ratio on bleaching efficiency of the Hi-lite vital bleaching system using a hematoporphyrin stained model. Hi-Lite paste was mixed in the powder/liquid ratios that should be 1:2 and 1:3, and placed onto the filter paper stained with 0.1% hematoporhyrin alcohol solution. The specimen was left for 3 minutes. Visible light (irradiances of 300 or 600mW/cm^2) was applied to the paste for 3 minutes. The control specimen was left for 3 minutes without light irradiation. The color difference (ΔE) values between the stained paper and bleached paper were calculated. The higher light intensity, the increased liquid ratio, and the interaction between the higher light intensity and the increased liquid ratio increased the bleaching efficiency of the Hi-Lite

Persistence and compliance to antidepressant treatment in patients with depression: A chart review

<p>Abstract</p> <p>Background</p> <p>Adherence has recently been suggested to be divided into these two components: persistence (i.e., whether patients continue treatment or not) and compliance (i.e., whether patients take doses as instructed). However, no study has yet assessed these two clinically relevant components at the same time in adherence to antidepressant treatment in the clinical outpatient setting.</p> <p>Methods</p> <p>In this retrospective chart-review, 6-month adherence to antidepressants was examined in 367 outpatients with a major depressive disorder (ICD-10) (170 males; mean ± SD age 37.6 ± 13.9 years), who started antidepressant treatment from April 2006 through March 2007. Additionally, we evaluated Medication Possession Rate (MPR), defined as the total days a medication was dispensed to patients divided by the treatment period.</p> <p>Results</p> <p>Only 161 patients (44.3%) continued antidepressant treatment for 6 months. Among 252 patients who discontinued their initial antidepressant, 63.1% of these patients did so without consulting their physicians. Sertraline use was associated with a higher persistence rate at month 6 (odds ratio 2.59 in comparison with sulpiride), and the use of anxiolytic benzodiazepines had a positive effect on persistence to antidepressant treatment only at month 1 (odds ratio 2.14). An overall MPR was 0.77; 55.6% of patients were considered compliant (i.e., a MPR of ≥ 0.8).</p> <p>Conclusion</p> <p>Given a high rate of antidepressant discontinuation without consulting their physicians, closer communication between patients and their physicians should be encouraged. Although the use of anxiolytic benzodiazepines was associated with a higher persistence to antidepressant treatment at month 1, the use of these drugs should be avoided as a rule, given their well-known serious adverse effects.</p

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Changes in Cerebral Hemodynamics during Complex Motor Learning by Character Entry into Touch-Screen Terminals

Introduction Studies of cerebral hemodynamics during motor learning have mostly focused on neurorehabilitation interventions and their effectiveness. However, only a few imaging studies of motor learning and the underlying complex cognitive processes have been performed. Methods We measured cerebral hemodynamics using near-infrared spectroscopy (NIRS) in relation to acquisition patterns of motor skills in healthy subjects using character entry into a touchscreen terminal. Twenty healthy, right-handed subjects who had no previous experience with character entry using a touch-screen terminal participated in this study. They were asked to enter the characters of a randomly formed Japanese syllabary into the touchscreen terminal. All subjects performed the task with their right thumb for 15 s alternating with 25 s of rest for 30 repetitions. Performance was calculated by subtracting the number of incorrect answers from the number of correct answers, and gains in motor skills were evaluated according to the changes in performance across cycles. Behavioral and oxygenated hemoglobin concentration changes across task cycles were analyzed using Spearman\u27s rank correlations. Results Performance correlated positively with task cycle, thus confirming motor learning. Hemodynamic activation over the left sensorimotor cortex (SMC) showed a positive correlation with task cycle, whereas activations over the right prefrontal cortex (PFC) and supplementary motor area (SMA) showed negative correlations. Conclusions We suggest that increases in finger momentum with motor learning are reflected in the activity of the left SMC. We further speculate that the right PFC and SMA were activated during the early phases of motor learning, and that this activity was attenuated with learning progress