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Patients with schizophrenia experience accelerated aging, accompanied by abnormalities in biomarkers such as shorter telomere length. Brain age prediction using neuroimaging data has gained attention in schizophrenia research, with consistently reported increases in brain-predicted age difference (brain-PAD). However, its associations with clinical symptoms and illness duration remain unclear.
Methods
We developed brain age prediction models using structural magnetic resonance imaging (MRI) data from 10,938 healthy individuals. The models were validated on an independent test dataset comprising 79 healthy controls, 57 patients with recent-onset schizophrenia, and 71 patients with chronic schizophrenia. Group comparisons and the clinical associations of brain-PAD were analyzed using multiple linear regression. SHapley Additive exPlanations (SHAP) values estimated feature contributions to the model, and between-group differences in SHAP values and group-by-SHAP value interactions were also examined.
Results
Patients with recent-onset schizophrenia and chronic schizophrenia exhibited increased brain-PAD values of 1.2 and 0.9 years, respectively. Between-group differences in SHAP values were identified in the right lateral prefrontal area (false discovery rate [FDR] p = 0.022), with group-by-SHAP value interactions observed in the left prefrontal area (FDR p = 0.049). A negative association between brain-PAD and Full-scale Intelligence Quotient scores in chronic schizophrenia was noted, which did not remain significant after correction for multiple comparisons.
Conclusions
Brain-PAD increases were pronounced in the early phase of schizophrenia. Regional brain abnormalities contributing to brain-PAD likely vary with illness duration. Future longitudinal studies are required to overcome limitations related to sample size, heterogeneity, and the cross-sectional design of this study.
The intensity attenuation of a high-power laser is a frequent task in the measurements of optical science. Laser intensity can be attenuated by inserting an optical element, such as a partial reflector, polarizer or absorption filter. These devices are, however, not always easily applicable, especially in the case of ultra-high-power lasers, because they can alter the characteristics of a laser beam or become easily damaged. In this study, we demonstrated that the intensity of a laser beam could be effectively attenuated using a random pinhole attenuator (RPA), a device with randomly distributed pinholes, without changing the beam properties. With this device, a multi-PW laser beam was successfully attenuated and the focused beam profile was measured without any alterations of its characteristics. In addition, it was confirmed that the temporal profile of a laser pulse, including the spectral phase, was preserved. Consequently, the RPA possesses significant potential for a wide range of applications.
It has been suggested that schizophrenia involves dysconnectivity between functional brain regions and also the white matter structural disorganisation. Thus, diffusion tensor imaging (DTI) has widely been used for studying schizophrenia. However, most previous studies have used the region of interest (ROI) based approach. We, therefore, performed the probabilistic tractography method in this study to reveal the alterations of white matter tracts in the schizophrenia brain.
Methods:
A total of four different datasets consisted of 189 patients with schizophrenia and 213 healthy controls were investigated. We performed retrospective harmonisation of raw diffusion MRI data by dMRIharmonisation and used the FMRIB Software Library (FSL) for probabilistic tractography. The connectivities between different ROIs were then compared between patients and controls. Furthermore, we evaluated the relationship between the connection probabilities and the symptoms and cognitive measures in patients with schizophrenia.
Results:
After applying Bonferroni correction for multiple comparisons, 11 different tracts showed significant differences between patients with schizophrenia and healthy controls. Many of these tracts were associated with the basal ganglia or cortico-striatal structures, which aligns with the current literature highlighting striatal dysfunction. Moreover, we found that these tracts demonstrated statistically significant relationships with few cognitive measures related to language, executive function, or processing speed.
Conclusion:
We performed probabilistic tractography using a large, harmonised dataset of diffusion MRI data, which enhanced the statistical power of our study. It is important to note that most of the tracts identified in this study, particularly callosal and cortico-striatal streamlines, have been previously implicated in schizophrenia within the current literature. Further research with harmonised data focusing specifically on these brain regions could be recommended.
Although the cardiovascular benefits of an increased urinary potassium excretion have been suggested, little is known about the potential cardiac association of urinary potassium excretion in patients with chronic kidney disease. In addition, whether the cardiac association of urinary potassium excretion was mediated by serum potassium levels has not been studied yet. We reviewed the data of 1633 patients from a large-scale multicentre prospective Korean study (2011–2016). Spot urinary potassium to creatinine ratio was used as a surrogate for urinary potassium excretion. Cardiac injury was defined as a high-sensitivity troponin T ≥ 14 ng/l. OR and 95 % (CI for cardiac injury were calculated using logistic regression analyses. Of 1633 patients, the mean spot urinary potassium to creatinine ratio was 49·5 (sd 22·6) mmol/g Cr and the overall prevalence of cardiac injury was 33·9 %. Although serum potassium levels were not associated with cardiac injury, per 10 mmol/g Cr increase in the spot urinary potassium to creatinine ratio was associated with decreased odds of cardiac injury: OR 0·917 (95 % CI 0·841, 0·998), P = 0·047) in multivariate logistic regression analysis. In mediation analysis, approximately 6·4 % of the relationship between spot urinary potassium to creatinine ratio and cardiac injury was mediated by serum potassium levels, which was not statistically significant (P = 0·368). Higher urinary potassium excretion was associated with lower odds of cardiac injury, which was not mediated by serum potassium levels.
Although disconnectivity among brain regions has been one of the main hypotheses for schizophrenia, the superficial white matter (SWM) has received less attention in schizophrenia research than the deep white matter (DWM) owing to the challenge of consistent reconstruction across subjects.
Methods:
We obtained the diffusion magnetic resonance imaging (dMRI) data of 223 healthy controls and 143 patients with schizophrenia. After harmonising the raw dMRIs from three different studies, we performed whole-brain two-tensor tractography and fibre clustering on the tractography data. We compared the fractional anisotropy (FA) of white matter tracts between healthy controls and patients with schizophrenia. Spearman’s rho was adopted for the associations with clinical symptoms measured by the Positive and Negative Syndrome Scale (PANSS). The Bonferroni correction was used to adjust multiple testing.
Results:
Among the 33 DWM and 8 SWM tracts, patients with schizophrenia had a lower FA in 14 DWM and 4 SWM tracts than healthy controls, with small effect sizes. In the patient group, the FA deviations of the corticospinal and superficial–occipital tracts were negatively correlated with the PANSS negative score; however, this correlation was not evident after adjusting for multiple testing.
Conclusion:
We observed the structural impairments of both the DWM and SWM tracts in patients with schizophrenia. The SWM could be a potential target of interest in future research on neural biomarkers for schizophrenia.
Substantial evidence indicates structural abnormalities in the cerebral cortex of patients with schizophrenia (SCZ), although their clinical implications remain unclear. Previous case-control studies have investigated group-level differences in structural abnormalities, although the study design cannot account for interindividual differences. Recent research has focused on the association between the heterogeneity of the cerebral cortex morphometric features and clinical heterogeneity.
Methods
We used neuroimaging data from 420 healthy controls and 695 patients with SCZ from seven studies. Four cerebral cortex measures were obtained: surface area, gray matter volume, thickness, and local gyrification index. We calculated the coefficient of variation (CV) and person-based similarity index (PBSI) scores and performed group comparisons. Associations between the PBSI scores and cognitive functions were evaluated using Spearman's rho test and normative modeling.
Results
Patients with SCZ had a greater CV of surface area and cortical thickness than those of healthy controls. All PBSI scores across cortical measures were lower in patients with SCZ than in HCs. In the patient group, the PBSI scores for gray matter volume and all cortical measures taken together positively correlated with the full-scale IQ scores. Patients with deviant PBSI scores for gray matter volume and all cortical measures taken together had lower full-scale IQ scores than those of other patients.
Conclusions
The cerebral cortex in patients with SCZ showed greater regional and global structural variability than that in healthy controls. Patients with deviant similarity of cortical structural profiles exhibited a lower general intelligence than those exhibited by the other patients.
Clozapine is generally considered as the treatment of choice for patients with treatment-resistant schizophrenia (TRS). However, its superiority has recently been questioned because olanzapine has been suggested as non-inferior to clozapine in its effectiveness.
Aims
We aimed to investigate the current status of clozapine prescriptions to identify any disparity between clinical guidelines and real-world practices.
Method
In this study, we utilised the Health Insurance Review Agency database in the Republic of Korea to investigate the real-world effectiveness of clozapine for patients with TRS. We compared differences in patient variables before and after clozapine administration, and we also performed survival analyses for both psychiatric admissions and emergency room visits among patients who used clozapine or olanzapine.
Results
This study investigated an incident cohort of 64 442 patients, and 2338 patients have been prescribed clozapine. Of these, 998 patients had TRS. In survival analysis, clozapine showed a worse survival rate for psychiatric admissions than olanzapine (hazard ratio 0.615). We also identified that clinicians tended to try a number of antipsychotics, as recommended, before starting patients on clozapine.
Conclusions
In conclusion, we found that olanzapine led to higher survival rates for psychiatric admissions than clozapine. Thus, considering the risk of serious adverse effects, clozapine may be used conservatively. Considering several studies advocating superior efficacy of clozapine, further studies with extensive data are recommended.
Current evidence on antipsychotic treatment and risk of psychiatric hospitalization in first-episode schizophrenia (FES) is largely based on the findings from randomized clinical trials (RCTs). However, the generalization of the findings to real-world patients is limited due to inherent caveats of the RCT. We aimed to investigate the treatment discontinuation and risk of psychiatric hospitalization using a nationwide population database.
Methods
The Health Insurance Review Agency database in South Korea was obtained, and the observation period started from 1 January 2009 to 31 December 2016. We defined the maintenance period as the period from 6-month after the diagnosis of schizophrenia, which is utilized for the main results. For a total of 44 396 patients with FES, a within-individual Cox regression model was used to compare the risk of the treatment discontinuation and psychiatric hospitalization.
Results
In group comparison, a long-acting injectable (LAI) antipsychotic group was associated with the lowest risk of the treatment discontinuation (0.64, 0.55–0.75) and psychiatric hospitalization (0.29, 0.22–0.38) in comparison with a typical antipsychotic group and no use, respectively. Among individual antipsychotics, the lowest risk of the treatment discontinuation was observed in LAI paliperidone (0.46, 0.37–0.66) compared to olanzapine. Clozapine was found to be the most effective antipsychotic in lowering the risk of psychiatric hospitalization as monotherapy compared to no use (0.23, 0.18–0.31).
Conclusions
In real-world patients with FES, LAI paliperidone and clozapine were associated with low treatment discontinuation and better effectiveness in lowering the risk of psychiatric hospitalization.
Network approach has been applied to a wide variety of psychiatric disorders. The aim of the present study was to identify network structures of remitters and non-remitters in patients with first-episode psychosis (FEP) at baseline and the 6-month follow-up.
Methods
Participants (n = 252) from the Korean Early Psychosis Study (KEPS) were enrolled. They were classified as remitters or non-remitters using Andreasen's criteria. We estimated network structure with 10 symptoms (three symptoms from the Positive and Negative Syndrome Scale, one depressive symptom, and six symptoms related to schema and rumination) as nodes using a Gaussian graphical model. Global and local network metrics were compared within and between the networks over time.
Results
Global network metrics did not differ between the remitters and non-remitters at baseline or 6 months. However, the network structure and nodal strengths associated with positive-self and positive-others scores changed significantly in the remitters over time. Unique central symptoms for remitters and non-remitters were cognitive brooding and negative-self, respectively. The correlation stability coefficients for nodal strength were within the acceptable range.
Conclusion
Our findings indicate that network structure and some nodal strengths were more flexible in remitters. Negative-self could be an important target for therapeutic intervention.
The experiments reported in this research paper aimed to determine the effect of supplementing different forms of L-methionine (L-Met) and acetate on protein synthesis in immortalized bovine mammary epithelial cell line (MAC-T cells). Treatments were Control, L-Met, conjugated L-Met and acetate (CMA), and non-conjugated L-Met and Acetate (NMA). Protein synthesis mechanism was determined by omics method. NMA group had the highest protein content in the media and CSN2 mRNA expression levels (P < 0.05). The number of upregulated and downregulated proteins observed were 39 and 77 in L-Met group, 62 and 80 in CMA group and 50 and 81 in NMA group from 448 proteins, respectively (P < 0.05). L-Met, NMA and CMA treatments stimulated pathways related to protein and energy metabolism (P < 0.05). Metabolomic analysis also revealed that L-Met, CMA and NMA treatments resulted in increases of several metabolites (P < 0.05). In conclusion, NMA treatment increased protein concentration and expression level of CSN2 mRNA in MAC-T cells compared to control as well as L-Met and CMA treatments through increased expression of milk protein synthesis-related genes and production of the proteins and metabolites involved in energy and protein synthesis pathways.
Traumatic brain injury (TBI) is an important public health concern because of the high mortality rate of young people and a high proportion among the trauma. According to studies, patients visiting the emergency department (ED) with TBI comprise 1.4% of all ED patients.
Aim:
The authors think that the characteristics of patients with TBI will vary according to the age group. Therefore, the purpose of this study is to investigate the clinical and social characteristics of patients with TBI visiting the ED by age group.
Methods:
Trauma patients who conducted brain CT at the ED of Korean University Hospital (three hospitals) for 3 years from March 2013 to February 2016 were enrolled. Medical records were investigated retrospectively. The GCS scores were estimated at initial ED arrival. The primary outcome was to determine the characteristics of each age groups with gender, severity (by GSC score), trauma mechanism, and admission rate.
Results:
A total of 15,567 TBI patients received brain CT evaluation during the investigation period. Based on age, patients in their 50s were the most common (16.5%). Regarding the severity, the ratio of mild was higher in under patients under 9 (99.3%); the ratio of severe was higher for patients in their 20s (4.6%). In almost every age group, the male ratio of TBI was higher, except for females aged 70 or older. Under 19 years of age, the ambulance utilization rate was lower than any other age group. The most common injury mechanism was a collision, the next was a traffic accident, and in under 9, a fall was the most common. 70.1% of patients returned home after treatments.
Discussion:
Identifying the characteristics of patients with TBI visiting ED is fundamental. Therefore, it is necessary to continuously collect basic data on TBI among patients visiting the ED.
Social media data are a highly contextual health information source. The objective of this study was to identify Korean keywords for detecting influenza epidemics from social media data.
Methods
We included data from Twitter and online blog posts to obtain a sufficient number of candidate indicators and to represent a larger proportion of the Korean population. We performed the following steps: initial keyword selection; generation of a keyword time series using a preprocessing approach; optimal feature selection; model building and validation using least absolute shrinkage and selection operator, support vector machine (SVM), and random forest regression (RFR).
Results
A total of 15 keywords optimally detected the influenza epidemic, evenly distributed across Twitter and blog data sources. Model estimates generated using our SVM model were highly correlated with recent influenza incidence data.
Conclusions
The basic principles underpinning our approach could be applied to other countries, languages, infectious diseases, and social media sources. Social media monitoring using our approach may support and extend the capacity of traditional surveillance systems for detecting emerging influenza. (Disaster Med Public Health Preparedness. 2018; 12: 352–359)
Hyperlipidaemia is a major cause of atherosclerosis and related CVD and can be prevented with natural substances. Previously, we reported that a novel Bacillus-fermented green tea (FGT) exerts anti-obesity and hypolipidaemic effects. This study further investigated the hypotriglyceridaemic and anti-obesogenic effects of FGT and its underlying mechanisms. FGT effectively inhibited pancreatic lipase activity in vitro (IC50, 0·48 mg/ml) and ameliorated postprandial lipaemia in rats (26 % reduction with 500 mg/kg FGT). In hypertriglyceridaemic hamsters, FGT administration significantly reduced plasma TAG levels. In mice, FGT administration (500 mg/kg) for 2 weeks augmented energy expenditure by 22 % through the induction of plasma serotonin, a neurotransmitter that modulates energy expenditure and mRNA expressions of lipid metabolism genes in peripheral tissues. Analysis of the gut microbiota showed that FGT reduced the proportion of the phylum Firmicutes in hamsters, which could further contribute to its anti-obesity effects. Collectively, these data demonstrate that FGT decreases plasma TAG levels via multiple mechanisms including inhibition of pancreatic lipase, augmentation of energy expenditure, induction of serotonin secretion and alteration of gut microbiota. These results suggest that FGT may be a useful natural agent for preventing hypertriglyceridaemia and obesity.
This study investigates the relationship between insomnia and cognitive dysfunctions including, subjective memory impairment (SMI), mild cognitive impairment (MCI), and dementia, by considering depression in a community sample of elderly individuals.
Methods:
Data for 1,740 elderly individuals aged 65 years and over were obtained from a nationwide dementia epidemiological study conducted in South Korea. Cognitive functional status was assessed by the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet Clinical Assessment Battery. Insomnia was defined as the presence of at least one of the four sleep complaints (difficulty in initiating sleep, difficulty in maintaining sleep, early morning awakening, and non-restorative sleep), accompanied by moderate to severe daytime consequences. Depression was evaluated using the Geriatric Depression Scale.
Results:
The prevalence of insomnia in the patients with SMI, MCI, and dementia was found to be 23.2%, 19.6%, and 31.0%, respectively. The patients with SMI, MCI, and dementia were significantly more likely to have insomnia and the four sleep complaints than the normal comparison patients. After adjusting for sociodemographic factors, the significant relationships between cognitive dysfunctional status and insomnia remained. However, after adjusting for sociodemographic factors and depression, no significant relationships with any of the sleep complaints or insomnia remained.
Conclusion:
Insomnia is a very common complaint in the elderly with SMI, MCI, and dementia. Depression might play an important factor in the relationship between insomnia and cognitive dysfunctional status in the elderly.
A life-threatening cardiopulmonary resuscitation (CPR)-related injury can cause recurrent arrest after return of circulation. Such injuries are difficult to identify during resuscitation, and their contribution to failed resuscitation can be missed given the limitations of conventional CPR. Extracorporeal cardiopulmonary resuscitation (ECPR), increasingly being considered for selected patients with potentially reversible etiology of arrest, may identify previously occult CPR-related injuries by restoring arterial pressure and flow. Herein, we describe two cases of severe CPR-related injuries contributing to recurrent arrest. Each case had ECPR implemented within 60 minutes of the start of CPR. After the presumed cardiac etiology had been addressed with percutaneous coronary intervention, life-threatening cardiovascular injuries with recurrent arrest were noted, and resuscitative thoracotomy was performed under ECPR. One patient survived to hospital discharge.
ECPR may provide an opportunity to identify and correct severe resuscitation-related injuries causing recurrent arrest. Chest compression depth >6 cm, especially in older women, may contribute to these injuries.
Lichenaria may be a representative of the most primitive stock of tabulate corals. The degree of paleobiologic complexity discovered in L. globularis and L. grandis is therefore surprising. Six types of corallite increase are recognized. All are lateral, which is the predominant mode in tabulates. Most types, however, are unique or are comparable to those in few other Ordovician taxa. Only Type 1 (L. globularis), yielding a single offset with a simple basal mural pore, is typical of tabulates. In Type 2 (L. globularis), one parent produces two offsets simultaneously, whereas in Type 3 (L. globularis), two offsets arise from separate parents at nearly the same time and join via a connective mural pore. Types 4 (L. globularis, L. grandis), 5 (L. grandis), and 6 (L. globularis, L. grandis), respectively, involve one, two, and two to four corallites in addition to the parent, which join via a connective mural pore at the site of offsetting.
Several features of L. globularis and L. grandis point to unexpectedly high levels of colony integration. Continuously fused common walls lacking back-to-back epithecae suggest soft tissue continuity among polyps above the corallum. Connective mural pores indicate temporary fusion of polyps. Coordinated behavior of polyps is suggested by the development of conjoined offsets from two parents during Type 3 increase, and by fusion during Types 4 to 6 increase. Attempts at certain types of increase sometimes failed to yield offsets, suggesting expendability of incipient buds, perhaps reflecting subjugation of individuals for the good of the colony.
In light of this study, genera that have previously been included in Lichenariidae and Lichenariida require reassessment and their phylogenetic relationships should be reconsidered. Unfortunately, this is hindered because fundamental characters such as corallite increase and wall structure remain inadequately known in most early tabulates.
Feasibility of multiwavelength Raman spectroscopy was studied as a potentialin-line monitoring technique for grain size distribution in channel poly-Si usedin three dimensional stacked NAND (3D NAND) Flash memory devices. Variouschannel poly-Si materials in 3D-NAND Flash memory devices, converted fromchemical vapor deposition (CVD) grown a-Si, were characterized usingnon-contact, multiwavelength Raman spectroscopy and high resolutioncross-sectional transmission electron microscopy (HRXTEM). The Ramancharacterization results were compared with HRXTEM images. The correlationbetween the grain size distribution characterized by multiwavelength Ramanspectroscopy and “on current” (ION) of 3D NANDFlash memory devices was investigated. Good correlation between these techniqueswas seen. Multiwavelength Raman spectroscopy is very promising as anon-destructive in-line monitoring technique for grain size distribution inchannel poly-Si used in 3D NAND Flash memory devices.
Genetic factors have been suggested to be one of the determinants of the variation of left ventricular (LV) structure and function. However, the heritability range of LV structure varies across studies and the influence of genetics on LV function is not well established, especially in Asian populations. Study subjects were 1,642 healthy Korean adults from 426 families, consisting of 298 pairs of monozygotic twins, 62 pairs of dizygotic twins, one set of triplets, 567 siblings, and 354 parents. LV structure and function were measured by M-mode and 2D echocardiography, and conventional and tissue Doppler imaging (TDI). Pairwise intra-class correlations for various familial relationships and heritability were estimated for LV structure and function. The heritability of LV mass, LV ejection fraction (LVEF), left atrial volume index, the ratio between early and late diastolic velocity of mitral inflow (E/A ratio), and the ratio between early diastolic velocity of mitral inflow and early diastolic mitral annular velocities (E/Ea ratio) was 0.44, 0.27, 0.44, 0.25, and 0.33, respectively. Bivariate genetic analysis showed that LV structural and functional traits had significant genetic correlations with cardiovascular risk factors. Additive genetic correlation (ρG) of LV mass with body mass index, systolic blood pressure, and high density lipoprotein cholesterol were 0.49, 0.42, and -0.15 respectively. LVEF (ρG = 0.33) and left atrial volume index (ρG = 0.24) also had a significant genetic correlation with systolic blood pressure. These findings support the theory that genetic factors have significant influence on these traits and necessitate further work to identify the specific genes involved.
To determine the influence of early pain relief for patients with suspected appendicitis on the diagnostic performance of surgical residents.
Methods
A prospective randomized, double-blind, placebo-controlled trial was conducted for patients with suspected appendicitis. The patients were randomized to receive placebo (normal saline intravenous [IV]) infusions over 5 minutes or the study drug (morphine 5 mg IV). All of the clinical evaluations by surgical residents were performed 30 minutes after administration of the study drug or placebo. After obtaining the clinical probability of appendicitis, as determined by the surgical residents, abdominal computed tomography was performed. The primary objective was to compare the influence of IV morphine on the ability of surgical residents to diagnose appendicitis.
Results
A total of 213 patients with suspected appendicitis were enrolled. Of these patients, 107 patients received morphine, and 106 patients received placebo saline. The negative appendectomy percentages in each group were similar (3.8% in the placebo group and 3.2% in the pain control group, p=0.62). The perforation rates in each group were also similar (18.9% in the placebo group and 14.3% in the pain control group, p=0.75). Receiver operating characteristic analysis revealed that the overall diagnostic accuracy in each group was similar (the area under the curve of the placebo group and the pain control group was 0.63 v. 0.61, respectively, p=0.81).
Conclusions
Early pain control in patients with suspected appendicitis does not affect the diagnostic performance of surgical residents.