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Predictive values of multiple serum biomarkers for suicidal behaviours (SBs) have rarely been tested. This study sought to evaluate and develop a panel of multiple serum biomarkers for predicting SBs in outpatients receiving a 12-month pharmacotherapy programme for depressive disorders.
Methods
At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics including previous suicidal attempt and present suicidal severity were evaluated in 1094 patients with depressive disorders without a bipolar diagnosis. Of these, 884 were followed for increased suicidal severity and fatal/non-fatal suicide attempt outcomes over a 12-month treatment period. Individual and combined effects of serum biomarkers on these two prospective SBs were estimated using logistic regression analysis after adjustment for relevant covariates.
Results
Increased suicidal severity and fatal/non-fatal suicide attempt during the 12-month pharmacotherapy were present in 155 (17.5%) and 38 (4.3%) participants, respectively. Combined cortisol, total cholesterol, and folate serum biomarkers predicted fatal/non-fatal suicide attempt, and these with interleukin-1 beta and homocysteine additionally predicted increased suicidal severity, with clear gradients robust to adjustment (p values < 0.001).
Conclusions
Application of multiple serum biomarkers could considerably improve the predictability of SBs during the outpatient treatment of depressive disorders, potentially highlighting the need for more frequent monitoring and risk appraisal.
Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies.
Methods
PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof.
Results
Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α, IL-6, CRP, but not IL-1β, are associated with depression.
Conclusions
These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported.
The role of childhood abuse and serum brain-derived neurotrophic factor (BDNF) levels in suicidal behaviour is controversial.
Aims
We aimed to investigate the individual and interactive effects of the childhood abuse and serum BDNF on suicidal behaviour before and after pharmacologic treatment in patients with depressive disorders.
Method
At baseline, reported childhood emotional, physical and sexual abuse were ascertained and serum BDNF levels were measured in 1094 patients with depressive disorder, 884 of whom were followed during a 1-year period of stepwise pharmacotherapy. Suicidal behaviours evaluated at baseline were previous suicide attempt and baseline suicide severity, and suicidal behaviours evaluated at follow-up were increased suicide severity and fatal/non-fatal suicide attempt. Individual and interactive associations of any childhood abuse and serum BDNF levels with four types of suicidal behaviours were analysed using logistic regression models, after adjusting relevant covariates.
Results
Individual associations of childhood abuse were significant only with previous suicide attempt, and no significant individual associations were found for serum BDNF with any suicide outcome. However, the presence of both childhood abuse and lower serum BDNF levels was associated with the highest prevalence/incidence of all four suicidal behaviours, with significant interactions for baseline suicide severity and fatal/non-fatal suicide attempt during follow-up.
Conclusions
Synergistic interactive effects of child abuse and serum BDNF levels on suicidal behaviours were found before and after pharmacologic treatment in patients with depressive disorders. Information combining childhood abuse and serum BDNF levels could improve predictions of suicidal behaviour in patients with depressive disorders.
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.
It has been reported that the follower in a tandem configuration with no wall (0W) reduces the time-averaged input power by utilizing the vortex interception mode (Zhu et al., Phys. Rev. Lett., vol. 113, 2014, p. 238105). In the present study, a numerical simulation is conducted with two self-propelled flexible fins in the tandem configuration near a single wall (1W) and two parallel walls (2W). Contrary to the vortex interception for 0W, the follower employs spontaneously a mixed mode (i.e. a combination of the vortex interception mode and the slalom mode) for 1W and the slalom mode for 2W. Although the lateral motion of the follower for 0W, 1W and 2W is synchronized with the induced lateral flow generated by the leader, the time-averaged input power of the follower for 1W and 2W is reduced significantly due to the enhanced lateral flow by the vortex–vortex interaction near the wall. The jet-like flow opposite to the moving direction continuously hinders the movement of the follower for 0W, whereas the follower for 1W and 2W utilizes the negative horizontal flow when passing between the main vortex and the induced vortex near the wall, leading to a decrease of the thrust force acting on the follower allowing the follower to keep pace with the leader. The global efficiency of the schooling fins is optimized with a small heaving amplitude of the follower and a critical value of phase difference between the leader and follower when the values of the wall proximity and bending rigidity are moderate.
Townsend's attached-eddy hypothesis (AEH) provides a theoretical description of turbulence statistics in the logarithmic region in terms of coherent motions that are self-similar with the wall-normal distance ($y$). This hypothesis was further extended by Perry and coworkers who proposed attached-eddy models that predict the coexistence of the logarithmic law in the mean velocity and streamwise turbulence intensity as well as spectral scaling for the streamwise energy spectra. The AEH can be used to predict the statistical behaviours of wall turbulence, yet revealing such behaviours has remained an elusive task because the proposed description is established within the limits of asymptotically high Reynolds numbers. Here, we show the self-similar behaviour of turbulence motions contained within wall-attached structures of streamwise velocity fluctuations using the direct numerical simulation dataset of turbulent boundary layer, channel, and pipe flows ($Re_{\tau } \approx 1000$). The physical sizes of the identified structures are geometrically self-similar in terms of height, and the associated turbulence intensity follows the logarithmic variation in all three flows. Moreover, the corresponding two-dimensional energy spectra are aligned along a linear relationship between the streamwise and spanwise wavelengths ($\lambda _x$ and $\lambda _z$, respectively) in the large-scale range ($12y < \lambda _x <3\text{--}4\delta$), which is reminiscent of self-similarity. Consequently, one-dimensional spectra obtained by integrating the two-dimensional spectra over the self-similar range show some evidence for self-similar scaling $\lambda _x \sim \lambda _z$ and the possible existence of $k_x^{-1}$ and $k_z^{-1}$ scaling regions in a similar subrange. The present results reveal that the asymptotic behaviours can be obtained by identifying the self-similar coherent structures in canonical wall turbulence, albeit in low-Reynolds-number flows.
Background: Recently, healthcare-associated infections (HAIs) in long-term care hospitals (LTCHs) have markedly increased, but no infection control policy has been established in South Korea. We investigated the current HAI surveillance system and executed a point-prevalence pilot study in LTCHs. Methods: HAIs were defined by newly established surveillance manual based on McGeer criteria revised in 2012. Three LTCHs in Seoul and Gyeonggi province were voluntarily recruited, and data were collected from up to 50 patients who were hospitalized on August 1. The medical records from September to November 2018 were retrospectively reviewed by a charge nurse for infection control per each hospitals after 1 day of training specific for LTCH surveillance. All data were reviewed by a senior researcher visiting onsite. Results: The participating hospitals had 272.33 ± 111.01 beds. Only 1 hospital had an onsite microbiological laboratory. In total, 156 patients were enrolled and 5 HAIs were detected, for a prevalence rate of 3.2%. The average patient age was 79.04 ± 9.92 years. The HAIs included 2 urinary tract infections, skin and soft-tissue infection, low respiratory infection, and conjunctivitis. Conclusions: This is the first survey of HAI in LTCHs in South Korea. The 3.2% prevalence rate is lower than those from previous reports from the European Union or the United States. This study supports the development of a national HAI surveillance and infection control system in LTCHs, although implementation may be limited due to the lack of laboratory support and infection control infrastructure in Korea.
Vitamin E is known to scavenge lipid peroxy radicals and has a purported role in preventing seed deterioration during storage. In our previous studies using 20 rice varieties from different variety groups, the specific ratio of vitamin E homologues rather than total vitamin E content was associated with seed longevity. To validate this result, we extended the experiment to a rice panel composed of 185 Aus (semi-wild rice) varieties. Seed longevity values were determined through storage experiments at 45°C and 10.9% seed moisture content (MC). Eight types of vitamin E homologues (α-, β-, γ- and δ-tocopherol/tocotrienol) were quantified by ultra-performance liquid chromatography. The theoretical initial viability in NED, Ki, was positively correlated with γ- and δ-tocopherols and negatively correlated with α-tocotrienol. The time for viability to fall to 50% during storage at elevated temperature and relative humidity, p50, was positively correlated with δ-tocopherol. The harvest MC was negatively correlated with all seed longevity traits. Taking this factor into account in a genome-wide association (GWA) analysis, we were able to correct false positives. A consistent major peak on chromosome 4 associated with −σ−1 was detected with a mixed linear analysis. Based on rice genome annotation and gene network ontology databases, we suggest that RNA modification, oxidation–reduction, protein–protein interactions and abscisic acid signal transduction play roles in seed longevity extension of Aus rice. Although major GWA regions were not overlapped across traits, three genetic markers, on chromosomes 1, 3 and 4, were associated with both δ-tocopherol and Ki and two markers on chromosome 1 and 8 were associated with both δ-tocopherol and p50.
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.
To investigate the impacts of depression screening, diagnosis and treatment on major adverse cardiac events (MACEs) in acute coronary syndrome (ACS).
Methods
Prospective cohort study including a nested 24-week randomised clinical trial for treating depression was performed with 5–12 years after the index ACS. A total of 1152 patients recently hospitalised with ACS were recruited from 2006 to 2012, and were divided by depression screening and diagnosis at baseline and 24-week treatment allocation into five groups: 651 screening negative (N), 55 screening positive but no depressive disorder (S), 149 depressive disorder randomised to escitalopram (E), 151 depressive disorder randomised to placebo (P) and 146 depressive disorder receiving medical treatment only (M).
Results
Cumulative MACE incidences over a median 8.4-year follow-up period were 29.6% in N, 43.6% in S, 40.9% in E, 53.6% in P and 59.6% in M. Compared to N, screening positive was associated with higher incidence of MACE [adjusted hazards ratio 2.15 (95% confidence interval 1.63–2.83)]. No differences were found between screening positive with and without a formal depressive disorder diagnosis. Of those screening positive, E was associated with a lower incidence of MACE than P and M. M had the worst outcomes even compared to P, despite significantly milder depressive symptoms at baseline.
Conclusions
Routine depression screening in patients with recent ACS and subsequent appropriate treatment of depression could improve long-term cardiac outcomes.
We examine the origin of very-large-scale motions (VLSMs) in fully developed turbulent pipe flow at friction Reynolds number, $\mathit{Re}_{\unicode[STIX]{x1D70F}}=934$, using data from a direct numerical simulation. The VLSMs and the packet-like large-scale motions (LSMs) found in this study are very similar to those found in earlier studies. Three-dimensional time-evolving instantaneous fields show that one component of the process leading to the large streamwise length of VLSMs is the concatenation of adjacent streamwise LSMs caused by the continuous elongation of LSMs due to the strain component of the mean shear. Spatial organization patterns of the VLSMs and LSMs and their properties are studied by separating auto-correlation of the streamwise velocity fluctuations into the components of the VLSM and the LSM defined by low-pass/high-pass filtering in the streamwise direction. The structures of the two-point spatial correlations of the streamwise velocity component of the VLSMs and the LSMs in the streamwise-azimuthal plane are characterized by multiple maxima and complex patterns that beg explanation in terms of patterned coherent arrangements of the LSMs. Using proper orthogonal decomposition (POD), it is found that the X-shape correlation pattern of the VLSMs results from the superposition of very long helically inclined structures and streamwise-aligned structures. Further explanation of the patterns in the correlations of the VLSMs and LSMs is provided through the study of synthetically constructed arrangements of simple hairpin packet models of the LSM. Head-to-tail alignment of the model packets along streamwise and helical directions suggested by the eigenvalues of the POD creates a pair of long roll-cells centred above the logarithmic layer, and bracketing the LSMs. These roll-cells are pure kinematic consequences of the induction within the LSM packets, but they may also serve to organize smaller packets.
Seeds of 15 diverse rice accessions, representing aus, indica, temperate japonica and tropical japonica subpopulations, were produced under temperate climate conditions in Korea and used for vitamin E analysis and seed storage experiments at 45°C and 10.9% seed moisture content. High γ-tocotrienol was significantly positively correlated with seed longevity. In addition, a high β-tocopherol proportion relative to δ-tocopherol was significantly negatively correlated with seed longevity. Using high-density single-nucleotide polymorphism marker data, DNA haplotype analysis showed clear allelic variations in the region of two S-adenosylmethionine synthetase genes: LOC_Os04g42095 and LOC_Os11g15410, which regulate the conversion of δ-tocopherol into β-tocopherol. Four indica accessions with rare and subpopulation-specific alleles showed a 2.3-fold lower β-/δ-tocopherol ratio compared with accessions from other subpopulations.
Given that only a subgroup of patients with schizophrenia responds to first-line antipsychotic drugs, a key clinical question is what underlies treatment response. Observations that prefrontal activity correlates with striatal dopaminergic function, have led to the hypothesis that disrupted frontostriatal functional connectivity (FC) could be associated with altered dopaminergic function. Thus, the aim of this study was to investigate the relationship between frontostriatal FC and striatal dopamine synthesis capacity in patients with schizophrenia who had responded to first-line antipsychotic drug compared with those who had failed but responded to clozapine.
Methods
Twenty-four symptomatically stable patients with schizophrenia were recruited from Seoul National University Hospital, 12 of which responded to first-line antipsychotic drugs (first-line AP group) and 12 under clozapine (clozapine group), along with 12 matched healthy controls. All participants underwent resting-state functional magnetic resonance imaging and [18F]DOPA PET scans.
Results
No significant difference was found in the total PANSS score between the patient groups. Voxel-based analysis showed a significant correlation between frontal FC to the associative striatum and the influx rate constant of [18F]DOPA in the corresponding region in the first-line AP group. Region-of-interest analysis confirmed the result (control group: R2 = 0.019, p = 0.665; first-line AP group: R2 = 0.675, p < 0.001; clozapine group: R2 = 0.324, p = 0.054) and the correlation coefficients were significantly different between the groups.
Conclusions
The relationship between striatal dopamine synthesis capacity and frontostriatal FC is different between responders to first-line treatment and clozapine treatment in schizophrenia, indicating that a different pathophysiology could underlie schizophrenia in patients who respond to first-line treatments relative to those who do not.
We trace Sn nanoparticles (NPs) produced from SnO2 nanotubes (NTs) during lithiation initialized by high energy e-beam irradiation. The growth dynamics of Sn NPs is visualized in liquid electrolytes by graphene liquid cell transmission electron microscopy. The observation reveals that Sn NPs grow on the surface of SnO2 NTs via coalescence and the final shape of agglomerated NPs is governed by surface energy of the Sn NPs and the interfacial energy between Sn NPs and SnO2 NTs. Our result will likely benefit more rational material design of the ideal interface for facile ion insertion.
Vitamin E (tocols) is a key metabolite for efficient scavenging of lipid peroxy radicals that cause membrane breakdown during seed ageing. However, in rice, this hypothesis has been tested for very few lines only and without considering intraspecific variation in genomic structure. Here, we present a correlation study between tocols and seed longevity using a diverse rice panel. Seeds of 20 rice accessions held in the International Rice Genebank at the International Rice Research Institute, representing Aus, Basmati/Sadri, Indica, temperate Japonica and tropical Japonica variety groups, were used for tocols analysis (quantification of α-, β-, γ- and δ-tocopherol/tocotrienol by ultra-performance liquid chromatography) and storage experiments at 45°C and 10.9% seed moisture content. To examine the effects of DNA-haplotype on the phenotype, the 700 K high-density single-nucleotide polymorphism marker dataset was utilized. Both seed longevity (time for viability to fall to 50%; p50) and tocols content varied across variety groups related to the heterogeneity in the genetic architecture. Among eight types of tocol homologues, α-tocopherol and γ-tocotrienol were significantly correlated with p50 (negatively and positively, respectively). While temperate Japonica varieties were most abundant in α-tocopherol, Indica varieties recorded 1.3- to 1.7-fold higher γ-tocotrienol than those of other groups. We conclude that the specific ratio of tocol homologues rather than total tocols content plays an important role in the seed longevity mechanism.
The purpose of the current study was to investigate the effects of working-memory (WM) capacity on age-related changes in abilities to comprehend passive sentences when the word order was systematically manipulated.
Methods:
A total of 134 individuals participated in the study. The sentence-comprehension task consisted of the canonical and non-canonical word-order conditions. A composite measure of WM scores was used as an index of WM capacity.
Results:
Participants exhibited worse performance on sentences with non-canonical word order than canonical word order. The two-way interaction between age and WM was significant, suggesting that WM effects were greater than age effects on the task.
Conclusions:
WM capacity effects on passive-sentence comprehension increased dramatically as people aged, suggesting that those who have larger WM capacity are less vulnerable to age-related changes in sentence-comprehension abilities. WM capacity may serve as a cognitive reserve associated with sentence-comprehension abilities for elderly adults.
The National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute neuropsychology protocol consists of only verbal tasks, and is proposed as a brief screening method for vascular cognitive impairment. We evaluated its feasibility within two weeks after stroke and ability to predict the development of post-stroke dementia (PSD) at 3 months after stroke.
Method:
We prospectively enrolled subjects with ischemic stroke within seven days of symptom onset who were consecutively admitted to 12 university hospitals. Neuropsychological assessments using the NINDS-CSN 5-minute and 60-minute neuropsychology protocols were administered within two weeks and at 3 months after stroke onset, respectively. PSD was diagnosed with reference to the American Heart Association/American Stroke Association statement, requiring deficits in at least two cognitive domains.
Results:
Of 620 patients, 512 (82.6%) were feasible for the NINDS-CSN 5-minute protocol within two weeks after stroke. The incidence of PSD was 16.2% in 308 subjects who had completed follow-up at 3 months after stroke onset. The total score of the NINDS-CSN 5-minute protocol differed significantly between those with and without PSD (4.0 ± 2.7, 7.4 ± 2.7, respectively; p < 0.01). A cut-off value of 6/7 showed reasonable discriminative power (sensitivity 0.82, specificity 0.67, AUC 0.74). The NINDS-CSN 5-minute protocol score was a significant predictor for PSD (adjusted odds ratio 6.32, 95% CI 2.65–15.05).
Discussion:
The NINDS-CSN 5-minute protocol is feasible to evaluate cognitive functions in patients with acute ischemic stroke. It might be a useful screening method for early identification of high-risk groups for PSD.