Comparative Interrupted Time Series Analysis of Long-term Direct Medical Costs in Patients With Hip Fractures and a Matched Cohort: A Large-database Study.

BACKGROUND: Previous studies on medical costs in patients with hip fractures have focused on medical costs incurred for a short period after the injury. However, patients often had comorbidities before their hip fractures that would have affected medical costs even had they not sustained a fracture. Consequently, these studies may have overestimated the costs associated with hip fractures and did not characterize the duration of increased medical costs adequately. Without knowing this crucial information, it is difficult to craft thoughtful health policy to support these patients' needs. QUESTIONS/PURPOSES: (1) To compare the direct medical costs for 5 years before fracture and up to 5 years after injury in a group of patients who underwent hip fracture surgery with a matched group of patients who did not experience a hip fracture, (2) to analyze the duration over which the increased direct medical costs associated with a hip fracture continues, and (3) to analyze whether there is a difference in direct medical costs according to age group using a nationwide claims database in South Korea. METHODS: The National Health Insurance Service Sample cohort in South Korea consisted of 1 million patients who were selected using a systematic, stratified, random sampling method from 48,222,537 individuals on December 31, 2006. Under a compulsory social insurance system established by the National Health Insurance Act, all patients were followed until 2015. Patients with hip fractures and matched controls were selected from the National Health Insurance Service sample of South Korea. Patients with hip fractures were defined as those who were hospitalized with a diagnosis of femoral neck fracture or intertrochanteric fracture and who underwent surgical treatment. We excluded patients with hip fractures before January 1, 2007 to ensure a minimum 5-year period that was free of hip fractures. Patients with hip fractures were matched with patients of the same age and gender at the date of admission to an acute care hospital for surgery (time zero). If patients with hip fractures died during the follow-up period, we performed matching among patients whose difference from the time of death was within 1 month. This method of risk-set matching was repeated sequentially for the next patient until the last patient with a hip fracture was matched. We then sequentially performed 1:5 random sampling for each risk set. A total of 3583 patients in the hip fracture cohort (patients with hip fractures) and 17,915 patients in the matched cohort (those without hip fractures) were included in this study. The mean age was 76 ± 9 years, and 70% were women in both groups. Based on the Charlson comorbidity index score, medication, and medical history, the patients with hip fractures had more comorbidities. Person-level direct medical costs per quarter were calculated for 5 years before time zero and up to 5 years after time zero. Direct medical costs were defined as the sum of that insurer's payments (that is, the National Health Insurance Service's payments), and that patient's copayments, excluding uncovered payments. We compared direct medical costs between patients with hip fractures and the patients in the matched cohort using a comparative interrupted time series analysis. The difference-in-difference estimate is the ratio of the differences in direct medical costs before and after time zero in the hip fracture cohort to the difference in direct medical costs before and after time zero in the matched cohort; the difference in difference estimates were calculated each year after injury. To identify changes in direct medical cost trends in patients with hip fractures and all subgroups, joinpoint regression was estimated using statistical software. RESULTS: The direct medical costs for the patients with hip fractures were higher than those for patients in the matched cohort at every year during the observation period. The difference in direct medical costs between the groups before time zero has increased every year. The direct medical costs in patients with hip fractures was the highest in the first quarter after time zero. Considering the differential changes in direct medical costs before and after time zero, hip fractures incurred additional direct medical costs of USD 2514 (95% CI 2423 to 2606; p < 0.01) per patient and USD 264 (95% CI 166 to 361; p < 0.01) per patient in the first and second years, respectively. The increase in direct medical costs attributable to hip fracture was observed for 1.5 to 2 years (difference-in-difference estimate at 1 year 3.0 [95% CI 2.8 to 3.2]; p < 0.01) (difference-in-difference estimate at 2 years 1.2 [95% CI 1.1 to 1.3]; p < 0.01; joinpoint 1.5 year). In the subgroups of patients younger than 65, patients between 65 and 85, and patients older than 85 years of age, the increase in direct medical costs attributable to hip fracture continued up to 1 year (difference-in-difference estimate ratio at 1 year 2.7 [95% CI 2.1 to 3.4]; p < 0.01; joinpoint 1 year), 1.5 to 2 years (difference-in-difference estimate ratio at 1 year 2.8 [95% CI 2.6 to 3.1]; p < 0.01; difference-in-difference estimate ratio at 2 years 1.2 [95% CI 1.1 to 1.3]; p < 0.01; joinpoint 1.5 years), and 39 months to 5 years (difference-in-difference estimate ratio at 1 year 5.2 [95% CI 4.4 to 6.2]; p < 0.01; difference-in-difference estimate ratio at 5 years 2.1 [95% CI 1.4 to 3.1]; p < 0.01; joinpoint 39 months) from time zero, respectively. CONCLUSION: The direct medical costs in patients with hip fractures were higher than those in the matched cohort every year during the 5 years before and after hip fracture. The increase in direct medical costs because of hip fractures was maintained for 1.5 to 2 years and was greater in older patients. Based on this, we suggest that health policies should focus on patients' financial and social needs, with particular emphasis on the first 2 years after hip fracture with stratification based on patients' ages. LEVEL OF EVIDENCE: Level II, economic analysis.

Effects of Stocking Density on Stress, Hematological Responses, and Growth of Black Rockfish Sebastes schlegelii.

The objective of the current study was to evaluate the effect of stocking density on juvenile Black Rockfish Sebastes schlegelii (average weight = 12 g) in terms of stress, hematological responses, and growth performance during a 4-month growth trial in a flow-through system. The initial stocking densities were 1.3 kg/m3 (low), 1.8 kg/m3 (medium), and 2.3 kg/m3 (high), and the final densities were 4.9 kg/m3 (low), 5.6 kg/m3 (medium), and 6.3 kg/m3 (high). At the end of the trial, the high stocking density significantly affected growth characteristics, levels of growth hormone and insulin-like growth factor 1, and hematological indices (hematocrit, red blood cell count, and hemoglobin level) compared to the medium and low stocking densities. The plasma cortisol and immunoglobulin-M levels were significantly higher at the high density than at the other two densities. Taken together, while the low and medium stocking densities (final densities of up to 5.6 kg/m3 ) did not affect stress and hematological indices or growth, the high stocking density (final density of 6.3 kg/m3 ) significantly impacted those variables, which suggests an allostatic load at that density. Thus, the use of a final stocking density less than 6.3 kg/m3 should be considered to avoid compromising the stress and health condition and growth of Black Rockfish at this size and temperature range.

SCF-Slimb is critical for Glycogen synthase kinase-3ß-mediated suppression of TAF15-induced neurotoxicity in Drosophila.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder characterized pathologically by motor neuron degeneration and associated with aggregation of RNA-binding proteins. TATA-binding protein-associated factor 15 (TAF15) accumulates as cytoplasmic aggregates in neuronal cells, and clearance of these aggregates is considered a potential therapeutic strategy for ALS. However, the exact pathogenic mechanism of TAF15-induced neurotoxicity remains to be elucidated. Glycogen synthase kinase-3 (GSK-3) plays a critical role in the protection of ALS pathology. In the present study, we use a transgenic fly model over-expressing human TAF15 to study the protective effects of Shaggy/GSK3ß on TAF15-induced neuronal toxicity in Drosophila brain. Transgenic flies were examined for locomotor activity and lithium treatment. The expression level and solubility of TAF15 were assessed with western blotting, whereas immunohistochemistry was used to assess TAF15 aggregation in Drosophila brain. We have revealed that Shaggy/GSK3ß was abnormally activated in neurons of TAF15-expressing flies and its inhibition can suppress the defective phenotypes, thereby preventing retinal degeneration and locomotive activity caused by TAF15. We have also found that Shaggy/GSK3ß inhibition in neuronal cells leads to a reduction in TAF15 levels. Indeed, the F-box proteins Slimb and archipelago genetically interact with TAF15 and control TAF15 protein level in Drosophila. Importantly, SCFslimb is a critical regulator for Shaggy/GSK3ß-mediated suppression of TAF15-induced toxicity in Drosophila. The present study has provided an in vivo evidence supporting the molecular mechanism of GSK3ß inhibition for protection against TAF15-linked proteinopathies.

Bayesian semiparametric mixed effects models for meta-analysis of the literature data : An application to cadmium toxicity studies.

We propose Bayesian semiparametric mixed effects models with measurement error to analyze the literature data collected from multiple studies in a meta-analytic framework. We explore this methodology for risk assessment in cadmium toxicity studies, where the primary objective is to investigate dose-response relationships between urinary cadmium concentrations and ß2 -microglobulin. In the proposed model, a nonlinear association between exposure and response is described by a Gaussian process with shape restrictions, and study-specific random effects are modeled to have either normal or unknown distributions with Dirichlet process mixture priors. In addition, nonparametric Bayesian measurement error models are incorporated to flexibly account for the uncertainty resulting from the usage of a surrogate measurement of a true exposure. We apply the proposed model to analyze cadmium toxicity data imposing shape constraints along with measurement errors and study-specific random effects across varying characteristics, such as population gender, age, or ethnicity.

Inhibition of biofilm and virulence properties of Pseudomonas aeruginosa by sub-inhibitory concentrations of aminoglycosides.

Aminoglycosides are a commonly used class of antibiotics; however, their application has been discontinued due to the emergence of multi-drug resistance bacterial strains. In the present study, the subinhibitory concentrations (sub-MIC) of several aminoglycosides were determined and tested as an antibiofilm and for their anti-virulence properties against Pseudomonas aeruginosa PAO1, which is an opportunistic foodborne pathogen. P. aeruginosa PAO1 exhibits multiple mechanisms of resistance, including the formation of biofilm and production of several virulence factors, against aminoglycoside antibiotics. The sub-MIC of these antibiotics exhibited biofilm inhibition of P. aeruginosa in alkaline TSB (pH 7.9). Moreover, various concentrations of these aminoglycosides also eradicate the mature biofilm of P. aeruginosa. In the presence of sub-MIC of aminoglycosides, the morphological changes of P. aeruginosa were found to change from rod-shaped to the filamentous, elongated, and streptococcal forms. Similar growth conditions and sub-MIC of aminoglycosides were also found to attenuate several virulence properties of P. aeruginosa PAO1. Molecular docking studies demonstrate that these aminoglycosides possess strong binding properties with the LasR protein, which is a well-characterized quorum-sensing receptor of P. aeruginosa. The present study suggests a new approach to revitalize aminoglycosides as antibiofilm and antivirulence drugs to treat infections caused by pathogenic bacteria.

Streptomycin mediated biofilm inhibition and suppression of virulence properties in Pseudomonas aeruginosa PAO1.

Pseudomonas aeruginosa is known as an opportunistic pathogen whose one of the antibiotic resistance mechanisms includes biofilm formation and virulence factor production. The present study showed that the sub-minimum inhibitory concentration (sub-MIC) of streptomycin inhibited the formation of biofilm and eradicated the established mature biofilm. Streptomycin at sub-MIC was also capable of inhibiting biofilm formation on the urinary catheters. In addition, the sub-MIC of streptomycin attenuated the bacterial virulence properties as confirmed by both phenotypic and gene expression studies. The optimal conditions for streptomycin to perform anti-biofilm and anti-virulence activities were proposed as alkaline TSB media (pH 7.9) at 35 °C. However, sub-MIC of streptomycin also exhibited a comparative anti-biofilm efficacy in LB media at similar pH level and temperature. Furthermore, this condition also improved the biofilm inhibition and eradication properties of streptomycin, tobramycin and tetracycline towards the biofilm formed by a clinical isolate of P. aeruginosa. Findings from the present study provide an important insight for further studies on the mechanisms of biofilm inhibition and dispersion of pre-existing biofilm by streptomycin as well as tobramycin and tetracycline under a specific culture environment.

Synthesis and characterization of chitosan oligosaccharide-capped gold nanoparticles as an effective antibiofilm drug against the Pseudomonas aeruginosa PAO1.

The infection caused by Pseudomonas aeruginosa is a serious concern in human health. The bacterium is an opportunistic pathogen which has been reported to cause nosocomial and chronic infections through biofilm formation and synthesis of several toxins and virulence factors. Furthermore, the formation of biofilm by P. aeruginosa is known as one of the resistance mechanisms against conventional antibiotics. Natural compounds from marine resources have become one of the simple, cost-effective, biocompatible and non-toxicity for treating P. aeruginosa biofilm-related infections. Furthermore, hybrid formulation with nanomaterials such as nanoparticles becomes an effective alternative strategy to minimize the drug toxicity problem and cytotoxicity properties. For this reason, the present study has employed chitosan oligosaccharide for the synthesis of chitosan oligosaccharide-capped gold nanoparticles (COS-AuNPs). The synthesized COS-AuNPs were then characterized by using UV-Visible spectroscopy, Dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), Field emission transmission electron microscopy (FE-TEM), and Energy dispersive X-ray diffraction (EDX). The synthesized COS-AuNPs were applied for inhibiting P. aeruginosa biofilm formation. Results have shown that COS-AuNPs exhibited inhibition to biofilm as well as eradication to pre-existing mature biofilm. Simultaneously, COS-AuNPs were also able to reduce bacterial hemolysis and different virulence factors produced by P. aeruginosa. Overall, the present study concluded that the hybrid nanoformulation such as COS-AuNPs could act as a potential agent to exhibit inhibitory properties against the P. aeruginosa pathogenesis arisen from biofilm formation.

Fucoidan-Stabilized Gold Nanoparticle-Mediated Biofilm Inhibition, Attenuation of Virulence and Motility Properties in Pseudomonas aeruginosa PAO1.

The emergence of antibiotic resistance in Pseudomonas aeruginosa due to biofilm formation has transformed this opportunistic pathogen into a life-threatening one. Biosynthesized nanoparticles are increasingly being recognized as an effective anti-biofilm strategy to counter P. aeruginosa biofilms. In the present study, gold nanoparticles (AuNPs) were biologically synthesized and stabilized using fucoidan, which is an active compound sourced from brown seaweed. Biosynthesized fucoidan-stabilized AuNPs (F-AuNPs) were subjected to characterization using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), field emission transmission electron microscopy (FE-TEM), dynamic light scattering (DLS), and energy dispersive X-ray diffraction (EDX). The biosynthesized F-AuNPs were then evaluated for their inhibitory effects on P. aeruginosa bacterial growth, biofilm formation, virulence factor production, and bacterial motility. Overall, the activities of F-AuNPs towards P. aeruginosa were varied depending on their concentration. At minimum inhibitory concentration (MIC) (512 µg/mL) and at concentrations above MIC, F-AuNPs exerted antibacterial activity. In contrast, the sub-inhibitory concentration (sub-MIC) levels of F-AuNPs inhibited biofilm formation without affecting bacterial growth, and eradicated matured biofilm. The minimum biofilm inhibition concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were identified as 128 µg/mL. Furthermore, sub-MICs of F-AuNPs also attenuated the production of several important virulence factors and impaired bacterial swarming, swimming, and twitching motilities. Findings from the present study provide important insights into the potential of F-AuNPs as an effective new drug for controlling P. aeruginosa-biofilm-related infections.

Enhanced synthesis and release of dopamine in transgenic mice with gain-of-function α6* nAChRs.

α6ß2* nicotinic acetylcholine receptors (nAChRs)s in the ventral tegmental area to nucleus accumbens (NAc) pathway are implicated in the response to nicotine, and recent work suggests these receptors play a role in the rewarding action of ethanol. Here, we studied mice expressing gain-of-function α6ß2* nAChRs (α6L9'S mice) that are hypersensitive to nicotine and endogenous acetylcholine. Evoked extracellular dopamine (DA) levels were enhanced in α6L9'S NAc slices compared to control, non-transgenic (non-Tg) slices. Extracellular DA levels in both non-Tg and α6L9'S slices were further enhanced in the presence of GBR12909, suggesting intact DA transporter function in both mouse strains. Ongoing α6ß2* nAChR activation by acetylcholine plays a role in enhancing DA levels, as α-conotoxin MII completely abolished evoked DA release in α6L9'S slices and decreased spontaneous DA release from striatal synaptosomes. In HPLC experiments, α6L9'S NAc tissue contained significantly more DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid compared to non-Tg NAc tissue. Serotonin (5-HT), 5-hydroxyindoleacetic acid, and norepinephrine (NE) were unchanged in α6L9'S compared to non-Tg tissue. Western blot analysis revealed increased tyrosine hydroxylase expression in α6L9'S NAc. Overall, these results show that enhanced α6ß2* nAChR activity in NAc can stimulate DA production and lead to increased extracellular DA levels.

Concurrent Acute Ischemic Stroke and Myocardial Infarction Associated With Atrial Fibrillation.

An 85-year-old man was admitted with dysarthria. Electrocardiography showed atrial fibrillation and prominent ST-segment elevation in V2-V6. Multiple acute cerebral infarctions were observed in brain images. Coronary angiography showed total occlusion of the mid left anterior descending artery. After thrombus aspiration, no atherosclerotic changes were observed on intravascular ultrasound.

A flucytosine-responsive Mbp1/Swi4-like protein, Mbs1, plays pleiotropic roles in antifungal drug resistance, stress response, and virulence of Cryptococcus neoformans.

Cryptococcosis, caused by the basidiomycetous fungus Cryptococcus neoformans, is responsible for more than 600,000 deaths annually in AIDS patients. Flucytosine is one of the most commonly used antifungal drugs for its treatment, but its resistance and regulatory mechanisms have never been investigated at the genome scale in C. neoformans. In the present study, we performed comparative transcriptome analysis by employing two-component system mutants (tco1Δ and tco2Δ) exhibiting opposing flucytosine susceptibility. As a result, a total of 177 flucytosine-responsive genes were identified, and many of them were found to be regulated by Tco1 or Tco2. Among these, we discovered an APSES-like transcription factor, Mbs1 (Mbp1- and Swi4-like protein 1). Expression analysis revealed that MBS1 was regulated in response to flucytosine in a Tco2/Hog1-dependent manner. Supporting this, C. neoformans with the deletion of MBS1 exhibited increased susceptibility to flucytosine. Intriguingly, Mbs1 played pleiotropic roles in diverse cellular processes of C. neoformans. Mbs1 positively regulated ergosterol biosynthesis and thereby affected polyene and azole drug susceptibility. Mbs1 was also involved in genotoxic and oxidative stress responses. Furthermore, Mbs1 promoted production of melanin and capsule and thereby was required for full virulence of C. neoformans. In conclusion, Mbs1 is considered to be a novel antifungal therapeutic target for treatment of cryptococcosis.

Dietary supplementation of high-performance Korean and Japanese judoists.

This research investigated patterns of the use of dietary supplement and doping awareness among high-ranked judoists from 2 countries. Korean (70 men and 31 women) and Japanese (37 men and 34 women) national judo team members were divided into 2 groups (high and low competitive performance levels) according to their international and national rankings. Fifty-nine percent of Korean and 61% of Japanese judoists consumed dietary supplements. Eighty-eight percent of high- and 51% of low-competitive-performance-level Korean judoists consumed dietary supplements. Sixty-eight percent of high- and 57% of low-competitive-performance-level Japanese judoists consumed dietary supplements. Oriental supplements (34%), vitamins (23%), and protein powder (12%) were the most commonly consumed dietary supplements in Korean judoists. Vitamins (45%), protein powder (33%), and minerals (15%) were the most commonly consumed dietary supplements in Japanese judoists. Thirty-eight percent of judoists from both countries had not received any proper education about antidoping, and 44% of judoists from both countries had not received knowledge of antidoping legislation. There was a significant difference in education about antidoping between high and low competitive-performance levels of Korean judoists (p < .001). Korean judoists received significantly less antidoping education than Japanese judoists (p < .001). The associations for antidoping education and knowledge of antidoping legislation with the use of dietary supplements were 3.46 (95% CI = 1.31-9.12) and 1.63 (95% CI = 0.71-3.76), respectively. Our findings showed that use of dietary supplements in judoists from both countries was increased after experiencing antidoping education.

Impacts of Temperature on the Growth, Feed Utilization, Stress, and Hemato-Immune Responses of Cherry Salmon (Oncorhynchus masou).

Cherry salmon (Oncorhynchus masou) hold commercial value in aquaculture, and there is a need for controlled laboratory studies to isolate the specific effects of temperature on their growth, feeding, and well-being. We examined the effects of different temperatures (10 °C, 14 °C, 18 °C, and 22 °C) on juvenile cherry salmon (average mass 29.1 g) in triplicate tanks per treatment over eight weeks. The key parameters assessed included growth rate, feed efficiency, stress response, and hemato-immune responses. Our objectives were to determine the most and less favorable temperatures among the four designated temperatures and to assess the adverse effects associated with these less favorable temperatures. The results showed that body weight, growth rates, feed intake, and feed efficiency were significantly higher at 10 °C and 14 °C compared to 18 °C and 22 °C. Reduced appetite and feeding response were observed at 22 °C. Red blood cell parameters were significantly lower at 22 °C. At 10 °C, the results showed significantly increased plasma cortisol levels, gill Na+/K+-ATPase activity, body silvering, and decreased condition factors, suggesting potential smoltification. The potential smoltification decreased with increasing temperatures and disappeared at 22 °C. Furthermore, the plasma lysozyme concentrations significantly increased at 18 °C and 22 °C. In conclusion, our study identifies 10 °C and 14 °C as the temperatures most conducive to growth and feed performance in juvenile cherry salmon under these experimental conditions. However, temperatures of 22 °C or higher should be avoided to prevent compromised feeding, reduced health, disturbed immune responses, impaired growth, and feed performance.

Relationship between childhood trauma and resilience in patients with mood disorders.

BACKGROUND: Childhood trauma has lasting negative impacts on individuals' psychological functioning. However, there is limited empirical evidence on the association between childhood trauma and resilience and none examining such relationship among diverse clinical populations. This study aimed to investigate the relationship in patients with major depressive disorder, bipolar I disorder, bipolar II disorder, and a comparison group. METHODS: In total, 787 psychiatric patients and 734 people from the general population participated in the study. The Childhood Trauma Questionnaire-Short Form and Connor-Davidson Resilience Scale were used to assess childhood trauma and resilience, respectively. RESULTS: Individuals with childhood trauma showed lower levels of resilience in all subjects; among them, those who experienced emotional abuse and emotional neglect exhibited even stronger associations than other types of childhood trauma. There was a significant difference in the negative relationship between childhood trauma and resilience by group, where the association was more prominent in the comparison group than in MDD and BD II patient groups. LIMITATIONS: The generalizability of our results may be limited due to unproportionate patient sample size. Also, we could not examine the causal relationship between childhood trauma and resilience. CONCLUSION: Childhood trauma and resilience had a significantly negative association. Our results suggest that people who have experienced emotional abuse and emotional neglect should be closely assisted to develop resilience. Interventions that promote resilience should be provided to individuals predisposed to psychological risks as a result of childhood trauma.

Multiple roles of Ypd1 phosphotransfer protein in viability, stress response, and virulence factor regulation in Cryptococcus neoformans.

Ypd1 is a key phosphorelay protein that controls eukaryotic two-component systems, but its function in Cryptococcus neoformans is not known. Here, we report that Ypd1 is required for the viability of C. neoformans via the Hog1 mitogen-activated protein kinase (MAPK) pathway but plays multiple cellular roles in both a Hog1-dependent and -independent manner.

Plasma concentration of dopamine varies depending on breed, sex, and the genotype of DRD4 in horses.

Dopamine (DA) is known to be a key modulator of animal behaviors. Thus, the plasma concentration of DA might be used as a biomarker for the behavioral characteristics of horses. The behavioral characteristics of horses vary depending on the breed, age, and sex. Moreover, the DA receptor genotypes are also related to horse behaviors. Thus, the aim of this study was to investigate the DA concentration variations of horse plasma by breed, age, sex, or genotype of its receptor. The horses were divided by breed into Thoroughbred (n = 13), Pony (n = 9), Warmblood (n = 4), and Haflinger (n = 5). The age variable was divided into three different groups: post-pubertal (2-5 years, n = 6), adult (6-13 years, n = 19), and aged horses (15-24 years, n = 6). The sex variable was divided into geldings (n = 8) and mares (n = 23). Approximately 10 mL of blood was collected, and an ELISA kit was used to measure the plasma concentration of DA. Polymerase chain reaction analysis was performed to identify the genetic variation in the DA D4 receptor gene (DRD4). SPSS statistical software was used for statistical analysis. The DA concentrations in geldings were significantly lower than those in mares. There was no significant difference in DA concentrations among breed and age groups. Horses with the GG and GA genotypes had significantly higher plasma concentrations of DA compared to horses with the AA genotype for the G292A gene. Briefly, the plasma concentration of DA varied depending on the sex and genotype of G292A. These factors should be considered when the concentration of DA is used as a biomarker for the behavioral characteristics of horses. In conclusion, the DA concentration or DRD4 genotype of horse plasma has the potential to be used as a biomarker that can predict the behavioral characteristics of horses.

Efficacy and safety of daily home-based transcranial direct current stimulation as adjunct treatment for bipolar depressive episodes: Double-blind sham-controlled randomized clinical trial.

Background: Although transcranial direct current stimulation (tDCS) is known to be a promising therapeutic modality for unipolar depression, the efficacy and safety of tDCS for bipolar depressive episodes (BD) are still unknown and clinical trials of home-based tDCS treatment are scarce. As a result, we set out to investigate the efficacy and safety of home-based tDCS for the treatment BD. Methods: Participants (n = 64), diagnosed as bipolar disorder as per the diagnostic and statistical manual of mental disorders (DSM-5), were randomly assigned to receive tDCS. Hamilton Depression Rating Scale (HDRS-17) scores were measured at the baseline, week 2, 4, and 6, and home-based tDCS (for 30 min with 2 mA) was self-administered daily. Results: Of the 64 patients (15.6% bipolar disorder I, 84.4% bipolar disorder II), 41 patients completed the entire assessment. In the intention-to-treat analysis, time-group interaction for the HDRS-17 [F (3, 146.36) = 2.060; p = 0.108] and adverse effect differences between two groups were not statistically significant, except the pain score, which was higher in the active group than the sham group (week 0-2: p < 0.01, week 2-4: p < 0.05, and week 4-6: p < 0.01). Conclusion: Even though we found no evidence for the efficacy of home-based tDCS for patients with BD, this tool was found to be a safe and tolerable treatment modality for BD. Clinical trial registration: [https://clinicaltrials.gov/show/NCT03974815], identifier [NCT03974815].

Predicting the Number of Graphene-Like Layers on Surface for Commercial Fumed Nanodiamonds with Raman Spectra and Model Calculations.

Nanoscale carbon materials have a broad range of applications in the field of surface and material sciences. Each vibration mode of a Raman and Fourier transform infrared (FT-IR) spectra corresponds to a specific frequency of a bond in the core and surface of the crystal, thus it is highly sensitive to morphology, implying that every band is sensitive to the orientation of the bonds and the atomic weight at either end of the bond. Accordingly, in this study we apply transmission electron microscope (TEM), Raman spectroscopies, and model calculations to study the relative content of carbon-carbon (C-C) bonds to the anhydrous and weakly aggregated elementary nanoscale carbon particles of detonation nanodiamonds. One point of the Raman bands at approximately 1300 cm-1 established that there are highly uniform C-C bonds in a tetrahedral crystal field environment not unlike that of diamonds. Another point at approximately 1600 cm-1 would be a hexagonal graphene-like sheet. By analyzing the relative content of carbon bonds using the area of intensity of the Raman peaks and a simulation of crystal morphology, we suggest that the number of graphene surface layers would be monolayers in nanodiamonds, comprising two kinds of C-C bonds, one being sp3 bonds of diamond in the core and the other being sp2 bonds of graphene on the surface.

Effects of risk factor numbers on the development of the metabolic syndrome.

This study was performed to identify the factors affecting the develop-ment of metabolic syndrome by comparing the numbers of risk factors of the syndrome and by identifying the factors influencing the develop-ment of metabolic syndrome. Two hundred forty-eight health screening of examinee were used for the study (101 males, 147 females). Diagnostic basis ratio of metabolic syndrome risk factors showed that 35.1% of the subjects had abdominal obesity, 32.7% for high blood pressure, 66.1% for high insulin blood sugar, 43.1% for high triglyceride lipidemia, and 7.3% for low high-density lipoprotein lipidemia. No significant difference of the incidence of metabolic syndrome was found between gender. The diagnostic number for male was the highest with 1 risk factor (31.7%) while the highest with 2 factors (30.6%) in female. Significant differences were found in age and body mass index (BMI) between normal group with no risk factor and metabolic syndrome group. There was significant difference in BMI between the syndrome group with 1 risk factor and 3 risk factors. BMI was significantly higher (5.282 times) compared to their counterpart (P<0.001). Significant difference was found in BMI between 2 risk factors and the syndrome group with more than 3 risk factors and the incidence was higher (4.094 times) in the overweight group than their counterpart (P<0.001).

Differential Seawater Adaptability in Three Different Sizes of Under-yearling Steelhead Trout.

Seawater adaptability of steelhead trout increases along with the increase in the size of the fish, independent of parr-smolt transformation. Three 96 h seawater challenge tests were conducted to determine the size at which seawater adaptability of steelhead trout develops. Plasma Na+ and Cl- levels, moisture content, gill Na+/K+ ATPase activity, and mortality during the 96 h after direct transfer to seawater (32 ppt) were determined. Plasma Na+ and Cl- levels in 50 g fish continuously increased during the 96 h after the transfer to seawater (p<0.05), but the levels in 100 and 150 g fish leveled off after 24 h (p<0.05). Both 100 and 150 g size steelhead trout maintained muscle moisture content (%) better than 50 g size fish (p<0.05). Gill Na+/K+ ATPase activity in the 100 g size group increased in a time-dependent manner after transfer to seawater (p<0.05), whereas activity in the 50 and 150 g sizes did not increase (p>0.05), for which a possible explanation was discussed. A mere 2.6% mortality in both the 50 and 150 g size groups was observed. In conclusion, the current results indicate that 50 g size steelhead trout did not show development of a high level of hypoosmoregulatory capacity, whereas fish in the 100 and 150 g size groups showed a high level in our experimental conditions. Therefore, the steelhead trout larger than a 100 g size is recommended for transfer to seawater culture.