Bone formation by Irisin-Poly vinyl alchol modified bioglass ceramic beads in the rabbit model.

In the aging society, slow bone regeneration poses a serious hindrance to the quality of life. To deal with this problem, in this study, we have combined irisin with the bioglass regular beads to enhance the bone regeneration process. For this purpose, highly porous bioglass was obtained as spherical beads by using sodium alginate. The bioglass was evaluated by various analytical techniques such as SEM, EDS, XRD, and pore size distribution. The results depicted that porous bioglass was prepared correctly and SEM analysis showed a highly porous bioglass was formulated. On this bioglass, irisin was loaded with the assistance of polyvinyl alcohol (PVA) in three concentrations (50 ng/ml, 100 ng/ml, and 150 ng/ml per 1 g of bioglass). SEM analysis showed that pores are covered with PVA. The irisin release profile showed a sustained release over the time period of 7 days. In vitro, biocompatibility evaluation by the MC3T3E1 cells showed that prepared bioglass and irisin loaded bioglass (BGI50, BGI100, and BG150) are highly biocompatible. Alizarin Red staining analysis showed that after 2 weeks BGI50 samples showed highest calcium nodule formation. In vivo in the rabbit femur model was conducted for 1 and 2 months. BGI150 samples showed highest BV/TV ratio of 37.1 after 2 months. The histological data showed new bone formation surrounding the beads and with beads loaded with irisin. Immunohistochemistry using markers OPN, RUNX, COL, and ALP supported the osteogenic properties of the irisin-loaded bioglass beads. The results indicated that irisin-loaded bioglass displayed remarkable bone regeneration.

Change in absolute neutrophil count after COVID-19 infection in patients using clozapine versus other antipsychotics.

It was reported that patients who contracted COVID-19 while taking clozapine exhibited a distinct hematological response. However, the absence of control groups made it difficult to attribute it to clozapine. The changes in absolute neutrophil counts (ANCs) during the 4 weeks after COVID-19 infection were compared between the two groups of patients with severe mental illnesses (SMIs) (49 patients using clozapine and 54 using other antipsychotics) using generalized additive modeling. Although the pattern of a transient drop in ANC followed by gradual recovery could be demonstrated in both groups, it was more pronounced in the clozapine group ( P  = 0.00025). Nevertheless, overall ANC remained at a higher level in the clozapine group. The results suggested potential interaction between clozapine and COVID-19 at the level of hematological dynamics. However, it did not necessarily indicate that such interaction is inevitably harmful or dangerous. It was more of a concern that some patients using other antipsychotics exhibited decreased ANC, which did not easily recover. Traditionally, clinicians have been concerned about the worsening of hematological side effects in clozapine patients after COVID-19 infection. However, the obtained result highlighted the necessity of hematological monitoring in patients using any type of antipsychotics for SMIs.

Incidence and outcomes of intraoperative periprosthetic acetabular fractures during cementless total hip arthroplasty: a prospective three-dimensional computer tomography-based study.

PURPOSE: Unlike periprosthetic femoral fractures, periprosthetic acetabular fractures during total hip arthroplasty (THA) have not been evaluated in detail. We prospectively evaluated the incidence, patterns, risk factors, and clinical outcomes of intraoperative periprosthetic acetabular fractures using pre- and postoperative computer tomography (CT). METHODS: In this prospective single-centre study, we evaluated 234 consecutive patients (250 hips) who underwent THA and three-dimensional CT before and after the surgery. We assessed the incidence, pattern of fractures, outcomes for each fracture pattern, reoperation and revision rates, Harris hip score, and visual analog scale (VAS) for pain. Multivariate regression models were used to identify risk factors for periprosthetic acetabular fractures. RESULTS: In total, 43 periprosthetic acetabular fractures (17.2%) were identified via CT. Fractures occurred most frequently at the superolateral wall. Early cup migration occurred in three hips. None of the patients underwent revision surgery for acetabular loosening. Regression modeling showed that rheumatoid arthritis was a significant predictor of periprosthetic acetabular fractures. CONCLUSIONS: Periprosthetic acetabular fractures are not infrequent during cementless THA and are more common in patients with rheumatoid arthritis.

Behavioral and transcriptional effects of repeated electroconvulsive seizures in the neonatal MK-801-treated rat model of schizophrenia.

RATIONALE: Electroconvulsive therapy (ECT) is an effective treatment modality for schizophrenia. However, its antipsychotic-like mechanism remains unclear. OBJECTIVES: To gain insight into the antipsychotic-like actions of ECT, this study investigated how repeated treatments of electroconvulsive seizure (ECS), an animal model for ECT, affect the behavioral and transcriptomic profile of a neurodevelopmental animal model of schizophrenia. METHODS: Two injections of MK-801 or saline were administered to rats on postnatal day 7 (PN7), and either repeated ECS treatments (E10X) or sham shock was conducted daily from PN50 to PN59. Ultimately, the rats were divided into vehicle/sham (V/S), MK-801/sham (M/S), vehicle/ECS (V/E), and MK-801/ECS (M/E) groups. On PN59, prepulse inhibition and locomotor activity were tested. Prefrontal cortex transcriptomes were analyzed with mRNA sequencing and network and pathway analyses, and quantitative real-time polymerase chain reaction (qPCR) analyses were subsequently conducted. RESULTS: Prepulse inhibition deficit was induced by MK-801 and normalized by E10X. In M/S vs. M/E model, Egr1, Mmp9, and S100a6 were identified as center genes, and interleukin-17 (IL-17), nuclear factor kappa B (NF-κB), and tumor necrosis factor (TNF) signaling pathways were identified as the three most relevant pathways. In the V/E vs. V/S model, mitophagy, NF-κB, and receptor for advanced glycation end products (RAGE) pathways were identified. qPCR analyses demonstrated that Igfbp6, Btf3, Cox6a2, and H2az1 were downregulated in M/S and upregulated in M/E. CONCLUSIONS: E10X reverses the behavioral changes induced by MK-801 and produces transcriptional changes in inflammatory, insulin, and mitophagy pathways, which provide mechanistic insight into the antipsychotic-like mechanism of ECT.

[Diagnosis and Treatment of GastroEsophageal Reflux Disease at the Primary Health Care Clinics in Korea].

Background/Aims: The prevalence of GERD and treatment costs are continuously rising in Korea, and the importance of primary health care clinics where the most treatment of actual patients is conducted is increasing. In this study, the diagnosis of GERD, selection of therapeutic drugs, and treatment methods in primary health care clininics were investigated through a large-scale multi-dimensional surveys. Methods: From January 2015 to December 2018, the study data of 18,010 patients with GERD were retrospectively investigated based on eletronic medical record at 542 primary health care clinics in Korea. Results: Among all GERD patients, endoscopy was used for diagnosis in 16.11% of cases, and the most frequently performed in gastroenterology department (28.85%). The average BMI and the proportion of patients in stages 1 to 3 of obesity were highest in the ERD group, and the majority of the severity of ERD group was mild. Symptoms of the patients with GERD were mainly heartburn, gastric acid reflux, and chest pain. Drug treatment was performed in most of the patients with GERD, and PPI was the main drug, and Esomeprazol was prescribed the most among the main ingredients, and the ratio of PPI alone was high. The rate of symptom improvement after GERD treatment was slightly higher in the ERD group (75.91%) and the NERD group (74.36%) than in the GERD diagnosed without endoscopy group (63.89%). Conclusions: In domestic primary health care clinics, the majority were diagnosed with GERD without endoscopy on the basis of symptoms. The most preferred treatment for GERD was PPI, which was prescribed alone in the majority.

Preparation and characterization of zwitterion-substituted lignin/Nafion composite membranes.

In this study, a novel zwitterion-substituted lignin (ZL) containing amino and sulfonic acid groups was synthesized, and ZL/Nafion composite membranes were fabricated as proton exchange membranes. Kraft lignin was modified using an aminosilane and 1,3-propanesultone via a continuous grafting reaction to provide zwitterionic moieties. Chemical structural analyses confirmed the successful introduction of the zwitterion moiety into lignin. In particular, the surface charge of ZL is positive in an acidic medium and negative in a basic medium, suggesting that ZL is a zwitterionic material. ZL was incorporated into a Nafion membrane to enhance its ion exchange capacity, thermal stability, and hydrophilicity. The proton conductivity of ZL/Nafion 0.5 %, 151.0 mS/cm, was 55.3 % higher than that of unmodified ML (methanol-soluble lignin)/Nafion 0.5 % (97.2 mS/cm), indicating that the zwitterion moiety of ZL enhances the proton transport ability. In addition, oxidative stability evaluation confirmed that ZL/Nafion 2 % was chemically more durable than pure Nafion. This confirmed that using lignin as a membrane additive yielded positive results in terms of chemical durability and oxidation stability in Nafion. Therefore, ZL is expected to be utilized as a multifunctional additive and exhibits the potential for fuel cell applications.

Association between initial clozapine titration and pneumonia risk among patients with schizophrenia in a Korean tertiary hospital.

Pneumonia is a significant adverse drug reaction (ADR) associated with clozapine, characterized by high mortality and potential linkage with other inflammatory responses. Despite the critical nature, research regarding the development of pneumonia during initial clozapine titration remains limited. This retrospective study included 1408 Korean inpatients with schizophrenia spectrum disorders. Data were collected from January 2000 to January 2023. Pneumonia developed in 3.5 % of patients within 8 weeks of clozapine initiation. Patients who developed pneumonia were taking a greater number and higher dose of antipsychotics at baseline (2.14 vs. 1.58, p < 0.001; 25.64 vs. 19.34, p = 0.012). The average onset occurred 17.24 days after initiation, on an average dose of 151.28 mg/day. Titration was either paused or slowed in most of these patients, with no reported fatalities. The types of pneumonia included aspiration pneumonia, mycoplasma pneumonia, bronchopneumonia, and COVID-19 pneumonia. Myocarditis, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, and urinary tract infections were also identified. Logistic regression analysis revealed that a greater number of concomitant antipsychotics (odds ratio [OR] = 1.59, p = 0.027) and concomitant benzodiazepine use (OR = 2.33, p = 0.005) at baseline were associated with an increased risk of pneumonia. Overall, pneumonia development during clozapine titration is linked with other inflammatory ADRs, suggesting a shared immunological mechanism. Close monitoring is recommended, especially for patients taking multiple antipsychotics and benzodiazepines. Further studies involving repeated measures of clozapine concentrations at trough and steady state, along with a more detailed description of pneumonia types, are warranted.

Association between initial pattern of clozapine titration, concentration-to-dose ratio, and incidence of fever in patients with schizophrenia spectrum disorders in a Korean tertiary hospital.

Safe and effective administration of clozapine requires careful monitoring for inflammatory reactions during the initial titration. The concentration-to-dose (C/D) ratio must be taken into account, which may vary among ethnicities. In this retrospective study, 1408 Korean schizophrenia inpatients were examined for during the first 8 weeks of clozapine titration. The average doses of clozapine administered during weeks 1, 2, 4, and 8 were 77.37, 137.73, 193.20, and 212.83 mg/day, with significantly lower doses for females than males. The average C/D ratio was significantly higher in females (1.75 ± 1.04 and 1.11 ± 0.67 ng/mL per mg/day). Patients with higher C/D ratios were more likely to experience fever and were prescribed lower doses of clozapine starting from week 4. In total, 22.1 % of patients developed a fever at an average of 15.74 days after initiating clozapine. Patients who developed a fever were younger, used more antipsychotics at baseline, had a higher C/D ratio, and had a higher incidence of an elevated C-reactive protein level. A higher C/D ratio, use of a greater number of antipsychotics at baseline, and concomitant olanzapine use were risk factors for the development of inflammatory reactions. The incidence of pneumonia, agranulocytosis, and myocarditis within 8 weeks were 3.7 %, 0.3 %, and 0.1 %. In summary, the target dose of clozapine titration is lower for Korean schizophrenia patients, with a higher C/D ratio and more frequent fever compared to Western patients; however, myocarditis occurs rarely. Our findings may contribute to the titration methods for clozapine for the East Asian population.

The bone-protective benefits of amino-conjugated calcium in an ovariectomized (OVX) rat model.

Low bone density, fragility, and microarchitectural disintegration are the symptoms of osteoporosis. An imbalance between bone growth and resorption can lead to osteoporosis. This study evaluated the effects of amino-calcium (AC) on bone protection in ovariectomized control group (NC) rats. Amino-calcium (AC) was characterized using Fourier-transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDS), and nuclear magnetic resonance spectroscopy analyses (NMR). After determining the biocompatibility of amino-calcium (AC) with MC3T3-E1 cells, alkaline phosphatase staining revealed significant changes on day 7. Three of the four groups underwent ovariectomy, whereas one group received a placebo. On micro-computed tomography, in vivo, data showed increased bone volume fraction in the femoral head and shaft areas in the amino-calcium (AC) group. Hematoxylin and eosin staining showed a bone mass and architectural protection in the amino-calcium (AC) group compared with the calcium carbonate and OVX control group. RNA sequencing analysis revealed high expression of osteogenesis-related genes in MC3T3-E1 cells. RNA sequencing revealed a significant fold change in the expression of integrin-binding sialoprotein (IBSP), bone gamma-carboxyglutamate proteins 1 and 2(BGLAP1 and BGLAP2), and periostin (POSTN). The study concluded that supplementing the OVX rats with calcium enhanced bone protection.

Increased Effect of Foot-and-Mouth Disease Virus Vaccine Structural Protein Antibody Positivity Rates in Piglets Orally Treated with Amino-Zinc Complex.

Foot-and-mouth disease (FMD) is a highly contagious animal disease that occurs in cloven-hoofed animals including pigs. To prevent FMD, vaccines and adjuvants are routinely used to induce an immune response; however, it requires an extended period of time to produce sufficient antibodies to prevent viral infection. In this study, we evaluated the increased effectiveness of the FMD vaccine structural protein (SP) antibody by administrating the Amino-Zn adjuvant to 100 pigs from 3 test pig farms in their feed. The FMD vaccine antibody titer and immunological index were analyzed using an enzyme-linked immunosorbent assay (ELISA) kit, and the hematological and blood biochemical parameters were analyzed using an automatic blood analyzer. The titer of the FMD vaccine SP antibodies in the 0.2% Amino-Zn-administered group was significantly increased compared to that of the positive control group only injected with FMD vaccine at 4 weeks after the first vaccination and at 4, 8, and 16 weeks after the second vaccination (p < 0.05). The FMD vaccine SP antibody positive rate was 100% until shipment. The IFN-γ and IgA levels were significantly increased by Amino-Zn administration 4 weeks after the first vaccination and 4 weeks after the second vaccination (p < 0.05). On the other hand, serum AST, and CPK (p < 0.001) were significantly decreased by Amino-Zn administration. These results show that the administration of Amino-Zn is effective in enhancing the antibody titer and immunogenicity of the FMD vaccine and can be used as an oral adjuvant (OrAd) to prevent viral diseases, such as FMD.

Decoration of sodium carboxymethylcellulose gel microspheres with modified lignin to enhanced methylene blue removal.

The introduction of active groups from biomass is currently the most promising alternative method for increasing the adsorption effect of dyes. In this study, modified aminated lignin (MAL) rich in phenolic hydroxyl and amine groups was prepared by amination and catalytic grafting. The factors influencing the modification conditions of the content of amine and phenolic hydroxyl groups were explored. Chemical structural analysis results confirmed that MAL was successfully prepared using a two-step method. The content of phenolic hydroxyl groups in MAL significantly increased to 1.46 mmol/g. MAL/sodium carboxymethylcellulose (NaCMC) gel microspheres (MCGM) with enhanced methylene blue (MB) adsorption capacity owing to the formation of a composite with MAL were synthesized by a sol-gel process followed by freeze-drying and using multivalent cations Al3+ as cross-linking agents. In addition, the effects of the MAL to NaCMC mass ratio, time, concentration, and pH on the adsorption of MB were explored. Benefiting from a sufficient number of active sites, MCGM exhibited an ultrahigh adsorption capacity for MB removal, and the maximum adsorption capacity was 118.30 mg/g. These results demonstrated the potential of MCGM for wastewater treatment applications.

Exosomes in ascites from patients with human pancreatic cancer enhance remote metastasis partially through endothelial-mesenchymal transition.

BACKGROUND: Despite advances in multidisciplinary treatment, the prognosis of pancreatic cancer remains poor. Since distant metastasis defines prognosis, elucidation of the mechanism of metastasis is important for improving survival. Exosomes are extracellular secretory vesicles and are responsible for intercellular communication. In this study, we investigated whether exosomes secreted by human pancreatic cancer cells are involved in promoting distant metastasis of cancer and the mechanism that underlies the promotion of metastasis. METHODS: Exosomes were isolated from ascites of a patient with pancreatic cancer and a patient with liver cirrhosis as a control. Three days after the administration of exosomes to nude mice, GFP-labeled human pancreatic cancer cells were injected via the spleen or tail vein, and then the liver and lungs were histologically analyzed. To elucidate the mechanism, vascular permeability was estimated using FITC-dextran in place of pancreatic cancer cells in vivo and human umbilical vascular endothelial cells (HUVECs) were used to analyze vascular permeability and the induction of endothelial-mesenchymal transition (EndMT) in vitro. RESULTS: Distant metastasis and vascular permeability were significantly enhanced in mice treated with exosomes from pancreatic cancer patients in comparison to exosomes from a control patient in vivo. In addition, exosomes from pancreatic cancer patients significantly enhanced vascular permeability and the induction of EndMT in HUVECs in vitro. CONCLUSION: Exosomes derived from pancreatic cancer cells form a pre-metastatic niche and promote the extravasation and colonization of pancreatic cancer cells to remote organs, partially through endothelial-mesenchymal transition.

Electroconvulsive Seizure Normalizes Motor Deficits and Induces Autophagy Signaling in the MPTP-Induced Parkinson Disease Mouse Model.

OBJECTIVE: Electroconvulsive seizure (ECS) is a potent treatment modality for various neuropsychiatric diseases, including Parkinson disease (PD). Recent animal studies showed that repeated ECS activates autophagy signaling, the impairment of which is known to be involved in PD. However, the effectiveness of ECS on PD and its therapeutic mechanisms have not yet been investigated in detail. METHODS: Systemic injection of a neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), which destroys dopaminergic neurons in the substantia nigra compacta (SNc), in mice was utilized to induce an animal model of PD. Mice were treated with ECS 3 times per week for 2 weeks. Behavioral changes were measured with a rotarod test. Molecular changes related to autophagy signaling in midbrain including SNc, striatum, and prefrontal cortex were analyzed with immunohistochemistry and immunoblot analyses. RESULTS: Repeated ECS treatments normalized the motor deficits and the loss of dopamiergic neurons in SNc of the MPTP PD mouse model. In the mouse model, LC3-II, an autophagy marker, was increased in midbrain while decreased in prefrontal cortex, both of which were reversed by repeated ECS treatments. In the prefrontal cortex, ECS-induced LC3-II increase was accompanied with AMP-activated protein kinase (AMPK)-Unc-51-like kinase 1-Beclin1 pathway activation and inhibition of mamalian target of rapamycin signaling which promotes autophagy initiation. CONCLUSION: The findings revealed the therapeutic effects of repeated ECS treatments on PD, which could be attributed to the neuroprotective effect of ECS mediated by AMPK-autophagy signaling.

Physico-biological and in vivo evaluation of irisin loaded 45S5 porous bioglass granules for bone regeneration.

In this study, we investigated the physico-biological and in-vivo evaluation of irisin loaded 45S5 bioglass bone graft for enhancing osteoblastic differentiation and bone regeneration in rat femur head defect model. Highly porous structure was obtained in the bioglass by burn-out process with varying the concentration of poly (methyl methacrylate) (PMMA) spheres. 10 % polyvinyl alcohol (PVA) was used as a binder for the sustain releasing of irisin on porous bioglass. Different concentrations of irisin were loaded on the selected bioglass samples and these were further evaluated for the biocompatibility and osteoblastic differentiation properties. The in vitro results demonstrated not only its biocompatibility but also that it stimulated pre-osteoblast differentiation. The in vivo data showed new bone formation as well as expression of osteogenic proteins like alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx-2), osteopontin (OPN), and collagen-1 (Col-1). Our results support the use of irisin loaded bioglass for the use of early bone regeneration.

Bifidobacterium bifidum DS0908 and Bifidobacterium longum DS0950 Culture-Supernatants Ameliorate Obesity-Related Characteristics in Mice with High-Fat Diet-Induced Obesity.

Probiotic supplements have promising therapeutic effects on chronic diseases. In this study, we demonstrated the anti-obesity effects of two potential probiotics, Bifidobacterium bifidum DS0908 (DS0908) and Bifidobacterium longum DS0950 (DS0950). Treatment with DS0908 and DS0950 postbiotics significantly induced the expression of the brown adipocyte-specific markers UCP1, PPARγ, PGC1α, PRDM16 and beige adipocyte-specific markers CD137, FGF21, P2RX5, and COX2 in C3H10T1/2 mesenchymal stem cells (MSCs). In mice with high-fat diet (HFD)-induced obesity, both potential probiotics and postbiotics noticeably reduced body weight and epididymal fat accumulation without affecting food intake. DS0908 and DS0950 also improved insulin sensitivity and glucose use in mice with HFD-induced obesity. In addition, DS0908 and DS0950 improved the plasma lipid profile, proved by reduced triglyceride, low-density lipoprotein, and cholesterol levels. Furthermore, DS0908 and DS0950 improved mitochondrial respiratory function, confirmed by the high expression of oxidative phosphorylation proteins, during thermogenesis induction in the visceral and epididymal fat in mice with HFD-induced obesity. Notably, the physiological and metabolic changes were more significant after treatment with potential probiotic culture-supernatants than those with the bacterial pellet. Finally, gene knockdown and co-treatment with inhibitor-mediated mechanistic analyses showed that both DS0908 and DS0950 exerted anti-obesity-related effects via the PKA/p38 MAPK signaling activation in C3H10T1/2 MSCs. Our observations suggest that DS0908 and DS0950 could potentially alleviate obesity as dietary supplements.

Eco-friendly and facile preparation of chitosan-based biofilms of novel acetoacetylated lignin for antioxidant and UV-shielding properties.

The development of eco-friendly, sustainable, biodegradable, and biocompatible green biopolymer composites is becoming increasingly important. In this study, acetoacetylated lignin (ATL) was obtained via an eco-friendly, facile one-step synthesis reaction, and chitosan (CS)-containing ATL films (CSL) were prepared. The chemical structural analysis of ATL confirmed that the acetoacetyl groups were successfully grafted onto kraft lignin (KL). ATL with adequate acetoacetyl groups exhibited enhanced molecular weight and antioxidant and ultraviolet (UV)-shielding properties. In particular, ATL, with a half maximal inhibitory concentration (IC50) of 23.8 µg·mL-1, exhibited superior antioxidant activity than butylated hydroxytoluene (38.3 µg·mL-1) and KL (50.0 µg·mL-1). When ATL was incorporated into the CS solution to prepare biofilms, the antioxidant activity, UV-shielding property, water resistance, and thermal stability of the CSL greatly improved. Notably, the UV-A and UV-B shielding properties of the 2 % CSL were 130 % and 78 % higher than those of the pure CS film, respectively. Therefore, ATL designed with lignin-derived multifunctional properties has potential applications as an antioxidant and UV-shielding bio-additive and shows significant prospects in food packaging and biomedical applications.

Utilizing Three-Dimensional Head-Lesser Trochanter Distance Could Further Reduce Leg Length Inequality in Primary Bipolar Hemiarthroplasty.

Background: The aim of this study was to investigate whether the use of three-dimensional (3-D) computed tomography (CT)-based head-lesser trochanter distance (HLD) could reduce leg length discrepancy (LLD) more than the use of a two-dimensional (2-D) plain film method in primary bipolar hemiarthroplasty. Methods: Propensity score matching (PSM) analysis was used to adjust the confounding factors. A retrospective comparative analysis of 128 patients was performed. In the control group, the leg length was equalized using the 2-D, plain film-based HLD. In the study group, primary bipolar hemiarthroplasty was performed using the 3-D CT-based HLD method. Postoperative LLDs were compared between the two groups using the method of Ranawat. In addition, the Harris hip score (HHS) was evaluated and compared at one year after surgery. Results: A significant difference was observed in mean postoperative LLD between the 2-D HLD group and the 3-D CT HLD group: 1.6 ± 1.2 mm (range, 0.1−6.0 mm) and 1.1 ± 1.2 mm (range, 0.1−5.1 mm), respectively (p < 0.05). Additionally, a higher percentage of patients in the 3-D CT HLD group had an LLD of less than 2 mm. The mean HHS at one year after surgery showed no significant difference between the two groups. Conclusions: To minimize the occurrence of LLD, HLD measurement from a CT scanner may be more accurate than an X-ray. The 2-D and 3-D HLD differences in the 3-D CT HLD group were statistically significant. Using a 3-D, CT-based HLD method might decrease the possibility of an LLD over 2 mm.

Clozapine Blood Concentration Predicts Corrected QT-Interval Prolongation in Patients With Psychoses.

BACKGROUND: Corrected QT-interval (QTc) prolongation (QTP) is a rare but fatal adverse effect of antipsychotics. Clozapine is the only antipsychotic recommended for treatment of resistant schizophrenia; however, clozapine has been reported to cause QTP. We sought factors predictive of QTP in patients who had antipsychotic polypharmacy involving clozapine. We explored whether the clozapine blood concentration might predict QTP. METHODS: We included 133 patients with schizophrenia spectrum disorder who had antipsychotic polypharmacy involving clozapine. We used the χ2 and nonparametric tests to compare clozapine therapeutic drug monitoring (TDM) values and QTc-prolonged person (QTPP) status. Multivariate regression and mediator models were used to identify risk factors for QTPP status and QTP. RESULTS: In total, 111 patients were prescribed clozapine. The QTPP rates were 31.3% (20) for men and 23.2% (16) for women. Compared with the non-QTPP group, the QTPP group exhibited significantly higher daily dose of all antipsychotics including clozapine, a higher clozapine dose, and elevated clozapine and norclozapine TDM values. Furthermore, such patients were prescribed a greater number of antipsychotics. Multivariate logistic regression revealed that only the clozapine TDM value could be predictive factor for QTPP status (P = 0.018). A clozapine TDM value above the therapeutic range (>600 mg/dL) was associated with a high risk of QTPP status (adjusted odds ratio, 6.5; 95% confidence interval, 1.7-25.2; P = 0.006). The mediator model revealed that the clozapine TDM values completely mediated the association between the clozapine dose and the QTc interval. CONCLUSIONS: The clozapine blood concentration reliably predicts QTP in patients with clozapine use.

Molybdenum Carbide Anchored on N,S Co-Doped Carbon Composite Derived from Lignosulfonate as a High Performance Electrocatalyst for Hydrogen Evolution Reaction.

A composite of Mo2C nanoparticles dispersed onto a nitrogen and sulfur co-doped carbon scaffold (Mo2C/N,S-C) was prepared by a simple and environmentally friendly method of one-pot annealing of MoCl5, urea, and lignosulfonate under a N2 atmosphere at 700 °C. Lignosulfonate, a by-product of the sulfite pulping process, was employed as a feedstock to fabricate the S-doped carbon scaffold and carbide simultaneously, and urea acted as a nitrogen source for N-doping to carbon. The as-prepared Mo2C/N,S-C catalyst showed high performance for the hydrogen evolution reaction (HER), with a small overpotential of 105 mV at 10 mAcm-2, and good stability for 3000 cycles. The improved HER performance of the Mo2C/N,S-C originated from the interplay between the highly active Mo2C nanoparticles and the N,S co-doped carbon scaffold with its high electrical conductivity and large surface area. Furthermore, N,S co-doping to carbon improved the hydrophilicity of the catalyst surface, thus further enhancing the HER activity.

SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence.

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA-target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC-MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.