Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials.

BACKGROUND: Results of previous studies on the safety and efficacy of adjunctive reboxetine for schizophrenia have been inconsistent. AIM: The aim of this study was to examine the efficacy and tolerability of reboxetine as an adjunct medication to antipsychotic treatment in a meta-analysis of randomized controlled trials (RCTs). METHODS: Two independent investigators extracted data for a random effects meta-analysis and assessed the quality of studies using risk of bias and the Jadad scale. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio (RR)±95% confidence intervals (CIs) were calculated. RESULTS: Nine RCTs (n=630) with double-blind design were identified. Reboxetine outperformed placebo in improving negative (9 RCTs, n=602, SMD: -0.47 [95% CI: -0.87, -0.07], p=0.02; I2=82%), but not the overall, positive, and general psychopathology scores. The significant therapeutic effect on negative symptoms disappeared in the sensitivity analysis after removing an outlying study and in 50% (6/12) of the subgroup analyses. Reboxetine outperformed placebo in reducing weight (3 RCTs, n=186, WMD: -3.83 kg, p=0.04; I2=92%) and body mass index (WMD: -2.23 kg/m2, p=0.04; I2=95%). Reboxetine caused dry mouth but was associated with less weight gain overall and weight gain of ≥7% of the initial weight. All-cause discontinuation and other adverse events were similar between reboxetine and placebo. CONCLUSION: Adjunctive reboxetine could be useful for attenuating antipsychotic-induced weight gain, but it was not effective in treating psychopathology including negative symptoms in schizophrenia.

Hypothalamic-pituitary-adrenal axis functioning and dysfunctional attitude in depressed patients with and without childhood neglect.

BACKGROUND: To date, the relationships between childhood neglect, hypothalamic-pituitary-adrenal (HPA) axis functioning and dysfunctional attitude in depressed patients are still obscure. METHODS: The Childhood Trauma Questionnaire (CTQ) was used to assess childhood emotional neglect and physical neglect. Twenty-eight depressed patients with childhood neglect and 30 depressed patients without childhood neglect from Guangzhou Psychiatric Hospital were compared with 29 age- and gender-matched control subjects without childhood neglect and 22 control subjects with childhood neglect. Cortisol awakening response, the difference between the cortisol concentrations at awakening and 30 minutes later, provided a measure of HPA axis functioning. The Dysfunctional Attitude Scale measured cognitive schema. RESULTS: HPA axis functioning was significantly increased in depressed patients with childhood neglect compared with depressed patients without childhood neglect (p < 0.001). HPA axis activity in the control group with childhood neglect was significantly higher than in the depressed group without childhood neglect (p < 0.001). Total scores of childhood neglect were positively correlated with HPA axis functioning and dysfunctional attitude scores, but not with severity of depression. We did not find correlations with HPA axis functioning and dysfunctional attitude or with the Hamilton Rating Scale for Depression scores. CONCLUSIONS: Childhood neglect may cause hyperactivity of the HPA axis functioning and dysfunctional attitude, but does not affect depression severity.

Development of pH-responsive intelligent films based on κ-carrageenan/straw lignin and anthocyanin from Padus virginiana peel for real-time monitoring of chicken.

A series of intelligent films with pH-responsive properties were prepared using Padus virginiana peel extract (PVE) as a smart response factor, κ-carrageenan (κC) as a matrix, and complexed with rice straw lignin (SL). Following the addition of 5 mL PVE at a concentration of 430.99 mg/L, tensile strength and elongation at break of the films increased to a maximum value of 21.25 ± 0.75 MPa and 24.04 ± 0.69 %, respectively. The water vapour permeability of the films decreased with increasing PVE addition, and the minimum value was 5.85 ± 0.09 × 10-11 g m-1 s-1 Pa-1. All the films had favourable thermal stability, transparency, haze and antioxidant properties. PVE-containing films all exhibited excellent pH and ammonia response properties. The higher the humidity of the environment, the faster the ammonia response, and the films were capable of rapid discoloration at 75 % relative humidity. κC/SL-PVE5 can be used to monitor the freshness of chicken breast meat. When the total volatile basic nitrogen of chicken breast meat was increased to 14.27 mg/100 g, κC/SL-PVE5 changed from pink to greyish-yellow. In conclusion, κC/SL-PVE intelligent films hold great promise for real-time monitoring of meat freshness.

A chitosan derivative/phytic acid polyelectrolyte complex endowing polyvinyl alcohol film with high barrier, flame-retardant, and antibacterial effects.

Films with high barrier, flame-retardant, and antibacterial properties are beneficial in terms of food and logistics safety. Herein, a polyelectrolyte complex (PEC) of N-(2-hydroxyl)-propyl-3-trimethylammonium chitosan chloride (HTCC, chitosan derivative) and phytic acid (PA) was successfully prepared and then incorporated into a polyvinyl alcohol (PVA) matrix to fabricate a composite film with satisfactory barrier, fire-retardant, and antibacterial properties. The influence of HTCC/PA (HTPA) on the structural, physical and functional properties of the PVA matrix was investigated. Compared with the PVA film, PVA-HTPA6 film exhibited 3.38 times of flexibility and 83.33 % and 80.64 % of water vapor permeability and oxygen permeability, respectively. Benefiting from HTPA, the PVA-HTPA6 film exhibited outstanding flame-retardant capacity, with a high LOI value (33.30 %) and immediate self-extinguishing behaviour. Furthermore, the HTPA endowed the films with excellent antibacterial properties. Compared with other films, the PVA-HTPA6 film effectively maintained the quality of pork during storage at 4 °C for 9 days. Our findings indicate that the films are promising for packaging and logistics safety with oil-containing foods.

An antibacterial and intelligent cellulose-based label self-assembled via electrovalent bonds for a multi-range sensing of food freshness.

Intelligent labels provide customers with food freshness information. However, the existing label response is limited and can only detect a single kind of food. Here, an intelligent cellulose-based label with highly antibacterial activity for a multi-range sensing freshness was developed to overcome the limitation. Cellulose fibers were modified using oxalic acid to graft -COO- followed by binding chitosan quaternary ammonium salt (CQAS), the remaining charges of which attached methylene red and bromothymol blue to form response fibers and to further self-assemble into the intelligent label. CQAS electrostatically gathered the dispersed fibers, resulting in an increase in TS and EB of 282 % and 16.2 %, respectively. After that, the rest positive charges fixed the anionic dyes to broaden pH response range of 3-9 effectively. More significantly, the intelligent label exhibited highly antimicrobial activity, killing 100 % of staphylococcus aureus. The rapid acid-base response revealed the potential for practical application in which the label color from green to orange represented the milk or spinach from fresh to close to spoiled, and from green to yellow, and to light green indicated the pork fresh, acceptable, and close to spoiled. This study paves a way for the preparation of intelligent labels in large-scale and promote the commercial application to improve food safety.

Effect of Repeated Intravenous Esketamine on Adolescents With Major Depressive Disorder and Suicidal Ideation: A Randomized Active-Placebo-Controlled Trial.

OBJECTIVE: Suicide is a major cause of death in adolescents with limited treatment options. Ketamine and its enantiomers have shown rapid anti-suicidal effects in adults with major depressive disorder (MDD), but their efficacy in adolescents is unknown. We conducted an active, placebo-controlled trial to determine the safety and efficacy of intravenous esketamine in this population. METHOD: A total of 54 adolescents (aged 13-18 years) with MDD and suicidal ideation were included from an inpatient setting and randomly assigned (1:1) to receive 3 infusions of esketamine (0.25 mg/kg) or midazolam (0.02mg/kg) over 5 days, with routine inpatient care and treatment. Changes from baseline to 24 hours after the final infusion (day 6) in the scores of the Columbia Suicide Severity Rating Scale (C-SSRS) Ideation and Intensity (primary outcome) and the Montgomery-Åsberg Depression Rating Scale (MADRS, key secondary outcome) were analyzed using linear mixed models. In addition, the 4-week clinical treatment response was a key secondary outcome. RESULTS: The mean changes in C-SSRS Ideation and Intensity scores from baseline to day 6 were significantly greater in the esketamine group than in the midazolam group (Ideation, -2.6 [SD = 2.0] vs -1.7 [SD = 2.2], p = .007; Intensity, -10.6 [SD = 8.4] vs -5.0 [SD = 7.4], p = .002), and the changes in MADRS scores from baseline to day 6 were significantly greater in the esketamine group than in the midazolam group (-15.3 [SD = 11.2] vs -8.8 [SD = 9.4], p = .004). The rates of anti-suicidal and antidepressant responses at 4 weeks posttreatment were 69.2% and 61.5% after esketamine, and were 52.5% and 52.5% after midazolam, respectively. The most common adverse events in the esketamine group were nausea, dissociation, dry mouth, sedation, headache, and dizziness. CONCLUSION: These preliminary findings indicate that 3-dose intravenous esketamine, added to routine inpatient care and treatment, was an effective and well-tolerated therapy for treating adolescents with MDD and suicidal ideation. CLINICAL TRIAL REGISTRATION INFORMATION: The efficacy and safety of esketamine combined with oral antidepressants in the treatment of major depressive disorder with suicidal ideation. http://www.chictr.org.cn. Chinese Clinical Trial Registry: ChiCTR2000041232. DIVERSITY & INCLUSION STATEMENT: We worked to ensure that the study questionnaires were prepared in an inclusive way. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. We actively worked to promote sex and gender balance in our author group.

Pluronic P85-coated poly(butylcyanoacrylate) nanoparticles overcome phenytoin resistance in P-glycoprotein overexpressing rats with lithium-pilocarpine-induced chronic temporal lobe epilepsy.

P-glycoprotein (Pgp) overexpression in the blood brain barrier (BBB) is hypothesized to lower brain drug concentrations and thus inhibit anticonvulsant effects in drug-resistant epilepsy. Recently, the poly(butylcyanoacrylate) (PBCA) nanoparticle system was shown to overcome the obstacle of the BBB to deliver drugs into the brain. To determine whether pluronic P85-coated phenytoin poly(butylcyanoacrylate) nanoparticles (P85-PHT-PBCA-NPs) target PHT to the brain, PHT-resistant rats overexpressing Pgp in the BBB were screened by response to PHT treatment after chronic temporal lobe epilepsy induced by lithium-pilocarpine, followed by direct verification of PHT transport via measurement of brain PHT concentrations using microdialysis. Thereafter, the PHT-resistant rats were divided into three groups, which were treated with PHT, PHT + tariquidar (TQD), or P85-PHT-PBCA-NPs. PHT + TQD and P85-PHT-PBCA-NPs showed anticonvulsant activity in the PHT-resistant rats and increased the ratio of the area under the curve of the PHT concentrations in the brain/plasma in comparison with that observed in animals subjected to PHT treatment. However, the ratios of the PHT concentrations in the liver/plasma and kidney/plasma following P85-PHT-PBCA-NPs treatment were much lower than those measured following PHT + TQD treatment. Thus, Pgp overexpression decreases therapeutic drug concentrations in the brains of subjects with drug-resistant epilepsy and P85-PHT-PBCA-NPs could increase these drug concentrations.