Treatment-resistant schizophrenia (TRS) is common and debilitating. A subgroup of patients even has clozapine-resistant schizophrenia (CRS). We aimed to evaluate the efficacy and safety of ...electroconvulsive therapy (ECT) augmentation of clozapine for CRS. Systematic literature search of randomized controlled trials (RCTs) reporting on ECT augmentation of clozapine in CRS. Co-primary outcomes included symptomatic improvement at post-ECT assessment and study endpoint. Eighteen RCTs (n = 1769) with 20 active treatment arms were identified and meta-analyzed. Adjunctive ECT was superior to clozapine regarding symptomatic improvement at post-ECT assessment (Standardized Mean Difference (SMD) = -0.88, 95% Confidence Interval (CI): −1.33 to −0.44; I2 = 86%, P = 0.0001) and endpoint assessment (SMD: −1.44, 95%CI: −2.05 to −0.84; I2 = 95%, P < 0.00001), separating as early as week 1–2 (SMD = −0.54, 95%CI: −0.88 to −0.20; I2 = 77%, P = 0.002). Adjunctive ECT was also superior regarding study-defined response at post-ECT assessment (53.6% vs. 25.4%, Risk Ratio (RR) = 1.94, 95%CI: 1.59–2.36; I2 = 0%, P < 0.00001, number-needed-to-treat (NNT) = 3, 95%CI: 3–5) and endpoint assessment (67.7% vs. 41.4%, RR = 1.66, 95%CI: 1.38–1.99; I2 = 47%, P < 0.00001, NNT = 4, 95%CI: 3–8), and remission at post-ECT assessment (13.3% vs. 3.7%, RR = 3.28, 95%CI: 1.80–5.99; I2 = 0%, P = 0.0001, NNT = 13, 95%CI: 6–100) and endpoint assessment (23.6% vs. 13.3%, RR = 1.80, 95%CI: 1.39 to 2.35; I2 = 5%, P < 0.0001, NNT = 14, 95%CI: 6–50). Patient-reported memory impairment (24.2% vs. 0%; RR = 16.10 (95%CI: 4.53–57.26); I2 = 0%, P < 0.0001, number-needed-to-harm (NNH) = 4, 95%CI: 2–14) and headache (14.5% vs 1.6%; RR = 4.03 (95%CI: 1.54–10.56); I2 = 0%, P = 0.005, NNH = 8, 95%CI: 4–50) occurred more frequently with adjunctive ECT. No significant group differences were found regarding discontinuation and other adverse effects. Despite increased frequency of self-reported memory impairment and headache, ECT augmentation of clozapine is a highly effective and relatively safe treatment for CRS.
CRD42018089959
•Treatment-resistant schizophrenia is common and debilitating, and clozapine-resistant schizophrenia (CRS) poses a particluar clinical dilemma.•ECT augmentation of clozapine is a highly effective and safe treatment for CRS.•ECT Augmentation of clozapine increased frequency of self-reported memory impairment and headache.
NiSe@NiOOH core–shell hyacinth-like nanostructures supported on nickel foam (NF) have been successfully synthesized by a facile solvothermal selenization and subsequent in situ electrochemical ...oxidation (ISEO). First, the unique NiSe/NF nanopillar arrays were prepared in N,N-dimethylformamide (DMF) as a precursor template that can provide a large surface area, excellent conductivity, and robust support. Next, amorphous NiOOH covering the surface of NiSe nanopillars was fabricated by ISEO, as confirmed by XPS andEDX spectroscopy. SEM images revealed the hyacinth-like morphology of NiSe@NiOOH/NF with NiOOH as the shell and NiSe as the core. The electrochemical performance of NiSe@NiOOH/NF for the oxygen evolution reaction (OER) was investigated. NiSe@NiOOH/NF demonstrates an obviously enhanced OER activity with much lower overpotential of 332 mV at 50 mA cm–2 compared to other Ni-based electrocatalysts. The low charge-transfer resistance (R ct), large electrochemical double-layer capacitance (C dl) of electrochemically active surface areas (ECSAs), and excellent long-term stability of NiSe@NiOOH/NF confirm the enhancement of its electrochemical performance for the OER, which can be ascribed to the large amount of active sites derived from the amorphous NiOOH shell and the good conductivity and stability derived from the NiSe core. In addition, the synergistic effect between the NiSe core and NiOOH shell could serve for a highly efficient OER electrocatalyst.
Abstract
A single biomarker is not adequate to identify patients with gastric cancer (GC) who have the potential to benefit from anti-PD-1/PD-L1 therapy, presumably owing to the complexity of the ...tumour microenvironment. The predictive value of tumour-infiltrating immune cells (TIICs) has not been definitively established with regard to their density and spatial organisation. Here, multiplex immunohistochemistry is used to quantify in situ biomarkers at sub-cellular resolution in 80 patients with GC. To predict the response to immunotherapy, we establish a multi-dimensional TIIC signature by considering the density of CD4
+
FoxP3
−
PD-L1
+
, CD8
+
PD-1
−
LAG3
−
, and CD68
+
STING
+
cells and the spatial organisation of CD8
+
PD-1
+
LAG3
−
T cells. The TIIC signature enables prediction of the response of patients with GC to anti-PD-1/PD-L1 immunotherapy and patient survival. Our findings demonstrate that a multi-dimensional TIIC signature may be relevant for the selection of patients who could benefit the most from anti-PD-1/PD-L1 immunotherapy.
•An improved AD configuration with THP post-treatment was developed.•High concentration of SCOD could be dissolved during THP post-treatment.•AD-THP performed much better than the THP pretreatment ...system.•The dewatering of post-THP sludge was excellent without addition of polymer.•The pH changed in opposite directions during pre- and post-THP treatment.
Thermal hydrolysis process (THP) is widely used as the pretreatment for sludge anaerobic digestion (AD), but with limited improvement of biogas production, dewaterability, and high energy consumption. In this study, an improved AD configuration based on post-THP treatment (AD-THP) was developed to overcome these limitations. The digested sludge was thermally hydrolyzed and then dewatered directly, the centrate was recirculated for re-digestion with raw sludge. Batch and semi-continuous experiments were conducted to investigate the differences between pre- and post-THP treatment and compare the process performances of three configurations, including conventional anaerobic digestion (CAD), thermal hydrolysis pretreatment (THP-AD), and post-treatment (AD-THP). Results showed that post-THP could further dissolve much SCOD from the digested sludge by disintegrating the recalcitrant organic matter of raw sludge and EPS generated during digestion, resulting in further improvement of methane production. The SCOD solubilization during THP post-treatment was depended on the degradation extent of digested sludge. The main difference between pre- and post-treatment was that the pH changed towards the opposite directions due to the different properties of raw and digested sludge. The maximum specific methane production and volatile solid reduction of the AD-THP system were 344.25 mL CH4/g VSadd and 62% during the CSTR experiments, respectively, significantly higher than those of THP-AD and CAD configurations. In addition, the dewaterability of THP treated sludge was always significantly better than the digested sludge, whether for THP pretreatment or post-treatment. The improved AD-THP configuration could be a promising alternative for the upgrading of sludge treatment.
Findings on the efficacy of intranasal oxytocin (IN-OT) in schizophrenia have been inconsistent. This meta-analysis of double-blind randomized controlled trials (RCTs) examined the efficacy and ...tolerability of adjunctive IN-OT in the treatment of schizophrenia.
Standardized mean differences or risk ratios (SMDs or RRs) with their 95% confidence intervals (CIs) were used to synthesize the results of studies included in the meta-analysis.
Ten RCTs (n = 344) with 172 schizophrenia subjects on adjunctive IN-OT range = 40–80 International Units (IU)/day and 172 schizophrenia subjects on adjunctive placebo over 2–16 weeks were included. No significant differences regarding total psychopathology measured with the total Positive and Negative Syndrome Scale (PANSS) or the Brief Psychiatric Rating Scale (BPRS) 8 RCTs, n = 203; SMD: −0.08 (95%CI: −0.53, 0.37), P = 0.74, I2 = 59% and the positive, negative and general symptom scores SMD: −0.20 to −0.04 (95%CI: −0.75, 0.36), P = 0.28 to 0.78; I2 = 0% to 72% were found between the IN-OT and placebo groups. Similarly, subgroup analyses for total psychopathology found no group differences. Dose-response effect analyses showed that only 80 IU/day IN-OT had superiority over placebo in improving total psychopathology (P = 0.02) and positive symptom score (P = 0.01). No group differences between adjunctive IN-OT and placebo regarding discontinuation due to any reason RR: 1.12 (95%CI: 0.67, 1.88), P = 0.67, I2 = 0% and adverse drug reactions were found.
Although the meta-analysis did not show a positive effect in general, the higher dose of adjunctive IN-OT (80 IU/day) appears to be efficacious and safe in improving total psychopathology and positive symptoms in schizophrenia.
CRD42017080856
Plant plastomes play crucial roles in species evolution and phylogenetic reconstruction studies due to being maternally inherited and due to the moderate evolutionary rate of genomes. However, ...patterns of sequence divergence and molecular evolution of the plastid genomes in the horticulturally- and economically-important
L. species are poorly understood. In this study, we collected the complete plastomes of seven
species and determined the various repeat sequence variations and protein sequence evolution by comparative genomic analysis. A total of 498 repeats were identified in plastid genomes, which included tandem (130), dispersed (277), and palindromic (91) types of repeat variations. Simple sequence repeat (SSR) elements analysis indicated the enriched SSRs in seven genomes to be mononucleotides, followed by tetra-nucleotides, dinucleotides, tri-nucleotides, hex-nucleotides, and penta-nucleotides. We identified 18 divergence hotspot regions (
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
intron, and
) that could be used as the potential molecular genetic markers for the further study of population genetics and phylogenetic evolution of
species. We found that a large number of repeat sequences were distributed in the divergence hotspots of plastid genomes. Interestingly, 16 genes were determined under positive selection, which included four genes for the subunits of ribosome proteins (
,
and
), three genes for the subunits of photosystem proteins (
,
and
), three NADH oxidoreductase genes (
,
, and
), two subunits of ATP genes (
and
), and four other genes (
,
,
, and
). Phylogenetic analysis based on the whole plastome demonstrated that the seven
species form a highly-supported monophyletic clade. The availability of these plastid genomes provides important genetic information for further species identification and biological research on
.
The development of adsorbents with outstanding adsorption capacities, wide versatility, and excellent recyclability for the removal of organic dyes remains a challenge. In this study, a quaternised ...chitosan-based aerogel (QCSA) was fabricated via a facile method to effectively treat concomitant anionic dyes. Porous QCSA with high hydrophilicity, nontoxicity, excellent thermal stability, and sustainability exhibits adsorption properties superior to most previously reported adsorbents. The equilibrium adsorption capacities for Congo red, Sunset yellow, and Methyl orange were 1259.6, 550.2, and 607.5 mg/g, respectively. Notably, the spent QCSA exhibits excellent cyclic performance. The multilayer adsorption, external–internal mass transfer resistance, and adsorption on the active site models were employed to enable a more accurate description of the dynamic characteristics, confirming that double-layer chemisorption was the dominant process. A quantitative analysis of the electrostatic potential and the independent gradient model further verified that electrostatic interactions, hydrogen bonding, and van der Waals forces led to the highly efficient adsorption of dye molecules. Therefore, the eco-friendly and recyclable QCSA is a promising adsorbent for trapping anionic dyes from aquatic systems.
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Abstract
The versatile manipulation of cross-scale droplets is essential in many fields. Magnetic excitation is widely used for droplet manipulation due to its distinguishing merits. However, facile ...magnetic actuation strategies are still lacked to realize versatile multiscale droplet manipulation. Here, a type of magnetically actuated Janus origami robot is readily fabricated for versatile cross-scale droplet manipulation including three-dimensional transport, merging, splitting, dispensing and release of daughter droplets, stirring and remote heating. The robot allows untethered droplet manipulation from ~3.2 nL to ~51.14 μL. It enables splitting of droplet, precise dispensing (minimum of ~3.2 nL) and release (minimum of ~30.2 nL) of daughter droplets. The combination of magnetically controlled rotation and photothermal properties further endows the robot with the ability to stir and heat droplets remotely. Finally, the application of the robot in polymerase chain reaction (PCR) is explored. The extraction and purification of nucleic acids can be successfully achieved.
•Adjunctive ketamine in electroconvulsive therapy (ECT) has been increasingly studied for treating major depressive disorder (MDD), but the findings have been mixed.•ketamine alone does not appear to ...improve the efficacy of ECT.•ketamine+other anesthetics combination may confer a short-term advantage in improving depressive symptom at the early stages of ECT.
Adjunctive ketamine with electroconvulsive therapy (ECT) has been investigated for treating major depressive disorder (MDD), but the findings have been inconsistent.
This is an updated meta-analysis of the efficacy and safety of ketamine augmentation of ECT in the treatment of MDD.
Randomized controlled trials (RCTs) reporting on the efficacy and safety of ketamine and ECT were identified and analyzed.
Seventeen RCTs (n = 1,035) compared ketamine alone or ketamine plus other anesthetic drugs (n = 557) with other anesthetic agents (n = 478) in MDD patients who received ECT. Ketamine+other anesthetic drugs was superior in improving depressive symptoms over other anesthetic medications at early study time point, but not at post-ECT or end of study time points. Ketamine alone was not more efficacious in treating depressive symptoms than other anesthetic drugs at early study, post-ECT and end of study time points. Sensitivity analysis and 19 of the 20 subgroup analyses also confirmed the lack of significance of these findings. Eleven RCTs testing the effects of ketamine on neurocognitive functions with various test batteries found mixed results. Ketamine alone significantly increased blood pressure more than other anesthetic drugs in MDD treated with ECT.
Compared to other anesthetic agents, ketamine alone does not appear to improve the efficacy of ECT. However, ketamine+other anesthetic combinations may confer a short-term advantage in improving depressive symptom at the early stages of ECT.
Abstract Neuroinflammation has been implicated in the neurobiological pathways of schizophrenia. This meta-analysis evaluated the efficacy and tolerability of adjunctive celecoxib as a noncompetitive ...anti-inflammation drug in treating schizophrenia. Data were searched, extracted, checked and entered into the RevMan (version 5.3) software by two independent investigators. Standardized/weighted mean differences (SMDs/WMDs), risk ratio (RR) and their 95% confidence intervals (CIs) were calculated, as appropriate. Included were 8 randomized controlled trials (RCTs) with a total of 626 patients with schizophrenia including 316 (50.5%) treated on celecoxib (400 mg/day) and 310 (49.5%) on placebo over 8.3 ± 2.3 weeks of treatment. Adjunctive celecoxib outperformed placebo with respect to total psychopathology 3 RCTs, n = 180; SMD: −0.47; 95%CI: −0.81, −0.14; P = 0.005; I2 = 18%; 'moderate quality', symptoms positive 3 RCTs, n = 180; SMD: −0.50; 95%CI: −0.79, −0.20; P = 0.001; I2 = 0%; 'moderate quality', negative symptoms 3 RCTs, n = 180; SMD: −0.32; 95%CI: −0.66, 0.02; P = 0.06; I2 = 22%; 'moderate quality', and general psychopathology scores 3 RCTs, n = 180; SMD: −0.35; 95%CI: −0.65, −0.06; P = 0.02; I2 = 0%; 'moderate quality' in first-episode, but not chronic patients. Additionally, superiority of celecoxib for the Positive and Negative Syndrome Scale (PANSS) total scores was moderated by higher PANSS positive scores and lower PANSS negative scores at baseline. All-cause discontinuation RR: 1.02; (95%CI: 0.56, 1.86); P = 0.94; I2 = 0% and adverse drug reactions were similar between the two groups. Adjunctive celecoxib appears to be an efficacious and safe treatment in improving psychotic symptoms, particularly in first-episode schizophrenia. Review registration CRD42016054233 ( http://www.crd.york.ac.uk/prospero/ ).
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