[Effects of Biogas Slurry Application on Soil Microbial Communities Structure and Function During Wheat-rice Stubble Period].

To reveal the effects of biogas slurry application on soil microbial community structure and function, a soil column experiment was constructed with three treatments[(no N addition, CM; conventional fertilization, SN; biogas slurry addition, SZ)]. The differences in composition, diversity, and structure of bacterial and fungal communities on day 1 and day 21 after soil flooding were evaluated, and their functions were predicted using Illumina high-throughput sequencing technology. The results of the analysis of α diversity showed that the fungal α-diversity indexes of CM, SN, and SZ treatments on day 1 were significantly higher than those on day 21, and there was no significant difference among the three treatments. However, the bacterial Simpson index differed among the three treatments on day 21, with SZ-21 showing a higher Simpson index but lower Chao1 index compared with those of SZ-21. The analysis of bacterial community structure showed that Firmicutes, Chloroflexi, and Actinobacteria in the SN-1 treatment were different from those in the other treatments on day 1, whereas the relative abundance of bacterial phyla in the SZ and SN treatments were similar on day 21. The analysis of fungal community structure showed that the relative abundance of Ascomycota and Zygomycota in the SZ-1 treatment were higher than those in the SN-1 and CM-1 treatments on day 1. The relative abundance of Ascomycota in the SN-21 and SZ-21 treatments were lower, whereas that of Zygomycota were higher compared with that in CM-21. The analysis of NMDS showed that the composition of bacterial and fungal communities in the SN and SZ treatments showed a gradually similar trend. The PICRUSt analysis showed that the function of the soil bacterial community was similar in the CM, SN, and SZ treatments. The FUNGuild function prediction reflected that the main differences in trophic type between the SN-21 and SZ-21 treatments occurred in saprotroph and pathotroph forms. Therefore, biogas slurry addition in the wheat-rice stubble stage could contribute to balancing soil nutrients and maintaining soil ecological function to a certain extent, but there may still be a risk of fungal disease.

Music therapy for people with substance use disorders.

BACKGROUND: Substance use disorder (SUD) is the continued use of one or more psychoactive substances, including alcohol, despite negative effects on health, functioning, and social relations. Problematic drug use has increased by 10% globally since 2013, and harmful use of alcohol is associated with 5.3% of all deaths. Direct effects of music therapy (MT) on problematic substance use are not known, but it may be helpful in alleviating associated psychological symptoms and decreasing substance craving. OBJECTIVES: To compare the effect of music therapy (MT) in addition to standard care versus standard care alone, or to standard care plus an active control intervention, on psychological symptoms, substance craving, motivation for treatment, and motivation to stay clean/sober. SEARCH METHODS: We searched the following databases (from inception to 1 February 2021): the Cochrane Drugs and Alcohol Specialised Register; CENTRAL; MEDLINE (PubMed); eight other databases, and two trials registries. We handsearched reference lists of all retrieved studies and relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials comparing MT plus standard care to standard care alone, or MT plus standard care to active intervention plus standard care for people with SUD. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included 21 trials involving 1984 people. We found moderate-certainty evidence of a medium effect favouring MT plus standard care over standard care alone for substance craving (standardised mean difference (SMD) -0.66, 95% confidence interval (CI) -1.23 to -0.10; 3 studies, 254 participants), with significant subgroup differences indicating greater reduction in craving for MT intervention lasting one to three months; and small-to-medium effect favouring MT for motivation for treatment/change (SMD 0.41, 95% CI 0.21 to 0.61; 5 studies, 408 participants). We found no clear evidence of a beneficial effect on depression (SMD -0.33, 95% CI -0.72 to 0.07; 3 studies, 100 participants), or motivation to stay sober/clean (SMD 0.22, 95% CI -0.02 to 0.47; 3 studies, 269 participants), though effect sizes ranged from large favourable effect to no effect, and we are uncertain about the result. There was no evidence of beneficial effect on anxiety (mean difference (MD) -0.17, 95% CI -4.39 to 4.05; 1 study, 60 participants), though we are uncertain about the result. There was no meaningful effect for retention in treatment for participants receiving MT plus standard care as compared to standard care alone (risk ratio (RR) 0.99, 95% 0.93 to 1.05; 6 studies, 199 participants). There was a moderate effect on motivation for treatment/change when comparing MT plus standard care to another active intervention plus standard care (SMD 0.46, 95% CI -0.00 to 0.93; 5 studies, 411 participants), and certainty in the result was moderate. We found no clear evidence of an effect of MT on motivation to stay sober/clean when compared to active intervention, though effect sizes ranged from large favourable effect to no effect, and we are uncertain about the result (MD 0.34, 95% CI -0.11 to 0.78; 3 studies, 258 participants). There was no clear evidence of effect on substance craving (SMD -0.04, 95% CI -0.56 to 0.48; 3 studies, 232 participants), depression (MD -1.49, 95% CI -4.98 to 2.00; 1 study, 110 participants), or substance use (RR 1.05, 95% CI 0.85 to 1.29; 1 study, 140 participants) at one-month follow-up when comparing MT plus standard care to active intervention plus standard care. There were no data on adverse effects. Unclear risk of selection bias applied to most studies due to incomplete description of processes of randomisation and allocation concealment. All studies were at unclear risk of detection bias due to lack of blinding of outcome assessors for subjective outcomes (mostly self-report). We judged that bias arising from such lack of blinding would not differ between groups. Similarly, it is not possible to blind participants and providers to MT. We consider knowledge of receiving this type of therapy as part of the therapeutic effect itself, and thus all studies were at low risk of performance bias for subjective outcomes.  We downgraded all outcomes one level for imprecision due to optimal information size not being met, and two levels for outcomes with very low sample size.  AUTHORS' CONCLUSIONS: Results from this review suggest that MT as 'add on' treatment to standard care can lead to moderate reductions in substance craving and can increase motivation for treatment/change for people with SUDs receiving treatment in detoxification and short-term rehabilitation settings. Greater reduction in craving is associated with MT lasting longer than a single session. We have moderate-to-low confidence in our findings as the included studies were downgraded in certainty due to imprecision, and most included studies were conducted by the same researcher in the same detoxification unit, which considerably impacts the transferability of findings.

Association of depressive symptoms with cognitive impairment in patients with never-treated first-episode schizophrenia: Analysis of the Depression in Schizophrenia in China (DISC) study.

OBJECTIVE: Depressive symptoms and cognitive dysfunction are common in patients with schizophrenia and depressive disorder. This study aimed at exploring whether and how depressive symptoms were correlated with neuro-cognitive impairment in patients with never-treated first-episode (NTFE) schizophrenia. METHODS: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was administered to 79 patients and 80 healthy controls to assess neuropsychological function. For all patients, the 17-item Hamilton Depression Rating Scale (HAMD-17) was adopted to evaluate depressive symptoms, and the Positive and Negative Syndrome Scale (PANSS) was utilized to assess psychopathological symptoms. RESULTS: Thirty-nine patients (49.37%) met the criteria for comorbid depressive symptoms. The RBANS total and the four index scores in the patients were significantly lower than those in the healthy controls. Further, compared with patients without depressive symptoms, patients with depressive symptoms scored lower in attention index, but higher in PANSS general psychopathology and total scores. The HAMD-17 total score was significantly correlated with attention, PANSS total, and PANSS general psychopathology scores. Moreover, multiple regression analysis identified education and HAMD-17 score as the contributors to attention. CONCLUSION: Our results suggest that the rate of depressive symptoms in NTFE schizophrenia is high, which is correlated with neuro-cognitive impairment, especially attention and psychopathology.

Population pharmacokinetics, safety and dosing optimization of voriconazole in patients with liver dysfunction: A prospective observational study.

AIMS: Voriconazole is a broad-spectrum antifungal agent for the treatment of invasive fungal infections. There is limited information about the pharmacokinetics and appropriate dosage of voriconazole in patients with liver dysfunction. This study aimed to explore the relationship between voriconazole trough concentration (Ctrough ) and toxicity, identify the factors significantly associated with voriconazole pharmacokinetic parameters and propose an optimised voriconazole dosing regimen for patients with liver dysfunction. METHODS: The study prospectively enrolled 51 patients with 272 voriconazole concentrations. Receiver operating characteristic curves were used to explore the relationship between voriconazole Ctrough and toxicity. The pharmacokinetic data was analysed with nonlinear mixed-effects method. Dosing simulations stratified by total bilirubin (TBIL, TBIL-1: TBIL < 51 µmol/L; TBIL-2: 51 µmol/L ≤ TBIL < 171 µmol/L; TBIL-3: TBIL ≥ 171 µmol/L) were performed. RESULTS: Receiver operating characteristic curve analysis revealed that voriconazole Ctrough of ≤ 5.1 mg/L were associated with significantly lower the incidence of adverse events. A 1-compartment pharmacokinetic model with first-order absorption and elimination was used to describe the data. Population pharmacokinetic parameters of clearance, volume of distribution and oral bioavailability were 0.88 L/h, 148.8 L and 88.4%, respectively. Voriconazole clearance was significantly associated with TBIL and platelet count. The volume of distribution increased with body weight. Patients with TBIL-1 could be treated with a loading dose of 400 mg every 12 hours (q12h) for first day, followed by a maintenance dose of 100 mg q12h administered orally or intravenously. TBIL-2 and TBIL-3 patients could be treated with a loading dose of 200 mg q12h and maintenance doses of 50 mg q12h or 100 mg once daily and 50 mg once daily orally or intravenously, respectively. CONCLUSIONS: Lower doses and longer dosing intervals should be considered for patients with liver dysfunction. TBIL-based dosing regimens provide a practical strategy for achieving voriconazole therapeutic range and therefore maximizing treatment outcomes.

[Effects of nitrogen management on soil microbial community structure at different growth stages under straw returning in paddy soils]. / 秸秆还田下氮肥运筹对水稻各生育期土壤微生物群落结构的影响.

Effects of different nitrogen application methods on microbial community structure of paddy soil at different rice growth stages were examined using phospholipid fatty acid analysis (PLFA) and Biolog technique. There were four treatments, no straw returning or fertilization (CK), straw returning +urea with the proportions of after wheat harvest, before rice transplanting, tillering stage and booting stage being 0:6:2:2 (T1) and 3:3:2:2 (T2), and straw returning+co-application of biogas slurry and urea with the proportion of after wheat harvest, before rice transplanting, tillering stage and booting stage being 3 (biogas slurry):3 (2biogas slurry+1urea):2 (urea):2 (urea)(T3). Results showed that T3 significantly increased soil available nitrogen contents at all growth stages, which was significantly higher at maturity stage than that at tillering and booting stages. T1-T3 had higher available phosphorus and available potassium contents at all growth stages compared with CK, which were higher at tillering stage than at booting and maturity stages. The interaction between growth stage and treatment in paddy soil significantly affected the contents of soil available nitrogen, available phosphorus and available potassium. Furthermore, carbohydrate, amino acid, polymer and carboxylic acid were the primary carbon sources for microbial community of paddy soil. T3 effectively enhanced soil carbon sources metabolic utilization intensity. The interaction between growth stage and treatment in paddy soil significantly affected the microbial utilization capacity of carbohydrates and carboxylic acids. Soil microbial biomass was significantly higher in T2 and T3 treatments. Moreover, T2 had high fungi/bacteria (F/B) value, indicating that fungi could benefit the stabilization of paddy soil. In summary, simultaneous nitrogen application (urea or biogas slurry) and straw returning could increase soil microbial activity and improve soil environment in paddy field.

Memory Retrieval-Extinction Combined With Virtual Reality Reducing Drug Craving for Methamphetamine: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Relapse, often precipitated by drug-associated cues that evoke craving, is a key problem in the treatment of methamphetamine use disorder (MUD). Drug-associated memories play a major role in the maintenance of relapse. Extinction training is a common method for decreasing drug craving by suppressing drug-associated memories. However, the effects are often not permanent, which is evident in form of spontaneous recovery or renewal of cue-elicited responses. Based on memory reconsolidation theory, the retrieval-extinction (R-E) paradigm may be more effective in decreasing spontaneous recovery or renewal responses than extinction. After the original memory reactivated to a labile state, extinction will be introduced within the reconsolidation window, thereby updating drug-associated memories. However, there are still some controversial results, which suggest that the reactivation of drug-associated memories and the 10 min-6 h of limited time window are two main elements in the R-E protocol. Virtual reality (VR) is supposed to promote memory reactivation by providing vivid drug-related stimuli when compared with movies. OBJECTIVE: The aim of this study is to examine the effectiveness of R-E training combined with VR on reducing spontaneous recovery or renewal of cue-elicited responses, in comparison to extinction, R-E training provided outside the time window of 6 h and R-E training retrieved using videos, in methamphetamine abusers. METHODS: The study is a parallel matched controlled study including 95 participants with MUD. Participants will be randomly assigned to either a R-10 min-E group (methamphetamine-related cues retrieval in VR followed by extinction after 10 min) or a NR-10 min-E group (neutral cues retrieval in VR followed by extinction after 10 min) or a R-6 h-E group (methamphetamine-related cues retrieval in VR followed by extinction after 6 h) or a RV-10 min-E group (methamphetamine-related cues retrieval in videos followed by extinction after 10 min). Cue-evoked craving and reactivity will be assessed at pre-test and at 1 day, 1 week, 1 month, and 6-month post-tests. DISCUSSION: To our knowledge, this study will probably be the first study to examine the efficacy of R-E training combined with VR to reduce cue-evoked responses in people with MUD. This innovative non-pharmacological intervention targeting drug-associated memories may provide significant clinical implications for reducing relapse, providing the study confirms its efficacy. CLINICAL TRIAL REGISTRATION: The trial is registered with Chinese Clinical Trial Registry at 17 October 2018, number: ChiCTR1800018899, URL: http://www.chictr.org.cn/showproj.aspx?proj=30854.

An in vitro study on interaction of anisodine and monocrotaline with organic cation transporters of the SLC22 and SLC47 families.

Current study systematically investigated the interaction of two alkaloids, anisodine and monocrotaline, with organic cation transporter OCT1, 2, 3, MATE1 and MATE2-K by using in vitro stably transfected HEK293 cells. Both anisodine and monocrotaline inhibited the OCTs and MATE transporters. The lowest IC50 was 12.9 µmol·L-1 of anisodine on OCT1 and the highest was 1.8 mmol·L-1 of monocrotaline on OCT2. Anisodine was a substrate of OCT2 (Km = 13.3 ± 2.6 µmol·L-1 and Vmax = 286.8 ± 53.6 pmol/mg protein/min). Monocrotaline was determined to be a substrate of both OCT1 (Km = 109.1 ± 17.8 µmol·L-1, Vmax = 576.5 ± 87.5 pmol/mg protein/min) and OCT2 (Km = 64.7 ± 14.8 µmol·L-1, Vmax = 180.7 ± 22.0 pmol/mg protein/min), other than OCT3 and MATE transporters. The results indicated that OCT2 may be important for renal elimination of anisodine and OCT1 was responsible for monocrotaline uptake into liver. However neither MATE1 nor MATE2-K could facilitate transcellular transport of anisodine and monocrotaline. Accumulation of these drugs in the organs with high OCT1 expression (liver) and OCT2 expression (kidney) may be expected.

[Transformation and distribution of straw-derived carbon in soil and the effects on soil organic carbon pool: A review]. / è¿˜ç”°ç§¸ç§†ç¢³åœ¨åœŸå£¤ä¸­çš„è½¬åŒ–åˆ†é åŠå¯¹åœŸå£¤æœ‰æœºç¢³åº“å½±å“çš„ç ”ç©¶è¿›å±•.

Farmland soil organic carbon (SOC) pool is a crucial component of global carbon cycle. Due to the widely-implemented straw returning, crop straws have become the primary exogenous carbon source for agricultural soils. The conversion and distribution of straw-derived carbon in soil directly affect the composition and contents of SOC, with further influence on soil nutrient cycling. Based on recent studies, this review investigated the factors impacting the transformation and distribution of straw-carbon; introduced the microbial composition that contributes to the assimilation of carbon from straw; and summarized the effects of straw-carbon on the composition, content, and turnover of SOC. Additionally, we proposed the future research regarding the effects of abiotic factors on the bio-transformation of straw-carbon; the interaction between biotic and abiotic factors during the straw carbon transformation processes; the coupling of carbon and nitrogen from straws into the soil carbon and nitrogen cycles; and the effective control over the transformation of straw-carbon that enters the active or stable soil organic carbon pool. The purpose was to reveal variation characteristics of SOC during straw returning, and provide theoretical basis and technical support for the efficient fertilization and carbon sequestration of straw returning.

Identifying factors affecting the pharmacokinetics of voriconazole in patients with liver dysfunction: A population pharmacokinetic approach.

Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections. Voriconazole has significant intraindividual and interindividual pharmacokinetics variability in different patient populations. Pharmacokinetic data of voriconazole in patients with liver dysfunction were limited. The aims of this study were to evaluate the population pharmacokinetics of voriconazole in patients with liver dysfunction and to identify the factors that affect voriconazole pharmacokinetics. A total of 166 samples taken from 57 patients with liver dysfunction were included in the study. A one-compartment pharmacokinetic model with first-order absorption and elimination was used to describe the data. Voriconazole clearance (CL) was 0.58 L/h, the volume of distribution (Vd ) was 134 L, and oral bioavailability (F) was 80.8%. This study showed that platelet count was significantly associated with voriconazole pharmacokinetic parameters. CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. Voriconazole CL was significantly decreased in patients with liver dysfunction. This study provides useful pharmacokinetics information for patients with liver dysfunction while highlighting the value of therapeutic drug monitoring in adjusting doses.

Psychophysiological and self-reported responses in individuals with methamphetamine use disorder exposed to emotional video stimuli.

Individuals with methamphetamine use disorder (MUD) exhibit irritability and compulsive emotional responses, yet the relevant study is scarce. The characteristic of their positive and negative emotional responses can provide effective targets for the clinical intervention. In this study, we compared the emotional responses of 60 participants with MUD and 30 healthy participants to visual stimuli. They watched four types of video to elicit anger, fear, amusement, and joy emotional responses. The self-report of emotional responses (i.e., arousal, valence, and proximity), skin conductance level, and startle response were measured. Comparing to the healthy controls, the methamphetamine group's subjective arousal level of fear is significantly lower (t = 3.763, p < .01); the skin conductance level of joy is significantly higher (t = 2.086, p < .05), and the level of anger is marginal significantly higher (t = 1.984, p = .05); the startle response level of anger (t = 2.069, p < .05) and joy (t = 2.406, p < .05) is significantly higher. The methamphetamine group exhibited an enhanced emotion response to anger and a decreased response to joy which may indicate the emotion dysregulation problem caused by drug. These results provide effective targets for clinical intervention in treating patients of MUD with emotion dysregulation problems.

Identification of the Features of Emotional Dysfunction in Female Individuals With Methamphetamine Use Disorder Measured by Musical Stimuli Modulated Startle Reflex.

Emotional dysregulation contributes to the development of substance use disorders (SUDs) and is highly associated with drug abuse and relapse. Music as a contextual auditory stimulus can effectively stimulate the reward circuitry, modulate memory associated with drug taking, and enhance emotional experiences during drug taking. However, the studies of the emotional responses to music in individuals with SUDs are scarce. Using startle reflex and self-reports, this study assessed the psychophysiological and cognitive emotional responses (i.e., valence, arousal and proximity) to happy, peaceful, and fearful music stimuli in 30 females with methamphetamine use disorder (MUD) and 30 healthy females. The results found that participants with MUD showed an inhibited startle response to fearful music compared to normal controls (t = 3.7, p < 0.01), and no significant differences were found in the startle responses to happy and peaceful music between the two groups. For the self-reported ratings, participants with MUD showed a decreased arousal in the response to fearful (t = 4.1, p < 0.01) and happy music (t = 3.8, p < 0.01), an increased valence in the response to fearful music (t = 4.4, p < 0.01), and a higher level of proximity in the response to fearful (t = 3.8, p < 0.01) and happy music (t = 2.2, p = 0.03). No significant differences were found in the rating of arousal to peaceful music, the valence to happy and peaceful music, as well as the proximity to peaceful music between the two groups. The females with MUD showed attenuated psychophysiological response and potentiated cognitive response (i.e., valence, arousal) to fearful music, as well as a high proximity to musical stimuli with high arousal regardless of its valence. These results have important implications for promoting the effectiveness of assessment and therapy selections for female MUD patients with impaired emotion regulation.

Mindfulness-based relapse prevention combined with virtual reality cue exposure for methamphetamine use disorder: Study protocol for a randomized controlled trial.

BACKGROUND: Mindfulness-based relapse prevention (MBRP) is a method that combines cognitive behavioral relapse prevention with mindfulness practice. Research suggests that MBRP can effectively reduce withdrawal/craving in people with substance use disorder (SUD). An important part of MBRP is to practice mindfulness meditation to cope with high-risk situations for relapse, such as stimuli and situations associated with drug taking. Virtual reality cue exposure (VRCE) may be a complementary approach to MBRP as it allows for controlled and graded presentations of various high-risk situations with distal and proximal drug cues. The aim of the study is to investigate the effects of MBRP combined with VRCE, in comparison to MBRP alone or treatment as usual, on craving and emotional responses in people with methamphetamine use disorders. METHOD/DESIGN: The study is a parallel randomized controlled study including 180 participants with methamphetamine use disorder. Three parallel groups will receive 8 weeks of MBRP combined with VRCE, MBRP alone, or treatment as usual, respectively. Craving, virtual cue reactivity, anxiety, depression, emotion regulation, mindfulness and drug-related attention bias will be assessed at pre-treatment, post-treatment, and 3 and 6 months of follow-up. DISCUSSION: This innovative study aims at investigating the effects of MBRP combined with VRCE in people with SUD. The combined intervention may have important clinical implications for relapse prevention due to its ease of application and high cost-effectiveness. This study may also stimulate research on the neuronal and psychological mechanisms of MBRP in substance use disorder. TRIAL REGISTRATION NUMBER: ChiCTR-INR-17013041.

Maternal high estradiol exposure alters CDKN1C and IGF2 expression in human placenta.

INTRODUCTION: The increased maternal estradiol (E2) concentrations induced by assisted reproductive technology (ART) result in lower birth weight of offspring, which is associated with increased risk of adult diseases. However, the exact mechanism remains unknown. The present study investigated the effect of high E2 exposure on the expression of imprinted genes CDKN1C and IGF2 in human placentas and the DNA methylation status of their differential methylation regions (DMRs). METHODS: The mRNA expression of CDKN1C and IGF2 in human placentas and the human trophoblast cells (HTR8) treated with E2 were investigated by reverse transcription-real time polymerase chain reaction (PCR). The DNA methylation of their DMRs were investigated by sodium bisulfite sequencing. RESULTS: CDKN1C and IGF2 were significantly up-regulated in ART conceived placentas. The mean birth weight of ART singletons was significantly lower than that of naturally conceived (NC) ones, with the increased percentage of small-for-gestational-age (SGA) birth. The DNA methylation was significantly down-regulated in the DMR of CDKN1C (KvDMR1) and up-regulated in the DMR of IGF2 (H19 DMR) in ART placentas. The treatment of E2 altered the expression of the two genes and the DNA methylation of their DMRs in HTR8 to a similar tendency as in vivo. DISCUSSION: The maternal high E2 levels after ART up-regulate the expression of imprinted genes in human placentas through epigenetic modifications, which influences the growth potential of the offspring. Further studies are needed to follow up the growth and development of the ART offspring.

The effect of music therapy on cognitive functions in patients with dementia: a systematic review and meta-analysis.

OBJECTIVES: The aim of the present study was to meta-analyze the effect of music therapy (MT) on cognitive functions in patients with dementia. METHOD: A systematic literature search was performed in Medline, PsycINFO, Embase, CINAHL and RILM up to 8 September 2016. We included all randomized controlled trials that compared MT with standard care, or other non-musical types of intervention, evaluating cognitive outcomes in patients with dementia. Outcomes included global cognition, complex attention, executive function, learning and memory, language, and perceptual-motor skills. RESULTS: From 1089 potentially relevant records, 110 studies were assessed for eligibility, and 7 met the inclusion criteria, of which 6 contained appropriate data for meta-analysis (330 participants, mean age range 78.8-86.3). Overall, random-effects meta-analyses suggested no significant effects of MT on all outcomes. Subgroup analysis found evidence of a beneficial effect of active MT on global cognition (SMD = 0.29, 95% CI 0.02 to 0.57, p = 0.04). CONCLUSION: Despite the limited evidence of the present review, it is important to continue supporting MT as a complementary treatment for older adults with dementia. RCTs with larger sample sizes are needed to better elucidate the impact of MT on cognitive functions.

Music therapy for depression.

BACKGROUND: Depression is a highly prevalent mood disorder that is characterised by persistent low mood, diminished interest, and loss of pleasure. Music therapy may be helpful in modulating moods and emotions. An update of the 2008 Cochrane review was needed to improve knowledge on effects of music therapy for depression. OBJECTIVES: 1. To assess effects of music therapy for depression in people of any age compared with treatment as usual (TAU) and psychological, pharmacological, and/or other therapies.2. To compare effects of different forms of music therapy for people of any age with a diagnosis of depression. SEARCH METHODS: We searched the following databases: the Cochrane Common Mental Disorders Controlled Trials Register (CCMD-CTR; from inception to 6 May 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; to 17 June 2016); Thomson Reuters/Web of Science (to 21 June 2016); Ebsco/PsycInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, and PubMed (to 5 July 2016); the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, the National Guideline Clearing House, and OpenGrey (to 6 September 2016); and the Digital Access to Research Theses (DART)-Europe E-theses Portal, Open Access Theses and Dissertations, and ProQuest Dissertations and Theses Database (to 7 September 2016). We checked reference lists of retrieved articles and relevant systematic reviews and contacted trialists and subject experts for additional information when needed. We updated this search in August 2017 and placed potentially relevant studies in the "Awaiting classification" section; we will incorporate these into the next version of this review as appropriate. SELECTION CRITERIA: All randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing music therapy versus treatment as usual (TAU), psychological therapies, pharmacological therapies, other therapies, or different forms of music therapy for reducing depression. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risk of bias, and extracted data from all included studies. We calculated standardised mean difference (SMD) for continuous data and odds ratio (OR) for dichotomous data with 95% confidence intervals (CIs). We assessed heterogeneity using the I2 statistic. MAIN RESULTS: We included in this review nine studies involving a total of 421 participants, 411 of whom were included in the meta-analysis examining short-term effects of music therapy for depression. Concerning primary outcomes, we found moderate-quality evidence of large effects favouring music therapy and TAU over TAU alone for both clinician-rated depressive symptoms (SMD -0.98, 95% CI -1.69 to -0.27, 3 RCTs, 1 CCT, n = 219) and patient-reported depressive symptoms (SMD -0.85, 95% CI -1.37 to -0.34, 3 RCTs, 1 CCT, n = 142). Music therapy was not associated with more or fewer adverse events than TAU. Regarding secondary outcomes, music therapy plus TAU was superior to TAU alone for anxiety and functioning. Music therapy and TAU was not more effective than TAU alone for improved quality of life (SMD 0.32, 95% CI -0.17 to 0.80, P = 0.20, n = 67, low-quality evidence). We found no significant discrepancies in the numbers of participants who left the study early (OR 0.49, 95% CI 0.14 to 1.70, P = 0.26, 5 RCTs, 1 CCT, n = 293, moderate-quality evidence). Findings of the present meta-analysis indicate that music therapy added to TAU provides short-term beneficial effects for people with depression if compared to TAU alone. Additionally, we are uncertain about the effects of music therapy versus psychological therapies on clinician-rated depression (SMD -0.78, 95% CI -2.36 to 0.81, 1 RCT, n = 11, very low-quality evidence), patient-reported depressive symptoms (SMD -1.28, 95% CI -3.75 to 1.02, 4 RCTs, n = 131, low-quality evidence), quality of life (SMD -1.31, 95% CI - 0.36 to 2.99, 1 RCT, n = 11, very low-quality evidence), and leaving the study early (OR 0.17, 95% CI 0.02 to 1.49, 4 RCTs, n = 157, moderate-quality evidence). We found no eligible evidence addressing adverse events, functioning, and anxiety. We do not know whether one form of music therapy is better than another for clinician-rated depressive symptoms (SMD -0.52, 95% CI -1.87 to 0.83, 1 RCT, n = 9, very low-quality evidence), patient-reported depressive symptoms (SMD -0.01, 95% CI -1.33 to 1.30, 1 RCT, n = 9, very low-quality evidence), quality of life (SMD -0.24, 95% CI -1.57 to 1.08, 1 RCT, n = 9, very low-quality evidence), or leaving the study early (OR 0.27, 95% CI 0.01 to 8.46, 1 RCT, n = 10). We found no eligible evidence addressing adverse events, functioning, or anxiety. AUTHORS' CONCLUSIONS: Findings of the present meta-analysis indicate that music therapy provides short-term beneficial effects for people with depression. Music therapy added to treatment as usual (TAU) seems to improve depressive symptoms compared with TAU alone. Additionally, music therapy plus TAU is not associated with more or fewer adverse events than TAU alone. Music therapy also shows efficacy in decreasing anxiety levels and improving functioning of depressed individuals.Future trials based on adequate design and larger samples of children and adolescents are needed to consolidate our findings. Researchers should consider investigating mechanisms of music therapy for depression. It is important to clearly describe music therapy, TAU, the comparator condition, and the profession of the person who delivers the intervention, for reproducibility and comparison purposes.

Music therapy for people with schizophrenia and schizophrenia-like disorders.

BACKGROUND: Music therapy is a therapeutic approach that uses musical interaction as a means of communication and expression. Within the area of serious mental disorders, the aim of the therapy is to help people improve their emotional and relational competencies, and address issues they may not be able to using words alone. OBJECTIVES: To review the effects of music therapy, or music therapy added to standard care, compared with placebo therapy, standard care or no treatment for people with serious mental disorders such as schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Study-Based Register (December 2010 and 15 January, 2015) and supplemented this by contacting relevant study authors, handsearching of music therapy journals and manual searches of reference lists. SELECTION CRITERIA: All randomised controlled trials (RCTs) that compared music therapy with standard care, placebo therapy, or no treatment. DATA COLLECTION AND ANALYSIS: Review authors independently selected, quality assessed and data extracted studies. We excluded data where more than 30% of participants in any group were lost to follow-up. We synthesised non-skewed continuous endpoint data from valid scales using a standardised mean difference (SMD). We employed a fixed-effect model for all analyses. If statistical heterogeneity was found, we examined treatment dosage (i.e. number of therapy sessions) and treatment approach as possible sources of heterogeneity. MAIN RESULTS: Ten new studies have been added to this update; 18 studies with a total 1215 participants are now included. These examined effects of music therapy over the short, medium, and long-term, with treatment dosage varying from seven to 240 sessions. Overall, most information is from studies at low or unclear risk of biasA positive effect on global state was found for music therapy compared to standard care (medium term, 2 RCTs, n = 133, RR 0.38 95% confidence interval (CI) 0.24 to 0.59, low-quality evidence, number needed to treat for an additional beneficial outcome NNTB 2, 95% CI 2 to 4). No binary data were available for other outcomes. Medium-term continuous data identified good effects for music therapy on negative symptoms using the Scale for the Assessment of Negative Symptoms (3 RCTs, n = 177, SMD - 0.55 95% CI -0.87 to -0.24, low-quality evidence). General mental state endpoint scores on the Positive and Negative Symptoms Scale were better for music therapy (2 RCTs, n = 159, SMD -0.97 95% CI -1.31 to -0.63, low-quality evidence), as were average endpoint scores on the Brief Psychiatric Rating Scale (1 RCT, n = 70, SMD -1.25 95% CI -1.77 to -0.73, moderate-quality evidence). Medium-term average endpoint scores using the Global Assessment of Functioning showed no effect for music therapy on general functioning (2 RCTs, n = 118, SMD -0.19 CI -0.56 to 0.18, moderate-quality evidence). However, positive effects for music therapy were found for both social functioning (Social Disability Screening Schedule scores; 2 RCTs, n = 160, SMD -0.72 95% CI -1.04 to -0.40), and quality of life (General Well-Being Schedule scores: 1 RCT, n = 72, SMD 1.82 95% CI 1.27 to 2.38, moderate-quality evidence). There were no data available for adverse effects, service use, engagement with services, or cost. AUTHORS' CONCLUSIONS: Moderate- to low-quality evidence suggests that music therapy as an addition to standard care improves the global state, mental state (including negative and general symptoms), social functioning, and quality of life of people with schizophrenia or schizophrenia-like disorders. However, effects were inconsistent across studies and depended on the number of music therapy sessions as well as the quality of the music therapy provided. Further research should especially address the long-term effects of music therapy, dose-response relationships, as well as the relevance of outcome measures in relation to music therapy.

Maternal High Estradiol Exposure is Associated with Elevated Thyroxine and Pax8 in Mouse Offspring.

Our previous studies have shown that maternal high estradiol (E2) environment increased the risk of thyroid dysfunction in offspring. However, the mechanism involved remains unexplored. To evaluate the thyroid function of offspring after high E2 exposure and to explore the underlying mechanism, we established a high E2 mouse model of early pregnancy, and detected thyroid hormones of their offspring. In thyroids of offspring, the expressions of Tg, Nis, Tpo, Pax8, and Titf1 and CpG island methylation status of Pax8 and genes involved in methylation were analyzed. We found that thyroxine (T4) and FT4 levels of offspring were obviously increased in the high-E2 group, especially in females. In both 3- and 8-week-old offspring of the high-E2 group, Pax8 was significantly up-regulated in thyroid glands, accompanied by the abnormal CpG island methylation status in the promoter region. Furthermore, Dnmt3a and Mbd1 were obviously down-regulated in thyroids of the high E2 group. Besides, the disturbance of thyroid function in females was more severe than that in males, implying that the effects were related to gender. In summary, our study indicated that maternal high E2 exposure disturbed the thyroid function of offspring through the dysregulation and abnormal DNA methylation of Pax8.

Species Comparison of Pre-systemic Bioactivation of Vicagrel, a New Acetate Derivative of Clopidogrel.

Previously we have found vicagrel, a new acetate derivative of clopidogrel, underwent hydrolysis to 2-oxo-clopidogrel and subsequent conversions to its pharmacological active metabolite (AM) and inactive carboxylic acid metabolite (CAM). This study demonstrated the interspecies differences of the vicagrel bioactivation by comparing the critical vicagrel metabolites formation in rats, dogs and human. The pharmacokinetic studies with rats and dogs were conducted after intragastric administration of vicagrel, followed by in vitro metabolism investigation in venous system, intestinal/hepatic microsomes from rats, dogs and human. An obvious disparity was observed in system exposure to AM (99.0 vs. 635.1 µg⋅h/L, p < 0.05) and CAM (10119 vs. 2634 µg⋅h/L, p < 0.05) in rats and dogs. It was shown that the cleavage of vicagrel was almost completed in intestine with great different clearance (53.28 vs. 3.643 L⋅h-1⋅kg-1, p < 0.05) in rats and dogs. With no further hydrolysis to CAM, the greatest clearance of AM (3.26 mL⋅h-1⋅kg-1) was found in dog intestine. In rat plasma, 2-oxo-clopidogrel was much more extensively hydrolyzed to CAM than in dog and human. Albeit similar hydrolysis clearance and AM production was observed among hepatic microsomes of the three species, the production velocity of CAM ranked highest in dogs (7.55 pmol/min/mg protein). Therefore, the unconformity of AM and CAM exposure cross species mainly came from the metabolism of 2-oxo-clopidogrel associated largely with tissue specificity and interspecies differences of esterases. In human, the pharmacokinetics of vicagrel might be more optimistic due to less inactivation hydrolysis before reaching liver.

Efficacy and safety of biapenem against lower respiratory tract infections in elderly Chinese patients and optimal dosing regimen based on pharmacokinetic/pharmacodynamic analysis.

The present study evaluated the efficacy and safety of biapenem in elderly Chinese patients with lower respiratory tract infections (LRTIs) and proposed optimal dosage regimen on the basis of pharmacokinetic/pharmacodynamic (PK/PD) analysis. The clinical efficacy, bacterial eradication and comprehensive therapeutic effect rates of biapenem were 70.3 (78/111), 68.5 (37/54) and 61.1% (33/54), respectively. Drug-related adverse reactions were seen in 12.6% of patients (14/111). The total protein level, Acute Physiology and Chronic Health Evaluation (APACHE) II score, %fT>MIC, fAUC24/MIC and fCmax/MIC values of patients had significant impacts (P < 0.05) on clinical and bacteriological efficacy. However, logistic regression analysis showed that only %fT>MIC independently influenced comprehensive therapeutic effect (P < 0.01, odds ratio = 1.064). The cut-off value for predicting comprehensive therapeutic effect using %fT>MIC was 75.0%; the sensitivity and specificity were 87.9 and 85.7%, respectively. Monte Carlo simulations revealed that the usual dosage regimen (300 mg every 12 hours, 0.5 hour infusion) was considered to be insufficient to obtain satisfactory therapeutic outcomes against low susceptible pathogens for elderly Chinese patients with LRTIs (CLcr = 70 ml/min).

Randomized Trial of Group Music Therapy With Chinese Prisoners: Impact on Anxiety, Depression, and Self-Esteem.

This study investigated the effects of group music therapy on improving anxiety, depression, and self-esteem in Chinese prisoners. Two-hundred male prisoners were randomly assigned to music therapy (n = 100) or standard care (n = 100). The music therapy had 20 sessions of group therapy compared with standard care. Anxiety (State and Trait Anxiety Inventory [STAI]), depression (Beck Depression Inventory [BDI]), and self-esteem (Texas Social Behavior Inventory [TSBI], Rosenberg Self-Esteem Inventory [RSI]) were measured by standardized scales at baseline, mid-program, and post-program. Data were analyzed based on the intention to treat principle. Compared with standard care, anxiety and depression in the music therapy condition decreased significantly at mid-test and post-test; self-esteem improved significantly at mid-test (TSBI) and at post-test (TSBI, RSI). Improvements were greater in younger participants (STAI-Trait, RSI) and/or in those with a lower level of education (STAI-State, STAI-Trait). Group music therapy seems to be effective in improving anxiety, depression, and self-esteem and was shown to be most beneficial for prisoners of younger age or with lower education level.