Interrelationships Between BDNF,Superoxide Dismutase,and Cognitive Impairment in Drug-Naive First-Episode Patients With Schizophrenia

The pathogenesis and etiology of schizophrenia (SCZ) remains unclear. Accumulating studies showed that complex interrelationships between brain-derived neurotrophic factor (BDNF) and an imbalanced redox system has a crucial role in the psychopathology of SCZ. However, the influence of the interrelationships of BDNF and superoxide dismutase (SOD) on cognitive impairment and clinical symptomatology in drug-naive first-episode (DNFE) SCZ patients has not been studied thoroughly. Serum BDNF levels, plasma total SOD, manganese-SOD (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD) activities, and malondialdehyde (MDA) levels were measured in 327 DNFE patients with SCZ and 391 healthy controls. Cognitive functions were measured using the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Compared with the controls, the DNFE patients had increased activities of total SOD and CuZn-SOD, and reduced levels of BDNF and MDA. BDNF levels were positively correlated with CuZn-SOD activity in patients. In addition, we found that elevated Mn-SOD and CuZn-SOD activities were related to PANSS depression factor. Moreover, an interactive effect of BDNF levels and Mn-SOD activity was associated with attentional index score in the patients. Therefore, our findings suggested that interrelationships between BDNF and antioxidant mechanisms might underlie the pathological mechanisms of cognitive impairments and symptomatology in the DNFE patients with SCZ.     

Predictors of subjective recovery from recent-onset psychosis in a developing country: a mixed-methods study

Purpose

This study was conducted to: (a) investigate the levels and progress of subjective recovery from recent-onset psychosis; (b) examine its predictive factors and; (c) describe perceived challenges and opportunities affecting recovery. The findings were expected to help inform recovery-oriented psychiatric care in low-income, particularly African, countries.

Methods

This sequential explanatory mixed-methods study involved 263 service users with recent-onset psychosis from Northwestern Ethiopia. For the quantitative part, a 9-month longitudinal study approach was employed with three time point measurements over 9 months. Predictor variables for subjective recovery from recent-onset psychosis were identified by hierarchical multiple linear regression tests. Following the quantitative survey, individual qualitative interviews were conducted with 19 participants. Interview data were transcribed and thematically analysed.

Results

High mean subjective recovery scores were recorded throughout the study (Questionnaire about the Process of Recovery score ranging from 44.17 to 44.65). Quality of life, internalized stigma, disability, hopelessness, satisfaction with social support, and central obesity were significant predictors of subjective recovery across the three time points. Participants’ perceived challenges and opportunities affecting their recovery were categorized into four themes.

Conclusion

In Ethiopia, a low percentage of individuals with SMIs initiate psychiatric treatment and many discontinue this to attend spiritual healing. In this study, the Ethiopian SMI patients engaged consistently in psychiatric treatment indicated high mean subjective recovery scores. Devising mechanisms to integrate the psychiatric treatment and spiritual healing sectors are suggested. Approaches to improve quality of life, functioning, hope, internalized stigma and provide need-based social support are suggested.

     

脑卒中早期康复

国内外的脑卒中康复指南均推荐脑卒中后应尽早进行康复训练,但是尽早康复的时机、强度以及包含的项目尚不明确。脑卒中急性期患者病情稳定后48 h内应召开初次康复评价会,根据患者整体评估和功能障碍评估的结果制定个体化、全面的康复方案和康复目标,并初步判断脑卒中的康复预后。脑卒中患者早期宜进行运动康复、吞咽功能康复及言语功能康复。如康复对象为重症脑卒中患者、大于75岁的老年卒中患者和儿童卒中患者,更需注重个体化的评估及康复方案。     

Decoding attention control and selection in visual spatial attention

Event‐related potentials (ERPs) are used extensively to investigate the neural mechanisms of attention control and selection. The univariate ERP approach, however, has left important questions inadequately answered. We addressed two questions by applying multivariate pattern classification to multichannel ERPs in two cued visual spatial attention experiments (N = 56): (a) impact of cueing strategies (instructional vs. probabilistic) on attention control and selection and (b) neural and behavioral effects of individual differences. Following cue onset, the decoding accuracy (cue left vs. cue right) began to rise above chance level earlier and remained higher in instructional cueing (~80 ms) than in probabilistic cueing (~160 ms), suggesting that unilateral attention focus leads to earlier and more distinct formation of the attention control set. A similar temporal sequence was also found for target‐related processing (cued target vs. uncued target), suggesting earlier and stronger attention selection under instructional cueing. Across the two experiments: (a) individuals with higher cue‐related decoding accuracy showed higher magnitude of attentional modulation of target‐evoked N1 amplitude, suggesting that better formation of anticipatory attentional state leads to stronger modulation of target processing, and (b) individuals with higher target‐related decoding accuracy showed faster reaction times (or larger cueing effects), suggesting that stronger selection of task‐relevant information leads to better behavioral performance. Taken together, multichannel ERPs combined with machine learning decoding yields new insights into attention control and selection that complement the univariate ERP approach, and along with the univariate ERP approach, provides a more comprehensive methodology to the study of visual spatial attention.     

Epigenetic priming with decitabine followed by low dose idarubicin and cytarabine in acute myeloid leukemia evolving from myelodysplastic syndromes and higher-risk myelodysplastic syndromes: a prospective multicenter single-arm trial

Patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS) or higher-risk MDS have limited treatment options and poor prognosis. Our previous single-center study of decitabine followed by low dose idarubicin and cytarabine (D-IA) in patients with myeloid neoplasms showed promising primary results. We therefore conducted a multicenter study of D-IA regimen in AML evolving from MDS and higher-risk MDS. Patients with AML evolving from MDS or refractory anemia with excess blasts type 2 (RAEB-2) (based on the 2008 WHO classification) were included. The D-IA regimen (decitabine, 20 mg/m² daily, days 1 to 3; idarubicin, 6 mg/m² daily, days 4 to 6; cytarabine 25 mg/m² every 12 hours, days 4 to 8; granulocyte colony stimulating factor [G-CSF], 5 μg/kg, from day 4 until neutrophil count increased to 1.0 × 10⁹/L) was administered as induction chemotherapy. Seventy-one patients were enrolled and treated, among whom 44 (62.0%) had AML evolving from MDS and 27 (38.0%) had RAEB-2. Twenty-eight (63.6%) AML patients achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi): 14 (31.8%) patients had CR and 14 (31.8%) had CRi. Six (22.2%) MDS patients had CR and 15 (55.6%) had marrow complete remission. The median overall survival (OS) was 22.4 months for the entire group, with a median OS of 24.2 months for AML and 20.0 months for MDS subgroup. No early death occurred. In conclusion, the D-IA regimen was effective and well tolerated, representing an alternative option for patients with AML evolving from MDS or MDS subtype RAEB-2.     

Mutation status and burden can improve prognostic prediction of patients with lower‐risk myelodysplastic syndromes

Patients with lower‐risk myelodysplastic syndromes (LR‐MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter‐individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS‐relevant genes in 159 patients with LR‐MDS using next‐generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129‐4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 (P < .001; HR = 4.306, 95% CI: 2.144‐8.650), TP53 (P = .004; HR = 4.863, 95% CI: 1.662‐14.230) and JAK2 (P = .002; HR = 5.466, 95%CI: 1.848‐16.169), as well as adjusted TET2 VAF ≥18% (P = .008; HR = 2.492, 95% CI: 1.273‐4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR‐MDS patients into three prognostically different groups (P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher‐risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS‐relevant genes may improve the prognostication of patients with LR‐MDS and could help identify those with worse‐than‐expected prognosis for more aggressive treatment.     

eIF4EBP3 was downregulated by methylation and acted as a tumor suppressor by targeting eIF4E/β-catenin in gastric cancer

Gastric Cancer - Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Through a methylome...     

Comparison of survival between adolescent and young adult vs older patients with hepatocellular carcinoma

BACKGROUNDDue to the special clinical features and biologic characteristics of adolescent and young adult (AYA) cancers, AYA cancers are different from cancers in children and elderly individuals. However, there are few reports on AYA hepatocellular carcinoma (HCC).AIMTo investigate the overall survival (OS) of AYA (15-39 years) and elderly (40-74 years) patients with HCC.METHODSThe data of all the HCC cases were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2015 and were then divided into two groups based on age: AYA group (15-39 years) and older group (40-74 years). Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups. Propensity score matching (PSM) was employed to analyze the OS difference between the two groups. The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTSCompared to elderly cancer patients, AYA patients with HCC had a worse Surveillance, Epidemiology, and End Results stage, including the distant stage (22.1% vs 15.4%, P < 0.001), and a more advanced American Joint Committee on Cancer (AJCC) stage, including AJCC III and IV (49.2% vs 38.3%, P < 0.001), and were more likely to receive surgery (64.5% vs 47.5%, P < 0.001). Before PSM, the AYA group had a longer survival in months (median: 20.00, interquartile range [IQR]: 5.00-62.50) than the older group (median: 15.00, IQR: 4.00-40.00) (P < 0.001). After PSM, the AYA group still had a longer survival in months (median: 21.00, IQR: 5.00-64.50) than the older group (median: 18.00, IQR: 6.00-53.00) (P < 0.001). The Cox proportional hazards regression model showed that advanced age (hazard ratio [HR] = 1.405, 95%CI: 1.218-1.621, P < 0.001) was a risk factor for OS of HCC patients. In the subgroup analysis, the Cox proportional hazards regression model showed that in AJCC I/II HCC patients, advanced age (HR = 1.749, 95%CI: 1.352-2.263, P < 0.001) was a risk factor for OS, while it was not a risk factor in AJCC III/IV HCC patients (HR = 1.186, 95%CI: 0.997-1.410, P = 0.054) before PSM. After PSM, advanced age (HR = 1.891, 95%CI: 1.356-2.637, P < 0.001) was still a risk factor for OS in AJCC I/II HCC patients, but was not a risk factor for OS in AJCC III/IV HCC patients (HR = 1.192, 95%CI: 0.934-1.521, P = 0.157) after PSM.CONCLUSIONAYA patients with HCC have different clinical characteristics from older adults. In different AJCC stages, the two groups of patients have different OS: In AJCC I/II HCC patients, advanced age is a risk factor for OS, but it is not a risk factor for OS in the AJCC III/IV HCC patient group.     

A novel prognostic scoring model for newly diagnosed FLT3-ITD-positive acute myeloid leukemia

FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is one of the most common somatic mutations in acute myeloid leukemia (AML). However, the molecular structure characteristics and widely accepted prognostic factors for FLT3-ITD are still not well described. This study aimed to retrospectively examine 81 patients with FLT3-ITD-positive AML diagnosed and treated at the First Affiliated Hospital of Zhejiang University from December 2013 to March 2018 using the next-generation sequencing 185-gene platform. High variant allele frequency (VAF) [> 0.48, P = 0.0089 for overall survival (OS), P = 0.13 for relapse-free survival (RFS)], multiple ITDs (> 1 ITDs, P = 0.011 for OS, P = 0.033 for RFS) and longer insertion length (> 69 bp, P = 0.14 for OS, P = 0.0078 for RFS) predicted poor survival. The study further proposed an easily applicable scoring model for OS using the Least Absolute Shrinkage and Selector Operation (LASSO) Cox regression model. Also, an independent cohort of 30 patients was used for external model validation. The mode was expressed as follows: 0.659 × FLT3-ITD VAF + 0.375 × FLT3-ITD number + 0.807 × Age + 0.688 × DNMT3A + 1.939 × U2AF1 (FLT3-ITD VAF > 0.48 scored 1; FLT3-ITD number scored 1 if carried 1 ITD, 2 if carried ≥ 2 ITDs; age > 44 years scored 1, the presence of DNMT3A or U2AF1 scored 1; 0 for other conditions). It categorized patients into low-risk (L-R, score < 1, n = 20) and high-risk (H-R, score ≥ 1, n = 61) groups based on the risk score with a significant difference in survival (3-year OS, P < 0.0001; 3-year RFS, P = 0.0005). A prognostic nomogram that integrated these five factors was developed with a concordance index calculation [OS: 0.68, 95% CI (0.64-0.72)].     

Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation

Orthotopic liver transplantation (OLT) can be a definitive treatment for patients with hepatocellular carcinoma (HCC). Prolonged waiting times for cadaveric livers, however, may lead to dropout from the waiting list or worsened post-OLT prognosis as a result of interval tumor progression. Percutaneous radiofrequency ablation (RFA) is widely used for local control of small unresectable HCC, but its pretransplant role remains unclear. We studied the outcome of 52 consecutive patients accepted for OLT bearing 87 HCC nodules and treated with percutaneous RFA. On initial staging, the tumor burden exceeded the Milan criteria in 10 patients. Complete tumor coagulation was observed in 74 of 87 (85.1%) nodules based on postablation imaging. After a mean of 12.7 months (range: 0.3-43.5) on the waiting list, 3 of 52 patients (5.8%) had dropped out due to tumor progression. Forty-one patients had undergone transplantation, with 1- and 3-year post-OLT survival rates of 85% and 76%, respectively. No patient developed HCC recurrence. There were three major complications in 76 RFA procedures (hepatic arterial hemorrhage, small bowel perforation, and liver decompensation salvaged by OLT), without resultant death or dropout. In conclusion, percutaneous RFA is an effective bridge to OLT for patients with compensated liver function and safely accessible tumors. Tumor-related dropout rate and post-OLT outcome compared favorably with published controls of patients with early-stage disease. This can be attributed to the efficacy of RFA in producing local cure or curbing tumor progression during the waiting period.