Negative symptoms represent an unmet need for schizophrenia treatment. The effect of theta frequency transcranial alternating current stimulation (theta-tACS) applied during working memory (WM) tasks on negative symptoms has not been demonstrated as of yet. We conducted a randomized, double-blind, sham-controlled trial of 36 stabilized schizophrenia patients, randomized to receive either twice daily, 6 Hz 2 mA, 20 min sessions of in-phase frontoparietal tACS or sham for five consecutive weekdays. Participants were concurrently engaged in WM tasks during stimulation. The primary outcome measure was the change over time in the Positive and Negative Syndrome Scale (PANSS) negative subscale score measured from baseline through to the 1-month follow-up. Secondary outcome measures were other symptom clusters, neurocognitive performance, and relevant outcomes. The intention-to-treat analysis demonstrated greater reductions in PANSS negative subscale scores at the end of stimulation in the active (−13.84%) than the sham (−3.78%) condition, with a large effect size (Cohen’s d = 0.96, p = 0.006). The positive effect endured for at least one month. Theta-tACS also showed efficacies for cognitive symptoms, WM capacity, and psychosocial functions. Online theta-tACS offers a novel approach to modulate frontoparietal networks to treat negative symptoms of schizophrenia. The promising results require large-scale replication studies in patients with predominantly negative symptoms.

Prostate cancer (PCa) is a reproductive system cancer in elderly men. We investigated the effects of betel nut arecoline on the growth of normal and cancerous prostate cells. Normal RWPE-1 prostate epithelial cells, androgen-independent PC-3 PCa cells, and androgen-dependent LNCaP PCa cells were used. Arecoline inhibited their growth in dose- and time-dependent manners. Arecoline caused RWPE-1 and PC-3 cell cycle arrest in the G2/M phase and LNCaP cell arrest in the G0/G1 phase. In RWPE-1 cells, arecoline increased the expression of cyclin-dependent kinase (CDK)-1, p21, and cyclins B1 and D3, decreased the expression of CDK2, and had no effects on CDK4 and cyclin D1 expression. In PC-3 cells, arecoline decreased CDK1, CDK2, CDK4, p21, p27, and cyclin D1 and D3 protein expression and increased cyclin B1 protein expression. In LNCaP cells, arecoline decreased CDK2, CDK4, and cyclin D1 expression; increased p21, p27, and cyclin D3 expression; had no effects on CDK1 and cyclin B1 expression. The antioxidant N-acetylcysteine blocked the arecoline-induced increase in reactive oxygen species production, decreased cell viability, altered the cell cycle, and changed the cell cycle regulatory protein levels. Thus, arecoline oxidant exerts differential effects on the cell cycle through modulations of regulatory proteins.

EEG studies indicated that schizophrenia patients had increased resting-state theta-band functional connectivity, which was associated with negative symptoms. We recently published the first study showing that theta (6 Hz) transcranial alternating current stimulation (tACS) over left prefrontal and parietal cortices during a working memory task for accentuating frontoparietal theta-band synchronization (in-phase theta-tACS) reduced negative symptoms in schizophrenia patients. Here, we hypothesized that in-phase theta-tACS can modulate theta-band large-scale networks connectivity in schizophrenia patients. In this randomized, double-blind, sham-controlled trial, patients received twice-daily, 2 mA, 20-min sessions of in-phase theta-tACS for 5 consecutive weekdays (n = 18) or a sham stimulation (n = 18). Resting-state electroencephalography data were collected at baseline, end of stimulation, and at one-week follow-up. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity across 84 cortical regions at theta frequency (5–7 Hz). EEG data from 35 patients were analyzed. We found that in-phase theta-tACS significantly reduced the LPS between the posterior cingulate (PC) and the parahippocampal gyrus (PHG) in the right hemisphere only at the end of stimulation relative to sham (p = 0.0009, corrected). The reduction in right hemispheric PC-PHG LPS was significantly correlated with negative symptom improvement at the end of the stimulation (r = 0.503, p = 0.039). Our findings suggest that in-phase theta-tACS can modulate theta-band large-scale functional connectivity pertaining to negative symptoms. Considering the failure of right hemispheric PC-PHG functional connectivity to predict improvement in negative symptoms at one-week follow-up, future studies should investigate whether it can serve as a surrogate of treatment response to theta-tACS.

(1) Background: The acute effects of ozone, cold temperature and particulate matter less than 2.5 μm (PM_2.5) in size related to asthma attacks are well known worldwide. The adverse effects of ozone and cold temperature on asthma morbidity in Taiwan are still inconclusive. (2) Methods: This retrospective study included patients who had asthma emergency room visits (ERVs) from 1 January 2016 to 31 December 2019 in a regional hospital in Taiwan. The short-term negative effects were estimated using Distributed Lag Non-Linear Models (DLNMs) for the relative risks (RRs) of asthma ERVs associated with PM_2.5, ozone and cold temperature exposures within 5 days. (3) Results: There was a significant association between a 10 ppm increase in PM_2.5 exposure and asthma ERVs at a 2-day lag (RR 1.166, 95% confidence interval (C.I.): 1.051–1.294). There was a significant association between ozone and asthma ERVs at a 1-day lag (RR 1.179, 95% C.I.: 1.034–1.345). The ambient temperature in cold weather compared with the temperature of minimum asthma ERV showed an RR of 1.214, 95% C.I.: 1.009–1.252 at a 1-day lag. (4) Conclusions: This study provides evidence that short-term exposure to fine suspended particulates, ozone and inverse temperature is associated with asthma exacerbation.

Foreign body (FB) ingestion is a common clinical problem in acute settings. Detecting FBs in the upper digestive tract is challenging. The conventional X-ray is usually the first-line imaging tool to detect FBs. However, its diagnostic performance is inconsistent in the literature. In this study, we performed a systematic review and meta-analysis to determine the diagnostic performance of the conventional X-ray for detecting FBs in the upper digestive tract. We conducted a systematic search of PubMed, Embase, Cochrane Library, Web of Science, and Scopus until 1 August 2020. Prospective or retrospective studies investigating the diagnostic accuracy of conventional X-rays for detecting FBs in the upper digestive tract in patients of all ages were included. The Quality Assessment of Studies of Diagnostic Accuracy-2 tool was used to review the quality of included studies. We used a bivariate random-effects model to calculate diagnostic accuracy parameters. Heterogeneity was assessed using I² statistics. We included 17 studies (n = 4809) in the meta-analysis. Of the 17 studies, most studies were rated as having a high risk of bias. Conventional X-rays had a pooled sensitivity of 0.58 (95% confidence interval [CI] = 0.36–0.77, I² = 98.52) and a pooled specificity of 0.94 (95% CI = 0.87–0.98, I² = 94.49) for detecting FBs in the upper digestive tract. The heterogeneity was considerable. The area under the summary receiver operating characteristic curve was 0.91 (95% CI = 0.88–0.93). Deek’s funnel plot asymmetry test results revealed no significant publication bias (p = 0.41). The overall sensitivity and specificity of conventional X-rays were low and high, respectively, for detecting FBs in the upper digestive tract. Hence, conventional X-rays to exclude patients without upper FBs in the digestive tract are not recommended. Further imaging or endoscopic examinations should be performed for at-risk patients.