BackgroundSeveral studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) may have a beneficial effect in Alzheimer’s disease (AD). Nevertheless, the clinical benefit of rTMS for AD remains inconclusive.ObjectiveThis systematic review and meta-analysis aimed to evaluate the efficacy and safety of rTMS in AD.MethodsWe searched PubMed, Embase and Cochrane for randomized controlled trials (RCTs) of rTMS for AD. We calculated pooled estimates of mean difference (MD) with 95% confidence intervals (CI). The protocol was registered at International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42018089990).ResultsFive RCTs involving 148 participants were included in this review. Compared with sham stimulation, high-frequency rTMS led to a significant improvement in cognition as measured by ADAS-cog (MD = -3.65, 95% CI -5.82 to -1.48, p = 0.001), but not MMSE (MD = 0.49, 95% CI -1.45 to 2.42, p = 0.62). High-frequency rTMS also improved the global impression in comparison to the placebo (MD = -0.79, 95% CI -1.24 to -0.34, p = 0.0006). There was no significant difference in mood (MD = -1.36, 95% CI -3.93 to 1.21, p = 0.30) and functional performance (MD = 0.59, 95% CI -1.21 to 2.38, p = 0.52) between high-frequency rTMS and sham groups. Only one trial included low-frequency rTMS reported no significant improvement in cognition, mood and functional performance. Few mild adverse events were observed in both the rTMS and sham groups.ConclusionsRTMS is relatively well tolerated, with some promise for cognitive improvement and global impression in patients with AD. Our findings also indicate the variability between ADAS-cog and MMSE in evaluating global cognitive impairment.

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Background. Chronic tinnitus affects approximately 10-15% of the population. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been considered as a promising and well-tolerated therapeutic strategy for chronic tinnitus. However, a recent large-scale multicenter clinical trial showed a negative result. Objective. This systematic review is aimed at assessing the efficacy and safety of low-frequency rTMS in chronic tinnitus. Methods. We searched PubMed, Embase, and Cochrane Library for randomized controlled studies of rTMS treatment of chronic tinnitus. A pooled analysis of standardized mean difference (SMD) was performed with 95% confidence intervals (CI). Results. Ten RCTs involving 567 participants were included in this review. Compared with sham stimulation, rTMS showed no significant efficacy in tinnitus severity and disability measured by Tinnitus Handicap Inventory (THI) in short-term (SMD=−0.04, 95% CI -0.23 to 0.16, P=0.72), medium-term (SMD=−0.13, 95% CI -0.43 to 0.17, P=0.41), and long-term (SMD=−0.16, 95% CI -0.38 to 0.05, P=0.14) follow-up. Tinnitus severity and disability measured by Tinnitus Questionnaire (TQ) also showed no significant improvement in short-term (SMD=−0.11, 95% CI -0.31 to 0.10, P=0.30), medium-term (SMD=−0.10, 95% CI -0.37 to 0.16, P=0.44), and long-term (SMD=−0.20, 95% CI -0.40 to 0.01, P=0.06) follow-up. Additionally, no statistically significant difference was shown in the changes of tinnitus loudness assessed by a visual analogue scale (VAS) between rTMS and sham groups in the short-term (SMD=−0.28, 95% CI -0.59 to 0.02, P=0.07), medium-term (SMD=−0.26, 95% CI -0.59 to 0.07, P=0.13), and long-term (SMD=−0.20, 95% CI -0.53 to 0.13, P=0.24) follow-up. Few mild or moderate adverse events were observed in both the rTMS and sham groups. Conclusion. Low-frequency rTMS is well tolerated but not effective in treating chronic tinnitus based on the current analysis of pooled data. Further studies with modified and uniform protocols are required to investigate the potential benefit of rTMS in chronic tinnitus.

BackgroundOver the last few decades intensive studies have been carried out on the molecular targets mediating general anesthesia as well as the effects of general anesthetics. The γ-aminobutyric acid type A receptor (GABAAR) has been indicated as the primary target of general anaesthetics such as propofol, etomidate and isoflurane, and sedating drugs including benzodiazepines and barbiturates. The GABAAR is also involved in drug tolerance and dependence. However, the involvement of other ion channels is possible.MethodsUsing reverse transcription and quantitative PCR techniques, we systematically investigated changes in the mRNA levels of ion channel genes in response to exposure to midazolam, pentobarbital and ketamine in a freshwater model animal, Daphnia pulex. To retrieve the sequences of Daphnia ion channel genes, Blast searches were performed based on known human or Drosophila ion channel genes. Retrieved sequences were clustered with the maximum-likelihood method. To quantify changes in gene expression after the drug treatments for 4 hours, total RNA was extracted and reverse transcribed into cDNA and then amplified using quantitative PCR.ResultsA total of 108 ion channel transcripts were examined, and 19, 11 and 11 of them are affected by midazolam (100 μM), pentobarbital (200 μM) and ketamine (100 μM), respectively, covering a wide variety of ion channel types. There is some degree of overlap with midazolam- and pentobarbital-induced changes in the mRNA expression profiles, but ketamine causes distinct changes in gene expression pattern.In addition, flumazenil (10 μM) eliminates the effect of midazolam on the mRNA expression of the GABAA receptor subunit Rdl, suggesting a direct interaction between midazolam and GABAA receptors.ConclusionsRecent research using high throughput technology suggests that changes in mRNA expression correlate with delayed protein expression. Therefore, the mRNA profile changes in our study may reflect the molecular targets not only in drug actions, but also in chronic drug addiction. Our data also suggest the possibility that hypnotic/anesthetic drugs are capable of altering the functions of the nervous system, as well as those non-nerve tissues with abundant ion channel expressions.