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.

Cyclooxygenase-2 (COX-2) is known to be involved in the pathogenesis of migraine, and some polymorphisms are known to affect the expression of COX-2. This retrospective casecontrol study aimed to explore the associations between the-765 G>C (rs20417),-1759 G>A (rs3218625), and-8473 C>T (rs5275) COX-2 polymorphisms and migraine in Chinese Han individuals. One hundred and ten unrelated Han Chinese patients with migraine and 108 healthy controls were recruited between 03/2014 and 08/2016 at the First Affiliated Hospital of Nanjing Medical University and the First People's Hospital of Lianyungang City. The genotypes of all polymorphisms in controls followed the Hardy-Weinberg equilibrium (P = 0.215, P = 0.884, and P = 0.689). There were differences in the genotype and allele distributions of the COX-2-1759G>A (Gly587Arg) polymorphism between the migraine and control groups (P = 0.038 and P = 0.040, respectively). Compared with the COX-2-1759AG genotype, GG genotype carriers had an increased risk of migraine (odds ratio (OR) = 8.720, 95% confidence interval (CI): 1.072-70.960, P = 0.038). The frequency of the COX-2-1759A allele in patients with migraine was significantly lower than the controls (OR = 0.119, 95%CI: 0.015-0.957, P = 0.040). Adjusted age and sex, a statistical difference was found in the dominant model of COX-2-1759 G>A (OR = 0.118, 95% CI 0.014 to 0.962, P = 0.046). No significant difference was detected regarding the-765G>C and-8473T>C polymorphisms between the two groups. The COX-2 1759A allele might be involved in the development of migraine in Chinese Han individuals, but this will have to be confirmed in large-scale studies.

Background. Migraine has a great impact on public health. Current acute therapies do not satisfy all migraineurs. The novel serotonin 5-HT1F receptor agonist appears more promising for aborting migraine attacks. Objective. To evaluate the clinical efficacy and safety of lasmiditan in treating acute migraine attacks. Methods. The literature search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) which assessed the effect and safety of lasmiditan on migraine. The risk of bias was assessed using the Cochrane Collaboration’s risk of bias tool. Results were extracted and pooled as risk ratios (RRs) with a fixed or random-effects model. Results. Based on the four included RCTs, pooled estimates showed that lasmiditan with the 50 mg, 100 mg, and 200 mg doses was superior to placebo at 2 h after the first dose in terms of pain freedom, absence of migraine-associated symptoms, headache relief, no/mild disability, and global impression of change (very much/much better) (RRs ranged from 1.13 to 1.96), except for nausea-free and vomiting-free. Both lasmiditan 100 mg and 200 mg resulted in significantly fewer patients using rescue medication (100 mg: RR = 0.75 , 95% CI (0.61, 0.92), P = 0.007 ; 200 mg: RR = 0.81 , 95% CI (0.66, 0.99), P = 0.04 ) at 2-24 h postdose, compared with placebo. Safety data showed that the proportion of patients reporting at least one treatment-emergent adverse event (TEAE) and the incidence of most common TEAEs such as dizziness, paresthesia, fatigue, somnolence, and nausea was higher in the lasmiditan groups (50 mg, 100 mg, and 200 mg), compared with placebo. There was no significant difference between lasmiditan and placebo in terms of cardiovascular-related TEAEs ( RR = 2.75 , 95% CI (0.81, 9.37), P = 0.11 ). Compared with lasmiditan 100 mg, lasmiditan 200 mg was more effective in pain freedom at 2 h after the first dose ( RR = 0.83 , 95% CI (0.74, 0.94), P = 0.004 ) but associated with a higher risk of reporting at least one TEAE ( RR = 0.88 , 95% CI (0.81, 0.96), P = 0.006 ). Conclusions. Lasmiditan with the 50 mg, 100 mg, and 200 mg doses are effective and safe in acute migraine treatment. Lasmiditan 200 mg is more effective than lasmiditan 100 mg in pain freedom, while lasmiditan 100 mg is better tolerated in the short-term follow-up. Further larger sample-size RCTs are required to verify the applicability and tolerability in the long term.

Alligator weed Alternanthera philoxeroides is a perennial, worldwide pernicious weed. The beetle Agasicles hygrophila is considered to be a classical biological agent used to control A. philoxeroides. In the insect peripheral olfactory system, the odorant receptor co-receptor (ORco) plays an important function in the perception of odors in insects. However, the function of ORco in the mating and host-finding behaviors of A. hygrophila remains unclear. In this study, we characterized the odorant receptor co-receptor of A. hygrophila (AhygOrco). Real-time quantitative PCR (qRT–PCR) showed that AhygOrco was predominantly expressed in the antennae of both male and female adults, and the difference between male and female antennae was not significant. The RNA interference (RNAi) results showed that compared to the control, the injection of AhygOrco dsRNA strongly reduced the expression of AhygOrco by 90% in male beetles and 89% in female beetles. The mate-seeking and feeding behavior of AhygOrco-silenced beetles were significantly inhibited. Male adults were significantly less successful in finding a mate compared to the control group. Furthermore, host allocation abilities toward A. philoxeroides of both adults were significantly repressed. These results indicated that AhygOrco is associated with A. hygrophila feeding and mate-seeking and that inhibition of AhygOrco expression is one of the causes of reduced host and mate recognition in A. hygrophila. Meanwhile, the study provides support for exploring gene functions based on RNAi.