Dexmedetomidine inhibited arrhythmia susceptibility to adrenergic stress in RyR2R2474S mice through regulating the coupling of membrane potential and intracellular calcium.

BACKGROUND: Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, can decrease the incidence of arrhythmias, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the underlying mechanisms by which DEX affects cardiac electrophysiological function remain unclear. METHODS: Ryanodine receptor (RyR2) heterozygous R2474S mice were used as a model for CPVT. WT and RyR2R2474S/+ mice were treated with isoproterenol (ISO) and DEX, and electrocardiograms were continuously monitored during both in vivo and ex vivo experiments. Dual-dye optical mapping was used to explore the anti-arrhythmic mechanism of DEX. RESULTS: DEX significantly reduced the occurrence and duration of ISO-induced of VT/VF in RyR2R2474S/+ mice in vivo and ex vivo. DEX remarkably prolonged action potential duration (APD80) and calcium transient duration (CaTD80) in both RyR2R2474S/+ and WT hearts, whereas it reduced APD heterogeneity and CaT alternans in RyR2R2474S/+ hearts. DEX inhibited ectopy and reentry formation, and stabilized voltage-calcium latency. CONCLUSION: DEX exhibited an antiarrhythmic effect through stabilizing membrane voltage and intracellular Ca2+. DEX can be used as a beneficial perioperative anesthetic for patients with CPVT or other tachy-arrhythmias.

Lactic acid bacteria modulate the CncC pathway to enhance resistance to ß-cypermethrin in the oriental fruit fly.

The gut microbiota of insects has been shown to regulate host detoxification enzymes. However, the potential regulatory mechanisms involved remain unknown. Here, we report that gut bacteria increase insecticide resistance by activating the cap "n" collar isoform-C (CncC) pathway through enzymatically generated reactive oxygen species (ROS) in Bactrocera dorsalis. We demonstrated that Enterococcus casseliflavus and Lactococcus lactis, two lactic acid-producing bacteria, increase the resistance of B. dorsalis to ß-cypermethrin by regulating cytochrome P450 (P450) enzymes and α-glutathione S-transferase (GST) activities. These gut symbionts also induced the expression of CncC and muscle aponeurosis fibromatosis. BdCncC knockdown led to a decrease in resistance caused by gut bacteria. Ingestion of the ROS scavenger vitamin C in resistant strain affected the expression of BdCncC/BdKeap1/BdMafK, resulting in reduced P450 and GST activity. Furthermore, feeding with E. casseliflavus or L. lactis showed that BdNOX5 increased ROS production, and BdNOX5 knockdown affected the expression of the BdCncC/BdMafK pathway and detoxification genes. Moreover, lactic acid feeding activated the ROS-associated regulation of P450 and GST activity. Collectively, our findings indicate that symbiotic gut bacteria modulate intestinal detoxification pathways by affecting physiological biochemistry, thus providing new insights into the involvement of insect gut microbes in the development of insecticide resistance.

Evaluation of Melatonin Therapy in Patients with Myocardial Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis.

Objectives: We conducted a meta-analysis to quantitatively evaluate the effect of melatonin therapy on patients with myocardial ischemia-reperfusion injury (MIRI) and explore the influencing factors. Background: Although preclinical studies have shown that melatonin can alleviate MIRI, its protective effect on MIRI in patients remains controversial. Methods: We searched PubMed, the Cochrane Library, and Embase. The primary outcome was cardiac function (left ventricular ejection fraction [LVEF], left ventricular end-diastolic volume [LVEDV], and left ventricular end-systolic volume [LVESV]) and myocardial infarct parameters (total left ventricular mass and infarct size). Results: We included nine randomized controlled clinical trials with 631 subjects. Our results showed that melatonin had no significant effects on the primary outcome, but subgroup analyses indicated that when melatonin was administered by intravenous and intracoronary injection at the early stage of myocardial ischemia, LVEF was improved (<3.5 h; standardized mean difference [SMD]:0.50; 95% CI: 0.06 to 0.94; P = 0.03) and the infarct size was reduced (<2.5 h, SMD: -0.86; 95% CI: -1.51 to -0.22; P = 0.01), whereas when melatonin was injected at the late stage of myocardial ischemia (≥3.5 h or 2.5 h), the results were the opposite. Furthermore, melatonin intervention reduced the level of cardiac injury markers, inflammatory cytokines, oxidation factors, and increased the level of antioxidant factors (P < 0.001). Conclusions: The results indicated that the cardioprotective function of melatonin for MIRI was influenced by the route and timing regimen of melatonin administration; the mechanism of which may be associated with the production of inflammatory cytokines, the balance of oxidation, and antioxidant factors.

Efficacy of cognitive therapy and behavior therapy for menopausal symptoms: a systematic review and meta-analysis.

BACKGROUND: T long-term effects of cognitive therapy and behavior therapy (CTBT) for menopausal symptoms are unknown, and whether the effects are different between natural menopause and treatment-induced menopause are currently unclear. Therefore, we sought to conduct an accurate estimate of the efficacy of CTBT for menopausal symptoms. METHODS: We conducted searches of Cochrane Library, EMBASE, PsycINFO, PubMed, and Web of Science databases for studies from 1 January 1977 to 1 November 2021. Randomized controlled trials (RCTs) comparing intervention groups to control groups for menopausal symptoms were included. Hedge's g was used as the standardized between-group effect size with a random-effects model. RESULTS: We included 14 RCTs comprising 1618 patients with a mean sample size of 116. CTBT significantly outperformed control groups in terms of reducing hot flushes [g = 0.39, 95% confidence interval (CI) 0.23-0.55, I2 = 45], night sweats, depression (g = 0.50, 95% CI 0.34-0.66, I2 = 51), anxiety (g = 0.38, 95% CI 0.23-0.54, I2 = 49), fatigue, and quality of life. Egger's test indicated no publication bias. CONCLUSIONS: CTBT is an effective psychological treatment for menopausal symptoms, with predominantly small to moderate effects. The efficacy is sustained long-term, although it declines somewhat over time. The efficacy was stronger for natural menopause symptoms, such as vasomotor symptoms, than for treatment-induced menopause symptoms. These findings provide support for treatment guidelines recommending CTBT as a treatment option for menopausal symptoms.

Meta-analysis of sleep deprivation effects on depression in rodents.

OBJECTIVE: To our knowledge, the relationship of sleep deprivation (SD) and depression on the rodents remains unclear. In this article, we performed a meta-analysis to provide a comprehensive evaluation of the experimental effects of SD on rodents and explore the heterogeneous factors that may be associated with outcomes. METHODS: PubMed, Embase, the Cochrane Library, and Web of Science were searched for articles before January 5th, 2022. The strains of rodents, SD method, and depression measurement tools were recorded. Standardized mean differences based on Hedge's g were calculated as measures of the effect size. RESULTS: In total, 19 studies involving 51 trials were included. The overall data suggested that SD had a large effect on exacerbating depression-like behaviors, but there was high heterogeneity [-1.09 (-1.57, -0.62); I2 = 90.3%; P < 0.05]. Subgroup analysis showed that tail suspension test better reflected the effect of SD in exacerbating depression-like behavior [-3.677 (-4.758, -2.597); I2 = 56.7%; P = 0.001] than forced swimming test [-0.821 (-1.439, -0.203); I2 = 91%; P = 0.009] and sucrose preference test [-1.033 (-1.709, -0.358); I2 = 81.6%; P = 0.003]. CONCLUSION: This study found that SD worsened depression-like behaviors by tail suspension test. Our results also indicated that the effects of SD on depression in rodents were related to different assessment methods, strains, SD methods and SD types.

Meta-Analysis of Sleep Deprivation Effects on Patients With Depression.

Objective: Depression is a common disorder with a high recurrence rate. Since the effect of sleep deprivation on depression in existing studies were inconsistent, the present study aimed to reassess the effects of SD on patients by performing a meta-analysis of updated research. Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched for articles before January 20th, 2021. Data on participant characteristics, SD characteristics, adjunctive method and tests for depression were extracted. A comprehensive analysis was conducted to assess the effect of SD on depression and subgroup analysis was used to determine the sources of heterogeneity. Results: In total, 8 articles were included. An SD time of <7 days slightly worsened depression levels [0.24 (-0.21, 0.69); I 2 = 0%; P = 0.43], a time of 7-14 days had antidepressant effects [-1.52 (-2.07, -0.97); I 2 = 19.6%; P = 0.288], and a time of more than 14 days also worsened depression [0.76 (0.12, 1.40); I 2 = 43.7%; P = 0.169]. Conclusion: SD may serve as an effective antidepressant measure in humans when the time was 7-14 days, while a time of <7 days and more than 14 days worsened depression.

Efficacy of Cognitive Behavioral Therapy on Mood Disorders, Sleep, Fatigue, and Quality of Life in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Objective: The aim of this study was to perform a quantitative analysis to evaluate the efficacy of cognitive behavioral therapy (CBT) on mood disorders, sleep, fatigue, and its impact on quality of life (QOL) in Parkinson's Disease (PD). Methods: We searched for randomized controlled trials in three electronic databases. Fourteen studies, including 507 patients with PD, met the inclusion criteria. We determined the pooled efficacy by standard mean differences and 95% confidence intervals, using I 2 to reveal heterogeneity. Results: The result showed CBT had a significant effect on depression [-0.93 (95%CI, -1.19 to -0.67, P < 0.001)] and anxiety [-0.76 (95%CI, -0.97 to -0.55, P < 0.001)]. Moderate effect sizes were noted with sleep disorders [-0.45 (95% CI, -0.70 to -0.20, P = 0.0004)]. There was no evident impact of CBT on fatigue or QOL. We found an intervention period >8 weeks was advantageous compared with <8 weeks, and CBT implemented in non-group was more effective than in group. Between the delivery methods, no significant difference was found. Conclusion: We found that CBT in patients with PD was an efficacious therapy for some non-motor symptoms in PD, but not efficacious for fatigue and QOL. These results suggest that CBT results in significant improvement in PD and should be used as a conventional clinical intervention.

Probiotics treatment improves cognitive impairment in patients and animals: A systematic review and meta-analysis.

The gut-brain axis has received considerable attention in recent years, and the "psychobiotics" concept indicates that probiotics have a potential positive effect on cognitive function. Therefore, the aim of this study was to quantitatively evaluate the influence of probiotics on cognition. We conducted a random-eff ;ects meta-analysis of 7 controlled clinical trials and 11 animals studies to evaluate the eff ;ects of probiotics on cognitive function. Probiotics supplementation enhanced cognitive function in both human (0.24 [0.05-0.42]; I2 = 0 %) and animal studies (0.90 [0.47-1.34]; I2 = 74 %). Subgroup analyses indicated that the effects of probiotics on cognitively impaired individuals (0.25 [0.05-0.45]; I2 = 0 %) were greater than those on healthy ones (0.15 [-0.30 to 0.60]; I2 = 0 %). Furthermore, compared with a multiple-probiotic supplement, a single strain of probiotics was more effective in humans. The meta-analysis provided some suggestions for probiotics intervention and tended to support a customized approach for different individuals to ameliorate cognitive disorders. Future additional clinical trials are necessary to evaluate therapeutic effect and influencing factors.

Does tachyphylaxis occur in long-term management of scalp seborrheic dermatitis with pyrithione zinc-based treatments?

BACKGROUND: Scalp seborrheic dermatitis and dandruff (SD/D) are chronic conditions requiring long-term treatment. There is a common belief that patients frequently experience decreasing benefits over time when using a single product. This physiologic accommodation is termed tachyphylaxis. AIM: To systematically investigate the anecdotal belief that tachyphylaxis occurs in long-term treatment of SD/D using quantitative clinical assessments. METHODS: An international questionnaire completed by 722 dermatologists assessed the belief of tachyphylaxis incidence with pyrithione zinc (PTZ)-based shampoos, time course, occurrence relative to active ingredients, and effect of switching products. Two double-blind, randomized, clinical evaluations were conducted, 24- and 48-week studies, whereby a 1% PTZ shampoo, a 2% PTZ shampoo, or a matched placebo control shampoo was used by each subject for the duration of the study. Dermatologists assessed the adherent scalp flaking (scale of 0-10) at baseline and at specified intervals. RESULTS: Sixty-four per cent of responding dermatologists believed tachyphylaxis occurred with PTZ products, and most felt that tachyphylaxis occurred within 3 months of use. Evaluation of mean treatment responses vs. placebo and individual responses as a function of study duration showed a consistent benefit for all products at all time points; therefore, no evidence for tachyphylaxis was found (within 48 weeks of treatment). CONCLUSION: No evidence for tachyphylaxis in SD/D treatment by PTZ-based shampoos was found. Compliance could explain the decreasing response rate seen over time; the solution is to choose an affordable therapeutic product that is effective long term without cosmetic trade-offs.

Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles.

BACKGROUND & AIMS: The aim of this study was to compare the response of symptoms and cytokine ratios in irritable bowel syndrome (IBS) with ingestion of probiotic preparations containing a lactobacillus or bifidobacterium strain. METHODS: Seventy-seven subjects with IBS were randomized to receive either Lactobacillus salivarius UCC4331 or Bifidobacterium infantis 35624, each in a dose of 1 x 10 10 live bacterial cells in a malted milk drink, or the malted milk drink alone as placebo for 8 weeks. The cardinal symptoms of IBS were recorded on a daily basis and assessed each week. Quality of life assessment, stool microbiologic studies, and blood sampling for estimation of peripheral blood mononuclear cell release of the cytokines interleukin (IL)-10 and IL-12 were performed at the beginning and at the end of the treatment phase. RESULTS: For all symptoms, with the exception of bowel movement frequency and consistency, those randomized to B infantis 35624 experienced a greater reduction in symptom scores; composite and individual scores for abdominal pain/discomfort, bloating/distention, and bowel movement difficulty were significantly lower than for placebo for those randomized to B infantis 35624 for most weeks of the treatment phase. At baseline, patients with IBS demonstrated an abnormal IL-10/IL-12 ratio, indicative of a proinflammatory, Th-1 state. This ratio was normalized by B infantis 35624 feeding alone. CONCLUSIONS: B infantis 35624 alleviates symptoms in IBS; this symptomatic response was associated with normalization of the ratio of an anti-inflammatory to a proinflammatory cytokine, suggesting an immune-modulating role for this organism, in this disorder.