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A large number of drugs have been implicated in causing depression by case reports and case series. For a few specific drugs, the association has subsequently been confirmed by appropriately designed studies. In other instances, a lack of substantiating evidence has lead to a gradual disappearance of concern about a potential association. The benzodiazepines represent a deviation from this pattern: they are widely believed to cause depression, but there is a lack of evidence to substantiate this claim. In DSM-IV, there is a category of mood disorder for drug-induced depression (substance-induced mood disorder), and the text of the manual specifically refers to benzodiazepines as a potential cause. Despite the apparently entrenched nature of this belief, there continues to be a lack of credible evidence that benzodiazepines can cause depression as a side effect.     

Insights into the pathogenesis of ATP1A1‐related CMT disease using patient‐specific iPSCs

The development of patient‐specific induced pluripotent stem cells (iPSCs) offered interesting insights in modeling the pathogenesis of Charcot‐Marie‐Tooth (CMT) disease and thus we decided to explore the phenotypes of iPSCs derived from a single CMT patient carrying a mutant ATP1A1 allele (p.Pro600Ala). iPSCs clones generated from CMT and control fibroblasts, were induced to differentiate into neural precursors and then into post‐mitotic neurons. Control iPSCs differentiated into neuronal precursors and then into post‐mitotic neurons within 6‐8 days. On the contrary, the differentiation of CMT iPSCs was clearly defective. Electrophysiological properties confirmed that post‐mitotic neurons were less mature compared to the normal counterpart. The impairment of in vitro differentiation of CMT iPSCs only concerned with the neuronal pathway, because they were able to differentiate into mesendodermal cells and other ectodermal derivatives. ATP1A1 was undetectable in the few neuronal cells derived from CMT iPSCs. ATP1A1 gene mutation (p.Pro600Ala), responsible for a form of axonal CMT disease, is associated in vitro with a dramatic alteration of the differentiation of patient‐derived iPSCs into post‐mitotic neurons. Thus, the defect in neuronal cell development might lead in vivo to a decreased number of mature neurons in ATP1A1‐CMT disease.     

Facile Fabrication of Fluorescent Cellulose with Aggregation-Induced Emission Characteristic in a CO2 Switchable Solvent

Fabrication of fluorescent cellulose with aggregation-induced emission (AIE) characteristics is usually achieved by grafting tetraphenylethylene (TPE) to the cellulose backbone using TPE derivatives with highly active functional groups such as carboxylic, isothiocyanate, and alkynyl groups. However, besides the complicated synthetic routes of these TPE derivatives, conversion of hydroxyl groups in the cellulose chain to more reactive groups such as amine or azide groups is usually involved, and the resulting products have a degree of substitution (DS) of TPE lower than 0.08. Herein, a facile one-pot strategy for the grafting of a TPE group to the cellulose backbone with high DS of up to 0.22 in a CO₂ switchable solvent under mild reaction conditions is reported. The hydroxyl groups in the cellulose are in situ converted to cellulose carbonate intermediately during the dissolution step. Subsequently, nucleophilic substitution between the intermediate and a halogenated TPE derivative with bromine atom as leaving group is carried out to achieve the effective grafting of TPE. The synthetic route for this promising TPE derivative is much more convenient than those of TPE derivatives reported in previous studies. This work suggests a new and facile pathway for the synthesis of high-emission fluorescent cellulose with AIE functionality.     

A study to evaluate the hepatoprotective effect of N- acetylcysteine on anti tuberculosis drug induced hepatotoxicity and quality of life

BackgroundDrug induced liver injury (DILI) is a serious adverse effect caused by first-line anti-TB (ATT) drugs, limiting the TB-treatment. The tissue inflammation induced by free radical burst and poor dietary intake in TB induces oxidative stress, which was proposed as one of the mechanisms responsible for ATT induced DILI. N-acetylcysteine (NAC) exerts a hepato-protective effect by enhancing the cellular antioxidant defense mechanism. There are few studies evaluating the effect of NAC on ATT induced DILI in Indian-population.MethodsThis is a prospective, randomized, double-blind, placebo-controlled, parallel-group study. Thirty-eight newly diagnosed TB patients on first-line ATT with normal liver function test (LFT) were recruited and randomized to receive either NAC 600 mg tablet or placebo twice daily for 4 weeks and followed-up for next 4 weeks. LFT [AST, ALT, ALP and Total bilirubin] was assessed at baseline, 2, 4 and 8 weeks. Oxidative-stress biomarkers [Malondialdehyde (MDA), Nitric Oxide (NO), Glutathione (GSH)] and quality of life (QOL) by SF-36 questionnaire were assessed at baseline, 4 and 8 weeks. Adverse Drug Reactions (ADRs) were monitored at every visit. Compliance was assessed by pill-count method.ResultsBaseline characteristics were homogenous among both the groups. In the NAC group, there was significant reduction in ALT (p < 0.01), ALP (p < 0.01), total bilirubin (p < 0.001) at 4 weeks compared to baseline. AST, MDA and NO showed a reduction of 19%, 21.6% and 5.5% respectively from baseline and GSH at showed an increase of 2.6% from baseline at 4 weeks in the NAC group, however these were not statistically significant. These effects in LFT and oxidative biomarkers persisted even at the end of 8 weeks.Significant improvement from baseline in QOL was observed in both the groups (p < 0.05). Between group analysis showed, significant reduction in ALT (p < 0.05) and AST (p < 0.05) in NAC group at 4 weeks, whereas bilirubin, MDA, NO and GSH showed improvement at 4 weeks compared to placebo in NAC group, however it was not statistically significant. This improvement in the LFT and oxidative biomarkers continued even at the end of 8 weeks. Itching and rashes were the most common ADRs, with similar incidence in both the groups. Compliance to treatment was good in both the groups.ConclusionSignificant improvement in liver function parameters is suggestive of hepatoprotective effect of NAC. This observed effect at 4 weeks was found to be persistent at 8 weeks, which signifies prolonged hepato-protective effect of NAC. Long duration studies with large sample size are required for further confirmation of hepato-protective action of NAC.     

Spatial correlation of left atrial low voltage substrate in sinus rhythm versus atrial fibrillation: The rhythm specificity of atrial low voltage substrate

Introduction

Improved sinus rhythm (SR) maintenance rates have been achieved in patients with persistent atrial fibrillation (AF) undergoing pulmonary vein isolation plus additional ablation of low voltage substrate (LVS) during SR. However, voltage mapping during SR may be hindered in persistent and long-persistent AF patients by immediate AF recurrence after electrical cardioversion. We assess correlations between LVS extent and location during SR and AF, aiming to identify regional voltage thresholds for rhythm-independent delineation/detection of LVS areas. (1) Identification of voltage dissimilarities between mapping in SR and AF. (2) Identification of regional voltage thresholds that improve cross-rhythm substrate detection. (3) Comparison of LVS between SR and native versus induced AF.

Methods

Forty-one ablation-naive persistent AF patients underwent high-definition (1 mm electrodes; >1200 left atrial (LA) mapping sites per rhythm) voltage mapping in SR and AF. Global and regional voltage thresholds in AF were identified which best match LVS < 0.5 mV and <1.0 mV in SR. Additionally, the correlation between SR-LVS with induced versus native AF-LVS was assessed.

Results

Substantial voltage differences (median: 0.52, interquartile range: 0.33–0.69, maximum: 1.19 mV) with a predominance of the posterior/inferior LA wall exist between the rhythms. An AF threshold of 0.34 mV for the entire left atrium provides an accuracy, sensitivity and specificity of 69%, 67%, and 69% to identify SR-LVS < 0.5 mV, respectively. Lower thresholds for the posterior wall (0.27 mV) and inferior wall (0.3 mV) result in higher spatial concordance to SR-LVS (4% and 7% increase). Concordance with SR-LVS was higher for induced AF compared to native AF (area under the curve[AUC]: 0.80 vs. 0.73). AF-LVS < 0.5 mV corresponds to SR-LVS < 0.97 mV (AUC: 0.73).

Conclusion

Although the proposed region-specific voltage thresholds during AF improve the consistency of LVS identification as determined during SR, the concordance in LVS between SR and AF remains moderate, with larger LVS detection during AF. Voltage-based substrate ablation should preferentially be performed during SR to limit the amount of ablated atrial myocardium.     

艾司氯胺酮在无痛人工流产术中的临床应用

目的 采用改良序贯测定艾司氯胺酮抑制无痛人工流产术体动反应的半数有效剂量(ED50),并观察艾司氯胺酮在无痛人工流产术中的临床应用效果和不良反应。方法 选取2021年9月至2021年11月在延安市人民医院择期行无痛人工流产术且ASA I～Ⅱ级的26例患者。采用改良序贯法操作,艾司氯胺酮的初始剂量为0.3 mg/kg,相邻患者剂量差0.05 mg/kg,若上一例患者术中发生体动反应(扭臀、抬手、动腿)影响手术操作为阳性,则下一例患者增加0.05 mg/kg,反之减少0.05 mg/kg,直至出现7个拐点结束研究。计算艾司氯胺酮抑制体动反应的ED50、ED95及95%可信区间(CI),记录苏醒时间、苏醒后5 min视觉模拟评分法(VAS)疼痛评分,记录低血压、呼吸抑制(SpO₂<90%)、术后谵妄、恶心呕吐、分泌物增加等不良反应发生情况。结果 艾司氯胺酮抑制人工流产手术体动反应的ED50为0.294(95%CI:0.256～0.332)mg/kg, ED95为0.370(95%CI:0.332～0.590)mg/kg,苏醒时间(11.3±1.2)min,苏醒后5...     

生脉胶囊对5-氟尿嘧啶致小鼠化疗性肠黏膜炎的保护作用研究

[目的]探讨生脉胶囊对5-氟尿嘧啶(5-FU)诱导的小鼠结肠黏膜损伤的保护作用。[方法]将20只雄性Balb/c小鼠随机分为正常组、模型组、生脉组。除正常组外,其余2组均采用腹腔注射5-FU(25 mg/kg)诱导建立结肠黏膜损伤小鼠模型。正常组和模型组每日灌胃等量蒸馏水,生脉组每日灌胃等量生脉胶囊悬液(350 mg/kg)。每日监测小鼠体质量和腹泻情况;测量小鼠结肠长度;检测小鼠血清中二胺氧化酶(DAO)活性;苏木精-伊红染色法(HE)观察结肠的组织病理变化;免疫组化法检测小鼠结肠黏膜中ki67表达水平;过典酸雪夫氏染色法(PAS)检测小鼠结肠黏膜中杯状细胞数量。[结果]与模型组比较,生脉组腹泻情况得到明显改善;结肠长度显著增加(P＜0.05);血清中DAO活性显著下降(P＜0.01);结肠黏膜结构明显改善;结肠黏膜中ki67表达显著增加(P＜0.000 1);杯状细胞数量明显增加。[结论]生脉胶囊对5-FU诱导的结肠黏膜损伤具有明显的保护作用。