Repeated

重复
  • 文章类型: Systematic Review
    背景:当与手术相关的风险超过潜在益处时,立体定向放射外科是治疗脑动静脉畸形(AVM)的首选选择。然而,一些患者在第一次手术后由于残留的AVM而需要再次进行放射外科治疗.本系统评价和荟萃分析旨在探讨反复手术治疗AVM的安全性和有效性。
    方法:根据PRISMA指南进行系统评价。搜索是在PubMed上进行的,Scopus,Embase,和WebofScience,使用预先设计的搜索字符串。包括研究首次单次放射外科手术后重复放射外科手术对残留AVM的疗效的研究。使用JBI工具评估偏倚风险。进行荟萃分析和met回归分析以收集和检查数据。
    结果:我们的荟萃分析,平均随访45.57个月,揭示了重复放射外科手术作为动静脉畸形(AVM)的可行选择,达到60.82%的消失率,平均消失时间为33.18个月。元回归将AVM体积和Spetzler-Martin(SM)等级确定为影响闭塞的因素,较小的体积和较低的SM等级与较高的费率相关。并发症包括10.33%的辐射引起的变化,5.26%放射外科术后出血,2.56%神经缺陷,和0.67%的囊肿形成。并发症的异质性主要归因于男性比例和SM等级,而影响放射外科术后出血的因素仍不清楚。放射外科的类型,无论是伽玛刀放射外科(GKRS)还是LINAC,不会显著影响结果。
    结论:重复放射外科手术是可行的,有效,以及初始放射外科失败后AVM的安全治疗。当用于适当的患者亚组时,它提供了可接受的风险-收益概况。需要进行特征研究以阐明其明确的适应症。
    BACKGROUND: Stereotactic radiosurgery is the preferred option for treating brain arteriovenous malformation (AVM) when the risks associated with surgery outweigh the potential benefits. However, some patients require repeat radiosurgery due to residual AVM after the first procedure. This systematic review and meta-analysis aimed to investigate the safety and efficacy of repeated procedure of radiosurgery for AVM.
    METHODS: A systematic review was conducted according to the PRISMA guideline. The search was conducted on PubMed, Scopus, Embase, and Web of Science, using a pre-designed search string. Studies investigating the efficacy of repeat radiosurgery for residual AVM following initial single session radiosurgery were included. The risk of bias was assessed using the JBI tool. Meta-analysis and met-regression were performed to pool and inspect data.
    RESULTS: Our meta-analysis, with a mean follow-up of 45.57 months, reveals repeat radiosurgery as a viable option for arteriovenous malformations (AVMs), achieving a 60.82% obliteration rate with a mean time to obliteration of 33.18 months. Meta-regression identifies AVM volume and Spetzler-Martin (SM) grade as factors influencing obliteration, with smaller volume and lower SM grades associated with higher rates. Complications include 10.33% radiation-induced changes, 5.26% post-radiosurgery hemorrhage, 2.56% neurologic deficits, and 0.67% cyst formation. Heterogeneity in complications is primarily attributed to male proportion and SM grade, while factors influencing post-radiosurgery hemorrhage remain unclear. The type of radiosurgery, whether Gamma Knife Radiosurgery (GKRS) or LINAC, does not significantly impact outcomes.
    CONCLUSIONS: Repeat radiosurgery is a feasible, effective, and safe treatment for AVMs following failure of initial radiosurgery. When utilized in appropriate patient subgroups, it provides an acceptable risk-to-benefit profile. Feature studies are required to clarify its clear indications.
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  • 文章类型: Journal Article
    目的:本研究的目的是确定成功率,疾病控制的持续时间,以及反复扳机指反复注射皮质类固醇成功的预测因素。
    方法:这项前瞻性队列研究涉及有反复触发指和皮质类固醇注射史的患者。总共114名患者接受了反复的皮质类固醇注射治疗,并随访了12个月。关于人口特征的数据,合并症条件,并比较了从病历回顾和患者直接访谈中获得成功治疗的可能预测因素。患者分为成功或失败组,三,六,在初次注射后12个月。采用多变量logistic回归分析假设预测因子与重复注射皮质类固醇后成功或失败之间的关系。
    结果:重复注射可的松后的总体成功率,三,六,12个月为97.4%,84.2%,68.4%,和49.1%,分别。多变量逻辑回归模型显示,高等级疾病(基于Quinnell系统的III级或IV级),体重指数(BMI)≥25kg/m2,以及先前注射后的无症状期短(<6个月)是症状复发的强预测因子(比值比=3.6[95%CI1.5-8.4],比值比=2.5[95%CI1.1-5.9],比值比=1.8[95%CI1.1-3.0],分别)。根据危险因素的数量,患者1年的平均成功率如下:三个危险因素中没有一个,73.3%;一个危险因素,54.2%至63.6%(III-IV级触发为54.2%,BMI≥25kg/m2为63.6%,<6个月无症状期为63.6%);两个危险因素,30%至75%(III-IV级和BMI≥25kg/m2的组合为30%,II-IV级和<6个月期间为45.5%,和75%,其中<6个月期和BMI≥25kg/m2);以及所有三个危险因素,11.8%。
    结论:对于喜欢非手术治疗的患者,应考虑反复注射皮质类固醇激素治疗,尤其是那些没有预测失败因素的人。
    方法:预后II.
    OBJECTIVE: The aim of this study was to determine the success rate, duration of disease control, and predictive factors of success of repeated corticosteroid injections for recurrent trigger finger.
    METHODS: This prospective cohort study involved patients who had recurrent trigger finger and a history of corticosteroid injections. A total 114 patients were treated with repeated corticosteroid injections and followed for 12 months. Data on demographic characteristics, comorbid conditions, and possible predictive factors for successful treatment from medical chart reviews and direct patient interviews were compared. Patients were classified into success or failure groups at one, three, six, and 12 months after the initial injection. The relationship between hypothesized predictors and success or failure after repeated corticosteroid injection was analyzed with multivariable logistic regression.
    RESULTS: The overall success rates from repeated cortisone injections after one, three, six, and 12 months were 97.4%, 84.2%, 68.4%, and 49.1%, respectively. Multivariable logistic regression modeling revealed that a high grade of disease (grade III or IV based on the Quinnell system), a body mass index (BMI) ≥ 25 kg/m2, and a short symptom-free period (< six months) after a previous injection were strong predictors of symptom recurrence (odds ratio = 3.6 [95% CI 1.5-8.4], odds ratio = 2.5 [95% CI 1.1-5.9], and odds ratio = 1.8 [95% CI 1.1-3.0], respectively). The average success rates for patients at 1-year according to the number of risk factors were as follows: none of the three risk factors, 73.3%; one risk factor, 54.2% to 63.6% (54.2% for grade III-IV triggering, 63.6% for BMI ≥ 25 kg/m2 and 63.6% for < 6-month symptom-free period); two risk factors, 30% to 75% (30% for a combination of grade III-IV and BMI ≥ 25 kg/m2, 45.5% with grade II-IV and < 6-month period, and 75% with a combination of < 6-month period and BMI ≥ 25 kg/m2); and all three risk factors, 11.8%.
    CONCLUSIONS: Repeated corticosteroid injections for recurrent trigger finger should be considered in patients who prefer nonsurgical treatment, especially in those without factors predictive of failure.
    METHODS: Prognostic II.
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  • 文章类型: Randomized Controlled Trial
    背景:脉冲场消融(PFA)用于重做手术的功效未知。
    目的:在本研究中,作者旨在评估PFA相对于慢性RFA(重做环境)进行PFA时的有效性.
    方法:这是一项3步体内研究。在步骤1(创建重做环境)中,6头猪在3个不同部位接受了射频消融(RFA),使用局部阻抗测量导管和带接触力的导管:右心房(RA)(有故意间隙的腔内线),左心房(LA)(肺静脉隔离[PVI]有故意间隙和浅层后壁消融),和左心室(LV)(短RFA应用[慢性RFA])。在步骤2(再消融)中,在~5周的生存期后,动物如下进行治疗:在RA中,先前腔内线上方的局灶性PFA导管;在LA中,使用pentasplinePFA导管的PVI;在LV中,将动物随机分配至局灶性PFA或RFA。在每一只手臂上,进行了2种类型的病变:急性或急性慢性。在步骤3(重新映射和安乐死)中,在额外的3到5天之后,所有动物被重新映射并处死。
    结果:在RA中,用PFA再次消融导致所有动物完全的腔室间阻滞,将不同的慢性RFA病变从4至7mm的宽度(慢性RFA)扩展和均质化到16至28mm的宽度(PFA超过慢性RFA)。在洛杉矶,用PFA重新消融导致完全PVI和PW的透壁消融。在LV中,急性RFA的平均深度(2-5天生存后)为7.6±1.3mm,而急性超过慢性RFA病变的平均深度为3.9±1.6mm(P<0.01)。相比之下,急性PFA的平均深度为7.0±1.6mm,与使用PFA消融而使用RFA消融时相似(7.1±1.3mm;P=0.94)。
    结论:PFA对于先前RFA后的消融非常有效,这对出现重做手术的患者可能是有益的。在心室,在消融慢性浅表RFA病变时,PFA导致的病变比RFA更深。
    BACKGROUND: The efficacy of pulsed field ablation (PFA) for redo procedures is unknown.
    OBJECTIVE: In this study, the authors aimed to evaluate the effectiveness of PFA when performing PFA over chronic RFA (redo environment).
    METHODS: This was a 3-step in vivo study. In step 1 (creation of redo environment), 6 swine underwent radiofrequency ablation (RFA) with a local impedance measuring catheter and a contact force-enabled catheter in 3 different sites: the right atrium (RA) (intercaval line with intentional gaps), the left atrium (LA) (pulmonary vein isolation [PVI] with intentional gaps and superficial posterior wall ablations), and the left ventricle (LV) (short RFA applications [chronic RFA]). In step 2 (re-ablation), following a survival period of ≈5 weeks, animals were retreated as follows: in the RA, a focal PFA catheter over the prior intercaval line; in the LA, PVI using a pentaspline PFA catheter; and in the LV, animals were randomized to focal PFA or RFA. In each arm, 2 types of lesions were performed: acute or acute over chronic. In step 3 (remapping and euthanization), following an additional 3 to 5 days, all animals were remapped and sacrificed.
    RESULTS: In the RA, re-ablation with PFA resulted in a complete intercaval block in all animals, expanding and homogenizing the disparate chronic RFA lesions from a width of 4 to 7 mm (chronic RFA) to a width of 16 to 28 mm (PFA over chronic RFA). In the LA, re-ablation with PFA resulted in complete PVI and transmural ablation of the PW. In the LV, the mean depth for acute RFA (post 2-5 days survival) was 7.6 ± 1.3 mm vs 3.9 ± 1.6 mm in the acute over chronic RFA lesions (P < 0.01). In contrast, the mean depth for acute PFA was 7.0 ± 1.6 mm, similar to when ablating with PFA over RFA (7.1 ± 1.3 mm; P = 0.94).
    CONCLUSIONS: PFA is highly efficient for ablation following prior RFA, which may be beneficial in patients presenting for redo procedures. In the ventricle, PFA resulted in lesions that are deeper than RFA when ablating over chronic superficial RFA lesions.
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  • 文章类型: Journal Article
    目的:这项工作的目的是评估光活化发色团重复治疗角膜炎交联(PACK-CXL)窗吸收(WA)的安全性和有效性。耐药性细菌性角膜炎(BK)。
    方法:这是一项回顾性临床队列研究。30眼临床怀疑和实验室证实的细菌性角膜炎,纳入标准抗微生物疗法(SAT)和一组PACK-CXLWA后,对适当抗生素疗法耐药2周,上皮形成失败4周.如果在PACK-CXL的第一个会话之后,在临床检查和AS-OCT上,角膜溃疡和基质浸润的大小减少以及上皮化的开始方面开始改善,一周后进行了另一次PACK-CXLWA,等等,直到细菌性角膜炎的完全愈合和解决,并通过细菌培养阴性证实。微生物的鉴定通过治疗前后的实验室研究完成。通过角膜检查和眼前节OCT(AS-OCT)评估角膜愈合。
    结果:本研究招募了30例患者的30只眼。他们是16名男性和14名女性,他们的平均年龄是44.3±5.38岁.平均溃疡大小为3.96±1.87(mm3),基质浸润的平均大小为4.52±2.24(mm3)。PACK-CXLWA治疗30只眼平均进行2.87次。在27眼(90%)的病例中观察到完全愈合和消退(成功治疗),仅在3眼(10%)中观察到上皮形成失败。据报道,90%的眼睛在术后第二个月完全角膜愈合。
    结论:PACK-CXLWA可能是有希望的,耐药性细菌性角膜炎的非侵入性治疗选择。其可与标准抗微生物处理(SAT)具有协同作用。此外,它可以克服在世界范围内迅速传播的抗生素耐药性。PACK-CXLWA的重复疗程可能比单个疗程更有效地治疗耐药性细菌性角膜炎,直到BK的完全上皮化和消退。然而,需要进一步的前瞻性和比较研究来支持结果.
    OBJECTIVE: The aim of this work is to evaluate the safety and efficacy of repeated sessions of photo-activated chromophore for keratitis-cross linking (PACK-CXL) window absorption (WA) for the treatment of resistant bacterial keratitis (BK).
    METHODS: This is a retrospective clinical cohort study. Thirty eyes with clinically suspected and lab-confirmed bacterial keratitis, resistant to appropriate antibiotic therapy- which was modified by sensitivity reports- for 2 weeks with failure of epithelialization for 4 weeks after the standard anti-microbial therapy (SAT) together with one setting of PACK-CXL WA were included. If after the first session of PACK-CXL, there is a start of improvement in the form of reduction of the size of corneal ulcer and stromal infiltrates together with the start of epithelialization on clinical examination and AS-OCT, another session of PACK-CXL WA was performed after one week, and so on, till the complete healing and resolution of bacterial keratitis and confirmation by negative bacterial culture. Identification of the micro-organisms was done by lab study before and after treatment. Corneal healing was evaluated by corneal examination and anterior segment OCT (AS-OCT).
    RESULTS: Thirty eyes of 30 patients were recruited in this study. They were 16 males and 14 females, their mean age was 44.3 ± 5.38 years. The mean ulcer size was 3.96 ± 1.87 (mm3), while the mean size of stromal infiltrates was 4.52 ± 2.24 (mm3). PACK-CXL WA treatment was performed an average of 2.87 times for the 30 eyes. Complete healing and resolution (Successful treatment) was observed in 27 eyes (90%) of cases and failure of epithelialization was observed only in 3 eyes (10%). Complete corneal healing was reported in the second month postoperatively in 90% of eyes.
    CONCLUSIONS: PACK-CXL WA may be a promising, non-invasive treatment option for resistant bacterial keratitis. It may have a synergistic effect with standard antimicrobial treatment (SAT). Also, it can overcome the antibiotics resistance that has become rapidly spreading worldwide. Repeated sessions of PACK-CXL WA may be more effective for the treatment of resistant bacterial keratitis till complete epithelialization and resolution of BK than a single session with few complications. However, further prospective and comparative studies to support the results are needed.
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  • 文章类型: English Abstract
    The article presents the results of analysis of issue of disability because of ovarian cancer in female population of the Chechen Republic. The object of study was total number of women, for the first time and repeatedly recognized as disabled ones. The analysis was applied to three age groups (the young, the middle aged and the elderly) in 2014-2020. It is established that dynamics of disability was characterized by negative trends of increasing of number of the disabled. The clear-cut age differentiation was revealed:the elderly disabled predominated. The study established that the disabled suffer of persistent malfunction of blood circulation system and of immune system that resulted in such life activity limitations as moving, self-service and work functions. The characteristics of structure of ovarian cancer disability according its severity were established. The disabled with second group of disability prevailed in all age groups. At that, percentage of women with first group of disability was higher in the middle-aged disabled. The results of the study testify actuality of optimization of onco-gynecological screening of female population for the purpose of early detection of risk factors and diagnosis of malignant process at initial stages of development. This is rational way to organ-preserving treatment and medical and social prevention of primary ovarian cancer disability. The results of the study can consider as scientific practical base for both targeted routing of preventive and therapeutic and rehabilitation measures.
    Представлены результаты изучения проблемы инвалидности вследствие рака яичников женского населения в Чеченской Республике. Объект исследования - общий контингент женщин, впервые и повторно признанных инвалидами. Анализ проведен по трем возрастным группам (молодые, среднего возраста и пожилые). Период исследования охватил 2014-2020 гг. Установлено, что динамика инвалидности характеризовалась негативными тенденциями роста численности инвалидов. Выявлена четкая возрастная дифференциация: преобладали инвалиды пожилого возраста. У инвалидов отмечались стойкие нарушения функций системы крови и иммунной системы и обусловленные ими ограничения жизнедеятельности (нарушения способностей к передвижению, самообслуживанию и трудовой деятельности). Установлены особенности структуры инвалидности вследствие рака яичников по тяжести. Во всех возрастных группах преобладали инвалиды со II группой инвалидности, при этом доля женщин с I группой инвалидности была выше среди инвалидов среднего возраста. Результаты исследования свидетельствуют об актуальности оптимизации онкогинекологического скрининга женского населения в плане раннего выявления факторов риска и диагностики злокачественного процесса на начальных этапах развития. Это рациональный путь к органосохраняющему лечению и медико-социальной профилактике первичной инвалидности вследствие рака яичников. Представленные результаты исследования являются научно-практической базой для проведения целенаправленной маршрутизации профилактических, лечебных и реабилитационных мероприятий.
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  • 文章类型: Journal Article
    本研究回顾性评估立体定向放射治疗(SBRT)的疗效,包括重复的SBRT,肝细胞癌。参与者包括2008年12月至2021年12月在广岛大学医院接受SBRT治疗的220例HCC患者。中位总生存期(OS)和无病生存期为52个月(范围,45-64个月)和17个月(范围,14-23个月),分别。5年局部肿瘤复发率为3.4%(95%可信区间(CI),1.3-6.9%)。53例患者接受了重复SBRT(两次,53例;三次,10例;四次,4例;五次,1例)。第一次和第二次SBRT之间的中位间隔为20个月。第一次SBRT的中位OS为76个月(95%CI,50-102个月)。在重复SBRT的患者中,只有1例患者在第二次SBRT后出现局部复发。重复SBRT后6~12个月,白蛋白-胆红素评分显著增加,在同一段和远程段中,但在同一细分市场中增长不明显。在反复接受SBRT治疗的患者中,仅观察到1例3级胆管狭窄。总之,重复SBRT提供了良好的局部控制和低的副作用风险。
    The present study retrospectively evaluated the efficacy of stereotactic body radiation therapy (SBRT), including repeated SBRT, for hepatocellular carcinoma. Participants comprised 220 HCC patients treated with SBRT in Hiroshima University Hospital between December 2008 and December 2021. Median overall survival (OS) and disease-free survival were 52 months (range, 45-64 months) and 17 months (range, 14-23 months), respectively. The 5-year local tumor recurrence rate was 3.4% (95% confidence interval (CI), 1.3-6.9%). Fifty-three patients underwent repeated SBRT (twice, 53 cases; three times, 10 cases; four times, 4 cases; five times, 1 case). Median interval between first and second SBRT was 20 months. Median OS from first SBRT was 76 months (95% CI, 50-102 months). Among patients with repeated SBRT, only one case showed local recurrence after second SBRT. Albumin-bilirubin score increased significantly from 6 to 12 months after repeated SBRT, both in the same segment and in remote segments, but the increase was not significant in the same segment. Only one case of grade 3 bile duct stricture was observed in patients who were treated with repeated SBRT. In conclusion, repeated SBRT provides good local control and a low risk of side effects.
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  • 文章类型: Journal Article
    角膜交联(CXL)已被证明可以通过稳定角膜几何形状和生物力学来治疗进行性圆锥角膜和其他角膜扩张症。然而,患者重复CXL治疗的必要性尚不清楚.本研究旨在探讨猫眼反复加速CXL(A-CXL)后角膜生物力学刚度和角膜组织病理学特征的变化。A-CXL用0.1%核黄素进行10分钟,然后在15只家猫中以30mW/cm2的紫外线A辐射在365nm处3分钟。角膜(n=30)分为三组:一次性加速角膜交联(A-CXL*1组),重复加速角膜交联(A-CXL*2组),和未经治疗的对照组。在A-CXL*2组中,以1个月的间隔重复A-CXL。术前和术后进行体内眼部检查。使用生物酯双轴测试系统进行生物力学分析。我们使用Mooney-Rivlin应变能函数来描述角膜材料的特性。在任何情况下均未观察到A-CXL后的感染。生物力学测试显示,A-CXL两组的应力-应变曲线与对照组比较差异有统计学意义(P<0.01),而A-CXL*2组的应力-应变曲线与A-CXL*1组相似(P>0.05)。术后1个月观察到上皮愈合延迟和浑浊。A-CXL*1组和A-CXL*2组用前谱域光学相干断层扫描测量的基质分界线深度分别为187.6±20.4和197.1±11.5μm,分别为(P>0.05)。这些结果表明A-CXL可以增加猫眼的角膜生物力学。以1个月的间隔用重复的A-CXL处理的猫角膜的生物力学增强与进行一次性A-CXL相似。短时间重复交联程序可能会增加不良反应的风险,在临床应用中应更加谨慎。
    Corneal cross-linking (CXL) has been proved efficiency for treating progressive keratoconus and other corneal ectasia diseases by stabilizing corneal geometry and biomechanics. However, the necessity of repeated CXL treatment in patients is unknown. This study aimed to investigate corneal biomechanical stiffness and change in corneal histopathological characteristics after repeated accelerated CXL (A-CXL) in cat eyes. A-CXL was performed with 0.1% riboflavin applied for 10 min, followed by ultraviolet A irradiation at 30 mW/cm2 for 3 min at 365 nm in 15 domestic cats. Corneas (n = 30) were divided into three groups: one-time accelerated corneal cross-linking (A-CXL*1 group), repeated accelerated corneal cross-linking (A-CXL*2 group), and an untreated control group. In A-CXL*2 group, A-CXL was repeated at 1-month intervals. In vivo ocular examinations were performed pre- and postoperatively. Biomechanical analysis was performed using a biotester biaxial testing system. We used the Mooney-Rivlin strain-energy function to describe corneal material properties. No infection in any case after A-CXL was observed. Biomechanical tests showed that the stress-strain curves of the two A-CXL groups were significantly different from those of the control group (P < 0.01), whereas stress-strain curve of the A-CXL*2 group was similar to that of the A-CXL*1 group (P > 0.05). Delayed epithelial healing and haze were observed 1 month after surgery. Stromal demarcation line depth measured with anterior spectral-domain optical coherence tomography was 187.6 ± 20.4 and 197.1 ± 11.5 μm for the A-CXL*1 and A-CXL*2 groups, respectively (P > 0.05). These results show that A-CXL can increase corneal biomechanics in cat eyes. The biomechanical enhancement of cat corneas treated with repeated A-CXL at 1-month intervals was similar to that of performing a one-time A-CXL. Repeated cross-linking procedures at short intervals may increase the risk of adverse reactions, and more caution should be taken in clinical applications.
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  • 文章类型: Journal Article
    目标:迷幻药引发亲社会,通过神经可塑性的抗抑郁和抗焦虑作用,神经传递和神经免疫调节机制。迷幻药是否会影响大脑内源性大麻素系统及其扩展版本,内源性大麻素(eCBome)或肠道微生物组,仍然未知。
    方法:向成年C57BL/6N雄性小鼠施用麦角酰二乙胺(LSD)或盐水7天。在直接的社交互动和三室测试中评估了社交能力。前额叶皮质和海马内源性大麻素,内源性大麻素样介质和代谢物通过高压液相色谱-串联质谱(HPLC-MS/MS)进行定量。通过HPLC-UV/荧光评估神经递质水平。通过16S核糖体DNA测序研究了肠道微生物组的变化。
    结果:LSD增加了社会偏好和新颖性,并降低了N-酰基乙醇胺N-亚油酰基乙醇胺(LEA)的海马水平,anandamide(N-花生四酰基乙醇胺)和N-二十二碳六酰基乙醇胺(DHEA);单酰基甘油1/2-二十二碳六酰基甘油(1/2-DHG);前列腺素D2(PGD2)和F2α(PGF2α);血栓素2和犬尿氨酸。前额叶eCBome介质和代谢物水平受治疗影响较小。LSD降低了肠道微生物群的Shannonα多样性,防止了在盐水处理的小鼠中观察到的Firmicutes:拟杆菌比率的降低,并改变了细菌类群双歧杆菌的相对丰度,肠杆菌,Dubosiella和RikenellaceaeRC9。
    结论:反复施用LSD引起的亲社会效应伴随着海马eCBome和犬尿氨酸水平的改变,和肠道微生物群的组成。海马eCBome和犬尿氨酸途径的调节可能代表迷幻药化合物引起亲社会效应并影响肠道微生物组的机制。
    Psychedelics elicit prosocial, antidepressant and anxiolytic effects via neuroplasticity, neurotransmission and neuro-immunomodulatory mechanisms. Whether psychedelics affect the brain endocannabinoid system and its extended version, the endocannabinoidome (eCBome) or the gut microbiome, remains unknown.
    Adult C57BL/6N male mice were administered lysergic acid diethylamide (LSD) or saline for 7 days. Sociability was assessed in the direct social interaction and three chambers tests. Prefrontal cortex and hippocampal endocannabinoids, endocannabinoid-like mediators and metabolites were quantified via high-pressure liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Neurotransmitter levels were assessed via HPLC-UV/fluorescence. Gut microbiome changes were investigated by 16S ribosomal DNA sequencing.
    LSD increased social preference and novelty and decreased hippocampal levels of the N-acylethanolamines N-linoleoylethanolamine (LEA), anandamide (N-arachidonoylethanolamine) and N-docosahexaenoylethanolamine (DHEA); the monoacylglycerol 1/2-docosahexaenoylglycerol (1/2-DHG); the prostaglandins D2 (PGD2 ) and F2α (PGF2α ); thromboxane 2 and kynurenine. Prefrontal eCBome mediator and metabolite levels were less affected by the treatment. LSD decreased Shannon alpha diversity of the gut microbiota, prevented the decrease in the Firmicutes:Bacteroidetes ratio observed in saline-treated mice and altered the relative abundance of the bacterial taxa Bifidobacterium, Ileibacterium, Dubosiella and Rikenellaceae RC9.
    The prosocial effects elicited by repeated LSD administration are accompanied by alterations of hippocampal eCBome and kynurenine levels, and the composition of the gut microbiota. Modulation of the hippocampal eCBome and kynurenine pathway might represent a mechanism by which psychedelic compounds elicit prosocial effects and affect the gut microbiome.
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  • 文章类型: Journal Article
    This study aimed to examine whether repeated exposures to low (2%) and moderate (4%) exercise-induced hypohydration may reverse the potentially deleterious effect of hypohydration on endurance performance. Using a randomized crossover protocol, ten volunteers (23 years, V˙O2max: 54 mL∙kg-1∙min-1) completed two 4-week training blocks interspersed by a 5-week washout period. During one block, participants replaced all fluid losses (EUH) while in the other they were fluid restricted (DEH). Participants completed three exercise sessions per week (walking/running, 55% V˙O2max, 40 °C): (1) 1 h while fluid restricted or drinking ad libitum, (2) until 2 and (3) 4% of body mass has been lost or replaced. During the first and the fourth week of each training block, participants completed a 12 min time-trial immediately after 2% and 4% body mass loss has been reached. Exercise duration and distance completed (14.1 ± 2.7 vs. 6.9 ± 1.5 km) during the fixed-intensity exercise bouts were greater in the 4 compared to the 2% condition (p < 0.01) with no difference between DEH and EUH. During the first week, heart rate, rectal temperature and perceived exertion were higher (p < 0.05) with DEH than EUH, and training did not change these outcomes. Exercise-induced hypohydration of 2% and 4% body mass impaired time-trial performance in a practical manner both at the start and end of the training block. In conclusion, exercise-induced hypohydration of 2% and 4% body mass impairs 12 min walking/running time-trial, and repeated exposures to these hypohydration levels cannot reverse the impairment in performance.
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  • 文章类型: Journal Article
    Agitation is a common symptom encountered among patients treated in psychiatric emergency settings. While there are many guidelines available for initial management of the acutely agitated patient, there is a notable dearth of guidelines that delineate recommended approaches to the acutely agitated patient in whom an initial medication intervention has failed. This manuscript aims to fill this gap by examining evidence available in the literature and providing clinical algorithms suggested by the authors for sequential medication administration in patients with persistent acute agitation in psychiatric emergency settings. We discuss risk factors for medication-related adverse events and provide options for patients who are able to take oral medications and for patients who require parenteral intervention. We conclude with a discussion of the current need for well-designed studies that examine sequential medication options in patients with persistent acute agitation.
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