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Targeting TGF-beta pathway with COVID-19 Drug Candidate ARTIVeda/PulmoHeal Accelerates Recovery from Mild-Moderate COVID-19 靶向tgf - β通路的COVID-19候选药物ARTIVeda/PulmoHeal加速轻中度COVID-19的恢复
Pub Date : 2021-02-01 DOI: 10.37532/2041-6792.2021.11(1).10-18
V. Trieu, Saran Saund, P. Rahate, Viljay B. Barge, K. Nalk, H. Windlass, F. Uckun
Our COVID-19 drug candidate ARTIVedaTM/PulmoHeal is a novel gelatin capsule formulation of the Artemisia extract Ayurveda for oral delivery of TGF-β targeting anti-malaria phytomedicine Artemisinin with documented anti-inflammatory and anti-SARS-CoV-2 activity. Here we report the safety and efficacy of ARTIVedaTM in adult COVID-19 patients with symptomatic mild-moderate COVID-19, who were treated in a randomized, open-label Phase 4 study in Bangalore, Karnataka, India (Clinical Trials Registry India identifier: CTRI/2020/09/028044). ARTIVeda showed a very favorable safety profile, and the only ARTIVeda-related adverse events were transient mild rash and mild hypertension. Notably, ARTIVeda, when added to the SOC, accelerated the recovery of patients with mild-moderate COVID-19. While all patients were symptomatic at baseline (WHO score=2-4), 31 of 39 (79.5%) of patients treated with ARTIVeda plus SOC became asymptomatic (WHO score=1) by the end of the 5-day therapy, including 10 of 10 patients with severe dry cough 7 of 7 patients with severe fever. By comparison, 12 of 21 control patients (57.1%) treated with SOC alone became asymptomatic on day 5 (p=0.028, Fisher’s exact test). This clinical benefit was particularly evident when the treatment outcomes of hospitalized COVID-19 patients (WHO score=4) treated with SOC alone versus SOC plus ARTIVeda were compared. The median time to becoming asymptomatic was only 5 days for the SOC plus ARTIVeda group (N=18) but 14 days for the SOC alone group (N=10) (p=0.004, Log-rank test). These data provide clinical proof of concept that targeting the TGF-β pathway with ARTIVeda may contribute to a faster recovery of patients with mild-moderate COVID-19 when administered early in the course of their disease.
我们的COVID-19候选药物ARTIVedaTM/PulmoHeal是一种新型明胶胶囊配方,由青蒿提取物阿育吠陀(Ayurveda)制成,用于口服TGF-β靶向抗疟疾植物药物青蒿素,具有抗炎和抗sars - cov -2活性。在这里,我们报告了ARTIVedaTM在印度卡纳塔克邦班加罗尔的一项随机、开放标签的4期研究中治疗的有症状的成人COVID-19患者的安全性和有效性(印度临床试验注册中心标识号:CTRI/2020/09/028044)。ARTIVeda显示出非常有利的安全性,唯一与ARTIVeda相关的不良事件是短暂的轻度皮疹和轻度高血压。值得注意的是,当ARTIVeda加入到SOC中时,可以加速轻中度COVID-19患者的康复。虽然所有患者在基线时均有症状(WHO评分=2-4),但在接受ARTIVeda + SOC治疗的39例患者中,有31例(79.5%)在5天治疗结束时无症状(WHO评分=1),包括10例严重干咳患者中的10例,7例严重发热患者中的7例。相比之下,单独使用SOC治疗的21例对照患者中有12例(57.1%)在第5天无症状(p=0.028, Fisher精确检验)。当比较单独使用SOC与SOC加ARTIVeda治疗的住院COVID-19患者(WHO评分=4)的治疗结果时,这种临床获益尤其明显。SOC加ARTIVeda组(N=18)到无症状的中位时间仅为5天,而SOC单独组(N=10)的中位时间为14天(p=0.004, Log-rank检验)。这些数据为ARTIVeda靶向TGF-β通路的概念提供了临床证明,如果在病程早期给药,可能有助于轻中度COVID-19患者更快康复。
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引用次数: 0
A Prospective on Allergic Rhinitis 变应性鼻炎的前瞻性研究
Pub Date : 2021-01-01 DOI: 10.37532/2041-6792.2021.11(2).49-50
J. Stewert
Allergic rhinitis is a chronic disease linked to asthma and conjunctivitis. It is typically a chronic condition that goes undetected in primary care. Popular symptoms include nasal cough, nasal itch, rhinorrhea, and sneezing. To diagnose allergic rhinitis, a comprehensive medical history, physical examination, and allergen skin testing are all required.
过敏性鼻炎是一种慢性疾病,与哮喘和结膜炎有关。它通常是一种慢性疾病,在初级保健中未被发现。常见的症状包括鼻咳嗽、鼻痒、鼻漏和打喷嚏。要诊断过敏性鼻炎,需要全面的病史、体格检查和过敏原皮肤测试。
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引用次数: 0
Use of Cladribine for multiple sclerosis treatment: An image article 使用克拉德宾治疗多发性硬化症:一篇图片文章
Pub Date : 2021-01-01 DOI: 10.37532/2041-6792.2021.11(1).31
J. Stewert
Cladribine reaches the cell via proteins that hold nucleoside. Cladribine is activated within the cell by three subsequent phosphorylations, the first being deoxycytidine kinase. The enzyme 5'-nucleotidase (5'-NTase), active cladribine can be inactivated by dephosphorylation.
克拉宾通过含有核苷的蛋白质到达细胞。Cladribine在细胞内通过三个随后的磷酸化被激活,第一个是脱氧胞苷激酶。活性克拉宾的5′-核苷酸酶(5′-NTase)可通过去磷酸化使其失活。
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引用次数: 0
Low Vitamin D Levels can Effect the Balance of Immun Mediators in Fibromyalgia Syndrome Objective 低维生素D水平影响纤维肌痛综合征免疫介质的平衡
Pub Date : 2021-01-01 DOI: 10.37532/2041-6792.2021.11(2).41-48
Pınar Ellergezen, A. Alp, S. Çavun, Gülce Sevdar Çeçen, A. Macunluoglu
Objective: To investigate the relationship between vitamin D levels and inflammatory cytokine levels in patients with Fibromyalgia Syndrome (FMS). Materials and Methods: 29 women with FMS who were diagnosed according to American College of Rheumatology (ACR) 2010 fibromyalgia diagnostic criteria and 25 healthy women as the control group was included in the study. Serum levels of vitamin D, Vitamin D Receptor (VDR) and Vitamin D Binding Protein (VDBP), and inflammatory cytokines (IL-2, IL-4, IL-6, IL-12, IFN-γ) were analyzed using by ELISA method. Widespread body pain, fatigue, morning stiffness, cognitive symptoms, somatic symptoms, Fibromyalgia Impact Questionnaire (FIQ) scores were evaluated in patients with FMS. Results: Vitamin D, VDR, and VDBP levels were found to be higher in the healthy individuals compared to the patients with FMS (p<0.001, p<0.002, p<0.001, respectively). Correspondingly, pro-inflammatory (IL-2, IL-12, IFN-γ), anti-inflammatory (IL-4), and both pro and anti-inflammatory (IL-6) cytokine levels of the control group were higher than the patients with FMS (p<0.001, p<0.006, p<0.004, p<0.001, p<0.049, respectively). Conclusion: Low vitamin D levels in FMS may negatively affect the release of inflammatory cytokines and this functional relationship may be in the etiology of this chronic pain disorder
目的:探讨纤维肌痛综合征(FMS)患者维生素D水平与炎性细胞因子水平的关系。材料与方法:29名根据美国风湿病学会(ACR) 2010纤维肌痛诊断标准诊断为FMS的女性和25名健康女性作为对照组。ELISA法检测血清维生素D、维生素D受体(VDR)、维生素D结合蛋白(VDBP)及炎症因子(IL-2、IL-4、IL-6、IL-12、IFN-γ)水平。对FMS患者普遍的身体疼痛、疲劳、晨僵、认知症状、躯体症状、纤维肌痛影响问卷(FIQ)评分进行评估。结果:健康个体的维生素D、VDR和VDBP水平均高于FMS患者(p<0.001, p<0.002, p<0.001)。对照组的促炎因子(IL-2、IL-12、IFN-γ)、抗炎因子(IL-4)及促炎因子和抗炎因子(IL-6)水平均高于FMS患者(p<0.001、p<0.006、p<0.004、p<0.001、p<0.049)。结论:FMS中维生素D水平低可能对炎性细胞因子的释放产生负面影响,这种功能关系可能与慢性疼痛疾病的病因有关
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引用次数: 0
Study the different incidences of Tramadol in different cities of Punjab, Pakistan 研究曲马多在巴基斯坦旁遮普省不同城市的不同发病率
Pub Date : 2021-01-01 DOI: 10.37532/2041-6792.2021.11(1).26-30
M. J. Iqbal, Mazhar Ali, Rizwan Ghafoor, A. khan, M. M. Raza
Aim and Objective: The objective of this case series is to evaluate the effectiveness of Tramadol according to prescribe-rs and patient's feedback. Methodology: A cross-sectional study to assess pain management practice among patients from different hospitals of Punjab. We conducted this study and collect data from August 2020 to October 2020. A total of 740 patients were included in our study and fulfilled the inclusion criteria. Results: In our results, we find that consumption of opioids in different pain types and concluded that tramadol is the most used opioid among all other opioids. We also found its stability, safety, and efficacy parameters. We confirmed from our study tramadol is used mostly to treat acute musculoskeletal pain. Conclusion: We concluded that tramadol has lower dependency as compare to other recent opioids and have more benefits.
目的与目的:本病例系列的目的是根据处方医生和患者的反馈来评估曲马多的有效性。方法:一项横断面研究来评估旁遮普不同医院患者的疼痛管理实践。我们从2020年8月到2020年10月进行了这项研究并收集了数据。我们的研究共纳入740例患者,符合纳入标准。结果:在我们的研究结果中,我们发现阿片类药物在不同疼痛类型的消费,并得出结论,曲马多是所有阿片类药物中使用最多的阿片类药物。我们还确定了其稳定性、安全性和有效性参数。我们从研究中证实曲马多主要用于治疗急性肌肉骨骼疼痛。结论:我们认为曲马多与其他近期阿片类药物相比具有更低的依赖性和更多的益处。
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引用次数: 2
Prophylactic administration of a clinically safe low dose of the COVID-19 drug candidate Rejuveinix (RJX) effectively prevents fatal cytokine storm and mitigates inflammatory organ injury in a mouse model of sepsis 在脓毒症小鼠模型中,预防性给予临床安全的低剂量COVID-19候选药物Rejuveinix (RJX)可有效预防致命的细胞因子风暴并减轻炎症性器官损伤
Pub Date : 2021-01-01 DOI: 10.37532/2041-6792.2021.11(1).1-9
F. Uckun, C. Orhan, I. Ozercan, N. Şahin, Joy Powell, Natalie M. Pizzimenti, A. VolkMichael, K. Şahin
Severe viral sepsis of coronavirus disease 2019 (COVID-19) is associated with a Cytokine Release Syndrome (CRS) and a high case fatality rate due to the development of Acute Respiratory Distress Syndrome (ARDS) and multi-organ failure in high-risk COVID-19 patients, including cancer patients undergoing chemotherapy. Here, we demonstrate that our COVID-19 drug candidate Rejuveinix (RJX) exhibits potent protective anti-inflammatory activity in the LPS-GalN mouse model of fatal sepsis and multi-organ failure at a dose level >10x lower than its maximum tolerated dose (MTD) for human subjects. In BALB/c mice challenged with an otherwise invariably fatal dose of LPS-GalN, prophylactic administration of 0.7 mL/kg RJX (Human equivalent dose=0.057 mL/ kg), corresponding to 7.5% of its clinical Maximum Tolerated Dose (MTD), prevented the cytokine storm, mitigated the oxidative stress and inflammatory tissue injury in lungs, liver, and heart, and significantly improved the survival outcome. Furthermore, RJX increased the levels of antioxidant enzymes SOD, CAT, and GSH-Px, and reduced oxidative stress in the brain. These results indicate that RJX has clinical potential as a prophylactic anti-inflammatory agent against severe sepsis, including viral sepsis in COVID-19 patients.
2019冠状病毒病(COVID-19)的严重病毒性败血症与细胞因子释放综合征(CRS)和高风险COVID-19患者(包括接受化疗的癌症患者)因急性呼吸窘迫综合征(ARDS)和多器官衰竭而导致的高病死率相关。在这里,我们证明了我们的COVID-19候选药物Rejuveinix (RJX)在LPS-GalN致死性脓毒症和多器官衰竭小鼠模型中显示出有效的保护性抗炎活性,剂量水平比人类受试者的最大耐受剂量(MTD)低10倍以上。在BALB/c小鼠中,预防性给药0.7 mL/kg RJX(人等效剂量=0.057 mL/kg),相当于其临床最大耐受剂量(MTD)的7.5%,可防止细胞因子风暴,减轻肺、肝和心脏的氧化应激和炎症组织损伤,并显著改善生存结果。此外,RJX增加了抗氧化酶SOD、CAT和GSH-Px的水平,并减少了大脑中的氧化应激。这些结果表明,RJX具有作为预防COVID-19患者严重脓毒症(包括病毒性脓毒症)的抗炎药的临床潜力。
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引用次数: 0
To assess AIDS awareness among the educated community of Lahore and Gujranwala, Pakistan 评估巴基斯坦拉合尔和古吉兰瓦拉受教育社区的艾滋病意识
Pub Date : 2021-01-01 DOI: 10.37532/2041-6792.2021.11(1).19-25
J. Cheema, A. Salam, Aqil Khan, M. Z. Zafar
Objective: To assess AIDS awareness among the educated community of Lahore and Gujranwala, Pakistan. Design: Cross-sectional qualitative study. Methods: A questionnaire was designed with the study objectives and distributed to the educated community of Lahore and Gujranwala, gathering the information including, demographic details (name, age, sex, and level of education), HIV-related knowledge (modes of transmission, prevention, and treatment), attitudes and risk perception. The reason for selecting the educated community was that they are the pioneer to educate and council illiterate communities. The results were recorded and data were analyzed. Results: 68.78% respondents have knowledge about the basics of AIDS, including, causative agent, and origin, behavior of society towards AIDS patients and incubation period of HIV/AIDS. 69.2% respondents have correct knowledge about modes of transmission of HIV/AIDS. 78.75% respondents are aware of prevention and treatment. 81% respondents think that media is playing some role in awareness about AIDS. Conclusion: Although respondents demonstrated a high level of knowledge concerning AIDS and HIV, considerable misconceptions were also noted. A need was felt to enhance awareness programs among educated community members of two different cities. There is an intense need for a mass media campaign against AIDS.
目的:了解巴基斯坦拉合尔和古吉兰瓦拉地区受教育人群的艾滋病意识。设计:横断面定性研究。方法:根据研究目标设计问卷,向拉合尔市和古吉兰瓦拉市受教育人群发放调查问卷,收集人口统计信息(姓名、年龄、性别、受教育程度)、艾滋病相关知识(传播方式、预防和治疗)、态度和风险认知等信息。选择受教育社区的理由是,他们是教育和教育文盲社区的先驱。记录结果并对数据进行分析。结果:68.78%的被调查者对艾滋病的基本知识有所了解,包括艾滋病的病原、来源、社会对艾滋病患者的行为、艾滋病的潜伏期等。69.2%的受访者对艾滋病毒/艾滋病传播方式有正确的认识。78.75%的受访者了解预防和治疗。81%的受访者认为媒体在提高人们对艾滋病的认识方面发挥了一定作用。结论:虽然受访者对艾滋病和艾滋病毒的知识水平较高,但也注意到相当大的误解。我们认为有必要在两个不同城市受过教育的社区成员中加强意识项目。迫切需要开展一场防治艾滋病的大众传播运动。
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引用次数: 0
Thalidomide may be an effective medicine for Blau Syndrome 沙利度胺可能是治疗布劳综合征的有效药物
Pub Date : 2021-01-01 DOI: 10.37532/2041-6792.2021.11(2).32-36
Wen Wang, L. Zhong, Wen-Dao Li, Shijing Wu, Hongmei Song
nucleotide-binding domain region of the NOD2/CARD15 gene. We reported the case of a patient with a typical triad of rash, arthritis, and uveitis. Sanger sequencing indicated a NOD2 missense variant (c.1759 C >T, p.R587C) in the patient that was inherited from the mother. After treatment with methotrexate, a TNF-α inhibitor, and corticosteroids, the patient’s clinical symptoms and inflammatory indicators remained uncontrolled. In the meantime, the patient experienced multiple side effects, such as hypertension and growth retardation attributed to prolonged use of corticosteroids. After treatment with thalidomide, the condition was controlled without recurrence or side effects, and corticosteroids were stopped as soon as possible. This report suggests that thalidomide may be an effective drug for BS treatment.
NOD2/CARD15基因的核苷酸结合区域。我们报告了一个典型的皮疹、关节炎和葡萄膜炎三联征的病例。Sanger测序显示NOD2错义变体(c.1759)C >T, p.R587C)在患者中遗传自母亲。经甲氨蝶呤、TNF-α抑制剂和皮质类固醇治疗后,患者的临床症状和炎症指标仍未得到控制。同时,患者出现了多种副作用,如长期使用皮质类固醇导致的高血压和生长迟缓。经沙利度胺治疗后,病情得到控制,无复发或副作用,并尽快停用皮质类固醇。本报告提示沙利度胺可能是治疗BS的有效药物。
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引用次数: 0
Burnout, Compassion Fatigue and Vicarious Trauma 倦怠、同情疲劳和替代性创伤
Pub Date : 2021-01-01 DOI: 10.37532/2041-6792.2021.11(2).37-40
Ruth Lourens
Compassion Fatigue (CF) in healthcare workers was first coined by Carla Joinson in 1992, in almost three decades following copious amounts of research have been done on this subject. Findings of the research indicate an astronomical growing problem, yet very little has been done to curb this problem. Today researchers agree that one of the major causes of compassion fatigue in nursing is a lack of education. Nurse’s education doesn’t include subjects dealing with self-care, burnout, vicarious trauma, and CF. Francoise Mathieu, an expert on CF, notes that after completing her degree and several courses in three different countries, she had not once heard the words self-care, burnout, and CF, and nor did I until it happened to me.
1992年,卡拉·乔森(Carla Joinson)首次提出了医疗工作者的同情疲劳(Compassion Fatigue, CF)这个概念,此后近三十年来,人们对这一主题进行了大量研究。这项研究的结果表明,一个日益严重的天文问题,然而,我们几乎没有采取任何措施来遏制这个问题。今天,研究人员一致认为,护理中同情心疲劳的主要原因之一是缺乏教育。护士的教育不包括自我照顾、倦怠、替代性创伤和CF。CF专家弗朗索瓦丝·马修(Francoise Mathieu)指出,在完成学位和在三个不同国家的几门课程后,她一次也没有听说过自我照顾、倦怠和CF这几个词,我也是如此,直到我遇到这些问题。
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引用次数: 1
Comparative Evaluation of MTA Pulpotomy and Laser-Assisted MTA Pulpotomy in Primary Teeth: A Randomized Clinical Trial MTA牙髓切开术与激光辅助MTA牙髓切开术在乳牙治疗中的比较评价:一项随机临床试验
Pub Date : 2020-01-01 DOI: 10.37532/2041-6792.2020.10(3).169
Kranthi Kumar, M. Das, Gautam Singh, M. L. Madhu, Jeswin M Thomas, A. Prabha
Context and Aim: Formocresol has been used as the material of choice (gold standard) for pulpotomy procedures because of the ease of use but was discouraged due to its potential immune sensitization and mutagenic effects. Laser irradiation was first applied for pulpotomy procedure in the year 1985. Recently, diode lasers have been used for pulpotomy in primary teeth and have shown clinical success rates comparable to formocresol. The present in-vivo study was carried out to compare the clinical and radiographic success rates of Mineral Trioxide Aggregate (MTA) alone and diode laser-MTA for pulpotomy in human primary molars. Materials and Methods: The present study was a randomized clinical trial in design wherein forty primary teeth requiring pulpotomy treatment which met the selection criteria (clinical and radiographic) were divided into two groups, group 1 (n=20) wherein the pulpotomy was performed with MTA alone and group 2 (n=20) wherein laser-assisted pulpotomy was performed with MTA (L-MTA). The patients were recalled after 3, 6 and 9 months respectively and evaluated clinically and radiographically. Statistical Analysis Used: The data were analyzed using the Statistical Package for the Social Sciences (SPSS) Version 22 (IBM corporation, Washington DC, United States). Descriptive statistics were used to analyze the data while the Pearson's correlation coefficient test was used to analyze the statistical correlation between the overall success rates observed in the clinical and radiographic findings of both the groups. p<0.05 was considered statistically significant. Results: The clinical success rate in the MTA group was 90%, 84.21% and 88.23% at 3, 6 and 9 months respectively with no clinical signs or, symptoms reported at the said follow-up visits while the radiographic success rate was found to be 85%, 84.21%, and 82.3% respectively. On the contrary, the clinical success rate in the L-MTA group was found to be 95%, 94.74% and 94.44% at 3, 6 and 9 months respectively with the radiographic success rate reported being 90%, 89.47%, and 88.89% respectively. Conclusion: The combination of diode laser and MTA yielded better clinical and radiographic success rates over the pulpotomy procedures done with the help of MTA alone.
背景和目的:由于使用方便,福摩甲酚已被用作髓切开术的首选材料(金标准),但由于其潜在的免疫致敏和致突变作用,不鼓励使用。激光照射于1985年首次应用于牙髓切开术。最近,二极管激光被用于乳牙的切髓术,并显示出与福摩甲酚相当的临床成功率。本研究比较了三氧化二矿骨料(Mineral Trioxide Aggregate, MTA)和二极管激光-MTA在人类第一磨牙髓切开术中的临床和影像学成功率。材料与方法:本研究是一项随机临床设计试验,将40颗符合临床和影像学选择标准的需要切髓治疗的乳牙分为两组,第1组(n=20)单独使用MTA进行切髓,第2组(n=20)使用激光辅助的MTA (L-MTA)进行切髓。分别于3个月、6个月和9个月后召回患者,并进行临床和影像学评估。使用的统计分析:使用社会科学统计软件包(SPSS)版本22 (IBM公司,华盛顿特区,美国)对数据进行分析。采用描述性统计对资料进行分析,采用Pearson相关系数检验分析两组临床观察到的总成功率与影像学表现之间的统计学相关性。P <0.05为差异有统计学意义。结果:MTA组3个月、6个月、9个月的临床成功率分别为90%、84.21%、88.23%,随访时无临床体征、症状报告,影像学成功率分别为85%、84.21%、82.3%。相反,L-MTA组在3个月、6个月和9个月的临床成功率分别为95%、94.74%和94.44%,影像学成功率分别为90%、89.47%和88.89%。结论:二极管激光联合MTA比单用MTA治疗有更好的临床和影像学成功率。
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引用次数: 1
期刊
Clinical investigation
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