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Toxicological Potential of the FDA-Approved Treatment against Monkeypox. Comment on Zovi et al. Pharmacological Agents with Antiviral Activity against Monkeypox Infection. Int. J. Mol. Sci. 2022, 23, 15941 fda批准的猴痘治疗的毒理学潜力。评论Zovi等人。具有抗猴痘感染抗病毒活性的药物。Int。生物医学工程学报,2002,23 (3):941 - 941
Pub Date : 2023-03-27 DOI: 10.3390/ijtm3020013
Gabriel Christian de Farias Morais, U. L. Fulco, E. D. da Silva, C. B. S. Oliveira, J. I. N. Oliveira
Recently, some drugs were approved to control Monkeypox (MPX), among them tecovirimat. This was recently approved by regulatory agencies around the world, the paper of Zovi et al entitled Pharmacological Agents with Antiviral Activity against Monkeypox Infection highlight it as safe and effective, although the safety data are still not very robust. In this Comment, we present some theoretical evaluations of its safety, considering that for use in humans it is essential to have a rich scientific literature in the area. After a series of analyses, a potential risk of liver, respiratory and kidney damage was found in addition to carcinogenic potential. Thus, while we agree that there is a need for rapid responses to infection, we reinforce that well-designed and adequately powered studies should not only focus on investigating the pharmacological efficacy of tecovirimat but also demonstrate its safety in humans. Therefore, in this Comment, we present some concerns that may help in formulating a safer treatment for patients infected with Monkeypox virus (MPXV).
近年来,一些药物被批准用于控制猴痘(MPX),其中包括替可韦莫。该药物最近得到了世界各地监管机构的批准,Zovi等人发表的题为《具有抗猴痘感染抗病毒活性的药理制剂》的论文强调了它的安全性和有效性,尽管安全性数据仍然不是很可靠。在这篇评论中,我们提出了一些关于其安全性的理论评估,考虑到在人类中使用它是必要的,在该领域有丰富的科学文献。经过一系列分析,除了潜在的致癌性外,还发现了对肝脏、呼吸系统和肾脏造成损害的潜在风险。因此,虽然我们同意有必要对感染做出快速反应,但我们强调,设计良好且有充分动力的研究不仅应关注研究tecovirimat的药理学功效,还应证明其在人体中的安全性。因此,在这篇评论中,我们提出了一些可能有助于制定更安全的猴痘病毒(MPXV)患者治疗方法的关注。
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引用次数: 0
The Genetic Basis of Future Pharmacological Strategies for the Management of Comorbid Obesity and Depression: A Scoping Review 未来治疗肥胖和抑郁的药理学策略的遗传基础:范围综述
Pub Date : 2023-03-08 DOI: 10.3390/ijtm3010012
R. Rajkumar
Depression and obesity are highly comorbid with one another, with evidence of bidirectional causal links between each disorder and a shared biological basis. Genetic factors play a major role in influencing both the occurrence of comorbid depression and obesity, their courses, and their response to existing treatments. The current paper is a scoping review of studies that have evaluated the contribution of specific genetic variants to the comorbidity between obesity and depression. Based on a search of the PubMed and EMBASE databases, 28 studies were included in this review, covering 54 candidate genes. Positive associations were identified for 14 genetic loci (AKR1C2, APOA5, COMT, DAT1, FTO, KCNE1, MAOA, MC4R, MCHR2, NPY2R, NR3C1, Ob, PCSK9, and TAL1). Replicated findings across two or more independent samples were observed for the FTO and MC4R genes. Many of these gene products represent novel molecular targets for the pharmacological management of obesity that interact with each other and are not pharmacologically influenced by existing anti-obesity or antidepressant medications. The implications of these associations for future drug development are discussed, with an emphasis on recent evidence on the polygenic architecture of comorbid depression and obesity and on a precision-medicine approach to these conditions.
抑郁症和肥胖是高度共病的,有证据表明,每种疾病之间存在双向因果关系,并具有共同的生物学基础。遗传因素在影响抑郁症和肥胖症合并症的发生、病程及其对现有治疗的反应方面起着重要作用。这篇论文是对一些研究的综述,这些研究评估了特定基因变异对肥胖和抑郁共病的影响。基于对PubMed和EMBASE数据库的检索,本综述纳入了28项研究,涵盖了54个候选基因。鉴定出14个基因位点(AKR1C2、APOA5、COMT、DAT1、FTO、KCNE1、MAOA、MC4R、MCHR2、NPY2R、NR3C1、Ob、PCSK9和TAL1)呈正相关。FTO和MC4R基因在两个或多个独立样本中观察到重复的结果。这些基因产物中的许多代表了肥胖药理学管理的新分子靶点,它们相互作用,不受现有抗肥胖或抗抑郁药物的药理学影响。本文讨论了这些关联对未来药物开发的影响,重点介绍了抑郁症和肥胖症共病的多基因结构的最新证据,以及针对这些疾病的精确医学方法。
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引用次数: 0
Radiation and Diabetic Retinopathy: A Dark Synergy 辐射与糖尿病视网膜病变:黑暗的协同作用
Pub Date : 2023-03-07 DOI: 10.3390/ijtm3010011
T. Gardiner, D. Archer, G. Silvestri, W. Amoaku
Exacerbation of the vascular pathology in radiation retinopathy as a result of pre-existing diabetes has been recognized for many years, as reflected by clinical reports and a few early experimental studies. However, the underlying pathogenetic mechanisms for the synergistic interaction of radiation retinopathy (RR) and diabetic retinopathy (DR) have not been compared and evaluated for insight on this phenomenon. The present work draws attention to the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as common mediators of both conditions and sources of ongoing cellular injury in the radiation-induced bystander effect (RIBE) and the senescence-associated secretory phenotype (SASP). Chronic hyperglycemia-mediated oxidative stress and depleted antioxidant defense in diabetes, together with impaired DNA damage sensing and repair mechanisms, were identified as the primary elements contributing to the increased severity of RR in diabetic patients. We conclude that apart from strategic genetic mutations affecting the DNA damage response (DDR), diabetes represents the most significant common risk factor for vascular injury as a side effect of radiotherapy.
多年来,临床报告和一些早期实验研究反映出,由于先前存在糖尿病而导致的放射性视网膜病变血管病理恶化已经被认识到。然而,放射性视网膜病变(RR)和糖尿病视网膜病变(DR)协同作用的潜在发病机制尚未被比较和评估,以了解这一现象。目前的工作引起了人们对活性氧(ROS)和活性氮(RNS)在辐射诱导的旁观者效应(RIBE)和衰老相关分泌表型(SASP)中作为持续细胞损伤条件和来源的常见介质的关注。糖尿病中慢性高血糖介导的氧化应激和抗氧化防御的缺失,以及DNA损伤感知和修复机制的受损,被认为是导致糖尿病患者RR严重程度增加的主要因素。我们的结论是,除了影响DNA损伤反应(DDR)的战略性基因突变外,糖尿病是放射治疗副作用中血管损伤的最重要的常见危险因素。
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引用次数: 0
Paclitaxel—A Valuable Tool for Inducing Visceral Pain in Preclinical Testing? 紫杉醇是临床前诱导内脏疼痛的有效工具?
Pub Date : 2023-02-27 DOI: 10.3390/ijtm3010010
Corina Andrei, A. Zanfirescu, D. Mihai, S. Negreș
Visceral pain is a unique clinical entity that lacks an effective and safe treatment. Proper preclinical models are essential for assessing new drugs developed for the treatment of this pathology. Few studies report that paclitaxel, an antineoplastic agent, can be used to induce visceral pain in laboratory animals. Our purpose was to investigate the reproducibility of these studies and to develop an animal method that would allow assessing consistent visceral pain. In this study, we used four doses of paclitaxel (3 mg × kg−1; 5 mg × kg−1; 10 mg × kg−1 and 15 mg × kg−1). Visceral pain was evaluated using a scale of abdominal pain immediately after the administration of a single dose of paclitaxel to rats. Tactile and thermal hypersensitivity were assessed using von Frey filaments and the tail flick test initially, at 24 h and 48 h after administration. Rats experienced visceral pain and mechanical and thermal hypersensitivity 24 h after the administration of paclitaxel. The intensity of the pain was increased in a dose-dependent manner with the highest intensity of effect being observed after the administration of a dose of 15 mg × kg−1. Paclitaxel induces visceral pain. The dosage varies depending on the employed strain of rat. This method allows for assessing the efficacy of analgesics to be useful against visceral pain if the paclitaxel dose is adjusted accordingly to the animal strain.
内脏疼痛是一种独特的临床实体,缺乏有效和安全的治疗。适当的临床前模型对于评估用于治疗这种病理的新药至关重要。很少有研究报道紫杉醇,一种抗肿瘤药物,可以用来诱导实验动物内脏疼痛。我们的目的是研究这些研究的可重复性,并开发一种动物方法来评估内脏疼痛的一致性。在这项研究中,我们使用了四种剂量的紫杉醇(3mg × kg−1;5 mg × kg−1;10mg × kg - 1和15mg × kg - 1)。在给大鼠单剂量紫杉醇后立即用腹痛量表评估内脏疼痛。在给药后24小时和48小时,采用von Frey纤维和甩尾试验评估触觉和热超敏反应。给药24 h后,大鼠出现内脏疼痛、机械和热超敏反应。疼痛强度呈剂量依赖性增加,在15 mg × kg−1剂量后观察到最大的效应强度。紫杉醇引起内脏疼痛。剂量根据所用大鼠的品系而定。如果紫杉醇剂量根据动物品系调整,这种方法允许评估镇痛药对内脏疼痛的有效性。
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引用次数: 0
Co-Occurrence of Filifactor alocis with Red Complex Bacteria in Type 2 Diabetes Mellitus Subjects with and without Chronic Periodontitis: A Pilot Study 伴有或不伴有慢性牙周炎的2型糖尿病患者中丝状因子与红色复合体细菌的共同发生:一项初步研究
Pub Date : 2023-02-09 DOI: 10.3390/ijtm3010009
H. Shaikh, Pratima U. Oswal, Manohar S. Kugaji, S. Katti, K. Bhat, Vinayak M. Joshi
The periodontal disease etiology has been a demesne of scrupulous research, with a myriad of bacterial phylotypes inhabiting the periodontal pockets. The aim of our study was to assess the frequency of Filifactor alocis in type 2 diabetes mellitus (DM) subjects having a healthy periodontium (DH) or chronic periodontitis (DCP) and its correlation with clinical parameters and red complex bacteria. Polymerase chain reaction was carried out for the detection of F. alocis and red complex bacteria from subgingival plaque samples. The data were analyzed using Fisher’s Exact Test and Pearson’s chi-square test. A p value < 0.05 was considered statistically significant. F. alocis was detected at considerably higher levels in DCP (p < 0.05). F. alocis presence was also positively correlated with T. forsythia detection and the clinical parameters PD and CAL (p < 0.05). Subjects with good glycemic control showed a considerably lower detection of F. alocis as compared to fair- and poor-glycemic-control subjects. This is the first paper reporting the co-occurrence of F. alocis and T. forsythia in diabetic subjects with chronic periodontitis. These findings show that F. alocis can play an important role in establishing synergistic collaborations with other pathogenic oral microorganisms and speeding up the course of periodontal disease in diabetics.
牙周病的病因学一直是一个严谨的研究,与无数的细菌种型居住在牙周袋。本研究的目的是评估具有健康牙周组织(DH)或慢性牙周炎(DCP)的2型糖尿病(DM)受试者中丝状因子alocis的频率及其与临床参数和红色复合体细菌的相关性。采用聚合酶链反应法对龈下菌斑标本中金黄色梭菌和红色复合体菌进行检测。采用Fisher精确检验和Pearson卡方检验对数据进行分析。p值< 0.05认为有统计学意义。F. alocis在DCP中含量显著高于对照组(p < 0.05)。F. alocis的存在与连翘检出率及临床参数PD、CAL呈正相关(p < 0.05)。血糖控制良好的受试者与血糖控制正常和血糖控制不佳的受试者相比,alocis的检出率明显较低。本文首次报道糖尿病患者慢性牙周炎伴发alocis和连翘t。这些结果表明,alocis在与其他口腔病原微生物建立协同作用,加速糖尿病患者牙周病的进程中发挥重要作用。
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引用次数: 0
Acknowledgment to the Reviewers of IJTM in 2022 感谢2022年IJTM审稿人
Pub Date : 2023-01-30 DOI: 10.3390/ijtm3010008
High-quality academic publishing is built on rigorous peer review [...]
高质量的学术出版建立在严格的同行评审的基础上[…]
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引用次数: 0
The Renal Manifestations of SARS-CoV-2: A Guide for Family Physicians SARS-CoV-2的肾脏表现:家庭医生指南
Pub Date : 2023-01-22 DOI: 10.3390/ijtm3010007
Austin Morrissey, Nagla Elzinad, Christelle El Hayek, Saran Lotfollahzadeh, V. Chitalia
COVID-19 is a devastating systemic disease characterized by multisystem involvement driven by exuberant hyperinflammatory and dysregulations in coagulation. In COVID-19 patients, renal failure contributes to morbidity and mortality, and its early detection and timely management are critical to minimize such untoward and irreversible complications. In the healthcare system, family physicians constitute the first node in the management of patients, yet there is a dearth of reports and guidelines focusing on them for specific organ affection. This review provides an overview of recent studies examining the renal manifestations following SARS-CoV-2 infection. We focus on the tell-tale signs and laboratory findings of renal affection in the pediatric and adult populations with COVID-19, specifically for family practitioners to assist in their appropriate triage. Among different manifestations, urinary abnormalities and a modest increase in creatinine are the early indicators of renal affection in COVID-19 patients. Although renal transplant patients are conventionally managed by specialized teams, they may present to family physicians during a pandemic. This review provides a framework for family physicians to promptly detect early indicators of renal involvement in patients infected with SARS-CoV-2, including providing triage guidance for kidney transplant recipients.
COVID-19是一种毁灭性的全身性疾病,其特征是由过度炎症和凝血失调驱动的多系统受累。在COVID-19患者中,肾功能衰竭会导致发病率和死亡率,早期发现和及时治疗对于尽量减少这种不可逆的不良并发症至关重要。在医疗保健系统中,家庭医生构成了患者管理的第一个节点,但缺乏针对特定器官影响的报告和指南。本文综述了最近关于SARS-CoV-2感染后肾脏表现的研究。我们重点关注儿童和成人COVID-19患者肾脏疾病的体征和实验室结果,特别是为家庭医生提供帮助,以帮助他们进行适当的分诊。在不同表现中,尿路异常和肌酐轻度升高是COVID-19患者肾功能受损的早期指标。虽然肾移植患者通常由专业团队管理,但在大流行期间,他们可能会去看家庭医生。本综述为家庭医生及时发现SARS-CoV-2感染患者肾脏受累的早期指标提供了一个框架,包括为肾移植受者提供分诊指导。
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引用次数: 0
Anatomical Distribution of Ultraviolet Radiation Depends on Phototherapy Unit Design and on Personal Height and Body Mass 紫外线辐射的解剖分布取决于光疗装置的设计和个人身高和体重
Pub Date : 2023-01-20 DOI: 10.3390/ijtm3010006
H. Wulf, P. Philipsen, J. Heydenreich
Phototherapy using ultraviolet radiation (UVR) treatment units of various designs is common in dermatology. The anatomical distribution of UVR should be even, regardless of individual body shapes. Using electronic dosimeters, we measured the irradiance at 31 body sites on 12 persons of different heights and body mass (BMI). Five different treatment unit designs were tested: cabinet units with standing patients, units with patients lying down, and a unit where patients rotated in front of flatly arranged UVR tubes. In treatment units with short tubes, persons taller than 170 cm received low irradiance on the face, neck, and shoulders. In cabinet-type units, higher BMI lowered the irradiance on the chest and belly. The relative standard deviation (RSD) of irradiance was smallest for the rotating unit, and for the unit with patients lying down while irradiated from above only. A higher RSD was found in the unit designs where patients stood inside cabinets, and where patients lay down and were simultaneously irradiated from both sides. In general, longer tubes lower the overall RSD. The irradiance of the different body areas is about 60% of the measured calibration values, but to avoid provoking any erythema, the treatment dose can only be increased by 10%.
使用各种设计的紫外线(UVR)治疗单元的光疗在皮肤病学中很常见。无论个体的体型如何,UVR的解剖分布应该是均匀的。使用电子剂量计,我们测量了12名不同身高和体重(BMI)的人在31个身体部位的辐照度。研究人员测试了五种不同的治疗单元设计:患者站立的柜式单元,患者躺着的单元,以及患者在平面排列的UVR管前旋转的单元。在使用短管的治疗单元中,身高超过170厘米的人的面部、颈部和肩部的辐照度较低。在柜式装置中,较高的BMI降低了胸部和腹部的辐照度。旋转单元辐照度的相对标准偏差(RSD)最小,仅从上方照射时患者躺着的单元辐照度最小。在病人站在柜子里和病人躺着同时从两侧照射的单元设计中,RSD更高。一般来说,试管越长,RSD越低。不同身体区域的辐照度约为测量校准值的60%,但为了避免引起任何红斑,治疗剂量只能增加10%。
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引用次数: 0
Advancements in the Diagnosis of Hepatocellular Carcinoma 肝细胞癌的诊断进展
Pub Date : 2023-01-11 DOI: 10.3390/ijtm3010005
N. Parra, H. M. Ross, Adnan Khan, M. Wu, R. Goldberg, L. Shah, Sarah Mukhtar, Jake Beiriger, Alexis Gerber, D. Halegoua-DeMarzio
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, with increasing global incidence. Morbidity and mortality associated with HCC remains high, and HCC is the leading cause of cancer death worldwide. Early detection and treatment of HCC can increase five-year survival by over 60%. Detection of HCC remains challenging, however, as HCC arises from a variety of environmental, genetic, and viral etiologies, and it demonstrates a complex pathophysiology and displays a heterogeneous morphology. Current diagnostic methods rely on abdominal ultrasound with or without concurrent AFP biomarker testing for high-risk individuals. This review provides an overview of HCC diagnostic modalities and highlights the promising nature of translational developments in biomarkers, next generation sequencing (NGS), artificial intelligence, molecular imaging, and liquid biopsy for earlier and more accurate diagnosis of HCC. Furthermore, we identify areas for improvement that must be addressed before the widespread usage and implementation of these methods.
肝细胞癌(HCC)是最常见的原发性肝脏恶性肿瘤,全球发病率不断上升。与HCC相关的发病率和死亡率仍然很高,HCC是世界范围内癌症死亡的主要原因。早期发现和治疗肝癌可使5年生存率提高60%以上。然而,HCC的检测仍然具有挑战性,因为HCC起源于各种环境,遗传和病毒病因,并且它表现出复杂的病理生理学和异质性形态。目前的诊断方法依赖于腹部超声与或不并发AFP生物标志物检测高危人群。本文综述了HCC的诊断方法,并强调了生物标志物、下一代测序(NGS)、人工智能、分子成像和液体活检在HCC早期和更准确诊断方面的应用前景。此外,我们确定了在广泛使用和实施这些方法之前必须解决的改进领域。
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引用次数: 3
Improving Sleep Quality to Prevent Perinatal Depression: The Obstetric Nurse Intervention 改善睡眠质量预防围产期抑郁:产科护士干预
Pub Date : 2023-01-05 DOI: 10.3390/ijtm3010004
A. Poeira, Maria Otília Brites Zangão
Throughout their life, women should pay attention to their mental health. Evidence indicates that poor sleep quality is related to depressive symptoms in pregnancy, justifying the intervention of health professionals in improving sleep quality to promote the mental health of pregnant women. The objective of our study is to analyze the relationship between sleep quality and perinatal depression, and to identify the obstetric nurse’s intervention in improving sleep quality in the perinatal period. A total of 53 pregnant women between the 28th week of pregnancy and the 7th day after delivery completed the Edinburgh Postnatal Depression Scale (EPDS) and Pittsburgh Sleep Quality Index (PSQI). Women were also asked about the strategies used by the obstetric nurse to improve their quality of sleep. Data analysis was performed using IBM SPSS Statistics software, version 25.0. The Mann–Whitney-U and Kruskal-Wallis tests were carried out. A p-value < 0.05 was considered statistically significant. The median PSQI score was 10 (±3.63), and 9.2% (n = 9) had good quality sleep. The median EPDS score was 12 (±4.43), and 27 participants (50.9%) had probable depression. The women with likely depression had worse sleep quality (p = 0.016). Most participants reported that the obstetric nurse showed no interest in their sleep quality during pregnancy. Women of other nationalities have a higher risk of depression (p = 0.013). Based on our results, it is crucial to assess sleep quality in the perinatal period to promote women’s health during the prenatal and postnatal periods, and more action is needed since we are facing one of the most significant challenges of this century, preventing depression.
在她们的一生中,女性都应该注意自己的心理健康。有证据表明,睡眠质量差与怀孕期间的抑郁症状有关,因此卫生专业人员有理由干预改善睡眠质量,以促进孕妇的心理健康。本研究旨在分析围生期睡眠质量与围生期抑郁的关系,探讨产科护士在改善围生期睡眠质量方面的干预措施。在妊娠28周至产后第7天共53名孕妇完成了爱丁堡产后抑郁量表(EPDS)和匹兹堡睡眠质量指数(PSQI)。妇女们还被问及产科护士用来改善她们睡眠质量的策略。采用IBM SPSS统计软件25.0进行数据分析。进行了Mann-Whitney-U和Kruskal-Wallis测试。p值< 0.05认为有统计学意义。PSQI评分中位数为10(±3.63),9.2% (n = 9)的患者睡眠质量良好。EPDS评分中位数为12(±4.43),27名参与者(50.9%)可能患有抑郁症。可能患有抑郁症的女性睡眠质量较差(p = 0.016)。大多数参与者报告说,产科护士在怀孕期间对她们的睡眠质量不感兴趣。其他国籍的女性患抑郁症的风险更高(p = 0.013)。根据我们的研究结果,评估围产期的睡眠质量对于促进妇女产前和产后的健康至关重要,我们需要采取更多的行动,因为我们正面临着本世纪最重大的挑战之一,预防抑郁症。
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引用次数: 1
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Journal of International Translational Medicine
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