Mite Infestations

螨感染
  • 文章类型: Journal Article
    在现代研究动物计划中,小鼠毛皮螨通常被排除在外,然而,由于检测和控制方面的挑战,感染继续存在。因为所有的诊断方法和治疗方案都有局限性,当试图根除这些外寄生虫时,程序必须做出许多操作决定。这项研究的主要目的是通过PCR测试和毛皮检查确定,评估伊维菌素复合饮食在消除小鼠中的Radfordiaaffinis的各种治疗时间。与当前的8周方案相比,较短的治疗持续时间将是非常有利的,因为它将最大限度地减少动物管理计划的成本和时间。研究的障碍,和伊维菌素药物对感染动物的影响。五个实验组的R.affinis阳性小鼠接受饮食伊维菌素0、2、4、6或8周。负毛螨,每8周向每个组中添加未处理的小鼠,以使侵染持续下去并扩增任何剩余的毛螨种群。在各自的治疗结束后16周,对所有处理组连同阳性对照组(未处理)进行PCR测试。还在每个时间点通过直接显微镜对毛皮进行螨虫和卵的视觉检查。如通过PCR测试和毛皮检查两者所证实的,在治疗结束后16周时,所有治疗的小鼠都没有亲缘的R.这些发现表明,饮食伊维菌素治疗持续时间短至2周有效地消除了。使成功的根除举措更容易实现。
    Murine fur mites are commonly excluded in modern research animal programs, yet infestations continue to persist due to challenges in detection and control. Because all diagnostic methods and treatment options have limitations, programs must make many operational decisions when trying to eradicate these ectoparasites. The primary aim of this study was to assess various durations of treatment time with an ivermectin-compounded diet in eliminating Radfordia affinis in mice as determined by PCR testing and pelt examination. A shorter treatment duration would be highly advantageous as compared with the current regimen of 8 wk as it would minimize cost and time for animal management programs, impediments to research, and ivermectin drug effects on infested animals. Five experimental groups of R. affinis -positive mice received dietary ivermectin for 0, 2, 4, 6, or 8 wk. A fur mite-negative, naïve mouse was added to each group every 8 wk to perpetuate the infestation and amplify any remaining populations of fur mites. At 16 wk after the respective treatment end, PCR testing was performed for all treated groups in conjunction with the positive control group (no treatment). Visual examination of pelts for mites and eggs via direct microscopy was also performed at each time point. All treated mice were free of R. affinis at 16 wk after the end of treatment as confirmed by both PCR testing and pelt examination. These findings indicate that a dietary ivermectin treatment duration of as little as 2 wk is effective in eliminating R. affinis, making successful eradication initiatives more achievable.
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  • 文章类型: Journal Article
    蠕形螨的增殖通常与酒渣鼻的发病机理有关。蠕形螨识别的黄金标准是标准化皮肤表面活检的显微镜检查。然而,这种采样方法可能令人痛苦和痛苦,尤其是在毛茸茸的地方进行时。在这项病例对照研究中,我们比较了PCR和显微镜检查诊断蠕形螨感染的敏感性。此外,我们调查了蠕形螨的存在与临床特征之间的可能相关性.总的来说,包括20例受丘疹性酒渣鼻影响的患者和10例对照。在显微镜检查和PCR中,酒渣鼻患者头皮和面部的阳性样本患病率高于对照组.显微镜在面部的敏感度为50%,在头皮的敏感度为46.7%。PCR在面部的灵敏度为93.75%,在头皮的灵敏度为86.7%。PCR阳性与面部丘疹和脓疱的发生频率较高有关。面部阳性的患者头皮阳性的频率更高。头皮可以代表蠕形螨的储库,应该用敏感和无痛的方法进行调查。应进一步研究对无痛收集的样品进行的PCR。
    Demodex mite proliferation is frequently involved in the pathogenesis of rosacea. The gold standard for Demodex identification is microscopic examination on a standardized skin surface biopsy. However, this method of sampling can be distressing and painful, especially when performed on hairy sites. In this case-control study, we compared the sensitivity of PCR and microscopic examination in diagnosing a Demodex infestation. Moreover, we investigated the possible correlations between the presence of Demodex mites and clinical characteristics. In total, 20 patients affected by papulopustular rosacea and 10 controls were included. At both microscopic examination and PCR, patients with rosacea presented a greater prevalence of positive samples than controls at the scalp and at the face. Microscopy had sensitivity of 50% at the face and of 46.7% at the scalp. PCR had sensitivity of 93.75% at the face and of 86.7% at the scalp. The positivity of PCR was associated to a higher frequency of facial papules and pustules. Patients with positivity at the face had a more frequent positivity at the scalp. The scalp could represent a reservoir for the Demodex mites, and should be investigated by sensitive and painless methods. PCR performed on painlessly collected samples should be further investigated.
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  • 文章类型: Journal Article
    牛皮会导致极度瘙痒,相关的压力是动物福利问题,由于牛的生产力下降和驱虫成本而导致经济损失。这项研究调查了绒毛膜螨的原因,C.牛和C.texanus,优先侵染尾根区域(rTR),并进行组织学和生化分析,重点是宿主气味的挥发性成分,这些成分是寄生节肢动物侵染的起点。皮肤样本取自rTR,外侧腹部,和中央按摩师,后两者被指定为比较地点。二维和三维组织学分析测量每单位体积的皮脂腺和汗腺百分比。q-PCR分析了ALDH1A1和LOC785756的表达水平,它们是与挥发性气味化合物相关的基因,这些化合物可作为壁虱的驱避性和有吸引力的信使。免疫组织化学用抗雄激素结合蛋白β样(ABPβ样)染色三个部位,由LOC785756,抗体编码。三维分析表明,与其他区域相比,rTR中的皮脂腺趋于更连续,并且存在更大的质量。LOC785756在rTR中的表达程度显著增高,免疫组织化学显示皮脂腺中存在ABPβ样,rTR中存在强阳性信号。这些结果表明,C.bovis/texanus选择性地感染rTR,因为皮肤有发达的皮脂腺,包括大量ABPβ样,充当螨引诱剂。
    Cattle mange causes extreme itchiness, and the associated stress is an animal welfare concern that leads to economic losses due to decreased cattle productivity and deworming costs. This study investigated the reason why Chorioptic mites, C. bovis and C. texanus, preferentially infest the tail root region (rTR) and performed histological and biochemical analysis focusing on the volatile components of host odors that serve as the starting point for infestation of parasitic arthropods. Skin samples were taken from the rTR, lateral abdominal, and central masseteric, with the latter two designated as comparison sites. The two and three-dimensional histological analysis measured each sebaceous and sweat gland percentage per unit volume. The q-PCR analyzed the expression levels of ALDH1A1 and LOC785756, which are genes associated with volatile odoriferous compounds that serve as repellency and attractive messengers for ticks. Immunohistochemistry stained three sites with anti-androgen binding protein beta-like (ABPβ-like), encoded by LOC785756, antibody. The three-dimensional analysis showed that sebaceous glands in the rTR tend to be more continuous and existed in larger masses than in other regions. The expression level of LOC785756 was significantly higher in the rTR, and immunohistochemistry revealed the presence of ABPβ-like in the sebaceous gland with strong positive signals in the rTR. These results suggest that C. bovis/texanus selectively infests the rTR because that skin has well-developed sebaceous glands, including a large amount of ABPβ-like, which acts as a mite attractant.
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  • 文章类型: Journal Article
    背景:Psoropticmange,由卵螨Psoroptes引起的,正在影响比利时蓝牛的福利和生产潜力。比利时蓝牛以其高度的肌肉运动而闻名,低饲料转化率和高牛肉质量-是这种疾病的高度易感。
    结果:在这项研究中,我们从商业牛肉农场的100多个不同群体中对1975年比利时蓝牛进行了表型分析,因为它们对腺体的易感性。在这些管理组中观察到了显著的个体差异,病变程度差异高达±15%。动物模型显示,对于螨的数量,病变程度和严重病变程度的估计遗传力较低(分别为0.07和0.09)和0.12。针对manage易感性的全基因组关联研究揭示了BTA6,BTA11,BTA15和BTA24上的信号。在这些地区,鉴定了候选基因GBA3、RAG2和TRAF6。
    结论:尽管由于筛选的时机在对视神经腺苷酸进行表型鉴定方面存在挑战,病变的不断演变和不同的管理条件,我们成功地进行了一项关于比利时蓝牛对视黄动物的遗传易感性的研究。我们的结果清楚地表明,视神经mange处于多基因控制之下,应更彻底地研究潜在的候选基因。这是第一个为这种复杂疾病提供候选基因的研究。这些结果对比利时蓝育种已经很有价值,然而,需要进一步的研究来解开这种疾病的结构并确定因果突变。
    BACKGROUND: Psoroptic mange, caused by Psoroptes ovis mites, is affecting Belgian Blue cattle\'s welfare and production potential. The Belgian Blue cattle-known for its high degree of muscling, low feed conversion ratio and high beef quality-is highly susceptible for this disease.
    RESULTS: In this study, we phenotyped 1975 Belgian Blue cattle from more than 100 different groups on commercial beef farms for their psoroptic mange susceptibility. Substantial individual differences were observed within these management groups, with lesion extent differences up to ± 15%. Animal models showed that estimated heritabilities were low for lesion extent and severe lesion extent (0.07 and 0.09, respectively) and 0.12 for the number of mites. A genome wide association study for mange susceptibility revealed signals on BTA6, BTA11, BTA15 and BTA24. In these regions, candidate genes GBA3, RAG2, and TRAF6 were identified.
    CONCLUSIONS: Despite the challenges in phenotyping for psoroptic mange due to the timing of screening, the continuous evolution of lesions and different management conditions, we successfully conducted a study on the genetic susceptibility to psoroptic mange in Belgian Blue cattle. Our results clearly indicate that psoroptic mange is under polygenic control and the underlying candidate genes should be studied more thoroughly. This is the first study providing candidate genes for this complex disease. These results are already valuable for Belgian Blue breeding, however, further research is needed to unravel the architecture of this disease and to identify causal mutations.
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  • 文章类型: Journal Article
    鸡皮病,家禽红螨(PRM),是一种食血性暂时性体外寄生虫,对全球蛋鸡养殖场造成严重的经济损失和动物健康损害。控制受到寄生虫隐藏的生活方式的限制,对使用化学杀螨剂的限制和对某些药物类别的耐药性的发展。因此,进行了研究,以探索替代控制方法。近年来,越来越多的报道称,大气压等离子体是化学杀螨剂防治害虫的替代品。这种物理方法在实验室条件下也显示出对PRM的希望。然而,详细的作用机制尚未阐明。在本研究中,使用数字摄像和光学相干断层扫描(OCT)研究了冷大气压等离子体对PRM的影响,一种可视化表面和内部结构形貌的成像技术。数字录像显示,血浆暴露后立即发生了肠道和排泄器官(Malpighian小管)内容物的重新分布。体液到达PRM的远端腿段,部分血沉显示出更白,更浓密的团块,表明血液成分凝固。OCT在横向和矢状截面图像以及三维图像重建中显示中空器官的边界丢失。此外,在暴露于血浆的螨虫中观察到idiosoma的背腹侧收缩,在血浆暴露后六分钟,其高度缩小到原来的44.0%。
    Dermanyssus gallinae, the poultry red mite (PRM), is a hematophagous temporary ectoparasite that causes serious economic losses and animal health impairment on laying hen farms worldwide. Control is limited by the parasite\'s hidden lifestyle, restrictions on the use of chemical acaricides and the development of resistance against certain drug classes. As a result, research was conducted to explore alternative control methods. In recent years, atmospheric pressure plasma has been increasingly reported as an alternative to chemical acaricides for pest control. This physical method has also shown promising against PRM under laboratory conditions. However, the detailed mechanisms of action have not yet been elucidated. In the present study, the effects of cold atmospheric pressure plasma on PRM were investigated using digital videography and optical coherence tomography (OCT), an imaging technique that visualizes the topography of surfaces and internal structures. Digital videography showed that a redistribution of the contents of the intestinal tract and excretory organs (Malpighian tubules) occurred immediately after plasma exposure. The body fluids reached the distal leg segments of PRM and parts of the haemocoel showed whiter and denser clumps, indicating a coagulation of the haemocoel components. OCT showed a loss of the boundaries of the hollow organs in transverse and sagittal sectional images as well as in the three-dimensional image reconstruction. In addition, a dorso-ventral shrinkage of the idiosoma was observed in plasma-exposed mites, which had shrunk to 44.0% of its original height six minutes after plasma exposure.
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  • 文章类型: Journal Article
    瓦螨,科学上认定为Varroa析构函数,对养蜂构成重大威胁,并导致影响蜜蜂种群的最具破坏性的疾病之一。这些寄生虫附着在蜜蜂身上,以他们的脂肪组织为食,削弱他们的免疫系统,减少他们的寿命,甚至导致殖民地崩溃。它们还在蜜蜂的想象前阶段在育卵细胞中进食。鉴于蜜蜂在授粉和全球食物供应中的关键作用,控制瓦螨是当务之急。用于评估蜂群中瓦螨侵染水平的最常用方法之一是计数落在放置在菌落底部的粘性板上的所有螨。然而,这通常是一个手动过程,需要相当长的时间。这项工作提出了一种深度学习方法,用于使用智能手机相机拍摄的粘板图像来定位和计数瓦螨。为此,已经建立了一个新的现实数据集:它包括包含大量伪影和模糊部分的图像,这使得任务具有挑战性。在测试了各种架构(主要基于具有特征金字塔网络的两级检测器)之后,结合超参数和一些图像增强技术,我们已经获得了一个系统,该系统在验证集上实现了0.9073的平均精度(mAP)度量。
    Varroa mites, scientifically identified as Varroa destructor, pose a significant threat to beekeeping and cause one of the most destructive diseases affecting honey bee populations. These parasites attach to bees, feeding on their fat tissue, weakening their immune systems, reducing their lifespans, and even causing colony collapse. They also feed during the pre-imaginal stages of the honey bee in brood cells. Given the critical role of honey bees in pollination and the global food supply, controlling Varroa mites is imperative. One of the most common methods used to evaluate the level of Varroa mite infestation in a bee colony is to count all the mites that fall onto sticky boards placed at the bottom of a colony. However, this is usually a manual process that takes a considerable amount of time. This work proposes a deep learning approach for locating and counting Varroa mites using images of the sticky boards taken by smartphone cameras. To this end, a new realistic dataset has been built: it includes images containing numerous artifacts and blurred parts, which makes the task challenging. After testing various architectures (mainly based on two-stage detectors with feature pyramid networks), combination of hyperparameters and some image enhancement techniques, we have obtained a system that achieves a mean average precision (mAP) metric of 0.9073 on the validation set.
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  • 文章类型: Journal Article
    蜜蜂的修饰行为是对抗瓦螨感染的重要自动保护机制。与蜜蜂相比,Apiscerana在从受感染的蜜蜂体内去除瓦螨方面表现出更有效的修饰行为。然而,调节修饰行为的潜在机制仍然难以捉摸。在这项研究中,我们评估了A.cerana和A.mellifera之间自动修饰行为的功效,并采用RNA测序技术来鉴定具有不同程度修饰行为强度的蜜蜂大脑中的差异表达基因(DEGs).我们观察到,与A.mellifera相比,A.cerana在第5天和第15天之间表现出更高的螨去除频率,第9天的蜜蜂显示出最高的螨去除频率。RNA测序结果揭示了HTR2A和SLC17A8基因在A中的差异表达。随后的同源性分析鉴定了A.cerana的HTR2A基因和SLC17A8基因与A.mellifera的HTR2A基因和SLC17A7基因同源。这些DEGs在神经活性配体-受体相互作用途径中被注释,谷氨酸能突触通路,和钙信号通路。此外,CCKAR,TpnC47D,HTR2A,和SLC17A7可能与A.mellifera的自动修饰行为密切相关,赋予对瓦螨侵染的抗性。我们的研究结果在分子水平上进一步解释了蜜蜂修饰行为与脑功能的关系,为进一步研究蜜蜂修饰行为的机制提供参考依据。
    The grooming behavior of honeybees serves as a crucial auto-protective mechanism against Varroa mite infestations. Compared to Apis mellifera, Apis cerana demonstrates more effective grooming behavior in removing Varroa mites from the bodies of infested bees. However, the underlying mechanisms regulating grooming behavior remain elusive. In this study, we evaluated the efficacy of the auto-grooming behavior between A. cerana and A. mellifera and employed RNA-sequencing technology to identify differentially expressed genes (DEGs) in bee brains with varying degrees of grooming behavior intensity. We observed that A. cerana exhibited a higher frequency of mite removal between day 5 and day 15 compared to A. mellifera, with day-9 bees showing the highest frequency of mite removal in A. cerana. RNA-sequencing results revealed the differential expression of the HTR2A and SLC17A8 genes in A. cerana and the CCKAR and TpnC47D genes in A. mellifera. Subsequent homology analysis identified the HTR2A gene and SLC17A8 gene of A. cerana as homologous to the HTR2A gene and SLC17A7 gene of A. mellifera. These DEGs are annotated in the neuroactive ligand-receptor interaction pathway, the glutamatergic synaptic pathway, and the calcium signaling pathway. Moreover, CCKAR, TpnC47D, HTR2A, and SLC17A7 may be closely related to the auto-grooming behavior of A. mellifera, conferring resistance against Varroa infestation. Our results further explain the relationship between honeybee grooming behavior and brain function at the molecular level and provide a reference basis for further studies of the mechanism of honeybee grooming behavior.
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  • 文章类型: Journal Article
    多宿主寄生虫对野生动物构成更大的健康风险,牲畜,和人类比单宿主寄生虫,然而,我们对生态和生物因素如何影响寄生虫宿主范围的理解仍然有限。这里,我们收集了关于永久性寄生哺乳动物螨的最大和最完整的数据集,并建立了一个预测模型,评估单宿主寄生虫成为多宿主的概率,同时考虑到潜在未观察到的宿主-寄生虫联系和类不平衡。该模型确定了与寄生虫相关的统计上显著的预测因子,主机,气候,和栖息地的干扰。最重要的预测因子包括寄生虫与宿主免疫系统的接触水平和表征宿主系统发育相似性和空间共同分布的两个变量。我们的模型揭示了与啮齿动物(啮齿动物)相关的螨虫的过度表达,翼翅目(蝙蝠),和食肉动物属于多宿主风险组。这突出了这些宿主对寄生虫侵扰的潜在脆弱性以及作为新宿主的寄生虫库的风险。此外,我们发现独立的宏观进化证据支持我们对Notoedres几种单宿主物种的预测,蝙蝠皮肤寄生虫,在多主机风险组中,展示了我们模型的预测潜力。
    Multi-host parasites pose greater health risks to wildlife, livestock, and humans than single-host parasites, yet our understanding of how ecological and biological factors influence a parasite\'s host range remains limited. Here, we assemble the largest and most complete dataset on permanently parasitic mammalian mites and build a predictive model assessing the probability of single-host parasites to become multi-hosts, while accounting for potentially unobserved host-parasite links and class imbalance. This model identifies statistically significant predictors related to parasites, hosts, climate, and habitat disturbance. The most important predictors include the parasite\'s contact level with the host immune system and two variables characterizing host phylogenetic similarity and spatial co-distribution. Our model reveals an overrepresentation of mites associated with Rodentia (rodents), Chiroptera (bats), and Carnivora in the multi-host risk group. This highlights both the potential vulnerability of these hosts to parasitic infestations and the risk of serving as reservoirs of parasites for new hosts. In addition, we find independent macroevolutionary evidence that supports our prediction of several single-host species of Notoedres, the bat skin parasites, to be in the multi-host risk group, demonstrating the forecasting potential of our model.
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  • 文章类型: Case Reports
    背景摩比汉病,也被称为Morbihan综合征,是一种罕见的医学疾病,其特征是慢性面部水肿主要影响面部的上三分之二。尽管几十年来一直在医学文献中得到认可,其真正的患病率和潜在的病理生理学仍然知之甚少。各种假设,包括淋巴引流受损,血管通透性异常,免疫失调,和蠕形螨感染的炎症反应,已提出解释病因。案例报告我们介绍了一例61岁的男性,面部上三分之一有组织的眼周水肿,最终导致莫比汉病的诊断。病人做了面部中部拉皮手术,允许组织检索用于眼睑水肿皮肤的组织病理学检查,显示慢性炎症,小淋巴管扩张,和蠕形螨在滤泡内定位的特征。这些发现并不具体,但与诊断假设一致.患者被转诊至风湿病学家进行进一步评估和治疗。他对全身性皮质类固醇和免疫抑制治疗反应不佳。相反,这导致水肿延伸到上眼睑。患者选择不接受进一步治疗。结论Morbihan病由于其罕见且临床特征与其他面部疾病重叠,常被误诊。它的管理具有挑战性,可能需要医疗和外科干预相结合。全身性皮质类固醇,免疫抑制剂,局部治疗取得了不同的成功。外科手术,如眼睑成形术或激光治疗,可以在严重的情况下考虑。早期识别和适当的管理对于改善患者预后和生活质量至关重要。
    BACKGROUND Morbihan disease, also known as Morbihan syndrome, is a rare medical condition characterized by chronic facial edema predominantly affecting the upper two-thirds of the face. Despite being recognized in medical literature for decades, its true prevalence and underlying pathophysiology remain poorly understood. Various hypotheses, including impaired lymphatic drainage, abnormal vascular permeability, immune dysregulation, and inflammatory reactions to demodex infestation, have been proposed to explain the etiology. CASE REPORT We present a case of a 61-year-old man with organized periocular edema of the upper third of the face, ultimately leading to Morbihan disease diagnosis. The patient underwent a midface lift, allowing for tissue retrieval for histopathological examination of the eyelid edematous skin, which revealed chronic inflammation, ectasia of small lymphatic vessels, and features of demodex intrafollicular localization. These findings were not specific, but consistent with the diagnostic hypothesis. The patient was referred to a rheumatologist for further evaluation and treatment. He did not respond well to systemic corticosteroids and immunosuppressive therapy. Rather, this resulted in extension of the edema to the upper eyelid. The patient opted not to undergo further treatment. CONCLUSIONS Morbihan disease is often misdiagnosed due to its rarity and overlapping clinical features with other facial conditions. Its management is challenging and can require a combination of medical and surgical interventions. Systemic corticosteroids, immunosuppressive agents, and topical treatments have had varying success. Surgical procedures, such as blepharoplasty or laser therapy, can be considered in severe cases. Early recognition and appropriate management are crucial to improving patient outcomes and quality of life.
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  • 文章类型: Journal Article
    人类蠕形螨是生活在毛囊皮脂腺单位中的寄生虫,可引起群虫病。虽然痴呆可能是一种原发性皮肤病,它也可能导致免疫抑制和局部或全身免疫抑制疗法。手术隆鼻是最常见的整容手术之一,它是各种皮肤并发症的原因,尤其是痤疮,因为它会影响皮肤的附件结构。因此,这项研究旨在调查手术鼻整形患者的皮肤变化是否使他们容易受到蠕形螨感染。
    接受过隆鼻手术的个体(患者)和年龄和性别匹配的健康志愿者(对照)被纳入这项前瞻性病例对照研究。要确定蠕形螨密度,使用标准浅表皮肤活检方法从患者和对照组的颌骨和鼻部区域收集样本。
    共有50名隆鼻患者和50名健康对照者参加了这项研究。鼻整形患者的鼻部蠕形螨密度明显较高(p=0.0001)。此外,与对照组相比,隆鼻患者的干燥和脓疱的频率显着升高(分别为p=0.046和p=0.001)。
    手术隆鼻术可能是引起痴呆的危险因素,经过适当的诊断和治疗,患者将在手术后更快地康复。
    UNASSIGNED: Human Demodex mites are parasites that live in the pilosebaceous unit and can cause demodicosis. While demodicosis may occur as a primary skin disease, it may also result from immunosuppression and topical or systemic immunosuppressive therapies. Surgical rhinoplasty is one of the most commonly performed cosmetic procedures, and it is the cause of a variety of cutaneous complications, particularly acne, as it affects the skin\'s adnexal structures. Thus, this study aimed to investigate whether the cutaneous changes in surgical rhinoplasty patients render them vulnerable to Demodex infestation.
    UNASSIGNED: Individuals who had undergone rhinoplasty (patients) and age- and sex-matched healthy volunteers (controls) were included in this prospective case-control study. To determine the Demodex density, samples were collected from the malar and nasal regions of both the patients and controls using the standard superficial skin biopsy method.
    UNASSIGNED: A total of 50 rhinoplasty patients and 50 healthy controls were enrolled in the study. The Demodex density on the nose was significantly higher in the rhinoplasty patients (p = 0.0001). Furthermore, the frequency of xerosis and pustules was significantly higher in the rhinoplasty patients compared to the control group (p = 0.046 and p = 0.001, respectively).
    UNASSIGNED: Surgical rhinoplasty may be a risk factor for demodicosis, and patients will recover faster after surgery with proper diagnosis and treatment.
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