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Infection-Associated Flares in Systemic Lupus Erythematosus. 系统性红斑狼疮的感染相关性发作。
IF 3.3 3区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-26 DOI: 10.3390/pathogens13110934
Giuseppe A Ramirez, Chiara Calabrese, Marta Secci, Luca Moroni, Gabriele D Gallina, Giovanni Benanti, Enrica P Bozzolo, Marco Matucci-Cerinic, Lorenzo Dagna

Systemic lupus erythematosus (SLE) is characterised by generalised immune dysfunction, including infection susceptibility. Infection-associated flares (IAFs) are common and might rapidly self-resolve, paralleling infection resolution, but their specific clinical phenotype is poorly understood. Therefore, we screened 2039 consecutive visits and identified 134 flares, defined as a loss of the lupus low disease activity state (LLDAS), from 1089 visits at risk spanning over multiple follow-up years, yielding an average yearly LLDAS deterioration rate of 17%. Thirty-eight IAFs were isolated from the total flares and were mostly related to bacterial and herpesvirus infections. When compared to other flares (OFs; n = 98), IAFs showed no milder patterns of organ involvement and similar rates of long-term damage accrual, as estimated by conventional clinimetrics. Arthritis in IAFs was more severe than that in OFs [median (interquartile range) DAS-28 2.6 (2.3-4.1) vs. 2.0 (1.6-2.7); p = 0.02]. Viral IAFs were characterised by atypically lower levels of anti-DNA antibodies (p < 0.001) and possibly abnormally high complement levels when compared to flares of different origin. These data suggest that IAFs are of comparable or even higher severity than OFs and may subtend distinct pathophysiological mechanisms that are poorly tackled by current treatments. Further research is needed to confirm these data.

系统性红斑狼疮(SLE)的特点是全身免疫功能失调,包括易感染。感染相关性复发(IAFs)很常见,可能在感染缓解的同时迅速自行消退,但对其具体的临床表型却知之甚少。因此,我们对2039例连续就诊者进行了筛查,并从跨越多个随访年的1089例风险就诊者中确定了134例复发,即狼疮低疾病活动状态(LLDAS)的丧失,平均每年LLDAS恶化率为17%。从所有复发病例中分离出38例IAF,大多与细菌和疱疹病毒感染有关。与其他病例(OFs;n = 98)相比,IAFs的器官受累程度并不轻,而且根据传统的临床测量法估算,其长期损害累积率也相似。IAFs的关节炎比OFs更严重[DAS-28中位数(四分位数间距)2.6 (2.3-4.1) vs. 2.0 (1.6-2.7); p = 0.02]。与不同原因引起的复发相比,病毒性IAF的特点是抗DNA抗体水平异常低(p < 0.001),补体水平也可能异常高。这些数据表明,IAFs的严重程度与OFs相当,甚至更高,而且可能具有不同的病理生理机制,但目前的治疗方法却无法很好地解决这些问题。要证实这些数据,还需要进一步的研究。
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引用次数: 0
Epidemiology of Bacteremia in Patients with Hematological Malignancies and Hematopoietic Stem Cell Transplantation and the Impact of Antibiotic Resistance on Mortality: Data from a Multicenter Study in Argentina. 血液恶性肿瘤和造血干细胞移植患者菌血症的流行病学以及抗生素耐药性对死亡率的影响:来自阿根廷一项多中心研究的数据。
IF 3.3 3区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-26 DOI: 10.3390/pathogens13110933
Fabián Herrera, Diego Torres, Ana Laborde, Rosana Jordán, Lorena Berruezo, Inés Roccia Rossi, Noelia Mañez, Lucas Tula, María Laura Pereyra, Andrea Nenna, Patricia Costantini, José Benso, María Luz González Ibañez, María José Eusebio, Nadia Baldoni, Laura Alicia Barcán, Sandra Lambert, Martín Luck, Fernando Pasterán, Alejandra Corso, Melina Rapoport, Federico Nicola, María Cristina García Damiano, Renata Monge, Ruth Carbone, Mariana Reynaldi, Graciela Greco, Miriam Blanco, María Laura Chaves, Marcelo Bronzi, Alberto Carena

The epidemiology of bacteremia and the antibiotic resistance profile (ARP) of Gram-negative bacilli (GNB) in hematological malignancies (HM) and hematopoietic stem cell transplant (HSCT) patients may differ according to geographic region. In addition, multidrug-resistant organisms (MDROs) may impact mortality. This is a prospective, observational, and multicenter study. The first episodes of bacteremia in adult patients with HM or HSCT were included. The risk factors for 30-day mortality were identified. One thousand two hundred and seventy-seven episodes were included (HM: 920; HSCT: 357). GNB were isolated in 60.3% of episodes, with Enterobacterales (46.9%) and P. aeruginosa (8.5%) being the most frequent. Gram-positive cocci were isolated in 41.9% of episodes, with coagulase-negative staphylococci (19.8%) and S. aureus (10.4%) being the most frequent. MDROs were isolated in 40.2% (24.4% GNB). The ARP of GNB in patients with HM vs. HSCT was cefepime: 36.8% vs. 45.7% (p = 0.026); piperacillin-tazobactam: 31.05% vs. 45.2% (p < 0.0001); carbapenems: 18.9% vs. 27.3% (p = 0.012); and aminoglycosides: 9.3% vs. 15.4% (p = 0.017), respectively. Overall mortality between patients with HM and HSCT was 17.5% vs. 17.6% (p = 0.951), respectively. The risk factors for mortality were relapsed and refractory underlying disease, corticosteroids use, respiratory source, septic shock, and GNB resistant to meropenem, while 7-day clinical response was a protective factor for survival. Bacteremia was frequently caused by GNB, with a large proportion of MDROs and a high level of antibiotic resistance, especially in patients with HSCT. Carbapenem-resistant GNB bacteremia was associated with a significant increase in mortality.

血液恶性肿瘤(HM)和造血干细胞移植(HSCT)患者的菌血症流行病学和革兰氏阴性杆菌(GNB)的抗生素耐药性概况(ARP)可能因地理区域而异。此外,耐多药生物(MDROs)可能会影响死亡率。这是一项前瞻性、观察性、多中心研究。研究纳入了首次发生菌血症的 HM 或造血干细胞移植成人患者。确定了 30 天死亡率的风险因素。研究共纳入 1277 例病例(HM:920 例;造血干细胞移植:357 例)。60.3%的病例分离出革兰氏阳性球菌,其中最常见的是肠杆菌(46.9%)和铜绿假单胞菌(8.5%)。41.9%的病例分离出革兰氏阳性球菌,其中以凝固酶阴性葡萄球菌(19.8%)和金黄色葡萄球菌(10.4%)最为常见。40.2%的患者(24.4%为 GNB)分离出 MDRO。与造血干细胞移植相比,HM 患者 GNB 的 ARP 分别为头孢吡肟:36.8% 对 45.7%(P = 0.026);哌拉西林-他唑巴坦:31.05% 对 45.7%(P = 0.026);哌拉西林-他唑巴坦:31.05% 对 45.7%(P = 0.026):31.05%对45.2%(P<0.0001);碳青霉烯类:18.9%对27.2%(P<0.0001):18.9%对 27.3%(p = 0.012);氨基糖苷类:9.3%对 15.3%(p = 0.0001):分别为 9.3% vs. 15.4% (p = 0.017)。HM和造血干细胞移植患者的总死亡率分别为17.5% vs. 17.6% (p = 0.951)。复发和难治性基础疾病、使用皮质类固醇、呼吸道来源、脓毒性休克和对美罗培南耐药的 GNB 是导致死亡的风险因素,而 7 天临床反应则是生存的保护因素。菌血症通常由GNB引起,其中MDRO占很大比例,抗生素耐药性很高,尤其是在造血干细胞移植患者中。对碳青霉烯类耐药的 GNB 菌血症与死亡率的显著增加有关。
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引用次数: 0
Pseudorabies Virus Prevalence in Lung Samples of Hunted Wild Boars in Northwestern Greece. 希腊西北部被猎杀野猪肺部样本中伪狂犬病病毒的流行情况。
IF 3.3 3区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-25 DOI: 10.3390/pathogens13110929
Konstantinos Papageorgiou, Aikaterini Stoikou, Dimitrios K Papadopoulos, Efpraxia Tsapouri-Kanoula, Ioannis A Giantsis, Dimitrios Papadopoulos, Efthymia Stamelou, Marina Sofia, Charalambos Billinis, Chrysanthi Karapetsiou, Evanthia Petridou, Spyridon K Kritas

Aujeszky's Disease, caused by the pseudorabies virus (PRV), is an acute, often fatal disease affecting mainly pigs and incidentally other animals. While eradicated in several countries, PRV persists in wild boar populations, posing a risk to domestic pigs. This study investigates PRV prevalence in wild boars in the region of Epirus, located in the northwest of Greece. During the 2021-2022 hunting season, 110 lung samples from hunted wild boars were collected and analyzed for PRV DNA and cytopathic effects in cell cultures. PRV DNA was detected in 19 samples (17.3%), 18 of which exhibiting cytopathic effects, allowing for virus titer determination. Notably, in one sample, PRV DNA was detected without a cytopathic effect. These findings underscore the continued presence of PRV in Greek wild boars, highlighting the need for ongoing monitoring to prevent transmission to domestic pigs and other animals.

由伪狂犬病毒(PRV)引起的奥杰斯基病是一种急性、往往致命的疾病,主要影响猪,也会偶然影响其他动物。虽然 PRV 已在多个国家根除,但在野猪种群中依然存在,对家猪构成威胁。本研究调查了希腊西北部伊庇鲁斯地区野猪中 PRV 的流行情况。在 2021-2022 年狩猎季节,研究人员收集了 110 份被猎杀野猪的肺部样本,并在细胞培养物中分析了 PRV DNA 和细胞病理效应。在 19 个样本(17.3%)中检测到了 PRV DNA,其中 18 个样本表现出细胞病理效应,可以进行病毒滴度测定。值得注意的是,在一个样本中检测到了 PRV DNA,但没有细胞病理效应。这些发现强调了希腊野猪中仍然存在 PRV,突出了持续监测以防止传染给家猪和其他动物的必要性。
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引用次数: 0
A Novel Immunochromatographic Test Strip Using Lanthanide-Labeled Fluorescent Nanoparticles for the Serological Detection of Toxoplasma gondii in Dogs and Cats. 使用镧系元素标记的荧光纳米粒子的新型免疫层析试纸,用于猫狗弓形虫血清学检测
IF 3.3 3区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-25 DOI: 10.3390/pathogens13110931
Manyu Zhang, Qi Liu, Ruifang Li, Wei Jiang, Hongjin Zhao, Wenwei Sheng, Luming Xia, Zengqiang Li, Qing Sun, Jingying Du, Lei Lei, Quan Wang

Toxoplasma gondii (T. gondii) is an important zoonotic pathogen which induces both acute and chronic toxoplasmosis. Timely diagnosis of T. gondii is crucial for effective disease management. Here, we present a pioneering approach using europium (III)-chelated nanoparticles (EuNPs) in a rapid lateral flow immunochromatographic test strip (ICTS) for detecting T. gondii antibodies in serum samples. By conjugating EuNPs with Staphylococcus aureus protein A, we efficiently captured T. gondii-specific antibodies, which bound to T. gondii antigens on the test line (T-line), generating a distinct fluorescent signal. Employing this novel method, we conducted an extensive epidemiological investigation of T. gondii infections among dogs and cats in Shanghai, China. This innovative ICTS allows for rapid results within 25 min, which include a qualitative result through naked-eye observation under an ultraviolet lamp and a quantitative one derived using a strip reader. With a detection limit of 1:6400 for dog positive serum and no cross-reactivity with other canine and feline pathogens, the EuNPs-ICTS demonstrated excellent consistency with standard enzyme-linked immunosorbent assay results for dogs (κ = 0.91) and cats (κ = 0.92). In addition, 20.38% of 996 dog serum samples and 14.18% of 416 cat serum samples revealed T. gondii antibodies, highlighting the efficacy of this approach. Our study presents a rapid, sensitive, specific, and reproducible EuNPs-ICTS, serving as a promising tool for on-the-spot diagnosis of T. gondii infections in dogs and cats.

弓形虫(T. gondii)是一种重要的人畜共患病原体,可诱发急性和慢性弓形虫病。及时诊断弓形虫对有效控制疾病至关重要。在这里,我们提出了一种在快速侧流免疫层析试纸条(ICTS)中使用铕(III)螯合纳米粒子(EuNPs)检测血清样本中淋球菌抗体的开创性方法。通过将 EuNPs 与金黄色葡萄球菌蛋白 A 共轭,我们有效地捕获了淋球菌特异性抗体,这些抗体与检测线(T 线)上的淋球菌抗原结合,产生了明显的荧光信号。利用这种新方法,我们对中国上海猫狗的淋病感染情况进行了广泛的流行病学调查。这种创新的信息和通信技术可在 25 分钟内快速得出结果,包括通过紫外灯下的肉眼观察得出的定性结果和使用条形阅读器得出的定量结果。EuNPs-ICTS对犬阳性血清的检测限为1:6400,且与其他犬科和猫科病原体无交叉反应,与标准酶联免疫吸附测定的犬检测结果(κ = 0.91)和猫检测结果(κ = 0.92)非常一致。此外,996 份狗血清样本中的 20.38% 和 416 份猫血清样本中的 14.18% 发现了淋病双球菌抗体,凸显了这种方法的有效性。我们的研究提出了一种快速、灵敏、特异和可重现的 EuNPs-ICTS,可作为现场诊断猫狗淋球菌感染的有效工具。
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引用次数: 0
Fungi Associated with Olive Tree (cv. 'Nocellara del Belice') Decay in Trapani Province (Sicily, Italy). 意大利西西里岛特拉帕尼省与橄榄树("Nocellara del Belice "品种)腐烂有关的真菌。
IF 3.3 3区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-25 DOI: 10.3390/pathogens13110932
Marika Lamendola, Giulia Mirabile, Josè Muratore, Livio Torta

Recently, in several locations in the province of Trapani (Sicily, Italy), olive growers have reported cases of decaying olive trees of cv. 'Nocellara del Belice', showing symptoms of defoliation, branch drying, xylem browning, and reduced production. Internal symptoms include white and brown wood rot, starting from the base of the trunk. These alterations have been observed in trees irrigated using a pipe system at the trunk with spray sprinklers. To identify the causal agents of decay, some trees were eradicated and dissected, and woody samples were processed to isolate and identify the associated fungal micro-organisms. The most common colonies were identified using morphological (macro- and microscopical observation) and molecular (PCR amplification of the rDNA-ITS region) analyses. Nine fungal taxa were identified, of which four were associated with this decay syndrome (Coriolopsis gallica, Fomitiporia mediterranea, Kirschsteiniothelia sp., and Pleurostoma richardsiae), three were considered ubiquitous and opportunistic fungi (Alternaria spp., Aspergillus amstelodami, and Trichoderma sp.), and the other two were mycelia sterilia. Artificial inoculation satisfied Koch's postulates, confirming the pathogenicity of the aforementioned fungi, even though the infections in the fields seem to be related to the irrigation system. This hypothesis would seem to be confirmed by the progression of decay over time in the trees subjected to the irrigation system described but not reported in olive groves differently managed. It is therefore considered appropriate to conduct further and more in-depth investigations aimed at studying the correlation between the irrigation system, presence of fungal agents, and manifestation of the syndrome. A further ongoing investigation is aimed at the use of biostimulants (Agrusaver, Savory Sun, VA LLC) on symptomatic trees, with the aim of both improving the vegetative performance of the host and limiting the symptoms detected in the field.

最近,在特拉帕尼省(意大利西西里岛)的一些地方,橄榄种植者报告了变种 "Nocellara del Belice "橄榄树腐烂的案例,表现出落叶、枝干干枯、木质部变褐和产量下降等症状。内部症状包括从树干基部开始的白色和棕色木质腐烂。在树干处使用管道系统和喷雾喷头灌溉的树木上也观察到了这些变化。为了确定腐烂的病原体,对一些树木进行了铲除和解剖,并对木质样本进行了处理,以分离和鉴定相关的真菌微生物。通过形态学(宏观和显微镜观察)和分子学(rDNA-ITS 区域的 PCR 扩增)分析,确定了最常见的菌落。共鉴定出 9 个真菌类群,其中 4 个与这种腐烂综合症有关(Coriolopsis gallica、Fomitiporia mediterranea、Kirschsteiniothelia sp.和 Pleurostoma richardsiae),3 个被认为是普遍存在的机会性真菌(Alternaria spp.、Aspergillus amstelodami 和 Trichoderma sp.),另外 2 个是菌丝体固着菌。人工接种符合科赫假说,证实了上述真菌的致病性,尽管田间感染似乎与灌溉系统有关。随着时间的推移,使用灌溉系统的果树腐烂的情况似乎也证实了这一假设,但在管理方式不同的橄榄园中却未见报道。因此,我们认为应该进一步开展更深入的调查,研究灌溉系统、真菌的存在和综合症表现之间的相关性。正在进行的另一项调查旨在对有症状的树木使用生物刺激剂(Agrusaver,Savory Sun,VA LLC),目的是改善寄主的植被表现,并限制在田间发现的症状。
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引用次数: 0
The Detection of Chlamydia pneumoniae, Helicobacter pylori and Cytomegalovirus in Non-Atherosclerotic Arteries of Patients with Coronary Artery Disease. 冠状动脉疾病患者非动脉粥样硬化动脉中肺炎衣原体、幽门螺旋杆菌和巨细胞病毒的检测。
IF 3.3 3区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-25 DOI: 10.3390/pathogens13110927
Dalila Šačić, Uroš Tomić, Jelena Milašin, Svetozar Putnik, Milena Jovanović, Sanja Radojević Škodrić, Sofija Glumac

Atherosclerotic coronary artery disease (ACAD) is a major cause of global morbidity and mortality, characterized as an inflammatory process due to damage to blood vessel walls by risk factors like aging, hyperlipidemia, hypertension, smoking, and diabetes. Infectious agents, including Chlamydia pneumoniae (Cpn), Cytomegalovirus (CMV), and Helicobacter pylori (HP), have been implicated in ACAD's pathophysiology. A study with 56 subjects undergoing coronary artery bypass grafting (CABG) aimed to detect Cpn, CMV, and HP DNA in unaffected artery segments and explore associations with disease progression and inflammation markers. The study found infectious agents' DNA in 21.4% of samples, HP in eight samples, and CMV and Cpn in four samples each. Significant correlations were observed between HP and overweight or obese subjects, as well as between the presence of infectious agents and inflammation marker values. An association between HP and renal function was also noted. The findings reaffirm previous discoveries of infectious agents in non-clinically affected arteries used as CABG grafts. Correlations identified between the presence of HP, CMV, and Cpn DNA in grafts and several biomarkers of inflammation and obesity emphasize the potential role of these infectious agents in ACAD pathogenesis.

动脉粥样硬化性冠状动脉疾病(ACAD)是全球发病率和死亡率的主要原因,其特点是由于老化、高脂血症、高血压、吸烟和糖尿病等危险因素对血管壁的损害而导致的炎症过程。包括肺炎衣原体(Cpn)、巨细胞病毒(CMV)和幽门螺旋杆菌(HP)在内的感染病原体与 ACAD 的病理生理学有关。一项针对 56 名接受冠状动脉旁路移植术(CABG)的受试者的研究旨在检测未受影响的动脉片段中的 Cpn、CMV 和 HP DNA,并探讨它们与疾病进展和炎症指标的关联。该研究在 21.4% 的样本中发现了传染性病原体 DNA,在 8 个样本中发现了 HP,在 4 个样本中分别发现了 CMV 和 Cpn。研究发现,HP 与超重或肥胖受试者之间以及感染病原体的存在与炎症标志物值之间存在显著相关性。此外,还发现 HP 与肾功能之间存在关联。研究结果再次证实了之前在作为 CABG 移植物的非临床受影响动脉中发现的感染性病原体。移植物中存在的 HP、CMV 和 Cpn DNA 与炎症和肥胖的几种生物标志物之间的相关性强调了这些感染病原体在 ACAD 发病机制中的潜在作用。
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引用次数: 0
Intestinal Parasites and Hematological Parameters in Children Living in Ambatoboeny District, Madagascar. 马达加斯加 Ambatoboeny 区儿童的肠道寄生虫和血液参数。
IF 3.3 3区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-25 DOI: 10.3390/pathogens13110930
Wanesa Richert, Daria Kołodziej, Danuta Zarudzka, Daniel Kasprowicz, Dariusz Świetlik, Krzysztof Korzeniewski

Madagascar is one of the poorest countries in the world. The country's extreme weather conditions, poor sanitation, and weak economy facilitate the spread of parasitic diseases. Infections with intestinal parasites are particularly dangerous for children because they can cause malnutrition and anemia, which, in turn, have a negative effect on children's cognitive functions and physical development. The aim of the present study was to analyze the prevalence of intestinal parasites and to assess hematological parameters in a group of children living in northern Madagascar. The screening was conducted in May 2024 in the Clinique Medicale Beyzym in Manerinerina, the Ambatoboeny district. It involved a sample of 208 children aged 0-17 years. Single stool samples were collected from all study participants. The samples were fixed in SAF fixative and then transported from Africa to Europe for further diagnostics at the Department of Epidemiology and Tropical Medicine, the Military Institute of Medicine-the National Research Institute in Poland. First, the samples were analyzed by light microscopy methods using three different diagnostic techniques (direct smear, decantation with distilled water, and the Fülleborn method). Next, they were tested by molecular biology methods (real-time PCR). Blood samples for the assessment of hematological parameters were collected at the healthcare center in Madagascar. The prevalence of intestinal parasites in the study sample was 61.5%. Helminths were found in 15.2% of the investigated children, and Giardia intestinalis (20.5%) was found to be the most prevalent parasite in the study population. Most infections were caused by potentially pathogenic stramenopila Blastocystis spp. (32.0%). Mean Hb, HCT, MCV, MCH, and MCHC levels in the study participants were below normal values. However, no correlation was found between the presence of a parasitic infection and low hematological parameters, which are a clinical sign of anemia. High rates of infections with intestinal parasites in children living in northern Madagascar support the necessity to introduce long-term preventive measures, which would limit the spread of parasitic diseases in the Malagasy population. Low hematological parameters in non-infected children may be indicative of persistent malnutrition or infection with other parasites, e.g., malaria or schistosomiasis.

马达加斯加是世界上最贫穷的国家之一。该国极端的气候条件、恶劣的卫生条件和薄弱的经济为寄生虫病的传播提供了便利。肠道寄生虫感染对儿童尤其危险,因为它们会导致营养不良和贫血,进而对儿童的认知功能和身体发育产生负面影响。本研究旨在分析马达加斯加北部一组儿童的肠道寄生虫感染率,并评估其血液学参数。筛查于 2024 年 5 月在 Ambatoboeny 区 Manerinerina 的 Beyzym 医疗诊所进行。抽样调查了 208 名 0-17 岁的儿童。所有研究参与者都采集了粪便样本。样本在 SAF 固定液中固定,然后从非洲运往欧洲,在波兰国家研究所军事医学研究院流行病学和热带医学系进行进一步诊断。首先,使用三种不同的诊断技术(直接涂片法、蒸馏水倾析法和福勒伯恩法)对样本进行光学显微镜分析。然后,用分子生物学方法(实时 PCR)进行检测。评估血液学参数的血样是在马达加斯加医疗中心采集的。研究样本中的肠道寄生虫感染率为 61.5%。在15.2%的受调查儿童中发现了蠕虫,而贾第虫(Giardia intestinalis)(20.5%)是研究人群中最常见的寄生虫。大多数感染是由潜在致病性葡萄球菌引起的(32.0%)。研究参与者的平均血红蛋白(Hb)、血细胞比容(HCT)、血浆胆固醇(MCV)、血浆胆固醇(MCH)和血浆胆红素(MCHC)水平均低于正常值。然而,寄生虫感染与低血液学参数(贫血的临床表现)之间并无关联。马达加斯加北部儿童的肠道寄生虫感染率很高,这说明有必要采取长期的预防措施,以限制寄生虫病在马达加斯加人口中的传播。未感染寄生虫的儿童血液参数偏低,可能表明他们持续营养不良或感染了其他寄生虫,如疟疾或血吸虫病。
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引用次数: 0
An In Silico Approach to Discover Efficient Natural Inhibitors to Tie Up Epstein-Barr Virus Infection. 一种发现高效天然抑制剂的硅学方法,用于抑制 Epstein-Barr 病毒感染。
IF 3.3 3区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-25 DOI: 10.3390/pathogens13110928
Ayan Das, Mumtaza Mumu, Tanjilur Rahman, Md Abu Sayeed, Md Mazharul Islam, John I Alawneh, Mohammad Mahmudul Hassan

Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a member of the herpes virus family. EBV is a widespread virus and causes infectious mononucleosis, which manifests with symptoms such as fever, fatigue, lymphadenopathy, splenomegaly, and hepatomegaly. Additionally, EBV is associated with different lymphocyte-associated non-malignant, premalignant, and malignant diseases. So far, no effective treatment or therapeutic drug is known for EBV-induced infections and diseases. This study investigated natural compounds that inhibit EBV glycoprotein L (gL) and block EBV fusion in host cells. We utilised computational approaches, including molecular docking, in silico ADMET analysis, and molecular dynamics simulation. We docked 628 natural compounds against gL and identified the four best compounds based on binding scores and pharmacokinetic properties. These four compounds, with PubChem CIDs 4835509 (CHx-HHPD-Ac), 2870247 (Cyh-GlcNAc), 21206004 (Hep-HHPD-Ac), and 51066638 (Und-GlcNAc), showed several interactions with EBV gL. However, molecular dynamics simulations indicated that the protein-ligand complexes of CID: 4835509 (CHx-HHPD-Ac) and CID: 2870247 (Cyh-GlcNAc) are more stable than those of the other two compounds. Therefore, CIDs 4835509 and 2870247 (Cyh-GlcNAc) may be potent natural inhibitors of EBV infection. These findings can open a new way for effective drug design against EBV and its associated infections and diseases.

爱泼斯坦-巴尔病毒(EBV)又称人类疱疹病毒 4,是疱疹病毒家族的一员。EBV 是一种广泛传播的病毒,可引起传染性单核细胞增多症,表现为发热、乏力、淋巴结肿大、脾脏肿大和肝脏肿大等症状。此外,EBV 还与不同的淋巴细胞相关的非恶性、恶性前和恶性疾病有关。迄今为止,还没有针对 EBV 引起的感染和疾病的有效治疗方法或治疗药物。本研究调查了抑制 EBV 糖蛋白 L(gL)和阻止 EBV 在宿主细胞中融合的天然化合物。我们采用了计算方法,包括分子对接、默克 ADMET 分析和分子动力学模拟。我们将 628 种天然化合物与 gL 进行了对接,并根据结合得分和药代动力学特性确定了四种最佳化合物。这四种化合物的 PubChem CID 分别为 4835509(CHx-HHPD-Ac)、2870247(Cyh-GlcNAc)、21206004(Hep-HHPD-Ac)和 51066638(Und-GlcNAc),它们与 EBV gL 发生了多次相互作用。然而,分子动力学模拟表明,CID: 4835509(CHx-HHPD-Ac)和 CID: 2870247(Cyh-GlcNAc)的蛋白质配体复合物比其他两种化合物更稳定。因此,CID 4835509 和 2870247(Cyh-GlcNAc)可能是有效的天然 EBV 感染抑制剂。这些发现将为针对 EBV 及其相关感染和疾病的有效药物设计开辟一条新途径。
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引用次数: 0
Predicting Treatment Outcomes in Patients with Drug-Resistant Tuberculosis and Human Immunodeficiency Virus Coinfection, Using Supervised Machine Learning Algorithm. 利用监督机器学习算法预测耐药结核病和人类免疫缺陷病毒双重感染患者的治疗结果
IF 3.3 3区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-24 DOI: 10.3390/pathogens13110923
Mojisola Clara Hosu, Lindiwe Modest Faye, Teke Apalata

Drug-resistant tuberculosis (DR-TB) and HIV coinfection present a conundrum to public health globally and the achievement of the global END TB strategy in 2035. A descriptive, retrospective review of medical records of patients, who were diagnosed with DR-TB and received treatment, was conducted. Student's t-test was performed to assess differences between two means and ANOVA between groups. The Chi-square test with or without trend or Fischer's exact test was used to test the degree of association of categorical variables. Logistic regression was used to determine predictors of DR-TB treatment outcomes. A decision tree classifier, which is a supervised machine learning algorithm, was also used. Python version 3.8. and R version 4.1.1 software were used for data analysis. A p-value of 0.05 with a 95% confidence interval (CI) was used to determine statistical significance. A total of 456 DR-TB patients were included in the study, with more male patients (n = 256, 56.1%) than female patients (n = 200, 43.9%). The overall treatment success rate was 61.4%. There was a significant decrease in the % of patients cured during the COVID-19 pandemic compared to the pre-pandemic period. Our findings showed that machine learning can be used to predict TB patients' treatment outcomes.

耐药性结核病(DR-TB)和艾滋病病毒(HIV)合并感染给全球公共卫生和实现 2035 年全球终结结核病战略带来了难题。我们对被诊断为 DR-TB 并接受治疗的患者的医疗记录进行了描述性、回顾性审查。采用学生 t 检验来评估两个均值之间的差异,并对组间差异进行方差分析。使用带或不带趋势的卡方检验(Chi-square test with or without trend)或费舍尔精确检验(Fischer's exact test)来检验分类变量之间的关联程度。逻辑回归用于确定 DR-TB 治疗结果的预测因素。还使用了决策树分类器,这是一种有监督的机器学习算法。数据分析使用了 Python 3.8 版和 R 4.1.1 版软件。统计显著性以 0.05 的 p 值和 95% 的置信区间 (CI) 为标准。研究共纳入 456 名 DR-TB 患者,其中男性患者(n = 256,56.1%)多于女性患者(n = 200,43.9%)。总体治疗成功率为 61.4%。与大流行前相比,COVID-19 大流行期间治愈患者的比例明显下降。我们的研究结果表明,机器学习可用于预测肺结核患者的治疗结果。
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引用次数: 0
Suppression by RNA Polymerase I Inhibitors Varies Greatly Between Distinct RNA Polymerase I Transcribed Genes in Malaria Parasites. 疟疾寄生虫中不同的 RNA 聚合酶 I 转录基因对 RNA 聚合酶 I 抑制剂的抑制作用差别很大。
IF 3.3 3区 医学 Q2 MICROBIOLOGY Pub Date : 2024-10-24 DOI: 10.3390/pathogens13110924
Hermela Samuel, Riward Campelo Morillo, Björn F C Kafsack

The transcription of ribosomal RNA (rRNA) by RNA Polymerase I (Pol I) is the rate-limiting step in ribosome biogenesis and a major determinant of cellular growth rates. Unlike other eukaryotes, which express identical rRNA from large tandem arrays of dozens to hundreds of identical rRNA genes in every cell, the genome of the human malaria parasite Plasmodium falciparum contains only a handful single-copy 47S rRNA loci that differ substantially from one another in length, sequence, and expression in different cell types. We found that the growth of the malaria parasite was acutely sensitive to the Pol I inhibitors 9-hydroxyellipticine and BMH-21 and demonstrated that they greatly reduce the transcription of 47S rRNAs as well as the transcription of other non-coding RNA genes. This makes P. falciparum only the second known organism where RNA Polymerase I transcribes genes other than the 47S rRNAs. We found that the various types of Pol I-transcribed genes differed by more than two orders of magnitude in their susceptibility to these inhibitors and explored the implications of these findings for the regulation of rRNA in P. falciparum.

RNA 聚合酶 I(Pol I)转录核糖体 RNA(rRNA)是核糖体生物发生过程中的限速步骤,也是细胞生长速度的主要决定因素。与其他真核生物不同,人类疟原虫的基因组只包含少数几个单拷贝的 47S rRNA 位点,这些位点在长度、序列和在不同细胞类型中的表达上都有很大差异。我们发现,疟原虫的生长对 Pol I 抑制剂 9-hydroxyellipticine 和 BMH-21 非常敏感,并证明这两种抑制剂大大降低了 47S rRNA 的转录以及其他非编码 RNA 基因的转录。这使恶性疟原虫成为第二种RNA聚合酶I转录47S rRNA以外基因的已知生物。我们发现,各种类型的 Pol I 转录基因对这些抑制剂的敏感性相差两个数量级以上,并探讨了这些发现对恶性疟原虫 rRNA 调控的影响。
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引用次数: 0
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Pathogens
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