Severe Neurological Complications Research Articles

A novel rapid visual nucleic acid detection technique for tick-borne encephalitis virus by combining RT-recombinase-aided amplification and CRISPR/Cas13a coupled with a lateral flow dipstick

Tick-borne encephalitis virus (TBEV), a zoonotic pathogen, can cause severe neurological complications and fatal outcomes in humans. Early diagnosis of TBEV infection is crucial for clinical practice. Although serological assays are frequently employed for detection, the lack of antibodies in the early stages of infection and the cross-reactivity of antibodies limit their efficacy. Conventional molecular diagnostic methods such as RT-qPCR can achieve early and accurate identification but require specialized instrumentation and professionals, hindering their application in resource-limited areas. Our study developed a rapid and visual TBEV molecular detection method by combining RT-recombinase-aided amplification, the CRISPR/Cas13a system, and lateral flow dipsticks. The diagnostic sensitivity of this method is 50 CFU/ml, with no cross-reactivity with a variety of viruses. The detection can be carried out within 1 h at a temperature between 37 and 42 °C, and the results can be visually determined without the need for complex instruments and professionals. Subsequently, this assay was used to analyze clinical samples from 15 patients suspected of TBEV infection and 10 healthy volunteers, and its sensitivity and specificity reached 100 %, which was consistent with the results of RT-qPCR. These results indicate that this new method can be a promising point-of-care test for the diagnosis of tick-borne encephalitis.

#2707 Prediction of plasma sodium changes in hypernatremic patients: the role of tissue sodium content

Abstract Background and Aims Hypo- and hypernatremia are frequently encountered electrolyte disturbances in clinical practice. Rapid correction of these dysnatremias can result in severe neurological complications. Therefore, various formulas have been developed to predict changes in plasma sodium concentration ([Na+]) after treatment. However, these kidney-centered formulas have been shown to be inaccurate. A potential explanation for the discrepancy between predicted and measured plasma [Na+] is the accumulation of sodium in the skin, which is not explicitly taken into account in these formulas. The purpose of this post-hoc analysis is to evaluate the association between factors related to tissue sodium accumulation and the discrepancy between measured and predicted plasma [Na+]. Method We used data from a hypernatremic intensive care unit (ICU) cohort with 66 patients and 1,034 ICU days with complete data on sodium, potassium and water balance. We excluded ICU days with incomplete balances, dialysis and severe diarrhea. The predicted plasma [Na+] was calculated using the Barsoum-Levine (BL) and the Nguyen-Kurtz (NK) formula. Then, we calculated the discrepancy between predicted and measured plasma [Na+] (∆[Na+]). We fitted a linear mixed-effect model to investigate the association between factors related to tissue sodium content and ∆[Na+]. Age, sex, blood pressure, eGFR, CRP, plasma albumin, total body water (TBW), baseline plasma [Na+] and changes in plasma [Na+] were incorporated as fixed effects in the model, while the subjects were introduced as a random effect. TBW was estimated as 60% of body weight for males and 50% of body weight for females, corrected for fluid balances on subsequent ICU days. Results A total of 613 ICU days of 66 patients were included in our analysis. The mean age was 58 ± 15 years and 38% was female. The mean plasma [Na+] at inclusion day was 145 ± 9 mmol/L and mean eGFR CKD-EPI was 52 ± 28 ml/min/1.73 m2. On average, the deviation between predicted and measured plasma [Na+] was 3.8 ± 3.3 mmol/L for the BL formula and 3.9 ± 3.4 mmol/L for the NK formula. For both formulas, TBW (p = 0.01), baseline plasma [Na+] (p < 0.001) and plasma [Na+] change (p < 0.001) were significantly associated with the discrepancy between predicted and measured plasma [Na+] (Table 1). Plasma albumin (p = 0.02) was also significantly associated with this discrepancy when the NK formula was used. Conclusion In a hypernatremic ICU cohort, baseline plasma [Na+], estimated TBW and plasma [Na+] changes are associated with the inaccurateness of plasma [Na+] prediction. As baseline plasma [Na+] and estimated TBW are available when initiating treatment, incorporation of these variables in the currently available formulas may improve the prediction of plasma [Na+].

Recent Progress in Innate Immune Responses to Enterovirus A71 and Viral Evasion Strategies.

Enterovirus A71 (EV-A71) is a major pathogen causing hand, foot, and mouth disease (HFMD) in children worldwide. It can lead to severe gastrointestinal, pulmonary, and neurological complications. The innate immune system, which rapidly detects pathogens via pathogen-associated molecular patterns or pathogen-encoded effectors, serves as the first defensive line against EV-A71 infection. Concurrently, the virus has developed various sophisticated strategies to evade host antiviral responses and establish productive infection. Thus, the virus-host interactions and conflicts, as well as the ability to govern biological events at this first line of defense, contribute significantly to the pathogenesis and outcomes of EV-A71 infection. In this review, we update recent progress on host innate immune responses to EV-A71 infection. In addition, we discuss the underlying strategies employed by EV-A71 to escape host innate immune responses. A better understanding of the interplay between EV-A71 and host innate immunity may unravel potential antiviral targets, as well as strategies that can improve patient outcomes.

Analysis of gene expression in microglial apoptotic cell clearance following spinal cord injury based on machine learning algorithms.

Spinal cord injury (SCI) is a severe neurological complication following spinal fracture, which has long posed a challenge for clinicians. Microglia play a dual role in the pathophysiological process after SCI, both beneficial and detrimental. The underlying mechanisms of microglial actions following SCI require further exploration. The present study combined three different machine learning algorithms, namely weighted gene co-expression network analysis, random forest analysis and least absolute shrinkage and selection operator analysis, to screen for differentially expressed genes in the GSE96055 microglia dataset after SCI. It then used protein-protein interaction networks and gene set enrichment analysis with single genes to investigate the key genes and signaling pathways involved in microglial function following SCI. The results indicated that microglia not only participate in neuroinflammation but also serve a significant role in the clearance mechanism of apoptotic cells following SCI. Notably, bioinformatics analysis and lipopolysaccharide + UNC569 (a MerTK-specific inhibitor) stimulation of BV2 cell experiments showed that the expression levels of Anxa2, Myo1e and Spp1 in microglia were significantly upregulated following SCI, thus potentially involved in regulating the clearance mechanism of apoptotic cells. The present study suggested that Anxa2, Myo1e and Spp1 may serve as potential targets for the future treatment of SCI and provided a theoretical basis for the development of new methods and drugs for treating SCI.

EV71 5’UTR interacts with 3D protein affecting replication through the AKT-mTOR pathway

BackgroundEV71 is one of the important pathogens of Hand-foot-and-mouth disease (HFMD), which causes serious neurological symptoms. Several studies have speculated that there will be interaction between 5′UTR and 3D protein. However, whether 5′UTR interacts with the 3D protein in regulating virus replication has not been clarified.MethodsFour 5'UTR mutation sites (nt88C/T, nt90-102-3C, nt157G/A and nt574T/A) and two 3D protein mutation sites (S37N and R142K) were mutated or co-mutated using virulent strains as templates. The replication of these mutant viruses and their effect on autophagy were determined.Results5'UTR single-point mutant strains, except for EGFP-EV71(nt90-102-3C), triggered replication attenuation. The replication ability of them was weaker than that of the parent strain the virulent strain SDLY107 which is the fatal strain that can cause severe neurological complications. While the replication level of the co-mutant strains showed different characteristics. 5 co-mutant strains with interaction were screened: EGFP-EV71(S37N-nt88C/T), EGFP-EV71(S37N-nt574T/A), EGFP-EV71(R142K-nt574T/A), EGFP-EV71(R142K-nt88C/T), and EGFP-EV71(R142K-nt157G/A). The results showed that the high replicative strains significantly promoted the accumulation of autophagosomes in host cells and hindered the degradation of autolysosomes. The low replicative strains had a low ability to regulate the autophagy of host cells. In addition, the high replicative strains also significantly inhibited the phosphorylation of AKT and mTOR.ConclusionsEV71 5'UTR interacted with the 3D protein during virus replication. The co-mutation of S37N and nt88C/T, S37N and nt574T/ A, R142K and nt574T/A induced incomplete autophagy of host cells and promoted virus replication by inhibiting the autophagy pathway AKT-mTOR. The co-mutation of R142K and nt88C/T, and R142K and nt157G/A significantly reduced the inhibitory effect of EV71 on the AKT-mTOR pathway and reduced the replication ability of the virus.

A cone beam computed tomographic study on foramen transversarium

The foramen transversarium is a vital feature found in the cervical vertebrae of the spine. It serves as a protective passageway for the vertebral artery and vertebral vein, supplying blood to the brain and spinal cord. Any compromise to these structures within the foramen can lead to severe neurological complications, emphasizing its clinical significance. The study was carried out on 83 subjects of typical cervical vertebrae. Among them were 42 males and 41 females. All the foramen transversaria were observed for any anatomical variations. The anteroposterior, transverse diameters of all the foramen transversaria and the distance between the medial margin of uncinate process to the foramen transversarium were measured. The average transverse diameter of typical cervical vertebrae and seventh cervical vertebrae were ± 0.84mm and 5.13 ± 1.22 mm respectively. The average anteroposterior diameters of typical and seventh cervical vertebrae were 4.84 ± 0.69 mm and 3.91 ± 1.17 mm respectively. The distance from medial border of uncinate process to foramen transversaria was 4.28 ± 0.77 mm in typical and 5.44 ± 1.28 mm in seventh cervical vertebrae. The incidence of double bubble foramen in typical cervical vertebrae was reported to be17.5%. The incidence of double foramen transversaria was 12.5% in the seventh cervical vertebrae. Osteophytes were obstructing the foramen transversarium and narrowing it in 25% of vertebrae. In cone beam computed tomography (CBCT), the foramen transversarium plays a pivotal role in precise imaging of the cervical spine. Its significance lies in providing clear visualization of anatomical structures and potential abnormalities, aiding in the accurate diagnosis and treatment planning for various spinal conditions, thus enhancing patient care.

Rotavirus hospitalization in early childhood: fine motor skills and cognition at six years old-Population-based cohort study.

Rotavirus is linked to severe childhood gastroenteritis and neurological complications, but its impact on neurodevelopment remains uncertain. We examined data from 1,420,941 Korean children born between 2009 and 2011, using the Korean National Health Insurance System. At age 6, we assessed neurodevelopmental outcomes using the validated Korean Developmental Test, covering six major domains. Utilizing propensity score-based Inverse Probability Weighting to ensure covariates including considering covariates including sex, birth weight, changes in body weight from birth to 4-6 months of age, head circumference at 4-6 months of age, residence at birth, economic status, infant feeding types, and birth year. The main analysis that encompassed 5,451 children with rotavirus hospitalization and 310,874 unexposed individuals reveled heightened odds of suspected delays in fine motor skills and cognition among exposed children. Our results suggest an association between rotavirus-related hospitalization in infancy and suspected delays in fine motor function and cognition in 6-year-olds.

Epidemiology and antimicrobial resistance patterns of bacterial meningitis among hospitalized patients at a tertiary care hospital in Saudi Arabia: a six-year retrospective study.

Bacterial meningitis poses significant medical challenges due to its acute inflammatory nature and potential for severe neurological complications, emphasizing the need for prompt diagnosis and treatment. Limited data exists on its epidemiology and antimicrobial resistance trends among hospitalized patients in Saudi Arabia. This study aimed to investigate these factors at a tertiary care hospital over six years. A retrospective analysis was conducted on cerebrospinal fluid samples results from 222 bacterial meningitis cases among hospitalized patients between 2018 and 2023. Demographic, clinical, microbiological data, and antibiotic susceptibility patterns were collected and analyzed. Pseudomonas aeruginosa (43%) was the predominant pathogen isolated. Neonates (16%) and children (47%) were most affected population. Nosocomial meningitis accounted for 92% of cases, mainly in the intensive care settings (50.45%). Extended-spectrum beta-lactamase was the leading resistance pattern (12.2%). Seasonal variation was observed, with a peak incidence in October-November. The study highlights the substantial burden of bacterial meningitis among hospitalized patients, especially among high-risk groups. Emerging antimicrobial resistance emphasizes the need for optimized surveillance and stewardship. Future prospective research employing molecular techniques across multiple centers in the country is warranted to enhance understanding and guide public health strategies in Saudi Arabia.

Modelling and simulation of anisotropic growth in brain tumours through poroelasticity: A study of ventricular compression and therapeutic protocols

AbstractMalignant brain tumours represent a significant medical challenge due to their aggressive nature and unpredictable locations. The growth of a brain tumour can result in a mass effect, causing compression and displacement of the surrounding healthy brain tissue and possibly leading to severe neurological complications. In this paper, we propose a multiphase mechanical model for brain tumour growth that quantifies deformations and solid stresses caused by the expanding tumour mass and incorporates anisotropic growth influenced by brain fibres. We employ a sharp interface model to simulate localised, non-invasive solid brain tumours, which are those responsible for substantial mechanical impact on the surrounding healthy tissue. By using patient-specific imaging data, we create realistic three-dimensional brain geometries and accurately represent ventricular shapes, to evaluate how the growing mass may compress and deform the cerebral ventricles. Another relevant feature of our model is the ability to simulate therapeutic protocols, facilitating the evaluation of treatment efficacy and guiding the development of personalized therapies for individual patients. Overall, our model allows to make a step towards a deeper analysis of the complex interactions between brain tumours and their environment, with a particular focus on the impact of a growing cancer on healthy tissue, ventricular compression, and therapeutic treatment.

Modulation of immune responses in the central nervous system by Zika virus, West Nile virus, and dengue virus.

Arthropod-borne viruses (arboviruses) pose significant threats to global public health by causing a spectrum of diseases ranging from mild febrile illnesses to severe neurological complications. Understanding the intricate interplay between arboviruses and the immune system within the central nervous system is crucial for developing effective strategies to combat these infections and mitigate their neurological sequelae. This review comprehensively explores the mechanisms by which arboviruses such as Zika virus, West Nile virus, and Dengue virus manipulate immune responses within the CNS, leading to diverse clinical manifestations.

Seizure and Intracranial Hemorrhage: An Early Complication of Bee Sting – A Case Report

Background: Bee sting is a common entity during the summer season and is rarely associated with devastating complications such as myocardial infarction, pulmonary edema, bleeding, and rhabdomyolysis, neurological complications can occur after multiple stings. However, single bee venom infestation resulting in such complications is rare. Patient’s Concern: Here, we are describing a young male, who presented to us with a seizure episode, soon after bitten by a bee sting around his lips. The patient did not have hypertension, diabetes, other risk factors for seizure, or any history of trauma but the patient’s computed tomography head showed cerebral hematoma. Intervention: The patient was managed immediately with an injection of antiepileptics with intravenous (IV) fluids, antihistaminics, and IV steroids. The patient had gross improvement in the sensorium and was seizure free for 48 h under observation. The patient was discharged on the 4th day of admission with 100% recovery. Conclusion: This case report emphasizes the potential for severe neurological complications following bee stings in the form of cerebral hematoma which is clinically important to recognize early and further research is required to better understand the mechanism and management strategies.

Severe Neurological Manifestation Associated With Coronavirus Disease 2019 in Children During the Omicron Variant-Predominant Period

BackgroundThe Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to be more infectious and less severe than the other variants. Despite the increasing number of symptomatic patients, severe neurological complications in children with the Omicron variant have been reported rarely, unlike with wild-type or Delta variants. This study aimed to investigate severe neurological complications in children with Omicron variant infection. MethodsWe conducted a retrospective study of 17 pediatric patients with severe neurological manifestations associated with coronavirus disease 2019 in Korea during the Omicron variant prevalence, from January 1 to April 30, 2022. ResultsAmong the 17 patients, 11 had pre-existing neurological disabilities and nine met the criteria for multisystem inflammatory syndrome in children (MIS-C). Four of the five vaccine-eligible patients (12 years and older) were unvaccinated. Severe neurological manifestations included acute necrotizing encephalopathy, acute fulminant cerebral edema, acute disseminated encephalomyelitis, basal ganglia encephalitis, unclassified severe encephalopathy/encephalitis, and refractory status dystonicus. Patients with MIS-C and underlying neurological disabilities had longer median hospital and intensive care unit stays compared with those without these conditions. Five patients survived with new neurological deficits at the one-year follow-up, and three died, all of whom had underlying neurological disabilities. ConclusionsThis study shows that severe neurological complications in pediatric patients with the Omicron variant of SARS-CoV-2 occur infrequently but may lead to significant morbidity and mortality, especially among those with pre-existing neurological disabilities and unvaccinated individuals. Continued efforts are necessary to prevent and manage such complications in these vulnerable populations.

The Adaptive Immune Response against Bunyavirales.

The Bunyavirales order includes at least fourteen families with diverse but related viruses, which are transmitted to vertebrate hosts by arthropod or rodent vectors. These viruses are responsible for an increasing number of outbreaks worldwide and represent a threat to public health. Infection in humans can be asymptomatic, or it may present with a range of conditions from a mild, febrile illness to severe hemorrhagic syndromes and/or neurological complications. There is a need to develop safe and effective vaccines, a process requiring better understanding of the adaptive immune responses involved during infection. This review highlights the most recent findings regarding T cell and antibody responses to the five Bunyavirales families with known human pathogens (Peribunyaviridae, Phenuiviridae, Hantaviridae, Nairoviridae, and Arenaviridae). Future studies that define and characterize mechanistic correlates of protection against Bunyavirales infections or disease will help inform the development of effective vaccines.

Immunoinformatics and computational approaches driven designing a novel vaccine candidate against Powassan virus

Powassan virus (POWV) is an arthropod-borne virus (arbovirus) capable of causing severe illness in humans for severe neurological complications, and its incidence has been on the rise in recent years due to climate change, posing a growing public health concern. Currently, no vaccines to prevent or medicines to treat POWV disease, emphasizing the urgent need for effective countermeasures. In this study, we utilize bioinformatics approaches to target proteins of POWV, including the capsid, envelope, and membrane proteins, to predict diverse B-cell and T-cell epitopes. These epitopes underwent screening for critical properties such as antigenicity, allergenicity, toxicity, and cytokine induction potential. Eight selected epitopes were then conjugated with adjuvants using various linkers, resulting in designing of a potentially stable and immunogenic vaccine candidate against POWV. Moreover, molecular docking, molecular dynamics simulations, and immune simulations revealed a stable interaction pattern with the immune receptor, suggesting the vaccine's potential to induce robust immune responses. In conclusion, our study provided a set of derived epitopes from POWV’s proteins, demonstrating the potential for a novel vaccine candidate against POWV. Further in vitro and in vivo studies are warranted to advance our efforts and move closer to the goal of combatting POWV and related arbovirus infections.

ATP-P2X7 signaling mediates brain pathology while contributing to viral control in perinatal Zika virus infection

Zika virus (ZIKV), the causative agent of Zika fever, is a flavivirus transmitted by mosquitoes of the Aedes genus. Zika virus infection has become an international concern due to its association with severe neurological complications such as fetal microcephaly. Viral infection can induce the release of ATP in the extracellular environment, activating receptors sensitized by extracellular nucleotides, such as the P2X7 receptor. This receptor is the primary purinergic receptor involved in neuroinflammation, neurodegeneration, and immunity. In this work, we investigated the role of ATP-P2X7 receptor signaling in Zika-related brain abnormalities. Wild-type mice (WT) and P2X7 receptor-deficient (P2X7-/-) C57BL/6 newborn mice were subcutaneously inoculated with 5 × 106plaque-forming units of ZIKV or mock solution. P2X7 receptor expression increased in the brain of Zika virus-infected mice compared to the mock group. Comparative analyses of the hippocampi from WT and P2X7-/-mice revealed that the P2X7 receptor increased hippocampal damage in CA1/CA2 and CA3 regions. Doublecortin expression decreased significantly in the brains of ZIKV-infected mice. WT ZIKV-infected mice showed impaired motor performance compared to P2X7-/- infected mice. WT ZIKV-infected animals showed increased expression of glial markers GFAP (astrocytes) and IBA-1 (microglia) compared to P2X7-/- infected mice. Although the P2X7 receptor contributes to neuronal loss and neuroinflammation, WT mice were more efficient in controlling the viral load in the brain than P2X7 receptor-deficient mice. This result was associated with higher induction of TNF-α, IFN-β, and increased interferon-stimulated gene expression in WT mice than P2X7-/-ZIKV-infected. Finally, we found that the P2X7 receptor contributes to inhibiting the neuroprotective signaling pathway AKT/mTOR while stimulating the caspase-3 activation, possibly two distinct pathways contributing to neurodegeneration. These findings suggest that ATP-P2X7 receptor signaling contributes to the antiviral response in the brain of ZIKV-infected mice while increasing neuronal loss, neuroinflammation, and related brain abnormalities.

Early Prone Position Ventilation in the Efficacy for Severe Hypoxemia and Neurological Complications Following Acute Type A Aortic Dissection (TAAD) Surgery

Objective To analyze the efficacy of early prone position ventilation in the treatment of severe hypoxemia after surgery for acute type A aortic dissection (TAAD). Methods The patients were divided into a control group and a treatment group. Parameters assessed included blood gas analysis indicators [arterial oxygen partial pressure (PaO2). Results: (1) Blood gas analysis: Before treatment, there was no significant difference in PaO2, SpO2, and OI levels between the two groups; after treatment, the PaO2, SpO2, and OI levels in both groups significantly increased compared to pre-treatment, with a more pronounced improvement in the treatment group than in the control group (p < 0.05). (2) Hemodynamics: Before treatment, there was no significant difference in MAP and HR levels between the two groups; after treatment, the MAP levels increased significantly in both groups compared to pre-treatment, while HR levels decreased significantly, with no significant difference between the groups. (3) Prognosis recovery: MV time, ICU stay, and total hospital stay were significantly lower in the treatment group than in the control group; the 30-day mortality rate was 14.58% in the control group and 12.50% in the treatment group, with no significant difference in 30-day mortality rate between the groups. Conclusion Early prone position ventilation has shown promising application in the treatment of severe hypoxemia after TAAD surgery. Compared to traditional supine position ventilation, the use of early prone position ventilation can further improve blood gas analysis indicators in patients, and shorten MV time, ICU stay, and total hospital stay, thereby accelerating patient recovery.

Caspase-8 activation regulates enterovirus D68 infection-induced inflammatory response and cell death

Enterovirus D68 (EV-D68) infection causes severe acute respiratory infection and severe neurological complications, such as acute flaccid myelitis (AFM), in children. However, although EV-D68 has pandemic potential, no effective drugs or vaccines are currently clinically available. Furthermore, EV-D68 infection-induced inflammatory response and cell death are not fully understood. In this study, we demonstrated that several inflammatory cytokines were upregulated in a multiplicity of infection (MOI) dependent manner in EV-D68-infected human rhabdomyosarcoma (RD) cells. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) confirmed that tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand-5 (CCL-5), and CXC motif chemokine ligand-5 (CXCL-5) mRNA levels were highly upregulated after EV-D68 infection. IL-1β processing and maturation mediated by caspase-8 was inhibited by the caspase-8 inhibitor Z-IETD-FMK. EV-D68 infection activates caspase-8 to mediate IL-1β maturation and secretion. Additionally, EV-D68 activated cell death-related proteins such as caspase-3, poly (ADP-ribose) polymerase 1 (PARP-1), phosphorylation of Mixed Lineage Kinase domain-like protein (pMLKL), and gasdermin E (GSDME). Thus, EV-D68 infection activates caspase-8, which triggers the necroptosis and apoptosis pathways. Overall, our data suggest that caspase-8 activation is associated with the inflammatory response and cell death in EV-D68-infected RD cells. This mechanism represents a novel target for the treatment of EV-D68 infection by inhibiting caspase-8 activation.

Advance in pediatric spinal cord injury

AbstractThe incidence rate of spinal cord injury in children is lower than that in adults, accounting for about 5% of all spinal cord injuries. Motor vehicle accidents are the main cause of spinal cord injuries in children. As the spine of children is still in the process of growth and development, the anatomical structure and biomechanics have unique characteristics, and its etiology, injury site, and clinical manifestations are different from those of adults. Misdiagnosis and delayed diagnosis can lead to severe spinal deformity and neurological complications. Children and adolescents with spinal cord injuries may suffer from lifelong disability, which will do great harm to children, families, and society. Early magnetic resonance imaging examination can effectively avoid underdiagnosis of spinal cord injury without radiographic abnormality and select appropriate treatment. In addition, it is also important to establish a family‐centered rehabilitation model to help the affected children reintegrate into society and achieve the goal of returning to normal life. This article reviews the etiology, epidemiology, clinical characteristics, complications, and treatment of spinal cord injury in children and adolescents.

Cordycepin Inhibits Enterovirus A71 Replication and Protects Host Cell from Virus-Induced Cytotoxicity through Adenosine Action Pathway.

Enterovirus A71 (EV-A71) infection typically causes mild illnesses, such as hand-foot-and-mouth disease (HFMD), but occasionally leads to severe or fatal neurological complications in infants and young children. Currently, there is no specific antiviral treatment available for EV-A71 infection. Thus, the development of an effective anti-EV-A71 drug is required urgently. Cordycepin, a major bioactive compound found in Cordyceps fungus, has been reported to possess antiviral activity. However, its specific activity against EV-A71 is unknown. In this study, the potency and role of cordycepin treatment on EV-A71 infection were investigated. Results demonstrated that cordycepin treatment significantly reduced the viral load and viral ribonucleic acid (RNA) level in EV-A71-infected Vero cells. In addition, EV-A71-mediated cytotoxicity was significantly inhibited in the presence of cordycepin in a dose-dependent manner. The protective effect can also be extended to Caco-2 intestinal cells, as evidenced by the higher median tissue culture infectious dose (TCID50) values in the cordycepin-treated groups. Furthermore, cordycepin inhibited EV-A71 replication by acting on the adenosine pathway at the post-infection stage. Taken together, our findings reveal that cordycepin could be a potential antiviral candidate for the treatment of EV-A71 infection.

Retro-Odontoid Pseudotumor due to Rheumatoid Arthritis Pannus and its Craniocervical Instability

Retro-Odontoid Pseudotumor due to Rheumatoid Arthritis Pannus and its Craniocervical Instability