Re-sensitization of mcr carrying multidrug resistant bacteria to colistin by silver.

Colistin is considered the last-line antimicrobial for the treatment of multidrug-resistant gram-negative bacterial infections. The emergence and spread of superbugs carrying the mobile colistin resistance gene (mcr) have become the most serious and urgent threat to healthcare. Here, we discover that silver (Ag+), including silver nanoparticles, could restore colistin efficacy against mcr-positive bacteria. We show that Ag+ inhibits the activity of the MCR-1 enzyme via substitution of Zn2+ in the active site. Unexpectedly, a tetra-silver center was found in the active-site pocket of MCR-1 as revealed by the X-ray structure of the Ag-bound MCR-1, resulting in the prevention of substrate binding. Moreover, Ag+effectively slows down the development of higher-level resistance and reduces mutation frequency. Importantly, the combined use of Ag+ at a low concentration with colistin could relieve dermonecrotic lesions and reduce the bacterial load of mice infected with mcr-1­carrying pathogens. This study depicts a mechanism of Ag+ inhibition of MCR enzymes and demonstrates the potentials of Ag+ as broad-spectrum inhibitors for the treatment of mcr-positive bacterial infection in combination with colistin.

Admission blood tests predicting survival of SARS-CoV-2 infected patients: a practical implementation of graph convolution network in imbalance dataset.

BACKGROUND: Predicting an individual's risk of death from COVID-19 is essential for planning and optimising resources. However, since the real-world mortality rate is relatively low, particularly in places like Hong Kong, this makes building an accurate prediction model difficult due to the imbalanced nature of the dataset. This study introduces an innovative application of graph convolutional networks (GCNs) to predict COVID-19 patient survival using a highly imbalanced dataset. Unlike traditional models, GCNs leverage structural relationships within the data, enhancing predictive accuracy and robustness. By integrating demographic and laboratory data into a GCN framework, our approach addresses class imbalance and demonstrates significant improvements in prediction accuracy. METHODS: The cohort included all consecutive positive COVID-19 patients fulfilling study criteria admitted to 42 public hospitals in Hong Kong between January 23 and December 31, 2020 (n = 7,606). We proposed the population-based graph convolutional neural network (GCN) model which took blood test results, age and sex as inputs to predict the survival outcomes. Furthermore, we compared our proposed model to the Cox Proportional Hazard (CPH) model, conventional machine learning models, and oversampling machine learning models. Additionally, a subgroup analysis was performed on the test set in order to acquire a deeper understanding of the relationship between each patient node and its neighbours, revealing possible underlying causes of the inaccurate predictions. RESULTS: The GCN model was the top-performing model, with an AUC of 0.944, considerably outperforming all other models (p < 0.05), including the oversampled CPH model (0.708), linear regression (0.877), Linear Discriminant Analysis (0.860), K-nearest neighbours (0.834), Gaussian predictor (0.745) and support vector machine (0.847). With Kaplan-Meier estimates, the GCN model demonstrated good discriminability between low- and high-risk individuals (p < 0.0001). Based on subanalysis using the weighted-in score, although the GCN model was able to discriminate well between different predicted groups, the separation was inadequate between false negative (FN) and true negative (TN) groups. CONCLUSION: The GCN model considerably outperformed all other machine learning methods and baseline CPH models. Thus, when applied to this imbalanced COVID survival dataset, adopting a population graph representation may be an approach to achieving good prediction.

Generative AI in Medical Imaging: Applications, Challenges, and Ethics.

Medical imaging is playing an important role in diagnosis and treatment of diseases. Generative artificial intelligence (AI) have shown great potential in enhancing medical imaging tasks such as data augmentation, image synthesis, image-to-image translation, and radiology report generation. This commentary aims to provide an overview of generative AI in medical imaging, discussing applications, challenges, and ethical considerations, while highlighting future research directions in this rapidly evolving field.

Deciphering molecular mechanism of silver by integrated omic approaches enables enhancing its antimicrobial efficacy in E. coli.

Despite the broad-spectrum antimicrobial activities of silver, its internal usage is restricted, owing to the toxicity. Strategies to enhance its efficacy are highly desirable but rely heavily on the understanding of its molecular mechanism of action. However, up to now, no direct silver-targeting proteins have been mined at a proteome-wide scale, which hinders systemic studies on the biological pathways interrupted by silver. Herein, we build up a unique system, namely liquid chromatography gel electrophoresis inductively coupled plasma mass spectrometry (LC-GE-ICP-MS), allowing 34 proteins directly bound by silver ions to be identified in Escherichia coli. By using integrated omic approaches, including metalloproteomics, metabolomics, bioinformatics, and systemic biology, we delineated the first dynamic antimicrobial actions of silver (Ag+) in E. coli, i.e., it primarily damages multiple enzymes in glycolysis and tricarboxylic acid (TCA) cycle, leading to the stalling of the oxidative branch of the TCA cycle and an adaptive metabolic divergence to the reductive glyoxylate pathway. It then further damages the adaptive glyoxylate pathway and suppresses the cellular oxidative stress responses, causing systemic damages and death of the bacterium. To harness these novel findings, we coadministrated metabolites involved in the Krebs cycles with Ag+ and found that they can significantly potentiate the efficacy of silver both in vitro and in an animal model. Our study reveals the comprehensive and dynamic mechanisms of Ag+ toxicity in E. coli cells and offers a novel and general approach for deciphering molecular mechanisms of metallodrugs in various pathogens and cells to facilitate the development of new therapeutics.

Oncogenic and tumor suppressor genes expression in myeloproliferative neoplasms: The hidden side of a complex pathology.

BACKGROUND: The present study aimed to explore the changes in the expressions of six tumor-related genes in myeloproliferative neoplasms (MPNs). The study population included 130 patients with MPNs (52 with chronic myeloid leukemia (CML), 49 with essential thrombocythemia (ET), 20 with polycythemia vera (PV), and 9 with primary myelofibrosis (PMF)) and 51 healthy individuals. METHODS: The expression profiling of six genes (ADAMTS18, CMTM5, CDKN2B, DCC, FHIT, and WNT5B) in the peripheral blood granulocyte cells was explored by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: The patients with MPNs showed significant downregulation of CMTM5 (EFC = 0.66) and DCC (EFC = 0.65) genes in contrast to a non-significant upregulation of ADAMTS18, CDKN2B, FHIT, and WNT5B genes. Downregulation of DCC was consistent in all subtypes of MPN (EFC range: 0.591-0.860). However, CMTM5 had a 1.22-fold upregulation in PMF in contrast to downregulation in other MPN subtypes (EFC range: 0.599-0.775). The results revealed a significant downregulation in CMTM5 and DCC at below 60-years of age. Furthermore, female patients showed a clear-cut downregulation in both CMTM5 and DCC (EFC DCC: 0.436 and CMTM5: 0.570), while male patients presented a less prominent downregulation with a borderline p-value only in DCC (EFC: 0.69; p = 0.05). CONCLUSIONS: Chronic myeloid leukemia cases showed a significant upregulation of WNT5B, as a known oncogenesis gene. Two tumor suppressor genes, namely DCC and CMTM5, were downregulated in the patients with MPNs, especially in females and patients below 60 years of age.

Effect of an Endoprosthetic Reconstruction Tube and Medial Gastrocnemius Flap on Extensor Mechanism Function After Oncologic Prosthesis Reconstruction of the Proximal Tibia.

BACKGROUND: Extensor mechanism reconstruction after the proximal tibial resection and implantation of a megaprosthesis is challenging. In this study, we evaluated the effectiveness of the Trevira tube and medial gastrocnemius flap in restoring extensor mechanism following the resection of proximal tibial tumor and implantation of megaprosthesis. METHODS: Forty patients who underwent endoprosthetic implantation following the resection of proximal tibial tumor and patellar tendon reconstruction with the Trevira tube and medial gastrocnemius flap were included. The outcome measures were knee range of motion, extensor mechanism function, patellar position, and limb function subjectively evaluated through Toronto Extremity Salvage Score and objectively through Musculoskeletal Tumor Society score. The mean follow-up of the patients was 6.1 years. RESULTS: The patellar position was normal in 28 (70%) patients, patella baja in 3 (7.5%) patients, and patella alta in 9 (22.5%) patients. The mean active knee range of motion was 98.9 ± 17° (range: 85°-125°). Extension lag was present in 7 (17.5%) patients (range: 5°-20°). The mean Toronto Extremity Salvage Score of patients was 92.1 ± 6.9% (range: 85-100). The mean Musculoskeletal Tumor Society score of the patients was 87.7 ± 13 (range: 73.3-100). Postoperative complications included aseptic wound dehiscence (2 patients), aseptic loosening of the tibial component (1 patient), periprosthetic fracture in the femur (2 patients), and wound infection (1 patient). CONCLUSION: Trevira tube combined with gastrocnemius flap augmentation is a suitable procedure for restoring extensor mechanism after proximal tibial resection and megaprosthesis implantation.

Effects of three months of treatment with vitamin E and N-acetyl cysteine on the oxidative balance in patients with transfusion-dependent ß-thalassemia.

Oxidative stress is a major mechanism contributing to the progression of ß-thalassemia. To assess the effect of vitamin E and N-acetyl cysteine (NAC) as antioxidant agents on total oxidative stress (TOS) status and total antioxidant capacity (TAC) in patients with transfusion-dependent ß-thalassemia (TDT). In this open-label randomized controlled trial, from May to August 2019, 78 eligible patients with TDT over the age of 18 were enrolled. All patients were registered at the Thalassemia Clinic of Shiraz University of Medical Sciences in Southern Iran. Patients were randomly allocated to the NAC group (10 mg/kg/day, orally), vitamin E group (10 U/kg/day, orally), and control group. The duration of the study was 3 months. The mean age of the participants was 28.5 ± 5.1 (range: 18-41) years. At the end of the study, TOS significantly decreased only in the vitamin E group (mean difference (MD), 95% confidence interval (CI): 0.27 (0.03-0.50), P = 0.026). TAC significantly decreased in both supplemented groups at the 3rd month of treatment (NAC group: MD (95% CI): 0.11 (0.04-0.18), P = 0.002 and vitamin E group: 0.09 (0.01-0.16), P = 0.022 respectively). Hemoglobin did not significantly change at the end of the study in each group (P > 0.05). Mild transient adverse events occurred in 4 patients of the NAC group and 5 patients of the vitamin E group with no need to discontinue the treatment. Vitamin E can be a safe and effective supplement in improving oxidative stress in patients with TDT. Moreover, it seems that a longer duration of using antioxidant supplements needs to make clinical hematologic improvement in TDT patients.

Metallochaperone UreG serves as a new target for design of urease inhibitor: A novel strategy for development of antimicrobials.

Urease as a potential target of antimicrobial drugs has received considerable attention given its versatile roles in microbial infection. Development of effective urease inhibitors, however, is a significant challenge due to the deeply buried active site and highly specific substrate of a bacterial urease. Conventionally, urease inhibitors are designed by either targeting the active site or mimicking substrate of urease, which is not efficient. Up to now, only one effective inhibitor-acetohydroxamic acid (AHA)-is clinically available, but it has adverse side effects. Herein, we demonstrate that a clinically used drug, colloidal bismuth subcitrate, utilizes an unusual way to inhibit urease activity, i.e., disruption of urease maturation process via functional perturbation of a metallochaperone, UreG. Similar phenomena were also observed in various pathogenic bacteria, suggesting that UreG may serve as a general target for design of new types of urease inhibitors. Using Helicobacter pylori UreG as a showcase, by virtual screening combined with experimental validation, we show that two compounds targeting UreG also efficiently inhibited urease activity with inhibitory concentration (IC)50 values of micromolar level, resulting in attenuated virulence of the pathogen. We further demonstrate the efficacy of the compounds in a mammalian cell infection model. This study opens up a new opportunity for the design of more effective urease inhibitors and clearly indicates that metallochaperones involved in the maturation of important microbial metalloenzymes serve as new targets for devising a new type of antimicrobial drugs.

Dermatochalasis Through Decades: A Histopathologic Study.

OBJECTIVES: Three prior studies (2008, 2011, 2018) histopathologically compared the eyelid specimens of patients with dermatochalasis (DC, undergoing blepharoplasty) with a control group and proposed that DC may begin with subclinical inflammation leading to elastolysis and lymphostasis. With growing number of younger patients consulting for blepharoplasty, the unanswered question is whether histopathologic changes of DC differ between the younger and the older. PATIENTS AND METHODS: In this prospective case series, 20 right upper eyelid skin of 20 nonsmoker, class 3 Fitzpatrik skin type women (30-68 years old) were histopathologically examined. Patients were divided into 2 age groups of 50 years or older and older than 50 years. Upper eyelid skin was preoperatively marked, intraoperatively removed, postoperatively divided into 3 sections: lateral (lateral limbus to lateral canthus), central (between medial and lateral limbi), and medial (medial limbus to medial canthus), and separately (totally 60 specimens) sent for histopathological examination. A masked pathologist recorded skin thickness in all specimens (60) as well as lymphatic vessels diameter and density, elastic fiber density, macrophage number, collagen intrafibril edema, and depth of collagen stromal bed in central sections (20 specimens). RESULTS: There were 10 patients at each age group. Histopathological measurements were not significantly different between the 2 age groups except mean lymphatic vessel diameter (P = 0.034) that was larger in the second group (>50 years). A significant positive correlation was also observed between the age and lymphatic vessel diameter (rs = 0.3, P = 0.009). CONCLUSIONS: Lymphangiectasia progresses significantly by age. Histopathological characteristics of DC are the same in the 2 age groups.

Prognostic value of non-smoking, non-alcohol drinking status in oral cavity cancer.

OBJECTIVES: To compare the treatment response and prognosis of oral cavity cancer between non-smoking and non-alcohol-drinking (NSND) patients and smoking and alcohol-drinking (SD) patients. METHODS: A total of 313 consecutively treated patients from 2000 to 2019 were included. Demographic, clinicopathologic, treatment, and prognosis information were obtained. Relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) were compared between NSND and SD groups using Kaplan-Meier plots, log-rank test, and multivariate Cox regression analysis. RESULTS: Sample prevalence of NSND patients was 54.6%. These patients were predominantly females in their eighth decade with lower prevalence of floor of the mouth cancers compared to SD patients (1.8% vs 14.8%). No difference in the RFS and DSS between both groups was found following multivariable analysis; however, NSND patients had better OS (HR (95% CI) - 0.47 (0.29-0.75); p = 0.002). Extracapsular extension was associated with significantly poorer OS, DSS, and RFS in this oral cavity cancer cohort. CONCLUSION: Treatment response and disease-specific prognosis are comparable between NSND and SD patients with oral cavity cancer. However, NSND patients have better OS. CLINICAL RELEVANCE: This study shows that oral cavity cancer in NSND is not less or more aggressive compared to SD patients. Although better survival is expected for NSND than SD patients, this is likely due to the reduced incidence of other chronic diseases in the NSND group.

MetaMarker: a pipeline for de novo discovery of novel metagenomic biomarkers.

SUMMARY: We present MetaMarker, a pipeline for discovering metagenomic biomarkers from whole-metagenome sequencing samples. Different from existing methods, MetaMarker is based on a de novo approach that does not require mapping raw reads to a reference database. We applied MetaMarker on whole-metagenome sequencing of colorectal cancer (CRC) stool samples from France to discover CRC specific metagenomic biomarkers. We showed robustness of the discovered biomarkers by validating in independent samples from Hong Kong, Austria, Germany and Denmark. We further demonstrated these biomarkers could be used to build a machine learning classifier for CRC prediction. AVAILABILITY AND IMPLEMENTATION: MetaMarker is freely available at https://bitbucket.org/mkoohim/metamarker under GPLv3 license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Association of Exon 14 of the SOX6 Gene Sequence Variations with Response to Hydroxyurea Therapy in Patients Carrying Non Transfusion-Dependent Thalassemia.

Hydroxyurea (HU) activates the γ-globin gene, resulting in increased Hb F synthesis. The SOX6 gene is a member of the Sox (Sry-type HMG box) family of transcription factors, characterized by minor groove binding domain. The DNA binding domain of this gene is encoded by exon 14. We assessed the relationship between response to HU and exon 14 of the SOX6 gene sequence variations in patients with non transfusion-dependent thalassemia (NTDT). One hundred NTDT patients from southern Iran underwent HU therapy randomly participated in this cross-sectional study between February 2013 and October 2014. Based on response to HU therapy, the patients were divided into two groups: good and poor responder. Sequence variations of exon 14 of the SOX6 gene was assayed by the Sanger sequencing technique. From all evaluated single nucleotide polymorphisms (SNPs) as above, we found no significant association between sequence variations of exon 14 of the SOX6 gene and response to HU therapy (p > 0.05). It seems that no SNPs in exon 14 of the SOX6 gene is associated with response to HU in NTDT patients, but more studies are needed for further evaluation.

A retrospective study on clinical manifestations of neonates with FXIII-A deficiency.

We assessed clinical presentations and the rate of central nervous system (CNS) bleeding in neonates with FXIIID who exhibited bleeding diathesis in the early days of their lives. A total of 27 neonates presented bleeding or abnormal clinical symptoms, diagnosed with FXIII deficiency were evaluated. Factor XIII concentrate was initiated as the first-line of treatment, and prophylactic therapy was given to all patients. Umbilical cord bleeding, delayed detachment of umbilical stunt, seizure, hematoma, and ecchymosis were concurrent complications in 27 (100%), 5 (18.5%), 5 (18.5%), 3 (11.1%), and 1 (3.7%) of the patients, respectively. History of having CNS bleeding was detected in 13 (48.1%) patients. There was no significant association between CNS bleeding and gender, familial history of FXIIID, or other clinical presentations. Also, there was no significant difference in the mean age of the patients who had CNS bleeding (3.4 ±â€¯0.9 days) and without CNS bleeding (2.9 ±â€¯0.7 days). However, a near significant threshold difference between the patients with and without CNS bleeding was found regarding the mean number of suspicious FXIIID death in their family (1.8 ±â€¯0.5 and 0.7 ±â€¯0.1, respectively, P = 0.05). Therefore, a suggested diagnostic algorithm based on prenatal diagnosis could be useful for timely detection of FXIII deficiency in neonates.

Novel Neural Network Approach to Predict Drug-Target Interactions Based on Drug Side Effects and Genome-Wide Association Studies.

AIMS: We propose a novel machine learning approach to expand the knowledge about drug-target interactions. Our method may help to develop effective, less harmful treatment strategies and to enable the detection of novel indications for existing drugs. METHODS: We developed a novel machine learning strategy to predict drug-target interactions based on drug side effects and traits from genome-wide association studies. We integrated data from the databases SIDER and GWASdb and utilized them in a unique way by a neural network approach. RESULTS: We validate our method using drug-target interactions from the STITCH database. In addition, we compare the chemical similarity of the predicted target to known targets of the drug under consideration and present literature-based evidence for predicted interactions. We find drug combination warnings for drugs we predict to target the same protein, hinting to synergistic effects aggravating harmful events. This substantiates the translational value of our approach, because we are able to detect drugs that should be taken together with care due to common mechanisms of action. CONCLUSION: Taken together, we conclude that our approach is able to generate a novel and clinically applicable insight into the molecular determinants of drug action.

Relationship Between Some Single-nucleotide Polymorphism and Response to Hydroxyurea Therapy in Iranian Patients With ß-Thalassemia Intermedia.

OBJECTIVE: To evaluate the possible relationship between hydroxyurea (HU) response and some single-nucleotide polymorphism (SNP) in patients affected by ß-thalassemia intermedia. MATERIALS AND METHODS: In this cross-sectional study, 100 ß-thalassemia intermedia patients who were taking HU with a dose of 8 to 15 mg/kg body weight per day for a period of at least 6 months were randomly selected between February 2013 and October 2014 in southern Iran. HU response was defined based on decrease or cessation of the blood transfusion need and evaluation of Hb level. RESULTS: In univariate analysis, from all evaluated SNPs, only rs10837814 SNP of olfactory receptors (ORs) OR51B2 showed a significant association with HU response (P=0.038) and from laboratory characteristics, only nucleated red blood cells showed significant associations (116%±183%) in good responders versus (264%±286%) in poor responders (P=0.045). In multiple logistic regression, neither laboratory variables nor different SNPs, showed significant association with HU response. Three novel nucleotide variations (-665 [A→C], -1301 [T→G],-1199 delA) in OR51B2 gene were found in good responders. CONCLUSIONS: None of the evaluated SNPs in our study showed significant association with HU response. Further larger studies and evaluation of other genes are suggested.

A review of combinations of electrokinetic applications.

Anthropogenic activities contaminate many lands and underground waters with dangerous materials. Although polluted soils occupy small parts of the land, the risk they pose to plants, animals, humans, and groundwater is too high. Remediation technologies have been used for many years in order to mitigate pollution or remove pollutants from soils. However, there are some deficiencies in the remediation in complex site conditions such as low permeability and complex composition of some clays or heterogeneous subsurface conditions. Electrokinetic is an effective method in which electrodes are embedded in polluted soil, usually vertically but in some cases horizontally, and a low direct current voltage gradient is applied between the electrodes. The electric gradient initiates movement of contaminants by electromigration (charged chemical movement), electro-osmosis (movement of fluid), electrolysis (chemical reactions due to the electric field), and diffusion. However, sites that are contaminated with heavy metals or mixed contaminants (e.g. a combination of organic compounds with heavy metals and/or radionuclides) are difficult to remediate. There is no technology that can achieve the best results, but combining electrokinetic with other remediation methods, such as bioremediation and geosynthetics, promises to be the most effective method so far. This review focuses on the factors that affect electrokinetic remediation and the state-of-the-art methods that can be combined with electrokinetic.

Effectiveness of ß-thalassemia prenatal diagnosis in Southern Iran: a cohort study.

AIM: The aim of this study was to evaluate the effectiveness of prenatal diagnosis (PND) for the prevention of thalassemia in Southern Iran. METHODS: From 2004 to 2012 1346 couples with ß-thalassemia minor were referred to our center. Mutation analyses utilized different methods including polymerase chain reaction-based technique of amplification refractory mutation system (ARMS), Restriction Fragment Length Polymorphism Analysis of PCR-Amplified Fragments (PCR-RFLP) and Gel Electrophoresis and direct sequencing. Haplotype analysis of the ß-globin gene cluster was done routinely using the PCR-RFLP technique. RESULTS: Of the 1346 couples, 884 (66%) requested PND. They had a total of 985 pregnancies (954 singleton and 31 twin pregnancies): the 1016 fetuses underwent chorionic villus sampling (CVS). Thalassemia major was diagnosed in 266 cases (26.2%), and termination of pregnancy was requested by the parents in 264 of them (99%). Thalassemia trait was detected in 499 (49.1%) and 251 cases (24.7%) showed no ß-thalassemia mutations. There were three misdiagnoses (0.4%) (affected children diagnosed as carriers at PND). A unique pattern of thalassemia mutations was present in the study population, with IVS II-I (G→A), C36-37(-T), IVS I-5(G>C), -25bpdel (252-276), IVS I-110(G>A) and C44 (-C) being present in 62% of cases. CONCLUSION: The pattern of distribution of thalassemia mutations differs among ethnic groups within the same country.

Eriophyoid mites (Acari: Prostigmata: Eriophyidae) associated with Compositae in Iran.

Five species of eriophyoid mites were identified during surveys of mite fauna associated with plant species of the family Compositae from Southwest of East Azerbaijan province during 2010 and 2011. Two of them, Aceria virgatae n. sp. from Centaurea virgata Lam. and Aceria xeranthenzis n. sp. from Xeranthemumn squarrosum Boiss., were found to be new to science. No damage symptoms were observed on their host plants. Aceria xeranthemis n. sp. is the first eriophyoid collected from the plant genus Xeranthenun. Aculops centaureae (Farkas, 1960) from Centaurea albonitens Turrill and Aceria cichorii Petanovic et al. 2000 from Cichorium intybus L. are new records for Iranian mite fauna. The deutogyne female of Aceria anthocoptes (Nalepa) was recorded for the first time in Iran, too. A key to the species collected on Compositae in Iran is given.

A review of the potential neurological adverse events of COVID-19 vaccines.

Despite the advantages of getting access to the coronavirus disease 2019 (COVID-19) vaccines, their potential ability to induce severe adverse events (AEs) has been a significant concern. Neurological complications are significant among the various adverse events following immunization (AEFI) due to their likely durability and debilitating sequelae. Neurological AEs following COVID-19 vaccination can either exacerbate or induce new-onset neuro-immunologic diseases, such as myasthenia gravis (MG) and Guillain-Barre syndrome (GBS). The more severe spectrum of AEs post-COVID19 vaccines has included seizures, reactivation of the varicella-zoster virus, strokes, GBS, Bell's palsy, transverse myelitis (TM), and acute disseminated encephalomyelitis (ADEM). Here, we discuss each of these neurological adverse effects separately.

Anticoagulant therapy in COVID-19: A narrative review.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest itself in several ways, including coagulopathy and thrombosis. These complications can be the first and sometimes only manifestations of SARS-CoV-2 infection and can occur early or late in the course of the disease. However, these symptoms are more prevalent in hospitalized patients with venous thromboembolism, particularly those admitted to intensive care units. Moreover, various forms of arterial and venous thrombosis, or micro- or macro-vasculature embolisms, have been reported during the current pandemic. They have led to harmful consequences, such as neurological and cardiac events, nearly all resulting from the hypercoagulable state caused by this viral infection. The severe hypercoagulability observed in patients with COVID-19 accounts for most cases of the disease that become critical. Therefore, anticoagulants seem to be one of the most vital therapeutics for treating this potentially life-threatening condition. In the current paper, we present a thorough review of the pathophysiology of COVID-19-induced hypercoagulable state and the use of anticoagulants to treat SARS-CoV-2 infections in different patient groups, as well as their pros and cons.