Impact of Embolisate Penetration, Type, and Technique on Results After Standalone Middle Meningeal Artery Embolization for Chronic Subdural Hematoma.

BACKGROUND AND OBJECTIVES: Middle meningeal artery embolization (MMAE) has emerged as a promising modality for chronic/subacute subdural hematoma treatment; however, consensus regarding embolization technique and embolisate has not been achieved. We thus sought to compare the efficacy of distinct MMAE techniques and embolisate. METHODS: An institutional registry was reviewed to identify patients undergoing standalone MMAE for symptomatic chronic/subacute subdural hematoma. Surgical rescue rate and time preceding 50% hematoma resolution were evaluated across 3 technical groups: aggressive penetration (AP), nonaggressive penetration with proximal coil embolization (NP-PC), and nonaggressive penetration alone (NP). Effect sizes were adjusted for demographic, neurological and radiological features through multivariable logistic and Cox regression. RESULTS: Among 117 procedures, 33.3% achieved AP, 36.8% had NP-PC, and 29.9% had NP. The rate of surgical rescue was 2.6% after AP, 9.3% for NP-PC, and 11.4% for NP. In patients not undergoing rescue surgery, 82.4% achieved hematoma resolution ≥50% at a median imaging follow-up of 56 days; AP or NP-PC were each statistically significantly associated with enhanced hematoma resolution as compared with NP (P = .02). Similarly, sensitivity analysis within medium-size hematoma and antiplatelet/anticoagulation-at-admission subgroups revealed a superiority of resolution after AP or NP-PC. A unique, comparative secondary analysis of liquid embolisate (Onyx vs n-butyl cyanoacrylate) revealed no impact on rate of surgical rescue or hematoma resolution. CONCLUSION: AP was associated with the lowest rate of surgical rescue, while both AP and NP-PC were associated with improved rates of hematoma resolution.

The strict regulation of HIF-1α by non-coding RNAs: new insight towards proliferation, metastasis, and therapeutic resistance strategies.

The hypoxic environment is prominently witnessed in most solid tumors and is associated with the promotion of cell proliferation, epithelial-mesenchymal transition (EMT), angiogenesis, metabolic reprogramming, therapeutic resistance, and metastasis of tumor cells. All the effects are mediated by the expression of a transcription factor hypoxia-inducible factor-1α (HIF-1α). HIF-1α transcriptionally modulates the expression of genes responsible for all the aforementioned functions. The stability of HIF-1α is regulated by many proteins and non-coding RNAs (ncRNAs). In this article, we have critically discussed the crucial role of ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), Piwi-interacting RNAs (piRNAs), and transfer RNA (tRNA)-derived small RNAs (tsRNAs)] in the regulation of stability and expression of HIF-1α. We have comprehensively discussed the molecular mechanisms and relationship of HIF-1α with each type of ncRNA in either promotion or repression of human cancers and therapeutic resistance. We have also elaborated on ncRNAs that are in clinical examination for the treatment of cancers. Overall, the majority of aspects concerning the relationship between HIF-1α and ncRNAs have been discussed in this article.

Soil erosion vulnerability and soil loss estimation for Siran River watershed, Pakistan: an integrated GIS and remote sensing approach.

Soil erosion is a problematic issue with detrimental effects on agriculture and water resources, particularly in countries like Pakistan that heavily rely on farming. The condition of major reservoirs, such as Tarbela, Mangla, and Warsak, is crucial for ensuring an adequate water supply for agriculture in Pakistan. The Kunhar and Siran rivers flow practically parallel, and the environment surrounding both rivers' basins is nearly identical. The Kunhar River is one of KP's dirtiest rivers that carries 0.1 million tons of suspended sediment to the Mangla reservoir. In contrast, the Siran River basin is largely unexplored. Therefore, this study focuses on the Siran River basin in the district of Manshera, Pakistan, aiming to assess annual soil loss and identify erosion-prone regions. Siran River average annual total soil loss million tons/year is 0.154. To achieve this, the researchers integrate Geographical Information System (GIS) and remote sensing (RS) data with the Revised Universal Soil Loss Equation (RUSLE) model. Five key variables, rainfall, land use land cover (LULC), slope, soil types, and crop management, were examined to estimate the soil loss. The findings indicate diverse soil loss causes, and the basin's northern parts experience significant soil erosion. The study estimated that annual soil loss from the Siran River basin is 0.154 million tons with an average rate of 0.871 tons per hectare per year. RUSLE model combined with GIS/RS is an efficient technique for calculating soil loss and identifying erosion-prone areas. Stakeholders such as policymakers, farmers, and conservationists can utilize this information to target efforts and reduce soil loss in specific areas. Overall, the study's results have the potential to advance initiatives aimed at safeguarding the Siran River watershed and its vital resources. Protecting soil resources and ensuring adequate water supplies are crucial for sustainable agriculture and economic development in Pakistan.

Peptide-Based Therapeutics in Cancer Therapy.

A monster called cancer is still one of the most challenging human problems and one of the leading causes of death in the world. Different types of treatment methods are used for cancer therapy; however, there are challenges such as high cost and harmful side effects in using these methods. Recent years have witnessed a surge in the development of therapeutic peptides for a wide range of diseases, notably cancer. Peptides are preferred over antibiotics, radiation therapy, and chemotherapy in the treatment of cancer due to a number of aspects, including flexibility, easy modification, low immunogenicity, and inexpensive cost of production. The use of therapeutic peptides in cancer treatment is a novel and intriguing strategy. These peptides provide excellent prospects for targeted drug delivery because of their high selectivity, specificity, small dimensions, good biocompatibility, and simplicity of modification. Target specificity and minimal toxicity are benefits of therapeutic peptides. Additionally, peptides can be used to design antigens or adjuvants for vaccine development. Here, types of therapeutic peptides for cancer therapy will be discussed, such as peptide-based cancer vaccines and tumor-targeting peptides (TTP) and cell-penetrating peptides (CPP).

The emerging role of microRNA-126 as a potential therapeutic target in cancer: a comprehensive review.

MicroRNA-126 (miR-126) has become a key player in the biology of cancer, playing a variety of functions in carcinogenesis and cancer development. The diagnostic and prognostic potential of miR-126 in diverse cancer types is summarized in this thorough analysis, with an emphasis on its role in tumor angiogenesis, invasion, metastasis, cell proliferation, apoptosis, and treatment resistance. MiR-126 dysregulation is linked to a higher risk of developing cancer and a worse prognosis. Notably, miR-126 affects tumor vascularization and development by targeting vascular endothelial growth factor-A (VEGF-A). Through its impact on genes involved in cell adhesion and migration, it also plays a vital part in cancer cell invasion and metastasis. Additionally, miR-126 controls drug resistance, apoptosis, and cell proliferation, which affects cancer cell survival and treatment response. It may be possible to develop innovative therapeutic approaches to stop tumor angiogenesis, invasion, and metastasis, as well as combat drug resistance by focusing on miR-126 or its downstream effectors. The versatility of miR-126's functions highlights the role that it plays in cancer biology. To understand the processes behind miR-126 dysregulation, pinpoint precise targets, and create efficient therapies, more investigation is required. Utilizing miR-126's therapeutic potential might have a significant influence on cancer treatment plans and patient outcomes.

NK cells direct the perspective approaches to cancer immunotherapy.

Natural killer (NK) cells are innate immune cells with cytotoxic potentials to kill cancerous cells in several mechanisms, which could be implied for cancer therapy. While potent, their antitumor activities specially for solid tumors impaired by inadequate tumor infiltration, suppressive tumor microenvironment, cancer-associated stroma cells, and tumor-supportive immune cells. Therefore, manipulating or reprogramming these barriers by prospective strategies might improve current immunotherapies in the clinic or introduce novel NK-based immunotherapies. NK-based immunotherapy could be developed in monotherapy or in combination with other therapeutic regimens such as oncolytic virus therapy and immune checkpoint blockade, as presented in this review.

PDE5 inhibitors and gastric mucosa: implications for the management of peptic ulcer disease.

Peptic ulcer disease (PUD) continues to be a cause of significant morbidity and mortality worldwide. Almost two-thirds of PUD cases are asymptomatic. In symptomatic patients, epigastric pain is the most common presenting symptom of PUD, which is manifested by nausea, abdominal fullness, bloating, and dyspepsia. Most PUD cases are associated with the use of COX inhibitors or Helicobacter pylori infection, or both. The traditional management of PUD includes the use of proton pump inhibitors to reduce the gastric acid secretion and antibacterial drugs to combat H. pylori. Timely diagnosis and treatment of PUD are vital to reduce the risk of associated morbidity and mortality, as is prevention of PUD among patients at high risk, including COX inhibitors users and those infected with H. pylori. PDE5 inhibitors have been used for the management of erectile dysfunction and pulmonary hypertension for decades. In recent years, studies have mentioned tremendous pleiotropic effects of PDE5 inhibitors on gastrointestinal, urogenital, musculoskeletal, reproductive, cutaneous, and neurologic disorders. Recent data shows that PDE5 inhibition augments gastric mucosa protection, and here, we review the most recent findings regarding the use of PDE5 inhibitors for the prevention and management of PUD.

Glycolysis in human cancers: Emphasis circRNA/glycolysis axis and nanoparticles in glycolysis regulation in cancer therapy.

The metabolism of cancer has been an interesting hallmark and metabolic reprogramming, especially the change from oxidative phosphorylation in mitochondria to glucose metabolism known as glycolysis occurs in cancer. The molecular profile of glycolysis, related molecular pathways and enzymes involved in this mechanism such as hexokinase have been fully understood. The glycolysis inhibition can significantly decrease tumorigenesis. On the other hand, circRNAs are new emerging non-coding RNA (ncRNA) molecules with potential biological functions and aberrant expression in cancer cells which have received high attention in recent years. CircRNAs have a unique covalently closed loop structure which makes them highly stable and reliable biomarkers in cancer. CircRNAs are regulators of molecular mechanisms including glycolysis. The enzymes involved in the glycolysis mechanism such as hexokinase are regulated by circRNAs to modulate tumor progression. Induction of glycolysis by circRNAs can significantly increase proliferation rate of cancer cells given access to energy and enhance metastasis. CircRNAs regulating glycolysis can influence drug resistance in cancers because of theirimpact on malignancy of tumor cells upon glycolysis induction. TRIM44, CDCA3, SKA2 and ROCK1 are among the downstream targets of circRNAs in regulating glycolysis in cancer. Additionally, microRNAs are key regulators of glycolysis mechanism in cancer cells and can affect related molecular pathways and enzymes. CircRNAs sponge miRNAs to regulate glycolysis as a main upstream mediator. Moreover, nanoparticles have been emerged as new tools in tumorigenesis suppression and in addition to drug and gene delivery, then mediate cancer immunotherapy and can be used for vaccine development. The nanoparticles can delivery circRNAs in cancer therapy and they are promising candidates in regulation of glycolysis, its suppression and inhibition of related pathways such as HIF-1α. The stimuli-responsive nanoparticles and ligand-functionalized ones have been developed for selective targeting of glycolysis and cancer cells, and mediating carcinogenesis inhibition.

Phosphatidylinositol 3-kinase signaling pathway and inflammatory bowel disease: Current status and future prospects.

Inflammatory bowel disease (IBD) is a chronic life-limiting disease of gastrointestinal tract characterized by widespread enteric inflammation. IBD is a multifactorial disease, and different environmental, microbial, and immune-related factors give rise to the development of disease. Among several factors, the preponderance of pro-inflammatory T helper 17 cells over the anti-inflammatory regulatory T cells augments inflammation in the intestinal mucosa. Prevailing evidence accentuates that PI3K signaling pathway plays a central role in the pathophysiology of the condition by regulating the inflammatory process in the gut mucosa. By recognizing the implications of PI3K in the pathogenesis of IBD, agents that could modulate this pathway have recently been at the focus of research, yielding encouraging results mainly in the experimental IBD models. In this review, we have summarized the recent advances, which may hold the keys to identify novel therapeutic strategies for IBD.

The Remarkable Roles of the Receptor for Advanced Glycation End Products (RAGE) and Its Soluble Isoforms in COVID-19: The Importance of RAGE Pathway in the Lung Injuries.

The respiratory symptoms of acute respiratory distress syndrome (ARDS) in the coronavirus disease 2019 (COVID-19) patients is associated with accumulation of pre-inflammatory molecules such as advanced glycation end-products (AGES), calprotectin, high mobility group box family-1 (HMGB1), cytokines, angiotensin converting enzyme 2 (ACE2), and other molecules in the alveolar space of lungs and plasma. The receptor for advanced glycation end products (RAGEs), which is mediated by the mitogen-activated protein kinase (MAPK), plays a critical role in the severity of chronic inflammatory diseases such as diabetes mellitus (DM) and ARDS. The RAGE gene is most expressed in the alveolar epithelial cells (AECs) of the pulmonary system. Several clinical trials are now being conducted to determine the possible association between the levels of soluble isoforms of RAGE (sRAGE and esRAGE) and the severity of the disease in patients with ARDS and acute lung injury (ALI). In the current article, we reviewed the most recent studies on the RAGE/ligands axis and sRAGE/esRAGE levels in acute respiratory illness, with a focus on COVID-19-associated ARDS (CARDS) patients. According to the research conducted so far, sRAGE/esRAGE measurements in patients with CARDS can be used as a powerful chemical indicator among other biomarkers for assessment of early pulmonary involvement. Furthermore, inhibiting RAGE/MAPK and Angiotensin II receptor type 1 (ATR1) in CARDS patients can be a powerful strategy for diminishing cytokine storm and severe respiratory symptoms.

Association of Endovascular Thrombectomy vs Medical Management With Functional and Safety Outcomes in Patients Treated Beyond 24 Hours of Last Known Well: The SELECT Late Study.

Importance: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well. Objective: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well. Design, Setting, and Participants: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well. Interventions: Endovascular thrombectomy or medical management (control). Main Outcomes and Measures: Primary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts. Results: Of 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P < .001) despite increased odds of sICH (10.1% for EVT vs 1.7% for control; IPTW aOR, 10.65; 95% CI, 2.19-51.69; P = .003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P = .047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P = .03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P = .04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P = .02). Conclusions and Relevance: In this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation.

Management of Latent Tuberculosis Infection in Saudi Arabia: Knowledge and Perceptions Among Healthcare Workers.

Background Tuberculosis (TB) continues to pose a serious threat to public health despite great efforts. For many years, management and screening for active TB cases have been the main focus of TB control programs. Latent TB is a stage where TB can be prevented and controlled. Therefore, designing a comprehensive TB control program that includes latent tuberculosis infection (LTBI) management diseases is needed to be implemented among the healthcare workers (HCWs) who have been found to be at a higher risk for active TB compared to the general population. The objective of the study The objective of the study is to assess the knowledge and perceptions of LTBI among HCWs. In addition to estimating the prevalence of LTBI among HCWs using closed-end questions in a self-administered questionnaire. Subjects and methods Through a cross-sectional study and non-random sampling technique, 324 (84%) healthcare workers who met the inclusion criteria completed and submitted the electronic questionnaire. Results Among all participants, the study reported a good knowledge about LTBI; however, a third of HCWs had poor knowledge about the difference between LTBI and active TB. Eighteen percent of participants were diagnosed with LTBI, and two-thirds accepted the treatment. Of all participants who started the treatment, 55% completed the treatment course. The compliance rate was high among young HCWs and physicians who had a short course of LTB treatment regimen.  Conclusion The study reported a low acceptance and completion rate of LTBI therapy among HCWs. Low knowledge about some clinical facts of LTBI, the long duration of treatment, and being the treatment optional in Saudi health institutes were all barriers to accepting and completing the treatment of LTBI. All of these factors need to be addressed to increase the compliance rate to LTBI treatment.

Mitofusin-2 in cancer: Friend or foe?

Cancer is a category of disorders characterized by excessive cell proliferation with the ability to infiltrate or disseminate to other organs of the body. Mitochondrial dysfunction, as one of the most prominent hallmarks of cancer cells, has been related to the onset and development of various cancers. Mitofusin 2 (MFN2) is a major mediator of mitochondrial fusion, endoplasmic reticulum (ER)-mitochondria interaction, mitophagy and axonal transport of mitochondria. Available data have shown that MFN2, which its alterations have been associated with mitochondrial dysfunction, could affect cancer initiation and progression. In fact, it showed that MFN2 may have a double-edged sword effect on cancer fate. Precisely, it demonstrated that MFN2, as a tumor suppressor, induces cancer cell apoptosis and inhibits cell proliferation via Ca2+ and Bax-mediated apoptosis and increases P21 and p27 levels, respectively. It also could suppress cell survival via inhibiting PI3K/Akt, Ras-ERK1/2-cyclin D1 and mTORC2/Akt signaling pathways. On the other hand, MFN2, as an oncogene, could increase cancer invasion via snail-mediated epithelial-mesenchymal transition (EMT) and in vivo tumorigenesis. While remarkable progress has been achieved in recent decades, further exploration is required to elucidate whether MFN2 could be a friend or it's an enemy. This study aimed to highlight the different functions of MFN2 in various cancers.

Functions and therapeutic interventions of non-coding RNAs associated with TLR signaling pathway in atherosclerosis.

Nowadays, emerging data demonstrate that the toll-like receptor (TLR) signaling pathway plays an important role in the progression of inflammatory atherosclerosis. Indeed, dysregulated TLR signaling pathway could be a cornerstone of inflammation and atherosclerosis, which contributes to the development of cardiovascular diseases. It is interesting to note that this pathway is heavily controlled by several mechanisms, such as epigenetic factors in which the role of non-coding RNAs (ncRNAs), particularly microRNAs and long noncoding RNAs as well as circular RNAs in the pathogenesis of atherosclerosis has been well studied. Recent years have seen a significant surge in the amount of research exploring the interplay between ncRNAs and TLR signaling pathway downstream targets in the development of atherosclerosis; however, there is still considerable room for improvement in this field. The current study was designed to review underlying mechanisms of TLR signaling pathway and ncRNA interactions to shed light on therapeutic implications in patients with atherosclerosis.

Assessment of Entamoeba gingivalis and Trichomonas tenax in Patients with Chronic Diseases and its Correlation with Some Risk Factors.

Trichomonas tenax (T. tenax) and Entamoeba gingivalis (E. gingivalis) are two oral protozoan parasites that are universal and found in patients with poor oral hygiene, as well as chronic and periodontal diseases. This study was conducted to assess the efficacy of some parameters, such as age, gender, education, residency, smoking, and dental cleaning routines, on the incidence of these parasites in the oral cavity of the patients participating in this study. A total of 230 individuals with chronic diseases, 97 of whom were patients (44 females and 53 males) participated in the present study. Dental plaque and saliva samples were collected from each patient and examined under light microscopy with Giemsa staining. Out of 230 dental plaque samples, 60 (26.08%) samples were positive for E. gingivalis, while 37 (16.08%) cases were positive for T. tenax. Diabetic patients showed high E. gingivalis percentage (n=12; 20%) (P=0.000*). However, thyroid disorders showed a low percentage. Hypertensive patients showed a high percentage for T. tenax (n=6; 16.21%) (P=0.000*), while tuberculosis patients showed the lowest percentage. Patients with hypertension, smoking, heart disease, and diabetes showed statistical significance for the presence of these parasites. Equally, patients older than 30 years have shown a higher rate of infection. According to the findings, E. gingivalis was detected in 58.33% and 41.66% of the urban and rural populations, respectively. Furthermore, T. tenax was detected in 81.08% and 18.91% of the urban and rural populations, respectively. Parasitic contagions were comparatively popular in patients with chronic and periodontal illness.

Aptasensor Based on Microfluidic for Foodborne Pathogenic Bacteria and Virus Detection: A Review.

In today's world, which is entangled with numerous foodborne pathogenic bacteria and viruses, it appears to be essential to rethink detection methods of these due to the importance of food safety in our lives. The vast majority of detection methods for foodborne pathogenic bacteria and viruses have suffered from sensitivity and selectivity due to the small size of these pathogens. Besides, these types of sensing approaches can improve on-site detection platforms in the fields of food safety. In recent, microfluidics systems as new emerging types of portable sensing approaches can introduce efficient and simple biodevice by integration with several analytical methods such as electrochemical, optical and colorimetric techniques. Additionally, taking advantage of aptamer as a selective bioreceptor in the sensing of microfluidics system has provided selective, sensitive, portable and affordable sensing approaches. Furthermore, some papers use increased data transferability ability and computational power of these sensing platforms by exploiting smartphones. In this review, we attempted to provide an overview of the current state of the recent aptasensor based on microfluidic for screening of foodborne pathogenic bacteria and viruses. Working strategies, benefits and disadvantages of these sensing approaches are briefly discussed.

Prevalence and molecular identification of Nematodirus helvetianus in camels in Iraq.

BACKGROUND AND AIM: Camels from the central part of Iraq are infected with multiple parasitic diseases that have an economic impact by decreasing meat and milk production. This study aimed to evaluate Nematodirus spp. in camels (Camelus dromedarius). MATERIALS AND METHODS: The study animals consisted of camels slaughtered in the central area of Iraq at the Al-Najaf slaughterhouse. All ages and sexes of camels were examined. Worms were recovered and identified microscopically. For molecular characterization, two Iraqi Nematodirus spp. partial ribosomal genes (ITS1 and ITS2) were sequenced and submitted to the NCBI database. RESULTS: Of 160 camels tested, 29 were infected with Nematodirus spp. (18.13%). Twenty-one nematodes containing the Nematodirus genes were identified in the small intestines of naturally infected camels. BLAST analysis revealed 88.1% sequence similarity with that of Nematodirus helvetianus isolated in China and 87.2% similarity with N. helvetianus isolated in the United States. CONCLUSION: The prevalence of N. helvetianus warrants the use of anti-helminthic drugs for these animals and a rationale for future control strategies to prevent the transmission of this infection to other livestock.

COVID-19, HHV6 and MOG antibody: A perfect storm.

BACKGROUND: Serious neurological complications of SARS-CoV-2 are increasingly being recognized. CASE: We report a novel case of HHV6 myelitis with parainfectious MOG-IgG in the setting of COVID-19-induced lymphopenia and hypogammaglobulinemia. The patient experienced complete neurological recovery with gancyclovir, high dose corticosteroids, and plasma exchange. To our knowledge, this is the first case of HHV6 reactivation in the central nervous system in the setting of COVID19 infection and the first case of MOG-IgG myelitis in the setting of SARS-CoV-2 and HHV6 coinfection. CONCLUSION: Patients with neurological manifestations in the setting of COVID19-related immunodeficiency should be tested for opportunistic infections including HHV6. Viral infection is a known trigger for MOG-IgG and therefore this antibody should be checked in patients with SARS-CoV-2 associated demyelination.