Potential neurological manifestations of COVID-19: a narrative review.

Neurological manifestations are increasingly reported in a subset of COVID-19 patients. Previous infections related to coronaviruses, namely Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS) also appeared to have neurological effects on some patients. The viruses associated with COVID-19 like that of SARS enters the body via the ACE-2 receptors in the central nervous system, which causes the body to balance an immune response against potential damage to nonrenewable cells. A few rare cases of neurological sequelae of SARS and MERS have been reported. A growing body of evidence is accumulating that COVID-19, particularly in severe cases, may have neurological consequences although respiratory symptoms nearly always develop prior to neurological ones. Patients with preexisting neurological conditions may be at elevated risk for COVID-19-associated neurological symptoms. Neurological reports in COVID-19 patients have described encephalopathy, Guillain-Barré syndrome, myopathy, neuromuscular disorders, encephalitis, cephalgia, delirium, critical illness polyneuropathy, and others. Treating neurological symptoms can pose clinical challenges as drugs that suppress immune response may be contraindicated in COVID-19 patients. It is possible that in some COVID-19 patients, neurological symptoms are being overlooked or misinterpreted. To date, neurological manifestations of COVID-19 have been described largely within the disease trajectory and the long-term effects of such manifestations remain unknown.

Ozone: A Novel Sterilizer for Personal Protective Equipment.

OBJECTIVE: Personal protective equipment (PPE) is urgently sought during public health crises. It is necessary for the safety of both the patient and the healthcare professional. Yet during the recent COVID-19 pandemic, PPE scarcity in many countries, including the United States, has impacted the level of care for patients and the safety of healthcare personnel. Additionally, the implementation of mandatory mask mandates for the general public in many countries forced individuals to either reuse PPE, which can contribute to poor hygiene, or buy PPE in bulk and thereby contribute to the scarcity of PPE. In this study, we investigate the possibility of using a cost-effective ozone sterilization unit on contaminated N95 masks as an alternative to current sterilization methods. METHOD: This protocol examined ozone's ability to decontaminate N95 mask fabric that was exposed to a surrogate virus (Escherichia coli bacteriophage MS2). Once the sterilization unit achieves an ozone concentration of ~30 ppm, a 60-minute or 120-minute sterilization cycle commences. Following the sterilization cycle, we investigated the amount of viable virus on the slide using a viral plaque assay and compared it to a non-sterilized, control slide. Furthermore, we carried out trials to investigate the safety of an ozone sterilization device, by measuring the levels of ozone exposure that individuals may experience when operating the sterilization unit post-cycle. RESULTS: We showed that a 120-minute sterilization cycle at ~30 ppm achieves a 3-log reduction in viral activity, thereby complying with industry and U.S. Food and Drug Administration (FDA) standards. Further, we demonstrated that when following our protocol, the ozone exposure levels for a simple sterilization unit to be used at home complied with federal and industry standards. CONCLUSION: Ozone may have the potential to decontaminate masks and other PPE.

Suicide by Opioid: Exploring the Intentionality of the Act.

Opioid toxicity can result in life-threatening respiratory depression. Opioid-overdose mortality in the United States is high and increasing, but it is difficult to determine what proportion of those deaths might actually be suicides. The exact number of Americans who died of an opioid overdose but whose deaths might be classified as suicide remains unknown. It is important to differentiate between those who take opioids with the deliberate and unequivocal objective of committing suicide, that is, those with active intent, from those with passive intent. The passive-intent group understands the risks of opioid consumption and takes dangerous amounts, but with a more ambiguous attitude toward suicide. Thus, among decedents of opioid overdose, a large population dies by accident, whereas a small population dies intending to commit suicide; but between them exists a sub-population with equivocal intentions, waxing and waning between their desire to live and the carelessness about death. There may be a passive as well as active intent to commit suicide, but less is known about the passive motivation. It is important for public health efforts aimed at reducing both suicides and opioid-use disorder to better understand the range of motivations behind opioid-related suicides and how to combat them.

Ketamine in the Past, Present, and Future: Mechanisms, Metabolites, and Toxicity.

PURPOSE OF REVIEW: While ketamine's analgesia has mostly been attributed to antagonism of N-methyl-D-aspartate receptors, evidence suggests multiple other pathways are involved in its antidepressant and possibly analgesic activity. These mechanisms and ketamine's role in the nociplastic pain paradigm are discussed. Animal studies demonstrating ketamine's neurotoxicity have unclear human translatability and findings from key rodent and human studies are presented. RECENT FINDINGS: Ketamine's metabolites, and (2R,6R)-hydroxynorketamine in particular, may play a greater role in its clinical activity than previously believed. The activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and the mammalian target of rapamycin by ketamine are mechanisms that are still being elucidated. Ketamine might work best in nociplastic pain, which involves altered pain processing. While much is known about ketamine, new studies will continue to define its role in clinical medicine. Evidence supporting ketamine's neurotoxicity in humans is lacking and should not impede future ketamine clinical trials.

Management of Musculoskeletal Pain: An Update with Emphasis on Chronic Musculoskeletal Pain.

Musculoskeletal pain is a challenging condition for both patients and physicians. Many adults have experienced one or more episodes of musculoskeletal pain at some time of their lives, regardless of age, gender, or economic status. It affects approximately 47% of the general population. Of those, about 39-45% have long-lasting problems that require medical consultation. Inadequately managed musculoskeletal pain can adversely affect quality of life and impose significant socioeconomic problems. This manuscript presents a comprehensive review of the management of chronic musculoskeletal pain. It briefly explores the background, classifications, patient assessments, and different tools for management according to the recently available evidence. Multimodal analgesia and multidisciplinary approaches are fundamental elements of effective management of musculoskeletal pain. Both pharmacological, non-pharmacological, as well as interventional pain therapy are important to enhance patient's recovery, well-being, and improve quality of life. Accordingly, recent guidelines recommend the implementation of preventative strategies and physical tools first to minimize the use of medications. In patients who have had an inadequate response to pharmacotherapy, the proper use of interventional pain therapy and the other alternative techniques are vital for safe and effective management of chronic pain patients.

Fact vs Fallacy: The Anti-Vaccine Discussion Reloaded.

In the light of the COVID-19 pandemic, anti-vaccine sentiments have been on the rise, with a recent seminal study on the development of anti-vaccine views in social media even making its way into Nature Communications. Yet, with the current scientific consensus being in overwhelming agreement over the safety and efficacy of vaccines, many scientists lose their grasp on the fears, concerns, and arguments that the opposition may hold. This paper discusses and evaluates vaccine-hesitant individuals on a socioeconomic, historical, and philosophical landscape. It also provides an analysis of common argumentative patterns and the psychological impact that these arguments may have on undecided individuals. The discussion also explores why anti-vaccine sentiments are on the rise, and how members of the scientific and medical community require a more structured approach to communicating key arguments. This is particularly important if vaccination rates and herd immunity are to be sustained. No longer is it sufficient to win arguments based on a factual and scientific basis, but rather scientists and medical practitioners have to focus on conveying confidence and reassurance on both an informative and emotional level to those with doubts and fears.

Pain Management During the COVID-19 Pandemic.

Chronic pain management during the coronavirus disease 2019 (COVID-19) pandemic is a challenging process, especially with growing evidence that COVID-19 infection is associated with myalgias, referred pain, and widespread hyperalgesia. In light of the limited data available for COVID-19-related impact on chronic pain patients, this review explores the changes in the healthcare delivery system due to social distancing and safety precautions to provide the appropriate management of chronic pain patients during the COVID-19 pandemic. Understanding both the general problems facing chronic pain patients as well as specific problems in the COVID-19 era including deconditioning, increased mental health concerns, financial burdens, and potential for medication-induced immune-suppression is vital in the appropriate management of patients. Telemedicine, the practice of caring for patients remotely when the provider and patient are not physically present with each other, is becoming increasingly used and recognized as a valuable tool to both health care providers and patients. This paper concentrates on the proper utilization of the available resources to help patients with the most severe conditions as well as the most vulnerable group. COVID-19 may be associated with a profound effect on both the health care system and patients with chronic pain. As a result, delaying, or stopping, treatment for chronic pain patients will have negative consequences, and strong pain evaluations must be administered to triage patients appropriately. Recent recommendations for the safe use of non-opioid analgesics, opioid analgesics, and interventional pain management procedures are vital to know and understand specifically during the pandemic era. Further researches are needed to identify the advance planning and rapid responses to reduce the impact of the pandemic.

Evolving Pharmacotherapies for Pain: Drug Development.

The Chronic pain epidemic is a pressing public health crises facing the United States. Currently, more than 100 million Americans suffer from chronic pain, with chronic pain being among the most prevalent conditions and the leading cause of disability. Chronic pain disproportionately affects certain populations including women, low-income individuals, and older adults. This article focuses primarily on new molecular entities in development targeting various chronic pain receptors and new delivery technologies.

An open-label pilot study evaluating the effectiveness of the heated lidocaine/tetracaine patch for the treatment of pain associated with carpal tunnel syndrome.

OBJECTIVES: Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median nerve at the wrist that is characterized by pain, paresthesias, weakness, and loss of dexterity. This pilot study was conducted to evaluate the heated lidocaine/tetracaine patch (HLT patch) as a conservative treatment for pain of CTS. METHODS: Twenty adult patients (mean age = 44 ± 12 years) with pain secondary to unilateral CTS and electrodiagnostic evidence of mild-to-moderate CTS enrolled in this open-label study. Patients were treated with a single HLT patch placed over the junction of forearm and wrist on the palmar aspect of the wrist twice daily (morning and evening at 12-hour intervals) for 2 hours. At baseline and during the 2-week study, patients graded their pain intensity with an 11-point numerical rating scale (0 = no pain, 10 = worst imaginable pain). Pain interference with general activity, work, and sleep was evaluated with a similar 0-to-10-point scale. RESULTS: Fifteen patients completed the 14-day treatment period. Mean average pain intensity score decreased from 5.1 ± 1.5 at baseline to 2.5 ± 1.6 at end of study in the per-protocol population (P < 0.001). Two-thirds of the patients demonstrated clinically meaningful pain relief (≥ 30% reduction in average pain score), with 40% of the patients reaching this threshold by the third treatment day. Similar improvements were observed for pain interference scores. The HLT patch was generally well tolerated. CONCLUSION: The HLT patch resulted in clinically meaningful reduction in pain intensity in the majority of patients with mild-to-moderate CTS and may represent a targeted nonsurgical treatment for pain associated with CTS.

Relationship between differential hepatic microRNA expression and decreased hepatic cytochrome P450 3A activity in cirrhosis.

BACKGROUND AND AIM: Liver cirrhosis is associated with decreased hepatic cytochrome P4503A (CYP3A) activity but the pathogenesis of this phenomenon is not well elucidated. In this study, we examined if certain microRNAs (miRNA) are associated with decreased hepatic CYP3A activity in cirrhosis. METHODS: Hepatic CYP3A activity and miRNA microarray expression profiles were measured in cirrhotic (n=28) and normal (n=12) liver tissue. Hepatic CYP3A activity was measured via midazolam hydroxylation in human liver microsomes. Additionally, hepatic CYP3A4 protein concentration and the expression of CYP3A4 mRNA were measured. Analyses were conducted to identify miRNAs which were differentially expressed between two groups but also were significantly associated with lower hepatic CYP3A activity. RESULTS: Hepatic CYP3A activity in cirrhotic livers was 1.7-fold lower than in the normal livers (0.28 ± 0.06 vs. 0.47 ± 0.07mL* min(-1)*mg protein(-1) (mean ± SEM), P=0.02). Six microRNAs (miR-155, miR-454, miR-582-5p, let-7f-1*, miR-181d, and miR-500) had >1.2-fold increase in cirrhotic livers and also had significant negative correlation with hepatic CYP3A activity (range of r = -0.44 to -0.52, P <0.05). Notably, miR-155, a known regulator of liver inflammation, had the highest fold increase in cirrhotic livers (2.2-fold, P=4.16E-08) and significantly correlated with hepatic CYP3A activity (r=-0.50, P=0.017). The relative expression (2(-ΔΔCt) mean ± SEM) of hepatic CYP3A4 mRNA was significantly higher in cirrhotic livers (21.76 ± 2.65 vs. 5.91 ± 1.29, P=2.04E-07) but their levels did not significantly correlate with hepatic CYP3A activity (r=-0.43, P=0.08). CONCLUSION: The strong association between certain miRNAs, notably miR-155, and lower hepatic CYP3A activity suggest that altered miRNA expression may regulate hepatic CYP3A activity.

Synthesis of silica-gold nanocomposites and their porous nanoparticles by an in-situ approach.

We demonstrate the one-step synthesis of a silica-gold nanocomposite by simultaneous hydrolysis and reduction of gold chloride. The aminophenyl group was used as a reducing agent, and the trimethoxy silane group acts a precursor for the formation of silica. The porous gold nanoparticles were formed by etching out the silica-gold nanocomposite by hydrofluoric acid. The electron diffraction of porous gold nanoparticles showed that the particle are polycrystalline with FCC structure. The silica-gold nanocomposite exhibited nonlinear current-voltage behavior, and the porous gold nanoparticles displayed linear current-voltage behavior.