inflammation

Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono-or bi-substituted/crosslinked adducts) or -OH groups (to form ester linkages). In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological and pathological processes. In particular, transglutaminase activity has been shown to be responsible for human autoimmune diseases, and Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, supranuclear palsy, Huntington’s disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. Here we describe the possible molecular mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.

Inflammation is a complex biological reaction induced by the alteration of tissue homeostasis, which occurs in response to the presence of a biological, chemical or physical agent in the body [1]. The acute inflammatory response is composed of an elaborate cascade of both proinflammatory and anti-inflammatory mediators, and balance between these mediators often determines the outcome after injury [2]. Generally during acute inflammation, cellular and molecular events and interactions reduce the risk of eventual injuries or infections. However, acute inflammation can become chronic, contributing to a variety of chronic inflammatory diseases [3]. Major micro circulatory events that occur during the inflammatory process include changes in vascular permeability, leukocyte recruitment and accumulation, and inflammatory mediator’s release [4]. 

Chronic rhinosinusitis (CRS) is an inflammatory condition involving nasal passages and the paranasal sinuses for 12 weeks or longer [1]. It can be subdivided into three types: CRS with nasal polyposis (CRS with NP), CRS without nasal polyposis (CRS without NP), and Allergic fungal rhinosinusitis (AFRS). To diagnose CRS we require at least two of four of its cardinal signs/symptoms (nasal obstruction, mucopurulent discharge, facial pain/pressure, and decreased sense of smell). In addition, direct visualization or imaging for objective documentation of mucosal inflammation is required. CRS therapy is aimed to reduce its symptoms and improve quality of life as it cannot be cured in most patients. Thus, the goals of its therapy include the following:

Xanthogranulomatous cholecystitis is a rare benign inflammatory disease of gallbladder that may be misdiagnosed as carcinoma of the gallbladder intraoperative or in pre-operative imaging. Intramural accumulation of lipid-laden macrophages and acute and chronic inflammatory cells is the hallmark of the disease. The xanthogranulomatous inflammation can be very severe and can spill over to the neighboring structures like liver, bowel and stomach resulting in dense adhesions, abscess formation, perforation, and fistulous communication with adjacent bowel [1-3]. Cholecysto-colic fistula is a rare and late complication of gallstones roughly found 1 in every 1,000 cholecystectomies. Clinical featuresThe clinical features are variable and non-specific. Patients with cholecysto-colonic fistula often present with symptoms of acute cholecystitis and preoperative diagnostic tools often fail to show the fistula. Hence most cases it is an on table diagnosis. ManagementTreatment involves closing the fistula and performing an open or laparoscopic cholecystectomy.

Purpose: This work is aimed at demonstrating that scraping cytology and scanning electron microscopy can successfully assist in the diagnosis of nontuberculous mycobacteria infection. For this purpose, we report the use of both these techniques in the diagnosis of cornel ulcer in a previously healthy young man. Methods: Cytological samples were achieved by scraping technique on the mucosa, both sub palpebral and temporal area of the eye tarsal conjunctiva. The obtained sample was affixed to a sanded rectangular slide, stained with the Pappenheim method, washed in bidistilled water, treated in Giemsa solution, washed again and subsequently dried on a hot plate and observed with a microscope at various magnifications. Results: After a therapy based on a 500 mg clarithromycin tablet administered every 12 hours for 30 days as systemic therapy, a complete recovery of the patient from left eye inflammation was observed and SEM cytology showed that NTM colonies had disappeared. Conclusion: Conjunctival cytology scraping and SEM technologies can be therefore exploited as new tools in diagnosis and fast identification of these newly discovered mycobacteria. In fact, they have a new way for studying ocular pathology, because of the simple execution and remarkable accuracy in the diagnosis. In fact, this technique allows to gather valuable information about all pathogens expression and the cellular action involved in pathology. As a further plus, this technique provides clinicians with the opportunity to repeat the SEM cytology for monitoring patients during therapy, hence leading to evaluate the efficacy of the pharmaceutical regimen in real time.

A case of oncocytic papillary cystadenoma in a 72-year old woman, a rare tumor of laryngeal seromucinous glands of unclear nature is presented. The patient had a history of chronic inflammation of laryngeal mucosa and both her age and tumor location were typical. The lesion was resected transorally without complications. Histological findings are shown in the present study. The controversial status of oncocytic papillary cystadenoma as either a true neoplasm or a combination of metaplastic and hyperplastic changes, its resemblance to Warthin’s tumor and optimal approach to treatment are discussed.

COVID-19 virus structural components: The 2019-nCoV, also called SARS-CoV-2, was first reported in Wuhan, China in December 2019. The disease was named Coronavirus Disease 2019 (COVID-19) and the virus responsible for it as the COVID-19 virus, respectively, by WHO. The 2019-nCoV has a round, elliptic or pleomorphic form with a diameter of 60–140 nm. It has single-stranded RNA genome containing 29891 nucleotides, a lipid shell, and spike, envelope, membrane and hemagglutinin-esterase (HE) proteins. Steps in progression of COVID-19 illness: Once inside the airways, the S protein on the viral surface recognizes and mediates the attachment to host ACE-2 receptors and gains access to endoplasmic reticulum. The HE protein facilitates the S protein-mediated cell entry and virus spread through the mucosa, helping the virus to attack the ACE2-bearing cells lining the airways and infecting upper as well as lower respiratory tracts. With the dying cells sloughing down and filling the airways, the virus is carried deeper into the lungs. In addition, the virus is able to infect ACE2-bearing cells in other organs, including the blood vessels, gut and kidneys. With the viral infestation, the activated immune system leads to inflammation, pyrexia and pulmonary edema. The hyperactivated immune response, called cytokine storm in extreme cases, can damage various organs apart from lungs and increases susceptibility to infectious bacteria especially in those suffering from chronic diseases. The current therapeutics for COVID-19: At present, there is no specific antiviral treatment available for the disease. The milder cases may need no treatment. In moderate to severe cases, the clinical management includes infection prevention and control measures, and symptomatic and supportive care, including supplementary oxygen therapy. In the critically ill patients, mechanical ventilation is required for respiratory failure and hemodynamic support is imperative for managing circulatory failure and septic shock. Conclusion: Confusion, despair and hopes: There is no vaccine for preexposure prophylaxis or postexposure management. There are no specific approved drugs for the treatment for the disease. A number of drugs approved for other conditions as well as several investigational drugs are being canned and studied in several clinical trials for their likely role in COVID-19 prophylaxis or treatment. The future seems afflicted with dormant therapeutic options as well as faux Espoir or false hopes. As obvious, not all clinical trials will be successful, but having so many efforts in progress, some may succeed and provide a positive solution. Right now, though, confusion and despair prevail.

Background: The development of COVID-19 having been set apart as the third presentation of an exceptionally pathogenic coronavirus into the human populace after the extreme intense SARS-COV and MERS-COV in the twenty-first century. The infection itself doesn’t make a crucial commitment to mortality, anyway “cytokine storm” created by the unreasonable invulnerable reaction activated by the virus can result in a hyperinflammatory response of lung tissues and deadly lung injury, and in this way increment death rate. In this manner, immunomodulatory medications ought to likewise be remembered for treatment of COVID-19. Presentation of the hypothesis: the virus particles invade the respiratory mucosa firstly and infect other cells, triggering a series of immune responses and the production of cytokine storm in the body, which may be associated with the critical condition of COVID-19 patients. Once a cytokine storm is formed, the immune system may not be able to kill the virus, but it will certainly kill many normal cells in the lung, which will seriously damage the of lung function. Patients will have respiratory failure until they die of hypoxia. It is not yet clear what the death rate of Covid-19 will be, though the best estimate right now is that it is around 1 percent, 10 times more lethal than seasonal flu due to cytokines storm which trigger a violent attack by the immune system to the body, cause acute respiratory distress syndrome (ARDS) and multiple organ failure, and finally lead to death in severe cases of COVID-19 infection. Therefore, inhibiting cytokine storm can significantly reduce inflammatory injury in lung tissues. Pyridostigmine (PDG), cholinergic anti-inflammatory pathway (CAP) is a neural mechanism that modulates inflammation through the release of acetylcholine (ACh), resulting in decreased synthesis of inflammatory cytokines such as TNF-α and IL-1. This finding emphasis, the nervous and immune systems work collaboratively during infection and inflammation. Implications of the hypothesis: Administrations of Pyridostigmine (PDG) as cholinergic agonist inhibits the inflammatory response and lower the mortality of COVID-19 patients. Likewise, activation of the CAP during systemic inflammation down-regulates the production and release of inflammatory cytokines. 

Corona Virus Disease-2019 (COVID-19) has become one of the most serious diseases in the history of mankind. It has captured the entire world and solutions are yet to be discovered to fight this global crisis. The outcomes of COVID-19 are influenced by a variety of pre-existing factors. The secondary microbial infections are one of the prominent ones that are major contributors for Antimicrobial Resistance (AMR) as they warrant the use of antimicrobial medications. The present review aimed at exploring the potential relationship between AMR under such circumstances and COVID-19 related outcomes. The published literature across the globe has delineated that the impact of COVID-19 may have worsened by a great degree due to the presence of secondary infections majorly bacterial ones. The consequences of COVID-19 have been fatal and a significant proportion can be a major attributor to AMR, either directly or indirectly. Although, there is a dearth of studies that can establish a very strong and direct relationship between AMR and negative COVID-19 outcomes so in-depth research on this topic is required to further explain this relationship in detail. 

Background: Combination of extracts from multiple plants are typically used in ethnomedicine to putatively offer more potent chemotherapeutic and chemopreventive effects than that of individual extracts from single plants. Aqueous extracts from two multipurpose plants Strophanthus hispidus (roots) and Aframomum meleguta (seeds) are topically co-administered in the nasal cavities for the ethnomedicinal management of chronic sinusitis. Aim: This study assessed the potential phytochemical synergy between constituent extracts of Strophanthus hispidus (roots) and Aframomum meleguta (seeds) in its anti-inflammation, anti-microbial and anti-oxidant effects. Methods and Materials: Broth dilution assay assessed anti-microbial activities. DPPH radical scavenging assay examined the scope of anti-oxidant activities and inhibition of carrageenan-induced 7-day old chick feet oedema revealed anti-inflammatory activities. Results: Anti-microbial activities of individual plant extracts in broth dilution assay showed comparable potency to that of the co-extract mixture. Similarly, individual extracts showed levels of DPPH radical scavenging activities in anti-oxidant assay that was comparable to those found for the co-extract mixture. In contrast to these two effects, inhibition of carrageenan-induced 7-day old chick feet oedema revealed an anti-inflammatory activity evoked by co-extract mixtures that was greater than the sum of the individual potencies of the two extracts. Conclusion: The potential phytochemical synergy of the two plants extracts in its anti-inflammatory response largely validates ethnomedicinal practice and generally confirms growing literature reports that ascribe the net pharmacological activities of herbal extracts to the combined multi-activities of unique phytochemical entities at multiple target sites.

High blood pressure (HBP) is a strong, independent and etiologically relevant risk factor for cardiovascular and therefore, the leading cause of preventable deaths worldwide. Hypertension has high medical and social costs. Due to its many associated complications, the use of medical services create high costs with medications which represent almost half of the estimated direct expenses. Free distribution of more than 15 medications for HyPERtension and DIAbetes (HIPERDIA program) clearly shows the important role of drugs in the Brazilian Government’s effort to tackle these two diseases. Notwithstanding, the prevalence of HBP is rising in parallel with other NCDs. It is known that HBP results from environmental and genetic factors, and interactions among them. Our ancestors were often faced with survival stresses, including famine, water and sodium deprivation. As results of natural selection, the survival pressures drove our evolution to shape a thrifty genotype, which favored/promoted energy-saving and sodium/water preservation. However, with the switch to a sodium- and energy-rich diets and sedentary lifestyle, the thrifty genotype and ancient frugal alleles, are no longer advantageous, and may be maladaptive to disease phenotype, resulting in hypertension, obesity and insulin resistance syndrome. Low-grade chronic inflammation and oxidative stress would be the underlying mechanisms for these diseases. HBP is often associated with unhealthy lifestyles such as consumption of high fat and/or high-salt diets and physical inactivity. Therefore, alternatively to medicine drugs, lifestyle and behavioral modifications are stressed for the prevention, treatment, and control of hypertension. A lifestyle modification program (LSM) involving dietary counseling and regularly supervised physical activity (“Move for Health”) has been used for decades, in our group, for NCDs primary care. Retrospective (2006-2016) data from 1317 subjects have shown the top quartile of blood pressure(142.2/88.5mmHg) differing from the lower quartile (120.6/69.2mmHg) by being older, with lower schooling, lower income and, lower physical activity and aerobic capacity. Additionally, the P75 showed higher intake of CHO, saturated fat and sodium along with lower-diet quality score with a more processed foods. They showed higher body fatness and prevalence of metabolic syndrome along with higher pro-inflammatory and peroxidative activities and insulin resistance. In this free-demand sample, the HBP rate was 51.2% for SBP and 42.7% for DBP. The rate of undiagnosed HBP was 9.8% and only 1/3 of medicated patients were controlled for HBP. After 10 weeks of LSM the HBP normalization achieved 17.8% for SBP and 9.3% for DBP with a net effectiveness of 8.5% and 2.4%, respectively. The reduction of HBP by LSM was followed by increased aerobic conditioning and reduced intake of processed foods along with decreased values of BMI, abdominal fatness, insulin resistance, pro-inflammatory and peroxydative activities. Importantly, once applied nationwide this LSM would save HBP medication for 3.1 million of hypertensives at an economic saving costs of US$ 1.47 billion a year!

Platelet vesiculation is common factor contributing in coagulation and thromboembolism in patients with atrial fibrillation (AF). Platelet-derived vesicles are involved in the coagulation, thromboembolism, microvascular inflammation, arterial stiffness, vascular calcification, atherosclerotic plaque shaping and rupture, endothelial dysfunction, cardiac remodelling, and kidney dysfunction. Recent clinical studies have revealed elevated concentrations of platelet-derived vesicles in peripheral blood of patients with current AF and history of AF. The aim of the mini review is to discuss the role of platelet-derived micro vesicles as predictive biomarker in AF. Serial measures of circulating levels of platelet-derived vesicules are discussed to be useful in stratification of AF patients at risk of thromboembolic complications, but there is limiting evidence regarding their predictive value that requires further investigations in large clinical trials.

Graphical abstract Biodegradation of implanted gold in human tissue. TEM images reveal markedly biodegradation of implanted gold and re-crystallization of dissolved gold as nanoparticle of different size, shape and crystallinity. Highly crystalline icosahedral Au nanoparticle and the corresponding power spectrum are shown on top. Background: Despite the importance of biodegradation for the durability of metal prosthesis and the widely use of gold implants, there exist a lack of knowledge regarding the stability of pure gold in tissue. Methods: We studied biodegradation of grids of pure gold, nickel, and copper as well as middle ear prosthesis of gold, platinum or titanium. Metals were implanted into rat skin and humans. Dissolution and re-crystallization process of the metals was analysed using SEM, TEM, power spectra as well as elemental analysis by EDX and EELS/ESI. Results: Biodegradation of gold was detected, presumably by solving and re-precipitation of gold around implants. Gold cluster, nanoparticles, and mesostructures were detected, formed by dissolution and re-crystallization process. This process results into a migration of gold into the farer off tissue. Cellular filaments as biomolecular templates facilitate the formation of mesostructures. Loss of function of middle ear prosthesis by biodegradation is caused by chronic inflammation and fibrosis. Indeed, similar processes were detected with platinum, but in a very lower level. Conclusion: Noble metal implants undergo biodegradation in oxidative environment in tissue. The dissolution – recrystallization process can be explained by enzyme catalysed redox processes comprising reactive oxygen species and reduction agents as ascorbic acid present in cells and body tissue. Enymes like myeloperoxidase inside lysosomes of inflammatory cells produce hypochloride ions and H2O2 which can dissolve the gold. General significance: The crucial role of the specific chemical environments of gold implants in tissue for their chemical stability and durability of function has been demonstrated. Due to widely use and importance of gold implants, this finding is of general interes.

The Federal and State governments have declared the presence of an opioid addiction pandemic in the United States claiming the lives of more than 55,000 in 2015 (Rudd RA, Seth P, David F and Scholl L. 2016). The pharmaceutical manufacturers of the numerous FDA-approved opioid drugs are raking in more than $5 billion per year with about 2 million chronic pain sufferers addicted. The irony of this narcotic use and abuse conundrum is the existence of evidence-based technology for drug-free pain management which is not covered for reimbursement among public and private third-party payers. Therefore, this paper is presented to propose a pilot study to demonstrate the efficacy of resolving the chronic inflammation, edema and ischemia that causes non-malignant chronic pain with PEMF therapy, a non-invasive, non-thermal radio transmission of electrical impulses, thereby invalidating the legitimacy of prescribing opioid analgesics in such cases.

The NIH has published treatment guidelines for treating COVID-19 patients in the hospital. However, as of this writing, there are no established protocols for treating COVID-19 positive patients in primary care. Accordingly, this investigator has taken on the task of reviewing the medical literature to be able to propose evidence-based protocols for treating COVID-19 positive patients in primary care. The CDC is advising people to do nothing when they find out they are positive for COVID-19 unless they have symptoms. The evidence from the literature irrefutably shows COVID-19 infection evokes a massive and deadly hyperinflammatory response called the “Cytokine storm” and that Cytokine levels in the blood have a predictive value in identifying an impending Cytokine storm. With such data primary care providers can effectively lower Cytokine levels and prevent critical illness and death. Accordingly, this paper presents identification of the problem of not having standard practices in primary care for people who are positive for COVID-19 and not knowing who is at risk. Moreover, the evidence shows that knowing vitamin D levels and correcting deficiencies can go a long way in reducing Cytokine levels. Additionally, the literature review presents evidence that undeniably shows the stark possibility that many of the COVID-19 related deaths can be prevented by identifying who is at risk for the Cytokine storm and other complications and providing early treatment even before symptoms appear.

Lichen Planopilaris is known as the form of Lichen Planus typical of the scalp. It is classified as a lymphatic disease and is characterized by chronic inflammation which leads to cicatricial alopecia. Its causes are not yet well characterized but its etiology seems to strongly correlates with infection, sensitization and pollution. A clear and objective diagnosis of Lichen Planopilaris is not simple but the evolution and strongly negative outcomes on scalp of people affected by, pose the need of an early diagnosis. In this work we report the case of a 27-year-old male and a 54-year-old female, respectively, in which a correct diagnosis of Lichen Planopilaris, followed the incorrect previous ones, was made by means of dermatoscopy and histopathological analysis, decisive tools for the diagnosis of this kind of pathology.

Purpose: Sacroiliac joints (SIJ) inflammation and pain is particularly common in patients with Spondyloarthritis. Intraarticular SIJs injections represent a valuable therapeutic option in this condition. In the rheumatological outpatient clinics this procedure is usually done by landmark guidance (LG) or ultrasound guidance (USG). Thus we aimed to compare the short term efficacy of USG vs. LG SIJ injections using five outcome measures: 1. Pain; 2. SIJ status (number of positive provocation tests per symptomatic SIJ on physical examination); 3. Disability; 4. Quality of the night sleep; 5. Patients’ satisfaction. Methods: We enrolled 44 consecutive spondyloarthritis patients with pain in the SIJs that did not respond to NSAIDS and that were otherwise on a stable medical treatment. All patients also had ≥ 3 positive pain provocation tests per SIJ on physical examination. Patients were randomly allocated to receive a single SIJ injection with 7 mg Betamethasone (1 ml) and 1% Lidocaine (1.5 ml) either under USG or with LG. Results: Both groups showed significant improvement in all outcome parameters. However, the USG approach performed significantly better than the LG ones in all parameters. In addition, there was a significant correlation between the improvement in all patient reported outcomes (VAS, RMDQ, JSEQ) and the reduction in the number of positive SIJ pain provocation tests per symptomatic joint. Conclusion: Both USG and LG SIJ injections proved to be an efficient treatment for SIJ pain in SpA patients. However, USG of the intervention led to statistically better results in the present study.

The global virome: The viruses have a global distribution, phylogenetic diversity and host specificity. They are obligate intracellular parasites with single- or double-stranded DNA or RNA genomes, and afflict bacteria, plants, animals and human population. The viral infection begins when surface proteins bind to receptor proteins on the host cell surface, followed by internalisation, replication and lysis. Further, trans-species interactions of viruses with bacteria, small eukaryotes and host are associated with various zoonotic viral diseases and disease progression. Virome interface and transmission: The cross-species transmission from their natural reservoir, usually mammalian or avian, hosts to infect human-being is a rare probability, but occurs leading to the zoonotic human viral infection. The factors like increased human settlements and encroachments, expanded travel and trade networks, altered wildlife and livestock practices, modernised and mass-farming practices, compromised ecosystems and habitat destruction, and global climate change have impact on the interactions between virome and its hosts and other species and act as drivers of trans-species viral spill-over and human transmission. Zoonotic viral diseases and epidemics: The zoonotic viruses have caused various deadly pandemics in human history. They can be further characterized as either newly emerging or re-emerging infectious diseases, caused by pathogens that historically have infected the same host species, but continue to appear in new locations or in drug-resistant forms, or reappear after apparent control or elimination. The prevalence of zoonoses underlines importance of the animal–human–ecosystem interface in disease transmission. The present COVID-19 infection has certain distinct features which suppress the host immune response and promote the disease potential. Treatment for epidemics like covid-19: It appears that certain nutraceuticals may provide relief in clinical symptoms to patients infected with encapsulated RNA viruses such as influenza and coronavirus. These nutraceuticals appear to reduce the inflammation in the lungs and help to boost type 1 interferon response to these viral infections. The human intestinal microbiota acting in tandem with the host’s defence and immune system, is vital for homeostasis and preservation of health. The integrity and balanced activity of the gut microbes is responsible for the protection from disease states including viral infections. Certain probiotics may help in improving the sensitivity and effectivity of immune system against viral infections. Currently, antiviral therapy is available only for a limited number of zoonotic viral infections. Because viruses are intracellular parasites, antiviral drugs are not able to deactivate or destroy the virus but can reduce the viral load by inhibiting replication and facilitating the host’s innate immune mechanisms to neutralize the virus. Conclusion: Lessons from recent viral epidemics - Considering that certain nutraceuticals have demonstrated antiviral effects in both clinical and animal studies, further studies are required to establish their therapeutic efficacy. The components of nutraceuticals such as luteolin, apigenin, quercetin and chlorogenic acid may be useful for developing a combo-therapy. The use of probiotics to enhance immunity and immune response against viral infections is a novel possibility. The available antiviral therapy is inefficient in deactivating or destroying the infecting viruses, may help in reducing the viral load by inhibiting replication. The novel efficient antiviral agents are being explored.

The biological changes caused by oxidative stress (OS) are known to be involved in the etiology of neurodegenerative disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. The brain is particularly vulnerable to OS due to its high lipid content and extensive consumption of oxygen. OS processes, particularly the excessive production of reactive oxygen species (ROS), play a critical role in how neurodegenerative disorders develop. This is evidenced by in vivo studies investigating various biomolecules related to OS, such as products of lipid and DNA oxidation. Accordingly, ROS can also cause oxidative-related damage in neurodegenerative disorders, including dopamine auto-oxidation, mitochondrial dysfunction, glial cell activation, α-synuclein aggregation, excessive free iron, and changes in calcium signaling. Furthermore, excessive levels of cellular oxidants reduce antioxidant defenses, which in turn propagate the cycle of OS. As such, it is increasingly important to determine the linkage between a high intake of antioxidants through dietary interventions and a lower risk of developing neurodegenerative diseases. Indeed, in addition to modulating the immune system, optimal nutritional status is capable of changing various processes of neuroinflammation known to be involved in the pathogenesis of neurodegeneration. Accordingly, a better understanding of the role ROS plays in the etiology of neurodegeneration is needed, along with the identification of dietary interventions that may lead to improved therapeutic strategies for both the treatment and prevention of neurodegenerative disorders. Therefore, this review presents a comprehensive summary of the role of ROS in the pathogenesis of neurodegenerative disorders. In addition, nutrients believed to be useful for mitigating and counteracting ROS are discussed. 

Objective: Atlantoaxial subluxation (AAS) occurs when there is misalignment of the atlantoaxial joint. Several etiologies confer increased risk of AAS in children, including neck trauma, inflammation, infection, or inherent ligamentous laxity of the cervical spine. Methods: A single-center, retrospective case review was performed. Thirty-four patients with an ICD-10 diagnosis of S13.1 were identified. Demographics and clinical data were reviewed for etiology, imaging techniques, treatment, and clinical outcome. Results: Out of thirty-four patients, twenty-two suffered cervical spine trauma, seven presented with Grisel’s Syndrome, four presented with ligamentous laxity, and one had an unrecognizable etiology. Most diagnoses of cervical spine subluxation and/or instability were detected on computerized tomography (CT), while radiography and magnetic resonance imaging (MRI) were largely performed for follow-up monitoring. Six patients underwent cervical spine fusion, five had halo traction, twelve wore a hard and/or soft collar without having surgery or halo traction, and eight were referred to physical therapy without other interventions. Conclusion: Pediatric patients with atlantoaxial subluxation may benefit from limited 3D CT scans of the upper cervical spine for accurate diagnosis. Conservative treatment with hard cervical collar and immobilization after reduction may be attempted, but halo traction and halo vest immobilization may be necessary. If non-operative treatment fails, cervical spine internal reduction and fixation may be necessary to maintain normal C1-C2 alignment.