Rejected

Ependymomas are usually found in the posterior fossa originating from the fourth ventricle. Primary ependymomas arising from cranial nerves are rare with only a handful of reported cases. Trigeminal neuralgia (TN) is rarely due to space occupying lesions.

Experimental evidence suggests that neuroinflammation is a key pathological event of many diseases affecting the nervous system. It has been well recognized that these devastating illnesses (e.g., Alzheimer's, Parkinson's, depression, and chronic pain) are multifactorial, involving many pathogenic mechanisms, reason why pharmacological treatments are unsatisfactory. The purpose of this study was to evaluate the efficacy of a vegetal mixture capable of offering a multiple approach required to manage the multifactoriality of neuroinflammation. A mixture composed of (150 mg kg), (20 mg kg), and (200 mg kg) was tested in a mouse model of systemic neuroinflammation induced by lipopolysaccharide (LPS, 1 mg kg). Repeated treatment with the vegetal mixture was able to completely counteract thermal and mechanical allodynia as reported by the Cold plate and von Frey tests, respectively, and to reduce the motor impairments as demonstrated by the Rota rod test. Moreover, the mixture was capable of neutralizing the memory loss in the Passive avoidance test and reducing depressive-like behavior in the Porsolt test, while no efficacy was shown in decreasing anhedonia as demonstrated by the Sucrose preference test. Finally, LPS stimulation caused a significant increase in the activation of glial cells, of the central complement proteins and of inflammatory cytokines in selected regions of the central nervous system (CNS), which were rebalanced in animals treated with the vegetal mixture. In conclusion, the vegetal mixture tested thwarted the plethora of symptoms evoked by LPS, thus being a potential candidate for future investigations in the context of neuroinflammation.

UDP-glucose dehydrogenase (UGDH) generates essential precursors of hyaluronic acid (HA) synthesis, however mechanisms regulating its activity are unclear. We used enzyme histostaining and quantitative image analysis to test whether cytokines that stimulate HA synthesis upregulate UGDH activity. Fibroblast-like synoviocytes (FLS, from N = 6 human donors with knee pain) were cultured, freeze-thawed, and incubated for 1 hour with UDP-glucose, NAD+ and nitroblue tetrazolium (NBT) which allows UGDH to generate NADH, and NADH to reduce NBT to a blue stain. Compared to serum-free medium, FLS treated with PDGF showed 3-fold higher UGDH activity and 6-fold higher HA release, but IL-1beta/TGF-beta1 induced 27-fold higher HA release without enhancing UGDH activity. In selected proliferating cells, UGDH activity was lost in the cytosol, but preserved in the nucleus. Cell-free assays led us to discover that diaphorase, a cytosolic enzyme, or glutathione reductase, a nuclear enzyme, was necessary and sufficient for NADH to reduce NBT to a blue formazan dye in a 1-hour timeframe. Primary synovial fibroblasts and transformed A549 fibroblasts showed constitutive diaphorase/GR staining activity that varied according to supplied NADH levels, with relatively stronger UGDH and diaphorase activity in A549 cells. Unilateral knee injury in New Zealand White rabbits (N = 3) stimulated a coordinated increase in synovial membrane UGDH and diaphorase activity, but higher synovial fluid HA in only 2 out of 3 injured joints. UGDH activity (but not diaphorase) was abolished by N-ethyl maleimide, and inhibited by peroxide or UDP-xylose. Our results do not support the hypothesis that UGDH is a rate-liming enzyme for HA synthesis under catabolic inflammatory conditions that can oxidize and inactivate the UGDH active site cysteine. Our novel data suggest a model where UGDH activity is controlled by a redox switch, where intracellular peroxide inactivates, and high glutathione and diaphorase promote UGDH activity by maintaining the active site cysteine in a reduced state, and by recycling NAD+ from NADH.

Chronic tension-type headache is the primary headache with the highest prevalence. The present study is aimed at analyzing the associations between patient self-efficacy and headache impact with pain characteristics, kinesiophobia, anxiety sensitivity, and physical activity levels in subjects with chronic tension-type headache.

SARS-CoV-2 infection can impair diaphragm function at the acute phase but the frequency of diaphragm dysfunction after recovery from COVID-19 remains unknown.

New research shows that the prevalence of neurodevelopmental disorders, such as attention-deficit/hyperactivity disorder (ADHD), is increased in children and adolescents as well as in adults with chronic pain, compared to those without chronic pain. Children and adolescents with ADHD also have an increased incidence of various physical conditions associated with pain, and they more frequently suffer from inflammatory diseases. Moreover, parents of children with ADHD can often suffer from pain conditions. These epidemiological and clinical observations form the scientific basis of our study, which aims to map the relationships between ADHD, altered pain experiences/central sensitization, and inflammation in children and adolescents. We will investigate the presence of central sensitization in children and adolescents with newly diagnosed ADHD and compare it with those who have not been diagnosed with ADHD. Participants (and their biological parents) will complete surveys about their somatic health, pain experience, and quality of life. Biological samples (saliva and stool) will be collected, aiming to utilize proteome and metabolome data to discover disease mechanisms and to predict, prevent and treat them. The results from our investigation should enable an expanded understanding of the pathophysiology behind both ADHD and pain/central sensitization. Presently, there are no established protocols for addressing psychiatric symptoms when examining patients with pain conditions in a somatic care setting, nor is there any knowledge of offering patients with ADHD or other neurodevelopmental disorders adapted treatments for pain conditions. Our results, therefore, can contribute to the development of new treatment strategies for pathological pain conditions in children and adolescents with ADHD. They may also increase awareness about and provide opportunities for the treatment of attention and impulse control problems in children and adolescents with pain syndromes.

Chronic pain remains highly prevalent. Current pharmacological and non-pharmacological strategies have not adequately managed chronic pain which has contributed to disability and high healthcare costs. With existing challenges in providing adequate pain care and access, we tested vAPA, a virtually delivered, self-management intervention using Auricular Point Acupressure (APA) by mobile app and virtual consultations (telehealth). Our key purpose was to evaluate the feasibility of the vAPA in self-managing chronic pain in preparation for a future randomized controlled trial.

Trauma is a relatively uncommon etiology of carotid artery dissection. Trauma is both penetrative and trivial, which can lead to carotid artery dissection. In the current study, we present an unusual case in which carotid artery dissection was potentially triggered by the damaging thermal effect of 7D High-Intensity Macro- and Micro-Focused Ultrasound (7D HIFU), which has been proposed as a safe and effective non-surgical modality for skin rejuvenation.

Immune checkpoint inhibitors have made remarkable breakthroughs in the treatment of lung cancer, bringing significant survival benefits to the patients. A number of adverse events aggravated by immunotherapy in patients with pre-existing autoimmune diseases have been reported in the past, especially skin toxicity, such as rash, pruritus, erythema, and vitiligo. However, whether the exacerbated autoimmune disease is reversible and when it will return to its original state after immunotherapy discontinuation is still inconclusive. In our report, we described a patient diagnosed with non-small cell lung cancer whose vitiligo was stable for about 10 years. We followed up and observed the patient's skin depigmentation for the complete time window, from aggravation of application anti-programmed cell death-1 receptor antibody (anti-PD-1 antibody) to recovery after the withdrawal. We presented the objective images at particular time points using reflectance confocal microscopy and wood's light. We found that the use of anti-PD-1 antibody aggravated in skin toxicity, but it was reversible, the time window from the beginning to recovery status was approximately 9 months. We used this real case scenario to explain the relationships between immunotherapy and autoimmune diseases.

Pain and inflammation typically manifest in patients with arthritis. It is now widely known that Ledeb (AP) and Bunge (SM) exert anti-inflammatory and antinociceptive effects. We have previously reported that the mixture extract (ME) from AP and SM produces antinociceptive and anti-inflammatory effects in gout arthritis and monoiodoacetate (MIA)-induced arthritis models. In the present study, we assessed the antinociceptive and anti-inflammatory effects on the collagen-induced arthritis (CIA) model. The antinociceptive effects in mice were measured using the von Frey test. ME administered once or for one week (once per day) once, and one-week reduced the pain in a dose-dependent manner (from 50 to 100 mg/kg) in the CIA-induced osteoarthritis (OA) model. ME treatment also reduced tumor necrosis factor (TNF)-α and C-reactive protein (CRP) levels in plasma and ankle tissues. Furthermore, COX-1, COX-2, NF-κB, TNF-α, and IL-6 expressions were attenuated after ME treatment. In most experiments, the antinociceptive and anti-inflammatory effects induced by ME treatment were almost equal to or slightly better than those induced by (PC) treatment, which was used as a positive control. Our results suggest that ME possesses antinociceptive and anti-inflammatory effects, indicating its potential as a therapeutic agent for arthritis treatment.