Rejected

Invasive cervical vagus nerve stimulation (VNS) is approved for the treatment of epilepsies, depression, obesity, and for stroke-rehabilitation. The procedure requires surgery, has side-effects, is expensive and not readily available. Consequently, transcutaneous VNS (tVNS) has been developed 20 years ago as non-invasive, less expensive, and easily applicable alternative. Since the vagus nerve reaches the skin at the outer acoustic canal and ear, and reflex-responses such as the ear-cough-reflex or the auriculo-cardiac reflex have been observed upon auricular stimulation, the ear seems well suited for tVNS. However, several sensory nerves with variable fiber-density and significant overlap innervate the outer ear: the auricular branch of the vagus nerve (ABVN), the auriculotemporal nerve, greater auricular nerve, and to some extent the lesser occipital nerve. VNS requires activation of Aβ-fibers which are far less present in the ABVN than the cervical vagus nerve. Thus, optimal stimulation sites and parameters, and tVNS-algorithms need to be further explored. Unravelling central pathways and structures that mediate tVNS-effects is another challenge. tVNS impulses reach the nucleus of the solitary tract and activate the locus-coeruleus-norepinephrine system. However, many more brain areas are activated or deactivated upon VNS, including structures of the central autonomic network and the limbic system. Still, the realm of therapeutic tVNS applications grows rapidly and includes medication-refractory epilepsies, depressive mood disorders, headaches including migraine, pain, heart failure, gastrointestinal inflammatory diseases and many more. tVNS might become a standard tool to enhance autonomic balance and function in various autonomic, neurological, psychiatric, rheumatologic, as well as other diseases.

We sought to obtain detailed information on the procedures and appraisal of screening for and diagnosing diabetic sensorimotor polyneuropathy (DSPN) in clinical practice.

Various side effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in analgesia have been reported. Among the NSAIDs, celecoxib has fewer side effects and is often used in therapeutic applications. However, the effect of celecoxib on aged skin is unknown. In this study, we investigated the effects of celecoxib administration on the skin of aged mice. We analyzed a 40-week-old mouse model and a 10-week-old mice as the control group. The animals were orally administered celecoxib for four consecutive days and then killed and dissected the day after the last dose. In aged mice treated with celecoxib, the water content of the stratum corneum, which is one of the markers of dry skin, was lower than that in the control and young mice groups. In addition, serum hyaluronic acid, creatinine, and inflammatory cytokines in the collected blood samples of aged mice were elevated compared to those in other mice groups, suggesting the onset of acute renal injury. Therefore, it was considered that acute renal injury occurred from the administration of celecoxib to aged mice, whereas dry skin developed by the promotion of inflammatory cytokine secretion and release into the bloodstream in this group.

Previous studies have demonstrated that psychosocial factors and comorbid depression are associated with worse preoperative baseline measures, clinical outcomes, and recovery in patients undergoing shoulder surgery. It is unknown whether this potential link would differ between those with traumatic vs. atraumatic shoulder instability, as symptoms may persist longer in atraumatic instability prior to surgical intervention. The purpose of this study was to determine if psychosocial factors and/or comorbid depression more heavily influence preoperative symptoms for patients with traumatic vs. atraumatic shoulder instability.

In recent years, experimental evidence suggested a possible role of the gut microbiota in the onset and development of several neurodegenerative disorders, such as AD and PD, MS and pain. Flavonoids, including anthocyanins, EGCG, the flavonol quercetin, and isoflavones, are plant polyphenolic secondary metabolites that have shown therapeutic potential for the treatment of various pathological conditions, including neurodegenerative diseases. This is due to their antioxidant and anti-inflammatory properties, despite their low bioavailability which often limits their use in clinical practice. In more recent years it has been demonstrated that flavonoids are metabolized by specific bacterial strains in the gut to produce their active metabolites. On the other way round, both naturally-occurring flavonoids and their metabolites promote or limit the proliferation of specific bacterial strains, thus profoundly affecting the composition of the gut microbiota which in turn modifies its ability to further metabolize flavonoids. Thus, understanding the best way of acting on this virtuous circle is of utmost importance to develop innovative approaches to many brain disorders. In this review, we summarize some of the most recent advances in preclinical and clinical research on the neuroinflammatory and neuroprotective effects of flavonoids on AD, PD, MS and pain, with a specific focus on their mechanisms of action including possible interactions with the gut microbiota, to emphasize the potential exploitation of dietary flavonoids as adjuvants in the treatment of these pathological conditions.

Sleep problems are common among older adults worldwide. The present study aims to determine the prevalence of poor sleep quality and its independent factors among retired people in health check-ups population in China.

The use of mouthwash is often recommended by dental experts for dental healing. A double-blind, randomized clinical study was conducted to evaluate the efficacy of two mouthwashes (myrrh and chlorhexidine gluconate) on postoperative pain and their effects on tissues after dental implant placement in 35 patients (18 in the myrrh group and 17 in the chlorhexidine gluconate group). Soft tissue healing was evaluated in terms of wound closure, soft tissue swelling, and the color of the gingiva at 1 week postoperative. To decrease the chances for error, only the participants who did not show preoperative symptoms of infection and those who committed to practicing better oral hygiene were included in the study. The samples were evaluated for the infiltration of inflammatory cells (using inflammatory extent and inflammatory cellularity grades), maturation of collagen (osteoblast activity), and arrangement of cells (for detecting the remodeling phase). A questionnaire pertaining to mouthwash satisfaction, the duration of postoperative pain after the procedure, the time of stoppage of bleeding at the surgical site, and any sensitivity at the surgical site was given to the patients. The Chi-square test and Mann-Whitney U-test were used to analyze the data. The difference in postoperative surgical swelling, pain, bleeding, and redness in the patients was not statistically significant between the myrrh and chlorhexidine gluconate mouthwash groups. However, in the acute phase, the myrrh mouthwash showed a positive impact on the process of wound healing after implant placement. The small sample size and inability to compare wound healing in different anatomical areas of the oral cavity were the study limitations.

To investigate the clinical and imaging features and to identify possible etiology of acute multiple small cerebellar infarction (MSCI).

Sickle-cell disease (SCD) is an inherited hemoglobinopathy, causing lifelong complications such as painful vaso-occlusive episodes, acute chest syndrome, stroke, chronic anemia, and end-organ damage, with negative effects on quality of life and life expectancy. Within the last five years, three new treatments have been approved: L-glutamine in 2017 and crizanlizumab and voxelotor in 2019. We conducted a literature search of these three medications, and of the 31 articles meeting inclusion criteria, 6 studied L-glutamine, 9 crizanlizumab, and 16 voxelotor. Treatment with L-glutamine was associated with decrease in pain crises, hospitalizations, and time to first and second crises, with a decrease in RBC transfusion rate. Barriers to filling and taking L-glutamine included insurance denial, high deductible, and intolerability, especially abdominal pain. Crizanlizumab was associated with a reduction in pain crises and time to first crisis, with reduction in need for opioid use. Adverse effects of crizanlizumab include headache, nausea, insurance difficulty, and infusion reactions. Voxelotor was associated with increased hemoglobin and decreased markers of hemolysis. Barriers for voxelotor use included insurance denial and side effects such as headache, rash, and diarrhea. These three medications represent exciting new therapies and are generally well-tolerated though price and insurance approval remain potential barriers to access. Other studies are ongoing, particularly in the pediatric population, and more real-world studies are needed. The objective of this article is to evaluate post-approval studies of crizanlizumab, voxelotor, and L-glutamine in SCD, with a focus on real-world efficacy, side effects, and prescribing data.

This study aimed to investigate the effect of therapy with peripheral nerve stimulation (PNS) and pulsed radiofrequency (PRF) combined or PNS and PRF separately in patients with herpes zoster ophthalmicus (HZO).