Rejected

Intervertebral disc degeneration (IDD) is the most common chronic skeletal muscle degeneration disease. Although the underlying mechanisms remain unclear, nucleus pulposus (NP) autophagy, senescence, and apoptosis are known to play a critical role in this process. Previous studies suggest that bromodomain-containing protein 4 (BRD4) promotes senescent and apoptotic effects in several age-related degenerative diseases. It is not known, however, if BRD4 inhibition is protective in IDD. In this study, we explored whether BRD4 influenced IDD. In human clinical specimens, the BRD4 level was markedly increased with the increasing Pfirrmann grade. At the cellular level, BRD4 inhibition prevented IL-1-induced senescence and apoptosis of NP cells and activated autophagy via the AMPK/mTOR/ULK1 signaling pathway. Inhibition of autophagy by 3-methyladenine (3-MA) partially reversed the antisenescence and antiapoptotic effects of BRD4. In vivo, BRD4 inhibition attenuated IDD. Taken together, the results of this study showed that BRD4 inhibition reduced NP cell senescence and apoptosis by induced autophagy, which ultimately alleviated IDD. Therefore, BRD4 may serve as a novel potential therapeutic target for the treatment of IDD.

Prevention of pain in rabbits is a priority for both welfare and validity of scientific data. We aimed to determine if the rabbit grimace scale (RbtGS) could be used as a viable, rapid assessment tool in two breeds of rabbit, Dutch belted (DB) and New Zealand white (NZW), following orchidectomy, as an adjunct to behavioral analysis. All animals received analgesia. Rabbits were filmed and their behavior was recorded at multiple time points pre- and post-orchidectomy. Observers then scored specific pain associated behaviors for analysis. Time matched footage was also scored using the rabbit grimace scale (RbtGS). Following surgery, rabbits showed significant increases in the duration spent displaying key pain associated behaviors at 1 and 5 h post-surgery. DB rabbits that received low dose meloxicam (0.2 mg/kg) showed significantly more pain behaviors at 1 and 5 h post-surgery compared to those administered a combination of higher dose meloxicam (0.6 mg/kg) and a lidocaine/bupivacaine local infusion. DB rabbits showed an increase in RbtGS score at both 1 and 5 h post-surgery. In the NZW rabbits, an increase in RbtGS score was only observed at 1 h post-surgery. Using behavioral analysis as the gold standard for comparison, the RbtGS was an effective means of determining when rabbits are painful following orchidectomy. Higher dose meloxicam (0.6 mg/kg) combined with local anesthetic was a more effective method of reducing pain, compared to lower dose meloxicam (0.2 mg/kg) alone.

Eosinophilic esophagitis (EoE) is an immune mediated chronic inflammatory disease resulting from antigen exposure and is characterized by mucosal inflammation with eosinophils. Diagnosis is based on the histological finding of at least 15 eosinophils per high power field in esophageal biopsy specimens from upper gastrointestinal endoscopies. These endoscopies are usually performed in the setting of esophageal dysfunction, however, EoE can occasionally be incidentally diagnosed during endoscopies performed for other indications like coeliac disease. The eosinophilia is in the absence of other causes of esophageal eosinophilia (e.g., parasitic infection, esophageal leiomyomatosis or Crohn's disease). Presentation can be wide ranging and often varies according to age. Infants and younger children can present with choking/gagging, feed refusal, failure to thrive, irritability and vomiting. Older children and adults commonly present with dysphagia, chest pain or food bolus obstruction. EoE was first described in the 1970s, but was only recognized as a distinct disease entity in the 1990s. It has been rising in incidence and prevalence, with reported prevalence ranging between 1 in 2,500 and 1 in 10,000. Although the diagnosis of EoE is dependent on clear histopathologic diagnostic criteria, there is a disconnect between the degree of esophageal eosinophilia and symptom severity especially that of reported dysphagia. Multiple anatomical changes can be seen in the spectrum of presentations of EoE which explain dysphagia, including isolated strictures, diffuse trachealisation, fixed rings, including Schatzki, as well as tissue remodeling and fibrotic changes. However, a majority of EoE patients do not have any of these findings and will still often report ongoing dysphagia. Some will report ongoing dysphagia despite histological remission. This suggests an underlying esophageal dysmotilty which cannot be assessed with endoscopy or correlated with histological changes seen in biopsies. This review will describe the types of motor disturbances seen and their prevalence, the pathophysiological basis of dysmotility seen in EoE, how best to investigate esophageal dysfunction in EoE and the role of manometry in the management of EoE.

Since coronavirus disease 2019 emergence, millions were infected and many were dying because of the virus. Clinical features and time to recovery of admitted clients vary across settings. Therefore showing clinical features and recovery time from COVID-19 in a different setting is necessary to design appropriate treatment and preventive measures. So, this study attempted to investigate the clinical features and time to recovery of admitted clients to Dilla University Referral Hospital treatment center, Ethiopia.

To investigate the efficacy of modified percutaneous balloon compression for simple third branch pain and its postoperative complications.

To assess the effectiveness and safety of Erenumab, a monoclonal antibody to calcitonin gene-related peptide receptors, in patients with high-frequency episodic migraine (HFEM) in real-life study.

Chemotherapy-induced peripheral neuropathy (CIPN) negatively impacts cancer survivors' quality of life and is challenging to treat with existing drugs for neuropathic pain. TNF-α is known to potentiate TRPV1 activity, which contributes to CIPN. Here, we assessed the role of TMI-1, a TNF-α-converting enzyme inhibitor, in paclitaxel (PAC)-induced neurotoxicity in dorsal root ganglion (DRG) cells. Immortalized DRG neuronal 50B11 cells were cultured and treated with PAC or PAC with TMI-1 following neuronal differentiation. Cell viability, analysis of neurite growth, immunofluorescence, calcium flow cytometry, western blotting, quantitative RT-PCR, and cytokine quantitation by ELISA were performed to determine the role of TMI-1 in neurotoxicity in neuronal cells. PAC administration decreased the length of neurites and upregulated the expression of TRPV1 in 50B11 cells. TMI-1 administration showed a protective effect by suppressing inflammatory signaling, and secretion of TNF-α. TMI-1 partially protects against paclitaxel-induced neurotoxicity by reversing the upregulation of TRPV1 and decreasing levels of inflammatory cytokines, including TNF-α, IL-1β, and IL-6 in neuronal cells.

Japan has no streamlined concussion education for collegiate athletes, and guidelines vary by sport. In particular, research on knowledge of, and attitudes toward, concussion is necessary for the establishment of concussion education for Japanese collegiate athletes. The aim of the present study was to assess the knowledge of, and attitudes toward, concussion in Japanese male collegiate athletes and to investigate their experiences with suspected concussion symptoms. An online questionnaire was administered to 390 collegiate athletes participating in the following five sports with a high incidence of concussion: rugby union, soccer, basketball, American football, and judo. Of the 121 valid responses, 91 (77.1%) indicated that they had experienced suspected concussion symptoms at least once and 46 of these 91 respondents had not reported their symptoms of suspected concussion at least once. Athletes who had never experienced concussion symptoms were significantly less likely to recognize the symptoms of concussion ( < 0.001). Most athletes recognized headache and dizziness as suspected concussion symptoms. However, the recognition rate for several symptoms was lower than the prevalence of these symptoms as shown in previous studies. This suggests that educational initiatives might be important to bridge the gap between athletes' knowledge and understanding of frequently occurring concussion symptoms and to improve reporting behavior.

Unlike the tick-borne diseases ehrlichiosis and Lyme disease, human granulocytic anaplasmosis is rarely associated with neurological complications. In this case report, we present a patient who developed a severe, lancinating headache shortly after known tick exposure. A tick-borne PCR panel was positive for and neurology evaluation yielded a concomitant diagnosis of new-onset trigeminal neuralgia. Our case explores the relationship between anaplasmosis infection and trigeminal neuralgia.

Arthritis gloves are frequently prescribed to people with undifferentiated inflammatory arthritis (UIA) or RA to help reduce hand pain and improve function. Nested within a randomized controlled trial testing the effectiveness of arthritis gloves (Isotoner gloves loose-fitting placebo gloves) in people with RA and UIA, this qualitative study aimed to explore participants' views on the impact of wearing arthritis gloves on their hand pain and function.