Rejected

Prevention and treatment for locomotive syndrome (LS) are important for extending healthy life expectancy. The 25-question geriatric locomotive function scale (GLFS-25) was developed to diagnose LS. The Fear-Avoidance model was proposed to explain pain chronicity. LS and chronic pain decrease activities of daily living; however, the relationships between LS and factors related to chronic pain in the Fear-Avoidance model are unknown. Objective of the current study was to assess the prevalence of LS and examine the factors of the Fear-Avoidance model and the GLFS-25 that affect the prevalence of LS in patients with chronic pain.

Most severe pain occurs within the first 72 hours after an operation, and current local anesthetics have a limited duration of action. HTX-011 is a dual-acting, local anesthetic containing bupivacaine, and low-dose meloxicam in an extended-release polymer. In a prior phase 3 inguinal herniorrhaphy study, HTX-011 alone provided superior pain relief for 72 hours and significantly decreased opioid use compared with saline placebo and bupivacaine hydrochloride. This open-label study assessed the safety, efficacy, and opioid-sparing properties of HTX-011 as the foundation of a scheduled, nonopioid, multimodal analgesia regimen in patients undergoing open inguinal herniorrhaphy.

Sevoflurane may reduce the occurrence of major adverse cardiovascular events (MACCEs) in surgical patients, although the mechanisms are poorly understood. We hypothesised that sevoflurane stabilises atherosclerotic plaques by inhibiting inflammation and enhancing prolyl-4-hydroxylase α1 (P4Hα1), the rate-limiting subunit for the P4H enzyme essential for collagen synthesis.

The neuropeptide calcitonin gene-related peptide (CGRP) and its receptor, calcitonin receptor-like receptor (CLR) complexing with receptor activity-modifiying protein 1 (RAMP1), have been shown to be crucially involved in the pathogenesis of migraine. However, CGRP also plays a pivotal role in regulating bone turnover and was suggested to contribute to the development of the metabolic syndrome. Therefore, our study was designed to characterize the effects of CGRP antagonism on bone and glucose metabolism in a murine model of diet-induced obesity (DIO). A subcutaneous pellet releasing the CGRP receptor antagonist BIBN 4096 (BIBN; olcegepant) was implanted in WT mice with DIO. Metabolic effects were assessed through body- and organ-weights, oral glucose tolerance (oGT), serum lipids, and gene-expression studies. Bone turnover was assessed through histomorphometry of non-decalcified bone sections and analyses of bone turnover markers in serum samples. BIBN treatment did not alter body weight gain or the levels of serum lipids including triacylglycerol and cholesterol during DIO. BIBN led to a moderate improvement of oGT which was accompanied by an increased expression of stearoyl-CoA desaturase in the liver. In skeletal tissue, BIBN treatment resulted in reduced bone volume. This was explained by decreased parameters of bone formation whereas bone resorption was not affected. Our results indicate that inhibition of CGRP signaling only moderately affects glucose metabolism during DIO but significantly impairs bone formation. As novel agents blocking CGRP or its receptor are currently introduced clinically for the treatment of migraine disorders, their potential negative impact on bone metabolism requires further clinical studies.

Patients seeking endodontic treatment commonly present with reduced mechanical pain thresholds- mechanical allodynia (MA) in the offending teeth. In patients with moderate to severe pain, mechanical allodynia may manifest in the teeth contralateral to the offending teeth due to the onset of central sensitization (CS). We hypothesize that there are quantitative differences in MA and CS in patients with different pulp and periradicular diagnoses METHODS: Patients (n=70) receiving endodontic treatment in Graduate Endodontic Clinic at UTHSA and healthy volunteers (n=10) were included in this cross-sectional study. Mechanical pain threshold from molar teeth was measured by a digital bite force transducer on the offending tooth (ipsilateral) and contralateral tooth. Ipsi- and contralateral MA among different endodontic diagnoses were analyzed using Kruskal-Wallis with Dunn's post-hoc test and Student's t-test for differences between sexes. Multivariate regression models analyzed predictors for MA and CS.

Osteolytic bone lesions are one of the central features of multiple myeloma (MM) and lead to bone pain, fractures, decreased quality of life, and decreased survival. Dysfunction of the osteoclast (OC)/osteoblast (OB) axis plays a key role in the development of myeloma-associated osteolytic lesions. Many signaling pathways and factors are associated with myeloma bone diseases (MBDs), including the RANKL/OPG and NF-κB pathways. NRF2, a master regulator of inflammatory signaling, might play a role in the regulation of bone metabolism via anti-inflammatory signaling and decreased reactive oxygen species (ROS) levels. The loss of NRF2 expression in OCs reduced bone mass via the RANK/RANKL pathway and other downstream signaling pathways that affect osteoclastogenesis. The NRF2 level in OBs could interfere with interleukin (IL)-6 expression, which is associated with bone metabolism and myeloma cells. In addition to direct impact on OCs and OBs, the activity of NRF2 on myeloma cells and mesenchymal stromal cells influences the inflammatory stress/ROS level in these cells, which has an impact on OCs, OBs, and osteocytes. The interaction between these cells and OCs affects the osteoclastogenesis of myeloma bone lesions associated with NRF2. Therefore, we have reviewed the effects of NRF2 on OCs and OBs in MBDs.

Tuberculosis (TB) is the most prevalent infectious disease in the world. In recent years there has been a significant increase in the incidence of TB due to the emergence of multidrug resistant strains of () and the increased numbers of highly susceptible immuno-compromised individuals. Central nervous system TB, includes TB meningitis (TBM-the most common presentation), intracranial tuberculomas, and spinal tuberculous arachnoiditis. Individuals with TBM have an initial phase of malaise, headache, fever, or personality change, followed by protracted headache, stroke, meningismus, vomiting, confusion, and focal neurologic findings in two to three weeks. If untreated, mental status deteriorates into stupor or coma. Delay in the treatment of TBM results in, either death or substantial neurological morbidity. This review provides latest developments in the biomedical research on TB meningitis mainly in the areas of host immune responses, pathogenesis, diagnosis, and treatment of this disease.

Patients with chronic idiopathic hypoparathyroidism may develop neurological complications, including calcification of the basal ganglia and other areas of the brain. In Fahr's syndrome, intracranial calcification is associated with an underlying disorder such as hypo or hyperparathyroidism. We report the case of a 37-year-old gentleman, with a history of bilateral cataract surgery and seizures, who presented with a new episode of seizure and was found to have severe hypocalcemia and bilateral symmetric intracranial calcification due to previously diagnosed primary hypoparathyroidism. He had symptoms and signs mimicking ankylosing spondylitis (AS), but with negative radiological and serological findings, not fitting into the diagnosis of axial spondyloarthropathies (SpA), as per standard criteria. Patients with long-standing idiopathic hypoparathyroidism can have severe calcification of soft tissues and bones, including vertebrae and paravertebral soft tissues, causing inflammatory back pain and stiffness. It is vital to report such cases as their occurrence is rare, and physicians should be aware of the possibility while evaluating patients with inflammatory back pain. Treatment in these cases is directed towards hypocalcemia and underlying primary pathology rather than spondyloarthropathy.

Sigma-1 receptors are found throughout the nervous system and play a role in regulating nociception. They are highly expressed in nerve injury, making them a potential target for the treatment of neuropathic pain. Although sigma-1 receptor antagonists have been shown to have anti-nociceptive and anti-allodynic effects, improved selectivity of these ligands is needed to further investigate their potential to treat neuropathic pain. MCI-92 is a novel, selective sigma-1 receptor ligand developed to address this need. A sensitive and rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of MCI-92 in mouse plasma and brain homogenate. A structural analog of the analyte, MCI-147, was used as the internal standard (IS). The chromatographic separation was achieved on an Acquity UPLC BEH C column using a mobile phase consisting of water acidified with 0.1 % v/v formic acid and acetonitrile with gradient elution over 3.2 min. The method was linear over a concentration range of 1-200 ng/mL. Multiple reaction monitoring in the positive ionization mode was used for the mass spectrometric quantitation using m/z transitions 369.2 > 126.0 for MCI-92 and 448.9 > 350.1 for the IS. The method was successfully applied to the analysis of plasma and brain samples obtained in the course of oral and intravenous pharmacokinetic studies in CD-1 mice. MCI-92 showed a high volume of distribution (11.3 ± 0.6 L/kg) and rapid clearance (6.1 ± 0.8 L/h/kg) from systemic circulation. The concentration of the MCI-92 was higher in the brain than in plasma throughout all terminal time points, indicating high blood-to-brain partitioning and slow brain clearance.