Rejected

To measure postoperative pain relief following the use of rectal diclofenac combined with intramuscular pentazocine compared with intramuscular pentazocine alone in patients undergoing a caesarean delivery.

Superior labrum from anterior to posterior (SLAP) lesions represent a significant cause of shoulder pain and disability among active duty members of the US military. However, few data exist regarding the surgical management of type VIII SLAP lesions.

Small-fiber neuropathies are a heterogeneous group of disorders affecting thinly myelinated Aδ and unmyelinated C fibers. Patients generally present with neuropathic pain, while dysesthesia, allodynia, pain, burning sensations, and cold sensations are frequently present in a length-dependent pattern. Additional autonomic features of the gastrointestinal, urinary, or cardiovascular systems are frequently observed. Deep-tendon reflexes and nerve conduction tests yield normal results. Skin biopsy is useful for the diagnosis, and can demonstrate the loss of intraepidermal nerve fibers in small-fiber neuropathy and has a diagnostic sensitivity of 80%. Although many causes of small-fiber neuropathy have been reported, the cause remains unknown in 30-50% of the cases. Treatment is directed at the underlying etiology and is supported with symptomatic treatment.

Transient receptor potential melastatin 2 (TRPM2) is a sub family of TRP channels which plays a central role in producing neuro pathophysiological diseases such as Alzheimer's, Parkinson's and other neuropathic pain which are major health concern worldwide. However, their pharmacological pathway has not been fully characterized which is a significant gap in our knowledge. TRPM2 is mainly expressed in brain, bone merrow, endocrine and endothelia cells. Under oxidative stress, TRPM2 increases intracellular Ca ions due to protein oxidation that causes several neurological disorders. Reactive oxygen species (ROS) production and oxidative stress are the primary cause of many pathological disease processes. Natural compounds with medicinal properties are useful and effective source for the treatment of various diseases since ancient times. Caffeic acid and its analogs, such as caffeic, chlorogenic, salvianolic A & B, and rosmarinic acid have anti-inflammatory, antimicrobial, antioxidant, anesthetic, and cytotoxic properties. There is a critical need for new drug planning that focuses on oxidative interaction in targeted TRPM2 ion channels and intracellular ion signaling, which will regulate neuropathological diseases by interacting other TRP channels. Our ongoing experiment demonstrate that increase in ROS was decreased by caffeic acid analogs salvianolic, and rosmarinic acid more than caffeic and chlorogenic acid which was reflected by GST inhibition activity assay. Our experiments also evaluate the analgesic effects of caffeic acid analogs on TRPM2 channel by measuring intracellular calcium. Therefore, this pilot project aims to identify caffeic acid analogs as lead compounds that target TRPM2 which is one of the key pathway players for controlling various neurodegenerative diseases.

Eosinophilic esophagitis (EoE) is a chronic immune mediated disease that affects populations of all ages. It is characterized by eosinophilic inflammation of the esophageal mucosa, decreased epithelial integrity, and lamina propria fibrosis. Clinically, the symptoms of EoE can range from mild (dysphagia, abdominal pain, vomiting), to severe (food impaction, inability to thrive), to complete loss of esophageal function in extreme cases. This disease, first described in 1993, is rising in incidence and prevalence. Unfortunately, the reason for disease emergence is unknown and environmental triggers have been postulated as a potential source. The role of environmental toxins, specifically herbicides, has never been examined in the pathophysiology of atopic disease. Glyphosate, the active ingredient in Roundup, is the most used herbicide in the United States, and is frequently used as a desiccant prior to harvest. Residual amounts can be detected in harvested crops and downstream food products, potentially leading to a diet of chronic exposure. Herein we sought to determine the effects of early life glyphosate treatment and the consequences of exposure on the development of eosinophilic esophagitis and the maintenance of epithelial integrity. We exposed mice to physiologic levels of glyphosate in utero and throughout their life cycle to simulate glyphosate consumption in the typical American diet. We then induced EoE in mice using our established protocol and evaluated epithelial integrity and inflammation. Interestingly, we found that chronic glyphosate treatment alone induced a 2-fold increase in esophageal eosinophils over baseline, similar to mice undergoing EoE. Secondarily, we exposed primary human esophageal and intestinal organoids to short term glyphosate treatment. We observed no changes in the esophageal organoids. However, we found increased gene expression of mucin 2 (MUC2) in organoids derived from terminal ileum and proximal colon. Taken together these results suggest that there is increased inflammation in the glyphosate treated mice and this may be due, in part, to a response generated in the small intestine by glyphosate exposure.

Opioids are extensively used for their analgesic properties but present a variety of unwanted side effects, including tolerance, dependence and respiratory depression. The analgesic effect of opioids is due to activation of µ-opioid receptors (MOR) in the central nervous system and no treatments are currently available to prevent respiratory depression without reducing their analgesic properties. The neural circuits and mechanisms regulating respiratory depression, sedation, and analgesia by opioids often overlap, therefore making challenging the identification of the mechanisms regulating respiratory depression. Neurons expressing tachykinin precursor 1 peptide (Tac1) located in the pre-Bötzinger complex (preBötC) also co-express neurokinin-1 receptors (NK1R) and MORs. NK1R neurons are preferentially inhibited by opioids and play an essential role in mediating opioid-induced respiratory depression.

Cybersickness is an array of symptoms associated with exposure to three-dimensional visualization technology (3DVT) environments, such as virtual reality (VR). It is thought that cybersickness is a type of motion sickness caused by a mismatch in sensory and vestibular input when using these modalities. Symptoms of cybersickness are often akin to those of traditional motion sickness, such as headache and nausea. In the literature, as many as 40-60% of VR users report symptoms of cybersickness, though in our laboratory approximately 20% of users report symptoms of cybersickness. Our past research has shown that the physical environment is often preferred by students, and more effective for learning anatomy, compared to 3DVT environments. We hypothesize that the preference for, and effectiveness of, the physical environment over 3DVT may be a result of cybersickness due to the isolation of the learner from the physical environment. However, no direct measurements of cybersickness or comparisons between 3DVT environments in anatomy are available.

Based on global burden of headache reports, migraine is a prevalent disorder that affect approximately 15% of the adult population. Generally migraine attacks are sporadic, however, some individuals develop a chronic disease form. To date, several researches have shown that migraine is associated with some gastrointestinal disorders such as Helicobacter pylori (HP) infection, irritable bowel syndrome (IBS), and celiac disease (CD). However, the mechanisms explaining how the gut and the brain may interact in patients with migraine are not entirely clear. In this study, we aimed to evaluate the role of the short-chain fatty acids (SCFAs), such as sodium propionate (SP) and sodium butyrate (SB) as mediators and modulators of host intestinal microbial ecology, in regulating the pathophysiology of migraine in a mouse model induced by nitroglycerine (NTG).

Eosinophilic Esophagitis (EoE) is a chronic condition characterized by esophageal dysfunction including dysphagia, abdominal pain and eosinophilic inflammation (>15/HPF) of the esophagus. At present, the most commonly used treatment for the management of EoE are steroids, both systemic as well as tropical, and dietary elimination. The advantage of the systemic steroids include ease of administration, rapid response, and very high response rate. However, poor solubility and the adverse effect related to prolonged steroid use are well documented. Moreover, there is a high relapse rate of EoE after the treatment is discontinued which limit the use of oral steroids as a maintenance therapy. Similarly, Ranitidine (Zantac), histamin-2 blocker, used to treat gastrointestinal reflux and heart burns, has been recently withdrawn from the market by FDA due to increased risk of cancer. Digestive Tea has been used at the Traditional Chinese Medicine (TCM) practice to improve gastrointestinal (GI) symptoms such as stomach pain, constipation and abnormal bowel movement. Different versions of Digestion Teas are further developed to address specific clinical GI symptoms. Compound 7, 4 Dihydroxy flavone (DHF) is a flavonoid purified from Glycyrrhiza uralensis from Digestive Tea. Previously our group has shown inhibition of Eotaxin, Th2 cytokines and IgE in-vitrousing DHF. The objective of this study is to reveal potential mechanisms underlying DHF improving symptoms related to EoE using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analyses, and in silico molecular docking. Based on the pathway analyses, the most important targets identified were TNF- α, IL-6, IL1β, MAPK1, MAPK3, AKT1, CASP3 and CCND in AGE-RAGE pathway. We further validated the targets of our computational modeling in human esophagus biopsy sample by ELISA and qRT-PCR. We found significant reduction in levels of TNF-α (p<0.001), IL-6 (p<0.001), IL-8 (p<0.001) and IL1-β (p<0.05) in the supernatant of biopsy sample cultured with DHF. Moreover, gene expression profile showed significant reduction in level of TNF- α (p<0.01), IL1-β (p<0.05), IL-6 (p<0.01) and CCND (p<0.05) in the biopsy sample cultured with DHF. Furthermore, our molecular docking analysis revealed that DHF can directly bind TNF- α with free binding energies of -7.7 kcal/mol. Taken together, the current study may lead to development of DHF as an active therapeutic candidate in treatment of EoE.

Chronic prostatitis (CP) has long been considered one of the common causes of male infertility. The influence of therapy for CP on spermatogenesis is well studied. However, recently, especially in the era of the new coronavirus infection (COVID-19), much attention has been paid to the effects of cytokines on the pathogenesis of the inflammatory process, and their impact on male fertility.