Rejected

Opioids, which are widely used for the treatment of chronic pain, have an analgesic effect by mainly activating mu-opioid receptor (MOR). Paradoxically, a high dose of naloxone, non-selective opioid receptor antagonist, is also known to induce analgesia, but the underlying mechanism remains unclear. Since kappa-opioid receptor (KOR) and dynorphin (KOR ligand) have been implicated in the naloxone-induced analgesia, we aimed to elucidate its mechanism by focusing on the kappa-opioid system in the brain under inflammatory pain condition. Systemic administration of naloxone (10 mg/kg, i.p.) decreased spontaneous pain behaviors only in complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model but not in the formalin-induced acute pain model. Immunohistochemistry analysis in the CFA model revealed both a significant decrease in MOR expression and an increase in prodynorphin density in the central nucleus of theamygdala (CeA) and nucleus accumbens (NAc) but not in other brain areas. Systemic administration of KOR antagonist (norbinaltorphimine, nor-BNI 10 mg/kg) also decreased spontaneous pain behaviors in the CFA model. Furthermore, microinjection of both naloxone and nor-BNI into NAc and CeA significantly reduced spontaneous chronic pain behavior. Taken together, our results suggest that naloxone-induced analgesia may be mediated by blocking facilitated kappa-opioid systems in the NAc and CeA.

To estimate the burden of disease through 4 complementary procedures to years lived with disability (YLDs) using the concept of attributable fraction and including analysis of subdomains of disability.

Lichen planus is a darkly pigmented skin disease that impairs the quality of life of patients. The effect of lichen planus on patient's quality of life (QoL) is not widely documented. The study's objective was to determine QoL impairment of LP patients, determine what aspect of QoL is impaired, and correlate clinical and sociodemographic characteristics with QOL impairment.

Oseltamivir caryboxylase is a potent inhibitor of the enzyme neuramidase of the influenza virus particle and it is active against both influenza A and B viruses. Oseltamivir is indicated for therapy or post-exposure prevention of influenza A and B. Side effects are uncommon and include mild nausea, gastrointestinal upset, dizziness and headache. Despite its widespread use, oseltamivir has not been associated with clinically apparent liver injury. To the best of our knowledge, this is the first case report in the literature linking the development of acute hepatitis to the consumption of oseltamivir in a patient suffering from influenza H1N1 infection.

Worldwide, gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths, which carries a poor prognosis as only 28.3% are expected to survive after five years. The incidence varies depending on the geographical locations and dietary patterns. Here, we present a case of a 59-year-old Hispanic male with a 10-month history of recurrent bilateral pneumonia and dysphagia. Diagnostic workup revealed metastatic gastric adenocarcinoma.

Patients undergoing open nephrectomy surgery experience severe perioperative pain, which is primarily due to incision of several muscles. Abdominal wall blocks are known to reduce pain without causing epidural-associated hypotension. We conducted this study to compare unilateral ultrasound-guided transmuscular quadratus lumborum block and posterior transversus abdominis block in combination with general anesthesia alone in terms of intraoperative and postoperative analgesics and hemodynamics and postoperative complications.

Postdural puncture headache (PDPH) is a common complication of neuraxial techniques which delays patients' discharge. Sphenopalatine ganglion block (SPGB) is a safe bedside technique with comparable efficacy to Epidural Blood Patch, the gold-standard treatment. There is no evidence on the ideal timing for SPGB performance. We aimed to evaluate the difference between early versus late SPGB concerning efficacy, symptom recurrence and hospital length of stay.

Abdominal Hysterectomy (AH) is associated with significant inflammatory response and can result in moderate to severe postoperative pain. This study aimed to evaluate the efficacy of magnesium infusion in reducing postoperative pain and analgesic consumption after AH under spinal anesthesia with Intrathecal Morphine (ITM).

Syphilitic myelitis, also known as tabes dorsalis, is a disease affecting the posterior columns of the spinal cord and dorsal roots and presents as sensory ataxia and neuropathic pain and less commonly as paresthesia and gastrointestinal disturbance. Tabes dorsalis is the clinical manifestation of a previous infection with syphilis, and the average latency period from initial infection to presentation of symptoms is approximately 25 years. This is a rarely encountered manifestation of syphilis since the widespread usage of antibiotics. Penicillin G is the mainstay therapy of neurosyphilis and has been shown to improve and resolve spinal cord lesions associated with tertiary syphilis. We present a case of tabes dorsalis in a 56-year-old female with a history of extensive autoimmune disease who initially presented with neck pain and numbness of the right lower extremity. The unique nature of this case lies in the patient's clinical course, as her symptoms were initially attributed to her history of autoimmune disease. A reactive CSF-VDRL (cerebrospinal fluid Venereal Disease Research Laboratory) test and MRI findings led clinicians to suspect neurosyphilis and begin penicillin G. The patient began to show significant clinical improvement after penicillin G therapy was begun and was discharged to a rehabilitation facility to continue antibiotics and begin aggressive physical therapy.

Despite decades of preclinical research, no experimentally derived therapies for sepsis have been successfully adopted into routine clinical practice. Factors that contribute to this crisis of translation include poor representation by preclinical models of the complex human condition of sepsis, bias in preclinical studies, as well as limitations of single-laboratory methodology. To overcome some of these shortcomings, multicentre preclinical studies-defined as a research experiment conducted in two or more research laboratories with a common protocol and analysis-are expected to maximize transparency, improve reproducibility, and enhance generalizability. The ultimate objective is to increase the efficiency and efficacy of bench-to-bedside translation for preclinical sepsis research and improve outcomes for patients with life-threatening infection. To this end, we organized the first meeting of the National Preclinical Sepsis Platform (NPSP). This multicentre preclinical  research collaboration of Canadian sepsis researchers and stakeholders was established to study the pathophysiology of sepsis and accelerate movement of promising therapeutics into early phase clinical trials. Integrated knowledge translation and shared decision-making were emphasized to ensure the goals of the platform align with clinical researchers and patient partners. 29 participants from 10 independent labs attended and discussed four main topics: (1) objectives of the platform; (2) animal models of sepsis; (3) multicentre methodology and (4) outcomes for evaluation. A PIRO model (predisposition, insult, response, organ dysfunction) for experimental design was proposed to strengthen linkages with interdisciplinary researchers and key stakeholders. This platform represents an important resource for maximizing translational impact of preclinical sepsis research.