Rejected

Pain is a protective physiological system essential for survival. However, it can malfunction and create a debilitating disease known as chronic pain (CP). CP is primarily treated with drugs that can have negative side effects (e.g., opioid addiction), and lose efficacy after long-term use. Electrical stimulation of the spinal cord or peripheral nerves is an alternative therapy that has great potential to reduce the need for drugs and has fewer negative side effects; but has been associated with suboptimal efficacy because its modulation mechanisms are unknown. Critical to advancing CP treatment is a deeper understanding of how pain is processed in the superficial and deep layers of the dorsal horn (DH), which is the first central relay station for pain processing in the spinal cord. Mechanistic models of the DH have been developed to investigate modulation mechanisms but are non-linear and high-dimensional and thus difficult to analyze. In this paper, we construct a tractable computational model of the DH in rats from LFP recordings of the superficial layer network and spiking activity of WDR neurons in the deep layer. By combining a deterministic linear time-invariant model with a stochastic point process model, we can accurately predict responses of the DH circuit to electrical stimulation of the peripheral nerve. The model is computationally efficient, low-dimensional, and able to capture the stochastic nature of neuronal dynamics in the DH; and is a first step in developing new therapies for CP.

Pain management after surgery is crucial to decrease perioperative morbidity and mortality. Acute pain services (APS) are multidisciplinary teams that represent a modern strategy to address pain inside hospitals. The APS defines and applies pain treatment protocols specific for each surgery. To evaluate the performance of the APS at our institute, we performed a large retrospective cohort study focusing on complications of epidural analgesia and intravenous opiates.

Hypertonic saline (HS) injections for decompressive neuroplasty (DN) can cause pain. We assessed whether a continuous infusion of HS through an infusion pump would reduce injection-related pain compared with repeated bolus administrations.

Treatments for rheumatoid arthritis (RA) over the last few decades have transformed the future outlook of the disease. Although patients with clinically apparent RA have a number of therapeutic options, all are associated with the risk of adverse events (AEs). Such therapeutics, facilitated by the identification of novel biomarkers and environmental and genetic factors to predict RA, may allow early detection, prompt treatment, and prevention before the future development of clinically apparent disease. Before choosing such treatments to make informed decisions in this context, however, accurate quantification of benefits and harms of such treatments is vital for participants without symptoms. This review summarizes the AEs reported in trials in preclinical or very early RA, the frequency and risk of primary AEs of concern associated with disease-modifying antirheumatic drugs (conventional, biologic, and targeted), glucocorticoids, and analgesia in clinically apparent RA. Also summarized is the evidence to date to support the quantification of benefit and harms incorporating patient preferences.

Infectious Mononucleosis is a common viral illness mainly of adolescent-young adult age group. Spontaneous splenic rupture is a rare but potentially fatal complication of Infectious Mononucleosis occurring in less than 0.5 % of the cases. A high index of suspicion especially if abdominal pain develops during Infectious Mononucleosis is very crucial to early diagnosis and intervention in the case of rupture. Here we discuss the case of a 24 year old male with no previous comorbidities and stable vitals who presented with febrile illness of one week duration associated with abdominal discomfort. Even though initial evaluation did not point towards any etiological clues, a CT imaging of the abdomen was opted due to his persistent abdominal symptoms which showed features suggestive of a contained rupture of spleen. The lack of a specific trauma history prompted further workup for an infective etiology and patient was subsequently found to be positive for Epstein Barr Virus antigen and was diagnosed to have Infectious Mononucleosis. Rupture being of lower grades, non-operative management was opted for and patient improved with conservative management over 4-8 weeks with no further complications. We also discuss the internationally accepted grading of splenic injury and the general consensus regarding management of the same. A general search of the available literature showed very few cases of spontaneous splenic rupture in Infectious Mononucleosis being reported especially from India and hence the importance of this case.

Cannabis legalization has led to significant health consequences, particularly to patients in emergency departments and hospitals in Colorado. The most concerning include psychosis, suicide, and other substance abuse. Deleterious effects on the brain include decrements in complex decision-making, which may not be reversible with abstinence. Increases in fatal motor vehicle collisions, adverse effects on cardiovascular and pulmonary systems, inadvertent pediatric exposures, cannabis contaminants exposing users to infectious agents, heavy metals, and pesticides, and hash-oil burn injuries in preparation of drug concentrates have been documented. Cannabis dispensary workers ("budtenders") without medical training are giving medical advice that may be harmful to patients. Cannabis research may offer novel treatment of seizures, spasticity from multiple sclerosis, nausea and vomiting from chemotherapy, chronic pain, improvements in cardiovascular outcomes, and sleep disorders. Progress has been slow due to absent standards for chemical composition of cannabis products and limitations on research imposed by federal classification of cannabis as illegal. Given these factors and the Colorado experience, other states should carefully evaluate whether and how to decriminalize or legalize non-medical cannabis use.

Due to the complex breast innervation, postoperative analgesia after breast surgery is a challenge for the anesthesiologists. The erector spinae plane block (ESPB) is a newly defined promising technique for this purpose. The main purpose of this study was to evaluate the analgesic efficacy of the ultrasound-guided ESPB in breast surgery, monitoring its effect on the postoperative opioid consumption.

Monosodium glutamate (MSG) is an umami substance widely used as flavor enhancer. Although it is generally recognized as being safe by food safety regulatory agencies, several studies have questioned its long-term safety. The purpose of this review was to survey the available literature on preclinical studies and clinical trials regarding the alleged adverse effects of MSG. Here, we aim to provide a comprehensive overview of the reported possible risks that may potentially arise following chronic exposure. Furthermore, we intend to critically evaluate the relevance of this data for dietary human intake. Preclinical studies have associated MSG administration with cardiotoxicity, hepatotoxicity, neurotoxicity, low-grade inflammation, metabolic disarray and premalignant alterations, along with behavioral changes. Moreover, links between MSG consumption and tumorigenesis, increased oxidative stress and apoptosis in thymocytes, as well as genotoxic effects in lymphocytes have been reported. However, in reviewing the available literature, we detected several methodological flaws, which led us to conclude that these studies have limited relevance for extrapolation to dietary human intakes of MSG risk exposure. Clinical trials have focused mainly on the effects of MSG on food intake and energy expenditure. Besides its well-known impact on food palatability, MSG enhances salivary secretion and interferes with carbohydrate metabolism, while the impact on satiety and post-meal recovery of hunger varied in relation to meal composition. Reports on MSG hypersensitivity, also known as 'Chinese restaurant syndrome', or links of its use to increased pain sensitivity and atopic dermatitis were found to have little supporting evidence. Based on the available literature, we conclude that further clinical and epidemiological studies are needed, with an appropriate design, accounting for both added and naturally occurring dietary MSG. Critical analysis of existing literature, establishes that many of the reported negative health effects of MSG have little relevance for chronic human exposure and are poorly informative as they are based on excessive dosing that does not meet with levels normally consumed in food products.