Rejected

Mirogabalin, a novel ligand for the αδ subunit of voltage-gated calcium channels, has been approved for the treatment of peripheral neuropathic pain including painful diabetic peripheral neuropathy (DPNP) and postherpetic neuralgia (PHN) in Japan. Mirogabalin showed potent and selective binding affinities for the αδ subunits, and slower dissociation rates for the αδ-1 subunit than for the αδ-2 subunit. It also showed potent and long-lasting analgesic effects in rat models of neuropathic pain, and wider safety margins for the central nervous system side effects. A pharmacological study using mutant mice demonstrated that the analgesic effects of mirogabalin were mediated by binding of the drug to the αδ-1 subunit, not the αδ-2 subunit. The pharmacological properties of mirogabalin can be associated with its unique binding characteristics. The bioavailability of mirogabalin is high and its plasma exposure increases dose-proportionally. Mirogabalin is mainly excreted via the kidneys in an unchanged form, thus, mirogabalin has a low possibility of undergoing drug-drug interaction, while dose adjustment based on the creatinine clearance level is specified in patients with renal impairment. In double-blind, placebo-controlled phase 3 studies in Asian patients with DPNP and PHN, mirogabalin showed significant and dose-dependent pain relief, and all tested doses of mirogabalin were well tolerated. In summary, mirogabalin has a balanced efficacy versus safety profile, and can provide an alternative therapeutic option for the treatment of peripheral neuropathic pain.

The management of nonspecific lumbar pain (NSLP) using laser irradiation remains controversial. A systematic review of recently published studies indicates that the effects of laser therapy are commonly assessed using only imperfect methods in terms of measurement error. The main objective of this study was to assess static postural stability using an objective tool in patients with chronic NSLP after laser irradiation at different doses and wavelengths. In total, 68 patients were included in the laser sessions and were randomly assigned into four groups: high-intensity laser therapy at 1064 nm and 60 J/cm2 for 10 min (HILT), sham (HILT placebo), low-level laser therapy at 785 nm and 8 J/cm2 for 8 min (LLLT), and sham (LLLT placebo). In addition, all patients were supplemented with physical exercises (standard stabilization training). To assess postural stability, a double-plate stabilometric platform was used. All measurements were performed pre- and post-laser sessions (three weeks) and at follow-up time points (one and three months). Laser procedures led to more balanced posture stability in patients, although these positive changes were significant mainly for short-term observation (after 4-week therapy). In the follow-up analysis, the parameters were gradually impaired. Kruskal-Wallis analysis of variance (ANOVA) for independent variables did not show any difference between the studied groups. Low- and high-intensity laser therapy does not lead to a significant improvement in postural sway in patients with NSLP compared with standard stabilization training based on short- and long-term observations.

The neurosurgical treatment of glossopharyngeal neuralgia includes microvascular decompression or rhizotomy of the nerve. When considering open section of the glossopharyngeal nerve, numerous authors have recommended additional sectioning of the 'upper rootlets' of the vagus nerve because these fibers can occasionally carry the pain fibers causing the patient's symptoms. Sacrifice of vagus nerve rootlets, however, carries the potential risk of dysphagia and dysphonia. In this study, the anatomy and physiology of the vagus nerve rootlets are characterized to provide guidance for surgical decision-making. Twelve patients who underwent posterior fossa craniotomy with intraoperative electrophysiological monitoring of the vagus nerve rootlets were included in this study. In the 7 patients with glossopharyngeal neuralgia, the clinical outcomes and complications were further analyzed. In half of the patients, electrophysiological data demonstrated pure sensory function in the rostral rootlet(s) of the vagus nerve and motor responses in its caudal rootlets. This orientation of the vagus nerve, with some pure sensory function in its most rostral rootlet(s), was defined as Type A. In the other half of patients, all vagus nerve rootlets (including the most rostral) had motor responses. This was defined as Type B. The surgical strategy was guided by whether the patient had a Type A or Type B vagus nerve. For those with Type B, no vagus nerve rootlets were sacrificed. None of the patients with glossopharyngeal neuralgia developed any permanent neurological deficits. We recommend intraoperative electrophysiological testing of the vagus nerve rootlets. If the testing reveals motor innervation in the rostral vagal rootlet (Type B), that rootlet may be decompressed but should not be sectioned to avoid a motor complication. Patients with pure sensory innervation of the rostral rootlet(s) (Type A) can have decompression or section of those rootlets without complication.

Malaria is endemic in Liberia with a prevalence rate of up to 60% in some regions, and it has been a major cause of death in children under 5 years of age. Prior to the recent Ebola epidemic, we undertook a prospective, hospital-based pilot study at the National Referral Hospital in Monrovia, to characterize the presentation, accuracy of diagnosis, and treatment outcomes of children presenting for treatment of malaria. From June 2013 to May 2014, we recruited children 5 years and under who presented to the JFK Medical Center with suspected malaria. We collected both clinical and laboratory data on admission and on discharge. We enrolled 477 patients with an average age of 1.6 years. Demographic factors associated with testing negative for malaria included regular bed net use and prior treatment for malaria. The most common presenting symptoms of severe malaria in this population were headache and seizures. Of 246 patients admitted and treated for severe malaria, 33% tested negative by rapid diagnostic test and blood smear for malaria. The case fatality rate was higher for the patients who tested negative for malaria (4.9%) versus those who tested positive (0.6%). Three children who tested negative for malaria showed evidence of undiagnosed infection. These results suggest that malaria may be overdiagnosed and that the diagnoses of other infectious diseases, which present in a similar fashion, may be neglected. These findings underscore the need to develop rapid diagnostic tests to screen for alternative causes of febrile illness.

The objectives of this study were to investigate the impact of pain mitigation at birth to assisted beef calves and determine the risk factors associated with transfer of passive immunity (TPI), health, and growth.

Adipsic Diabetes Insipidus is a rare hypothalamic disorder characterized by a loss of thirst in response to hypernatraemia accompanied by diabetes insipidus. These occur secondary to a congregation of defects in the homeostatic mechanisms of water balance. A 27-year old Chinese female presented with Adipsic Diabetes Insipidus after cerebral arteriovenous malformation (AVM) surgery. Initial diagnosis and management was extremely challenging. Long term management required a careful interplay between low dose vasopressin analog treatment and fluids. Detailed charts of medication and sodium balance are described in the case presentation. We performed a literature search of similarly reported cases and describe the possible pathogenesis, etiology, clinical presentation, acute and chronic management, and prognosis.

Complete spinal cord injury is a devastating occurrence afflicting millions of people worldwide with no available treatment for functional motor recovery. In this report, we describe a procedure in which we used parts of a device available for chronic pain treatment to provide a neuromodulation of motor nerve roots in a case with complete motor and sensory paraplegia. By using a retrograde trans-foraminal approach to implant electrodes close to L2-S1 motor nerve roots bilaterally, we were able to stimulate those nerves and induce precise movements at the joints of lower extremity in a T5 complete spinal cord injury case. We believe that our approach shows potential of the device as a rehabilitation system with the possibility of a parallel electric circuitry that can bridge a damaged spinal cord.

Chronic recurrent multifocal osteomyelitis is a rare autoinflammatory, immunologic disorder. It may involve recurrent inflammatory bone pain associated with aseptic osteomyelitis. If the diagnosis is delayed, it negatively influences quality of life by leading to persistent symptoms or joint damage. Herein, we report a 16-year-old male patient who presented with left hip and right knee pain lasting for the last two months and was diagnosed as having chronic recurrent multifocal osteomyelitis as a result of further evaluation. Improvement was achieved with prednisolone and methotrexate treatment that was initiated when no response to ibuprofen treatment could be obtained. Chronic recurrent multifocal osteomyelitis must be considered in the differential diagnosis in patients presenting with joint symptoms when clinical and radiologic bone lesions are found, no microorganism growth is observed, and no response to antibiotic treatment is obtained.

Chronic pain is known as a complex disease due to its comorbidities with other symptoms and the lack of effective treatments. As a consequence, chronic pain seems to be under-diagnosed in more than 75% of patients. At the same time, the advance in brain imaging, the popularization of machine learning techniques and the development of new diagnostic tools based on these technologies have shown that these tools could be an option in supporting decision-making of healthcare professionals. In this study, we computed functional brain connectivity using resting-state fMRI data from one hundred and fifty participants to assess the performance of different machine learning models, including deep learning (DL) neural networks in classifying chronic pain patients and pain-free controls. The best result was obtained by training a convolutional neural network fed with data preprocessed using the MSDL probabilistic atlas and using the dynamic time warping (DTW) as connectivity measure. DL models had a better performance compared to other less costly models such as support vector machine (SVM) and RFC, with balanced accuracy ranged from 69 to 86%, while the area under the curve (ROC) ranged from 0.84 to 0.93. Also, DTW overperformed correlation as connectivity measure. These findings support the notion that resting-state fMRI data could be used as a potential biomarker of chronic pain conditions.

: Considering the poorly understood etiology and complex symptoms of chronic neuropathic pain (NP), the lack of effective treatments, and sex-dependent differences in the neuroimmune system as well as in antinociceptive responses to existing pharmacological agents, the potential to therapeutically target the endocannabinoid system as a means of treating this type of intractable pain is clinically relevant and timely. Chronic NP may involve the utilization of distinct immune cell populations in males and females that differentially affect supraspinal and spinal neuromodulation. It is therefore important to investigate the effects of cannabidiol (CBD) on chronic NP-induced nociceptive responses in both sexes. : Evaluating whether the expression of markers associated with CD4 T cells are affected by CBD in a sexually dimorphic manner will provide key insights into the contribution of these adaptive immune cells to the onset and progression of NP. : Future research will be directed toward examining the potential sex-dependent effects of this nonpsychotropic cannabinoid relative to vehicle in a preclinical model of chronic postsurgical NP. Specifically, (1) differences in nociceptive behavior, (2) chronic changes in neural firing patterns, and (3) up- or downregulation of markers associated with CD4 T cells in relevant tissues will be evaluated to better understand CBD-mediated neuroimmune modulatory effects in males and females. : Chronic postsurgical pain is a growing clinical problem. Current treatment strategies rely on opioid-based therapeutics, which affect patient quality of life and are associated with addiction and withdrawal. Treatment of nerve injuries with CBD could provide an effective alternative to manage NP. Understanding its mechanisms of action will provide important insights into the sex-dependent application of this nonpsychoactive cannabinoid, setting the groundwork for large-scale Canadian clinical trials in women and men presenting with chronic pain.