Rejected

A 46-year-old female presented at the outpatient clinic with nasal congestion, purulent discharge, facial pain with pressure sensation, headache, hyposmia, and fever (38.2 Cº) that had persisted for four months. This symptomatology was worse at night or upon awakening in the morning. Three months before, she was initially treated with antibiotics (amoxicillin/clavulanate) for a period of 10 days but did not improve. An anterior rhinoscopy examination demonstrated bilateral nasal mucosal oedema, dense purulent rhinorrhoea, a deviated nasal septum, and nasal polyps. Posterior pharyngeal drainage was also noticed. Her clinical history highlights the existence of hypertension, obesity (body mass index = 33), hypercholesterolaemia, and poorly controlled insulin-diabetes.

Encephalopathy and encephalitis are major and devastating SARS-CoV-2 virus-associated CNS complications. Hypoxic/metabolic changes produced by intense inflammatory response against the virus triggers cytokine storm and subsequently ARDS and multiple organ failure. Hypoxic/metabolic changes result in encephalopathy. The presence of comorbidities predisposes to hypoxic/metabolic changes responsible for encephalopathy. Altered consciousness, ranging from mild confusion, delirium, to deep coma, is hallmark clinical features. Cortical and subcortical T2/FLAIR signal changes are common neuroimaging abnormalities. In a few isolated case reports of SARS-CoV-2 encephalitis, the virus has been demonstrated in CSF. The presence of anosmia and ageusia can help in differentiation from other encephalopathies. We analysed published reports on COVID-19 associated-encephalopathy. Encephalopathy is common in older patients, the majority are more than 50 years of age. The patients having encephalopathy/encephalitis are either severely or critically ill. Many patients were already on mechanical ventilation. Lung abnormalities are noted in almost all of the patients, presenting with encephalopathy. Encephalopathy is always preceded by commoner clinical features, like, fever, cough, dyspnoea, and headache. In majority, patients are already in the intensive care unit, when encephalopathy develops. This article is protected by copyright. All rights reserved.

Structure-based drug design enabled the discovery of 8, HTL22562, a CGRP receptor antagonist. The structure of 8 complexed with the CGRP receptor was determined at 1.6 Å resolution. Compound 8 is a highly potent, selective, metabolically stable and soluble compound suitable for a range of administration routes that have the potential to provide rapid systemic exposures with resultant high levels of receptor coverage (e.g. subcutaneous). The low lipophilicity coupled with a low anticipated clinically efficacious plasma exposure for migraine also suggests a reduced potential for hepatotoxicity. These properties have led to 8 being taken forward as a clinical candidate for acute treatment of migraine.

A variety of studies have proposed that transient receptor potential vanilloid 1 (TRPV1) is involved in the progression of multiple diseases, including neuropathic pain. Although increased expression of TRPV1 in chronic constriction injury was described earlier, the underlying regulatory mechanisms of TRPV1 in neuropathic pain remain largely unknown. In our study, we constructed a chronic constriction injury (CCI) rat model to deeply analyze the mechanisms underlying TRPV1. RT-qPCR-indicated TRPV1 mRNA and protein expression were extremely upregulated in CCI rat dorsal spinal cord tissues. Then, TRPV1 was corroborated to interact with N-terminal EF-hand Ca-binding protein 2 (NECAB2). The mRNA and protein levels of NECAB2 were increased in CCI tissues. Moreover, TRPV1 and NECAB2 together regulated nociceptive procession-associated protein metabotropic glutamate receptor 5 (mGluR5), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and Ca in isolated microglia of CCI rats. Moreover, TRPV1 upregulation apparently increased mechanical allodynia and thermal hyperalgesia as well as the expression of inflammation-associated genes (COX-2, TNF-α, and IL-6). In addition, downregulation of NECAB2 significantly decreased mechanical allodynia and thermal hyperalgesia as well as the expression of COX-2, TNF-α, and IL-6. Furthermore, TRPV1 was confirmed to be a downstream target of miR-338-3p. TRPV1 overexpression abolished the inhibitory effect by miR-338-3p elevation on neuropathic pain development. In summary, this study proved TRPV1, targeted by miR-338-3p, induced neuropathic pain by interacting with NECAB2, which provides a potential therapeutic target for neuropathic pain treatment.

Bardoxolone methyl (Bard), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator regulates multiple oxidative and inflammatory diseases. However, the role of Bard in painful diabetic neuropathy (DN) remains unknown. Bard administration at two dose levels (15 & 30 mg/kg/day) to STZ (55 mg/kg, i.p) induced diabetic rats for last two weeks of eight week study significantly improved motor nerve conduction velocity (61.84 ± 1.9 vs. 38.57 ± 1.08 m/s), sensory nerve conduction velocity (66.86 ± 5.1 vs. 39.43 ± 3.3 m/s), nerve blood flow (86.28 ± 6.4 vs. 56.56 ± 1.62 PU), and intraepidermal nerve fiber density. Additionally, Bard treatment attenuated thermal and mechanical hyperalgesia in diabetic rats. Further molecular investigation on dorsal root ganglions (DRG) tissue isolated from L4-L6 regions of diabetic rats and High glucose (HG) exposed PC12 cells displayed decreased expression and transcriptional activity of Nrf2 which might have resulted in depleted antioxidant enzymes and mitochondrial chaperones. Bard treatment significantly reversed these effects in diabetic rats and also in HG exposed PC12 cells. Moreover, mitochondrial complex activities were diminished in DRG mitochondrial fractions of diabetic rats and mitochondrial isolates of HG exposed PC12 cells and Bard treatment significantly reversed these effects. Furthermore, Bard treatment significantly impeded the impact of hyperglycemic insults on mitochondrial membrane potential, ROS production and mitochondrial oxygen consumption rate (OCR) (Basal respiration, Maximal respiration, ATP production and spare respiratory capacity) in PC12 cells. Collectively our data suggests that Bard treatment to STZ induced diabetic rats robustly reduces DN which may be due to its effect on Keap1-Nrf2-ARE pathway and have contributed to improvement in mitochondrial function.

This review aims to summarize the efficacy data for naldemedine, a member of the novel peripherally acting μ-opioid receptor antagonists (PAMORAs), which gained US FDA approval for the treatment of opioid-induced constipation in adults with chronic noncancer pain-related syndromes in 2017. In Phase III trials, patients receiving naldemedine were significantly more likely to meet the primary end point ≥3 spontaneous bowel movements/week and an increase of ≥1 spontaneous bowel movement/week from baseline for at least 9/12 weeks compared to placebo (p < 0.0001). The most frequent adverse events were abdominal pain (8%) and diarrhea (7%). Based on available data, naldemedine appears to be an effective and safe first-line therapy for the treatment of opioid-induced constipation in adults with chronic noncancer pain.

School nurses occasionally deal with students presenting with serious infections associated with common chief complaints. Although rare, the implications of missing the signs and symptoms of these infections are potentially life-threatening and devastating, with both immediate and long-term complications. Rapid recognition and stabilization, with immediate transfer to the closest emergency department via emergency medical services for antibiotic administration, is the key to reducing morbidity and mortality associated with these serious infections. We discuss three students presenting with febrile illnesses associated with chest pain, headache, and back pain, focusing on the initial assessment and management of these students and their common presenting complaints.

Opioids are one of the most prescribed treatments for chronic pain (CP). However, their long-term use (>3 months) has been surrounded by controversy, due to loss of beneficial effects.

Not only an association between benign paroxysmal positional vertigo (BPPV) and migraine have been recognized in the literature, but also, there are close similarities between BPPV and vestibular migraine (VM) presentations as both can be presented by very similar positional nystagmus. To prescribe relatively uncommon cases of positional nystagmus caused by VM that mimics positioning nystagmus of BPPV. 12 patients were reviewed retrospectively in this study. All were subjected to full history taking, videonystagmography testing (VNG) and brain magnetic resonance imaging (MRI) with contrast. Provisionally, they were diagnosed with BPPV. After three attempts of repositioning sessions none of them improved. After exclusion of central insults using brain MRI, trial of anti-migraine medical treatment (50-100 Topiramate tablets once per day) for at least one month was prescribed to them. 10 patients were completely cured on medical treatment and finally were diagnosed VM. Only 2 patients did not improve on medical treatment (for one month), were managed again by repeated repositioning maneuvers till finally improved and were diagnosed as resistant BPPV. VM positional nystagmus can mimic BPPV nystagmus in some patients.

The inflammatory response plays important roles in acne vulgaris and pain pathogenesis. In previous study, Esc-1GN with anti-inflammatory, antimicrobial, and lipopolysacchride (LPS) binding activity was identified from the skin of the frog Hylarana guentheri. Here, we report its therapeutic potentials for acne vulgaris and inflammatory pain. Esc-1GN destroyed the cell membrane of Propionibacteria acnes in the membrane permeability assays. In addition, bacterial agglutination test suggested that Esc-1GN triggered the agglutination of P. acnes, which was affected by LPS and Ca . Meanwhile, in vivo anti-P. acnes and anti-inflammatory effects of Esc-1GN were confirmed by reducing the counts of P. acnes in mice ear, relieving P. acnes-induced mice ear swelling, decreasing mRNA expression and the production of pro-inflammatory cytokines, and attenuating the infiltration of inflammatory cells. Moreover, Esc-1GN also displayed antinociceptive effect in mice induced by acetic acid and formalin. Therefore, Esc-1GN is a promising candidate drug for treatment of acne vulgaris and inflammatory pain.