Rejected

Adequate treatment of trauma pain is an integral part of the management of trauma patients, not just for ethical reasons but also because undertreated pain can lead to increased morbidities and worse long-term outcomes. Trauma pain management presents challenges in the pre-hospital setting, particularly in adverse or hostile environments as well as in busy emergency departments (EDs). Inhaled methoxyflurane, administered at analgesic doses via a disposable inhaler, has recently become available in Europe for the emergency treatment of moderate to severe pain in conscious adult trauma patients. A growing body of evidence demonstrates that inhaled methoxyflurane is well tolerated and effective in providing a rapid onset of analgesia. In this paper, we discuss the rationale for methoxyflurane use in trauma pain management, data from clinical trials recently conducted in Europe, its efficacy and safety profile compared to current standard treatments, its place in therapy and organizational impact. We conclude that inhaled methoxyflurane represents an effective treatment option in the different settings where trauma patients require rapid and flexible pain resolution, with potential organizational advantages.

The mammalian diving response (DR) is a remarkable behavior that was first formally studied by Laurence Irving and Per Scholander in the late 1930s. The DR is called such because it is most prominent in marine mammals such as seals, whales, and dolphins, but nevertheless is found in all mammals studied. It consists generally of breathing cessation (apnea), a dramatic slowing of heart rate (bradycardia), and an increase in peripheral vasoconstriction. The DR is thought to conserve vital oxygen stores and thus maintain life by directing perfusion to the two organs most essential for life-the heart and the brain. The DR is important, not only for its dramatic power over autonomic function, but also because it alters normal homeostatic reflexes such as the baroreceptor reflex and respiratory chemoreceptor reflex. The neurons driving the reflex circuits for the DR are contained within the medulla and spinal cord since the response remains after the brainstem transection at the pontomedullary junction. Neuroanatomical and physiological data suggesting brainstem areas important for the apnea, bradycardia, and peripheral vasoconstriction induced by underwater submersion are reviewed. Defining the brainstem circuit for the DR may open broad avenues for understanding the mechanisms of suprabulbar control of autonomic function in general, as well as implicate its role in some clinical states. Knowledge of the proposed diving circuit should facilitate studies on elite human divers performing breath-holding dives as well as investigations on sudden infant death syndrome (SIDS), stroke, migraine headache, and arrhythmias. We have speculated that the DR is the most powerful autonomic reflex known.

Xtampza ER (XER) is a long-acting oxycodone formulation which was designed to be abuse-deterrent and to overcome capsule-swallowing issues. This pilot study evaluated the effectiveness of XER at reducing swallowing difficulty while providing effective analgesia in the setting of chronic pain.

Familial Mediterranean fever (FMF) is an autosomal-recessive auto-inflammatory disorder characterized by recurrent episodes of fever with serositis. Sacroiliitis associated with FMF is very rare, especially in children. We aimed to describe the demographic, clinical, laboratory features, and treatment responses of pediatric patients with FMF -related sacroiliitis.

Gouty arthritis is an inflammatory joint disease closely related to hyperuricemia. It is characterized by deposition of monosodium urate crystals in the joints, resulting in an intense inflammatory process and pain. Control of hyperuricemia and anti-inflammation treatments are the main therapeutic approaches. However, the commonly used drugs for inhibiting uric acid and acute gouty arthritis have obvious gastrointestinal and renal toxicity; thus, there is an urgency to develop new alternative therapeutic drugs. An extract of (TTC), a compound drug used in traditional Chinese medicine, has been widely applied to the clinical treatment of arthritis. In this study, we investigated the therapeutic effects of TTC on gouty arthritis. In this study, an animal model of acute gouty arthritis with hyperuricemia was established using potassium oxonate and monosodium urate crystals. After treatment with TTC, the results showed obvious therapeutic effects on the rat model of acute gouty arthritis. The treatment significantly attenuated the degree of ankle swelling, inflammation, and dysfunction index, and the levels of proinflammatory cytokines. In addition, TTC has significant antihyperuricemia activity in rats with hyperuricemia induced by potassium oxonate. Histological evaluation showed that TTC relieved pathological damage in rats with acute gouty arthritis induced by monosodium urate crystals. All the groups treated with TTC showed improvement in cartilage degeneration, cell degeneration, synovial hyperplasia, and inflammatory cell invasion in the ankle joint of rats. TTC significantly alleviated swelling, inflammation, and bleeding of the renal corpuscle and convoluted tubules of rats. The results of this study suggest that TTC is capable of treating gouty arthritis and decreasing ankle injury through the control of uric acid and inflammation.

(Aristolochiaceae) is one of the common herbs used to relieve exterior syndromes. Some volatile components of which have toxic effect may cause adverse reactions such as headache, general tension, unconsciousness, and respiratory paralysis. Therefore, is normally processed to reduce such toxicity and adverse effects. The bioactive ingredients contained in different herbs vary significantly; this variation may be attributed to their differences in species, origins, or processing methods. In this study, 16 batches of herbs were collected, and their species were identified using DNA barcoding, which is a method for distinguishing plant species, coupled with microscopy. A gas chromatography-mass spectrometry (GC-MS) method for simultaneous determination of 10 compounds was established to evaluate the contents of raw and processed herbs. Multivariate analysis was then applied to compare different batches of herbs based on the GC-MS data. DNA barcoding identified the herbs as being derived from four sources, and herbs from different origins showed different microscopic features. The results demonstrated that most of the samples were clearly clustered into distinct groups that corresponded to species types. All raw and processed samples were classified by partial least squares discriminant analysis (PLS-DA) based on the 10 analyzed compounds. The findings suggested that safrole and methyleugenol with a variable importance in the project (VIP) > 1 are unique compounds that can be used to differentiate between species. Safrole, methyleugenol, and 2,6,6-trimethylcyclohepta-2,4-dien-1-one were identified as significant constituents, the presence of which can be used to differentiate between raw and processed samples. These results indicate that species and processing methods show important effects on the composition of herbs.

We present a case of a 46-year-old woman admitted to the emergency department for acute swelling and erythema of the right eyelid for 3 days. Ophthalmological examination was notable for 10/10, P2 best visual acuity, and inflammatory periorbital edema, without exophthalmia nor extraocular motility disturbance. Intraocular pressure was 14 mmHg and fundoscopic examination was not notable for any abnormality. Preseptal cellulitis diagnosis was made, and oral antibiotherapy was immediately started; after 72 hours, the patient did not improve and started complaining of pain on ocular movements. Brain and orbit MRI scan revealed right retroseptal cellulitis associated with homolateral pansinusitis. Intravenous antibiotherapy with oral corticosteroid was started simultaneously leading to full remission but with steroid dependency; 5 days after finishing prednisone, orbital cellulitis symptoms reappeared. The same treatment protocol was given but with corticosteroid tapering over weeks. Nevertheless, steroid dependency persisted. Except for the inflammatory syndrome, complete biological examinations did not disclose any abnormalities. The patient underwent maxillary sinus and fat orbital biopsy; however, histopathological examination was not contributory. Persistence of steroid dependency, chronic atypical rhinosinusitis, normal paraclinical investigations, and age of patient let us suspect lymphoma origin hidden by chronic corticosteroid. We carried out for the second time a maxillary sinus biopsy after stopping steroids, which disclosed primitive non-Hodgkin lymphoma of the maxillary sinus. The aim of this observation is firstly to evoke though it is exceptional the diagnosis of maxillary lymphoma in case of atypical orbital cellulitis and secondly to incite clinicians to be more vigilant in prescribing corticosteroid even if there is an emergency character of orbital cellulitis.

We prepared the three-dimensional model of the SARS-CoV-2 (aka 2019-nCoV) 3C-like protease (3CL ) using the crystal structure of the highly similar (96% identity) ortholog from the SARS-CoV. All residues involved in the catalysis, substrate binding and dimerisation are 100% conserved. Comparison of the polyprotein PP1AB sequences showed 86% identity. The 3C-like cleavage sites on the coronaviral polyproteins are highly conserved. Based on the near-identical substrate specificities and high sequence identities, we are of the opinion that some of the previous progress of specific inhibitors development for the SARS-CoV enzyme can be conferred on its SARS-CoV-2 counterpart.  With the 3CL molecular model, we performed virtual screening for purchasable drugs and proposed 16 candidates for consideration. Among these, the antivirals ledipasvir or velpatasvir are particularly attractive as therapeutics to combat the new coronavirus with minimal side effects, commonly fatigue and headache.  The drugs Epclusa (velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) could be very effective owing to their dual inhibitory actions on two viral enzymes.

The aspects of disruption of venous blood outflow from face region into skull are well-known; they can occur at any age – from neonatal to old age, however, the possible compensation mechanisms for such disorders are usually difficult to identify. A description is given of a unique case of unilateral epistaxis and a homolateral (right-sided) headache that developed much later. Examination revealed hypoplasia of the left sigmoid sinus and blood overflow of the right sigmoid sinus. After prescription of betahistine in a dose of 24 mg before bedtime and after awakening the headache and nosebleeds disappeared on the second day. The effect was persistent. The case demonstrates previously unknown compensation mechanisms for venous outflow – a retrograde outflow from the skull to the face region.