Rejected

Long non-coding RNAs are novel regulators in neuropathic pain. In this study, we aimed to explore the role and the mechanism of lncRNA FIRRE in regulating the secretion of microglial cells-derived proinflammatory cytokines in neuropathic pain. The female mouse model of neuropathic pain was established by bilateral chronic constriction injury (CCI) surgery. The mouse primary microglial cells were induced by lipopolysaccharide (LPS). The interaction between FIRRE and high mobility group box 1 (HMGB1) was assessed by RNA immunoprecipitation, RNA pull-down, and ubiquitination assays. FIRRE expression was upregulated in the spinal cord tissue of female CCI mice and LPS-induced microglial cells. The concentrations of IL-1β, TNF-α, and IL-6 from LPS-induced microglial cells were reduced by FIRRE knockdown. FIRRE bound to HMGB1 and negatively regulated its protein level. The ubiquitination degradation of HMGB1 was promoted by FIRRE silence. The HMGB1 over-expression reversed the inhibitory effect of FIRRE silence on the secretion of IL-1β, TNF-α, and IL-6 from LPS-induced microglial cells. The in vivo experiment showed that FIRRE knockdown alleviated neuropathic pain of CCI female mice. Our findings indicated that lncRNA FIRRE downregulation inhibits the secretion of microglial cells-derived proinflammatory cytokines by decreasing HMGB1 expression, thereby relieving neuropathic pain of female mice.

One class of molecules that are now coming to be recognized as essential for our understanding of the nervous system are the lysophospholipids. One of the major signaling lysophospholipids is lysophosphatidic acid, also known as LPA. LPA activates a variety of G protein-coupled receptors (GPCRs) leading to a multitude of physiological responses. In this review, I describe our current understanding of the role of LPA and LPA receptor signaling in the development and function of the nervous system, especially the central nervous system (CNS). In addition, I highlight how aberrant LPA receptor signaling may underlie neuropathological conditions, with important clinical application.

Combination regimens of direct-acting antiviral agents (DAAs) for chronic genotype 1 hepatitis C virus (HCV) infection given for 8 or 12 weeks have high cure rates. Shortened treatment durations that maintain high cure rates may lessen treatment barriers related to affordability and drug adherence. We enrolled 12 treatment-naïve adults with chronic genotype 1 HCV infection without cirrhosis in a single-center, open-label trial to receive 2 weeks of the highly potent and selective non-nucleoside inhibitor (NNI) CDI-31244 concurrent with 6 weeks of sofosbuvir/velpatasvir. The main efficacy endpoints were sustained virologic response at 12 (SVR12) and 24 (SVR24) weeks after treatment completion. In all patients, plasma HCV RNA levels rapidly decreased during the first 2 days of treatment and were below the lower limit of quantification by the end of the 6-week treatment period. Eight of 12 (67%) patients achieved both SVR12 and SVR24. Four patients had virological relapse at week 10, 4 weeks after end of treatment. The most common adverse event was headache, occurring in five (42%) patients. Pharmacokinetic analysis showed no relevant drug interactions between CDI-31244, sofosbuvir, and velpatasvir. In this pilot study of short-duration combination therapy involving a novel NNI with a fixed-combination DAA, 8 of 12 treatment-naïve patients with chronic genotype 1 HCV infection without cirrhosis achieved virologic cure. Future trials might evaluate whether extending the NNI duration beyond 2 weeks with combination DAAs results in higher cure rates comparable with currently approved longer duration therapy. This article is protected by copyright. All rights reserved.

Avian schistosomes are of medical and veterinary importance as they are responsible for the annually occurring cercarial dermatitis outbreaks. For Austria, so far, only Trichobilharzia szidati Neuhaus 1952 was confirmed on species level as causative agent of cercarial dermatitis. Here we present the first record of Trichobilharzia franki Müller & Kimmig 1994 in Austria. The species was detected during a survey of digenean trematodes in Upper Austrian water bodies. Furthermore, we provide DNA barcodes of T. franki as well as measurements of several parasite individuals to indicate the intraspecific diversity. We also recommend the usage of an alternative primer pair, since the "standard COI primer pair" previously used for Schistosomatidae amplified an aberrant fragment in the sequence of T. franki. Overall, our study shows how limited our knowledge about occurrence and distribution of avian schistosomes in Austria is and how important it is to acquire such a knowledge to estimate ecological and epidemiological risks in the future.

The prevalence of vertebral deformities in long-term survivors of childhood ALL is unknown. Our objectives were to identify the prevalence of vertebral deformities and their risk factors among long-term childhood ALL survivors.

BACKGROUND Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease with a myriad of clinical presentations. The diagnosis is often challenging because there is no specific confirmatory test. Uncommon presentations can delay the proper diagnosis and management. CASE REPORT A 26-year-old woman presented with a history of urticaria for 2 years that had failed to respond to many types of treatment. Cutaneous biopsy showed neutrophilic urticaria. A diagnosis of AOSD was made after infectious, drug-related, neoplastic, and rheumatic etiologies had been excluded and based on the triad of fever, evanescent rash, and joint pain. Besides leukocytosis and increased levels of inflammatory markers, the patient's laboratory results showed an extremely high D-dimer concentration and an increased antistreptolysin O (ASO) titer. Treatment with prednisolone and methotrexate resulted in resolution of the woman's symptoms. Once clinical remission had been achieved, all laboratory markers returned to normal, yet the patient's ASO titer remained elevated during 18 months of follow-up. CONCLUSIONS Urticaria is a rare cutaneous manifestation of AOSD. Histopathology typically shows predominant neutrophilic infiltrates, which is a unique entity called neutrophilic urticarial dermatosis (NUD). Identifying diseases associated with NUD will facilitate prompt diagnosis and treatment of AOSD, as therapies for it largely differ depending on the underlying cause. Known etiologies of AOS include systemic lupus erythematosus (SLE), Schnitzler syndrome, hereditary autoinflammatory periodic syndromes, and serum sickness-like drug eruption. An elevated ASO titer is unusual, and in our case, it did not seem to follow the patient's clinical course. An elevated D-dimer concentration can be an indicator of disease activity and testing might be beneficial in a subset of patients with normal ferritin levels.

An adult male was found to have a variation of the left basal vein of Rosenthal after presenting with complaints of headache and balance issues. In this case, the vein drained directly into the left superior petrosal sinus (SPS) instead of the great vein of Galen. Anatomical variation of the basal vein is likely due to embryonic development of the deep cerebral venous system as primitive structures either differentiate regress or further with age. These changes may result in the uncommon presentation seen in this case. To our knowledge, this is the first case that shows the basal vein drains into the SPS. The normal and variant anatomy of this vessel are discussed.

Acute mountain sickness (AMS) is the mildest form of acute altitude illnesses, and consists of non-specific symptoms when unacclimatized persons ascend to elevation of ≥2500 m. Risk factors of AMS include: the altitude, individual susceptibility, ascending rate and degree of pre-acclimatization. In the current study, we examined whether physiological response at low altitude could predict the development of AMS.

The effectiveness of manipulation versus mobilization for the management of spinal conditions, including cervicogenic headache, is conflicting. However, a pragmatic approach comparing manipulation to mobilization has not been examined in a patient population with cervicogenic headache.

Extracorporeal shock wave lithotripsy (ESWL) is considered a safe technique, but not without complications, though the vast majority are minor complications. We describe a rare case of splenic injury after ESWL. A 33-year-old male presented to the emergency department (ED) after three weeks experiencing severe intermittent left-sided flank pain that he contributed to a previous motor vehicle accident. Then computerized tomography (CT) revealed a left renal stone. ESWL was performed after three weeks. After being discharged home, he returned the same day to the ED with persistent, worsening abdominal pain, hypotension, and multiple syncopes. CT demonstrated the presence of active contrast extravasation from the spleen likely due to active bleeding. Initial resuscitation was with intravenous fluids and blood products. The following day, the embolization of the splenic artery was done. The patient was discharged home after nine days of conservative management. After one month, he had shortness of breath due to a large left-sided pleural effusion and lung collapse managed with thoracocentesis and thoracoscopic surgery. Subsequent follow-up reveals much improvement and successful conservative management. Splenic injury is a rare complication of ESWL, and all of the 11 reported cases in the literature were managed with splenectomy. Our case is unique in being successfully managed conservatively.