Rejected

Oxidative stress-related cartilage degeneration, synovitis, and joint pain play vital roles in the progress of osteoarthritis (OA). Anti-oxidative stress agents not only prevent structural damage progression but also relieve OA-related pain. In this study, we investigated the therapeutic effect of methylene blue (MB), a classical and important anti-oxidant with strong neural affinity. Experimental OA was established in rats by radial transection of medial collateral ligament and medial meniscus (MCLT + MMT) of the right knee joint. The OA rats received intra-articular injection of MB (1 mg/kg) every week starting one week after surgery. We showed that MB administration exerted significant cartilage protection, synovitis inhibition as well as pain relief in OA rats. In human chondrocytes and fibroblast-like synoviocytes, MB significantly attenuated tert-butyl hydroperoxide (TBHP)-induced inflammatory response and oxidative stress. We demonstrated that these effects of MB resulted from dual targets of important antioxidant enzymes, Nrf2 and PRDX1, which also mutually reinforcing and participated in an interaction. Furthermore, we found that calcitonin gene-related peptide (CGRP), a neural inflammatory mediator, was accumulated around the vessel in synovium and subchondral bone in OA rats and in TBHP-treated primary cortical neurons; MB administration significantly inhibited CGRP expression through upregulation of Nrf2 and PRDX1. Taken together, these results suggest that MB ameliorates oxidative stress via Nrf2/PRDX1 regulation to prevent progression and relieve pain of OA.

Interleukin (IL)-31 is a cytokine involved in allergic inflammation which induces pruritus across species including dogs. Using recombinant canine IL-31 we have developed a model of pruritus in the dog to evaluate onset of action and duration of effect of therapeutic drugs.

The introduction of regional analgesia in the past decades have revolutionized postoperative pain management for various types of surgery, particularly orthopedic surgery. Nowadays, they are being constantly introduced into other types of surgeries including cardiac surgeries. Neuraxial and paravertebral plexus blocks for cardiac surgery are considered as deep blocks and have the risk of hematoma formation in the setting of anticoagulation associated with cardiac surgeries. Moreover, hemodynamic compromise resulting from sympathectomy in patients with limited cardiac reserve further limits the use of neuraxial techniques. A multitude of fascial plane blocks involving chest wall have been developed, which have been shown the potential to be included in the regional analgesia armamentarium for cardiac surgery. In myofascial plane blocks, the local anesthetic spreads passively and targets the intermediate and terminal branches of intercostal nerves. They are useful as important adjuncts for providing analgesia and are likely to be included in "Enhanced Recovery after Cardiac Surgery (ERACS)" protocols. There are several small studies and case reports that have shown efficacy of the regional blocks in reducing opioid requirements and improving patient satisfaction. This review article discusses the anatomy of various fascial plane blocks, mechanism of their efficacy, and available evidence on outcomes after cardiac surgery.

We aimed to evaluate whether the duration and stage of acute kidney injury (AKI) are associated with the occurrence of chronic kidney disease (CKD) in patients undergoing cardiac or thoracic aortic surgery. A total of 2009 cases were reviewed. The patients with postoperative AKI stage 1 and higher stage were divided into transient (serum creatinine elevation ≤48 h) or persistent (>48 h) AKI, respectively. Estimated glomerular filtration rate (eGFR) values during three years after surgery were collected. Occurrence of new-onset CKD stage 3 or higher or all-cause mortality was determined as the primary outcome. Multivariable Cox regression and Kaplan-Meier survival analysis were performed. The Median follow-up of renal function after surgery was 32 months. The cumulative incidences of our primary outcome at one, two, and three years after surgery were 19.8, 23.7, and 26.1%. There was a graded significant association of AKI with new-onset CKD during three years after surgery, except for transient stage 1 AKI (persistent stage 1: HR 3.11, 95% CI 2.62-4.91; transient higher stage: HR 4.07, 95% CI 2.98-6.11; persistent higher stage: HR 13.36, 95% CI 8.22-18.72). There was a significant difference in survival between transient and persistent AKI at the same stage. During three years after cardiac surgery, there was a significant and graded association between AKI stages and the development of new-onset CKD, except for transient stage 1 AKI. This association was stronger when AKI lasted more than 48 h at the same stage. Both duration and severity of AKI provide prognostic value to predict the development of CKD.

Lateral periodontal cyst (LPC) is an uncommon form of developmental odontogenic cyst. LPC can be suspected when there is a round, well-circumscribed radiolucency, usually of small diameter, along the lateral surface of vital erupted teeth, predominantly in the mandibular premolar region. Histopathological analysis allows LPC to be diagnosed based on its characteristic features such as a thin cuboidal to stratified squamous non-keratinizing epithelium containing epithelial plaques and glycogen-rich clear cells. The aim of this article was to report two cases of atypical LPC associated either with an impacted lower left canine (tooth #33) or with a lower right third molar (tooth #48).

Subthalamic nucleus (STN) deep brain stimulation (DBS) has become a routine treatment of advanced Parkinson's disease (PD). DBS surgery is commonly performed under local anesthesia (LA) to obtain reliable microelectrode recordings. However, procedural sedation and/or analgesia (PSA) is often desirable to improve patient comfort. The impact of PSA in addition to LA on outcome is largely unknown. Therefore, we performed an observational study to assess the effect of PSA compared to LA alone during STN DBS surgery on outcome in PD patients.

Xanthogranulomatous pyelonephritis (XGP) is an inflammatory condition of the kidney and its treatment most often involves a combination of antibiotics and nephrectomy. This study aimed to define the clinical features and management of XGP, focusing on microbiological aspects and antibiotic therapy.

Cannabinoids comprise different classes of compounds, which aroused interest in recent years because of their several pharmacological properties. Such properties include analgesic activity, bodyweight reduction, the antiemetic effect, the reduction of intraocular pressure and many others, which appear correlated to the affinity of cannabinoids towards CB and/or CB receptors. Within the search aiming to identify novel chemical scaffolds for cannabinoid receptor interaction, the CB antagonist/inverse agonist pyrazole-based derivative rimonabant has been modified, giving rise to several tricyclic pyrazole-based compounds, most of which endowed of high affinity and selectivity for CB or CB receptors. The aim of this review is to present the synthesis and summarize the SAR study of such tricyclic pyrazole-based compounds, evidencing, for some derivatives, their potential in the treatment of neuropathic pain, obesity or in the management of glaucoma.

Elderberry has traditionally been used to prevent and treat respiratory problems. During the COVID-19 pandemic, there has been interest in elderberry supplements to treat or prevent illness, but also concern that elderberry might overstimulate the immune system and increase the risk of 'cytokine storm'. We aimed to determine benefits and harms of elderberry for the prevention and treatment of viral respiratory infections, and to assess the relationship between elderberry supplements and negative health impacts associated with overproduction of pro-inflammatory cytokines.

Janus kinase (JAK) inhibitors are promising treatments for atopic dermatitis (AD). The aim of this study was to assess the efficacy and safety of JAK inhibitors for AD treatment via the "Grading of Recommendations Assessment, Development, and Evaluation" approach. We identified 15 randomized controlled trials comparing oral or topical JAK inhibitors against placebo to treat AD. A random-effects meta-analysis was performed, and the numbers-needed-to-treat (NNTs)/numbers-needed-to-harm (NNHs) were calculated. Patients treated with JAK inhibitors were associated with higher rates of achieving eczema area and severity index-75 (rate ratio (RR): 2.84; 95% confidence interval (CI): 2.20-3.67; I: 38.9%; NNT = 3.97), Investigator's Global Assessment response (RR: 2.99; 95% CI: 2.26-3.95; I: 0%; NNT = 5.72), and pruritus numerical rating scale response (RR: 2.52; 95% CI: 1.90-3.35; I: 39.4%; NNT = 4.91) than those treated with placebo. Moreover, patients treated with JAK inhibitors had a higher risk of treatment-emergent adverse events (RR: 1.14; 95% CI: 1.02-1.28; I: 52%; NNH = 14.80) but not adverse events leading to drug discontinuation. According to the evidence-based results, JAK inhibitors are potentially effective strategies (certainty of evidence: "moderate") for treating AD with tolerable side effects (certainty of evidence: "low"). Nevertheless, long-term follow-up is required.