Rejected

Surgical trauma can induce an inflammatory response in the central nervous system. Neuroinflammation is a crucial pathological mechanism of perioperative neurocognitive disorders (PND). Dexmedetomidine (Dex) is an alpha (α)-2 adrenoceptor agonist that is widely used in the perioperative period. Previous studies have shown that Dex has neuroprotection in various nerve injury models, but its role in PND remains unclear. Our study aimed to observe the neuroprotective effect of Dex pretreatment on postoperative cognitive change and explore the effects of hippocampal neuroinflammation, microglial polarization and HMGB1/RAGE/NF-κB signaling pathway involved in Dex on PND in rats. Rats were pretreated with Dex alone or in combination with yohimbine (α-2 adrenoceptor antagonist) before surgery. Behavioral tests results showed that Dex ameliorated surgery-induced cognitive impairment in rats. Nissl, immunohistochemistry and TUNEL-NeuN staining results indicated that Dex reduced hippocampus damage and neuronal apoptosis caused by surgery. Dex preconditioning reduced the expression of the proinflammatory cytokines IL-1β, TNF-α and IL-6 in hippocampus. Immunohistochemical and immunofluorescence results showed that Dex preconditioning inhibited the activation of glial cells induced by surgery. Western blot analysis showed that Dex preconditioning downregulated the expression of M1 phenotype markers (CD86 and iNOS), HMGB1, RAGE and nuclear NF-κB and upregulated the expression of M2 phenotype markers (Arginase 1 and CD206) and cytoplasmic NF-κB. Yohimbine could inhibit the neuroprotective effect of Dex. These results indicated that Dex pretreatment could improve postoperative short-term cognitive impairment, and the neuroprotective mechanism may involve the suppression of hippocampal neuroinflammation, regulation of M1/M2 polarization, and inhibition of HMGB1/RAGE/NF-κB signal transduction.

Musculoskeletal disorders represent one of the most common complains among video display terminal (VDT) users and are responsible for an important burden of disease in white collars.

The purpose of this study was to evaluate longitudinal associations with incident and persistent intrusive pain among rural South Africans.

Pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) remains poorly understood, as well as its effective diagnosis and therapy. Studying changes in tissue glycosylation patterns under pathological conditions is a promising way of discovering novel biomarkers and therapeutic targets. The glycobiology of IC/BPS is largely understudied, therefore we compared glycosylation patterns of normal human urothelium with the urothelium of IC/BPS patients using a selection of 10 plant-based lectins with different monosaccharide preferences. We also compared lectin binding to human urothelium with the two most cited experimental models of IC/BPS, specifically, TNFα-treated human urothelial cell line RT4 and cyclophosphamide-induced chronic cystitis in C57BL6/J mice. Furthermore, binding of four of the selected lectins (ConA, DSL, Jacalin and WGA) was evaluated qualitatively by means of fluorescence microscopy, and quantitatively by fluorescence intensity (F.I.) measurements. Our results reveal a significant reduction in F.I. of Jacalin, as well as a prominent change in the WGA labeling pattern in the urothelium of IC/BPS patients, suggesting their potential use as promising additional biomarkers for histopathological diagnosis of IC/BPS. We have also shown that urothelial glycosylation patterns between selected experimental models and patients with IC/BPS are similar enough to offer an adequate platform for preclinical study of IC/BPS glycobiology.

To prospectively compare the efficacy and safety of intra-articular injections of platelet-rich plasma (PRP) with hyaluronic acid (HA) and glucocorticosteroid (CS) control groups for knee osteoarthritis (KOA) in a randomized, triple-parallel, single-center clinical trial.

Coumaric acid (CouH), an antioxidant molecule assimilated by food consumption, was intercalated into layered double hydroxide (LDH) nanocarrier, having zinc and aluminium ions in the layers (LDH-Cou), to evaluate its pharmacological activity through in vitro and in vivo assays in mice. Therefore, the following tests were performed: coumarate delivery in saline solution, fibroblasts' cell viability using neutral red, peritonitis induced by carrageenan, formalin test, acetic-acid-induced writhing, and tail-flick assay, for the non-intercalated CouH and the intercalated LDH-Cou system. Furthermore, different pharmacological pathways were also investigated to evaluate their possible anti-inflammatory and antinociceptive mechanisms of action, in comparison to traditionally used agents (morphine, naloxone, caffeine, and indomethacin). The LDH-Cou drug delivery system showed more pronounced anti-inflammatory effect than CouH but not more than that evoked by the classic non-steroidal anti-inflammatory drug (NSAID) indomethacin. For the analgesic effect, according to the tail-flick test, the treatment with LDH-Cou expressively increased the analgesia duration ( < 0.001) by approximately 1.7-1.8 times compared to CouH or indomethacin. Thus, the results pointed out that the LDH-Cou system induced in vivo analgesic and anti-inflammatory activities and possibly uses similar mechanisms to that observed for classic NSAIDs, such as indomethacin.

Butorphanol and dexmedetomidine (DXM) can produce analgesia in birds. Intranasal (IN) route of drug administration is easier, and free of risks such as pain and tissue damage compared with intravenous, intramuscular or subcutaneous routes in bird species, including wild birds. Although previous studies have demonstrated the use of IN route for producing sedation, no studies are available on the pharmacokinetics and pharmacodynamics of IN drugs in birds. This study analyzed the pharmacokinetics and sedative-analgesic efficacy of intranasal butorphanol (2 mg/kg), dexmedetomidine (80 µg/kg) and their combination (butorphanol, 2 mg/kg; DXM, 80 µg/kg) in healthy, male, Ross broiler chickens ( = 6/group) aged between 6 and 8 weeks. Maximum plasma concentration (Cmax, = 0.01), area under the plasma concentration-time curve from time zero to 120 min (AUC, = 0.02) and apparent volume of distribution at steady state (Vss, = 0.02) of DXM were significantly higher than that of DXM co-administered with butorphanol. The mechanical nociceptive thresholds and the sedation scores of DXM group were significantly higher than the baseline value. Dexmedetomidine (80 µg/kg, IN) was effective in chickens, and the drug absorption was more rapid than that of DXM with butorphanol. However, the duration of action of DXM was short. Lower value of Cmax and nociceptive thresholds showed the nonsignificant efficacy of butorphanol at a dose of 2 mg/kg after IN administration in broiler chickens.

With the increase in long-term survivorship of head and neck cancer (HNC), the functional outcomes are gaining importance. We reported the functional outcomes of HNC patients using the HNC-Functional InTegrity (FIT) Scales, which is a validated tool for the rapid clinical assessment of functional status based on observable clinical criteria. Patients with newly diagnosed HNC treated at the Medical University of Innsbruck between 2008 and 2020 were consecutively included, and their status in the six functional domains of food-intake, breathing, speech, pain, mood, and neck and shoulder mobility was scored by the treating physician at oncological follow-up visits on a scale from 0 (loss of function) to 4 (full function). HNC-FIT scales were available for 681 HNC patients at a median of 35 months after diagnosis. The response status was complete remission in 79.5%, 18.1% had recurrent or persistent disease, and 2.4% had a second primary HNC. Normal or near-normal scores (3 and 4) were seen in 78.6% for food intake, 88.7% for breathing, 83.7% for speech, 89% for pain, 91.8% for mood, and 87.5% for neck and shoulder mobility. A normal or near-normal outcome in all six functional domains was observed in 61% of patients. Clinically relevant impairment (score 1-2) in at least one functional domain was observed in 30%, and 9% had loss of function (score 0) in at least one functional domain. The main factors associated with poor functional outcome in a multivariable analysis were recurrence or persistent disease, poor general health (ASA III and IV), and higher T stage. Particularly, laryngeal and hypopharyngeal tumors impaired breathing and speech function, and primary radiation therapy or concomitant systemic therapy and radiotherapy worsened food intake. Clinically relevant persistent functional deficits in at least one functional domain must be expected in 40% of the patients with HNC. The treatment of these functional deficits is an essential task of oncologic follow-up.

The incidence and mortality rates of cervical cancer are rising among young women in Japan. In November 2021, the Japanese Ministry of Health, Labour, and Welfare reinstated the active recommendation for the human papillomavirus (HPV) vaccine, which was discontinued in June 2013 due to reports of adverse reactions, including chronic pain and motor dysfunction, following vaccination. However, vaccine hesitancy among the younger generation remains, and it is essential to identify the barriers in vaccination uptake. Therefore, we aimed to conduct a randomized study using different methods of providing educational contents to improve health literacy regarding cervical cancer and HPV vaccination among female students in Japan. Here, we present the results of our preliminary report and discuss current topics related to HPV vaccination in Japan. Data were collected from 27 female students-divided into three groups: no intervention, print-based intervention, and social networking service-based intervention-using the health literacy scale and communicative and critical health literacy scale. Our primary results indicate that participants' knowledge and health literacy improved post-intervention. Therefore, medical professionals must provide accurate scientific knowledge regarding routine HPV vaccination and the risk of cervical cancer to young women to improve their health literacy and subsequently increase the HPV vaccination rates.