Rejected

The most common joint disease in the elderly is knee osteoarthritis (OA). It is distinguished by cartilage degradation, subchondral bone loss, and a decrease in joint space. We studied the effects of carnosine (CA) on knee OA in male Wistar rats. OA is induced by anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) method and in vitro studies are conducted in fibroblast-like synoviocyte cells (FLS). The pain was assessed using weight-bearing and paw-withdrawal tests. CA supplementation significantly reduced pain. The enzyme-linked immunosorbent assay (ELISA) method was used to detect inflammatory proteins in the blood and intra-articular synovial fluid (IASF), and CA reduced the levels of inflammatory proteins. Histopathological studies were performed on knee-tissue samples using toluidine blue and hematoxylin and eosin (H and E) assays. CA treatment improved synovial protection and decreased cartilage degradation while decreasing zonal depth lesions. Furthermore, Western blotting studies revealed that the CA-treated group activated nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase (HO-1) and reduced the expression of cyclooxygenase-2 (COX-2). FLS cells were isolated from the knee joints and treated with IL-1β to stimulate the inflammatory response and increase reactive oxygen species (ROS). The matrix metalloproteinase protein (MMP's) levels (MMP-3, and MMP-13) were determined using the reverse transcription-polymerase chain reaction (RT-PCR), and CA treatment reduced the MMP's expression levels. When tested using the 2',7'-dicholorodihydrofluroscene diacetate (DCFDA) assay and the 5,5',6,6'-tetracholoro-1,1',3,3'-tertraethylbenzimidazolcarboc janine iodide (JC-1) assay in augmented ROS FLS cells, CA reduced the ROS levels and improved the mitochondrial membrane permeability. This study's investigation suggests that CA significantly alleviates knee OA both in vitro and in vivo.

To evaluate the relationship of GLASS stages with clinical outcomes in patients with chronic limb threatened ischemia (CLTI) submitted to distal bypasses using venous graft.

Liver regeneration is a necessary but complex process involving multiple cell types besides hepatocytes. Mechanisms underlying liver regeneration after partial hepatectomy (PHx) and acute liver injury (ALI) have been well described. However, in patients with chronic and severe liver injury, the remnant liver cannot completely restore the liver mass and function, thereby involving liver progenitor-like cells (LPLCs) and various immune cells.

Limited data exist regarding the full array of clinical signs seen in dogs with pancreatitis and potential risk factors for the disease. Laboratory submissions from the Gastrointestinal Laboratory at Texas A&M University were retrospectively reviewed for dogs with an increased serum pancreatic lipase immunoreactivity (cPLI) concentration (≥400 µg/L), and an internet-based survey was distributed to the attending veterinarian and/or technician on each case. The survey contained questions related to (i) clinical signs, (ii) prior gastrointestinal upset, (iii) comorbidities, (iv) pre-existing medical therapies, and (v) dietary history. One hundred and seventy (170) survey responses were recorded. The top three clinical signs reported were inappetence (62%), diarrhea (53%), and vomiting (49%). Abdominal pain was noted in only 32% of dogs, likely associated with poor pain detection. Additionally, the majority of dogs (71%) had prior episodes of gastrointestinal upset within the past 12 months, lending support for the commonality of recurrent acute pancreatitis, or acute on chronic disease. Hepatobiliary abnormalities (24%) were the most common concurrent disease, and endocrine disorders were seen in a low proportion of respondents (5-8%). Adult maintenance diets (65%), dog treats (40%), and human foods (29%) were commonly consumed by dogs prior to the discovery of increased cPLI concentration.

A series of alkyl/aryl/aralkylamines or amino acids appended tetrahydro-2H-1,3,5-thiadiazine-2-thiones (4a-i, 5a-g, 6 and 7) were synthesized via one pot domino synthesis. The synthesis involved reacting alkyl/aryl/aralkylamines or amino acids with carbon disulfide employing basic aqueous medium and further cyclization with formaldehyde and alkyl/aryl/aralkylamines or amino acids. In addition, the carboxy-functionalized 1,3,5-thiadiazine-2-thione 6 was further subjected to esterification. All the structures were confirmed through spectral techniques i.e IR, H NMR, C NMR, and MS analysis. Furthermore, the newly synthesized compounds were biologically assessed via in vitro COX-2 and 5-LOX assays, in vivo anti-nociceptive and anti-inflammatory activities. Among the screened compounds, 6, 5f, and 7 exhibited highest inhibitory potency against COX-2 with IC values of 11.96, 13.54, and 13.93 μM, respectively. Moreover, compounds 6 and 7 exhibited excellent inhibitory potential against 5-LOX with IC values of 14.01 and 14.13 μM. The in-vivo anti-inflammatory bioassay studies showed that compounds 6, 7 and 5f dramatically reduced the paw edema size at 1 h and 3 h time intervals. In the anti-nociceptive activity, compound 6 showed pain protection comparative to Tramadol in all tested time intervals. In addition, studies of molecular docking revealed the compounds binding modes in the allosteric site of COX-2 and active site of 5-LOX, where these compounds exhibited higher binding scores and good binding interactions.

Trigeminal neuralgia (TN) is a neuropathic pain syndrome that typically exhibits paroxysmal pain. However, the true mechanism of pain processing is unclear. We aim to evaluate the neural activity changes, before and after radiofrequency rhizotomy, in TN patients using functional MRI (fMRI) with sensory and motor stimulations.

Dietary behavior can have a consequential and wide-ranging influence on human health. Intermittent fasting, which involves intermittent restriction in energy intake, has been shown to have beneficial cellular, physiological, and system-wide effects in animal and human studies. Despite the potential utility in preventing, slowing, and reversing disease processes, the clinical application of intermittent fasting remains limited. The health benefits associated with the simple implementation of a 12 to 16 h fast suggest a promising role in the treatment of chronic pain. A literature review was completed to characterize the physiologic benefits of intermittent fasting and to relate the evidence to the mechanisms underlying chronic pain. Research on different fasting regimens is outlined and an overview of research demonstrating the benefits of intermittent fasting across diverse health conditions is provided. Data on the physiologic effects of intermittent fasting are summarized. The physiology of different pain states is reviewed and the possible implications for intermittent fasting in the treatment of chronic pain through non-invasive management, prehabilitation, and rehabilitation following injury and invasive procedures are presented. Evidence indicates the potential utility of intermittent fasting in the comprehensive management of chronic pain and warrants further investigation.

Whiplash injury-related neck pain frequently hinders daily life activities, resulting in poor quality of life. Recovery time is prolonged in many patients. Long-term outcomes of refractory whiplash injury-related neck pain remain poorly understood.

The use of total intravenous anaesthesia (TIVA) has been well established as an anaesthetic technique over the last few decades. Significant variation in practice exists however, and volatile agents are still commonly used. This study aims to determine the motivations and barriers for using TIVA over the use of volatile agents by analysing the opinion of several international anaesthetists with specific expertise or interests. The Delphi method was used to gain the opinions of expert panellists with a range of anaesthetic subspecialty expertise. Twenty-nine panellists were invited to complete three survey rounds containing statements regarding the use of TIVA. Anonymised data were captured through the software REDCap and analysed for consensus and prioritisation across statements. Starting with 12 statements, strong consensus was defined as ≥75% agreement. Stability was assessed between rounds. Strong consensus was achieved for four statements regarding considerations for the use of TIVA. These statements addressed whether TIVA is useful in paediatric anaesthesia, the importance of TIVA in reducing the incidence of postoperative nausea and vomiting, its positive impact on the environment and effect on patient physiology, such as airway and haemodynamic control. Using the Delphi method, this international consensus showed that cost, lack of familiarity or training and the risk of delayed emergence are not considered obstacles to TIVA use. It appears, instead, that the primary motivations for its adoption are the impact of TIVA on patient experience, especially in paediatrics, and the benefit to the overall procedure outcome. The effect of TIVA on postoperative nausea and vomiting and patient physiology, as well as improving its availability in paediatrics were considered as priorities. We also identified areas where the debate remains open, generating new research questions on geographical variation and the potential impact of local availability of monitoring equipment.