Rejected

Various heteroaryl and bicyclo-aliphatic analogues of zwitterionic biaryl P2Y receptor (P2YR) antagonists were synthesized, and affinity was measured in P2YR-expressing Chinese hamster ovary cells by flow cytometry. Given this series' low water solubility, various polyethylene glycol derivatives of the distally binding piperidin-4-yl moiety of moderate affinity were synthesized. Rotation of previously identified 1,2,3-triazole attached to the central -benzoic acid core () provided moderate affinity but not indole and benzimidazole substitution of the aryl-triazole. The corresponding P2YR region is predicted by homology modeling as a deep, sterically limited hydrophobic pocket, with the outward pointing piperidine moiety being the most flexible. Bicyclic-substituted piperidine ring derivatives of naphthalene antagonist , e.g., quinuclidine (MRS4608, IC ≈ 20 nM at hP2YR/mP2YR), or of triazole , preserved affinity. Potent antagonists , , , and (10 mg/kg) protected in an ovalbumin/ mouse asthma model, and PEG conjugate reduced chronic pain. Thus, we expanded P2YR antagonist structure-activity relationship, introducing diverse physical-chemical properties.

Hip arthroscopy has become the standard for the operative treatment of symptomatic femoroacetabular impingement. Given the high levels of postoperative pain associated with hip arthroscopy, optimal analgesia is critical to ensure patient comfort and safety after discharge.

Uremic pruritus is common in patients with chronic kidney disease (CKD). The retention of uremic solutes is thought to be associated with uremic pruritus. Meanwhile, activation of protease-activated receptor-2 (PAR-2) has been suggested to play an important role in pruritus. The present study was performed to investigate the effects of uremic solutes on the expression of PAR-2 in the skin.

COVID-19 is a pandemic caused by human coronavirus (HCoV) SARS-CoV-2, which originated in Wuhan, China, at the end of 2019 and spread globally during 2020. Due to the difficulty of clinical decision-making during this period, our study group reviewed current literature focusing on the neurological and psychiatric aspects of COVID-19. Despite the knowledge on this newly discovered virus which is constantly evolving, different pieces of evidence reported an association between COVID-19 and neurological symptoms like headache, dizziness, taste and smell disorders and complications involving the nervous system eventually triggered by the pathologic processes elicited by SARS-CoV-2. It seems that younger patients are less prone to develop severe forms of COVID-19. However, neurological signs have been reported in paediatric patients as well, and in some cases, the infection presented neurological sequelae. Furthermore, children with particular neurological diseases or treated with specific drugs (e.g. immune-suppressant therapies) must be carefully monitored during this pandemic. Neurologists should be aware of the main drug-drug interactions and the neurological side effects of COVID-19 treatments. Notably, adverse mental health impact has been reported in patients with SARS-CoV-2, which could be related either to the social strain or to the eventual neurotropic effects of the virus, which in other infections have been proven to promote the onset of psychiatric symptoms. Further, psychiatric population may be more vulnerable to the infection and at higher risk for adverse outcomes.

Tumour necrosis factor (TNF) inhibitors are known to induce autoimmune diseases, such as lupus-like syndrome; in rare cases, TNF inhibitor-induced myositis has been reported. This report documents the case of a male patient with ulcerative colitis (UC) complicated by TNF inhibitor-induced myositis. After UC diagnosis and treatment with azathioprine and infliximab, he was evaluated for a recent 5-month history of muscle weakness and pain. Laboratory tests revealed elevated muscle enzymes, such as serum creatine kinase (CK) and aldolase. He also tested positive for anti-nuclear antibodies and anti-double stranded DNA antibodies. High-intensity signals in his quadriceps on magnetic resonance image (MRI) and fibrillation potentials in his proximal muscles on electromyography were demonstrated. Muscle biopsy revealed the endomysial infiltration of mononuclear cells surrounding myofibers. Eventually, the patient fulfilled the classification criteria for idiopathic inflammatory myopathies. Although an adverse drug reaction of infliximab had been speculated, his muscle involvements did not improve in 6 weeks from the last administration of infliximab; therefore, treatment with prednisolone was initiated. Subsequently, his muscle symptoms ameliorated, and his serum CK levels returned to normal. Repeat MRI revealed a complete resolution of the signal intensity, and he reported no symptoms of UC or myositis while prednisolone was tapered without resumption of infliximab. Clinicians should consider the diagnosis of drug-induced myositis if muscle symptoms develop in patients treated with TNF inhibitors.

The face aging processes are associated with physiologic and biochemical alteration that produces wrinkles, skin pigmentation and benign growths. The aim of this study was to evaluate the clinical efficacy of voltaic arc dermabrasion with plasma to remove benign facial skin lesions.

Neuropathic pain is one of the most intense types of chronic pain; it constitutes a pervasive complaint throughout the public health system. With few effective treatments, it remains a significant challenge. Commercially available drugs for neuropathic pain are still limited and have disappointing efficacy. Therefore, chronic neuropathic pain imposes a tremendous burden on patients' quality of life. Recently, the introduction and application of nanotechnology in multiple fields has accelerated the development of new drugs. This review highlights the application of poly(lactic-co-glycolic acid) nanomaterial-based vehicles for drug delivery and how they improve the therapeutic outcomes for neuropathic pain treatment. Finally, future developments for pain research and effective management are presented.

To determine the associations between comorbidities, health-related quality of life (HRQoL) and functional impairment in people with mild-to-moderate chronic kidney disease (CKD) in primary care.