Rejected

Chronic scrotal pain may be due to an identifiable cause, may be multifactorial, or may be idiopathic. Successful treatment often requires multimodal therapy with a multidisciplinary approach. Conservative options may be offered initially, but if symptoms fail to improve with conservative interventions, more invasive therapies may be required. A nerve block may be attempted and patients who experience improvement in pain following nerve blocks may be good candidates for surgical denervation of the spermatic cord. Alternative surgical treatment options including proximal nerve blocks, neuromodulation, cryoablation, vasectomy reversal, varicocelectomy, and even orchiectomy have been described. The aim of this review is to discuss the treatment options for chronic scrotal pain with a focus on surgical treatment options.

Chronic inflammatory skin diseases pose significant challenges for both patients and clinicians worldwide. Atopic dermatitis (AD), the most common of these diseases, affects up to 8% of the adult population depending on geographic location and demographic group, while prurigo nodularis (PN) is a less common disease that causes significant burden. In these inflammatory skin conditions, pruritus is a cardinal symptom. Interleukin 31 (IL-31), described as a neuroimmune modulator, has been shown to have a prominent role in both inflammation and itch. IL-31 acts through a receptor complex consisting of IL-31 receptor α (IL-31RA) and oncostatin M receptor β (OSMRβ). IL-31 is produced by a variety of cells, including type 2 helper T cells, and IL-31 signaling can activate three important pathways: JAK/STAT, P13K/AKT, and ERK/MAPK. IL-31 is elevated in AD and PN, and is thought to induce chemokine genes CCL1, CCL17, and CCL22. The chemokines recruit T cells to affected skin, where more IL-31 is secreted. The IL-31 receptor complex is also abundant in dorsal root ganglia in human tissue, home of primary sensory neurons and the distal source of "itch sensations". IL-31 and its receptor complex have an important role in chronic inflammatory diseases, including AD and PN, and blocking the IL-31/IL-31RA signaling may represent an important new therapeutic approach for these diseases, which continue to have significant unmet medical needs.

As of January 8, 2022, a global pandemic caused by infection with severe acute respiratory syndrome coronavirus (SARS-CoV)-2, a new RNA virus, has resulted in 304,896,785 cases in over 222 countries and regions, with over 5,500,683 deaths (www.worldometers.info/coronavirus/). Reports of neurological and psychiatric symptoms in the context of coronavirus infectious disease 2019 (COVID-19) range from headache, anosmia, and dysgeusia, to depression, fatigue, psychosis, seizures, delirium, suicide, meningitis, encephalitis, inflammatory demyelination, infarction, and acute hemorrhagic necrotizing encephalopathy. Moreover, 30-50% of COVID-19 survivors develop long-lasting neurologic symptoms, including a dysexecutive syndrome, with inattention and disorientation, and/or poor movement coordination. Detection of SARS-CoV-2 RNA within the central nervous system (CNS) of patients is rare, and mechanisms of neurological damage and ongoing neurologic diseases in COVID-19 patients are unknown. However, studies demonstrating viral glycoprotein effects on coagulation and cerebral vasculature, and hypoxia- and cytokine-mediated coagulopathy and CNS immunopathology suggest both virus-specific and neuroimmune responses may be involved. This review explores potential mechanistic insights that could contribute to COVID-19-related neurologic disease.

Over the last few years, novel therapeutic approaches based on the use of monoclonal antibodies against cytokines, or their cognate receptors, involved in psoriasis progression have shown remarkable results, being capable to reduce disease progression and increase patient's quality of life. Among these is etanercept (Enbrel®, Pfizer, Sandwich, UK) and its biosimilar compound SB4 (Benepali®, Samsung Bioepis, Delft, The Netherlands), both approved for the treatment of moderate to severe psoriasis. Aim of the present study was to evaluate in a less controlled environment, such as real-life, the actual bioequivalence between the etanercept (ETN) and the SB4 in term of safety, efficacy and patient's quality of life.

Cultural beliefs and values are increasingly understood to influence the experience of pain, health-seeking, and pain management behaviours. Research exploring cultural beliefs about pain is particularly needed for Indian migrants, who have a high prevalence of pain and are among the largest migrant communities in Australia and internationally. The objective of this study was to explore pain-related beliefs and coping strategies of Hindi-speaking Indian migrants with chronic back pain living in Sydney. Indian migrants (n = 26) completed a demographic survey, standardised pain questionnaires (RMDQ, PSEQ and BBQ) and participated in one of five focus group discussions. This cohort had low levels of disability: Mean (SD) [RMDQ 5.04 (3.2)], high self-efficacy [PSEQ 44.6 (8.8)], and relatively positive beliefs about back pain [BBQ 28.6 (4.4)]. Three categories of interconnected beliefs emerged from the focus groups: causative, treatment/coping-related, and prognostic beliefs underpinned by a core cultural belief in 'the philosophy of Karma'. Within this core philosophy, three cultural values were central to the experience of pain and the construction of pain-related beliefs: collectivism and contribution, gendered roles, and mind-body wellness. The incorporation of holistic approaches to back pain management with an emphasis on mindfulness, exercise, and physical activity aligned with family-oriented goals could be considered for management of chronic back pain among Indian migrant communities. CONTRIBUTION OF THE PAPER.

There has been a substantial increase in nonoperating room anesthesia procedures over the years along with an increase in the complexity and severity of cases. These procedures pose unique challenges for anesthesia providers requiring meticulous planning and attention to detail. Advancements in the delivery of sedation and analgesia in this setting will help anesthesia providers navigate these challenges and improve patient safety and outcomes.

Moderate-to-severe atopic dermatitis (AD) is associated with negative impact on general health-related quality of life and work productivity. The objective was to investigate the improvement of work productivity and activity impairment associated to ameliorated general health in moderate-to severe AD patients during dupilumab treatment.

Septic cavernous sinus thrombosis (SCST) is a rare but life-threatening condition that commonly arises from infections, including paranasal sinusitis, otitis media, and skin infection. Meanwhile, head trauma as a predisposing factor of SCST has been scarcely reported. We report a case of SCST complicated by meningitis after minor head trauma, even in the absence of identifiable fractures.

Identification of bioactive principles from natural products is considered a challenging task in drug discovery. Recently, ligand fishing has been growing in interest as a sustainable strategy. In this study, a yeast-based drug discovery strategy was investigated to screen and fish active ingredients from natural products. Human monoacylglycerol lipase (MAGL) was first displayed on the cell wall of Pichia pastoris. The expression of MAGL on the cell surface was confirmed by immunofluorescence analysis. The activity toward 7-HCA which was consistent with free enzymes in solution. Recombinant yeast strains were used to screen the potential inhibitors from traditional Chinese medicines. Preliminary screening showed that the extracts of 12 herbs showed inhibition on MAGL activity, among which Corydalis Rhizoma had the highest inhibition rate of 60.66 ± 2.44%. Recombinant yeast fishing combined with HPLC-Q-TOF-MS/MS analysis was further used to identify the potential MAGL inhibitors. Finally, dehydrocorydaline (DHC) in Corydalis Rhizoma was determined as a ligand to MAGL with the IC value at 154.7 μΜ. Corydalis Rhizoma has been used as a pain reliever in TCM. Intraperitoneal injection of 7 mg kg DHC in chronic constriction injury model rats significantly attenuated the mechanical allodynia and thermal hyperalgesia. Meanwhile, 2-arachidonoylglycerol, the major MAGL substrate in the brain, was significantly increased both in the hippocampus and striatum. In conclusion, yeast-based ligand fishing combined with HPLC-Q-TOF-MS/MS is a powerful strategy for drug discovery in complex mixtures and DHC from Corydalis Rhizoma was confirmed with high inhibitory activity to MAGL either in vitro or in vivo .