Rejected

Nakai (AGN) root is a medicinal herbal widely used in traditional medicine in Korea. AGN root ethanolic extract dietary supplements are marketed in the United States for memory health and pain management. We comprehensively reviewed the anticancer, analgesic, pro-memory and other bio-activities of AGN extract and its signature phytochemicals decursin, decursinol angelate, and decursinol a decade ago in 2012 and updated their anticancer activities in 2015. In the last decade, significant progress has been made for understanding the pharmacokinetics (PK) and metabolism of these compounds in animal models and single dose human PK studies have been published by us and others. In addition to increased knowledge of the known bioactivities, new bioactivities with potential novel health benefits have been reported in animal models of cerebral ischemia/stroke, anxiety, sleep disorder, epilepsy, inflammatory bowel disease, sepsis, metabolic disorders, osteoporosis, osteoarthritis, and even male infertility. Herein, we will update PK and metabolism of pyranocoumarins, review bioactivities from animal models and human studies, and critically appraise the relevant active compounds, the cellular and molecular pharmacodynamic targets, and pertinent mechanisms of action. Knowledge gaps include whether human pyranocoumarin PK metrics are AGN dose dependent and subjected to metabolic ceiling, or metabolic adaptation after repeated use. Critical clinical translation challenges include sourcing of AGN extracts, product consistency and quality control, and AGN dose optimization for different health conditions and disease indications. Future research directions are articulated to fill knowledge gaps and address these challenges.

Fibromyalgia and migraine frequently coexist. We aimed to compare the burden caused by fibromyalgia (FM), migraine (M) and comorbid fibromyalgia and migraine (FM + M) by assessing psychosocial variables and the use of healthcare resources. A survey was posted to the websites of different patients' associations. It included sociodemographic data, the Patient Health Questionnaire-9, the Insomnia Severity Index, the EuroQOL-5D-5L and a questionnaire evaluating the use of healthcare resources during the past six months. In total, 139 FM patients, 169 M patients and 148 FM + M patients participated in the survey. Mean depression and insomnia scores were clinically relevant in every group and significantly higher in FM + M (16.3 ± 5.4 for depression, 18.5 ± 5.6 for insomnia) than in FM (14.3 ± 5.7 for depression, 16.8 ± 5.5 for insomnia) or M (11.7 ± 5.4 for depression, 13.1 ± 5.9 for depression), where < 0.001 in both cases. Suicidal ideation was frequent in every group, but significantly more frequent in FM + M (63% vs. 45% in FM and 35% in M; < 0.001). EQ-5D-5L (0.656 ± 0.1 in FM + M, 0.674 ± 0.1 in FM, 0.827 ± 0.1 in M, < 0.001) and EQ-5D-5L VAS scores (38.2 ± 21.9 in FM + M, 45.6 ± 21.8 in FM, 63.5 ± 23.7 in M, < 0.00) were lower than the reported mean population values and the lowest in FM + M. FM and FM + M used more healthcare resources than M. It is concluded that the psychosocial burden was high in the three samples. FM and FM + M had a more relevant impact on patients' wellbeing and required more medical attention than M. The burden caused by FM + M was higher than in both individual diseases.

Pharmacological synergism is a current strategy for the treatment of pain. However, few studies have been explored to provide evidence of the possible synergism between a non-steroidal anti-inflammatory drug (NSAID) and a cannabinoid agonist, in order to establish which combinations might be effective to manage pain. The aim of this study was to explore the synergism between ibuprofen (IBU) and the synthetic cannabinoid WIN 55,212-2 (WIN) to improve pain relief by analyzing the degree of participation of the CB and CB cannabinoid receptors in the possible antinociceptive synergism using an experimental model of pain in Wistar rats. First, the effective dose thirty (ED) of IBU (10, 40, 80, and 160 mg/kg, subcutaneous) and WIN (3, 10, and 30 µg/p, intraplantar) were evaluated in the formalin test. Then, the constant ratio method was used to calculate the doses of IBU and WIN to be administered in combination (COMB) to determine the possible synergism using the isobolographic method. The participation of the CB and CB receptors was explored in the presence of the antagonists AM281 and AM630, respectively. The combination of these drugs produced a supra-additive response with an interaction index of 0.13. In addition, AM281 and AM630 antagonists reversed the synergistic effect in 45% and 76%, respectively, suggesting that both cannabinoid receptors are involved in this synergism, with peripheral receptors playing a relevant role. In conclusion, the combination of IBU + WIN synergism is mainly mediated by the participation of the CB receptor, which can be a good option for the better management of pain relief.

: Spontaneous intracranial hypotension (SIH) is a rare syndrome characterized by heterogeneity of presentation and prognosis, which can occasionally result in serious complications, such as the formation of subdural hematomas (SDHs). This case series aims to emphasize that SIH remains a diagnostic and therapeutic challenge; it can present with a broad clinical spectrum of symptoms, can lead to SDH and, if conservative treatment fails, an epidural blood patch (EBP) is a viable treatment option. Although the exact etiology of SIH is not known, it is believed to be due to cerebrospinal fluid (CSF) leak or a low CSF pressure. : Three patients (two males and one female) with ages ranging between 38 and 53 years old who presented with complaints of not only an orthostatic headache, but also a variety of symptoms of SIH, including the formation of two SDHs in one of them, were included in this series. These patients did not respond to conservative management and, subsequently, given the clinical and radiological evidence of SIH, were referred to the Anesthesiology Department for an EBP. Diagnostic workup was facilitated by imaging modalities, including magnetic resonance imaging (MRI) of the brain and spinal cord, prior to the EBP. All three patients were subjected to an EBP with an 18-gauge epidural needle. A total of between 30 and 43 mL of autologous blood was collected from the patients and was injected into the epidural space under strict aseptic conditions. Two lumbar (L-L, L-L) EBPs and one thoracic (T-T) EBP were performed on the three patients, respectively. All patients reported complete resolution of symptoms following the EBPs, while MRI improved substantially. : This report describes three cases of SIH with CSF leak originating from the cervical, the thoracic and the lumbar level. The EBP restored CSF pressure and relieved the patients' persistent symptoms. MRI helps in revealing indirect signs of a low volume of CSF, though it may not be possible to locate the actual site of the leak. In conclusion, EBP is a well-accepted and beneficial treatment modality for SIH when conventional measures fail.

Chronic Urticaria (CU), a common skin disorder known as Yin Zhen in Chinese medicine, is characterized by recurrent, pruritic, pink-to-red edematous lesions and wheals on the skin. Xiao-Feng Powder (XFP, meaning Wind-Dispersing Powder), is reported to be one of the most frequently used Chinese herbal formulae for CU. In this study, we aim to investigate the effectiveness and safety of modified Xiao-Feng Powder (mXFP) for the treatment of CU.

Recurrent painful ophthalmoplegic neuropathy (RPON) is a rare disorder with a unilateral headache accompanied by ipsilateral episodes of painful ocular cranial nerve neuropathy, which typically occurs in childhood.

Workplace and labor market conditions are associated with the health of the working population. A longitudinal study was conducted among young adults with rheumatic disease to examine workplace activity limitations and job insecurity and their relationship with disease symptom trajectories.

Chronic hip pain due to osteoarthritis or hip dysplasia has been shown to negatively affect many daily life aspects. One aspect, however, which persists underestimated is sexual health. The number of total hip arthroplasties (THA) are increasing, especially in young patients who have high functional expectations, not only to pain relief, but to an increase in hip mobility and quality of life as well as sexual activity.

Connection with nature has well-established physical and psychological benefits. However, women with metastatic breast cancer (MBC) are often unable to access nature because of physical limitations, psychological barriers, and treatment demands. Virtual reality (VR) nature experiences offer an alternative means of connecting with nature and may be of particular benefit to patients with cancer who are house- or hospital-bound.

Non-surgical interventions are recommended for osteoarthritis (OA). However, how interventions change pain and physical function is unclear. Therefore, the objectives of this scoping review were to: (1) identify what potential mediators of non-surgical interventions on pain and physical function have been evaluated and (2) summarise the findings according to intervention, joint and outcome.