Rejected

Individuals with migraine aura show differences in visual perception compared to control groups. Measures of contrast sensitivity have suggested that people with migraine aura are less able to exclude external visual noise, and that this relates to higher variability in neural processing. The current study compared contrast sensitivity in migraine with aura and control groups for narrow-band grating stimuli at 2 and 8 cycles/degree, masked by Gaussian white noise. We predicted that contrast sensitivity would be lower in the migraine with aura group at high noise levels. Contrast sensitivity was higher for the low spatial frequency stimuli, and decreased with the strength of the masking noise. We did not, however, find any evidence of reduced contrast sensitivity associated with migraine with aura. We propose alternative methods as a more targeted assessment of the role of neural noise and excitability as contributing factors to migraine aura.

Until recently, glia were considered to be a structural support for neurons, however further investigations showed that glial cells are equally as important as neurons. Among many different types of glia, enteric glial cells (EGCs) found in the gastrointestinal tract, have been significantly underestimated, but proved to play an essential role in neuroprotection, immune system modulation and many other functions. They are also said to be remarkably altered in different physiopathological conditions. A nutraceutical is defined as any food substance or part of a food that provides medical or health benefits, including prevention and treatment of the disease. Following the description of these interesting peripheral glial cells and highlighting their role in physiological and pathological changes, this article reviews all the studies on the effects of nutraceuticals as modulators of their functions. Currently there are only a few studies available concerning the effects of nutraceuticals on EGCs. Most of them evaluated molecules with antioxidant properties in systemic conditions, whereas only a few studies have been performed using models of gastrointestinal disorders. Despite the scarcity of studies on the topic, all agree that nutraceuticals have the potential to be an interesting alternative in the prevention and/or treatment of enteric gliopathies (of systemic or local etiology) and their associated gastrointestinal conditions.

Vulvodynia is one the most common causes of pain during sexual intercourse in premenopausal women. The burden of vulvodynia in a woman's life can be devastating due to its consequences in the couple's sexuality and intimacy, in activities of daily living, and psychological well-being. In recent decades, there has been considerable progress in the understanding of vulvar pain. The most significant change has been the differentiation of vulvar pain secondary to pathology or disease from vulvodynia. However, although it is currently proposed that vulvodynia should be considered as a primary chronic pain condition and, therefore, without an obvious identifiable cause, it is still believed that different inflammatory, genetic, hormonal, muscular factors, etc. may be involved in its development. Advances in pain neuroscience and the central sensitization paradigm have led to a new approach to vulvodynia from a neurobiological perspective. It is proposed that vulvodynia should be understood as complex pain without relevant nociception. Different clinical identifiers of vulvodynia are presented from a neurobiological and psychosocial perspective. In this case, strategies to modulate altered central pain processing is necessary, changing the patient's erroneous cognitions about their pain, and also reducing fear avoidance-behaviors and the disability of the patient.

Dihydroartemisinin (DHA), a natural product isolated from the traditional Chinese herb Artemisia annua and one of the clinical frontline drugs against malarial infections, has recently been discovered as a Toll-like Receptor 4 (TLR4) antagonist. However, the TLR4 antagonistic activity of DHA is modest and it exhibits cellular toxicity. In this work, the structure-activity relationship (SAR) of DHA as TLR4 antagonist was explored. Since destroying the sesquiterpene endoperoxide scaffold substantially compromised the TLR4 antagonistic activity and molecular dynamics analysis showed that the C-10 hydroxyl group formed a hydrogen bond with E72 of myeloid differentiation factor 2 (MD2) to prevent it moving deeper into MD2, SAR of DHA was focused on the C-10 hemiacetal position. With extending the length of the linear alkane chain at C10 position, the TLR4 antagonistic activity of DHA analogs increased first and then decreased with the best TLR4 antagonism occurring at the length of the carbon chain of 3-4 carbons. In contrast, the cellular toxicity of DHA analogs was raised with the increasing length of the linear alkane chain. The TLR4 antagonistic activity of DHA derivatives with substituted halogen as the terminal functional group decreased with the decrease of electronegativity of the substituted halogen, which implies the electron-rich functional group at the end of the alkane chain appears preferred. Therefore, DHA derivative 2k with alkynyl as the end functional group, exhibited 14 times more potent TLR4 antagonistic activity than DHA. Moreover, 2k showed less cellular toxicity than DHA. Cellular signaling characterizations indicated that 2k inhibited LPS-induced TLR4 dimerization and endocytosis and suppressed LPS-induced NF-κB but not MAPKs activation, culminating in blocking LPS-induced TLR4 signaling downstream pro-inflammatory factors NO and IL-1β. Further, 2k was active in vivo; it significantly increased and prolonged morphine analgesia. Collectively, this study provides a structural guidance to reposition DHA derivatives as TLR4 antagonists.

Due to the high demand for information regarding COVID-19 vaccination in people with epilepsy (PWE), we assessed the symptoms and seizure control of PWE following their COVID-19 vaccination.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. Although anti-fibrotic treatments, such as pirfenidone, are available that reduce the rate of disease progression, these medications have limitations in tolerability, and IPF patients still have poor prognoses. GDC-3280, an orally available small molecule that was designed to improve upon pirfenidone's activity, has anti-fibrotic activity in animal models. This first-in-human, phase 1 trial evaluated GDC-3280 to determine its safety, tolerability, and pharmacokinetics (PK).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is responsible for the first pandemic of the 21 century. As found in adults, signs and symptoms related to the disease mainly involve the respiratory tract in the paediatric population. However, a considerable number of children present with gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. The purpose of this review is an accurate description, from pathogenesis to clinical presentation, diagnosis and treatment, of COVID-19 effects on the gastrointestinal system at a paediatric age. SARS-CoV-2 can be identified in stool specimens of affected children by real-time polymerase chain reaction techniques. Positivity can last for several weeks after the end of the symptomatic phase. Gastrointestinal signs and symptoms are generally self-limited, can correlate with blood tests and imaging alterations, and may require supportive treatment such as hydration. However, they can precede severe disease manifestations such as the COVID-19-related multisystem inflammatory syndrome. Children belonging to risk categories such as those affected by celiac disease, inflammatory bowel disease, and hepatic disease seem to not have a more severe course than the others, even if they are undergoing immunosuppressant treatment. Medical follow-ups of patients with chronic diseases need to be revised during the pandemic period in order to postpone unnecessary tests, mainly endoscopic ones.

Patients with chronic pancreatitis often experience severe, unrelenting abdominal pain, which can significantly impact their quality of life. Pain control, therefore, remains central to the overall management of chronic pancreatitis. Most of the strategies aimed at treating the pain of chronic pancreatitis are based on expert opinion and vary from one institution to another, as there are no uniform guidelines to direct a stepwise approach towards achieving this goal. In this editorial, we comment on best practice strategies targeted towards pain control in chronic pancreatitis, specifically highlighting the use of opioid medications in this patient population. We discuss various safe and efficacious prescription monitoring practices in this article.

To observe the therapeutic effect of swertiamarin on diabetic peripheral neuropathy (DPN) in rats and explore the molecular mechanism in light of the NOXS/ROS/NLRP3 signal pathway.