Rejected

In France, shisha (narghile) smoking is increasingly popular among adolescents and young adults and is generally thought to be less harmful and addictive than cigarettes. This systematic review of data on carbon monoxide (CO) poisoning in active or passive shisha tobacco smokers selected 17 studies. Sixteen case reports, including 39 patients (mean age: 22.3 years; males: 51.3%), described acute carbon monoxide poisoning in active shisha smokers. The most common symptoms were dizziness, headache, and nausea. Loss of consciousness occurred in 43.6% of patients. Two patients had an epileptic seizure. The mean carboxy-haemoglobin (HbCO) blood level was 17.3%. Electrocardiographic changes were present in five patients. Most patients were treated with normobaric oxygen therapy while only four received hyperbaric oxygen therapy; two of whom were non tobacco smokers exposed to shisha smoke during their work. The outcome was favourable in all patients. Shisha use must be suspected in cases of CO poisoning, especially in adolescents and young adults. Practitioners must help shisha users to stop their consumption.

Migraine, a benign yet disturbing condition, is one of the frequent neurological disorders, affecting up to 15-20% of the worldwide population […].

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective, widely used analgesics. For the past 2 decades, considerable attention has been focused on their cardiovascular safety. After early studies indicating an association between NSAID use and increased risks of heart failure and elevated blood pressure, subsequent studies found a link between NSAID use and an increased risk of thrombotic events. Selective cyclooxygenase 2 (COX2) inhibitors (also known as coxibs) have been associated with the greatest risk of adverse vascular effects but concern also relates to non-selective NSAIDs, especially those with strong COX2 inhibition such as diclofenac. Although NSAID use is discouraged in patients with cardiovascular disease, pain-relief medication is often required and, in the absence of analgesics that are at least as effective but safer, NSAIDs are frequently prescribed. Furthermore, non-prescription use of NSAIDs, even among people with underlying cardiovascular risks, is largely unsupervised and varies widely between countries. As concern mounts about the disadvantages of alternatives to NSAIDs (such as opioids) for pain management, the use of NSAIDs is likely to rise. Given that the pharmaceutical development pipeline lacks new analgesics, health-care professionals, patients and medicine regulatory authorities are focused on optimizing the safe use of NSAIDs. In this Review, we summarize the current evidence on the cardiovascular safety of NSAIDs and present an approach for their use in the context of holistic pain management.

Atopic dermatitis (AD) has a significant impact on patients' quality of life, and due to pruritus it particularly affects sleep. Actigraphy is a well-recognized objective tool that is used in sleep medicine. Its relevance for assessing sleep in patients with AD has been shown by several studies. This study aimed to evaluate the sleep of patients with AD and to compare it with that of healthy volunteers using wrist actigraphy and a smartphone application.

Pharmacies provide accessible sources of naloxone to caregivers, patients taking opioids, and individuals using drugs. While laws permit expanded pharmacy naloxone access, prior work identified barriers like concerns about stigma of addiction and time constraints that inhibit scale-up. We sought to examine similarities and differences in experiences obtaining naloxone at the pharmacy over a 1-year period in 2 states, and to explore reactions from people with opioid use disorder, patients taking opioids for chronic pain, caregivers of opioid users, and pharmacists to communication tools and patient outreach materials designed to improve naloxone uptake.

The recent alarming reports relating to "opioid crisis" necessitates the development of safer and effective analgesics without unwanted side effects. Thus, there needs to be alternative target or strategy for the development of drugs for the treatment of opioid use/abuse. As one of the novel targets, in these two decades, ligands targeting opioid receptor "heteromerization" including mu opioid receptor (MOPr)-delta opioid receptor (DOPr) heteromer has been proposed and the pharmacological advancement of reduced side effects has been broadly accepted and well recognized. In this review, I will introduce some of the ligands targeting both MOPr and DOPr or MOPr-DOPr heteromers especially focusing on their pharmacological effects in vivo.

Chikungunya virus (CHIKV) is an important re-emerging human pathogen transmitted by mosquitoes. The virus causes an acute febrile illness, chikungunya fever, which is characterized by headache, rash and debilitating (poly)arthralgia that can reside for months to years after infection. Currently, effective antiviral therapies and vaccines are lacking. Due to the high morbidity and economic burden in the countries affected by CHIKV, there is a strong need for new strategies to inhibit CHIKV replication. The serotonergic drug, 5-nonyloxytryptamine (5-NT), was previously identified as a potential host-directed inhibitor for CHIKV infection. In this study, we determined the mechanism of action by which the serotonin receptor agonist 5-NT controls CHIKV infection. Using time-of-addition and entry bypass assays we found that 5-NT predominantly inhibits CHIKV in the early phases of the replication cycle; at a step prior to RNA translation and genome replication. Intriguingly, however, no effect was seen during virus-cell binding, internalization, membrane fusion and gRNA release into the cell cytosol. Additionally, we show that the serotonin receptor antagonist MM also has antiviral properties towards CHIKV and specifically interferes with the cell entry process and/or membrane fusion. Taken together, pharmacological targeting of 5-HT receptors may represent a potent way to limit viral spread and disease severity.The rapid spread of mosquito-borne viral diseases in humans puts a huge economic burden on developing countries. For many of these infections, including Chikungunya virus (CHIKV), there are no specific treatment possibilities to alleviate disease symptoms. Understanding the virus:host interactions that are involved in the viral replication cycle is imperative for the rational design of therapeutic strategies. In this study, we discovered an antiviral compound and elucidated the mechanism of action and propose serotonergic drugs as potential host-directed antivirals for CHIKV.

Pyoderma Gangrenosum (PG) is a rare neutrophilic ulcerative dermatosis that poses a high burden of morbidity due to underdiagnosis, resistance to therapy and limited therapeutic options. Optimization of wound care strategies and multimodal anti-inflammatory approaches are necessary to mitigate multiple converging pathways of inflammation leading to delayed healing, which is further complicated by additional factors such as pathergy.

Tinnitus is the perception of sound in the absence of an external source. Genetic studies on families, twins, and adoptees cohorts have been conducted supporting tinnitus heritability, with higher heritability in men with bilateral tinnitus at any age, and young women with bilateral tinnitus, but not in unilateral tinnitus. The condition is associated with several comorbidities such as hearing loss, Meniere disease, sleep disorders, depression, and migraine and may lead toward suicidal attempts in extreme cases. Several studies have reported few regulatory allelic variants in candidate genes and pathways associated with tinnitus development, but replication studies are needed to validate them.

Neuropathic pain is caused by damage to or dysfunction of the somatosensory nervous system. The main mechanisms underlying neuropathic pain including ectopic activity in nociceptive nerves, peripheral and central sensitization, impaired inhibitory modulation, and microglial activation. Fibroblast growth factors (FGFs) make up a large family of growth factors that mediate neural development, metabolism, and function through three main key signaling pathways, including RAS/MAP kinase pathway, PI3 kinase/Akt pathway, and PLCγ. An association between the members of the FGF system and improvement of neuropathic pain has become evident, recently. These signaling molecules may be expected to provide new drug targets for the treatment of neuropathic pain. To our best knowledge, it is the first that reviews the relationship between some members of the FGF system and neuropathic pain.