Rejected

Latent herpes virus reactivation has been demonstrated in astronauts during shuttle (10-16 days) and International Space Station (≥180 days) flights. Following reactivation, viruses are shed in the body fluids of astronauts. Typically, shedding of viral DNA is asymptomatic in astronauts regardless of mission duration; however, in some cases, live/infectious virus was recovered by tissue culture that was associated with atopic-dermatitis or skin lesions during and after spaceflight. Hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes activation during spaceflight occurs as indicated by increased levels of stress hormones including cortisol, dehydroepiandrosterone, epinephrine, and norepinephrine. These changes, along with a decreased cell mediated immunity, contribute to the reactivation of latent herpes viruses in astronauts. Currently, 47/89 (53%) astronauts from shuttle-flights and 14/23 (61%) astronauts from ISS missions shed one or more herpes viruses in saliva/urine samples. Astronauts shed Epstein-Barr virus (EBV), varicella-zoster virus (VZV), and herpes-simplex-1 (HSV-1) in saliva and cytomegalovirus (CMV) in urine. Larger quantities and increased frequencies for these viruses were found during spaceflight as compared to before or after flight samples and their matched healthy controls. The shedding did not abate during the longer ISS missions, but rather increased in frequency and amplitude. These findings coincided with the immune system dysregulation observed in astronauts from shuttle and ISS missions. VZV shedding increased from 41% in space shuttle to 65% in ISS missions, EBV increased 82 to 96%, and CMV increased 47 to 61%. In addition, VZV/CMV shed ≤30 days after ISS in contrast to shuttle where VZV/CMV shed up to 5 and 3 days after flight respectively. Continued shedding of infectious-virus post-flight may pose a potential risk for crew who may encounter newborn infants, sero-negative adults or any immunocompromised individuals on Earth. Therefore, developing spaceflight countermeasures to prevent viral reactivation is essential. Our spaceflight-developed technologies for saliva collection/rapid viral detection have been extended to include clinical applications including zoster patients, chicken pox, post-herpetic neuralgia, multiple sclerosis, and various neurological disorders. These protocols are employed in various clinics and hospitals including the CDC and Columbia University in New York, as well as overseas in Switzerland and Israel.

Immunoglobulin G4- (IgG4-) related inflammatory abdominal aortic aneurysm (AAA) has been recognized as a manifestation of IgG4-related disease (IgG4-RD). We experienced one patient with multiple consecutive manifestations before and after endovascular stent grafting for IgG4-related inflammatory AAA (IAAA). A 71-year-old man was diagnosed with IgG4-RD due to increased IgG4 serum concentration, typical findings of parotid gland biopsy, and periaortitis in another hospital 2 years and 7 months before visiting our hospital. He came to our hospital because of abdominal pain and IAAA. He developed paraplegia after hospitalization and underwent endovascular stent grafting for the IAAA. About one month after stent grafting, he developed perforation of the sigmoid colon due to enteritis. He also had myocardial infarction. Finally, he died of intestinal bleeding. Here, we describe this case with rare, multiple, consecutive manifestations of IgG4-RD, some of which might be caused by IgG4-related IAAA or side effects of treatments rather than by IgG4-RD itself. We report this case because the clinical course seemed rare for IgG4-RD or IgG4-related IAAA. For treating IgG4-RD with IgG4-related IAAA, we should consider factors causing the symptoms and carefully select the proper treatment.

Neonates are too vulnerable that low birth weight (LBW) and preterm birth can easily threaten their lives. Demographic, social and environmental factors as well as health care are contributing factors for LBW. The study was conducted in 10 provinces of Iran to investigate the association between LBW and mother's diseases.

Primary hepatic tuberculosis is a rare presentation and sporadically reported in the literature, mostly from our part of the world. Sometimes the presentation can be atypical and mimics hepatic tumor and poses diagnostic challenge. We, herein, present a case of a 58-year-old man who presented to us with abdominal pain and weight loss. Raised serum alkaline phosphatase (ALP) and imaging raised a suspicion of gall bladder carcinoma with hepatic invasion. Peroperative frozen section revealed hepatic chronic granulomatous inflammation with caseous necrosis consistent with the diagnosis of hepatic tuberculosis. Surgery was postponed and he was put on antituberculous treatment. It is important to consider tuberculosis in the differential diagnosis of the space occupying lesion of liver in a patient with vague symptoms and abnormal findings on imaging.

has over 60 species and is found mainly in the temperate regions of Asia and Europe. One of these species, Boiss, is known to have a number of medicinal properties and active ingredients in many parts of the world. Despite being an endemic wild-flowering plant of great importance, the plant is currently considered endangered in Iran. Besides, there is paucity of information on the significance of the medicinal properties and active constituents of among the Iranian people. On that account a systematic review of studies reporting on the medicinal properties and active ingredients and its significance to human and animal health was conducted and the existing knowledge gaps were identified.

[This corrects the article DOI: 10.3389/fnmol.2019.00037.].

Atopic dermatitis (eczema) is a common chronic disease that is described as severe itching associated with recurrent eczematous lesions. In 2017 the US Food and Drug Administration approved dupilumab for treatment of adults with moderate to severe atopic dermatitis not well controlled with topical therapies or when other therapies are inadvisable. Dupilumab is a monoclonal antibody that inhibits interleukin-4 (IL-4) and IL-13 signaling by specifically binding to the IL-4R-alpha subunit shared by the IL-4 and IL-13 receptor complexes. There are many adverse effects reported after dupilumab therapy; commonly reported adverse effects include local injection site reactions, conjunctivitis, headache, and nasopharyngitis. Some adverse effects are rare, eg, alopecia areata and cicatricial extropion. We report a new case of a 28-year-old female who experienced face and neck rash after dupilumab injection.

Clinically active drugs for the treatment of acute pain have their prescription limited due to the significant side effects they induce. An increase in reactive oxygen species (ROS) has been linked to several conditions, including inflammation and pain processing. Therefore, new or repurposed drugs with the ability of reducing ROS-triggered responses are promising candidates for analgesic drugs. Vinpocetine is a clinically used nootropic drug with antioxidant, anti-inflammatory, and analgesic properties. However, the effects of vinpocetine have not been investigated in a model with a direct relationship between ROS, inflammation, and pain. Based on that, we aimed to investigate the effects of vinpocetine in a model of superoxide anion-induced pain and inflammation using potassium superoxide (KO) as a superoxide anion donor to trigger inflammation and pain. In the KO model, vinpocetine dose-dependently reduced pain-like behaviors (spontaneous pain and hyperalgesia), paw edema, and neutrophil and mononuclear cell recruitment to the paw skin (assessed by H&E staining, fluorescence, and enzymatic assays) and to the peritoneal cavity. Vinpocetine also restored tissue endogenous antioxidant ability and and mRNA expression and reduced superoxide anion production and mRNA expression. We also observed the inhibition of IB degradation by vinpocetine, which demonstrates a reduction in the activation of NF-B explaining the diminished production of IL-33, IL-1, and TNF-. Collectively, our data show that vinpocetine alleviates pain and inflammation induced by KO, which is a mouse model with a direct role of ROS in triggering pain and other inflammatory phenomena. Thus, the results suggest the repurposing of vinpocetine as an anti-inflammatory and analgesic drug.

The increase of oxidant compounds is the most well-known reasons for the tolerance to the analgesic properties of Morphine. Additionally, the production of proxy-nitrite impairs receptors, proteins and enzymes involved in the signaling pathways of analgesia, apoptosis and necrosis. Also, we revised all patents relating to opioid tolerance control methods.

The high prevalence of chronic pain conditions combined with an over-reliance on opioid prescriptions has resulted in an opioid epidemic and a desperate need for solutions. There is some debate about whether cannabis might play a role in addressing chronic pain conditions as well as the opioid epidemic. Recent surveys suggest that a large number of people are using cannabis as a treatment for pain and to reduce use of opioids, and cannabis-derived products demonstrate at least modest efficacy in the treatment of pain in randomized controlled trials. In addition, surveillance studies from countries that have approved the use of Sativex, which is a cannabis-based product, have demonstrated that a combination of Δ9-tetrahydrocannabinol and cannabidiol has low potential for harm, is well tolerated, and is helpful to patients. Given the number of people in the United States who are already using cannabis to manage pain and opioid use in state-regulated markets, it is imperative to conduct additional research in these areas, and to disseminate information on how to minimize harm and maximize any benefits of using cannabinoids to mitigate pain and reduce opioid use. The purpose of this article is to call attention to the fact that cannabis is being used in the management of chronic pain. Thus, this article also provides a set of guidelines on how to approach using cannabis to treat pain.