Rejected

Over the past decades, envenomation by caterpillars of spp. became an increasing health problem in Latin America. Accidental contact with the stinging spines of these caterpillars cause acute local pain, itching, inflammation and skin rashes that persists for days. Even when the cause is obvious, the exact molecular mechanisms responsible for the observed symptoms are yet to be elucidated. Here, we describe for the first time, an active compound in the venom and the study of the bioactivity of the venom extracted from the spines of the caterpillar . Electrophysiological screening of a library of membrane proteins important for pain and itch enabled us to investigate and reveal the mode of action of the venom of . Further mass spectrometric analysis (Q-TOF-MS) made it possible to establish a link between the bioactivity and the components found in the venom. We show that the spine extract of contains histamine that potently activates the four types of the human histamine receptors (H1R, H2R, H3R and H4R) with a selectivity preference towards H3R and H4R. Furthermore, a modulation of the target MRGPRX2 was found. Together, these findings are the first to explain the symptomology of envenomation, enabling us a better understanding of caterpillar envenomation and predict that the hurdle of the scarce efficacy of the currently used antihistaminic drugs can be overcome by including H3R and H4R blockers in the clinical used medication. Such an approach might be used for other caterpillar envenomation in the world and represent a significant improvement for the well-being of the patient.

The Society of Interdisciplinary Placebo Studies (SIPS) was one of many organizations that hosted a virtual scientific conference in response to the COVID-19 pandemic restrictions. Retaining essential benefits of an in-person conference experience was a primary objective for the SIPS conference planning committee and guided the selection of a virtual platform on which to host the 2021 meeting. This article reports on the methods used to design and analyze an engaging, virtual scientific conference, along with the findings and implications for future meetings.

Rotational Chair Test (RCT) is considered one of the most critical measures for vestibular functionality, which generally includes the sinusoidal harmonic acceleration test (SHAT), velocity step test (VST), and visual suppression (VS). The purpose of this study was to establish normal values for different age groups on the RCT and investigate whether motion susceptibility, such as with a history of motion sickness or migraine, has any effects on test metrics.

Sebaceous glands (SGs) originate from hair follicular stem cells and secrete lipids to lubricate the skin. The coordinated effects of intrinsic and extrinsic aging factors generate degradation of SGs at a late age. Senescence of SGs could be a mirror of the late aging of both the human body and skin. The procedure of SG aging goes over an initial SG hyperplasia at light-exposed skin areas to end with SG atrophy, decreased sebum secretion, and altered sebum composition, which is related to skin dryness, lack of brightness, xerosis, roughness, desquamation, and pruritus. During differentiation and aging of SGs, many signaling pathways, such as Wnt/β-catenin, c-Myc, aryl hydrocarbon receptor (AhR), and p53 pathways, are involved. Random processes lead to random cell and DNA damage due to the production of free radicals during the lifespan and neuroendocrine system alterations. Extrinsic factors include sunlight exposure (photoaging), environmental pollution, and cigarette smoking, which can directly activate signaling pathways, such as Wnt/β-catenin, Notch, AhR, and p53 pathways, and are probably associated with the de-differentiation and hyperplasia of SGs, or indirectly activate the abovementioned signaling pathways by elevating the inflammation level. The production of ROS during intrinsic SG aging is less, the signaling pathways are activated slowly and mildly, and sebocytes are still differentiated, yet terminal differentiation is not completed. With extrinsic factors, relevant signaling pathways are activated rapidly and fiercely, thus inhibiting the differentiation of progenitor sebocytes and even inducing the differentiation of progenitor sebocytes into keratinocytes. The management of SG aging is also mentioned.

Varicose veins are convoluted, expanded, and stretched subcutaneous veins of the lower leg and are the most frequently reported medical condition. This condition has a higher prevalence in Western and developed countries. Inadequacy of the valves results in reflux of blood in the veins of the lower leg. The present study aims to describe the epidemiology and contributing factors (risk factors and pathological factors) in the development of varicose veins disease. PubMed/Medline, Science Direct, Google Scholar, SciFinder, Scopus, and Web of Science databases were explored to include potential research and review articles. Finally, 65 articles were considered appropriate to include in the study. Pain, swelling, heaviness, and tingling of the lower limbs are the most common sign and symptoms caused by varicose veins while in some individuals it is asymptomatic. The Prevalence of varicose veins varies geographically. Currently, it is reported that globally about 2%-73% of the population is affected by varicose veins while the prevalence rate in Pakistan is 16%-20%. Different risk factors associated with the advancement of varicose veins are age, gender, occupation, pregnancy, family history, smoking, BMI and obesity, exercise, genetic factor, and current lifestyle. In varicose veins, some contributory elements may also play an important role in the disease development, incorporating constant venous wall aggravation, hereditary variation, and persistent venous hypertension. This condition has now turned into a curable issue that was previously viewed broadly as less important for treatment, determining the individual's satisfaction. Moreover, the mechanisms behind the risk factors involve diet, physical work, and hormonal contribution. These are more likely to be explored.

Migraine is one of the leading causes of disability worldwide, especially in women younger than 50 years old. Migraine has three times higher prevalence in women than in men and tends to decrease after the menopausal transition. Migraine has different clinical features in people of different ages. Clinical symptoms and factors associated with migraine can be various in women and men. Women have special types of migraine, such as pure menstrual migraine and menstrually related migraine. Besides, clinical symptoms of migraine can change during pregnancy, postpartum and lactation. Women are significantly more often than men consulting a doctor because of migraine. These features of migraine lead to different treatment and management strategies in females and males of different ages. Migraine therefore is a disorder that demonstrates the necessity of a personalization of healthcare-ensuring the proper treatment for the right patient, at the right time. Considering all the available literature and guidelines, in this chapter several strategies for management of acute and prophylactic treatments of migraine, according to sex and age differences, are discussed. The purpose of this chapter is to provide a useful piece of information improving the treatment and management of migraine.

Back braces are commonly utilized in the management of low back pain (LBP).

Mitochondrial dysfunction, which can be regulated by mitophagy, plays a central role in diabetic neuropathic pain (DNP). Mitophagy that was involved in nerve damage-induced neuropathic pain has been reported. Hyperglycemia and cellular hypoxic were the two main characters of diabetes. Hypoxia-inducible factor 1 subunit (HIF-1) plays a vital role in mitochondrial homeostasis under hypoxia. However, it remains unclear whether mitophagy was changed and could be regulated by HIF-1 in DNP. In this study, the results showed that mitophagy was activated and HIF-1 was upregulated in the spinal cord of diabetic mice. HIF-1 agonist dimethyloxalylglycine (DMOG) could further elevate HIF-1 and Parkin protein, enhance mitophagy, decrease mitochondrial dysfunction, and hyperalgesia. Furthermore, Park2 (encoding Parkin) knockout aggravated hyperalgesia and mitochondrial dysfunction in diabetic mice. Furthermore, mitophagy could not be activated and induced by HIF-1 agonist DMOG in Park2 diabetic mice. In this study, we first demonstrated that HIF-1 could upregulate mitophagy in the spinal cord of mice with DNP through modulating the Parkin signaling pathway, promoting new insights into the mechanisms and research of treatment strategies for patients with DNP.

During follow-up, patients severely affected by coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation (IMV), show symptoms of Post-Intensive Care Syndrome (PICS) such as cognitive impairment, psychological disability, and neuromuscular deconditioning. In COVID-19 pandemic, it is a priority to develop multidisciplinary post-acute care services to address the long-term multisystemic impact of COVID-19.

Leukocyte infiltration and persistence within peripheral nerves have been implicated in chronic nociception pathogenesis in murine peripheral neuropathy models. Endoneurial cytokine and chemokine expression contribute to leukocyte infiltration and maintenance of a pro-inflammatory state that delays peripheral nerve recovery and promotes chronic pain behaviors in these mice. However, there has been a failure to translate murine model data into safe and effective treatments for chronic neuropathic pain in peripheral neuropathy patients, or develop reliable biomarkers that may help diagnose or determine treatment responses in affected patients. Initial work showed that persistent sciatic nerve CD11b+ CD45+ leukocyte infiltration was associated with disease severity in three mouse models of inflammatory and traumatic peripheral neuropathies, implying a direct contributing role in disease pathogenesis. In support of this, CD11b+ leukocytes were also seen in the sural nerve biopsies of chronic neuropathic pain patients with three different peripheral neuropathies. Systemic CD11b antagonism using a validated function-neutralizing monoclonal antibody effectively treated chronic nociception following unilateral sciatic nerve crush injury (a representative traumatic neuropathy model associated with axonal degeneration and increased blood-nerve barrier permeability) and does not cause drug addiction behaviors in adult mice. These data suggest that CD11b could be an effective molecular target for chronic neuropathic pain treatment in inflammatory and traumatic peripheral neuropathies. Despite known murine peripheral neuropathy model limitations, our initial work suggests that early expression of pro-inflammatory cytokines, such as tissue inhibitor of metalloproteinases-1 may predict subsequent chronic nociception development following unilateral sciatic nerve crush injury. Studies aligning animal model investigation with observational data from well-characterized human peripheral neuropathies, including transcriptomics and proteomics, as well as animal model studies using a human clinical trial design should foster the identification of clinically relevant biomarkers and effective targeted treatments with limited addiction potential for chronic neuropathic pain in peripheral neuropathy patients.