Rejected

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.

Chronic pain affects almost 38% of the Portuguese adult population, with high costs for both patients and society. Those who suffer with chronic pain frequently complain of feeling misunderstood and of lack of support. These complaints are the main reason why support telephone lines for chronic pain were created in some countries. However, there is no scientific data supporting their creation or evaluating their performance. This paper presents a qualitative study protocol to assess patients and healthcare professionals' perspectives on the creation of a telephone support line for chronic pain. It constitutes the first step to attain the main goal of developing and implementing a functioning support line for chronic pain in Portugal. The methodology to assess patients and healthcare professionals' perspectives and needs is presented. In order to gather information as close to reality as possible, focus groups interviews were chosen as data sources. Given the present context of the COVID-19 pandemic, meetings will take place online, using a digital platform. All interviews will be transcribed verbatim, coded and synthesised into categories and main themes. Thematic analysis will be conducted using NVivo® V12 software, employing an iterative and reflexive approach. Finally, comparative and relational analysis will be performed in order to identify topics where patients and professionals converge or greatly diverge. The findings will be useful for grounding the creation of a telephone support line for chronic pain patients. Results dissemination will be important for policy-makers to develop a new perspective towards chronic pain services available.

Fibro-adipose vascular anomaly (FAVA) is a recently described complex and painful benign lesion found in young adults and the pediatric population composed of intramuscular vascular, fibrous, and adipose tissues. A previous report has identified the presence of somatic mosaic mutations in the gene for the catalytic subunit of phosphatidylinositol 3-kinase () in cases of FAVA. Herein, we present a case of FAVA found in a 23-year-old male patient who presented with chronic wrist pain associated with a mass, and we identified an associated somatic activating mutation (H1047R) in . We briefly review the relevant literature surrounding the identification and histology of FAVA, the known mutational spectrum, downstream signaling pathways, and relevant treatment modalities. Our case highlights the association between FAVA and somatic mosaic activating mutations.