Rejected

To review the evidence of acupuncture for acute and preventive treatment of migraine for further awareness of the effect of acupuncture for migraine.

Spinal cord injury (SCI) is a highly debilitating disease and is increasingly being recognized as an important global health priority. However, the mechanisms underlying SCI have not yet been fully elucidated, and effective therapies for SCI are lacking. Long noncoding RNAs (lncRNAs), which form a major class of noncoding RNAs, have emerged as novel targets for regulating several physiological functions and mediating numerous neurological diseases. Notably, gene expression profile analyses have demonstrated aberrant changes in lncRNA expression in rats or mice after traumatic or nontraumatic SCI. LncRNAs have been shown to be associated with multiple pathophysiological processes following SCI including inflammation, neural apoptosis, and oxidative stress. They also play a crucial role in the complications associated with SCI, such as neuropathic pain. At the same time, some lncRNAs have been found to be therapeutic targets for neural stem cell transplantation and hydrogen sulfide treatment aimed at alleviating SCI. Therefore, lncRNAs could be promising biomarkers for the diagnosis, treatment, and prognosis of SCI. However, further researches are required to clarify the therapeutic effects of lncRNAs on SCI and the mechanisms underlying these effects. In this study, we reviewed the current progress of the studies on the involvement of lncRNAs in SCI, with the aim of drawing attention towards their roles in this debilitating condition.

Hemorphins are hemoglobin β-chain-derived peptides initially known for their analgesic effects binding to the opioid receptors belonging to the family of G protein-coupled receptor (GPCR), as well as their physiological action on blood pressure. However, their molecular mechanisms in the regulation of blood pressure are not fully understood. Studies have reported an antihypertensive action the inhibition of the angiotensin-converting enzyme, a key enzyme in the renin-angiotensin system. In this study, we hypothesized that hemorphins may also target angiotensin II (AngII) type 1 receptor (AT1R) as a key GPCR in the renin-angiotensin system. To investigate this, we examined the effects of LVV-hemorphin-7 on AT1R transiently expressed in human embryonic kidney (HEK293) cells using bioluminescence resonance energy transfer (BRET) technology for the assessment of AT1R/Gαq coupling and β-arrestin 2 recruitment. Interestingly, while LVV-hemorphin-7 alone had no significant effect on BRET signals between AT1R and Gαq or β-arrestin 2, it nicely potentiated AngII-induced BRET signals and significantly increased AngII potency. The BRET data were also correlated with AT1R downstream signaling with LVV-hemorphin-7 potentiating the canonical AngII-mediated Gq-dependent inositol phosphate pathway as well as the activation of the extracellular signal-regulated kinases (ERK1/2). Both AngII and LVV-hemorphin-7-mediated responses were fully abolished by AT1R antagonist demonstrating the targeting of the active conformation of AT1R. Our data report for the first time the targeting and the positive modulation of AT1R signaling by hemorphins, which may explain their role in the physiology and pathophysiology of both vascular and renal systems. This finding further consolidates the pharmacological targeting of GPCRs by hemorphins as previously shown for the opioid receptors in analgesia opening a new era for investigating the role of hemorphins in physiology and pathophysiology the targeting of GPCR pharmacology and signaling.

Necrotising fasciitis is a rare but deadly bacterial infection causing soft tissue and fascial necrosis. It is associated with a mortality rate of 25%. It is characterised by; erythematous skin, which turns dusky blue before haemorrhagic bullae develop; localised pain; and inflammation. It is most commonly found in the extremities, the abdomen or the perineum but is rarely seen in the breast.

Chronic pain can pose a serious challenge in everyday life for many individuals globally, especially in developing countries, but studies explicitly exploring risk factors of chronic pain beyond demographic characteristics using survey data have been scarce. To address this problem, this study analyzed World Health Organization data on chronic pain in Ukraine to explore demographic, psychological, and treatment perception-related risk factors to chronic pain. We replicated previous reports of older age, female sex, married status, inadequate financial resources, and comorbidity of other physical conditions as significant demographic risk factors for chronic pain diagnosis but not necessarily for severe pain. We also found evidence for psychological risk factors and treatment perceptions as significant predictors for chronic pain diagnosis and its severity. These results provide a first step in examining beyond demographic risk factors for chronic pain diagnosis and severity and, instead, assessing potential psychological risk factors.

Opioid analgesics hijack the body's innate wellness machinery (eg, naloxone blocks the placebo effect) and alleviate both physical and emotional pain. Starting in the 1980s, marketing and advocacy created an opioid-centric pain relief strategy based on the idea that physicians undermanage pain and worry too much about addiction. The increase of prescription opioids in the ecosystem (along with a resurgence in heroin use) contributed to dependence, misuse, overdoses, and overdose deaths. Laws punishing undermanagement of pain from the opioid crisis combined with more recent laws punishing overprescription of opioids add to the difficulties orthopaedic surgeons have in managing the pain of surgery and acute injury. The substantial variation in pain intensity for nociception (actual or potential tissue damage) and the persistent use of opioids after healing is well established are both accounted for largely by psychosocial factors (stress, distress, and less effective coping strategies). When a patient has more pain than expected, surgeons should first rule out compartment syndrome and infection and then focus on a comprehensive team- and strategy-based approach that addresses these psychosocial factors.

Painful diabetic peripheral neuropathy (pDPN) is a debilitating complication of diabetes. The aim of this retrospective study was to investigate the effectiveness of a Chinese herbal medicine regimen-the modified Huangqi Guizhi Wuwu Decoction (HGWD)-in the treatment of moderate-severe pDPN. The primary objective was to estimate the improvement in neuropathic pain severity. The secondary objective was to assess the response of common symptoms to the treatment. The change in patients' blood glucose level during the whole treatment was also evaluated. By searching through our medical records of all the diabetic patients from January 2006 to January 2012, we identified and enrolled 30 moderate and severe pDPN patients in the study, for whom the treatment of neuropathic pain by regular pharmacotherapies had failed. The modified HGWD treatment was administered orally twice a day for 6 months. The numerical rating scale (NRS) level at month 6 was 2.57 ± 2.30, significantly improved compared with the baseline level of 6.03 ± 1.83 ( < 0.05). The amelioration of 3 common symptoms, namely, limb pain, limb numbness, and insomnia, was evident, and the major response of common symptoms at month 6 including limb pain, insomnia, and limb coldness was significantly increased compared with the results at month 3 ( < 0.05). Moreover, 2-hour postprandial blood glucose (2hPG) level decreased from 10.77 ± 1.29 mmol/L at baseline to 9.66 ± 0.60 mmol/L at month 6 ( < 0.05). No serious adverse events occurred throughout the treatment period. The modified HGWD was effective in the treatment of moderate and severe pDPN and can thus be offered as a new alternative treatment option for pDPN patients who failed to respond to regular pharmaceutical therapies.

Flunarizine (Fz) is a first-line prophylactic medication that is widely used in migraine. However, Fz has been recognized as a potential cause of drug-induced parkinsonism for a long time. However, to our knowledge, there has been no population-based subgroup analyses for Fz-induced parkinsonism (FIP) in migraine patients. Data were obtained from the Taiwan's National Health Insurance Research Database. The study comprised 6,470 migraine patients who were divided into two groups, based on their exposure or non-exposure to Fz. During the study period (2000-2012), the incidence rate of parkinsonism was 1.92 and 8.72 per 1,000 person-years in the control and Fz -treated groups, respectively. In the study population, the adjusted hazard ratio was 4.07 (95% confidence interval CI: 2.84-5.85). In 45-64-year old subjects and ≥ 65-year old subjects, the risk of FIP was 3.18 times (95% CI = 1.63-6.20) and 4.89 times (95% CI = 3.09-7.72) more than that in the controls. The Fz-treated subjects with comorbidities also had a higher risk (4.54, 95% CI: 3.14-6.57). An average annual cumulative Fz dose > 445 mg was accompanied by the greatest risk of FIP; Fz use for >60 days is a cut-off point for predicting future FIP. At the population level, this study showed a complete picture of FIP in migraine patients. FIP is associated with older age, history of comorbidities, exposure to high-dose of Fz, and longer duration of exposure to Fz.

The aim of the study was to assess the safety and efficacy of switching an etanercept originator to an etanercept biosimilar in rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, and ankylosing spondylitis patients.

Background Dengue is the most common vector-borne disease worldwide. It poses a significant health burden in tropical and subtropical countries. Common clinical presentations include retro-orbital pain, fever, headache, nausea, vomiting and aches and pains in the body. A severe form of dengue fever is known as dengue hemorrhagic fever (DHF) that includes signs of hemorrhage. Besides the typical signs and symptoms, atypical presentations of dengue include myositis, hepatitis and encephalitis. Hepatic involvement in dengue has varied presentations. This study aims to highlight the importance of acute hepatitis, an atypical presentation in dengue patients. Methods  We conducted a descriptive, cross-sectional study in the Medical Unit-1 of Bahawal Victoria Hospital, Bahawalpur, a tertiary-care hospital serving the area of Southern Punjab, Pakistan. The relevant medical records of 63 patients admitted with dengue-associated hepatitis to the Medical Unit-1 of Bahawal Victoria Hospital, Bahawalpur, between January 1, 2015 and December 1, 2016, were reviewed. Informed consent was given. Information regarding demographic variables and disease course was collected and analyzed. Results  This study included 55 men (87.3%) and eight (12.7%) women. Fifty (79.3%) patients were diagnosed with dengue fever (DF). Thirteen patients were managed on the lines of DHF. Out of the total 63 patients, only six were locals. The common clinical presentations in these patients included high fever, retro-orbital pain, severe headache, rash, dark-colored urine, bleeding problems and hepatomegaly. Higher levels of aspartate aminotransferase (AST) were noted in comparison to alanine transferase (ALT). Despite the complicated clinical course in some patients, all patients were managed successfully and discharged, except one. Conclusion The frequency of acute hepatitis in dengue patients is high, especially in young men. Early diagnosis and prompt treatment are necessary for better prognosis. Although no specific treatment guidelines are available, supportive treatment in a timely fashion can prevent complications. Transfusion with packed cell volume (PCV) and N-acetyl cysteine (NAC) has produced promising results.