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The noble gas argon has the potential to protect neuronal cells from cell death. So far, this effect has been studied in treatment after acute damage. Preconditioning using argon has not yet been investigated. In this study, human neuroblastoma SH-SY5Y cells were treated with different concentrations of argon (25%, 50%, and 74%; 21% O, 5% CO, balance nitrogen) at different time intervals before inflicting damage with rotenone (20 µM, 4 hours). Apoptosis was determined by flow cytometry after annexin V and propidium iodide staining. Surface expressions of Toll-like receptors 2 and 4 were also examined. Cells were also processed for analysis by western blot and qPCR to determine the expression of apoptotic and inflammatory proteins, such as extracellular-signal regulated kinase (ERK1/2), nuclear transcription factor-κB (NF-κB), protein kinase B (Akt), caspase-3, Bax, Bcl-2, interleukin-8, and heat shock proteins. Immunohistochemical staining was performed for TLR2 and 4 and interleukin-8. Cells were also pretreated with OxPAPC, an antagonist of TLR2 and 4 to elucidate the molecular mechanism. Results showed that argon preconditioning before rotenone application caused a dose-dependent but not a time-dependent reduction in the number of apoptotic cells. Preconditioning with 74% argon for 2 hours was used for further experiments showing the most promising results. Argon decreased the surface expression of TLR2 and 4, whereas OxPAPC treatment partially abolished the protective effect of argon. Argon increased phosphorylation of ERK1/2 but decreased NF-κB and Akt. Preconditioning inhibited mitochondrial apoptosis and the heat shock response. Argon also suppressed the expression of the pro-inflammatory cytokine interleukin-8. Immunohistochemistry confirmed the alteration of TLRs and interleukin-8. OxPAPC reversed the argon effect on ERK1/2, Bax, Bcl-2, caspase-3, and interleukin-8 expression, but not on NF-κB and the heat shock proteins. Taken together, argon preconditioning protects against apoptosis of neuronal cells and mediates its action via Toll-like receptors. Argon may represent a promising therapeutic alternative in various clinical settings, such as the treatment of stroke.

The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes. Its special anatomical and physiological structure renders it susceptible to nerve injury. The etiology of most primary trigeminal neuralgia is closely related to microvascular compression of the trigeminal root entry zone. This study aimed to develop an efficient in vitro model mimicking the glial environment of trigeminal root entry zone as a tool to investigate the effects of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor on the structural and functional integrity of trigeminal root entry zone and modulation of cellular interactions. Primary astrocytes and Schwann cells isolated from trigeminal root entry zone of postnatal rats were inoculated into a two-well silicon culture insert to mimic the trigeminal root entry zone microenvironment and treated with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. In monoculture, glial cell line-derived neurotrophic factor promoted the migration of Schwann cells, but it did not have effects on the migration of astrocytes. In the co-culture system, glial cell line-derived neurotrophic factor promoted the bidirectional migration of astrocytes and Schwann cells. Brain-derived neurotrophic factor markedly promoted the activation and migration of astrocytes. However, in the co-culture system, brain-derived neurotrophic factor inhibited the migration of astrocytes and Schwann cells to a certain degree. These findings suggest that glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor are involved in the regulation of the astrocyte-Schwann cell interaction in the co-culture system derived from the trigeminal root entry zone. This system can be used as a cell model to study the mechanism of glial dysregulation associated with trigeminal nerve injury and possible therapeutic interventions.

T cells are essential for a healthy life, performing continuously: immune surveillance, recognition, protection, activation, suppression, assistance, eradication, secretion, adhesion, migration, homing, communications, and additional tasks. This paper describes five aspects of normal beneficial T cells in the healthy or diseased brain. First, normal beneficial T cells are essential for normal healthy brain functions: cognition, spatial learning, memory, adult neurogenesis, and neuroprotection. T cells decrease secondary neuronal degeneration, increase neuronal survival after central nervous system (CNS) injury, and limit CNS inflammation and damage upon injury and infection. Second, while pathogenic T cells contribute to CNS disorders, recent studies, mostly in animal models, show that specific subpopulations of normal beneficial T cells have protective and regenerative effects in several neuroinflammatory and neurodegenerative diseases. These include Multiple Sclerosis (MS), Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), stroke, CNS trauma, chronic pain, and others. Both T cell-secreted molecules and direct cell-cell contacts deliver T cell neuroprotective, neuroregenerative and immunomodulatory effects. Third, normal beneficial T cells are abnormal, impaired, and dysfunctional in aging and multiple neurological diseases. Different T cell impairments are evident in aging, brain tumors (mainly Glioblastoma), severe viral infections (including COVID-19), chronic stress, major depression, schizophrenia, Parkinson's disease, Alzheimer's disease, ALS, MS, stroke, and other neuro-pathologies. The main detrimental mechanisms that impair T cell function are activation-induced cell death, exhaustion, senescence, and impaired T cell stemness. Fourth, several physiological neurotransmitters and neuropeptides induce by themselves multiple direct, potent, beneficial, and therapeutically-relevant effects on normal human T cells, via their receptors in T cells. This scientific field is called "Nerve-Driven Immunity". The main neurotransmitters and neuropeptides that induce directly activating and beneficial effects on naïve normal human T cells are: dopamine, glutamate, GnRH-II, neuropeptide Y, calcitonin gene-related peptide, and somatostatin. Fifth, "Personalized Adoptive Neuro-Immunotherapy". This is a novel unique cellular immunotherapy, based on the "Nerve-Driven Immunity" findings, which was recently designed and patented for safe and repeated rejuvenation, activation, and improvement of impaired and dysfunctional T cells of any person in need, by ex vivo exposure of the person's T cells to neurotransmitters and neuropeptides. Personalized adoptive neuro-immunotherapy includes an early ex vivo personalized diagnosis, and subsequent ex vivo → in vivo personalized adoptive therapy, tailored according to the diagnosis. The Personalized Adoptive Neuro-Immunotherapy has not yet been tested in humans, pending validation of safety and efficacy in clinical trials, especially in brain tumors, chronic infectious diseases, and aging, in which T cells are exhausted and/or senescent and dysfunctional.

Nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain, including neuropathic pain, bone cancer pain, inflammatory pain, and morphine tolerance. The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase, which leads to subsequent production of cGMP. cGMP then activates cGMP-dependent protein kinase (PKG), resulting in the activation of multiple targets such as the opening of ATP-sensitive K channels. The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules, as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain. In dorsal root ganglion neurons, natriuretic peptide binds to particulate guanylyl cyclase, generating and further activating the cGMP/PKG pathway, and it also contributes to the development of chronic pain. Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models. Notably the NO/cGMP signaling pathway induces expression of downstream effectors, exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain. These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain, and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy.

Colonoscopy-assisted percutaneous sigmoidopexy is a simple and swift procedure that does not require general anesthesia. While we first developed this procedure for treating sigmoid volvulus, we herein present the first case in which we used it to correct a complete rectal prolapse in an older patient. Existing treatment modalities for rectal prolapses are limited by high recurrence rates, greater invasiveness, and greater complications; thus, there is a need for minimally invasive techniques that are associated with lower recurrence rates and fewer complications. In this case, a woman in her 90s complained of persistent fecal incontinence, dysuria, anal pain, and difficulty in walking. She was diagnosed with a complete rectal prolapse of 15 cm and was treated with colonoscopy-assisted percutaneous sigmoidopexy. The sigmoid colon was tractioned colonoscopically and fixed to the abdominal wall to immobilize the prolapsed rectum. The patient developed no complications intraoperatively and postoperatively and experienced no recurrence during a 5-year postoperative period. This report documents the first case wherein colonoscopy-assisted percutaneous sigmoidopexy was used successfully to correct a complete rectal prolapse.

pioids are commonly used for treating chronic pain. However, with continued use, they may induce tolerance and/or hyperalgesia, which limits therapeutic efficacy. The human mechanisms of opioid-induced tolerance and hyperalgesia are significantly understudied, in part, because current models cannot fully recapitulate human pathology. Here, we engineered novel human spinal microphysiological systems (MPSs) integrated with plug-and-play neural activity sensing for modeling human nociception and opioid-induced tolerance. Each spinal MPS consists of a flattened human spinal cord organoid derived from human stem cells and a 3D printed organoid holder device for plug-and-play neural activity measurement. We found that the flattened organoid design of MPSs not only reduces hypoxia and necrosis in the organoids, but also promotes their neuron maturation, neural activity, and functional development. We further demonstrated that prolonged opioid exposure resulted in neurochemical correlates of opioid tolerance and hyperalgesia, as measured by altered neural activity, and downregulation of μ-opioid receptor expression of human spinal MPSs. The MPSs are scalable, cost-effective, easy-to-use, and compatible with commonly-used well-plates, thus allowing plug-and-play measurements of neural activity. We believe the MPSs hold a promising translational potential for studying human pain etiology, screening new treatments, and validating novel therapeutics for human pain medicine.

Chronic ischemic gastritis (CIG) requires early diagnosis and treatment as complications of thromboembolism can be fatal. Although computed tomography (CT) is useful in the diagnosis of CIG, it is difficult to diagnose from a patient's history, endoscopic findings, and tissue biopsy. Identification of the key findings that motivate computed tomography is an important issue. We report a case of CIG diagnosed by endoscopic findings of white patches of mucosa over time. A 63-year-old man presented with epigastric pain. He had a history of repeated gastric ulcers of an undetermined cause. We performed upper endoscopy and observed the appearance of multiple white patches on the gastric mucosa. Central vessel stenosis was considered, and aortic computed tomography revealed complete occlusion of the superior mesenteric artery and stenosis of the celiac artery. We carried out a surgical bypass and found no postoperative endoscopic mucosal changes or abdominal pain. White patch changes in the gastric mucosa over time during endoscopy may indicate CIG. This finding may help in the future diagnosis of CIG.

To describe the microscopic epithelial changes and the clinical outcomes of a patient treated with amniotic membrane eye drops (AMED) because of a persistent epithelial defect (PED) and a partial limbal stem cell deficiency (LSCD) after simple limbal epithelial transplantation (SLET) and deep anterior lamellar keratoplasty (DALK).

To report the clinical and anatomical features of an unusual case of acute idiopathic blind spot enlargement syndrome (AIBSES) with retinal vasculitis.

A 31-year-old woman presented with a headache and nausea. At presentation, her blood pressure was 114/71 mm Hg with left hemiparesis. Computed tomography revealed a large hyperdense mass in the right temporal lobe accompanied by intralesional calcifications and ventricular perforation. Spot signs were not identified, and cerebral angiography did not reveal any abnormal vasculature. The patient underwent emergency craniotomy assuming an intracerebral hemorrhage. Intraoperatively, grayish tumor tissue was found to intermingle with the clots. Microscopic findings of the tumor revealed neoplastic cells possessing perinuclear halo and cell atypia, and diffusely stained with glial fibrillary acidic protein, which were consistent with anaplastic oligodendrogliomas. However, genomic analyses of the tumor showed non-mutant isocitrate dehydrogenase 1 and telomerase reverse transcriptase, in addition to wild-type O6-methylguanine DNA-methyltransferase. These are equivalent to glioblastoma multiforme. Based on the results, we assumed that anaplastic oligodendrogliomas may develop apoplectic intratumoral hemorrhages that mimic intracerebral hemorrhage. Genomic exploration is recommended for such tumors, coupled with careful follow-up, owing to its potentially aggressive nature.

Intestinal malrotation in children is a rare aberration, due to a halt in the rotation and attachment of the primitive gut, it can be asymptomatic if the rotation terminates at 90 degrees, which manifests itself in unusual forms of appendicitis as in our observation, or dangerous in cases of inadequate common mesentery and worsened by small intestine volvulus. This 12-year-old boy experienced abdominal discomfort in the hypogastrium and left iliac fossa 4 days before admission. The pain had been developing in a feverish setting, and the clinical examination had revealed abdominal sensitivity. A biological inflammatory syndrome was detected throughout the biological workup, the CT scan allowed the diagnosis of acute appendicitis on a complete common mesentery, and the patient underwent a laparotomy appendectomy. Even though children frequently experience acute appendicitis in its conventional form, it is nevertheless highly challenging to identify in its atypical forms when intestinal malrotation is involved. An abdominopelvic CT scan is used to make the diagnosis, and appendectomy, preferably with laparoscopy, is the recommended course of action.

Back pain is a common condition affecting millions of individuals each year. A biopsychosocial approach to back pain provides the best clinical framework. A detailed history and physical examination with a thorough workup are required to exclude emergent or nonoperative etiologies of back pain. The treatment of back pain first uses conventional therapies including lifestyle modifications, nonsteroidal anti-inflammatory drugs, physical therapy, and cognitive behavioral therapy. If these options have been exhausted and pain persists for greater than 6 weeks, imaging and a specialist referral may be indicated.

Polytrauma patients often require medications to treat pain, treat agitation, and facilitate painful procedures. Though analgesia will be deferred in obtunded patients in profound shock, reduced-dose opioids or ketamine should be administered to unstable patients with severe pain with good mental status. Agitation commonly complicates polytrauma presentations, and is treated according to the danger it presents to patient and staff. Severe agitation can be effectively managed with dissociative-dose ketamine, which facilitates ongoing resuscitation, including CT. Severely painful procedures can be effectively facilitated by propofol or dissociative-dose ketamine, with continuous attention to ventilation and application of a step-by-step response to hypoventilation.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed pharmacologic therapies worldwide due to their therapeutic analgesic efficacy and relative tolerability. In the past several decades, various cardiovascular (CV) adverse events have emerged regarding both traditional NSAIDs (tNSAIDs) and cyclo-oxygenase 2 (COX-2) selective (coxibs). This review will provide an updated report on the CV risk profile of NSAIDs, focusing on several of the larger clinical trials, meta-analyses, and registry studies. We aim to provide rheumatologists with a framework for NSAID use in the context of rheumatologic chronic pain management. Recent findings: In patients with and without CV diseases, the use of NSAIDs, both tNSAIDs and coxibs, is associated with an increased risk of adverse CV events, myocardial infarction, heart failure, and cerebrovascular events. These CV risks have increased within weeks of coxib use and higher doses of tNSAIDs. The risk of adverse CV events is heterogenous across NSAIDs; naproxen and low-dose ibuprofen appear to have lower increased CV risk among NSAIDs. A variation in CV risk is associated with multiple factors, including NSAID class, COX-2 selectivity, treatment dose and duration, and baseline patient risk. Summary: Many important questions remain regarding the safety of NSAIDs and whether the culmination of research performed could inform us whether specific patient subtypes or NSAID class may have a more favorable profile. tNSAIDs such as naproxen and low-dose ibuprofen may have a lower CV risk profile, while coxibs have a more favorable GI risk profile. In general, any NSAID can be optimized if used at the lowest effective dose for the shortest amount of time, especially among individuals with increased CV risk.

Trigeminal neuralgia is characterized classically by recurrent, evocable, unilateral brief, electric, shocklike pains with an abrupt onset and cessation that affects one or more divisions of the trigeminal nerve. In recent years, the classification of trigeminal neuralgia has been updated based on further understanding. In this manuscript, the authors aim to explain the current understanding of the pathophysiology of trigeminal neuralgia, current diagnosis criteria, and the pharmacologic management and surgical treatments of options currently available.

Posterior reversible encephalopathy syndrome (PRES) following spine surgery was first documented in 2011. Reports have been rare, and sufficient consensus has not been established for clinical application. We presented a case of PRES following spine surgery. The patient was a 35-year-old woman with a history of hypertension who successfully received microendoscopic L5-S1 lumbar discectomy for lumbar disc herniation at L5-S1 under general anesthesia. Six hours after surgery, she suffered from headache, nausea, visual disturbance, and seizures. Magnetic resonance imaging revealed vasogenic edema in the occipital lobe, and she was diagnosed with PRES. Prompt symptomatic treatment resulted in a full recovery at 3 days after surgery. Subsequently, we reviewed the literature pertaining to PRES following spine surgery. The review of the relevant literature on PRES following spine surgery identified 12 cases (male, n = 2; female, n = 10; average age, 59.5 years). Approximately 92% patients received multi-level decompressive laminectomy and/or fusion. This case and the review of the relevant literature suggest that even minimally invasive spine surgery in a young woman with specific characteristics (eg, hypertension) can cause PRES.

Migraine is the second leading cause of years lived with disability. Patients with chronic migraine (CM) face enormous barriers in accessing care and in receiving an accurate diagnosis and appropriate treatment. This article reviews the following: epidemiology, definition, pathophysiology, medication overuse, and acute and preventive treatment.

Pruritus can be associated with chronic liver disease, particularly cholestatic liver disease. Although the pathophysiology is uncertain, there are a few proposed mechanisms and much is still being discovered. Workup involves an assessment to rule out a dermatologic, neurologic, psychogenic, or other underlying systemic disorder. First-line therapy is cholestyramine, which is generally well tolerated and effective. In those who fail cholestyramine, alternative drugs including rifampicin and μ-opioid receptor antagonists can be considered. If medical therapy is ineffective and pruritus is significant, alternative experimental therapies such as albumin dialysis, photopheresis, plasmapheresis, and biliary diversion can be considered.

Venous thromboembolism (VTE), which includes deep venous thrombosis and pulmonary embolism, is a cardiovascular event whose risk is increased in most inflammatory rheumatic diseases (IRDs). Mechanisms that increase VTE risk include antiphospholipid antibodies (APLs), particularly anticardiolipin antibodies, anti-beta2glycoprotein I antibodies and lupus anticoagulant present together, and inflammation-mediated endothelial injury. Patients with IRDs should receive long-term anticoagulation drugs when the risk of VTE recurrence is high. In the light of recent warnings from regulatory agencies regarding heightened VTE risk with Janus kinase inhibitors, these drugs should be initiated only after a careful assessment of VTE risk in those with IRDs.

We describe a unique case of 43-year-old male who presented with a persistent lateral knee pain caused by impingement between a femoral surgical screw and the iliotibial band, which was treated with surgical resection of the screw debris. The patient had reincidence of the symptoms and a magnetic resonance showed a wide and unrepairable tear of the iliotibial band, which was treated with interposition of a folded fasciae latae allograf. After the procedure, the patient had excellent clinical results and imaging evaluation showed progressive allograft integration. This case highlights the imaging findings and surgical aspects of an iliotibial band reconstruction, a novel surgical procedure that could be considered in patients with an unrepairable iliotibial band injury.

The most common headache disorders in adolescents are tension-type headache, migraine, and posttraumatic headache. These disorders in adolescents may have different characteristics than in adults but can be similarly disabling. This review highlights the emerging abortive and preventive treatment options for the adolescent population. Although future high-quality headache studies in this age group are still needed, current evidence for the safety and efficacy of various treatment modalities is also discussed.

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory condition of the breast. IGM is a benign condition, and is more typical in women of child-bearing age, with a recent history of pregnancy and breast feeding. Its clinical presentation can mimic inflammatory breast cancer or breast abscess. The etiology of IGM is not well defined, but proposed to be a localized immune reaction to the breast tissue without the presence of an underlying infectious condition. Here we report a case of a healthy 35-year-old female, with no story of pregnancy and lactation, who presented with sudden left breast lump, swelling and pain. She underwent first diagnostic ultrasound of the affected breast, then breast MR imaging was performed. A biopsy of the lesion was obtained, which revealed chronic granulomatous inflammation, confirming the diagnosis of GM. Furthermore, the patient was found to have had hyperprolactinemia secondary to a prolactinoma of the pituitary gland (PitNET) many years before, during her 20s, for which she had been treated with surgery.

Circulating polyunsaturated fatty acids (PUFAs) and lipid mediators were extracted from human red blood cells and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method encompassed 13 different PUFAs and lipid mediators, however, due to instrument capability only five were confidently quantified (EPA, ALA, AA, DHA, and LA). The extraction focused on free polyunsaturated fatty acids since they have a strong correlation with health in humans. The study design was a secondary analysis of the OPPERA-2 study of chronic overlapping pain conditions in adults. The data included are: a) raw LC-MS/MS data (.raw); b) processed data (.xlsx) including chromatographic peak area for each compound and a concentration (ng/mL) based on external calibration with internal standardization using pure analytical grade standards and heavy-isotope labeled internal standards; c) study participant demographics and phenotypes (.xlsx). This dataset consisting of circulating PUFA quantities measured in 605 humans has been made publicly available for analysis and interpretation.

Herpes zoster (HZ)-associated pain can lead to severe pain and reduced quality of life. Exploring effective treatment and the risk factors of zoster-associated pain has become important.

Cannabidiol (CBD) products are available nearly nationwide in the US and can coexist with medical or recreational programs. North Carolina (NC) is an example of a state with a program dedicated to integrating hemp cultivation and medicinal CBD exclusively, containing a multitude of retailers selling it as a primary product. The Food and Drug Administration (FDA) mandates that non-FDA approved CBD products cannot be marketed using medical or health-related claims and has sent warning letters to retailers violating these terms. We aim to characterize the online content of the NC CBD market by analyzing retailers' websites to determine whether hemp/CBD shops comply with FDA regulations in terms of medical claims and analyze the claimed CBD content and price of products offered online.

Felicola subrostratus is the only species of louse affecting domestic cats. Although it is considered a rare ectoparasite of pet cats, it occurs mainly in stray or shelter animals and is sometimes associated with intense pruritus and secondary bacterial infections. The aim of the present study was to evaluate the efficacy of a single dose of the topical formulation of esafoxolaner, eprinomectin and praziquantel (NexGard Combo, Boehringer Ingelheim) in cats for the treatment of naturally acquired chewing lice infestation in a multi-site, positive-control, blinded clinical field study. Thirty-one domestic cats presenting natural F. subrostratus infestation were included in the study. The animals had not been treated with any ectoparasiticide within the previous 60 days. After inclusion, each cat was randomly assigned to one of the two groups: group 1, 14 cats treated with NexGard Combo or group 2, 17 cats treated with Frontline Combo. A clinical evaluation was performed at days 0 (inclusion), 14 and 30 and consisted in scoring the skin lesions and symptoms and scoring the presence of lice. On day 30, all cats from both groups scored 0 for the presence of live lice and no dead lice were found, demonstrating 100% efficacy. The clinical scores significantly improved from day 0 to day 30 in both groups. During the 30 days of surveillance, no reinfestations due to the hatching of eggs were observed and none of the cats had any adverse reactions. Esafoxolaner demonstrated high efficacy for the treatment of F. subrostratus infestation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children typically results in similar symptoms with other viral respiratory agents including human adenoviruses (HAdVs). Mixed HAdV and SARS-CoV-2 infection (co-infection) in children might result in enhanced or reduced disease severity compared with single infections. The present study aims to investigate the rate of SARS-CoV2 and HAdV infection and also their coinfection and compare the two infections regarding their laboratory and clinical characteristics at hospital admission. A total of 360 combined oropharyngeal and nasopharyngeal swab samples from hospitalized children were examined by real-time PCR for the existence of the SARS-CoV-2 and HAdVs. The symptoms, the clinical characteristics and laboratory findings were retrieved and compared in SARS-CoV-2 and HAdVs positive cases. Of the total 360 suspected COVID-19 hospitalized children, 45 (12.5%) and 19 (5.3%) specimens were PCR-positive for SARS-CoV-2 and HAdV respectively. SARS-CoV-2 and HAdV co-infection was detected in 4 cases (1.1%). Regarding symptoms at hospital admission, fever in SARS-CoV-2 positive group was significantly higher than that in HAdV positive group [34 (85%) vs. 7 (46.7%), p = 0.012]. However, percentages of cases with sore throat, headache, fatigue, lymphadenopathy and conjunctivitis in HAdV positive group were significantly higher than those in SARS-CoV-2 positive group. SARS-CoV-2 and HAdV co-infected children showed mild respiratory symptoms. The present study revealed that SARS-CoV-2 positive children often appear to have a milder clinical course than children with respiratory HAdV infection and children co-infected with SARSCoV-2 and HAdV had less-severe disease on presentation.

Postherpetic neuralgia (PHN) is a clinical puzzle, especially in patients who still suffered from moderate and severe pain after standard treatment. This single-center, double-blinded, randomized controlled, prospective, and non-inferiority study observed the safety and effectiveness of the epidural application of morphine or hydromorphone, trying to provide an alternative method for those patients with refractory PHN. Eighty PHN patients with a visual analogue scale (VAS) still greater than 50 mm after routine management were randomly divided into two groups according to 1:1, respectively. One group received epidural morphine (EMO group), and the other group received epidural hydromorphone (EHM group). VAS, the number of breakthrough pain, quality of life (QOL), and anxiety/depression assessment (GAD-7 and PHQ-9 scores) were also observed before treatment, at 1, 3, 7, 14, 21, 28, 60, and 90 days after treatment, as well as side effects. Opioid withdrawal symptoms (OWSs) were also measured from 3 to 28 days after treatment. The EHM group was non-inferior to the EMO group in terms of the VAS decrease relative to baseline (VDRB) after 1-week treatment. The VAS of the two groups on all days after treatment was significantly lower than the corresponding baseline findings ( < 0.05). The breakthrough pain (BTP) decreased significantly after treatment and lasted until 14 days after treatment ( < 0.05). There was no significant difference in BTP between the two groups at each time point ( > 0.05). In terms of the QOL, GAD-7, and PHQ-9 outcomes, those were significantly improved after treatment ( < 0.05), and there was no difference between the two groups ( > 0.05). No significant AE difference across the two groups was observed in this study. Few reports of OWS were found in this trial, and there were no significant differences between the two groups ( > 0.05). EHM was non-inferior to EMO in terms of the VDRB after 1-week treatment. For patients with VAS still greater than 50 mm after standard treatment, short-term application of EMO or EHM can ameliorate intractable pain, improve the quality of life, and have no obvious side effects. Short-term epidural opioid application will not lead to the appearance of OWS.

Osteoarthritis (OA) is an age-related chronic progressive degenerative disease that induces persistent pain and disabilities. The development of OA is a complex process, and the risk factors are various, including aging, genetics, trauma and altered biomechanics. Inflammation and immunity play an important role in the pathogenesis of OA. JAK/STAT pathway is one of the most prominent intracellular signaling pathways, regulating cell proliferation, differentiation, and apoptosis. Inflammatory factors can act as the initiators of JAK/STAT pathway, which is implicated in the pathophysiological activity of chondrocyte. In this article, we provide a review on the importance of JAK/STAT pathway in the pathological development of OA. Potentially, JAK/STAT pathway becomes a therapeutic target for managing OA.

Patients suffering from severe trauma experience substantial immunological stress. Lung injury is a known risk factor for the development of posttraumatic complications, but information on the long-term course of the pulmonary inflammatory response and treatment with mild hypothermia are scarce.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can potentially develop after SARS-CoV-2 infection in children. Gastrointestinal manifestation in MIS-C can mimic acute abdomen, potentially leading to unnecessary surgical treatment. Immune-mediated mechanisms seem to be a determining factor in its pathogenesis, and histological studies can help to shed light on this aspect. We describe three cases of children diagnosed with MIS-C that underwent appendectomy.

Names are a reflection of identity and often have personal meaning. The chronic mispronunciation of names can undermine one's identity and be experienced as a microaggression. This workshop aims to provide historical context for names as well as resources for correct name pronunciation.

Wounds can be divided into two categories, acute and chronic. Acute wounds heal through the normal wound healing process. However, chronic wounds take longer to heal, leading to inflammation, pain, serious complications, and an economic burden of treatment costs. In addition, diabetes and burns are common causes of chronic wounds that are difficult to treat. The rapid and thorough treatment of chronic wounds, including diabetes wounds and burns, represents a significant unmet medical need. Wound dressings play an essential role in chronic wound treatment. Various biomaterials for wound healing have been developed. Among these, hydrogels are widely used as wound care materials due to their good biocompatibility, moisturizing effect, adhesion, and ductility. Wound healing is a complex process influenced by multiple factors and regulatory mechanisms in which stem cells play an important role. With the deepening of stem cell and regenerative medicine research, chronic wound treatment using stem cells has become an important field in medical research. More importantly, the combination of stem cells and stem cell derivatives with hydrogel is an attractive research topic in hydrogel preparation that offers great potential in chronic wound treatment. This review will illustrate the development and application of advanced stem cell therapy-based hydrogels in chronic wound healing, especially in diabetic wounds and burns.

The opioid crisis brought scrutiny to opioid prescribing. Understanding how opioid prescribing patterns and corresponding patient outcomes changed during the epidemic is essential for future targeted policies. Many studies attempt to model trends in opioid prescriptions therefore understanding the temporal shift in opioid prescribing patterns across populations is necessary. This study characterized postoperative opioid prescribing patterns across different populations, 2010-2020.

Arterial dissections, which involve an abrupt tear in the wall of a major artery resulting in the intramural accumulation of blood, are a family of catastrophic disorders causing major, potentially fatal sequelae. Involving diverse vascular beds, including the aorta or coronary, cervical, pulmonary, and visceral arteries, each type of dissection is devastating in its own way. Traditionally they have been studied in isolation, rather than collectively, owing largely to the distinct clinical consequences of dissections in different anatomical locations – such as stroke, myocardial infarction, and renal failure. Here, we review the shared and unique features of these arteriopathies to provide a better understanding of this family of disorders. Arterial dissections occur commonly in the young to middle-aged, and often in conjunction with hypertension and/or migraine; the latter suggesting they are part of a generalized vasculopathy. Genetic studies as well as cellular and molecular investigations of arterial dissections reveal striking similarities between dissection types, particularly their pathophysiology, which includes the presence or absence of an intimal tear and vasa vasorum dysfunction as a cause of intramural hemorrhage. Pathway perturbations common to all types of dissections include disruption of TGF-β signaling, the extracellular matrix, the cytoskeleton or metabolism, as evidenced by the finding of mutations in critical genes regulating these processes, including , collagen genes, fibrillin and TGF-β receptors, or their coupled pathways. Perturbances in these connected signaling pathways contribute to phenotype switching in endothelial and vascular smooth muscle cells of the affected artery, in which their physiological quiescent state is lost and replaced by a proliferative activated phenotype. Of interest, dissections in various anatomical locations are associated with distinct sex and age predilections, suggesting involvement of gene and environment interactions in disease pathogenesis. Importantly, these cellular mechanisms are potentially therapeutically targetable. Consideration of arterial dissections as a collective pathology allows insight from the better characterized dissection types, such as that involving the thoracic aorta, to be leveraged to inform the less common forms of dissections, including the potential to apply known therapeutic interventions already clinically available for the former.

Along with uric acid, which is the primary driving factor of gout, downstream inflammatory mediators have been shown to be involved in the pathogenesis of gouty arthritis flares. Extracorporeal haemadsorption is an emerging technology for the treatment of dysregulated inflammatory states by effectively removing cytokines from the bloodstream. Whether haemadsorption was effective in refractory gout flares has not been reported in the literature.

The aim: To evaluate the clinical characteristics of complications and side effects of CSE and DPE as a method of analgesia.

To explore the effect of rapid rehabilitation nursing on inflammation and liver function in patients with primary liver cancer (PLC) after laparoscopic radical resection.

Mood disorders, such as anxiety and depression, are commonly found in people suffering from chronic pain. Serotonin-norepinephrine reuptake inhibitors (SNRIs) are potential in alleviating chronic pain and are the first-line option for anxiety disorder. The anterior cingulate cortex (ACC) plays a vital role in chronic pain-induced anxiety, but its role in the therapeutic effects of SNRIs remains largely unclear. We used complete Freund's adjuvant (CFA) in this current study to induce chronic inflammatory pain. Von Frey test was used to measure the mechanical withdrawal threshold. The elevated plus maze test (EPM) and the novelty-suppressed feeding test (NSF) were used to measure anxiety-like behaviors. Twenty-one days after the modeling, anxiety-like behaviors were successfully induced in CFA mice, and a 3-day intraperitoneal injection of duloxetine attenuated such behaviors. While, mechanical hyperalgesia was also improved. Then, we locally infused duloxetine in ACC for 3 days only to find out its analgesic effect in CFA mice. Furthermore, we used fiber photometry to discover decreased glutamatergic excitability and enhanced serotonin concentration in ACC after intraperitoneal injection of duloxetine. Overall, this study proposed a potential mechanism for the analgesic effect of duloxetine and shed light on further studies on the mechanism of its anxiolytic effect in chronic pain-induced anxiety.

Children with underlying medical conditions potentially develop severe illness from Coronavirus disease 2019 (COVID-19). The use of vaccines against COVID-19 is currently recommended for the pediatric population. The COVID-19 vaccine has a temporal association with the occurrence of myocarditis. Although most patients with COVID-19 vaccination-associated myocarditis (C-VAM) exhibit a mild clinical course and rapid recovery, C-VAM potentially causes electrical instability and sudden cardiac death. Herein, we report the case of a 17-year-old woman who presented with chest pain and syncope following the first dose of the messenger RNA COVID-19 vaccine. The patient's heart function was impaired, and nonsustained ventricular tachycardia was frequent. Cardiac magnetic resonance (CMR) imaging satisfied the criteria for myocarditis. Despite the administration of immunomodulatory drugs, the patient's heart function was not fully restored, and the concentration of cardiac enzymes remained above the normal range. Persistence of late gadolinium enhancement was observed on short-term follow-up CMR imaging. Although most patients with C-VAM exhibit mild symptoms, significant cardiac arrhythmias potentially occur. Furthermore, some patients with C-VAM demonstrate prolonged impaired heart function and sustained late gadolinium enhancement on follow-up CMR imaging. Therefore, monitoring of electrical and functional cardiac abnormalities in patients with C-VAM is crucial and the long-term outcomes and prognosis of patients with C-VAM require further investigation.

A third of patients with primary biliary cholangitis (PBC) experience poorly understood cognitive symptoms, with a significant impact on quality of life (QOL), and no effective medical treatment. Allopregnanolone, a neurosteroid, is a positive allosteric modulator of gamma-aminobutyricacid-A (GABA-A) receptors, associated with disordered mood, cognition, and memory. This study explored associations between allopregnanolone and a disease-specific QOL scoring system (PBC-40) in PBC patients.

Functional Motor Disorders (FMDs) represent nosological entities with no clear phenotypic characterization, especially in patients with multiple (combined FMDs) motor manifestations. A data-driven approach using cluster analysis of clinical data has been proposed as an analytic method to obtain non-hierarchical unbiased classifications. The study aimed to identify clinical subtypes of combined FMDs using a data-driven approach to overcome possible limits related to "a priori" classifications and clinical overlapping.

Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is an acronym for synovitis, pustulosis, acne, hyperostosis, and osteitis, and clinically manifests as dermatological and musculoskeletal damage. Two major manifestations that co-occur in a single patient are rare.

Prurigo nodularis (PN) is a chronic heterogeneous inflammatory skin disease.

Calcitonin gene-related peptide (CGRP) pathway-targeted treatments have been shown to be efficacious in the prevention of episodic and chronic migraine. Currently approved therapies include monoclonal antibodies (mAbs) that target CGRP (eptinezumab, fremanezumab, and galcanezumab) and the CGRP receptor (erenumab), and small molecule CGRP receptor antagonists (atogepant and rimegepant). While CGRP pathway-targeted treatments are generally well-tolerated, in a review article by Holzer and Holzer-Petsche published in the January 2022 issue of the authors discussed the role of the CGRP pathway in gastrointestinal physiology, with a specific focus on constipation associated with the use of CGRP pathway-targeted treatments. The authors state that real-world surveys have shown constipation to be a "major adverse event" reported in "more than 50% of patients treated with erenumab, fremanezumab or galcanezumab." As described in the current commentary, the limited data from the cited references in the review article by Holzer and Holzer-Petsche do not support that statement.

The term 'opioids' refers to both the natural compounds ('opiates') which are extracted from the opium poppy plant () and their semi-synthetic and synthetic derivatives. They all possess relatively similar biochemical profiles and interact with the opioid receptors within the human body to produce a wide range of physiological effects. They have historically been used for medicinal purposes, their analgesic and sedative effects, and in the management of chronic and severe pain. They have also been used for non-medicinal and recreational purposes to produce feelings of relaxation, euphoria and well-being. Over the last decade, the emergence of an illegal market in new synthetic opioids has become a major global public health issue, associated with a substantial increase in unintentional overdoses and drug-related deaths. Synthetic opioids include fentanyl, its analogues and emerging non-fentanyl opioids. Their popularity relates to changes in criminal markets, pricing, potency, availability compared to classic opioids, ease of transport and use, rapid effect and lack of detection by conventional testing technologies. This article expands on our previous review on new psychoactive substances. We now provide a more in-depth review on synthetic opioids and explore the current challenges faced by people who use drugs, healthcare professionals, and global public health systems.

Medical cannabis is commonly and increasingly used by Canadians to manage chronic pain. As of March 2021, Health Canada reported that approximately 300,000 Canadians who were authorized to access medical cannabis, which is more than a 1000% increase from the 24,000 registered in 2015. Physicians, however, receive limited information on therapeutic cannabis during their training, and their perceptions regarding this therapeutic option are uncertain. This study focused on exploring attitudes and beliefs of pain physicians regarding medical cannabis for the management of chronic noncancer pain.

Temozolomide is an oral alkylating agent with moderate side effects compared to other agents. However, the development of secondary malignancies following temozolomide has been reported. We describe the first case of primary central nervous system lymphoma (PCNSL) occurrence following glioblastoma treatment. A 69-year-old male was admitted to our hospital with a chief complaint of headache and dysnomia for six months. A ring-enhanced mass of the left temporal lobe was observed and gross total removal was performed. The tumor was pathologically diagnosed as isocitrate dehydrogenase (IDH)-wildtype glioblastoma and he received 60 Gy of local irradiation in 30 fractions, with concurrent temozolomide at a dose of 75 mg/m. Grade 2 lymphopenia was discovered during treatment. Within 6 months, the patient developed a right parietal intra-axial tumor without local recurrence and was given 150-200 mg/m oral temozolomide for five consecutive days of a 28-day cycle. Within five cycles of temozolomide, complete remission was observed; however, after the eighth cycle, a new lesion in the right temporal lobe was discovered. Surgical removal was performed and histological findings were consistent with diffuse large B-cell lymphoma, and the final diagnosis of Epstein-Barr virus negative PCNSL was established.

The selection strategy of non-steroidal anti-inflammatory drugs (NSAIDs) for migraine is hard to judge whether it is effective, leading to unnecessary exposure to insufficient or lengthy treatment trials. The goal of the study was to investigate potential predictors of NSAIDs efficacy in migraine therapy and to explore their influence on efficacy. 610 migraine patients were recruited and assigned into responders and non-responders. Potential predictors among demographic and clinical characteristics for NSAIDs efficacy were extracted using multivariable logistic regression (LR) analysis, and were applied to construct prediction models machine learning (ML) algorithms. Finally, Cochran-Mantel-Haenszel tests were used to examine the impact of each predictor on drug efficacy. Multivariate LR analysis revealed migraine-related (disease duration, headache intensity and frequency) and psychiatric (anxiety, depression and sleep disorder) characteristics were predictive of NSAIDs efficacy. The accuracies of ML models using support vector machine, decision tree and multilayer perceptron were 0.712, 0.741, and 0.715, respectively. Cochran-Mantel-Haenszel test showed that, for variables with homogeneity of odds ratio, disease duration, frequency, anxiety, and depression and sleep disorder were associated with decreased likelihood of response to all NSAIDs. However, the variabilities in the efficacy of acetaminophen and celecoxib between patients with mild and severe headache intensity were not confirmed. Migraine-related and psychiatric parameters play a critical role in predicting the outcomes of acute migraine treatment. These models based on predictors could optimize drug selection and improve benefits from the start of treatment.

Myofascial pain syndrome (MPS) is one of the most common causes of chronic skeletal muscle pain, which is closely related to skeletal muscle myofascial trigger point (MTRP). Since there is no first-line treatment for MPS, we investigated Loxoprofen Sodium Cataplasm combined with physiotherapy as a non-invasive therapy in patients at different levels to a protocol with superior efficacy that is safe and easy to promote. Moreover, this treatment could represent an alternative therapeutic strategy for low-income patients to a safer, more convenient, and more economical treatment scheme.

Electro-acupuncture (EA) has promising effects on diastasis rectus abdominis (DRA), defined as a separation of the two muscle bellies of rectus abdominis. To study, there is scant knowledge or scarce high-quality evidence.

Endometriosis is a common gynecological disease, characterized by the presence of endometrial-like lesions outside the uterus. This debilitating disease causes chronic pelvic pain and infertility with limited therapeutics. Chemerin is a secretory protein that acts on CMKLR1 (Chemokine-Like Receptor 1) to execute functions vital for immunity, adiposity, and metabolism. Abnormal chemerin/CMKLR1 axis underlies the pathological mechanisms of certain diseases including cancer and inflammatory diseases, but its role in endometriosis remains unknown. Herein, our results showed that chemerin and CMKLR1 are up-regulated in endometriotic lesions by analyzing the human endometriosis database and murine model. Knockdown of chemerin or CMKLR1 by shRNA led to mesenchymal-epithelial transition (MET) along with compromised viability, migration, and invasion of hEM15A cells. Most importantly, 2-(α-naphthoyl) ethyltrimethylammonium iodide (α-NETA), a small molecule antagonist for CMKLR1, was evidenced to exhibit profound anti-endometriosis effects (anti-growth, anti-mesenchymal features, anti-angiogenesis, and anti-inflammation) and . Mechanistically, α-NETA exhibited a dual inhibition effect on PI3K/Akt and MAPK/ERK signaling pathways in hEM15A cells and murine endometriotic grafts. This study highlights that the chemerin/CMKLR1 signaling axis is critical for endometriosis progression, and targeting this axis by α-NETA may provide new options for therapeutic intervention.

Patients with the genetic blistering skin condition epidermolysis bullosa (EB) report severe pain as a consequence of skin and mucous membrane lesions including blisters, wounds, and scars. Adequate symptom alleviation is not often achieved using conventional pharmacologic interventions. Finding novel approaches to pain care in EB is imperative to improve the quality of life of patients living with EB. There are several anecdotal reports on the use of cannabinoid-based medicines (CBMs) by EB patients to reduce the burden of symptoms. However, controlled clinical investigations assessing these reported effects are lacking. As the pain quality "unpleasantness" delineates EB pain, we hypothesize the modulation of affective pain processing in the brain by way of intervention with CBMs comprising the cannabinoids Δ-9-tetrahydrocannabinol and cannabidiol-objectified by functional magnetic resonance imaging (fMRI). The C4EB study is an investigator-initiated, single-centre, randomized, double-blind, placebo-controlled and crossover trial. Adult patients with the diagnosis epidermolysis bullosa, reporting chronic pain will be eligible to participate. Following baseline measurements, participants will be randomized to receive the sublingually administered interventions placebo and Transvamix® in forward or reversed orders, each for two weeks and separated by a washout. The primary outcome is the difference in numeric rating scale pain scores between grouped interventions, using affective descriptors within the Short-form McGill Pain Questionnaire-2. Secondary outcomes include pain self-efficacy, concomitant analgesic medication-use and adverse events. Additionally, fMRI will be employed to assess brain connectivity related to neuroanatomic pain circuits at baseline, placebo and Transvamix® interventions. The study was approved by the ethical committee at the University Medical Center of Groningen in the Netherlands. Results will be submitted for publication in a peer-reviewed journal. Trial registration number: Netherlands Trial Register: NL9347 (Acronym: C4EB).

Chronic pain is often accompanied by emotional dysfunction. Transcranial direct current stimulation (tDCS) has been used for reducing pain, depressive and anxiety symptoms in chronic pain patients, but its therapeutic effect remains unknown.

Patients with Gaucher disease (GD) have progressive bone involvement that clinically presents with debilitating bone pain, structural bone changes, bone marrow infiltration (BMI), Erlenmeyer (EM) flask deformity, and osteoporosis. Pain is referred by the majority of GD patients and continues to persist despite the type of therapy. The pain in GD is described as chronic deep penetrating pain; however, sometimes, patients experience severe acute pain. The source of bone pain is mainly debated as nociceptive pain secondary to bone pathology or neuropathic or inflammatory origins. Osteocytes constitute a significant source of secreted molecules that coordinate bone remodeling. Osteocyte markers, sclerostin (SOST) and Dickkopf-1 (DKK-1), inactivate the canonical Wnt signaling pathway and lead to the inhibition of bone formation. Thus, circulated sclerostin and DKK-1 are potential biomarkers of skeletal abnormalities. This study aimed to assess the circulating levels of sclerostin and DKK-1 in patients with GD and their correlation with clinical bone pathology parameters: pain, bone mineral density (BMD), and EM deformity. Thirty-nine patients with GD were classified into cohorts based on the presence and severity of bone manifestations. The serum levels of sclerostin and DKK-1 were quantified by enzyme-linked immunosorbent assays. The highest level of sclerostin was measured in GD patients with pain, BMI, and EM deformity. The multiparameter analysis demonstrated that 95% of GD patients with pain, BMI, and EM deformity had increased levels of sclerostin. The majority of patients with elevated sclerostin also have osteopenia or osteoporosis. Moreover, circulating sclerostin level increase with age, and GD patients have elevated sclerostin levels when compared with healthy control from the same age group. Pearson's linear correlation analysis showed a positive correlation between serum DKK-1 and sclerostin in healthy controls and GD patients with normal bone mineral density. However, the balance between sclerostin and DKK-1 waned in GD patients with osteopenia or osteoporosis. In conclusion, the osteocyte marker, sclerostin, when elevated, is associated with bone pain, BMI, and EM flask deformity in GD patients. The altered sclerostin/DKK-1 ratio correlates with the reduction of bone mineral density. These data confirm that the Wnt signaling pathway plays a role in GD-associated bone disease. Sclerostin and bone pain could be used as biomarkers to assess patients with a high risk of BMI and EM flask deformities.

The incidence of thyroid diseases has tripled in the last three decades, and the prevalence is rising rapidly irrespective of gender and genetics. This study aimed to assess the Knowledge, awareness of risk factors, and perceptions of thyroid disease among the Saudi Community in Saudi Arabia.

Ganciclovir (GCV) is a prodrug nucleoside analogue and is clinically used as antiviral drug for the treatment of cytomegalovirus (CMV) and other infections. Based on the potential anti-inflammatory activity of GCV, this study aimed to investigate the therapeutic effects of ganciclovir on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC), which may involve cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathways. Our results demonstrated that incubation of GCV (50 μM) inhibited cGAS-STING pathway in macrophage RAW264.7 cells. Then, it was found that intestinal cGAS-STING pathways were upregulated in UC patients, Crohn's disease colitis (CD) patients, and DSS-induced colitis mice. Intraperitoneal injection of low-dose GCV (10 mg/kg/day) attenuated DSS-induced colitis and abdominal pain in mice. GCV treatment significantly inhibited the upregulation of cGAS-STING pathway in DSS-induced colitis mice. Moreover, DSS-induced colitis and gut dysbiosis was markedly attenuated in STING deficient mice compared with that of wild-type (WT) mice. Finally, there was lacking therapeutic effect of GCV on DSS-induced colitis in STING deficient mice. Together, our results indicated that low-dose GCV ameliorated DSS-induced UC in mice, possibly through inhibiting STING signaling in colonic macrophages, indicating that GCV may be useful for the treatment of UC.

Low back pain is a heterogeneous disease. Myofascial pain and enthesopathy of the quadratus lumborum muscle are important causes of lower back and/or buttock pain. However, a concrete, safe, and effective injection technique for the treatment of trigger points and enthesopathy in the quadratus lumborum muscle has not yet been developed.

Children and adolescents with chronic pain are at an increased risk of suicidality. This narrative review article aims to inform clinical practice in the assessment and management of suicidality in youth with chronic pain. The article begins with a survey of the background and prevalence of youth with chronic pain. A review of the current evidence behind the increased risk of suicidality in youth with chronic pain follows. Contextualization of this data with general tenets of child and adolescent suicide risk and risk assessment is provided. Suicidology theory including the interpersonal theory of suicide is overviewed to help clinicians to conceptualize the reviewed data. Guiding parameters for the suicide risk assessment and management planning is presented. Concluding recommendations are made to guide clinical practice in the assessment and management of suicidality in youth with chronic pain.

Considerable evidence suggests that there are significant ethnic/racial differences in the experience of pain among individuals suffering from chronic musculoskeletal conditions. Additionally, low levels of vitamin D have been associated with pain severity. Further, vitamin D deficiency is more prevalent in Non-Hispanic Black (NHB) individuals compared to Non-Hispanic Whites (NHW).

Internal jugular agenesis is a vascular malformation that is often associated with a history of recurrent headache. Due to the resulting abnormalities in intracranial venous drainage, it may be complicated by neurological dysfunction, such as intracranial hypertension, intracranial micro-thromboses, and neurodegenerative diseases such as multiple sclerosis. The simultaneous presence of jugular vein agenesis and thrombosis is possible in cases of acute illness, hormonal treatment, pregnancy, hypomobility, or venous drainage abnormalities (VDA) (e.g., May-Thurner syndrome). In particular, the literature still lacks data on thromboprophylaxis in pregnant women with jugular vein agenesis. Here, we report a positive experience with prophylaxis using enoxaparin during pregnancy in a patient with internal jugular agenesis.

Spontaneous internal carotid artery dissection (CAD) is a relatively rare disease, with patients, including those with bilateral CAD, often recovering after conservative therapy. However, patients with symptomatic and progressive disease require urgent carotid artery stenting (CAS). If CAD extends to the petrous portion of the internal carotid artery (ICA), it is difficult to treat with a carotid stent alone. This report describes a rare case of consecutive spontaneous bilateral CAD that required an intracranial stent with an interval of 4 years between the first and second CAS. A 58-year-old man with a history of dyslipidemia was admitted for transient ischemic attacks. He underwent CAS with carotid and intracranial stents on the third day for the left CAD due to exacerbation of symptoms under antithrombotic therapy and new stroke on magnetic resonance imaging (MRI). He recovered well. However, 4 years after the initial treatment, the patient was admitted again because of a sudden headache, photophobia, and transient weakness of the left lower limb. He was diagnosed with CAD on the contralateral side. He underwent CAS with carotid and intracranial stents due to progressive neurological deterioration under antithrombotic therapy. After treatment, he was clinically stable without any new infarctions on a follow-up MRI. He was discharged without neurological deficit. Our case of bilateral internal CAD treatment demonstrated that early revascularization with immediate stenting with carotid and intracranial stents in CAD contributes to the prevention of extensive neurological damage, thereby providing a favorable outcome in some cases.

Opioids have been commonly used to treat chronic pain, but they are associated with significant morbidity and mortality. Cannabis has been advocated as an alternative; however, a growing number of patients are now using a combination of opioid and cannabis and the impact of this combination is not well-studied.

Fibromyalgia (FM) is a diagnostically controversial syndrome characterized by chronic widespread pain, fatigue, sleep difficulties, cognitive dysfunction, and mental health symptoms. Though online peer support groups (OPSGs) may help persons with FM access support and information, there are concerns that such groups can be harmful.

Systematic review.

Chronic pain is one of the major health problems worldwide in recent years, and acupuncture-related therapies have been reported to have definite analgesic effects. However, it is still unclear which treatment is the most effective. Our systematic review and network meta-analysis protocol aims to summarize the evidence and determine the most effective method to treat the chronic musculoskeletal pain.

A number of different medications are used in combination with intrathecal bupivacaine for cesarean section anesthesia, but their relative efficacy has not been well established.

Osteoarthritis (OA) is a major cause of pain, disability, and social burden in the elderly throughout the world. Although many studies focused on the molecular mechanism of OA, its etiology remains unclear. Therefore, more biomarkers need to be explored to help early diagnosis, clinical outcome measurement, and new therapeutic target development. Our study aimed to retrieve the potential hub genes of osteoarthritis (OA) by weighted gene co-expression network analysis (WGCNA) and assess their clinical utility for predicting OA. Here, we integrated WGCNA to identify novel OA susceptibility modules and hub genes. In this study, we first selected 477 and 834 DEGs in the GSE1919 and the GSE55235 databases, respectively, from the Gene Expression Omnibus (GEO) website. Genes with -value<0.05 and | logFC | > 1 were included in our analysis. Then, WGCNA was conducted to build a gene co-expression network, which filtered out the most relevant modules and screened out 23 overlapping WGCNA-derived hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses elucidated that these hub genes were associated with cell adhesion molecules pathway, leukocyte activation, and inflammatory response. In addition, we conducted the protein-protein interaction (PPI) network in 23 hub genes, and the top four upregulated hub genes were sorted out (CD4, SELL, ITGB2, and CD52). Moreover, our nomogram model showed good performance in predicting the risk of OA (C-index = 0.76), and this model proved to be efficient in diagnosis by ROC curves (AUC = 0.789). After that, a single-sample gene set enrichment (ssGSEA) analysis was performed to discover immune cell infiltration in OA. Finally, human primary synoviocytes and immunohistochemistry study of synovial tissues confirmed that those candidate genes were significantly upregulated in the OA groups compared with normal groups. We successfully constructed a co-expression network based on WGCNA and found out that OA-associated susceptibility modules and hub genes, which may provide further insight into the development of pre-symptomatic diagnosis, may contribute to understanding the molecular mechanism study of OA risk genes.

Dehydroevodiamine (DHE) is a quinazoline alkaloid isolated from (EF, in Chinese, Rutaceae family), a well-known traditional Chinese medicine (TCM) which is clinically applied to treat headache, abdominal pain, menstrual pain, abdominal distension, vomiting, acid regurgitation, Modern research demonstrates that DHE is one of the main components of EF. In recent years, DHE has received extensive attention due to its various pharmacological activities. This review is the first to comprehensively summarize the current studies on pharmacokinetics profiles, pharmacological properties, and toxicological risks of DHE in diverse diseases. Pharmacokinetic studies have shown that DHE has a relatively good oral absorption effect in the mean concentration curves in rat plasma and high absorption in the gastrointestinal tract. In addition, distribution re-absorption and enterohepatic circulation may lead to multiple blood concentration peaks of DHE in rat plasma. DHE possesses a wide spectrum of pharmacological properties in the central nervous system, cardiovascular system, and digestive system. Moreover, DHE has anti-inflammatory effects downregulating pro-inflammatory cytokines and inflammatory mediators. Given the favorable pharmacological activity, DHE is expected to be a potential drug candidate for the treatment of Alzheimer's disease, chronic stress, amnesia, chronic atrophic gastritis, gastric ulcers, and rheumatoid arthritis. In addition, toxicity studies have suggested that DHE has proarrhythmic effects and can impair bile acid homeostasis without causing hepatotoxicity. However, further rigorous and well-designed studies are needed to elucidate the pharmacokinetics, pharmacological effects, potential biological mechanisms, and toxicity of DHE.

Dietary pattern may be the determinant of migraine prognosis through various mechanisms such as systemic inflammation, vasodilation, cerebral glucose metabolism, and mitochondrial dysfunction.This study was conducted to examine the relationship of the symptoms and signs of migraine with dietary polyphenols and the phytochemical intake and the quality of the diet.

Chronic pain often leads to cognitive impairment. Resveratrol (Res), a natural polyphenol existing in Polygonum cuspidatum, has been widely investigated for its antinociceptive, anti-inflammatory, and neuroprotective properties. Our aim was to explore the ameliorating effects of resveratrol on pain-related behaviors and learning and memory deficits induced by cobra venom-induced trigeminal neuralgia (TN). The TN model of rats was established by injecting cobra venom solution beneath the epineurium of the infraorbital nerve. Resveratrol was intragastrically administered at a dose of 40 mg/kg twice daily beginning on postoperative day 15. CREB inhibitor 666-15 was intraperitoneally administered at a dose of 10 mg/kg from POD 35-42 after morning resveratrol treatment. Mechanical allodynia was measured via von Frey filaments. Rat free movement was videotaped and analyzed. Spatial learning and memory were evaluated via the Morris water maze test. Ultrastructures of the hippocampal DG region and infraorbital nerve were observed by transmission electron microscopy. We found that resveratrol alleviated TN-induced allodynia, ameliorated learning and memory deficits, restored the ultrastructure of hippocampal neurons and synapses, repaired the damaged myelin sheath of the infraorbital nerve, and activated the CREB/BDNF pathway in the hippocampus of TN rats. CREB inhibitor administration suppressed the resveratrol-rescued abnormal hippocampal ultrastructural changes and aggravated spatial learning and memory impairment by inhibiting CREB/BDNF pathway activation in the hippocampus. Our findings indicated that resveratrol alleviated pain and improved cognitive deficits, probably by regulating neural ultrastructure remodelling and the CREB/BDNF pathway.

Sciatica is a pain disorder often caused by the herniated disk compressing the lumbosacral nerve roots. Neuroimaging studies have identified functional abnormalities in patients with chronic sciatica (CS). However, few studies have investigated the neural marker of CS using brain structure and the classification value of multidimensional neuroimaging features in CS patients is unclear.

Circumcision is often performed in neonates and is associated with significant pain. This study was conducted to compare the anesthetic efficacy of two methods of local anaesthesia for neonatal circumcision: topical eutectic mixture of local anesthetics (EMLA) cream and dorsal penile nerve block (DPNB) with lidocaine.

The ability of non-invasive brain stimulation to induce neuroplasticity and cause long-lasting functional changes is of considerable interest for the reversal of chronic pain and disability. Stimulation of the primary motor cortex (M1) has provided some of the most encouraging after-effects for therapeutic purposes, but little is known about its underlying mechanisms. In this study we combined transcranial Direct Current Stimulation (tDCS) and fMRI to measure changes in task-specific activity and interregional functional connectivity between M1 and the whole brain. Using a randomized counterbalanced sham-controlled design, we applied anodal and cathodal tDCS stimulation over the left M1. In agreement with previous studies, we demonstrate that tDCS applied to the target region induces task-specific facilitation of local brain activity after anodal tDCS, with the stimulation effects having a negative relationship to the resting motor threshold. Beyond the local effects, tDCS also induced changes in multiple downstream regions distinct from the motor system that may be important for therapeutic efficacy, including the operculo-insular and cingulate cortex. These results offer opportunities to improve outcomes of tDCS for the individual patient based on the degree of presumed neuroplasticity. Further research is still warranted to address the optimal stimulation targets and parameters for those with disease-specific symptoms of chronic pain.

This study analyses the 2020 survey and reviews the 2009, 2014 surveys to ascertain which Behçet's symptoms, personal and family status, patients' lifestyle, and work-related outcomes impacted on Health-Related Quality of Life (HRQoL).

Adenomyosis is an estrogen-dependent gynecological disease. The pathogenesis of chronic pain, the main clinical symptom of adenomyosis, remains undefined. As a combination lymphocyte with both T-cell and natural killer (NK)-cell properties, NK T (NKT) cells play a role in immune defense against numerous diseases and modulate cell differentiation.

Spinal α-adrenoceptor induces analgesia by neuronal inhibition of primary afferent fibers. This family receptor coupled to G proteins can be subdivided into three functional subtypes: α, α and α-adrenoceptors, and current evidence on spinal analgesia supports the relevance of α and seems to exclude the role of α, but the functional contribution of α-adrenoceptors remains elusive. The present study was designed to pharmacologically dissect the contribution of spinal α-adrenoceptor subtypes modulating tonic or acute peripheral nociception. Using male Wistar rats, we analyzed the effect of spinal clonidine (a non-selective ααα-adrenoceptor agonist) and/or selective subtype α-adrenoceptor antagonists on: 1) tonic nociception induced by subcutaneous formalin (flinching behavior) or 2) acute nociception induced by peripheral electrical stimulus in extracellular recordings of spinal dorsal horn second-order wide dynamic range (WDR) neurons. Clonidine inhibited the nocifensive behavior induced by formalin, an effect blocked by BRL 44408 (α-adrenoceptor antagonist) but not by imiloxan (α-adrenoceptor antagonist) or JP 1302 (α-adrenoceptor antagonist). Similarly, spinal BRL 44408 reversed the clonidine-induced inhibition of nociceptive WDR activity. Interestingly, spinal JP 1302 produced behavioral antinociception (an effect blocked by bicuculline, a preferent GABA channel blocker), but no correlation was found with the electrophysiological experiments. These data imply that, at the spinal level, 1) presynaptic α-adrenoceptor activation produces antinociception during acute or tonic nociceptive stimuli; and 2) under tonic nociceptive (inflammatory) input, spinal α-adrenoceptors are pronociceptive, probably by the inactivation of GABAergic transmission. This result supports a differential role of α and α-adrenoceptors modulating nociception.

Lichen planus is a chronic disease with often disappointing and less than optimal treatment options. Apremilast modulates inflammatory signalling pathways which play a central role in the pathogenesis of lichen planus, thus making it useful in the management of such patients.

Cancer-induced bone pain (CIBP) is a moderate to severe pain and seriously affects patients' quality of life. Spinal cord plays critical roles in pain generation and maintenance. Identifying differentially expressed proteins (DEPs) in spinal cord is essential to elucidate the mechanisms of cancer pain.

[This corrects the article DOI: 10.3389/fphar.2022.923188.].

To determine the epidemiology and clinical features of giant cell arteritis (GCA) in Canterbury, Aotearoa New Zealand, with a particular focus on extra-cranial large vessel disease.

Studies investigating the association between functional capacity and quality of life (QoL) in individuals with chronic Chagas cardiomyopathy (CCC) usually do not include a gold-standard evaluation of functional capacity, limiting the validity and the interpretation of the results. The present study is a cross-section analysis aiming to evaluate the association between functional capacity (quantified by cardiopulmonary exercise test [CPET]) and QoL in individuals with CCC. QoL was assessed using the SF-36 questionnaire. Sociodemographic, anthropometric, clinical, cardiac function and maximal progressive CPET variables were obtained from PEACH study. Generalized linear models adjusted for age, sex, and left ventricular ejection fraction were performed to evaluate the association between CPET variables and QoL. After adjustments, VO2 peak and VO2 AT were both associated with physical functioning (β = +0.05 and β = +0.05, respectively) and physical component summary (β = +0.03 and β = +0.03, respectively). Double product was associated with physical functioning (β = +0.003), general health perceptions (β = +0.003), physical component summary (β = +0.002), and vitality (β = +0.004). HRR≤12bpm was associated with physical functioning (β = -0.32), role limitations due to physical problems (β = -0.87), bodily pain (β = -0.26), physical component summary (β = -0.21), vitality (β = -0.38), and mental health (β = -0.19). VE/VCO2 slope presented association with all mental scales of SF-36: vitality (β = -0.028), social functioning (β = -0.024), role limitations due to emotional problems (β = -0.06), mental health (β = -0.04), and mental component summary (β = -0.02). The associations between CPET variables and QoL demonstrate the importance of CPET inclusion for a more comprehensive evaluation of individuals with CCC. In this setting, intervention strategies aiming to improve functional capacity may also promote additional benefits on QoL and should be incorporated as a treatment strategy for patients with CCC.

Central and peripheral nervous systems are all involved in type 2 diabetic polyneuropathy mechanisms, but such subclinical changes and associations remain unknown. This study aims to explore subclinical changes of the central and peripheral and unveil their association.

Methotrexate is one of the cornerstones of rheumatoid arthritis (RA) therapy. Genetic factors or single nucleotide polymorphisms (SNPs) are responsible for 15%-30% of the variation in drug response. Identification of clinically effective SNP biomarkers for predicting methotrexate (MTX) sensitivity has been a challenge. The aim of this study was to explore the association between the disease related outcome of MTX treatment and 23 SNPs in 8 genes of the MTX pathway, as well as one pro-inflammatory related gene in RA patients naïve to MTX. Categorical outcomes such as Disease Activity Score (DAS)-based European Alliance of Associations for Rheumatology (EULAR) non-response at 4 months, The American College of Rheumatology and EULAR (ACR/EULAR) non-remission at 6 months, and failure to sustain MTX monotherapy from 12 to 24 months were assessed, together with continuous outcomes of disease activity, joint pain and fatigue. We found that the SNPs rs1801394 in the gene, rs408626 in gene, and rs2259571 in gene were significantly associated with disease activity relevant continuous outcomes. Additionally, SNP rs1801133 in the gene was identified to be associated with improved fatigue. Moreover, associations with values at uncorrected significance level were found in SNPs and different categorical outcomes: 1) rs1476413 in the gene and rs3784864 in gene are associated with ACR/EULAR non-remission; 2) rs1801133 in the gene is associated with EULAR response; 3) rs246240 in the gene, rs2259571 in the gene, rs2274808 in the gene and rs1476413 in the gene are associated with failure to MTX monotherapy after 12-24 months. The results suggest that SNPs in genes associated with MTX activity may be used to predict MTX relevant-clinical outcomes in patients with RA.

Chronic low back pain (CLBP) is a very common problem throughout the world. One treatment possibility is the multidisciplinary programme (MP) in a rehabilitation centre, which provides intensive rehabilitation through physical exercise to quickly improve the patient conditions. Patients nevertheless do not always continue the exercises when they return home. This study thus evaluated compliance with a personalised home-based programme for CLBP patients post-MP.

To identify the factors associated with Upright Delivery (UD) performed in hospitals linked to the Rede Cegonha (RC) in Brazil.

Despite the prevalence of opioid misuse, opioids remain the frontline treatment regimen for severe pain. However, opioid safety is hampered by side-effects such as analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, or reward. These side effects promote development of opioid use disorders and ultimately cause overdose deaths due to opioid-induced respiratory depression. The intertwined nature of signaling via μ-opioid receptors (MOR), the primary target of prescription opioids, with signaling pathways responsible for opioid side-effects presents important challenges. Therefore, a critical objective is to uncouple cellular and molecular mechanisms that selectively modulate analgesia from those that mediate side-effects. One such mechanism could be the transactivation of receptor tyrosine kinases (RTKs) via MOR. Notably, MOR-mediated side-effects can be uncoupled from analgesia signaling via targeting RTK family receptors, highlighting physiological relevance of MOR-RTKs crosstalk. This review focuses on the current state of knowledge surrounding the basic pharmacology of RTKs and bidirectional regulation of MOR signaling, as well as how MOR-RTK signaling may modulate undesirable effects of chronic opioid use, including opioid analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, and reward. Further research is needed to better understand RTK-MOR transactivation signaling pathways, and to determine if RTKs are a plausible therapeutic target for mitigating opioid side effects.

Migraine is a neurovascular disorder that affects the quality of life of more than 1 billion people worldwide. Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulation tool that uses pulsed magnetic fields to modulate the cerebral cortex. This meta-analysis ascertained the therapeutic or preventive effect of rTMS on chronic migraine.

Tuberculosis is a real public health problem in developing countries. The aim of our article was to study the epidemiological, clinical, diagnostic characteristics of female genital tuberculosis in Togo. This was a descriptive and cross-sectional study on all cases concerning histologically diagnosed female genital tuberculosis in the department of pathological anatomy of Lomé in 1997-2018 (20 years). We collected 22 cases of women's Genital tuberculosis (GT), representing 2.2% (1008 cases) of extra-pulmonary tuberculosis. The mean age of the patients was 33.8 ± 0.2 years. Nine (9) patients had a history of treated GT. Depending on the location, the ovaries and fallopian tubes were the most affected (n=9 cases, 40.9%). Eighteen patients (81.8%) had at least one immunosuppression factor including HIV in 13 patients (72.2%). The reasons for consultation were metrorrhagia and pelvic pain with an associated mass in 7 women discovered on clinical examination and imaging. The macroscopic appearance of the specimens was suggestive of the diagnosis of genital tuberculosis in 12 cases (54.5%). Histology revealed caseous necrosis isolated in 3 patients (13.6%) and associated with gigantocellular epithelioid granulomas in 19 patients (86.4%). The patients received standard antibiotic treatment combining rifampicin, isoniazid, ethambutol and pyrazinamide. Genital tuberculosis is a rare extra-pulmonary location in Togo, often occurring in women with HIV, and the clinical polymorphism can lead to confusion with gynecological cancers.

Low intraneuronal chloride in spinal cord dorsal horn (SCDH) pain relay neurons is of critical relevance for physiological transmission of primary sensory afferents because low intraneuronal chloride dictates GABA-ergic and glycin-ergic neurotransmission to be inhibitory. If neuronal chloride rises to unphysiological levels, the primary sensory gate in the spinal cord dorsal horn becomes corrupted, with resulting behavioral hallmarks of hypersensitivity and allodynia, for example in pathological pain. Low chloride in spinal cord dorsal horn neurons relies on the robust gene expression of and sustained transporter function of the KCC2 chloride-extruding electroneutral transporter. Based on a recent report where we characterized the GSK3-inhibitory small molecule, kenpaullone, as a gene expression-enhancer that potently repaired diminished expression and KCC2 transporter function in SCDH pain relay neurons, we extend our recent findings by reporting (i) effective pain control in a preclinical model of taxol-induced painful peripheral neuropathy that was accomplished by topical application of a TRPV4/TRPA1 dual-inhibitory compound (compound 16-8), and was associated with the repair of diminished gene expression in the SCDH; and (ii) potent functioning of kenpaullone as an antipruritic in a DNFB contact dermatitis preclinical model. These observations suggest that effective peripheral treatment of chemotherapy-induced painful peripheral neuropathy impacts the pain-transmitting neural circuit in the SCDH in a beneficial manner by enhancing gene expression, and that chronic pruritus might be relayed in the primary sensory gate of the spinal cord, following similar principles as pathological pain, specifically relating to the critical functioning of gene expression and the KCC2 transporter function.

Postoperative nausea and vomiting (PONV) is a still highly relevant problem and is known to be a distressing side effect in patients. The aim of this study was to develop a machine learning model to predict PONV up to 24 h with fentanyl-based intravenous patient-controlled analgesia (IV-PCA).

The Green Bush Viper, Atheris squamigera, is native to West and Central Africa and has few well reported envenomations. Bite victims experience dizziness, nausea, headache, regional lymphadenopathy, and localized edema. Most reports also detail severe effects including thrombocytopenia, coagulopathy, hemolysis, hemorrhage, or renal failure. Fatalities are reported, but poorly described. There is no specific antivenom for A. squamigera, but non-species specific antivenom has been reported helpful in several cases. We report the case of a 36-year-old woman who was bitten by a green bush viper and was treated with several non-species specific antivenoms. There were no complications to antivenom administration and the patient experienced a milder envenomation than detailed in previous reports.

Total knee arthroplasty (TKA) is the final treatment option for patients with advanced knee osteoarthritis (OA). Unfortunately, TKA surgery is accompanied by acute postoperative pain that is more severe than arthroplasty performed in other joints. Elucidating the molecular mechanisms specific to post-TKA pain necessitates an animal model that replicates clinical TKA procedures, induces acute postoperative pain, and leads to complete functional recovery. Here, we present a new preclinical TKA model in rats and report on functional and behavioral outcomes indicative of pain, analgesic efficacy, serum cytokine levels, and dorsal root ganglia (DRG) transcriptomes during the acute postoperative period. Following TKA, rats exhibited marked deficits in weight bearing that persisted for 28 days. Home cage locomotion, rearing, and gait were similarly impacted and recovered by day 14. Cytokine levels were elevated on postoperative days one and/or two. Treatment with morphine, ketorolac, or their combination improved weight bearing while gabapentin lacked efficacy. When TKA was performed in rats with OA, similar functional deficits and comparable recovery time courses were observed. Analysis of DRG transcriptomes revealed upregulation of transcripts linked to multiple molecular pathways including inflammation, MAPK signaling, and cytokine signaling and production. In summary, we developed a clinically relevant rat TKA model characterized by resolution of pain and functional recovery within five weeks and with pain-associated behavioral deficits that are partially alleviated by clinically administered analgesics, mirroring the postoperative experience of TKA patients.

This work studied the molecular mechanism of the – herb pair (SAHP) in migraine treatment.

Chronic, abdominal pain remains a problem in a subset of patients after cholecystectomy. The cause is often obscure but central sensitization may be an important component and could theoretically be mediated by spinal PGE2, which is regulated by several cytokines. The aim of the study was to examine cerebrospinal fluid (CSF) of participants with post cholecystectomy syndrome and healthy volunteers for signs of PGE2 and cytokine mediated central sensitization.

[This retracts the article DOI: 10.1155/2021/7344102.].

Migraine is frequently reported in patients with irritable bowel syndrome (IBS), and emerging evidence suggests that gut microbiota plays a role in migraine and IBS. However, alterations in the gut microbiome in migraine patients with IBS remain unknown. This study aimed to explore the compositions of gut microbiota in migraine patients with IBS in a Chinese Han population.

The POINT project aims to provide evidence to optimise chronic pain management, prevent adverse consequences of opioids, and improve chronic pain patients' pain relief, functional capacity, and quality of life. We describe the outline of the project and its work packages. More specifically, we describe a cohort of persons with chronic pain and a cohort of long-term opioid users identified from a national registry linkage.

Endocrine complications have been described in patients affected by RASopathies but no systematic assessment has been reported. In this study, we investigate the prevalence of endocrine disorders in a consecutive unselected cohort of patients with RASopathies.

The association between reporting adverse coronavirus disease 2019 (COVID-19) vaccination effects and those with a history of audiovestibular difficulties is unknown. The aim of this research is therefore to investigate adverse vaccination effects in adults with a history of Ménière's disease. Specifically, the incidence of adverse effects, the factors associated with those reporting adverse effects and the relationship between the reporting of audiovestibular and other adverse effects. A mixed-methods exploratory cross-sectional survey study design was used. Data were collected from 333 members of the Finnish Ménière Association. The survey was designed to obtain demographic information that may be associated with having adverse effects or not, vaccination-specific information and adverse vaccination effects. Both health and audiovestibular adverse events were identified. Data analysis included comparing those reporting and not reporting adverse vaccination effects. The mean age was 63 years with 81% being female. Of the 327 respondents who had one of the COVID-19 vaccinations (Comirnatry/ Pfizer, Astra Zeneca, or Moderna), 203 (62%) reported no adverse effects. The type of or number of vaccinations were not related to the reporting of adverse effects. The most frequently reported adverse effects were injection site tenderness (38%), arm pain (21%), fever (15%) and headaches (15%). Post-vaccination tinnitus and vertigo (both 7%) were the most frequently reported audiovestibular-related symptoms, followed by aural fullness (6%) and hearing loss (4%). Those reporting previous pre-vaccination vertigo were more likely to have post-vaccination vertigo. The presence of post-vaccination tinnitus, hearing loss, and aural fullness, predicted the presence of post-vaccination vertigo. A small proportion of patients with a history of Ménière's disease may experience adverse post-vaccination effects. Further research is required to explore whether adverse post-vaccination audiovestibular effects are more prevalent in those with a history of otological disorders compared with the general population.

Pain management requires a multidisciplinary approach and a collaborative relationship between patient-provider in which communication is crucial. This study examines the communication experiences of Aboriginal and Torres Strait Islander patients and Aboriginal and Torres Strait Islander Hospital Liaison Officers (ATSIHLOs), to improve understanding of how pain is managed in and through patient-health professional communication.

The aim of this study was to evaluate the latency, extent of analgesia, and duration of motor block of levobupivacaine alone and combined with methadone or dexmedetomidine after epidural administration during and after mastectomy in dogs. Twenty-four mature, mixed-breed female dogs were randomly divided into three experimental groups with eight animals each, according to the agents used in lumbosacral epidural analgesia: levobupivacaine 0.75% alone (1.5mg/kg – control group), levobupivacaine 0.75% (1.5 mg/kg) + methadone 1% (0.3 mg/kg), or levobupivacaine 0.75% (1.5 mg/kg) + dexmedetomidine 0.05% (3 µg/kg). During surgery, cardiorespiratory parameters were evaluated. Rescue analgesia was given when there were signs of nociception and was necessary in all three treatment groups. Since all animals received rescue analgesia during the surgery and immediately post-surgery, the duration of the sensitive block were not evaluated. The extent of sensory block was between the 12º and 13º thoracic vertebrae for the control group, 7º thoracic vertebra to 5º lumbar vertebra (methadone group), and 8º thoracic vertebra to 4º lumbar vertebra for the dexmedetomidine group. Methadone or dexmedetomidine combined with levobupivacaine increased the extent of the sensory block and the duration of the motor block in bitches when administered via the epidural route.

The objective of this study was to investigate the prevalence, clinical features, and factors related to personal protective-associated headaches.

The experience of anxiety is central to the development of chronic pain. Music listening has been previously shown to exert analgesic effects. Here we tested if an active engagement in music making is more beneficial than music listening in terms of anxiety and pain levels during physical activity that is often avoided in patients with chronic pain. We applied a music feedback paradigm that combines music making and sports exercise, and which has been previously shown to enhance mood. We explored this method as an intervention to potentially reduce anxiety in a group of patients with chronic pain (= 24, 20 female and 4 men; age range 34-64, 51.67,  = 6.84) and with various anxiety levels. All participants performed two conditions: one condition, , where exercise equipment was modified with music feedback so that it could be played like musical instruments by groups of three. Second, a where groups of three performed exercise on the same devices but where they listened to the same type of music passively. Participants' levels of anxiety, mood, pain and self-efficacy were assessed with standardized psychological questionnaires before the experiment and after each condition. Results demonstrate that exercise with musical feedback reduced anxiety values in patients with chronic pain significantly as compared to conventional workout with passive music listening. There were no significant overall changes in pain, but patients with greater anxiety levels compared to those with moderate anxiety levels were observed to potentially benefit more from the music feedback intervention in terms of alleviation of pain. Furthermore, it was observed that patients during more strongly perceived motivation through others. The observed diminishing effects of on anxiety have a high clinical relevance, and in a longer term the therapeutic application could help to break the Anxiety Loop of Pain, reducing chronic pain. The intervention method, however, also has immediate benefits to chronic pain rehabilitation, increasing the motivation to work out, and facilitating social bonding.

Sickle cell disease is an autosomal recessive disorder characterized by the presence of sickle hemoglobin that leads to chronic hemolysis and vaso-occlusive crisis. After decades of limited therapy options, crizanlizumab is a humanized monoclonal antibody approved by the Food and Drug Administration (FDA) in 2019 for sickle cell-related pain crises for patients 16 years of age and above. Although rare, infusion-related reactions, including painful crises, occurred in 3% as per the package insert. However, the data on how to deal with such reactions and about further treatment outcomes are limited as most patients stopped crizanlizumab after the reaction. Herein, we report the good outcome of 13 doses of crizanlizumab in a 19-year-old female patient with sickle cell disease on hydroxyurea, despite experiencing a severe infusion-related painful crisis during the second infusion. Additional benefits of crizanlizumab, in this case, were preventing new episodes of acute chest syndrome, quitting chronic narcotics use, and a remarkable improvement in quality of life and overall performance.

Interleukin-6 (IL-6) is a pro-inflammatory and bone-resorptive cytokine that also regulates bone formation. We previously showed that prostaglandin E1 (PGE1) induces the synthesis of IL-6 by activating p44/p42 mitogen-activated protein kinase (MAPK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38 MAPK in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether heat shock protein 70 (HSP70), a molecular chaperone that coordinates protein folding and homeostasis, affects PGE1-stimulated IL-6 synthesis in MC3T3-E1 cells through the MAPK activation. The osteoblast-like MC3T3-E1 cells were treated with HSP70 inhibitors-VER-155008 and YM-08-, PD98059, SB203580 or SP600125 and then stimulated with PGE1. IL-6 synthesis was evaluated using an IL-6 enzyme-linked immunosorbent assay kit. IL-6 mRNA expression was measured by real-time RT-PCR. The phosphorylation of p38 MAPK was evaluated by Western blotting. We found that VER-155008, an HSP70 inhibitor, enhanced the PGE1-stimulated IL-6 release and IL-6 mRNA expression. YM-08, another HSP70 inhibitor, also enhanced PGE1-stimulated IL-6 release. PD98059, a p44/p42 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, upregulated PGE1-stimulated IL-6 release. On the other hand, SB203580, a p38 MAPK inhibitor, suppressed PGE1-stimulated IL-6 release. YM-08 stimulated the PGE1-induced phosphorylation of p38 MAPK. SB203580 suppressed the amplification by YM-08 of the PGE1-stimulated IL-6 release. Our results suggest that HSP70 inhibitors upregulate the PGE1-stimulated IL-6 synthesis through p38 MAPK in osteoblasts and therefore affect bone remodeling.

Topiramate is an anticonvulsant from sulfamate-substituted monosaccharides that is increasingly used to treat migraines. Serious topiramate intoxications have been described. Unfortunately, indications for and the effect of interventions, including hemodialysis, in severe intoxications seem expert-based and lack empirical evidence. We aim to review the literature on topiramate intoxication cases and to describe the first topiramate intoxication with toxicokinetic data following treatment with hemodialysis.

Very often in clinical practice, an inflamed pelvic appendix shows left lower quadrant abdominal pain as the primary painful area. The clinicians are anchored to the most prominent symptom, thereby taking an unnecessary detour in reaching an accurate diagnosis. A 40-year-old man presented to our emergency department with persistent lower left abdominal pain with a fever of 38 oC from a day earlier. He had a good appetite and repeatedly complained of severe constipation at the time of his visit. Physical examination revealed tenderness in the lower left abdomen without a peritoneal sign. Abdominal ultrasound and non-contrast-enhanced computed tomography revealed a left hydroureter. The next day, a radiologist pointed out the possibility of appendicitis. An urgent laparoscopic appendectomy was performed. The intriguing point of this case is the diagnostic delay because of three anchoring biases. First, the typical right lower abdominal pain of appendicitis was shielded by the intense left lower abdominal pain. Moreover, the presence of a left hydroureter distracted the physicians from the actual location of the pain. Furthermore, the presence of constipation anchored the physicians to constipation as the cause of abdominal pain. In overcoming these biases, specific diagnostic strategies to avoid biases should be implemented.

Endometriosis is a common gynecological disease, that often leads to pain and infertility. At present, the specific pathogenesis of endometriosis has not been clarified, but it may be closely related to an imbalance of sex hormones in the body, ectopic hyperplasia stimulated by immune inflammation, and invasion and escape based on tumor characteristics. Gut microbiota is associated with many inflammatory diseases. With the further study of the gut microbiota, people are paying increasing attention to its relationship with endometriosis. Studies have shown that there is an association between the gut microbiota and endometriosis. The specific ways and mechanisms by which the gut microbiota participates in endometriosis may involve estrogen, immune inflammation, and tumor characteristics, among others. Therefore, in the future, regulating gut microbiota disorders in various ways can help in the treatment of endometriosis patients. This study reviewed the research on the gut microbiota and endometriosis in order to provide ideas for clinical diagnosis and treatment.

The article presents the work of a multidisciplinary team of experts from various fields of medicine to optimize the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology» for use in clinical practice. The survey of respondents was conducted from June 28 to September 28, 2021. As a result of this survey, by repeatedly making edits and clarifications during communication with respondents, the final version was obtained, which allows assessing the patient's subjective sensations by the nature and localization of pelvic pain, sensitivity disorders and pelvic organ function. The main objective of this Questionnaire is to differentiate patients with neurogenic pain from a huge number of patients with chronic pelvic pain. This aspect will allow a more targeted approach to the diagnosis and pathogenetically justified treatment of patients, including after appropriate instrumental examinations. The work of a multidisciplinary team implies a higher degree of objectification and terminological accuracy of the Questionnaire under discussion. The presented version of the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology» will be primarily used in coloproctological patients with pelvic pain problems and anal incontinence and obstructive defecation. Further studies will be directed to the clinical evaluation of the results of the work carried out.

One of the common negative effects of a stroke that seriously lowers patients' quality of life is post-stroke pain (PSP). Thus, exercise in PSP management has become a hot research topic. The main advantages of exercise therapy are affordability and ease of acceptance by patients compared to other treatment methods. Therefore, this article reviews the effectiveness and possible mechanisms of exercise interventions for PSP. Exercise training for patients with PSP not only improves physical function but also effectively reduces pain intensity and attenuates the behavioral response to pain. In addition, exercise therapy can improve brain function and modulate levels of pro-inflammatory and neurotrophic factors to exert specific analgesic effects. Potential mechanisms for exercise intervention include modulation of synaptic plasticity in the anterior cingulate gyrus, modulation of endogenous opioids , reversal of brain-derived neurotrophic factor overexpression, inhibition of purinergic receptor (P2X4R, P2X7R) expression, and inhibition of microglia activation. However, current research on exercise for PSP remains limited, and the sustainable benefits of exercise interventions for PSP need to be further investigated.

The occurrence of three or more of the following signs and symptoms, such as headache, dizziness, exhaustion, irritability, sleeplessness, difficulties in concentrating, or memory problems, following a head injury is referred to as post-concussion syndrome (PCS). Even though post-concussion syndrome has not been studied in Ethiopia, the productive age group is frequently affected by health issues related to head trauma, which either directly or indirectly affect the growth of the nation.

Remifentanil patient-controlled analgesia (rPCA) and epidural analgesia (EA) has been used for pain relief in labor. We aimed to evaluate the efficacy and safety of rPCA versus EA in labor, to provide evidence support for clinical analgesia and pain care.

Curvularia is a ubiquitous fungus found in tropical climates and has been reported to grow on marijuana leaves. Rarely, it can infect humans and propagate from the nasal sinuses into the brain.

Comorbid chronic pain and post-traumatic stress disorder (PTSD) complicate the treatment of both conditions. Previous research has identified pain catastrophizing as a potentially important variable contributing to the relationship between chronic pain and PTSD. However, little is known regarding how the different dimensions of pain catastrophizing-rumination, magnification, and helplessness-uniquely contribute to the relationship between PTSD symptomatology and measures of pain outcome.

Osteoarthritis (OA) is the most prevalent articular disease, especially in aged population. Caused by multi-factors (e.g., trauma, inflammation, and overloading), OA leads to pain and disability in affected joints, which decreases patients' quality of life and increases social burden. In pathophysiology, OA is mainly characterized by cartilage hypertrophy or defect, subchondral bone sclerosis, and synovitis. The homeostasis of cell-cell communication is disturbed as well in such pro-inflammatory microenvironment, which provides clues for the diagnosis and treatment of OA. MicoRNAs (miRNAs) are endogenous non-coding RNAs that regulate various processes post-transcriptional mechanisms. The miR-17-92 cluster is an miRNA polycistron encoded by the host gene called MIR17HG. Mature miRNAs generated from MIR17HG participate in biological activities such as oncogenesis, neurogenesis, and modulation of the immune system. Accumulating evidence also indicates that the expression level of miRNAs in the miR-17-92 cluster is tightly related to the pathological processes of OA, such as chondrocyte apoptosis, extracellular matrix degradation, bone remodeling, and synovitis. In this review, we aim to summarize the roles of the miR-17-92 cluster in the underlying molecular mechanism during the development and progression of OA and shed light on the new avenue of the diagnosis and treatment of OA.

Within the tactical aviation community, human performance research lags in considering potential psychophysiological differences between male and female aviators due to little inclusion of females during the design and development of aircraft systems. A poor understanding of how male and female aviators differ with respect to human performance results in unknown potential sex differences on aeromedically relevant environmental stressors, perchance leading to suboptimal performance, safety, and health guidelines. For example, previous hypoxia studies have excluded female participants or lacked a sizeable sample to examine sex comparisons. As such, progress toward sensor development and improving hypoxia familiarization training are stunted due to limited knowledge of how individual differences, including sex, may or may not underlie hypoxia symptoms and performance impairment. Investigating sex differences bridges the gap between aerospace medicine and operational health, and addressing hypoxia is one of many facets yet to be studied. In the current study, we retrospectively examined N = 6 hypoxia studies with male-female participant samples (total, N = 189; male, = 118; female, = 71). We explored sex as a predictor of physiological response, sensory deficits, the severity of cognitive performance declines, and symptom manifestation linear and binary logistic regression models. We found that the female sex predicted lower peripheral oxygen saturation and the likelihood of headache reporting in response to hypoxic challenge, yet explained little variance when combined with age and body mass index. The sensory and cognitive performance models did not converge, suggesting high intra-individual variability. Together, sex, age, and body mass index were not the most robust predictors in responses to hypoxic challenge; we cannot infer this for sensory deficits and cognitive performance within an experimentally induced hypoxic environment. The findings have implications for improving hypoxia familiarization training, monitoring sensor development, and emergency response and recovery protocols in case of a hypoxia occurrence suitable for all aircrew. We recommend continuing to elucidate the impact of sex and intrapersonal differences in hypoxia and other aeromedically relevant stressors in tactical aviation.

Chronic pancreatitis (CP) is a chronic progressive inflammatory disease of the pancreas, caused by multiple factors and accompanied by irreversible impairment of pancreatic internal and external secretory functions. Pathologically, atrophy of the pancreatic acini, tissue fibrosis or calcification, focal edema, inflammation, and necrosis are observed. Clinical manifestations include recurrent or persistent abdominal pain, diarrhea, emaciation, and diabetes. In addition, CP is prone to develop into pancreatic cancer(PC) due to persistent inflammation and fibrosis. The disease course is prolonged and the clinical prognosis is poor. Currently, clinical treatment of CP is still based on symptomatic treatment and there is a lack of effective etiological treatment. Encouragingly, experiments have shown that a variety of active substances have great potential in the etiological treatment of chronic pancreatitis. In this paper, we will review the pathogenesis of CP, as well as the research progress on anti-inflammatory and anti-fibrotic therapies, which will provide new ideas for the development of subsequent clinical studies and formulation of effective treatment programs, and help prevent CP from developing into pancreatic cancer and reduce the prevalence of PC as much as possible.

Paracoccidioidomycosis is a systemic infection caused by the fungus Paracoccidioides. It may present in two forms: an acute/subacute form, whose most frequent manifestations include weight loss, fever, anemia, and adenopathy, and a chronic condition with mainly respiratory symptoms. Digestive symptoms, although they may occur, are not frequently reported. Paracoccidioidomycosis usually affects adult male agricultural workers; thus, its presentation in children is rare.

There are abundant studies on headache and migraine in women but few or none about their occurrence during labor, delivery, and postpartum (2 hours after delivery) owing to the low incidence. A headache attack can be debilitating when a woman is trying to manage labor pain. Research at our Women's Headache Center within the Department of Gynecology and Obstetrics has begun to shed light on this potential association.

Activated microglia play a critical role in the development of lumbar disc degeneration (LDD), which is a severe disease that causes neuropathic pain in affected people. Interleukin 1β (IL-1β) is a proinflammatory cytokine produced and secreted by activated microglia to induce the inflammation and the subsequent degradation of the disease discs. Recent findings suggest that activation of IL-1β in cells usually requires the involvement of NACHT, LRR and PYD domains-containing protein 3 (NLRP3)-induced formation of inflammasome. However, the importance of NLRP3 in spinal microglia in LDD is not known and thus addressed in the current study.

Neuropathic pain (NP) is a chronic health condition that presents a significant burden on patients, society, and even healthcare systems. However, in recent years, an emerging field in the treatment of neuropathic pain – optogenetic technology has dawned, heralding a new era in the field of medicine, and which has brought with it unlimited possibilities for studying the mechanism of NP and the treatment of research. Optogenetics is a new and growing field that uses the combination of light and molecular genetics for the first time ever. This rare combination is used to control the activity of living cells by expressing photosensitive proteins to visualize signaling events and manipulate cell activity. The treatments for NP are limited and have hardly achieved the desirable efficacy. NP differs from other types of pain, such as nociceptive pain, in that the treatments for NP are far more complex and highly challenging for clinical practice. This review presents the background of optogenetics, current applications in various fields, and the findings of optogenetics in NP. It also elaborates on the basic concepts of neuropathy, therapeutic applications, and the potential of optogenetics from the bench to the bedside in the near future.

The psychological flexibility model can be seen as a basis for an integrated and progressive psychological approach to chronic pain management. Some researchers suggest that psychological flexibility and inflexibility represent distinct processes and constructs. This meta-analysis is the first to provide a summary estimate of the overall effect size for the relationship between psychological (in)flexibility and common outcomes among chronic pain patients. The research protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, https://www.crd.york.ac.uk/PROSPERO/), registration number CRD42021285705. Four databases were searched (PsycINFO; PubMed; Web of Science, CINAHL) along with reference lists. Thirty-six cross-sectional studies were included (7,779 participants). Meta-analyses (random effects model) indicated a significant medium negative association between psychological flexibility and pain intensity or functional impairment. The present study also indicated a significant small to medium association between psychological inflexibility and pain intensity, a nearly large association between psychological inflexibility and functional impairment as well as the quality of life, and a large association between psychological inflexibility and anxiety/depression. Due to the limited number of included studies, the relationship between risk behavior and psychological inflexibility may not be significant. Types of countries and instruments measuring psychological inflexibility may explain part of the heterogeneity. These findings may carry significant implications for chronic pain patients regarding the potential relationship between psychological inflexibility or flexibility and these outcomes. It may consequently form the basis for more robust testing of causal and manipulable relationships.

After peripheral nerve injury, pain signals are transmitted from primary sensory neurons in the dorsal root ganglion (DRG) to the central nervous system. Epigenetic modification affects neuropathic pain through alterations in the gene expression in pain-related areas and glial cell activation. Recent studies have shown that non-coding RNA and n6-methyladenosine (m6A) methylation modification play pivotal regulatory roles in the occurrence and maintenance of neuropathic pain. Dysregulation of the RNA m6A level dynamic changes in methyltransferase and demethylase after central or peripheral nerve injury commonly regulates pain-associated genes, contributing to the induction and maintenance of neuropathic pain. The dynamic process has significant implications for the development and maintenance of neuropathic pain. However, the underlying mechanisms by which non-coding RNA and m6A RNA modification regulate neuropathic pain are not well-characterized. This article elucidates the multiple mechanisms of non-coding RNA and m6A methylation in the context of neuropathic pain, and summarizes its potential functions as well as recent advances.

As the discussion of first-line anagrelide treatment is ongoing, we aimed to prospectively examine the efficacy and safety of anagrelide in cytoreduction therapy-naïve high risk essential thrombocythemia (ET) patients in Korea. Seventy patients from 12 centers were treated with anagrelide monotherapy for up to 8 weeks, followed up until 24 months. At week 8, 50.0% of the patients were able to achieve platelet < 600 x 10/L, and by 12 months, 55/70 (78.6%) patients stayed on anagrelide, and 40.0% patients showed platelet normalization. 14 patients required additional hydroxyurea (HU) for cytoreduction. The median daily dose of needed HU was 500mg (range 250mg – 1500mg). The efficacy was independent of the somatic mutation status. There were 4 thromboembolic events and 7 bleeding events during the follow-up period. The most common adverse events associated with anagrelide use were headache, followed by palpitation/chest discomfort, edema and generalized weakness/fatigue. 7 patients wished to discontinue anagrelide treatment due to adverse events (3 due to headache; 2 due to edema; 1 due to palpitation and 1 due to skin eruption). All in all, first-line anagrelide treatment showed a favorable response with tolerable safety profiles regardless of somatic mutation status.

Adhesive capsulitis is an inflammatory disease of the joint capsule, clinically manifested as pain, stiffness, and dysfunction of the shoulder. We subjectively observed an increased incidence of adhesive capsulitis, and raised the hypothesis that adhesive capsulitis was more frequent in magnetic resonance imaging examinations performed during the COVID-19 pandemic as compared with examinations prior to this period.

Brucellosis is an endemic systemic infectious disease, the most common complication is bone and joint involvement. Sacroiliac joint infections and spinal joint infections commonly affect adults, but ankle infections are extremely rare. We report a case of recurrent ankle arthritis caused by .

Proton pump inhibitors (PPIs) and H blockers are commonly prescribed medications to treat ulcers in the stomach and the upper part of the small intestine and prescribed for some other common gastrointestinal complications such as gastroesophageal reflux disease, esophagitis, irritable bowel syndrome, and dyspepsia. Previous studies claimed that, apart from other side effects, these anti-ulcerant therapies significantly altered bone mineral density by interfering with intestinal reabsorption of minerals and vitamin B12, and the most widely prescribed PPIs were significantly associated with increased risks of hip and spine fractures. However, the potential skeletal side effects of these antiulcerants are unknown in Bangladesh.

Suboptimal neonatal circumcision analgesia causes a significant stress response. There is continued search for more effective analgesia for neonatal circumcision. We aimed to determine whether lidocaine-prilocaine cream (LPC) prior to dorsal penile nerve block (DPNB) offers better analgesia than DPNB alone.

Appendicular neoplasms are rare tumors, with an incidence of less than 0.05% among all gastrointestinal tumors. This work presents the case of a 52-year-old patient who manifested colicky pain in the right iliac fossa. Laboratory test results with bandemia and hyperbilirubinemia. Abdominal tomography with an acute appendicular inflammatory process, for which the patient was admitted for surgery. A dependent tumor of the cecum and appendicular region is observed, which compromises the ileocecal valve. The histopathological diagnosis was "low-grade appendiceal mucinous neoplasm." Appendiceal tumors are often incidental findings due to their low frequency; however, their possibility should not be dismissed.

Hydroxyanthracene derivatives are widely distributed in the plant kingdom, mainly in botanicals such as the and genera. For centuries, plants containing hydroxyanthracene derivatives have been used as herbal remedies, mainly as laxatives. The root and underground stem (rhizome) are used to make medicine, primarily for digestive complaints including constipation, diarrhoea, heartburn, stomach pain, gastrointestinal bleeding, and preparation for certain gastrointestinal diagnostic procedures. The use of hydroxyanthracene-containing botanicals has raised the attention of European Food Safety Authority (EFSA) for the potential genotoxicity activity, that in 2018 concluded "". No genotoxic activity has been reported with other constituents such as rhein, physcion and chrysophanol. In the present study, Rhubarb ethanolic extract of ground rhubarb rhizome (hydroxyanthracene total content 1.39 %) was tested in the Ames Assay in and , up to 5000 µg/plate and up to 5000 µg/mL in human lymphocytes Micronucleus Test (OECD 471 and 487 respectively) in vitro mutagenic and genotoxic effects. Under the experimental conditions used, the rhubarb rhizome extract showed no genotoxic activity.

Kimura's disease (KD) is a rare chronic inflammatory condition of unknown aetiology. It is a benign disease that might mimic a neoplastic process. It primarily affects the head and neck region, presenting as deep subcutaneous masses, and is often accompanied by triad regional lymphadenopathy, salivary gland involvement, and high serum immunoglobulin (IgE) levels. Here, we report the second documented case of KD in Palestine diagnosed in a 28-year-old male patient who presented with lymphadenopathy and increased serum immunoglobulin and (IgE and IgG) associated with intermittent abdominal pain, generalised fatigue, hepatomegaly, cardiomyopathy, reactive airway disease, peripheral vasculopathy, peripheral neuropathy, and focal segmental glomerulosclerosis. The patient was managed with steroids and an immunosuppressant (Azathioprine) with a moderate response for two years. In 2021, treatment with Mycophenolate Mofetil was initiated, which was more effective than Azathioprine.

Evaluation of the clinical efficacy of the drug holisal» according to the results of domestic and foreign studies on modern methods for treatment of inflammatory diseases of the oral mucosa mouth and periodontium.

Peripheral nerve injury leads to severe neuropathic pain. Previous studies have highlighted the beneficial effects of physical exercise on alleviating neuropathic pain. Exercise regulating transforming growth factor-1 (TGF-1) can improve several diseases and relieve neuropathic pain induced by peripheral nerve injury. Here, we investigated whether exercise could alleviate neuropathic pain by modulating TGF-1 expression. We assessed mechanical and cold pain behavior and conducted molecular evaluation of the spinal cord. We found that spared nerve injury (SNI) led to mechanical and cold allodynia in the hind paw, elevated the expression of latency-associated peptide- (LAP-) TGF-1, and activated astroglial in the spinal cord. Exercise decreases allodynia, astroglial activation, and LAP-TGF-1 in SNI mice. Intrathecal injection of a TGF-type I receptor inhibitor attenuated exercise analgesia and enhanced astroglial activation. These findings demonstrate that exercise induces analgesia by promoting TGF-1 activation and inhibiting astrogliosis. Our study reveals a new underlying mechanism for exercise-attenuated neuropathic pain in the maintenance stage of neuropathic pain after nerve injury.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disease characterized by abdominal pain and defecation disorders. Acupuncture therapy positively affects IBS, with ST25 being the main point. However, ST25 has mostly been used in conjunction with other acupoints. This study aimed to observe the therapeutic effect of electroacupuncture at ST25 alone in IBS and the neurobiological mechanism of ST25 associated with the colon. First, we observed the effect of electroacupuncture at ST25 on the visceral pain threshold and slow-wave discharge of the colon in IBS model rats. Second, we explored the neurobiological mechanism of ST25 associated with the colon using a neural tracer technique. The results showed that (1) electroacupuncture at ST25 alone can alleviate visceral hypersensitivity and restore normal slow-wave frequency and rhythm of the colon in IBS rats; (2) there is a close neuroanatomical connection between ST25 and the colon, i.e., in the dorsal root ganglion (DRG), ST25 is similar in innervation to the colon, mainly in the T8-L1 segment, while the presence of double-labeled positive neurons is present in a part of the DRG; retrogradely labeled motor neurons associated with ST25 were observed in the anterior horn of the spinal cord, and retrogradely labeled sympathetic postganglionic neurons associated with ST25 were observed in the sympathetic nerve chain. These findings suggested that the DRGs and the dorsal horn of the spinal cord are important targets for electroacupuncture at ST25 to reduce visceral hypersensitivity in IBS rats. The sympathetic ganglia may be an important site for ST25 to regulate intestinal motility. The neurobiological mechanism of ST25 action in IBS rats should be further investigated in the future by combining related techniques, such as pseudorabies virus, optogenetics, calcium imaging, and electrophysiology.

The consequences of the second wave hitting India have drastically laid a huge impact on the mental state of patients. The second wave had proven to be far more dangerous and hence the psychological evaluation needed to be conducted to know the scenario of patients suffering from SARS-CoV-2.

Bone-marrow mesenchymal stem cells (BM-MSCs) have not yet proven any significant therapeutic efficacy in spinal cord injury (SCI) clinical trials, due to the hostile microenvironment of the injured spinal cord at the acute phase. This study aims to modulate the inflammatory milieu by lipopolysaccharide (LPS) and granulocyte colony-stimulating factor (G-CSF) to improve the BM-MSCs therapy. For this purpose, we determined the optimum injection time and sub-toxic dosage of LPS following a T10 contusion injury. Medium-dose LPS administration may result in a local anti-inflammatory beneficial role. This regulatory role is associated with an increase in NF-200-positive cells, significant tissue sparing, and improvement in functional recovery compared to the SCI control group. The second aim was to examine the potential ability of LPS and LPS + G-CSF combination therapy to modulate the lesion site before BM-MSC (1 × 105 cells) intra-spinal injection. Our results demonstrated combination therapy increased potency to enhance the anti-inflammatory response (IL-10 and Arg-1) and decrease inflammatory markers (TNF-α and CD86) and caspase-3 compared to BM-MSC monotherapy. Histological analysis revealed that combination groups displayed better structural remodeling than BM-MSC monotherapy. In addition, Basso-Beattie-Bresnahan (BBB) scores show an increase in motor recovery in all treatment groups. Moreover, drug therapy shows faster recovery than BM-MSC monotherapy. Our results suggest that a sub-toxic dose of LPS provides neuroprotection to SCI and can promote the beneficial effect of BM-MSC in SCI. These findings suggest that a combination of LPS or LPS + G-CSF prior BM-MSC transplantation is a promising approach for optimizing BM-MSC-based strategies to treat SCI. However, because of the lack of some methodological limitations to examine the survival rate and ultimate fate of transplanted BM-MSCs followed by LPS administration in this study, further research needs to be done in this area. The presence of only one-time point for evaluating the inflammatory response (1 week) after SCI can be considered as one of the limitations of this study. We believed that the inclusion of additional time points would provide more information about the effect of our combination therapy on the microglia/macrophage polarization dynamic at the injured spinal cord.

Dengue viral infection is considered endemic in Ecuador. It is more frequent during winter, caused by an RNA virus in the Flavivirus group. Its presentation can range from an asymptomatic state to hemorrhagic fever with shock signs. Acute pancreatitis could be a rare form of acute abdomen presentation associated with dengue virus infection. This case illustrates a 26-year-old man who presents to the hospital with cramp-like pain in the epigastrium and radiation to the right upper quadrant, accompanied by nausea and vomiting. He also endorsed additional symptoms such as throbbing-like headache, myoarthralgias, and fever of 40.4°C (104.72°F). Laboratory tests revealed elevated hematocrit, thrombocytopenia, elevated pancreatic enzymes, transaminitis, elevated alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT). Ultrasonography of the abdomen revealed hepatic steatosis, free fluid in the abdominal cavity, and small bilateral pleural effusions. Additional testing revealed IgM and IgG antibodies positivity to dengue virus. The patient was treated conservatively with intravenous (IV) fluid hydration and bowel rest. Acute pancreatitis should be considered when a patient presents with a suspected acute abdomen in the emergency department, and a detailed medical history is necessary to make a correct approach to the differential diagnosis.

Headache is frequently reported as a neurological manifestation of myeloproliferative neoplasms (MPNs), including polycythemia vera and essential thrombocythaemia. This study sought to clarify the clinical characteristics and response to treatment of headaches in patients with MPNs.

Post-acute coronavirus disease 2019 (COVID-19) syndrome, also known as long COVID, is a prolonged illness after the acute phase of COVID-19. Hospitalized patients were known to have persisting symptoms of fatigue, headache, dyspnea, and anosmia. There is a need to describe the characteristics of individuals with post-COVID-19 symptoms in comparison to the baseline characteristics.

Recent epidemiological studies have reported an association between the ABO blood group and the acquisition, symptom severity, and mortality rate of coronavirus disease 2019 (COVID-19). However, the association between the ABO blood group antigens and the type and severity of COVID-19 vaccine-related adverse reactions has not been elucidated. We conducted a cross-sectional, questionnaire-based study in Saudi Arabia from February to April 2022. The study cohort included adults who had received or were willing to receive at least two doses of a COVID-19 vaccine of any type. We used Chi-square test to assess the association between the ABO blood groups and vaccine-related adverse reactions. values of <0.05 were considered significant. Of the 1180 participants, approximately half were aged 18-30 years old, 69.2% were female, and 41.6% reported their blood group as O. The most frequent COVID-19 vaccine-related adverse reactions were fatigue (65%), pain at the injection site (56%), and headache (45.9%). These adverse reactions demonstrated significant correlations with the education level ( = 0.003) and nationality ( = 0.018) of the participants following the first dose, with gender ( < 0.001) following the second dose, and with the general health status ( < 0.001) after all the doses. Remarkably, no correlation was observed between the severity of the vaccine-related adverse reactions and ABO blood groups. Our findings do not support a correlation between the severity of COVID-19 vaccine-related adverse reactions and the ABO blood groups of the vaccinees. The creation of a national database is necessary to account for population differences.

We report a very rare case of referred pain associated with entrapment of the greater occipital nerve (GON) occurring not only in the ipsilateral hemiface but also in the ipsilateral limb. There is an extensive convergence of cutaneous, tooth pulp, visceral, neck, and muscle afferents onto nociceptive and nonnociceptive neurons in the trigeminal nucleus caudalis (medullary dorsal horn). In addition, nociceptive input from trigeminal, meningeal afferents projects into trigeminal nucleus caudalis and dorsal horn of C1 and C2. Together, they form a functional unit, the trigeminocervical complex (TCC). The nociceptive inflow from suboccipital and high cervical structures is mediated with small-diameter afferent fibers in the upper cervical roots terminating in the dorsal horn of the cervical cord extending from the C2 segment up to the medullary dorsal horn. The major afferent contribution is mediated by the spinal root C2 that is peripherally represented by the greater occipital nerve (GON). Convergence of afferent signals from the trigeminal nerve and the GON onto the TCC is regarded as an anatomical basis of pain referral in craniofacial pain and primary headache syndrome. Ipsilateral limb pain occurs long before the onset of the referred facial pain. The subsequent severe hemifacial pain suggested GON entrapment. The occipital nerve block provided temporary relief from facial and extremity pain. Imaging studies found a benign osteoma in the ipsilateral suboccipital bone, but no direct contact with GON was identified. During GON decompression, severe entrapment of the GON was observed by the tendinous aponeurotic edge of the trapezius muscle, but the osteoma had no contact with the nerve. Following GON decompression, the referred trigeminal and extremity pain completely disappeared. The pain referral from GON entrapment seems to be attributed to the sensitization and hypersensitivity of the trigeminocervical complex (TCC). The clinical manifestations of TCC hypersensitivity induced by chronic entrapment of GONs are diverse when considering the occurrence of extremity pain as well as facial pain.