Rejected

Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP). However, effective therapeutic drugs for IDD remain to be further explored. Inflammatory cytokines play a pivotal role in the onset and progression of IDD. Dihydroartemisinin (DHA) has been well reported to have powerful anti-inflammatory effects, but whether DHA could ameliorate the development of IDD remained unclear. In this study, the effects of DHA on extracellular matrix (ECM) metabolism and cellular senescence were firstly investigated in nucleus pulposus cells (NPCs) under tumor necrosis factor alpha (TNF)-induced inflammation. Meanwhile, AKT agonist sc-79 was used to determine whether DHA exerted its actions through regulating PI3K/AKT and NF-B signaling pathways. Next, the therapeutic effects of DHA were tested in a puncture-induced rat IDD model. Finally, we detected the activation of PI3K/AKT and NF-B signaling pathways in clinical degenerative nucleus pulposus specimens. We demonstrated that DHA ameliorated the imbalance between anabolism and catabolism of extracellular matrix and alleviated NPCs senescence induced by TNF. Further, we illustrated that DHA mitigated the IDD progression in a puncture-induced rat model. Mechanistically, DHA inhibited the activation of PI3K/AKT and NF-B signaling pathways induced by TNF, which was undermined by AKT agonist sc-79. Molecular docking predicted that DHA bound to the PI3K directly. Intriguingly, we also verified the activation of PI3K/AKT and NF-B signaling pathways in clinical degenerative nucleus pulposus specimens, suggesting that DHA may qualify itself as a promising drug for mitigating IDD.

Case 1, a 6-year-old, spayed female Pug, presented with severe systemic urticaria, edema, and erythema. The dog had received a famotidine injection as a treatment for repeated vomiting in another hospital. On physical examination, hyperthermia was observed. Moderate pancytopenia, hypoalbuminemia, and increased CRP and D-dimer were also observed in blood tests. Hyposthenuric proteinuria, pulmonary interstitial infiltration, and hepatomegaly were found in other tests. In the histology of the skin, dermal edema and infiltration of inflammatory cells were observed. Therefore, she was diagnosed with acute systemic hypersensitivity. Case 2, a 13-month-old, neutered male Pembroke welsh corgi, presented with severe and patchy systemic ulcerative skin lesions. The dog had a history of soft feces and pain around the anus 2 days before. Thrombocytopenia, and increased CRP and D-dimer were observed in blood tests. In histology, epidermal necrolysis, separation of the epidermis and dermis, and infiltration of inflammatory cells were observed. Therefore, he was diagnosed with an immune-mediated disease with necrolysis dermatitis. Case 3, a 12-year-old, spayed female Pomeranian, presented with severe systemic alopecia, pustule, and crust on the skin. The dog had received an infection treatment from a local hospital. Severe regenerative anemia (hematocrit 15.3%, negative saline agglutination test, negative slide agglutination test, negative Coomb's test, prominent spherocytes) elevated liver enzymes, and increased CRP and D-dimer were observed in blood tests. On histopathology of the skin, pustules, acantholytic cells, and inflammatory cells were observed in the keratin layer of the epithelium. Therefore, she was diagnosed with concurrent with immune-mediated hemolytic anemia. The 3 cases were diagnosed with fatal immune-mediated skin disease concurrently with hematological and systemic abnormalities. All the cases were treated with immune-suppressive drugs, prednisolone, and cyclosporine. In cases 2 and 3, the dogs also received human intravenous immunoglobulin as an immune modulator. The treatment was successful with significant improvements in all the 3 cases.

We report the case of an 8-year-old child with a complex neurodevelopmental disorder, including severe developmental coordination disorder with dysgraphia, anxiety and depression, mild social functioning impairments, headache and chronic musculoskeletal pain, secondary to Ehlers-Danlos syndrome (EDS) hypermobility type. We explored whether wearing whole-body compressive garments (CGs) could improve his motor skills assessed through standardized and experimental procedures. In addition to the effectiveness of CGs on pain, we found partial improvements in his motor skills, specifically postural control, hand movements, and body schema representation, after wearing CGs for 15 days. During an experimental motor imitation task with a virtual tightrope walker, we found improvements in interpersonal synchronization with performances closer to those of typical developing (TD) controls. We conclude that CGs appear to be an innovative and interesting adjuvant treatment for motor skill impairments in children with multidimensional impairments involving EDS. These promising results require confirmation by further evidence-based research.

Primary dysmenorrhea (PDM) is a common gynecological disease and chronic pain disorder. Moxibustion, a form of traditional Chinese medicine therapy, has proven to be effective for PDM. However, the central mechanisms of PDM and moxibustion for PDM are still unclear. This study aims to explore the potential central mechanism of PDM and clarify the possible mechanism of moxibustion for relieving pain.

Systemic lupus erythematosus (SLE) involves dysregulation of the immune system, consequently affecting multiple organ systems, including the cardiovascular, neuropsychiatric, renal, and musculoskeletal systems. Optic neuritis and intracranial hypertension are conditions that rarely occur in SLE, and their coexistence has not been reported to date. Herein, we report the first case of a patient who was diagnosed with SLE complicated by concurrent intracranial hypertension and bilateral optic neuritis. An 11-year-old Thai girl had a low-grade fever, discoid rash, oral ulcer, chronic headache, and fluctuating diplopia. She experienced bilateral vision loss just before presentation. She was diagnosed with juvenile SLE. We believe that her headache, which was probably a symptom of optic disc edema, was due to intracranial hypertension. Furthermore, she exhibited vision loss and color vision deficit and was diagnosed with bilateral optic neuritis. Her condition improved on treatment with corticosteroids (intravenous pulse methylprednisolone for 3 days, followed by 1 mg/kg/day oral prednisolone tapered over 3 months). The occurrence of optic neuritis and intracranial hypertension during an active SLE inflammation and a rapid response to high-dose corticosteroids support the fact that SLE was the etiology of these neuropsychiatric conditions. Early diagnosis and prompt treatment in such cases can lead to favorable outcomes.

Cervical Artery Dissection (CeAD) is a frequent stroke etiology for patients younger than 50 years old. The most common immediate complications related to CeAD are headache and neck pain (65-95%), TIA/ischemic stroke (>50%), and partial Horner's syndrome (25%). The prevailing hypothesis regarding the pathogenesis of sCeAD is that the underlying constitutional vessel wall weakness of patients with sCeAD is genetically determined and that environmental factors could act as triggers. The stroke prevention treatment of CeAD remains controversial, involving anticoagulation or antiplatelet therapy and potentially emergent stenting and/or thrombectomy or angioplasty for selected cases of carotid artery dissection with occlusion. The treatment of headache associated with CeAD depends on the headache phenotype and comorbidities. Radiographically, more than 75% of CeAD cases present with occlusion or non-occlusive stenosis. Many patients demonstrate partial and complete healing, more commonly in the carotid arteries. One-fifth of the patients develop dissecting pseudoaneurysm, but this is a benign clinical entity with an extremely low rupture and stroke recurrence risk. Good recovery is achieved in many CeAD cases, and mortality remains low. Family history of CeAD, connective tissue disorders like Ehlers-Danlos syndrome type IV, and fibromuscular dysplasia are risk factors for recurrent CeAD, which can occur in 3-9% of the cases. This review serves as a comprehensive, updated overview of CeAD, emphasizing etiopathogenesis and management.

Accumulating evidence suggests a role of the brainstem in tinnitus generation and modulation. Several studies in chronic tinnitus patients have reported latency and amplitude changes of the different peaks of the auditory brainstem response, possibly reflecting neural changes or altered activity. The aim of the systematic review was to assess if alterations within the brainstem of chronic tinnitus patients are reflected in short- and middle-latency auditory evoked potentials (AEPs).

To determine the clinical efficacy of recombinant human epidermal growth factor (rh-EGF) combined with povidone-iodine (PVI) on patients with pressure ulcers (PUs).

Celiac disease (CD) is a chronic autoimmune condition with intestinal and extra-intestinal features. Extra intestinal features including hematological, neurological, and endocrine symptoms are seen more frequently in elder children. A 4 years 7 months old male child presented in clinic with history of abdominal pain and diarrhea on and off for 1 year. On examination, he was hemodynamically stable, pale, and malnourished with distended abdomen. He was investigated for CD, Anti TTG IgA <0.1 (positive >10), Anti TTG IgG 13 (positive >10). To confirm celiac disease, Esophagogastroduodenoscopy (EGD) was done which was consistent with diagnosis of Celiac disease (MARSH Type 3a). Gluten free diet was advised. Later, after 12 days he again presented with jaundice, fever, anorexia, and dark colored urine and irritability. He was admitted for fulminant hepatic failure, his workup revealed direct hyperbilirubenemia, ANA +ve, and hyper IgG. Liver biopsy confirmed autoimmune hepatitis. Further workup for anemia showed reticulocyte count 7.1, LDH 423, direct and indirect coombs test was positive confirming autoimmune hemolytic anemia. Child responded well to Azathioprine and prednisolone with clinical improvement. We report a rare presentation of celiac disease with polyautoimmunity in a young child. Case reports of autoimmune hepatitis with CD patients have been reported in adult patients. Association of celiac disease with autoimmune hemolytic anemia and autoimmune hepatitis is a distinct and rare condition.

Neurovascular disorders is a heterogenous group of diseases, including one of the most time critical disorders in emergency medicine; stroke. Sex differences are extensively described in neurovascular disorders, ranging from differences in symptom presentation, risk factors, treatment and outcomes. For example, women with stroke, more often present with generalized weakness, reduced consciousness and headache than men. Furthermore, there are differences in risk factors, outcomes and in the effect of secondary prevention. Women have a higher risk of cerebral venous thrombosis and developing cerebral aneurysms. In general, women have been underrepresented in trials on neurovascular disorders. This chapter provides an extensive overview of sex differences in stroke in general and in the differences specially seen in ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage and in cerebral venous thrombosis.