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Synthesis of 2-(2-(4-thioxo-3H-1,2-dithiole-5-yl) phenoxy)ethyl)isoindole-1,3-thione, a novel hydrogen sulfide-releasing phthalimide hybrid, and evaluation of its activity in models of inflammatory pain.

Hydrogen sulfide (HS) is a gaseous mediator that modulates several physiological and pathological processes. Phthalimide analogues, substances that have the phthalimide ring in the structure, belong to the group of thalidomide analogues. Both HS donors and phthalimide analogues exhibit activities in models of inflammation and pain. As molecular hybridization is an important strategy aiming to develop drugs with a better pharmacological profile, in the present study we synthesized a novel HS-releasing phthalimide hybrid, 2-(2-(4-thioxo-3H-1,2-dithiole-5-yl) phenoxy)ethyl)isoindole-1,3-thione (PTD-HS), and evaluated its activity in models of inflammatory pain in mice. Per os (p.o.) administration of PTD-HS (125 or 250 mg/kg) reduced mechanical allodynia induced by carrageenan and lipopolysaccharide. Intraperitoneal (i.p.) administration of PTD-HS (25 mg/kg), but not equimolar doses of its precursors 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (14.2 mg/kg) and 2-phthalimidethanol (12 mg/kg), reduced mechanical allodynia induced by lipopolysaccharide. The antiallodynic effect induced by PTD-HS (25 mg/kg, i.p.) was more sustained than that induced by the HS donor NaHS (8 mg/kg, i.p.). Previous administration of hydroxocobalamin (300 mg/kg, i.p.) or glibenclamide (40 mg/kg, p.o.) attenuated PTD-HS antiallodynic activity. In conclusion, we synthesized a novel HS-releasing phthalimide hybrid and demonstrated its activity in models of inflammatory pain. PTD-HS activity may be due to HS release and activation of ATP-sensitive potassium channels. The demonstration of PTD-HS activity in models of pain stimulates further studies aiming to evaluate HS-releasing phthalimide hybrids as candidates for analgesic drugs.

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An Association Study of ESR1-XbaI and PvuII Gene Polymorphism in Migraine Susceptibility in the Jammu Region.

Migraine is a neurovascular disorder and is clinically characterized by episodic attacks of mild to severe headaches. Due to the involvement of multiple environmental and genetic factors, it has become a much more complex neurological condition to understand. Apart from the environmental variables, a plethora of genes have been implicated, and one such example is ESR1. The present study was focused to find out the association of two important polymorphisms, namely, PvuII and XbaI of the ESR1 with migraine in the population of Jammu and Kashmir (UT).

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Cryptococcal osteomyelitis of the left acetabulum: A case report.

Cryptococcus, as a classical "opportunistic" fungal pathogen, is capable of disseminating an invasive infection in immunocompromised hosts. The primary sites of infection include the respiratory and central nervous systems, and skeletal infection was rarely reported. In this case, we describe a case of cryptococcal osteomyelitis involving the left side of the acetabulum in a Chinese patient with chronic hepatitis B.

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Skin biopsy reveals generalized small fibre neuropathy in hypermobile Ehlers-Danlos syndromes.

Ehlers-Danlos syndromes are hereditary disorders of connective tissue that are characterized by joint hypermobility, skin hyperextensibility and tissue fragility. The most common subtype is the hypermobile type. In addition to symptoms of small fibre neuropathy (SFN) due to damage to the small peripheral nerve fibres with degeneration of the distal nerve endings, autonomic disorders such as postural tachycardia syndrome are frequently reported features in patients with hypermobile Ehlers-Danlos syndromes (hEDS). To date, the underlying pathophysiological mechanisms are still not completely understood.

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Is prednisone still a reasonable option in the treatment of withdrawal headache in patients with chronic migraine and medication overuse headache in the age of CGRP antibodies? A narrative review.

Along with the development of novel migraine therapies as the monoclonal antibodies against calcitonin gene-related peptide (CGRP) and its receptor, the question arises if the treatment of chronic migraine (CM) and medication overuse headache (MOH) must be reconsidered. Have previous therapeutic approaches, including glucocorticoids, lost their role in the management of this debilitating disorder? In this narrative review, we present an overview of the available treatment options in CM and MOH in light of CGRP antibodies as well as an evaluation of the role of glucocorticoids in withdrawal therapy.

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Treatment of multiple sclerosis-related trigeminal neuralgia with onabotulinumtoxinA.

The effectiveness of onabotulinumtoxinA (BTX-A) has been established in primary trigeminal neuralgia (TN). However, to the best of our knowledge, the efficacy of BTX-A in secondary TN has not yet been studied.

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Comparison of ultrasound-guided supraclavicular and costoclavicular brachial plexus blocks in pediatric patients: a randomized clinical trial.

Costoclavicular brachial plexus block has been described recently as a new technique in adults and pediatric patients. In this study, we aimed to compare the supraclavicular and costoclavicular approaches, which are claimed to be effective and practical in pediatric patients.

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Reverse total shoulder arthroplasty pain and function: new perspectives from a 10-year multicenter study at the 7-year follow-up.

Reverse total shoulder arthroplasty (RTSA) can decrease shoulder pain and improve function. However, results reportedly deteriorate as patients approach mid-term follow-up and little is known about how this impacts physical health-related quality of life (PHRQOL) and mental health-related quality of life (MHRQOL). The study hypothesis was that shoulder function, pain, and medication use for pain would influence PHRQOL and MHRQOL.

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Post-traumatic instability of the first metatarsophalangeal joint: a novel surgical technique of capsular reconstruction in a young kickboxer.

Aim To report a novel surgical technique of capsular reconstruction of post-traumatic instability of the first metatarsophalangeal joint (MTPJ). Methods The clinical case is related to a 24-year-old male athlete whose clinical symptoms began with pain and spontaneous dislocation of the left first MTPJ during a kickboxing fight. He received conservative treatment (cryotherapy and rest) at first. Afterwards, he referred persistent hallux instability associated with moderate pain, despite normal anatomic alignment with no evidence of first ray deformity. Plain traditional x-rays of the left foot, magnetic resonance imaging (MRI), static and dynamic ultrasonography (US) and clinical tests were performed in order to diagnose capsular ligamentous structure lesions. Results The plain x-rays showed angle of 3°. The MRI and US demonstrated a rupture of the lateral capsular ligamentous structures and detachment of the abductor tendon. The pull out medium-lateral of the capsule with the abductor suture was performed as a treatment for dynamic hallux varus deformity. At six-month follow up, the patient walked without lameness with complete active and passive range of motion and with a stable first MTPJ. Conclusion The patient presented with the post traumatic instability of the first metatarsophalangeal joint treated with a novel surgical technique of capsular reconstruction. The patient returned to the full weight-bearing in only 2 months of rehab. To the best of our knowledge, the surgical correction proposed has not been previously described.

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Spinal cord stimulation in chronic pain treatment – first experiences in Bosnia and Herzegovina.

Aim To describe results of spinal cord stimulation technique when the conventional multidisciplinary treatment of neuropathic or mixed pain failed. Methods The research was conducted at the Institute for Physical Medicine and Rehabilitation "Dr. Miroslav Zotović", Banjaluka. Ten patients, who had chronic pain resistant to other therapeutic options and a failed back surgery, were sent for an evaluation. Each patient underwent a 4-week evaluation by a team of medical specialists, phychologist and social workers. Additional diagnostic methods (MRI of the lumbosacral spine, electromyoneurography of lower extermities, congnitive assessment tests) were also performed to establish a proper indication for implantation of the system for spinal cord stimulation. Leads of a system for spinal cord stimulation were implanted percutaneously or surgically at the epidural space. Functional outcome measures (visual analogue scale, Oswestry index, anxiety and depression scales) were taken before the implantation of the system and on several followups. Results Four patients did not meet critea for the inclusion in the study (two were not ready, two showed psychopathological symptoms). One patient had a percutaneous lead implant, but it was removed after six months due to paresthesia. The remaining five had surgicaly implanted epidural leads and showed significant improvement in pain control, Oswestry index had lower values, and all except one patient had improvement registered by anxiety and depression scales. Conclusion. Short-term and long-term follow up showed a long lasting pain reduction and improvement of functionality in all patients.

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