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Chloride – The Underrated Ion in Nociceptors.

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Overuse of opioids for acute migraine in an Australian emergency department.

Acute migraine is associated with significant personal, economic and work-related disability. Management guidelines advise the use of simple analgesia, triptans, chlorpromazine and anti-emetics based on severity, with avoidance of opioids. We aimed to determine consistency of prescribing patterns in our ED with national guidelines.

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Rimegepant: First Approval.

The orally disintegrating tablet (ODT) formulation of rimegepant (NURTEC ODT) is a small molecule, highly-selective, calcitonin gene-related peptide antagonist that was developed by Biohaven Pharmaceutical Holding Company Ltd as an acute treatment for migraine. A conventional tablet formulation of the drug is being investigated for the acute treatment (under FDA review in the USA) and prevention of migraine and the treatment of refractory trigeminal neuralgia. In February 2020, rimegepant ODT received its first global approval in the USA for the acute treatment of migraine (± aura) in adults. This article summarizes the milestones in the development of rimegepant leading to its first global approval for acute treatment of migraine (± aura) in adults.

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The polymorphisms of IL-6/STAT3 signaling pathway may contribute to cutaneous T-cell lymphomas susceptibility.

IL-6/STAT3 signaling pathway has been suggested to play a role in CTCL pathogenesis. Polymorphisms in STAT3 signaling pathway-related genes might be a risk factor for CTCL. However, the exact role of inherited gene polymorphisms of IL-6 and STAT3 in the pathogenesis of CTCL is still not fully understood. The aim was to examine whether IL-6 cytokine and polymorphisms of IL-6 and STAT3 gene are associated with CTCL susceptibility, stage of disease and pruritus intensity. We compared the IL-6 serum level and the frequency of selected single nucleotide polymorphisms of IL-6 and STAT3 in 106 CTCL and 198 control group using polymerase chain reaction with sequence-specific primers method and ELISA. We have found that serum IL-6 level in CTCL patients was significantly higher than in healthy controls (p < 0.05). We also demonstrated that two genotypes, CC of IL-6 and GG of STAT3, were overexpressed in CTCL patients compared to healthy controls, and that they increase the risk of malignancy development (OR = 1.8, p = 0.04 for IL-6 and OR 2.53, p = 0.0064 for STAT3). Moreover, the GG genotype of STAT3 polymorphism seems to be associated with lack of pruritus or mild pruritus in CTCL patients. Our results indicate that IL-6 is involved in pathogenesis of CTCL but not pruritus. Moreover, CC of IL-6 and GG genotype of STAT3 genes might be considered as the risk factor for development of CTCL.

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Medication as a risk factor for hospitalization due to heart failure and shock: a series of case-crossover studies in Swiss claims data.

Heart failure is among the leading causes for hospitalization in Europe. In this study, we evaluate potential precipitating factors for hospitalization for heart failure and shock.

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[Paraganglioma of urinary bladder: a clinicopathological features analysis of 23 cases].

To investigate the clinicopathological features, diagnosis, differential diagnosis and immunohistochemical (IHC) characteristics of paraganglioma of urinary bladder (PUB). The clinical and pathological data of 23 cases of PUB were collected at the Second Affiliated Hospital of Fujian Medical University (7 cases); Fujian Provincial Hospital (8 cases); Fujian Medical University Union Hospital (6 cases); and First Affiliated Hospital of Fujian Medical University (2 cases) from May 2010 to November 2018. IHC staining for CK, GATA3, CD56, Syn, CgA, S-100 protein, HMB45, SDHB, OCT3/4 and Ki-67 was done using EliVision method; and the relevant literature was reviewed. There were 14 women and 9 men, aged ranged from 21 to 73 years (median 51 years). Clinically, patients presented with headache, vertigo, palpitation, hypertensive crisis during micturition, hypertension, blurred vision, gross hematuria and paroxysmal pallor. The tumor sizes ranged from 0.9 to 6 cm (mean2.5 cm). Macroscopically, most tumors were exophytic and well delineated within the lamina propria or muscularis propria. The tumors were firm and nodular and showed grayish-tan cut surface. Histologically,the tumor growth pattern was expansive or showed interpenetrating infiltrative growth within the lamina propria or muscularis propria; the tumor cells were typically arranged in distinctive nests (Zellballen) with organoid arrangement; pseudo-rosette were seen in some cases. The cells were rounded or polygonal and had rich, acidophilic or amphophilic cytoplasm and may contain pigmented granules and vacuoles; the nuclei were central or eccentric, with small nucleoli, although occasionally some nuclei were pleomorphic and hyperchromatic. Spindled sustentacular cells could be seen around the nests of tumor cells in some cases. There were abundant vessels that were fissure-like, hemangioma-like or dilated. By IHC, the tumor cells were positive for GATA3 (2/23), OCT3/4 (2/23), CD56 (22/23), Syn (23/23), CgA (22/23), S-100 (sustentacular cell, 23/23) and SDHB (23/23); and negative for CK and HMB45; Ki-67 index was 1%-5%. At follow-up, there was no recurrence or metastasis in 18 cases. The diagnosis of PUB relies on the morphologic and IHC features; but there may be histomorphologic heterogeneity. The most important differential diagnosis is invasive urothelial carcinoma. The tumor cells may show aberrant cytoplasmic expression of OCT3/4; there is no clear correlation between SDHB and OCT3/4 expression in the group.

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Sustained virologic response and changes in liver fibrosis parameters following 12-wk administration of generic sofosbuvir and daclatasvir in HIV/HCV-coinfected patients with HCV genotype 4 infection.

Novel direct-acting antiviral agents have shown great efficacy and tolerability in HCV-monoinfected patients. However, data are lacking regarding their efficacy and safety in HIV/HCV-genotype (GT) 4-coinfected patients.

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Protein Signature in Saliva of Temporomandibular Disorders Myalgia.

In the last years, several attempts have been made to study specific biological markers of temporomandibular disorders (TMD). So far, no laboratory tests have been appropriately validated for the diagnosis and prognosis of these disorders. This study aimed to investigate the proteomic profile of the whole stimulated saliva of TMD myalgia patients in order to evaluate potential diagnostic and/or prognostic salivary candidate proteins which could be useful for the management of TMD. Twenty patients diagnosed with TMD myalgia according to the validated Diagnostic Criteria for TMD (DC/TMD) and 20 matched healthy pain-free controls were enrolled. Saliva samples were collected in the morning. Comparative proteomic analysis was performed with two-dimensional gel electrophoresis followed by identification with liquid chromatography-tandem mass spectrometry. Statistical analysis of the quantitative proteomics data revealed that 20 proteins were significantly altered in patients compared to controls. Among these proteins, 12 showed significantly increased levels, and 8 showed significantly decreased levels in patients with TMD myalgia compared to controls. The identified proteins are involved in metabolic processes, immune response, and stress response. This proteomic study shows that the salivary protein profile can discriminate patients with TMD myalgia from healthy subjects, but the protein signature has no correlation with the clinical features of TMD myalgia. Additional studies are needed to validate our observations in additional sample sets and to continue assessing the utility of saliva as a suitable sample for studying processes related to TMD myalgia.

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Yoga and Mindfulness as a Tool for Influencing Affectivity, Anxiety, Mental Health, and Stress among Healthcare Workers: Results of a Single-Arm Clinical Trial.

Mindfulness-based interventions have emerged as unique approaches for addressing a range of clinical and subclinical difficulties such as stress, chronic pain, anxiety, or recurrent depression. Moreover, there is strong evidence about the positive effects of yoga practice on stress management and prevention of burnout among healthcare workers. The aim of this study was to conduct a single-arm clinical trial to assess the effectiveness of an intervention based on mindfulness-based stress reduction and yoga in improving healthcare workers' quality of life. Healthcare workers of two hospitals in Rome were enrolled in a 4-week yoga and mindfulness course. Four questionnaires were administered at different times (Short Form-12 (SF-12), State-Trait Anxiety Inventory (STAI) Y1 and Y2, and Positive and Negative Affect Schedule (PANAS)) to evaluate the efficacy of the intervention. Forty participants took part to the study (83.3 %). The Mental Composite Score-12, that is part of the quality of life assessment, passed from a median of 43.5 preintervention to 48.1 postintervention ( = 0.041), and the negative affect passed from a score of 16 in the preintervention to 10 in the postintervention ( < 0.001). Both the forms of the STAI questionnaires showed a decrease after the intervention. Yoga and mindfulness administered together seem to be effective to reduce stress and anxiety in healthcare workers, providing them with more consciousness and ability to manage work stressful demands.

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Characterization of the Antinociceptive Activity from Cav.

Cav. (Asteraceae), widely found in Guatemala, is used to treat gastrointestinal problems. The aim of this study was to demonstrate the antinociceptive and anti-inflammatory effects of the essential oil (EO) and the mechanism of action.

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