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CGRP physiology, pharmacology, and therapeutic targets: Migraine and beyond.

Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse physiological functions. Its two isoforms (α and β) are widely expressed throughout the body in sensory neurons, as well as in other cell types, such as motor neurons and neuroendocrine cells. CGRP acts via at least two G protein-coupled receptors that form unusual complexes with receptor activity-modifying proteins. These are the CGRP receptor and the AMY receptor; in rodents, additional receptors come into play. Although CGRP is known to produce many effects, the precise molecular identity of the receptor(s) that mediate CGRP effects is seldom clear. Despite the many enigmas still in CGRP biology, therapeutics that target the CGRP axis to treat or prevent migraine are a bench to bedside success story. This review provides a contextual background on the regulation and sites of CGRP expression and CGRP receptor pharmacology. The physiological actions of CGRP in the nervous system are discussed, along with updates on CGRP actions in the cardiovascular, pulmonary, gastrointestinal, immune, hematopoietic, and reproductive systems, and metabolic effects of CGRP in muscle and adipose tissues. We cover how CGRP in these systems is associated with disease states, most notably migraine. In this context, we discuss how CGRP actions in both the peripheral and central nervous systems provide a basis for therapeutic targeting of CGRP in migraine. Finally, we highlight potentially fertile ground for the development of additional therapeutics and combinatorial strategies that could be designed to modulate CGRP signaling for migraine and other diseases.

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Applying patient-reported outcome measures (PROMs) in physiotherapy: an evaluation based on the QUALITOUCH Activity Index.

Patient-reported outcome measures (PROMs) are tools to screen a population, to monitor the subjective progress of a therapy, to enable patient-centred care and to evaluate the quality of care. The QUALITOUCH Activity Index (AI) is such a tool, used in physiotherapy. This study aimed to provide reference values for expected AI outcomes.

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Acquired uterine arteriovenous malformation in a patient with cornual pregnancy: A case report.

Acquired uterine arteriovenous malformation (uAVM) is a rare disease and could occur after dilation and curettage, cesarean section, or neoplastic processes.

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Comparing the Efficacy of Dorsal Root Ganglion Stimulation With Conventional Medical Management in Patients With Chronic Postsurgical Inguinal Pain: Post Hoc Analyzed Results of the SMASHING Study.

Approximately 10% of patients who undergo inguinal hernia repair or Pfannenstiel incision develop chronic (> three months) postsurgical inguinal pain (PSIP). If medication or peripheral nerve blocks fail, a neurectomy is the treatment of choice. However, some patients do not respond to this treatment. In such cases, stimulation of the dorsal root ganglion (DRG) appears to significantly reduce chronic PSIP in selected patients.

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Medio-dorsal thalamic dysconnectivity in chronic knee pain: A possible mechanism for negative affect and pain comorbidity.

The reciprocal interaction between pain and negative affect is acknowledged but pain-related alterations in brain circuits involved in this interaction, such as the mediodorsal thalamus (MDThal), still require a better understanding. We sought to investigate the relationship between MDThal circuitry, negative affect and pain severity in chronic musculoskeletal pain. For these analyses, participants with chronic knee pain (CKP, n=74) and without (n=36) completed magnetic resonance imaging scans and questionnaires. Seed-based MDThal functional connectivity (FC) was compared between groups. Within CKP group, we assessed the interdependence of MDThal FC with negative affect. Finally, post-hoc moderation analysis explored whether burden of pain influences affect-related MDThal FC. The CKP group showed altered MDThal FC to hippocampus, ventromedial prefrontal cortex, and subgenual anterior cingulate. Furthermore, in CKP group, MDThal connectivity correlated significantly with negative affect in several brain regions, most notably the medial prefrontal cortex, and this association was stronger with increasing pain burden and absent in pain-free controls. In conclusion, we demonstrate mediodorsal thalamo-cortical dysconnectivity in chronic pain with areas linked to mood disorders and associations of MDThal FC with negative affect. Moreover, burden of pain seems to enhance affect sensitivity of MDThal FC. These findings suggest mediodorsal thalamic network changes as possible drivers of the detrimental interplay between chronic pain and negative affect.

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Prophylactic antibiotics induce early postcraniotomy seizures in neurosurgery patients: A case series.

Antibiotics can cause central nervous system disturbances, manifesting as dizziness, confusion, headache, and seizures. Seizures due to antibiotic administration are related to increased excitatory neurotransmission because antibiotics act as competitive antagonists of the γ-aminobutyric acid type A receptor.

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Effects of esketamine on analgesia and postpartum depression after cesarean section: A randomized, double-blinded controlled trial.

The aim of this randomized double-blind placebo controlled clinical trial was to investigate the effects of different doses of esketamine combined with sufentanil for postoperative intravenous controlled analgesia after cesarean section and the incidence of postpartum depression.

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An unusual case report of porokeratosis ptychotropica on the buttocks.

Porokeratosis ptychotropica represents an unusual form of porokeratosis characterized by symmetrical dyskeratotic skin lesions on the gluteal clefts. Herein, we report a case of porokeratosis ptychotropica.

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Clinician-administered performance-based tests via telehealth in people with chronic lower limb musculoskeletal disorders: Test-retest reliability and agreement with in-person assessment.

Uptake of telehealth has surged, yet no previous studies have evaluated the clinimetric properties of clinician-administered performance-based tests of function, strength, and balance via telehealth in people with chronic lower limb musculoskeletal pain. This study investigated the: (i) test-retest reliability of performance-based tests via telehealth, and (ii) agreement between scores obtained via telehealth and in-person.

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Symptom perception and self-care practice for uraemic pruritus in patients receiving haemodialysis.

Due to the recurrent nature of uraemic pruritus among patients receiving haemodialysis, self-care can offer patients a means to ameliorate this symptom. Qualitative data on self-care of uraemic pruritus are limited.

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