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- Evolution of the glucagon-like system across fishPublication . Cardoso, João CR; Félix, Rute C.; Costa, Carina; PFS, Palma; Canario, Adelino; Power, DeborahIn fishes, including the jawless lampreys, the most ancient lineage of extant vertebrates, plasma glucose levels are highly variable and regulation is more relaxed than in mammals. The regulation of glucose and lipid in fishes in common with mammals involves members of the glucagon (GCG)-like family of gastrointestinal peptides. In mammals, four peptides GCG, glucagon-like peptide 1 and 2 (GLP1 and GLP2) and glucose-dependent insulinotropic peptide (GIP) that activate four specific receptors exist. However, in lamprey and other fishes the glucagon-like family evolved differently and they retained additional gene family members (glucagon-related peptide, gcrp and its receptor, gcrpr) that are absent from mammals. In the present study, we analysed the evolution of the glucagon-like system in fish and characterized gene expression of the family members in the European sea bass (Dicentrarchus labrax) a teleost fish. Phylogenetic analysis revealed that multiple receptors and peptides of the glucagon-like family emerged early during the vertebrate radiation and evolved via lineage specific events. Synteny analysis suggested that family member gene loss is likely to be the result of a single gene deletion event. Lamprey was the only fish where a putative glp1r persisted and the presence of the receptor gene in the genomes of the elephant shark and coelacanth remains unresolved. In the coelacanth and elephant shark, unique proglucagon genes were acquired which in the former only encoded Gcg and Glp2 and in the latter, shared a similar structure to the teleost proglucagon gene but possessed an extra exon coding for Glp-like peptide that was most similar to Glp2. The variable tissue distribution of the gene transcripts encoding the ligands and receptors of the glucagon-like system in an advanced teleost, the European sea bass, suggested that, as occurs in mammals, they have acquired distinct functions. Statistically significant (p < .05) down-regulation of teleost proglucagon a in sea bass with modified plasma glucose levels confirmed the link between these peptides and metabolism. The tissue distribution of members of the glucagon-like system in sea bass and human suggests that evolution of the brain-gut-peptide regulatory loop diverged between teleosts and mammals despite the overall conservation and similarity of glucagon-like family members.
- Clinical and epidemiological characteristics of patients with functional stroke mimics: a case–control study from Southern PortugalPublication . Figueira Domingos, Miguel; Silva, Vítor Hugo; Schuh, Sara; Correia, Helena; Palma, Pedro; Pedro, João Pedroso; Nova, Bruno Vila; Marreiros, Ana; Félix, Ana Catarina; Nzwalo, HipólitoBackground: Patients with functional neurological disorder presenting as stroke mimics or functional stroke mimics (FSMs) pose significant diagnostic challenges. In the acute phase, especially when patients are present within the therapeutic window for acute reperfusion treatments, a misdiagnosis of FSM can lead to unnecessary and costly interventions. Despite its clinical importance, the literature on the risk factors for FSM is limited. This study aims to compare the clinical and epidemiological characteristics of patients with FSM to those with confirmed acute ischemic stroke (AIS). Methods: This case-control study involved temporal matching between consecutive series of patients with FSM and controls with AIS from a single tertiary university hospital in southern Portugal. Results: A total of 188 patients were included: 64 cases (FSM) and 188 controls (AIS). The rate of stroke code activation and use of ambulance between was comparable between the two groups. The group of patients with FSM was younger (53.2 years vs. 69.5 years, p < 0.001) and had a higher proportion of females (52.4% vs. 47.6%, p = 0.001). There was no difference in terms of clinical severity at presentation. The proportion of specific signs, such as transcortical aphasia (3.1% vs. 20.9%, p = 0.014), gait abnormalities (15.6% vs. 33.9%, p = 0.004), and cranial nerve abnormalities (31.2% vs. 43.5%, p = 0.042), was lower in the FSM group compared to the AIS group. The proportion of patients on antithrombotic therapy (90.9% vs. 9.1%, p = 0.007) and antihypertensive drugs (78.5%, vs. 21.5%, p < 0.001) prior to the event was significantly higher in the AIS group. Likewise, the prevalence of cerebrovascular risk factors such as diabetes mellitus (14.3% vs. 85.7%, p = 0.005), arterial hypertension (23.8% vs. 76.2%, p = 0.001), and smoking (43.7% vs. 56.3%, p = 0.005) was lower in the FSM group compared to the AIS group. No statistically significant differences were observed in cholesterol levels or the prevalence of dyslipidemia between the two groups. Psychiatric comorbidities, including generalized anxiety disorder (71.4% vs. 28.6%, p = 0.05) and major depressive disorder (61.9% vs. 28.1%, p = 0.01), were more prevalent in the FSM group. Conclusions: Patients with FSM display different clinical and epidemiological profiles, with a higher likelihood of being younger, female, having prior psychiatric conditions, and lacking traditional cerebrovascular risk factors.