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Introduction: Preclinical data implicate large conductance calcium-activated potassium (BKCa) channels in the pathogenesis of headache and migraine, but the exact role of these channels is still unknown. Here, we investigated whether opening of BKCa channels would cause headache and vascular effects in healthy volunteers.Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 21 healthy volunteers aged 18-39 years were randomly allocated to receive an intravenous infusion of 0.05 mg/min BKCa channel opener MaxiPost and placebo on two different days. The primary endpoints were the difference in incidence of headache and the difference in area under the curve (AUC) for headache intensity scores (0-12 hours) and for middle cerebral artery blood flow velocity (VMCA) (0-2 hours) between MaxiPost and placebo. The secondary endpoints were the differences in area under the curve for superficial temporal artery and radial artery diameter (0-2 hours) between MaxiPost and placebo.Results: Twenty participants completed the study. Eighteen participants (90%) developed headache after MaxiPost compared with six (30%) after placebo (p = 0.0005); the difference of incidence is 60% (95% confidence interval 36-84%). The area under the curve for headache intensity (AUC0-12 hours, p = 0.0003), for mean VMCA (AUC0-2 hours, p = 0.0001), for superficial temporal artery diameter (AUC0-2 hours, p = 0.003), and for radial artery diameter (AUC0-2 hours, p = 0.03) were significantly larger after MaxiPost compared to placebo.Conclusion: MaxiPost caused headache and dilation in extra- and intracerebral arteries. Our findings suggest a possible role of BKCa channels in headache pathophysiology in humans. ClinicalTrials.gov, ID: NCT03887325. [ABSTRACT FROM AUTHOR]

While the prevalence of supernumerary teeth (ST) is high in permanent dentition, the etiology of ST in humans remains unclear. However, multiple murine models of ST have elaborated on dated mechanisms traditionally ascribed to ST etiology: one involves the rescue of rudimental teeth, and the second considers the contribution of odontogenic epithelial stem cells. It remains unclear whether these mechanisms of ST formation in mice are applicable to humans. The third dentition is usually regressed apoptotic-that is, the teeth do not completely form in humans. Recently, it was suggested that ST result from the rescue of regression of the third dentition in humans. The present investigation evaluates the proportion of collected general ST cases that evinced a third dentition based on the clinical definition of ST derived from the third dentition. We also investigated the contribution of SOX2-positive odontogenic epithelial stem cells to ST formation in humans. We collected 215 general ST cases from 15,008 patients. We confirmed that the general characteristics of the collected ST cases were similar to the results from previous reports. Of the 215 cases, we narrowed our analysis to the 78 patients who had received a computed tomography scan. The frequency of ST considered to have been derived from the third dentition was 26 out of 78 cases. Evidence of a third dentition was especially apparent in the premolar region, was more common in men, and was more likely among patients with ≥3 ST. SOX2-positive odontogenic epithelial stem cells within the surrounding epithelial cells of developing ST were observed in non-third dentition cases and not in third dentition cases. In conclusion, the third dentition is the main cause of ST in humans. The odontogenic epithelial stem cells may contribute to ST formation in cases not caused by a third dentition. [ABSTRACT FROM AUTHOR]

Preclinical work suggests that GET 73 (N-[4-(trifluoromethyl)benzyl]-4-methoxybutyramide), a novel metabotropic glutamate receptor subtype 5 negative allosteric modulator, may represent a novel pharmacological treatment for alcohol use disorder. Two independent experiments evaluated the effect of acutely administered GET 73 (0, 30, and 100 mg/kg, intragastrically) on alcohol-induced hypolocomotion ( n=72) and sedation/hypnosis ( n=36) in rats. In healthy male volunteers ( n=14), an open-label, randomised, crossover study was conducted to compare adverse events and pharmacokinetic parameters, in two experiments in which 300 mg GET 73 was administered, with and without alcohol, once and thrice. In rats, when administered with alcohol-vehicle, 100 mg/kg, but not 30 mg/kg, GET 73 reduced spontaneous locomotor activity. When administered with alcohol, no dose of GET 73 altered either alcohol-induced hypolocomotion or sedation/hypnosis. In humans, both single and thrice 300 mg GET 73 administration were well tolerated, in the presence and absence of alcohol, with no differences in adverse events. There were no significant differences in relative bioavailability between administering 300 mg GET 73 in the presence or absence of alcohol. [ABSTRACT FROM AUTHOR]

Purpose: To compare two intensity levels (standard vs. enhanced) of a nutrition and physical activity intervention vs. a control (usual programs) on nutrition knowledge, body mass index, fitness, academic performance, behavior, and medication use among elementary school students.Design: Quasi-experimental with three arms.Setting: Elementary schools, students' homes, and a supermarket.Subjects: A total of 1487 third-grade students.Intervention: The standard intervention (SI) provided daily physical activity in classrooms and a program on making healthful foods, using food labels. The enhanced intervention (EI) provided these plus additional components for students and their families.Measures: Body mass index (zBMI), food label literacy, physical fitness, academic performance, behavior, and medication use for asthma or attention-deficit hyperactivity disorder (ADHD).Analysis: Multivariable generalized linear model and logistic regression to assess change in outcome measures.Results: Both the SI and EI groups gained less weight than the control (p < .001), but zBMI did not differ between groups (p = 1.00). There were no apparent effects on physical fitness or academic performance. Both intervention groups improved significantly but similarly in food label literacy (p = .36). Asthma medication use was reduced significantly in the SI group, and nonsignificantly (p = .10) in the EI group. Use of ADHD medication remained unchanged (p = .34).Conclusion: The standard intervention may improve food label literacy and reduce asthma medication use in elementary school children, but an enhanced version provides no further benefit. [ABSTRACT FROM AUTHOR]