Methylamine but not mafenide mimics insulin-like activity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism

It has been reported that benzylamine reduces blood glucose in rabbits, stimulates hexose uptake, and inhibits lipolysis in mouse, rabbit, and human adipocytes. In the presence of vanadate, benzylamine is also able to improve glucose disposal in normoglycaemic and diabetic rats. Such insulin-mimicking properties are the consequence of hydrogen peroxide production during benzylamine oxidation by semicarbazide-sensitive amine oxidase (SSAO). The aim of the study was to determine whether other SSAO-substrates could share such potential antidiabetic properties. Thus, mafenide, a synthetic antimicrobial sulfonamide structurally related to benzylamine, and which has been recently reported to interact with SSAO, was tested in the above mentioned models, in parallel with methylamine, a proposed endogenous SSAO-substrate. All tested amines stimulated glucose uptake and inhibited lipolysis in rat and mouse fat cells. Methylamine and benzylamine, but not mafenide, reduced the hyperglycaemic response during a glucose tolerance test in rabbits while the three amines tested were devoid of insulin-releasing activity under both in vivo and in vitro conditions. In human adipocytes, mafenide did not stimulate glucose transport since it was not a high-affinity substrate for SSAO and generated less hydrogen peroxide than benzylamine or methylamine. Therefore, mafenide could not be considered as an antidiabetic drug despite being oxidized and exhibiting insulin-mimicking effects in rat and mouse adipocytes. By contrast, the endogenous substrate methylamine improved glucose utilization in all in vitro and in vivo models, leading to consider novel SSAO substrates as drugs with potential anti-hyperglycaemic properties.     

Correlation between diminished vagal tone and somatic dysfunction severity in very and extremely low birth weight preterm infants assessed with frequency spectrum heart rate variability and salivary cortisol

Osteopathic manipulative treatment (OMT) is evolving in the neonatal intensive care unit (NICU) setting. Studies showed its efficacy in length of stay and hospitalization costs reduction. Moreover, it was suggested that OMT has a modulatory effect on the preterm infants’ autonomic nervous system (ANS), influencing saturation and heart rate. Even if OMT is based on the palpatory examination of the somatic dysfunctions (SD), there are controversies about its identification and clinical relevance. The objective of this study was to evaluate the inter-rater reliability, clinical characteristics, and functional correlation of the SD Grade score with the heart rate variability (HRV) and the salivary cortisol (sCor) using a multivariate linear model approach. To evaluate those features, we implemented an ad hoc SD examination for preterm infants that was performed by 2 trained osteopaths. It was based on the new variability model of SD that includes an SD Grade assessment procedure. The ANS features were assessed by frequency parameters of HRV studying high frequency (HF), low frequency (LF), and HF/LF, whereas sCor was tested with a radioimmunoassay. The ANS assessment was standardized and performed before SD testing. Sixty-nine premature infants were eligible. SD Grade showed excellent concordance between the blinded raters. Using SD Grade as a grouping variable, the infants presented differences in GA, Apgar, pathological findings, length of stay, and ventilatory assistance. In our multivariate model, HF, LF, and LF/HF resulted linearly correlated with SD Grade. Instead, sCor presented a linear correlation with 5’ Apgar and respiratory distress syndrome but not with SD Grade. SD Grade was in line with the natural history of the underdevelopment due to prematurity. Our models indicate that the cardiac vagal tone is linearly related with SD Grade. This finding may improve the multidisciplinary decision making inside NICU and the management of modifiable factors, like SD, for cardiac vagal tone regulation.     

Prevalence of Galen's anastomosis: an anatomical and comparative study

An anatomical study of 50 fresh adult human cadavers was performed in order to verify prevalence of Galen's anastomosis (GA) and to evaluate whether factors such as gender, ethnicity, side of the neck, and individual stature may interfere with GA prevalence. The results were analysed using the Chi-square test, Student t-test, and F-Snedecor test. GA was observed in 87 of 100 dissections. There was no statistically significant difference regarding GA prevalence between groups separated by ethnicity (p = 0.853), gender (p = 0.198), side of the neck (p = 0.766), or individual height (p = 0.199). Therefore, the GA was a frequent anatomical finding, and this result was not influenced by any studied factor. Comparing our data with previous studies, we also concluded that the GA seems to play an important role in the innervation of the larynx, even though its function remains unclear. Also, it is reasonable to consider GA a constant anatomical constituent.     

Searching for bridges between psychopathology and real-world functioning in first-episode psychosis: A network analysis from the OPTiMiSE trial

BackgroundNetwork analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains. The current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes.MethodsBaseline data from the OPTiMiSE trial were analyzed. The sample included 446 participants (age 40.0 ± 10.9 years, 70% males). The network was estimated with a Gaussian graphical model, using scores on individual items of the positive and negative syndrome scale (PANSS), the Calgary depression scale for schizophrenia, and the personal and social performance scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes.ResultsNodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network. The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganization, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value.ConclusionsThe current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset.