Phenomenology, socio-demographic factors and outcome upon discharge of manic and mixed episodes in hospitalized adolescents

Background: The existence of bipolar disorder type I (BD-I) during adolescence is now clearly established whereas there are still some controversies on BD-II and BD-NOS diagnosis, mainly in Europe (O'Dowd in Br Med J 29, 2006). Little is known on the phenomenology and potential short-term prognosis factors of bipolar episodes in this age population. In particular, very few studies examine this issue on inpatients in the European context of free access to care. Objective: To describe the phenomenology of acute manic and mixed episodes in hospitalized adolescents and to analyse potential predictive factors associated with clinical improvement at discharge and length of hospitalization. Methods: A total of 80 subjects, aged 12–20 years, consecutively hospitalized for a manic or mixed episode. Socio-demographic and clinical data were extracted by reviewing patients' charts. We used a multivariate analysis to evaluate short-term outcome predictors. Results: The sample was characterized by severe impairment, high rates of psychotic features (N = 50, 62.5%), a long duration of stay (mean 80.4 days), and an overall good improvement (86% very much or much improved). Thirty-three (41.3 %) patients had a history of depressive episodes, 13 (16.3%) had manic or brief psychotic episodes but only 3 (3.7%) had a history of attention deficit/ hyperactivity disorders. More manic episodes than mixed episodes were identified in subjects with mental retardation (MR) and in subjects from migrant and/or low socio-economic families. Overall severity and female gender predicted better improvement in GAF scores. Poor insight and the existence of psychotic features predicted longer duration of stay. Conclusion: These results suggest that severe manic and mixed episodes in adolescents with BD-I need prolonged inpatient care to improve and that socio-cultural factors and MR should be examined more closely in youth with BD

Nutri-Score and NutrInform Battery: Effects on Performance and Preference in Italian Consumers

In May 2020, the European Commission announced a proposal for a mandatory front-of-pack label (FoPL) for all European Union (EU) countries. Indeed, FoPLs have been recognized by several public institutions as a cost-effective measure to guide consumers toward nutritionally favorable food products. The aim of this study was to compare the performance and consumer preference of two FoPLs currently proposed or implemented in EU countries, the interpretive format Nutri-Score and the non-interpretive format NutrInform Battery, among Italian consumers. The experimental study was conducted in 2021 on a representative sample of 1064 Italian adults (mean age = 46.5 +/- 14.1 years; 48% men). Participants were randomized to either Nutri-Score or NutrInform and had to fill out an online questionnaire testing their objective understanding of the FoPL on three food categories (breakfast products, breakfast cereals and added fats) as well as purchase intention, subjective understanding and perception. Multivariable logistic regressions and t-tests were used to analyze the answers. In terms of the capacity of participants to identify the most nutritionally favorable products, Nutri-Score outperformed NutrInform in all food categories, with the highest odds ratio being observed for added fats (OR = 21.7 [15.3-31.1], p < 0.0001). Overall, with Nutri-Score, Italian participants were more likely to intend to purchase nutritionally favorable products than with NutrInform (OR = 5.29 [4.02-6.97], p < 0.0001). Focusing on olive oil, participants of the Nutri-Score group had higher purchase intention of olive oil compared to those in the NutrInform group (OR = 1.92 [1.42-2.60], p < 0.0001) after manipulating the label. The interpretive format Nutri-Score appears to be a more efficient tool than NutrInform for orienting Italian consumers towards more nutritionally favorable food choices

KIF1C Variants Are Associated with Hypomyelination, Ataxia, Tremor, and Dystonia in Fraternal Twins

Background: KIF1C (Kinesin Family Member 1C) variants have been associated with hereditary spastic paraplegia and spastic ataxia. Case report: We report fraternal twins presenting with cerebellar ataxia and dystonic tremor. Their brain MRI showed a hypomyelinating leukoencephalopathy. Whole exome sequencing identified a homozygous KIF1C variant in both patients. Discussion: KIF1C variants can manifest as a complex movement disorder with cerebellar ataxia and dystonic tremor. KIF1C variants may also cause a hypomyelinating leukoencephalopathy

RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia

The Rad50 interacting protein 1 (Rint1) is a key player in vesicular trafficking between the ER and Golgi apparatus. Biallelic variants in RINT1 cause infantile-onset episodic acute liver failure (ALF). Here, we describe 3 individuals from 2 unrelated families with novel biallelic RINT1loss-of-function variants who presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, and dysmorphic features, broadening the previously described phenotype. Our functional and lipidomic analyses provided evidence that pathogenic RINT1 variants induce defective lipid-droplet biogenesis and profound lipid abnormalities in fibroblasts and plasma that impact both neutral lipid and phospholipid metabolism, including decreased triglycerides and diglycerides, phosphatidylcholine/phosphatidylserine ratios, and inhibited Lands cycle. Further, RINT1 mutations induced intracellular ROS production and reduced ATP synthesis, affecting mitochondria with membrane depolarization, aberrant cristae ultrastructure, and increased fission. Altogether, our results highlighted the pivotal role of RINT1 in lipid metabolism and mitochondria function, with a profound effect in central nervous system development

Consumption of dairy products and cardiovascular disease risk: results from the French prospective cohort NutriNet-Santé

In France, dairy products contribute to dietary saturated fat intake, of which reduced consumption is often recommended for cardiovascular disease (CVD) prevention. Epidemiological evidence on the association between dairy consumption and CVD risk remains unclear, suggesting either null or inverse associations. This study aimed to investigate the associations between dairy consumption (overall and specific foods) and CVD risk in a large cohort of French adults. This prospective analysis included participants aged ≥ 18 years from the NutriNet-Santé cohort (2009–2019). Daily dietary intakes were collected using 24h-dietary records. Total dairy, milk, cheese, yogurts, fermented and reduced-fat dairy intakes were investigated. CVD cases (n=1,952) included cerebrovascular (n=878 cases) and coronary heart diseases (CHD, n=1,219 cases). Multivariable Cox models were performed to investigate associations. This analysis included n=104,805 French adults (mean age at baseline 42.8 years (SD 14.6), mean follow-up 5.5 years (SD 3.0, i.e. 579,155 persons years). There were no significant associations between dairy intakes and total CVD or CHD risks. However, the consumption of at least 160 g/d of fermented dairy (e.g. cheese and yogurts) was associated with a reduced risk of cerebrovascular diseases compared to intakes below 57 g/d (HR=0.81 [0.66-0.98], p-trend=0.01). Despite being a major dietary source of saturated fats, dairy consumption was not associated with CVD or CHD risks in this study. However, fermented dairy was associated with a lower cerebrovascular disease risk. Robust randomized controlled trials are needed to further assess the impact of consuming different dairy foods on CVD risk and potential underlying mechanisms

Insights into metazoan evolution from Alvinella pompejana cDNAs.

International audienceBACKGROUND: Alvinella pompejana is a representative of Annelids, a key phylum for evo-devo studies that is still poorly studied at the sequence level. A. pompejana inhabits deep-sea hydrothermal vents and is currently known as one of the most thermotolerant Eukaryotes in marine environments, withstanding the largest known chemical and thermal ranges (from 5 to 105°C). This tube-dwelling worm forms dense colonies on the surface of hydrothermal chimneys and can withstand long periods of hypo/anoxia and long phases of exposure to hydrogen sulphides. A. pompejana specifically inhabits chimney walls of hydrothermal vents on the East Pacific Rise. To survive, Alvinella has developed numerous adaptations at the physiological and molecular levels, such as an increase in the thermostability of proteins and protein complexes. It represents an outstanding model organism for studying adaptation to harsh physicochemical conditions and for isolating stable macromolecules resistant to high temperatures. RESULTS: We have constructed four full length enriched cDNA libraries to investigate the biology and evolution of this intriguing animal. Analysis of more than 75,000 high quality reads led to the identification of 15,858 transcripts and 9,221 putative protein sequences. Our annotation reveals a good coverage of most animal pathways and networks with a prevalence of transcripts involved in oxidative stress resistance, detoxification, anti-bacterial defence, and heat shock protection. Alvinella proteins seem to show a slow evolutionary rate and a higher similarity with proteins from Vertebrates compared to proteins from Arthropods or Nematodes. Their composition shows enrichment in positively charged amino acids that might contribute to their thermostability. The gene content of Alvinella reveals that an important pool of genes previously considered to be specific to Deuterostomes were in fact already present in the last common ancestor of the Bilaterian animals, but have been secondarily lost in model invertebrates. This pool is enriched in glycoproteins that play a key role in intercellular communication, hormonal regulation and immunity. CONCLUSIONS: Our study starts to unravel the gene content and sequence evolution of a deep-sea annelid, revealing key features in eukaryote adaptation to extreme environmental conditions and highlighting the proximity of Annelids and Vertebrates

Alternative Splicing at a NAGNAG Acceptor Site as a Novel Phenotype Modifier

Approximately 30% of alleles causing genetic disorders generate premature termination codons (PTCs), which are usually associated with severe phenotypes. However, bypassing the deleterious stop codon can lead to a mild disease outcome. Splicing at NAGNAG tandem splice sites has been reported to result in insertion or deletion (indel) of three nucleotides. We identified such a mechanism as the origin of the mild to asymptomatic phenotype observed in cystic fibrosis patients homozygous for the E831X mutation (2623G>T) in the CFTR gene. Analyses performed on nasal epithelial cell mRNA detected three distinct isoforms, a considerably more complex situation than expected for a single nucleotide substitution. Structure-function studies and in silico analyses provided the first experimental evidence of an indel of a stop codon by alternative splicing at a NAGNAG acceptor site. In addition to contributing to proteome plasticity, alternative splicing at a NAGNAG tandem site can thus remove a disease-causing UAG stop codon. This molecular study reveals a naturally occurring mechanism where the effect of either modifier genes or epigenetic factors could be suspected. This finding is of importance for genetic counseling as well as for deciding appropriate therapeutic strategies

Are Child and Adolescent Responses to Placebo Higher in Major Depression than in Anxiety Disorders? A Systematic Review of Placebo-Controlled Trials

BACKGROUND: In a previous report, we hypothesized that responses to placebo were high in child and adolescent depression because of specific psychopathological factors associated with youth major depression. The purpose of this study was to compare the placebo response rates in pharmacological trials for major depressive disorder (MDD), obsessive compulsive disorder (OCD) and other anxiety disorders (AD-non-OCD). METHODOLOGY AND PRINCIPAL FINDINGS: We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalized disorders, restricting our review to double-blind studies including a placebo arm. Placebo response rates were pooled and compared according to diagnosis (MDD vs. OCD vs. AD-non-OCD), age (adolescent vs. child), and date of publication. From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication (mainly non-tricyclic antidepressants) involving youth with MDD, 7 pertaining to youth with OCD, and 10 pertaining to youth with other anxiety disorders (N = 2533 patients in placebo arms). As hypothesized, the placebo response rate was significantly higher in studies on MDD, than in those examining OCD and AD-non-OCD (49.6% [range: 17-90%] vs. 31% [range: 4-41%] vs. 39.6% [range: 9-53], respectively, ANOVA F = 7.1, p = 0.002). Children showed a higher stable placebo response within all three diagnoses than adolescents, though this difference was not significant. Finally, no significant effects were found with respect to the year of publication. CONCLUSION: MDD in children and adolescents appears to be more responsive to placebo than other internalized conditions, which highlights differential psychopathology

Caractéristiques botaniques, chimiques et dermatologiques de plantes responsables d'eczéma et d'urticaire de contact

LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF