The Journal of Nutrition Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions Divalent Minerals Decrease Micellarization and Uptake of Carotenoids and Digestion Products into Caco-2 Cells 1-3

Abstract Carotenoids are lipophilic, dietary antioxidants with the potential to prevent chronic and age-related diseases. Prior to their availability for physiological functions, carotenoids require micellarization and intestinal uptake, both constituting marginally understood processes. Based on an in vitro digestion model coupled to Caco-2 cells, we assessed the effect of dietary abundant divalent ions on spinach-derived carotenoid micellarization and cellular uptake: calcium (Ca) and magnesium (Mg) ranging from 7.5 to 25 mmol/L in the digesta and zinc (Zn) and iron (Fe) ranging from 3.8 to 12.5 mmol/L. Both micellarization and uptake were significantly inhibited by minerals in a concentration-dependent manner, with stronger effects for Fe and Zn compared to Ca and Mg. Compared to controls (no mineral addition), fractional micellarization and uptake were decreased to the greatest extent (to 22.5 and 5.0%, respectively; P , 0.001) by 12.5 mmol/L Fe. Effects of Mg were of the least magnitude; at 25 mmol/L, only uptake was decreased significantly to 69.2% of the control value (P , 0.001). Total cellular carotenoid uptake from test meals decreased similarly compared to micellarization; however, decreased b-carotene micellarization was counterbalanced by improved fractional cellular uptakes from the micelles for all ions. Compared to controls, fractional b-carotene uptake from the micelles was greater in samples digested in the presence of Fe, Ca, and Zn, by up to 5-10 times at the highest concentrations of each ion (P , 0.001). Like for the above carotenoids, a high cellular uptake of the epoxycarotenoid conversion products neochrome (from neoxanthin) and luteoxanthin+auroxanthin (from violaxanthin) was also observed. The present results indicate that divalent ions may inhibit carotenoid micellarization and uptake. J. Nutr

J Med Genet

was previously implicated in periventricular nodular heterotopia (PVNH) in only five individuals and systematic clinical characterisation was not available. The aim of this study is to provide a comprehensive description of the phenotypic and genotypic spectrum of -related neurodevelopmental disorder. We collected detailed phenotypes of an international cohort of individuals (n=17) with variants assembled through the GeneMatcher platform. Missense variants were structurally modelled, and the impact of several were functionally validated. De novo variants (10 missense, 1 frameshift, 1 splice altering resulting in 9 residues insertion) in were identified among 17 unrelated individuals. Detailed phenotypes included intellectual disability (ID), microcephaly, seizures and PVNH. No specific facial characteristics were consistent across all cases, however microretrognathia was common. Various hearing and visual defects were recurrent, and interestingly, some inflammatory features were reported. MRI of the brain frequently showed abnormalities consistent with a neuronal migration disorder. We confirm the role of in an autosomal dominant syndrome with a phenotypic spectrum including severe ID, microcephaly, seizures and PVNH due to impaired neuronal migration

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Effect of organic matter removal on U-series signal in clay minerals

Clay minerals hold some key information on time and rate of weathering processes that could be deciphered by U-series disequilibria. However a removal of organic matter is generally required prior to clay mineral chemical analyses, especially in soils. The impact of two protocols of organic matter removal on the U-series disequilibria in three different clay minerals was therefore investigated. Natural or commercial kaolinite, illite and montmorillonite were treated with hydrogen peroxide and by calcination. Both investigated treatments impact the U-series signature of clay minerals. Yet the extent of this impact strongly depends on the clay-type: while kaolinite remains almost insensitive to the treatments, illite shows some equivocal shifts since the activity ratios measured after calcination could describe more accurately the pure clay signal than initial activity ratios, and montmorillonite displays the larger reactivity. Overall, the H2O2 treatment seems to induce more disturbance than the calcination process, mostly on U isotopes in illite and montmorillonite. Due to the oxidizing power of H2O2, the redox state of U held in the clays, i.e.: U(IV) or U(VI), strongly influences the extent of U leaching. In addition, a preferential leaching of U-234 relative to U-238 was observed in montmorillonite sample only, resulting to a U isotopic ratio fractionation. Conversely, during calcination, the most pronounced effect arises for Th isotopes. The congruent feature of Th loss, i.e.: Th loss approximate to mass loss, affecting the three clay minerals suggests a loss of Th through volatilization during this treatment. U or Ra are also affected, but to a lesser extent, by this volatilization. Overall, calcination causes a two- or three-fold reduced change of the (Th-230/U-234) and (U-234/U-238) activity ratios relative to H2O2 treatment. The (Ra-226/Th-230) ratio was clearly the less sensitive to any treatment. It was only slightly affected in kaolinite after calcination, and the observed change suggests an improvement of the measured value due to a removal of a Th-bearing external matter. Albeit not perfect, calcination should therefore be preferred to H2O2 treatment for organic matter removal before U-series analyses

Bacterial Pathogens Associated with Hidradenitis Suppurativa, France

Hidradenitis suppurativa (HS) is a skin disease characterized by recurrent nodules or abscesses and chronic suppurating lesions. In the absence of clear pathophysiology, HS is considered to be an inflammatory disease and has no satisfactory medical treatment. Recently, prolonged antimicrobial treatments were shown to improve or resolve HS lesions. We prospectively studied the microbiology of 102 HS lesions sampled from 82 patients using prolonged bacterial cultures and bacterial metagenomics on 6 samples. Staphylococcus lugdunensis was cultured as a unique or predominant isolate from 58% of HS nodules and abscesses, and a polymicrobial anaerobic microflora comprising strict anaerobes, milleri group streptococci, and actinomycetes was found in 24% of abscesses or nodules and in 87% of chronic suppurating lesions. These data show that bacteria known to cause soft tissue and skin infections are associated with HS lesions. Whether these pathogens are the cause of the lesions or are secondary infectious agents, these findings support targeted antimicrobial treatment of HS

A Central Role of Telomere Dysfunction in the Formation of a Unique Translocation within the Sub-Telomere Region Resulting in Duplication and Partial Trisomy

Telomeres play a major role in maintaining genome stability and integrity. Putative involvement of telomere dysfunction in the formation of various types of chromosomal aberrations is an area of active research. Here, we report a case of a six-month-old boy with a chromosomal gain encompassing the 11q22.3q25 region identified by SNP array analysis. The size of the duplication is 26.7 Mb and contains 170 genes (OMIM). The duplication results in partial trisomy of the region in question with clinical consequences, including bilateral renal dysplasia, delayed development, and a heart defect. Moreover, the karyotype determined by R-banding and chromosome painting as well as by hybridization with specific sub-telomere probes revealed the presence of an unbalanced t(9;11)(p24;q22.3) translocation with a unique breakpoint involving the sub-telomere region of the short arm of chromosome 9. The karyotypes of the parents were normal. Telomere integrity in circulating lymphocytes from the child and from his parents was assessed using an automated high-throughput method based on fluorescence in situ hybridization (FISH) with telomere- and centromere-specific PNA probes followed by M-FISH multicolor karyotyping. Very short telomeres, as well as an increased frequency of telomere loss and formation of telomere doublets, were detected in the child&rsquo;s cells. Interestingly, similar telomere profiles were found in the circulating lymphocytes of the father. Moreover, an assessment of clonal telomere aberrations identified chromosomes 9 and 11 with particularly high frequencies of such aberrations. These findings strongly suggest that telomere dysfunction plays a central role in the formation of this specific unbalanced chromosome rearrangement via chromosome end-to-end fusion and breakage&ndash;fusion&ndash;bridge cycles

Correction to: A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency

International audienceThe original version of the article contained error regarding the presentation of the institutional authors in the PDF and html versions