Search

Chemical studies by inductively coupled plasma absorption emission spectrometry, x-ray diffraction, and infrared were carried out to determine the composition of major and trace elements in the doped hydroxyapatite, and the crystallographic structure. The extended x-ray absorption fine structure experimental station of LURE is used to clarify the atomic surroundings of zinc in doped hydroxyapatite structure and transformations induced in initial lattice.

Derivative complexes of Gd(tpp)(acac) are studied to investigate if the structures are conserved when the metal is changed or when the ligand is changed. The results on the selected monoporphyrinates may help to understand the differences on the redox properties and the arising pi-pi interactions in the corresponding bisporphyrinates.

Early life gut microbiota-influencing factors may play an important role in programming individuals long-term health and substantial efforts have been devoted into studying the development of the gut microbiota in relation to early life events. This study aimed to examine in a single study, the persistence of associations between 20 factors occurring in the early life and the gut microbiota at 3.5 years of 798 children from two French nationwide birth cohorts, EPIPAGE 2 (very preterm children) and ELFE (late preterm and full-term children). Gut microbiota profiling was assessed using 16S rRNA gene sequencing-based method. Upon thorough adjustment of confounding factors, we demonstrated that gestational age was one of the factors most associated with gut microbiota differences with a noticeable imprint of prematurity at 3.5 years of age. Children born by cesarean section harbored lower richness and diversity and a different overall gut microbiota composition independently of preterm status. Children who had ever received human milk were associated with a Prevotella -driven enterotype (P_type) compared to those who had never received human milk. Living with a sibling was associated with higher diversity. Children with siblings and those attending daycare centers were associated with a P_type enterotype. Maternal factors including the country of birth and preconception maternal body mass index were associated with some microbiota characteristics: children born to overweight or obese mothers showed increased gut microbiota richness. This study reveals that multiple exposures operating from early life imprint the gut microbiota at 3.5 years that is a pivotal age when the gut microbiota acquires many of its adult characteristics.

In the present work, two photosensitizing drugs, Temoporfin and Verteporfin have been studied. Both have regular approval in Europe, Temoporfin for the treatment of head and neck cancers and Verteporfin for the treatment of age-related macular degeneration (AMD). The treatment modality, known as "Photodynamic Therapy" (PDT), involves drug activation with visible light in the presence of oxygen and production of reactive oxygen species (ROS) to destroy the pathological tissues. Both drugs are inactive in the absence of light, presenting only few side effects. The incorporation of the two drugs into a SOPC bilayer -used as a model membrane- was studied by ATR-FTIR. An original approach was applied, involving lyotropic transitions and a very slow dehydration rate of the sample. In low water content and dry film, Temoporfin highly affects stretching vibrations of SOPC chains and polar groups, showing that Temoporfin is inserted into the bilayer in both apolar and polar regions. In fully hydrated layers, Temoporfin - SOPC interactions still take place but only impact Temoporfin vibration bands. Verteporfin shows smaller effect on both chain and polar groups' vibrations of SOPC, with the exception of choline group, suggesting that Verteporfin is inserted into the bilayer to a lesser extent and remains at the bilayer polar interface. These results can be used to better understand drugs behavior in biological media., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Large response of steroid precursors, including 17-hydroxyprogesterone, to adrenocorticotropic hormone (ACTH) has been described in adrenocortical tumors, suggesting the existence of intra-tumoral enzymatic deficiencies. This study aimed to compare steroidogenesis enzymes activity in unilateral and bilateral benign tumors using serum steroid profiling in liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in the basal state and after ACTH 1-24 stimulation., Design and Methods: A serum profile of seven consecutive adrenal steroids was determined in LC-MS/MS in the basal state (T0) and after ACTH 1-24 stimulation (T60) in 35 patients with bilateral adrenocortical tumors (BL), 38 patients with unilateral tumors (UL) and 37 control subjects (CT). Response amplitude of each individual steroid was evaluated by T60/T0 ratio, whereas enzymatic activity was assessed by the downstream/upstream steroid ratio. Adrenal volume was quantified by a semi-automatic segmentation method., Results: For the seven steroids assayed, the amplitude of response to ACTH was higher in BL than in UL and in CT. The difference between BL and UL persisted even after matching patients on adrenal volume. On glucocorticoids pathway, enzymatic activity of CYP11B1 was significantly decreased in BL (78.3 (43.1-199.4)) in comparison to both UL (122.7 (13.8-228.4), P = 0.0002) and CT (186.8 (42.1-1236.3), P < 0.0001). On mineralocorticoids and androgens pathways, the enzymatic activity of CYP11B2 and CYP17A1-17,20 lyase was also lower in BL than UL and CT., Conclusions: Decreased activity of distal steroidogenesis enzymes CYP11B1, CYP11B2 and CYP17A1-17,20 lyase, responsible for an explosive response to ACTH of upstream precursors in bilateral tumors, limits the synthesis of bioactive steroids, in particular cortisol, despite the increase in adrenal mass., Significance Statement: Activity of distal steroidogenesis enzymes (CYP11B1, CYP11B2 and CYP17A1 on glucocorticoids, mineralocorticoids and androgens pathways, respectively) is decreased in adrenocortical benign tumors. This decrease is more pronounced in bilateral lesions and seems to depend more on the nature of the lesion than on the increase in adrenal volume. It is responsible for the explosive response to ACTH of steroid precursors located upstream of these enzymes. It probably allows bioactive steroids, particularly cortisol, to stay in the normal range for a long time despite the increase in adrenal mass.

Objectives: Given the scope of rheumatology and its prevalence of pain, it seems needed that a study should focus on prescription habits, in the midst of the international opioid epidemic and given the moderate efficacy of strong opioids in chronic musculoskeletal conditions. We compared rheumatologists' opioid prescribing patterns in non-cancer pain with recommended practice., Methods: We performed a cross-sectional study of the French health insurance database, including all patients aged 16 years or over reimbursed for at least one strong opioid prescription from a rheumatologist in 2015. A nationwide survey of all registered rheumatologists in France was performed with a 47-item questionnaire in June 2015., Results: Only 2.4% of the patients receiving a strong opioid in 2015 (n=700,946) had at least one prescription from a rheumatologist. Rheumatologists prescribed mostly morphine, and significantly less oxycodone and fentanyl (P<0.00001) than other specialists. Rheumatologists prescribed a mean of 35.8mg morphine equivalent/day. A response rate of 33.7% was obtained to the questionnaire. Acute musculoskeletal pain was the principal condition for strong opioids prescription, with 94.5% re-evaluating opioid treatment within two weeks of initiation. For efficacy, 80% said that they stopped treatment if no benefit was observed after a test period (mean=1.2 months). Rheumatologists with pain management training were significantly more likely to evaluate pain before prescribing strong opioids (P=0.001), evaluate efficacy within three months (P=0.01) and screen for risk factors for misuse at initiation (P<0.0001)., Conclusions: For non-cancer pain, rheumatologists generally prescribe opioids for short periods, at low doses, mostly according to national recommendations. Pain education strongly affected opioid prescription by rheumatologists., (Copyright © 2020 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Cow's milk allergy is a worldwide public health issue, especially since there is no effective treatment, apart from milk and dairy product avoidance. The aim of this study was to assess the beneficial role of three probiotic strains previously selected for their prophylactic properties in a mouse model of β-lactoglobulin allergy. Administration of Lactobacillus rhamnosus LA305, L. salivarius LA307, or Bifidobacterium longum subsp. infantis LA308 for 3 weeks post-sensitization and challenge modified the composition of the gut microbiota, with an increase in the Prevotella NK3B31 group and a decrease in Marvinbryantia , belonging to the Lachnospiraceae family. Although no impact on markers of sensitization was detected, modifications of foxp3 , tgfβ , and il10 ileal gene expression, as well as plasma metabolomic alterations in the tryptophan pathway, were observed. Moreover, ex vivo studies showed that all probiotic strains induced significant decreases in cytokine production by β-lactoglobulin-stimulated splenocytes. Taken together, these results suggest that the three probiotic strains tested lead to alterations in immune responses, i.e., induction of a tolerogenic anergy and anti-inflammatory responses. This anergy could be linked to cecal microbiota modifications, although no impact on fecal short-chain fatty acid (SCFA) concentrations was detected. Anergy could also be linked to a direct impact of probiotic strains on dendritic cells, since costimulatory molecule expression was decreased following coincubation of these strains with bone marrow-derived dendritic cells (BMDCs). To conclude, all three candidate probiotic strains induced strain-specific gut microbiota and metabolic changes, which could potentially be beneficial for general health, as well as anergy, which could contribute to oral tolerance acquisition. IMPORTANCE We showed previously that three probiotic strains, i.e., Lactobacillus rhamnosus LA305, L. salivarius LA307, and Bifidobacterium longum subsp. infantis LA308, exerted different preventive effects in a mouse model of cow's milk allergy. In this study, we evaluated their potential benefits in a curative mouse model of cow's milk allergy. When administered for 3 weeks after the sensitization process and a first allergic reaction, none of the strains modified the levels of sensitization and allergic markers. However, all three strains affected gut bacterium communities and modified immune and inflammatory responses, leading to a tolerogenic profile. Interestingly, all three strains exerted a direct effect on dendritic cells, which are known to play a major role in food sensitization through their potentially tolerogenic properties and anergic responses. Taken together, these data indicate a potentially beneficial role of the probiotic strains tested in this model of cow's milk allergy with regard to tolerance acquisition., (Copyright © 2020 Esber et al.)

Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioides difficile infection. Recent studies have reported protocols using capsules of either frozen or freeze-dried stool allowing oral administration in in- and out-patient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti- Clostridioides difficile properties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance of Clostridioides difficile infection in a preclinical murine model with a survival rate of 70% versus 53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment of Clostridioides difficile infection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.

Acute graft-versus-host disease (aGVHD) is the main complication of hematopoietic stem cell transplantation (HSCT). Changes in gut microbiota composition have been associated with subsequent aGVHD, and reconstitution of healthy microbiota is currently being explored as a therapeutic approach. However, the specific actors in the intestinal ecosystem involved in the pathologic process at the time of aGVHD onset are not yet fully known. We prospectively collected stool samples from patients who underwent allogeneic HSCT. Patients sampled at aGVHD onset were compared with non-GVHD patients. To identify phylogenetic and functional signatures of the disease process, we determined fecal short-chain fatty acid (SFCA) profiles and used high-throughput DNA sequencing and real-time quantitative polymerase chain reaction to assess the microbiota composition. Microbiota alterations were highly specific of gastrointestinal (GI) aGVHD severity. Bacterial biomass and α-diversity were lower in severe aGVHD. We identified several bacterial signatures associated with severe aGVHD at disease onset; a negative correlation was observed with anaerobic bacteria of the Lachnospiraceae, especially the Blautia genus, and Ruminococcaceae families. In parallel, in severe aGVHD patients, we showed a dramatic decrease in the levels of the main SFCAs: acetate (75.8%), propionate (95.8%), and butyrate (94.6%). Mild aGVHD patients were characterized by conserved levels of propionate and Blautia propionate producers. Butyrate was significantly decreased in all GI aGVHD stages, representing a potential diagnostic marker of the disease. Specific microbiota and metabolic alterations were thus associated with aGVHD severity and may be useful for diagnostic and pathophysiologic purposes., (© 2020 by The American Society of Hematology.)

Ornithine δ-aminotransferase (OAT, E.C. 2.6.1.13) catalyzes the transfer of the δ-amino group from ornithine (Orn) to α-ketoglutarate (aKG), yielding glutamate-5-semialdehyde and glutamate (Glu), and vice versa. In mammals, OAT is a mitochondrial enzyme, mainly located in the liver, intestine, brain, and kidney. In general, OAT serves to form glutamate from ornithine, with the notable exception of the intestine, where citrulline (Cit) or arginine (Arg) are end products. Its main function is to control the production of signaling molecules and mediators, such as Glu itself, Cit, GABA, and aliphatic polyamines. It is also involved in proline (Pro) synthesis. Deficiency in OAT causes gyrate atrophy, a rare but serious inherited disease, a further measure of the importance of this enzyme.

Missing data are unavoidable in environmental epidemiologic surveys. The aim of this study was to compare methods for handling large amounts of missing values: omission of missing values, single and multiple imputations (through linear regression or partial least squares regression), and a fully Bayesian approach. These methods were applied to the PARIS birth cohort, where indoor domestic pollutant measurements were performed in a random sample of babies' dwellings. A simulation study was conducted to assess performances of different approaches with a high proportion of missing values (from 50% to 95%). Different simulation scenarios were carried out, controlling the true value of the association (odds ratio of 1.0, 1.2, and 1.4), and varying the health outcome prevalence. When a large amount of data is missing, omitting these missing data reduced statistical power and inflated standard errors, which affected the significance of the association. Single imputation underestimated the variability, and considerably increased risk of type I error. All approaches were conservative, except the Bayesian joint model. In the case of a common health outcome, the fully Bayesian approach is the most efficient approach (low root mean square error, reasonable type I error, and high statistical power). Nevertheless for a less prevalent event, the type I error is increased and the statistical power is reduced. The estimated posterior distribution of the OR is useful to refine the conclusion. Among the methods handling missing values, no approach is absolutely the best but when usual approaches (e.g. single imputation) are not sufficient, joint modelling approach of missing process and health association is more efficient when large amounts of data are missing.

Objective: Aging is associated with a blunted anabolic response to dietary intake, possibly related to a decrease in systemically available amino acids (AAs), which in turn may stem from increased splanchnic AA metabolism. Splanchnic sequestration can be saturated by pulse feeding (80% of daily protein intake in a single meal), enabling increased protein synthesis. The aim of this study was to explore whether protein pulse feeding increased postprandial AA concentrations, and if so whether this increase persisted after 6 wk of dietary treatment., Methods: This prospective randomized study enrolled 66 elderly malnourished or at-risk patients in an inpatient rehabilitation unit. All were given a controlled diet for 6 wk. In a spread diet (SD) group (n = 36), dietary protein was spread over the four daily meals. In a pulse diet (PD) group (n = 30), 72% of dietary protein (averaging 1.31 g/kg body weight daily) was consumed in one meal at noon. The patients were evaluated on day 1 and at 6 wk for plasma postprandial (five times from 0 to +180 min) AA concentrations (expressed as area under the curve above baseline)., Results: Protein pulse feeding was more efficient than protein spread feeding at increasing plasma postprandial AA concentrations, notably of essential AAs. This increased postprandial AA bioavailability was maintained after 6 wk., Conclusions: This study demonstrates that increased postprandial AA bioavailability induced by protein pulse feeding persists after 6 wk (i.e., that there is no metabolic adaptation blunting AA bioavailability)., (Copyright © 2014 Elsevier Inc. All rights reserved.)