Retraction Note: Study of liver toxicity and DNA damage due to exposure to the pesticide Mancozeb in an experimental animal model - A pilot model.

The article "Study of liver toxicity and DNA damage due to exposure to the pesticide Mancozeb in an experimental animal model - A pilot model", by N.D. Suarez Uribe, M.F. Pezzini, J. Dall'Agnol, N. Marroni, S. Benitez, D. Benedetti, J. Da Silva, C.T. Cerski, E. Dallegrave, S. Macedo, S.C.W.S.E.F. de Oliveira, D. Joveleviths, published in Eur Rev Med Pharmacol Sci 2023; 27 (13): 6374-6383-DOI: 10.26355/eurrev_202307_32997-PMID: 37458654 has been retracted by the Editor in Chief for the following reasons: After publication, concerns were raised by an unidentified reader who underlined some similarities between this publication and a previous publication published in the Journal of Clinical and Experimental Gastroenterology. After being informed, the authors claimed the previous journal published the article without consent, and, therefore, the authors promptly withdrew the previous publication. The retraction published by the other journal does not contain any information regarding the reason for withdrawal. As a matter of fact, the journal does not have any evidence about the authors' claim and still considers this research a duplicate publication. For the above-mentioned reasons, the Editor in Chief decided to withdraw the manuscript. This manuscript has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/32997.

Immunoglobulin A Antibodies Against Myelin Oligodendrocyte Glycoprotein in a Subgroup of Patients With Central Nervous System Demyelination.

Importance: Differential diagnosis of patients with seronegative demyelinating central nervous system (CNS) disease is challenging. In this regard, evidence suggests that immunoglobulin (Ig) A plays a role in the pathogenesis of different autoimmune diseases. Yet little is known about the presence and clinical relevance of IgA antibodies against myelin oligodendrocyte glycoprotein (MOG) in CNS demyelination. Objective: To investigate the frequency of MOG-IgA and associated clinical features in patients with demyelinating CNS disease and healthy controls. Design, Setting, and Participants: This longitudinal study comprised 1 discovery and 1 confirmation cohort derived from 5 centers. Participants included patients with suspected or confirmed demyelinating diseases and healthy controls. MOG-IgA, MOG-IgG, and MOG-IgM were measured in serum samples and cerebrospinal fluid (CSF) of patients, who were assessed from September 2012 to April 2022. Main Outcomes and Measures: Frequency and clinical features of patients who were seropositive for MOG-IgA and double-seronegative for aquaporin 4 (AQP4) IgG and MOG-IgG. Results: After the exclusion of 5 participants with coexisting AQP4-IgG and MOG-IgA, MOG-IgG, and/or MOG-IgM, 1339 patients and 110 healthy controls were included; the median follow-up time was 39 months (range, 0-227 months). Of included patients with isolated MOG-IgA, 11 of 18 were female (61%), and the median age was 31.5 years (range, 3-76 years). Among patients double-seronegative for AQP4-IgG and MOG-IgG (1126/1339; 84%), isolated MOG-IgA was identified in 3 of 50 patients (6%) with neuromyelitis optica spectrum disorder, 5 of 228 patients (2%) with other CNS demyelinating diseases, and 10 of 848 patients (1%) with multiple sclerosis but in none of the healthy controls (0/110). The most common disease manifestation in patients seropositive for isolated MOG-IgA was myelitis (11/17 [65%]), followed by more frequent brainstem syndrome (7/16 [44%] vs 14/75 [19%], respectively; P = .048), and infrequent manifestation of optic neuritis (4/15 [27%] vs 46/73 [63%], respectively; P = .02) vs patients with MOG-IgG. Among patients fulfilling 2017 McDonald criteria for multiple sclerosis, MOG-IgA was associated with less frequent CSF-specific oligoclonal bands (4/9 [44%] vs 325/351 [93%], respectively; P < .001) vs patients with multiple sclerosis who were MOG-IgG/IgA seronegative. Further, most patients with isolated MOG-IgA presented clinical attacks after recent infection or vaccination (7/11 [64%]). Conclusion and Relevance: In this study, MOG-specific IgA was identified in a subgroup of patients who were double-seronegative for AQP4-/MOG-IgG, suggesting that MOG-IgA may be a novel diagnostic biomarker for patients with CNS demyelination.

Study of liver toxicity and DNA damage due to exposure to the pesticide Mancozeb in an experimental animal model - A pilot model.

OBJECTIVE: Mancozeb is one of the most widely used Ethylenebisdithiocarbamates fungicides in Brazil. A pilot experimental model was created to evaluate its potential hepatotoxic effect. MATERIALS AND METHODS: An experimental study was performed with 27 male Wistar rats (3 groups). The Control Group received a saline solution, while Intervention Groups I and II received 250 mg/kg and 500 mg/kg of Mancozeb respectively, once a week, for 12 weeks. Anthropometric measurements were carried out, and the marker of biological exposure in urine was dosed. Biochemical tests, evaluation micronucleus count, comet and oxidative stress markers assay, and histological assessment of the liver were also performed. RESULTS: The hepatotoxic effect of Mancozeb was confirmed by anthropometric measurements, genotoxicity, and oxidative stress. Statistically significant results were found when the exposed groups were compared to the control group. CONCLUSIONS: These results were supported by inflammatory infiltration and balloonization in the treated groups. The experimental model effectively demonstrated the deleterious effect of Mancozeb on the liver.

Unequal Impact of COL1A1 and COL1A2 Variants on Dentinogenesis Imperfecta.

Dentinogenesis imperfecta (DI) is the main orodental manifestation of osteogenesis imperfecta (OI) caused by COL1A1 or COL1A2 heterozygous pathogenic variants. Its prevalence varies according to the studied population. Here, we report the molecular analysis of 81 patients with OI followed at reference centers in Brazil and France presenting COL1A1 or COL1A2 variants. Patients were submitted to clinical and radiographic dental examinations to diagnose the presence of DI. In addition, a systematic literature search and a descriptive statistical analysis were performed to investigate OI/DI phenotype-genotype correlation in a worldwide sample. In our cohort, 50 patients had COL1A1 pathogenic variants, and 31 patients had COL1A2 variants. A total of 25 novel variants were identified. Overall, data from a total of 906 individuals with OI were assessed. Results show that DI was more frequent in severe and moderate OI cases. DI prevalence was also more often associated with COL1A2 (67.6%) than with COL1A1 variants (45.4%) because COL1A2 variants mainly lead to qualitative defects that predispose to DI more than quantitative defects. For the first time, 4 DI hotspots were identified. In addition, we showed that 1) glycine substitution by branched and charged amino acids in the α2(I) chain and 2) substitutions occurring in major ligand binding regions-MLRB2 in α1(I) and MLBR 3 in α2(I)-could significantly predict DI (P < 0.05). The accumulated variant data analysis in this study provides a further basis for increasing our comprehension to better predict the occurrence and severity of DI and appropriate OI patient management.

Case report of Curtobacterium isolated from a catheter tip sample misidentified as Cronobacter.

The Curtobacterium genus is a member of the family Microbacteriaceae, and Curtobacterium species are recognized as plant pathogens. The aim of this study was to investigate a dubious result of species identification for an infection located on a catheter tip of a patient with Covid-19. A strain isolated from a catheter tip sample, identified by VITEK® 2 as Cronobacter spp., was submitted to polyphasic analysis: Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) using VITEK® MS, real-time polymerase chain reaction targeting dnaG gene, and 16S rRNA full gene Sanger sequencing analysis for confirmation. The strain presented negative result using qPCR and could not identified by MALDI-TOF MS. 16S rRNA full gene Sanger sequencing analysis identified the strain as Curtobacterium spp. The Gram-variable characteristic (Gram-negative instead of Gram-positive) of the isolated strain was the responsible for the misidentification by VITEK® 2 and VITEK® MS did not identify the strain. 16S rRNA full gene sequencing analysis identified the strain as Curtobacterium genus, but other complementary techniques are necessary to identify at species level.

Selective carbonaceous-based (nano)composite sensors for electrochemical determination of paraquat in food samples.

A novel electrochemical sensor based on activated biochar (AB4) and reduced graphene oxide (rGO) was developed and tested for detection of paraquat (PQ) in food samples. Precursor biochar was obtained by the pyrolysis of water hyacinth biomass at 400, 500, and 600 °C, followed by a chemical activation step using HNO3 to increase the amount of oxygenated and nitrogenated groups. The modified electrodes (rGO-AB4) were tested in different experimental conditions, and exhibited good response under the optimized conditions, showing linearity from 0.74 to 9.82 µmol L-1 and a limit of detection and limit of quantification of 0.02 µmolL-1 and 0.07 µmol L-1, respectively. Interfering species such as glyphosate caused insignificant changes in the peak current of paraquat, and the selectivity of the method was tested using blank and spiked samples of coconut water, wastewater, honey, lettuce and lemon. Recovery ranged from 87.70±2.07% to 103.80±3.94%.

Acute and chronic effects of cortisol on milk yield, the expression of key receptors, and apoptosis of mammary epithelial cells in Saanen goats.

Cortisol (CORT) induces mammary development in late gestation and is fundamental to the differentiation of mammary epithelial cells and lactogenesis. The objective of this study was to investigate the relationship between CORT, insulin, prolactin, growth hormone, and insulin-like growth factor-1 in milk as well as the effect of CORT on the expression of receptors of insulin (INSR), prolactin (PRLR), growth hormone (GHR); we also studied the insulin-like growth factor-1 (IGF1R), glucocorticoid (NR3C1), mineralocorticoid (NR3C2), B-cell lymphoma 2 (BCL2), BCL-2-like protein X (BAX) genes, and the apoptosis rate of mammary epithelial cells of lactating Saanen goats in vivo and in vitro. The following experiments were conducted: (1) comparing hormone release in milk and blood after ACTH or a placebo administration; (2) evaluating the effect of acute CORT increases in mammary gland expression and milk yield in vivo; and (3) evaluating the effect of a chronic increase in CORT concentration in epithelial mammary cell apoptosis in vitro. In vivo, ACTH administration significantly increased CORT release but did not affect insulin, prolactin, growth hormone, and insulin-like growth factor-1 release in plasma and milk versus placebo. The results show also that a low CORT release after ACTH administration increased the expression of GHR and PRLR genes in the mammary tissue. Indeed, CORT release significantly increased the milk yield from goats subjected to ACTH versus goats subjected to the placebo. However, a higher amount of CORT added in vitro upregulated the NR3C1, GHR, PRLR, and BAX genes and downregulated the IGF1R and INSR genes, which could negatively modulate the apoptosis of mammary epithelial cells. Finally, the effect of CORT in vivo after ACTH administration demonstrated the increased expression of the PRLR and GHR genes, which may improve epithelial cell responsiveness and be associated with the positive effect of CORT observed on milk yield at mid-end lactation.

Polyenvironmental and polygenic risk scores and the emergence of psychotic experiences in adolescents.

Psychotic experiences (PE) are forms of hallucinations and delusions neither reaching the intensity and functional impairment required to be regarded as full psychotic symptoms nor a psychotic disorder. Here we investigated the ability to predict PE using multiple models (regressions, mediation and moderation) using polygenic risk score for psychotic experiences (PE-PRS), polygenic risk score for schizophrenia (SCZ-PRS), and polyenvironmental risk score (PERS) in youth from a Brazilian sample. The scores were not able to predict outcome, either when both scores were combined (PERS + PE-PRS and PERS + SCZ-PRS) or separately. Our results show that there is no association between PE and PRS or PERS among adolescents in our Brazilian sample. The lack of association may be a result of the absence of better representativeness regarding genetic and environmental factors of our population.

Zymosan enhances in vitro phagocyte function and the immune response of mice infected with Paracoccidioides brasiliensis.

Paracoccidioides brasiliensis is the major etiologic agent of Paracoccidioidomycosis (PCM), the most frequent human deep mycosis in Latin America. It is proposed that masking of ß-glucan in P. brasiliensis cell wall is a critical virulence factor that contributes to the development of a chronic disease characterized by a long period of treatment, which is usually toxic. In this context, the search for immunomodulatory agents for therapeutic purposes is highly desirable. One strategy is to use pattern recognition receptors (PRRs) ligands to stimulate the immune response mediated by phagocytes. Here, we sought to evaluate if Zymosan, a ß-glucan-containing ligand of the PRRs Dectin-1/TLR-2, would enhance phagocyte function and the immune response of mice challenged with P. brasiliensis. Dendritic cells (DCs) infected with P. brasiliensis and treated with Zymosan showed improved secretion of several proinflammatory cytokines and expression of maturation markers. In addition, when cocultured with splenic lymphocytes, these cells induced the production of a potential protective type 1 and 17 cytokine patterns. In macrophages, Zymosan ensued a significant fungicidal activity associated with nitric oxide production and phagolysosome acidification. Importantly, we observed a protective effect of Zymosan-primed DCs delivered intranasally in experimental pulmonary PCM. Overall, our findings support the potential use of ß-glucan-containing compounds such as Zymosan as an alternative or complementary antifungal therapy. LAY SUMMARY: We report for the first time that Paracoccidioides brasiliensis-infected phagocytes treated with Zymosan (cell wall extract from bakers' yeast) show enhanced cytokine production, maturation, and fungal killing. Also, Zymosan-primed phagocytes induce a protective immune response in infected mice.

Hypoxia enhances ILC3 responses through HIF-1α-dependent mechanism.

Group 3 innate lymphoid cells (ILC3) have a prominent role in the maintenance of intestine mucosa homeostasis. The hypoxia-inducible factor (HIF) is an important modulator of immune cell activation and a key mechanism for cellular adaptation to oxygen deprivation. However, its role on ILC3 is not well known. In this study, we investigated how a hypoxic environment modulates ILC3 response and the subsequent participation of HIF-1 signaling in this process. We found increased proliferation and activation of intestinal ILC3 at low oxygen levels, a response that was phenocopied when HIF-1α was chemically stabilized and was reversed when HIF-1 was blocked. The increased activation of ILC3 relied on a HIF-1α-dependent transcriptional program, but not on mTOR-signaling or a switch to glycolysis. HIF-1α deficiency in RORyt compartment resulted in impaired IL-17 and IL-22 production by ILC3 in vivo, which reflected in a lower expression of their target genes in the intestinal epithelium and an increased susceptibility to Clostridiodes difficile infection. Taken together, our results show that HIF-1α activation in intestinal ILC3 is relevant for their functions in steady state and infectious conditions.

Biodegradable films based on commercial κ-carrageenan and cassava starch to achieve low production costs.

Biodegradable films have been a great alternative compared to non-renewable sources because of their cytocompatibility, biodegradability, and antimicrobial features. These properties may raise the foodstuff shelf life, reducing costs and economic losses. Indeed, biodegradable films can also reduce the environmental pollution promoted by non-biodegradable conventional packs. For the first time, biodegradable films were produced by casting commercials kappa-carrageenan (κ-car) and cassava starch at different κ-carrageenan/cassava starch weight ratios. Physical, thermal, and mechanical properties were evaluated. Apparent opacity and color analyses suggest that the films present high transparency. The sample 0κ-c supported a film with high water solubility (39.22%) and a low swelling degree (391.6%). The lowest water vapor permeability (WVP) was observed for 50κ-c (3.01×10-8g (Pams)-1). The oil permeability varied from 0.0033 to 0.0043mmm2 d-1. The 100κ-c and 75κ-c films (with high κ-carrageenan contents) had higher stiffness (19.23 and 25.88MPa, respectively) than the 25κ-c and 0κ-c films with elongation at break (ε) of 21.60 and 67.65%, respectively. The thermal stability increased as the starch concentration raised in the blend. We produced low-cost biodegradable films from commercial polysaccharides. These films can be used as food packs.

Helminths associated with Norops fuscoauratus (Squamata, Dactyloidae) in highland marshes of the Brazilian semi-arid.

Helminthological studies may contribute with valuable information on host biology and conservation. Herein, we provide new data on helminths infecting the lizard Norops fuscoauratus, testing one of the factors considered most important in parasitic ecology: host size. We analysed 25 specimens of N. fuscoauratus from three highland marshes in the Brazilian semi-arid. Eight taxa of helminths belonging to Nematoda, Trematoda and Acanthocephala were found. Physaloptera sp. showed the higher prevalence (40%), with a mean intensity of infection of 3.3 ± 1.46 (1-16) and mean abundance 1.32 ± 0.65 (0-16). Norops fuscoauratus represents four new host records for the helminths Cyrtosomum sp., Pharyngodon travassosi, Strongyloides sp. and Centrorhynchus sp. There is no relationship of host body size (P = 0.79) and mass (P = 0.50) with parasite richness. In addition, the present study contributes to the knowledge of the parasitic fauna of N. fuscoauratus and the Neotropical region.

Effect of heat stress in late gestation on subsequent lactation performance and mammary cell gene expression of Saanen goats.

Little is known about the effects of heat stress during the late gestation period on lactation in dairy goats. For this reason, 32 Saanen goats were randomly assigned to 1 of 2 groups, control (CT; n = 16) or heat stress (HS; n = 16), during late gestation. The HS goats were housed in a climatic chamber before parturition and subjected to heat stress for the last 45 d. After parturition, the HS goats were housed in the same conditions as the CT group. Mammary gland biopsies were performed on 7 goats per treatment at -30, -15, 15, and 30 d relative to parturition, so that the expression levels of several genes could be determined. The HS goats produced less milk than the CT goats did during the first half of lactation, but not during the rest of lactation. Before parturition, apoptosis-related transcripts (TP53 and BAX) were higher in the mammary glands of the HS goats than in those of the CT goats. The HS goats also had higher levels of HSPB1 gene expression during gestation and lactation. However, expression of the prolactin receptor gene was lower after parturition in the mammary glands of HS, suggesting downregulation of prolactin signaling. In summary, heat stress during final gestation reduces milk yield in the subsequent lactation. Although the upregulation of apoptosis signaling in the HS goats suggests that heat stress affects mammary cell number, the loss of the effect on milk production is more compatible with an effect on cell activity, which could be due to a downregulation of prolactin signaling.

PIMA: A population informative multiplex for the Americas.

We describe an ancestry-informative autosomal SNP multiplex designed to be a small-scale, flexible panel that can complement uniparental markers in assessing the American variability (i.e. pre-Colombian) found in contemporary indigenous American populations. This study centered on choosing SNPs with the specific characteristics of: 1) extreme allele frequency differences between indigenous Americans and the African, European and East Asian population groups that contribute to present-day population variation in the Americas; 2) high informativeness-for-assignment In values; and 3) well-spaced genomic distribution and chromosomal separation from existing small-scale forensic ancestry marker sets. The resulting capillary electrophoresis SNaPshot single base extension test was named: PIMA (Population Informative Multiplex for the Americas), comprising 26 autosomal SNPs, a single X-chromosome SNP plus the amelogenin sex marker adapted for SNaPshot. PIMA complements the established 34plex forensic ancestry panel to provide a powerful and simple tool for the analysis of American populations, including those with admixed histories, commonly encountered in America. Comparing the results obtained with the combined marker panels of PIMA and 34plex to SNP data from a much larger ancestry panel allowed us to gauge their relative efficiency. PIMA+34plex gives equivalent power to the 314-SNP 'LACE' genomic ancestry control panel, while requiring a much smaller genotyping effort. The ancestry profiles and genetic structure of 22 populations spread across the American continent were estimated using PIMA+34plex data, and those estimates were contrasted with information provided by uniparental markers (mtDNA and Y-chromosome loci) for a small set of admixed individuals from Venezuela. Our results indicate that an American genetic component is efficiently detected in contemporary American populations using a small set of ancestry informative SNPs, and these co-ancestry estimates are consistent with the known history and demography of the Americas. The small scale and high population differentiation power of PIMA, particularly when combined with 34plex, provides a practical and powerful tool for genetic studies of American populations as well as forensic DNA analyses.

Short-chain fatty acids and FFAR2 as suppressors of bone resorption.

Short-chain fatty acids (SCFAs) exert a variety of immune and metabolic functions by binding to G-protein-coupled receptors, mainly free fatty acid receptor 2 (FFAR2). However, the effects of SCFAs and FFARs on bone remodeling, especially in alveolar bone, have been less explored. In this study, we investigated the influence of the SCFA/FFAR2 axis on alveolar bone. Bone samples from wild-type (WT) and FFAR2-deficient mice (FFAR2-/-) were analyzed using micro-CT, histology and qPCR. WT and FFAR2-/- animals received a high-fiber diet (HFD) reported to increase circulating levels of SCFAs. Additionally, we analyzed the effects of SCFAs and a synthetic FFAR2 agonist, phenylacetamide-1 (CTMB), on bone cell differentiation. The participation of histone deacetylase inhibitors (iHDACs) in the effects of SCFAs was further assessed in vitro. CTMB treatment was also evaluated in vivo during orthodontic tooth movement (OTM). FFAR2-/- mice exhibited deterioration of maxillary bone parameters. Consistent with this, FFAR2-/- mice exhibited a significant increase of OTM and changes in bone cell numbers and in the expression of remodeling markers. The HFD partially reversed bone loss in the maxillae of FFAR2-/- mice. In WT mice, the HFD induced changes in the bone markers apparently favoring a bone formation scenario. In vitro, bone marrow cells from FFAR2-/- mice exhibited increased differentiation into osteoclasts, while no changes in osteoblasts were observed. In line with this, differentiation of osteoclasts was diminished by SCFAs and CTMB. Moreover, CTMB treatment significantly reduced OTM. Pretreatment of osteoclasts with iHDACs did not modify the effects of SCFAs on these cells. In conclusion, SCFAs function as regulators of bone resorption. The effects of SCFAs on osteoclasts are dependent on FFAR2 activation and are independent of the inhibition of HDACs. FFAR2 agonists may be useful to control bone osteolysis.

Genetic diversity, population structure and rickettsias in Amblyomma ovale in areas of epidemiological interest for spotted fever in Brazil.

Amblyomma ovale (Ixodida: Ixodidae) Koch, 1844 is widely-reported in the neotropical region and is the main vector in the epidemic cycle of Rickettsia parkeri strain Atlantic rainforest, a bioagent of a milder variety of spotted fever (SF). Because species with wide geographical distributions are known to exhibit variations that influence their vectorial capacity, the present study aimed to analyze genetic diversity and rickettsia infection of A. ovale collected during the investigation and surveillance of SF cases in the Cerrado and Atlantic rainforest (ARF) Brazilian biomes. Samples had their DNA extracted, amplified and sequenced for 16S rDNA, 12S rDNA, cytochrome oxidase subunit II and D-loop markers for tick analyses, as well as the gltA, htrA, ompA and ompB genes for rickettsia detection. Between 11 and 33 A. ovale haplotypes were identified, all of them exclusive to areas within individual analyzed biome areas. The A. ovale populations appeared to be structured, with Cluster I restricted to Cerrado + ARF isolated in Caatinga and Cluster II to ARF continuous area. Rickettsia bellii, R. parkeri strain Atlantic rainforest (first report for Goiás state, Cerrado), Rickettsia asemboensis (first record in A. ovale for Brazil) and Rickettsia felis (first detection in this ixodid) were identified. A. ovale clusters were not associated with rickettsia types.

Effect of acute stressors, adrenocorticotropic hormone administration, and cortisol release on milk yield, the expression of key genes, proliferation, and apoptosis in goat mammary epithelial cells.

Cortisol is essential to milk synthesis; however, different acute stressors and the exogenous administration of adrenocorticotropic hormone (ACTH) decrease milk yield. Therefore, the effect of cortisol on milk yield and its influence on the survival of mammary epithelial cells have not been fully elucidated. In this context, the objective of this study was to evaluate the effect of cortisol on the expression of growth hormone receptor (GHR), insulin-like growth factor type 1 (IGF1), insulin-like growth factor type 1 receptor (IGF1R), insulin-like growth factor-binding protein 3 and 5 (IGFBP3 and IGFBP5), BAX, and BCL2 genes on the proliferation and apoptotic rates of mammary epithelial cells, and on milk yield in Saanen goats. In the present study, 3 experiments were conducted: (1) comparing the in vivo effects of first milking, vaccination, vermifugation, preventive hoof trimming, and the administration of ACTH or a placebo on cortisol release in dairy goats; (2) studying the in vivo effects of immediate increases in cortisol on the mammary gland of lactating goats; and (3) studying the in vitro effects of a prolonged increase in cortisol on mammary epithelial cells obtained from lactating goats. Cortisol release by goats increased significantly after ACTH administration compared with that observed after a placebo, and the cortisol profiles after first milking, vaccination, vermifugation, hoof trimming, and ACTH administration were similar. However, there was no effect of the immediate increase in cortisol in vivo on IGF-1 release, milk yield, milk quality, or the apoptosis and proliferation rates, nor was there any effect on the expression of the target genes. Furthermore, no interaction was observed between IGF-1 and cortisol in either the in vivo or in vitro experiments. However, the addition of cortisol in vitro significantly increased the expression of the GHR and IGF1R genes, which stimulate cell proliferation, and the BAX gene, which causes apoptosis. These contrasting results can explain why cortisol did not change the rates of proliferation or apoptosis in epithelial cells. Indeed, cortisol supplementation in vitro did not change the number or apoptotic rate of epithelial cells over the course of 5 d. Finally, further studies must be performed to understand the effect of cortisol on the expression of the GHR, IGF1R, and BAX genes by epithelial cells and the roles of these genes in milk synthesis during early lactation.

A first step towards a consensus static in vitro model for simulating full-term infant digestion.

In vitro alternatives to clinical trials are used for studying human food digestion. For simulating infant digestion, only a few models, lacking physiological relevance, are available. Thanks to an extensive literature review of the in vivo infant digestive conditions, a gastrointestinal static in vitro model was developed for infants born at term and aged 28days. The model was applied to the digestion of a commercial infant formula. Kinetics of digestion, as well as the structural evolution, were compared with those obtained while submitting the same formula to the adult international consensus protocol of in vitro static digestion. The kinetics of proteolysis and lipolysis differed according to the physiological stage resulting mainly from the reduced level of enzymes and bile salts, as well as the higher gastric pH in the infant model. This in vitro static model of infant digestion is of interest for scientists, food or pharmaceutical manufacturers.