Extracraniofacial anomalies in Treacher Collins syndrome: A multicentre study of 248 patients.

Treacher Collins syndrome (TCS) is a congenital malformation of the craniofacial structures derived from the first and second pharyngeal arches. The craniofacial deformities are well described in the literature. However, little is known about whether there are associated extracraniofacial anomalies. A retrospective study was conducted using data from four craniofacial units. Medical charts were reviewed for the presence and type of extracraniofacial anomalies, as well as age at diagnosis. A possible correlation between the severity of the phenotype and the presence of extracraniofacial anomalies was assessed using the Hayashi classification. A total of 248 patients with TCS were identified; 240 were confirmed to have TCS, of whom 61 (25.4%) were diagnosed with one or more extracraniofacial anomalies. Ninety-five different extracraniofacial anomalies were found; vertebral (n=32) and cardiac (n=13) anomalies were most frequently seen, followed by reproductive system (n=11), central nervous system (n=7), and limb (n=7) anomalies. No correlations between tracts were found. Extracraniofacial anomalies were more prevalent in these patients with TCS compared to the general population (25.4% vs 0.001-2%, respectively). Furthermore, a positive trend was seen between the severity of the syndrome and the presence of extracraniofacial anomalies. A full clinical examination should be performed on any new TCS patient to detect any extracraniofacial anomalies on first encounter with the craniofacial team.

Exploring determinants of recalled in-task affective valence during recreational exercise.

Exercise-related affective responses, particularly in-task, have been implicated as influencing behavioral maintenance. An extensive body of literature, primarily using aerobic modes in laboratory settings, has identified a relatively consistent inverse relationship between intensity and affect. This relationship is purported to be partially accounted for by the saliency of interoceptive sensations (i.e., respiratory and heart rates, muscular effort), such that increased saliency elicits decreased affect. In naturalistic settings, exercise is volitional, individuals have comparatively more autonomy over exercise components (i.e., volume, duration, exercise intensity), and less is known regarding contributing factors of affective responses. Recalled affect may be perceived as a less invasive, more logistically feasible construct to measure in such settings. Thus, the purpose of the current study is to explore the basis of recalled affective valence following an acute bout of volitional exercise. Upon leaving the designated exercise area of a university recreation center, respondents (N = 236, 23y±10, 176cm±9.5, 76.9kg±16.2, 31.8% identified women, 68.2% identified men) were asked to complete a pen-and-paper survey regarding the bout they had just completed. Recalled affective valence was rated via 100 mm Visual Analog Scale, and respondents were asked to provide written explanation for the basis of recalled affective valence scores. Recalled affective valence scores were non-normally distributed (Mdn=81; IQR=30.5). Qualitative results indicate that interpretation of exertion and salient interoceptive sensations were mixed, resulting in both pleasant and unpleasant affective responses. Pre-exercise readiness factors (i.e., energy levels, substrate intake, and physical components) also contribute to recalled affective valence and could potentially explain variance in the interpretation of interoceptive sensations. Further research should expand on these findings through a more in-depth interview process and measuring factors of readiness before exercise.

A model of COVID-19 transmission to understand the effectiveness of the containment measures: application to data from France.

The main objective of this paper is to address the following question: are the containment measures imposed by most of the world governments effective and sufficient to stop the epidemic of COVID-19 beyond the lock-down period? In this paper, we propose a mathematical model which allows us to investigate and analyse this problem. We show by means of the reproductive number, ${\cal R}_0$ that the containment measures appear to have slowed the growth of the outbreak. Nevertheless, these measures remain only effective as long as a very large fraction of population, p, greater than the critical value $1-1/{\cal R}_0$ remains confined. Using French current data, we give some simulation experiments with five scenarios including: (i) the validation of model with p estimated to 93%, (ii) the study of the effectiveness of containment measures, (iii) the study of the effectiveness of the large-scale testing, (iv) the study of the social distancing and wearing masks measures and (v) the study taking into account the combination of the large-scale test of detection of infected individuals and the social distancing with linear progressive easing of restrictions. The latter scenario was shown to be effective at overcoming the outbreak if the transmission rate decreases to 75% and the number of tests of detection is multiplied by three. We also noticed that if the measures studied in our five scenarios are taken separately then the second wave might occur at least as far as the parameter values remain unchanged.

Prevalence of Salmonella in flocks housed in enriched cages.

Salmonellosis is a foodborne disease of humans and animals caused by infection with Salmonella. The aim of this paper is to improve a deterministic model (DM) and an individual-based model (IBM) with reference to Salmonella propagation in flocks of laying hens taking into account variations in hens housed in the same cage and to compare both models. The spatio-temporal evolution, the basic reproduction number, R 0, and the speed of wave propagation were computed for both models. While in most cases the DM allows summary of all the features of the model in the formula for computation of R 0, slight differences between individuals or groups may be observed with the IBM that could not be expected from the DM, especially when initial environmental contamination is very low and some cages may get rid of bacteria. Both models suggest that the cage size plays a role on the risk and speed of propagation of the bacteria, which should be considered when designing new breeding systems.

Effect of intense pulsed light treatment on human skin in vitro: analysis of immediate effects on dermal papillae and hair follicle stem cells.

BACKGROUND: Hair follicles house a permanent pool of epithelial stem cells. Intense pulsed light (IPL) sources have been successfully used for hair removal, but long-term hair reduction may require several treatments. Many questions remain regarding the impact of IPL treatment on the structure of the hair follicle, more specifically on hair follicular stem cells and dermal papilla cells, a group of specialized cells that orchestrate hair growth. OBJECTIVES: To characterize the destruction of human hair follicles and surrounding tissues following IPL treatment, with more attention paid to the bulge and the bulb regions. METHODS: Human scalp specimens of Fitzpatrick skin phototype II were exposed ex vivo to IPL pulses and were then processed for histological analysis, immunodetection of stem cell-associated keratin 19, and revelation of the endogenous alkaline phosphatase activity expressed in dermal papilla cells. RESULTS: Histological analysis confirmed that pigmented structures, such as the melanin-rich matrix cells of the bulb in anagen follicles and the hair shaft, are principally targeted by IPL treatment, while white hairs and epidermis remained unaffected. Damage caused by heat sometimes extended over the dermal papilla cells, while stem cells were mostly spared. CONCLUSIONS: IPL epilation principally targets pigmented structures. Our results suggest that, under the tested conditions, collateral damage does not deplete stem cells. Damage at the dermal papilla was observed only with high-energy treatment modalities. Extrapolated to frequently treated hairs, these observations explain why some hairs grow back after a single IPL treatment.

[Iron metabolism: State of the art]. / Actualité du métabolisme du fer.

About 60% of body iron is associated with hemoglobin in circulating red blood cells and daily erythropoiesis requires about 25 to 30mg iron per day. This iron is provided by macrophages through recycling of heme iron following phagocytosis of senescent red blood cells and heme catabolism. Intestinal iron absorption (1 to 2mg per day) only compensates for daily iron losses. Hepcidin, a 25 amino-acid peptide synthesized in hepatocytes, secreted in plasma and rapidly removed in urines, is a negative regulator of both intestinal iron absorption and heme iron recycling by macrophages. Hepcidin synthesis is stimulated by iron or by inflammation (mostly by IL-6) and is repressed by iron deficiency and by all conditions that stimulate bone marrow erythropoiesis such as anemia, bleeding, hemolysis, dyserythropoiesis or erythropoietin injections. A defect in the activation of hepcidin normally triggered by iron excess is the underlying mechanism for all juvenile or adult forms of hemochromatosis whereas a defect in hepcidin repression is responsible for an iron deficiency iron refractory anemia (IRIDA). Reduced hepcidin filtration in renal insufficiency contributes to the associated anemia and stimulation of hepcidin synthesis by inflammation is a major determinant of the anemia of chronic disorders. New therapeutic perspectives are currently underway such as the development of agonists or antagonists of hepcidin or siRNA approaches aiming at reducing hepcidin synthesis. The validation of hepcidin assays in a near future will allow identifying the patients most likely to benefit from intravenous iron therapy.

[Iron therapy: Indications, limitations and modality]. / Supplémentation en fer : indications, limites et modalités.

During the past 10 years, the knowledge of iron metabolism has been revolutionized by the discovery of the main regulatory hormone of body iron: hepcidin. Meanwhile, new formulations of intravenous iron have been developed and are already or readily available. In this article, we review the recent pathophysiological mechanisms underlying anemia of chronic disease or due to iron deficiency. We describe the various treatment modalities of iron deficiency anemia using oral or intravenous route and the emerging indications of treatment with iron. Finally, we discuss the situations in which iron supplementation may be harmful.

[Diagnosis of hypochromic microcytic anemia in children]. / Exploration d'une anémie microcytaire chez l'enfant.

Iron deficiency is the most frequent cause of hypochromic microcytic anemia in children, but other causes, some of them requiring specific management, may be involved. Checking the iron-status is absolutely mandatory. When iron-status parameters are low, inadequate intake, malabsorption, blood loss, and abnormal iron utilization must be tested. In absence of iron deficiency, α- and ß-globin and heme biosynthetic gene status must be checked. Assessing the iron stock level is difficult, because there is an overlap between the values observed in iron-replete and iron-deprived patients, so that at least 2 iron-status parameters must be below normal for diagnosing iron deficiency. Furthermore, inflammation may also mimic some characteristics of iron deficiency. Diagnosing iron deficiency leads to prescribing iron supplementation with follow-up at the end and 3 months after cessation of treatment. When iron stores are not replete at the end of treatment, compliance and dosage must be reevaluated and occult bleeding sought. The latter is also required when the iron store decreases 3 months after cessation of iron replacement.

[The 5-word test in 37 depressed patients compared with 36 normal controls and 35 patients with mild Alzheimer's disease]. / Évaluation de la mémoire au moyen du Test des 5 mots chez 37 dépressifs comparés à 36 témoins et 35 patients ayant une forme légère de maladie d'Alzheimer.

OBJECTIVES: Patients with major depression (MD) express frequent memory complaints leading to consultations in memory clinics. The 5-word test (5WT) is a verbal memory test with semantic cueing, which has shown its sensitivity and its specificity in identifying patients with Alzheimer's disease (AD). Our objective was to evaluate memory performances of aged patients with MD compared with controls and AD patients. METHODS: Characteristics of the 5WT were investigated in a sample of 37 patients with MD (66.8±7.5 years) compared with 36 normal controls (67.3±6.8 years) and 35 mild AD patients (67.5±6.1 years). RESULTS: Duration of depression was 15.3±11.5 years. Memory complaints of MD patients were ancient (4.6±5.5 years) and severe (McNair memory questionnaire=47.6±20.7). The Total score of MD patients did not differ from controls but was greater than those of AD patients. Learning and Memory scores of MD patients were significantly lower than those of controls and significantly greater than those of AD patients. Forgetting rate between Learning and Memory scores was more important in AD (72.4%) than in controls (2.8%) and MD (13.6%). No intrusions were recorded in controls, three MD patients each made one intrusion, whereas 80% of AD patients made between one to six intrusions (mainly during cued delayed recall). Receiver operating characteristic curves determined the most significant cut-off scores of the Total score. It appeared easy to discriminate AD patients from controls (cut-off=9, sensitivity=94.3%, specificity=100%) or MD patients (cut-off=8, sensitivity=88.5%, specificity=89.2%) whereas it was more difficult to discriminate MD patients from controls (cut-off=10, specificity=88.9%, sensitivity=37.8%). DISCUSSION: MD patients had significant difficulties with the 5WT as compared to controls, without being of the magnitude of those observed in AD patients. CONCLUSION: The 5WT allows a reliable evaluation of memory in MD patients. The presence of true memory deficits with the 5WT could not be ascribed to depression but to other pathological conditions. Consequently, further memory testing should be conducted.

Use of a reduced set of single nucleotide polymorphisms for genetic evaluation of resistance to Salmonella carrier state in laying hens.

Salmonella propagation by apparently healthy chickens could be decreased by the selection and use of chicken lines that are more resistant to carrier state. Using a reduced set of markers, this study investigates, for the first time to the authors' knowledge, the feasibility of a genomic selection approach for resistance to carrier state in hen lines. In this study, commercial laying hen lines were divergently selected for resistance to Salmonella carrier state at 2 different ages: young chicks and adults at the peak of lay. A total of 600 birds were typed with 831 informative SNP markers and artificially infected with Salmonella Enteritidis. Phenotypes were collected 28 d (389 young animals) or 38 d (208 adults) after infection. Two types of variance component analyses, including SNP data or not, were performed and compared. The set of SNP used was efficient in capturing a large part of the genetic variation. Average accuracies from mixed model equations did not change between analyses, showing that using SNP data does not increase information in this data set. These results confirm that genomic selection for Salmonella carrier state resistance in laying hens is promising. Nevertheless, a denser SNP coverage of the genome on a greater number of animals is still needed to assess its feasibility and efficiency.

[The five-word test in three age-groups of mild Alzheimer's disease (60, 70 and 80 year-old patients): Utility of the Total Score, Total Weighted Score, Learning Score and Memory Score]. / Le Test des cinq mots dans les formes légères de maladie d'Alzheimer : comparaison du score total, du Score Total Pondéré, du Score d'apprentissage et du Score de mémoire dans trois classes d'âge (60 ans, 70 ans, 80 ans).

INTRODUCTION: The five-word test (5WT) is a serial verbal memory test with semantic cuing. It is proposed to rapidly evaluate memory of aging people and has previously shown its sensitivity and its specificity in identifying patients with AD. It measures the efficacy of free and cued recalls during a procedure of immediate and delayed recalls. METHODS: The 5WT was compared in a group of 202 normal subjects and a group of 302 mild AD patients (MMS of 20 or more) aged from 60 to 92 years, in three age classes (60 years, 70 years, 80 years). Nine scores were measured (Total Score, Total Weighted Score, Free Immediate Recall, Learning Score=total of Immediate Recalls, Free Delayed Recall, Memory Score=total of Delayed Recalls, Forgetting Rate, Percentage of Immediate Cuing, Percentage of Delayed Cuing) as well as the presence of intrusions. For each age class, Receiver Operating Characteristic curves determined the most significant cut-off scores. RESULTS: For each score of the 5WT, AD patients differed significantly from controls. The cut-off scores were not the same according to age. For the Total Score, the cut-off scores were 10 (60 years), 9 (70 years) and 8 (80 years), whereas the cut-off scores of the Total Weighted Score were 17 (60 years), 16 (70 years) and 14 (80 years). As suggested by Cowppli-Bony et al. (2005), the Total Weighted Score (which gives a higher coefficient to free recalls) was better than the Total Score for discriminating mild AD. The 5WT is useful to discriminate normal controls and mild AD patients. Normal aged subjects displayed good encoding, efficient stocking and consolidation (few forgetting, efficient cued recall), intrusions were rare. Mild AD patients were characterized by weak encoding of words and severe deficit for stocking and consolidation (important forgetting, impaired cued recall), they made numerous intrusions. This psychometric profile is characteristic of the amnestic hippocampal syndrome found in AD. CONCLUSION: The 5WT is a simple and reliable test for investigating memory in elderly people above 60 years old. According to age, different cut-offs are needed for the Total Score and the Total Weighted Score, the latter appearing more discriminating than the Total Score for the diagnosis of mild AD. It is also interesting to evaluate the presence of intrusions. Lastly, it is important to consider the forgetting rate (between Learning and Memory Scores) in order to confirm the presence of a hippocampal amnesia.

[Validation of the Rapid BAttery of Denomination (BARD) in 382 controls and 1004 patients of a memory clinic]. / Validation de la batterie rapide de dénomination (BARD) chez 382 témoins et 1004 patients d'une consultation mémoire.

INTRODUCTION: The Rapid BAttery of Denomination (BARD) is a short 10-item naming test derived from the 60-item Boston Naming Test. It is easily performed in less than 15 seconds by normal controls independently of age, gender and education (Croisile, 2005,2007,2008). Our aim was to evaluate the BARD in various conditions seen in a memory clinic. PATIENTS AND METHODS: The BARD was used in 382 normal subjects (165 men and 217 women, aged from 20 to 97 years) and 1004 patients attending a memory clinic. Three groups of 505 patients with Alzheimer's disease (AD) were compared: mild patients (n=402), moderate patients (n=84) and moderately severe patients (n=19). The BARD was also used in 499 patients with a Mini Mental Status (MMSE)>or=20: 173 patients with amnestic Mild Cognitive Impairment (aMCI), 56 patients with frontotemporal dementia (FTD), 41 patients with Lewy Body dementia (LBD), 36 patients with nonfluent primary progressive aphasia (NFPPA), 27 patients with semantic dementia (SD), 16 patients with posterior cortical atrophy (PCA), 150 patients with anxiety or depression (ADD). RESULTS: The performance of the patients was not affected by age, gender or education. aMCI had a score of 9.97+/-0.18, ADD a score of 9.97+/-0.2. A mild anomia was observed in three groups: mild AD (9.78+/-0.5), FTD (9.79+/-0.65) et LBD (9.98+/-0.16). A more pronounced anomia was present in moderate AD (9.10+/-1.06), moderately severe AD (8.05+/-1.27), PCA (8.12+/-3.28) and NFPPA (8.44+/-1.61). The anomia was severe in SD (5.85+/-2.46). The 10 items were perfectly named by 98 % of ADD, 96.53 % of aMCI, 82.09 % of mild AD, 87.5 % of FTD patients, 97.56 % of LBD patients, 68.75 % of PCA patients, but only 45.24 % moderate AD, 5.26 % of moderately severe AD, 27.78 % of NFPPA, and 3.7 % of SD. In the patients with MMS>or=20, Anova showed that the BARD scores of the ADD, aMCI, mild AD, FTD and LBD groups were significantly greater than the BARD scores of NFPPA, SD and PCA. PCA and NFPPA groups did not differ for BARD scores whereas they were significantly better than SD. A ROC curve comparing the 822 mild anomic patients (AD, FTD, LBD, aMCI, ADD) with the 79 more anomic patients (NFPPA, SD, PCA) showed that for a BARD score of 10, sensitivity was 72.2 %, specificity was 89.2 %, and 87.7 % of the patients were correctly classified. CONCLUSION: The BARD is a quick and useful tool for identifying naming disorders in a memory clinic. In patients with MMSE>or=20, making one error at the BARD is highly abnormal and significantly characteristic of cognitive disorders: the more frequent the errors are, the more probable is the presence of a visual agnosia (PCA), an aphasia (NFPPA), or a semantic disorder (SD).

The European experience in poultry welfare--a decade ahead.

Farm animal welfare is a major issue in Europe, which resulted in regulations and development of research dedicated to animal welfare, especially on standard poultry production, which is often considered as resulting in very poor welfare. The effect of selection is also often questioned. Indeed, capacities of adaptation have been very little considered during the first years of commercial selection and thus have been reduced. Nowadays, a much greater importance is given to welfare-related traits and genomic selection should alleviate the need for their measurements in the short-term. However, the choice of the fittest selection criteria is still to be made. Because behavioral traits are highly dependent on environment, general reactivity may be more efficient. For example, selection against undesirable behavior such as feather pecking has been proven to be efficient, but selection for reduced mortality rates in collective cages proved to be preferable. Most often, selection should not exacerbate extreme values, which are most often detrimental, as in the case of social motivation, which, when increased to too large of an extent, results in increased aggressivity. Moreover, a general propensity will not result in overall improvement; for example, reducing fearfulness has positive effects but does not modify response to social stress. Detrimental effects on other traits may also be observed: although genetic resistance to diseases should increase animal welfare, it may also result in increased frequency of silent carriers and in turn to human transmission. Indeed, an optimum must be found. Studying lines selected for or against these traits will be of great help to choose the best strategy of selection. Another and longer term concern should be on links with other production traits but also on sustainability, which will probably be of greater importance in the coming years.

Mapping QTL for growth and shank traits in chickens divergently selected for high or low body weight.

An F(2) population (695 individuals) was established from broiler chickens divergently selected for either high (HG) or low (LG) growth, and used to localize QTL for developmental changes in body weight (BW), shank length (SL9) and shank diameter (SD9) at 9 weeks. QTL mapping revealed three genome-wide QTL on chromosomes (GGA) 2, 4 and 26 and three suggestive QTL on GGA 1, 3 and 5. Most of the BW QTL individually explained 2-5% of the phenotypic variance. The BW QTL on GGA2 explained about 7% of BW from 3 to 7 weeks of age, while that on GGA4 explained 15% of BW from 5 to 9 weeks. The BW QTL on GGA2 and GGA4 could be associated with early and late growth respectively. The GGA4 QTL also had the largest effect on SL9 and SD9 and explained 7% and 10% of their phenotypic variances respectively. However, when SL9 and SD9 were corrected with BW9, a shank length percent QTL was identified on GGA2. We identified novel QTL and also confirmed previously identified loci in other chicken populations. As the foundation population was established from commercial broiler strains, it is possible that QTL identified in this study could still be segregating in commercial strains.

Use of the entero-test, a novel approach for the noninvasive capture of biliary metabolites in dogs.

Preclinical information on the biliary metabolites of a drug candidate is typically obtained through the collection of bile after surgical cannulation of the bile duct. In this study, we describe a novel approach using the Entero-Test, a simple device that facilitates the noninvasive sampling of duodenal bile. The Entero-Test was used to collect bile from six fasted dogs that had been dosed either orally with simvastatin (SV) or intravenously with simvastatin hydroxy acid (SVA), compounds that have been previously reported to undergo extensive metabolism and biliary secretion in the dog. The devices, consisting of a weighted gelatin capsule containing 90 cm of a highly absorbent nylon string, were swallowed by each dog with the proximal end of the string taped to the animal's face. Once the weighted string had reached the duodenum, gallbladder contraction was stimulated to release bile. Each bile-stained string was then retrieved via the mouth and, after solvent extraction, samples were analyzed for drug-related material by ultraperformance liquid chromatography-mass spectrometry and NMR spectroscopy. Numerous metabolites of SV and SVA were observed, and, in general, the major metabolites have been reported previously from studies with bile duct-cannulated animals dosed with [14C]SV or [14C]SVA. The results from this study demonstrate the utility of deploying the Entero-Test in absorption, distribution, metabolism, and elimination studies to provide information on the nature of biliary metabolites, which, on occasion, may be sufficient to negate the need for more invasive sampling techniques. The benefits and limitations of the technique are discussed.

QTL for resistance to Salmonella carrier state confirmed in both experimental and commercial chicken lines.

The ability of chickens to carry Salmonella without displaying disease symptoms is responsible for Salmonella propagation in poultry stocks and for subsequent human contamination through the consumption of contaminated eggs or meat. The selection of animals more resistant to carrier state might be a way to decrease the propagation of Salmonella in poultry stocks and its transmission to humans. Five QTL controlling variation for resistance to carrier state in a chicken F(2) progeny derived from the White Leghorn inbred lines N and 6(1) had been previously identified using a selective genotyping approach. Here, a second analysis on the whole progeny was performed, which led to the confirmation of two QTL on chromosomes 2 and 16. To assess the utility of these genomic regions for selection in commercial lines, we tested them together with other QTL identified in an [Nx6(1)] x N backcross progeny and with the candidate genes SLC11A1 and TLR4. We used a commercial line divergently selected for either low or high carrier-state resistance both in young chicks and in adult hens. In divergent chick lines, one QTL on chromosome 1 and one in the SLC11A1 region were significantly associated with carrier-state resistance variations; in divergent adult lines, one QTL located in the major histocompatibility complex on chromosome 16 and one in the SLC11A1 region were involved in these variations. Genetic studies conducted on experimental lines can therefore be of potential interest for marker-assisted selection in commercial lines.

Excessive erythrocyte PPIX influences the hematologic status and iron metabolism in patients with dominant erythropoietic protoporphyria.

Partial deficiency of the last enzyme of the heme biosynthetic pathway (namely ferrochelatase, FECH) in humans is responsible for erythropoietic protoporphyria (EPP). This disorder is characterised by painful photosensitivity, due to excessive production of protoporphyrin IX (PPIX) by erythrocytes. Controversial hypotheses have been proposed to explain the hematologic and iron status of EPP patients. In the present work, we explored these parameters in 55 patients with dominant EPP recruited at the French Center of Porphyrias (Colombes, France) and confirmed by molecular analysis. Our data show that erythrocyte accumulation of PPIX in EPP patients influences hematologic and iron status. Patients studied had a mild anemia and thrombocytopenia, as shown by the downward shift of hematologic parameters, which positively correlated with the amount of erythrocyte PPIX. Interestingly, erythropoiesis did not seem to be limited by iron supply in patients, since serum iron and soluble transferring (Tf) receptor (sTfR) were normal. However, iron and Tf saturation negatively correlated with erythrocyte PPIX. Moreover, and as previously described in a mouse model of EPP, we noted a positive correlation between erythrocyte PPIX and Tf levels. Altogether, these results suggest a positive effect of PPIX on the synthesis on Tf, which could facilitate the mobilization of tissue iron stores to meet erythropoiesis requirement. Based on these observations and previous results in EPP mouse model, we propose that the PPIX-liver transferrin pathway plays a role in the orchestration of iron distribution between peripheral iron stores, the spleen and the bone marrow.