Associations among diet, inflammation and iron status in young adults

Obesity is a risk factor for poor iron status due to the chronic, low-grade inflammation of adipose tissue hypertrophy. Among other positive acute phase proteins, the hepatic peptide hormone hepcidin is secreted during inflammation, inhibiting systemic iron efflux from enterocytes and downregulating systemic iron recycling by suppressing iron release from the mononuclear phagocyte system. Conversely, production and secretion of the iron transport protein transferrin by the liver is reduced during inflammation. In addition to increasing adiposity, certain foods are also known to promote inflammatory states and may contribute to these same effects in concert with, or independent of obesity. In this study, we evaluated how inflammatory diets are related to inflammatory and iron status biomarkers among 98 young adults with normal weight, overweight and obesity. Three-day dietary records and biomarker data for iron status and inflammation from two cross-sectional studies of similar design (Diet and Inflammation Study, n= 39 and the Selenium and Inflammation Study, n= 59) were used in this study. Dietary Inflammatory Index (DII) scores were calculated for each subject using nutrients and other dietary components from the dietary records, and subjects were further classified into two DII categories using cluster analysis. Using ANOVA we compared iron status and inflammatory markers among subjects with normal weight, overweight and obesity. We determined the association between DII scores or DII category and C-reactive protein (CRP), hepcidin, serum iron and total iron binding capacity (TIBC). Statistical significance was set at P< 0.05. Mean + SEM were reported for continuous variables except for skewed variables in which case geometric means (geometric mean +1SEM interval) were reported. CRP concentration differed significantly by BMI category (p < 0.05 for all comparisons) and serum iron (SI) was lower in the obese category compared to normal weight (p=0.014). Results from the regression analysis showed that high DII scores were associated with increased CRP concentration and decreasing TIBC. Similarly, subjects in the anti-inflammatory diet group showed higher TIBC compared to those in the inflammatory diet group. In conclusion, our study showed that inflammatory diets may impair iron status by reducing the capacity of the iron transport protein transferrin to transport iron in the blood

Relationship between Selenium and Hematological Markers in Young Adults with Normal Weight or Overweight/Obesity

Selenium deficiency has been linked to anemia of inflammation, which is mediated by hepcidin. However, there are few studies providing evidence of the role of hepcidin in this relationship. In this study, we investigated the interrelationships among selenium biomarkers, hepcidin concentration, and iron status among individuals with overweight/obesity compared to their normal weight counterparts, since obesity is associated with chronic inflammation. A total of 59 college students were recruited for this study. Fasting blood samples were collected for the analysis of iron status, plasma selenoproteins (glutathione peroxidase (GPX) activity and selenoprotein P (SEPP1)), and plasma hepcidin. Subjects completed three-day dietary records to determine average daily nutrient intakes. SEPP1 concentration, GPX activity, and iron status biomarkers (serum iron, transferrin saturation, and hemoglobin concentration) were lower among individuals with overweight/obesity compared with individuals with normal weight, but these differences were not significant (p > 0.05). Regression analysis showed that GPX activity (β = −0.018, p = 0.008) and SEPP1 concentration (β = −1.24, p = 0.03) were inversely associated with hepcidin concentration. The inverse association between selenoproteins and hepcidin concentration supports a potential role of hepcidin as a mediator between selenium and iron status and warrants further studies to better understand this relationship

MN1 C-terminal truncation syndrome is a novel neurodevelopmental and craniofacial disorder with partial rhombencephalosynapsis

MN1 encodes a transcriptional co-regulator without homology to other proteins, previously implicated in acute myeloid leukaemia and development of the palate. Large deletions encompassing MN1 have been reported in individuals with variable neurodevelopmental anomalies and non-specific facial features. We identified a cluster of de novo truncating mutations in MN1 in a cohort of 23 individuals with strikingly similar dysmorphic facial features, especially midface hypoplasia, and intellectual disability with severe expressive language delay. Imaging revealed an atypical form of rhombencephalosynapsis, a distinctive brain malformation characterized by partial or complete loss of the cerebellar vermis with fusion of the cerebellar hemispheres, in 8/10 individuals. Rhombencephalosynapsis has no previously known definitive genetic or environmental causes. Other frequent features included perisylvian polymicrogyria, abnormal posterior clinoid processes and persistent trigeminal artery. MN1 is encoded by only two exons. All mutations, including the recurrent variant p.Arg1295* observed in 8/21 probands, fall in the terminal exon or the extreme 3' region of exon 1, and are therefore predicted to result in escape from nonsense-mediated mRNA decay. This was confirmed in fibroblasts from three individuals. We propose that the condition described here, MN1 C-terminal truncation (MCTT) syndrome, is not due to MN1 haploinsufficiency but rather is the result of dominantly acting C-terminally truncated MN1 protein. Our data show that MN1 plays a critical role in human craniofacial and brain development, and opens the door to understanding the biological mechanisms underlying rhombencephalosynapsis.status: publishe

Children living with HIV in Europe: do migrants have worse treatment outcomes?

International audienceTo assess the effect of migrant status on treatment outcomes among children living with HIV in Europe

Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: A 2-y randomized controlled trial of calorie restriction in nonobese humans

Background: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition.Objective: We evaluated the effect of a 2-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m2) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multicenter, randomized controlled trial.Design: Participants were 218 nonobese (BMI: 21.9-28.0) adults aged 21-51 y who were randomly assigned to 25% CR (CR, n = 143) or ad libitum control (AL, n = 75) in a 2:1 ratio. Measures at baseline and 12 and 24 mo included body weight, waist circumference, fat mass (FM), fat-free mass (FFM), and appendicular mass by dual-energy X-ray absorptiometry; activity-related energy expenditure (AREE) by doubly labeled water; and dietary protein intake by self-report. Values are expressed as means ± SDs.Results: The CR group achieved 11.9% ± 0.7% CR over 2-y and had significant decreases in weight (-7.6 ± 0.3 compared with 0.4 ± 0.5 kg), waist circumference (-6.2 ± 0.4 compared with 0.9 ± 0.5 cm), FM (-5.4 ± 0.3 compared with 0.5 ± 0.4 kg), and FFM (-2.0 ± 0.2 compared with -0.0 ± 0.2 kg) at 24 mo relative to the AL group (all between-group P < 0.001). Moreover, FFM as a percentage of body weight at 24 mo was higher, and percentage of FM was lower in the CR group than in the AL. AREE, but not protein intake, predicted preservation of FFM during CR (P < 0.01). Men in the CR group lost significantly more trunk fat (P = 0.03) and FFM expressed as a percentage of weight loss (P < 0.001) than women in the CR group.Conclusions: Two years of CR had broadly favorable effects on both whole-body and regional adiposity that could facilitate health span in humans. The decrements in FFM were commensurate with the reduced body mass; although men in the CR group lost more FFM than the women did, the percentage of FFM in the men in the CR group was higher than at baseline. CALERIE was registered at clinicaltrials.gov as NCT00427193

The value of open-source clinical science in pandemic response: lessons from ISARIC

International audienc

Association of Country Income Level With the Characteristics and Outcomes of Critically Ill Patients Hospitalized With Acute Kidney Injury and COVID-19

Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods: This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results: Among patients with COVID-19 admitted to the intensive care unit, AKI incidence was highest in patients in LLMIC, followed by patients in upper-middle income countries (UMIC) and high-income countries (HIC) (53%, 38%, and 30%, respectively), whereas dialysis rates were lowest among patients with AKI from LLMIC and highest among those from HIC (27% vs. 45%). Patients with AKI in LLMIC had the largest proportion of community-acquired AKI (CA-AKI) and highest rate of in-hospital death (79% vs. 54% in HIC and 66% in UMIC). The association between AKI, being from LLMIC and in-hospital death persisted even after adjusting for disease severity. Conclusions: AKI is a particularly devastating complication of COVID-19 among patients from poorer nations where the gaps in accessibility and quality of healthcare delivery have a major impact on patient outcomes