Iron bioavailability in two commercial cultivars of wheat: a comparison between wholegrain and white flour and the effects of nicotianamine and 2'-deoxymugineic acid on iron uptake into Caco-2 cells

Iron bioavailability in unleavened white and wholegrain bread made from two commercial wheat varieties was assessed by measuring ferritin production in Caco-2 cells. The breads were subjected to simulated gastrointestinal digestion and the digests applied to the Caco-2 cells. Although Riband grain contained a lower iron concentration than Rialto, iron bioavailability was higher. No iron was taken up by the cells from white bread made from Rialto flour or from wholegrain bread from either variety, but Riband white bread produced a small ferritin response. The results probably relate to differences in phytate content of the breads, although iron in soluble monoferric phytate was demonstrated to be bioavailable in the cell model. Nicotianamine, an iron chelator in plants involved in iron transport, was a more potent enhancer of iron uptake into Caco-2 cells than ascorbic acid or 2'-deoxymugineic acid, another metal chelator present in plants

Neonatal erythropoiesis and subsequent anemia in HIV-positive and HIV-negative Zimbabwean babies during the first year of life: a longitudinal study

BACKGROUND: Anemia is common in HIV infection and independently associated with disease progression and mortality. The pathophysiology of HIV-related anemia is not well understood especially in infancy. METHODS: We conducted a longitudinal cohort study nested within the Zimbabwe Vitamin A for Mothers and Babies Project. We measured hemoglobin, erythropoietin (EPO), serum transferrin receptor (TfR) and serum ferritin at 6 weeks, 3 and 6 months of age and hemoglobin at 9 and 12 months in 3 groups of randomly selected infants: 136 born to HIV-negative mothers, and 99 born to HIV-positive mothers and who were infected themselves by 6 weeks of age, and 324 born to HIV-positive mothers but who did not become infected in the 6 months following birth. RESULTS: At one year of age, HIV-positive infants were 5.26 (adjusted odds ratio, P < 0.001) times more likely to be anemic compared to HIV-negative infants. Among, HIV-negative infants, EPO was or tended to be inversely associated with hemoglobin and was significantly positively associated with TfR throughout the first 6 months of life; TfR was significantly inversely associated with ferritin at 6 months; and EPO explained more of the variability in TfR than did ferritin. Among infected infants, the inverse association of EPO to hemoglobin was attenuated during early infancy, but significant at 6 months. Similar to HIV-negative infants, EPO was significantly positively associated with TfR throughout the first 6 months of life. However, the inverse association between TfR and ferritin observed among HIV-negative infants at 6 months was not observed among infected infants. Between birth and 6 months, mean serum ferritin concentration declined sharply (by ~90%) in all three groups of babies, but was significantly higher among HIV-positive compared to HIV-negative babies at all time points. CONCLUSION: HIV strongly increases anemia risk and confounds interpretation of hematologic indicators in infants. Among HIV-infected infants, the EPO response to anemia is attenuated near the time of infection in the first weeks of life, but normalizes by 6 months

Mental Health and School Functioning for Girls in the Child Welfare System : the Mediating Role of Future Orientation and School Engagement

This study investigated the association between mental health problems and academic and behavioral school functioning for adolescent girls in the child welfare system and determined whether school engagement and future orientation meditated the relationship. Participants were 231 girls aged between 12 and 19 who had been involved with the child welfare system. Results indicated that 39% of girls reported depressive symptoms in the clinical range and 54% reported posttraumatic symptoms in the clinical range. The most common school functioning problems reported were failing a class (41%) and physical fights with other students (35%). Participants reported a mean number of 1.7 school functioning problems. Higher levels of depression and PTSD were significantly associated with more school functioning problems. School engagement fully mediated the relationship between depression and school functioning and between PTSD and school functioning, both models controlling for age, race, and placement stability. Future orientation was not significantly associated with school functioning problems at the bivariate level. Findings suggest that school engagement is a potentially modifiable target for interventions aiming to ameliorate the negative influence of mental health problems on school functioning for adolescent girls with histories of abuse or neglect

Parametric exploration of the liver by magnetic resonance methods

MRI, as a completely noninvasive technique, can provide quantitative assessment of perfusion, diffusion, viscoelasticity and metabolism, yielding diverse information about liver function. Furthermore, pathological accumulations of iron and lipids can be quantified. Perfusion MRI with various contrast agents is commonly used for the detection and characterization of focal liver disease and the quantification of blood flow parameters. An extended new application is the evaluation of the therapeutic effect of antiangiogenic drugs on liver tumours. Novel, but already widespread, is a histologically validated relaxometry method using five gradient echo sequences for quantifying liver iron content elevation, a measure of inflammation, liver disease and cancer. Because of the high perfusion fraction in the liver, the apparent diffusion coefficients strongly depend on the gradient factors used in diffusion-weighted MRI. While complicating analysis, this offers the opportunity to study perfusion without contrast injection. Another novel method, MR elastography, has already been established as the only technique able to stage fibrosis or diagnose mild disease. Liver fat content is accurately determined with multivoxel MR spectroscopy (MRS) or by faster MRI methods that are, despite their widespread use, prone to systematic error. Focal liver disease characterisation will be of great benefit once multivoxel methods with fat suppression are implemented in proton MRS, in particular on high-field MR systems providing gains in signal-to-noise ratio and spectral resolution

The immune microenvironment in hormone receptor-positive breast cancer before and after preoperative chemotherapy

Purpose: Hormone receptor-positive/HER2-negative (HR+/HER2_) breast cancer is associated with low levels of stromal tumor-infiltrating lymphocytes (sTIL) and PD-L1, and demonstrates poor responses to checkpoint inhibitor therapy. Evaluating the effect of standard chemotherapy on the immune microenvironment may suggest new opportunities for immunotherapy-based approaches to treating HR+/HER2_ breast tumors. Experimental Design: HR+/HER2_ breast tumors were analyzed before and after neoadjuvant chemotherapy. sTIL were assessed histologically; CD8+ cells, CD68+ cells, and PD-L1 staining were assessed immunohistochemically; whole transcriptome sequencing and panel RNA expression analysis (NanoString) were performed. Results: Ninety-six patients were analyzed from two cohorts (n = 55, Dana-Farber cohort; n = 41, MD Anderson cohort). sTIL, CD8, and PD-L1 on tumor cells were higher in tumors with basal PAM50 intrinsic subtype. Higher levels of tissuebased lymphocyte (sTIL, CD8, PD-L1) and macrophage (CD68) markers, as well as gene expression markers of lymphocyte or macrophage phenotypes (NanoString or CIBERSORT), correlated with favorable response to neoadjuvant chemotherapy, but not with improved distant metastasis-free survival in these cohorts or a large gene expression dataset (N = 302). In paired pre-/postchemotherapy samples, sTIL and CD8+ cells were significantly decreased after treatment, whereas expression analyses (NanoString) demonstrated significant increase of multiple myeloid signatures. Single gene expression implicated increased expression of immunosuppressive (M2-like) macrophage-specific genes after chemotherapy. Conclusions: The immune microenvironment of HR+/ HER2_ tumors differs according to tumor biology. This cohort of paired pre-/postchemotherapy samples suggests a critical role for immunosuppressive macrophage expansion in residual disease. The role of macrophages in chemoresistance should be explored, and further evaluation of macrophagetargeting therapy is warranted

Prevalence of anaemia in older persons: systematic review

<p>Abstract</p> <p>Background</p> <p>Ageing populations will impact on healthcare provision, especially since extra years are not necessarily spent in good health. It is important to identify and understand the significance of common medical problems in older people. Anaemia may be one such problem. We report on the prevalence of anaemia in cohorts of elderly people in the general population. The presence of anaemia is associated with a worse prognosis for both morbidity and mortality.</p> <p>Methods</p> <p>Electronic searching and reference lists of published reports were used to identify studies that reported on prevalence of anaemia in cohorts of at least 100 individuals predominantly aged 65 years and over living in developed countries, together with criteria used to define anaemia. Studies of anaemia prevalence in specific disease groups or published before 1980 were excluded. Prevalence data for the entire cohort, for men and women separately and for different age bands were extracted.</p> <p>Results</p> <p>Forty-five studies contributed data. Thirty-four studies (n = 85,409) used WHO criteria to define anaemia. The weighted mean prevalence was 17% (3–50%) overall, and 12% (3–25%) in studies based in the community (27, n = 69,975), 47% (31–50%) in nursing homes (3, n = 1481), and 40% (40–72%) in hospital admissions (4, n = 13,953). Anaemia prevalence increased with age, was slightly higher in men than women, and was higher in black people than white. Most individuals classified as anaemic using WHO criteria were only mildly anaemic.</p> <p>Conclusion</p> <p>Anaemia, as defined by WHO criteria, is common in older people living in the community and particularly common in nursing home residents and hospital admissions. Predicted demographic changes underline the need to understand more about anaemia in older people.</p