Table_1_Maternal diabetes and the role of neonatal reticulocyte hemoglobin content as a biomarker of iron status in the perinatal period.docx

AimsWe aimed to evaluate the effects of maternal diabetes on neonatal iron status, measuring erythrocyte indices including hemoglobin, hematocrit, reticulocytes, mean corpuscular volume (MCV), percent (%) hypochromia, ferritin, and additionally mean reticulocyte hemoglobin content (MCHr) as an early marker of iron deficiency, and examine the association between neonatal MCHr, red cell indices, and ferritin.Materials and MethodsWe conducted a hospital-based prospective cohort study in a tertiary neonatal unit of a University Hospital from 2018 to 2020. We enrolled 126 maternal-infant pairs of mothers whose pregnancy was associated with diabetes and 74 maternal-infant pairs from uncomplicated pregnancies. Erythrocyte indices were analyzed within the first twelve hours after birth. Erythrocyte parameters were compared between infants of the diabetes and the non-diabetic group. We examined the correlation of the neonatal MCHr with perinatal characteristics, including gestation, birth weight, maternal body mass index, the erythrocytic indices, maternal diabetes, maternal obesity, prematurity, small-for-gestational-age status, maternal preeclampsia, and maternal anemia. Finally, we evaluated the discordance between neonatal MCHr and neonatal ferritin.ResultsInfants of the diabetes group had a significantly lower MCHr (32.6 pg vs. 34.2 pg, p=0.003) compared with infants of uncomplicated pregnancies. Neonatal MCHr was significantly correlated with maternal hypochromia (r=-0.237, p=0.004) and neonatal MCV (r=0.674, pConclusionsMCHr was significantly lower in infants of mothers whose pregnancy was associated with diabetes compared with infants of non-diabetic mothers and correlated with neonatal and maternal red cell indices of iron deficiency. Since there was significant discordance between neonatal MCHr and ferritin during the first postnatal day, it is possible that MCHr could be used as a screening test for iron deficiency, especially in infants.</p

Table_2_Maternal diabetes and the role of neonatal reticulocyte hemoglobin content as a biomarker of iron status in the perinatal period.docx

AimsWe aimed to evaluate the effects of maternal diabetes on neonatal iron status, measuring erythrocyte indices including hemoglobin, hematocrit, reticulocytes, mean corpuscular volume (MCV), percent (%) hypochromia, ferritin, and additionally mean reticulocyte hemoglobin content (MCHr) as an early marker of iron deficiency, and examine the association between neonatal MCHr, red cell indices, and ferritin.Materials and MethodsWe conducted a hospital-based prospective cohort study in a tertiary neonatal unit of a University Hospital from 2018 to 2020. We enrolled 126 maternal-infant pairs of mothers whose pregnancy was associated with diabetes and 74 maternal-infant pairs from uncomplicated pregnancies. Erythrocyte indices were analyzed within the first twelve hours after birth. Erythrocyte parameters were compared between infants of the diabetes and the non-diabetic group. We examined the correlation of the neonatal MCHr with perinatal characteristics, including gestation, birth weight, maternal body mass index, the erythrocytic indices, maternal diabetes, maternal obesity, prematurity, small-for-gestational-age status, maternal preeclampsia, and maternal anemia. Finally, we evaluated the discordance between neonatal MCHr and neonatal ferritin.ResultsInfants of the diabetes group had a significantly lower MCHr (32.6 pg vs. 34.2 pg, p=0.003) compared with infants of uncomplicated pregnancies. Neonatal MCHr was significantly correlated with maternal hypochromia (r=-0.237, p=0.004) and neonatal MCV (r=0.674, pConclusionsMCHr was significantly lower in infants of mothers whose pregnancy was associated with diabetes compared with infants of non-diabetic mothers and correlated with neonatal and maternal red cell indices of iron deficiency. Since there was significant discordance between neonatal MCHr and ferritin during the first postnatal day, it is possible that MCHr could be used as a screening test for iron deficiency, especially in infants.</p

DataSheet_1_Maternal diabetes and the role of neonatal reticulocyte hemoglobin content as a biomarker of iron status in the perinatal period.docx

AimsWe aimed to evaluate the effects of maternal diabetes on neonatal iron status, measuring erythrocyte indices including hemoglobin, hematocrit, reticulocytes, mean corpuscular volume (MCV), percent (%) hypochromia, ferritin, and additionally mean reticulocyte hemoglobin content (MCHr) as an early marker of iron deficiency, and examine the association between neonatal MCHr, red cell indices, and ferritin.Materials and MethodsWe conducted a hospital-based prospective cohort study in a tertiary neonatal unit of a University Hospital from 2018 to 2020. We enrolled 126 maternal-infant pairs of mothers whose pregnancy was associated with diabetes and 74 maternal-infant pairs from uncomplicated pregnancies. Erythrocyte indices were analyzed within the first twelve hours after birth. Erythrocyte parameters were compared between infants of the diabetes and the non-diabetic group. We examined the correlation of the neonatal MCHr with perinatal characteristics, including gestation, birth weight, maternal body mass index, the erythrocytic indices, maternal diabetes, maternal obesity, prematurity, small-for-gestational-age status, maternal preeclampsia, and maternal anemia. Finally, we evaluated the discordance between neonatal MCHr and neonatal ferritin.ResultsInfants of the diabetes group had a significantly lower MCHr (32.6 pg vs. 34.2 pg, p=0.003) compared with infants of uncomplicated pregnancies. Neonatal MCHr was significantly correlated with maternal hypochromia (r=-0.237, p=0.004) and neonatal MCV (r=0.674, pConclusionsMCHr was significantly lower in infants of mothers whose pregnancy was associated with diabetes compared with infants of non-diabetic mothers and correlated with neonatal and maternal red cell indices of iron deficiency. Since there was significant discordance between neonatal MCHr and ferritin during the first postnatal day, it is possible that MCHr could be used as a screening test for iron deficiency, especially in infants.</p

Pulmonary arteriolar remodeling in HO-1^−/− animals exposed to chronic hypoxia for seven weeks and treated with CO or Biliverdin, as indicated.

<p>(A) Quantification of percent wall thickness. Bars represent means ^+/− SEM. Each dot represents one animal and ten vessels were averaged for each animal. * = p<0.05 as assessed by Mann-Whitney U test. (B) Representative pulmonary arterioles of HO-1^−/− mice stained with H&E for each of the different conditions and treatments above.</p

Bilirubin protects cardiomyocytes from anoxia-reoxygenation (A-R) injury and has an anti-apoptotic effect.

<p>(A) Cell survival ratio relative to untreated normoxic controls as assessed by calcein/ethidium staining. Mean ^+/− SEM for 6 wells per condition is shown and graph is representative of three independent experiments. (B) Lactate dehydrogenase (LDH) measured by absorbance at 490 in the media of cardiomyocytes exposed to A-R. Means ^+/− SEM are shown. (C) Flow cytometric analysis of Annexin V-positive, 7AAD-negative cardiomyocytes after A-R. Bars represent the percentage of 10,000 counted cells that fell into this category. Data are an average of three different experiments. * = p<0.05, ** = p<0.01, *** = p<0.005 as assessed by Mann-Whitney U test.</p

PASMC proliferation and migration in response to hypoxia.

<p>(A) Effect of bilirubin and CO on PASMC proliferation in response to hypoxia by BrdU incorporation. Average fold change of relative light units over unstimulated (no PDGF) controls from four experiments are shown. (B) Effect of bilirubin and CO on PASMC migration in hypoxia. Average fold change of relative light units over unstimulated (no PDGF) controls from three experiments is shown. * = p,0.05, *** = p<0.005 as assessed by Mann-Whitney U test.</p

Right ventricular wall injury in HO-1^−/− mice exposed to chronic hypoxia for seven weeks.

<p>(A) Biventricular (short-axis) sections of the heart at the papillary muscle level stained with H&E reveal RV dilation and thrombus in the hypoxic HO-1^−/− controls and the CO-treated hypoxic HO-1^−/− mice but not the hypoxic HO-1^−/− mice treated with BV. (B,C) Masson's trichrome stained right ventricular sections from an untreated HO-1^−/− mouse at 40× (B) and 100× (C) power. A fibrotic area of RV wall is evident with overlying mural thrombus. (D,E) Carbon monoxide-treated HO-1^−/− mouse RVs stained with Masson's trichrome at 100× (D) and 200× (E) power showing an area of RV wall fibrosis and overlying mural thrombus. (F,G) TUNEL-stained RV (F) and LV (G) wall from an area of full-thickness wall fibrosis in an untreated HO-1^−/− mouse at 200× magnification. The LV has TUNEL stained luminal debris but is otherwise negative for TUNEL-staining. (H) Quantification of the percentage of HO-1^−/− animals in each group developing an area of Masson's trichrome-positive fibrosis spanning the full thickness of the RV wall. (I) Survival curve of HO-1 hemizygous and null mice in 8.5–9% oxygen for seven weeks in response to treatment with CO or Biliverdin.</p