Zika virus (ZIKV), an emergent flaviviral pathogen, has been linked to microcephaly in neonates. Although the risk is greatest during the first trimester of pregnancy in humans, timing alone cannot explain why maternal ZIKV infection leads to severe microcephaly in some fetuses, but not others. The antigenic similarities between ZIKV and dengue virus (DENV), combined with high levels of DENV immunity among ZIKV target populations in recent outbreaks, suggest that anti-DENV maternal antibodies could promote ZIKV-induced microcephaly. We demonstrated maternal-to-fetal ZIKV transmission, fetal infection, and disproportionate microcephaly in immunocompetent mice. We show that DENV-specific antibodies in ZIKV-infected pregnant mice enhance vertical ZIKV transmission and result in a severe microcephaly-like syndrome, which was dependent on the neonatal Fc receptor, FcRN. This novel immune-mediated mechanism of vertical transmission of viral infection is of special concern because ZIKV epidemic regions are also endemic to DENV.
Women of reproductive age are at a high risk of iron deficiency, often as a result of diets low in bioavailable iron. In some settings, the iron content of domestic groundwater sources is high, yet its contribution to iron intake and status has not been examined. In a rural Bangladeshi population of women deficient in dietary iron, we evaluated the association between groundwater iron intake and iron status. In 2008, participants (n = 209 with complete data) were visited to collect data on 7-d food frequency, 7-d morbidity history, 24-h drinking water intake, and rice preparation, and to measure the groundwater iron concentration. Blood was collected to assess iron and infection status. Plasma ferritin (μg/L) and body iron (mg/kg) concentrations were [median (IQR)] 67 (46, 99) and 10.4 ± 2.6, respectively, and the prevalence of iron deficiency (ferritin < 12 μg/L) was 0%. Daily iron intake from water [42 mg (18, 71)] was positively correlated with plasma ferritin (r = 0.36) and total body iron (r = 0.35) (P < 0.001 for both). In adjusted linear regression analyses, plasma ferritin increased by 6.1% (95% CI: 3.8, 8.4%) and body iron by 0.3 mg/kg (0.2, 0.4) for every 10-mg increase in iron intake from water (P < 0.001). In this rural area of northern Bangladesh, women of reproductive age had no iron deficiency likely attributable to iron consumed from drinking groundwater, which contributed substantially to dietary intake. These findings suggest that iron intake from water should be included in dietary assessments in such settings.
Acute acidosis was induced in sheep, and gastrointestinal permeability was assessed by using lactulose as a permeability marker. Metabolism was evaluated by monitoring blood metabolites. Four rams (72.5 ± 4.6 kg BW) were used in a 2 × 2 changeover design experiment. The experimental period lasted 96 h from -24 to 72 h. After 24 h of fasting (from -24 to 0 h) for both controls and acidosis-induced rams (ACID), 0.5 kg of wheat flour was orally dosed at 0 and 12 h of the experimental period to ACID, while the basal diet (grass hay, ad libitum) was restored to control. At 24 h, a lactulose solution (30 g of lactulose in 200 mL of water) was orally administered. Blood samples were collected at -24, 0, 24, 48, and 72 h of the experimental periods for the analysis of metabolic profiles and during the 10 h after lactulose dosage to monitor lactulose changes in blood. In addition, rumen and fecal samples were collected at 24 h of the experimental period. The acidotic challenge markedly reduced (P < 0.01) rumen pH and VFA but increased rumen d- and l-lactic acid (P < 0.01). Concurrently, a decrease of fecal pH and VFA occurred in ACID (P < 0.01), together with an abrupt increase (P < 0.01) of lactate and fecal alkaline phosphatase. Blood lactulose was significantly increased in ACID peaking 2 h after lactulose dosage. Blood glucose, β-hydroxybutyrate, Ca, K, Mg, and alkaline phosphatase showed a significant reduction (P < 0.05) at 24 h, whereas urea and NEFA declined (P < 0.05) from 48 to 72 h. A strong inflammatory acute phase response with oxidative stress in ACID group was observed from 24 to 72 h; higher values of haptoglobin (P < 0.01) were measured from 24 to 72 h and of ceruloplasmin from 48 (P < 0.05) to 72 h (P < 0.01). Among the negative acute phase reactants, plasma albumin, cholesterol, paraoxonase, and Zn concentration also decreased (P < 0.05) in ACID at different time points between 24 and 72 h after acidotic challenge start. A rise (P < 0.05) of reactive oxygen metabolites and a drop of vitamin E (P< 0.01) between 24 and 72 h were indicative of oxidative stress in ACID. The perturbation of these blood metabolites suggests that acute acidosis was effectively induced by our model. The increase of lactulose in blood in ACID indicates that gastrointestinal permeability for the marker increased and the large increment after 2 h from dosage suggests that most of the passage occurred through the rumen or abomasal walls.
BackgroundGlucose-6-Phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy worldwide, no reliable bedside diagnostic tests to quantify G6PD activity exist. This study evaluated two novel quantitative G6PD diagnostics.MethodsParticipants with known G6PD activity were enrolled in Bangladesh. G6PD activity was measured by spectrophotometry, Biosensor (BS; AccessBio/CareStart, USA) and STANDARD G6PD (SG; SDBiosensor, ROK). G6PD activity was measured repeatedly in a subset of samples stored at room temperature and 4°C.Results158 participants were enrolled, 152 samples tested by BS, 108 samples by SG and 102 samples were tested by all three methods. In comparison to spectrophotometry BS had sensitivity and specificity of 72% (95%CI: 53–86) and 100% (95%CI: 97–100) at 30% cut off respectively, while SG had a sensitivity of 100% (95%CI: 88–100) and specificity of 97% (95%CI: 91–99) at the same cut off. The sensitivity and specificity at 70% cut off activity were 71% (95%CI: 59–82) and 98% (95%CI, 92–100) respectively for BS and 89% (95%CI: 77–96) and 93% (95%CI: 83–98) respectively for SG. When an optimal cut-off was applied the sensitivity of the BS at 70 cut off rose to 91% [95%CI: 80–96] and specificity to 82% [95%CI: 83–89]; a diagnostic accuracy comparable to that of the SG (p = 0.879). G6PD activity dropped significantly (-0.31U/gHb, 95%CI: -0.61 to -0.01, p = 0.022) within 24 hours in samples stored at room temperature, but did not fall below 90% of baseline activity until day 13 (-0.87U/gHb, 95%CI: (-1.11 to -0.62), p<0.001).ConclusionBS and SG are the first quantitative diagnostics to measure G6PD activity reliably at the bedside and represent suitable alternatives to spectrophotometry in resource poor settings. If samples are stored at 4°C, G6PD activity can be measured reliably for at least 7 days after sample collection.
To verify the potential relevance of proinflammatory cytokine (PIC) with periparturient health problems and performances, the changes of plasma interleukin-1beta (IL-1β) and interleukin-6 (IL-6) have been investigated in 21 Holstein-Friesian cows from 35 d before to 28 d after parturition. The overall PIC concentration was higher during late pregnancy compared to the first month of lactation, but showed a high variability among the cows. Therefore, cows were retrospectively divided in 3 groups according to the values of area under the concentration curve of IL-1β concentrations from-35 d before to the day of parturition and designated as up (UPIL1), intermediate (INIL1) and low (LOIL1) IL-1β group. The concentrations of IL-6 and to some extent the concentrations of albumin and reactive oxygen metabolites (ROMs) were well related to the grouping based on IL-1β concentrations. After calving the UPIL1 cows showed a more severe acute phase reaction (APR), based on the marked increase of haptoglobin and the lower plasma albumin concentrations during the first week of lactation, and the highest oxidative stress, based on the higher concentrations of ROMs. Moreover, the UPIL1 group showed higher number of mastitis, lower feed intake and milk yield compared with INIL1 and LOIL1. Our results demonstrated that cows with the highest PIC concentrations in the last month of pregnancy showed the worse health status in early lactation (clinical and subclinical problems) and a lower milk yield. Thus, these data support the utility of PIC measurement in late pregnancy as prognostic markers for a risky transition period.
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