Background It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. Objective This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. Study Design This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21 st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. Results We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32–2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25–2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17–3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99–2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99–5.49) and 6.26 (95% confidence interval, 4.35–9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63–2.86; risk ratio, 2.53; 95% confidence interval, 1.44–4.45; and risk ratio, 2.84; 95% confidence interval, 1.67–4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32–2.35), 2.07 (95% confidence interval, 1.20–3.57), and 2...

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Most members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) families transduce signals via a canonical pathway involving the MyD88 adapter and the interleukin-1 receptor-associated kinase (IRAK) complex. This complex contains four molecules, including at least two (IRAK-1 and IRAK-4) active kinases. In mice and humans, deficiencies of IRAK-4 or MyD88 abolish most TLR (except for TLR3 and some TLR4) and IL-1R signaling in both leukocytes and fibroblasts. TLR and IL-1R responses are weak but not abolished in mice lacking IRAK-1, whereas the role of IRAK-1 in humans remains unclear. We describe here a boy with X-linked MECP2 deficiency-related syndrome due to a large de novo Xq28 chromosomal deletion encompassing both MECP2 and IRAK1. Like many boys with MECP2 null mutations, this child died very early, at the age of 7 mo. Unlike most IRAK-4-or MyD88-deficient patients, he did not suffer from invasive bacterial diseases during his short life. The IRAK-1 protein was completely absent from the patient's fibroblasts, which responded very poorly to all TLR2/6 (PAM 2 CSK 4 , LTA, FSL-1), TLR1/2 (PAM 3 CSK 4 ), and TLR4 (LPS, MPLA) agonists tested but had almost unimpaired responses to IL-1β. By contrast, the patient's peripheral blood mononuclear cells responded normally to all TLR1/2, TLR2/6, TLR4, TLR7, and TLR8 (R848) agonists tested, and to IL-1β. The death of this child precluded long-term evaluations of the clinical consequences of inherited IRAK-1 deficiency. However, these findings suggest that human IRAK-1 is essential downstream from TLRs but not IL-1Rs in fibroblasts, whereas it plays a redundant role downstream from both TLRs and IL-1Rs in leukocytes.IRAK-1 | IRAK-4 | Toll-like receptor | interleukin-1 receptor | primary immunodeficiency

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Background: Fetal programming during in utero life defines the set point of physiological and metabolic responses that lead into adulthood; events happening in "the first 1,000 days" (from conception to 2-years of age), play a role in the development of non-communicable diseases (NCDs). The infant gut microbiome is a highly dynamic organ, which is sensitive to maternal and environmental factors and is one of the elements driving intergenerational NCDs' transmission. The A.MA.MI (Alimentazione MAmma e bambino nei primi MIlle giorni) project aims at investigating the correlation between several factors, from conception to the first year of life, and infant gut microbiome composition. We described the study design of the A.MA.MI study and presented some preliminary results.Methods: A.MA.MI is a longitudinal, prospective, observational study conducted on a group of mother-infant pairs (n = 60) attending the Neonatal Unit, Fondazione IRCCS Policlinico San Matteo, Pavia (Italy). The study was planned to provide data collected at T0, T1, T2 and T3, respectively before discharge, 1,6 and 12 months after birth. Maternal and infant anthropometric measurements were assessed at each time. Other variables evaluated were: pre-pregnancy/gestational weight status (T0), maternal dietary habits/physical activity (T1-T3); infant medical history, type of feeding, antibiotics/probiotics/supplements use, environment exposures (e.g cigarette smoking, pets, environmental temperature) (T1-T3). Infant stool samples were planned to be collected at each time and analyzed using metagenomics 16S ribosomal RNA gene sequence-based methods. Results: Birth mode (cesarean section vs. vaginal delivery) and maternal pre pregnancy BMI (BMI < 25 Kg/m 2 vs. BMI ≥ 25 Kg/m 2 ), significant differences were found at genera and species levels (T0). Concerning type of feeding (breastfed vs. formula-fed), gut microbiota composition differed significantly at genus and species level (T1).Conclusion: These preliminary and explorative results confirmed that pre-pregnancy, mode of delivery and infant factors likely impact infant microbiota composition at different levels. Trial registration: ClinicalTrials.gov identifier: NCT04122612.

The bactericidal activity of beta-caryophyllene photooxidized in acetonitrile was examined for 5 Gram-positive and 4 Gram-negative foodborne bacteria. The beta-caryophyllene (5 x 10(-3) M) was photooxidized in acetonitrile containing Rose Bengal (6.25 x 10(-4) M) for 24 h under fluorescent light. The antimicrobial activities of samples were determined by the agar-disc diffusion method. Active compounds from the photooxidized beta-caryophyllene were isolated by silica gel open-column chromatography in conjunction with recyclic high-performance liquid chromatography (HPLC), and were identified by infrared spectroscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. The antimicrobial activity of the photooxidized beta-caryophyllene was strongly enhanced against Streptococcus aureus and Vibrio parahaemolyticus, relative to that of beta-caryophyllene, but was weakly enhanced against other tested bacteria. The photooxidized beta-caryophyllene contained 3 active compounds specific for these 2 bacteria, and the compounds were identified as 5-alpha-hydroxycaryophylla-4(12),8(13)-diene, 5-alpha-hydroxycaryophylla-3(4),8(13)-diene, and 5-beta-hydroxycaryophylla-3(4),8(13)-diene. The efficacies of these compounds were similar, but the efficacy of 5-beta-hydroxycaryophylla-3(4),8(13)-diene was slightly higher than that of the other 2 compounds. The results suggest that the antibacterial activities of beta-caryophyllene for S. aureus and V. parahaemolyticus could be enhanced by dye-sensitized photooxidation, and the photooxidized beta-caryophyllene and the isolated individual compounds could be useful antimicrobial agents to control the growth of S. aureus and V. parahaemolyticus in certain food systems.

Background: Brain vulnerability in the critically ill preterm newborn may be related to the burden of cerebral hypoxygenation and hypoperfusion during the immediate postnatal period. Objective: We determined the association between adverse outcomes [death or high grade intraventricular hemorrhage (IVH)] and continuous cerebral tissue oxygen saturation (rSO₂), superior vena cava flow (SVCf) and cerebral fractional oxygen extraction (CFOE) in very low birth weight (VLBW) infants during the first 48 h of life. Methods: We studied a prospective cohort of 60 VLBW infants admitted to our neonatal intensive care unit within the first 6 h of life between March 2010 and June 2012. rSO₂ (expressed as a number of summary measures) was continuously monitored with near-infrared spectroscopy (INVOS 5100 Somanetic) during the first 48 h of life, SCVf was measured at 4-6, 12, 24 and 48 h after birth, and CFOE was calculated. Results: The mean gestational age was 27.9 (SD 2.39); 8 infants died (13.3%) and 7 developed IVH grade III-IV: 1 in the alive group and 6 in the deceased group (p < 0.001). The odds ratio for death was 1.08 (95% CI: 1.015-1.15, p = 0.016) for each 10 periods of rSO₂ values <40% in the first 48 h, and 4.2 (95% CI: 1.27-14.05, p = 0.019) for SVCf values <40 ml/kg/min. Among alive babies, mean CFOE decreased at 24, 36 and 48 h; among deceased babies it did not (p < 0.001). In the multivariate analyses, these results retained significance. Conclusions: Both rSO₂ ≤40% and SVCf <40 ml/kg/min independently increase the risk of death. The trend in CFOE supports the ischemic-hypoperfusion hypothesis as a mechanism for cerebral damage.