To determine the effect of a two-week reduced fat and sugar and increased fibre maternal dietary intervention on the maternal faecal and human milk (HM) microbiomes.
Faecal swabs and HM samples were ...collected from mothers (n = 11) immediately pre-intervention, immediately post-intervention, and 4 and 8 weeks post-intervention, and were analysed using full-length 16S rRNA gene sequencing. Maternal macronutrient intake was assessed at baseline and during the intervention. Maternal fat and sugar intake during the intervention were significantly lower than pre-intervention (P = <0.001, 0.005, respectively). Significant changes in the bacterial composition of maternal faeces were detected after the dietary intervention, with decreases in the relative abundance of Bacteroides caccae (P = <0.001) and increases in the relative abundance of Faecalibacillus intestinalis (P = 0.006). In HM, the diet resulted in a significant increase in Cutibacterium acnes (P = 0.001) and a decrease in Haemophilus parainfluenzae (P = <0.001). The effect of the diet continued after the intervention, with faecal swabs and HM samples taken 4 and 8 weeks after the diet showing significant differences compared to baseline.
This pilot study demonstrates that short-term changes in maternal diet during lactation can alter the bacterial composition of the maternal faeces and HM.
Antenatal corticosteroids (ACS) are the standard of care for maturing the fetal lung and improving outcomes for preterm infants. Antenatal corticosteroid dosing remains nonoptimized, and there is ...little understanding of how different treatment-to-delivery intervals may affect treatment efficacy. The durability of a lung maturational response is important because the majority of women treated with antenatal corticosteroids do not deliver within the widely accepted 1- to 7-day window of treatment efficacy.
We used a sheep model to test the duration of fetal exposures for efficacy at delivery intervals from 1 to 10 days.
For infusion studies, ewes with single fetuses were randomized to receive an intravenous bolus and maintenance infusion of betamethasone phosphate to target 1–4 ng/mL fetal plasma betamethasone for 36 hours, with delivery at 2, 4 ,or 7 days posttreatment or sterile saline solution as control. Animals receiving the clinical treatment were randomised to receive either a single injection of 0.25 mg/kg with a 1:1 mixture of betamethasone phosphate + betamethasone acetate with delivery at either 1 or 7 days posttreatment, or 2 treatments of 0.25 mg/kg betamethasone phosphate + betamethasone acetate spaced at 24 hours (giving ∼48 hours of fetal steroid exposure) with delivery at 2, 5, 7, or 10 days posttreatment. Negative control animals were treated with saline solution. All lambs were delivered at 121 ± 3 days gestational age and ventilated for 30 minutes to assess lung function.
Preterm lambs delivered at 1 or 2 days post–antenatal corticosteroid treatment had significant improvements in lung maturation for both intravenous and single-dose intramuscular treatments. After 2 days, the efficacy of 36-hour betamethasone phosphate infusions was lost. The single dose of 1:1 betamethasone phosphate + betamethasone acetate also was ineffective at 7 days. In contrast, animals treated with 2 doses had significant improvements in lung maturation at 2, 5, and 7 days, with treatment efficacy reduced by 10 days.
In preterm lambs, the durability of antenatal corticosteroids treatment depends on the duration of fetal exposure and is independent of the intravenous or intramuscular maternal route of administration. For acute 24- to 48-hour posttreatment deliveries, a 24-hour fetal antenatal corticosteroids exposure was sufficient for lung maturation. A fetal exposure duration of at least 48 hours was necessary to maintain long-term treatment durability. A single-dose ACS treatment should be sufficient for women delivering within <48 hours of antenatal corticosteroids treatment.
One of the great advantages of organic–inorganic metal halides is that their structures and properties are highly tuneable and this is important when optimizing materials for photovoltaics or other ...optoelectronic devices. One of the most common and effective ways of tuning the electronic structure is through anion substitution. Here, we report the inclusion of bromine into the layered perovskite H3N(CH2)6NH3PbBr4 to form H3N(CH2)6NH3PbBr4·Br2, which contains molecular bromine (Br2) intercalated between the layers of corner-sharing PbBr6 octahedra. Bromine intercalation in H3N(CH2)6NH3PbBr4·Br2 results in a decrease in the band gap of 0.85 eV and induces a structural transition from a Ruddlesden–Popper-like to Dion–Jacobson-like phase, while also changing the conformation of the amine. Electronic structure calculations show that Br2 intercalation is accompanied by the formation of a new band in the electronic structure and a significant decrease in the effective masses of around two orders of magnitude. This is backed up by our resistivity measurements that show that H3N(CH2)6NH3PbBr4·Br2 has a resistivity value of one order of magnitude lower than H3N(CH2)6NH3PbBr4, suggesting that bromine inclusion significantly increases the mobility and/or carrier concentration in the material. This work highlights the possibility of using molecular inclusion as an alternative tool to tune the electronic properties of layered organic–inorganic perovskites, while also being the first example of molecular bromine inclusion in a layered lead halide perovskite. By using a combination of crystallography and computation, we show that the key to this manipulation of the electronic structure is the formation of halogen bonds between the Br2 and Br in the PbBr4∞ layers, which is likely to have important effects in a range of organic–inorganic metal halides.
Drawing on agency and configurations theories, this study examines how perceived level of control over the entrepreneur influences venture capitalist (VC) decision making. We model the direct effects ...of perceived control and the interactive effects of control with entrepreneurial prestige and opportunity attractiveness to determine how various combinations of factors influence VCs’ willingness to invest. We test our conceptualizations using conjoint analyses of 552 VC investment decisions. The results show that perceived control is directly related to investment likelihood, but different configurations of control, entrepreneur prestige, and opportunity attractiveness result in different outcomes. Our findings support a configurational perspective of VC decision making.
Abstract Streptococcus agalactiae is the leading cause of early-onset neonatal sepsis. Culture-based screening methods lack the sensitivity of molecular assays and do not indicate serotype; a ...potentially important virulence marker. We aimed to develop a multiplex PCR to detect S. agalactiae while simultaneously identifying serotypes Ia, Ib, and III; commonly associated with infant disease. Primers were designed to target S. agalactiae serotype-specific cps genes and the dltS gene. The assay was validated with 512 vaginal specimens from pregnant women. 112 (21.9%) were dltS positive, with 14.3%, 0.9% and 6.3% of these identified as cps Ia, Ib and III, respectively. Our assay is a specific and sensitive method to simultaneously detect S. agalactiae and serotypes Ia, Ib and III in a single step. It is of high significance for clinical diagnostic applications and also provides epidemiological data on serotype, information that may be important for vaccine development and other targeted non-antibiotic therapies.
Streptococcus agalactiae, or group B streptococcus (GBS), is a leading neonatal pathogen that causes sepsis, meningitis and pneumonia. Globally, strategies have been implemented to address vertical ...transmission, and in Western Australia (WA), culture-based screening at 35-37 weeks' gestation is part of routine care and guides antibiotic administration. Previous Australian studies have focused on other regions or included low sample-size representatives; we aimed to describe antenatal GBS colonization in WA.
A cohort of 814 pregnant women attending antenatal clinics (2015-2017) self-collected vaginal and rectal swabs at ≤22 weeks (n=814) and ≥33 weeks' (n=567) gestation. These were assessed for GBS presence using culture and PCR, and serotyping was conducted using molecular methods. Lifestyle questionnaires and medical data were collected.
We observed an overall GBS colonization rate of 24%, with 10.6 % of positive participants transiently colonized. Ethnicity (Aboriginal, Torres Strait Islander and African), maternal age ≥25 years, vitamin use, frequent sexual intercourse (≥5 times/week) and use of sex toys were associated with GBS colonization. The dominant serotypes identified were Ia (27.9%), III (20.9%), II (16.3%), V (15.8%), Ib (8.4%), VI (5.1%), IV (2.8%), NT (1.9), VIII (0.5%) and IX (0.5%) at visit one, with V (18.9%) preceding serotype II (18.2%) at visit two. Serotype VII was not detected.
This is the first cohort study to assess GBS colonization in Western Australian pregnant women and will be highly beneficial for guiding clinical practice and future therapeutic options, in particular, the selection of suitable vaccine candidates.
Chorioamnionitis, inflammation of the fetal membranes during pregnancy, is often caused by intra-amniotic (IA) infection with single or multiple microbes. Chorioamnionitis can be either acute or ...chronic and is associated with adverse postnatal outcomes of the intestine, including necrotizing enterocolitis (NEC). Neonates with NEC have structural and functional damage to the intestinal mucosa and the enteric nervous system (ENS), with loss of enteric neurons and glial cells. Yet, the impact of acute, chronic, or repetitive antenatal inflammatory stimuli on the development of the intestinal mucosa and ENS has not been studied. The aim of this study was therefore to investigate the effect of acute, chronic, and repetitive microbial exposure on the intestinal mucosa, submucosa and ENS in premature lambs.
A sheep model of pregnancy was used in which the ileal mucosa, submucosa, and ENS were assessed following IA exposure to lipopolysaccharide (LPS) for 2 or 7 days (acute),
(UP) for 42 days (chronic), or repetitive microbial exposure (42 days UP with 2 or 7 days LPS).
IA LPS exposure for 7 days or IA UP exposure for 42 days caused intestinal injury and inflammation in the mucosal and submucosal layers of the gut. Repetitive microbial exposure did not further aggravate injury of the terminal ileum. Chronic IA UP exposure caused significant structural ENS alterations characterized by loss of PGP9.5 and S100β immunoreactivity, whereas these changes were not found after re-exposure of chronic UP-exposed fetuses to LPS for 2 or 7 days.
The
loss of PGP9.5 and S100β immunoreactivity following chronic UP exposure corresponds with intestinal changes in neonates with NEC and may therefore form a novel mechanistic explanation for the association of chorioamnionitis and NEC.
Intrauterine infection and inflammation are responsible for the majority of early (<32 weeks) spontaneous preterm births (PTBs). Anti-inflammatory agents, delivered intra-amniotically together with ...antibiotics, may be an effective strategy for preventing PTB. In this study, the effects of four cytokine-suppressive anti-inflammatory drugs (CSAIDs: N-acetyl cysteine (NAC), SB239063, TPCA-1 and NEMO binding domain inhibitor (NBDI)) were assessed on human and ovine gestational membrane inflammation. Full-thickness membranes were collected from healthy, term, human placentas delivered by Caesarean section (n=5). Using a Transwell model, they were stimulated ex vivo with γ-irradiation-killed Escherichia coli applied to the amniotic face. Membranes from near-term, ovine placentas were stimulated in utero with lipopolysaccharide, Ureaplasma parvum or saline control and subjected to explant culture. The effects of treatment with CSAIDs or vehicle (1% DMSO) on accumulation of PGE2 and cytokines (human interleukin 6 (IL6), IL10 and TNFα; ovine IL8 (oIL8)) were assessed in conditioned media at various time points (3-20 h). In human membranes, the IKKβ inhibitor TPCA-1 (7 μM) and p38 MAPK inhibitor SB239063 (20 μM) administered to the amniotic compartment were the most effective in inhibiting accumulation of cytokines and PGE2 in the fetal compartment. NAC (10 mM) inhibited accumulation of PGE2 and IL10 only; NBDI (10 μM) had no significant effect. In addition to the fetal compartment, SB239063 also exerted consistent and significant inhibitory effects in the maternal compartment. TPCA-1 and SB239063 suppressed oIL8 production, while all CSAIDs tested suppressed ovine PGE2 production. These results support the further investigation of intra-amniotically delivered CSAIDs for the prevention of inflammation-mediated PTB.
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