Presence of distinctive microbiome in the first-pass meconium of newborn infants

AbstractWe critically evaluated the fetal microbiome concept in 44 neonates with placenta, amniotic fluid, and first-pass meconium samples. Placental histology showed no signs of inflammation. Meconium samples were more often bacterial culture positive after vaginal delivery. In next-generation sequencing of the bacterial 16S gene, before and after removal of extracellular and PCR contaminant DNA, the median number of reads was low in placenta (48) and amniotic fluid (46) and high in meconium samples (14,556 C-section, 24,860 vaginal). In electron microscopy, meconium samples showed extracellular vesicles. Utilizing the analysis of composition of microbiomes (ANCOM) against water, meconium samples had a higher relative abundance of Firmicutes, Lactobacillus, Streptococcus, and Escherichia-Shigella. Our results did not support the existence of the placenta and amniotic fluid microbiota in healthy pregnancies. The first-pass meconium samples, formed in utero, appeared to harbor a microbiome that may be explained by perinatal colonization or intrauterine colonization via bacterial extracellular vesicles.

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Oxygen Consumption in Platelets of Newborn Infants before and after Stimulation by Thrombin.

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647969 ◽

1976 ◽

Vol 35 (03) ◽

pp. 712-716 ◽

Cited By ~ 3

Author(s):

D. Del Principe ◽

G Mancuso ◽

A Menichelli ◽

G Maretto ◽

G Sabetta

Keyword(s):

Oxygen Consumption ◽

Cord Blood ◽

Umbilical Cord ◽

Newborn Infant ◽

Umbilical Cord Blood ◽

Newborn Infants ◽

O2 Consumption ◽

Adult Control ◽

Healthy Newborn ◽

Before And After

SummaryThe authors compared the oxygen consumption in platelets from the umbilical cord blood of 36 healthy newborn infants with that of 27 adult subjects, before and after thrombin addition (1.67 U/ml). Oxygen consumption at rest was 6 mμmol/109/min in adult control platelets and 5.26 in newborn infants. The burst in oxygen consumption after thrombin addition was 26.30 mμmol/109/min in adults and 24.90 in infants. Dinitrophenol did not inhibit the burst of O2 consumption in platelets in 8 out of 10 newborn infants, while the same concentration caused a decrease in 9 out of 10 adult subjects. Deoxyglucose inhibited the burst in O2 consumption in newborn infant and adult platelets by about 50%. KCN at the concentration of 10−4 M completely inhibited basal oxygen consumption but did not completely inhibit the burst after thrombin. At the concentration of 10−3 M, it inhibited both basal O2 consumption and the burst in infants and adult subjects.

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Different miRNA Profiles in Plasma Derived Small and Large Extracellular Vesicles from Patients with Neurodegenerative Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22052737 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2737

Author(s):

Daisy Sproviero ◽

Stella Gagliardi ◽

Susanna Zucca ◽

Maddalena Arigoni ◽

Marta Giannini ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Extracellular Vesicles ◽

Small Rnas ◽

Biomarker Discovery ◽

Toll Like Receptor ◽

Neurotrophin Signaling ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing ◽

Lateral Sclerosis ◽

Glycosphingolipid Biosynthesis

Identifying biomarkers is essential for early diagnosis of neurodegenerative diseases (NDs). Large (LEVs) and small extracellular vesicles (SEVs) are extracellular vesicles (EVs) of different sizes and biological functions transported in blood and they may be valid biomarkers for NDs. The aim of our study was to investigate common and different miRNA signatures in plasma derived LEVs and SEVs of Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Dementia (FTD) patients. LEVs and SEVs were isolated from plasma of patients and healthy volunteers (CTR) by filtration and differential centrifugation and RNA was extracted. Small RNAs libraries were carried out by Next Generation Sequencing (NGS). MiRNAs discriminate all NDs diseases from CTRs and they can provide a signature for each NDs. Common enriched pathways for SEVs were instead linked to ubiquitin mediated proteolysis and Toll-like receptor signaling pathways and for LEVs to neurotrophin signaling and Glycosphingolipid biosynthesis pathway. LEVs and SEVs are involved in different pathways and this might give a specificity to their role in the spreading of the disease. The study of common and different miRNAs transported by LEVs and SEVs can be of great interest for biomarker discovery and for pathogenesis studies in neurodegeneration.

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Amniotic Fluid Stem Cell-Derived Extracellular Vesicles Counteract Steroid-Induced Osteoporosis In Vitro

International Journal of Molecular Sciences ◽

10.3390/ijms22010038 ◽

2020 ◽

Vol 22 (1) ◽

pp. 38

Author(s):

Martina Gatti ◽

Francesca Beretti ◽

Manuela Zavatti ◽

Emma Bertucci ◽

Soraia Ribeiro Luz ◽

...

Keyword(s):

Amniotic Fluid ◽

Extracellular Vesicles ◽

Culture Medium ◽

Cell Potential ◽

Osteoblast Cell Line ◽

Local Bone ◽

Current Therapies ◽

Amniotic Fluid Stem Cell ◽

Related Proteins

Background—Osteoporosis is characterized by defects in both quality and quantity of bone tissue, which imply high susceptibility to fractures with limitations of autonomy. Current therapies for osteoporosis are mostly concentrated on how to inhibit bone resorption but give serious adverse effects. Therefore, more effective and safer therapies are needed that even encourage bone formation. Here we examined the effect of extracellular vesicles secreted by human amniotic fluid stem cells (AFSC) (AFSC-EV) on a model of osteoporosis in vitro. Methods—human AFSC-EV were added to the culture medium of a human pre-osteoblast cell line (HOB) induced to differentiate, and then treated with dexamethasone as osteoporosis inducer. Aspects of differentiation and viability were assessed by immunofluorescence, Western blot, mass spectrometry, and histological assays. Since steroids induce oxidative stress, the levels of reactive oxygen species and of redox related proteins were evaluated. Results—AFSC-EV were able to ameliorate the differentiation ability of HOB both in the case of pre-osteoblasts and when the differentiation process was affected by dexamethasone. Moreover, the viability was increased and parallelly apoptotic markers were reduced. The presence of EV positively modulated the redox unbalance due to dexamethasone. Conclusion—these findings demonstrated that EV from hAFSC have the ability to recover precursor cell potential and delay local bone loss in steroid-related osteoporosis.

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Impact of the pan-Canadian Oncology Drug Review on provincial concordance with respect to cancer drug funding decisions and time to funding

Current Oncology ◽

10.3747/co.24.3648 ◽

2017 ◽

Vol 24 (5) ◽

pp. 295 ◽

Cited By ~ 2

Author(s):

A. Srikanthan ◽

H. Mai ◽

N. Penner ◽

E. Amir ◽

A. Laupacis ◽

...

Keyword(s):

Linear Models ◽

Drug Product ◽

Median Number ◽

Cancer Drug ◽

Cancer Drugs ◽

Oncology Drug ◽

Before And After ◽

Canadian Provinces ◽

The Impact ◽

Drug Review

Background The pan-Canadian Oncology Drug Review (pcodr) was implemented in 2011 to address uneven drug coverage and lack of transparency with respect to the various provincial cancer drug review processes in Canada. We evaluated the impact of the pcodr on provincial decision concordance and time from Notice of Compliance (noc) to drug funding.Methods In a retrospective review, Health Canada’s Drug Product Database was used to identify new indications for cancer drugs between January 2003 and May 2014, and provincial formulary listings for drug-funding dates and decisions between 1 January 2003 and 31 December 2014 were retrieved. Multiple linear models and quantile regressions were used to evaluate changes in time to decision-making before and after the implementation of the pcodr. Agreement of decisions between provinces was evaluated using kappa statistics.Results Data were available from 9 provinces (all Canadian provinces except Quebec), identifying 88 indications that represented 51 unique cancer drugs. Two provinces lacked available data for all 88 indications at the time of data collection. Interprovincial concordance in drug funding decisions significantly increased after the pcodr’s implementation (Brennan-Prediger coefficient: 0.54 pre-pcodr vs. 0.78 post-pcodr; p = 0.002). Nationwide, the median number of days from Health Canada’s noc date to the date of funding significantly declined (to 393 days from 522 days, p < 0.001). Exploratory analyses excluding provinces with incomplete data did not change the results.Conclusions After the implementation of the pcodr, greater concordance in cancer drug funding decisions between provinces and decreased time to funding decisions were observed.

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The respiratory tract microbial biogeography in alcohol use disorder

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00277.2017 ◽

2018 ◽

Vol 314 (1) ◽

pp. L107-L117 ◽

Cited By ~ 3

Author(s):

Derrick R. Samuelson ◽

Ellen L. Burnham ◽

Vincent J. Maffei ◽

R. William Vandivier ◽

Eugene E. Blanchard ◽

...

Keyword(s):

Alcohol Use ◽

Respiratory Tract ◽

Lower Respiratory Tract ◽

Distress Syndrome ◽

Microbial Biogeography ◽

Mechanistic Pathway ◽

Lung Microbiome ◽

16S Gene ◽

Increased Risk ◽

Bacterial 16S Gene

Individuals with alcohol use disorders (AUDs) are at an increased risk of pneumonia and acute respiratory distress syndrome. Data of the lung microbiome in the setting of AUDs are lacking. The objective of this study was to determine the microbial biogeography of the upper and lower respiratory tract in individuals with AUDs compared with non-AUD subjects. Gargle, protected bronchial brush, and bronchoalveolar lavage specimens were collected during research bronchoscopies. Bacterial 16S gene sequencing and phylogenetic analysis was performed, and the alterations to the respiratory tract microbiota and changes in microbial biogeography were determined. The microbial structure of the upper and lower respiratory tract was significantly altered in subjects with AUDs compared with controls. Subjects with AUD have greater microbial diversity [ P < 0.0001, effect size = 16 ± 1.7 observed taxa] and changes in microbial species relative abundances. Furthermore, microbial communities in the upper and lower respiratory tract displayed greater similarity in subjects with AUDs. Alcohol use is associated with an altered composition of the respiratory tract microbiota. Subjects with AUDs demonstrate convergence of the microbial phylogeny and taxonomic communities between distinct biogeographical sites within the respiratory tract. These results support a mechanistic pathway potentially explaining the increased incidence of pneumonia and lung diseases in patients with AUDs.

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Reduction of exposure to blood donors in preterm infants submitted to red blood cell transfusions using pediatric satellite packs

Revista Paulista de Pediatria ◽

10.1590/s0103-05822013000300003 ◽

2013 ◽

Vol 31 (3) ◽

pp. 285-292 ◽

Cited By ~ 1

Author(s):

Cristina Lika Uezima ◽

Ariane Moreira Barreto ◽

Ruth Guinsburg ◽

Akemi Kuroda Chiba ◽

José Orlando Bordin ◽

...

Keyword(s):

Birth Weight ◽

Preterm Infants ◽

Blood Donor ◽

Blood Donors ◽

Newborn Infants ◽

Median Number ◽

Erythrocyte Transfusion ◽

Factors Associated ◽

Group 2 ◽

Group 1

OBJECTIVE: In preterm newborn infants transfused with erythrocytes stored up to 28 days, to compare the reduction of blood donor exposure in two groups of infants classified according to birth weight. METHODS: A prospective study was conducted with preterm infants with birth weight <1000g (Group 1) and 1000-1499g (Group 2), born between April, 2008 and December, 2009. Neonates submitted to exchange transfusions, emergency erythrocyte transfusion, or those who died in the first 24 hours of life were excluded. Transfusions were indicated according to the local guideline using pediatric transfusion satellite bags. Demographic and clinical data, besides number of transfusions and donors were assessed. . Logistic regression analysis was performed to determine factors associated with multiple transfusions. RESULTS: 30 and 48 neonates were included in Groups 1 and 2, respectively. The percentage of newborns with more than one erythrocyte transfusion (90 versus 11%), the median number of transfusions (3 versus 1) and the median of blood donors (2 versus 1) were higher in Group 1 (p<0.001), compared to Group 2. Among those with multiple transfusions, 14 (82%) and one (50%) presented 50% reduction in the number of blood donors, respectively in Groups 1 and 2. Factors associated with multiple transfusions were: birth weight <1000g (OR 11.91; 95%CI 2.14-66.27) and presence of arterial umbilical catheter (OR 8.59; 95%CI 1.94-38.13), adjusted for confounders. CONCLUSIONS: The efficacy of pediatrics satellites bags on blood donor reduction was higher in preterm infants with birth weight <1000g.

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Autophagy is impaired in fetal hypoplastic lungs and rescued by administration of amniotic fluid stem cell extracellular vesicles

10.1101/2022.01.12.476078 ◽

2022 ◽

Author(s):

Kasra Khalaj ◽

Lina Antounians ◽

Rebeca Lopes Figueira ◽

Martin Post ◽

Augusto Zani

Keyword(s):

Stem Cell ◽

Amniotic Fluid ◽

Extracellular Vesicles ◽

Pulmonary Hypoplasia ◽

Fetal Lung ◽

Branching Morphogenesis ◽

Lung Epithelial Cells ◽

Normal Lung ◽

Amniotic Fluid Stem Cell ◽

Human Fetal Lung

Rationale: Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by reduced branching morphogenesis, which is responsible for poor clinical outcomes. Administration of amniotic fluid stem cell extracellular vesicles (AFSC-EVs) rescues branching morphogenesis in rodent fetal models of pulmonary hypoplasia. Herein, we hypothesized that AFSC-EVs exert their regenerative potential by affecting autophagy, a process required for normal lung development. Objectives: To evaluate autophagy in hypoplastic lungs throughout gestation and establish whether AFSC-EV administration improves branching morphogenesis through autophagy-mediated mechanisms. Methods: EVs were isolated from c-kit+ AFSC conditioned medium by ultracentrifugation and characterized for size, morphology, and EV markers. Branching morphogenesis was inhibited in rat fetuses by nitrofen administration to dams and in human fetal lung explants by blocking RAC1 activity with NSC23766. Expression of autophagy activators (BECN1 and ATG5) and adaptor (SQSTM1/p62) was analyzed in vitro (rat and human fetal lung explants) and in vivo (rat fetal lungs). Mechanistic studies on rat fetal primary lung epithelial cells were conducted using inhibitors for microRNA-17 and -20a contained in the AFSC-EV cargo and known to regulate autophagy. Measurements and Main Results: Rat and human models of fetal pulmonary hypoplasia showed reduced autophagy mainly at pseudoglandular and canalicular stages. AFSC-EV administration restored autophagy in both pulmonary hypoplasia models by transferring miR-17~92 cluster members contained in the EV cargo. Conclusions: AFSC-EV treatment rescues branching morphogenesis partly by restoring autophagy through miRNA cargo transfer. This study enhances our understanding of pulmonary hypoplasia pathogenesis and creates new opportunities for fetal therapeutic intervention in CDH babies.

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Amniotic fluid stem cell extracellular vesicles promote fetal lung branching and cell differentiation in experimental congenital diaphragmatic hernia

10.1101/2022.01.10.475632 ◽

2022 ◽

Author(s):

Kasra Khalaj ◽

Rebeca Lopes Figueira ◽

Lina Antounians ◽

Sree Gandhi ◽

Matthew Wales ◽

...

Keyword(s):

Amniotic Fluid ◽

Congenital Diaphragmatic Hernia ◽

Extracellular Vesicles ◽

Diaphragmatic Hernia ◽

Lung Development ◽

Pulmonary Hypoplasia ◽

Fetal Lung ◽

Branching Morphogenesis ◽

Neuroendocrine Cells ◽

Beta Catenin

Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired branching morphogenesis and differentiation. We have previously demonstrated that administration of extracellular vesicles derived from rat amniotic fluid stem cells (AFSC-EVs) rescues development of hypoplastic lungs at the pseudoglandular and alveolar stages in rodent models of CDH. Herein, we tested whether AFSC-EVs exert their regenerative effects at the canalicular and saccular stages, as these are translationally relevant for clinical intervention. To induce fetal pulmonary hypoplasia, we gavaged rat dams with nitrofen at embryonic day 9.5 and demonstrated that nitrofen-exposed lungs had impaired branching morphogenesis, dysregulated signaling pathways relevant to lung development (FGF10/FGFR2, ROBO/SLIT, Ephrin, Neuropilin 1, beta-catenin) and impaired epithelial and mesenchymal cell marker expression at both stages. AFSC-EVs administered to nitrofen-exposed lung explants rescued airspace density and increased the expression levels of key factors responsible for branching morphogenesis. Moreover, AFSC-EVs rescued the expression of alveolar type 1 and 2 cell markers at both canalicular and saccular stages, and restored markers of club, ciliated epithelial, and pulmonary neuroendocrine cells at the saccular stage. AFSC-EV treated lungs also had restored markers of lipofibroblasts and PDGFRA+ cells to control levels at both stages. EV tracking showed uptake of AFSC-EV RNA cargo throughout the fetal lung and an mRNA-miRNA network analysis identified that several miRNAs responsible for regulating lung development processes were contained in the AFSC-EV cargo. These findings suggest that AFSC-EV based therapies hold potential for restoring fetal lung growth and maturation in babies with pulmonary hypoplasia secondary to CDH.

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Landmark-guided Versus Modified Ultrasound-assisted Paramedian Techniques in Combined Spinal-epidural Anesthesia for Elderly Patients with Hip Fractures: A Randomized Controlled Trial

10.21203/rs.3.rs-30630/v2 ◽

2020 ◽

Author(s):

Bo Qu ◽

Luying Chen ◽

Yuling Zhang ◽

Mengting Jiang ◽

Caineng Wu ◽

...

Keyword(s):

Elderly Patients ◽

Success Rate ◽

Hip Fractures ◽

Controlled Trial ◽

Median Number ◽

Needle Insertion ◽

Success Rates ◽

First Pass ◽

Ultrasound Assisted ◽

Ultrasound Group

Abstract Background: Combined spinal-epidural (CSE) anesthesia is considerably challenging for elderly patients with hip fractures due to spine degeneration and limitations in positioning. This study aimed to investigate the ability of a modified preprocedural ultrasound-guided technique to improve the success rate and efficacy of CSE anesthesia for elderly patients with hip fractures. Methods: This prospective, single-blinded, parallel-group randomized controlled trial included 80 patients (aged ≥ 65 years) who were scheduled for elective hip fracture surgery with CSE anesthesia. Patients were randomly allocated into landmark group (n = 40) or the ultrasound group (n = 40). The primary outcome was first-pass success rate. Secondary outcomes included first-attempt success rate; number of needle insertion attempts; number of needle passes; locating, puncture, and total time; level of block; procedural adverse reactions and postoperative complications; and patient satisfaction score. Patients were blinded to group allocation.Results: 80 patients completed the study and were included in the final analysis. The first-pass success rates for the landmark and ultrasound groups were 20% and 70%, respectively (P < 0.001). The first-attempt success rates in the landmark and ultrasound groups were 42.5% and 85%, respectively (P < 0.001). The median number of attempts was lower in ultrasound-assisted group (1[1,1]) than landmark-guided group (2[1,2]), P < 0.001). The median number of needle passes was lower in ultrasound group (1[1,2]) than in landmark-guided group (3[2,4], P < 0.001). The locating time (P < 0.001) and total time (P = 0.001) were longer in the ultrasound group, while puncture time was shorter (P = 0.003). No significant difference was found regarding the incidence of adverse reactions and complications. More patients in the ultrasound group had a high satisfaction score of 4–5 (P = 0.007). Interestingly, subgroup analysis demonstrated benefits for ultrasound in patients with scoliosis.Conclusions: Modified ultrasound-assisted CSE anesthesia increases first-pass and first-attempt success rates, and reduces needle insertion attempts, passes, and puncture time for elderly patients with hip fracture, especially those with scoliosis. This technique improves patient satisfaction and warrants consideration for application in clinical practice.Trial registration: Chinese Clinical Trial Register (identifier, ChiCTR1900020819; date of registration, January 20, 2019).

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EXCRETION OF 15α-HYDROXYOESTRIOL AND OESTRIOL IN URINE OF NEWBORN INFANTS AND IN MATERNAL URINE BEFORE AND AFTER DELIVERY

Journal of Endocrinology ◽

10.1677/joe.0.0520119 ◽

1972 ◽

Vol 52 (1) ◽

pp. 119-128 ◽

Cited By ~ 5

Author(s):

JORMA HEIKKILÄ

Keyword(s):

Pregnant Women ◽

Linear Function ◽

Newborn Infant ◽

Newborn Infants ◽

Urine Samples ◽

Maternal Urine ◽

Before And After

SUMMARY The amounts of oestriol and 15α-hydroxyoestriol (oestetrol) were determined in 24-h urine samples collected from pregnant women before and after delivery. In addition, the concentrations of these oestrogens were estimated in the urine of the newborn infants born to these mothers. The excretion of both these oestrogens decreased exponentially in maternal urine after delivery, the rate of decrease being significantly slower for oestetrol. The concentration of oestriol and oestetrol in the urine of the newborn infants also fell rapidly after delivery, the reduction being a linear function of time. The concentration of oestetrol in the urine of the newborn infant was relatively high in comparison to that of oestriol, and during the first day of life was the same as in maternal urine before delivery.

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