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Intrauterine growth restriction and congenital malformations: a retrospective epidemiological study

BACKGROUND: Intrauterine growth restriction (IUGR) and small for gestational age (SGA) birth have been considered possible indicators of the presence of malformations. The aim of this study is to evaluate such relationships in a population of newborns, along with other epidemiological and auxological parameters, in particular the ponderal index (PI). METHODS: We analyzed the birth data of 1093 infants, classified according to weight for gestational age as SGA, appropriate for gestational age (AGA) or large for gestational age (LGA). The prevalence of malformations was analyzed in relation to weight percentile at birth and SGA birth, maternal smoking, pregnancy diseases and PI. RESULTS: Our analysis showed no significant relationship between the prevalence of malformations and SGA birth. Maternal smoking and pregnancy diseases were strongly related to SGA birth, but not to a higher prevalence of malformations. PI, however, had a significant relationship with a higher prevalence of malformations, if analyzed as either a continuous variable or a categorical variable (cutoff: < 2.4). CONCLUSIONS: The association between congenital malformations and birth weight for gestational age seems to be weak. As part of diagnostic screening for malformations in the neonatal period, PI could be considered a better predictor of risk than weight percentile

Pre-Implantation Mouse Embryos Cultured In Vitro under Different Oxygen Concentrations Show Altered Ultrastructures

Assisted Reproductive Technologies routinely utilize different culture media and oxygen (O2) concentrations to culture human embryos. Overall, embryos cultured under physiological O2 tension (5%) have improved development compared to embryos cultured under atmospheric O2 conditions (20%). The mechanisms responsible for this remain unclear. This study aimed to evaluate the effect of physiologic (5%) or atmospheric O2 (20%) tension on the microscopic ultrastructure of pre-implantation mouse embryos using Transmission Electron Microscopy (TEM). Embryos flushed out of the uterus after natural mating were used as the control. For use as the control, 2-cells, 4-cells, morulae, and blastocysts were flushed out of the uterus after natural fertilization. In vitro fertilization (IVF) was performed using potassium simplex optimized medium (KSOM) under different O2 tensions (5% and 20%) until the blastocyst stage. After collection, embryos were subjected to the standard preparative for light microscopy (LM) and TEM. We found that culture in vitro under 5% and 20% O2 results in an increase of vacuolated shaped mitochondria, cytoplasmic vacuolization and presence of multi-vesicular bodies at every embryonic stage. In addition, blastocysts generated by IVF under 5% and 20% O2 showed a lower content of heterochromatin, an interruption of the trophectodermal and inner cell mass cell membranes, an increased density of residual bodies, and high levels of glycogen granules in the cytoplasm. In conclusion, this study suggests that in vitro culture, particularly under atmospheric O2 tension, causes stage-specific changes in preimplantation embryo ultrastructure. In addition, atmospheric (20%) O2 is associated with increased alterations in embryonic ultrastructure; these changes may explain the reduced embryonic development of embryos cultured with 20% O2

Oxygen concentration alters mitochondrial structure and function in in vitro fertilized preimplantation mouse embryos.

Study questionDoes the oxygen concentration in the culture medium [either physiologic (5%) or atmospheric (20%)] affect mitochondrial ultrastructure and function in preimplantation mouse embryos generated by IVF?Summary answerEmbryos cultured in 20% oxygen show increased mitochondrial abnormalities compared to embryos cultured in 5% oxygen.What is known alreadyART are widely used and have resulted in the birth of more than 8 million children. A variety of media and oxygen concentrations are used to culture embryos. Embryos cultured under physiological O2 tension (5%) reach the blastocyst stage faster and have fewer alterations in gene expression when compared with embryos cultured under atmospheric oxygen conditions (20%). The mechanisms by which oxygen tension affects preimplantation development remain unclear, but mitochondria are believed to play an important role. The aim of this study was to evaluate how mitochondrial ultrastructure and function in IVF embryos were affected by culture under physiologic (5%) or atmospheric (20%) oxygen concentrations.Study design, size, durationZygotes, 2-cell, 4-cell, morula and blastocyst were flushed out of the uterus after natural fertilization and used as controls. IVF was performed in CF1 x B6D2F1 mice and embryos were cultured in Potassium simplex optimized medium (KSOM) with amino acids (KAA) under 5% and 20% O2 until the blastocyst stage. Embryo development with the addition of antioxidants was also tested.Participants/materials, setting, methodsMitochondrial function was assessed by measuring mitochondrial membrane potential, reactive oxygen species (ROS) production, ATP levels, and the expression of selected genes involved in mitochondrial function. Mitochondria ultrastructure was evaluated by transmission electron microscopy (TEM).Main results and the role of chanceEmbryos cultured under 20% O2 had fewer mitochondria and more vacuoles and hooded (abnormal) mitochondria compared to the other groups (P &lt; 0.05). At the blastocyst stage the mitochondria of IVF embryos cultured in 20% O2 had lower mtDNA copy number, a denser matrix and more lamellar cristae than controls. Overall IVF-generated blastocysts had lower mitochondrial membrane potential, higher ROS levels, together with changes in the expression of selected mitochondrial genes (P &lt; 0.05). ATP levels were significantly lower than controls only under 5% O2, with the 20% O2 IVF group having intermediate levels. Unexpectedly, adding antioxidant to the culture medium did not improve development.Large scale dataN/A.Limitations, reasons for cautionFindings in mice embryos might be different from human embryos.Wider implications of the findingsThis study suggests that changes in the mitochondria may be part of the mechanism by which lower oxygen concentration leads to better embryo development and further emphasize the importance of mitochondria as a locus of reprogramming.Study funding/competing interest(s)This study was funded by R01 HD 082039 to PFR, the Department of Life, Health and Environmental Sciences, University of L'Aquila, Italy (RIA 2016-2018) and the Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, La Sapienza University of Rome, Italy (University grants 2016-2017). The authors declare no competing interests

Surveillance of Multidrug-Resistant Pathogens in Neonatal Intensive Care Units of Palermo, Italy, during SARS-CoV-2 Pandemic

Background: Antimicrobial resistance (AMR) is a topic of concern, especially in high-level care departments like neonatal intensive care units (NICUs). The systematic use of an “active” epidemiological surveillance system allows us to observe and analyze any changes in microbial distribution, limiting the risk of healthcare-associated infection (HAI) development. Methods: We have conducted a longitudinal observational study in the five NICUs of Palermo, comparing the “pre-pandemic period” (March 2014–February 2020) with the “pandemic” one (March 2020–February 2022). The primary aim of the study was to evaluate the cumulative prevalence of carriage from multi-drug resistant (MDR) bacteria in the cumulative NICUs (NICU C). Results: During the “pre-pandemic period”, 9407 swabs were collected (4707 rectal, 4700 nasal); on the contrary, during the “pandemic period”, a total of 2687 swabs were collected (1345 rectal, 1342 nasal). A statistically significant decrease in MDR-Gram-negative bacteria (GNB) carriage prevalence was detected during the pandemic. At the same time, there was a general worsening of the carriage of carbapenemase-forming MDR-GNB (CARBA-R+) and methicillin-resistant Staphylococcus aureus (MRSA) during the pandemic period. A significant reduction in methicillin-susceptible Staphylococcus aureus (MSSA) carriage was detected too. Conclusions: The surveillance of MDRO carriage in NICUs is fundamental for limiting the social and economic burden of HAIs

The role of a monthly active surveillance programme for multidrug-resistant Gram-negative bacteria in a neonatal intensive care unit: impact evaluation of preventive measures

Background: Antimicrobial resistance is a public health threat. Neonatal Intensive Care Unit (NICU) patients are particularly at risk, due to the large use of invasive devices and antimicrobial treatment. Since 2014 an active surveillance program of multidrug-resistant organisms is in place in the five NICUs of Palermo, Italy. High prevalence of multidrug-resistant Gram-negative bacteria (MDR-GNB) carriage observed in one NICU suggested the need of a long-lasting approach to achieve effective control of MDR-GNB circulation. Materials/methods: Rectal swabs were obtained every month from each hospitalized new-born. Samples were enriched in liquid cultures, plated in McConkey Agar with three antimicrobial discs (amoxicillin-clavulanate, meropenem, ceftazidime). Resistant colonies were isolated, identified and submitted for antimicrobial susceptibility testing and ESBL detection. Molecular characterization of MDR-GNB was performed using pulsed-field gel electrophoresis (PFGE). From November 2017 multiple intervention measures were done: - Strengthening of sample collection for two months; - Stakeholders meetings; - Standardized protocols for antimicrobial therapy and common procedures. Prevalence of MDR-GNB carriage between the pre-intervention (November 2016-October 2017) and the post-intervention period (November 2017-October 2018) was compared by chi-square test. Clinical features were analysed in a subgroup of patients to identify possible risk factors. All associated variables with p-values &lt;0.25 were included in a multivariate logistic regression model. P&lt;0.05 was considered significant. Results: 39 patients were included in the 2 months of strengthened microbiological surveillance. MDR-GNB and ESBL-Klebsiella pneumoniae (KP) were detected in rectal swabs (34.8%; 23.2%), nasal swabs (24.6%; 14.5%), oral swabs (14.5%; 5.4%), milk samples (32.1%; 17.9%) soother swabs (30.8%; 17.9%). ESBL-KP was also detected from a sub-intensive room surface. Thirteen ESBL-KP strains isolated from clinical and environmental samples showed identical or closely related PFGE patterns suggesting a common origin for all tested strains. Prevalence of MDR-GNB and ESBL-KP carriage after intervention significantly decreased compared to the year before (61.1% vs 20.6%; p&lt;0.001 and 94.5% vs 53.8%; p&lt;0.001). Admission in post-intervention period significantly reduced the risk of MDR-GNB carriage (OR=0.15, p=0.01). Conclusions: MDR-GNB broadly circulate in NICU setting, can colonize different body sites and spread by various vehicles. Cooperation between epidemiologist and clinicians can effectively reduce diffusion of antimicrobial-resistant bacteria

A Snapshot on MRSA Epidemiology in a Neonatal Intensive Care Unit Network, Palermo, Italy

Objectives. We performed a one-year prospective surveillance study on MRSA colonization within the five NICUs of the metropolitan area of Palermo, Italy. The purpose of the study was to assess epidemiology of MRSA in NICU from a network perspective.Methods. Transfer of patients between NICUs during 2014 was traced based on the annual hospital discharge records. In the period February 2014 – January 2015, in the NICU B, at the University teaching hospital, nasal swabs from all infants were collected weekly, whereas in the other four NICUs (A, C, D, E) at four week-intervals of time. MRSA isolates were submitted to antibiotic susceptibility testing, SCCmec typing, PCR to detect lukS-PV and lukF-PV (lukS/F-PV) genes and the gene encoding the toxic shock syndrome toxin (TSST-1), multilocus variable number tandem repeat fingerprinting (MLVF) and multilocus sequence typing (MLST). Results. In the period under study, 587 nasal swabs were obtained from NICU B, whereas 218, 180, 157 and 95 from NICUs A, C, D and E, respectively. Two groups of NICUs at high prevalence and low prevalence of MRSA colonization were recognized. Overall, 113 isolates of MRSA were identified from 102 infants. Six MLVF types (A-F) were detected, with type C being subdivided into five subtypes. Five sequence types (STs) were found with ST22-IVa being the most frequent type in all NICUs. All the MRSA molecular subtypes, except for ST1-IVa, were identified in NICU B. Conclusions. Our findings support the need to approach surveillance and infection control in NICU in a network perspective, prioritizing referral healthcare facilities

A novel family of highly conserved antigens that induce protective immunity against Staphylococcus aureus

ABSTRACT In the human pathogen Staphylococcus aureus there exists an enormous diversity of proteins containing domains of unknown function (DUF). Here, we characterized the family of conserved staphylococcal antigens (Csa) classified as DUF576 and taxonomically restricted to S. aureus. The 18 Csa paralogs in S. aureus Newman are highly similar at the sequence level yet were found to be expressed in multiple cellular localizations. Extracellular Csa1A was shown to be post-translationally processed and released. Molecular interaction studies revealed a dynamic complex formation of Csa1A with several Csa paralogs regulated by metal ions. Interestingly, the paralogs presented various modes of interaction with Csa1A, suggesting that the proteins are involved in the same cellular process in which each paralog might contribute with a particular role. The structures of Csa1A and Csa1B were determined by X-ray crystallography, unveiling a peculiar structure with limited structural similarity to other known proteins, confirming the uniqueness of this family. Since immunization with Csa proteins protected mice from lethal challenge with S. aureus, we propose these antigens as potential vaccine candidates