Macrophage Migration Inhibitory Factor -173 G/C Polymorphism is Not Associated with An Increased Risk of Necrotizing Enterocolitis in Preterm Neonates in NICU

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Antibiotic prophylaxis for ophthalmia neonatorum in Italy: results from a national survey and the Italian intersociety new position statements

Background: Ophthalmia neonatorum is an acute conjunctivitis that occurs in newborns within the first month of life. The most serious infections are due to Chlamydia trachomatis and Neisseria gonorrhoeae, that may cause permanent damages. The use of ophthalmic prophylaxis varies widely around the world, according to the different health and socio-economic contexts. To date in Italy there is no a clear legislation regarding ophthalmia neonatorum prophylaxis at birth. Methods: We invited all birth centers in Italy to carry out a retrospective survey relating the last three years. We collected data regarding demographics of neonates, drugs used for ophthalmic prophylaxis and results of the screening of pregnant women for Chlamydia trachomatis and Neisseria gonorrhoeae vaginal infections. Results: Among 419 birth centers, 302 (72,1%) responded to the survey. Overall 1041384 neonates, 82,3% of those born in the three years considered, received ophthalmic prophylaxis. Only 4,585 (0,4%) of them received one of the drugs recommended by the WHO. The Centers that participated to the survey reported 12 episodes of Chlamydial conjunctivitis and no Gonococcal infection in the three years. Only 38% of the Centers performed vaginal swabs to pregnant women: 2,6% screened only for Neisseria, 9,6% only for Chlamydia and 25,8% for both germs. Conclusions: The data obtained from the survey showed a low incidence of neonatal conjunctivitis due to either Neisseria gonorrhoeae or Chlamydia trachomatis in Italy. Due to the lack of legislation regulating the prophylaxis of ophthalmia neonatorum in newborns, the Italian Society of Neonatology, the Italian Society of Obstetrics and Gynecology and the Italian Society of Perinatal Medicine have recently issued new recommendations on this topic

The APMAP interactome reveals new modulators of APP processing and beta-amyloid production that are altered in Alzheimer's disease.

The adipocyte plasma membrane-associated protein APMAP is expressed in the brain where it associates with γ-secretase, a protease responsible for the generation of the amyloid-β peptides (Aβ) implicated in the pathogenesis of Alzheimer's disease (AD). In this study, behavioral investigations revealed spatial learning and memory deficiencies in our newly generated mouse line lacking the protein APMAP. In a mouse model of AD, the constitutive deletion of APMAP worsened the spatial memory phenotype and led to increased Aβ production and deposition into senile plaques. To investigate at the molecular level the neurobiological functions of APMAP (memory and Aβ formation) and a possible link with the pathological hallmarks of AD (memory impairment and Aβ pathology), we next developed a procedure for the high-grade purification of cellular APMAP protein complexes. The biochemical characterization of these complexes revealed a series of new APMAP interactomers. Among these, the heat shock protein HSPA1A and the cation-dependent mannose-6-phosphate receptor (CD-M6PR) negatively regulated APP processing and Aβ production, while clusterin, calnexin, arginase-1, PTGFRN and the cation-independent mannose-6-phosphate receptor (CI-M6PR/IGF2R) positively regulated APP and Aβ production. Several of the newly identified APMAP interactomers contribute to the autophagy-lysosome system, further supporting an emergent agreement that this pathway can modulate APP metabolism and Aβ generation. Importantly, we have also demonstrated increased alternative splicing of APMAP and lowered levels of the Aβ controllers HSPA1A and CD-M6PR in human brains from neuropathologically verified AD cases

Dissecting abdominal aortic aneurysm in Ang II-infused mice: suprarenal branch ruptures and apparent luminal dilatation.

AIMS In this work, we provide novel insight into the morphology of dissecting abdominal aortic aneurysms in angiotensin II-infused mice. We demonstrate why they exhibit a large variation in shape and, unlike their human counterparts, are located suprarenally rather than infrarenally. METHODS AND RESULTS We combined synchrotron-based, ultra-high resolution ex vivo imaging (phase contrast X-Ray tomographic microscopy) with in vivo imaging (high-frequency ultrasound and contrast-enhanced micro-CT) and image-guided histology. In all mice, we observed a tear in the tunica media of the abdominal aorta near the ostium of the celiac artery. Independently we found that, unlike the gradual luminal expansion typical for human aneurysms, the outer diameter increase of angiotensin II-induced dissecting aneurysms in mice was related to one or several intramural haematomas. These were caused by ruptures of the tunica media near the ostium of small suprarenal side branches, which had never been detected by the established small animal imaging techniques. The tear near the celiac artery led to apparent luminal dilatation, while the intramural haematoma led to a dissection of the tunica adventitia on the left suprarenal side of the aorta. The number of ruptured branches was higher in those aneurysms that extended into the thoracic aorta, which explained the observed variability in aneurysm shape. CONCLUSION Our results are the first to describe apparent luminal dilatation, suprarenal branch ruptures, and intramural haematoma formation in dissecting abdominal aortic aneurysms in mice. Moreover, we validate and demonstrate the vast potential of phase contrast X-ray tomographic microscopy in cardiovascular small animal applications

RIP4 inhibits STAT3 signaling to sustain lung adenocarcinoma differentiation.

Loss of epithelial differentiation and extracellular matrix (ECM) remodeling are known to facilitate cancer progression and are associated with poor prognosis in patients with lung cancer. We have identified Receptor-interacting serine/threonine protein kinase 4 (RIP4) as a regulator of tumor differentiation in lung adenocarcinoma (AC). Bioinformatics analyses of human lung AC samples showed that poorly differentiated tumors express low levels of RIP4, whereas high levels are associated with better overall survival. In vitro, lung tumor cells expressing reduced RIP4 levels showed enhanced activation of STAT3 signaling and had a greater ability to invade through collagen. In contrast, overexpression of RIP4 inhibited STAT3 activation, which abrogated interleukin-6-dependent induction of lysyl oxidase, a collagen cross-linking enzyme. In an autochthonous mouse model of lung AC initiated by Kras(G12D) expression with loss of p53, Rip4 knockdown tumors progressed to a poorly differentiated state marked by an increase in Hmga2, reduced Ttf1, and enrichment of genes regulating extracellular remodeling and Jak-Stat signaling. Tail vein injections of cells overexpressing Rip4 showed a reduced potential to invade and form tumors, which was restored by co-expression of Stat3. Altogether, our work has identified that loss of RIP4 enhances STAT3 signaling in lung cancer cells, promoting the expression of ECM remodeling genes and cancer dedifferentiation

A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study

Background: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. Methods: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. Findings: On July 1, 2019, 26 of infants (580/2,265; range, 0�100; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received �1 antimicrobial agent (92, antibacterial; 19, antifungal; 4, antiviral). The most common reasons for antibiotic therapy were �rule-out� sepsis (32) and �culture-negative� sepsis (16) with ampicillin (40), gentamicin (35), amikacin (19), vancomycin (15), and meropenem (9) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26), amikacin (20), and meropenem (16) were the most prescribed agents. Length of therapy for culture-positive and �culture-negative� infections was 12 days (median; IQR, 8�14) and 7 days (median; IQR, 5�10), respectively. Mortality was 6 (42, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0·02). Interpretation: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. Funding: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship © 2021 The Author

Intravenous propofol allows fast intubation in neonates and young infants undergoing major surgery

Aim of the study: In selected surgical neonates and infants, the rapidity of induction and intubation may represent an important factor for their safety. Propofol is an anesthetic characterized by a rapid onset and fast recovery time that may reduce time of anesthetic induction and improve post-anesthetic outcome. The aim of this study was to evaluate the safety and efficacy of anesthesia induction in full-term neonates and young infants after propofol bolus administration.Methods: A retrospective case-control study including infants below 6 months of age, undergoing general anesthesia between 2011 and 2013, was carried out. Patients that received intravenous propofol bolus to induce anesthesia were compared to patients who received inhaled sevoflurane. Time to reach successful orotracheal intubation (OTI) was measured in seconds. The quality of OTI was defined as "excellent," "good," and "poor," based on established classification and was reported. Hemodynamic parameters as systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), heart rate (HR), and oxygen saturation (SaO2) were collected before OTI (t0), at OTI (t1), and at spontaneous breathing recovery (t2). Main adverse effects were recorded for both groups. Results are median (IQ range) or prevalence; rho < 0.05 was considered significant.Results: 160 infants were enrolled in the study, 80 received propofol and 80 inhaled sevoflurane. Major surgery (involving organs in the thoracic, abdominal, or pelvic cavities) was performed in 64 and 54% of patients in the propofol and sevoflurane group, respectively (p = 0.07). Patients in the propofol group showed a shorter time for OTI [11.5 (4.0-65) vs. 360.0 (228.0-720.0) seconds, (p < 0.0001)]. No difference was found in the quality of OTI between the two groups. No significant complications were recorded in either group.Conclusions: Propofol is a safe and effective anesthetic in neonates and infants permitting rapid induction of anesthesia and rapid intubation, without negative impact on the quality of intubation and haemodynamic compromise