Sustaining the Continued Effectiveness of an Antimicrobial Stewardship Program in Preterm Infants.

BACKGROUND: There are wide variations in antibiotic use in neonatal intensive care units (NICUs). Limited data are available on antimicrobial stewardship (AS) programs and long-term maintenance of AS interventions in preterm very-low-birth-weight (VLBW) infants. METHODS: We extended a single-centre observational study carried out in an Italian NICU. Three periods were compared: I. "baseline" (2011-2012), II. "intervention" (2016-2017), and III. "maintenance" (2020-2021). Intensive training of medical and nursing staff on AS occurred between periods I and II. AS protocols and algorithms were maintained and implemented between periods II and III. RESULTS: There were 111, 119, and 100 VLBW infants in periods I, II, and III, respectively. In the "intervention period", there was a reduction in antibiotic use, reported as days of antibiotic therapy per 1000 patient days (215 vs. 302, p < 0.01). In the "maintenance period", the number of culture-proven sepsis increased. Nevertheless, antibiotic exposure of uninfected VLBW infants was lower, while no sepsis-related deaths occurred. Our restriction was mostly directed at shortening antibiotic regimens with a policy of 48 h rule-out sepsis (median days of early empiric antibiotics: 6 vs. 3 vs. 2 in periods I, II, and III, respectively, p < 0.001). Moreover, antibiotics administered for so-called culture-negative sepsis were reduced (22% vs. 11% vs. 6%, p = 0.002), especially in infants with a birth weight between 1000 and 1499 g. CONCLUSIONS: AS is feasible in preterm VLBW infants, and antibiotic use can be safely reduced. AS interventions, namely, the shortening of antibiotic courses in uninfected infants, can be sustained over time with periodic clinical audits and daily discussion of antimicrobial therapies among staff members.

Experimental certification of contextuality, coherence, and dimension in a programmable universal photonic processor.

Quantum superposition of high-dimensional states enables both computational speed-up and security in cryptographic protocols. However, the exponential complexity of tomographic processes makes certification of these properties a challenging task. In this work, we experimentally certify coherence witnesses tailored for quantum systems of increasing dimension using pairwise overlap measurements enabled by a six-mode universal photonic processor fabricated with a femtosecond laser writing technology. In particular, we show the effectiveness of the proposed coherence and dimension witnesses for qudits of dimensions up to 5. We also demonstrate advantage in a quantum interrogation task and show it is fueled by quantum contextuality. Our experimental results testify to the efficiency of this approach for the certification of quantum properties in programmable integrated photonic platforms.

Marine plastics alter the organic matter composition of the air-sea boundary layer, with influences on CO2 exchange: a large-scale analysis method to explore future ocean scenarios.

Microplastics are substrates for microbial activity and can influence biomass production. This has potentially important implications in the sea-surface microlayer, the marine boundary layer that controls gas exchange with the atmosphere and where biologically produced organic compounds can accumulate. In the present study, we used six large scale mesocosms to simulate future ocean scenarios of high plastic concentration. Each mesocosm was filled with 3 m3 of seawater from the oligotrophic Sea of Crete, in the Eastern Mediterranean Sea. A known amount of standard polystyrene microbeads of 30 µm diameter was added to three replicate mesocosms, while maintaining the remaining three as plastic-free controls. Over the course of a 12-day experiment, we explored microbial organic matter dynamics in the sea-surface microlayer in the presence and absence of microplastic contamination of the underlying water. Our study shows that microplastics increased both biomass production and enrichment of carbohydrate-like and proteinaceous marine gel compounds in the sea-surface microlayer. Importantly, this resulted in a ∼3 % reduction in the concentration of dissolved CO2 in the underlying water. This reduction was associated to both direct and indirect impacts of microplastic pollution on the uptake of CO2 within the marine carbon cycle, by modifying the biogenic composition of the sea's boundary layer with the atmosphere.

Warming and eutrophication interactively drive changes in the methane-oxidizing community of shallow lakes.

Freshwater ecosystems are the largest natural source of the greenhouse gas methane (CH4), with shallow lakes a particular hot spot. Eutrophication and warming generally increase lake CH4 emissions but their impacts on the sole biological methane sink-methane oxidation-and methane-oxidizer community dynamics are poorly understood. We used the world's longest-running freshwater climate-change mesocosm experiment to determine how methane-oxidizing bacterial (MOB) abundance and composition, and methane oxidation potential in the sediment respond to eutrophication, short-term nitrogen addition and warming. After nitrogen addition, MOB abundance and methane oxidation potential increased, while warming increased MOB abundance without altering methane oxidation potential. MOB community composition was driven by both temperature and nutrient availability. Eutrophication increased relative abundance of type I MOB Methyloparacoccus. Warming favoured type II MOB Methylocystis over type I MOB Methylomonadaceae, shifting the MOB community from type I dominance to type I and II co-dominance, thereby altering MOB community traits involved in growth and stress-responses. This shift to slower-growing MOB may explain why higher MOB abundance in warmed mesocosms did not coincide with higher methane oxidation potential. Overall, we show that eutrophication and warming differentially change the MOB community, resulting in an altered ability to mitigate CH4 emissions from shallow lakes.

From PARP1 to TNKS2 Inhibition: A Structure-Based Approach.

Tankyrases (TNKSs) have recently gained great consideration as potential targets in Wnt/ß-catenin pathway-dependent solid tumors. Previously, we reported the 2-mercaptoquinazolin-4-one MC2050 as a micromolar PARP1 inhibitor. Here we show how the resolution of the X-ray structure of PARP1 in complex with MC2050, combined with the computational investigation of the structural differences between TNKSs and PARP1/2 active sites, provided the rationale for a structure-based drug design campaign that with a limited synthetic effort led to the discovery of the bis-quinazolinone 5 as a picomolar and selective TNKS2 inhibitor, endowed with antiproliferative effects in a colorectal cancer cell line (DLD-1) where the Wnt pathway is constitutively activated.

Usefulness of the Infant Driven Scale in the early identification of preterm infants at risk for delayed oral feeding independency.

BACKGROUND: Very preterm infants frequently experience difficulties in achieving feeding independency. The availability of feeding assessment instruments has been recommended to evaluate an infant's readiness for oral feeding and enable preterm infants' caregivers to document each infant's feeding readiness and advancements. AIMS: To investigate the implementation of the Infant Driven Scale in neonatal intensive care units and to identify a cut off value associated with delayed feeding independency. STUDY DESIGN: Prospective, observational, single-centre study. SUBJECTS: A total of 47 infants born at a gestational age≤32weeks, consecutively admitted to a tertiary neonatal unit between July 2015 and March 2016. OUTCOMES MEASURES: The infant's feeding readiness and the postmenstrual age at achievement of feeding independency. RESULTS: Mean postmenstrual age at feeding independency was 35.6±1.34weeks. A linear regression analysis showed that a score≤8 at 32weeks of postmenstrual age was associated with a delay of 1.8weeks in achieving feeding independency. CONCLUSION: The Infant Driven Scale appears to be a useful additional instrument for the assessment of preterm infants' oral feeding readiness and the early identification of the infants at risk for delayed feeding independency.

New anticancer agents mimicking protein recognition motifs.

The novel tetrasubstituted pyrrole derivatives 8g, 8h, and 8i showed selective cytotoxicity against M14 melanoma cells at low micromolar concentration. Structure-activity relationships (SARs) indicated the presence of three aromatic substituents on the pyrrole core as necessary for biological activity. Computational studies strongly suggest that the peculiar 3D orientation of these substituents is able to reproduce the hydrophobic side chains in LxxLL-like protein recognition motifs. Biological results showed altered p53 expression and nuclear translocation in cells sensitive to the compounds, suggesting p53 involvement in their anticancer mechanism of action. Unfortunately, because of poor solubility of the active analogues, it was not possible to perform further investigation by NMR techniques. Pharmacophore models were generated and used to perform 3D searches in molecular databases. Results indicated that two compounds share the same pharmacological profile and the same pharmacophoric features with our new derivatives, and one of them inhibited MDM2-MDM4 heterodimer formation.

Does a personalized approach improve patient satisfaction in thoracic oncology?

OBJECTIVE: To evaluate patients' quality of life (QOL) at admission to permit definition and implementation of a personalized plan of multidimensional care. METHODS: In 2007, patients hospitalized for more than 24 hours at the Thoracic Surgery Department of a tertiary referral cancer center received QOL assessment at admission by European Organisation for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30 and LC13. Patients were asked to anonymously express their satisfaction with care at discharge by using the EORTC IN-PATSAT32 questionnaire. During the second part of the study (July-December 2007), specific interventions were proposed in critical areas identified by the questionnaires. RESULTS: During 2007, 898 patients completed QOL assessment at admission and 805 patients anonymously expressed their satisfaction with care at discharge. Overall patient satisfaction significantly improved in the second part of the study (85.4 +/- 16.7 vs 91.9 +/- 13.1; P = .009). The most significant improvement was recorded in nurses' information provision (67.7 +/- 24.1 vs 80.2 +/- 20.2; P = .0014) and availability (70.4 +/- 22.8 vs 84.3 +/- 19.2; P <.001). Surprisingly, the third-ranking improvement was recorded for the hospital access scale, which was the item with the lowest score in both periods and for which no specific modification occurred during the study period. CONCLUSIONS: Use of a simple and reliable evaluation of QOL at admission contributed to improved quality of administered care. This approach permits focused management of ongoing problems, close cooperation between caregivers, and a more flexible response to patient needs.

Outpatient operative polypectomy using a 5 mm-hysteroscope without anaesthesia and/or analgesia: advantages and limits.

OBJECTIVE: To assess the predictors of office-based operative hysteroscopic polypectomy using a 5.2mm continuous flow office hysteroscope without anaesthesia and/or analgesia for the treatment of endometrial and/or isthmic polyps and to define procedure limits. STUDY DESIGN: Women with hysteroscopic diagnosis of endometrial or isthmic polyps were offered to proceed in the same session with operative hysteroscopy after 15 min without anaesthesia and/or analgesia. All procedures were performed using a 5.2 mm continuous flow office hysteroscope. Patient procedure compliance was assessed by means of a visual analogue scale (VAS) using a rating scale with 11 categories. A VAS < or = 4 was considered as patient procedure compliance. Regression analysis was performed to correlate the following variables: time required, size and number of polyps with VAS. A ROC analysis was performed to assess the cut-off of the strongest predictors. The influence of previous vaginal delivery and menopausal status was correlated with the VAS. RESULTS: A total of 217 women underwent the office-based hysteroscopic procedure and 253 polyps were removed, among them 170 were endometrial and 83 isthmic polyps. There were 181 women with single polyps and 36 women presented multiple polyps. The size of polyps ranged from 0.5 to 5 cm. Median time of the procedure was 10 min (range 3-30 min). Regression analysis showed a statistical significative correlation between VAS and size of polyps and between VAS and operating time independent to the number of polyps. Using the ROC analysis a VAS < or = 4 was obtained when polyps were < or = 2 cm and/or time of the procedure lasted < or = 15 min. Menopausal status and previous vaginal deliveries were not significantly correlated to the VAS. CONCLUSIONS: Office-based hysteroscopic polypectomy is a safe and feasible procedure and should be addressed in patients with endometrial or isthmic polyps < or = 2 cm in diameter, and the procedure limits in terms of patient procedure compliance are size of polyps and operating time, independent from menopausal status and previous vaginal delivery.