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Most extremely premature infants have respiratory instability that can manifest as frequent episodes of intermittent hypoxemia. Although caregivers target clinically recommended ranges of arterial oxygen saturation (oxygen saturation as measured by pulse oximetry [Spo 2 ]), consistent maintenance of these ranges is not always achieved. Excessive administration of supplemental oxygen combined with limited staff resources increases exposure to extreme Spo 2 levels. In this population, exposure to hyperoxemia and prolonged episodes of intermittent hypoxemia have been associated with damage to the eye and lung and impaired neurodevelopment. To improve Spo 2 targeting, various systems for automated control of inspired oxygen have been developed recently., Competing Interests: Conflict of interest statement Drs N. Claure and E. Bancalari developed and patented a system for automated control of inspired oxygen discussed in this article. The University of Miami, the assignee for this patent, has a licensing agreement with Vyaire Medical. Vyaire Medical supported some of the clinical studies to evaluate this system., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Lactic acid bacteria (LAB) are involved in producing a considerable number of fermented products consumed worldwide. Many of those LAB fermented foods are recognized as beneficial for human health due to probiotic LAB or their metabolites produced during food fermentation or after food digestion. In this review, we aim to gather and discuss available information on the health-related effects of LAB-fermented foods. In particular, we focused on the most widely consumed LAB-fermented foods such as yoghurt, kefir, cheese, and plant-based products such as sauerkrauts and kimchi.

Objective: To evaluate whether change in patent ductus arteriosus (PDA) management strategies over time had an impact on respiratory outcomes in premature infants., Study Design: Prospectively collected data were included from all preterm infants born at 23-30 weeks gestational age with PDA admitted to the Children's Hospital of the University of Miami/Jackson Memorial Medical Center from January 1, 2005 to December 31, 2007 (epoch 1) and January 1, 2011 to December 31, 2015 (epoch 2). The 2 epochs were compared for approach with PDA diagnosis and subsequent management strategies and respiratory outcomes., Results: Significantly fewer infants were treated for PDA in epoch 2 (54%) compared with epoch 1 (90%). Multivariable logistic regression analysis demonstrated that infants in epoch 2, with later PDA diagnosis and less frequent PDA treatment, had greater odds of bronchopulmonary dysplasia (BPD), composite of BPD or death, and more treatment with postnatal steroids than in epoch 1., Conclusions: The change in approach to diagnosis and management of PDA, from a more proactive and aggressive approach during the earlier epoch 1 to a more expectant approach during the subsequent epoch 2, was associated with worse respiratory outcomes, including increase in BPD and in BPD or death., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To evaluate the short-term respiratory effects of PND in a cohort of ventilator-dependent premature infants., Study Design: Clinical data from 106 infants 23-28 weeks gestation who received PND for weaning from MV during 2011-2017 were evaluated. PND was started at a dose of 0.1 mg/kg/d tapered over 5-7 d. Treatment success was defined as extubated and free from MV on d14 after start of treatment., Result: Treatment was successful in 83 (78%) infants. Demographics and age of treatment did not differ between groups. In the failure group, a higher proportion were on HFOV and FiO 2  ≥ 0.50 before treatment, compared to the successful group., Conclusion: In most infants, PND resulted in successful weaning from MV. Reduced need for oxygen in infants not extubated may be beneficial, but it is unknown if this offsets the risks. The long-term effects PND in ventilator dependent infants need to be evaluated., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Over the last 10 years, new techniques to administer surfactant have been promoted, based on their presumed lesser invasiveness and they have been generally called LISA (less invasive surfactant administration). We believe that the clinical potential of LISA techniques is currently overestimated. LISA lacks biological and pathophysiological background justifying its potential benefits. Moreover, LISA has been investigated in clinical trials without previous translational data and these trials are affected by significant flaws. The available data from these trials only allow to conclude that LISA is better than prolonged, unrestricted invasive ventilation with loosely described parameters, a mode of respiratory support that should be anyway avoided in preterm infants. We urge the conduction of high-quality studies to understand how to choose and titrate analgesia/sedation and optimize surfactant administration in preterm neonates. We offer a comprehensive, evidence-based review of the clinical data on LISA, their biases and the lack of physiopathology background., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study aims at proposing the use of Arthrospira platensis, commonly known as Spirulina, extract as a non-invasive method to attenuate the growth rate of non-starter adjunct cultures, thus preventing the over-acidification that may occur during cheese manufacturing. A preliminary screening using four different concentrations (0.20%, 0.30%, 0.50%, and 0.70%) of A. platensis extract and four starter and three non-starter lactic acid bacteria strains was performed by impedometric analysis. This allowed us to select one starter and one non-starter strain to be used in the in vitro simulation of a co-culture in milk with the best antimicrobial concentration (0.3%). The growth dynamics of the two selected strains, starter Lactococcus lactis 1426 and non-sarter Lacticaseibacillus rhamnosus 1473, co-cultured for 120 h was monitored by three different approaches: (i) plate counting on M17, for the enumeration of lactococci, and MRS for lactobacilli; (ii) fluorescence microscopic counting of viable and non-viable coccoid Lactococcus lactis 1426 and rod-shaped Lacticaseibacillus rhamnosus 1473 cells; (iii) the overall estimation of co-culture growth behavior by impedometric parameters Lag, Rate, and yEnd. All the data obtained from the in vitro simulation were in agreement, revealing that a slowdown of non-starter growth occurred, while the starter strain was not affected, or slightly stimulated, from the antimicrobial presence. In particular, the growth of Lb. rhamnosus 1473 was delayed without adversely compromise the cells' integrity, connected with metabolic functions, showing a great potential for use in cheese production.

Background: Biologically appropriate raw food (BARF) diet is becoming more and more popular among pet owners in Europe. However, there are documented microbiological risks associated with raw feeding, and this study aimed to determine the presence of human pathogens in commercially frozen BARF products sold in Italy., Methods: Salmonella species, Escherichia coli O157:H7, Listeria monocytogenes and Campylobacter species were identified. The general microbiological quality of BARF products and hygiene were also evaluated. Sample size was limited and therefore the study may not be representative of a larger sample., Results: None of the tested samples showed total bacterial count (TBC) higher than the limit set to consider a sample unacceptable. However, 14 out of 21 samples showed TBC higher than the limit set to consider a sample marginally acceptable. A high percentage of samples were contaminated by the aforementioned pathogens, highlighting the need for pet owners to be aware of the risks of this feeding strategy both to themselves and to their pets., Conclusions: Considering that BARF diet meals can be prepared at home using the hands, as well as tools and spaces that could be shared, guidelines on safer handling of these pet food products should be recommended by veterinarians and nutritionists., Competing Interests: Competing interests: None declared., (© British Veterinary Association 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Cheese microbiota contribute significantly to the final characteristics of cheeses due to the growth and interaction between cheese microorganisms during processing and ripening. For raw milk cheeses, such as Parmigiano Reggiano (PR), the microbiota derive from the raw milk itself, the dairy environment, and the starter. The process of cheese making and time of ripening shape this complex ecosystem through the selection of different species and biotypes that will drive the quality of the final product by performing functions of their metabolism such as proteolysis. The diversity in the final peptide and amino acid composition of the cheese is thus mostly linked to the diversity of this microbiota. The purpose of this study was to get more insight into the factors affecting PR cheese diversity and, more specifically, to evaluate whether the composition of the bacterial community of cheeses along with the specific peptide composition are more affected by the ripening times or by the cheese making process. To this end, the microbiota and the peptide fractions of 69 cheese samples (from curd to cheese ripened 24 months) were analyzed during 6 complete PR production cycles, which were performed in six different dairies located in the PR production area. The relation among microbial dynamics, peptide evolution, and ripening times were investigated in this unique and tightly controlled production and sampling set up. The study of microbial and peptide moieties in products from different dairies - from curd to at least 12 months, the earliest time from which the cheese can be sold, and up to a maximum of 24 months of ripening - highlighted the presence of differences between samples coming from different dairies, probably due to small differences in the cheese making process. Besides these differences, however, ripening time had by far the greatest impact on microbial dynamics and, consequently, on peptide composition., (Copyright © 2020 Bottari, Levante, Bancalari, Sforza, Bottesini, Prandi, De Filippis, Ercolini, Nocetti and Gatti.)

Fetal exposure to infection and inflammation can result in accelerated lung maturation and simultaneously altered lung development. This alteration is characterized by reduced alveolar and vascular formation that is one of the hallmarks of the changes observed in animal models and in infants with bronchopulmonary dysplasia (BPD). These opposite effects on maturation and on lung development can explain the reduced severity of respiratory distress syndrome (RDS) but increased incidence of BPD observed in infants exposed to antenatal infections. This also explains why infants born to mothers with chorioamnionitis or colonized with ureaplasma urealitycum have an increased risk of lung injury and BPD. Despite the negative effects of infection on lung development, there is no clear evidence that antibiotic therapy improves the respiratory course in these infants. While the administration of azithromycin to ureaplasma colonized infants is effective in eradicating airway colonization, the effect on BPD is inconclusive. One of the few interventions that have been shown to improve respiratory outcome and reduce BPD in infants with severe RDS is the modulation of inflammation by the administration of systemic or intratracheal steroids early after birth. KEY POINTS: · Antenatal infection can reduce RDS.. · Fetal exposure to infection can alter lung development and increase BPD.. · The detrimental effect of infection is enhanced by mechanical ventilation.., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Caciotta is the name used to define a type of Italian semi-hard cheese Caciotta-type cheese. Due to the short ripening time, pasteurization is necessary to eliminate the potential pathogenic bacteria, which may be present in raw milk, causing also the reduction of ripened cheese flavor. The purpose of this research was to evaluate the effect of a selected wild Lactobacillus paracasei strain experimentally used as adjunct culture to enhance the flavour formation in a short-ripened caciotta-type cheese. An integrated polyphasic approach was used to compare the experimental and control Caciotta produced in a company located in Emilia Romagna region (Italy). It was demonstrated how the L. paracasei 4341 was able to develop in curd and cheese interacting with the acidifying commercial starter. The main acidifying starter species, were differently affected by the presence of the adjunct culture. Streptococcus thermophilus shown comparable behavior in all cheese-making step of control and experimental Caciotta, while Lactobacillus delbrueckii subsp bulgaricus, growth was slowed down by the presence of the adjunct culture during the whole ripening time. The higher amount of volatile compounds and organic acids due to the adjunct L. paracasei 4341 lead to a clear differentiation of the experimental Caciotta respect to the control, in terms of aromatic profile, color, texture and sensorial perception., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Displaying heart rate characteristic (HRC) scores was associated with lower sepsis-associated mortality in very low birth weight (VLBW) infants in a multicenter randomized controlled trial (HeRO trial). The aim of this study was to test whether HRC indices rise before diagnosis of urinary tract infection (UTI) or meningitis, with and without concomitant BSI., Methods: Blood, urine, and cerebrospinal fluid (CSF) culture data after 3 days of age and within 120 days of study enrollment were analyzed from 2989 VLBW infants. The HRC index was analyzed 12 h prior to positive cultures compared to 36 h prior, using paired signed-rank tests., Results: UTI, meningitis, and BSI were diagnosed in 10%, 2%, and 24% of infants, respectively. The mean hourly HRC index was significantly higher 12 h prior to diagnosis of UTI and BSI compared to 36 h prior (UTI 2.07 versus 1.81; BSI 2.62 versus 2.25, both p < 0.0001). The baseline HRC index was higher for meningitis, compared to UTI or BSI, but without a statistically significant rise in the day prior to meningitis diagnosis., Conclusions: In a large cohort of VLBW infants enrolled in the HeRO trial, the HRC index increased in the 24-h period prior to diagnosis of UTI and BSI but not meningitis.

Arthrospira platensis, commercially known as Spirulina, is a fresh-water cyanobacterium that has been gaining increasing attention in recent years due to its high biological and nutritional value. For this reason, it has been employed in several food applications, to obtain or enhance functional and technological properties of cheese, yogurt, bread, cookies or pasta. The aim of this work was to evaluate the potential boosting effect of two different concentrations (0.25% and 0.50% w / v ) of A. platensis on the fermentation capability of several starter lactic acid bacteria (LAB) strains, 1 probiotic and 4 commercial mix culture. These strains were used to ferment three different substrates and their fermentation behaviors were evaluated by impedance analyses together with rheological and color measurements. In tryptic soy broth (TSB), the A. platensis boosting effect was significantly higher if compared to yeast extract for all the starter LAB strains except for Lb. casei , which was equally stimulated. Different results were found when the same LAB strains were cultivated in SSM. The most evident boosting effect was found for S. thermophilus and Lb. casei. LAB growth was promoted by A. platensis , confirming that it could be a useful tool in the production of novel functional fermented dairy foods. The potential boosting effect was evaluated on four commercial mix cultures used to produce milk and soy fermented beverages. It was demonstrated that the booster effect took place, but it was variable and dependent not only on the mix culture used, but also on the substrate and A. platensis concentration. Also, rheological and color modifications were found to be dependent on these factors.

Plant derived beverages have recently gained consumers' interest, particularly due to their intrinsic functional properties. They can also act as non-dairy carriers for probiotics and prebiotics, meeting the needs of lactose allergic/intolerant people and vegans. Direct fermentation of fruit and vegetables juices by probiotic lactic acid bacteria could be a tool to increase safety, shelf-life, nutrients bioavailability and to improve sensorial features of plant derived juices. This study aims to screen wild Lactobacillus casei -group strains isolated from dairy matrices for probiotic features, such as acid and bile salts resistance, and test them for the potentiality to ferment celery and orange juices. Strains' ability to produce exopolysaccharides (EPS) in situ is also checked. These evaluations were performed for the first time in fruit and vegetables matrices by means of an impedometric analysis, recently shown to be a suitable and rapid method to measure microorganisms' growth, acidification performances and EPS production. This study allowed the selection of three potentially probiotic L. casei -group wild strains able to ferment fruit and vegetable juices and also producing EPS. These strains with three-in-one abilities could be used to produce new functional fermented plant derived juices.

Despite the fact that strains belonging to Weissella species have not yet been approved for use as starter culture, recent toxicological studies open new perspectives on their potential employment. The aim of this study was to evaluate the ability of a wild Weissella minor ( W 4451) strain to modify milk viscosity compared to Lactobacillus delbrueckii subsp. bulgaricus , which is commonly used for this purpose in dairy products. To reach this goal, milk viscosity has been evaluated by means of two very different instruments: one rotational viscometer and the Ford cup. Moreover, water holding capacity was evaluated. W 4451, previously isolated from sourdough, was able to acidify milk, to produce polysaccharides in situ and thus improve milk viscosity. The ability of W 4451 to produce at the same time lactic acid and high amounts of polysaccharides makes it a good candidate to improve the composition of starters for dairy products. Ford cup turned out to be a simple method to measure fermented milk viscosity by small- or medium-sized dairies., (Copyright © 2020 Bancalari, Alinovi, Bottari, Caligiani, Mucchetti and Gatti.)

Autochthonous lactic acid bacteria (LAB) play a key role in the development of cheese flavor. As the pasteurization treatment on raw milk causes the elimination of LAB, secondary starter cultures are used in cheese manufacture to obtain cheeses with improved and standardized flavors. In this work, strains of the L. casei group isolated from traditional Italian cheeses were screened for their phenotypic features of technological interest for use as secondary starters. Their milk acidifying performance and the production of volatile compounds when grown in milk were evaluated. Simultaneously, the acetoin metabolic pathway presence was screened in the strains and assessed for its transcriptional activation. The results showed that the analyzed strains, despite belonging to taxonomically-related species, vary greatly according to the measured phenotypes. Four strains among the fourteen screened could be potentially used as adjunct cultures for cheese-making processes. The strain that showed the highest production of acetoin upregulated the aspartate pathway. An increased knowledge of volatile compounds' production and acidifying properties of LAB strains isolated from traditional dairy products might guide the selection of strains for industrial applications.

Introduction: Positive pressure ventilation (PPV) with T-Piece and self-inflating bag (SIB) during neonatal resuscitation after birth is associated with variability in ventilation. The use of a ventilator with respiratory function monitoring (RFM) for PPV, however, has not been evaluated., Objective: To determine if ventilator + RFM can reduce ventilation variability compared to T-Piece and SIB in a preterm manikin at different combinations of target tidal volume (VT) and lung compliance (CL)., Methods: Twenty clinicians provided PPV via mask and endotracheal tube (ETT) using SIB, T-Piece, T-Piece + RFM and Ventilator + RFM to a manikin with adjustable lung CL. Three combinations of CL and target VT: Low CL-Low VT, Low CL-High VT and High CL-Low VT were used in a random order., Results: The use of ventilator + RFM for PPV via ETT during High CL-Low VT period reduced the proportion of breaths with expiratory VT above target when compared to the other 3 devices (56 ± 35%, 85 ± 20%, 90 ± 25%, 92 ± 12% for ventilator + RFM, T-Piece + RFM, T-Piece, SIB, respectively; p < 0.05). During PPV via both mask and ETT, ventilator + RFM maintained the set Ti and rate, whereas SIB and T-Piece use resulted in higher rates, and T-Piece in higher proportion of breaths with prolonged Ti. During PPV via mask, ventilator + RFM reduced gas leakage compared to other devices., Conclusion: In this simulation study, use of a mechanical ventilator with RFM led to an overall improvement in volume targeting at different settings of CL and reduced the gas leak during mask ventilation. The efficacy and safety of using this strategy to neonatal resuscitation in the delivery room needs to be evaluated., (© 2019 S. Karger AG, Basel.)

Fetal to neonatal transition after birth is a complex, well-coordinated process involving multiple organ systems. Any significant derangement in this process increases the risk of death and other adverse outcomes, underlying the importance of continuous monitoring to promptly detect and correct these derangements by effective resuscitative support. In recent years, there has been increasing efforts to move from subjective and discontinuous monitoring to more objective and continuous monitoring of different physiological parameters. Some of them like pulse oximetry for arterial oxygen saturation and electrocardiography for heart rate monitoring are now part of resuscitation guidelines whereas others like respiratory function monitoring, near infrared spectroscopy, or amplitude integrated electroencephalography are being evaluated. In this review, we describe some of the physiological parameters that can be monitored during delivery room emergencies and review the evidence for some of the monitoring technologies currently being evaluated., (© 2019 Elsevier Ltd. All rights reserved.)

Bacterial production of exopolysaccharides (EPS) is of increasing interest near food manufacturers, biotechnology industries and nutritionists because of their different roles. Several analytical methods are available for recovery, quantification and characterization of EPS from lactic acid bacteria (LAB) in food. However, direct screening method for production of EPS is still based on the visual observation of filamentous texture of the colonies developed on supplemented solid growth media. To overcome weaknesses of many currently used screening methods, we propose adopting impedance microbiology to evaluate the EPS production from LAB in milk. In this work we have proven that the peculiar shape of capacitance curve of Lactobacillus delbrueckii subsp. bulgaricus 2214, measured in milk by means of a BacTrac 4300® system, is due to production of EPS. Besides the pH measurement, the amounts of EPS evaluated after 0, 8, 13 and 55 h of incubation in milk, were in agreement with the evaluation of gene expression and confirmed by the observations by confocal laser scanning microscopy and by transmission electron microscopy. With the aim to verify the applicability of the proposed method, the drop entity of the capacitance curve (ΔE%) of 22 EPS-producing (EPS+) LAB strains and one negative (EPS-) control was evaluated both in broth medium and in milk. The positive ΔE% value found for all of the strains cultivated in the clear broth medium allowed to confirm the EPS production, simply observing a strain-dependent amount of EPS on surface of the measurement electrodes of the device. When the same EPS+ strains were cultivated in milk, the obtained ΔE% values showed that only a few of them were able to produce EPS in this environment, supporting their diversified ability to utilize lactose for this purpose. Results obtained by this multidisciplinary study demonstrate that impedance microbiology represents a suitable method to overcome the limits of the most commonly used methods to screen LAB for EPS production in milk. Moreover, these results also open a door to the application to other food and beverages, in which the EPS produced in situ could be of great interest for food industry., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Exposure to hyperoxemia from excessive oxygen supplementation and episodes of intermittent hypoxemia have been associated with damage to the eye, lung, and central nervous system in premature infants. The inherent respiratory instability of the premature infant combined with limited staffing or equipment resources often affect SpO 2 targeting and increase exposure to extreme SpO 2 levels. Multiple systems for closed loop control of inspired oxygen have been developed to improve SpO 2 targeting. This article reviews the evidence provided by clinical studies evaluating the efficacy of these systems in extreme premature infants., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The evolution of neonatal respiratory support has been one of the cornerstones for the advancements in neonatal-perinatal medicine, allowing survival of infants previously considered not viable. There is an increasing focus on developing strategies which are not only lifesaving but also minimize lung and other organ systems injury, thereby reducing long-term morbidities. Respiratory support immediately after birth is an area that had lagged behind in terms of evidence base and technological advancements until recently. Some of these advancements include use of a respiratory function monitors for measuring flow and tidal volume, new evidence for oxygen supplementation and monitoring, and the efforts to formulate an ideal strategy for establishing functional residual capacity after birth. Increasing evidence for the benefits of avoiding invasive ventilation on reduction of bronchopulmonary dysplasia has resulted in efforts to further reduce the need for endotracheal intubation by applying newer strategies such as less invasive surfactant instillation, noninvasive high-frequency oscillatory ventilation, or use of high flow nasal cannula oxygen. For infants requiring mechanical ventilation, newer strategies such as volume targeted ventilation or neurally adjusted ventilation are being evaluated to reduce ventilator induced lung injury. Despite these advances, there are significant challenges, including lack of conclusive evidence base for many of currently used respiratory strategies, no reduction in the incidence of bronchopulmonary dysplasia in the last decade, and difficulties in defining outcome measures that better reflect long-term respiratory health., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: The increasing incidence of bronchopulmonary dysplasia in premature babies may be due in part to immature ventilatory control, contributing to hypoxemia. The latter responds to ventilation and/or oxygen therapy, treatments associated with adverse sequelae. This is an overview of the Prematurity-Related Ventilatory Control Study which aims to analyze the under-utilized cardiorespiratory continuous waveform monitoring data to delineate mechanisms of immature ventilatory control in preterm infants and identify predictive markers., Methods: Continuous ECG, heart rate, respiratory, and oxygen saturation data will be collected throughout the NICU stay in 500 infants < 29 wks gestation across 5 centers. Mild permissive hypercapnia, and hyperoxia and/or hypoxia assessments will be conducted in a subcohort of infants along with inpatient questionnaires, urine, serum, and DNA samples., Results: Primary outcomes will be respiratory status at 40 wks and quantitative measures of immature breathing plotted on a standard curve for infants matched at 36-37 wks. Physiologic and/or biologic determinants will be collected to enhance the predictive model linking ventilatory control to outcomes., Conclusions: By incorporating bedside monitoring variables along with biomarkers that predict respiratory outcomes we aim to elucidate individualized cardiopulmonary phenotypes and mechanisms of ventilatory control contributing to adverse respiratory outcomes in premature infants.

Background: The influence of severity of anemia and cardiac output (CO) on cerebral oxygenation (CrSO 2 ) and on the change in CrSO 2 following packed red blood cell (PRBC) transfusion in preterm infants has not been evaluated. The objectives of the current study were to evaluate the effect of pre-transfusion hemoglobin (Hb) and CO-weighted oxygen delivery index (ODI) on CrSO 2 and on the post-transfusion CrSO 2 change., Methods: Preterm infants of <32 weeks gestational age (GA) receiving PRBC transfusion were enrolled. Infants received 15 ml/kg PRBC over 3 h. CrSO 2 by near-infrared spectroscopy and CO by electrical velocimetry were recorded for 1 h pre-ransfusion and post transfusion. ODI was defined as pre-transfusion Hb × CO., Results: Thirty infants of 26.6 ± 2.0 weeks GA were studied at 19 ± 12 days. Pre-transfusion Hb was 9.8 ± 0.6 g/dl. Pre-transfusion CrSO 2 correlated with pre-transfusion ODI (R 2  = 0.1528, p = .044) but not with Hb level. The pre-transfusion to post-transfusion CrSO 2 change correlated with pre-transfusion ODI (R 2  = 0.1764, p = .029) but not with Hb level. CrSO 2 increased from 66 ± 6% to 72 ± 7% post transfusion (p < .001), while arterial oxygen saturation, heart rate, and CO did not change., Conclusion: In these infants, the pre-transfusion ODI was a better indicator of brain oxygenation and its improvement post transfusion than Hb alone. The role of CO and tissue oxygenation monitoring in assessing the need for transfusion should be evaluated.

Background: Preeclampsia (PE) is a pregnancy complication characterized by an anti-angiogenic environment. This can affect fetal pulmonary vascular and alveolar development but data of the impact of PE on respiratory outcome in extremely premature infants are inconclusive. The objective of this study was to determine if PE is associated with an increased risk for severe respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in extremely premature infants., Methods: Prospectively collected single center data from a cohort of infants born at 23-28 w gestational age between January 2005 and December 2015 were analyzed. Logistic regression analysis and generalized estimating equations were used to model the association between PE and severe RDS (≥30% supplemental oxygen on d1), BPD and severe BPD [supplemental oxygen and ≥30% oxygen at 36 w postmenstrual age (PMA), respectively]., Results: The cohort included 1218 infants of whom 23% were exposed to PE. PE was associated with increased risk for severe RDS as well as severe BPD among infants alive at 36w PMA., Conclusion: Exposure to preeclampsia is independently associated with an increased risk for severe RDS and adverse respiratory outcome in extreme premature infants. The mechanisms behind these associations need to be investigated.

Background: In extremely premature infants, arterial hypotension in the first days after birth has been associated with an increased risk for bronchopulmonary dysplasia (BPD). Some infants present with hypotension at a later postnatal age, but the relationship between late onset hypotension (LOH) and BPD has not been evaluated., Objective: To evaluate the association between LOH and BPD and to identify pre- and postnatal factors associated with LOH., Methods: Prospectively collected data from a cohort of 23-28 weeks gestational age (GA) infants born during years 2005-2015 and alive at day 28 were analyzed. LOH was defined as the receipt of vasopressor treatment during days 8-28. BPD was defined as need for oxygen at 36 weeks postmenstrual age. Late mortality was defined as death after day 28., Results: Of 1,058 infants in the cohort, 90 (9%) had LOH during days 8-28. Infants with LOH had a higher incidence of BPD than normotensive infants (55 vs. 21%, p < 0.001). Multivariate logistic regression analysis (LRA) showed that LOH was associated with an increased risk for BPD (OR 1.87, 95% CI 1.10-3.17). LOH was also associated with an increased risk for late mortality. LRA showed the risk for LOH increased with lower GA, sepsis and patent ductus arteriosus during days 8-28., Conclusions: In this cohort of extremely premature infants, LOH was associated with an increased the risk for BPD. This association could be secondary to underlying factors that predispose to LOH and BPD or to the deleterious effects of LOH or its treatments on the lung. Further investigation is needed to assess causality., (© 2018 S. Karger AG, Basel.)

Bronchopulmonary dysplasia (BPD) is one of the few diseases in neonatal medicine that has continued to evolve since its first description about 50 years ago. Over these years, advancements in neonatal medicine such as antenatal steroids and exogenous surfactant therapy have significantly reduced neonatal mortality and lowered the limits of viability for preterm infants. Although the incidence of BPD continues to be high, especially in extremely low birth weight infants, the clinical picture has evolved into a milder disease with low mortality or significant morbidities. This new BPD is the result of complex interactions between altered alveolar and vascular development, injury by ante- and postnatal pathogenic factors, and reparative processes in the lung. There has been significant progress in our understanding of risk factors for BPD, but challenges persist in its definition, and in finding effective preventive strategies. There are promising developments with newer preventive interventions such as mesenchymal stem cells, exosomes, immunomodulators, and growth factors, but they are still in preclinical stage. The future challenges include finding ways to define BPD based on the severity of lung pathology, which can better predict long-term outcomes, development of early predictors of lung disease, and finding innovative and evidence-based preventive and management strategies., (© 2019 S. Karger AG, Basel.)

The length-heterogeneity PCR is a low throughput molecular biology methods explored to monitor bacteria populations in different environments. It could be more used in food microbiology analysis, not only for fingerprinting analysis, but it has been hampered until now by a limiting factor which relates to the high percentage of secondary peaks. With the aim to overcome this problem, different experiments were performed focusing on changing PCR parameters in order to obtain more specific amplicon patterns and also to reduce the complexity of community patterns. With this purpose, different annealing temperatures were tested on complex fermented food matrices taken from both animal and vegetable origin and also on the bacteria isolated from the same food source. In particular, the optimal annealing temperature identified for the fermented food samples is 59 °C and the optimal for bacterial strains varied between 63 °C and 65 °C. The approach allowed the modification of the LH-PCR protocol increasing the amplification efficiency and therefore the bacteria species discrimination. These temperatures also allowed the implementation of the previous LH-PCR published database. The modification in the level of accuracy of the LH-PCR technique could also allow an improvement in the relative species quantification by the peak area evaluation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To examine the effect of heart rate characteristics (HRC) monitoring on length of stay among very low birth weight (VLBW; <1500 g birth weight) neonates in the HeRO randomized controlled trial (RCT)., Study Design: We performed a retrospective analysis of length of stay metrics among 3 subpopulations (all patients, all survivors, and survivors with positive blood or urine cultures) enrolled in a multicenter, RCT of HRC monitoring., Results: Among all patients in the RCT, infants randomized to receive HRC monitoring were more likely than controls to be discharged alive and prior to day 120 (83.6% vs 80.1%, P = .014). The postmenstrual age at discharge for survivors with positive blood or urine cultures was 3.2 days lower among infants randomized to receive HRC monitoring when compared with controls (P = .026). Although there were trends in other metrics toward reduced length of stay in HRC-monitored patients, none reached statistical significance., Conclusions: HRC monitoring is associated with reduced mortality in VLBW patients and a reduction in length of stay among infected surviving VLBW infants., Trial Registration: ClinicalTrials.gov: NCT00307333., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants., Study Design: Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation., Results: Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10-41 days) and control groups (median, 20 days; IQR, 9-43 days; P = .7). An interim analysis at 75% enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22%]) and control groups (5 [12%]; P = .22)., Conclusions: Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available., Trial Registration: ClinicalTrials.gov: NCT01751724., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The advances in obstetric and neonatal care over the last half century have resulted in changes in pathophysiology and clinical presentation of bronchopulmonary dysplasia (BPD). In contrast to the original description of BPD by Northway et al as a severe lung injury in relatively mature preterm infants, the most common form of BPD currently is characterized by chronic respiratory insufficiency in extremely preterm infants. This evolution in the presentation of BPD, along with changes in respiratory support strategies such as increased use of nasal cannula oxygen, has presented a unique challenge to find a definition that describes the severity of lung damage and predict the long-term respiratory outcomes with some accuracy.The limitations of current definitions of BPD include inconsistent correlation with long-term respiratory outcomes, inability to classify infants dying from severe respiratory failure prior to 36 weeks' postmenstrual age, and potential inappropriate categorization of infants on nasal cannula oxygen or with extrapulmonary causes of respiratory failure. In the long term, the aim for a new definition of BPD is to develop a classification based on the pathophysiology and objective lung function evaluation providing a more accurate assessment for individual patients. Until then, a consensus definition that encompasses current clinical practices, provides reasonable prediction of later respiratory outcomes, and is relatively simple to use should be achieved., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Oxygenation instability is a very common problem in the premature infant that manifests as intermittent hypoxemia episodes (HEs). These are particularly frequent in premature infants who are on mechanical ventilation beyond the first weeks after birth. However, they can also occur in spontaneously breathing infants. Some of these episodes are due to central apnea, but in ventilated infants, they are frequently due to contractions of the abdominal musculature that can splint the respiratory pump, resulting in periods of decreased lung volume and hypoventilation. HEs are often followed by periods of hyperoxemia that results from excessive oxygen supplementation given to correct the hypoxemia. These episodes increase in frequency with postnatal age and are more common in infants with chronic lung disease. Although the evidence is not conclusive, their detrimental effects on the infant's neurologic, ocular, and respiratory system may be significant. There is no specific treatment for HEs, but several interventions are available to ameliorate the severity and duration of the episodes. Further research is needed to define the impact of HEs on the preterm infant's developing central nervous system and other organ systems and to develop effective strategies to prevent these episodes., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Pectin oligosaccharides (POS) have been indicated as a new class of potential prebiotic compounds, which can be produced from pectin-rich food byproducts. In the present study, different technological means of POS production were explored to produce tailor-made POS mixtures starting from sugar beet pulp. The overall POS production process consisted of two steps: the extraction of pectin and the hydrolysis of pectin to tailored POS by combined hydrolysis/fractionation approaches. Different extraction as well as hydrolysis and fractionation methodologies were applied. The obtained POS were characterized for their total galacturonic acid content and, at a deeper level, using a HILIC-ESI/MS methodology, for the POS structure and composition. The composition of POS fractions was studied as a function of the technology used to obtain them. Finally, the potential prebiotic properties of the POS mixtures obtained were thoroughly explored by several in vitro experiments aimed at detecting lactic acid bacteria (LAB) stimulation by POS fractions. Several fractions were very efficient in stimulation, in a species-dependent manner. The overall best fractions were in general those rich in arabinans having a low degree of polymerization, obtained from the enzymatic extraction of biomass and subsequent fractionation with low-medium molecular weight cut-off. Quite interestingly, no POS fraction was able to stimulate pathogenic E. coli strains. The data reported here clearly indicate the possibility to obtain diverse fractions with different prebiotic properties starting from the same biomass, and outline clear potential for POS obtained from sugar beet pulp with the appropriate technology to act as prebiotic compounds.

Background: Hypoxemia episodes (HE) occur frequently in ventilated preterm infants and hinder the achievement of arterial oxygen saturation (SpO2) targets. These episodes may increase the risk for retinopathy of prematurity and neurodevelopmental disability. There are no data on the variation in HE and SpO2 targeting between day and night., Objective: The aim of this study was to evaluate the difference between day and night on the frequency and severity of HE and achievement of SpO2 targets., Methods: Twenty-four mechanically ventilated preterm infants with ≥4 episodes of SpO2 <75% over an 8-h period were enrolled. The fraction of inspired oxygen (FiO2), SpO2, and ventilator parameters were recorded over 24 h. Data from the day (9 a.m. to 5 p.m.) were compared to the night (9 p.m. to 5 a.m.) for the frequency of HE and proportion of time within and outside the target SpO2 range (90-95%)., Results: The frequency of severe HE (SpO2 <75, ≥20 s) and prolonged severe HE (SpO2 <75, ≥60 s) was lower during the night compared to the day (1.6 ± 1.0 vs. 2.4 ± 1.3 episodes/h, p = 0.008, and 0.53 ± 0.35 vs. 0.90 ± 0.54 episodes/h, p = 0.018). There was no difference in mean episode duration. The frequency and duration of mild HE (SpO2 <85, ≥20 s) were lower during the night compared to the day (5.9 ± 2.7 vs. 7.1 ± 2.5 episodes/h, p = 0.003, and 72 ± 15 vs. 87 ± 25 s, p = 0.01, respectively). The proportion of time in severe hypoxemia (SpO2 <75%) was smaller, whereas time in hyperoxemia (SpO2 >95%) was greater, during the night compared to the day. The mean FiO2 did not differ between day and night., Conclusion: In this group of infants with frequent HE, nighttime was associated with fewer episodes when compared to daytime. This is likely due to less handling and sensory stimulation during the night. The increase in time spent with hyperoxemia during the night is likely to be due to more tolerance of high SpO2 with less proactive weaning of FiO2., (© 2017 S. Karger AG, Basel.)

Lactic acid bacteria are commonly used in dairy industries to acidify milk and to enhance the flavour of the end products thanks to their metabolisms. The formation routes of aroma compounds mainly rely on the specific ability of different species and strains to convert precursors derived from carbohydrate and amino acids catabolism. It is well known that the strains largely involved in the aroma formation of the very appreciated Italian long ripened cheeses belong to the Lactobacillus casei group and origin from raw milk. In this study, a spontaneous fermentation of Parmigiano Reggiano raw milks was carried out to isolate new strains potentially usable as adjunctive aromatic starter. For this reason, specific selection criteria were chosen to isolate strains belonging to L. casei, and L. paracasei species. An integrated approach, by mean of impedance microbiology and SPME GC-MS analysis, was applied to investigate the acidifying performance and the production of volatile compounds of seven strains in UHT whole milk. One of these strains, L. paracasei 4341, appear to be the most interesting one from the technological point of view both for its acidifying and aromatic features. This approach could be employed for selection of the aromatic strains to be potentially used as adjunct starter in dairy sector., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Bronchopulmonary dysplasia (BPD) is one of the few diseases affecting premature infants that have continued to evolve since its first description about half a century ago. The current form of BPD, a more benign and protracted respiratory failure in extremely preterm infants, is in contrast to the original presentation of severe respiratory failure with high mortality in larger premature infants. This new BPD is end result of complex interplay of various antenatal and postnatal factors causing lung injury and subsequent abnormal repair leading to altered alveolar and vascular development. The change in clinical and pathologic picture of BPD over time has resulted in new challenges in developing strategies for its prevention and management. While some of these strategies like Vitamin A supplementation, caffeine and volume targeted ventilation have stood the test of time, others like postnatal steroids are being reexamined with great interest in last few years. It is quite clear that BPD is unlikely to be eliminated unless some miraculous strategy cures prematurity. The future of BPD prevention will probably be a combination of antenatal and postnatal strategies acting on multiple pathways to minimize lung injury and abnormal repair as well as promote normal alveolar and vascular development.

The present study compared two culture-independent methods, polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) and length-heterogeneity polymerase chain reaction (LH-PCR), for their ability to reveal food bacterial microbiota. Total microbial DNA and RNA were extracted directly from fourteen fermented and unfermented foods, and domain A of the variable regions V1 and V2 of the 16S rRNA gene was analyzed through LH-PCR and PCR-DGGE. Finally, the outline of these analyses was compared with bacterial viable counts obtained after bacterial growth on suitable selective media. For the majority of the samples, RNA-based PCR-DGGE revealed species that the DNA-based PCR-DGGE was not able to highlight. When analyzing either DNA or RNA, LH-PCR identified several lactic acid bacteria (LAB) and coagulase negative cocci (CCN) species that were not identified by PCR-DGGE. This phenomenon was particularly evident in food samples with viable loads<5.0 Logcfug -1 . Furthermore, LH-PCR was able to detect a higher number of peaks in the analyzed food matrices relative to species identified by PCR-DGGE. In light of these findings, it may be suggested that LH-PCR shows greater sensitivity than PCR-DGGE. However, PCR-DGGE detected some other species (LAB included) that were not detected by LH-PCR. Therefore, certain LH-PCR peaks not attributed to known species within the LH-PCR database could be solved by comparing them with species identified by PCR-DGGE. Overall, this study also showed that LH-PCR is a promising method for use in the food microbiology field, indicating the necessity to expand the LH-PCR database, which is based, up to now, mainly on LAB isolates from dairy products., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Inflammatory injury, particularly the production of active interleukin (IL)-1β plays a major role in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. The release of active IL-1β is controlled by posttranscriptional modifications of its proform (pro-IL-1β) through the inflammasome. Rac1 is a member of the Rho family of GTPases that regulate the inflammatory process., Objective: This study tested the hypothesis that Rac1 signaling increases inflammasome activation that results in damaging inflammation, and that the inhibition of Rac1 signaling prevents lung injury, by inhibiting inflammasome activation in a newborn rat model of BPD induced by hyperoxia., Methods: Newborn rat pups were exposed to room air or hyperoxia (85% O2) and received daily intraperitoneal injections of placebo (normal saline) or NSC23766, a specific Rac1 inhibitor, for 10 days. The effects on lung inflammation, alveolarization, vascular development, vascular remodeling, right ventricular systolic pressure, and right ventricular hypertrophy (RVH) were then assessed., Results: Hyperoxia exposure upregulated Rac1 and increased the production of active IL-1β, which was accompanied by increasing expression of the inflammasome. In addition, hyperoxia induced the pathological hallmarks of BPD. However, treatment with NSC23766 significantly decreased inflammasome activation and macrophage infiltration, improved alveolar and vascular development, and reduced pulmonary vascular remodeling and RVH., Conclusion: These results indicate that Rac1 signaling regulates the expression of the inflammasome and plays a pivotal role in the pathogenesis of hyperoxia-induced neonatal lung injury. Therefore, targeting Rac1 signaling may provide a novel strategy to prevent and treat BPD in preterm infants., (© 2016 S. Karger AG, Basel.)

Impedance microbiology is a method that enables tracing microbial growth by measuring the change in the electrical conductivity. Different systems, able to perform this measurement, are available in commerce and are commonly used for food control analysis by mean of measuring a point of the impedance curve, defined "time of detection." With this work we wanted to find an objective way to interpret the metabolic significance of impedance curves and propose it as a valid approach to evaluate the potential acidifying performances of starter lactic acid bacteria to be employed in milk transformation. To do this it was firstly investigated the possibility to use the Gompertz equation to describe the data coming from the impedance curve obtained by mean of BacTrac 4300®. Lag time (λ), maximum specific M% rate (μmax), and maximum value of M% (Yend) have been calculated and, given the similarity of the impedance fitted curve to the bacterial growth curve, their meaning has been interpreted. Potential acidifying performances of eighty strains belonging to Lactobacillus helveticus, Lactobacillus delbrueckii subsp. bulgaricus, Lactococcus lactis , and Streptococcus thermophilus species have been evaluated by using the kinetics parameters, obtained from Excel add-in DMFit version 2.1. The novelty and importance of our findings, obtained by means of BacTrac 4300®, is that they can also be applied to data obtained from other devices. Moreover, the meaning of λ, μmax, and Yend that we have extrapolated from Modified Gompertz equation and discussed for lactic acid bacteria in milk, can be exploited also to other food environment or other bacteria, assuming that they can give a curve and that curve is properly fitted with Gompertz equation.

The patency of the ductus arteriosus is very common in extremely premature infants. The increased pulmonary blood flow that results from left-to-right ductal shunting can produce an acute deterioration in lung function and some data suggest that it may increase the risk of chronic lung damage. However, there is no clear evidence that prophylactic or early closure of the patent ductus arteriosus (PDA) results in a clear reduction in bronchopulmonary dysplasia. For this reason, and because of the side effects of the available therapies to close the ductus, there is a wide variation in the approach to the PDA in this population and most clinicians will intervene to close the ductus only in cases of significant shunt with hemodynamic decompensation., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)