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Breast milk (BM) is a unique food due to its nutritional composition and anti-inflammatory characteristics. Evidence has emerged on the role of Presepsin (PSEP) as a reliable marker of early sepsis diagnosis. In the present study, we aimed to investigate the measurability of PSEP in BM according to different maturation stages (colostrum, C; transition, Tr; and mature milks, Mt) and corrected for delivery mode and gender. We conducted a multicenter prospective case–control study in women who had delivered 22 term (T) and 22 preterm (PT) infants. A total of 44 human milk samples were collected and stored at −80 °C. BM PSEP (pg/mL) levels were measured by using a rapid chemiluminescent enzyme immunoassay. PSEP was detected in all samples analyzed. Higher (p < 0.05) BM PSEP concentrations were observed in the PT compared to the T infants. According to the grade of maturation, higher (p < 0.05) levels of PSEP in C compared to Tr and Mt milks were observed in the whole study population. The BM subtypes' degrees of maturation were delivery mode and gender dependent. We found that PSEP at high concentrations supports its antimicrobial action both in PT and T infants. These results open the door to further studies investigating the role of PSEP. [ABSTRACT FROM AUTHOR]

Background. Human Milk (HM) is a dynamic nourishment; its composition is influenced by several conditions such as gestational age, maternal diet and ethnicity. It appears important to evaluate the impact that gestational pathologies have on HM components and if their presence, as a source of oxidative stress in the mother, influence milk's redox homeostasis. To assess the effect of Preeclampsia (PE) and Gestational Diabetes Mellitus (GDM) on some aspects of human milk redox homeostasis, we chose to investigate both oxidative and antioxidant aspects, with, respectively, Lipid hydroperoxides (LOOHs) and Glutathione (GSH). Methods. Women with PE, GDM and who were healthy were recruited for this study. Colostrum, transitional and mature milk samples were collected. GSH and LOOHs levels were measured using a spectrophotometric test. To investigate the effect of pathology on redox homeostasis, a mixed linear model with unistructural covariance structure was performed. Results. A total of 120 mothers were recruited. The GSH concentration results were significantly lower in GDM women than in healthy women only in colostrum (p < 0.01). No other differences emerged. LOOHs was not detectable in almost all the samples. Discussion. Our study is the first to extensively evaluate these components in the HM of women with these gestational pathologies. The main observation is that GDM can alter the GSH level of HM, mainly in colostrum. [ABSTRACT FROM AUTHOR]

Background: It is known that preeclampsia affects lactogenesis. However, data on the effects of this pathology on human milk neurobiomarker composition are not available. The aim of this study is to investigate the effects of this gestational pathology on activin A levels, a neurobiomarker known to play an important role in the development and protection of the central nervous system. Methods: The women recruited were divided in two different study groups: preeclamptic or normotensive women. All the human milk samples were collected using the same procedure. Activin A was quantified using an Enzyme-linked immunosorbent assay (ELISA) test. To investigate the effect of preeclampsia on the activin A concentration in the three lactation phases, a mixed linear model with a unistructural covariance structure, with the mother as the random effect, and fixed effects were performed. Results: Activin A was detected in all samples. There were no significant differences between preeclamptic and normotensive women. The only significant effect is related to the lactation phase: the difference between colostrum and mature milk (p < 0.01) was significant. In conclusion, these results allow us to affirm that breast milk's beneficial properties are maintained even if preeclampsia occurs. [ABSTRACT FROM AUTHOR]

When a mother's milk is unavailable, the best alternative is donor milk (DM). Milk delivered to Human Milk Banks should be pasteurized in order to inactivate the microbial agents that may be present. Currently, pasteurization, performed at 62.5 °C for 30 min (Holder Pasteurization, HoP), is recommended for this purpose in international guidelines. Several studies have been performed to investigate the effects of HoP on the properties of DM. The present paper has the aim of reviewing the published papers on this topic, and to provide a comparison of the reported variations of biologically-active DM components before and after HoP. This review was performed by searching the MEDLINE, EMBASE, CINHAL and Cochrane Library databases. Studies that clearly identified the HoP parameters and compared the same DM samples, before and after pasteurization, were focused on. A total of 44 articles satisfied the above criteria, and were therefore selected. The findings from the literature report variable results. A possible explanation for this may be the heterogeneity of the test protocols that were applied. Moreover, the present review spans more than five decades, and modern pasteurizers may be able to modify the degradation kinetics for heat-sensitive substances, compared to older ones. Overall, the data indicate that HoP affects several milk components, although it is difficult to quantify the degradation degree. However, clinical practices demonstrate that many beneficial properties of DM still persist after HoP. [ABSTRACT FROM AUTHOR]

Background: The Mediterranean diet (MD) is associated with significant health benefits, including prevention of noncommunicable diseases (NCDs). Given the important migratory flow from Romania to Italy in recent decades, this study seeks to evaluate the differences between the nutritional habits of Romanian children and adolescents in Romania compared with those of Romanian children who moved to Italy or were born in Italy from both Romanian parents. Method: To assess adherence to MD, parents of Romanian children in Romania (RCR) and Romanian children in Italy (RCI) answered questions from an adapted version of the KIDMED test. Results: The results show that the high KIDMED index among RCI is significantly higher than the same index among RCR (68.09 versus 17.76, p < 0.05). RCR obtained a higher KIDMED score on different items: they had a lower consumption of fast food and sweets but an increased consumption of nuts, yogurts, and cheese. Conclusions: RCI have a better adherence to MD, but, at the same time, they are more exposed to westernized diet and practice less physical activity. Nutrition education is an important tool for improving health outcome. [ABSTRACT FROM AUTHOR]

Italy was one of the first industrialized countries to implement a program of routine vaccination against hepatitis B virus (HBV) infection. However, currently, no HBV vaccine is administered at birth if the screened mother is HBsAg negative, whilst babies born to HBsAg positive mothers are given vaccine and hepatitis B immunoglobulin, within 12–24 post-delivery hours. A single center retrospective analysis of policies and practices to prevent mother-to-child transmission of HBV was carried out, to evaluate their adherence to HBV care guidelines. Paired maternal-infant medical records for consecutive live births, between January 2015 and December 2019, were reviewed at the AOU Città della Salute e Scienza di Torino, where a total of 235/35,506 babies (0.7%) were born to HBsAg positive mothers. Markers of active viral replication, i.e., HBV DNA level and/or HBeAg, were reported in only 66/235 (28%) of the mothers' medical records. All newborns had immunoprophylaxis at birth: 61% at <12 h, 31% between 12 and 24 h, 7% between 24 and 36 h and 1% at >36 h. In 2019, two cases of vertical HBV transmission occurred, despite timely immunoprophylaxis, as their mothers' viral load was detected too late for antiviral prophylaxis. Missed early identification of pregnant women with high viremia levels or late vaccinations may contribute to perinatal HBV infection. Immunoprophylaxis should be given to babies born to HBsAg positive mothers at the latest within 12 h. In Italy, policies aimed at achieving the WHO 2030 goal of eliminating viral hepatitis should be further implemented. [ABSTRACT FROM AUTHOR]

Background: The aim of this systematic review is to analyze the available literature on the introduction of allergenic foods and gluten among preterm infants. Methods: A systematic review of published studies concerning the introduction of gluten and allergenic foods in preterm infants was performed on PubMed and on the Cochrane Library. Results: Of the 174 PubMed results, 15 papers were considered suitable for the review. A total of 83 records were identified through the Cochrane Library search; eight papers were included in the review. Additional papers were identified from the reference lists of included studies. A secondary search was conducted on the same databases to find recommendations and advice regarding healthy full-term infants that could be translated to preterm infants. Therefore, 59 additional papers were included in the review. Conclusions: Current guidelines for the introduction of solid food cannot be directly transposed to preterm infants. Further research is needed to provide evidence-based guidelines regarding weaning in preterm infants. To date, we can suggest that in preterm infants allergenic foods and gluten may be introduced when complementary feeding is started, any time after 4 months of corrected age, avoiding delayed introduction and irrespective of infants' relative risk of developing allergy. Avoiding large amounts of gluten during the first few weeks after gluten introduction and during infancy is advised, despite limited evidence to support this recommendation. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of our study was to assess the effects of Bisphenols exposure on pregnancy and neonatal life. In this optic, we have: (a) determined Bisphenols concentration levels (Bisphenol A and Bisphenol S) in a group of newborns and their mothers, (b) identified factors, habits and devices possibly responsible for Bisphenols uptake, and (c) determined some possible health effect of Bipshenols exposure. The statistical analyses showed no significant correlations between maternal and neonatal Bisphenols concentration levels. In newborns, on the contrary, a positive correlation between pacifier use and Bisphenol S total and free concentration was detected. Beside, a significant correlation was also found between oral glucose administration and concentration levels of free Bisphenols A. Our study points to a central role of lifestyle, hospital procedures and neonatal devices in inducing Bisphenols exposure during perinatal period. This is the first report of Bisphenols contamination in newborns due to widely non-alimentary products destined for newborn care (glucose solution containers for Bisphenol A and the pacifiers for the Bisphenol S). Further studies are advocated to clarify both the impact of such other Bisphenols forms on human health and the potential Bisphenol A exposure sources during neonatal and childhood life. The aim of the present study was to assess the effects of bisphenol (BP) exposure on pregnancy and neonatal life. We have (a) determined BP (BPA and BPS) concentration levels in a group of newborns and their mothers; (b) identified factors, habits, and devices possibly responsible for BP uptake; and (c) determined the effect of BP exposure. No significant correlations were detected between maternal and neonatal BP concentration levels. In newborns, positive correlations between pacifier use and BPS total (p = 0.04) and free BPS (p = 0.03) concentrations were detected. A significant correlation was also found between oral glucose administration and concentration levels of free BPA (p < 0.05). Our study points to a central role of lifestyle, hospital procedures, and neonatal devices in inducing BP exposure, especially during the perinatal period. This is the first report of BP contamination in newborns due to widely non-alimentary products designed for newborn care, such as glucose-solution containers for BPA and pacifiers for BPS. Further studies are advocated in order to clarify both the impact of other BP forms on human health and development, as well as potential BPA exposure sources during neonatal and childhood life. [ABSTRACT FROM AUTHOR]

In recent years, the role of human microbiota as a short- and long-term health promoter and modulator has been affirmed and progressively strengthened. In the course of one's life, each subject is colonized by a great number of bacteria, which constitute its specific and individual microbiota. Human bacterial colonization starts during fetal life, in opposition to the previous paradigm of the "sterile womb". Placenta, amniotic fluid, cord blood and fetal tissues each have their own specific microbiota, influenced by maternal health and habits and having a decisive influence on pregnancy outcome and offspring outcome. The maternal microbiota, especially that colonizing the genital system, starts to influence the outcome of pregnancy already before conception, modulating fertility and the success rate of fertilization, even in the case of assisted reproduction techniques. During the perinatal period, neonatal microbiota seems influenced by delivery mode, drug administration and many other conditions. Special attention must be reserved for early neonatal nutrition, because breastfeeding allows the transmission of a specific and unique lactobiome able to modulate and positively affect the neonatal gut microbiota. Our narrative review aims to investigate the currently identified pre- and peri-natal factors influencing neonatal microbiota, before conception, during pregnancy, pre- and post-delivery, since the early microbiota influences the whole life of each subject. [ABSTRACT FROM AUTHOR]

Adequate nutrition is fundamental to neonatal survival and short-term outcomes, but it also has long-term consequences on quality of life and neurologic development of preterm infants. Donkey milk has been suggested as a valid alternative for children allergic to cows' milk proteins, due to its biochemical similarity to human milk; we, hence, hypothesized that donkey milk could be a suitable basis for developing an innovative human milk fortifier for feeding preterm infants. The aim of the current study was to extend the findings and to evaluate the neurodevelopmental outcomes at 18 months of corrected age of the infants enrolled in the clinical trial named "Fortilat". Infants born ≤1500 g and <32 weeks of gestational age were randomized to receive either a combination of bovine milk-based multicomponent fortifier and protein supplement or a combination of a novel multicomponent fortifier and protein supplement derived from donkey milk. The followed fortification protocol was the same for the two groups and the two diets were designed to be isoproteic and isocaloric. All infants enrolled were included in a developmental assessment program. The neurodevelopmental assessment was performed at 18 ± 6 months of corrected age. Minor and major neurodevelopmental impairment and General Quotient (GQ) at the Griffiths-II Mental Development Scale were considered. The GQ was considered both in continuous and as two classes: lower than and higher than (or equal to) a defined cutoff (GQcl). The difference in GQ and GQcl between the two arms was estimated using Mann–Whitney–Wilcoxon test or Fischer exact test, respectively, on the assumption of casual loss at follow-up. A further analysis was performed using generalized linear models. There were 103 children (bovine milk-derived fortifier arm = 54, donkey milk-derived fortifier arm = 49) included for the neurodevelopmental follow-up. All observations were included in the interval of 18 ± 6 months of corrected age. No significant difference was observed between the two arms in the incidence of neurologic sequelae and the GQs were similar in the two arms. Our results demonstrated no difference for the donkey milk-derived fortifier compared to standard bovine-derived fortifier regarding long-term neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Human milk fortification is a routine clinical practice for feeding preterm infants. We hypothesized that donkey milk can be a suitable basis for developing an innovative human milk fortifier. Our randomized controlled single-blind clinical trial, named "Fortilat", evaluated the feeding tolerance, growth and clinical short-term outcomes in a population of preterm infants fed with a novel multi-component fortifier and a protein concentrate derived from donkey milk. The aim of the current study is to extend the previous findings and to evaluate the auxological outcomes of the infants enrolled in the "Fortilat" trial at 18 months of age. In the previous trial "Fortilat", the fortification protocol followed was the same for the two groups, and the two diets were designed to be isoproteic and isocaloric. All infants enrolled in the trial were included in a premature infant developmental evaluation program consisting of hospital visits at 40 ± 1 weeks of postmenstrual age, and at 6, 12 and 18 months of corrected age. Weight, head circumference and length were expressed in z-score using neonatal Intergrowth21st and INeS charts at birth, and WHO 0–5 years growth charts at 18 months. 122 children (Bovine-arm = 62, Donkey-arm = 60) were included in this study. All the observations were recorded in the interval of 18 ± 3 months of the correct age. The two groups did not differ for head circumference, length or weight at 18 months of age. Our data show that fortifiers derived from donkey milk had not different long term auxological outcomes of standard bovine-derived fortifier, but the new donkey milk fortifier was well tolerated in our population. [ABSTRACT FROM AUTHOR]

Fortification of human milk (HM) for preterm and very low-birth weight (VLBW) infants is a standard practice in most neonatal intensive care units. The optimal fortification strategy and the most suitable protein source for achieving better tolerance and growth rates for fortified infants are still being investigated. In a previous clinical trial, preterm and VLBW infants receiving supplementation of HM with experimental donkey milk-based fortifiers (D-HMF) showed decreased signs of feeding intolerance, including feeding interruptions, bilious gastric residuals and vomiting, with respect to infants receiving bovine milk-based fortifiers (B-HMF). In the present ancillary study, the urinary metabolome of infants fed B-HMF (n = 27) and D-HMF (n = 27) for 21 days was analyzed by 1H NMR spectroscopy at the beginning (T0) and at the end (T1) of the observation period. Results showed that most temporal changes in the metabolic responses were common in the two groups, providing indications of postnatal adaptation. The significantly higher excretion of galactose in D-HMF and of carnitine, choline, lysine and leucine in B-HMF at T1 were likely due to different formulations. In conclusion, isocaloric and isoproteic HM fortification may result in different metabolic patterns, as a consequence of the different quality of the nutrients provided by the fortifiers. [ABSTRACT FROM AUTHOR]

Background: Feeding intolerance is a frequent diagnosis in very preterm infants. As seen in the FortiLat trial, human milk fortification with the new donkey milk-derived human milk fortifier (DF) seems to improve feeding tolerance in these infants. The aim of this study was to evaluate the effects of using the DF compared with bovine milk-derived fortifier (BF) on gastroesophageal reflux (GER) in very low birth weight (VLBW) infants. Methods: Over a total of 156 preterm infants were enrolled into the FortiLat trial (GA <32 weeks and birth weight <1500 g) and randomized into the BF arm or DF arm, and we selected all infants with clinical signs of GER and cardiorespiratory (CR) symptoms. All the infants underwent CR and multichannel intraluminal impedance and pH (MII/pH) monitoring associated with gastric ultrasound to evaluate GER and gastric emptying time. Results: 10 infants were enrolled, and 5 were in the DF arm. At MII/pH, infants enrolled into the DF arm showed a lower GER frequency than BF arm infants (p = 0.036). Half gastric emptying time was similar in DF and BF arm infants (p = 0.744). Conclusion: The use of donkey-derived human milk fortifier reduced the GER frequency and consequently should be recommended in infants with feeding intolerance. [ABSTRACT FROM AUTHOR]

Breast milk is a complex biofluid that nourishes infants, supports their growth and protects them from diseases. However, at the same time, breastfeeding is a transmission route for human cytomegalovirus (HCMV), with preterm infants being at a great risk of congenital disease. The discrepancy between high HCMV transmission rates and the few reported cases of infants with severe clinical illness is likely due to the protective effect of breast milk. The aim of this study was to investigate the anti-HCMV activity of human preterm colostrum and clarify the role of colostrum-derived extracellular vesicles (EVs). Preterm colostrum samples were collected and the EVs were purified and characterized. The in vitro anti-HCMV activity of both colostrum and EVs was tested against HCMV, and the viral replication step inhibited by colostrum-purified EVs was examined. We investigated the putative role EV surface proteins play in impairing HCMV infection using shaving experiments and proteomic analysis. The obtained results confirmed the antiviral action of colostrum against HCMV and demonstrated a remarkable antiviral activity of colostrum-derived EVs. Furthermore, we demonstrated that EVs impair the attachment of HCMV to cells, with EV surface proteins playing a role in mediating this action. These findings contribute to clarifying the mechanisms that underlie the protective role of human colostrum against HCMV infection. [ABSTRACT FROM AUTHOR]

Extrauterine Growth Restriction (EUGR) refers to inadequate growth during hospitalization. Current definitions for EUGR are varied and can be classified as cross-sectional (weight at a given t-time <10th centile) or longitudinal (weight loss between birth and a given t-time >1SD). Different t-times are also considered in literature, such as 36 weeks of gestational age (GA) or age at discharge. The aim of this study is to investigate whether EUGR could predict the auxological outcome at 24–30 months, and to evaluate the agreement between cross-sectional and longitudinal definitions. In total, 1589 infants with GA <30 weeks or birthweight ≤ 1500 g and without major congenital anomalies were included in this study. Cross-sectional and longitudinal EUGR were calculated at 36 and 40 weeks of GA, at discharge, and at 28 days. The concordance between the two definitions was estimated by Kappa coefficient. At 24–30 months, 803 infants were measured again. The agreement between the two definitions of EUGR was low. Both EUGR and not-EUGR groups were at lower centiles for weight, but at higher centiles for head circumference at 24–30 months than at birth. Longitudinal EUGR was associated with a poorer growth outcome for weight and height circumference than cross-sectional EUGR. No differences were observed for length. An agreed definition of EUGR is highly desirable in clinical practice to assess medical and nutritional interventions in preterm neonates. Based on the results of this study, we recommend the use of the longitudinal evaluation, that proved to better predict the auxological long-term outcome with respect to the cross-sectional one. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) is the leading cause of congenital infection. Its occurrence is phenotypically heterogeneous. The type of maternal infection, primary or non-primary, is an important factor related to the symptomatic disease, the primary infection was long considered the only cause of severe neonatal disease. We aimed to analyze the association of primary and non-primary infection with pathological outcomes in infants and with long-term sequelae at follow-up. This was a monocentric retrospective observational study on a population of 91 infants diagnosed with a CMV infection at the Neonatal Care Unit of Neonatology at the Sant'Anna Hospital of Turin during the period of June 2005 to December 2018. Infants underwent clinical, laboratory, and neuroradiological evaluations at birth. Subsequently, the patients were monitored in an auxological, neurodevelopment, and audiological follow-up. Regarding primary vs. non-primary infection, we found a higher percentage of incidence of symptomatic and neurological localized infection, as well as long-term sequelae in the latter. However, no significant difference between the two populations was found. We underline the possibility of re-infection in previously immunized mothers (non-primary infection) with unfavorable neonatal and long-term outcomes. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV), a linear double-stranded DNA betaherpesvirus belonging to the family of Herpesviridae, is characterized by widespread seroprevalence, ranging between 56% and 94%, strictly dependent on the socioeconomic background of the country being considered. Typically, HCMV causes asymptomatic infection in the immunocompetent population, while in immunocompromised individuals or when transmitted vertically from the mother to the fetus it leads to systemic disease with severe complications and high mortality rate. Following primary infection, HCMV establishes a state of latency primarily in myeloid cells, from which it can be reactivated by various inflammatory stimuli. Several studies have shown that HCMV, despite being a DNA virus, is highly prone to genetic variability that strongly influences its replication and dissemination rates as well as cellular tropism. In this scenario, the few currently available drugs for the treatment of HCMV infections are characterized by high toxicity, poor oral bioavailability, and emerging resistance. Here, we review past and current literature that has greatly advanced our understanding of the biology and genetics of HCMV, stressing the urgent need for innovative and safe anti-HCMV therapies and effective vaccines to treat and prevent HCMV infections, particularly in vulnerable populations. [ABSTRACT FROM AUTHOR]

Human milk (HM) is a unique nourishment believed to contain biological factors contributing to both short and long-term benefits. Considering that a mother's own milk is often considered the first choice for nutrition of neonates, an aspect of increased interest is the possible effect of diabetes on the mammary gland and therefore on breast milk composition. This article aims to review the published literature on this topic, and to offer additional insights on the role of this disease on the composition of HM. This review was performed by searching the MEDLINE, EMBASE, CINHAL and Cochrane Library databases. A total of 50 articles were selected, focused specifically on one of the two types of diabetes: gestational diabetes mellitus (21 studies) and insulin-dependent diabetes mellitus (8 studies). Overall, the findings from the literature suggest that diabetes can alter the composition of HM. Nevertheless, the studies in this field are scarce, and the related protocols present some limitations, e.g., evaluating the variability of just a few specific milk biochemical markers in association with this syndrome. [ABSTRACT FROM AUTHOR]

Preterm and low birth weight infants require specific nutrition to overcome the accumulated growth deficit, and to prevent morbidities related to postnatal growth failure. In order to guarantee an adequate nutrient-intake, mother's own milk, when available, or donor human milk, are usually fortified with additional nutrients, in particular proteins. Fortification with processed ingredients may result in additional intake in oxidative compounds, deriving from extensive heat treatments, that are applied during processing. The aim of the present work was to compare the in vitro antioxidant activity and oxidative compound content conveyed by different preterm infant foods and fortifiers, namely raw and pasteurized human milk, two different preterm infant formulas, three bovine milk-based fortifiers and two experimental donkey milk-based fortifiers. Univariate and multivariate statistical analyses revealed significant differences between the different products. The use of human milk minimizes the intake of dietary oxidative compound in comparison to infant formulas, irrespective of pasteurization or fortification, especially as far as malondialdehyde content is concerned. The addition of fortifiers to human milk increases its antioxidant capacity, and the choice of the protein source (hydrolysed vs. whole proteins) differently impacted the resulting total antioxidant capacity of the diet. [ABSTRACT FROM AUTHOR]

Due to increasing attention from consumers on non-bovine milk types, and to the increase in the number of small dairy donkey farms in Italy, farmers require more advanced and reliable processing devices, in order to guarantee a safe product of high quality. To this aim, a new small-scale High-Temperature Short-Time (HTST) pasteurizer (72 °C for 15 s), prototyped by the authors, was tested on donkey milk. The efficacy of the HTST device was tested on raw donkey milk microflora by enumeration of total aerobic bacteria, Enterobacteriaceae and Bacillus cereus. The biochemical quality was assessed by determining the protein profile by monodimensional electrophoresis and by measuring lysozyme activity. The HTST apparatus was able to reduce the total bacteria count, and to completely eradicate Enterobacteriaceae. Bacillus cereus, when present, was decreased with low efficiency. Changes in the protein profile were observed in milk pasteurized in accordance with both processes, although HTST seemed to limit casein degradation. Lysozyme activity was not substantially affected in comparison to raw donkey milk. In conclusion, a tailored small-volume HTST device could be safely applied to pasteurize donkey milk in on-farm pasteurization processes on small dairy donkey farms., Competing Interests: The authors have competing interests, since they are the inventors of a pending patent application on the HTST pasteurizer for small volumes of liquid foods used in the study (Patent n. EP 15176792.8-1358/2014).