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Abstract: The etiopathogenesis of necrotizing enterocolitis (NEC) remains unclear, but increasing information suggests that the risk and severity of NEC may be influenced by single nucleotide polymorphisms in many genes. In this article, we have reviewed gene variations that have either been specifically identified in NEC or have been noted in other inflammatory bowel disorders with similar histopathological abnormalities. We present evidence from our own peer-reviewed laboratory studies and data from an extensive literature search in the databases PubMed, EMBASE, and Scopus. To avoid bias in the identification of existing studies, search keywords were short-listed both from our own studies and from PubMed’s Medical Subject Heading (MeSH) thesaurus.

The incomplete understanding of the etiopathogenesis of necrotizing enterocolitis (NEC) contributes to the lack of timely diagnosis and limited therapeutic options. Non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression in various pathways that can modulate various physiological and pathological processes. Despite several studies revealing the role of ncRNAs in intestinal inflammatory diseases in adults, these remain largely unexplored in NEC. In this article, we review the information on ncRNAs that have been specifically identified in NEC or have been noted in other inflammatory bowel disorders that share some of the histopathological abnormalities seen frequently in NEC. We have assimilated the most current research findings on ncRNAs in intestinal diseases. This is an attempt to explore a novel field that has immense potential for future translational and clinical research in preventing, detecting, and treating NEC.

Various Staphylococcus species colonize skin and upper airways of warm-blooded animals. They compete successfully with many other microorganisms under the hostile and nutrient-poor conditions of these habitats using mechanisms that we are only beginning to appreciate. Small-molecule mediators, whose biosynthesis requires complex enzymatic cascades, so-called secondary metabolites, have emerged as crucial components of staphylococcal microbiome interactions. Such mediators belong to a large variety of compound classes and several of them have attractive properties for future drug development. They include, for instance, bacteriocins such as lanthipeptides, thiopeptides, and fibupeptides that inhibit bacterial competitor species; signaling molecules such as thiolactone peptides that induce or inhibit sensory cascades in other bacteria; or metallophores such as staphyloferrins and staphylopine that scavenge scant transition metal ions. For some secondary metabolites such as the aureusimines, the exact function remains to be elucidated. How secondary metabolites shape the fitness of Staphylococcus species in the complex context of other microbial and host defense factors remains a challenging field of future research. A detailed understanding will help to harness staphylococcal secondary metabolites for excluding the pathogenic species Staphylococcus aureus from the nasal microbiomes of at-risk patients, and it will be instrumental for the development of advanced anti-infective interventions.

Volatile constituents and odor-active compounds of two varieties of Habanero pepper (Capsicum chinense Jacq.) were analyzed by GC–MS, GC–O and AEDA. A total of 118 volatile compounds were obtained from Habanero pepper varieties Mayapan and Jaguar by simultaneous distillation–extraction technique. Compounds such as esters, terpenes, aldehydes, alcohols and ketones comprised 78% of volatiles found in both varieties. By means of AEDA technique, 24 odor-contributing compounds (esters, terpenes, aldehydes and alcohols) were identified. Compounds such as δ-cadinene (FD = 729), 3-methylbutyl 2-methylpropanoate and 3,3-dimethylcyclohexanol (FD = 243) were the major odor-active compounds in Mayapan variety aroma, whereas 3-methylbutyl 2-methylpropanoate (FD = 729) and 2-methylpropyl 2-methylbutanoate, hexyl pentanoate and δ-cadinene (FD = 243) were characteristic in Jaguar variety. An intense pungent odor was notorious in Mayapan variety, due mainly to 3,3-dimethylcyclohexanol. On the basis of FD values, sweet and pungent were characteristic notes in Mayapan variety, whereas sweet and fruity notes were predominant in Jaguar variety. This suggests that aroma variability among Habanero pepper varieties might be related to their genotypic diversity.

Non-destructive testing (NDT) data in civil engineering is regularly used for scientific analysis. However, there is no uniform representation of the data yet. An analysis of distributed data sets across different test objects is therefore too difficult in most cases. To overcome this, we present an approach for an integrated data management of distributed data sets based on Semantic Web technologies. The cornerstone of this approach is an ontology, a semantic knowledge representation of our domain. This NDT-CE ontology is later populated with the data sources. Using the properties and the relationships between concepts that the ontology contains, we make these data sets meaningful also for machines. Furthermore, the ontology can be used as a central interface for database access. Non-domain data sources can be integrated by linking them with the NDT ontology, making them directly available for generic use in terms of digitization. Based on an extensive literature research, we outline the possibilities that result for NDT in civil engineering, such as computer-aided sorting and analysis of measurement data, and the recognition and explanation of correlations. A common knowledge representation and data access allows the scientific exploitation of existing data sources with data-based methods (such as image recognition, measurement uncertainty calculations, factor analysis or material characterization) and simplifies bidirectional knowledge and data transfer between engineers and NDT specialists.

Lugdunin is the first reported nonribosomally synthesized antibiotic from human microbiomes. Its production by the commensal Staphylococcus lugdunensis eliminates the pathogen Staphylococcus aureus from human nasal microbiomes. The cycloheptapeptide lugdunin is the founding member of the new class of fibupeptide antibiotics, which have a novel mode of action and represent promising new antimicrobial agents. How S. lugdunensis releases and achieves producer self-resistance to lugdunin has remained unknown., Lugdunin is the first reported nonribosomally synthesized antibiotic from human microbiomes. Its production by the commensal Staphylococcus lugdunensis eliminates the pathogen Staphylococcus aureus from human nasal microbiomes. The cycloheptapeptide lugdunin is the founding member of the new class of fibupeptide antibiotics, which have a novel mode of action and represent promising new antimicrobial agents. How S. lugdunensis releases and achieves producer self-resistance to lugdunin has remained unknown. We report that two ABC transporters encoded upstream of the lugdunin-biosynthetic operon have distinct yet overlapping roles in lugdunin secretion and self-resistance. While deletion of the lugEF transporter genes abrogated most of the lugdunin secretion, the lugGH transporter genes had a dominant role in resistance. Yet all four genes were required for full-level lugdunin resistance. The small accessory putative membrane protein LugI further contributed to lugdunin release and resistance levels conferred by the ABC transporters. Whereas LugIEFGH also conferred resistance to lugdunin congeners with inverse structures or with amino acid exchange at position 6, they neither affected the susceptibility to a lugdunin variant with an exchange at position 2 nor to other cyclic peptide antimicrobials such as daptomycin or gramicidin S. The obvious selectivity of the resistance mechanism raises hopes that it will not confer cross-resistance to other antimicrobials or to optimized lugdunin derivatives to be used for the prevention and treatment of S. aureus infections.

Cytokines and growth factors play diverse roles in the uninflamed fetal/neonatal intestinal mucosa and in the development of inflammatory bowel injury during necrotizing enterocolitis (NEC). During gestational development and the early neonatal period, the fetal/premature intestine is exposed to high levels of many "inflammatory" cytokines and growth factors, first via swallowed amniotic fluid in utero and then, after birth, in colostrum and mother's milk. This article reviews the dual, seemingly counter-intuitive roles of cytokines, where these agents play a "trophic" role and promote maturation of the uninflamed mucosa, but can also cause inflammation and promote intestinal injury during NEC.

Background Thrombocytopenia is frequently encountered in infants with necrotizing enterocolitis (NEC). To develop a preclinical model of NEC-related thrombocytopenia, we measured serial platelet counts in 10-day-old (P10) mouse pups with trinitrobenzene sulfonic acid (TNBS)-induced NEC-like injury. We also measured platelet volume indices, immature platelet fraction (IPF), and megakaryocyte number/ploidy in these animals. Methods Platelet counts, platelet volume indices, and IPF were measured in control (N=65) and TNBS-treated pups (N=104) using an automated hematology analyzer. Bone marrow megakaryocyte number, ploidy and CD41 expression were measured by flow cytometry. These findings were confirmed in a small cohort of P3 mice with NEC-like injury. Results Murine pups with TNBS-mediated NEC-like injury developed thrombocytopenia at 15–24h after exposure to TNBS. Intestinal injury was associated with increased platelet volume indices (mean platelet volume, platelet-to-large cell ratio, and platelet distribution width), and IPF, indicating increased thrombopoiesis. These mice also showed increased megakaryocyte number, ploidy, and CD41 expression, indicating increased megakaryocyte differentiation. Conclusions Similar to human NEC, murine NEC-like injury was also associated with decreased platelet counts. There was evidence of increased megakaryocyte differentiation and thrombopoiesis, which favors peripheral consumption of platelets as the likely mechanism of thrombocytopenia in these animals, over decreased platelet production.

In recent decades, some quinoxaline 1,4-di-N-oxide derivatives have been shown to have better trypanocidal activity than the reference drugs; however, their mechanism of action is not yet clear, although it is suggested that they mainly produce reactive oxygen species that cause oxidative stress and parasite death. Trypanosoma cruzi relies on the enzyme trypanothione reductase, among others, to defend itself against oxidative stress. With the aim of contributing to the elucidation of the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives on Trypanosoma cruzi, this study was carried out to evaluate the effect of methyl 2-amide-3-methylquinoxaline-7-carboxylate 1,4-di-N-oxide (compound M-8) on the expression of the trypanothione reductase gene in an in vitro model on Trypanosoma cruzi epimastigotes of the CL-Brener strain. The results show that compound M-8 does not cause a significant effect on the trypanothione reductase gene, suggesting a mechanism of action not related to oxidative stress.

We have shown previously that enteral administration of 2, 4, 6-trinitrobenzene sulfonic acid in 10-d-old C57BL/6 pups produces an acute necrotizing enterocolitis with histopathological and inflammatory changes similar to human necrotizing enterocolitis (NEC). To determine whether murine neonatal 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-mediated intestinal injury could be used as a NEC model, we compared gene expression profiles of TNBS-mediated intestinal injury and NEC.Whole-genome microarray analysis was performed on proximal colon from control and TNBS-treated pups (n = 8/group). For comparison, we downloaded human microarray data of NEC (n = 5) and surgical control (n = 4) from a public database. Data were analyzed using the software programs Partek Genomics Suite and Ingenuity Pathway Analysis.We detected extensive changes in gene expression in murine TNBS-mediated intestinal injury and human NEC. Using fold-change cut-offs of ±1.5, we identified 4,440 differentially-expressed genes (DEGs) in murine TNBS-mediated injury and 1,377 in NEC. Murine TNBS-mediated injury and NEC produced similar changes in expression of orthologous genes (r = 0.611, P0.001), and also activated nearly-identical biological processes and pathways. Lipopolysaccharide was top predicted upstream regulator in both the murine and human datasets.Murine neonatal TNBS-mediated enterocolitis and human NEC activate nearly-identical biological processes, signaling pathways, and transcriptional networks.

BackgroundPremature infants often develop enteric dysbiosis with a preponderance of Gammaproteobacteria, which has been related to adverse clinical outcomes. We investigated the relationship between increasing fecal Gammaproteobacteria and mucosal inflammation, measured by fecal calprotectin (FC).MethodsStool samples were collected from very-low-birth weight (VLBW) infants at ≤2, 3, and 4 weeks' postnatal age. Fecal microbiome was surveyed using polymerase chain reaction amplification of the V4 region of 16S ribosomal RNA, and FC was measured by enzyme immunoassay.ResultsWe enrolled 45 VLBW infants (gestation 27.9 ± 2.2 weeks, birth weight 1126 ± 208 g) and obtained stool samples at 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. FC was positively correlated with the genus Klebsiella (r = 0.207, p = 0.034) and its dominant amplicon sequence variant (r = 0.290, p = 0.003), but not with the relative abundance of total Gammaproteobacteria. Klebsiella colonized the gut in two distinct patterns: some infants started with low Klebsiella abundance and gained these bacteria over time, whereas others began with very high Klebsiella abundance.ConclusionIn premature infants, FC correlated with relative abundance of a specific pathobiont, Klebsiella, and not with that of the class Gammaproteobacteria. These findings indicate a need to define dysbiosis at genera or higher levels of resolution.

The developing neonate is exposed to a plethora of antigens and must evolve innate and adaptive immune responses to combat pathogenic microorganisms and at the same time, develop tolerance to self-antigens and commensal microbes. While some components of the immune system are functionally at par with adults, immaturity in others may result in a state of immunodeficiency in the neonate. This chapter highlights the qualitative and quantitative differences in distribution and function of leukocyte populations that together shape the immune responses in the fetus, neonate and the adult. Knowledge of these differences may enable a better understanding of the inherent susceptibility of the neonate to various infections.

Although Balamuthia mandrillaris was identified more than two decades ago as an agent of fatal granulomatous encephalitis in humans and other animals, little is known about its ecological niche, biological behavior in the environment, food preferences and predators, if any. When infecting humans or other animals, Balamuthia feeds on tissues; and in vitro culture, it feeds on mammalian cells (monkey kidney cells, human lung fibroblasts, and human microvascular endothelial cells). According to recent reports, it is believed that Balamuthia feeds on small amebae, for example, Acanthamoeba that are present in its ecological niche. To test this hypothesis, we associated Balamuthia on a one-on-one basis with selected protozoa and algae. We videotaped the behavior of Balamuthia in the presence of a potential prey, its ability to hunt and attack its food, and the time required to eat and cause damage to the target cell by direct contact. We found that B. mandrillaris ingested trophozoites of Naegleria fowleri, Naegleria gruberi, Acanthamoeba spp., Trypanosoma cruzi epimastigotes, Toxoplasma gondii tachyzoites, and Giardia. However, it did not feed on Acanthamoeba cysts or algae. Balamuthia caused cytolysis of T. cruzi epimastigotes and T. gondii tachyzoites by direct contact. Balamuthia trophozoites and cysts were, however, eaten by Paramecium sp.

We conducted a retrospective study designed to assess the impact of antenatal combined treatment with betamethasone and TRH on preterm neonates receiving prophylactic Exosurf at birth. Of 71 neonates entered in the study, 35 received Exosurf alone and 36 were exposed prenatally to both hormones and also received Exosurf. Gestational age and birth weight were comparable in both groups (29.0 ± 2.9 weeks and 1.17 ± 0.35 kg versus 29.0 ± 3.2 weeks and 1.15 ± 0.34 kg, mean ± SD, respectively). Likewise, the proportion of neonates intubated at 72 h after birth and their ventilatory settings at that time were similar. Significant decreases of retinopathy of prematurity and death or need for mechanical ventilation at 28 days were noted in surfactant-treated neonates exposed to prenatal hormones. However, severe PIVH, PDA and need for supplemental O2 beyond 28 days after birth occurred in the same proportion of neonates from either group. Although overall mortality and air leaks occurred less frequently in neonate...

To compare the efficacy and safety of two surfactant preparations in the treatment of respiratory distress syndrome (RDS).We conducted a randomized, masked comparison trial at 21 centers. Infants with RDS who were undergoing mechanical ventilation were eligible for treatment with two doses of either a synthetic (Exosurf) or natural (Infasurf) surfactant if the ratio of arterial to alveolar partial pressure of oxygen was less than or equal to 0.22. Crossover treatment was allowed within 96 hours of age if severe respiratory failure (defined as two consecutive arterial/alveolar oxygen tension ratiosor = 0.10) persisted after two doses of the randomly assigned surfactant. Four primary outcome measures of efficacy (the incidence of pulmonary air leak (or = 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of survival without bronchopulmonary dysplasia (BPD) at 28 days after birth) were compared by means of linear regression techniques.The primary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study surfactant. Preentry demographic characteristics and respiratory status were similar for the two treatment groups, except for a small but significant difference in mean gestational age (0.5 week) that favored the infasurf treatment group. Pulmonary air leak (or = 7 days) occurred in 21% of Exosurf- and 11% of infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; por = 0.0001). During the 72 hours after the initial surfactant treatment, the average fraction of inspired oxygen (+/-SEM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for infasurf-treated infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p0.0001); the average mean airway pressure (+/-SEM) was 8.6 +/- 0.1 cm H2O; for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infants (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H2O; p0.0001). The incidences of RDS-related death, total respiratory death, death to discharge, and survival without bronchopulmonary dysplasia at 28 days after birth did not differ. The number of days of more than 30% inspired oxygen and of assisted ventilation, but not the duration of hospitalization, were significantly lower in Infasurf-treated infants.Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak complications.

El tema de investigación de esta tesis es el desarrollo de un material de origen polimérico sustentable proveniente de los huesos y cartílagos de las aves de corral de los cuales se obtiene el colágeno que es esencial para hacer la polimerización por condensación, que pueda ser aplicado en la manufactura de partes automotrices. El problema que se quiere resolver con este trabajo es reducir el impacto que representan las autopartes fabricadas con polímeros de origen fósil desde su obtención, procesamiento hasta su desecho, tal problemática involucra un alto consumo de recursos energéticos en sus primeras etapas del ciclo de vida y un consumo de energía adicional en su reciclaje además de la contaminación ambiental que producen las partes que no se reciclan. Los biopolímeros a base de colágeno no se han usado en autopartes debido a que no se ha considerado el uso de materiales que ayuden a mejorar sus propiedades mecánicas y térmicas. Para resolver este problema se uso el bórax, la grenetina y un retardante a la flama, en conjunto con los parámetros de tiempo y temperatura controlados para obtener las resistencias deseadas. La investigación se realizó en base a los fundamentos de la polimerización que en junto con la metodología diseño de experimentos se logró obtener la mejor combinación de los principales componentes del biopolímero. Los mayores hallazgos fueron la buena resistencia mecánica y térmica del biopolímero ligeramente superior a un polímero de uso automotriz como el polipropileno. La aportación de este trabajo es la obtención de un material amigable con el medio ambiente que cumple con normas automotrices en lo referente a la flamabilidad, envejecimiento y resistencia al calor, el cual se aplicó en el diseño y la manufactura de una cortina automotriz, como una opción al problema de la incandescencia que produce la luz del sol al conducir o de viajar en coche. The investigation theme of this thesis is the development of a material of sustainable polymeric origin coming from poultry bones and cartilage of which obtains the collagen that is essential to make the step condensation in order to apply it in automotive parts manufacturing. The problem that wants to solve with this work is reducing the impact that represents the automotive parts fabricated of fossil origin polymers from their obtaining, processing and disposal, such problem involves a high consumption of energetic resources in their first stages of lifecycle and an additional consumption of energy in their recycling besides of the environmental pollution that produce the automotive part that do not recycle. The biopolymers based on collagen have not used in automotive parts due to it has not considered the using of materials that help theirs mechanical and thermal properties. To solve this problem, it used borax, grenetin and a flame retarder altogether with controlled time and temperature parameters to obtain the desired strengths. The investigation made based on polymerization fundamentals that together with design of experiments methodology, it achieved to get the best combination of the main components of the biopolymer. The major findings were the good mechanical and thermal strength of the biopolymer slightly superior to an automotive polymer like polypropylene. The contribution of this work is the obtaining of an environmental friendly material that meets the automotive standards regarding to flammability, aging and thermal strength, which applied in the design and manufacture of an automotive blind, as an option to the incandescence that sunlight produces when driving or traveling by car.