Clinical and prostate multiparametric magnetic resonance imaging findings as predictors of general and clinically significant prostate cancer risk: A retrospective single-center study.

Background: To evaluate the predictive values of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2), prostate-specific antigen (PSA) level, PSA density (PSAD), digital rectal examination findings, and prostate volume, individually and in combination, for the detection of prostate cancer (PCa) in biopsy-naive patients. Methods: We retrospectively analyzed 630 patients who underwent transrectal systematic prostate biopsy following prostate multiparametric magnetic resonance imaging. A standard 12-core biopsy procedure was performed. Univariate and multivariate analyses were performed to determine the significant predictors of clinically significant cancer but not PCa. Results: The median age, PSA level, and PSAD were 70 years, 8.6 ng/mL, and 0.18 ng/mL/mL, respectively. A total of 374 (59.4%) of 630 patients were biopsy-positive for PCa, and 241 (64.4%) of 374 were diagnosed with clinically significant PCa (csPCa). The PI-RADS v2 score and PSAD were independent predictors of PCa and csPCa. The PI-RADS v2 score of 5 regardless of the PSAD value, or PI-RADS v2 score of 4 plus a PSAD of <0.3 ng/mL/mL, was associated with the highest csPCa detection rate (36.1%-82.1%). Instead, the PI-RADS v2 score of <3 and PSAD of <0.3 ng/mL/mL yielded the lowest risk of csPCa. Conclusion: The combination of the PI-RADS v2 score and PSAD could prove to be a helpful and reliable diagnostic tool before performing prostate biopsies. Patients with a PI-RADS v2 score of <3 and PSAD of <0.3 ng/mL/mL could potentially avoid a prostate biopsy.

Human intelectin-1 (ITLN1) genetic variation and intestinal expression.

Intelectins are ancient carbohydrate binding proteins, spanning chordate evolution and implicated in multiple human diseases. Previous GWAS have linked SNPs in ITLN1 (also known as omentin) with susceptibility to Crohn's disease (CD); however, analysis of possible functional significance of SNPs at this locus is lacking. Using the Ensembl database, pairwise linkage disequilibrium (LD) analyses indicated that several disease-associated SNPs at the ITLN1 locus, including SNPs in CD244 and Ly9, were in LD. The alleles comprising the risk haplotype are the major alleles in European (67%), but minor alleles in African superpopulations. Neither ITLN1 mRNA nor protein abundance in intestinal tissue, which we confirm as goblet-cell derived, was altered in the CD samples overall nor when samples were analyzed according to genotype. Moreover, the missense variant V109D does not influence ITLN1 glycan binding to the glycan ß-D-galactofuranose or protein-protein oligomerization. Taken together, our data are an important step in defining the role(s) of the CD-risk haplotype by determining that risk is unlikely to be due to changes in ITLN1 carbohydrate recognition, protein oligomerization, or expression levels in intestinal mucosa. Our findings suggest that the relationship between the genomic data and disease arises from changes in CD244 or Ly9 biology, differences in ITLN1 expression in other tissues, or an alteration in ITLN1 interaction with other proteins.

Reliability of multi-purpose offshore-facilities: Present status and future direction in Australia.

Sustainable use of the ocean for food and energy production is an emerging area of research in different countries around the world. This goal is pursued by the Australian aquaculture, offshore engineering and renewable energy industries, research organisations and the government through the "Blue Economy Cooperative Research Centre". To address the challenges of offshore food and energy production, leveraging the benefits of co-location, vertical integration, infrastructure and shared services, will be enabled through the development of novel Multi-Purpose Offshore-Platforms (MPOP). The structural integrity of the designed systems when being deployed in the harsh offshore environment is one of the main challenges in developing the MPOPs. Employing structural reliability analysis methods for assessing the structural safety of the novel aquaculture-MPOPs comes with different limitations. This review aims at shedding light on these limitations and discusses the current status and future directions for structural reliability analysis of a novel aquaculture-MPOP considering Australia's unique environment. To achieve this aim, challenges which exist at different stages of reliability assessment, from data collection and uncertainty quantification to load and structural modelling and reliability analysis implementation, are discussed. Furthermore, several solutions to these challenges are proposed based on the existing knowledge in other sectors, and particularly from the offshore oil and gas industry. Based on the identified gaps in the review process, potential areas for future research are introduced to enable a safer and more reliable operation of the MPOPs.

Malnutrition, poor post-natal growth, intestinal dysbiosis and the developing lung.

In extremely preterm infants, poor post-natal growth, intestinal dysbiosis and bronchopulmonary dysplasia are common, and each is associated with long-term complications. The central hypothesis that this review will address is that these three common conditions are interrelated. Challenges to studying this hypothesis include the understanding that malnutrition and poor post-natal growth are not synonymous and that there is not agreement on what constitutes a normal intestinal microbiota in this evolutionarily new population. If this hypothesis is supported, further study of whether "correcting" intestinal dysbiosis in extremely preterm infants reduces postnatal growth restriction and/or bronchopulmonary dysplasia is indicated.

Determining the prognostic significance of IKKα in prostate cancer.

BACKGROUND: As the survival of castration-resistant prostate cancer (CRPC) remains poor, and the nuclear factor-κB (NF-κB) pathways play key roles in prostate cancer (PC) progression, several studies have focused on inhibiting the NF-κB pathway through generating inhibitory κB kinase subunit α (IKKα) small molecule inhibitors. However, the identification of prognostic markers able to discriminate which patients could benefit from IKKα inhibitors is urgently required. The present study investigated the prognostic value of IKKα, IKKα phosphorylated at serine 180 (p-IKKα S180) and threonine 23 (p-IKKα T23), and their relationship with the androgen receptor (AR) and Ki67 proliferation index to predict patient outcome. METHODS: A cohort of 115 patients with hormone-naïve PC (HNPC) and CRPC specimens available were used to assess tumor cell expression of proteins within both the cytoplasm and the nucleus by immunohistochemistry. The expression levels were dichotomized (low vs high) to determine the associations between IKKα, AR, Ki67, and patients'Isurvival. In addition, an analysis was performed to assess potential IKKα associations with clinicopathological and inflammatory features, and potential IKKα correlations with other cancer pathways essential for CRPC growth. RESULTS: High levels of cytoplasmic IKKα were associated with a higher cancer-specific survival in HNPC patients with low AR expression (hazards ratio [HR], 0.33; 95% confidence interval [CI] log-rank, 0.11-0.98; P = .04). Furthermore, nuclear IKKα (HR, 2.60; 95% CI, 1.27-5.33; P = .01) and cytoplasmic p-IKKα S180 (HR, 2.10; 95% CI, 1.17-3.76; P = .01) were associated with a lower time to death from recurrence in patients with CRPC. In addition, high IKKα expression was associated with high levels of T-cells (CD3+ P = .01 and CD8+ P = .03) in HNPC; however, under castration conditions, high IKKα expression was associated with high levels of CD68+ macrophages (P = .04), higher Gleason score (P = .01) and more prostate-specific antigen concentration (P = .03). Finally, we identified crosstalk between IKKα and members of the canonical NF-κB pathway in the nucleus of HNPC. Otherwise, IKKα phosphorylated by noncanonical NF-κB and Akt pathways correlated with members of the canonical NF-κB pathway in CRPC. CONCLUSION: The present study reports that patients with CRPC expressing high levels of nuclear IKKα or cytoplasmic p-IKKα S180, which associated with a lower time to death from recurrence, may benefit from IKKα inhibitors.

Lipocalin-2 is an anorexigenic signal in primates.

In the mouse, the osteoblast-derived hormone Lipocalin-2 (LCN2) suppresses food intake and acts as a satiety signal. We show here that meal challenges increase serum LCN2 levels in persons with normal or overweight, but not in individuals with obesity. Postprandial LCN2 serum levels correlate inversely with hunger sensation in challenged subjects. We further show through brain PET scans of monkeys injected with radiolabeled recombinant human LCN2 (rh-LCN2) and autoradiography in baboon, macaque, and human brain sections, that LCN2 crosses the blood-brain barrier and localizes to the hypothalamus in primates. In addition, daily treatment of lean monkeys with rh-LCN2 decreases food intake by 21%, without overt side effects. These studies demonstrate the biology of LCN2 as a satiety factor and indicator and anorexigenic signal in primates. Failure to stimulate postprandial LCN2 in individuals with obesity may contribute to metabolic dysregulation, suggesting that LCN2 may be a novel target for obesity treatment.

Obesity has reached epidemic proportions worldwide and affects more than 40% of adults in the United States. People with obesity have a greater likelihood of developing type 2 diabetes, cardiovascular disease or chronic kidney disease. Changes in diet and exercise can be difficult to follow and result in minimal weight loss that is rarely sustained overtime. In fact, in people with obesity, weight loss can lower the metabolism leading to increased weight gain. New drugs may help some individuals achieve 5 to 10% weight loss but have side effects that prevent long-term use. Previous studies in mice show that a hormone called Lipocalin-2 (LCN2) suppresses appetite. It also reduces body weight and improves sugar metabolism in the animals. But whether this hormone has the same effects in humans or other primates is unclear. If it does, LCN2 might be a potential obesity treatment. Now, Petropoulou et al. show that LCN2 suppressed appetite in humans and monkeys. In human studies, LCN2 levels increased after a meal in individuals with normal weight or overweight, but not in individuals with obesity. Higher levels of LCN2 in a person's blood were also associated with a feeling of reduced hunger. Using brain scans, Petropoulou et al. showed that LCN2 crossed the blood-brain barrier in monkeys and bound to the hypothalamus, the brain center regulating appetite and energy balance. LCN2 also bound to human and monkey hypothalamus tissue in laboratory experiments. When injected into monkeys, the hormone suppressed food intake and lowered body weight without toxic effects in short-term studies. The experiments lay the initial groundwork for testing whether LCN2 might be a useful treatment for obesity. More studies in animals will help scientists understand how LCN2 works, which patients might benefit, how it would be given to patients and for how long. Clinical trials would also be needed to verify whether it is an effective and safe treatment for obesity.

Differences and Similarities in the Peptide Profile of Preterm and Term Mother's Milk, and Preterm and Term Infant Gastric Samples.

Our previous studies revealed that milk proteases begin to hydrolyze proteins in the mammary gland and that proteolytic digestion continues within the infant stomach. No research has measured how the release of milk peptides differs between the gastric aspirates of term and premature infants. This study examined the presence of milk peptides in milk and gastric samples from term and preterm infants using an Orbitrap Fusion Lumos mass spectrometer. Samples were collected from nine preterm-delivering and four term-delivering mother-infant pairs. Our study reveals an increased count and ion abundance of peptides and decreased peptide length from mother's milk to the infant stomach, confirming that additional break-down of the milk proteins occurred in both preterm and term infants' stomachs. Protein digestion occurred at a higher level in the gastric contents of term infants than in gastric contents of preterm infants. An amino acid cleavage site-based enzyme analysis suggested that the observed higher proteolysis in the term infants was due to higher pepsin/cathepsin D activity in the stomach. Additionally, there was a higher quantity of antimicrobial peptides in term infant gastric contents than in those of preterm infants, which could indicate that preterm infants benefit less from bioactive peptides in the gut.

Inflammatory infiltration is associated with AR expression and poor prognosis in hormone naïve prostate cancer.

BACKGROUND: Tumor microenvironment inflammatory infiltration is proposed as a protumorigenic mechanism for prostate cancer with proinflammatory cytokines stimulating androgen receptor (AR) activity. However, association with patient prognosis remains unclear. This study derives an inflammatory gene signature associated with AR expression and investigates CD3+ and CD8+ T-lymphocyte infiltration association with AR and prognosis. METHODS: Gene profiling of inflammatory related genes was performed on 71 prostate biopsies. Immunohistochemistry on 243 hormone-naïve prostate cancers was performed for CD3, CD8, AR, and phosphorylated AR tumor expression. RESULTS: Multiple proinflammatory genes were differentially expressed in association with high AR expression compared with low AR expression including PI3KCA and MAKP8 (adjusted P < .05). High CD3+ and high CD8+ infiltration associated with reduced cancer-specific survival (P = .018 and P = .020, respectively). High CD3+ infiltration correlated with high tumor cytoplasmic AR expression and if assessed together, they associated with reduced cancer-specific and 5-year survival from 90% to 56% (P = .000179). High CD8+ cytotoxic infiltration associated with high androgen-independent tumor nuclear AR serine 213 phosphorylation (correlation coefficient = 0.227; P = .003) and when assessed together associated with poor clinico-pathological features including perineural invasion (P = .001). Multiple genes involved in proinflammatory signaling pathways are upregulated in high AR expressing prostate samples. CONCLUSION: T-lymphocyte infiltration in hormone-naïve disease associates with androgen-independent driven disease and provides possible therapeutic targets to reduce transformation from hormone-naïve to castrate-resistant disease.

Androgen receptor phosphorylation at serine 81 and serine 213 in castrate-resistant prostate cancer.

BACKGROUND: Despite increases in diagnostics and effective treatments, over 300,000 men die from prostate cancer highlighting the need for specific and differentiating biomarkers. AR phosphorylation associates with castrate-resistance, with pARser213 promoting transcriptional activity. We hypothesise that combined pARser81 and pARser213 reduces survival and would benefit from dual-targeting androgen-dependent and Akt-driven disease. METHODS: Immunohistochemistry and immunofluorescence were performed on matched hormone-naive and castrate-resistant prostate cancer samples. TempO-Seq gene profiling was analysed using DESeq2 package. LNCaP-AI cells were stimulated with DHT or EGF. WST-1 assays were performed to determine effects of Enzalutamide and BKM120 on cell viability. RESULTS: Following the development of castrate-resistance, pARser81 expression reduced and pARser213 expression increased. Castrate-resistance pARser81 expression was not associated with survival but high pARser213 expression was associated with reduced survival from relapse. Combined high pARser81 and pARser213 was associated with reduced survival from relapse. pARser81 expression was induced by 10 nM DHT or 10 nM EGF and pARser213 expression was induced by treatment with 10 nM EGF in LNCaP-AI cells. Cell viability was reduced following treatment with 10 nM Enzalutamide and 10 nM BKM120. Eight genes were differentially expressed between hormone-naive and castrate-resistant tumours and twenty-five genes were differentially expressed between castrate-resistant tumours with high and low pARser213 expression. CONCLUSION: Combined pARser81 and pARser213 provides a novel prognostic biomarker for castrate-resistant disease and a potential predictive and therapeutic target for prostate cancer. Further studies will be required to investigate the combined effects of targeting AR and PI3K/AKT signalling.

Intestinal Dysbiosis and the Developing Lung: The Role of Toll-Like Receptor 4 in the Gut-Lung Axis.

Background: In extremely premature infants, postnatal growth restriction (PNGR) is common and increases the risk of developing bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). Mechanisms by which poor nutrition impacts lung development are unknown, but alterations in the gut microbiota appear to play a role. In a rodent model, PNGR plus hyperoxia causes BPD and PH and increases intestinal Enterobacteriaceae, Gram-negative organisms that stimulate Toll-like receptor 4 (TLR4). We hypothesized that intestinal dysbiosis activates intestinal TLR4 triggering systemic inflammation which impacts lung development. Methods: Rat pups were assigned to litters of 17 (PNGR) or 10 (normal growth) at birth and exposed to room air or 75% oxygen for 14 days. Half of the pups were treated with the TLR4 inhibitor TAK-242 from birth or beginning at day 3. After 14 days, pulmonary arterial pressure was evaluated by echocardiography and hearts were examined for right ventricular hypertrophy (RVH). Lungs and serum samples were analyzed by western blotting and immunohistochemistry. Results: Postnatal growth restriction + hyperoxia increased pulmonary arterial pressure and RVH with trends toward increased plasma IL1ß and decreased IκBα, the inhibitor of NFκB, in lung tissue. Treatment with the TLR4 inhibitor attenuated PH and inflammation. Conclusion: Postnatal growth restriction induces an increase in intestinal Enterobacteriaceae leading to PH. Activation of the TLR4 pathway is a promising mechanism by which intestinal dysbiosis impacts the developing lung.

Peptidomics Analysis of Milk Protein-Derived Peptides Released over Time in the Preterm Infant Stomach.

Over the course of milk digestion, native milk proteases and infant digestive proteases fragment intact proteins into peptides with potential bioactivity. This study investigated the release of peptides over 3 h of gastric digestion in 14 preterm infant sample sets. The peptide content was extracted and analyzed from milk and gastric samples via Orbitrap tandem mass spectrometry. The relative ion intensity (abundance) and count of peptides in each sample were compared over time and between infants fed milk fortified with bovine milk fortifier and infants fed unfortified milk. Bioactivity of the identified peptides was predicted by sequence homology to known bioactive milk peptides. Both total and bioactive peptide abundance and count continuously increased over 3 h of gastric digestion. After accounting for infant weight, length, and postconceptual age, fortification of milk limited the release of peptides from human milk proteins. Peptides that survived further gastric digestion after their initial release were structurally more similar to bioactive peptides than nonsurviving peptides. This work is the first to provide a comprehensive profile of milk peptides released during gastric digestion over time, which is an essential step in determining which peptides are most likely to be biologically relevant in the infant. Data are available via ProteomeXchange with identifier PXD012192.

Probiotics and the prevention of necrotizing enterocolitis.

BACKGROUND: Immaturity of the host immune system and alterations in the intestinal microbiome appear to be key factors in the pathogenesis of necrotizing enterocolitis (NEC). The aim of this paper is to weigh the evidence for the use of probiotics to prevent NEC in premature infants. METHODS: Animal studies, randomized controlled trials, observational cohort studies and meta-analyses involving administration of probiotic products for the prevention of NEC were reviewed. This review of the evidence summarizes the available preclinical and clinical data. RESULTS: In animal models probiotic microbes alter the intestinal microbiome, decrease inflammation and intestinal permeability and decrease the incidence and severity of experimental NEC. In randomized, placebo-controlled trials and cohort studies of premature infants, probiotic microbes decrease the risk of NEC, death and sepsis. CONCLUSION: Evidence is strong for the prevention of NEC with the use of combination probiotics in premature infants who receive breast milk. The potential risks and benefits of probiotic administration to premature infants should be carefully reviewed with parents. TYPE OF STUDY: Therapeutic. LEVEL OF EVIDENCE: I.

A review on the interactions between the tumor microenvironment and androgen receptor signaling in prostate cancer.

Prostate cancer growth is controlled by androgen receptor signaling via both androgen-dependent and androgen-independent pathways. Furthermore, the prostate is an immune competent organ with inflammatory changes both within the systemic and local environment contributing to the reprogramming of the prostatic epithelium with consistently elevated lymphocyte infiltration and proinflammatory cytokines being found in prostate cancer. The crosstalk between the tumor microenvironment and androgen receptor signaling is complex with both protumorigenic and antitumorigenic roles observed. However, despite an increase in immune checkpoint inhibitors and inflammatory signaling blockades available for a range of cancer types, we are yet to see substantial progress in the treatment of prostate cancer. Therefore, this review aims to summarize the tumor microenvironment and its impact on androgen receptor signaling in prostate cancer.

Somatic growth and the risks of bronchopulmonary dysplasia and pulmonary hypertension: connecting epidemiology and physiology 1.

In the premature infant, poor growth in utero (fetal growth restriction) and in the first weeks of life (postnatal growth restriction) are associated with increased risk for bronchopulmonary dysplasia and pulmonary hypertension. In this review, we summarize the epidemiologic data supporting these associations, present a novel rodent model of postnatal growth restriction, and review 5 promising mechanisms by which poor nutrition may affect the developing lung. These observations support the hypothesis that nutritional and (or) pharmacologic interventions early in life may be able to decrease risk of the pulmonary complications of extreme prematurity.

Release of functional peptides from mother's milk and fortifier proteins in the premature infant stomach.

Digestion of milk proteins in the premature infant stomach releases functional peptides; however, which peptides are present has not been reported. Premature infants are often fed a combination of human milk and bovine milk fortifiers, but the variety of functional peptides released from both human and bovine milk proteins remains uncharacterized. This study applied peptidomics to investigate the peptides released in gastric digestion of mother's milk proteins and supplemental bovine milk proteins in premature infants. Peptides were assessed for homology against a database of known functional peptides-Milk Bioactive Peptide Database. The peptidomic data were analyzed to interpret which proteases most likely released them from the parent protein. We identified 5,264 unique peptides from bovine and human milk proteins within human milk, fortifier or infant gastric samples. Plasmin was predicted to be the most active protease in milk, while pepsin or cathepsin D were predicted to be most active in the stomach. Alignment of the peptide distribution showed a different digestion pattern between human and bovine proteins. The number of peptides with high homology to known functional peptides (antimicrobial, angiotensin-converting enzyme-inhibitory, antioxidant, immunomodulatory, etc.) increased from milk to the premature infant stomach and was greater from bovine milk proteins than human milk proteins. The differential release of bioactive peptides from human and bovine milk proteins may impact overall health outcomes in premature infants.

Drug screening of biopsy-derived spheroids using a self-generated microfluidic concentration gradient.

Performing drug screening of tissue derived from cancer patient biopsies using physiologically relevant 3D tumour models presents challenges due to the limited amount of available cell material. Here, we present a microfluidic platform that enables drug screening of cancer cell-enriched multicellular spheroids derived from tumour biopsies, allowing extensive anticancer compound screening prior to treatment. This technology was validated using cell lines and then used to screen primary human prostate cancer cells, grown in 3D as a heterogeneous culture from biopsy-derived tissue. The technology enabled the formation of repeatable drug concentration gradients across an array of spheroids without external fluid actuation, delivering simultaneously a range of drug concentrations to multiple sized spheroids, as well as replicates for each concentration. As proof-of-concept screening, spheroids were generated from two patient biopsies and a panel of standard-of-care compounds for prostate cancer were tested. Brightfield and fluorescence images were analysed to provide readouts of spheroid growth and health, as well as drug efficacy over time. Overall, this technology could prove a useful tool for personalised medicine and future drug development, with the potential to provide cost- and time-reduction in the healthcare delivery.

Umbilical cord blood metabolomics reveal distinct signatures of dyslipidemia prior to bronchopulmonary dysplasia and pulmonary hypertension.

Pulmonary hypertension (PH) is a common consequence of bronchopulmonary dysplasia (BPD) and remains a primary contributor to increased morbidity and mortality among preterm infants. Unfortunately, at the present time, there are no reliable early predictive markers for BPD-associated PH. Considering its health consequences, understanding in utero perturbations that lead to the development of BPD and BPD-associated PH and identifying early predictive markers is of utmost importance. As part of the discovery phase, we applied a multiplatform metabolomics approach consisting of untargeted and targeted methodologies to screen for metabolic perturbations in umbilical cord blood (UCB) plasma from preterm infants that did ( n = 21; cases) or did not ( n = 21; controls) develop subsequent PH. A total of 1,656 features were detected, of which 407 were annotated by metabolite structures. PH-associated metabolic perturbations were characterized by reductions in major choline-containing phospholipids, such as phosphatidylcholines and sphingomyelins, indicating altered lipid metabolism. The reduction in UCB abundances of major choline-containing phospholipids was confirmed in an independent validation cohort consisting of UCB plasmas from 10 cases and 10 controls matched for gestational age and BPD status. Subanalyses in the discovery cohort indicated that elevations in the oxylipins PGE1, PGE2, PGF2a, 9- and 13-HOTE, 9- and 13-HODE, and 9- and 13-KODE were positively associated with BPD presence and severity. This expansive evaluation of cord blood plasma identifies compounds reflecting dyslipidemia and suggests altered metabolite provision associated with metabolic immaturity that differentiate subjects, both by BPD severity and PH development.

Survival of Immunoglobulins from Human Milk to Preterm Infant Gastric Samples at 1, 2, and 3 h Postprandial.

BACKGROUND: Human milk immunoglobulins (Ig) are an important support for the naïve infant immune system; yet the extent to which these proteins survive within the infant digestive tract, particularly for preterm infants, is poorly studied. OBJECTIVES: Our objective was to evaluate the survival of human milk Igs in the preterm stomach across postprandial time. METHODS: Human milk and infant gastric samples were collected from 11 preterm (23-32 weeks gestational age) mother-infant pairs within 7-98 days postnatal age. Preterm gastric samples were collected 1, 2, and 3 h after the beginning of the feeding. Samples were analyzed for concentration of total IgA (secretory IgA [SIgA]/IgA), total secretory component (SC/SIgA/SIgM), total IgM (SIgM/IgM), and IgG via enzyme-linked immunosorbent assay. Ig-chain fragment peptides were determined using peptidomic analysis. One-way analysis of variance with repeated measures followed by Tukey's multiple comparison tests was applied. RESULTS: Concentrations of total IgA were lower in the gastric contents at 3 h postprandial compared with human milk and gastric contents at 1 and 2 h. Human milk SC/SIgA/SIgM, IgG, and total IgM concentrations remained stable in the preterm stomach across postprandial time. Peptide counts from the Ig alpha-chain and the Ig gamma-chain increased in gastric contents from 1 to 2 h postprandial. Peptide counts from the human milk Ig-chain, Ig-chain, and SC were stable across postprandial time. These peptides from Ig-chains were not present in human milk but were released in the stomach due to their partial degradation. CONCLUSIONS: Human milk total SC (SIgA/SC/SIgM), total IgM, and IgG survived mostly intact through the preterm infant stomach, while total IgA was -partially digested.

Comparison of Human Milk Immunoglobulin Survival during Gastric Digestion between Preterm and Term Infants.

Human milk provides immunoglobulins (Igs) that supplement the passive immune system of neonates; however, the extent of survival of these Igs during gastric digestion and whether this differs between preterm and term infants remains unknown. Human milk, and infant gastric samples at 2 h post-ingestion were collected from 15 preterm (23⁻32 week gestational age (GA)) mother-infant pairs and from 8 term (38⁻40 week of GA) mother-infant pairs within 7⁻98 days postnatal age. Samples were analyzed via ELISA for concentration of total IgA (secretory IgA (SIgA)/IgA), total secretory component (SC/SIgA/SIgM), total IgM (SIgM/IgM), and IgG as well as peptidomics. Total IgA concentration decreased by 60% from human milk to the preterm infant stomach and decreased by 48% in the term infant stomach. Total IgM and IgG concentrations decreased by 33% and 77%, respectively, from human milk to the term infant stomach but were stable in the preterm infant stomach. Release of peptides from all Ig isotypes in the term infant stomach was higher than in the preterm stomach. Overall, the stability of human milk Igs during gastric digestion is higher in preterm infant than in term infants, which could be beneficial for assisting the preterm infants' immature immune system.