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Background: Maternal carotenoid intake during pregnancy may be associated with decreased infantile atopic dermatitis (AD) odds. This study aimed to elucidate the association between maternal and infant carotenoid levels and AD development. Methods: This prospective study included 267 newborns with a family history of allergies as part of the Chiba High-risk Birth Cohort for Allergy study. Serum was collected from the cord blood of mothers at 36 weeks of gestation and 1-year-old infants, together with post-childbirth colostrum and breast milk samples at 1 and 6 months after birth. These were used to determine total and specific carotenoids, α-tocopherol, and retinol levels, and the results were compared between AD-positive and -negative infants. Univariate and multivariate analyses were conducted, and variables were selected for the multivariate analysis using variable importance in projection scores calculated by partial least squares regression. Results: Specific carotenoid levels in the serum and breast milk, and total carotenoids in the maternal blood, were associated with lower odds of AD development at 1 year of age. Seven predictive variables among the carotenoid data were selected for the multivariate analysis. Presence of eczema at 6 months (odds ratio [OR], 34.5; P < 0.0001), maternal blood lutein level (unit OR, 0.002; P = 0.002), and blood lycopene level in infants at 1 year (unit OR, 0.01; P = 0.007) were significantly related to AD at 1 year of age. Conclusions: Carotenoid intake is associated with decreased risk of developing infantile AD. The potential benefits of carotenoid supplementation during pregnancy warrant investigation.

Introduction and importance With the widespread use of laparoscopic inguinal hernia repair, it is known that some clinically evident inguinal hernias lack a peritoneal sac and are referred to as “sacless hernias”. Presentation of case A 61-year-old man presented with a left inguinal bulge. On physical examination, the diagnosis of bilateral inguinal hernias was made, and laparoscopic transabdominal repair was performed. Intraoperatively, the left peritoneal hernia orifice was not identified from the peritoneal cavity and there was only a lipoma. Pressing the lipoma with forceps from inside the peritoneum confirmed the presence of a hernia. The preperitoneal space was opened and the hernia orifice revealed. Discussion The terminology and definition of sacless hernias are poorly defined, even though this is not a rare condition. Consistent with Russell's dogma, there are arguments that any prolapse can only be called a hernia if there is an accompanying peritoneal sac. The proportion of patients with sacless hernias and pure cord lipomas are very similar and these conditions are often confused. Detailed and repeated physical examination may distinguish a sacless hernia from a pure lipoma. A watchful waiting strategy is useful and ensures safety. Conclusion Once the diagnosis of inguinal hernia is made on physical examination, open the preperitoneal cavity if a peritoneal hernia orifice was not identified during laparoscopy., Highlights • The exact terminology and definition of a “sacless hernia” is still unclear and there were very few literatures, despite this situation has been commonly known. • Attention should be paid not to confuse a sacless hernia with a spermatic cord lipoma. Preoperative physical examination and diagnosis is a key to distinguish them. • Once a robust diagnosis of inguinal hernia is made by physical examination, open the preperitoneal cavity if the peritoneal hernia orifice was not identified during laparoscopy.

Chemokine (C-C motif) ligand 17 (CCL17) is a pro-allergic factor: high CCL17 levels in cord blood (CB) precede later allergic predisposition. Short-chain fatty acid (SCFA) treatment during pregnancy has been shown to protect mouse pups against allergic diseases. The maternal microbial metabolome during pregnancy may affect fetal allergic immune responses. We therefore examined the associations between CB CCL17 and gut SCFA levels in healthy pregnant Japanese women. CB CCL17 serum levels at birth, and maternal non-specific IgE levels in maternal sera at 32 weeks of gestation were measured. Maternal stool samples were collected at 12 (n = 59) and 32 (n = 58) weeks of gestation for gut microbiota analysis, based on barcoded 16S rRNA sequencing and metabolite levels. The CB CCL17 levels correlated negatively with butyrate concentrations and positively with isobutyrate at 12 weeks, CB CCL17 correlated positively with valerate and lactate at 32 weeks. Similarly, butyrate levels correlated negatively with maternal non-specific IgE levels, whereas the lactate concentration correlated positively with IgE levels. At 32 weeks, the Shannon diversity index (SDI) of Firmicutes and Proteobacteria correlated negatively with CB CCL17 levels, while those of the total microbiota correlated positively with the CB CCL17 levels. These metabolites may alter fetal immune responses. This study provides the first link between maternal metabolites during pregnancy and the risk of allergic diseases in human offspring.

BACKGROUND: Chemokine (C-C motif) ligand 17 (CCL17; also known as thymus and activation-regulated chemokine or TARC) is a pro-allergic factor, and high CCL17 levels in cord blood (CB) precede the allergic predisposition later in life. Offspring of pregnant mice treated with short-chain fatty acid (SCFA) have been shown to be protected against allergic diseases. The maternal microbial metabolome during pregnancy may affect foetal allergic immune responses. To examine this, the associations between CB CCL17 and gut SCFA levels in pregnant Japanese women were investigated here. METHODS: This study was conducted as part of the Chiba Study of Mother and Child Health; 434 healthy pregnant women were recruited. The CB CCL17 and maternal non-specific IgE levels were measured using CB sera at birth and maternal sera at 32 weeks of gestation. Stool samples were collected from pregnant women at 12 (n = 59) and 32 (n = 58) weeks of gestation and used for gut microbiota analysis, based on barcoded 16S rRNA sequencing and metabolite levels. RESULTS: The CB CCL17 levels correlated negatively with butyrate concentrations at 12 weeks of gestation. In contrast, CB CCL17 levels correlated positively with isobutyrate levels at 12 weeks of gestation, and valerate and lactate concentrations at 32 weeks of gestation in maternal faeces. CONCLUSION: The metabolites in maternal faeces may alter the foetal immune responses. This study provides the first link between maternal metabolites during pregnancy and the risk of allergic diseases in human offspring, even before birth.

Background: The prenatal maternal microbiome, including the gut microbiota, has been suggested to influence the incidence of allergies in offspring. Moreover, epidermal barrier dysfunction in early infancy has been attributed to the development of subsequent allergies. We hypothesized that the prenatal microbiome may affect the gut microbiota, acting as an initial trigger to alter immune development in the foetus. The maternal microbial composition may be linked to the prevalence of dermatitis in early infancy (DEI) of the offspring, leading to subsequent allergic symptoms. Methods: This study was conducted as part of the Chiba Study of Mother and Child Health (C-MACH) birth cohort that was initiated in 2013; 434 healthy pregnant women at

Increasing evidence supports that harmful chemicals accumulating in the human body may pose a significant threat to infant health through foetal exposure. Persistent organic pollutants (POPs) are thought to enhance the risk for later development of allergic disease like atopic dermatitis (AD). However, few studies have evaluated the effect of foetal exposure to various POPs on the development of AD in early infancy. Here, we describe the impact of foetal exposure to a number of POPs on the occurrence of AD in 7-month-old infants. The participants were 81 infants with or without AD who participated in a birth cohort study, where the concentrations of 15 polychlorinated biphenyl (PCBs) congeners, dichlorodiphenyltrichloroethane (p,p'-DDT), dichlorodiphenyldichloroethylene (p,p'-DDE), β-hexachlorocyclohexane (β-HCH), hexachlorobenzene (HCB), cis-nonachlor, trans-nonachlor, mirex, oxychlordane, and 27 polybrominated diphenyl ether (PBDEs) congeners were measured in the umbilical cord tissues collected immediately after birth. At 7 months, 27 of the 81 infants (33.8%) were diagnosed with AD. Of all POPs examined, total concentrations of 27 PBDE congeners were associated with a significantly decreased incidence of AD. Notably, the concentration of 27 PBDEs was significantly lower in AD infants than in non-AD infants (P

Background: There are reports that the maternal diet during pregnancy may affect development of babies' eczema. We sought to investigate the association between the maternal diet during pregnancy and the risk of eczema in infancy in Japan.Methods: A birth cohort was set up at 2 hospitals in Chiba city. Dietary habits concerning fish, butter, margarine, yogurt and natto during pregnancy was obtained from mothers just after delivery. The intake frequencies of these foods were classified into four groups: 1) daily, 2) 2-3 times a week, 3) once a week and 4) once a month or less. Diagnosis of eczema at 6 months of age was made by the presence of an itchy rash that persisted more than two months.Results: Valid data on 650 mother-baby pairs were obtained. No relationship between frequencies of the maternal intake of fish, margarine and yogurt during pregnancy and the onset rate of the babies' eczema were observed. For butter consumption, the incidence of babies' eczema was significantly higher in the group with daily intake than in those with an intake 2-3 times a week or less (p=0.044). For natto, incidence of babies' eczema was significantly lower in the group with everyday intake than those eating it 2-3 times a week or less (p=0.020).Conclusions: High frequency intake of natto during pregnancy possibly reduces the incidence of eczema in children at 6 months of age.

// Yoshitaka Sato 1 , Shingo Ochiai 1 , Takayuki Murata 1 , Teru Kanda 2 , Fumi Goshima 1 and Hiroshi Kimura 1 1 Department of Virology, Nagoya University Graduate School of Medicine, Showa-Ku, Nagoya 466-8550, Japan 2 Division of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Aoba-Ku, Sendai 981-8558, Japan Correspondence to: Hiroshi Kimura, email: hkimura@med.nagoya-u.ac.jp Keywords: EBV, LMP1, cell competition, cell-cell communication, gastric cancer Received: July 06, 2016 Accepted: March 28, 2017 Published: April 10, 2017 ABSTRACT Epstein-Barr virus (EBV) latently infects malignant epithelial cells in approximately 10% of all gastric cancers. Latent membrane protein 1 (LMP1), an oncogenic protein, plays an important role in malignant transformation in EBV-associated nasopharyngeal carcinoma and B-cell lymphoma; however, its expression has not been detected in EBV-associated gastric cancer. To address why LMP1 has not been detected in EBV-positive gastric tumors, we focused on the interactions between LMP1-positive and -negative cells and stably expressed LMP1 in the gastric cancer cell line AGS. We showed that the number of LMP1-positive cells decreased gradually with each cell passage when the cells were co-cultured with LMP1-negative cells. Time-lapse imaging showed that LMP1-positive cells were eliminated from a monolayer of LMP1-negative cells. Furthermore, LMP1-positive cells stimulated the proliferation of surrounding LMP1-negative cells, but not LMP1-positive cells, via exosome-mediated EGFR activation. Our data indicate that LMP1 expression drives cell competition between LMP1-positive and -negative cells, affecting the behavior of the cells within gastric tissue.

Background: A few studies have reported that the quantity of selected cytokines/chemokines in breast milk might be associated with atopic dermatitis (AD). Using the multiplex cytokine assay system, we examined cytokines/chemokines in human milk in order to identify new biomarkers related to AD. Methods: We recruited 49 infants with or without AD who participated in a birth cohort and measured the concentrations of cytokines/chemokines in the colostrum (collected within 4–5 days after birth) and mature milk (collected at 1 month postpartum) received by the infants. Results: There were significant differences in the concentrations of interleukin (IL)-1β and IL-12p40 in the colostrum, and in those of IL-4, eotaxin, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-α2 and MIP-1α in the mature milk between the milk received by infants who developed AD at the age of 6 months and that received by the control infants. There was weak to moderate correlation between those 6 cytokines/chemokines in mature milk. Atopic history and IgE levels of mothers were not related to cytokine/chemokine concentrations in breast milk. Logistic regression analyses showed that high levels of eotaxin in the mature milk were a risk for the development of AD at 6 months of age. Conclusion: These results suggest that several cytokines/chemokines, especially eotaxin, are potential biomarkers for development of AD in early infancy.

T U E S D A Y 852 Activity of Natural Moisturizing Factor Forming Enzyme Bleomycin Hydrolase in Atopic Dermatitis Affected By Disease Control Status and Seasonal Change Takeshi Chiba, MD; Division of Allergy, National Center for Child Health and Development, Tokyo, Japan. RATIONALE: Bleomycin hydrolase (BH) is thought to have an important physiological role by localizing at the stratum corneum (SC) in mammalian skin, and generating free amino acids from citrullinated peptides in the last step of filaggrin degradation pathway. In this study, we investigated whether disease activity and seasonal change affected BH activity. METHODS: We recruited 11 poorly controlled AD children (SCORAD>25), 51 well-controlled AD children (SCORAD