HM Group Research Articles

Stool microbiome, pH and short/branched chain fatty acids in infants receiving extensively hydrolyzed formula, amino acid formula, or human milk through two months of age

BackgroundEarly infant feeding with intact or extensively hydrolyzed (EH) proteins or free amino acids (AA) may differentially affect intestinal microbiota composition and immune reactivity. This multicenter, double-blind, controlled, parallel-group, pilot study compared stool microbiota from Baseline (1–7 days of age) up to 60 days of age in healthy term infants who received mother’s own milk (assigned to human milk [HM] reference group) (n = 25) or were randomized to receive one of two infant formulas: AA-based (AAF; n = 25) or EH cow’s milk protein (EHF; n = 28). Stool samples were collected (Baseline, Day 30, Day 60) and 16S rRNA genes were sequenced. Alpha (Shannon, Simpson, Chao1) and beta diversity (Bray Curtis) were analyzed. Relative taxonomic enrichment and fold changes were analyzed (Wilcoxon, DESEq2). Short/branched chain fatty acids (S/BCFA) were quantified by gas chromatography. Mean S/BCFA and pH were analyzed (repeated measures ANOVA).ResultsAt baseline, alpha diversity measures were similar among all groups; however, both study formula groups were significantly higher versus the HM group by Day 60. Significant group differences in beta diversity at Day 60 were also detected, and study formula groups were compositionally more similar compared to HM. The relative abundance of Bifidobacterium increased over time and was significantly enriched at Day 60 in the HM group. In contrast, a significant increase in members of Firmicutes for study formula groups were detected at Day 60 along with butyrate-producing species in the EHF group. Stool pH was significantly higher in the AAF group at Days 30 and 60. Butyrate increased significantly from Baseline to Day 60 in the EHF group and was significantly higher in study formula groups vs HM at Day 60. Propionate was also significantly higher for EHF and AAF at Day 30 and AAF at Day 60 vs HM. Total and individual BCFA were higher for AAF and EHF groups vs HM through Day 60.ConclusionsDistinct patterns of early neonatal microbiome, pH, and microbial metabolites were demonstrated for infants receiving mother’s own milk compared to AA-based or extensively hydrolyzed protein formula. Providing different sources of dietary protein early in life may influence gut microbiota and metabolites.Trial registrationClinicalTrials.gov Identifier: NCT02500563. Registered July 28, 2015.

Multigene Expression Assay for Assessment of the Immune Status of Atlantic Salmon.

We report the development of a multigene gene expression assay on the BioMark HD platform for the evaluation of immune competence (ImCom) in farmed Atlantic salmon. The first version of the assay included 92 genes selected on the basis of transcriptome analyses in 54 trials that challenged the immune system; annotations were taken into account to represent the key pathways of innate and adaptive immunity. ImCom was tested on samples collected from seven independent projects. Fish were reared from the start feeding to eight months in the sea at eight units in different parts of Norway. Several tissues were analyzed. Linear discriminant analysis (LDA) showed that no more than 10 genes were required to separate groups, and a set of 46 immune genes was sufficient for any task. The second version of the assay was tested in the gills of two groups of high-performing healthy smolts and in groups with intermediate and high mortality rates (IM and HM, respectively). A set of 645 gill samples from clinically healthy Atlantic salmon was used as a reference. The IM group showed general suppression of immunity. All HM group salmon were above the threshold by the squared deviation from the reference. This group showed marked upregulation of genes involved in acute stress and inflammation: mmp-9, mmp-13, hsp70, il-1b, lect2, and cathelicidin. Further work will clarify the boundaries of the norm and explore various cases of impaired immunity.

Oxidative Stress is Associated with Reduced Sperm Motility in Normal Semen.

Infertility is among the most serious medical problems worldwide. Male factors contribute to 40%–50% of all infertility cases, and approximately 7% of men worldwide are affected by infertility. Spermatozoa are extremely vulnerable to oxidative insult. Oxidative stress results in axonemal damage and increased midpiece sperm morphological defects, which lead to reduced sperm motility. The aim of the study is to evaluate the association between sperm motility and the levels of selected antioxidants, cytokines, and markers of oxidative damage in the seminal plasma.The study group included 107 healthy males, who were split into two subgroups based on the percentage of motile spermatozoa after 1 hr: low motility (LM, n = 51) and high motility (HM, n = 56).The glucose-6-phosphate dehydrogenase (G6PD) activity was 52% lower in the LM group compared to that in the HM group. The level of malondialdehyde (MDA) was 12% higher in the LM group compared to that in the HM group. Similarly, the median values of interleukin (IL)-1β, IL-10, IL-12, and tumor necrosis factor alpha (TNF-α) were higher in the LM group than those in the HM group. Results of the present study revealed that the percentage of motile spermatozoa after 1 hr correlated positively with the levels of IL-1β, IL-10, IL-12, and TNFα.The lower motility of spermatozoa in healthy men is associated with a decreased activity of G6PD and increased levels of cytokines, which may be related to increased oxidative stress in seminal plasma that manifests as an increased level of MDA.

Accelerating Onset of Puberty Through Modification of Early Life Nutrition Induces Modest but Persistent Changes in Bull Sperm DNA Methylation Profiles Post-puberty.

In humans and model species, alterations of sperm DNA methylation patterns have been reported in cases of spermatogenesis defects, male infertility and exposure to toxins or nutritional challenges, suggesting that a memory of environmental or physiological changes is recorded in the sperm methylome. The objective of this study was to ascertain if early life plane of nutrition could have a latent effect on DNA methylation patterns in sperm produced post-puberty. Holstein-Friesian calves were assigned to either a high (H) or moderate (M) plane of nutrition for the first 24 weeks of age, then reassigned to the M diet until puberty, resulting in HM and MM groups. Sperm DNA methylation patterns from contrasted subgroups of bulls in the HM (ejaculates recovered at 15 months of age; n = 9) and in the MM (15 and 16 months of age; n = 7 and 9, respectively) were obtained using Reduced Representation Bisulfite Sequencing. Both 15 and 16 months were selected in the MM treatment as these bulls reached puberty approximately 1 month after the HM bulls. Hierarchical clustering demonstrated that inter-individual variability unrelated to diet or age dominated DNA methylation profiles. While the comparison between 15 and 16 months of age revealed almost no change, 580 differentially methylated CpGs (DMCs) were identified between the HM and MM groups. Differentially methylated CpGs were mostly hypermethylated in the HM group, and enriched in endogenous retrotransposons, introns, intergenic regions, and shores and shelves of CpG islands. Furthermore, genes involved in spermatogenesis, Sertoli cell function, and the hypothalamic–pituitary–gonadal axis were targeted by differential methylation when HM and MM groups were compared at 15 months of age, reflecting the earlier timing of puberty onset in the HM bulls. In contrast, the genes still differentially methylated in MM bulls at 16 months of age were enriched for ATP-binding molecular function, suggesting that changes to the sperm methylome could persist even after the HM and MM bulls reached a similar level of sexual maturity. Together, results demonstrate that enhanced plane of nutrition in pre-pubertal calves associated with advanced puberty induced modest but persistent changes in sperm DNA methylation profiles after puberty.

Transcriptome Profiling of Pacu (Piaractus mesopotamicus) Challenged With Pathogenic Aeromonas hydrophila: Inference on Immune Gene Response.

Pacu (Piaractus mesopotamicus) is a Neotropical fish of major importance for South American aquaculture. Septicemia caused by Aeromonas hydrophila bacteria is currently considered a substantial threat for pacu aquaculture that have provoked infectious disease outbreaks with high economic losses. The understanding of molecular aspects on progress of A. hydrophila infection and pacu immune response is scarce, which have limited the development of genomic selection for resistance to this infection. The present study aimed to generate information on transcriptome of pacu in face of A. hydrophila infection, and compare the transcriptomic responses between two groups of time-series belonging to a disease resistance challenge, peak mortality (HM) and mortality plateau (PM) groups of individuals. Nine RNA sequencing (RNA-Seq) libraries were prepared from liver tissue of challenged individuals, generating ∼160 million 150 bp pair-end reads. After quality trimming/cleanup, these reads were assembled de novo generating 211,259 contigs. When the expression of genes from individuals of HM group were compared to individuals from control group, a total of 4,413 differentially expressed transcripts were found (2,000 upregulated and 2,413 downregulated candidate genes). Additionally, 433 transcripts were differentially expressed when individuals from MP group were compared with those in the control group (155 upregulated and 278 downregulated candidate genes). The resulting differentially expressed transcripts were clustered into the following functional categories: cytokines and signaling, epithelial protection, antigen processing and presentation, apoptosis, phagocytosis, complement system cascades and pattern recognition receptors. The proposed results revealing relevant differential gene expression on HM and PM groups which will contribute to a better understanding of the molecular defense mechanisms during A. hydrophila infection.

Growth Through 24 Months of Age in Infants Receiving Formulas with or Without Added Bovine Milk Fat Globule Membrane (MFGM) or Human Milk Through the First Year of Life: An RCT

Abstract Objectives To evaluate growth through 24 months of age in infants receiving added bovine milk fat globule membrane (MFGM) in infant formula through 12 months of age. Concentration of MFGM from bovine milk fractions and incorporation in infant formula may better approximate the composition of complex milk lipids in human milk. Methods In the double-blind, randomized, controlled Chilean Infant Nutrition Trial (ChiNuT; NCT0262613), term infants whose mothers chose to initiate exclusive infant formula feeding before 4 months of age were randomized to receive: a standard cow's milk-based infant formula (SF, n = 174) or a similar formula with added whey protein-lipid concentrate (5 g/L; source of bovine MFGM) (bMFGM, n = 176). A reference group of infants exclusively receiving human milk (HM, n = 236) was also recruited. Growth through 24 months of age was the primary outcome. Length-for-age (LAZ), weight-for-age (WAZ) and body mass index (BMI)-for-age (BAZ) growth z-scores were analyzed by mixed-effects multiple linear regression models adjusted by sex, age (days), and maternal pregestational BMI (kg/m2). Results No significant group differences in sex, gestational age at birth, birthweight, maternal age and maternal education were detected, with the exception of maternal pregestational BMI (mean(SD)) (HM: 27.0(5.2) lower vs SF: 28.6(6.2) or bMFGM: 28.9(6.1); P = 0.002). Groups were similar at baseline (weight, length, WAZ, BAZ) with the exception of LAZ (lower in the bMFGM compared to HM group; P < 0.05). No significant differences in growth z-scores (absolute at 6, 9, 12, and 24 months of age or change between baseline and each study time point) were detected between SF and MFGM groups. Both randomized study formula groups were associated with higher growth z-score increases from baseline compared to the HM reference group between 6 and 24 months (P less than 0.05). Mean growth z-scores fell within the range of −1 to 1 (16th to 84th percentile) for SF, bMFGM, and HM groups at all study time points. Conclusions Added bovine MFGM in a routine cow's milk-based infant formula through 12 months of age supported normal growth through 24 months of age. Funding Sources The study was funded by Mead Johnson Nutrition (MJN). Teresa Murguia-Peniche, Steven Wu, and Jennifer Wampler are currently employed by MJN. Carol Lynn Berseth was previously employed by MJN.

Prevalence, Epidemiology, Etiology, and Sensitivity of Invasive Bacterial Infections in Pediatric Patients Undergoing Oncological Treatment: A Multicenter Nationwide Study.

Background: Infectious complications (IC) caused by bacterial strains often impede anticancer therapy. The study aimed to retrospectively analyze bacterial IC that could help predict the risk and optimize the empirical treatment for bacterial infections in pediatric cancer patients. Patients and Methods: Over a 72-month period, all-in 5,599 children with cancer: 2,441 patients with hematological malignancy (HM including acute leukemias, Hodgkin and non-Hodgkin lymphomas [NHLs], and Langerhans cell histiocytosis) and 3,158 with solid tumors (STs including central nervous system tumors, neuroblastoma, Wilms' tumor, soft tissue sarcoma, germ cell tumors, Ewing sarcoma, osteosarcoma, hepatoblastoma, and others) were enrolled into the study. Episodes of bacterial infectious complications (EBICs) confirmed by microbiological findings were reported by each hospital and analyzed centrally. Results: At least 1 EBIC was diagnosed in 2,155 (36.8%) children (1,281 [59.4%] with HM and 874 [40.6%] with ST; p < 0.001). All-in 4,860 EBICs were diagnosed including 62.2% episodes in children with HM and 37.8% in children with ST (p < 0.001). Having analyzed the source of infections, blood stream infections predominated, apart from NHL patients in whom the most common type was gut infections. The profile of bacteria strains was different in HM and ST groups (p < 0.001). However, in both groups the most common Gram-negative pathogen was Enterobacteriaceae, with the rate being higher in the HM group. Among Gram-negative strains low susceptibility to ceftazidime, whereas among Enterococcus spp. low susceptibility to vancomycin was noticed. The rate of multidrug-resistant (MDR) pathogens was high, especially for Gram negatives (47.7% vs. 23.9%; p < 0.001). The survival after infections was comparable for HM and ST patients (p = 0.215). Conclusions: The risk of bacterial IC in HM patients was higher than in the ST group. The high rate of MDR strains was detected in pediatric cancer patients, especially in those with HM.

Maternal dietary methionine supplementation influences egg production and the growth performance and meat quality of the offspring

This study aimed to investigate the effects of maternal dietary coated methionine (Met) on egg production and the quality, growth performance, carcass traits, and meat quality of the offspring. In total, 288 female Ross parental chickens were randomly assigned to 3 groups with 3 replicates of 32 chickens each. From week 37 to 46, the hens of different groups were fed diets containing low (0.27% Met), adequate (0.27% Met + 0.1% coated Met) (AM), and high (0.27% Met + 0.2% coated Met) (HM) Met. There was a positive response in laying rate and albumen weight in AM and HM groups. For the offspring at market age, BW, eviscerated weight, and muscle weight were increased in the AM group (P < 0.05), whereas excessive supplementation was proven to be negative with those traits. The meat quality (color, pH, and shear force) of breast muscle was significantly influenced by different supplementation levels. The lightness and yellowness were increased in the HM group (P < 0.05, P < 0.01, respectively), and redness was decreased in the AM group (P < 0.05). A lower pH value occurred in chickens of the HM group (P < 0.05). The expressions of meat quality–related genes were altered in the supplementation groups. The pH-related genes PRDX4 and PRKAG2 were found to be significantly differentially expressed (P < 0.05, P < 0.01, respectively) and consistent with pH changes. The meat color–related gene BCO1 was also differentially expressed (P < 0.01) and showed a corresponding change with yellowness value. Collectively, the best production performance was in the offspring with 0.1% coated Met supplementation (AM group). Supplementation with 0.2% coated Met (HM group) seemed to be excessive, but laying rate was increased in the HM group. Both results of phenotypic measurements and gene expression demonstrated that maternal-coated Met supplementation resulted in fluctuation of some meat quality indices in the offspring, but all values were still within the range found in normal chickens.

Effect of arginine or glutamine supplementation and milk feeding allowance on small intestine development in calves

The development of the small intestine (SI) is important for the health and growth of neonatal calves. This study evaluated the effect of arginine (Arg) and glutamine (Gln) supplementation and 2 levels of milk allowance on the histomorphological development of the SI in preweaning calves. Sixty mixed-sex Friesian × Jersey calves (3-5 d of age) were offered reconstituted whole milk (125 g/L, 26% fat, 26% protein) at either high (20% of arrival body weight/d; HM) or low (10% of arrival body weight/d; LM) milk allowance without (Ctrl) or with supplementary Arg or Gln (at 1% of milk dry matter) in a 2 × 3 factorial design (n = 10/treatment). After 35 d on the diets, all calves were slaughtered to collect tissues for examination of SI development. Calves in the HM group had higher milk intake, total weight gain, and average daily gain compared with LM calves, but no effect of AA supplementation nor an interaction between milk allowance and AA supplementation was observed. For the duodenum, we observed an AA by milk allowance interaction for villus height and width, and goblet cell number per villus (HM-Arg > HM-Gln > HM-Ctrl), and villus height to crypt depth ratio (HM-Arg > HM-Gln = HM-Ctrl), but no effect of AA supplementation in the LM group. Goblet cell numbers per 100 µm of SI were greater in Arg-supplemented calves than in unsupplemented controls, with Gln-supplemented calves intermediate to but not different from the other groups. Epithelium thickness was greater in LM than in HM calves. Villus density, crypt depth, and muscle thickness did not differ between groups. For the jejunum, there was an AA by milk allowance interaction for villus height, villus surface area, and villus height to crypt depth ratio (HM-Arg = HM-Gln > HM-Ctrl), with no effect of AA supplementation in the LM groups. Amino acid supplementation affected goblet cell number per villus (HM-Gln > HM-Ctrl calves, HM-Arg intermediate), and both LM-Arg and LM-Gln calves had greater numbers than LM-Ctrl calves. Villus width, crypt depth, and muscle thickness were greater in HM than LM calves but there was no effect of AA supplementation. Villus density, goblet cell number per 100 µm of SI, and epithelium thickness were unaffected by AA supplementation and milk allowance. Milk allowance and AA supplementation had no effect on SI morphology in the ileum. Increasing milk allowance improved villus height, width, and surface area but only in Arg- or Gln-supplemented calves, not in control calves. The observed changes in development may be important for intestinal functionality, integrity, and barrier function in preweaning calves, potentially through increased cell growth and proliferation or reduced levels of cellular atrophy.

Chemistry and Toxicity of Bottom Sediments in Small Watercourses of St. Petersburg

The article gives the results of integrated studies of bottom sediments in four watercourses in the central St. Petersburg: the rivers of Ekateringofka, Okhta, Fontanka, and Chernaya Rechka. The river sediments are shown to be highly polluted by heavy metals and polycyclic aromatic hydrocarbons. Bioassay tests are used to show a considerable toxicity of sediments with elements of HM group (Ni, Zn, Cu, Cr, Mn, Cd) with a high probability of biological effects. However, studies by correlation and regression analysis have not demonstrated the contribution of polyarenes to the formation of sediment toxicity. This result is in agreement with estimates of sediment toxicity by PAH concentration converted to total organic carbon, and by characteristics of potential risk of biological effects TEC (Threshold Effects Concentrations), MEC (Median Effects Concentrations) and EEC (Extreme Effects Concentrations). Among the examined watercourses, of greatest hazard are the sediments of the Chernaya Rechka and Ol’khovka, especially, near wastewater discharge sites of plants of chemical (paint and varnish) industry and accumulator battery production.

Light or Dark Pigmentation of Engineered Skin Substitutes Containing Melanocytes Protects Against Ultraviolet Light-Induced DNA Damage In Vivo.

Engineered skin substitutes (ESS) containing autologous fibroblasts and keratinocytes provide stable wound closure in patients with large, full-thickness burns, but are limited by hypopigmentation due to absence of added melanocytes. DNA damage caused by ultraviolet radiation (UV) increases risk for skin cancer development. In human skin, melanocytes provide pigmentation that protects skin from UV-induced DNA damage. This study investigated whether inclusion of human melanocytes (hM) affects the response of ESS to UV in vivo. Specifically, pigmentation and formation of cyclobutane pyrimidine dimers (CPDs), the most prevalent UV-induced DNA photoproduct, were analyzed. Three groups of ESS were prepared with fibroblasts and keratinocytes, ± melanocytes, and grafted orthotopically to immunodeficient mice: ESS without melanocytes (ESS-hM), ESS with light skin-derived (Caucasian) melanocytes (ESS+hM-L), and ESS with dark skin-derived (African-American) melanocytes (ESS+hM-D). Pigmentation of ESS+hM-L and ESS+hM-D increased significantly after grafting; pigmentation levels were significantly different among groups. Mean melanocyte densities in ESS+hM-L and ESS+hM-D were similar to each other and to densities in normal human skin. After 8 weeks in vivo, grafts were irradiated with 135 mJ/cm2 UV; non-UV-treated mice served as controls. UV modestly increased pigmentation in the ESS+hM groups. UV significantly increased CPD levels in ESS-hM, and levels in ESS-hM were significantly greater than in ESS+hM-L or ESS+hM-D. The results demonstrate that light or dark melanocytes in ESS decreased UV-induced DNA damage. Therefore, melanocytes in ESS play a photoprotective role. Protection against UV-induced DNA damage is expected to reduce skin cancer risk in patients grafted with ESS containing autologous melanocytes.

Pulmonary Hypertension Remodels the Genomic Fabrics of Major Functional Pathways

Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. We analyzed the right-ventricular systolic pressure (RVSP), right-ventricular hypertrophy (RVH), lung histology, and transcriptomes of six-week-old male rats with PH induced by (1) hypoxia (HO), (2) administration of monocrotaline (CM), or (3) administration of monocrotaline and exposure to hypoxia (HM). The results in PH rats were compared to those in control rats (CO). After four weeks exposure, increased RVSP and RVH, pulmonary arterial wall thickening, and alteration of the lung transcriptome were observed in all PH groups. The HM group exhibited the largest alterations, as well as neointimal lesions and obliteration of the lumen in small arteries. We found that PH increased the expression of caveolin1, matrix metallopeptidase 2, and numerous inflammatory and cell proliferation genes. The cell cycle, vascular smooth muscle contraction, and oxidative phosphorylation pathways, as well as their interplay, were largely perturbed. Our results also suggest that the upregulated Rhoa (Ras homolog family member A) mediates its action through expression coordination with several ATPases. The upregulation of antioxidant genes and the extensive mitochondrial damage observed, especially in the HM group, indicate metabolic shift toward aerobic glycolysis.

Age-Related Physiologic Thinning Rate of the Retinal Nerve Fiber Layer in Different Levels of Myopia.

Purpose To investigate the effect of refractive error on the physiologic thinning rate of the retinal nerve fiber layer (RNFL) in healthy eyes. Materials and Methods. This study analyzed 223 eyes of 141 healthy subjects followed for more than 5 years and underwent at least five serial spectral domain optical coherence tomography (SD-OCT) examinations. Longitudinal RNFL measurements were analyzed by linear mixed models incorporating follow-up duration, baseline RNFL thickness, spherical equivalent (SE), age, intraocular pressure, and visual field mean deviation. Thinning rates were classified according to SE into three groups: nonmyopic (NM; >0 D), mild-to-moderately myopic (MM; >–6 D and ≤0 D), and highly myopic (HM; ≤–6 D). Results The overall slopes of change in RNFL thickness over time in the NM, MM, and HM groups were −0.305 ± 0.128, −0.294 ± 0.068, and −0.208 ± 0.097 μm/yr, respectively. Slopes of RNFL thickness changes in these groups were −0.514 ± 0.248, −0.520 ± 0.133, and −0.528 ± 0.188 μm/yr, respectively. Slopes of RNFL thickness changes in these groups were −0.514 ± 0.248, −0.520 ± 0.133, and −0.528 ± 0.188 μm/yr, respectively. Slopes of RNFL thickness changes in these groups were −0.514 ± 0.248, −0.520 ± 0.133, and −0.528 ± 0.188 μm/yr, respectively. Slopes of RNFL thickness changes in these groups were −0.514 ± 0.248, −0.520 ± 0.133, and −0.528 ± 0.188 μm/yr, respectively. Slopes of RNFL thickness changes in these groups were −0.514 ± 0.248, −0.520 ± 0.133, and −0.528 ± 0.188 Conclusions Refractive error did not affect the physiologic thinning rate of RNFL when assessed by SD OCT.

The effect of meconium thickness level on neonatal outcome

BackgroundDespite its prevalence and potential maternal and neonatal implications, the literature on the thickness levels of meconium stained amniotic fluid (MSAF) and its impact on neonatal outcomes is relatively outdated and relies on relatively small sample sizes. AimsTo study if different thickness levels of MSAF correlate with adverse neonatal outcome. Study designA retrospective cohort study. SubjectsThe medical records and neonatal charts of all women with a singleton pregnancy, who underwent a trial of labor, at 37 + 0/7 weeks or beyond, between 10/2008 and 7/2018 were reviewed. Outcome measuresThe cohort was divided according to the level of meconium reported during labor into four groups: Clear (C group), Light meconium (LM group), Intermediate meconium (IM group), and Heavy meconium (HM group). Composite neonatal outcome included at least one of the following: umbilical artery pH ≤ 7.1, sepsis, need for blood transfusion, need for phototherapy, respiratory distress syndrome, meconium aspiration syndrome, need for mechanical ventilation support, necrotizing enterocolitis, intraventricular hemorrhage, hypoxic ischemic encephalopathy, periventricular leukomalacia, seizures, hypoglycemia, hypothermia, and death. Continuous parameters were compared with Anova's test or Kruskal Wallis, and categorical variables by chi-square test or Fisher exact test, as appropriate. Multivariant logistic regression was performed in order to eliminate possible cofounders. ResultsOverall, 24,445 deliveries were reviewed (C-20,185, LM-1074, IM-2736, HM-450). Composite adverse neonatal outcome was more common with increasing thickness of MSAF. On multivariable analysis, IM and HM were independently associated with composite adverse neonatal outcome. ConclusionThe degree of meconium thickness independently correlates with composite adverse neonatal outcome.

The effects of feeding high or low milk levels in early life on growth performance, fecal microbial count and metabolic and inflammatory status of Holstein female calves

Gut microbial colonization and immune response may be affected by milk feeding method. The objective of this study was to determine the effects of feeding high or low volumes of milk on fecal bacterial count, inflammatory response, blood metabolites and growth performance of Holstein female calves. Colostrum-fed calves (n = 48) were randomly assigned to either high milk (HM; n = 24) or low milk (LM; n = 24) feeding groups. Low milk-fed calves were fed pasteurized whole milk at 10% of BW until weaning. In HM group, milk was offered to calves at 20% of BW for the first 3 weeks of life. Then, milk allowance was decreased gradually to reach 10% of BW on day 26 and remained constant until weaning on day 51. Calves were allowed free access to water and starter throughout the experiment. Body weight was measured weekly, and blood samples were taken on days 14, 28 and 57. Fecal samples were collected on days 7, 14 and 21 of age for the measurement of selected microbial species. By design, HM calves consumed more nutrients from milk during the first 3 weeks and they were heavier than LM calves on days 21, 56 and 98. High milk-fed calves had greater serum glucose and triglyceride levels on day 14 with no significant difference between groups on days 28 and 57. Blood urea nitrogen was higher in LM calves on day 14, but it was lower in HM calves on day 28. Calves in LM group had significantly greater blood tumor necrosis factor-α (TNF-α) than HM calves throughout the experiment. Serum amyloid A (SAA) concentration was higher in LM calves on day 14. However, HM calves showed higher levels of SAA at the time of weaning. Feeding high volumes of milk resulted in lower serum cortisol levels on days 14 and 28 but not at the time of weaning in HM calves compared to LM counterparts. Lactobacillus count was higher in feces sample of HM calves. Conversely, the numbers of Escherichia coli was greater in the feces of LM calves. Calves in HM group showed fewer days with fever and tended to have fewer days treated compared to LM group. In conclusion, feeding higher amounts of milk during the first 3 weeks of life improved gut microbiota, inflammation and health status and growth performance of Holstein dairy calves.

P664Impact of dynamic change in the status of metabolic syndrome associated with the risk of atrial fibrillation: a nationwide population-based study

Abstract Background/Introduction Metabolic syndrome (MetS) is a well-known risk factor for new-onset atrial fibrillation (AF). However, there is a paucity of information on whether the change of MetS status has an impact on the risk of new-onset AF. Objective We aimed to evaluate the risk of AF according to the change of MetS status and to find whether components of metabolic syndrome control may affect AF risk. Methods A total of 7,565,531 subjects (≥20-year-old, mean age 47.2±13.7 years, male 55.6%) without prevalent AF who underwent 2 times of serial health checkup were identified from the Korean National Health Insurance Service. MetS was defined as having ≥3 of the following risk factors: increased waist circumference (ethnicity-specific, in Asian, ≥80 cm in women or ≥90 cm in men), increased triglycerides (≥150 mg/dL), decreased high-density lipoprotein-cholesterol level (&lt;40 mg/dL in males, &lt;50 mg/dL in females), increased blood pressure (≥130/85 mmHg), and increased fasting glucose level (≥100 mg/dL). Subjects stratified into four groups according to the change of MetS status during the follow-up period: 1,388,850 patients persistent MetS in the serial checkup (MM group), 608,158 in previous healthy but newly diagnosed MetS at 2nd checkup (HM group), 798,555 in the previous MetS but became healthy in 2nd checkup (MH group), and 4,769,968 patients without MetS in both (HH group). Incident AF was followed up till December 2017. Results Among those with MetS, 798,555 patients had improved to be healthy (10.6%). In those previous without MetS, 608,158 patients had newly diagnosed as MetS (8.0%) in 2nd checkup. During a mean follow-up of 7.9±0.9 years, incident AF was diagnosed in 135,600 patients (2.3 per 1000 person-year). MM, MH, and HM groups showed an increased risk of AF compared to HH group (Figure). Also, MH group showed a lower risk of AF compared to those with MM group. Regardless of the type of component that meets the MetS criteria, the risk of AF became different according to changing the number of MetS components. The risk of AF increased as the number of MetS components increased, whereas the risk of AF decreased as the number of MetS components decreased. Risk of AF according to change of MetS Conclusion The risk of AF showed association with the dynamic change of MetS status and the variation in the number of MetS components. AF risk was reduced by the improvement in metabolic syndrome and each of MetS components.

Herbal medicine for insomnia in elderly with hypertension: A systematic review and meta-analysis

IntroductionHerbal medicine (HM) may be beneficial for geriatrics with multiple pathological conditions. The objective of this study was to systematically analyze the effectiveness and safety of HM for insomnia in the hypertensive elderly. MethodsThirteen databases were comprehensively searched from their inception dates to August 28, 2018, to identify relevant randomized control trials (RCTs). The results of meta-analyses were presented as relative risk (RR) or mean difference (MD) with 95% confidence intervals. The quality of evidence (QoE) was evaluated using the GRADE approach. ResultsEight RCTs were included in this review. Based on routine antihypertensive therapies in most cases, compared to the hypnotics group, HM group had a significantly higher total effective rate (TER) for improvement of insomnia (RR 1.24 [1.12, 1.39]). Compared to no intervention group, HM group showed a significantly higher TER for improving insomnia (RR 1.70 [1.25, 2.33]), and lowering systolic (MD -5.63 mmHg [-7.18, -4.09]) and diastolic blood pressures (MD -4.40 mmHg [-5.63, -3.18]). Pittsburgh sleep quality index (MD -4.11 [-5.72, -2.50]), Zung self-rating anxiety scale (MD -6.60 [-7.79, -5.41]), and Zung self-rating depression scale (MD -6.15 [-7.43, -4.87]). There was no significant difference in the incidence of adverse events between the HM and no intervention groups. The QoE ranged from “Very low” to “Moderate.” ConclusionHM might have some beneficial effects including improving insomnia, blood pressure, and mental health, for the hypertensive elderly with insomnia. Since the methodological quality of the included studies and QoE were not high, well-designed RCTs are important to confirm these results.

Stool Microbiota in Infants Receiving Extensively Hydrolyzed Formula, Amino Acid Formula, or Human Milk Through Two Months of Age (FS04-07-19)

ObjectivesInfant feeding practices play a central role in development of gut microbiome and community structure. Our goal was to test the hypothesis that diets with intact or extensively hydrolyzed proteins or free amino acids may differentially affect the intestinal microbiota composition and immune reactivity. MethodsThis multicenter, double-blind, controlled, parallel-group, pilot study compared stool microbiota outcomes from Baseline (1-7 days of age) up to 60 days of age in healthy term infants. Infants received mother’s own milk (assigned to human milk [HM] reference group) (n = 25) or were randomized to receive one of two infant formulas: amino-acid based (AAF; n = 25) or extensively hydrolyzed cow’s milk protein (EHF; n = 28). Neither study formula included added Lactobacillus rhamnosus GG. DNA was extracted (Baseline, Day 30, Day 60), 16S rRNA genes were amplified and sequenced (Illumina MiSeq), and exact amplicon sequence variants (ASV) were assigned using the DADA2 model. Alpha (Shannon, Simpson, Chao1) and beta diversity (Bray Curtis distance) and differential abundance in taxa were analyzed. Relative ASV enrichment (Baseline vs Day 60) was visualized using heat maps and taxa abundance was analyzed by DESEq2 in R (ver 3.4.3). ResultsComplete stool data (all study time points) were available for 49 participants. Baseline alpha diversity measures were similar among groups. The HM group remained stable throughout the study. However, alpha diversity measures by Day 60 were significantly higher for AAF and EHF groups compared to HM. Significant group differences in beta diversity at Day 60 were detected (P < 0.001); AAF and EHF clustered more closely compared to the HM group. Relative Bifidobacterium abundance increased over time and was significantly enriched at Day 60 in the HM group (Figure, A). At Day 60, a significant increase in members of Firmicutes was detected for AAF and EHF groups; a decrease in Enterobacteriaceae (Escherichia) was observed for EHF (Figure, B). ConclusionsDistinct patterns of early neonatal microbiome establishment were demonstrated for infants receiving mother’s own milk compared to amino acid-based or extensively hydrolyzed protein infant formulas. Providing different sources of dietary protein early in life may impact gut microbiome development. Funding SourcesMead Johnson Pediatric Nutrition Institute. Supporting Tables, Images and/or Graphs▪▪

The chromatic symmetry of twins and allotwins.

The symmetry of twins is described by chromatic point groups obtained from the intersection group {\cal H}^* of the oriented point groups of the individuals {\cal H}_i extended by the operations mapping different individuals. This article presents a revised list of twin point groups through the analysis of their groupoid structure, followed by the generalization to the case of allotwins. Allotwins of polytypes with the same type of point group can be described by a chromatic point group like twins. If the individuals are all differently oriented, the chromatic point group is obtained in the same way as in the case of twins; if they are mapped by symmetry operation of the individuals, the chromatic point group is neutral. If the same holds true for some but not all individuals, then the allotwin can be seen as composed of twinned regions described by a twin point group, that are then allotwinned and described by a colour identification group; the allotwin is then described by a chromatic group obtained as an extension of the former by the latter, and requires the use of extended symbols reminiscent of the extended Hermann-Mauguin symbols of space groups. In the case of allotwins of polytypes with different types of point groups, as well as incomplete (allo)twins, a chromatic point group does not reveal the full symmetry: the groupoid has to be specified instead.

Maternal Weight Variation in Different Intrauterine Environments: An Important Role of Hypertension.

Different intrauterine environments may influence the maternal prepregnancy body weight (BW) variation up to 6 months postpartum. The objective of the present study was to verify the association of sociodemographic, obstetric, nutritional, and behavioral factors with weight variation in women divided into four groups: hypertensive (HM), diabetic (DM), smokers (SM), and control mothers (CM). It was a convenience sample of 124 postpartum women recruited from 3 public hospitals in the city of Porto Alegre, state of Rio Grande do Sul, Brazil, between 2011 and 2016. Multiple linear regressions and generalized estimating equations (GEE) were conducted to identify the factors associated with maternal weight variation. For all GEE, the maternal weight measurements were adjusted for maternal height, parity, educational level, and the type of delivery, and 3 weight measurements (prepregnancy, preceding delivery, and 15 days postpartum) were fixed. A hierarchical model closely associated the maternal diagnosis of hypertension and a prepregnancy body mass index (BMI) classified as overweight with maternal weight gain measured up to the 6th month postpartum (the difference between the maternal weight at 6 months postpartum and the prepregnancy weight). These results showed that the BW of the HM group and of overweight women increased ∼ 5.2 kg 6 months postpartum, compared with the other groups. Additionally, women classified as overweight had a greater BW variation of 3.150 kg. This evidence supports the need for specific nutritional guidelines for gestational hypertensive disorders, as well as great public attention for overweight women in the fertile age.