Attosecond-pump attosecond-probe x-ray spectroscopy of liquid water.

Attosecond-pump/attosecond-probe experiments have long been sought as the most straightforward method for observing electron dynamics in real time. Although there has been much success with overlapped near-infrared femtosecond and extreme ultraviolet attosecond pulses combined with theory, true attosecond-pump/attosecond-probe experiments have been limited. We used a synchronized attosecond x-ray pulse pair from an x-ray free-electron laser to study the electronic response to valence ionization in liquid water through all x-ray attosecond transient absorption spectroscopy (AX-ATAS). Our analysis showed that the AX-ATAS response is confined to the subfemtosecond timescale, eliminating any hydrogen atom motion and demonstrating experimentally that the 1b1 splitting in the x-ray emission spectrum is related to dynamics and is not evidence of two structural motifs in ambient liquid water.

Correlation between 2D and 3D Fetal Brain MRI Biometry and Neurodevelopmental Outcomes in Fetuses with Suspected Microcephaly and Macrocephaly.

BACKGROUND AND PURPOSE: Definitions of fetal microcephaly and macrocephaly are debatable. A better understanding of their long-term prognoses would help guide parental education and counseling. This study aimed to explore the correlation between 2D and 3D fetal brain MR imaging biometry results and the long-term neurodevelopmental outcomes. MATERIALS AND METHODS: This analysis is a historical cohort study. Fetal brain biometry was measured on 2D and 3D MR imaging using a volumetric MR imaging semiautomated algorithm. We measured and assessed the following brain structures: the supratentorial brain volume and cerebellar volume and cerebellar volume/supratentorial brain volume ratio, in addition to commonly used 2D brain MR imaging biometric variables, including occipitofrontal diameter, biparietal diameter, and transcerebellar diameter. Microcephaly was defined as ≤ 3rd percentile; and macrocephaly, as ≥ 97th percentile, corresponding to -2 SDs and +2 SDs. The neurodevelopmental outcome of this study cohort was evaluated using the Vineland-II Adaptive Behavior Scales, and the measurements were correlated to the Vineland standard scores. RESULTS: A total of 70 fetuses were included. No significant correlation was observed between the Vineland scores and either the supratentorial brain volume, cerebellar volume, or supratentorial brain volume/cerebellar volume ratio in 3D or 2D MR imaging measurements, after correction for multiple comparisons. No differences were found among fetuses with macrocephaly, normocephaly, or microcephaly regarding the median Vineland standard scores. CONCLUSIONS: Provided there is normal brain structure on MR imaging, the developmental milestone achievements in early years are unrelated to 2D and 3D fetal brain MR imaging biometry, in the range of measurements depicted in this study.

The KSHV ORF20 Protein Interacts with the Viral Processivity Factor ORF59 and Promotes Viral Reactivation.

Upon Kaposi's Sarcoma-associated herpesvirus (KSHV) lytic reactivation, rapid and widespread amplification of viral DNA (vDNA) triggers significant nuclear reorganization. As part of this striking shift in nuclear architecture, viral replication compartments are formed as sites of lytic vDNA production along with remarkable spatial remodeling and the relocalization of cellular and viral proteins. These viral replication compartments house several lytic gene products that coordinate viral gene expression, vDNA replication, and nucleocapsid assembly. The viral proteins and mechanisms that regulate this overhaul of the nuclear landscape during KSHV replication remain largely unknown. KSHV's ORF20 is a widely conserved lytic gene among all herpesviruses, suggesting it may have a fundamental contribution to the progression of herpesviral infection. Here, we utilized a promiscuous biotin ligase proximity labeling method to identify the proximal interactome of ORF20, which includes several replication-associated viral proteins, one of which is ORF59, the KSHV DNA processivity factor. Using coimmunoprecipitation and immunofluorescence assays, we confirmed the interaction between ORF20 and ORF59 and tracked the localization of both proteins to KSHV replication compartments. To further characterize the function of ORF20, we generated an ORF20-deficient KSHV and compared its replicative fitness to that of wild-type virus. Virion production was significantly diminished in the ORF20-deficient virus as observed by supernatant transfer assays. Additionally, we tied this defect in viable virion formation to a reduction in viral late gene expression. Lastly, we observed an overall reduction in vDNA replication in the ORF20-deficient virus, implying a key role for ORF20 in the regulation of lytic replication. Taken together, these results capture the essential role of KSHV ORF20 in progressing viral lytic infection by regulating vDNA replication alongside other crucial lytic proteins within KSHV replication compartments. IMPORTANCE Kaposi's Sarcoma-associated herpesvirus (KSHV) is a herpesvirus that induces lifelong infection, and as such, its lytic replication is carefully controlled to allow for efficient dissemination from its long-term reservoir and for the spread of the virus to new hosts. Viral DNA replication involves many host and viral proteins, coordinating both in time and space to successfully progress through the viral life cycle. Yet, this process is still not fully understood. We investigated the role of the poorly characterized viral protein ORF20, and through proximity labeling, we found that ORF20 interacts with ORF59 in replication compartments and affects DNA replication and subsequent steps of the late viral life cycle. Collectively, these results provide insights into the possible contribution of ORF20 to the complex lytic DNA replication process and suggest that this highly conserved protein may be an important modulator of this key viral mechanism.

Growth, tolerance, and DHA and ARA status of healthy term infants receiving formula with two different ARA concentrations: Double-blind, randomized, controlled trial.

Circulating docosahexaenoic acid (DHA) and arachidonic acid (ARA) in total red blood cells (RBC) are considered indicators of fatty acid status. In this study, healthy term infants received study formula through 120 days of age. All study formulas had 17 mg DHA/100 kcal. Investigational formulas had 1) 25 g ARA/100 kcal and no added prebiotic blend (ARA-25; n = 29) or 2) 34 mg ARA/100 kcal and a prebiotic blend (1:1 ratio; 4 g/L) of polydextrose and galactooligosaccharides (PDX/GOS; n = 20). The control formula had 34 mg ARA/100 kcal and no added prebiotic blend (Control: n = 31). Fatty acids in total RBCs and plasma phospholipids (PPLs) at 120 days and buccal epithelial PLs at 14 and 120 days of age were assessed by capillary column gas chromatography. The calculated 90% confidence interval (CI) of each investigational formula relative to the Control for total RBC ARA (ARA-25: 93-105%; PDX/GOS: 96-110%) and total RBC DHA (ARA-25: 95-113%; PDX/GOS: 94-113%) fell within the pre-specified equivalence limit (85-118%), establishing study formula equivalence with respect to ARA and DHA. At day 120, total RBC and buccal epithelia PL ARA (µg/ml) were not significantly correlated (r = 0.041; p = 0.732); correlation in total RBC and buccal epithelia PL DHA was low, albeit significant (r = 0.324; p = 0.006). Consequently, buccal epithelial may not provide a suitable substitute for RBC when assessing fatty acid status and availability. The present RBC data suggest availability of DHA for central nervous system development and function is equivalent among infants receiving formulas that had 34 or 25 mg/100 kcal ARA and 17 mg/100 kcal DHA.

Volumetric MRI Study of the Brain in Fetuses with Intrauterine Cytomegalovirus Infection and Its Correlation to Neurodevelopmental Outcome.

BACKGROUND AND PURPOSE: In recent years, effort has been made to study 3D biometry as a method for fetal brain assessment. In this study, we aimed to compare brain volumes of fetuses with cytomegalovirus infection and noninfected controls. Also, we wanted to assess whether there is a correlation to their neurodevelopmental outcome as observed after several years. MATERIALS AND METHODS: A retrospective cohort study examined MR imaging brain scans of 42 fetuses (at 30-34 weeks' gestational age) that were diagnosed with intrauterine cytomegalovirus infection. Volumetric measurements of 6 structures were assessed using a semiautomated designated program and were compared with a control group of 50 fetuses. Data collected included prenatal history and MR imaging and sonographic and neurodevelopmental follow-up. RESULTS: We found that all brain volumes measured were smaller in the cytomegalovirus-infected group and that there was a correlation between smaller cerebellar volume and lower Vineland II Adaptive Behavior Scales questionnaire scores, especially in the fields of daily living and communication skills. CONCLUSIONS: In this study, we found that brain volumes are affected by intrauterine cytomegalovirus infection and that it has a developmental prognostic meaning. Such information, which should be supported by further research, may help clinicians further analyze imaging data to treat and make a better assessment of these fetuses.

Neurodevelopmental outcome of fetal isolated ventricular asymmetry without dilation: a cohort study.

OBJECTIVE: Fetal isolated ventricular asymmetry (IVA) is a relatively common finding in pregnancy, but data regarding its effect on neurodevelopmental outcome are scarce and founded principally on ultrasound-based studies. The purpose of this study was to assess the neurodevelopmental outcome of IVA cases in a magnetic resonance imaging (MRI)-based study. METHODS: Cases referred for fetal brain MRI as part of the assessment of IVA without ventriculomegaly (lateral ventricular atrial diameter ≤ 10 mm), identified during routine ultrasound examination, were assessed for possible inclusion. Asymmetry was defined as a difference in width of ≥ 2 mm between the two lateral ventricles. Forty-three cases were included in the study group and compared with a control group of 94 normal cases without IVA. Children were assessed at ages 13-74 months using the Vineland-II Adaptive Behavior Scales (VABS-II). RESULTS: VABS-II scores were within normal range. There was no significant difference in composite VABS-II score between the study and control groups (106.5 vs 108.0; P = 0.454). VABS-II scores did not differ between the groups when matched for gender and age at VABS-II interview (109.6 in study group vs 107.8 in control group; P = 0.690). CONCLUSION: In cases of IVA without ventriculomegaly on MRI, neurodevelopmental test scores were normal and did not differ from cases without IVA. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Volumetric Brain MRI Study in Fetuses with Congenital Heart Disease.

BACKGROUND AND PURPOSE: It is well-established that a high prevalence of infants with congenital heart defects surviving to childhood have neurodevelopmental abnormalities. The etiology is not clear. In this study, we aimed to find prenatal neuroanatomic changes in fetuses with congenital heart disease to better understand the pathophysiology behind these sequelae. MATERIALS AND METHODS: A retrospective study of 46 fetal brain MR imaging scans was performed at a tertiary medical center during a 4-year period. Clinical data were collected from electronic medical charts. Volumes of the supratentorial brain, right hemisphere, left hemisphere, and cerebellum were measured using a semiautomated method and were compared with the normal growth percentiles. RESULTS: We found that cerebellar volume and the cerebellar-supratentorial volume ratio were significantly lower among fetuses with congenital heart disease. Supratentorial and hemisphere volumes showed no difference between groups. This difference was not observed in fetuses with septation defects. CONCLUSIONS: Fetuses with congenital heart disease have smaller cerebellar volumes than healthy fetuses. Additional research is needed to assess this finding as a radiologic marker for long-term outcome.

DHA and ARA addition to infant formula: Current status and future research directions.

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are present in breast milk and play important roles in early infant development. A supply of these fatty acids in infant formula (typically following breast milk as a model with ARA > DHA) is thought to be important since endogenous synthesis is insufficient to maintain tissue levels equivalent to breast-fed infants. Intervention studies assessing the impact of DHA- and ARA-supplemented formulas have resulted in numerous positive developmental outcomes (closer to breast-fed infants) including measures of specific cognition functions, visual acuity, and immune responses. A critical analysis of outcome assessment tools reveals the essentiality of selecting appropriate, focused techniques in order to provide accurate evaluation of DHA- and ARA-supplemented formulas. Future research directions should encompass in-depth assessment of specific cognitive outcomes, immune function, and disease incidence, as well as sources of experimental variability such as the status of fatty acid desaturase polymorphisms.

Immune Function in Critically Ill Dogs.

BACKGROUND: People with critical illness (CI) commonly develop various forms of immune dysfunction, however, there is limited information concerning immune dysfunction in dogs with CI. HYPOTHESIS: The immune response in CI dogs differs from that of healthy dogs. ANIMALS: Immunologic variables were compared between 14 dogs with CI, defined as APPLEfast score of >20 points, admitted to the University of Missouri Veterinary Health Center Small Animal Clinic Intensive Care Unit and healthy controls (n = 15). METHODS: Cohort study evaluating constitutive and lipopolysaccharide (LPS)-stimulated TNF-α, IL-6, and IL-10 production, phagocytosis of opsonized E. coli and respiratory burst capacity after opsonized E. coli or phorbol 12-myristate 13-acetate (PMA) stimulation, peripheral blood lymphocyte phenotype, and monocyte expressions of HLA-DR and TLR-4. RESULTS: Lipopolysaccharide-stimulated leukocyte TNF-α (median, Q1, Q3; CI, 49, 49, 120; control, 655, 446, 1174 pg/mL; P = < 0.001), IL-6 (median, Q1, Q3; CI, 49, 49, 64; control, 100, 49, 166 pg/mL; P = 0.029), and IL-10 (CI, 49, 49, 56; control, 96, 49, 203 pg/mL; P = 0.014) production and both E. coli (median, Q1, Q3; CI, 60.5, 43, 88.5; control, 86.6, 81, 89.2%; P = 0.047) and PMA (CI, 40, 11.7, 70; control, 93, 83, 97.6%; P = < 0.001)-stimulated respiratory burst capacity significantly decreased in CI dogs. Percentage of monocytes expressing TLR-4 greater in the CI dogs (median, Q1, Q3; CI, 46.9, 24.3, 64.2; control, 16.4, 9.4, 26.2%; P = 0.005). CONCLUSION: These findings suggest dogs with CI develop immune system alterations that result in reduced respiratory burst function and cytokine production despite upregulation of TLR-4.

Volume of Structures in the Fetal Brain Measured with a New Semiautomated Method.

BACKGROUND AND PURPOSE: Measuring the volume of fetal brain structures is challenging due to fetal motion, low resolution, and artifacts caused by maternal tissue. Our aim was to introduce a new, simple, Matlab-based semiautomated method to measure the volume of structures in the fetal brain and present normal volumetric curves of the structures measured. MATERIALS AND METHODS: The volume of the supratentorial brain, left and right hemispheres, cerebellum, and left and right eyeballs was measured retrospectively by the new semiautomated method in MR imaging examinations of 94 healthy fetuses. Four volume ratios were calculated. Interobserver agreement was calculated with the intraclass correlation coefficient, and a Bland-Altman plot was drawn for comparison of manual and semiautomated method measurements of the supratentorial brain. RESULTS: We present normal volumetric curves and normal percentile values of the structures measured according to gestational age and of the ratios between the cerebellum and the supratentorial brain volume and the total eyeball and the supratentorial brain volume. Interobserver agreement was good or excellent for all structures measured. The Bland-Altman plot between manual and semiautomated measurements showed a maximal relative difference of 7.84%. CONCLUSIONS: We present a technologically simple, reproducible method that can be applied prospectively and retrospectively on any MR imaging protocol, and we present normal volumetric curves measured. The method shows results like manual measurements while being less time-consuming and user-dependent. By applying this method on different cranial and extracranial structures, anatomic and pathologic, we believe that fetal volumetry can turn from a research tool into a practical clinical one.

Fibroblasts drive an immunosuppressive and growth-promoting microenvironment in breast cancer via secretion of Chitinase 3-like 1.

Cancer-Associated Fibroblasts (CAFs) are the most prominent stromal cell type in breast tumors. CAFs promote tumor growth and metastasis by multiple mechanisms, including by mediating tumor-promoting inflammation. Immune modulation in the tumor microenvironment plays a central role in determining disease outcome. However, the functional interactions of CAFs with immune cells are largely unknown. Here we report a novel signaling axis between fibroblasts, cancer cells and immune cells in breast tumors that drives an immunosuppressive microenvironment, mediated by CAF-derived Chi3L1. We demonstrate that Chi3L1 is highly upregulated in CAFs isolated from mammary tumors and pulmonary metastases of transgenic mice, and in the stroma of human breast carcinomas. Genetic ablation of Chi3L1 in fibroblasts in vivo attenuated tumor growth, macrophage recruitment and reprogramming to an M2-like phenotype, enhanced tumor infiltration by CD8+ and CD4+ T cells and promoted a Th1 phenotype. These results indicate that CAF-derived Chi3L1 promotes tumor growth and shifts the balance of the immune milieu towards type 2 immunity. Taken together, our findings implicate fibroblast-derived Chi3L1 as a novel key player in the complex reciprocal interactions of stromal cells that facilitate tumor progression and metastasis, and suggest that targeting Chi3L1 may be clinically beneficial in breast cancer.

Macrophage migration inhibitory factor downregulation: a novel mechanism of resistance to anti-angiogenic therapy.

Anti-angiogenic therapies for cancer such as VEGF neutralizing antibody bevacizumab have limited durability. While mechanisms of resistance remain undefined, it is likely that acquired resistance to anti-angiogenic therapy will involve alterations of the tumor microenvironment. We confirmed increased tumor-associated macrophages in bevacizumab-resistant glioblastoma patient specimens and two novel glioblastoma xenograft models of bevacizumab resistance. Microarray analysis suggested downregulated macrophage migration inhibitory factor (MIF) to be the most pertinent mediator of increased macrophages. Bevacizumab-resistant patient glioblastomas and both novel xenograft models of resistance had less MIF than bevacizumab-naive tumors, and harbored more M2/protumoral macrophages that specifically localized to the tumor edge. Xenografts expressing MIF-shRNA grew more rapidly with greater angiogenesis and had macrophages localizing to the tumor edge which were more prevalent and proliferative, and displayed M2 polarization, whereas bevacizumab-resistant xenografts transduced to upregulate MIF exhibited the opposite changes. Bone marrow-derived macrophage were polarized to an M2 phenotype in the presence of condition-media derived from bevacizumab-resistant xenograft-derived cells, while recombinant MIF drove M1 polarization. Media from macrophages exposed to bevacizumab-resistant tumor cell conditioned media increased glioma cell proliferation compared with media from macrophages exposed to bevacizumab-responsive tumor cell media, suggesting that macrophage polarization in bevacizumab-resistant xenografts is the source of their aggressive biology and results from a secreted factor. Two mechanisms of bevacizumab-induced MIF reduction were identified: (1) bevacizumab bound MIF and blocked MIF-induced M1 polarization of macrophages; and (2) VEGF increased glioma MIF production in a VEGFR2-dependent manner, suggesting that bevacizumab-induced VEGF depletion would downregulate MIF. Site-directed biopsies revealed enriched MIF and VEGF at the enhancing edge in bevacizumab-naive patients. This MIF enrichment was lost in bevacizumab-resistant glioblastomas, driving a tumor edge M1-to-M2 transition. Thus, bevacizumab resistance is driven by reduced MIF at the tumor edge causing proliferative expansion of M2 macrophages, which in turn promotes tumor growth.

Misreport of energy intake assessed with food records and 24-h recalls compared with total energy expenditure estimated with DLW.

BACKGROUND/OBJECTIVES: The accuracy of dietary assessment methods has rarely been validated using precise techniques. The objective of this work was to evaluate the validity of energy intake (EI) estimated with food records (FRs) and 24-h recalls (24hRs) against total energy expenditure (EE) estimated by the doubly labeled water (DLW) method. In addition, the magnitude of EI under-reporting was assessed along with its associated characteristics. SUBJECTS/METHODS: The studied group included 83 adults between 20 and 60 years of age who were recruited from a population-based sample. Within-person variation-adjusted means of EI estimated from two FRs and three 24hRs were compared with EE estimated using the DLW method multiple-point protocol. The Wilcoxon signed-rank test was used to assess the differences between EI and EE, whereas Bland-Altman and survival-agreement plots assessed the agreement between the estimates. RESULTS: The mean EE (2540 kcal) was greater than the mean reported EI for both dietary assessment methods (FR: 1774 kcal; 24hR: 1658 kcal, P<0.01). The frequency of under-reporting was lower (20%) for EI estimated with the 24hR than that estimated with the FR (32%). Men presented lower magnitude of under-reported EI than women did. For women, differences between EI and EE were lower with FR than with 24hR. Overall, FR and 24hR showed similar performance. The mean under-reported EI was ~30% for both methods. CONCLUSIONS: Irregular meal habits, smoking and low education were associated with the under-report of EI. Both FR and 24hR are subjected to bias suggesting the need of refining the procedures applied in dietary assessment methods.

Growth retardation at early life and metabolic adaptation among North Korean children.

The high prevalence of obesity is a major public health issue and contributes to the 'double burden' of disease in developing countries. Early exposure to poor nutrition may cause metabolic adaptations that, when accompanied by exposure to 'affluent' nutrition, may increase the risk for obesity and other metabolic disorders. The aim of this study was to determine differences in energy metabolism and nutritional status between normal-height and growth-retarded North Korean children living in South Korea. A total of 29 children were recruited and underwent measurements of resting energy expenditure (REE), respiratory quotient (RQ), anthropometrics and dietary intake. There was no difference in REE or any assessment of obesity between the growth-retarded and normal-height children. Children who were classified as growth retarded (HAZ<-1.0) or stunted (HAZ<-2.0) had a significantly higher RQ (ß=0.036 or 0.060, respectively, P=0.018 or 0.016), independent of sex, age, fat-free mass, fat mass and food quotient, compared with children with normal height. The results from this study, the first from an Asian population, add to the growing body of literature suggesting that undernutrition early in life results in adaptations in energy metabolism that favor fat deposition, increasing the risk of stunted children becoming overweight or obese later in life. Continued research on this topic is warranted, given the continued rise in the prevalence of the double burden in transitional countries.

Immediate and extended effects of abrasion on stratum corneum natural moisturizing factor.

BACKGROUND: Natural moisturizing factor (NMF), principally comprised of hygroscopic amino acids and derivatives that absorb moisture from the surrounding environment, serves as the primary humectant of the stratum corneum (SC). Acute barrier disruption has been shown to differentially affect the concentration of NMF in the SC. This study measured the recovery kinetics of NMF after mechanical damage of the SC, which is not well understood. METHODS: The study population included 20 healthy female volunteers (18-72-year old) with no history of dermatological disorders. Transepidermal water loss (TEWL), erythema, and SC water and NMF were measured at all sites before abrasion, 30 min following abrasion, and 1-3, 6, 8, and 10 days following abrasion. Measurements obtained from the abraded site were compared with those obtained from an untreated site. RESULTS: As expected, both TEWL and erythema increased significantly with abrasion. Erythema and TEWL values remained higher at the abraded site for 2 and 6 days, respectively, after abrasion. No changes in NMF component levels in the SC were observed at 30 min after abrasion. One day following abrasion, reduced levels of glycine, histidine pH4, trans-urocanic acid (tUca) pH4, and tUca pH8 were observed. In addition, a significantly lower level of serine was observed at the abraded site 2 and 6 days following abrasion. Within 8 days after abrasion, these components returned to levels comparable to those observed in untreated skin. Throughout the study, no differences were observed in the level of water in the SC. CONCLUSION: These results demonstrate that acute barrier disruption induced by mechanical abrasion has relatively little impact on biochemical events responsible for NMF generation. Though reductions in certain NMF components were observed, abrasion had no measureable effect on SC water content over the duration of the study. This implies that the reduced NMF components may not contribute substantially to water retention in the SC. The reduced components belong to a group of NMF molecules thought to be principally derived through degradation of S-100 proteins in the epidermis. NMF components measured in this study that are derived from sweat and/or urea cycling were not impacted. These data imply that while abrasion elicits clinical signs of barrier disruption within the SC, effects on its biochemical constituents and ability to retain water are relatively minor.

Consumption of ultra-processed food products and its effects on children's lipid profiles: a longitudinal study.

BACKGROUND AND AIMS: Cardiovascular disease development is related to known risk factors (such as diet and blood lipids) that begin in childhood. Among dietary factors, the consumption of ultra-processing products has received attention. This study investigated whether children's consumption of processed and ultra-processing products at preschool age predicted an increase in lipid concentrations from preschool to school age. METHODS AND RESULTS: Cohort study conducted with 345 children of low socioeconomic status from São Leopoldo, Brazil, aged 3-4 years and 7-8 years. Blood tests were done to measure lipid profile. Dietary data were collected through 24-h recalls and the children's processed and ultra-processing product intake was assessed. Linear regression analysis was used to assess the relationship between processed and ultra-processed product intake at 3-4 years on changes in lipid concentrations from preschool to school age. The percentage of daily energy provided by processed and ultra-processed products was 42.6 ± 8.5 at preschool age and 49.2 ± 9.5 at school age, on average. In terms of energy intake, the main products consumed were breads, savoury snacks, cookies, candy and other sweets in both age groups. Ultra-processed product consumption at preschool age was a predictor of a higher increase in total cholesterol (ß = 0.430; P = 0.046) and LDL cholesterol (ß = 0.369; P = 0.047) from preschool to school age. CONCLUSION: Our data suggest that early ultra-processed product consumption played a role in altering lipoprotein profiles in children from a low-income community in Brazil. These results are important to understanding the role of food processing and the early dietary determinants of cardiovascular disease.

Liquid human milk fortifier significantly improves docosahexaenoic and arachidonic acid status in preterm infants.

We report the fatty acid composition of mother׳s own human milk from one of the largest US cohorts of lactating mothers of preterm infants. Milk fatty acid data were used as a proxy for intake at enrollment in infants (n=150) who received human milk with a powder human milk fortifier (HMF; Control) or liquid HMF [LHMF; provided additional 12mg docosahexaenoic acid (DHA), 20mg arachidonic acid (ARA)/100mL human milk]. Mothers provided milk samples (n=129) and reported maternal DHA consumption (n=128). Infant blood samples were drawn at study completion (Study Day 28). Human milk and infant PPL fatty acids were analyzed using capillary column gas chromatography. DHA and ARA were within ranges previously published for US term and preterm human milk. Compared to Control HMF (providing no DHA or ARA), human milk fortified with LHMF significantly increased infant PPL DHA and ARA and improved preterm infant DHA and ARA status.

Immediate and extended effects of sodium lauryl sulphate exposure on stratum corneum natural moisturizing factor.

OBJECTIVES: Natural moisturizing factor (NMF) serves as the primary humectant of the stratum corneum (SC), principally comprised of hygroscopic amino acids and derivatives that absorb moisture. Barrier disruption has been shown to differentially affect the levels of specific NMF components, though the kinetics of NMF component restoration following disruption have not been examined. Here, we investigated the impact of barrier disruption caused by surfactant exposure on a subset of NMF components immediately following exposure and out to 10 days post-exposure. METHODS: Volunteers wore patches containing either 1% w/v sodium lauryl sulphate (SLS) or distilled water on their forearms for 24 h. Measurements of transepidermal water loss, erythema, SC water content and a subset of SC NMF and lipid components were obtained at both sites before treatment, the day of patch removal, and 1, 2, 3, 6, and 10 days following treatment. RESULTS: Most measured NMF components decreased in response to SLS exposure. Exceptions were increases in lactate, ornithine and urea, and no difference in proline levels. In the days following exposure, reduced levels of several NMF components continued at the SLS site; however, all measured NMF components demonstrated equivalence to the vehicle control within 10 days. Histidine pH 7, lactate, ornithine and urea were the first to achieve levels equivalent to the vehicle control site, normalizing within 1 day after patch removal. CONCLUSION: Results imply that NMF components derived from sweat and urea cycling are least impacted by SLS exposure whereas NMF components derived from degradation of filaggrin and/or other S-100 proteins are most impacted. This implies the restoration of the processes responsible for S-100 protein processing into free amino acids takes several days to return to normal. Further examination of the enzymes involved in S-100 protein processing following barrier disruption would provide insight into the pathway(s) for NMF restoration during SC recovery.

Hierarchical radial and polar organisation of chromosomes in human sperm.

It is well established that chromosomes occupy distinct positions within the interphase nuclei, conferring a potential functional implication to the genome. In addition, alterations in the nuclear organisation patterns have been associated with disease phenotypes (e.g. cancer or laminopathies). The human sperm is the smallest cell in the body with specific DNA packaging and the mission of delivering the paternal genome to the oocyte during fertilisation. Studies of nuclear organisation in the sperm have postulated nonrandom chromosome position and have proposed a chromocentre model with the centromeres facing toward the interior and the telomeres toward the periphery of the nucleus. Most studies have assessed the nuclear address in the sperm longitudinally predominantly using centromeric or telomeric probes and to a lesser extent with whole chromosome paints. To date, studies investigating the radial organisation of human sperm have been limited. The purpose of this study was to utilise whole chromosome paints for six clinically important chromosomes (18, 19, 21, 22, X, and Y) to investigate nuclear address by assessing their radial and longitudinal nuclear organisation. A total of 10,800 sperm were analysed in nine normozoospermic individuals. The results have shown nonrandom chromosome position for all chromosomes using both methods of analysis. We present novel radial and polar analysis of chromosome territory localization within the human sperm nucleus. Specifically, a hierarchical organisation was observed radially with chromosomes organised from the interior to the periphery (chromosomes 22, 21, Y, X, 19, and 18 respectively) and polar organisation from the sperm head to tail (chromosomes X, 19, Y, 22, 21, and 18, respectively). We provide evidence of defined nuclear organisation in the human sperm and discuss the function of organisation and potential possible clinical ramifications of these results in regards to male infertility and early human development.