Associations between breastfeeding duration and adherence to complementary feeding recommendations in Scotland.

We aimed to describe how breastfeeding relates to adherence to complementary feeding (CF) recommendations, diet diversification and feeding skills development and whether sociodemographic factors explain any differences observed. The Scottish Maternal Infant and Nutrition Survey for infants aged 8-12 months collected breastfeeding history, CF practices, diet and sociodemographic data using a self-completion questionnaire. Non-healthful CF practices were starting CF < 6 months, any consumption of sugar-sweetened beverages (SSBs), sweet or salty snacks (treats) or unmodified cow's milk and regular consumption of commercial baby foods. Diet diversification and feeding skills were assessed by amount of self-feeding and number of food groups, meals and snacks eaten daily. Of the 2730 mothers, 20% were solely infant formula fed (IFF) and 48% continued breastfeeding ≥6 months. Compared to IFF babies, mothers who gave any breast milk ≥6 months were more likely to start CF ≥ 6 months compared to those IFF (66% vs. 37%) and less likely to give treats (15% vs. 45%), SSBs (11% vs. 20%) and commercial baby foods (31% vs. 53%). These associations remained highly significant (p < 0.001) even after sociodemographic factor adjustment. Despite starting CF later, infants breastfed ≥6 months ate the same number of food groups and meals as those IFF, were just as likely to self-feed purees and more likely to self-feed finger foods daily (87% vs. 81% p < 0.001). Mothers who breastfeed beyond 6 months adhere more to CF recommendations and start CF later compared to IFF, but their babies eat a similarly diverse diet and have similar feeding skills.

Does planning to mixed feed undermine breastfeeding?

Continued breastfeeding is important for infants' health, but it is unclear whether mixed feeding increases the risk of breastfeeding cessation. We aimed to explore associations of mixed feeding and lactation problems with early cessation of breastfeeding. We analysed data from mothers who completed the Scottish National Maternal and Infant Feeding Survey and had previously breastfed their infants. At age 8-12 weeks, mothers (N = 1974) reported their feeding history and intentions, lactation problems and reasons for giving formula milk. The main outcome measure was cessation of breastfeeding before 6-8 weeks and time to cessation. By 6 weeks, 65% had mixed fed at some point, 32% had ceased breastfeeding, 22% were currently mixed feeding and 46% were exclusively breastfeeding. Lactation problems before 2 weeks were common (65%), and strongly associated with stopping breastfeeding (relative risk [RR]: 3.23, 95% confidence interval [CI]: 2.0-5.3) and with mixed feeding (RR: 3.14, 95% CI: 2.5-4.0). However, even after adjustment for breastfeeding problems mothers who planned to mixed feed (RR: 3.39, 95% CI: 2.4-4.9) and those who introduced formula for practicalities (RR: 3.21, 95% CI: 2.3-4.4) were more likely to stop breastfeeding. These variables also predicted later lactation insufficiency (planned mixed feeding RR: 1.39, 95% CI: 1.0-2.0; formula for practicalities RR: 1.76, 95% CI: 1.3-2.3). Mothers who received specialist lactation support were less likely to cease breastfeeding (RR: 0.63, 95% CI: 0.5-0.9) but nonspecialist input was unrelated to risk of cessation (RR: 1.06, 95% CI: 0.2-4.9). In conclusion, choosing to mix feed an infant is strongly associated with stopping breastfeeding, even in the absence of lactation problems.

50th Anniversary of the Nucleosome Discovery: a Brief Essay.

50th Anniversary of the Nucleosome Discovery.

The transcriptome of acute dehydration in myeloid leukemic cells.

Human myeloid leukemia cells (HL-60/S4) exposed to hyperosmotic stress with sucrose undergo dehydration and cell shrinkage. Interphase chromatin and mitotic chromosomes congeal, exhibiting altered phase separation (demixing) of chromatin proteins. To investigate changes in the transcriptome, we exposed HL-60/S4 cells to hyperosmotic sucrose stress (~600 milliOsmolar) for 30 and 60 minutes. We employed RNA-Seq of polyA mRNA to identify genes with increased or decreased transcript levels relative to untreated control cells (i.e., differential gene expression). These genes were examined for over-representation of Gene Ontology (GO) terms.  In stressed cells, multiple GO terms associated with transcription, translation, mitochondrial function and proteosome activity, as well as "replication-dependent histones", were over-represented among genes with increased transcript levels; whereas, genes with decreased transcript levels were over-represented with transcription repressors. The transcriptome profiles of hyperosmotically-stressed cells suggest acquisition of cellular rebuilding, a futile homeostatic response, as these cells are ultimately doomed to a dehydrated death.

Biomarkers of Fibrosis in Patients with COVID-19 One Year After Hospital Discharge: A Prospective Cohort Study.

Beyond the acute infection of coronavirus disease (COVID-19), concern has arisen about long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of our study was to analyze if there is any biomarker of fibrogenesis in patients with COVID-19 pneumonia capable of predicting post-COVID-19 pulmonary sequelae. We conducted a multicenter, prospective, observational cohort study of patients admitted to a hospital with bilateral COVID-19 pneumonia. We classified patients into two groups according to severity, and blood sampling to measure matrix metalloproteinase 1 (MMP-1), MMP-7, periostin, and VEGF and respiratory function tests and high-resolution computed tomography were performed at 2 and 12 months after hospital discharge. A total of 135 patients were evaluated at 12 months. Their median age was 61 (interquartile range, 19) years, and 58.5% were men. We found between-group differences in age, radiological involvement, length of hospital stay, and inflammatory laboratory parameters. Differences were found between 2 and 12 months in all functional tests, including improvements in predicted forced vital capacity (98.0% vs. 103.9%; P = 0.001) and DlCO <80% (60.9% vs. 39.7%; P = 0.001). At 12 months, 63% of patients had complete high-resolution computed tomography resolution, but fibrotic changes persisted in 29.4%. Biomarker analysis demonstrated differences at 2 months in periostin (0.8893 vs. 1.437 ng/ml; P < 0.001) and MMP-7 (8.7249 vs. 15.2181 ng/ml; P < 0.001). No differences were found at 12 months. In multivariable analysis, only 2-month periostin was associated with 12-month fibrotic changes (odds ratio, 1.0013; 95% confidence interval, 1.0006-1.00231; P = 0.003) and 12-month DlCO impairment (odds ratio, 1.0006; 95% confidence interval, 1.0000-1.0013; P = 0.047). Our data suggest that early periostin postdischarge could predict the presence of fibrotic pulmonary changes.

PREVALENCE OF SARS-CoV-2 RNA AND ANTIBODY DETECTION, AND VACCINATION STATUS IN PATIENTS WITH OCULAR VASCULAR OCCLUSION.

PURPOSE: To analyze the annual prevalence of ocular vascular occlusion in relation to COVID-19 infection and vaccination status in a prospective study. METHODS: All patients were examined for an active severe acute respiratory syndrome coronavirus 2 infection by RNA detection and for a previous infection by virus-specific antibody detection, and their vaccination status was documented. Data from pandemic year 2020 and previous years, before COVID-19 (2019, 2018, 2017), were retrospectively analyzed. RESULTS: In 2021, a total of 103 patients with the first diagnosis of ocular vascular occlusion were treated. Most frequent subdiagnoses were central retinal vein occlusion (20.4%), nonarteritic anterior ischemic optic neuropathy (18.4%), central retinal artery occlusion (13.6%), and branch retinal artery occlusion (12.6%). Thereof, only three patients (2.9%) presented with virus-specific severe acute respiratory syndrome coronavirus 2 antibodies, and none was PCR positive. Patients with preceded severe acute respiratory syndrome coronavirus 2 vaccination (59.2%) presented with comparable characteristics as unvaccinated patients with vascular occlusion regarding age, gender distribution, systemic risk factors, duration of symptoms, visual acuity, and the present subdiagnoses ( P > 0.05). The total number of cases in 2021 (103 cases) was comparable with the pandemic year 2020, at which no vaccination was available (114 cases), and to earlier years 2017, 2018, and 2019 without COVID-19 pandemic (100, 120, and 119 cases). Furthermore, we did not reveal any differences between pandemic and reference years regarding patients' characteristics ( P > 0.05). CONCLUSION: Our study did not reveal an increased annual prevalence of ocular vascular occlusions during COVID-19 pandemic years 2020 and 2021. Patients with previous COVID-19 vaccination did not present differences regarding the risk profile nor symptoms, compared with unvaccinated individuals.

Interphase epichromatin: last refuge for the 30-nm chromatin fiber?

"Interphase epichromatin" describes the surface of chromatin located adjacent to the interphase nuclear envelope. It was discovered in 2011 using a bivalent anti-nucleosome antibody (mAb PL2-6), now known to be directed against the nucleosome acidic patch. The molecular structure of interphase epichromatin is unknown, but is thought to be heterochromatic with a high density of "exposed" acidic patches. In the 1960s, transmission electron microscopy of fixed, dehydrated, sectioned, and stained inactive chromatin revealed "unit threads," frequently organized into parallel arrays at the nuclear envelope, which were interpreted as regular helices with ~ 30-nm center-to-center distance. Also observed in certain cell types, the nuclear envelope forms a "sandwich" around a layer of closely packed unit threads (ELCS, envelope-limited chromatin sheets). Discovery of the nucleosome in 1974 led to revised helical models of chromatin. But these models became very controversial and the existence of in situ 30-nm chromatin fibers has been challenged. Development of cryo-electron microscopy (Cryo-EM) gave hope that in situ chromatin fibers, devoid of artifacts, could be structurally defined. Combining a contrast-enhancing phase plate and cryo-electron tomography (Cryo-ET), it is now possible to visualize chromatin in a "close-to-native" situation. ELCS are particularly interesting to study by Cryo-ET. The chromatin sheet appears to have two layers of ~ 30-nm chromatin fibers arranged in a criss-crossed pattern. The chromatin in ELCS is continuous with adjacent interphase epichromatin. It appears that hydrated ~ 30-nm chromatin fibers are quite rare in most cells, possibly confined to interphase epichromatin at the nuclear envelope.

Lung function and radiological findings 1 year after COVID-19: a prospective follow-up.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has already affected more than 400 million people, with increasing numbers of survivors. These data indicate that a myriad of people may be affected by pulmonary sequelae of the infection. The aim of this study was to evaluate pulmonary sequelae in patients with bilateral COVID-19 pneumonia according to severity 1 year after hospital discharge. METHODS: COVID-FIBROTIC is a multicenter prospective observational cohort study for admitted patients with bilateral COVID-19 pneumonia. Pulmonary functional outcomes and chest computed tomography sequelae were analyzed 12 months after hospital discharge and we classified patients into three groups according to severity. A post hoc analysis model was designed to establish how functional test changed between groups and over time. A multivariable logistic regression model was created to study prognostic factors for lung diffusion impairment and radiological fibrotic-like changes at 12 months. RESULTS: Among 488 hospitalized patients with COVID-19 pneumonia, 284 patients had completed the entire evaluation at 12 months. Median age was 60.5 ± 11.9 and 55.3% were men. We found between-group differences in male sex, length of hospital stay, radiological involvement and inflammatory laboratory parameters. The functional evaluation of pulmonary sequelae showed that severe patients had statistically worse levels of lung diffusion at 2 months but no between group differences were found in subsequent controls. At 12-month follow up, however, we found impaired lung diffusion in 39.8% unrelated to severity. Radiological fibrotic-like changes at 12 months were reported in 22.7% of patients (102/448), only associated with radiological involvement at admission (OR: 1.55, 95% CI 1.06-2.38; p = 0.02) and LDH (OR: 0.99, 95% CI 0.98-0.99; p = 0.046). CONCLUSION: Our data suggest that a significant percentage of individuals would develop pulmonary sequelae after COVID 19 pneumonia, regardless of severity of the acute process. Trial registration clinicaltrials.gov NCT04409275 (June 1, 2020).

Acute effect of oat ß-glucan on the bioavailability of orange juice flavanones.

The impact of ß-glucan on the bioavailability of orange juice (OJ) flavanones was investigated in a randomised controlled trial. Volunteers consumed 500 mL of OJ without or with either 3 g (OB-3) or 6 g (OB-6) of ß-glucan. Urine samples, collected 12 h before and over a 0-24 h period post-supplementation, were analysed by high-performance liquid chromatography-high resolution mass spectrometry. The overall 0-24 h urinary excretion of the 17 flavanone metabolites identified and quantified in urine after OJ ingestion corresponded to 29.7 µmol, and 25.0 and 9.3 µmol, respectively, after OB-3 and OB-6 intake. This corresponds to 9.3, 7.9, and 2.9% recoveries of the 318 µmol of the ingested flavanones. The acute ingestion of OJ with 6 g, but not 3 g of ß-glucan led to a significant reduction (p < 0.05) in the excretion of flavanone metabolites compared with consumption of OJ alone.

Prevalence and overlap of known undernutrition risk factors in children in Nairobi Kenya.

We aimed to describe the co-occurrence of known risk factors for undernutrition and the prevalence of modifiable risks in wasted, stunted and healthy children. Quota sampling was used to recruit healthy [weight for age Z scores (WAZ) > -2 SD] and undernourished [weight for length (WLZ) or WAZ scores ≤ -2 SD] children aged 6-24 months from seven clinics in low-income areas of Nairobi. Structured interviews were used to identify exposure to socioeconomic, water and hygiene, infant feeding, dietary and behavioural risks (low interest in food, high food refusal and force feeding). We recruited 92 wasted WLZ ≤ -2 SD, 133 stunted (length for age Z scores LAZ ≤ -2 SD) and 172 healthy (LAZ and WLZ > 2SD) children. Nearly all children were exposed to hygiene risks (90%) and low dietary diversity (95%) regardless of nutritional status. Stunted children were more likely to be exposed to socio-economic risks (54% healthy, 64% wasted and 72% stunted; P = 0.001). Compared with healthy children, wasted and stunted children were more likely to be exposed to infant feeding (25% healthy, 40% wasted and 41% stunted; P = 0.02) and behaviour risks (24% healthy, 49% wasted, and 44% stunted; P = 0.004). Overall, wasted and stunted children were twice as likely to be exposed to more than three risks (23% healthy, 48% wasted, and 50% stunted; P = <0.001). They were also more likely to be exposed to more than three modifiable risks (dietary, handwashing and behaviour risks). Wasting and stunting are associated with exposure to multiple risk factors, many of which are potentially modifiable using targeted advice.

Hi-C detects novel structural variants in HL-60 and HL-60/S4 cell lines.

Cancer cell lines often have large structural variants (SVs) that evolve over time. There are many reported differences in large scale SVs between HL-60 and HL-60/S4, two cell lines derived from the same acute myeloid leukemia sample. However, the stability and variability of inter- and intra-chromosomal structural variants between different sources of the same cell line is unknown. Here, we used Hi-C and RNA-seq to identify and compare large SVs in HL-60 and HL-60/S4 cell lines. Comparisons with previously published karyotypes identified novel SVs in both cell lines. Hi-C was used to characterize the known expansion centered on the MYC locus. The MYC expansion was integrated into known locations in HL-60/S4, and a novel location (chr4) in HL-60. The HL-60 cell line has more within-line structural variation than the HL-60/S4 derivative cell line. Collectively we demonstrate the usefulness of Hi-C and with RNA-seq data for the identification and characterization of SVs.

Mesoscale Modeling of Nucleosome-Binding Antibody PL2-6: Mono- versus Bivalent Chromatin Complexes.

Interactions of chromatin with bivalent immunoglobin nucleosome-binding antibodies and their monovalent (papain-derived) antigen-binding fragment analogs are useful probes for examining chromatin conformational states. To help interpret antibody-chromatin interactions and explore how antibodies might compete for interactions with chromatin components, we incorporate coarse-grained PL2-6 antibody modeling into our mesoscale chromatin model. We analyze interactions and fiber structures for the antibody-chromatin complexes in open and condensed chromatin, with and without H1 linker histone (LH). Despite minimal and transient interactions at physiological salt, we capture significant differences in antibody-chromatin complex configurations in open fibers, with more intense interactions between the bivalent antibody and chromatin compared to monovalent antigen-binding fragments. For these open chromatin fiber morphologies, antibody binding to histone tails is increased and compaction is greater for bivalent compared to monovalent and antibody-free systems. Differences between monovalent and bivalent binding result from antibody competition with internal chromatin fiber components (nucleosome core and linker DNA) for histone tail (H3, H4, H2A, H2B) interactions. This antibody competition for tail contacts reduces tail-core and tail-linker interactions and increases tail-antibody interactions. Such internal structural changes in open fibers resemble mechanisms of LH condensation, driven by charge screening and entropy changes. For condensed fibers at physiological salt, the three systems are much more similar overall, but some subtle tail interaction differences can be noted. Adding LH results in less-dramatic changes for all systems, except that the bivalent complex at physiological salt shows cooperative effects between LH and the antibodies in condensing chromatin fibers. Such dynamic interactions that depend on the internal structure and complex-stabilizing interactions within the chromatin fiber have implications for gene regulation and other chromatin complexes such as with LH, remodeling proteins, and small molecular chaperones that bind and modulate chromatin structure.

Saturated and monounsaturated fatty acids in membranes are determined by the gene expression of their metabolizing enzymes SCD1 and ELOVL6 regulated by the intake of dietary fat.

PURPOSE: We investigated the effect of dietary fats on the incorporation of saturated (SAFAs) and monounsaturated dietary fatty acids (MUFAs) into plasma phospholipids and the regulation of the expression of lipid-metabolizing enzymes in the liver. METHODS: Mice were fed different diets containing commonly used dietary fats/oils (coconut fat, margarine, fish oil, sunflower oil, or olive oil) for 4 weeks (n = 6 per diet group). In a second experiment, mice (n = 6 per group) were treated for 7 days with synthetic ligands to activate specific nuclear hormone receptors (NHRs) and the hepatic gene expression of CYP26A1 was investigated. Hepatic gene expression of stearoyl-coenzyme A desaturase 1 (SCD1), elongase 6 (ELOVL6), and CYP26A1 was examined using quantitative real-time PCR (QRT-PCR). Fatty acid composition in mouse plasma phospholipids was analyzed by gas chromatography (GC). RESULTS: We found significantly reduced hepatic gene expression of SCD1 and ELOVL6 after the fish oil diet compared with the other diets. This resulted in reduced enzyme-specific fatty acid ratios, e.g., 18:1n9/18:0 for SCD1 and 18:0/16:0 and 18:1n7/16:1n7 for ELOVL6 in plasma phospholipids. Furthermore, CYP26A1 a retinoic acid receptor-specific target was revealed as a new player mediating the suppressive effect of fish oil-supplemented diet on SCD1 and ELOVL6 hepatic gene expression. CONCLUSION: Plasma levels of MUFAs and SAFAs strongly reflect an altered hepatic fatty acid-metabolizing enzyme expression after supplementation with different dietary fats/oils.

Design and implementation of a clinical decision support tool for primary palliative Care for Emergency Medicine (PRIM-ER).

BACKGROUND: The emergency department is a critical juncture in the trajectory of care of patients with serious, life-limiting illness. Implementation of a clinical decision support (CDS) tool automates identification of older adults who may benefit from palliative care instead of relying upon providers to identify such patients, thus improving quality of care by assisting providers with adhering to guidelines. The Primary Palliative Care for Emergency Medicine (PRIM-ER) study aims to optimize the use of the electronic health record by creating a CDS tool to identify high risk patients most likely to benefit from primary palliative care and provide point-of-care clinical recommendations. METHODS: A clinical decision support tool entitled Emergency Department Supportive Care Clinical Decision Support (Support-ED) was developed as part of an institutionally-sponsored value based medicine initiative at the Ronald O. Perelman Department of Emergency Medicine at NYU Langone Health. A multidisciplinary approach was used to develop Support-ED including: a scoping review of ED palliative care screening tools; launch of a workgroup to identify patient screening criteria and appropriate referral services; initial design and usability testing via the standard System Usability Scale questionnaire, education of the ED workforce on the Support-ED background, purpose and use, and; creation of a dashboard for monitoring and feedback. RESULTS: The scoping review identified the Palliative Care and Rapid Emergency Screening (P-CaRES) survey as a validated instrument in which to adapt and apply for the creation of the CDS tool. The multidisciplinary workshops identified two primary objectives of the CDS: to identify patients with indicators of serious life limiting illness, and to assist with referrals to services such as palliative care or social work. Additionally, the iterative design process yielded three specific patient scenarios that trigger a clinical alert to fire, including: 1) when an advance care planning document was present, 2) when a patient had a previous disposition to hospice, and 3) when historical and/or current clinical data points identify a serious life-limiting illness without an advance care planning document present. Monitoring and feedback indicated a need for several modifications to improve CDS functionality. CONCLUSIONS: CDS can be an effective tool in the implementation of primary palliative care quality improvement best practices. Health systems should thoughtfully consider tailoring their CDSs in order to adapt to their unique workflows and environments. The findings of this research can assist health systems in effectively integrating a primary palliative care CDS system seamlessly into their processes of care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03424109. Registered 6 February 2018, Grant Number: AT009844-01.

Eating and feeding behaviours in children in low-income areas in Nairobi, Kenya.

Child eating and caregiver feeding behaviours are critical determinants of food intake, but they are poorly characterized in undernourished children. We aimed to describe how appetite, food refusal and force-feeding vary between undernourished and healthy children aged 6-24 months in Nairobi and identify potential variables for use in a child eating behaviour scale for international use. This cross-sectional study was conducted in seven clinics in low-income areas of Nairobi. Healthy and undernourished children were quota sampled to recruit equal numbers of undernourished children (weight for age [WAZ] or weight for length [WLZ] Z scores ≤2SD) and healthy children (WAZ > 2SD). Using a structured interview schedule, questions reflecting child appetite, food refusal and caregiver feeding behaviours were rated using a 5-point scale. Food refusal and force-feeding variables were then combined to form scores and categorized into low, medium and high. In total, 407 child-caregiver pairs, aged median [interquartile range] 9.98 months [8.7 to 14.1], were recruited of whom 55% were undernourished. Undernourished children were less likely to 'love food' (undernourished 78%; healthy 90% p = < 0.001) and more likely to have high food refusal (18% vs. 3.3% p = <0.001), while their caregivers were more likely to use high force-feeding (28% vs. 16% p = 0.03). Undernourished children in low-income areas in Nairobi are harder to feed than healthy children, and force-feeding is used widely. A range of discriminating variables could be used to measure child eating behaviour and assess the impact of interventions.

Does early introduction of solid feeding lead to early cessation of breastfeeding?

Mixed milk feeding increases the likelihood of breastfeeding cessation, but it is not known if solid feeding (SF) has the same effect. We have identified 10,407 infants breastfed for at least 8-10 weeks from three large U.K. studies (Avon Longitudinal Study of Parents and Children [ALSPAC; born 1990-1991], Southampton Woman's Survey [SWS; 1998-2008], and Infant Feeding Survey 2010 [IFS 2010]) to investigate the associations between early SF and breastfeeding cessation. In the earliest study (ALSPAC), 67% had started SF before the age of 4 months, but in the latest (IFS), only 23% had started before 4 months. Solid food introduction before 4 months was associated with stopping breastfeeding before 6 months in all three cohorts, with little effect of adjustment for maternal sociodemographic characteristics (Poisson regression, adjusted prevalence ratios: ALSPAC 1.55, [95% confidence interval 1.4, 1.8], SWS 1.13 [1.0, 1.3], IFS 1.10 [1.1, 1.3]). Using Cox regression, adjusted hazard ratios for breastfeeding cessation compared with SF after 5 months were 2.07 (1.8, 2.4) for SF before 4 and 1.51 (1.3, 1.8) at 4-5 months for ALSPAC and 1.25 (1.1, 1.5) and 1.15 (1.0, 1.3) for SWS. Earlier introduction of solids was associated with a shorter duration of breastfeeding, particularly in cohorts where earlier introduction of solids was the norm, with a dose-response relationship, which was not explained by background social characteristics. As mothers most commonly introduced solids in the month prior to the then recommended age, continuing to recommend deferring solids to the age of 6 months is important to support sustained breastfeeding.

Development of a biochemical marker to detect current breast milk intake.

The WHO recommends exclusive breastfeeding for 6 months, but despite interventions, breastfeeding rates remain stubbornly low. Financial voucher incentives have shown promise but require a biomarker for validation of intake. This study aimed to develop a simple biochemical assay of infant urine that would tell if an infant was receiving any breast milk to validate maternal report. Urine samples were collected and snap frozen from 34 infants attending with minor illness or feeding problems, of whom 12 infants were exclusively breastfed, nine exclusively formula fed, and 11 mixed breast/formula fed. High-performance anion exchange chromatography was used to identify discriminating patterns of monosaccharide composition of unconjugated glycans in a sequence of three experiments. The absolute concentration of all human milk oligosaccharides measured blind could detect "any breastfeeding" only with a sensitivity of 48% and specificity of 78%. Unblinded examination of N-acetylglucosamine (GlcNAc) measured as GlcNH2 after hydrolysis of GlcNAc improved sensitivity to 75% at the expense of a specificity of 28%. Estimation of the relative abundance of GlcNH2 (GlcNH2[%]) or the ratio of GlcNH2 to endogenous mannose (Man) improved accuracy. In a further blind experiment, the GlcNH2/Man ratio with a cut-off of 1.5 correctly identified all those receiving "any breast milk," while excluding exclusively formula fed infants. The GlcNH2/Man ratio in infant urine is a promising test to provide biochemical confirmation of any breastfeeding for trials of breastfeeding promotion.

Migration through a small pore disrupts inactive chromatin organization in neutrophil-like cells.

BACKGROUND: Mammalian cells are flexible and can rapidly change shape when they contract, adhere, or migrate. The nucleus must be stiff enough to withstand cytoskeletal forces, but flexible enough to remodel as the cell changes shape. This is particularly important for cells migrating through confined spaces, where the nuclear shape must change in order to fit through a constriction. This occurs many times in the life cycle of a neutrophil, which must protect its chromatin from damage and disruption associated with migration. Here we characterized the effects of constricted migration in neutrophil-like cells. RESULTS: Total RNA sequencing identified that migration of neutrophil-like cells through 5- or 14-µm pores was associated with changes in the transcript levels of inflammation and chemotaxis-related genes when compared to unmigrated cells. Differentially expressed transcripts specific to migration with constriction were enriched for groups of genes associated with cytoskeletal remodeling. Hi-C was used to capture the genome organization in control and migrated cells. Limited switching was observed between the active (A) and inactive (B) compartments after migration. However, global depletion of short-range contacts was observed following migration with constriction compared to migration without constriction. Regions with disrupted contacts, TADs, and compartments were enriched for inactive chromatin. CONCLUSION: Short-range genome organization is preferentially altered in inactive chromatin, possibly protecting transcriptionally active contacts from the disruptive effects of migration with constriction. This is consistent with current hypotheses implicating heterochromatin as the mechanoresponsive form of chromatin. Further investigation concerning the contribution of heterochromatin to stiffness, flexibility, and protection of nuclear function will be important for understanding cell migration in relation to human health and disease.

Health staff understanding, application, and interpretation of growth charts in Nigeria.

We aimed to compare plotting accuracy and interpretation of weight gain patterns in average and small infants on road-to-health (RTH) and the new World Health Organization (WHO) growth charts in Enugu, Nigeria. Child health staff plotted standard weights on both formats. Twelve plotted charts were created, permutating three different weight trajectories (fast, steady, and slow) ending at two attained weights (average and small), with each plotted on both chart formats. Respondents were shown four of these charts and asked to describe the weight gain pattern shown and what action this pattern would prompt. There were 222 respondents, of whom 78% were hospital based; 54% were nurses, 32% medical doctors, and 13% nutritionists. Plotting accuracy was good on both the WHO and RTH charts, but rating of weight gain was generally poor. On the RTH chart, slow weight gain was correctly recognized in only 19% average and 35% small infants, and responses were not significantly associated with the pattern shown. On the WHO charts, slow weight gain was correctly recognized in 40% average and 65% small infants (p = .002 and <.001), but they were also more likely to rate small children with normal growth as slow weight gain. In a logistic regression model, final weight predicted a slow weight gain rating more strongly (OR = 2.4; 1.8-3.2) than an actual slow weight gain pattern (OR 1.8; 1.1-1.6). Health staff seemed unable to recognize slow weight gain and were influenced more by current weight than actual weight gain pattern, though the new WHO format improved recognition.

A Review About Lycopene-Induced Nuclear Hormone Receptor Signalling in Inflammation and Lipid Metabolism via still Unknown Endogenous Apo-10´-Lycopenoids.

Lycopene is the red pigment in tomatoes and tomato products and is an important dietary carotenoid found in the human organism. Lycopene-isomers, oxidative lycopene metabolites and apo-lycopenoids are found in the food matrix. Lycopene intake derived from tomato consumption is associated with alteration of lipid metabolism and a lower incidence of cardiovascular diseases (CVD). Lycopene is mainly described as a potent antioxidant but novel studies are shifting towards its metabolites and their capacity to mediate nuclear receptor signalling. Di-/tetra-hydro-derivatives of apo-10´-lycopenoic acid and apo-15´-lycopenoic acids are potential novel endogenous mammalian lycopene metabolites which may act as ligands for nuclear hormone mediated activation and signalling. In this review, we postulate that complex lycopene metabolism results in various lycopene metabolites which have the ability to mediate transactivation of various nuclear hormone receptors like RARs, RXRs and PPARs. A new mechanistic explanation of how tomato consumption could positively modulate inflammation and lipid metabolism is discussed.