bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse childhood experiences and depressive symptomatology among pregnant women
Authors: Ångerud Katja , Annerbäck Eva‐Maria , Tydén Tanja , Boddeti Santosh , Kristiansson Per 
Published: February 2018

AbstractIntroductionAdverse childhood experiences (ACE) result in somatic and mental health disturbances. Their influence on antenatal depression is scarcely studied. This study examined the association between experience of ACE and antenatal depressive symptomatology.Material and methods1257 women from 172 antenatal clinics in Sweden were surveyed during pregnancy and 1 year after delivery. Demographics, previous medical history and Edinburgh Postpartum Depression Scale (EPDS) were collected in pregnancy and postpartum and ACE 1 year postpartum. ACEs were partitioned into 10 categories. Statistical analyses used linear and logistic regression with EPDS score as main outcome measure.Results736 (58.6%) women reported at least one ACE category and 88 women (7%) reported five or more ACE categories. An EPDS score of ≥13, which qualifies for a probable depression diagnosis, was reported by 277 (23%) women. In simple regression analyses the EPDS score was positively associated with the number of ACEs, cigarette smoking before pregnancy, body mass index and psychiatric disorders, whereas education level was inversely associated. In a multiple regression analysis, ACEs, education level and psychiatric disorder remained associated to the EPDS score. Among women with an ACE score ≥5, the odds ratio of having an EPDS score indicating probable depression was 4.2 (CI 2.5–7.0).ConclusionsACE was commonly reported. ACE and depressive symptomatology in late pregnancy were strongly associated in a dose–response manner. Women with several ACEs had high odds of depressive symptomatology in late pregnancy and were more likely to report depressive symptoms both in late pregnancy and postpartum.
Medical treatment in the management of deep endometriosis infiltrating the proximal rectum and sigmoid colon: a comprehensive literature review
Authors: Vercellini Paolo , Buggio Laura , Borghi Alessandra , Monti Ermelinda , Gattei Umberto , Frattaruolo Maria P. 
Published: February 2018

AbstractA comprehensive literature review was performed to evaluate the effect of various hormonal therapies, in terms of variations of intestinal and pain complaints and of patient satisfaction with treatment, in women with symptomatic, non‐severely sub‐occlusive endometriosis infiltrating the proximal rectum and sigmoid colon. A MEDLINE search through PubMed from 2000 to 2018 was conducted to identify all original English language articles published on medical treatment for colorectal endometriosis. Additional reports were identified by systematically reviewing reference lists and using the “similar articles” function in PubMed. A total of 420 women with colorectal endometriosis treated with combined oral contraceptives, progestins, gonadotropin releasing‐hormone (GnRH) agonists and aromatase inhibitors have been described in eight case series, two retrospective cohort studies and four case reports. Published data consistently suggest that several hormonal medications can control most symptoms associated with intestinal endometriosis, provided the relative bowel lumen stenosis is less than 60%. Patients with irritative‐type symptoms appear to respond better than those with constipation. Overall, about two‐thirds of women were satisfied with the treatment received, independently of the drug used. Progestins are the compound supported by the largest body of evidence. The addition of aromatase inhibitors or, alternatively, the use of GnRH agonists does not seem to be associated with better outcomes. Long‐term treatment with a progestin should be proposed as an alternative to surgery to patients with non‐severely sub‐occlusive endometriosis infiltrating the proximal rectum and sigmoid colon who are not seeking conception. The final decision should be shared together with the woman, respecting her preferences and priorities.
The Weanling: Iron for All or One
Authors: SIIMES M. A. , SALMENPERÄ L. 
Published: February 2018

Siimes M. A. and Salmenperä, L. (Children's Hospital, University of Helsinki, Finland). The weanling: Iron for all or one.Mild iron deficiency remains to be a problem of healthy infants even in Europe. In this paper we discuss some of the potential reasons. There are physiological variations which result in elevated need of iron during infancy. These include growth that is unusually rapid, change in hemoglobin level from low normal to high normal and quality of milk nutrition during infancy. Prolonged exclusive breast feeding is a particularly interesting mode of nutrition since the iron absorption seems to be extremely effective. Infants may compensate their increased needs of iron either by stimulation of intestinal absorption of iron or of mobilization of iron from the relatively large tissue stores. We conclude that healthy full‐term Infants need to be fed with iron supplemented infant milk formulas or solid foods fortified with iron to order guarantee an optimal iron nutrition.
Fortification of the Diet as a Strategy for Preventing Iron Deficiency
Authors: MacPHAIL A. P. , BOTHWELL T. H. 
Published: February 2018

MacPhail, A. P. and Bothwell, T. H. (Joint University and MRC Iron and Red Cell Metabolism Unit, University of the Witwatersrand Medical School, Parktown, Johannesburg, South Africa). Fortification of the diet as a strategy for preventing iron deficiency.Progress in the fortification of food with iron is reviewed in the light of the different circumstances prevailing in the developed and developing world. Although fortification programmes are well established in developed countries many were not based on sound principles and there is no good evidence that they have proved effective. The important steps in establishing a fortification programme include accurate establishment of the need for iron fortification in a particular group or population, the choice of an appropriate combination of food vehicle and iron compound which is both stable and acceptable, and confirmation that the iron in the chosen blend is bioavailable and in different dietary settings. Only after the successful completion of controlled field trials using the chosen combination is the establishment of a regional or national fortification programme worthwhile. These points are illustrated by the success of field trials in the developing world, at least one of which has led to the implementation of a national programme directed to infants and children. Finally, a case study is described in which these principles were followed in the planning and execution of a successful field trial in an iron deficient Indian population in South Africa. The vehicle was curry powder and the iron compound Fe(111)EDTA.
Iron for the Suckling
Authors: AGGETT P. J. , BARCLAY S. , WHITLEY J. E. 
Published: February 2018

Aggett, P. J., Barclay, S. and Whitley, J. E. (Department of Child Health, University of Aberdeen, Aberdeen, and Scottish Universities' Research and Reactor Centre, East Kilbride, Scotland). Iron for the suckling.Knowledge of the metabolism of iron by young infants is incomplete but combining practical studies based on detecting the onset of iron depletion with isotopic studies of iron economy may improve our understanding of iron metabolism in infants and our strategies for ensuring their iron supply. The iron accumulated by the fetus is enough to delay the risk of iron deficiency until four, and two months of age in term and preterm infants respectively. Breast fed term infants may not need extra iron until they are six months or older; but whereas low iron formulas are adequate for other infants until about four months of age, therafter infants need extra iron which can be provided effectively in iron fortified formulas. Breast fed low birth weight infants need iron supplements from two months of age but those fed specific low birth weight formulas which are iron fortified should not need extra iron.
Review article: predictors of response to vedolizumab and ustekinumab in inflammatory bowel disease
Authors: Barré A. , Colombel J.‐F. , Ungaro R. 
Published: February 2018

SummaryBackgroundIncreased knowledge of pathways involved in the pathogenesis of IBD has led to the development of new treatment options for Crohn's disease (CD) and ulcerative colitis (UC). Two new biological agents have been recently approved for IBD: vedolizumab and ustekinumab. They have different therapeutic targets (α4β7 integrin for vedolizumab and interleukin‐12/23 pathways for ustekinumab) than the primary biological class, anti‐tumour necrosis factor alpha (anti‐TNF) agents. As the armamentarium for IBD increases in coming years, it will become important to understand factors associated with response in order to best position and personalise therapy.AimTo summarise the current data on predictors of response to vedolizumab and ustekinumab in IBD patients.MethodsWe conducted a comprehensive literature review. A PubMed search was performed using pre‐defined key words and terms to identify relevant studies on predictors of response.ResultsPatients with severe disease (by clinical activity and inflammatory biomarkers), or prior anti‐TNF exposure are less likely to respond to vedolizumab. Ileocolonic disease, no prior surgery and uncomplicated phenotype were associated with better responses to ustekinumab in CD. Initial response seems to predict a better long‐term maintenance in both therapies (P < 0.001). Contrary to anti‐TNF therapies, immunogenicity appears to play less of a role in response.ConclusionAs the number of new biological therapies increase in IBD, identifying patients who are most likely to benefit from specific agents is of paramount importance to help best position IBD therapies.
Short‐chain fatty acids induce tissue plasminogen activator in airway epithelial cells via GPR41&43
Authors: Imoto Y. , Kato A. , Takabayashi T. , Sakashita M. , Norton J. E. , Suh L. A. , Carter R. G. , Weibman A. R. , Hulse K. E. , Stevens W. , Harris K. E. , Peters A. T. , Grammer L. C. , Tan B. K. , Welch K. , Conley D. B. , Kern R. C. , Fujieda S. , Schleimer R. P. 
Published: February 2018

SummaryBackgroundChronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease generally divided based on the presence or absence of nasal polyps (NPs). One of the features of NPs is excessive fibrin deposition, which is associated with down‐regulation of tissue plasminogen activator (t‐PA) in NPs. As t‐PA is expressed in epithelial cells, and epithelium is readily accessible to topical therapies, identifying compounds that can mediate the induction of t‐PA would be a potential new strategy for the treatment of NPs.ObjectiveThe objective of this study was to determine whether short‐chain fatty acids (SCFAs) can induce t‐PA in airway epithelial cells via their known receptors GPR41 and GPR43.MethodsWe performed immunohistochemistry (IHC) to determine whether receptors for SCFAs, known as G protein‐coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3) and GPR43/FFAR2, are expressed in nasal tissue. Primary normal human bronchial epithelial (NHBE) cells were stimulated with different concentrations of SCFAs to test induction of t‐PA, which was analysed by expression of mRNA and protein. Mediation of responses by SCFA receptors was evaluated by specific receptor gene silencing with siRNA.ResultsImmunohistochemistry study revealed that airway epithelial cells expressed GPR41 and GPR43. Acetic acid, propionic acid, butyric acid and valeric acid significantly induced t‐PA expression from two‐ to tenfolds. The strongest inducer of t‐PA from NHBE cells was propionic acid; cells stimulated with propionic acid released t‐PA into the supernatant in its active form. Gene silencing of GPR41 and GPR43 revealed that induction of t‐PA by SCFAs was dependent upon both GPR41 and GPR43.Conclusions and Clinical RelevanceShort‐chain fatty acids were shown to induce airway epithelial cell expression of t‐PA via GPR41 and GPR43. Topical delivery of potent compounds that activate these receptors may have value by reducing fibrin deposition and shrinking nasal polyp growth.
Immunoassay methods used in clinical studies for the detection of anti-drug antibodies to adalimumab and infliximab
Authors: Gorovits B , Baltrukonis D J , Bhattacharya I , Birchler M A , Finco D , Sikkema D , Vincent M S , Lula S , Marshall L , Hickling T P 
Published: February 2018

Summary
We examined the assay formats used to detect anti-drug antibodies (ADA) in clinical studies of the anti-tumour necrosis factor (TNF) monoclonal antibodies adalimumab and infliximab in chronic inflammatory disease and their potential impact on pharmacokinetic and clinical outcomes. Using findings of a recent systematic literature review of the immunogenicity of 11 biological/biosimilar agents, we conducted an ancillary qualitative review of a subset of randomized controlled trials and observational studies of the monoclonal antibodies against anti-TNF factor adalimumab and infliximab. Among studies of adalimumab and infliximab, the immunoassay method used to detect antibodies was reported in 91 of 111 (82%) and 154 of 206 (75%) adalimumab and infliximab studies, respectively. In most adalimumab and infliximab studies, an enzyme-linked immunosorbent assay or radioimmunoassay was used [85 of 91 (93%) and 134 of 154 (87%), respectively]. ADA incidence varied widely among assays and inflammatory diseases (adalimumab, 0–87%; infliximab, 0–79%). Pharmacokinetic and clinical outcomes were only reported for ADA-positive patients in 38 of 91 (42%) and 61 of 154 (40%) adalimumab and infliximab studies, respectively. Regardless of assay format or biological used, ADA formation was associated with lower serum concentrations, reduced efficacy and elevated rates of infusion-related reactions. Consistent with previous recommendations to improve interpretation of immunogenicity data for biologicals, greater consistency in reporting of assay methods and clinical consequences of ADA formation may prove useful. Additional standardization in immunogenicity testing and reporting, application of modern, robust assays that satisfy current regulatory expectations and implementation of international standards for marketed products may help to improve our understanding of the impact of immunogenicity to biologics.
Separation of plasma-derived exosomes into CD3(+) and CD3(−) fractions allows for association of immune cell and tumour cell markers with disease activity in HNSCC patients
Authors: Theodoraki M-N , Hoffmann T K , Whiteside T L 
Published: February 2018

Summary
Head and neck squamous cell carcinoma (HNSCC) is a highly immunosuppressive malignancy. Exosomes in HNSCC patients' plasma are enriched in inhibitory cargo and mediate immunosuppression. As these exosomes are products of various cells, the cellular origin of immunoregulatory proteins they carry is unknown. To test whether tumour- or T cell-derived exosomes in patients' plasma are immunosuppressive and impact upon disease activity, we separated CD3(−) from CD3(+) exosomes by immunocapture using anti-CD3 antibodies. The exosome protein cargo was evaluated for immunoregulatory proteins using on-bead flow cytometry. Tumour protein-enriched CD3(−) exosomes were CD44v3(+). Surprisingly, mean levels of programmed death ligand 1 (PD-L1), cytotoxic T lymphocyte antigen 4 (CTLA-4) and cyclooxygenase-2 (COX-2) were similar in CD3(+) and CD3(−) exosomes, although the latter induced higher (P &lt; 0·0025) ex-vivo apoptosis of CD8(+) T cells and greater (P &lt; 0·005) conversion of CD4+ T cells to CD4(+)CD39(+) regulatory T cells (Treg). CD3(+) and CD3(−) exosomes carrying high levels of immunosuppressive proteins were highly effective in mediating these functions. Exosomes of patients with Union for International Cancer Control (UICC) stages III/IV disease had higher levels of PD-L1 and COX-2 than stages I/II patients (P &lt; 0·005). Patients with nodal involvement had exosomes with the higher inhibitory protein content than N0 patients (P &lt; 0·03). CD3(+) and CD3(−) exosomes of HNSCC patients had higher PD-L1, COX-2 and CD15s levels than healthy donors' exosomes (P &lt; 0·009), although levels of immunostimulatory OX40 or OX40L were not different. By isolating CD3(−)/CD44v3-enriched and CD3(+) exosomes from plasma, the cellular origins of immunoregulatory proteins they carry were identified. Association of exosome molecular profiles with disease progression supports the exosome potential as future cancer biomarkers.
Correction of T cell deficiency in ZAP-70 knock-out mice by simple intraperitoneal adoptive transfer of thymocytes
Authors: Kugyelka R , Kohl Z , Olasz K , Prenek L , Berki T , Balogh P , Boldizsár F 
Published: February 2018

SummaryThe tyrosine kinase zeta chain-associated protein of 70 kDa (ZAP-70) plays a key role in T cell development and signalling. In the absence of ZAP-70, T cell development is arrested in the CD4+CD8+ double-positive stage, thus ZAP-70 homozygous knockout (ZAP-70−/−) mice have no mature T cells in their peripheral lymphoid organs and blood, causing severe immunodeficiency. We investigated the early kinetics and long-term effects of wild-type thymocyte transfer on T cell repopulation in ZAP-70−/− mice. We used a single intraperitoneal (i.p.) injection to deliver donor thymocytes to the recipients. Here, we show that after i.p. injection donor thymocytes leave the peritoneum through milky spots in the omentum and home to the thymus, where donor-originated CD4−CD8− double-negative thymocytes most probably restore T cell development and the disrupted thymic architecture. Subsequently, newly developed, donor-originated, single-positive αβ T cells appear in peripheral lymphoid organs, where they form organized T cell zones. The established chimerism was found to be stable, as donor-originated cells were present in transferred ZAP-70−/− mice as late as 8 months after i.p. injection. We demonstrate that a simple i.p. injection of ZAP-70+/+ thymocytes is a feasible method for the long-term reconstitution of T cell development in ZAP-70-deficient mice.
Past, present, and future of a freshwater fish metapopulation in a threatened landscape
Authors: Vera‐Escalona Iván , Senthivasan Shreeram , Habit Evelyn , Ruzzante Daniel E. 
Published: February 2018

AbstractIt is well documented that hydropower plants can affect the dynamics of fish populations through landscape alterations and the creation of new barriers. Less emphasis has been placed on the examination of the genetic consequences for fish populations of the construction of dams. The relatively few studies that focus on genetics often do not consider colonization history and even fewer tend to use this information for conservation purposes. As a case study, we used a 3‐pronged approach to study the influence of historical processes, contemporary landscape features, and potential future anthropogenic changes in landscape on the genetic diversity of a fish metapopulation. Our goal was to identify the metapopulation's main attributes, detect priority areas for conservation, and assess the consequences of the construction of hydropower plants for the persistence of the metapopulation. We used microsatellite markers and coalescent approaches to examine historical colonization processes, traditional population genetics, and simulations of future populations under alternate scenarios of population size reduction and gene flow. Historical gene flow appeared to have declined relatively recently and contemporary populations appeared highly susceptible to changes in landscape. Gene flow is critical for population persistence. We found that hydropower plants could lead to a rapid reduction in number of alleles and to population extirpation 50–80 years after their construction. More generally, our 3‐pronged approach for the analyses of empirical genetic data can provide policy makers with information on the potential impacts of landscape changes and thus lead to more robust conservation efforts.
PLCγ2 promotes apoptosis while inhibits proliferation in rat hepatocytes through PKCD/JNK MAPK and PKCD/p38 MAPK signalling
Authors: Chen Xiaoguang , Lv Qiongxia , Ma Jun , Liu Yumei 
Published: February 2018

AbstractObjectivesThe PLCG2 (PLCγ2) gene is a member of PLC gene family encoding transmembrane signalling enzymes involved in various biological processes including cell proliferation and apoptosis. Our earlier study indicated that PLCγ2 may be involved in the termination of regeneration of the liver which is mainly composed of hepatocytes, but its exact biological function and molecular mechanism in liver regeneration termination remains unclear. This study aims to examine the role of PLCγ2 in the growth of hepatocytes.Materials and methodsA recombinant adenovirus expressing PLCγ2 was used to infect primary rat hepatocytes. PLCγ2 mRNA and protein levels were detected by qRT‐PCR and Western blot. The subcellular location of PLCγ2 protein was tested by an immunofluorescence assay. The proliferation of hepatocytes was measured by MTT assay. The cell cycle and apoptosis were analysed by flow cytometry. Caspase‐3, ‐8 and ‐9 activities were measured by a spectrophotometry method. Phosphorylation levels of PKCD, JNK and p38 in the infected cells were detected by Western blot. The possible mechanism underlying the role of PLCγ2 in hepatocyte growth was also explored by adding a signalling pathway inhibitor.ResultsHepatocyte proliferation was dramatically reduced, while cell apoptosis was remarkably increased. The results demonstrated that PLCγ2 increased the phosphorylation of PKCD, p38 and JNK in rat hepatocytes. After PKCD activity was inhibited by the inhibitor Go 6983, the levels of both p‐p38 and p‐JNK MAPKs significantly decreased, and PLCγ2‐induced cell proliferation inhibition and cell apoptosis were obviously reversed.ConclusionsThis study showed that PLCγ2 regulates hepatocyte growth through PKCD‐dependently activating p38 MAPK and JNK MAPK pathways; this result was experimentally based on the further exploration of the effect of PLCγ2 on hepatocyte growth in vivo.
Cannabis use is associated with lower rates of initiation of injection drug use among street‐involved youth: A longitudinal analysis
Authors: Reddon Hudson , DeBeck Kora , Socias Maria Eugenia , Dong Huiru , Wood Evan , Montaner Julio , Kerr Thomas , Milloy Michael‐John 
Published: February 2018

AbstractIntroduction and AimsStreet‐involved youth are known to be at elevated risk of initiating injection drug use. However, the impact of so‐called ‘gateway’ drugs, such as cannabis, on injection initiation is unknown. The objective of this study was to examine the association between cannabis use and initiation of injection drug use among a prospective cohort of street‐involved youth in Vancouver, Canada.Design and MethodsData for this study were collected from the At‐Risk Youth Study. From September 2005 to May 2015, participants aged 14–26 who reported illicit drug use were recruited into this open prospective cohort study. An extended Cox regression model with time‐updated covariates was used to identify factors independently associated with injection initiation.ResultsDuring the study period, 481 street‐involved youth were included in this study. Of these, 228 (47.4%) reported at least daily cannabis use, and 103 (21.4%) initiated injection drug use. In a multivariable analysis, ≥daily cannabis use was associated with slower rates of injection initiation (adjusted relative hazard 0.66, 95% confidence interval 0.45–0.98; P = 0.038). Sub‐analyses revealed that cannabis use was negatively associated with initiation of injection stimulants but not initiation of injection opioids.Discussion and ConclusionsGiven the expansion of cannabis legalisation throughout North America, it is encouraging that cannabis use was associated with slower time to initiation of injection drug use in this cohort. This finding challenges the view of cannabis as a gateway substance that precipitates the progression to using harder and more addictive drugs.