Prevalence of Gastroesophageal Reflux Disease in Congenital Diaphragmatic Hernia Survivors From Infancy to Adulthood

Background: Gastroesophageal reflux disease (GERD) is a common comorbidity associated with congenital diaphragmatic hernia (CDH), with reported cases of Barrett's esophagus (BE) and esophageal adenocarcinoma before the age of 25. The prevalence and natural course of GERD in CDH survivors remain uncertain due to variations in diagnostic methods. We aimed to analyse the GERD prevalence from infancy through young adulthood. Methods: We retrospectively analyzed pH-impedance measurements and endoscopic findings in 96 CDH survivors evaluated as routine care using well established clinical protocols. GERD was defined as an abnormal acid exposure time for pH-MII measurements and as presence of reflux esophagitis or BE at upper endoscopy. Clinical data including symptoms at time of follow-up and use of antireflux medication were collected. Results: GERD prevalence remained consistently low (≤10%) across all age groups, yet many patients experienced GER symptoms. Histological abnormalities were observed in 80% of adolescents and young adults, including microscopic esophagitis in 50%. BE was diagnosed in 7% before the age of 18, all had GER symptoms. CDH severity, anatomy at the time of CDH correction, alcohol usage, and smoking did not emerge as significant risk factors for GERD. Conclusions: Given the low GERD prevalence in CDH survivors, a symptom-driven approach to diagnosis and follow-up is warranted. We advise long-term follow-up for all adult patients due to the early onset of BE and the limited evidence available. The longitudinal course and impact of GERD on other long-term CDH-related comorbidities should be explored in larger cohorts.</p

Development of an in vitro airway epithelial–endothelial cell culture model on a flexible porous poly(Trimethylene carbonate) membrane based on calu‐3 airway epithelial cells and lung microvascular endothelial cells

Due to the continuing high impact of lung diseases on society and the emergence of new respiratory viruses, such as SARS‐CoV‐2, there is a great need for in vitro lung models that more accurately recapitulate the in vivo situation than current models based on lung epithelial cell cultures on stiff membranes. Therefore, we developed an in vitro airway epithelial–endothelial cell culture model based on Calu‐3 human lung epithelial cells and human lung microvascular endothelial cells (LMVECs), cultured on opposite sides of flexible porous poly(trimethylene carbonate) (PTMC) membranes. Calu‐3 cells, cultured for two weeks at an air–liquid interface (ALI), showed good expression of the tight junction (TJ) protein Zonula Occludens 1 (ZO‐1). LMVECs cultured submerged for three weeks were CD31‐positive, but the expression was diffuse and not localized at the cell membrane. Barrier functions of the Calu‐3 cell cultures and the co‐cultures with LMVECs were good, as determined by electrical resistance measurements and fluorescein isothiocya-nate‐dextran (FITC‐dextran) permeability assays. Importantly, the Calu‐3/LMVEC co‐cultures showed better cell viability and barrier function than mono‐cultures. Moreover, there was no evidence for epithelial‐ and endothelial‐to‐mesenchymal transition (EMT and EndoMT, respec-tively) based on staining for the mesenchymal markers vimentin and α‐SMA, respectively. These results indicate the potential of this new airway epithelial–endothelial model for lung research. In addition, since the PTMC membrane is flexible, the model can be expanded by introducing cyclic stretch for enabling mechanical stimulation of the cells. Furthermore, the model can form the basis for biomimetic airway epithelial–endothelial and alveolar–endothelial models with primary lung epithelial cells.</p

Modulation of airway epithelial innate immunity and wound repair by M(GM-CSF) and M(M-CSF) macrophages

Airway epithelial cells and macrophages participate in inflammatory responses to external noxious stimuli, which can cause epithelial injury. Upon injury, epithelial cells and macrophages act in concert to ensure rapid restoration of epithelial integrity. The nature of the interactions between these cell types during epithelial repair is incompletely understood. We used an in vitro human coculture model of primary bronchial epithelial cells cultured at the air-liquid interface (ALI-PBEC) and polarized primary monocyte-derived macrophages. Using this coculture, we studied the contribution of macrophages to epithelial innate immunity, wound healing capacity, and epithelial exposure to whole cigarette smoke (WCS). Coculture of ALI-PBEC with lipopolysaccharide (LPS)-activated M(GM-CSF) macrophages increased the expression ofDEFB4A,CXCL8, andIL6at 24 h in the ALI-PBEC, whereas LPS-activated M(M-CSF) macrophages only increased epithelialIL6expression. Furthermore, wound repair was accelerated by coculture with both activated M(GM-CSF) and M(M-CSF) macrophages, also following WCS exposure. Coculture of ALI-PBEC and M(GM-CSF) macrophages resulted in increasedCAMPexpression in M(GM-CSF) macrophages, which was absent in M(M-CSF) macrophages.CAMPencodes LL-37, an antimicrobial peptide with immune-modulating and repair-enhancing activities. In conclusion, dynamic crosstalk between ALI-PBEC and macrophages enhances epithelial innate immunity and wound repair, even upon concomitant cigarette smoke exposure.Pathogenesis and treatment of chronic pulmonary disease

Modulation of Airway Epithelial Innate Immunity and Wound Repair by M(GM-CSF) and M(M-CSF) Macrophages

Airway epithelial cells and macrophages participate in inflammatory responses to external noxious stimuli, which can cause epithelial injury. Upon injury, epithelial cells and macrophages act in concert to ensure rapid restoration of epithelial integrity. The nature of the interactions between these cell types during epithelial repair is incompletely understood. We used an in vitro human coculture model of primary bronchial epithelial cells cultured at the air-liquid interface (ALI-PBEC) and polarized primary monocyte-derived macrophages. Using this coculture, we studied the contribution of macrophages to epithelial innate immunity, wound healing capacity, and epithelial exposure to whole cigarette smok

Фразеологические единицы с компонентом deve в крымскотатарском и турецком языках

Цель и задачи статьи - выявить и охарактеризовать фразеологические единицы крымскотатарского и турецкого языков с компонентом deve/верблюд в структуре национальной когнитивной картины мира

Attenuated PDGF signaling drives alveolar and microvascular defects in neonatal chronic lung disease

Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O2). Regardless, the primary molecular driver of the disease remains elusive. We discover significant enrichment for SNPs in the PDGF-Rα gene in preterms with nCLD and directly test the effect of PDGF-Rα haploinsufficiency on the development of nCLD using a preclinical mouse model of MV-O2. In the context of MV-O2, attenuated PDGF signal

Using Y-chromosome capture enrichment to resolve haplogroup H2 shows new evidence for a two-Path Neolithic expansion to Western Europe

Uniparentally-inherited markers on mitochondrial DNA (mtDNA) and the non-recombining regions of the Y chromosome (NRY), have been used for the past 30 years to investigate the history of humans from a maternal and paternal perspective.Researchers have preferred mtDNA due to its abundance in the cells, and comparatively high substitution rate. Conversely, the NRY is less susceptible to back mutations and saturation, and is potentially more informative than mtDNA owing to its longer sequence length. However, due to comparatively poor NRY coverage via shotgun sequencing, and the relatively low and biased representation of Y-chromosome variants on capture arrays such as the 1240K, ancient DNA studies often fail to utilize the unique perspective that the NRY can yield.Here we introduce a new DNA enrichment assay, coined YMCA (Y-mappable capture assay), that targets the “mappable” regions of the NRY. We show that compared to low-coverage shotgun sequencing and 1240K capture, YMCA significantly improves the coverage and number of sites hit on the NRY, increasing the number of Y-haplogroup informative SNPs, and allowing for the identification of previously undiscovered variants.To illustrate the power of YMCA, we show that the analysis of ancient Y-chromosome lineages can help to resolve Y-chromosomal haplogroups. As a case study, we focus on H2, a haplogroup associated with a critical event in European human history: the Neolithic transition. By disentangling the evolutionary history of this haplogroup, we further elucidate the two separate paths by which early farmers expanded from Anatolia and the Near East to western Europe.Competing Interest StatementThe authors have declared no competing interest.Introduction Results and Discussion - Validating the performance of YMCA - Application of YMCA to YHG H2 as a case study - Identifying diagnostic SNPs for improved YHG H2 resolution Discussion Materials and Methods - Data - Contamination quality filtering - Method of Y Haplogroup Assignment - Comparing the Performance of our Y-capture Array Phylogenetic Tree Reconstructio

Investigating mitochondrial DNA relationships in Neolithic Western Europe through serial coalescent simulations

Recent ancient DNA studies on European Neolithic human populations have provided persuasive evidence of a major migration of farmers originating from the Aegean, accompanied by sporadic hunter-gatherer admixture into early Neolithic populations, but increasing toward the Late Neolithic. In this context, ancient mitochondrial DNA data collected from the Neolithic necropolis of Gurgy (Paris Basin, France), the largest mitochondrial DNA sample obtained from a single archeological site for the Early/Middle Neolithic period, indicate little differentiation from farmers associated to both the Danubian and Mediterranean Neolithic migration routes, as well as from Western European hunter-gatherers. To test whether this pattern of differentiation could arise in a single unstructured population by genetic drift alone, we used serial coalescent simulations. We explore female effective population size parameter combinations at the time of the colonization of Europe 45000 years ago and the most recent of the Neolithic samples analyzed in this study 5900 years ago, and identify conditions under which population panmixia between hunter-gatherers/Early-Middle Neolithic farmers and Gurgy cannot be rejected. In relation to other studies on the current debate of the origins of Europeans, these results suggest increasing hunter-gatherer admixture into farmers' group migrating farther west in Europe.European Journal of Human Genetics advance online publication, 28 December 2016; doi:10.1038/ejhg.2016.180

CD200 Receptor Controls Sex-Specific TLR7 Responses to Viral Infection

Immunological checkpoints, such as the inhibitory CD200 receptor (CD200R), play a dual role in balancing the immune system during microbial infection. On the one hand these inhibitory signals prevent excessive immune mediated pathology but on the other hand they may impair clearance of the pathogen. We studied the influence of the inhibitory CD200-CD200R axis on clearance and pathology in two different virus infection models. We find that lack of CD200R signaling strongly enhances type I interferon (IFN) production and viral clearance and improves the outcome of mouse hepatitis corona virus (MHV) infection, particularly in female mice. MHV clearance is known to be dependent on Toll like receptor 7 (TLR7)-mediated type I IFN production and sex differences in TLR7 responses previously have been reported for humans. We therefore hypothesize that CD200R ligation suppresses TLR7 responses and that release of this inhibition enlarges sex differences in TLR7 signaling. This hypothesis is supported by our findings that in vivo administration of synthetic TLR7 ligand leads to enhanced type I IFN production, particularly in female Cd200−/− mice and that CD200R ligation inhibits TLR7 signaling in vitro. In influenza A virus infection we show that viral clearance is determined by sex but not by CD200R signaling. However, absence of CD200R in influenza A virus infection results in enhanced lung neutrophil influx and pathology in females. Thus, CD200-CD200R and sex are host factors that together determine the outcome of viral infection. Our data predict a sex bias in both beneficial and pathological immune responses to virus infection upon therapeutic targeting of CD200-CD200R

Screening for multi-drug-resistant Gram-negative bacteria: what is effective and justifiable?

Effectiveness is a key criterion in assessing the justification of antibiotic resistance interventions. Depending on an intervention's effectiveness, burdens and costs will be more or less justified, which is especially important for large scale population-level interventions with high running costs and pronounced risks to individuals in terms of wellbeing, integrity and autonomy. In this paper, we assess the case of routine hospital screening for multi-drug-resistant Gram-negative bacteria (MDRGN) from this perspective. Utilizing a comparison to screening programs for Methicillin-Resistant Staphylococcus aureus (MRSA) we argue that current screening programmes for MDRGN in low endemic settings should be reconsidered, as its effectiveness is in doubt, while general downsides to screening programs remain. To accomplish justifiable antibiotic stewardship, MDRGN screening should not be viewed as a separate measure, but rather as part of a comprehensive approach. The program should be redesigned to focus on those at risk of developing symptomatic infections with MDRGN rather than merely detecting those colonised