Publications by authors named "Ravi Misra"

72 Publications

Electrospun core-shell nanofibers with encapsulated enamel matrix derivative for guided periodontal tissue regeneration.

Dent Mater J 2021 Jun 12. Epub 2021 Jun 12.

Center for Musculoskeletal Research, University of Rochester, School of Medicine and Dentistry.

The osteogenic effect of a composite electrospun core-shell nanofiber membrane encapsulated with Emdogain (EMD) was evaluated. The membrane was developed through coaxial electrospinning using polycaprolactone as the shell and polyethylene glycol as the core. The effects of the membrane on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) were examined using Alizarin Red S staining and qRT-PCR. Characterization of the nanofiber membrane demonstrated core-shell morphology with a mean diameter of ~1 µm. Examination of the release of fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) from core-shell nanofibers over a 22-day period showed improved release profile of encapsulated proteins as compared to solid nanofibers. When cultured on EMD-containing core-shell nanofibers, PDLSCs showed significantly improved osteogenic differentiation with increased Alizarin Red S staining and enhanced osteogenic gene expression, namely OCN, RUNX2, ALP, and OPN. Core-shell nanofiber membranes may improve outcomes in periodontal regenerative therapy through simultaneous mechanical barrier and controlled drug delivery function.
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http://dx.doi.org/10.4012/dmj.2020-412DOI Listing
June 2021

E-cigarette exposures, respiratory tract infections, and impaired innate immunity: a narrative review.

Pediatr Med 2021 Feb 28;4. Epub 2021 Feb 28.

Department of Pediatrics, Pulmonology, University of Rochester Medical Center, Rochester NY, USA.

Electronic cigarettes (e-cigarettes) are commonly used devices by adolescents and young adults. Since their introduction, the popularity of e-cigarettes has increased significantly with close to twenty percent of United States high school students reporting current use in 2020. As the number of e-cigarette users has increased, so have reports of vaping related health complications. Overall, respiratory tract infections remain one of the top ten leading causes of death in the US for every age group. Specific to the pediatric population, lower respiratory tract infections are the leading cause for hospitalization. This review highlights the current evidence behind e-cigarette exposure and its association with impaired innate immune function and the risk of lower respiratory tract infections. To date, various preclinical models have evaluated the direct effects of e-cigarette exposure on the innate immune system. More specifically, e-cigarette exposure impairs certain cell types of the innate immune system including the airway epithelium, lung macrophage and neutrophils. Identified effects of e-cigarette exposure common to the lung's innate immunity include abnormal mucus composition, reduced epithelial barrier function, impaired phagocytosis and elevated systemic markers of inflammation. These identified impairments in the lung's innate immunity have been shown to increase adhesion of certain bacteria and fungi as well as to increase virulence of common respiratory pathogens such as influenza virus, or . Information summarized in this review will provide guidance to healthcare providers, policy advocates and researchers for making informed decisions regarding the associated respiratory health risks of e-cigarette use in pediatric and young adults.
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http://dx.doi.org/10.21037/pm-20-97DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177080PMC
February 2021

Ontology-guided segmentation and object identification for developmental mouse lung immunofluorescent images.

BMC Bioinformatics 2021 Feb 23;22(1):82. Epub 2021 Feb 23.

Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA.

Background: Immunofluorescent confocal microscopy uses labeled antibodies as probes against specific macromolecules to discriminate between multiple cell types. For images of the developmental mouse lung, these cells are themselves organized into densely packed higher-level anatomical structures. These types of images can be challenging to segment automatically for several reasons, including the relevance of biomedical context, dependence on the specific set of probes used, prohibitive cost of generating labeled training data, as well as the complexity and dense packing of anatomical structures in the image. The use of an application ontology helps surmount these challenges by combining image data with its metadata to provide a meaningful biological context, modeled after how a human expert would make use of contextual information to identify histological structures, that constrains and simplifies the process of segmentation and object identification.

Results: We propose an innovative approach for the semi-supervised analysis of complex and densely packed anatomical structures from immunofluorescent images that utilizes an application ontology to provide a simplified context for image segmentation and object identification. We describe how the logical organization of biological facts in the form of an ontology can provide useful constraints that facilitate automatic processing of complex images. We demonstrate the results of ontology-guided segmentation and object identification in mouse developmental lung images from the Bioinformatics REsource ATlas for the Healthy lung database of the Molecular Atlas of Lung Development (LungMAP1) program CONCLUSION: We describe a novel ontology-guided approach to segmentation and classification of complex immunofluorescence images of the developing mouse lung. The ontology is used to automatically generate constraints for each image based on its biomedical context, which facilitates image segmentation and classification.
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http://dx.doi.org/10.1186/s12859-021-04008-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901098PMC
February 2021

Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia.

Front Immunol 2020 21;11:563473. Epub 2021 Jan 21.

Division of Neonatology, Department of Pediatrics, University of Rochester, Rochester, NY, United States.

Many premature babies who are born with neonatal respiratory distress syndrome (RDS) go on to develop Bronchopulmonary Dysplasia (BPD) and later Post-Prematurity Respiratory Disease (PRD) at one year corrected age, characterized by persistent or recurrent lower respiratory tract symptoms frequently related to inflammation and viral infection. Transcriptomic profiles were generated from sorted peripheral blood CD8+ T cells of preterm and full-term infants enrolled with consent in the NHLBI Prematurity and Respiratory Outcomes Program (PROP) at the University of Rochester and the University at Buffalo. We identified outcome-related gene expression patterns following standard methods to identify markers for oxygen utilization and BPD as outcomes in extremely premature infants. We further identified predictor gene sets for BPD based on transcriptomic data adjusted for gestational age at birth (GAB). RNA-Seq analysis was completed for CD8+ T cells from 145 subjects. Among the subjects with highest risk for BPD (born at <29 weeks gestational age (GA); n=72), 501 genes were associated with oxygen utilization. In the same set of subjects, 571 genes were differentially expressed in subjects with a diagnosis of BPD and 105 genes were different in BPD subjects as defined by physiologic challenge. A set of 92 genes could predict BPD with a moderately high degree of accuracy. We consistently observed dysregulation of , and -associated pathways in BPD. Using gene expression data from both premature and full-term subjects (n=116), we identified a 28 gene set that predicted the PRD status with a moderately high level of accuracy, which also were involved in signaling. Transcriptomic data from sort-purified peripheral blood CD8+ T cells from 145 preterm and full-term infants identified sets of molecular markers of inflammation associated with independent development of BPD in extremely premature infants at high risk for the disease and of PRD among the preterm and full-term subjects.
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http://dx.doi.org/10.3389/fimmu.2020.563473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859626PMC
May 2021

The dietary practices and beliefs of British South Asian people living with inflammatory bowel disease: a multicenter study from the United Kingdom.

Intest Res 2021 Jan 6. Epub 2021 Jan 6.

Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.

Background/aims: Epidemiological associations have implicated factors associated with Westernization, including the Western diet, in the development of inflammatory bowel disease (IBD). The role of diet in IBD etiopathogenesis, disease control and symptom management remains incompletely understood. Few studies have collected data on the dietary habits of immigrant populations living with IBD. Our aim was to describe the dietary practices and beliefs of British South Asians with IBD.

Methods: A 30-item questionnaire was developed and consecutively administered to 255 British South Asians with IBD attending gastroenterology clinics in the United Kingdom.

Results: Fifty-one percent of participants believed diet was the initiating factor for their IBD and 63% felt diet had previously triggered disease relapse. Eighty-nine percent avoided certain dietary items in the belief that this would prevent relapse. The most commonly avoided foods and drinks were spicy and fatty foods, carbonated drinks, milk products, alcohol, coffee, and red meat. A third of patients had tried a whole food exclusion diet, most commonly lactose- or gluten-free, and this was most frequently reported amongst those with clinically active IBD (P= 0.02). Almost 60% of participants avoided eating the same menu as their family, or eating out, at least sometimes, to prevent IBD relapse.

Conclusions: British South Asians with IBD demonstrate significant dietary beliefs and food avoidance behaviors with increased frequency compared to those reported in Caucasian IBD populations. Studies in immigrant populations may offer valuable insights into the interaction between diet, Westernization and cultural drift in IBD pathogenesis and symptomatology.
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http://dx.doi.org/10.5217/ir.2020.00079DOI Listing
January 2021

Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV2 host genes.

Elife 2020 11 9;9. Epub 2020 Nov 9.

NIH, Bethesda, United States.

Respiratory failure associated with COVID-19 has placed focus on the lungs. Here, we present single-nucleus accessible chromatin profiles of 90,980 nuclei and matched single-nucleus transcriptomes of 46,500 nuclei in non-diseased lungs from donors of ~30 weeks gestation,~3 years and ~30 years. We mapped candidate -regulatory elements (cCREs) and linked them to putative target genes. We identified distal cCREs with age-increased activity linked to SARS-CoV-2 host entry gene in alveolar type 2 cells, which had immune regulatory signatures and harbored variants associated with respiratory traits. At the 3p21.31 COVID-19 risk locus, a candidate variant overlapped a distal cCRE linked to , a gene expressed in alveolar cells and with known functional association with the SARS-CoV-2 receptor ACE2. Our findings provide insight into regulatory logic underlying genes implicated in COVID-19 in individual lung cell types across age. More broadly, these datasets will facilitate interpretation of risk loci for lung diseases.
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http://dx.doi.org/10.7554/eLife.62522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688309PMC
November 2020

The use of 5-aminosalicylate for patients with Crohn's disease in a prospective European inception cohort with 5 years follow-up - an Epi-IBD study.

United European Gastroenterol J 2020 10 26;8(8):949-960. Epub 2020 Jul 26.

Hull University Teaching Hospitals NHS Trust, Hull, UK.

Background: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice.

Aims: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease.

Methods: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists.

Results: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)).

Conclusion: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.
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http://dx.doi.org/10.1177/2050640620945949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707880PMC
October 2020

Bacteroides thetaiotaomicron-derived outer membrane vesicles promote regulatory dendritic cell responses in health but not in inflammatory bowel disease.

Microbiome 2020 06 8;8(1):88. Epub 2020 Jun 8.

Antigen Presentation Research Group, Imperial College London, Northwick Park & St. Mark's Hospital Campus, Watford Rd, Harrow, Greater London, HA1 3UJ, UK.

Background: Bacteroides thetaiotaomicron (Bt) is a prominent member of the human intestinal microbiota that, like all gram-negative bacteria, naturally generates nanosized outer membrane vesicles (OMVs) which bud off from the cell surface. Importantly, OMVs can cross the intestinal epithelial barrier to mediate microbe-host cell crosstalk involving both epithelial and immune cells to help maintain intestinal homeostasis. Here, we have examined the interaction between Bt OMVs and blood or colonic mucosa-derived dendritic cells (DC) from healthy individuals and patients with Crohn's disease (CD) or ulcerative colitis (UC).

Results: In healthy individuals, Bt OMVs stimulated significant (p < 0.05) IL-10 expression by colonic DC, whereas in peripheral blood-derived DC they also stimulated significant (p < 0.001 and p < 0.01, respectively) expression of IL-6 and the activation marker CD80. Conversely, in UC Bt OMVs were unable to elicit IL-10 expression by colonic DC. There were also reduced numbers of CD103 DC in the colon of both UC and CD patients compared to controls, supporting a loss of regulatory DC in both diseases. Furthermore, in CD and UC, Bt OMVs elicited a significantly lower proportion of DC which expressed IL-10 (p < 0.01 and p < 0.001, respectively) in blood compared to controls. These alterations in DC responses to Bt OMVs were seen in patients with inactive disease, and thus are indicative of intrinsic defects in immune responses to this commensal in inflammatory bowel disease (IBD).

Conclusions: Overall, our findings suggest a key role for OMVs generated by the commensal gut bacterium Bt in directing a balanced immune response to constituents of the microbiota locally and systemically during health which is altered in IBD patients. Video Abstract.
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http://dx.doi.org/10.1186/s40168-020-00868-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282036PMC
June 2020

The Importance of Vaccinating Children and Pregnant Women against Influenza Virus Infection.

Pathogens 2019 Nov 26;8(4). Epub 2019 Nov 26.

Department of Pediatrics Division of Pediatric Infectious Diseases, The University of Rochester Medical Center, Rochester, NY 14623, USA.

Influenza virus infection is responsible for significant morbidity and mortality in the pediatric and pregnant women populations, with deaths frequently caused by severe influenza-associated lower respiratory tract infection and acute respiratory distress syndrome (ARDS). An appropriate immune response requires controlling the viral infection through activation of antiviral defenses, which involves cells of the lung and immune system. High levels of viral infection or high levels of inflammation in the lower airways can contribute to ARDS. Pregnant women and young children, especially those born prematurely, may develop serious complications if infected with influenza virus. Vaccination against influenza will lead to lower infection rates and fewer complications, even if the vaccine is poorly matched to circulating viral strains, with maternal vaccination offering infants protection via antibody transmission through the placenta and breast milk. Despite the health benefits of the influenza vaccine, vaccination rates around the world remain well below targets. Trust in the use of vaccines among the public must be restored in order to increase vaccination rates and decrease the public health burden of influenza.
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http://dx.doi.org/10.3390/pathogens8040265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963306PMC
November 2019

CX3CR1 as a respiratory syncytial virus receptor in pediatric human lung.

Pediatr Res 2020 04 14;87(5):862-867. Epub 2019 Nov 14.

Division of Neonatology, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.

Background: Data on the host factors that contribute to infection of young children by respiratory syncytial virus (RSV) are limited. The human chemokine receptor, CX3CR1, has recently been implicated as an RSV receptor. Here we evaluate a role for CX3CR1 in pediatric lung RSV infections.

Methods: CX3CR1 transcript levels in the upper and lower pediatric airways were assessed. Tissue localization and cell-specific expression was confirmed using in situ hybridization and immunohistochemistry. The role of CX3CR1 in RSV infection was also investigated using a novel physiological model of pediatric epithelial cells.

Results: Low levels of CX3CR1 transcript were often, but not always, expressed in both upper (62%) and lower airways (36%) of pediatric subjects. CX3CR1 transcript and protein expression was detected in epithelial cells of normal human pediatric lung tissues. CX3CR1 expression was readily detected on primary cultures of differentiated pediatric/infant human lung epithelial cells. RSV demonstrated preferential infection of CX3CR1-positive cells, and blocking CX3CR1/RSV interaction significantly decreased viral load.

Conclusion: CX3CR1 is present in the airways of pediatric subjects where it may serve as a receptor for RSV infection. Furthermore, CX3CR1 appears to play a mechanistic role in mediating viral infection of pediatric airway epithelial cells in vitro.
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http://dx.doi.org/10.1038/s41390-019-0677-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774023PMC
April 2020

Ethnic differences in inflammatory bowel disease: Results from the United Kingdom inception cohort epidemiology study.

World J Gastroenterol 2019 Oct;25(40):6145-6157

Gastroenterology, St. Mark's Hospital and Academic Institute, London HA1 3UJ, United Kingdom.

Background: The current epidemiology of inflammatory bowel disease (IBD) in the multi-ethnic United Kingdom is unknown. The last incidence study in the United Kingdom was carried out over 20 years ago.

Aim: To describe the incidence and phenotype of IBD and distribution within ethnic groups.

Methods: Adult patients (> 16 years) with newly diagnosed IBD (fulfilling Copenhagen diagnostic criteria) were prospectively recruited over one year in 5 urban catchment areas with high South Asian population. Patient demographics, ethnic codes, disease phenotype (Montreal classification), disease activity and treatment within 3 months of diagnosis were recorded onto the Epicom database.

Results: Across a population of 2271406 adults, 339 adult patients were diagnosed with IBD over one year: 218 with ulcerative colitis (UC, 64.3%), 115 with Crohn's disease (CD, 33.9%) and 6 with IBD unclassified (1.8%). The crude incidence of IBD, UC and CD was 17.0/100000, 11.3/100000 and 5.3/100000 respectively. The age adjusted incidence of IBD and UC were significantly higher in the Indian group (25.2/100000 and 20.5/100000) compared to White European (14.9/100000, = 0.009 and 8.2/100000, < 0.001) and Pakistani groups (14.9/100000, = 0.001 and 11.2/100000, = 0.007). The Indian group were significantly more likely to have extensive disease than White Europeans (52.7% 41.7%, = 0.031). There was no significant difference in time to diagnosis, disease activity and treatment.

Conclusion: This is the only prospective study to report the incidence of IBD in an ethnically diverse United Kingdom population. The Indian ethnic group showed the highest age-adjusted incidence of UC (20.5/100000). Further studies on dietary, microbial and metabolic factors that might explain these findings in UC are underway.
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http://dx.doi.org/10.3748/wjg.v25.i40.6145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824277PMC
October 2019

Stratification of inflammatory bowel disease outpatients by disease activity and risk of complications to guide out-of-hospital monitoring: a patient-centred quality improvement project.

BMJ Open Qual 2019 1;8(3):e000546. Epub 2019 Aug 1.

St Mark's Hospital, London, UK.

Background: Inflammatory bowel disease (IBD) is a chronic relapsing-remitting condition affecting 600 000 people in the UK. Traditionally, patients attend outpatient clinics for monitoring regardless of their symptoms or risk of developing complications. This can lead to a mismatch between need and access: patients in remission given elective appointments displace those in need of urgent specialist attention. Novel initiatives implemented in the UK to improve outpatient monitoring have often required a well-maintained patient registry, empowered patients and significant information technology support.

Design And Strategy: In this large-scale quality improvement project at St Mark's Hospital, a tertiary centre for IBD, we stratified over 1000 patients attending three non-complex IBD clinics over 12 months according to disease activity and risk profile. The aim was to offer a choice and subsequently transfer 50% of eligible patients to specialist nurse-led telephone clinics and demonstrate non-inferior satisfaction levels to existing outpatient follow-up. We also sought to ensure there was timely access to a newly established rapid access clinic for patients requiring urgent specialist attention.A core project team consisting of healthcare professionals, patients and quality improvement scientists met regularly. The team tested and scaled up interventions using 'Plan-Do-Study-Act' cycles within the 'Model for Improvement' framework and analysed data continuously using statistical process charts.

Results: Over 12 months, the average number of eligible patients transferred to telephone clinics rose from 17.6% (42/239) using a questionnaire method to 59.3% (73/123) using active discussion in clinic. Patient satisfaction scores remained high and non-inferior to baseline scores in face-to-face clinics. The median waiting time to be seen in the rapid access clinic was 6.5 days.

Conclusion: This is the first published study to report on the successful stratification of patients with IBD based on disease activity and risk of complications to create a more responsive, sustainable and patient-centred model for IBD monitoring.
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http://dx.doi.org/10.1136/bmjoq-2018-000546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683110PMC
August 2019

A case control study of clinical and biochemical parameters of metabolic syndrome with special attention among young and middle aged population.

Diabetes Metab Syndr 2019 Jul - Aug;13(4):2653-2659. Epub 2019 Jul 12.

Division of Clinical and Experimental Medicine, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Vistar, Lucknow, 226031, India.

Background: Metabolic syndrome (MS) increases the risk of heart disease, stroke, and other complications.

Aim: The aim of this study was to assess the clinical and biochemical parameters of MS and its complications (cerebrovascular accidents, cardiovascular accidents, DN or chronic kidney disease (CKD) compared with healthy controls especially among the younger population in Northern India.

Material And Methods: A total of 245 (healthy, MS and it's complicated) aged 18-70 years participated in the Open-Label, Single Centered; hospital-based random selection case-control comparative study. All anthropometric and biochemical assessment was done after proper consent. The metabolic syndrome was determined by IDF criteria.

Results: The key risk parameters in three groups i.e. Control, Metabolic syndrome, and Complicated was TG (96.5 ± 46.9, 194.1 ± 87.8, 148.0 ± 102.2). LDL (91.2 ± 27.2, 114.0 ± 31.8, 69.1 ± 42.5, BP (120.1 ± 9.9, 139.3 ± 13.3, 132.1 ± 15.0) and high fasting glucose (81.1 ± 13.7, 164.5 ± 84.3, 138.0 ± 74.5). The hs-CRP is also significantly increased in the complicated group. The subanalysis of data also indicates that younger middle age (36-55 years) group both male and female is obese, hypertensive, diabetic with lipid abnormality according to IDF criteria.

Conclusion: The risk factors like high TG, low HDL, high BP, and high fasting glucose were found higher particularly in younger population which may lead to diagnosis & complications of diabetes, hypertension and lipid abnormality. Due to changing physiology in young and middle age population these individuals are moving towards metabolic syndrome easily and needs frequent monitoring, preventive checkups, and lifestyle changes to prevent complications.
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http://dx.doi.org/10.1016/j.dsx.2019.07.031DOI Listing
January 2020

Integration of transcriptomic and proteomic data identifies biological functions in cell populations from human infant lung.

Am J Physiol Lung Cell Mol Physiol 2019 09 3;317(3):L347-L360. Epub 2019 Jul 3.

The Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Systems biology uses computational approaches to integrate diverse data types to understand cell and organ behavior. Data derived from complementary technologies, for example transcriptomic and proteomic analyses, are providing new insights into development and disease. We compared mRNA and protein profiles from purified endothelial, epithelial, immune, and mesenchymal cells from normal human infant lung tissue. Signatures for each cell type were identified and compared at both mRNA and protein levels. Cell-specific biological processes and pathways were predicted by analysis of concordant and discordant RNA-protein pairs. Cell clustering and gene set enrichment comparisons identified shared versus unique processes associated with transcriptomic and/or proteomic data. Clear cell-cell correlations between mRNA and protein data were obtained from each cell type. Approximately 40% of RNA-protein pairs were coherently expressed. While the correlation between RNA and their protein products was relatively low (Spearman rank coefficient ~0.4), cell-specific signature genes involved in functional processes characteristic of each cell type were more highly correlated with their protein products. Consistency of cell-specific RNA-protein signatures indicated an essential framework for the function of each cell type. Visualization and reutilization of the protein and RNA profiles are supported by a new web application, "LungProteomics," which is freely accessible to the public.
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http://dx.doi.org/10.1152/ajplung.00475.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766718PMC
September 2019

T-bet Transcription Factor Promotes Antibody-Secreting Cell Differentiation by Limiting the Inflammatory Effects of IFN-γ on B Cells.

Immunity 2019 05 7;50(5):1172-1187.e7. Epub 2019 May 7.

Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address:

Although viral infections elicit robust interferon-γ (IFN-γ) and long-lived antibody-secreting cell (ASC) responses, the roles for IFN-γ and IFN-γ-induced transcription factors (TFs) in ASC development are unclear. We showed that B cell intrinsic expression of IFN-γR and the IFN-γ-induced TF T-bet were required for T-helper 1 cell-induced differentiation of B cells into ASCs. IFN-γR signaling induced Blimp1 expression in B cells but also initiated an inflammatory gene program that, if not restrained, prevented ASC formation. T-bet did not affect Blimp1 upregulation in IFN-γ-activated B cells but instead regulated chromatin accessibility within the Ifng and Ifngr2 loci and repressed the IFN-γ-induced inflammatory gene program. Consistent with this, B cell intrinsic T-bet was required for formation of long-lived ASCs and secondary ASCs following viral, but not nematode, infection. Therefore, T-bet facilitates differentiation of IFN-γ-activated inflammatory effector B cells into ASCs in the setting of IFN-γ-, but not IL-4-, induced inflammatory responses.
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http://dx.doi.org/10.1016/j.immuni.2019.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929688PMC
May 2019

Ultrahigh-Performance Liquid Chromatography Tandem Mass Spectrometry with Electrospray Ionization Quantification of Tryptophan Metabolites and Markers of Gut Health in Serum and Plasma-Application to Clinical and Epidemiology Cohorts.

Anal Chem 2019 04 25;91(8):5207-5216. Epub 2019 Mar 25.

Division of Integrative Systems and Digestive Medicine, Department of Surgery and Cancer , Imperial College London , Sir Alexander Fleming Building, South Kensington Campus , London SW7 2AZ , United Kingdom.

A targeted ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization (UHPLC-ESI-MS/MS) method has been developed for the quantification of tryptophan and its downstream metabolites from the kynurenine and serotonin pathways. The assay coverage also includes markers of gut health and inflammation, including citrulline and neopterin. The method was designed in 96-well plate format for application in multiday, multiplate clinical and epidemiology population studies. A chromatographic cycle time of 7 min enables the analysis of two 96-well plates in 24 h. To protect chromatographic column lifespan, samples underwent a two-step extraction, using solvent protein precipitation followed by delipidation via solid-phase extraction (SPE). Analytical validation reported accuracy of each analyte <20% for the lowest limit of quantification and <15% for all other quality control (QC) levels. The analytical precision for each analyte was 2.1-12.9%. To test the applicability of the method to multiplate and multiday preparations, a serum pool underwent periodic repeat analysis during a run consisting of 18 plates. The % CV (coefficient of variation) values obtained for each analyte were <15%. Additional biological testing applied the assay to samples collected from healthy control participants and two groups diagnosed with inflammatory bowel disease (IBD) (one group treated with the anti-inflammatory 5-aminosalicylic acid (5-ASA) and one group untreated), with results showing significant differences in the concentrations of picolinic acid, kynurenine, and xanthurenic acid. The short analysis time and 96-well plate format of the assay makes it suitable for high-throughput targeted UHPLC-ESI-MS/MS metabolomic analysis in large-scale clinical and epidemiological population studies.
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http://dx.doi.org/10.1021/acs.analchem.8b05884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503468PMC
April 2019

Clinical Characteristic and Risk Factors of Acute Kidney Injury among Dengue Viral Infections in Adults: A Retrospective Analysis.

Indian J Nephrol 2019 Jan-Feb;29(1):15-21

Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India.

Dengue is a growing public health problem in India, and acute kidney injury (AKI) is one of the least studied complications of dengue virus infection (DVI). This study was conducted to investigate the incidence, clinical characteristics, and risk factors for AKI in DVI. This was a retrospective study of patients with confirmed DVI presenting as dengue fever (DF) or dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) at our center over a period of 2 years. A total of 620 subjects fulfilling inclusion criteria were studied. Patients were divided into two cohorts (90 patients with AKI and 530 patients without AKI) to determine independent predictors of AKI. Among 620 patients, 454 (73.22%) had classical DF, 141 (22.74%) patients had DHF, and 25 (4.03%) patients had DSS. AKI was present in 90 (16.36%) patients; approximately one-third (31, 34.45%) had AKIN stage 1, 33 (36.66%) patients had AKIN stage 2, and 26 (28.88%) had AKIN stage 3. Among those with AKI, 14 patients expired and all had DHF/DSS. On multivariate logistic regression, AKI was associated with male gender [odds ratio (OR): 2.9], DHF (OR: 7.9), rhabdomyolysis (OR: 8.2), multiple-organ dysfunction (OR: 18.2), hypertension (OR: 0.7), diabetes mellitus (OR: 4.8), delayed hospitalization (OR: 2.2), and use of nephrotoxic drugs (OR: 2.86). In all, 320 patients (51.61%) had hospital stay >3 days. We found that AKI was an independent predictor for longer duration of hospital stay (OR: 7.2, 95% confidence interval: 4.8-10.7). AKI in DVI is associated with significant morbidity, mortality and longer hospital stay.
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http://dx.doi.org/10.4103/ijn.IJN_437_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375009PMC
March 2019

A novel in vitro model of primary human pediatric lung epithelial cells.

Pediatr Res 2020 02 18;87(3):511-517. Epub 2019 Feb 18.

Division of Neonatology, University of Rochester Medical Center, Rochester, NY, USA.

Background: Current in vitro human lung epithelial cell models derived from adult tissues may not accurately represent all attributes that define homeostatic and disease mechanisms relevant to the pediatric lung.

Methods: We report methods for growing and differentiating primary Pediatric Human Lung Epithelial (PHLE) cells from organ donor infant lung tissues. We use immunohistochemistry, flow cytometry, quantitative RT-PCR, and single cell RNA sequencing (scRNAseq) analysis to characterize the cellular and transcriptional heterogeneity of PHLE cells.

Results: PHLE cells can be expanded in culture up to passage 6, with a doubling time of ~4 days, and retain attributes of highly enriched epithelial cells. PHLE cells can form resistant monolayers, and undergo differentiation when placed at air-liquid interface. When grown at Air-Liquid Interface (ALI), PHLE cells expressed markers of airway epithelial cell lineages. scRNAseq suggests the cultures contained 4 main sub-phenotypes defined by expression of FOXJ1, KRT5, MUC5B, and SFTPB. These cells are available to the research community through the Developing Lung Molecular Atlas Program Human Tissue Core.

Conclusion: Our data demonstrate that PHLE cells provide a novel in vitro human cell model that represents the pediatric airway epithelium, which can be used to study perinatal developmental and pediatric disease mechanisms.
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http://dx.doi.org/10.1038/s41390-019-0340-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698433PMC
February 2020

Disease course of inflammatory bowel disease unclassified in a European population-based inception cohort: An Epi-IBD study.

J Gastroenterol Hepatol 2019 Jun 21;34(6):996-1003. Epub 2019 Jan 21.

Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece.

Background And Aim: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible, and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following 5 years.

Methods: The Epi-IBD study is a prospective population-based cohort of 1289 IBD patients diagnosed in centers across Europe. Clinical data were captured prospectively throughout the follow-up period.

Results: Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n = 20, 71%) or CD (n = 8, 29%) after a median of 6 months (interquartile range: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n = 6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n = 107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU.

Conclusions: In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after 5 years of follow-up. One in four patients with IBDU eventually was classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.
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http://dx.doi.org/10.1111/jgh.14563DOI Listing
June 2019

Natural Disease Course of Ulcerative Colitis During the First Five Years of Follow-up in a European Population-based Inception Cohort-An Epi-IBD Study.

J Crohns Colitis 2019 Feb;13(2):198-208

IBD Clinical and Research Centre, ISCARE, Prague, Czech Republic.

Background And Aims: Few population-based cohort studies have assessed the disease course of ulcerative colitis [UC] in the era of biological therapy and widespread use of immunomodulators. The aim of this study was to assess the 5-year outcome and disease course of patients with UC in the Epi-IBD cohort.

Methods: In a prospective, population-based inception cohort of unselected patients with UC, patients were followed up from the time of their diagnosis, which included the collection of their clinical data, demographics, disease activity, medical therapy, and rates of surgery, cancers, and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.

Results: A total of 717 patients were included in the study. During follow-up, 43 [6%] patients underwent a colectomy and 163 [23%] patients were hospitalised. Of patients with limited colitis [distal to the left flexure], 90 [21%] progressed to extensive colitis. In addition, 92 [27%] patients with extensive colitis experienced a regression in disease extent, which was associated with a reduced risk of hospitalisation (hazard ratio [HR]: 0.5 95% CI: 0.3-0.8]. Overall, patients were treated similarly in both geographical regions; 80 [11%] patients needed biological therapy and 210 [29%] patients received immunomodulators. Treatment with immunomodulators was found to reduce the risk of hospitalisation [HR: 0.5 95% CI: 0.3-0.8].

Conclusions: Although patients in this population-based cohort were treated more aggressively with immunomodulators and biological therapy than in cohorts from the previous two decades, their disease outcomes, including colectomy rates, were no different. However, treatment with immunomodulators was found to reduce the risk of hospitalisation.
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http://dx.doi.org/10.1093/ecco-jcc/jjy154DOI Listing
February 2019

Cell type-resolved human lung lipidome reveals cellular cooperation in lung function.

Sci Rep 2018 09 7;8(1):13455. Epub 2018 Sep 7.

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99352, USA.

Cell type-resolved proteome analyses of the brain, heart and liver have been reported, however a similar effort on the lipidome is currently lacking. Here we applied liquid chromatography-tandem mass spectrometry to characterize the lipidome of major lung cell types isolated from human donors, representing the first lipidome map of any organ. We coupled this with cell type-resolved proteomics of the same samples (available at Lungmap.net). Complementary proteomics analyses substantiated the functional identity of the isolated cells. Lipidomics analyses showed significant variations in the lipidome across major human lung cell types, with differences most evident at the subclass and intra-subclass (i.e. total carbon length of the fatty acid chains) level. Further, lipidomic signatures revealed an overarching posture of high cellular cooperation within the human lung to support critical functions. Our complementary cell type-resolved lipid and protein datasets serve as a rich resource for analyses of human lung function.
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http://dx.doi.org/10.1038/s41598-018-31640-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128932PMC
September 2018

Vitamin D deficiency in a European inflammatory bowel disease inception cohort: an Epi-IBD study.

Eur J Gastroenterol Hepatol 2018 11;30(11):1297-1303

Pekka Collin Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.

Background: Serum vitamin D level is commonly low in patients with inflammatory bowel disease (IBD). Although there is a growing body of evidence that links low vitamin D level to certain aspects of IBD such as disease activity and quality of life, data on its prevalence and how it varies across disease phenotype, smoking status and treatment groups are still missing.

Materials And Methods: Patients diagnosed with IBD between 2010 and 2011 were recruited. Demographic data and serum vitamin D levels were collected. Variance of vitamin D level was then assessed across different treatment groups, disease phenotype, disease activity and quality of life scores.

Results: A total of 238 (55.9% male) patients were included. Overall, 79% of the patients had either insufficient or deficient levels of vitamin D at diagnosis. Patients needing corticosteroid treatment at 1 year had significantly lower vitamin D levels at diagnosis (median 36.0 nmol/l) (P=0.035). Harvey-Bradshaw Index (P=0.0001) and Simple Clinical Colitis Activity Index scores (P=0.0001) were significantly lower in patients with higher vitamin D level. Serum vitamin D level correlated significantly with SIBQ score (P=0.0001) and with multiple components of SF12. Smokers at diagnosis had the lowest vitamin D levels (vitamin D: 34 nmol/l; P=0.053).

Conclusion: This study demonstrates the high prevalence of low vitamin D levels in treatment-naive European IBD populations. Furthermore, it demonstrates the presence of low vitamin D levels in patients with IBD who smoke.
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http://dx.doi.org/10.1097/MEG.0000000000001238DOI Listing
November 2018

Dissociation, cellular isolation, and initial molecular characterization of neonatal and pediatric human lung tissues.

Am J Physiol Lung Cell Mol Physiol 2018 10 5;315(4):L576-L583. Epub 2018 Jul 5.

Division of Neonatology, Department of Pediatrics, University of Rochester Medical Center , Rochester, New York.

Human lung morphogenesis begins by embryonic life and continues after birth into early childhood to form a complex organ with numerous morphologically and functionally distinct cell types. Pulmonary organogenesis involves dynamic changes in cell proliferation, differentiation, and migration of specialized cells derived from diverse embryonic lineages. Studying the molecular and cellular processes underlying formation of the fully functional lung requires isolating distinct pulmonary cell populations during development. We now report novel methods to isolate four major pulmonary cell populations from pediatric human lung simultaneously. Cells were dissociated by protease digestion of neonatal and pediatric lung and isolated on the basis of unique cell membrane protein expression patterns. Epithelial, endothelial, nonendothelial mesenchymal, and immune cells were enriched by fluorescence-activated cell sorting. Dead cells and erythrocytes were excluded by 7-aminoactinomycin D uptake and glycophorin-A (CD235a) expression, respectively. Leukocytes were identified by membrane CD45 (protein tyrosine phosphatase, receptor type C), endothelial cells by platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial cadherin (CD144), and both were isolated. Thereafter, epithelial cell adhesion molecule (CD326)-expressing cells were isolated from the endothelial- and immune cell-depleted population to enrich epithelial cells. Cells lacking these membrane markers were collected as "nonendothelial mesenchymal" cells. Quantitative RT-PCR and RNA sequencing analyses of population specific transcriptomes demonstrate the purity of the subpopulations of isolated cells. The method efficiently isolates major human lung cell populations that we announce are now available through the National Heart, Lung, and Blood Institute Lung Molecular Atlas Program (LungMAP) for their further study.
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http://dx.doi.org/10.1152/ajplung.00041.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230879PMC
October 2018

Proteomic Analysis of Single Mammalian Cells Enabled by Microfluidic Nanodroplet Sample Preparation and Ultrasensitive NanoLC-MS.

Angew Chem Int Ed Engl 2018 09 14;57(38):12370-12374. Epub 2018 Jun 14.

Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.

We report on the quantitative proteomic analysis of single mammalian cells. Fluorescence-activated cell sorting was employed to deposit cells into a newly developed nanodroplet sample processing chip, after which samples were analyzed by ultrasensitive nanoLC-MS. An average of circa 670 protein groups were confidently identified from single HeLa cells, which is a far greater level of proteome coverage for single cells than has been previously reported. We demonstrate that the single-cell proteomics platform can be used to differentiate cell types from enzyme-dissociated human lung primary cells and identify specific protein markers for epithelial and mesenchymal cells.
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http://dx.doi.org/10.1002/anie.201802843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261339PMC
September 2018

Epidemiology of inflammatory bowel disease in racial and ethnic migrant groups.

World J Gastroenterol 2018 Jan;24(3):424-437

Department of Gastroenterology, St. Marks Academic Institute, London HA1 3UJ, United Kingdom.

Aim: To summarise the current literature and define patterns of disease in migrant and racial groups.

Methods: A structured key word search in Ovid Medline and EMBASE was undertaken in accordance with PRISMA guidelines. Studies on incidence, prevalence and disease phenotype of migrants and races compared with indigenous groups were eligible for inclusion.

Results: Thirty-three studies met the inclusion criteria. Individual studies showed significant differences in incidence, prevalence and disease phenotype between migrants or race and indigenous groups. Pooled analysis could only be undertaken for incidence studies on South Asians where there was significant heterogeneity between the studies [95% for ulcerative colitis (UC), 83% for Crohn's disease (CD)]. The difference between incidence rates was not significant with a rate ratio South Asian: Caucasian of 0.78 (95%CI: 0.22-2.78) for CD and 1.39 (95%CI: 0.84-2.32) for UC. South Asians showed consistently higher incidence and more extensive UC than the indigenous population in five countries. A similar pattern was observed for Hispanics in the United States. Bangladeshis and African Americans showed an increased risk of CD with perianal disease.

Conclusion: This review suggests that migration and race influence the risk of developing inflammatory bowel disease. This may be due to different inherent responses upon exposure to an environmental trigger in the adopted country. Further prospective studies on homogenous migrant populations are needed to validate these observations, with a parallel arm for in-depth investigation of putative drivers.
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http://dx.doi.org/10.3748/wjg.v24.i3.424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5776404PMC
January 2018

Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study.

Gut 2019 03 23;68(3):423-433. Epub 2018 Jan 23.

IBD Clinical and Research Centre, ISCARE, Prague, Czech Republic.

Objective: The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn's disease (CD).

Design: Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.

Results: In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).

Conclusion: Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.
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http://dx.doi.org/10.1136/gutjnl-2017-315568DOI Listing
March 2019

Plasma cell and serum antibody responses to influenza vaccine in preterm and full-term infants.

Vaccine 2017 09 12;35(38):5163-5171. Epub 2017 Aug 12.

Departments of Microbiology & Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA; Department of Medicine, Emory University School of Medicine, 1648 Pierce Drive NE, Atlanta, GA 30307, USA.

Background: Preterm (PT) infants are at greater risk for severe influenza infection and experience decrements in long-term antibody responses to vaccines. This may related to defects in antibody secreting cell (ASC) generation.

Objective: To investigate the relationships among the frequencies of influenza-specific antibody secreting cells, ASC numbers and subsets, and antibody responses to influenza vaccines (IV) among PT and full-term (FT) infants.

Design/methods: We enrolled 11 former PT (≤32weeks' gestation, ≤1500 g' birth weight) and 11FT infants, 6-17months of age, receiving their first influenza immunizations. Infants received two doses of inactivated trivalent (T)IV or quadrivalent (Q)IV during the 2012-2013 and 2013-2014 influenza seasons, respectively, at 0 and 28days, and blood was drawn at 0, 10, 35, and 56days and 9months. Vaccine-specific antibody was measured by hemagglutination inhibition (HAI) at 0 and 56days and 9months, vaccine-specific ASC numbers by enzyme linked immunospot (ELISPOT) at 10 and 35days, and ASC subsets by flow cytometry at 0, 10 and 35days.

Results: PT infants had post-vaccine HAI titers to all 4 vaccine strains at least equal to FT infants at 56days and 9months after beginning immunization. Influenza-specific ASC ELISPOT responses at 35days were higher among PT than FT infants (median 100 v. 30 per 10 PBMC, p=0.04). ASC numbers at 35days were positively correlated with serum HAI titers at 56days (ρ=0.50-0.80). There were no statistical differences between PT and FT infants in the frequency of five ASC subsets and no specific ASC subset correlated with durability of serum antibody titers.

Conclusions: Influenza-specific ASC numbers in both FT and PT infants correlated with peak antibody titers, but ASC subsets did not correlate with durability of antibody response.
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http://dx.doi.org/10.1016/j.vaccine.2017.07.115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603201PMC
September 2017

Oxygen-dependent changes in lung development do not affect epithelial infection with influenza A virus.

Am J Physiol Lung Cell Mol Physiol 2017 Nov 10;313(5):L940-L949. Epub 2017 Aug 10.

Department of Pediatrics, School of Medicine and Dentistry, University of Rochester, Rochester, New York; and

Infants born prematurely often require supplemental oxygen, which contributes to aberrant lung development and increased pulmonary morbidity following a respiratory viral infection. We have been using a mouse model to understand how early-life hyperoxia affects the adult lung response to influenza A virus (IAV) infection. Prior studies showed how neonatal hyperoxia (100% oxygen) increased sensitivity of adult mice to infection with IAV [IAV (A/Hong Kong/X31) H3N2] as defined by persistent inflammation, pulmonary fibrosis, and mortality. Since neonatal hyperoxia alters lung structure, we used a novel fluorescence-expressing reporter strain of H1N1 IAV [A/Puerto Rico/8/34 mCherry (PR8-mCherry)] to evaluate whether it also altered early infection of the respiratory epithelium. Like Hong Kong/X31, neonatal hyperoxia increased morbidity and mortality of adult mice infected with PR8-mCherry. Whole lung imaging and histology suggested a modest increase in mCherry expression in adult mice exposed to neonatal hyperoxia compared with room air-exposed animals. However, this did not reflect an increase in airway or alveolar epithelial infection when mCherry-positive cells were identified and quantified by flow cytometry. Instead, a modest increase in the number of CD45-positive macrophages expressing mCherry was detected. While neonatal hyperoxia does not alter early epithelial infection with IAV, it may increase the activity of macrophages toward infected cells, thereby enhancing early epithelial injury.
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http://dx.doi.org/10.1152/ajplung.00203.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5792176PMC
November 2017

Low-Dimensional Organic-Inorganic Halide Perovskite: Structure, Properties, and Applications.

ChemSusChem 2017 10 28;10(19):3712-3721. Epub 2017 Aug 28.

Institute of Chemistry, Casali Center for Applied Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.

Three-dimensional (3 D) perovskite has attracted a lot of attention owing to its success in photovoltaic (PV) solar cells. However, one of its major crucial issues lies in its stability, which has limited its commercialization. An important property of organic-inorganic perovskite is the possibility of forming a layered material by using long organic cations that do not fit into the octahedral cage. These long organic cations act as a "barrier" that "caps" 3 D perovskite to form the layered material. Controlling the number of perovskite layers could provide a confined structure with chemical and physical properties that are different from those of 3 D perovskite. This opens up a whole new batch of interesting materials with huge potential for optoelectronic applications. This Minireview presents the synthesis, properties, and structural orientation of low-dimensional perovskite. It also discusses the progress of low-dimensional perovskite in PV solar cells, which, to date, have performance comparable to that of 3 D perovskite but with enhanced stability. Finally, the use of low-dimensional perovskite in light-emitting diodes (LEDs) and photodetectors is discussed. The low-dimensional perovskites are promising candidates for LED devices, mainly because of their high radiative recombination as a result of the confined low-dimensional quantum well.
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http://dx.doi.org/10.1002/cssc.201701026DOI Listing
October 2017

Awareness and Outcome of Changing Trends in Clinical Profile of Dengue Fever: A Retrospective Analysis of Dengue Epidemic from January to December 2014 at a Tertiary Care Hospital.

J Assoc Physicians India 2017 May;65(5):42-46

Professor and Head, Department of Medicine, King George Medical University, Lucknow, Uttar Pradesh.

Background: Dengue fever is caused by mosquito-borne arboviral infection that has become a public health concern globally. Recently, an alarming rise of dengue has also been seen in India. Hence the study was undertaken to know profile of clinical manifestations and laboratory findings during the evolution of dengue fever.

Methods: In this study, retrospective data analysis was done in 216 seropositive dengue patients admitted between January to December 2014 in department of medicine at a north Indian care hospital. The tests analyzed were blood counts, serum electrolytes, liver function tests, kidney function tests, chest x-ray and other relevant investigations.

Results: Males were commonly affected and the most exposed age group was found to be18-35 years. The seropositive case rate for dengue was 56% for NS1 antigen and 36% for IgM. There was rural dominancy of cases with a peak in September. Fever was the most common clinical feature followed by headache, myalgia, backache, nausea and abdominal pain. Petechia was most common haemorrhagic manifestation. Common laboratory findings included 89.35% decreased Platelet counts (<100 000/cmm), 67.59% increased hematocrit (>45%) and 58.33% deranged liver function test. There was no reported mortality in dengue.

Conclusions: From prompt and proper treatment could prevent deaths in moderate and severe dengue. Atypical presentations of dengue should be kept in mind so as not to miss the cases. Increased community awareness and vector control measures need to be strengthened during peri-monsoon period to reduce burden of dengue cases.
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May 2017