Pantoea agglomerans bacteremia: A rare case of spontaneous human infection by a plant pathogen in an immunocompromised host.

Introduction: Pantoea agglomerans is a Gram negative ubiquitous bacteria commonly isolated from plant surfaces, seeds, fruits and animal/human feces usually introduced to human by ingestion of infected fruits/vegetables, thorn pricks and gastrointestinal translocation in lack of stomach acidity. However, the pathogen can also cause opportunistic human infection especially when the immune system is impaired. The aim of this case report is to investigate clinical features in a patient with P. agglomerans bacteremia and bring attention the opportunistic infection by this rare bacteria. Case presentation: We present a case of 57 year old caucasian lady with past medical history of Chronic Obstructive Pulmonary Disease, Atrial fibrillation, Immunoglobulin (IgG) deficiency, recurrent pneumonia, urine infection, oral/vaginal candidiasis, Gastro-esophageal reflux disease who presents with one week history of increased shortness of breath, chest tightness and productive cough without fever/chills. She also had high INR of 4.7 (target 2-3) despite taking normal dose of warfarin. She denies plant exposure. Her vitals were stable, saturation maintained with oxygen supplementation. Chest exam revealed very poor air entry bilaterally suggesting exacerbation of COPD. Oral thrush was present. Recent IgG level within last 6 months was low. Blood culture grew Pantoea agglomerans, pan-sensitive to most of the antibiotics. Chest X ray, CT scan abdomen and urine studies could not localize the source of infection. She was treated with Ceftriaxone, INR normalized to therapeutic range and she improved to baseline after 10 days of treatment. Discussion and conclusion: P. agglomerans is a rare cause of bacteremia which usually presents as fever, chills and general toxicity, however could also present as a cause of exacerbation of chronic diseases. Spontaneous infection can occur in a immunocompromised host, however the pathogen is of low virulence. The link between upper GI symptoms along with antacid receipt and spontaneous P. agglomerans infection could be possible, however needs further study. Hence, P. agglomerans should be considered one of the possible cause of spontaneous bacteremia in a immunocompromised host

A genome-wide association study for corneal astigmatism: The CREAM Consortium

Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis was performed of genome-wide association studies (GWAS) of corneal astigmatism undertaken for 14 European ancestry (N = 22,250) and 8 Asian ancestry (N = 9,120) cohorts by the CREAM Consortium. Cases were defined as having >0.75 D of corneal astigmatism. For the meta-analysed results of European ancestry cohorts, subsequent gene-based and gene-set analyses were performed using VEGAS2 and MAGMA software. Additionally, estimates of SNP-based heritability for corneal and refractive astigmatism and spherical equivalent were calculated for Europeans using LD score regression. Results: Meta-analysis of all cohorts identified a genome-wide significant locus near the gene PDGFRA (platelet derived growth factor receptor alpha): top SNP: rs7673984, odds ratio = 1.12 (95% CI: 1.08-1.16), P = 5.55 x 10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified 3 novel candidate genes for corneal astigmatism in Europeans: CLDN7 (claudin-7), ACP2 (acid phosphatase 2, lysosomal) and TNFAIP8L3 (TNF alpha induced protein 8 like 3). Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified 3 novel candidate genes CLDN7, ACP2 and TNFAIP8L3 that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors to the development of astigmatism

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Funder: NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme; Grant(s): IS-BRC-1215-20014Background: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. Methods and findings: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]–InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1–standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. Conclusions: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D

A genome-wide association study of corneal astigmatism:The CREAM Consortium

Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08–1.16), p=5.55×10−9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans—claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.peerReviewe

ISSN 2347-954X (Print) Innovative Approach -Liquid Supported Denture: A Case Report

Abstract: Conventional complete denture lacks retention and stability in patients with fibrous hyperplasic tissue. The ideal properties of a denture are adequate rigidity of polished surface to bear masticatory forces and at the same time, flexibility and softness for better stress distribution. In conventional denture, there is uneven distribution of load due to rigidity of tissue surface, especially in the case of flabby, atrophic ridge. A Liquid supported denture allows uniform stress distribution due to its flexible tissue surface and improve the patient&apos;s acceptance

Decreased Lymphocytic Bronchitis Severity in the Era of Azithromycin Prophylaxis

Large-airway lymphocytic inflammation (LB), assessed on endobronchial biopsies, has been associated with acute cellular rejection and chronic lung allograft dysfunction (CLAD). Azithromycin (AZI) prophylaxis has been used to prevent airway inflammation and subsequent CLAD, with inconsistent results. We hypothesized that AZI prophylaxis would be associated with reduced LB, changes in bronchoalveolar lavage (BAL) immune cell populations, and improved CLAD-free survival.MethodsWe compared frequencies of LB from endobronchial biopsies before (N = 1856) and after (N = 975) protocolized initiation of AZI prophylaxis at our center. LB was classified as none, minimal, mild, or moderate by histopathologic analysis. LB grades were compared using ordinal mixed-model regression. Corresponding automated BAL leukocyte frequencies were compared using mixed-effects modeling. The effect of AZI prophylaxis on CLAD-free survival was assessed by a Cox proportional hazards model adjusted for age, sex, ethnicity, transplant indication, and cytomegalovirus serostatus.ResultsBiopsies in the pre-AZI era had 2-fold increased odds (95% confidence interval, 1.5-2.7; P &lt; 0.001) of higher LB grades. LB was associated with BAL neutrophilia in both eras. However, there was no difference in risk for CLAD or death between AZI eras (hazard ratio 1.3; 95% confidence interval, 0.7-2.0; P = 0.45).ConclusionsDecreased airway inflammation in the era of AZI prophylaxis may represent a direct effect of AZI therapy or reflect other practices or environmental changes. In this cohort, AZI prophylaxis was not associated with improved CLAD-free survival

Die SAGAT-Methode: Welche Informationen muss der Towerlotse erfassen?

<div><p>DNA methylation regulates gene expression in many organisms. In eukaryotes, DNA methylation is associated with gene repression, while it exerts both activating and repressive effects in the Proteobacteria through largely locus-specific mechanisms. Here, we identify a critical DNA methyltransferase in <i>M. tuberculosis</i>, which we term MamA. MamA creates N⁶-methyladenine in a six base pair recognition sequence present in approximately 2,000 copies on each strand of the genome. Loss of MamA reduces the expression of a number of genes. Each has a MamA site located at a conserved position relative to the sigma factor −10 binding site and transcriptional start site, suggesting that MamA modulates their expression through a shared, not locus-specific, mechanism. While strains lacking MamA grow normally <i>in vitro</i>, they are attenuated in hypoxic conditions, suggesting that methylation promotes survival in discrete host microenvironments. Interestingly, we demonstrate strikingly different patterns of DNA methyltransferase activity in different lineages of <i>M. tuberculosis</i>, which have been associated with preferences for distinct host environments and different disease courses in humans. Thus, MamA is the major functional adenine methyltransferase in <i>M. tuberculosis</i> strains of the Euro-American lineage while strains of the Beijing lineage harbor a point mutation that largely inactivates MamA but possess a second functional DNA methyltransferase. Our results indicate that MamA influences gene expression in <i>M. tuberculosis</i> and plays an important but strain-specific role in fitness during hypoxia.</p></div

Improvements in frailty contribute to substantial improvements in quality of life after lung transplantation in patients with cystic fibrosis

BACKGROUND: While lung transplantation (LTx) improves health related quality of life (HRQL) in cystic fibrosis (CF), the determinants of this improvement are unknown. In other populations, frailty—a syndrome of vulnerability to physiologic stressors—is associated with disability and poor HRQL. We hypothesized that improvements in frailty would be associated with improved disability and HRQL in adults with CF undergoing LTx. METHODS: In a single-center prospective cohort study from 2010–2017, assessments of frailty, disability, and HRQL were performed before and at 3- and 6-months after LTx. We assessed frailty by the Short Physical Performance Battery (SPPB). We assessed disability with the Lung Transplant Valued Life Activities Scale (LT-VLA) and HRQL by the Medical Outcomes Study Short Form Physical and Mental Component Summary scales (SF12-PCS, -MCS), the Airway Questionnaire 20-Revised (AQ20R), and the Euroqol 5D (EQ5D). We tested the association of concurrent changes in frailty and lung function on disability and HRQL by linear mixed effects models adjusted for sex and body mass index. RESULTS: Among 23 participants with CF, improvements in frailty and lung function were independently associated with improved disability and some HRQL measures. For example, each 1-point improvement in SPPB or 200mL improvement in FEV(1) was associated with improved LT-VLA disability by 0.14 (95%CI: 0.08 to 0.20) and 0.07 (95%CI: 0.05 to 0.09) points and improved EQ5D by 0.05 (95%CI: 0.03 to 0.07) and 0.02 (95%CI: 0.01 to 0.03) points, respectively. CONCLUSION: Improvement in frailty is a novel determinant of improved disability and HRQL in adults with CF undergoing LTx