Adenovirus infection in the lung results in graft failure after lung transplantation

AbstractObjectives: Our goal was to examine the relationship between viral pneumonia and outcome in pediatric patients undergoing lung or heart-lung transplantation. Methods: Prospective surveillance for common respiratory viruses of childhood was performed in all patients undergoing lung or heart-lung transplantation. Specimens were examined for the presence of replicating virus (by culture), viral genome (by polymerase chain reaction), and viral antigen (by immunofluorescence and immunohistochemical staining). The relationship between viral infection and outcome was examined. Results: Sixteen patients underwent 19 transplants during the study period, with follow-up of 1 to 26 months. Virus was identified in the transplanted lung in 29 instances; adenovirus was identified most commonly (8/16 patients) and had the greatest impact on outcome. In 2 patients with early, fulminant infection, adenovirus was also identified in the donor. Adenovirus was significantly associated with respiratory failure leading to death or graft loss and with the histologic diagnosis of obliterative bronchiolitis (P ≤ .002 in each case). Conclusions: Adenovirus infection in the transplanted lung is significantly associated with graft failure, histologic obliterative bronchiolitis, and death. Health care personnel and families must be vigilant in preventing exposure of transplant recipients to this virus. Availability of a rapid and reliable test for adenovirus in donors and recipients would have an impact on management and could improve outcome for pediatric lung recipients. (J Thorac Cardiovasc Surg 1998;116:617-23

Budesonide Oral Suspension Improves Symptomatic, Endoscopic, and Histologic Parameters Compared With Placebo in Patients With Eosinophilic Esophagitis

Background & Aims Pharmacologic treatment of eosinophilic esophagitis (EoE) is limited to off-label use of corticosteroids not optimized for esophageal delivery. We performed a randomized, controlled phase 2 trial to assess the ability of budesonide oral suspension (BOS), a novel muco-adherent topical steroid formulation, to reduce symptoms and esophageal eosinophilia in adolescents and adults with EoE. Methods In this multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, 93 EoE patients between the ages of 11 and 40 years with dysphagia and active esophageal eosinophilia were randomized to receive either BOS 2 mg or placebo twice daily for 12 weeks. Co-primary outcomes were change in Dysphagia Symptom Questionnaire (DSQ) score from baseline, and proportion of patients with a histologic response (≤6 eosinophils/high-power field) after treatment. Endoscopic severity scores and safety parameters were assessed. Results At baseline, mean DSQ scores were 29.3 and 29.0, and mean peak eosinophil counts were 156 and 130 per hpf in the BOS and placebo groups, respectively. After treatment, DSQ scores were 15.0 and 21.5, and mean peak eosinophil counts were 39 and 113 per high-power field, respectively (P < .05 for all). For BOS vs placebo, change in DSQ score was −14.3 vs −7.5 (P = .0096), histologic response rates were 39% vs 3% (P < .0001), and change in endoscopic severity score was −3.8 vs 0.4 (P < .0001). Adverse events were similar between groups. Conclusions Treatment with BOS was well tolerated in adolescent and young adult patients with EoE and resulted in improvement in symptomatic, endoscopic, and histologic parameters using validated outcome instruments

Long-term outcome of infants with single ventricle and total anomalous pulmonary venous connection

AbstractBackground and methods: Between January 1, 1984, and December 1, 1997, 73 infants with functional single ventricle and total anomalous pulmonary venous connection were admitted to our institution. A retrospective review was undertaken to determine factors influencing survival. Results: Heterotaxy syndrome was present in 52 patients and hypoplastic left heart syndrome in 14. Obstructed total anomalous pulmonary venous connection was present in 21 patients. The pulmonary venous connection was supracardiac in 32 patients, cardiac in 21 patients, infracardiac in 13, and mixed in 7. Twelve patients died before the operation. The remaining 61 patients underwent surgery at a median age of 5 days (range 1 day–2.5 years). Overall survival was 45% at 6 months of age, 37% at 1 year, and 19% at 5 years. Survival for patients undergoing surgery was 54% at 6 months of age, 44% at 1 year, and 23% at 5 years. By univariate analysis with the Cox proportional hazards model, younger age at the time of the initial operation and repair of total anomalous pulmonary venous connection were predictors of mortality. Lung tissue from 14 patients was available for histologic examination. The pulmonary veins were dilated and wall thickness was increased. Increased muscularization of the arteries was seen in 11 patients. Conclusions: The long-term prognosis for children undergoing staged reconstructive operations for single ventricle and total anomalous pulmonary venous connection is poor. Early mortality is high and late death is a continuing risk. Development of the pulmonary vasculature, especially the pulmonary veins, is abnormal, even in children without clinical evidence of pulmonary venous obstruction. (J Thorac Cardiovasc Surg 1999;117:506-14

Genomic Scans across Three Eucalypts Suggest that Adaptation to Aridity is a Genome-Wide Phenomenon

Widespread species spanning strong environmental (e.g., climatic) gradients frequently display morphological and physiological adaptations to local conditions. Some adaptations are common to different species that occupy similar environments. However, the genomic architecture underlying such convergent traits may not be the same between species. Using genomic data from previous studies of three widespread eucalypt species that grow along rainfall gradients in southern Australia, our probabilistic approach provides evidence that adaptation to aridity is a genome-wide phenomenon, likely to involve multiple and diverse genes, gene families and regulatory regions that affect a multitude of complex genetic and biochemical processes

Identification of ovarian cancer metastatic miRNAs

Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2–4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.<br/

Implicating municipalities in addressing household food insecurity in Canada: A pan-Canadian analysis of news print media coverage

Objectives: Household food insecurity (HFI) affects approximately 13% of Canadian households and is especially prevalent among low-income households. Actions to address HFI have been occurring primarily at the local level, despite calls for greater income supports from senior governments to reduce poverty. News media may be reinforcing this trend, by emphasizing food-based solutions to HFI and the municipal level as the site where action needs to take place. The objective of this study was to examine the level and framing of print news media coverage of HFI action in Canada. Methods: Using a quantitative newspaper content analysis approach, we analyzed 547 articles gathered from 2 national and 16 local/regional Englishlanguage newspapers published between January 2007 and December 2012. Results: News coverage increased over time, and over half was produced from Ontario (33%) and British Columbia (22%) combined. Of the 374 articles that profiled a specific action, community gardens/urban agriculture was most commonly profiled (17%), followed by food banks/meal programs (13%); 70% of articles implicated governments to take action on HFI, and of these, 43% implicated municipal governments. Article tone was notably more negative when senior governments were profiled and more neutral and positive when municipal governments were profiled. Conclusion: News media reporting of this issue in Canada may be placing pressure on municipalities to engage in food-based actions to address HFI. A more systematic approach to HFI action in Canada will require more balanced media reporting that acknowledges the limitations of food-based solutions to the income-based problem of HFI

Newly Developed and Validated Eosinophilic Esophagitis Histology Scoring System and Evidence that it Outperforms Peak Eosinophil Count for Disease Diagnosis and Monitoring

Eosinophilic esophagitis is diagnosed by symptoms, and at least 15 intraepithelial eosinophils per high power field in an esophageal biopsy. Other pathologic features have not been emphasized. We developed a histology scoring system for esophageal biopsies that evaluates eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities were scored using a 4 point scale (0 normal; 3 maximum change). Reliability was demonstrated by strong to moderate agreement among 3 pathologists who scored biopsies independently (p≤0.008). Several features were often abnormal in 201 biopsies (101 distal, 100 proximal) from 104 subjects (34 untreated, 167 treated). Median grade and stage scores were significantly higher in untreated compared to treated subjects (p≤0.0062). Grade scores for features independent of eosinophil counts were significantly higher in biopsies from untreated compared to treated subjects (basal zone hyperplasia p≤0.024 and dilated intercellular spaces p≤0.005), and were strongly correlated (r-square\u3e0.67). Principal components analysis identified 3 principal components that explained 78.2% of the variation in the features. In logistic regression models, 2 principal components more closely associated with treatment status than log distal peak eosinophil count (r-square 17, area under the curve 77.8 vs r-square 9, area under the curve 69.8). In summary, the eosinophilic esophagitis histology scoring system provides a method to objectively assess histologic changes in the esophagus beyond eosinophil number. Importantly, it discriminates treated from untreated patients, uses features commonly found in such biopsies, and is utilizable by pathologists after minimal training. These data provide rationales and a method to evaluate esophageal biopsies for features in addition to peak eosinophil count

Peer-led walking programme to increase physical activity in inactive 60- to 70-year-olds: Walk with Me pilot RCT

Background Levels of physical activity decline with age. Some of the most disadvantaged individuals in society, such as those with a lower rather than a higher socioeconomic position, are also the most inactive. Peer-led physical activity interventions may offer a model to increase physical activity in these older adults and thus help reduce associated health inequalities. This study aims to develop and test the feasibility of a peer-led, multicomponent physical activity intervention in socioeconomically disadvantaged community-dwelling older adults. Objectives The study aimed to develop a peer-led intervention through a rapid review of previous peer-led interventions and interviews with members of the target population. A proposed protocol to evaluate its effectiveness was tested in a pilot randomised controlled trial (RCT). Design A rapid review of the literature and the pilot study informed the intervention design; a pilot RCT included a process evaluation of intervention delivery. Setting Socioeconomically disadvantaged communities in the South Eastern Health and Social Care Trust and the Northern Health and Social Care Trust in Northern Ireland. Participants Fifty adults aged 60–70 years, with low levels of physical activity, living in socioeconomically disadvantaged communities, recruited though community organisations and general practices. Interventions ‘Walk with Me’ is a 12-week peer-led walking intervention based on social cognitive theory. Participants met weekly with peer mentors. During the initial period (weeks 1–4), each intervention group participant wore a pedometer and set weekly step goals with their mentor’s support. During weeks 5–8 participants and mentors met regularly to walk and discuss step goals and barriers to increasing physical activity. In the final phase (weeks 9–12), participants and mentors continued to set step goals and planned activities to maintain their activity levels beyond the intervention period. The control group received only an information booklet on active ageing. Main outcome measures Rates of recruitment, retention of participants and completeness of the primary outcome [moderate- and vigorous-intensity physical activity measured using an ActiGraph GT3X+ accelerometer (ActiGraph, LLC, Pensacola, FL, USA) at baseline, 12 weeks (post intervention) and 6 months]; acceptability assessed through interviews with participants and mentors. Results The study planned to recruit 60 participants. In fact, 50 eligible individuals participated, of whom 66% (33/50) were female and 80% (40/50) were recruited from general practices. At 6 months, 86% (43/50) attended for review, 93% (40/43) of whom returned valid accelerometer data. Intervention fidelity was assessed by using weekly step diaries, which were completed by both mentors and participants for all 12 weeks, and checklists for the level of delivery of intervention components, which was high for the first 3 weeks (range 49–83%). However, the rate of return of checklists by both mentors and participants diminished thereafter. Outcome data indicate that a sample size of 214 is required for a definitive trial. Limitations The sample was predominantly female and somewhat active. Conclusions The ‘Walk with Me’ intervention is acceptable to a socioeconomically disadvantaged community of older adults and a definitive RCT to evaluate its effectiveness is feasible. Some modifications are required to ensure fidelity of intervention delivery is optimised. Future research needs to identify methods to recruit males and less active older adults into physical activity interventions

Symbiotic organs shaped by distinct modes of genome evolution in cephalopods.

Microbes have been critical drivers of evolutionary innovation in animals. To understand the processes that influence the origin of specialized symbiotic organs, we report the sequencing and analysis of the genome of Euprymna scolopes, a model cephalopod with richly characterized host-microbe interactions. We identified large-scale genomic reorganization shared between E. scolopes and Octopus bimaculoides and posit that this reorganization has contributed to the evolution of cephalopod complexity. To reveal genomic signatures of host-symbiont interactions, we focused on two specialized organs of E. scolopes: the light organ, which harbors a monoculture of Vibrio fischeri, and the accessory nidamental gland (ANG), a reproductive organ containing a bacterial consortium. Our findings suggest that the two symbiotic organs within E. scolopes originated by different evolutionary mechanisms. Transcripts expressed in these microbe-associated tissues displayed their own unique signatures in both coding sequences and the surrounding regulatory regions. Compared with other tissues, the light organ showed an abundance of genes associated with immunity and mediating light, whereas the ANG was enriched in orphan genes known only from E. scolopes Together, these analyses provide evidence for different patterns of genomic evolution of symbiotic organs within a single host