Angiogenesis gene expression in murine endothelial cells during post-pneumonectomy lung growth

Although blood vessel growth occurs readily in the systemic bronchial circulation, angiogenesis in the pulmonary circulation is rare. Compensatory lung growth after pneumonectomy is an experimental model with presumed alveolar capillary angiogenesis. To investigate the genes participating in murine neoalveolarization, we studied the expression of angiogenesis genes in lung endothelial cells. After left pneumonectomy, the remaining right lung was examined on days 3, 6, 14 and 21days after surgery and compared to both no surgery and sham thoracotomy controls. The lungs were enzymatically digested and CD31+ endothelial cells were isolated using flow cytometry cell sorting. The transcriptional profile of the CD31+ endothelial cells was assessed using quantitative real-time polymerase chain reaction (PCR) arrays. Focusing on 84 angiogenesis-associated genes, we identified 22 genes with greater than 4-fold regulation and significantly enhanced transcription (p <.05) within 21 days of pneumonectomy. Cluster analysis of the 22 genes indicated that changes in gene expression did not occur in a single phase, but in at least four waves of gene expression: a wave demonstrating decreased gene expression more than 3 days after pneumonectomy and 3 sequential waves of increased expression on days 6, 14, and 21 after pneumonectomy. These findings indicate that a network of gene interactions contributes to angiogenesis during compensatory lung growth

Cardiac Complications in Patients with Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Observational Studies

Vicente Corrales-Medina and colleagues report estimates of the risk of cardiac complications among patients with community-acquired pneumonia from a systematic review and meta-analysis

The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design

<p>Abstract</p> <p>Background</p> <p>The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO_2peak), patient-reported outcomes, and the organ components that govern VO_2peakin post-operative non-small cell lung cancer (NSCLC) patients.</p> <p>Methods/Design</p> <p>Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO_2peakfor aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO_2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression.</p> <p>Discussion</p> <p>VO_2peakis becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum.</p> <p>Trial Registration</p> <p>NCT00018255</p

Final inversion of the Midcontinent Rift during the Rigolet Phase of the Grenvillian Orogeny

Despite being a prominent continental-scale feature, the late Mesoproterozoic North American Midcontinent Rift did not result in the break-up of Laurentia, and subsequently underwent structural inversion. The timing of inversion is critical for constraining far-field effects of orogenesis and processes associated with the rift’s failure. The Keweenaw fault in northern Michigan (USA) is a major thrust structure associated with rift inversion; it places ca. 1093 Ma rift volcanic rocks atop the post-rift Jacobsville Formation, which is folded in its footwall. Previous detrital zircon (DZ) U-Pb geochronology conducted by laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) assigned a ca. 950 Ma maximum age to the Jacobsville Formation and led researchers to interpret its deposition and deformation as postdating the ca. 1090–980 Ma Grenvillian Orogeny. In this study, we reproduced similar DZ dates using LA-ICP-MS and then dated 19 of the youngest DZ grains using high-precision chemical abrasion–isotope dilution–thermal ionization mass spectrometry (CA-ID-TIMS). The youngest DZ dated by CA-ID-TIMS at 992.51 ± 0.64 Ma (2σ) redefines the maximum depositional age of the Jacobsville Formation and overlaps with a U-Pb LA-ICP-MS date of 985.5 ± 35.8 Ma (2σ) for late-kinematic calcite veins within the brecciated Keweenaw fault zone. Collectively, these data are interpreted to constrain deposition of the Jacobsville Formation and final rift inversion to have occurred during the 1010–980 Ma Rigolet Phase of the Grenvillian Orogeny, following an earlier phase of Ottawan inversion. Far-field deformation propagated &gt;500 km into the continental interior during the Ottawan and Rigolet phases of the Grenvillian Orogeny

An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials