Vascular Remodeling in Pulmonary Hypertension

Pulmonary hypertension (PH) is a rare but deadly disease whose victims bear a 40% chance of mortality within the first five years of diagnosis. Although current treatment strategies have been successful at subduing symptoms of PH, they have done little to prolong the survival of those afflicted. PH is characterized histopathologically by, among other characteristics, hyperplasia and hypertrophy of the smooth muscle cells (SMCs) that constitute the medial layer of the pulmonary resistance arteries and which are thought to decrease the compliance and increase the resistance of the pulmonary vasculature. Over time, these changes increase the burden on the right heart and ultimately lead to its failure and patient death. While recent advances have greatly increased our understanding of pulmonary vascular remodeling, knowledge of these mechanisms is far from complete. Furthermore, the translation of putative mechanisms to animal models is hindered by inadequate tools to quantify medial thickening. Here we present a new method for the quantification of vascular remodeling. In addition, we describe a novel mechanism whereby a conserved 20 amino acid peptide (SR20) in the carboxyterminal domain (CTD) of macrophage elastase (MMP12) induces the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL is known to preferentially induce apoptosis in tumor cells, and we demonstrate the efficacy of SR20 and the MMP12 CTD in vitro and in vivo as a cytotoxic agent against tumor cells. TRAIL is also known to paradoxically increase the proliferation of vascular SMCs, and we present evidence that the MMP12 CTD increases the proliferation of pulmonary arterial SMCs through upregulation of TRAIL with potential links to PH. Finally, we present the results of a genome-wide association study in 36 inbred and wild-derived mouse strains exposed to a chronic high-fat diet-induced model of PH to uncover novel candidate genes linked to PH pathogenesis. The results of these studies should aid investigators in all areas of basic PH research through the provision of superior methods. Meanwhile, the identification of the MMP12 CTD as a mitogen for pulmonary SMCs, and the identification of genomic regions linked to PH development, will help improve our understanding of PH pathogenesis

Atrial fibrillation and survival in colorectal cancer

BACKGROUND: Survival in colorectal cancer may correlate with the degree of systemic inflammatory response to the tumour. Atrial fibrillation may be regarded as an inflammatory complication. We aimed to determine if atrial fibrillation is a prognostic factor in colorectal cancer. PATIENTS AND METHODS: A prospective colorectal cancer patient database was cross-referenced with the hospital clinical-coding database to identify patients who had underwent colorectal cancer surgery and were in atrial fibrillation pre- or postoperatively. RESULTS: A total of 175 patients underwent surgery for colorectal cancer over a two-year period. Of these, 13 patients had atrial fibrillation pre- or postoperatively. Atrial fibrillation correlated with worse two-year survival (p = 0.04; log-rank test). However, in a Cox regression analysis, atrial fibrillation was not significantly associated with survival. CONCLUSION: The presence or development of atrial fibrillation in patients undergoing surgery for colorectal cancer is associated with worse overall survival, however it was not found to be an independent factor in multivariate analysis

Microfiber release from real soiled consumer laundry and the impact of fabric care products and washing conditions

Fiber release during domestic textile washing is a cause of marine microplastic pollution, but better understanding of the magnitude of the issue and role of fabric care products, appliances and washing cycles is needed. Soiled consumer wash loads from U.K. households were found to release a mean of 114 ± 66.8 ppm (mg microfiber per kg fabric) (n = 79) fibers during typical washing conditions and these were mainly composed of natural fibers. Microfiber release decreased with increasing wash load size and hence decreasing water to fabric ratio, with mean microfiber release from wash loads in the mass range 1.0–3.5 kg (n = 57) found to be 132.4 ± 68.6 ppm, significantly (p = 3.3 x 10−8) higher than the 66.3 ± 27.0 ppm of those in the 3.5–6.0 kg range (n = 22). In further tests with similar soiled consumer wash loads, moving to colder and quicker washing cycles (i.e. 15°C for 30 mins, as opposed to 40°C for 85 mins) significantly reduced microfiber generation by 30% (p = 0.036) and reduced whiteness loss by 42% (p = 0.000) through reduced dye transfer and soil re-deposition, compared to conventional 40°C cycles. In multicycle technical testing, detergent pods were selected for investigation and found to have no impact on microfiber release compared to washing in water alone. Fabric softeners were also found to have no direct impact on microfiber release in testing under both European and North American washing conditions. Extended testing of polyester fleece garments up to a 48-wash cycle history under European conditions found that microfiber release significantly reduced to a consistent low level of 28.7 ± 10.9 ppm from eight through 64 washes. Emerging North American High-Efficiency top-loading washing machines generated significantly lower microfiber release than traditional top-loading machines, likely due to their lower water fill volumes and hence lower water to fabric ratio, with a 69.7% reduction observed for polyester fleece (n = 32, p = 7.9 x 10−6) and 37.4% reduction for polyester T-shirt (n = 32, p = 0.0032). These results conclude that consumers can directly reduce the levels of microfibers generated per wash during domestic textile washing by using colder and quicker wash cycles, washing complete (but not overfilled) loads, and (in North America) converting to High-Efficiency washing machines. Moving to colder and quicker cycles will also indirectly reduce microfiber release by extending the lifetime of clothing, leading to fewer new garments being purchased and hence lower incidence of the high microfiber release occurring during the first few washes of a new item

The Role of Counselor Educators in Preparing Active Duty Military Students Utilizing Online Courses: An Initial Primer

Given today’s diverse educational opportunities afforded through online courses, the implications for counselor educators working with active military students are examined. A literature review is presented summarizing current research addressing online education as well as meeting the specific needs of active duty military students. Suggested best practices for preparing these students to be competent counselors are presented, addressing their unique situations taking online courses while serving in active military roles. Recommendations for future research are also presented

Draft Genome Sequence of Rhodococcus sp. Strain ATCC 49988, a Quinoline-Degrading Bacterium.

We report here the 4.9-Mb genome sequence of a quinoline-degrading bacterium, Rhodococcus sp. strain ATCC 49988. The draft genome data will enable the identification of genes and future genetic modification to enhance traits relevant to heteroaromatic compound degradation