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We aimed to assess lung fluid balance before and after gradual ascent to 5150m. Lung diffusion capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO) and ultrasound lung comets (ULCs) were assessed in 12 healthy lowlanders at sea-level, and on Day 1, Day 5 and Day 9 after arrival at Mount Everest Base Camp (EBC). EBC was reached following an 8-day hike at progressively increasing altitudes starting at 2860m. DLCO was unchanged from sea-level to Day 1 at EBC, but increased on Day 5 (11±10%) and Day 9 (10±9%) vs. sea-level (P≤0.047). DmCO increased from sea-level to Day 1 (9±6%), Day 5 (12±8%), and Day 9 (17±11%) (all P≤0.001) at EBC. There was no change in ULCs from sea-level to Day 1, Day 5 and Day 9 at EBC. These data provide evidence that interstitial lung fluid remains stable or may even decrease relative to at sea-level following 8days of gradual exposure to high-altitude in healthy humans.

Objective It is well documented that cognitive performance may be altered with ascent to altitude, but the association of various cognitive performance tests with symptoms of acute mountain sickness (AMS) is not well understood. Our objective was to assess and compare cognitive performance during a high-altitude expedition using several tests and to report the association of each test with AMS, headache, and quality of sleep. Methods During an expedition to Mount Everest, 3 cognitive tests (Stroop, Trail Making, and the real-time cognitive assessment tool, an in-house developed motor accuracy test) were used along with a questionnaire to assess health and AMS. Eight team members were assessed pre-expedition, postexpedition, and at several time points during the expedition. Results There were no significant differences (P >.05) found among scores taken at 3 time points at base camp and the postexpedition scores for all 3 tests. Changes in the Stroop test scores were significantly associated with the odds of AMS (P

Background: Bronchopulmonary dysplasia (BPD), a common adverse outcome of extreme preterm birth, can be caused by oxygen-related lung injury and is characterized by arrested alveolar development. Mesenchymal stromal cells (MSCs) have lung protective effects. Conversely, BPD is associated with increased MSCs in tracheal aspirates. This apparent discrepancy is unexplored. We hypothesized that endogenous lung (L-)MSCs are perturbed in an oxygen-induced rat model mimicking BPD. Methods: Rat pups were exposed to 21% or 95% O2 from postnatal day 0 to 10. On day 12, CD146+ L-MSCs were isolated and characterized. Epithelial and vascular repair potential were tested by scratch assay and endothelial network formation respectively, immune function by mixed lymphocyte reaction assay. Microarray analysis was performed using GSEA software. Results: L-MSCs isolated from hyperoxia rat pups had decreased CD73 expression and inhibited lung endothelial network formation. L-MSCs indiscriminately promoted epithelial wound healing and limited T-cell proliferation. Expression of anti-angiogenic genes of the axonal guidance cue pathway was increased after in vivo hyperoxia, whereas genes of the anti-inflammatory JAK/STAT and lung/vascular growth promoting FGF pathways were decreased. Conclusions: In vivo hyperoxia exposure alters the pro-angiogenic effects and FGF expression of L-MSCs. Additionally, decreased CD73 and JAK/STAT expression suggest decreased immune function. L-MSC function may be perturbed and contribute to BPD pathogenesis. These findings may lead to improvements in manufacturing exogenous MSCs with superior repair capabilities.

Background and Objectives: This study aimed to investigate the possible association between exclusive breastfeeding duration during early infancy and susceptibility to allergy and influenza in adulthood. Furthermore, we also investigated the association of breastfeeding duration with DNA methylation at two sites in the promoter of the toll-like receptor-1 (TLR1) gene, as well as the association between DNA methylation of the toll-like receptor-1 (TLR1) gene and susceptibility to different diseases. Materials and Methods: Blood samples were collected from 100 adults and classified into two groups according to breastfeeding duration (&lt, 6 months and &ge, 6 months) during infancy. Subjects were asked to complete a questionnaire on their susceptibilities to different diseases and sign a consent form separately. Fifty-three samples underwent DNA extraction, and the DNA samples were divided into two aliquots, one of which was treated with bisulfite reagent. The promoter region of the TLR1 gene was then amplified by polymerase chain reaction (PCR) and sequenced. Results: We found a significant association between increased breastfeeding duration and a reduction in susceptibility to influenza and allergy, as well asa significant reduction in DNA methylation within the promoter of the TLR1 gene. No association was found between DNA methylation and susceptibility to different diseases. Conclusions: The findings demonstrate the significance of increased breastfeeding duration for improved health outcomes at the gene level.

As the most common arthritis and a leading cause of chronic disability, osteoarthritis is associated with substantial cost to the individual and to society. Epidemiologic studies have supplied, in addition to incidence, prevalence and risk factor data, much of what is known about the natural history of osteoarthritis.Especially given the anticipated increase in osteoarthritis prevalence, the need to identify risk factors for incident osteoarthritis, osteoarthritis progression, osteoarthritis-associated physical function decline, and disability is a high priority. As this review illustrates, the emphasis has shifted in osteoarthritis epidemiology towards the identification of risk factors for osteoarthritis progression rather than incidence.Several risk factors for progression are emerging, many of which are impairments or pathology in the local joint organ environment. This shift in focus relates in part to the concept that local risk factors might ultimately be targeted to delay osteoarthritis progression or to enhance the effect of a disease-modifying drug.

Right from the onset, rheumatoid arthritis is an aggressive disease that can quickly alter joint structure and integrity. Such rapid pathogenesis requires that the diagnosis be established early and aggressive therapy initiated swiftly. In this article, Drs Issa and Ruderman describe what is known about the cause, progression, and outcomes of rheumatoid arthritis. They review the steps toward its diagnosis and urge that treatment be started promptly--to both contain disease and reduce joint destruction as soon as possible.

SummaryTumor expression of the lymphangiogenic factor VEGF-C is correlated with metastasis and poor prognosis, and although VEGF-C enhances transport to the draining lymph node (dLN) and antigen exposure to the adaptive immune system, its role in tumor immunity remains unexplored. Here, we demonstrate that VEGF-C promotes immune tolerance in murine melanoma. In B16 F10 melanomas expressing a foreign antigen (OVA), VEGF-C protected tumors against preexisting antitumor immunity and promoted local deletion of OVA-specific CD8+ T cells. Naive OVA-specific CD8+ T cells, transferred into tumor-bearing mice, were dysfunctionally activated and apoptotic. Lymphatic endothelial cells (LECs) in dLNs cross-presented OVA, and naive LECs scavenge and cross-present OVA in vitro. Cross-presenting LECs drove the proliferation and apoptosis of OVA-specific CD8+ T cells ex vivo. Our findings introduce a tumor-promoting role for lymphatics in the tumor and dLN and suggest that lymphatic endothelium in the local microenvironment may be a target for immunomodulation.

Osteoarthritis is the most common form of arthritis and is a leading cause of disability in the elderly. Given the anticipated increase in osteoarthritis prevalence, the need to identify risk factors for incident osteoarthritis, osteoarthritis progression, osteoarthritis-associated physical function decline, and disability is an especially high priority. Findings have implicated several factors, including genetic factors, aging, joint deformity and injury, obesity, and hormonal deficiencies in the pathogenesis of osteoarthritis. Recent studies have identified risk factors associated with progression of the disease including varus-valgus alignment, bone marrow edema lesions, varus thrust, a reduced hip abduction moment, and obesity. Predictors of function decline in osteoarthritis include lower self-efficacy, knee laxity, less aerobic exercise, worse joint proprioception, and greater knee pain.