Cohesive sediment forms flocs of various sizes and structures in the natural turbulent environment. Understanding flocculation is critical in accurately predicting sediment transport and ...biogeochemical cycles. In addition to aggregation and breakup, turbulence also reshapes flocs toward more stable structures. An Eulerian-Lagrangian framework has been implemented to investigate the effect of turbulence on flocculation by capturing the time-evolution of individual flocs. We have identified two floc reshaping mechanisms, namely breakage-regrowth and restructuring by hydrodynamic drag. Surface erosion is found to be the primary breakup mechanism for strong flocs, while fragile flocs tend to split into fragments of similar sizes. Aggregation of flocs of sizes comparable to or greater than the Kolmogorov scale is modulated by turbulence with lower aggregation efficiency. Our findings highlight the limiting effects of turbulence on both floc size and structure.
Climate change will alter environmental risks that influence pulmonary health, including heat, air pollution, and pollen. These exposures disproportionately burden populations already at risk of ill ...health, including those at vulnerable life stages, with low socioeconomic status, and systematically targeted by oppressive policies. Climate change can exacerbate existing environmental injustices by affecting future exposure, as well as through differentials in the ability to adapt; this is compounded by disparities in rates of underlying disease and access to health care. Climate change is therefore a dire threat not only to individual and population health but also to health equity.
Alcohol use disorder affects over 14 million adults and causes 88,000 deaths each year in the United States. Chronic alcohol use significantly increases people’s risk of developing lung infections ...and acute respiratory distress syndrome (ARDS). This increased sensitivity to injury is a condition known as alcoholic lung syndrome, and it is caused by dysfunction of the lung immune system and alveolar epithelial barrier. However, little is known about how alcohol impacts epithelial cells in the conducting airway, i.e. the trachea and bronchi, which is the first line of defense against infectious pathogens in the lungs. We hypothesize that in vitro ethanol exposure decreases barrier function of human primary bronchial epithelial cells. To test this, we dosed cells with ethanol at various timepoints: 1) during both the basal‐cell expansion and differentiation stages 2) the first 14 days of differentiation on Transwell permeable supports at air liquid interface (ALI); 3) beginning on day 14 of differentiation and continuing for 10 days. We treated cells with 10mM, 60mM or 100mM ethanol almost daily and measured barrier function by transepithelial electrical resistance (TER). We found that ethanol caused a dose‐dependent decrease in barrier function, but only in the group treated during both the expansion and differentiation stages. This suggests that chronically dosing basal cells with ethanol is required for barrier dysfunction of a fully differentiated cell monolayer. Additionally, we cultured primary airway epithelial cells isolated from healthy and alcoholic patients on Transwell permeable supports and differentiated them in vitro to determine if in vivo exposure caused long‐term changes to tight junction protein levels. It is known that the transmembrane protein junctional adhesion molecule A (JAM‐A) regulates barrier function by controlling the paracellular flow of small molecules as part of the tight junction barrier. Our results show in response to alcohol exposure, cells have lower JAM‐A protein expression compared to healthy cells. Together, these results indicate that chronic alcohol exposure detrimentally alters the conducting airway epithelial cell barrier potentially through the loss of JAM‐A. Future directions include determining if other tight junction proteins are altered by alcohol and whether the alcohol‐induced reduction in JAM‐A is sufficient to cause barrier dysfunction in airway cells.
Abstract
Alcohol use disorders (AUD) increase susceptibility to respiratory infections by 2- to 4-fold in part because of impaired alveolar macrophage (AM) immune function. Alcohol causes AM ...oxidative stress, diminishing AM phagocytic capacity and clearance of microbes from the alveolar space. Alcohol increases AM NADPH oxidases (Noxes), primary sources of AM oxidative stress, and reduces peroxisome proliferator–activated receptor γ (PPARγ) expression, a critical regulator of AM immune function. To investigate the underlying mechanisms of these alcohol-induced AM derangements, we hypothesized that alcohol stimulates CCAAT/enhancer-binding protein β (C/EBPβ) to suppress Nox-related microRNAs (miRs), thereby enhancing AM Nox expression, oxidative stress, and phagocytic dysfunction. Furthermore, we postulated that pharmacologic PPARγ activation with pioglitazone would inhibit C/EBPβ and attenuate alcohol-induced AM dysfunction. AM isolated from human AUD subjects or otherwise healthy control subjects were examined. Compared with control AM, alcohol activated AM C/EBPβ, decreased Nox1-related miR-1264 and Nox2-related miR-107, and increased Nox1, Nox2, and Nox4 expression and activity. These alcohol-induced AM derangements were abrogated by inhibition of C/EBPβ, overexpression of miR-1264 or miR-107, or pioglitazone treatment. These findings define novel molecular mechanisms of alcohol-induced AM dysfunction mediated by C/EBPβ and Nox-related miRs that are amenable to therapeutic targeting with PPARγ ligands. These results demonstrate that PPARγ ligands provide a novel and rapidly translatable strategy to mitigate susceptibility to respiratory infections and related morbidity in individuals with AUD.
Abstract
Objectives
To study the prevalence, correlates, and outcomes of GI manifestations in a prospectively enrolled nationwide cohort of SLE in India (INSPIRE).
Methods
It is an observational ...cohort study with analysis of the baseline database of the INSPIRE cohort with early outcomes assessed till 10 April 2023. Cases with GI manifestations as per the BILAG index were selected, pertinent clinical and laboratory data were retrieved for analysis. Patients with GI manifestations were compared with the rest of the cohort and factors associated with death were determined.
Results
Of the 2503 patients with SLE enrolled in the INSPIRE cohort, 243 (9.7%) had GI manifestations observed early in the disease course (1, 0–3 months). Ascites (162, 6.5%), followed by enteritis (41,1.6%), pancreatitis (35, 1.4%) and hepatitis (24, 0.9%) were the most prevalent manifestations. All patients received immunosuppressive therapy, and four patients required surgery. Twenty-nine patients died (11.9%), with uncontrolled disease activity (17, 58.6%) and infection (6, 20.7%) accounting for the majority of deaths. Low socioeconomic class lower Hazard Ratio (95% confidence intervals, CI) 2.8 (1.1–7.9); upper lower 7.5 (2–27.7); reference as upper class and SLEDAI 2K 1.06 (1.02–1.11) were associated with death in the GI group. GI manifestations were significantly associated with age odds ratio and 95% CI 0.97 (0.96–0.99), pleural effusion 4.9 (3.6–6.7), thrombocytopenia 1.7 (1.2–2.4), myositis 1.7 (1.1–2.7), albumin 0.7 (0.5–0.8), alkaline phosphatase (ALP) 1.01 (1.0–1.002), low C3 1.9 (1.3–2.5), total bilirubin 1.2 (1.03–1.3), alopecia 0.62 (0.5–0.96, elevated anti-dsDNA 0.5 (0.4–0.8), and anti-U1RNP antibody 0.8 (0.5–0.7) in model one; and age 0.97 (0.96–0.99), creatinine 1.2 (1.03–1.4), total bilirubin 1.2 (1.03–1.3), ALP 1.01 (1.0–1.002), albumin 0.6 (0.5–0.7), andanti-U1RNP antibody 0.6 (0.5–0.8) in model two in multivariate analysis compared with patients without GI features. The mortality was higher in the GI group (11.9% and 6.6%, P = 0.01) as compared with controls.
Conclusion
GI manifestations were observed in 9.7% of the cohort and were always associated with systemic disease activity and had higher mortality.
Alcohol use disorders cause oxidative stress in the lower airways and increase susceptibility to pneumonia and lung injury. Currently, no therapeutic options exist to mitigate the pulmonary ...consequences of alcoholism.
We recently determined in an animal model that alcohol ingestion impairs pulmonary zinc metabolism and causes alveolar macrophage immune dysfunction. The objective of this research is to determine the effects of alcoholism on zinc bioavailability and alveolar macrophage function in human subjects.
We recruited otherwise healthy alcoholics (n = 17) and matched control subjects (n = 17) who underwent bronchoscopy for isolation of alveolar macrophages, which were analyzed for intracellular zinc, phagocytic function, and surface expression of granulocyte-macrophage colony-stimulating factor receptor; all three of these indices are decreased in experimental models.
Alcoholic subjects had normal serum zinc, but significantly decreased alveolar macrophage intracellular zinc levels (adjusted means SE, 718 41 vs. 948 25 RFU/cell; P < 0.0001); bacterial phagocytosis (adjusted means SE, 1,027 48 vs. 1,509 76 RFU/cell; P < 0.0001); and expression of granulocyte-macrophage colony-stimulating factor receptor β subunit (adjusted means SE, 1,471 42 vs. 2,114 35 RFU/cell; P < 0.0001. Treating alveolar macrophages with zinc acetate and glutathione in vitro increased intracellular zinc levels and improved their phagocytic function.
These novel clinical findings provide evidence that alcohol abuse is associated with significant zinc deficiency and immune dysfunction within the alveolar space and suggest that dietary supplementation with zinc and glutathione precursors could enhance airway innate immunity and decrease the risk for pneumonia or lung injury in these vulnerable individuals.
Alcohol use, and misuse, has been a part of human culture for thousands of years. In the modern medical era, a great deal of attention has been justifiably focused on elucidating the mechanisms ...underlying the psychological and biological addiction to alcohol. However, a significant percentage, if not the majority, of alcohol-related morbidity and mortality occurs in individuals who do not meet the formal diagnostic criteria for alcohol use disorders. For example, many serious medical consequences of chronic alcohol ingestion can occur in individuals who do not have signs or symptoms of alcohol dependence. There is now clear evidence that even in otherwise healthy-appearing individuals who chronically consume excessive amounts of alcohol, alveolar macrophage immune capacity is impaired and, as a consequence, these individuals are at significantly increased risk of pneumonia. This brief review summarizes some of the key mechanisms underlying this phenomenon and proposes a hypothetical scheme by which alcohol interferes with zinc bioavailability within the alveolar space and thereby dampens macrophage function.
Abstract
Measurements in the mesotidal Tamar estuary (UK) reported previously indicate a dependence of the floc settling velocity on the shear rate and the suspended fine sediment concentration or ...volume fraction. Typical time-independent analytic formulas for the floc settling velocity tend to follow the mean trend but fail to provide an explanation for the characteristic data spread. Moreover, they assume floc diameter to be single-valued such as the mean or the median. Given this constraint, an examination of tide-induced trends in the Tamar settling velocities is attempted by simple time-dependent modeling of aggregation, i.e., the dynamics of floc growth and breakup. The effect of aggregation on the settling velocity and diameter is simulated over a representative one-half tidal cycle. Starting at low water (LW) slack at the onset of the sediment erosional phase during the first quarter tide, as the shear rate and volume fraction increase, floc growth is shown to increase the settling velocity that peaks at a shear rate in the range of 15−30 s−1. At higher shear rates, as floc breakup supersedes the effect of sediment concentration in promoting growth, the settling velocity gradually decreases until the shear rate reaches its maximum value on the order of 102 s−1 at the strength of flow. During the following depositional phase in the second quarter tide, as the shear rate decreases the settling velocity increases continually until high water (HW) slack when it achieves its overall maximum value as the shear rate approaches zero. Thus, the loci of settling velocity versus shear rate differ between the quarter tides and result in shear rate versus settling velocity hysteresis. Moreover, it is shown that in the Tamar, tidal variation prevents the settling velocity and diameter from always achieving the equilibrium assumed in analytic formulas. Thus, aggregation modeling serves as a useful guide for resolving temporal trends in floc properties.
Wave, current, acoustic backscatter and suspended sediment concentration measurements (both single‐point and vertical profiles estimated by conversion of acoustic backscatter data) are used to ...investigate wave‐current‐cohesive sediment interaction on the muddy Atchafalaya inner shelf. During an energetic storm, we propose that bed state follows a cycle of dilation due to fluidization, erosion, deposition with fluid mud formation and consolidation. A one‐dimensional‐vertical cohesive sediment transport model is calibrated using current and concentration profiles to estimate the physical parameters that could not be measured directly, e.g., bottom stresses. Estimated bed position and computed bottom stresses suggest that the critical erosion threshold is in the range of 0.3 Pa to 0.5 Pa. The study site is impacted by a sediment‐laden fresh water plume coming from the Atchafalaya River mouth. Bed density evolution during the storm is estimated from vertical sediment exchange between the water column and the bed excluding the duration of passage of a sediment‐carrying water front. The values are in the range of 1,030 kg/m3 to 1,200 kg/m3and indicate that the bed density increases during the erosion phase and decreases during deposition. At the end of the storm, it shows a steady increasing trend during hindered settling and exceeds the space‐filling value during consolidation. Both the critical erosion shear stress and bed density values are consistent with the results of laboratory tests on samples from the experimental site.
Key Points
Bed state and density evolution during a storm is investigated
Critical shear stress for erosion at the experimental site is found
Bed response to hydrodynamic forcing, and role of sediment advection are studied
Alcohol use disorder (AUD) is a significant risk factor for severe acute respiratory distress syndrome. We found that AUD causes a phenotypic shift in gene expression in human bronchial epithelial ...cells, enhancing expression of epidermal genes. AUD cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had higher levels of proinflammatory cytokine secretion and barrier dysfunction not present in infected non-AUD cells, consistent with increased early COVID-19 severity due to AUD.
Alcohol use disorder (AUD) is a significant public health concern and people with AUD are more likely to develop severe acute respiratory distress syndrome (ARDS) in response to respiratory infections. To examine whether AUD was a risk factor for more severe outcome in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we examined early responses to infection using cultured differentiated bronchial epithelial cells derived from brushings obtained from people with AUD or without AUD. RNA-seq analysis of uninfected cells determined that AUD cells were enriched for expression of epidermal genes as compared with non-AUD cells. Bronchial epithelial cells from patients with AUD showed a significant decrease in barrier function 72 h postinfection, as determined by transepithelial electrical resistance. In contrast, barrier function of non-AUD cells was enhanced 72 h after SARS-CoV-2 infection. AUD cells showed claudin-7 that did not colocalize with zonula occludens-1 (ZO-1), indicative of disorganized tight junctions. However, both AUD and non-AUD cells showed decreased β-catenin expression following SARS-CoV-2 infection. To determine the impact of AUD on the inflammatory response to SARS-CoV-2 infection, cytokine secretion was measured by multiplex analysis. SARS-CoV-2-infected AUD bronchial cells had enhanced secretion of multiple proinflammatory cytokines including TNFα, IL-1β, and IFNγ as opposed to non-AUD cells. In contrast, secretion of the barrier-protective cytokines epidermal growth factor (EGF) and granulocyte macrophage-colony stimulating factor (GM-CSF) was enhanced for non-AUD bronchial cells. Taken together, these data support the hypothesis that AUD is a risk factor for COVID-19, where alcohol primes airway epithelial cells for increased inflammation and increased barrier dysfunction and increased inflammation in response to infection by SARS-CoV-2.
NEW & NOTEWORTHY Alcohol use disorder (AUD) is a significant risk factor for severe acute respiratory distress syndrome. We found that AUD causes a phenotypic shift in gene expression in human bronchial epithelial cells, enhancing expression of epidermal genes. AUD cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had higher levels of proinflammatory cytokine secretion and barrier dysfunction not present in infected non-AUD cells, consistent with increased early COVID-19 severity due to AUD.
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