Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells

Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincided with high-titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro-inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet-derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis.     

Expression of extracellular matrix metalloproteases inducer on micrometastatic and primary mammary carcinoma cells.

PURPOSE: EMMPRIN (extracellular matrix metalloprotease inducer) is a glycosylated member of the immunoglobulin superfamily known to stimulate the production of matrix metalloproteases (MMPs) 1, 2, and 3 and MT1-MMP in peritumoral fibroblasts. We here evaluated whether EMMPRIN expression is related to tumor progression in human breast cancer. EXPERIMENTAL DESIGN: An immunohistochemical study using high-density tissue microarrays (n = 2222 breast cancer samples) and EMMPRIN-specific antibodies HIM6 and MEM-M6/1 was performed, and staining results were statistically correlated with various clinicopathological parameters. To analyze the putative association between EMMPRIN expression and bone marrow (BM) micrometastasis, an additional set of 55 breast tumors from patients with or without micrometastatic cells as determined with anti-cytokeratin antibody A45-B/B3 were included in our study. Cytokeratin-positive cells in BM were costained with EMMPRIN-specific antibody 1G6.2. RESULTS: Positive EMMPRIN staining correlated significantly with various histopathological risk factors (higher tumor grade, increased tumor size, negative estrogen receptor status and progesterone receptor status, and higher mitotic index) as well as decreased tumor-specific survival (log-rank, P = 0.0027). In particular, in patients > 50 years (i.e., postmenopausal women), EMMPRIN expression was an independent prognosticator as shown by Cox regression analysis (relative risk = 1.7, 95% confidence interval 1.4-4.3, P = 0.036). An involvement of EMMPRIN in tumor progression was also supported by the fact that it was expressed on approximately 90% of micrometastatic cells in BM. CONCLUSIONS: EMMPRIN expression in primary tumor predicts an unfavorable prognosis in breast cancer, suggesting a crucial role of EMMPRIN in progression of human mammary carcinomas.     

Lost working days, productivity, and restraint use among occupants of motor vehicles that crashed in the United States

BACKGROUND: In 2001, 6.3 million passengers were involved in motor vehicle crashes. This study aimed to determine the number of work days lost as a result of motor vehicle crashes and factors that influenced people's return to work. METHODS: This was a retrospective, population based cohort study of occupants in motor vehicles involved in crashes from the 1993-2001 Crashworthiness Data System produced by the National Highway Traffic Safety Administration. The sample population of people aged 18-65 years included two groups: occupants who survived and were working before the crash and occupants who were injured fatally and were estimated to have been working before the crash. Multivariate linear regression was used to analyze the impact of restraint use and injury type on return to work. RESULTS: Overall, 30.1% of occupants of vehicles that crashed missed one or more days of work. A crash resulted in a mean 28.0 (95% confidence interval 15.8 to 40.1) days lost from work, including losses associated with fatalities. The 2.1 million working occupants of vehicles that crashed in 2001 lost a total of 60 million days of work, resulting in annual productivity losses of over $7.5 billion (2964 to 12 075). Unrestrained vehicle occupants accounted for $5.6 billion in lost productivity. CONCLUSIONS: Motor vehicle crashes result in large and potentially preventable productive losses that are mostly attributable to fatal injuries.     

Genotoxicity of Natural Water during the Mass Development of Cyanobacteria Evaluated by the Allium Test Method: A Model Experiment with Microcosms

Cyanobacteria, which develop abundantly in aquatic ecosystems, can be harmful to humans and animals not only by releasing toxins that cause poisoning but also by provoking cytogenetic effects. The influence of the mass development of cyanobacteria on the genotoxic properties of natural water has been studied in model ecosystems (microcosms) with different compositions of biotic components (zooplankton, amphipods and fish). The validated plant test system “Allium test” was used in this study. Genotoxic effects were detected at microcystin concentrations below those established by the World Health Organization (WHO) for drinking water. In all experimental treatments, cells with disorders such as polyploidy and mitotic abnormalities associated with damage to the mitotic spindle, including c-mitosis, as well as lagging chromosomes were found. Genotoxic effects were associated with the abundance of cyanobacteria, which, in turn, depended on the composition of aquatic organisms in the experimental ecosystem. Fish, to a greater extent than other aquatic animals, maintain an abundance of cyanobacteria. After one month, in microcosms with fish, mitotic abnormalities and polyploidy continued to be detected, whereas in other treatments, there were no statistically significant genotoxic effects. In microcosms with amphipods, the number and biomass of cyanobacteria decreased to the greatest extent, and only one parameter of genotoxic activity (frequency of polyploidy) significantly differed from the control.     

Changes in Anti-SARS-CoV-2 IgG Subclasses over Time and in Association with Disease Severity

IgG is the most prominent marker of post-COVID-19 immunity. Not only does this subtype mark the late stages of infection, but it also stays in the body for a timespan of at least 6 months. However, different IgG subclasses have different properties, and their roles in specific anti-COVID-19 responses have yet to be determined. We assessed the concentrations of IgG1, IgG2, IgG3, and IgG4 against different SARS-CoV-2 antigens (N protein, S protein RBD) using a specifically designed method and samples from 348 COVID-19 patients. We noted a statistically significant association between severity of COVID-19 infection and IgG concentrations (both total and subclasses). When assessing anti-N protein and anti-RBD IgG subclasses, we noted the importance of IgG3 as a subclass. Since it is often associated with early antiviral response, we presumed that the IgG3 subclass is the first high-affinity IgG antibody to be produced during COVID-19 infection.     

Estimating Low- and High-Cyclic Fatigue of Polyimide-CF-PTFE Composite through Variation of Mechanical Hysteresis Loops

The fatigue properties of neat polyimide and the “polyimide + 10 wt.% milled carbon fibers + 10 wt.% polytetrafluoroethylene” composite were investigated under various cyclic loading conditions. In contrast to most of the reported studies, constructing of hysteresis loops was performed through the strain assessment using the non-contact 2D Digital Image Correlation method. The accumulation of cyclic damage was analyzed by calculating parameters of mechanical hysteresis loops. They were: (i) the energy losses (hysteresis loop area), (ii) the dynamic modulus (proportional to the compliance/stiffness of the material) and (iii) the damping capacity (calculated through the dissipated and total mechanical energies). On average, the reduction in energy losses reached 10–18% at the onset of fracture, whereas the modulus variation did not exceed 2.5% of the nominal value. The energy losses decreased from 20 down to 18 J/m³ (10%) for the composite, whereas they reduced from 30 down to 25 J/m³ (17%) for neat PI in the low-cycle fatigue mode. For high-cycle fatigue, energy losses decreased from 10 to 9 J/m³ (10%) and from 17 to 14 J/m³ (18%) for neat PI and composite, respectively. For this reason, the changes of the energy losses due to hysteresis are of prospects for the characterization of both neat PI and the reinforced PI-based composites.