Markers of Fungal Translocation Are Elevated During Post-Acute Sequelae of SARS-CoV-2 Infection and Induce NF-κB Triggered Inflammation.

Long COVID, a type of Post-Acute Sequelae of SARS CoV-2 infection (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the pathophysiological mechanisms that drive this inflammation remain unknown. Inflammation during acute Coronavirus Disease 2019 (COVID-19) could be exacerbated by microbial translocation (from the gut and/or lung) to the blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We found higher levels of fungal translocation - measured as {beta}-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared to those without PASC or SARS-CoV-2 negative controls. The higher {beta}-glucan correlated with higher levels of markers of inflammation and elevated levels of host metabolites involved in activating N-Methyl-D-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neuro-toxic properties. Mechanistically, {beta}-glucan can directly induce inflammation by binding to myeloid cells (via the Dectin-1 receptor) and activating Syk/NF-{kappa}B signaling. Using an in vitro Dectin-1/NF-{kappa}B reporter model, we found that plasma from individuals experiencing PASC induced higher NF-{kappa}B signaling compared to plasma from SARS-CoV-2 negative controls. This higher NF-{kappa}B signaling was abrogated by the Syk inhibitor Piceatannol. These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.

Evaluation of Sickle Cell Module for Quality of Life in Egyptian Children and Adolescents Patients: Impact of Psychiatric and Disease Specific Variables.

Sickle cell disease (SCD) impacts the physical, emotional, and psychological aspects of life. We aimed to study the quality of life (QoL) in Egyptian children and adolescents with SCD using the sickle cell module in relations to social, psychological and disease variables. A cross sectional study included 40 patients with SCD between 5 and 18 years. Details of diagnosis, SCD related complications, socioeconomic status were revised. Psychological assessment was done using children depression inventory, revised Children's Manifest anxiety scale and Health related QoL for both patients and parents using a validated Arabic age specific version of sickle cell module. Significant better scores for communication problems in mothers with college degree was found compared with other academic levels with no significant difference in QoL in relation to father education and significant higher communication problems with high rate of hospitalization (P = .021). Pain score was higher in 8-13 years compared with 13-18 years age groups. Significant worse scores for worrying was found in females, P = 0.033; Depression was found in 90% of studied patients. The main determinants of QoL in patients with SCD were maternal education and frequency of hospitalization. Depression is of alarming frequency for intervention.

COVID-19 Severity Is Associated with Differential Antibody Fc-mediated Innate Immune Functions

Beyond neutralization, antibodies elicit several innate immune functions including complement deposition (ADCD), phagocytosis (ADCP), and cytotoxicity (ADCC). These functions can be both beneficial (by clearing pathogens) and/or detrimental (by inducing inflammation). We tested the possibility that qualitative differences in SARS-CoV-2 specific antibody-mediated innate immune functions contribute to Coronavirus disease 2019 (COVID-19) severity. We found that antibodies from hospitalized COVID-19 patients elicited higher ADCD but lower ADCP compared to antibodies from non-hospitalized COVID-19 patients. Consistently, higher ADCD was associated with higher systemic inflammation during COVID-19. Our study points to qualitative, differential features of anti-SARS-CoV-2 antibodies as potential contributors to COVID-19 severity.

Severe COVID-19 Is Fueled by Disrupted Gut Barrier Integrity

A disruption of the crosstalk between the gut and the lung has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.

Ameliorative effect of 2-methoxyestradiol on radiation-induced lung injury.

AIMS: Radiation-induced lung injury (RILI) is a serious complication of radiation therapy. Development of an effective drug that selectively protects normal lung tissues and sensitizes tumor cells to radiotherapy is an unmet need. 2-Methoxyestradiol (2ME2) possesses polypharmacological properties, which qualifies it as an effective radioprotector. Our aim is to explore the potential protective effects of 2ME2 against early and late stages of RILI and the underlying mechanisms. MAIN METHODS: BALB/c mice were either treated with 2ME2 (50 mg/kg/day i.p., for 4 weeks); or received a single dose of 10 Gy ionizing radiation (IR) delivered to the lungs; or 10 Gy IR and 2ME2. Animal survival and pulmonary functions were evaluated. Immune-phenotyping of alveolar macrophages (AM) in the broncho-alveolar lavage fluids (BALF) was determined by flow cytometry. ELISA was used to evaluate the expression levels of TNF-α, TGF-ß; and IL-10 in BALF. Lung tissues were used for histopathological examination or immunofluorescence staining for CD68 (pan-macrophage marker), Arginase-1 (Arg1, M2-specific marker), inducible nitric oxide synthase (iNOS, M1-specific marker) and HIF-1α. VEGF and γH2AX expression in lung tissues were detected by western blot. KEY FINDINGS: The results demonstrated that 2ME2 improved the survival, lung functions and histopathological parameters of irradiated mice. Additionally, it attenuated the radiation-induced AM polarization and reduced the pneumonitis and fibrosis markers in lung tissues. Significant reduction of TNF-α and TGF-ß with concomitant increase in IL-10 concentrations were observed. Moreover, the expression of HIF-1α, VEGF and γH2AX declined. SIGNIFICANCE: 2ME2 is a promising radioprotectant with fewer anticipated side effects.

Histological and Anthropometric Changes in the Aging Nose.

BACKGROUND: Rhinoplasty in the elderly requires different surgical approaches due to the morphological and structural changes affecting the nose over time. OBJECTIVES: In this study, the authors aimed to evaluate the age-related cellular and architectural changes of nasal cartilages and soft tissue attachments. METHODS: This prospective study included 80 patients who underwent rhinoplasty. Patients were divided into 2 groups according to age. Group I included 40 patients ranging in age from 19 to 39 years. Group II included 40 patients aged at least 40 years. Samples from nasal cartilages (upper lateral, lower lateral, and septum) and nasal attachments (interdomal, inter-cartilaginous, and septo-crural) were taken. All specimens were evaluated histologically to detect age-related changes. A modified version of the Mankin grading scale was used to score each nasal cartilage sample. All attachment samples were examined by image analysis for quantitative assessment. The results were correlated to preoperative anthropometric measurements of nasolabial angle and nasal projection. RESULTS: Histologically, in group II, the cartilage matrix showed fibrinoid degeneration with a significant decrease in the number of chondrocytes and increased perichondrial fibrosis compared with group I. Attachments in group II showed a lower number of blood vessels and decreased percentage of collagen bundles. Modified Mankin scores were significantly higher in group II, indicating weak cartilages compared with group I. There was negative correlation and significance between projection, nasolabial angle, cartilages, and attachments in study groups. The linear regression model revealed that the lower lateral cartilage is the cartilage that is most affected by the aging process. CONCLUSIONS: These findings not only enhance our current understanding of the natural changes that occur in the nose during aging but may also affect surgical decision-making when grafting or suturing are considered during rhinoplasty.Level of Evidence: 2.

Virtual CT morphometry of lower limb long bones for estimation of the sex and stature using postmortem Japanese adult data in forensic identification.

The application of computed tomography (CT) is useful for the documentation of whole-body anatomical data on routine autopsy, virtual reconstruction of skeletal structure, objective measurements, and reassessment by repetitive analyses. In addition, CT data processing facilitates volumetric and radiographic density analyses. Furthermore, a recently developed automated analysis system markedly improved the performance and accuracy of three-dimensional (3D) reconstruction. The present study investigated virtual CT morphometry of lower limb long bones, including the femur, tibia, fibula, and first metatarsus, to estimate the sex and stature using postmortem CT data of forensic autopsy cases of Japanese over 19 years of age (total n = 259, 150 males and 109 females). Bone mass volumes, lengths, and total CT attenuation values of bilateral femurs, tibias, and fibulas correlated with the stature; however, the mean CT attenuation (HU) values showed age-dependent decreases. Correlations with the stature were similar for the lengths and mass volumes of the femur, tibia, and fibula (r = 0.77-0.85) but were higher for the mass volume of the first metatarsus (r = 0.77 for right and r = 0.58 for left). In addition, the ratio of the bone volume to the length of each bone showed the most significant sex-related differences (males > females with accuracy of 75.8-98.1 %). These findings indicate the usefulness of virtual CT morphometry of individual lower limb long bones, including volumetry, to estimate the sex and stature in identification.

CO2 sequestration using accelerated gas-solid carbonation of pre-treated EAF steel-making bag house dust.

Mineral CO2 sequestration is a promising process for the reduction of carbon dioxide emissions to the atmosphere. In this paper, alkaline calcium-rich dust particles collected from bag filters of electric arc furnaces (EAF) for steel making were utilized as a viable raw material for mineral CO2 sequestration. The dust particles were pre-treated through hydration, drying and screening. The pre-treated particles were then subjected to direct gas-solid carbonation reaction in a fluidized-bed reactor. The carbonated products were characterized to determine the overall sequestration capacity and the mineralogical structures. Leaching tests were also performed to measure the extracted minerals from the carbonated dust and evaluate the carbonation process on dust stabilization. The experimental results indicated that CO2 could be sequestered using the pre-treated bag house dust. The maximum sequestration of CO2 was 0.657 kg/kg of dust, based on the total calcium content. The highest degree of carbonation achieved was 42.5% and the carbonation efficiency was 69% at room temperature.

Efficacy of automated three-dimensional image reconstruction of the femur from postmortem computed tomography data in morphometry for victim identification.

Besides conventional radiology, postmortem computed tomography (PM-CT) is nowadays widely used for victim identification in forensic routines to detect anatomical characteristics and specific pathologies as well as to estimate the stature and sex. A major advantage of PM-CT is virtual reconstruction of skeletal structures independent of the status of recovered remains. The present study investigated the efficacy of a recently provided automated analyzer to reconstruct three-dimensional (3-D) images using CT data for skeletal morphometry, measuring the whole bone mass volume of the femur (60 bones in 30 cases) as an index of reproducibility. Manual cursoring could reconstruct bilateral femurs with high reproducibility, showing mass volume fluctuations by repetition and between two independent observers of 0.2-2.1% and 3.5-6.7%, respectively, partly depending on the data analysis system, but was time-consuming, while automated reconstruction was very rapid and highly reproducible virtually without detectable fluctuation; there was a high correlation between bone mass volumes reconstructed by manual and automated procedures (r=0.9976, p<0.0001). The reproducibility of the automated procedure was 98.64-100.81% in 5 cases scanned twice under the same CT conditions. Preliminary analysis showed a substantial correlation of the whole femur mass volume with the body height and a significant sex-related difference in the femur mass volume/body height ratio (males>females). These findings indicate the accuracy and practical feasibility of the automated procedure to reconstruct single bone 3-D CT images for virtual skeletal morphometry in victim identification.

Solidification of cement kiln dust using sulfur binder.

The present study aims to offer a new methodology for consuming two industrial wastes; sulfur, from petroleum and natural gas industries, and cement kiln dust (CKD), from Portland cement industries, in construction industry. Sulfur solidified cement kiln dust material (SSCKDM) was manufactured by mixing molten sulfur, treated sulfur, CKD and sand at a controlled temperature in excess of 120°C. The hot mixture was subsequently cast and shaped into the desired mold and was then allowed to solidify at a specified cooling rate. Solidified materials were immersed for time periods up to 28 days in distilled water at different temperatures of 25 and 60°C, sea water, and acidic and basic universal buffer solutions of pH4 and pH9, respectively. Solidified material performance as function of time and type of aqueous solution exposed to was evaluated in view of compressive strength variations and leachability of metal and heavy metal ions. The results indicated that the solidified articles exhibit homogenous and compact internal microstructure with excellent mechanical properties. However, it showed durability problem upon exposure to aqueous solution environments due to the initial chemical composition of the CKD, whose leached test showed release of relatively high amounts of sulfates and alkali metals. Durability of SSCKDM articles in relation to strength reduction and crack formations control was improved by addition of glass fiber while, the use of anti-leaching agent such as anhydrous sodium sulfide resulted in reduction of leached heavy metals without any measurable decrease in leached amounts of alkali metals and anions from the solidified matrix. Furthermore, based on leachability index method of calculation, potential chemical mobility of metal and heavy metal ions from the solidified matrix was characterized as medium.

Externalities of fugitive dust.

It is known that fugitive dust can cause human health and environmental problems, alone or in combination with other air pollutants. These problems are referred to as 'external costs' that have been traditionally ignored. However, there is a growing interest towards quantifying externalities to assist policy and decision-making. With this in mind, the present study aimed at discussing the environmental regulations that deal with fugitive dust, the impact of fugitive dust on human health and global climate system, and the available methods for calculating fugitive dust externalities. The damage cost associated with human health and global environmental problems was predicted based on the environmental strategy priority model. The damage cost estimated by the model ranged from 40 to 374 EUR/kg of emitted fugitive dust with a mean value of 120 EUR/kg of emitted fugitive dust. It was also found that PM(2.5) and PM(10) have contributed to about 60% and 36% of the estimated damage cost, respectively. The remaining 4% was attributed to both nitrate and sulfate aerosols.