Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction.

Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts' increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR

Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort

The COVID-19 pandemic has affected all individuals across the globe in some way. Despite large numbers of reported seroprevalence studies, there remains a limited understanding of how the magnitude and epitope utilization of the humoral immune response to SARS-CoV-2 viral anti-gens varies within populations following natural infection. Here, we designed a quantitative, multi-epitope protein microarray comprising various nucleocapsid protein structural motifs, including two structural domains and three intrinsically disordered regions. Quantitative data from the microarray provided complete differentiation between cases and pre-pandemic controls (100% sensitivity and specificity) in a case-control cohort (n = 100). We then assessed the influence of disease severity, age, and ethnicity on the strength and breadth of the humoral response in a multi-ethnic cohort (n = 138). As expected, patients with severe disease showed significantly higher antibody titers and interestingly also had significantly broader epitope coverage. A significant increase in antibody titer and epitope coverage was observed with increasing age, in both mild and severe disease, which is promising for vaccine efficacy in older individuals. Additionally, we observed significant differences in the breadth and strength of the humoral immune response in relation to ethnicity, which may reflect differences in genetic and lifestyle factors. Furthermore, our data enabled localization of the immuno-dominant epitope to the C-terminal structural domain of the viral nucleocapsid protein in two independent cohorts. Overall, we have designed, validated, and tested an advanced serological assay that enables accurate quantitation of the humoral response post natural infection and that has revealed unexpected differences in the magnitude and epitope utilization within a population

Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction

Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts’ increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR

Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction

Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts' increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR

Antibiotics in hospital effluent and domestic wastewater treatment plants in Doha, Qatar

Wastewater samples were collected from the main hospital’s effluent (HWW), influents and effluents of the old wastewater treatment plant (OWWTP) built in 1990 and the new one (NWWTP) built in 2010 located in Doha, Qatar. Analytical methods were optimized to determine the concentrations of eight selected antibiotics (ABs): penicillin, amoxicillin, gentamicin, ciprofloxacin, tetracycline, erythromycin, metronidazole, and clavulanic acid. Samples were prepared through automated solid phase extraction (SPE) before analysis using liquid chromatography - mass spectrometry (LC–MS) with positive ion electrospray. Among the eight target compounds tested, recoveries were obtained in the range of 47.5–98%. The highest concentration of metronidazole and ciprofloxacin were detected in the HWW at levels of 5.46 μg/L and 1.99 μg/L, respectively. In effluents samples collected from both WWTPs, clavulanic acid was the most prominent compound at concentration of 84.74 μg/L. The highest concentration of erythromycin (7.20 μg/L) was detected in the influent sample collected from OWWTP. Amoxicillin, penicillin, and erythromycin were below the detection limit (0.1 μg/L). There was a significant statistical correlation between the concentrations of most of the studied antibiotics. Ciprofloxacin was highly correlated with erythromycin, clavulanic acid, and metronidazole in all influent samples, whereas the concentration of erythromycin was highly correlated with those of amoxicillin, ciprofloxacin, tetracycline and penicillin in all effluent samples. No significant difference (P ≥ 0.05) was found between concentrations of the targeted antibiotics in the NWWTP and OWWTP. Generally, both treatment plants showed effective removal rates (99.44%) of penicillin and metronidazole. However, clavulanic acid and ciprofloxacin were not removed from the effluent of either plant, even though the effluent passed through the ultrafiltration stage in the new WWTP. The findings reveal that HWW is not the only source of ABs in wastewater but direct disposal onto the sewer system could be the major source. The study calls for further investigation of additional pharmaceuticals and other emerging contaminants in the wastewater of Qatar as well as their metabolites and biodegradation products as well as application of advanced treatment technologies for highest removal rate and safe water reuse options.We thank Dr. Muhammad Al-Sayrafi, Thomas Michael, Haira Binti Mokhtar, Noor Al-Motawa, Dr. Hany Hussein, Dr. Mohammad Al-Ghouti, Munshi Masudul Haq, and Dr. Mohammed Abu-Dieyeh for various assistances on the project. This study was made possible by a grant from Qatar University Office of Academic Research ( QUST-CAS-FALL-14/15-30 ).Scopu

Hyperhydration using different hydration agents does not affect the haematological markers of the athlete biological passport in euhydrated volunteers

Athlete Biological Passport (ABP) is an indirect approach, implemented by WADA, aimed at detecting blood manipulation based on abnormal changes in haematological markers. Cases report the use of hyperhydration as masking method during anti-doping urine sample collection which could potentially mask suspicious fluctuations on ABP profiles. This study investigated the hyperhydration effect on haemoglobin concentration, reticulocyte percentage and OFF-hr score (an algorithm based on haemoglobin concentration and reticulocyte percentage), with and without recombinant human erythropoietin (rHuEPO) administration. A five-week clinical study performed; Baseline and rHuEPO Phase. Water and a sports drink were used as hyperhydration agents. To examine the hyperhydration effect on the normal ABP profile per volunteer, hyperhydration was implemented at 0, 24 and 48 hours during the baseline. During the rHuEPO phase, volunteers received Epoetin beta (3000 IU) with hyperhydration to be implemented at 0, 24 and 48 hours after drug administration. Blood and urine samples were collected and analysed according to WADA guidelines. No significant effect on ABP markers was observed due to hyperhydration at any time during the study. Pre- and post-hyperhydration data were not statistically different compared to individual baseline data. In conclusion, hyperhydration does not affect the ABP haematological markers under the examined conditions. © 2020, © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

Prognostic tools and candidate drugs based on plasma proteomics of patients with severe COVID-19 complications

AbstractCOVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from 50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients.</jats:p

In-house assays for detecting anti-SARS-CoV-2 antibodies in serum and urine: Correlation with COVID-19 severity from a cohort study in Qatar

Background: Serological assays targeting antibodies against key viral proteins, including the Spike (S1), Receptor Binding Domain (RBD), and Nucleocapsid, play a critical role in understanding immunity and supporting diagnostic efforts during COVID-19 pandemic, and afterward. This study aimed to develop and validate in-house assays for detecting anti-SARS-CoV-2 antibodies in serum and urine. Methods: ELISA-based assay was developed to detect IgG and IgM antibodies against SARS-CoV-2. The assay was examined in serum and urine samples of two different cohort of patients affected by COVID-19 disease with different severity and compared to age and sex matched control group. Neutralizing antibody activity was evaluated using an RBD-ACE2 binding inhibition assay. Additionally, a Sengenics protein microarray platform was employed to assess epitope-specific antibody responses. Results: The in-house ELISA assay reliably detected antibodies in both 163 serum and 64 urine samples compared to 50 serum samples from healthy control, with strong correlations observed between antibody levels in the two biofluids. Neutralizing antibody levels correlated positively with disease severity, highlighting their clinical relevance. The performance of the in-house assays was comparable to commercial kits, and the Sengenics microarray provided detailed insights into antibody profiles, identifying dominant epitopes within the Nucleocapsid core domain and RBD. Conclusions: The developed in-house assay demonstrated robust performance and versatility, offering a cost-effective and scalable alternative to commercial kits. Their ability to detect antibodies in both serum and urine highlighted their potential as non-invasive diagnostic tools. These findings contribute to advancing sero-diagnostic capabilities, improving understanding of immune responses to SARS-CoV-2, and supporting global efforts to monitor and manage COVID-19 effectively

Red blood cell derived extracellular vesicles during the process of autologous blood doping

The purpose of this pilot study was to investigate the effects of the transfusion of one erythrocyte concentrate on the number of circulating red blood cell extracellular vesicles (RBC-EVs) and their clearance time. Six, healthy volunteers donated their blood and were transfused with their RBC concentrate after 35–36 days of storage. One K2EDTA and one serum sample were collected before donation, at four timepoints after donation and at another six timepoints after transfusion. RBC-EVs were analyzed on a Cytek Aurora flow cytometer. A highly significant increase (p 3/μL) at baseline to 179.3 ± 84.7 (103/μL) in the first 1–3 h after transfusion could be observed. Individual differences in the response to transfusion became apparent with one volunteer showing no increase and another an increased concentration at one timepoint after donation due to an influenza infection. We concluded that in an individualized passport approach, increased RBC-EVs might be considered as additional evidence when interpreting suspicious Athletes Biological Passport (ABPs) but for this additional research related to sample collection and transport processes as well as method development and harmonization would be necessary.  Other Information Published in: Drug Testing and Analysis License: http://creativecommons.org/licenses/by-nc-nd/4.0/ See article on publisher's website: http://dx.doi.org/10.1002/dta.3157</p