Non-infected Controls Research Articles

Dengue Virus Infection and Risk of Parkinson's Disease: A Nationwide Longitudinal Study.

Background: Increasing evidence suggests a potential relationship between viral infection and Parkinson’s disease (PD). Objective: Herein, we explore the association between infection by dengue virus and PD. Methods: Between 1997 and 2012, we recruited 1,422 patients with dengue fever and 14,220 matched controls (age, sex, time of enrollment, and medical and mental comorbidities) from the Taiwan National Health Insurance Research Database. We identified new onset of PD to the end of 2013. The Kaplan-Meier method was used to estimate the incidence rate of PD. Cox-regression analysis was applied to calculate the hazard ratios (HRs) with 95% confidence intervals (CIs) after adjustment for confounders. Results: During the follow up period, the dengue group had higher incidence of PD than the control group (1.2% vs. 0.4% , p = 0.001). Patients with dengue fever had a significantly higher risk of developing PD [HR, 2.59; 95% CI, 1.51–4.44] compared with the controls, after adjustments for demographic data, PD-related comorbidities, and all-cause clinical visits. The subgroup analysis, stratified by age and sex, found that higher risk for PD was statistically significant for male (HR, 3.51; 95% CI, 1.76–7.00) and patients aged >60 years (HR, 2.96; 95% CI, 1.62–5.41). Conclusion: The risk of PD was 2.59-fold higher in patients with dengue fever than in non-infected controls during the follow-up period. Clinicians need to monitor signs of PD during patient recovery from dengue fever. Additional studies are needed to confirm our results and investigate the mechanisms linking PD and dengue virus infection.

Upregulation of sialyltransferases ST3Gal1 and ST6Gal1 promotes stabilization of erythrocyte mass and recovery of anemia in Trypanosoma brucei brucei-infected pigs

The role of Sialyltransferases (STs) specifically subfamilies ST3Gal1 and ST6Gal1 tissue expression was investigated in the liver and kidney of Trypanosoma brucei brucei-infected and uninfected control pigs. The study was aimed to provide emerging target for treatment. Pigs were experimentally infected with 2 × 106 T. b. brucei (Federe strain); parasitemia was monitored by microscopy and tissue expression levels of ST3Gall and ST6Gall in the liver and kidney were assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Parasitemia were undulating and anemia occurred significantly (P < 0.01) on day 13 in the infected pigs with an attempt to recover toward the termination of the study on day 21. The gene expressions for hepatic and renal ST3Gal1 and ST6Gal1 were significantly (P < 0.0001) upregulated 5–42 folds in the infected pig compared to the non-infected control group. It was concluded from the findings in this study that increased tissue expression of ST3Gal1 and ST6Gal1 in T b. brucei-infected pigs may play a pivotal role in the resialylation of desialylated red blood cells, thereby promoting recovery of the red blood cells and stabilization of erythrocyte mass in trypanosome-infected pigs. It is recommended that the expression of serum ST3Gal1 and ST6Gal1 be investigated further, in trypano-susceptible against trypano-tolerant breeds of animals to determine the role of these genes in trypano-tolerance.

Effects of 1,25-Dihydroxyvitamin D3 and 25-Hydroxyvitamin D3 on PBMCs From Dairy Cattle Naturally Infected With Mycobacterium avium subsp. paratuberculosis.

The role of vitamin D3 in modulating immune responses has been well-established for over two decades; however, its specific functions have not been extensively detailed in cattle, particularly cattle in different stages of infection with Mycobacterium avium subspecies paratuberculosis (MAP). Consistent with previous work in our lab, the present study showed that infected cattle in the clinical stage of disease have reduced serum 25-hydroxyvitamin D3 [25(OH)D3]. Additionally, effects of vitamin D3 on peripheral blood mononuclear cells (PBMCs) from naturally infected dairy cattle in subclinical (n = 8) or clinical (n = 8) stages of infection were compared to non-infected control cows (n = 8). Briefly, PBMCs were isolated and cultured in vitro with 4 ng/ml 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or 100 ng/ml 25(OH)D3. Treatment with 1,25(OH)2D3 resulted in decreased secretion for some pro-inflammatory cytokines in clinical animals, including IL-1β, IL-6, and IFN-γ. Similar responses for IL-1β and IL-6 were noted with the addition of 25(OH)D3. Additionally, pro-inflammatory cytokine gene expression tended to be upregulated in PBMCs from clinical animals after treatment with 1,25(OH)2D3. In contrast, PBMCs from clinical animals treated with 25(OH)D3 showed downregulation of pro-inflammatory cytokine gene expression, although only significant for IL1B. Following 25(OH)D3 treatment, clinical animals showed significant reduction in CD4+CD25+ T cells. CYP27B1 gene expression was notably decreased in clinical and control animals following 25(OH)D3 treatment but increased in subclinical cows. 1,25(OH)2D3 treatment reduced CYP24A1 gene expression in all groups, while 25(OH)D3 treatment only significantly reduced expression for control cows. Lastly, serum 25(OH)D3 levels were significantly lower in clinical animals. Taken together, these data show vitamin D3 modulates cytokine signaling in cattle at different stages of MAP infection and, therefore, may have implications on disease progression.

Clinicopathological Parameters and Sialyltransferase Activity in Trypanosoma Congolense-Infected Sheep

Cleavage of erythrocyte surface sialic acid (SA) by the sialidase produced by trypanosomes is implicated in the pathogenesis of anaemia in African animal trypanosomiasis (AAT). Sialyltransferase (ST) mediates the attachment of SA to cell surface glycoproteins and glycolipids of desialylated erythrocytes. ST activities in Trypanosoma congolense-infected sheep and control groups were investigated and variations in their physio-biochemical properties were evaluated. Six (6) apparently healthy Nigerian Yankassa breed of sheep comprising of T. congolense-infected (n=3) and non-infected (n=3) groups were used for the experiment. Parasitaemia and packed cell volume (PCV) were determined daily over a 5-week period. Enzyme kinetics of partially purified ST from the thyroid gland were also evaluated. Anaemia (mean PCV= 18.83±0.71%) was observed in the T. congolense-infected sheep when compared with the non-infected control group (mean PCV 39.75±0.35%) and the observed differences were significant (p &lt; 0.05) after five weeks post infection. Variations were also observed in the physio-biochemical properties (pH, temperature, activation energy) of the ST isolated from the T. congolense-infected and control sheep. This finding is believed to have been an induced response by the host to parasite’s activity and could be exploited further as a possible target in the control of AAT.

Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients

BackgroundCOVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology.MethodsTo better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients.ResultsAltered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients.ConclusionsOur results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.

Psychological Distress of Healthcare Workers in Québec (Canada) During the Second and the Third Pandemic Waves.

We aimed to measure the prevalence of psychological distress among Quebec healthcare workers (HCWs) during the second and third pandemic waves and to assess the effect of psychosocial risk factors (PSRs) on work-related psychological distress among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected (cases) and non-infected (controls) HCWs. A self-administered survey was used to measure validated indicators of psychological distress (K6 scale) and PSR (questions based on Karasek and Siegrist models, value conflicts, and work-life balance). Adjusted robust Poisson models were used to estimate prevalence ratios. Four thousand sixty eight cases and 4152 controls completed the survey. Prevalence of high work-related psychological distress was 42%; it was associated with PSRs (mainly work-life balance, value conflicts, and high psychological demands) but not with SARS-CoV-2 infection. Primary prevention measures targeting PSRs are needed to reduce mental health risks of HCWs.

Exogenous Vitamin D3 Modulates Response of Bovine Macrophages to Mycobacterium avium subsp. paratuberculosis Infection and Is Dependent Upon Stage of Johne's Disease.

Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of ruminant enteritis, targets intestinal macrophages. During infection, macrophages contribute to mucosal inflammation and development of granulomas in the small intestine which worsens as disease progression occurs. Vitamin D3 is an immunomodulatory steroid hormone with beneficial roles in host-pathogen interactions. Few studies have investigated immunologic roles of 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in cattle, particularly cattle infected with MAP. This study examined the effects of exogenous vitamin D3 on immune responses of monocyte derived macrophages (MDMs) isolated from dairy cattle naturally infected with MAP. MDMs were pre-treated with ± 100 ng/ml 25(OH)D3 or ± 4 ng/ml 1,25(OH)2D3, then incubated 24 hrs with live MAP in the presence of their respective pre-treatment concentrations. Following treatment with either vitamin D3 analog, phagocytosis of MAP by MDMs was significantly greater in clinically infected animals, with a greater amount of live and dead bacteria. Clinical cows had significantly less CD40 surface expression on MDMs compared to subclinical cows and noninfected controls. 1,25(OH)2D3 also significantly increased nitrite production in MAP infected cows. 1,25(OH)2D3 treatment played a key role in upregulating secretion of pro-inflammatory cytokines IL-1β and IL-12 while downregulating IL-10, IL-6, and IFN-γ. 1,25(OH)2D3 also negatively regulated transcripts of CYP24A1, CYP27B1, DEFB7, NOS2, and IL10. Results from this study demonstrate that vitamin D3 compounds, but mainly 1,25(OH)2D3, modulate both pro- and anti-inflammatory immune responses in dairy cattle infected with MAP, impacting the bacterial viability within the macrophage.

Glucose and Lactate Reference Intervals for White Sturgeon and Evaluation of Two Point-of-Care Devices in Sturgeon Infected with Veronaea botryosa.

White Sturgeon Acipenser transmontanus are cultured for human consumption as well as for conservation purposes. In this study, two commercially available portable devices for measuring glucose and lactate were compared to a benchtop analyzer and blood reference intervals were generated using heparin plasma collected from 43 healthy White Sturgeon yearlings. The generated normal ranges were used to compare plasma values collected from Veronaea botryosa-infected White Sturgeon at 10, 20, and 30 d postchallenge (dpc). In the 43 healthy yearlings, significantly different glucose and lactate values were obtained when comparing the portable devices to the benchtop analyzer. In the portable devices, blood glucose showed a consistent bias of 12.3 mg/dL and blood lactate showed a proportional bias. The detected blood glucose values in infected sturgeon were significantly different from those in noninfected controls when using the benchtop analyzer at 20 and 30 dpc and when using the portable device at 20 dpc. However, blood glucose in infected individuals and controls was within the reference interval on either device. No significant difference was noted for lactate measurements in infected sturgeon. The results of this study indicate that portable devices for blood glucose and blood lactate evaluation in White Sturgeon may be useful in a setting where relative values are an acceptable approximation of absolute values.

Retrospective study of post-operative infections in implantable cardiac devices in a cardiac tertiary care center.

BACKGROUND: The rise in the incidence of implantation is one of the main causes behind the increased rate of CIED infection, which is considered as a serious life-threatening complication. The need of risk factor assessment has become a necessity to prevent further complications and provide prompt management.OBJECTIVES: Identify the risk factors of infection postoperatively among patients who have implantable cardiac devices.DESIGN: A retrospective case-control study.SETTINGS: Cardiac center for adults.PATIENTS AND METHODS: The study included all adult patients (≥14 years of age) of all nationalities who underwent cardiac electronic device implantation that was managed in the cardiac center between January 2012 to December 2018.MAIN OUTCOME MEASURES: Cardiac device infection and associated risk factors.SAMPLE SIZE: 213, including 23 (10.8%) infected case patients and 190 (89.2%) non-infected controls.RESULTS: The mean (SD) age of non-infected patients was 45.0 (12.7) years compared with 61.7 (13.7) for infected patients (P<.0001). Anticoagulant use, hypertension, dysplipdemia and age were the most common patient-related risk factors associated with infection. For procedural and post-procedural risk factors, the risk of infection increased as the number of leads and length of procedure increased. The device most often related to infection was the pacemaker. In the multivariate analysis, longer procedure, greater number of leads, older age, anticoagulant use, and implanted pacemaker device were independently associated with infection.CONCLUSION: We advise the prompt use of strict preoperative antiseptic prophylaxis measures and follow-up for post-implant patients along with patient education for early signs of infections, which will lead to improvement of both diagnosis and treatment quality for our patients in addition to reducing the economic impact on the health care system by minimizing infectious complications.LIMITATIONS: Single tertiary center study, small sample size.CONFLICT OF INTEREST: None.

Isolation and identification of Salmonella species isolated from diseased broiler Japanese quail with an experimental treatment trial

This study was performed to investigate salmonella infection in Japanese quails, also its incidence, clinical signs, postmortem lesion, serotypes, antibiotic resistance, and virulence with an experimental treatment trial. A total of 100 samples were collected from quails suffering from diarrhea and mortalities from 10 farms (10 birds from each) at Kafr El-Sheikh Governorate, Egypt. Samples were aseptically collected and were processed for the isolation and identification of salmonella spp. Incidence of salmonella infections was (17%), detected serotypes were S. infantis 58.8 %( 10/17), S. salame17.6% (3/17), S. Kentucky 11.8 %( 2/17), S. Isangi 5.8% (1/17), S. Colorado 5.8% (1/17). Virulence genes such as invA and sopB were detected in all examined isolates while no one had pefA and for antibiotics resistance genes all 10 isolates carried tetB, 3 isolates, and 2 isolates of them carrying qnrS and blaMox respectively. Susceptibility of isolated Salmonella serotypes to antimicrobial agents showed 100% resistance to oxytetracycline and erythromycin and serotypes were sensitive to fosfomycin (16/17) (94.11%). In the experimental design, one hundred and twenty, one-day-old Salmonella free quail chicks, were used to study the pathogenicity of Salmonella isolates (S. Infantis). Quails Chicks were divided into 6 groups (20 per group), the first group (G1) was kept as non-infected control and group 2 (G2) as infected control, group 3 (G3) was non-infected and given organium oil from1-19 days, group 4 (G4) was infected and treated with fosfomycin on the 2nd-day post-infection for 5 days, group 5 (G5) was infected and given organium oil from 1-19 day and, group 6 (G6) was infected and treated with fosfomycin on the 2nd-day post-infection for 5 days and given organium oil from1-19 day. The birds in groups (2, 4, 5, and 6) were infected orally with 0.5 ml of S. Infantis containing 107CFU on the 10th-day of age. Observation of the chicks daily for clinical signs and mortalities was done for 2 weeks post-infection. PM examination of dead and very sick chicks and bacteriological re-isolation. Our results showed that the birds that received fosfomycin and organium oil together (G6) showed more favorable clinical signs, mortality rate, post-mortem lesions, recovery rate, and shedding rate then (G4), and (G5), respectively than (G2). In the experimental design, blood samples were collected at 12 and 19 days of age (5 birds from each group each time) for Serum analysis, and total and differential leukocytes count, the analysis of variance showed that positive significant effect on treated groups (G3, G5, G6) with organium oil on total protein, albumin, globulin, and albumin globulin ratio (P

Increased angiogenesis parallels cardiac tissue remodelling in experimental acute Trypanosoma cruzi infection.

Angiogenesis has been implicated in tissue injury in several noninfectious diseases, but its role in Chagas disease (CD) physiopathology is unclear. The present study aimed to investigate the effect of Trypanosoma cruzi infection on cardiac angiogenesis during the acute phase of experimental CD. The signalling pathway involved in blood vessel formation and cardiac remodelling was evaluated in Swiss Webster mice infected with the Y strain of T. cruzi. The levels of molecules involved in the regulation of angiogenesis, such as vascular endothelial growth factor-A (VEGF-A), Flk-1, phosphorylated extracellular-signal-regulated protein kinase (pERK), hypoxia-inducible factor-1α (HIF-1α), CD31, α-smooth muscle actin (α-SMA) and also the blood vessel growth were analysed during T. cruzi infection. Hearts were analysed using conventional histopathology, immunohistochemistry and western blotting. In this study, our data demonstrate that T. cruzi acute infection in mice induces exacerbated angiogenesis in the heart and parallels cardiac remodelling. In comparison with noninfected controls, the cardiac tissue of T. cruzi-infected mice presented higher levels of (i) HIF-1α, VEGF-A, Flk-1 and pERK; (ii) angiogenesis; (iii) α-SMA+ cells in the tissue; and (iv) collagen -1 deposition around blood vessels and infiltrating throughout the myocardium. We observed cardiac angiogenesis during acute experimental T. cruzi infection parallels cardiac inflammation and remodelling.

Saliva metabolomic profile of COVID-19 patients associates with disease severity.

IntroductionCoronavirus disease 2019 (COVID-19) is strongly linked to dysregulation of various molecular, cellular, and physiological processes that change abundance of different biomolecules including metabolites that may be ultimately used as biomarkers for disease progression and severity. It is important at early stage to readily distinguish those patients that are likely to progress to moderate and severe stages.ObjectivesThis study aimed to investigate the utility of saliva and plasma metabolomic profiles as a potential parameter for risk stratifying COVID-19 patients.MethodLC–MS/MS-based untargeted metabolomics were used to profile the changes in saliva and plasma metabolomic profiles of COVID-19 patients with different severities.ResultsSaliva and plasma metabolites were screened in 62 COVID-19 patients and 18 non-infected controls. The COVID-19 group included 16 severe, 15 moderate, 16 mild, and 15 asymptomatic cases. Thirty-six differential metabolites were detected in COVID-19 versus control comparisons. SARS-CoV-2 induced metabolic derangement differed with infection severity. The metabolic changes were identified in saliva and plasma, however, saliva showed higher intensity of metabolic changes. Levels of saliva metabolites such as sphingosine and kynurenine were significantly different between COVID-19 infected and non-infected individuals; while linoleic acid and Alpha-ketoisovaleric acid were specifically increased in severe compared to non-severe patients. As expected, the two prognostic biomarkers of C-reactive protein and D-dimer were negatively correlated with sphingosine and 5-Aminolevulinic acid, and positively correlated with l-Tryptophan and l-Kynurenine.ConclusionSaliva disease-specific and severity-specific metabolite could be employed as potential COVID-19 diagnostic and prognostic biomarkers.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s11306-022-01936-1.

Effects of hyperbaric oxygen therapy on functional and structural connectivity in post-COVID-19 condition patients: A randomized, sham-controlled trial

IntroductionPost-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. Abnormalities in brain connectivity were found in recovered patients compared to non-infected controls. This study aims to evaluate the effect of hyperbaric oxygen therapy (HBOT) on brain connectivity in post-COVID-19 patients. MethodsIn this randomized, sham-controlled, double-blind trial, 73 patients were randomized to receive 40 daily sessions of HBOT (n = 37) or sham treatment (n = 36). We examined pre- and post-treatment resting-state brain functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) scans to evaluate functional and structural connectivity changes, which were correlated to cognitive and psychological distress measures. ResultsThe ROI-to-ROI analysis revealed decreased internetwork connectivity in the HBOT group which was negatively correlated to improvements in attention and executive function scores (p < 0.001). Significant group-by-time interactions were demonstrated in the right hippocampal resting state function connectivity (rsFC) in the medial prefrontal cortex (PFWE = 0.002). Seed-to-voxel analysis also revealed a negative correlation in the brief symptom inventory (BSI-18) score and in the rsFC between the amygdala seed, the angular gyrus, and the primary sensory motor area (PFWE = 0.012, 0.002). Positive correlations were found between the BSI-18 score and the left insular cortex seed and FPN (angular gyrus) (PFWE < 0.0001). Tractography based structural connectivity analysis showed a significant group-by-time interaction in the fractional anisotropy (FA) of left amygdala tracts (F = 7.81, P = 0.007). The efficacy measure had significant group-by-time interactions (F = 5.98, p = 0.017) in the amygdala circuit. ConclusionsThis study indicates that HBOT improves disruptions in white matter tracts and alters the functional connectivity organization of neural pathways attributed to cognitive and emotional recovery in post-COVID-19 patients. This study also highlights the potential of structural and functional connectivity analysis as a promising treatment response monitoring tool.

Biochemical and Haematological Effect of Kaempferol in Stress Induced By Experimental Eimeria Tenella Infection in Two Weeks Old Broiler Chickens

In this study, biochemical and haematological effects of kaempferol in stress induced by experimental Eimeria tenella infection in two weeks old broiler chickens was investigated. Sixty-day old broilers were randomly allotted into six groups (I-VI) of ten broilers each and brooded for two weeks with commercial broiler feed (vital feed®) and provided water ad libitum. At two weeks of age broilers in group I served as non-infected control. Broilers in groups II- VI were infected with Eimeria tenella sporulated oocyst (104/ml) via oral inoculation. After infection was established, broilers in groups II-IV were treated per os with 1 mg/kg, 1.5 mg/kg and 2 mg/kg of kaempferol respectively. Broilers in group V were treated for five days with amprolium, 1.25 g/L in drinking water. Broilers in group VI served as infected untreated control. Five days post infection; all broilers were sacrificed by severing their jugular veins. Blood sample was collected from each broiler in a plane sample container devoid of anticoagulant so as to harvest serum for serology while Ethylenediamine tetra-acetic acid (EDTA) bottles were used to collect 1 ml of blood from each bird for haematology. Concentrations of antioxidant (GPx, CAT and SOD) and liver enzymes (ALT, AST and ALP) were determined. Data obtained was analyzed using pad prism version 5.0. There were statistically significant (P&lt;0.05) reductions in the mean values of liver enzymes (ALT, AST, ALP) in groups II, III and IV in a dose dependent manner when compared to group VI. Similarly, the mean values of antioxidant (GPx, CAT and SOD) enzymes increased significantly significant (P&lt;0.05) in groups II, III and IV in a dose dependent manner when compared to group VI. No significant (P&gt;0.05) difference in the mean values of antioxidants and liver enzymes were recorded between groups II, III and IV and when compared to group V. Mean Packed Cell Volume (PCV), haemoglobin (Hb) concentration and Red Blood Cell (RBC) count significantly (P&lt;0.05) increased in groups II, III, and IV in a dose dependent manner. Similarly, PCV, Hb concentration and RBC count were significantly (P&lt;0.05) increased in groups II, III, and IV when compared with VI. No significant (P&gt;0.05) difference in the mean values of PCV, Hb and RBC were recorded in groups treated with kaempferol and group treated with amprolium. It was observed in this study that kaempferol improved the serum level of antioxidants and liver enzymes as well as and haematological parameters and also reduced the level of pathology in the caecum of broilers infected with Eimeria tenella in this study.

Alteration of the gut microbiota following SARS-CoV-2 infection correlates with disease severity in hamsters

ABSTRACT Mounting evidence suggests that the gut-to-lung axis is critical during respiratory viral infections. We herein hypothesized that disruption of gut homeostasis during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may associate with early disease outcomes. To address this question, we took advantage of the Syrian hamster model. Our data confirmed that this model recapitulates some hallmark features of the human disease in the lungs. We further showed that SARS-CoV-2 infection associated with mild intestinal inflammation, relative alteration in intestinal barrier property and liver inflammation and altered lipid metabolism. These changes occurred concomitantly with an alteration of the gut microbiota composition over the course of infection, notably characterized by a higher relative abundance of deleterious bacterial taxa such as Enterobacteriaceae and Desulfovibrionaceae. Conversely, several members of the Ruminococcaceae and Lachnospiraceae families, including bacteria known to produce the fermentative products short-chain fatty acids (SCFAs), had a reduced relative proportion compared to non-infected controls. Accordingly, infection led to a transient decrease in systemic SCFA amounts. SCFA supplementation during infection had no effect on clinical and inflammatory parameters. Lastly, a strong correlation between some gut microbiota taxa and clinical and inflammation indices of SARS-CoV-2 infection severity was evidenced. Collectively, alteration of the gut microbiota correlates with disease severity in hamsters making this experimental model valuable for the design of interventional, gut microbiota-targeted, approaches for the control of COVID-19. Abbreviations: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease 2019; SCFAs, short-chain fatty acids; dpi, day post-infection; RT-PCR, reverse transcription polymerase chain reaction; IL, interleukin. ACE2, angiotensin converting enzyme 2; TMPRSS2, transmembrane serine protease 2.

Disinfection of environmental objects against coccidia oocysts in broiler chickens

The purpose of the research is developing a method for disinfection of environmental objects against coccidia oocysts in broiler chickens.Materials and methods. At the VNIIP – FSC VIEV vivarium, a bioassay test was performed to experimentally infect 60 chickens aged 14 days which were divided into six equivalent groups of 10 birds each and kept isolated in cages. Chickens from the first, second and third groups were administered orally, using a micropipette, 1 ml of an Eimeria oocyst suspension treated with 4, 5 and 6% solutions of the combined eimeriocide agent. Chickens from the fourth group were administered 1 ml of Eimeria oocyst suspension treated with 4% phenol solution (base drug). Chickens from the fifth group received 1 ml of a buffered solution and were used as a noninfected control. Chickens from the sixth group received 1 ml of suspension containing 2000 oocysts/mL and were used as an infected control. The efficacy of disinfection with eimeriocide and the basic drug was determined based on the percentage of decrease in the recovery of Eimeria oocysts after being exposed to drugs as compared to chickens of the infected control. The efficacy of 5% eimeriocide against poultry coccidia oocysts in a production test was determined empirically with the set of oocysts on control sites as compared with the basic drug on a poultry farm in the Moscow Region.Results and discussion. The intense-effectiveness of 4% eimeriocide against coccidia oocysts was 99.31%, and the 5 and 6% combined agent showed 100% efficacy. The basic drug, 4% phenol showed 74.65% intense-effectiveness. The results obtained in the production test of 5% eimeriocide at a dose of 0.5 l per 1 m2 with a 2 hour-exposure indicate its high efficacy for disinfection against coccidia oocysts in broiler chickens. The intense-effectiveness was 97.25% versus 59.03% efficacy of the base drug, phenol.

Differential expression of maturation and activation markers on NK cells in patients with active and latent tuberculosis.

NK cells were recently suggested to be important for the initial control of M. tuberculosis infection. The phenotypes of the 3 main NK blood subsets, CD56bright , CD56dim , and CD56neg cells, were characterized by flow cytometry in a cohort of 81 prospectively enrolled subjects (21 untreated patients with active tuberculosis -aTB-, 35 latently TB infected -LTBI- subjects, and 25 non-infected controls), using 9 different mAbs added to whole blood. Compared to LTBI subjects, patients with aTB had lower proportions of total NK cells, lower proportions and numbers of CD56neg cells expressing early maturation markers (CD161, NKp30, NKp46), but higher density of NKp30 and NKp46 expression on both CD56neg and CD56dim subsets, associated with higher expression of granzymes A/B. They also had higher proportions of activated CD69pos cells within all 3 NK cell subsets and, the percentage of CD69pos CD56dim cells among CD69pos and/or NKG2Cpos NK cells was identified as a potential biomarker to discriminate aTB from LTBI. LTBI subjects were in contrast characterized by higher expression of late maturation markers (CD57, KIR molecules) on the CD56neg subset, by higher proportions of NKG2Cpos KIRpos CD56dim NK cells, and by higher in vitro IFN-γ production than patients with aTB. Thus, the in-depth phenotypic characterization of blood NK cell subsets provides new insights on possible functional modifications and the potential role of NK cells in the control of M. tuberculosis infection in humans.

APOE \u03b54 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study

Apolipoprotein E ε4 allele (APOE4) has been shown to associate with increased susceptibility to SARS-CoV-2 infection and COVID-19 mortality in some previous genetic studies, but information on the role of APOE4 on the underlying pathology and parallel clinical manifestations is scarce. Here we studied the genetic association between APOE and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that APOE4 carriership associates with severe COVID-19 in intensive care patients compared with non-infected population controls after matching for age, sex and cardiovascular disease status. Histopathological examination of brain autopsy material of 21 COVID-19 cases provided evidence that perivascular microhaemorrhages are more prevalent in APOE4 carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that APOE4 carriership independently associates with higher mental fatigue compared to non-carriers at six months after initial illness. In conclusion, the present data on Finns suggests that APOE4 is a risk factor for severe COVID-19 and post-COVID mental fatigue and provides the first indication that some of this effect could be mediated via increased cerebrovascular damage. Further studies in larger cohorts and animal models are warranted.

Effects of Salmonella enterica ser. Enteritidis and Heidelberg on host CD4+CD25+ regulatory T cell suppressive immune responses in chickens.

Poultry infected with Salmonella mount an immune response initially, however the immune responses eventually disappear leading the bird to be a carrier of Salmonella. The hypothesis of this study is that Salmonella infection induces T regulatory cell numbers and cytokine production and suppress host T cells locally in the gut to escape the host immune responses. An experiment was conducted to comparatively analyze the effect of S. enterica ser. Enteritidis (S. Enteritidis) and S. enterica ser. Heidelberg (S. Heidelberg) infection on CD4+CD25+ T regulatory cell properties in chickens. A total of 144 broiler chicks were randomly distributed into three experimental groups of non-infected control, S. Enteritidis infected and S. Heidelberg infected groups. Chickens were orally inoculated with PBS (control) or 5x106 CFU/mL of either S. Enteritidis or S. Heidelberg at 3 d of age. Each group was replicated in six pens with eight chickens per pen. Chickens infected with S. Enteritidis had 6.2, 5.4, and 3.8 log10 CFU/g, and chickens infected with S. Heidelberg had 7.1, 4.8, and 4.1 log10 CFU/g Salmonella in the cecal contents at 4, 11, and 32 dpi, respectively. Both S. Enteritidis and S. Heidelberg were recovered from the liver and spleen 4 dpi. At 4, 11, and 32 dpi, chickens infected with S. Enteritidis and S. Heidelberg had increased CD4+CD25+ cell numbers as well as IL-10 mRNA transcription of CD4+CD25+ cells compared to that in the control group. CD4+CD25+ cells from S. Enteritidis- and S. Heidelberg-infected chickens and restimulated with 1 μg antigen in vitro, had higher (P < 0.05) IL-10 mRNA transcription than the CD4+CD25+ cells from the non-infected controls Though at 4dpi, chickens infected with S. Enteritidis and S. Heidelberg had a significant (P < 0.05) increase in CD4+CD25- IL-2, IL-1β, and IFNγ mRNA transcription, the CD4+CD25- IL-2, IL-1β, and IFNγ mRNA transcription, were comparable to that in the control group at 11 and 32dpi identifying that the host inflammatory response against Salmonella disappears at 11 dpi. It can be concluded that S. Enteritidis and S. Heidelberg infection at 3 d of age induces a persistent infection through inducing CD4+CD25+ cells and altering the IL-10 mRNA transcription of CD4+CD25+ cell numbers and cytokine production in chickens between 3 to 32 dpi allowing chickens to become asymptomatic carriers of Salmonella after 18 dpi.

Evaluation of immune responses and oxidative stress in donkeys: Immunological studies provoked by Parascaris equorum infection

This study aimed to assess the effects of Parascaris equorum (P. equorum) in infected donkeys through evaluation the oxidative stress and different gene parameters in infected tissues. Fifty donkeys were examined in Giza Zoo abattoir from the period of January to March 2021. Blood and sera samples were collected from each examined donkey. P. equorum were subjected for identification through scanning electron microscope study and the infected tissues were subjected into gene expression analysis using two genes; interleukin 1β (IL1- β); and pro-inflammatory cytokines (TNF-α) with assessment of the antioxidant and free radicals released from the animals during the infection. Eighteen donkeys were positive for P. equorum adult or larvae by postmortem examination of the intestine and abdomen with prevalence rate of 36 %. The examined infected donkeys with P. equorum showed significantly higher of Total antioxidant capacity (TAC) levels and the serum malondialdehyde (MDA) 2.45 ± 0.53 than that in non-infected control donkeys. The levels of AST enzyme were 278.54 ± 0.45 while ALT enzyme was 14.97 ± 0.87 which was significantly higher than that of control negative donkeys. The infected donkeys with P. equorum showed significantly upregulation of the TNF-α and IL-1β which classify according to number of collected worms. The P. equorum infected donkeys exerted at least 100 eggs of parasite in feces. The fecal egg count was marked decreased after treatment with moxidectin. Moxidectin is considered a novel active ingredient that has a marvelous result with high persistency and protection for long time, in addition to, broad spectrum activity and low or no resistance. We recommend the periodical deworming with different molecules as more economic and lifesaving over a single treatment every 12 months parallel with parasitic testing.