Species differences and human relevance of the toxicity of 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors and a new approach method in vitro for investigation.

The mode of action (MoA) of the 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor herbicides in mammals is well described and is generally accepted to be due to a build-up of excess systemic tyrosine which is associated with the range of adverse effects reported in laboratory animals. What is less well accepted is the basis for the marked difference in the effects of HPPD inhibitors that has been observed across experimental species and humans, where some species show significant toxicities whereas in other species exposure causes few effects. The activity of the catabolic enzyme tyrosine aminotransferase (TAT) varies across species including humans and it is hypothesized that this primarily accounts for the different levels of tyrosinemia observed between species and leads to the subsequent differences in toxicity. The previously reported activities of TAT in different species showed large variation, were inconsistent, have methodological uncertainties and could lead to a reasonable challenge to the scientific basis for the species difference in response. To provide clarity, a new method was developed for the simultaneous and systematic measurement of TAT in vitro using robust methodologies in a range of mammalian species including human. The results obtained showed general correlation between high TAT activity and low in vivo toxicity when using a model based on hepatic cytosol and a very convincing correlation when using a primary hepatocyte model. These data fully support the role of TAT in explaining the species differences in toxicity. Moreover, this information should give greater confidence in selecting the most appropriate animal model (the mouse) for human health risk assessment and for key classification and labeling decision-making.

[ACTIV SARS-CoV-2 registry (Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients). Assessment of impact of combined original comorbid diseases in patients with COVID-19 on the prognosis].

AIM: Study the impact of various combinations of comorbid original diseases in patients infected with COVID-19 later on the disease progression and outcomes of the new coronavirus infection. MATERIALS AND METHODS: The ACTIV registry was created on the Eurasian Association of Therapists initiative. 5,808 patients have been included in the registry: men and women with COVID-19 treated at hospital or at home. CLINICALTRIALS: gov ID NCT04492384. RESULTS: Most patients with COVID-19 have original comorbid diseases (oCDs). Polymorbidity assessed by way of simple counting of oCDs is an independent factor in negative outcomes of COVID-19. Search for most frequent combinations of 2, 3 and 4 oCDs has revealed absolute domination of cardiovascular diseases (all possible variants). The most unfavorable combination of 2 oCDs includes atrial hypertension (AH) and chronic heart failure (CHF). The most unfavorable combination of 3 oCDs includes AH, coronary heart disease (CHD) and CHF; the worst combination of 4 oCDs includes AH, CHD, CHF and diabetes mellitus. Such combinations increased the risk of lethal outcomes 3.963, 4.082 and 4.215 times respectively. CONCLUSION: Polymorbidity determined by way of simple counting of diseases may be estimated as a factor in the lethal outcome risk in the acute phase of COVID-19 in real practice. Most frequent combinations of 2, 3 and 4 diseases in patients with COVID-19 primarily include cardiovascular diseases (AH, CHD and CHF), diabetes mellitus and obesity. Combinations of such diseases increase the COVID-19 lethal outcome risk.

Paraquat pharmacokinetics in primates and extrapolation to humans.

By extending our Paraquat (PQ) work to include primates we have implemented a modelling and simulation strategy that has enabled PQ pharmacokinetic data to be integrated into a single physiologically based pharmacokinetic (PBPK) model that enables more confident extrapolation to humans. Because available data suggested there might be differences in PQ kinetics between primates and non-primates, a radiolabelled study was conducted to characterize pharmacokinetics and excretion in Cynomolgus monkeys. Following single intravenous doses of 0.01 or 0.1 mg paraquat dichloride/kg bw, plasma PQ concentration-time profiles were dose-proportional. Excretion up to 48 h (predominantly urinary) was 82.9%, with ca. 10% remaining unexcreted. In vitro blood binding was similar across Cynomolgus monkeys, humans and rat. Our PBPK model for the rat, mouse and dog, employing a single set of PQ-specific parameters, was scaled to Cynomolgus monkeys and well represented the measured plasma concentration-time profiles over 14 days. Addition of a cartilage compartment to the model better captured the percent remaining in the monkeys at 48 h, whilst having negligible effect on model predictions for the other species. The PBPK model performed well for all four species, demonstrating there is little difference in PQ kinetics between non-primates and primates enabling a more confident extrapolation to humans. Scaling of the PBPK model to humans, with addition of a human-specific dermal submodel based on in vitro human dermal absorption data, provides a valuable tool that could be employed in defining internal dosimetry to complement human health risk assessments.

Integration of paraquat pharmacokinetic data across species using PBPK modelling.

Paraquat dichloride (PQ) is a non-selective herbicide which has been the subject of numerous toxicology studies over more than 50 years. This paper describes the development of a physiologically-based pharmacokinetic (PBPK) model of PQ kinetics for the rat, mouse and dog, firstly to aid the interpretation of studies in which no kinetic measurements were made, and secondly to enable the future extension of the model to humans. Existing pharmacokinetic data were used to develop a model for the rat and mouse. Simulations with this preliminary model were then used to identify key data gaps and to design a new blood binding study to reduce uncertainty in critical aspects of the model. The new data provided evidence to support the model structure, and its predictive performance was then assessed against dog and rat datasets not used in model development. The PQ-specific model parameters are the same for all three species, with only the physiological parameters varying between species. This consistency across species provides a strong basis for extrapolation to other species, as demonstrated here for the dog. The model enables a wide range of PQ data to be linked together to provide a broad understanding of PQ pharmacokinetics in rodents and the dog, showing that the key aspects of PQ kinetics in these species are understood and adequately encapsulated within the model.

Analysis of influence of background therapy for comorbidities in the period before infection on the risk of the lethal COVID outcome. Data from the international ACTIV SARS-CoV-2 registry («Analysis of chronic non-infectious diseases dynamics after COVID-19 infection in adult patients SARS-CoV-2¼).

Aim      To study the effect of regular drug therapy for cardiovascular and other diseases preceding the COVID-19 infection on severity and outcome of COVID-19 based on data of the ACTIVE (Analysis of dynamics of Comorbidities in paTIents who surVived SARS-CoV-2 infEction) registry.Material and methods  The ACTIVE registry was created at the initiative of the Eurasian Association of Therapists. The registry includes 5 808 male and female patients diagnosed with COVID-19 treated in a hospital or at home with a due protection of patients' privacy (data of nasal and throat smears; antibody titer; typical CT imaging features). The register territory included 7 countries: the Russian Federation, the Republic of Armenia, the Republic of Belarus, the Republic of Kazakhstan, the Kyrgyz Republic, the Republic of Moldova, and the Republic of Uzbekistan. The registry design: a closed, multicenter registry with two nonoverlapping arms (outpatient arm and in-patient arm). The registry scheduled 6 visits, 3 in-person visits during the acute period and 3 virtual visits (telephone calls) at 3, 6, and 12 mos. Patient enrollment started on June 29, 2020 and was completed on October 29, 2020. The registry completion is scheduled for October 29, 2022. The registry ID: ClinicalTrials.gov: NCT04492384. In this fragment of the study of registry data, the work group analyzed the effect of therapy for comorbidities at baseline on severity and outcomes of the novel coronavirus infection. The study population included only the patients who took their medicines on a regular basis while the comparison population consisted of noncompliant patients (irregular drug intake or not taking drugs at all despite indications for the treatment).Results The analysis of the ACTIVE registry database included 5808 patients. The vast majority of patients with COVID-19 had comorbidities with prevalence of cardiovascular diseases. Medicines used for the treatment of COVID-19 comorbidities influenced the course of the infectious disease in different ways. A lower risk of fatal outcome was associated with the statin treatment in patients with ischemic heart disease (IHD); with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists and with beta-blockers in patients with IHD, arterial hypertension, chronic heart failure (CHF), and atrial fibrillation; with oral anticoagulants (OAC), primarily direct OAC, clopidogrel/prasugrel/ticagrelor in patients with IHD; with oral antihyperglycemic therapy in patients with type 2 diabetes mellitus (DM); and with long-acting insulins in patients with type 1 DM. A higher risk of fatal outcome was associated with the spironolactone treatment in patients with CHF and with inhaled corticosteroids (iCS) in patients with chronic obstructive pulmonary disease (COPD).Conclusion      In the epoch of COVID-19 pandemic, a lower risk of severe course of the coronavirus infection was observed for patients with chronic noninfectious comorbidities highly compliant with the base treatment of the comorbidity.

[International register "Analysis of Chronic Non-infectious Diseases Dynamics After COVID-19 Infection in Adult Patients (ACTIV SARS-CoV-2)"].

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Dietary administration of diquat for 13 weeks does not result in a loss of dopaminergic neurons in the substantia nigra of C57BL/6J mice.

Male and female C57BL/6J mice were administered diquat dibromide (DQ∙Br2) in their diets at concentrations of 0 (control), 12.5 and 62.5 ppm for 13 weeks to assess the potential effects of DQ on the nigrostriatal dopaminergic system. Achieved dose levels at 62.5 ppm were 6.4 and 7.6 mg DQ (ion)/kg bw/day for males and females, respectively. A separate group of mice was administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) ip as a positive control. The comparative effects of DQ and MPTP on the substantia nigra pars compacta (SNpc) and/or striatum were assessed using neurochemical, neuropathological and stereological endpoints. Morphological and stereological assessments were performed by investigators who were "blinded" to dose group. DQ had no effect on striatal dopamine concentration or dopamine turnover. There was no evidence of neuronal degeneration, astrocytic or microglial activation, or a reduction in the number of tyrosine hydroxylase positive (TH(+)) neurons in the SNpc or neuronal processes in the striatum of DQ-treated mice. These results are consistent with the rapid clearance of DQ from the brain following a single dose of radiolabeled DQ. In contrast, MPTP-treated mice exhibited decreased striatal dopamine concentration, reduced numbers of TH(+) neurons in the SNpc, and neuropathological changes, including neuronal necrosis, as well as astrocytic and microglial activation in the striatum and SNpc.

Specific light uptake rates can enhance astaxanthin productivity in Haematococcus lacustris.

Lumostatic operation was applied for efficient astaxanthin production in autotrophic Haematococcus lacustris cultures using 0.4-L bubble column photobioreactors. The lumostatic operation in this study was performed with three different specific light uptake rates (q(e)) based on cell concentration, cell projection area, and fresh weight as one-, two- and three-dimensional characteristics values, respectively. The q(e) value from the cell concentration (q(e1D)) obtained was 13.5 × 10⁻8 µE cell⁻¹ s⁻¹, and the maximum astaxanthin concentration was increased to 150 % compared to that of a control with constant light intensity. The other optimum q e values by cell projection area (q(e2D)) and fresh weight (q( e3D)) were determined to be 195 µE m⁻² s⁻¹ and 10.5 µE g⁻¹ s⁻¹ for astaxanthin production, respectively. The maximum astaxanthin production from the lumostatic cultures using the parameters controlled by cell projection area (2D) and fresh weight (3D) also increased by 36 and 22% over that of the controls, respectively. When comparing the optimal q e values among the three different types, the lumostatic cultures using q(e) based on fresh weight showed the highest astaxanthin productivity (22.8 mg L⁻¹ day⁻¹), which was a higher level than previously reported. The lumostatic operations reported here demonstrated that more efficient and effective astaxanthin production was obtained by H. lacustris than providing a constant light intensity, regardless of which parameter is used to calculate the specific light uptake rate.

Development of a floating photobioreactor with internal partitions for efficient utilization of ocean wave into improved mass transfer and algal culture mixing.

Culturing microalgae in the ocean has potentials that may reduce the production cost and provide an option for an economic biofuel production from microalgae. The ocean holds great potentials for mass microalgal cultivation with its high specific heat, mixing energy from waves, and large cultivable area. Suitable photobioreactors (PBRs) that are capable of integrating marine energy into the culture systems need to be developed for the successful ocean cultivation. In this study, prototype floating PBRs were designed and constructed using transparent low-density polyethylene film for microalgal culture in the ocean. To improve the mixing efficiency, various types of internal partitions were introduced within PBRs. Three different types of internal partitions were evaluated for their effects on the mixing efficiency in terms of mass transfer (k(L)a) and mixing time in the PBRs. The partition type with the best mixing efficiency was selected, and the number of partitions was varied from one to three for investigation of its effect on mixing efficiency. When the number of partitions is increased, mass transfer increased in proportion to the number of partitions. However, mixing time was not directly related to the number of partitions. When a green microalga, Tetraselmis sp. was cultivated using PBRs with the selected partition under semi-continuous mode in the ocean, biomass and fatty acid productivities in the PBRs were increased by up to 50 % and 44% at high initial cell density, respectively, compared to non-partitioned ones. The results of internally partitioned PBRs demonstrated potentials for culturing microalgae by efficiently utilizing ocean wave energy into culture mixing in the ocean.

Dietary administration of paraquat for 13 weeks does not result in a loss of dopaminergic neurons in the substantia nigra of C57BL/6J mice.

Several investigations have reported that mice administered paraquat dichloride (PQ·Cl2) by intraperitoneal injection exhibit a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). In this study, male and female C57BL/6J mice were administered PQ·Cl2 in the diet at concentrations of 0 (control), 10, and 50ppm for a duration of 13weeks. A separate group of mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) during week 12 as positive controls to produce a loss of dopaminergic neurons in the SNpc. The comparative effects of PQ and MPTP on the SNpc and/or striatum were assessed using neurochemical, neuropathological, and stereological endpoints. Morphological and stereological assessments were performed by investigators 'blinded' to the origin of the tissue. Neither dose of PQ·Cl2 (10 or 50 ppm in the diet) caused a loss of striatal dopamine or dopamine metabolite concentrations in the brains of mice. Pathological assessments of the SNpc and striatum showed no evidence of neuronal degeneration or astrocytic/microglial activation. Furthermore, the number of tyrosine hydroxylase-positive (TH(+)) neurons in the SNpc was not reduced in PQ-treated mice. In contrast, MPTP caused a decrease in striatal dopamine concentration, a reduction in TH(+) neurons in the SNpc, and significant pathological changes including astrocytic and microglial activation in the striatum and SNpc. The MPTP-induced effects were greater in males than in females. It is concluded that 13weeks of continuous dietary exposure of C57BL/6J mice to 50ppm PQ·Cl2 (equivalent to 10.2 and 15.6mg PQ ion/kg body weight/day for males and females, respectively) does not result in the loss of, or damage to, dopaminergic neurons in the SNpc.

Complete genome sequence of Levilactobacillus brevis NSMJ23, makgeolli isolate with antimicrobial activity.

We report the complete genome sequence of Levilactobacillus brevis NSMJ23 with probiotic properties. The final genome assembly consisted of a 2,389,998-bp chromosome and seven plasmids with 45.59% GC content, which comprised 2,624 genes including 2,457 protein coding sequences.

Development of machine learning models for the surveillance of colon surgical site infections.

BACKGROUND: Conventional surgical site infection (SSI) surveillance is labour-intensive. We aimed to develop machine learning (ML) models for the surveillance of SSIs for colon surgery and to assess whether the ML could improve surveillance process efficiency. METHODS: This study included cases who underwent colon surgery at a tertiary center between 2013 and 2014. Logistic regression and four ML algorithms including random forest (RF), gradient boosting (GB), and neural networks (NNs) with or without recursive feature elimination (RFE) were first trained on the entire cohort, and then re-trained on cases selected based on a previous rule-based algorithm. We assessed model performance based on the area under the curve (AUC), sensitivity, and positive predictive value (PPV). The estimated proportion of reduction in workload for chart review based on the ML models was evaluated and compared with the conventional method. RESULTS: At a sensitivity of 95%, the NN with RFE using 29 variables had the best performance with an AUC of 0.963 and PPV of 21.1%. When combining both the rule-based algorithm and ML algorithms, the NN with RFE using 19 variables had a higher PPV (28.9%) than with the ML algorithm alone, which could decrease the number of cases requiring chart review by 83.9% compared with the conventional method. CONCLUSION: We demonstrated that ML can improve the efficiency of SSI surveillance for colon surgery by decreasing the burden of chart review while providing high sensitivity. In particular, the hybrid approach of ML with a rule-based algorithm showed the best performance in terms of PPV.

G16R single nucleotide polymorphism but not haplotypes of the ß(2)-adrenergic receptor gene alters cardiac output in humans.

Variation in genes encoding the ß(2)-adrenergic receptor (ADRB2) and angiotensin-converting enzyme (ACE) may influence Q (cardiac output). The 46G>A (G16R) SNP (single nucleotide polymorphism) has been associated with ß(2)-mediated vasodilation, but the effect of ADRB2 haplotypes on Q has not been studied. Five SNPs within ADRB2 (46G>A, 79C>G, 491C>T, 523C>A and 1053G>C by a pairwise tagging principle) and the I/D (insertion/deletion) polymorphism in ACE were genotyped in 143 subjects. Cardiovascular variables were evaluated by the Model flow method at rest and during incremental cycling exercise. Only the G16R polymorphism was associated with Q. In carriers of the Arg(16) allele, Q(rest) (resting Q) was 0.4 [95% CI (confidence interval), 0.0-0.7] l/min lower than in G16G homozygotes (P=0.048). During exercise, the increase in Q was by 4.7 (95% CI, 4.3-5.2) l/min per litre increase in pulmonary Vo(2) (oxygen uptake) in G16G subjects, but the increase was 0.5 (0.0-0.9) l/min lower in Arg16 carriers (P=0.035). A similar effect size was observed for the Arg16 haplotypes ACCCG and ACCCC. No interaction was found between ADRB2 and ACE polymorphisms. During exercise, the increase in Q was 0.5 (CI, 0.0 -1.0) l/min greater in ACE I/I carriers compared with I/D and D/D subjects (P=0.054). In conclusion, the ADRB2 Arg16 allele in humans is associated with a lower Q both at rest and during exercise, overriding the effects of haplotypes.

A 24-hour ambulatory ecg monitoring in assessment of qt interval duration and dispersion in rowers with physiological myocardial hypertrophy.

UNLABELLED: Myocardial hypertrophy (MH) due to cardiac pathology is characterized by an increase in QT interval duration and dispersion, while the findings for exercise-induced myocardial hypertrophy are contradictory. The majority of published research findings have not explored this relationship, but there have only been a few conducted studies using 24-hour ECG monitoring. The aim of the study was to determine the QT interval duration and dispersion in short-term and 24-hour ECG in endurance athletes with myocardial hypertrophy and without it. METHODS: A total of 26 well-trained rowers underwent a resting 12-lead ECG, 24-hour ECG monitoring and echocardiography. RESULTS: Athletes with MH (n = 7) at rest did not show any increase in QTc interval duration and dispersion, or mean and maximal QTc duration in Holter monitoring compared to athletes without MH (n = 19). Left ventricular mass was not significantly correlated with any QTc characteristics. Furthermore, athletes with MH had significantly longer mean QT (P = 0.01) and maximal QT (P = 0.018) intervals in Holter monitoring and higher 24-hour heart rate variability indexes due to stronger vagal effects. CONCLUSIONS: The present study demonstrated that athlete's heart syndrome with myocardial hypertrophy as a benign phenomenon does not lead to an increase in QT interval duration, or increases in maximal and mean duration in a 24-hour ECG. An increase in QT interval duration in athletes may have an autonomic nature.

Mychonastes sp. 246 Suppresses Human Pancreatic Cancer Cell Growth via IGFBP3-PI3K-mTOR Signaling.

Previously, we confirmed that Mychonastes sp. 246 methanolic extract (ME) markedly reduced the viability of BxPC-3 human pancreatic cancer cells. However, the underlying mechanism ME remained unclear. Hence, we attempted to elucidate the anticancer effect of ME on BxPC-3 human pancreatic cancer cells. First, we investigated the components of ME and their cytotoxicity in normal cells. Then, we confirmed the G1 phase arrest mediated growth inhibitory effect of ME using a cell counting assay and cell cycle analysis. Moreover, we found that the migration-inhibitory effect of ME using a Transwell migration assay. Through RNA sequencing, Gene Ontology-based network analysis, and western blotting, we explored the intracellular mechanisms of ME in BxPC-3 cells. ME modulated the intracellular energy metabolism-related pathway by altering the mRNA levels of IGFBP3 and PPARGC1A in BxPC-3 cells and reduced PI3K and mTOR phosphorylation by upregulating IGFBP3 and 4E-BP1 expression. Finally, we verified that ME reduced the growth of three-dimensional (3D) pancreatic cancer spheroids. Our study demonstrates that ME suppresses pancreatic cancer proliferation through the IGFBP3-PI3K-mTOR signaling pathway. This is the first study on the anticancer effect of the ME against pancreatic cancer, suggesting therapeutic possibilities and the underlying mechanism of ME action.

Improvement of Lutein and Zeaxanthin Production in Mychonastes sp. 247 by Optimizing Light Intensity and Culture Salinity Conditions.

In this study, we sought to improve lutein and zeaxanthin production in Mychonastes sp. 247 and investigated the effect of environmental factors on lutein and zeaxanthin productivity in Mychonastes sp. The basic medium selection and N:P ratio were adjusted to maximize cell growth in one-stage culture, and lutein and zeaxanthin production conditions were optimized using a central composite design for two-stage culture. The maximum lutein production was observed at a light intensity of 60 µE/m2/s and salinity of 0.49%, and the maximum zeaxanthin production was observed at a light intensity of 532 µE/m2/s and salinity of 0.78%. Lutein and zeaxanthin production in the optimized medium increased by up to 2 and 2.6 folds, respectively, compared to that in the basic medium. Based on these results, we concluded that the optimal conditions for lutein and zeaxanthin production are different and that optimization of light intensity and culture salinity conditions may help increase carotenoid production. This study presents a useful and potential strategy for optimizing microalgal culture conditions to improve the productivity of lutein and zeaxanthin, which has applications in the functional food field.

Impact of Polymorphism in the ß2-Receptor Gene on the Metabolic Response to Epinephrine After Repeated Hypoglycemia.

The ß2-receptor mediates the metabolic response to epinephrine. This study investigates the impact of the ß2-receptor gene (ADRB2) polymorphism Gly16Arg on the metabolic response to epinephrine before and after repetitive hypoglycemia. Twenty-five healthy men selected according to ADRB2 genotype being homozygous for either Gly16 (GG) (n = 12) or Arg16 (AA) (n = 13) participated in 4 trial days (D1-4): D1pre and D4post with epinephrine 0.06 µg kg-1 ⋅ min-1 infusion and D2hypo1-2 and D3hypo3 with three periods of hypoglycemia by an insulin-glucose clamp. At D1pre, the insulin (mean ± SEM of area under the curve 44 ± 8 vs. 93 ± 13 pmol ⋅ L-1 h; P = 0.0051), glycerol (79 ± 12 vs. 115 ± 14 µmol ⋅ L-1 h; P = 0.041), and free fatty acid (724 ± 96 vs. 1,113 ± 140 µmol ⋅ L-1 h; P = 0.033) responses to epinephrine were decreased in AA participants compared with GG participants but without a difference in glucose response. There were no differences in response to epinephrine between genotype groups after repetitive hypoglycemia at D4post. The metabolic substrate response to epinephrine was decreased in AA participants compared with GG participants but without a difference between genotype groups after repetitive hypoglycemia. ARTICLE HIGHLIGHTS: This study investigates the impact of the ß2-receptor gene (ADRB2) polymorphism Gly16Arg on the metabolic response to epinephrine before and after repetitive hypoglycemia. Healthy men homozygous for either Gly16 (n = 12) or Arg16 (n = 13) participated in the study. Healthy people with the Gly16 genotype have increased metabolic response to epinephrine compared with the Arg16 genotype but without a difference between genotypes after repetitive hypoglycemia.

Effect of Dietary Chlorella vulgaris or Tetradesmus obliquus on Laying Performance and Intestinal Immune Cell Parameters.

A feeding trial was conducted to investigate the effect of dietary supplementation of Chlorella vulgaris (CV) or Tetradesmus obliquus (TO) on laying performance, egg quality, and gut health indicators of laying hens. A total of 144 Hy-Line Brown laying hens aged 21 weeks were randomly assigned to one of three dietary treatments with eight replicates of six hens. Dietary treatments were as follows: CON, basal diet; CV, basal diet + 5 g C. vulgaris/kg of diet; TO, basal diet + 5 g T. obliquus/kg of diet. The results showed that diets supplemented with CV or TO had insignificant effects on laying performance, egg quality (i.e., Haugh unit and eggshell strength and thickness), jejunal histology, cecal short-chain fatty acids, and antioxidant/immune markers in ileal mucosa samples of laying hens. Compared with the control group, the egg yolk color score was higher (p < 0.05) in laying hens fed on diets containing CV and TO, although the former was a more intense yellow than the latter. Small intestinal lamina propria cells were isolated using flow cytometry to examine the percentages of immune cell subpopulations. Dietary microalgae did not affect B cells or monocytes/macrophages but altered the percentage of CD4+ T cells and CD8- TCR γδ T cells. Collectively, diets supplemented with C. vulgaris or T. obliquus can improve egg yolk color and would modulate host immune development and competence in laying hens.

Intestinal Immune Cell Populations, Barrier Function, and Microbiomes in Broilers Fed a Diet Supplemented with Chlorella vulgaris.

This study aimed to evaluate the effects of dietary Chlorella vulgaris (CV) on the distribution of immune cells, intestinal morphology, intestinal barrier function, antioxidant markers, and the cecal microbiome in 10-day-old broiler chickens. A total of 120 day-old Ross 308 male broiler chicks were assigned to two dietary treatments using a randomized complete block design, with body weight as the blocking factor. Birds fed a diet containing CV showed an increase in CD4+ T cells (p < 0.05) compared to those fed the control diet. The relative mRNA expression of intestinal epithelial barrier function-related markers (occludin and avian ß-defensin 5) was elevated (p < 0.05) in the CV-supplemented group compared to the control group. The alpha diversity indices (Chao1 and observed features) of the cecal microbiome in 10-day-old birds increased (p < 0.05), indicating higher richness within the cecal bacterial community. In the microbiome analysis, enriched genera abundance of Clostridium ASF356 and Coriobacteriaceae CHKCI002 was observed in birds fed the diet containing CV compared to those fed the control diet. Taken together, dietary CV supplementation might alter intestinal barrier function, immunity, and microbiomes in 10-day-old broiler chickens.

[The impact of BMI on the course of the acute SARS-COV-2 infection and the risks that emerge during the first year after the hospital discharge. Subanalysis evidence of the AKTIV and AKTIV 2 registries].

BACKGROUND: There is enough evidence of the negative impact of excess weight on the formation and progression of res piratory pathology. Given the continuing SARS-CoV-2 pandemic, it is relevant to determine the relationship between body mass index (BMI) and the clinical features of the novel coronavirus infection (NCI). AIM: To study the effect of BMI on the course of the acute SARS-COV-2 infection and the post-covid period. MATERIALS AND METHODS: AKTIV and AKTIV 2 are multicenter non-interventional real-world registers. The АКТИВ registry (n=6396) includes non-overlapping outpatient and inpatient arms with 6 visits in each. The АКТИВ 2 registry (n=2968) collected  the  data  of  hospitalized  patients  and  included  3  visits.  All  subjects  were  divided  into  3  groups:  not  overweight  (n=2139), overweight (n=2931) and obese (n=2666). RESULTS: A higher BMI was significantly associated with a more severe course of the infection in the form of acute kidney injury (p=0.018), cytokine storm (p<0.001), serum C-reactive protein over 100 mg/l (p<0.001), and the need for targeted therapy (p<0.001) in the hospitalized patients. Obesity increased the odds of myocarditis by 1,84 times (95% confidence interval [CI]: 1,13-3,00) and the need for anticytokine therapy by 1,7 times (95% CI: 1,30-2,30).The  patients  with  the  1st  and  2nd  degree  obesity,  undergoing  the  inpatient  treatment,  tended  to  have  a  higher  probability  of  a  mortality  rate.  While  in  case  of  morbid  obesity  patients  this  tendency  is  the  most  significant  (odds  ratio  -  1,78; 95% CI: 1,13-2,70). At the same time, the patients whose chronical diseases first appeared after the convalescence period, and those who had certain complaints missing before SARS-CoV-2 infection, more often had BMI of more than 30 kg/m2 (p<0,001).Additionally, the odds of death increased by 2,23 times (95% CI: 1,05-4,72) within 3 months after recovery in obese people over the age of 60 yearsCONCLUSION.  Overweight  and/or  obesity  is  a  significant  risk  factor  for severe  course  of  the  new  coronavirus  infection  and  the associated cardiovascular and kidney damage Overweight people and patients with the 1st and 2nd degree obesity tend to have a high risk of death of SARS-CoV-2 infection in both acute and post-covid periods. On top of that, in case of morbid obesity patients this tendency is statistically significant. Normalization of body weight is a strategic objective of modern medicine and can contribute to prevention of respiratory conditions, severe course and complications of the new coronavirus infection.