Modelling effects of phytobiotic administration on coherent responses to Salmonella infection in laying hens

Practice of layer poultry farming and commercial egg production relies on the optimal use and improvement of the welfare and genetically determined functional abilities of laying hens, their efficient intake of feed and its components, adaptation to housing conditions and resistance to infectious diseases including salmonellosis. Previous studies were focussed on relationships of chicken performance and resistance with the expression profiles of individual genes involved in metabolic processes and immune system, or with genetic markers that can be closely associated with these processes in chickens. In this study, mathematical models of coherent changes in laying hens were developed for the expression of eight genes involved in immunity and metabolism, on the one hand, and biochemical and immunological blood parameters, on the other hand, in response to Salmonella infection and administration of a phytobiotic Intebio. The proposed modelling approach can be a further basis for an in-depth research of the relationship between the gene expression, functional state and welfare of poultry, impact of pathogenic microorganisms and use of immunomodulatory drugs

Examination of the expression of immunity genes and bacterial profiles in the caecum of growing chickens infected with Salmonella Enteritidis and fed a phytobiotic

This study was performed to investigate the differential expression of eight immunity genes and the bacterial profiles in the caecum of growing chickens challenged with Salmonella enterica serovar Enteritidis (SE) at 1 and 23 days post inoculation (dpi) in response to SE infection at 19 days of age and administration of the phytobiotic Intebio. Following infection, the genes CASP6 and IRF7 were upregulated by greater than twofold. Chicks fed Intebio showed at 1 dpi upregulation of AvBD10, IL6, IL8L2, CASP6 and IRF7. At 23 dpi, expression of AvBD11, IL6, IL8L2, CASP6 and IRF7 lowered in the experiment subgroups as compared with the control. Examination of the caecal contents at 1 dpi demonstrated a significant decrease in the microbial biodiversity in the infected subgroup fed normal diet. Bacterial content of Lactobacillus and Bacillus declined, while that of Enterobacteriaceae rose. In the infected subgroup fed Intebio, a pronounced change in composition of the microflora was not observed. In the early infection stages, the phytobiotic seemed to promote response to infection. Subsequently, an earlier suppression of the inflammatory reaction took place in chickens fed Intebio. Thus, use of Intebio as a drug with phytobiotic activity in chickens, including those infected with Salmonella, proved to be promising

Genomic features of resistant <i>Klebsiella pneumonia</i>, isolated from the bloodstream and cerebrospinal fluid of pediatric hospital patients

Introduction. Carbapenemase-producing Klebsiella pneumoniae (CP-Kp), which are international high-risk clones, have become a problem of utmost importance. CP-Kps, adapting to the hospital environment, evolve into convergent pathotypes. Such variants combine traits of two genetic lineages: multidrug resistant (MDR) and hypervirulent. The pathotypes, along with MDR K. pneumoniae, pose an exceptional threat to young patients during systemic infection. The objective of this study is the detailed molecular genetic analysis of MDR isolates of K. pneumoniae detected during the monitoring of resistant Gram-negative bacteria at the National Medical Research Center for Children’s Health in 2014–2021. Materials and methods. Whole-genome sequencing with a subsequent bioinformatics analysis of eight MDR isolates from the bloodstream and cerebrospinal fluid. Results. MDR isolates belonged to 4 sublineages (SL): SL307, SL395, SL29 and SL1198. In the genomes of 6 pangrug-resistant (PDR) isolates, genes associated with resistance to all categories of antibiotics recommended for Enterobacteriaceae therapy were identified. Plasmids were present in all genomes. In 6 isolates, plasmids contained heavy metal ion resistance operons in addition to antibiotic resistance genes. Prophages within the plasmids were also involved in the transfer of resistance genes. The ST395 isolate from the cerebrospinal fluid belonged to the convergent pathotype in terms of resistance and virulence. Comparison of genomes within SLs revealed recombination events in the K- and O-locus regions and the Yersiniabactin operon. Conclusion. Thus, in a sample of resistant K. pneumoniae isolated from bloodstream and cerebrospinal fluid, 6 PDR isolates were detected, one of which belongs to the convergent pathotype ST395

Effects of essential oils-based supplement and Salmonella infection on gene expression, blood parameters, cecal microbiome and egg production in laying hens

Simple Summary Salmonellosis is one of the most severe zoonotic diseases transmitted to humans through animal products (especially poultry meat and eggs). Essential oils (EOs)-based feed additives in poultry nutrition are a possible alternative replacement of antimicrobials to fight this infection. In the present study on laying hens, we tested a phytobiotic, Intebio®, and elucidated formation of immune response and changes in cecal microbiocenosis and biochemical/immunological variables in blood caused by Salmonella. Changes in differential gene expression were observed at both one and seven days post-inoculation in the hens’ intestines, revealing similarities with known mammalian/human tissue-specific expression. The results of this study suggest that the challenge of birds with Salmonella had a negative effect, while phytobiotic intake had a positive effect on the status of their gastrointestinal microbiome, their level of metabolism, and their performance. Abstract One of the main roles in poultry resistance to infections caused by Salmonella is attributed to host immunity and intestinal microbiota. We conducted an experiment that involved challenging Lohmann White laying hens with Salmonella Enteritidis (SE), feeding them a diet supplemented with an EOs-based phytobiotic Intebio®. At 1 and 7 days post-inoculation, the expression profiles of eight genes related to immunity, transport of nutrients in the intestine, and metabolism were examined. Cecal microbiome composition and blood biochemical/immunological indices were also explored and egg production traits recorded. As a result, the SE challenge of laying hens and Intebio® administration had either a suppressive or activating effect on the expression level of the studied genes (e.g., IL6 and BPIFB3), the latter echoing mammalian/human tissue-specific expression. There were also effects of the pathogen challenge and phytobiotic intake on the cecal microbiome profiles and blood biochemical/immunological parameters, including those reflecting the activity of the birds’ immune systems (e.g., serum bactericidal activity, β-lysine content, and immunoglobulin levels). Significant differences between control and experimental subgroups in egg performance traits (i.e., egg weight/number/mass) were also found. The phytobiotic administration suggested a positive effect on the welfare and productivity of poultry

[Mathematical assessment of BAC-based interspecies hybridization data in the process of genomic mapping in the white-throated sparrow as an avian behavioral model] Математическая оценка данных межвидовой БАК-гибридизации в процессе геномного картирования у белошейной зонотрихии как модели поведения птиц

The white-throated sparrow (Zonotrichia albicollis) known for its morphological, behavioral and chromosomal polymorphisms represents a quite new model system to study genomic mechanisms underlying variable behavioral repertoire interwoven with population biology, reproduction and adaptation in this species. It was previously shown that these polymorphisms could be due to chromosomal rearrangements (inversions) on sparrow chromosome 2 (ZAL2) that is characterized by a heterogeneity in two distinct morphs, tan (ZAL2/ZAL2) and white (ZAL2/ZAL2m). To construct a comparative genomic map of ZAL2 and other chromosomes, we used a sparrow genomic BAC library, CHORI-264. Following a cross-species overgo hybridization approach, we screened the library and developed a first-generation BAC-based comparative physical map using the chicken and zebra finch reference genomes. The map includes 640 BAC-gene assignments for 77 loci and serves for further refining the genomic regions and identifying candidate genes that are affected by rearrangements and contribute to the observed behavioral polymorphisms. Mathematical assessment of the BAC-based hybridization data was undertaken to show evolutionary relationships of avian genomes. В настоящей работе представлена математическая оценка межвидовой БАК-гибридизации в процессе геномного картирования у белошейной зонотрихии – вида воробьев, рассматриваемого в качестве удобной модели поведения птиц

Investigating adverse effects of chronic dietary exposure to herbicide glyphosate on zootechnical characteristics and clinical, biochemical and immunological blood parameters in broiler chickens

Although the herbicide glyphosate is widely used globally and considered safe, more evidence of its adverse effects on animals and humans is accumulating. The present investigation was aimed at evaluating the impact of different glyphosate concentrations on zootechnical characteristics and clinical, biochemical and immunological blood parameters in Ross 308 broiler chickens. Four groups were employed, including untreated control and three experimental groups fed diets enriched with glyphosate at doses of 10, 20 and 100 ppm that conformed to 0.5, 1 and 5 maximum residue limits, respectively. The results showed that glyphosate is a stress factor triggering a multifaceted effect on important blood parameters (e.g., white blood cell and phagocytic counts), which was shown for the first time in the experiments involving productive meat-type poultry. It was first revealed that glyphosate-induced changes in blood parameters may be related to a negative impact on the zootechnical characteristics including the digestive tract organ development and body weight gain. The study findings suggested that exposure to glyphosate in the feedstuffs can adversely affect the physiological condition and productivity of broilers

[Determination of intestinal microbiocenoses of chickens of the Hisex breed by the T-RFLP method in ontogenesis] Определение микробиоценозов кишечника кур породы «Хайсекс» методом T-RFLP в онтогенезе

Организаторы: Сибирское отделение Российской академии наук; Институт химической биологии и фундаментальной медицины Лаптев Г.Ю., Ильина Л.А., Никонов И.Н., Кочиш И.И., Романов М.Н., Смоленский В.И., Панин А.Н., Йылдырым Е.А., Новикова Н.И., Филиппова В.А., Дубровин А.В. Цель работы: выявление структуры и таксономического состава микроорганизмов слепых отростков ЖКТ кур породы «Хайсекс» в онтогенезе с применением комплекса молекулярно-генетических методов. Исследования состава бактериального сообщества слепых отростков кишечника 40-, 155- и 315-суточных кур-несушек (по 3 из каждой группы) проводили молекулярно-генетическими методами (Т-RFLP и ПЦР в реальном времени). У исследуемой птицы в онтогенезе происходило развитие микробного сообщества ЖКТ, изменение содержания и появление новых микроорганизмов. Отмечено, что спектр выявляемых бактерий был выше у 40- и 155-суточной птицы (221 11 и 258 9 филотипов соответственно) по сравнению с 315-суточными курами-несушками (178 8 филотипов). Также у 315-суточной птицы выявлено наименьшее содержание неидентифицированных филотипов. В слепых отростках ЖКТ взрослой птицы выявлено изменение доминирующих таксономических групп микроорганизмов - более высокая доля бактерий кислот-утилизирующих бактерий класса Negativicutes, целлюлозолитиков класса Clostridia. Обратная тенденция наблюдалась в отношении бактерий классов Bifidobacteriales, Bacillales. Большее содержание лактобактерий порядка Lactobacillales наблюдалась у 315-суточных кур-несушек (33,15 1,05%) по сравнению с 40- (5,13 0,23%) и 155-суточной (24,58 0,86%) птицей. Разнообразие и количество бактерий в слепых отростков ЖКТ, которых традиционно относят к возбудителям различных заболеваний птицы, из родов Enterobacter, Pantoea, Listeria, Acinetobacter, Mycoplasma, семейств Campylobacteraceae, Pasteurellaceae, филума Fusobacteria увеличивается с возрастом птицы. Таким образом, в ходе молекулярно-генетических исследований был определен видовой состав микробиоценозов слепых отростков ЖКТ кур яичной породы «Хайсекс» в онтогенезе. Исследования выполнены при поддержке Министерства образования и науки Российской Федерации, Договор № 14.W03.31.0013 от 20.02.2017 г

Safety and efficacy of convalescent plasma for COVID-19: the preliminary results of a clinical trial

Background. The lack of effective etiotropic therapy for COVID-19 has prompted researchers around the globe to seekr various methods of SARS-CoV-2 elimination, including the use of convalescent plasma. Aim. The aim of this work was to study the safety and efficacy of the convalescence plasma treatment of severe COVID-19 using the plasma containing specific antibodies to the receptor binding domain (RBD) of SARS-CoV-2 S protein in a titer of at least 1:1000. Methods. A single-center, randomized, prospective clinical study was performed at the FRCC FMBA of Russia with the participation of 86 patients who were stratified in two groups. The first group included 20 critically ill patients who were on mechanical ventilation the second group included 66 patients with moderate to severe COVID-19 and with spontaneous respiration. The patients in the second group were randomized into two cohorts in a ratio of 2:1. In the first cohort (46 patients), pathogen-reduced convalescent plasma was transfused (twice, 320 ml each), in the second cohort (20 patients) a similar amount of non-immune freshly frozen plasma was transfused to the patients. Results. The use of plasma of convalescents in patients with severe COVID-19 being on mechanical ventilation does not affect the disease outcome in these patients. The mortality rate in this group was 60%, which corresponds to the average mortality of COVID patients on mechanical ventilation in our hospital. In the second group, clinical improvement was detected in 75% and 51%, for convalescent and non-immune plasma, respectively. Of the 46 people who received convalescent plasma, three patients (6.5%) were transferred to mechanical ventilation, two of them died. In the group receiving non-immune plasma, the need for mechanical ventilation also arose in three patients (15%), of which two died. The hospital mortality in the group of convalescent plasma was 4.3%, which is significantly lower than the average COVID-19 hospital mortality at our Center (6.73%) and more than two times lower than the hospital mortality in the control group (n=150), matched by age and by the disease severity. Conclusions. Thus, we demonstrated a relative safety of convalescent plasma transfusion and the effectiveness of such therapy for COVID-19 at least in terms of the survival of hospitalized patients with severe respiratory failure without mechanical ventilation. In the absence of bioengineered neutralizing antibodies and effective etiotropic therapy, the use of hyperimmune convalescent plasma is the simplest and most effective method of specific etiopathogenetic therapy of severe forms of COVID-19

[Guidelines for the use of a feed additive tested in an industrial environment on highly productive commercial laying hens] Методические рекомендации по использованию кормовой добавки, прошедшей испытания в промышленных условиях на высокопродуктивных промышленных курах-несушках

Methodological recommendations were developed within the framework of the Grant Agreement No. 14.W03.31.0013 dated February 20, 2017 as part of the implementation of the Russian Federation Government Resolution No. 220 dated April 9, 2010 on the topic Development of modern biotechnologies for assessing gene expression in connection with productivity and resistance to diseases in poultry farming. Methodical recommendations are intended for specialists and managers of poultry farms, farmers, researchers, teachers, graduate students and students of agricultural universities, students of the advanced training system. Методические рекомендации разработаны в рамках Договора о выделении гранта № 14.W03.31.0013 от 20 февраля 2017 г. в рамках реализации постановления Правительства Российской Федерации от 9 апреля 2010 г. № 220 по теме  Разработка современных биотехнологий для оценки экспрессии генов в связи с продуктивностью и устойчивостью к заболеваниям в птицеводстве. Методические рекомендации предназначены для специалистов и руководителей птицеводческих хозяйств, фермеров, научных работников, преподавателей, аспирантов и студентов сельскохозяйственных вузов, слушателей системы повышения квалификации

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p&nbsp;&lt;.001. Over 24&nbsp;months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10&nbsp;ml/min/1.73&nbsp;m2 decrease), that was most notable in patients with eGFR &lt;30&nbsp;ml/min/1.73&nbsp;m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90&nbsp;ml/min/1.73&nbsp;m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF