Metagenomic profiling of viral and microbial communities from the pox lesions of lumpy skin disease virus and sheeppox virus-infected hosts

IntroductionIt has been recognized that capripoxvirus infections have a strong cutaneous tropism with the manifestation of skin lesions in the form of nodules and scabs in the respective hosts, followed by necrosis and sloughing off. Considering that the skin microbiota is a complex community of commensal bacteria, fungi and viruses that are influenced by infections leading to pathological states, there is no evidence on how the skin microbiome is affected during capripoxvirus pathogenesis.MethodsIn this study, shotgun metagenomic sequencing was used to investigate the microbiome in pox lesions from hosts infected with lumpy skin disease virus and sheep pox virus.ResultsThe analysis revealed a high degree of variability in bacterial community structures across affected skin samples, indicating the importance of specific commensal microorganisms colonizing individual hosts. The most common and abundant bacteria found in scab samples were Fusobacterium necrophorum, Streptococcus dysgalactiae, Helcococcus ovis and Trueperella pyogenes, irrespective of host. Bacterial reads belonging to the genera Moraxella, Mannheimia, Corynebacterium, Staphylococcus and Micrococcus were identified.DiscussionThis study is the first to investigate capripox virus-associated changes in the skin microbiome using whole-genome metagenomic profiling. The findings will provide a basis for further investigation into capripoxvirus pathogenesis. In addition, this study highlights the challenge of selecting an optimal bioinformatics approach for the analysis of metagenomic data in clinical and veterinary practice. For example, direct classification of reads using a kmer-based algorithm resulted in a significant number of systematic false positives, which may be attributed to the peculiarities of the algorithm and database selection. On the contrary, the process of de novo assembly requires a large number of target reads from the symbiotic microbial community. In this work, the obtained sequencing data were processed by three different approaches, including direct classification of reads based on k-mers, mapping of reads to a marker gene database, and de novo assembly and binning of metagenomic contigs. The advantages and disadvantages of these techniques and their practicality in veterinary settings are discussed in relation to the results obtained

Modulation of Behavioral and Neurochemical Responses of Adult Zebrafish by Fluoxetine, Eicosapentaenoic Acid and Lipopolysaccharide in the Prolonged Chronic Unpredictable Stress Model

Long-term recurrent stress is a common cause of neuropsychiatric disorders. Animal models are widely used to study the pathogenesis of stress-related psychiatric disorders. The zebrafish (Danio rerio) is emerging as a powerful tool to study chronic stress and its mechanisms. Here, we developed a prolonged 11-week chronic unpredictable stress (PCUS) model in zebrafish to more fully mimic chronic stress in human populations. We also examined behavioral and neurochemical alterations in zebrafish, and attempted to modulate these states by 3-week treatment with an antidepressant fluoxetine, a neuroprotective omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), a pro-inflammatory endotoxin lipopolysaccharide (LPS), and their combinations. Overall, PCUS induced severe anxiety and elevated norepinephrine levels, whereas fluoxetine (alone or combined with other agents) corrected most of these behavioral deficits. While EPA and LPS alone had little effects on the zebrafish PCUS-induced anxiety behavior, both fluoxetine (alone or in combination) and EPA restored norepinephrine levels, whereas LPS + EPA increased dopamine levels. As these data support the validity of PCUS as an effective tool to study stress-related pathologies in zebrafish, further research is needed into the ability of various conventional and novel treatments to modulate behavioral and neurochemical biomarkers of chronic stress in this model organism. © 2021, The Author(s).This research was supported solely by the Russian Science Foundation (RSF) grant 19‐15‐00053. K.A.D. is supported by the Special Rector’s Productivity Fellowship for SPSU PhD Students, and the lab is supported by St. Petersburg State University state budgetary funds (project ID 73026081). A.V.K. is the Chair of the International Zebrafish Neuroscience Research Consortium (ZNRC) and President of the International Stress and Behavior Society (ISBS, www.stress-and-behavior.com) that coordinated this collaborative multi-laboratory project. The consortium provided a collaborative idea exchange platform for this study, it is not considered as affiliation and did not fund the study. A.V.K. lab is supported by the Southwest University (SWU) Zebrafish Platform Construction Fund (Chongqing, China). The authors thank Professor Raul R. Gainetdinov (Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia) for his generous assistance with the HPLC studies in his laboratory. The funders had no role in the design, analyses, and interpretation of the submitted study, or decision to publish

ОРТОТОПИЧЕСКАЯ ТРАНСПЛАНТАЦИЯ ПЕЧЕНИ: РОЛЬ ИНТЕРВЕНЦИОННОЙ РАДИОЛОГИИ

To study therapeutic modalities of interventional radiology in patients (pts) before and after orthotopic liver trans- plantation (OLT). OLT was performed in 53 pts between 1998 and 2008. Endovascular treatments were performed in 20 pts. Pre-OLT interventional procedures included transcatheter arterial chemoembolization (5 patients) and TIPS (8 patients). Post-OLT procedures were: dilatation or/and stenting of biliary strictures (4), stenting of IVC (2), balloon dilatation of cava-caval anastomosis (1), partial splenic embolization (PSE) in steel syndrome (1). All IR procedures were technically successful. There was no mortality or serious complication. After chemoemboliza- tion, there was partial tumor response in all 5 patients with HCC; two successfully transplanted are alive without recurrence in 11 and 15 months. After TIPS, 3 pts underwent OLT. Satisfactory biliary passage was achieved in all pts with strictures. Clinical symptoms and liver function improved in three pts with venous strictures. After PSE, steal syndrome regressed rapidly. All pts are asymptomatic and well in 5–24 mo after IR treatment. IR procedures prolong long-term patient survival before OLT and may improve outcomes in pts after OLT. В работе обсуждается эффективность интервенционных радиологических процедур у больных перед и после ортотопической трансплантации печени (ОТП). За период 1998–2008 гг. ОТП выполнена 53 паци- ентам. Лечебные эндоваскулярные вмешательства осуществлены у 20 из этих больных. Предоперацион- ные процедуры выполнены у 13 пациентов: масляная химиоэмболизация печеночной артерии (МХЭПА, n = 5), наложение внутрипеченочного портокавального шунта (TIPS, n = 8). У 7 больных произведены 8 послеоперационных вмешательств: дренирование и/или стентирование желчных протоков (n = 4), ре- канализация и стентирование стеноза/окклюзии нижней полой вены (НПВ, n = 2), баллонная дилатация кава-кавального анастомоза (n = 1), эмболизация селезеночной артерии (n = 1). После МХЭПА отмечено уменьшение злокачественной опухоли или замедление ее роста у всех 5 пациентов, ОТП к настоящему времени осуществлена у 3 из них. В результате TIPS снижение портальной гипертензии произошло у всех больных, ОТП выполнена в 3 наблюдениях. Все послеоперационные процедуры были также технически и клинически успешны. Методы интервенционной радиологии позволяют продлить время ожидания до- норской печени у больных, которым требуется ОТП. Рентгеноэндоваскулярные вмешательства позволяют устранить послеоперационные билиарные и сосудистые стриктуры, а также другие осложнения ОТП.

Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish

Stress-related neuropsychiatric disorders are widespread, debilitating and often treatment-resistant illnesses that represent an urgent unmet biomedical problem. Animal models of these disorders are widely used to study stress pathogenesis. A more recent and historically less utilized model organism, the zebrafish (Danio rerio), is a valuable tool in stress neuroscience research. Utilizing the 5-week chronic unpredictable stress (CUS) model, here we examined brain transcriptomic profiles and complex dynamic behavioral stress responses, as well as neurochemical alterations in adult zebrafish and their correction by chronic antidepressant, fluoxetine, treatment. Overall, CUS induced complex neurochemical and behavioral alterations in zebrafish, including stable anxiety-like behaviors and serotonin metabolism deficits. Chronic fluoxetine (0.1 mg/L for 11 days) rescued most of the observed behavioral and neurochemical responses. Finally, whole-genome brain transcriptomic analyses revealed altered expression of various CNS genes (partially rescued by chronic fluoxetine), including inflammation-, ubiquitin- and arrestin-related genes. Collectively, this supports zebrafish as a valuable translational tool to study stress-related pathogenesis, whose anxiety and serotonergic deficits parallel rodent and clinical studies, and genomic analyses implicate neuroinflammation, structural neuronal remodeling and arrestin/ubiquitin pathways in both stress pathogenesis and its potential therapy. © 2020, The Author(s).The research was supported by the Russian Science Foundation (RSF) Grant 19‐15‐00053. KAD is supported by the President of Russia Graduate Fellowship, the Special Rector’s Productivity Fellowship for SPSU PhD Students, and the Russian Foundation for Basic Research (RFBR) grant 18‐34‐00996. ADP was supported by St. Petersburg University (project ID 51555422). The research team was supported by St. Petersburg State University state budgetary funds (project ID 51130521). AVK is the Chair of the International Zebrafish Neuroscience Research Consortium (ZNRC) and President of the International Stress and Behavior Society (ISBS, www.stress-and-behavior.com) that coordinated this collaborative multi-laboratory project. The consortium provided a collaborative idea exchange platform for this study. It is not considered as an affiliation, and did not fund the study. AVK is supported by the Southwest University Zebrafish Platform Construction Fund. TGA’s research is supported by the budgetary funding for basic research from the Scientific Research Institute of Physiology and Basic Medicine (AAAA-A16-116021010228-0, Novosibirsk, Russia). This study utilized equipment of the Core Facilities Centre “Centre for Molecular and Cell Technologies” of St. Petersburg State University. The funders had no role in the design, analyses, and interpretation of the submitted study, or decision to publish

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Hypoxic Pulmonary Vasoconstriction in Humans:Tale or Myth

Hypoxic Pulmonary vasoconstriction (HPV) describes the physiological adaptive process of lungs to preserves systemic oxygenation. It has clinical implications in the development of pulmonary hypertension which impacts on outcomes of patients undergoing cardiothoracic surgery. This review examines both acute and chronic hypoxic vasoconstriction focusing on the distinct clinical implications and highlights the role of calcium and mitochondria in acute versus the role of reactive oxygen species and Rho GTPases in chronic HPV. Furthermore it identifies gaps of knowledge and need for further research in humans to clearly define this phenomenon and the underlying mechanism

Pharmacology of modern ACE inhibitors: moexipril example

ACE inhibitors are widely used in the treatment of arterial hypertension, chronic heart failure, and other cardiovascular pathology. The article is devoted to ACE pharmacology and their optimal use in clinical practice