Detection of genetic material of causative agents of animal viral diseases in blood-sucking dipterans from the Tyumen Region

The purpose of the research is to test blood-sucking dipterans collected in the Tyumen Region for genetic material of viruses that cause dangerous diseases in live-stock animals.Materials and methods. From May to October 2021, blood-sucking insects of the Diptera order whose species membership was established by tabular keys were collected on pastures and farms in ten Tyumen Region districts. In 60 samples formed from the captured insects according to the taxonomic affiliation and the period and place of collection, the presence of genetic material of the leukemia provirus and the dermatitis nodularis virus of cattle (bovine) and the African swine fever virus was evaluated by polymerase chain reaction (PCR) in real time.Results and discussion. Adult insects collected for the PCR analysis were blood-sucking flies (family Muscidae, genus Stomoxys), mosquitoes (family Culicidae, genus Aedes), midges (family Simuliidae, genera Byssodon and Schoenbaueria), horseflies (family Tabanidae, genera Hybomitra, Tabanus and Haematopota), and biting midges (family Ceratopogonidae, genus Culicoides). As a result of the PCR testing of the samples for the bovine leukemia provirus DNA, 1 out of 13 samples of Stomoxys spp. (7.7%) and 1 of 13 samples of Hybomitra spp. (7.7%) were positive. The bovine leukemia provirus DNA detected in blood-sucking insects indicates the presence of this pathogen in the insect collection area as well as their possible involvement in its spread. Further research is needed on the Stomoxys spp. and Hybomitra spp. vector competence in vivo, considering natural and climatic features of the Tyumen Region

Выявление в кровососущих двукрылых насекомых Тюменской области генетического материала возбудителей вирусных болезней животных

The purpose of the research is to test blood-sucking dipterans collected in the Tyumen Region for genetic material of viruses that cause dangerous diseases in live-stock animals.Materials and methods. From May to October 2021, blood-sucking insects of the Diptera order whose species membership was established by tabular keys were collected on pastures and farms in ten Tyumen Region districts. In 60 samples formed from the captured insects according to the taxonomic affiliation and the period and place of collection, the presence of genetic material of the leukemia provirus and the dermatitis nodularis virus of cattle (bovine) and the African swine fever virus was evaluated by polymerase chain reaction (PCR) in real time.Results and discussion. Adult insects collected for the PCR analysis were blood-sucking flies (family Muscidae, genus Stomoxys), mosquitoes (family Culicidae, genus Aedes), midges (family Simuliidae, genera Byssodon and Schoenbaueria), horseflies (family Tabanidae, genera Hybomitra, Tabanus and Haematopota), and biting midges (family Ceratopogonidae, genus Culicoides). As a result of the PCR testing of the samples for the bovine leukemia provirus DNA, 1 out of 13 samples of Stomoxys spp. (7.7%) and 1 of 13 samples of Hybomitra spp. (7.7%) were positive. The bovine leukemia provirus DNA detected in blood-sucking insects indicates the presence of this pathogen in the insect collection area as well as their possible involvement in its spread. Further research is needed on the Stomoxys spp. and Hybomitra spp. vector competence in vivo, considering natural and climatic features of the Tyumen Region.Цель исследований – тестирование кровососущих двукрылых насекомых, собранных на территории Тюменской области, на наличие генетического материала вирусов – возбудителей опасных заболеваний сельскохозяйственных животных.Материалы и методы. В период с мая по октябрь 2021 г. на пастбищах и фермах десяти районов Тюменской области были проведены сборы кровососущих насекомых отряда Diptera, видовая принадлежность которых была установлена по определительным таблицам. В 60 пробах, сформированных из отловленных насекомых в соответствии с таксономической принадлежностью, периодом и местом сбора, оценивали наличие генетического материала провируса лейкоза и вируса нодулярного дерматита крупного рогатого скота (КРС), вируса африканской чумы свиней методом полимеразной цепной реакции (ПЦР) в режиме реального времени.Результаты и обсуждение. Собранные для ПЦР-исследования взрослые особи насекомых были представлены кровососущими мухами (сем. Muscidae, род Stomoxys), комарами (сем. Culicidae, род Aedes), мошками (сем. Simuliidae, роды Byssodon и Schoenbaueria), слепнями (сем. Tabanidae, роды Hybomitra, Tabanus и Haematopota), мокрецами (сем. Ceratopogonidae, род Culicoides). В результате ПЦР-тестирования проб на наличие ДНК провируса лейкоза КРС положительными оказались 1 из 13 проб Stomoxys spp. (7,7%) и 1 из 13 проб Hybomitra spp. (7,7%). Выявление ДНК провируса лейкоза КРС в кровососущих насекомых указывает на присутствие данного возбудителя на территории сбора насекомых, а также на возможное их участие в его распространении. Необходимы дальнейшие исследования векторной компетентности Stomoxys spp. и Hybomitra spp. в естественных условиях с учетом природно-климатических особенностей Тюменской области

Metabolomic Analysis in Severe Childhood Pneumonia in The Gambia, West Africa: Findings from a Pilot Study

Pneumonia remains the leading cause of death in young children globally and improved diagnostics are needed to better identify cases and reduce case fatality. Metabolomics, a rapidly evolving field aimed at characterizing metabolites in biofluids, has the potential to improve diagnostics in a range of diseases. The objective of this pilot study is to apply metabolomic analysis to childhood pneumonia to explore its potential to improve pneumonia diagnosis in a high-burden setting. and Random Forests (RF). ‘Unsupervised’ (blinded) data were analyzed by Principal Component Analysis (PCA), while ‘supervised’ (unblinded) analysis was by Partial Least Squares-Discriminant Analysis (PLS-DA) and Orthogonal Projection to Latent Structures (OPLS). Potential markers were extracted from S-plots constructed following analysis with OPLS, and markers were chosen based on their contribution to the variation and correlation within the data set. The dataset was additionally analyzed with the machine-learning algorithm RF in order to address issues of model overfitting and markers were selected based on their variable importance ranking. Unsupervised PCA analysis revealed good separation of pneumonia and control groups, with even clearer separation of the groups with PLS-DA and OPLS analysis. Statistically significant differences (p<0.05) between groups were seen with the following metabolites: uric acid, hypoxanthine and glutamic acid were higher in plasma from cases, while L-tryptophan and adenosine-5′-diphosphate (ADP) were lower; uric acid and L-histidine were lower in urine from cases. The key limitation of this study is its small size.Metabolomic analysis clearly distinguished severe pneumonia patients from community controls. The metabolites identified are important for the host response to infection through antioxidant, inflammatory and antimicrobial pathways, and energy metabolism. Larger studies are needed to determine whether these findings are pneumonia-specific and to distinguish organism-specific responses. Metabolomics has considerable potential to improve diagnostics for childhood pneumonia

Bioinformatics tools for cancer metabolomics

It is well known that significant metabolic change take place as cells are transformed from normal to malignant. This review focuses on the use of different bioinformatics tools in cancer metabolomics studies. The article begins by describing different metabolomics technologies and data generation techniques. Overview of the data pre-processing techniques is provided and multivariate data analysis techniques are discussed and illustrated with case studies, including principal component analysis, clustering techniques, self-organizing maps, partial least squares, and discriminant function analysis. Also included is a discussion of available software packages

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Номограмма для прогнозирования госпитальной летальности у пациентов с COVID-19, находившихся в отделении реанимации и интенсивной терапии

The objective: to develop a predictive model for assessing the risk of death in patients with COVID-19 admitted to the intensive care unit (ICU).Subjects and Methods. This was a single-center retrospective cohort study of hospital mortality in patients admitted to ICU of V.P. Demikhov City Clinical Hospital from March 6 to June 3, 2020.Results. Case histories of 403 patients were analyzed. In-hospital 30-day mortality among patients treated in ICU was 44.9% (181/403 patients). A multivariate analysis showed that significant predictors of death in patients with COVID-19 were the age of 60 years or more (adj. OR 3.84; 95% CI 1.56‒9.44, p = 0.003), COPD (adj. OR 2.35; 95% CI 1.12‒4.95, p = 0.024), peripheral artery diseases (adj. OR: 5.08; 95% CI 1.87‒13.76, p = 0.001) and CKD stage 3b and higher (adj. OR 4.58; 95% CI 2.36‒8.90, p &lt; 0.001), LDH 300 IU/l or more (adj. OR 3.05; 95% CI 1.23‒7.58, p = 0.016), and CRP 200 mg/l or more (adj. OR 3.65; 95% CI 1.95‒6.85, p &lt; 0.001). Predictive model quality: AUC = 0.811 [0.733‒0.874], p &lt; 0.001.Conclusions. A nomogram to assess the risk of death in patients with COVID-19 has been developed. It includes the assessment of age, history of COPD, CKD stage 3b and higher, peripheral artery diseases, and monitoring of LDH and CRP.Цель: разработать прогностическую модель оценки риска развития летального исхода в течение 30 дней после госпитализации у пациентов с COVID-19, проходивших лечение в отделении реанимации и интенсивной терапии (ОРИТ).Материалы и методы. Проведено одноцентровое ретроспективное когортное исследование госпитальной летальности пациентов, находящихся на лечении в ОРИТ ГБУЗ «ГКБ им. В. П. Демихова ДЗМ» в период с 6 марта по 3 июня 2020 г.Результаты. Проведен анализ историй болезней 403 пациентов. Итоговая 30-дневная летальность составила 44,9% (181/403). Значимыми предикторами летального исхода у пациентов с COVID-19 оказались: возраст 60 лет и более (adj. OR 3,84; 95%-ный ДИ 1,56‒9,44, p = 0,003), наличие в анамнезе хронической обструктивной болезни легких (adj. OR 2,35; 95%-ный ДИ 1,12‒4,95, p = 0,024), заболеваний периферических артерий (adj. OR 5,08; 95%-ный ДИ 1,87‒13,76, p = 0,001) и хронической болезни почек 3b стадии и выше (adj. OR 4,58; 95%-ный ДИ 2,36‒8,90, p &lt; 0,001), значение уровня лактатдегидрогеназы 300 МЕ/л и более (adj. OR 3,05; 95%-ный ДИ 1,23‒7,58, p = 0,016) и С-реактивного белка 200 мг/л и более (adj. OR 3,65; 95%-ный ДИ 1,95‒6,85, p &lt; 0,001). Качество прогностической модели: AUC = 0,811 [0,733‒0,874], p &lt; 0,001.Выводы. Разработана номограмма для оценки риска наступления летального исхода у пациентов с COVID-19, предполагающая оценку возраста, наличия в анамнезе хронической обструктивной болезни легких, хронической болезни почек 3b стадии и выше, заболеваний периферических артерий, мониторинг лактатдегидрогеназы и С-реактивного белка

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Nuclear Magnetic Resonance metabolomics reveals an excretory metabolic signature of renal cell carcinoma

RCC usually develops and progresses asymptomatically and, when detected, it is frequently at advanced stages and metastatic, entailing a dismal prognosis. Therefore, there is an obvious demand for new strategies enabling an earlier diagnosis. The importance of metabolic rearrangements for carcinogenesis unlocked a new approach for cancer research, catalyzing the increased use of metabolomics. The present study aimed the NMR metabolic profiling of RCC in urine samples from a cohort of RCC patients (n = 42) and controls (n = 49). The methodology entailed variable selection of the spectra in tandem with multivariate analysis and validation procedures. The retrieval of a disease signature was preceded by a systematic evaluation of the impacts of subject age, gender, BMI, and smoking habits. The impact of confounders on the urine metabolomics profile of this population is residual compared to that of RCC. A 32-metabolite/resonance signature descriptive of RCC was unveiled, successfully distinguishing RCC patients from controls in principal component analysis. This work demonstrates the value of a systematic metabolomics workflow for the identification of robust urinary metabolic biomarkers of RCC. Future studies should entail the validation of the 32-metabolite/resonance signature found for RCC in independent cohorts, as well as biological validation of the putative hypotheses advanced