Evaluation of Hormone-Induced Stress Responses Using Endogenous Cortisol in Carp (Cyprinus carpio)

With stress studies in fish it is often difficult to determine the degree of response to various stressors, and the interpretation of this influence is usually based on an increase in endogenous cortisol levels. Simulation of stress with synthetic corticosteroids is widely used in ichthyological practice, which raises the question of whether endogenous cortisol is the most appropriate parameter for measuring stress levels in such studies. This work presents the dynamics of the plasma cortisol level in simulating acute and chronic stress in 24 carps by a single injection of dexamethasone in the first experimental group and betamethasone in the second experimental group, in comparison with the control group (without injection) for 21 days. The analysis was performed before injection, as well as after 7, 14 and 21 days of treatment. The hormonal response was compared with that of fish stressed by natural factors (hypoxia). It was found that betamethasone inactivates the production of endogenous cortisol during all subsequent days of the experiment after injection from 353.68±66.39 ng/ml to 7.28±1.27 ng/ml by day 21, while the effect of dexamethasone caused multidirectional fluctuations in its level: from 346.25±43.16 ng/ml to 242.25±58.49 ng/ml on the 7th day, 388.25±37.51 ng/ml on the 14th day and 264.25±21.21 ng/ml on day 21 compared with smooth dynamics in control fish: 376.25±44.04 ng/ml, 366.75±42.82 ng/ml, 335.33±8.57 ng/ml and 366.00±89.22 ng/ml, respectively. It was concluded that measuring the level of endogenous cortisol is not recommended when assessing the degree of stress imitation by these hormones, and in studies of this type it is necessary to search for other indicators. Keywords: carp, cortisol, stress, dexamethasone, betamethasone, hormon

Сонографические показатели диафрагмы и их корреляции со спирометрическими данными у здоровых лиц: проспективное клиническое исследование

ЦЕЛЬ ИССЛЕДОВАНИЯ: Выявить корреляционные взаимосвязи сонографических показателей функционирования диафрагмы со спирометрическими данными у здоровых лиц. МАТЕРИАЛЫ И МЕТОДЫ: На базе ФГБУ «НМИЦ им. В.А. Алмазова» у 50 здоровых добровольцев (женщин — 30) оценили структурное (толщину) и функциональное (индекс утолщения и экскурсию) состояние диафрагмы с помощью ультразвукового исследования, а также спирометрические характеристики аппарата внешнего дыхания с помощью аппарата искусственной вентиляции легких. После чего провели статистическую обработку и корреляционный анализ. РЕЗУЛЬТАТЫ: Толщину диафрагмы (слева и справа) и ее экскурсию (справа) удалось оценить у всех испытуемых; экскурсию диафрагмы слева — только у 20 % испытуемых. Спирометрию выполнили у всех испытуемых. Полученные данные согласуются с литературными. В частности, ультразвуковые и спирометрические показатели для здоровых лиц находились в рамках референтных значений. Сила инспираторных мышц также оказалась сопоставимой с литературными данными. Корреляционный анализ не выявил статистически значимых взаимосвязей между изученными ультразвуковыми и спирометрическими параметрами. Также не было выявлено взаимосвязи между возрастом и ультразвуковыми показателями диафрагмы. Найдены слабые статистически значимые связи между структурно-функциональным состоянием диафрагмы и антропометрическими характеристиками обследованных: массой тела и индексом массы тела. ВЫВОДЫ: Ультразвуковые показатели работы диафрагмы не коррелируют или плохо коррелируют со спирометрическими. У здоровых лиц нет оснований использовать ультразвуковое исследование диафрагмы, так как оно практически не дает дополнительной информации о состоянии аппарата внешнего дыхания

ДОСВІД ВИЗНАЧЕННЯ ІНТРАТЕКАЛЬНОГО СИНТЕЗУ АНТИТІЛ У ПАЦІЄНТІВ З УРАЖЕННЯМИ ЦЕНТРАЛЬНОЇ НЕРВОВОЇ СИСТЕМИ

The aim of the work – to study the frequency of intrathecal synthesis of specific antibodies at patients with inflammatory lesions of the central nervous system.Patients and methods. In this work the data of the determination of intrathecal synthesis of specific antibodies (ITSA) in 90 patients are given who were treated at the Lev Hromashevskyi Institute of Epidemiology and Infectious Diseases. The research included quantitative definition of antibodies of the class IgG in serum (S) and cerebrospinal fluid (CSF) to neurotropic pathogens: herpes simplex virus 1/2, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, rubella virus, Borrelies. Calculations of ITSA indicators were carried out according to the method of Reiber H. The condition of a hematoencephalic barrier (HEB) was estimated by means of coefficient of albumine (Qalb) taking into account age norms.Results. ITSA was established in (25.6±4.6) % of the examined patients with damages of the central nervous system. In patients with ITSA most often (in 52.2 %) simultaneously present antibodies to several neurotropic pathogens. Detection of ITSA at the examined patients didn’t depend on concentration of specific antibodies in S and CSF and wasn’t followed by malfunction of HEB. The incidence of HEB dysfunction at patients with ITSA and without ITSA appeared with an identical frequency (13,0 % and 13,6 % respectively).Мета роботи. Вивчити частоту інтратекального синтезу специфічних антитіл у пацієнтів зі запальними ураженнями центральної нервової системи.Пацієнти і методи. В роботі наведені дані визначення інтратекального синтезу специфічних антитіл (ІТСА) у 90 пацієнтів, які проходили лікування в клініці ДУ «Інститут епідеміології та інфекційних хвороб ім. Л.В. Громашевського». Дослідження включало кількісне визначення антитіл класу Ig G в сироватці крові (СК) та спинномозковій рідині (СМР) до нейротропних збудників: вірусу простого герпесу 1/2 типу, цитомегаловірусу, вірусу Епштейна-Барр, вірусу оперізувального лишаю, вірусу кору, вірусу краснухи, бореліям. Розрахунки показників ІТСА проведені за методикою Reiber H. Стан гематоенцефалічного бар’єру (ГЕБ) оцінювали за допомогою коефіцієнту альбуміну (Qalb) з урахуванням вікових норм.Результати. ІТСА встановлений у (25,6±4,6) % обстежених пацієнтів з ураженнями ЦНС. У пацієнтів з ІТСА найчастіше (у 52,2 %) одночасно були присутні антитіла до декількох нейротропних збудників. Виявлення ІТСА в обстежених пацієнтів не залежало від концентрації специфічних антитіл у СК і СМР і не супроводжувалося порушенням функції ГЕБ. Випадки дисфункції ГЕБ у пацієнтів з ІТСА та без ІТСА виявлялися з однаковою частотою (13,0 та 13,6 % відповідно)

ЭЛЕКТРОЭНЦЕФАЛОГРАММА, ИМИТИРУЮЩАЯ УМИРАНИЕ ГОЛОВНОГО МОЗГА, ПРИ ОСТРОМ ОТРАВЛЕНИИ БАКЛОФЕНОМ

We report a case of acute baclofen poisoning in a 23-year-old female patient, who committed suicide, which led to the development of a deep coma. The electroencephalogram on the first day recorded the phenomenon of “burst suppression”, which was seen as a sign of a dying brain. Subsequent studies have shown positive changes of the electroencephalogram and regression of neurological symptoms. Thus, the phenomenon of “burst suppression” in the depression of consciousness to deep coma and given adequate treatment, can be reversible.Описывается случай острого отравления баклофеном с суицидальной целью пациентки 23 лет, приведшего к развитию глубокой комы. На электроэнцефалограмме при этом в 1-е сутки регистрировался феномен «вспышка–подавление», который рассматривается как признак умирания головного мозга. При последующих исследованиях показана положительная динамика изменений электроэнцефалограммы; также отмечался регресс неврологической симптоматики. Таким образом, регистрируемый в электроэнцефалограмме феномен «вспышка–подавление» при угнетении уровня бодрствования до глубокой комы с учетом адекватной терапии может иметь обратимый характер

ДИНАМИКА ПОКАЗАТЕЛЕЙ СУММАРНОЙ СПОНТАННОЙ ЭЛЕКТРИЧЕСКОЙ АКТИВНОСТИ ГОЛОВНОГО МОЗГА И ВЫЗВАННОГО ПОТЕНЦИАЛА, СВЯЗАННОГО С СОБЫТИЕМ (Р300) У БОЛЬНЫХ С ЭНЦЕФАЛОПАТИЕЙ ПРИ ОСТРЫХ ОТРАВЛЕНИЯХ ХИМИЧЕСКОЙ ЭТИОЛОГИИ НА ЭТАПЕ РЕАБИЛИТАЦИИ

RELEVANCE. Patients with encephalopathy due to acute chemical agents poisoning have some brain functioning changes and a cognitive impairment during the rehabilitation program. These changes require correction of appropriate diagnostic protocol and treatment.AIM. The aim of this study was to estimate changes of electroencephalography (EEG) and the P3 component of the event related potential (P300 ERP) that are observed in patients with encephalopathy due to acute chemical agents poisoning during stage of rehabilitation.MATERIAL AND METHODS. The study was included 25 patients (age 37 (32; 51)) poisoned different kind of neurotoxic substances (drugs, ethanol) and complicated by toxic and hypoxic encephalopathy. They have got the treatment of encephalopathy by mexidol intravenously, mesodiencephalic modulation (MDM) and hyperbaric oxygen therapy (HBOT). All patients were recoded EEG (electroencephalograph of “MBN” company, Russia) and P300 ERP (“Neuron-Spectrum-5/EP” of “Neurosoft”, Russia) according to the international recommendations of clinical neurophysiologists. Neuropsychological testing was used for the assessment of cognitive functions.RESULTS. There were some disturbances in primary electroencephalograms of all subjects. The follow-up EEG recording showed the main group of patients who had got the treatment (mexidol, MDM, HBOT) had more often (11 patients) the EEG improvements compared to the controls (1 patient). The main group had more rarely the EEG impairments compared to the control group. 6 patients of main group and 3 patients of controls did not have EEG changes during the follow-up EEG recordings. All controls and 17 patients of the main group patients had different cognitive disturbances. After the treatment 15 patients of the main group had improved on neuropsychological tests (MMSE, Munsterberg test, Schulte table, Number Connecting Test). They also had a decrease in the N200, P300 peak latency and an increase in the N200, P300 peak amplitude. Only 3 patients of controls had improved on neuropsychological tests.CONCLUSION. The results of this study show that mexidol, MDM, HBOT using in the treatment of patients with acute chemical agents poisoning leads to the improvement of brain state and cognitive function compared to the controls. The findings of study have allowed making a preliminary conclusion that using in the treatment this kind of patients the combination HBOT+mexidol or MDM+HBOT+mexidol improves the results of neuropsychological examination. АКТУАЛЬНОСТЬ. У больных с энцефалопатией при острых отравлениях химической этиологии на этапе реабилитации отмечаются изменения функционального состояния головного мозга, а также нарушения когнитивных функций, требующие для своей коррекции соответствующих диагностических и лечебных мероприятий.ЦЕЛЬ ИССЛЕДОВАНИЯ. Оценка динамики показателей суммарной спонтанной электрической активности головного мозга (ЭЭГ) и вызванного потенциала, связанного с событием (ССП) у больных с энцефалопатией при острых отравлениях химической этиологии на этапе реабилитации на фоне различных методов лечения.МАТЕРИАЛ И МЕТОДЫ. Всего обследовано 25 больных (ср. возраст — 37 (32; 51) с отравлениями различными нейротоксическими веществами (психофармакологические средства, наркотики, этанол), течение которых осложнилось токсико-гипоксической энцефалопатией. Основную группу составили 18 больных (ср. возраст — 37 (32; 52)), для лечения которых использовали внутривенное капельное введение мексидола, а также немедикаментозные методы лечения в виде мезодиэнцефальной модуляции (МДМ) и гипербарической оксигенации (ГБО). Контрольную группу составили 7 обследуемых (ср. возраст — 41 (31; 51)), которым не применяли вышеуказанные методы лечения. Всем больным регистрировали ЭЭГ на картографе фирмы МБН (Россия) и слуховой ССП на установке «Нейрон-Спектр–5/ВП», фирмы «НейроСофт» (Россия) согласно международным рекомендациям клинических нейрофизиологов. Для оценки когнитивных функций в работе использовали нейропсихологическое тестирование.РЕЗУЛЬТАТЫ. Первичное ЭЭГ-исследование выявило нарушения спонтанной электрической активности у всех обследованных больных как основной, так и контрольной групп. В ходе динамического наблюдения в основной группе (после проведенного лечения: мексидол, мезодиэнцефальная модуляция — МДМ, гипербарическая оксигенация — ГБО) по сравнению с контрольной группой положительная динамика в виде нормализации спонтанной электрической активности отмечалась у 11 пациентов, а в контрольной — только у одного; отрицательная динамика была выявлена у одного пациента основной группы и 3 пациентов контрольной группы. При этом отсутствие динамики, по данным ЭЭГ, было выявлено у 6 пациентов основной группы и у 3 пациентов контрольной группы. Результаты первичного психофизиологического исследования показали, что в основной группе в 17 случаях и у всех больных контрольной группы выявлялись нарушения когнитивной деятельности различной степени выраженности. После проведенного лечения у пациентов основной группы в большинстве случаев (15 больных) улучшились показатели по тестам mini-mental state examination (MMSE) — краткая шкала оценки психического статуса, батареи лобной дисфункции (БЛД), таблицам Шульте, тесту Мюнстерберга, тесту «Связь чисел», отмечалось сокращение показателей латентного периода (ЛП) компонентов N200, P300, нарастание амплитуды ответа. В контрольной группе положительная динамика была выявлена только в 3 наблюдениях по меньшему числу показателей (по тестам MMSE, таблицам Шульте, тесту «Связь чисел», по трем субтестам (1, 2, 3) из шести БЛД и менее выраженная по сравнению с основной группой).ЗАКЛЮЧЕНИЕ Использование мексидола, ГБО и МДМ в реабилитационном периоде отравлений нейротоксикантами, относительно контроля, приводит к более выраженному улучшению функционального состояния мозга в целом и показателей когнитивных функций.

Analysis of Clostridium beijerinckii NCIMB 8052's transcriptional response to ferulic acid and its application to enhance the strain tolerance

Background: Plant-based cellulose presents the best source of renewable sugars for biofuel production. However, the lignin associated with plant cellulose presents a hurdle as hydrolysis of this component leads to the production of inhibitory compounds, such as ferulic acid. Results: The impacts of ferulic acid, a phenolic compound commonly found in lignin hydrolysates, on the growth, solvent production, and transcriptional responses of Clostridium beijerinckii NCIMB 8052 were determined. Addition of ferulic acid to growing cultures resulted in a decrease in the growth and solvent production by 30% and 25%, respectively, when compared to the control cultures. To better understand the toxicity of this compound, microarray analyses were performed using samples taken from these cultures at three different growth states. Several gene ontology terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified showing significant change at each status, including ATP-binding cassette (ABC) transporters, two component system, and oxidoreductase activity. Moreover, genes related with efflux systems and heat shock proteins were also strongly up-regulated. Among these, expression of the groESL operon was induced by more than fourfold and was consequently selected to improve C. beijerinckii tolerance to ferulic acid. Real-time quantitative PCR (RT-qPCR) analysis confirmed that C. beijerinckii harboring the plasmid, pSAAT-ptb_Gro, had a two-to fivefold increased groESL operon expression during growth of these cultures. Moreover, this strain was more tolerant to ferulic acid as the growth of this recombinant strain and its bioconversion of glucose into solvents were both improved. Conclusions: Using transcriptomics, we identified numerous genes that are differentially expressed when C. beijerinckii cultures were exposed to ferulic acid for varying amounts of time. The operon expressing groESL was consistently up-regulated, suggesting that this gene cluster may contribute to strain tolerance. This was confirmed as recombinant cultures showed both an enhanced growth and solvent yield in the presence of 0.5 g/L ferulic acidopen00

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes

Background: Hansen’s disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease’s complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period. Results: Here, we reconstructed 19 ancient M. leprae genomes to further investigate M. leprae’s genetic variation in Europe, with a dedicated focus on bacterial genomes from previously unstudied regions (Belarus, Iberia, Russia, Scotland), from multiple sites in a single region (Cambridgeshire, England), and from two Iberian leprosaria. Overall, our data confirm the existence of similar phylogeographic patterns across Europe, including high diversity in leprosaria. Further, we identified a new genotype in Belarus. By doubling the number of complete ancient M. leprae genomes, our results improve our knowledge of the past phylogeography of M. leprae and reveal a particularly high M. leprae diversity in European medieval leprosaria. Conclusions: Our findings allow us to detect similar patterns of strain diversity across Europe with branch 3 as the most common branch and the leprosaria as centers for high diversity. The higher resolution of our phylogeny tree also refined our understanding of the interspecies transfer between red squirrels and humans pointing to a late antique/early medieval transmission. Furthermore, with our new estimates on the past population diversity of M. leprae, we gained first insights into the disease’s global history in relation to major historic events such as the Roman expansion or the beginning of the regular transatlantic long distance trade. In summary, our findings highlight how studying ancient M. leprae genomes worldwide improves our understanding of leprosy’s global history and can contribute to current models of M. leprae’s worldwide dissemination, including interspecies transmissions

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes.

Funder: Max-Planck SocietyFunder: St John’s College, CambridgeFunder: Fondation Raoul FollereauFunder: University of Zurich’s University Research Priority Program “Evolution in Action: From Genomes to Ecosystems”Funder: the Senckenberg Centre for Human Evolution and Palaeoenvironment (S-HEP) at the University of TübingenBackgroundHansen's disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease's complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period.ResultsHere, we reconstructed 19 ancient M. leprae genomes to further investigate M. leprae's genetic variation in Europe, with a dedicated focus on bacterial genomes from previously unstudied regions (Belarus, Iberia, Russia, Scotland), from multiple sites in a single region (Cambridgeshire, England), and from two Iberian leprosaria. Overall, our data confirm the existence of similar phylogeographic patterns across Europe, including high diversity in leprosaria. Further, we identified a new genotype in Belarus. By doubling the number of complete ancient M. leprae genomes, our results improve our knowledge of the past phylogeography of M. leprae and reveal a particularly high M. leprae diversity in European medieval leprosaria.ConclusionsOur findings allow us to detect similar patterns of strain diversity across Europe with branch 3 as the most common branch and the leprosaria as centers for high diversity. The higher resolution of our phylogeny tree also refined our understanding of the interspecies transfer between red squirrels and humans pointing to a late antique/early medieval transmission. Furthermore, with our new estimates on the past population diversity of M. leprae, we gained first insights into the disease's global history in relation to major historic events such as the Roman expansion or the beginning of the regular transatlantic long distance trade. In summary, our findings highlight how studying ancient M. leprae genomes worldwide improves our understanding of leprosy's global history and can contribute to current models of M. leprae's worldwide dissemination, including interspecies transmissions

Palaeogenomics of Upper Palaeolithic to Neolithic European hunter-gatherers

Modern humans have populated Europe for more than 45,000 years1,2. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period3. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe4, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants

Population genomics of post-glacial western Eurasia.

Western Eurasia witnessed several large-scale human migrations during the Holocene <sup>1-5</sup> . Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations