Современный взгляд на проблему врожденной цитомегаловирусной инфекции: диагностика, лечение и профилактика

A literature review of the works of foreign and domestic authors is devoted to modern approaches to the diagnosis, treatment and prevention of congenital cytomegalovirus infection (cCMV). The data of international consensuses are presented: «Congenital Cytomegalovirus: A European Expert Consensus Statement on Diagnosis and Management» adopted by the cCMV group from the European society for pediatric infectious diseases (ESPID) in Leipzig, Germany in 2015, and «Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy» by an informal International Congenital Cytomegalovirus Recommendations Group (ICCRG), established in Brisbane, Australia in 2015 as part of the 5th International cCMV Conference about evidence-based treatment cCMV using antiviral drugs and immunotherapy. Particular attention is paid to the prevention of cCMV in both pregnant and newborns, as well as data from international studies on the cytomegalovirus vaccination.Литературный обзор работ зарубежных и отечественных авторов посвящен современным подходам к диагностике, лечению и профилактике врожденной цитомегаловирусной инфекции (ВЦМВИ). Представлены данные международных консенсусов: «Консенсусное заявление европейских экспертов по диагностике и лечению ВЦМВИ», принятого группой по ВЦМВИ от Европейской ассоциации детских инфекционных болезней (ESPID) в Лейпциге (Германия) в 2015 году, и «Врожденная цитомегаловирусная инфекция у беременных и новорожденных: консенсуальные рекомендации по профилактике, диагностике и терапии» неофициальной Интернациональной группой по ВЦМВИ (ICCRG), созданной в Брисбене (Австралия) в 2015 году в рамках 5-й Международной конференции по врожденной цитомегалии, о доказательной базе лечения ВЦМВИ с применением противовирусных препаратов и иммунотерапии. Особое внимание уделено профилактике ЦМВИ как у беременных, так и у новорожденных, а также данные международных исследований о вакцинопрофилактике ЦМВИ

Hydrogenation of alkylaromatics over Rh/silica

The hydrogenation, and competitive hydrogenation, of toluene, ethylbenzene, propylbenzene and the xylenes has been studied over a rhodium catalyst in the liquid phase at 323 K and 3 bar(g). The reactivity of the aromatics gave an order of para-xylene > ortho-xylene > meta-xylene > toluene > ethylbenzene ≫ propylbenzene. Kinetic analysis revealed that the order of reaction in hydrogen was typically first order while the reaction order in toluene was zero order and negative half order for ethylbenzene. The reaction order for propylbenzene and the xylenes was negative first order. Apparent activation energies were calculated and all were in the range 26–46 kJ mol−1. Competitive hydrogenation between toluene, ethylbenzene and propylbenzene revealed that the propylbenzene was the most strongly adsorbed aromatic in agreement with the strongly negative reaction order. The xylenes gave an order of reactivity of para > ortho > meta following the increasing negative reaction order. Reactions with deuterium revealed an inverse kinetic isotope effect, most likely related to the change in hybridization of the carbon from sp2 to sp3, for all reactions, except that of ortho-xylene. Rapid exchange of the methyl group hydrogens was observed with all the xylenes, whereas total exchange was noted with toluene. The generation of trans-1,2-dimethylcyclohexane was explained by the formation of two intermediates, 1,2-dimethylcyclohexene and 1,6-dimethylcyclohexene, which give the cis-1,2-dimethylcyclohexane and trans-1,2-dimethylcyclohexane, respectively

Современный взгляд на проблему врожденной цитомегаловирусной инфекции

Congenital cytomegalovirus infection (CMVI) ranks first among congenital infections, making contribution significantly to the variety of congenital defects formation. The review describes in details the pathogenic mechanisms of the virus effects on the fetus and newborn. Congenital CMVI develops as a result of infection of the mother with the virus or its reactivation, causing an active infection. CMV is pantropic. Infected cells acquire the characteristic appearance of an «owl’s eye» due to a 3—4-fold increase in size, and the cytoplasm is visualized only in the form of a thin strip due to the large diameter of the nucleus. With a congenital CMV infection, the virus itself, its DNA or antigens is detected in biological media up to 14—21 days of life. The manifest and asymptomatic form of infection is distinguished.Attention is drawn to the various clinical findings and long-term outcomes of the infection. When the fetus is infected in the early stages of pregnancy, various malformations of the central nervous system, cardiovascular, kidneys, etc. are formed. When infected in the late stages of pregnancy, a variety of diseases and pathological conditions are revealed in newborns. In 40—90% of newborns with manifest CMVI, there are long-term neurological consequences and hearing loss, as well as damage to the organ of vision.Цитомегаловирусная инфекция занимает первое место среди врожденных инфекций, внося большой вклад в формирование разнообразных пороков развития. В обзоре литературы описываются патогенетические механизмы воздействия вируса на организм плода и новорожденного. Врожденная ЦМВИ развивается вследствие заражения матери вирусом или его реактивации, обуславливая активную инфекцию. ЦМВ обладает пантропностью. Инфицированные клетки приобретают характерный вид «совиного глаза» вследствие увеличения в размерах в 3—4 раза, цитоплазма из-за большого диаметра ядра визуализируется лишь в виде тонкой полоски. При врожденной ЦМВ-инфекции выявляют сам вирус, его ДНК или антигены в биологических средах до 14—21 дня жизни. Выделяют манифестную и бессимптомную форму инфекции.Особое внимание уделено разнообразию клинической картины инфекции и ее отдаленным последствиям. При инфицировании плода на ранних сроках беременности формируются разнообразные пороки развития ЦНС, сердечно-сосудистой, почек и др. При заражении в поздние сроки беременности у новорожденных выявляют разнообразные заболевания и патологические состояния. У 40—90% новорожденных при манифестной ЦМВИ имеют место отдаленные неврологические последствия и снижение слуха, а также поражения органа зрения

Современный взгляд на проблему врожденной цитомегаловирусной инфекции: клинические наблюдения

Тhis work is a continuation of the literature review «The modern view of congenital cytomegalovirus infection» and is devoted to the clinical cases. Particular attention is paid to the severity of congenital cytomegalovirus infection (CCMVI), as well as the its clinical variability, including developmental anomalies. The variety of clinical forms requires a wide range of examinations to identify all this infection manifestations in a newborn child and children in the first months of life, as well as the doctors alertness regarding the timely diagnosis of intrauterine infections based on the existing clinical features. The presented cases demonstrate the CCMVI clinical manifestations: the «classical» generalized manifest form, with a specific clinical, laboratory and instrumental findings, the severe generalized CCMVI with kidney congenital malformation and postnatal development of congenital cataract.Данная работа является продолжением литературного обзора «Современный взгляд на проблему врожденной цитомегаловирусной инфекции» и посвящена разбору клинических случаев. Особое внимание уделено тяжести течения врожденной цитомегаловирусной инфекции (ВЦМВИ), а также клиническому полиморфизму заболевания, в т.ч. с формированием аномалий развитий. Многообразие клинических форм ВЦМВИ требует проведения широкого спектра обследований для выявления всех проявлений данной инфекции у новорожденного ребенка и детей первых месяцев жизни, а также настороженности врачей в отношении своевременной диагностики внутриутробной инфекции на основании имеющейся клинической картины. Представленные случаи демонстрируют особенности клинических вариантов ВЦМВИ: «классической» манифестной формы с генерализованным течением, с характерной клинической картиной и изменениями в лабораторных и инструментальных данных, тяжелого генерализованного течения ВЦМВИ с внутриутробным формированием порока развития почки и постнатальным развитием врожденной катаракты

Temporal and spatial variations in the parasitoid complex of the horse chestnut leafminer during its invasion of Europe

The enemy release hypothesis posits that the initial success of invasive species depends on the scarcity and poor adaptation of native natural enemies such as predators and parasitoids. As for parasitoids, invading hosts are first attacked at low rates by a species-poor complex of mainly generalist species. Over the years, however, parasitoid richness may increase either because the invading host continuously encounters new parasitoid species during its spread (geographic spread-hypothesis) or because local parasitoids need different periods of time to adapt to the novel host (adjustment-hypothesis). Both scenarios should result in a continuous increase of parasitoid richness over time. In this study, we reconstructed the development of the hymenopteran parasitoid complex of the invasive leafminer Cameraria ohridella (Lepidoptera, Gracillariidae). Our results show that the overall parasitism rate increases as a function of host residence time as well as geographic and climatic factors, altogether reflecting the historic spread of C. ohridella. The same variables also explain the individual parasitism rates of several species in the parasitoid complex, but fail to explain the abundance of others. Evidence supporting the “geographic spread-hypothesis” was found in the parasitism pattern of Cirrospilus talitzkii (Hymenoptera, Eulophidae), while that of Pediobius saulius, another eulophid, indicated an increase of parasitism rates by behavioral, phenological or biological adjustments. Compared to fully integrated host-parasitoid associations, however, parasitism rates of C. ohridella are still very low. In addition, the parasitoid complex lacks specialists, provided that the species determined are valid and not complexes of cryptic (and presumably more specialized) species. Probably, the adjustment of specialist parasitoids requires more than a few decades, particularly to invaders which establish in ecological niches free of native hosts, thus eliminating any possibility of recruitment of pre-adapted parasitoids

Epithelial maturation and molecular biology of oral HPV

Human papillomavirus (HPV) is widespread and can cause latent infection in basal cells, with low HPV DNA copy-number insufficient for transmission of infection; can cause subclinical infection that is active but without clinical signs; or can cause clinical infection leading to benign, potentially malignant or malignant lesions. The HPV cycle is influenced by the stage of maturation of the infected keratinocytes, and the production of virions is restricted to the post-mitotic suprabasal epithelial cells where all the virus genes are expressed

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD. © 2021, The Author(s).EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking

The modern view of congenital Сytomegalovirus infection

Congenital cytomegalovirus infection (CMVI) ranks first among congenital infections, making contribution significantly to the variety of congenital defects formation. The review describes in details the pathogenic mechanisms of the virus effects on the fetus and newborn. Congenital CMVI develops as a result of infection of the mother with the virus or its reactivation, causing an active infection. CMV is pantropic. Infected cells acquire the characteristic appearance of an «owl’s eye» due to a 3—4-fold increase in size, and the cytoplasm is visualized only in the form of a thin strip due to the large diameter of the nucleus. With a congenital CMV infection, the virus itself, its DNA or antigens is detected in biological media up to 14—21 days of life. The manifest and asymptomatic form of infection is distinguished.Attention is drawn to the various clinical findings and long-term outcomes of the infection. When the fetus is infected in the early stages of pregnancy, various malformations of the central nervous system, cardiovascular, kidneys, etc. are formed. When infected in the late stages of pregnancy, a variety of diseases and pathological conditions are revealed in newborns. In 40—90% of newborns with manifest CMVI, there are long-term neurological consequences and hearing loss, as well as damage to the organ of vision