ВЛИЯНИЕ СЕВОФЛЮРАНА И АЦЕТИЛЦИСТЕИНА НА ИШЕМИЧЕСКИ-РЕПЕРФУЗИОННОЕ ПОВРЕЖДЕНИЕ ПЕЧЕНИ ДОНОРА СО СМЕРТЬЮ МОЗГА

Aim. The purpose of our work was to estimate the impact of preconditioning with acetylcysteine and sevoflurane on ischemia-reperfusion injury of cadaveric donor liver with marginal features. Methods and results. In this prospective randomized controlled trial we recruited 21 heart beating donors with brain death. We assigned 11 donors to the study group, and 10 donors to the control group. Morphological characteristics of ischemia- reperfusion injury in both groups were analyzed. Conclusion. Use of pharmacological preconditioning with acetylcysteine and sevoflurane resulted in necrosis and hepatocyte apoptosis reduction as compared to the control group, thereby had a protective effect against ischemia-reperfusion injury. Целью нашей работы явилась оценка влияния прекондиционирования ацетилцистеином и севофлюра- ном на степень ишемически-реперфузионного повреждения печени умерших доноров с признаками мар- гинальности. Методы и результаты. Дизайн исследования – проспективное, контролируемое, рандо- мизированное исследование. Исследование было проведено на 21 доноре с умершим головным мозгом и бьющимся сердцем. В основную группу исследования вошли 11 доноров, в контрольную группу 10. В основной группе определялись морфологические признаки ишемически-реперфузионного поврежде- ния после прекондиционирования ацетилцистеином и севофлюраном, в группе сравнения – без прекон- диционирования. Заключение. Применение фармакологического прекондиционирования севофлюраном и ацетилцистеином достоверно привело к уменьшению степени некроза и апоптоза гепатоцитов по срав- нению с группой сравнения, т. е. обладает протективным эффектом от ишемически-реперфузионного повреждения.

The Lsm1-7/Pat1 complex binds to stress-activated mRNAs and modulates the response to hyperosmotic shock

RNA-binding proteins (RBPs) establish the cellular fate of a transcript, but an understanding of these processes has been limited by a lack of identified specific interactions between RNA and protein molecules. Using MS2 RNA tagging, we have purified proteins associated with individual mRNA species induced by osmotic stress, STL1 and GPD1. We found members of the Lsm1-7/Pat1 RBP complex to preferentially bind these mRNAs, relative to the non-stress induced mRNAs, HYP2 and ASH1. To assess the functional importance, we mutated components of the Lsm1-7/Pat1 RBP complex and analyzed the impact on expression of osmostress gene products. We observed a defect in global translation inhibition under osmotic stress in pat1 and lsm1 mutants, which correlated with an abnormally high association of both non-stress and stress-induced mRNAs to translationally active polysomes. Additionally, for stress-induced proteins normally triggered only by moderate or high osmostress, in the mutants the protein levels rose high already at weak hyperosmosis. Analysis of ribosome passage on mRNAs through co-translational decay from the 5' end (5P-Seq) showed increased ribosome accumulation in lsm1 and pat1 mutants upstream of the start codon. This effect was particularly strong for mRNAs induced under osmostress. Thus, our results indicate that, in addition to its role in degradation, the Lsm1-7/Pat1 complex acts as a selective translational repressor, having stronger effect over the translation initiation of heavily expressed mRNAs. Binding of the Lsm1-7/Pat1p complex to osmostress-induced mRNAs mitigates their translation, suppressing it in conditions of weak or no stress, and avoiding a hyperresponse when triggered

International consensus statement for the screening, diagnosis, and treatment of adolescents with concurrent Attention-Deficit/Hyperactivity Disorder and substance use disorder

Education and Child Studie

Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis

Objective: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. / Methods: A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty‐four clinical and serologic variables were used for clustering. / Results: Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. / Conclusion: Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis

Mental health interventions for traumatized asylum seekers and refugees: What do we know about their efficacy?

Background: The prevalence of trauma-related problems among refugees and asylum seekers is extremely high due to adverse experiences associated with forced migration. Although the literature presents a considerable number of guidelines and theoretical frameworks for working with traumatized refugees and asylum seekers, the efficacy, feasibility and applicability of these interventions have little empirical evidence. Aims: The purpose of this article is to critically review the literature to provide a rationale for developing culturally sensitive, evidence-based interventions for refugees and asylum seekers. Methods: A literature review integrating research findings on interventions designed especially for traumatized asylum seekers and refugees was conducted. Retained studies had to use some quantitative measurements of post-traumatic stress and to have pre- and post-measurements to evaluate the efficacy of the intervention. Studies included in this review cover a wide variety of interventions, including trauma-focused interventions, group therapy, multidisciplinary interventions and pharmacological treatments. Results: The majority of studies with traumatized refugees and asylum seekers reported positive outcomes of the intervention in reducing trauma-related symptoms. There is evidence to support the suitability of cognitive-behavioral therapy (CBT) and narrative exposure therapy (NET) in certain populations of refugees. Other intervention studies are limited by methodological considerations, such as lack of randomization, absence of control group and small samples. Conclusions: This review has again highlighted the shortage of guiding frameworks available to investigators and clinicians who are interested in tailoring interventions to work with refugees and asylum seekers. Theoretical, ethical and methodological considerations for future research are discussed

Clinical and Neurological Features of the Course and Cognitive Impairment in Orthostatic Hypotension in Patients with Neurodegenerative Diseases

Aim: To optimize the diagnostics of cognitive impairments in patients with neurodegenerative diseases and orthostatic hypotension, based on the estimation of the character of interrelations between clinical-pathogenetic features, degree of cognitive functions impairments and several indices of hemodynamics.Materials and methods. There was realized the general clinical, neurological examination, neuropsychological testing: MMSE, MoCA, FAB, test of memorization of 12 words, drawing of a watch, phonetic speed of speech, semantic speed of speech; orthostatic test. There were examined 105 patients: the first group – patients with AD (33 patients), the second – with PD (35 patients), the third, control group (37 examined persons) – practically healthy people. Groups 1 and 2 were divided in the subgroup А (with orthostatic hypotension) and the subgroup B (with the normal orthostatic reaction).Results. The clinical picture of patients of the subgroup A demonstrated complaints, typical for OH episodes, reliably more often than the one of the subgroup B and control. Complaints for the memory worsening and difficulties at trying to choose a proper word, falling were observed statistically reliably more often in patients with PD and OH. Positive axial reflexes, revival of tendon and periosteal reflexes were revealed more often in the subgroup 1A than in 1B at the neurological examination; in the subgroup 2А – nystagmus, positive axial reflexes, postural instability.According to the results of the neuropsychological test, points of MoCA scale, test of semantic speed of speech, memorization of 12 words; memory and attention domains by subtests of MoCA scale in patients of 1A group were statistically reliably less than in 1B subgroup. Points of patients of 2A subgroup were statistically reliably less than in 2B subgroup by MoCA, FAB scales, by the test of phonetic speed of speech, semantic speed of speech, memorization of 12 words; by subtests of ruling functions, memory and attention of MoCA scale .Conclusions 1. MoCA scale, test of drawing a watch, test of memorization of 12 words, test for semantic and phonetic speed of speech turned out to be more sensitive at orthostatic hypotension.2. At orthostatic hypotension impairments in domains of memory, attention, speech, occur more often in patients with Alzheimer's disease, in ones with Parkinson disease – impairments of memory, attention, ruling functions, thinkin