Organization and development of cholinergic input to the mouse visual thalamus.

Cholinergic signaling plays a vital role in modulating the flow of sensory information through thalamic circuits in a state-dependent manner. In the dorsal lateral geniculate nucleus (dLGN), the thalamic visual relay, release of acetylcholine (ACh) contributes to enhanced thalamocortical transfer of retinal signal during behavioral states of arousal, wakefulness, and sleep/wake transitions. Moreover, ACh modulates activity of the thalamic reticular nucleus (TRN), a structure which provides inhibitory input to dLGN. While several cholinergic nuclei have been shown to innervate dLGN and TRN, it is unclear how projections from each area are organized. Furthermore, little is known of how or when cholinergic fibers arrive and form functional synapses during development. To address these questions, we used a genetically modified mouse (ChAT-Cre) mouse to selectively visualize cholinergic projections to dLGN and TRN. We conducted anterograde viral tracing, demonstrating a mainly contralateral cholinergic projection from the parabigeminal nucleus to dLGN. In addition, we saw a sparse ipsilateral projection from the rostral pedunculopontine tegmentum to dLGN and TRN. Next, we used a fluorescent reporter line (Ai9) to visualize cholinergic innervation in dLGN and TRN during early postnatal life. In dLGN, innervation began by the end of the first week, increased steadily with age, and reached an adult-like state by the end of the first month. Furthermore, using a model of visual deafferentation (math5-/-), we showed that the absence of retinal input resulted in disruptions in the trajectory, rate, and pattern of cholinergic innervation in dLGN. In TRN, innervation began during week 1 in the ventral non-visual sectors, proceeded into the dorsal visual sector during week 2, and reached adult-like levels by week 3. To assess the functional maturation of cholinergic synapses within TRN, we used a channelrhodopsin-2 reporter and selectively stimulated cholinergic afferents while conducting recordings from TRN neurons. Postsynaptic responses appeared in non-visual sectors of TRN during the first postnatal week, and in the visual sector by week 2. By the end of the first month, all sectors of TRN exhibited adult-like biphasic responses. Together, these studies shed light on the organizational pattern and developmental progression of cholinergic input to the visual thalamus

About Testing the Hypothesis of Equality of Two Bernoulli Regression Curves

The limiting distribution of an integral square deviation between two kernel type estimators of Bernoulli regression functions is established in the case of two independent samples. The criterion of testing is constructed for both simple and composite hypotheses of equality of two Bernoulli regression functions. The question of consistency is studied. The asymptotics of behavior of the power of test is investigated for some close alternatives. Keywords: Bernoulli Regression Function, Power of Test, Consistency, Composite Hypothesi

Estimation of a distribution function by an indirect sample

The problem of estimation of a distribution function is considered in the case where the observer has access only to a part of the indicator random values. Some basic asymptotic properties of the constructed estimates are studied. The limit theorems are proved for continuous functionals related to the estimation of F^n(x) in the space C[a, 1 - a], 0 < a < 1/2.Розглянуто задачу оцінювання функції розподілу у випадку, коли спостерігач має доступ лише до деяких індикаторних випадкових значень. Вивчено деякі базові асимптотичні властивості побудованих оцінок. У статгі доведено граничні теореми для неперервних функціоналів щодо оцінки Fn(x) у просторі C[a,1−a],0 < a < 1/2

Reproductive function and pregnancy outcomes in women treated for idiopathic hyperprolactinemia: A non-randomized controlled study

Background: Few studies have focused to determine the peculiarities of the course of pregnancy and pregnancy outcomes after treatment in women with idiopathic hyperprolactinemia. Objective: To determine the peculiarities of the course of pregnancy and pregnancy outcomes in women treated for idiopathic hyperprolactinemia, with history of infertility and/or recurrent pregnancy loss. Materials and Methods: A non-randomized controlled study was conducted at the Center for Reproductive Medicine “Universe” and Medical Clinic “Medhealth” during 2016-2018, involving 96 women with idiopathic hyperprolactinemia, aged 20-44 yr with infertility and/or a history of recurrent pregnancy loss. Prolactin (PRL), follicle-stimulating hormone, luteinizing hormone, estradiol (E2), free testosterone, and progesterone were studied in blood serum using immunoassay analysis method. Before the occurrence of pregnancy, hyperprolactinemia was treated with bromocriptine. Dydrogesterone was used to support the luteal phase. Results: PRL levels decreased significantly and normalized within two-five months, regular menstrual cycle was restored in two-four months, ovulation was restored in three-seven months, and pregnancy was achieved in three-fourteen months. E2 and progesterone levels increased significantly (p &lt; 0.001). Prior to the treatment, significant negative correlation between PRL and E2 (r = -0.386, p = 0.007), PRL and progesterone (r = -0.420, p = 0.003) was detected. Threatened early abortion prevailed among pregnancy complications. Pregnancy loss in the first trimester was recorded in 3.12% of cases. Conclusion: Pregnancy outcomes in women with idiopathic hyperprolactinemia are improved by prolonged and continuous treatment with bromocriptine before pregnancy and administration of dydrogesterone in support of the luteal insufficiency. Key words: Hyperprolactinemia, Pregnancy outcome, Bromocriptine, Dydrogesterone

СОЦИАЛЬНАЯ АКТИВНОСТЬ РОССИЙСКОЙ МОЛОДЕЖИ: МАСШТАБЫ И ФАКТОРЫ СДЕРЖИВАНИЯ

In recent years, both experts and public opinion tend to assess the involvement of the Russian youth in social activities as rather low: the post-Soviet generations are called apolitical and indifferent to anything except personal well-being and interests. At the same time, the largest research centers (Public Opinion Foundation, Russian Public Opinion Research Center, Levada Center, and Institute of Sociology) conduct sociological studies of various aspects of social and civil activities, political participation and protest potential of younger generations and Russian society as a whole. The article presents some recent data that prove the low level of political and social activity of the Russian population. The author believes that this level is higher among the younger generations, especially the students. To prove that, first, the author considers the category 'social activity': its motives (primarily socially significant needs), subjective 'measurement' (personal needs and interests), goals (pragmatic and altruistic, collective and personal, etc.), forms (personal, collective, etc.) and external and internal factors. Secondly, to assess the motives and restraining factors of the youth social activity, the article presents some results of the surveys conducted in the RUDN University and of the Russian public opinion polls. The author identifies reasons for the youth's lack of interest in public activities (lack of material benefits, desire/time/motivation, information, and negative image of public associations), motives of social activity (social, selective, mobilization, etc.) and for becoming a member of public associations (self-realization, the desire to change the world, combination of the two, etc.), and factors that determine the youth's perception of social activity in general (estimates of social situation, value orientations and social well-being).В последние годы экспертные и обыденные оценки вовлеченности российской молодежи в об-щественную деятельность мало расходятся: постсоветские поколения называют аполитичными, ин-дифферентными, безразличными к чему бы то ни было, кроме личного благополучия и интересов. В то же время изучением разных аспектов социальной и гражданской активности, политического участия и протестного потенциала не только молодежи, но российского общества в целом занима-ются крупнейшие исследовательские центры (Фонд «Общественное мнение», Всероссийский центр изучения общественного мнения, Левада-Центр, Институт социологии Российской академии наук), и в статье представлены их опросные данные за несколько последних лет, позволяющие диагности-ровать весьма низкий уровень политической вовлеченности и социальной активности российского населения. Полагая, что этот показатель может оказаться существенно выше для молодых поколе-ний, особенно студенчества, автор предпринимает два последовательных шага. Во-первых, про-рабатывает категорию «социальная активность», уточняя ее содержательное наполнение, в том числе движущие мотивы (в первую очередь, социально значимые потребности), субъектное «изме-рение» (личные потребности и интересы), типы целей (прагматичные и альтруистичные, коллек-тивные и личностные и т.д.), формы осуществления (личностная, групповая и др.) и внешние и внут-ренние факторы. Во-вторых, чтобы оценить мотивы и сдерживающие факторы вовлечения молодежи в общественную деятельность и обоснованность оценок молодых поколений как индифферентных, в статье представлены результаты ряда опросов, проведенных на выборке студентов Российского университета дружбы народов, которые подкреплены данными опросов общественного мнения. Автор уточняет причины незаинтересованности молодежи в общественной деятельности (отсутствие материальной выгоды; отсутствие интереса/желания/времени/мотивации; плохая информирован-ность; негативный образ общественных объединений), мотивы социальной активности (социальные, селективные, компетентностные, мобилизационные) и вступления в общественные объединения (самореализация; желание изменить мир; сочетание того и другого; совпадение личных интересов с деятельностью организации), а также факторы, определяющие отношение молодежи к общест-венной деятельности в целом (оценки ситуации в обществе, ценностные ориентации и социаль-ное самочувствие)

Integral Functionals of the Gasser–Muller Regression Function

For integral functionals of the Gasser–Muller regression function and its derivatives, we consider the plug-in estimator. The consistency and asymptotic normality of the estimator are shown.Для інтегральних функцiоналiв Функції регресії Гассера-Мюллера та їх похідних розглядається оцінка, що підключається. Встановлено обґрунтованість та асимптотичну нормальність цієї оцінки

Immune, Autonomic, and Endocrine Dysregulation in Autism and Ehlers-Danlos Syndrome/Hypermobility Spectrum Disorders Versus Unaffected Controls

Background: A growing body of literature suggests etiological overlap between Ehlers-Danlos syndrome (EDS)/hypermobility spectrum disorders (HSD) and some cases of autism, although this relationship is poorly delineated. In addition, immune, autonomic, and endocrine dysregulation are reported in both conditions and may be relevant to their respective etiologies. Aims: To study symptom overlap in these two comorbid spectrum conditions. Methods and Procedures: We surveyed 702 adults aged 25+ years on a variety of EDS/HSD-related health topics, comparing individuals with EDS/HSD, autism, and unaffected controls. Outcomes and Results: The autism group reported similar though less severe symptomology as the EDS/HSD group, especially in areas of immune/autonomic/endocrine dysregulation, connective tissue abnormalities (i.e., skin, bruising/bleeding), and chronic pain. EDS/HSD mothers with autistic children reported more immune symptoms than EDS/HSD mothers without, suggesting the maternal immune system could play a heritable role in these conditions (p = 0.0119). Conclusions and Implications: These data suggest that EDS/HSD and autism share aspects of immune/autonomic/endocrine dysregulation, pain, and some tissue fragility, which is typically more severe in the former. This overlap, as well as documented comorbidity, suggests some forms of autism may be hereditary connective tissue disorders (HCTD)

The Role of Opportunistic Microflora in the Development of Pre-term Delivery and Late Abortions

Purpose: Estimation of correction efficiency of a microbiocenosis of a vagina at pregnant women in risk group with application Vaginorma-C.Materials and Methods: 171 woman with interrupted pregnancy in II trimester were studied. An expanded patomorphological research of fetoplacental material was carried.Results: The given pathology is caused in 82% of cases by an placenta infection with conditional-pathogenic microflora. In 70% of cases bacterial vaginosis was founded. The risk of premature birth and amniorrhea increase in 2,6-3 times.Summary: The new approach to the preventive measures was suggested during the bacterialveginosis – oxidation of vaginal medium with the usage of the drug Vaginorm-С

ЭЭГ БИОУПРАВЛЕНИЕ УЛУЧШАЕТ СФОКУСИРОВАННОЕ ВНИМАНИЕ ПРИ СИНДРОМЕ ДЕФИЦИТА ВНИМАНИЯ И ГИПЕРАКТИВНОСТИ

EEG biofeedback (so called neurofeedback) is considered as an efficacious treatment for ADHD. We propose that operant conditioning of EEG in neurofeedback training mode, aimed to mitigate inattention and low arousal in ADHD, will be accompanied by changes in EEG bands' relative power. Patients were 18 children diagnosed with ADHD. The neurofeedback protocol (“Focus/Alertness” by Peak Achievement Trainer, Neurotek, KY) used to train patients has focused attention training procedure, which according to specifications, represents wide band EEG amplitude suppression training. Quantitative EEG analysis was completed on each of 25 min long twelve sessions to determine the relative power of each of the EEG bands of interest throughout each session, and from the first session to the last session. Additional statistical analysis was performed to determine significant changes in relative power within sessions (from minute 1 to minute 25), and between sessions (from session 1 to session 12) for an individual patient. We performed analysis of relative power of Theta, Alpha, Low and High Beta, Theta/Alpha, Theta/Beta, and Theta/Low Beta and Theta/High Beta ratios. We performed also analysis between the “Focus”measure and changes in relative power of above EEG rhythms and their ratios. Additional secondary measures of patients’ post-neurofeedback outcomes were assessed using an audio-visual selective attention test (IVA + Plus) and behavioral evaluation scores from Aberrant Behavior Checklist. We found that, as expected, Theta/Low Beta and Theta/Alpha ratios decreased significantly from Session 1 to Session 12 and from minute 1 to minute 25 within sessions. The ‘Focus” measure of protocol showed high negative correlation with both Theta/Alpha and Theta/Beta ratios. The findings regarding EEG changes resulting from self-regulation training along with behavioral evaluations will help in elucidation of neural mechanisms of neurofeedback aimed to improve focused attention and alertness in ADHD.Электроэнцефалографическое биоуправление, или нейробиоуправление, – эффективная технология при лечении синдрома дефицита внимания и гиперактивности (СДВГ). Предполагалось, что оперантное обусловливание электроэнцефалографии (ЭЭГ) в тренинге нейробиоуправления, направленном на снижение невнимательности и низкой активности детей с СДВГ, будет сопровождаться изменениями относительной мощности в разных ЭЭГ-частотных диапазонах. Пациентами были 18 детей с диагнозом «синдром дефицита внимания и гиперактивности». Протокол нейробиоуправления (Focus/Alertness, Peak Achievement Trainer, Neurotek, KY), используемый для тренинга, включал обучающие процедуры фокусировки внимания, которые, согласно спецификации, представляли собой интерактивные процедуры, направленные на подавление амплитуды в широком ЭЭГ-диапазоне. Количественный анализ ЭЭГ был проведен для двенадцати 25-минутных сессий, чтобы определить относительную мощность каждого из интересующих частотных диапазонов ЭЭГ в ходе каждой сессии, а также с первой по последнюю сессию. Проведен дополнительный статистический анализ определения значимых изменений относительной мощности внутри сессии (от 1-й до 25-й мин) и в период между сессиями (от 1-й до 12-й мин) для конкретного пациента. Проанализированы относительная мощность в диапазонах тета, альфа, низкочастотного и высокочастотного бета, а также их соотношений: тета/альфа, тета/бета, тета/низкочастотный бета и тета/высокочастотный бета. Сравнивались динамика показателя «фокус» и изменения относительной мощности вышеперечисленных ритмов ЭЭГ и их соотношений.Дополнительные повторные измерения результатов нейробиоуправления у пациентов оценивались с использованием аудиовизуального теста селективного внимания (IVA + Plus) и поведенческих оценок из опросника Aberrant Behavior Checklist. Как и ожидалось, соотношения диапазонов тета/низкочастотный бета и тета/альфа значимо снижались с 1-й до 12-й сессии и с 1-й до 25-й мин внутри сессии. Показатель «фокус» в протоколе обнаружил высокую отрицательную корреляцию как с тета/альфа-, так и с тета/бета-коэффициентами. Полученные результаты, касающиеся изменений ЭЭГ вследствие обучения саморегуляции, наряду с поведенческими оценками могут способствовать выяснению нейрональных механизмов нейробиоуправления, направленных на увеличение фокусировки внимания и активности при СДВГ

Moral enhancement: do means matter morally?

One of the reasons why moral enhancement may be controversial, is because the advantages of moral enhancement may fall upon society rather than on those who are enhanced. If directed at individuals with certain counter-moral traits it may have direct societal benefits by lowering immoral behavior and increasing public safety, but it is not directly clear if this also benefits the individual in question. In this paper, we will discuss what we consider to be moral enhancement, how different means may be used to achieve it and whether the means we employ to reach moral enhancement matter morally. Are certain means to achieve moral enhancement wrong in themselves? Are certain means to achieve moral enhancement better than others, and if so, why? More specifically, we will investigate whether the difference between direct and indirect moral enhancement matters morally. Is it the case that indirect means are morally preferable to direct means of moral enhancement and can we indeed pinpoint relevant intrinsic, moral differences between both? We argue that the distinction between direct and indirect means is indeed morally relevant, but only insofar as it tracks an underlying distinction between active and passive interventions. Although passive interventions can be ethical provided specific safeguards are put in place, these interventions exhibit a greater potential to compromise autonomy and disrupt identity