Mathematical model of elastic ribbed shell dynamics interaction with viscous liquid under vibration

The mechanical model of the system, formed by two surfaces of the coaxial cylindrical shells interacting with viscous incompressible liquid between them under vibration, is considered. The outer shell is geometrically irregular, and inner one is an absolutely rigid cylinder. The mathematical model of this system, consisting of differential equations in partial derivatives for describing dynamics of viscous incompressible liquid and an elastic ribbed shell together with boundary conditions is constructed. The expressions for amplitude frequency characteristics of outer geometrically irregular shell are discovered

Perspectives of healthcare providers, service users, and family members about mental illness stigma in primary care settings: A multi-site qualitative study of seven countries in Africa, Asia, and Europe

Background: Stigma among healthcare providers is a barrier to the effective delivery of mental health services in primary care. Few studies have been conducted in primary care settings comparing the attitudes of healthcare providers and experiences of people with mental illness who are service users in those facilities. Such research is necessary across diverse global settings to characterize stigma and inform effective stigma reduction. Methods: Qualitative research was conducted on mental illness stigma in primary care settings in one low-income country (Nepal), two lower-middle income countries (India, Tunisia), one upper-middle-income country (Lebanon), and three high-income countries (Czech Republic, Hungary, Italy). Qualitative interviews were conducted with 248 participants: 64 primary care providers, 11 primary care facility managers, 111 people with mental illness, and 60 family members of people with mental illness. Data were analyzed using framework analysis. Results: Primary care providers endorsed some willingness to help persons with mental illness but reported not having appropriate training and supervision to deliver mental healthcare. They expressed that people with mental illness are aggressive and unpredictable. Some reported that mental illness is incurable, and mental healthcare is burdensome and leads to burnout. They preferred mental healthcare to be delivered by specialists. Service users did not report high levels of discrimination from primary care providers; however, they had limited expectations of support from primary care providers. Service users reported internalized stigma and discrimination from family and community members. Providers and service users reported unreliable psychiatric medication supply and lack of facilities for confidential consultations. Limitations of the study include conducting qualitative interviews in clinical settings and reliance on clinician-researchers in some sites to conduct interviews, which potentially biases respondents to present attitudes and experiences about primary care services in a positive manner. Conclusions: Primary care providers' willingness to interact with people with mental illness and receive more training presents an opportunity to address stigmatizing beliefs and stereotypes. This study also raises important methodological questions about the most appropriate strategies to accurately understand attitudes and experiences of people with mental illness. Recommendations are provided for future qualitative research about stigma, such as qualitative interviewing by non-clinical personnel, involving non-clinical staff for recruitment of participants, conducting interviews in non-clinical settings, and partnering with people with mental illness to facilitate qualitative data collection and analysis

Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock

Mice deficient in the circadian transcription factor BMAL1 (brain and muscle ARNT-like protein) have impaired circadian behavior and demonstrate loss of rhythmicity in the expression of target genes. Here we report that Bmal1(−/−) mice have reduced lifespans and display various symptoms of premature aging including sarcopenia, cataracts, less subcutaneous fat, organ shrinkage, and others. The early aging phenotype correlates with increased levels of reactive oxygen species in some tissues of the Bmal1(−/− )animals. These findings, together with data on CLOCK/BMAL1-dependent control of stress responses, may provide a mechanistic explanation for the early onset of age-related pathologies in the absence of BMAL1

BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system

Mammalian CLOCK and BMAL1 are two members of bHLH-PAS-containing family of transcription factors that represent the positive elements of circadian autoregulatory feedback loop. In the form of a heterodimer, they drive transcription from E-box enhancer elements in the promoters of responsive genes. We have examined abundance, posttranslational modifications, cellular localization of endogenous and ectopically expressed CLOCK and BMAL1 proteins. Nuclear/cytoplasm distribution of CLOCK was found to be under circadian regulation. Analysis of subcellular localization of CLOCK in embryo fibroblasts of mice carrying different germ-line circadian mutations showed that circadian regulation of nuclear accumulation of CLOCK is BMAL1-dependent. Formation of CLOCK/BMAL1 complex following ectopic coexpression of both proteins is followed by their codependent phosphorylation, which is tightly coupled to CLOCK nuclear translocation and degradation. This binding-dependent coregulation is specific for CLOCK/BMAL1 interaction, as no other PAS domain protein that can form a complex with either CLOCK or BMAL1 was able to induce similar effects. Importantly, all posttranslational events described in our study are coupled with active transactivation complex formation, which argues for their significant functional role. Altogether, these results provide evidence for an additional level of circadian system control, which is based on regulation of transcriptional activity or/and availability of CLOCK/BMAL1 complex

Содержание нейроспецифических пептидов, маркеров нейромессенджера и нейрорецептора в сыворотке крови детей с вариативными сенсорными расстройствами, легкими когнитивными нарушениями и другой нейропатологией

Background. The role of recently discovered neurospecific peptides in the pathogenesis of acute and progressive neurologic disorders, their neuroprotective features, and possibilities to use them as markers for the course and prognosis of certain diseases have been actively studied in recent decades. However, neurospecific peptides are almost not studied in chronic residual diseases. In our study we measured the levels of neurospecific peptides and some other markers to achieve understanding of general neurophysiological trends in congenital and acquired chronic non-progressive brain pathology with reference to the selection of relevant groups — study objects. Objective. The aim of the study is to study patterns of neurospecific peptides, neurotransmitters and neuroreceptor markers distribution in the serum of children with various pathogenetic variants of chronic neuropathology. Methods. The study included children from 3 to 16 years old with different pathologies. The sample was divided into groups by pathology type: no sensory and neurological disorders, congenital sensory deficit due to mutation of genes expressed and not expressed in the brain, early acquired sensory deficit of multifactorial nature, congenital mild and severe organic disorders of central nervous system (CNS) in residual stage without baseline sensory deficit, acquired functional CNS disorders without baseline organic defect and sensory deficit. The following laboratory data (neurophysiological components) was studied: nerve growth factor, brain-derived neurotropic factor, neurotrophin-3, neurotrophin-4, neuregulin-1-beta-1, beta-secretase, sirtuin-1, synaptophysin, neuronal nitric oxide synthase, and anti-NR2 glutamate receptor antibodies. The parameters of cognitive activity, sense of vision, sense of smell, and acoustic sense were also evaluated. Results. The study included 274 participants. Neuropeptides and markers have shown a variable degree and range in the group spectrum of differences from normal levels. The most variable in the examined sample was NO-synthase, as well as levels of both neurotrophins, beta-secretase, and glutamate receptor marker. All visual deficits were associated with increased NO-synthase levels (p < 0.001). Neuroplasticity peptides (beta-secretase, neurotrophin-3 and 4) have been activated in all pathological conditions. Nerve growth factor and brain-derived neurotropic factor were specifically activated in mild organic CNS lesions (mild cognitive impairments), while neuregulin — in congenital genetically determined visual deficits. There was no specific activation of neuropeptides and NO-synthase level tended to decrease in cases of severe CNS lesions. Conclusion. The study results suggest that all types of early visual impairment are associated with increased physiological neuronal activity, and non-organic neurological functional disorders — mainly with increased physiological synaptic activity. General neuroplasticity processes were activated in all cases of visual deficits but more specific. However, more specific and well-studied processes were activated in mild organic CNS lesions, and neuroplasticity processes did not activate adequately in severe organic CNS lesions probably due to the limited neuronal and synaptic resources.Обоснование. В последние десятилетия активно исследуются вклад недавно открытых нейроспецифических пептидов в патогенез ряда острых и прогрессирующих заболеваний нервной системы, их нейропротективные свойства и возможности их использования для маркирования течения и прогноза некоторых заболеваний. При этом нейроспецифические пептиды почти не изучаются при хронических резидуальных состояниях. В нашем исследовании мы использовали определение уровней нейроспецифических пептидов и некоторых других маркеров для достижения понимания генеральных нейрофизиологических тенденций при врожденной и приобретенной хронической непрогрессирующей патологии мозга на основании подбора соответствующих групп — объектов исследования. Цель исследования — изучить закономерности распределения комплекса нейроспецифических пептидов, маркеров нейромессенджера и нейрорецептора в сыворотке крови детей с различными патогенетическими вариантами хронической нейропатологии. Методы. В исследование были включены дети с различной патологией в возрасте от 3 до 16 лет. Выборка была поделена на группы по типу патологии: отсутствие сенсорных и неврологических нарушений, врожденный сенсорный дефицит вследствие мутации генов, экспрессируемых и не экспрессируемых в мозге, рано приобретенный сенсорный дефицит полиэтиологической природы, врожденные легкие и тяжелые органические нарушения функций центральной нервной системы (ЦНС) в резидуальной стадии без исходного сенсорного дефицита, приобретенные функциональные расстройства ЦНС без исходного органического дефекта и сенсорного дефицита. В батарею измеряемых лабораторно в крови нейрофизиологических компонентов включили фактор роста нервов, нейротрофический фактор мозга, нейротрофин-3, нейротрофин-4, нейрегулин-1-бета-1, бета-секретазу, сиртуин-1, синаптофизин, нейрональную синтазу оксида азота и антитела к глутаматному рецептору NR2. Также оценивались параметры когнитивной деятельности, зрения, обоняния и слухового восприятия. Результаты. В исследование включены 274 участника. Установлено, что нейропептиды и маркеры показали вариативную степень и широту по групповому спектру отличий от нормы. Наиболее изменчивой в обследуемой выборке показала себя NO-синтаза, также часто различались уровни обоих нейротрофинов, бета-секретазы и маркера рецептора глутамата. При любых дефицитах зрения с большой достоверностью был повышен уровень NO-синтазы (р < 0,001). При всех патологических состояниях активировались пептиды нейропластичности — бета-секретаза, нейротрофины-3 и -4. При легких органических поражениях ЦНС (легкие когнитивные нарушения) специфично активировались фактор роста нервов и мозговой нейротрофический фактор, а при врожденных генетически детерминированных зрительных дефицитах специфично активировался нейрегулин. При тяжелых поражениях ЦНС специфической активации нейропептидов не определялось, а уровень NO-синтазы демонстрировал тенденцию к снижению по сравнению с нормой. Заключение. Результаты исследования позволяют предположить, что при всех типах раннего слабовидения происходит повышенная напряженность физиологической нейрональной деятельности, а при неорганических неврологических функциональных расстройствах — преимущественно повышение физиологической синаптической активности. При всех дефицитах зрения активированы процессы общей нейропластичности, но более специфические и изученные из них активируются при легких органических поражениях ЦНС, при тяжелых же органических поражениях ЦНС процессы нейропластичности недостаточно активны, вероятно, вследствие ограниченности нейрональных и синаптических ресурсов