Мои воспоминания об Иване Георгиевиче Спасском

Стислі спогади автора про відомого вченого-нумізмата й музейника І.Г. Спаського та його сім’ю.Краткие воспоминания автора об известном ученом-нумизмате и музейщике И.Г. Спасском и его семье.Short author’s memories about known scientist-numismatist and museum-worker I.G. Spassky and his family

Influence of freedom of movement on the health of people with demnetia:A systematic review

Background and Objectives To protect residents with dementia from harm, nursing homes (NHs) often have closed-door policies. However, current research suggests a positive influence of freedom of movement, that is, the right to (decide to) independently move from one place to another, on the health of NH residents with dementia. This systematic review aims to collate, summarize, and synthesize the scientific evidence published to date on the influence of freedom of movement on health among NH residents with dementia. Research Design and Methods Multiple databases were searched up until March 2021. Peer-reviewed qualitative, quantitative, and mixed methods studies were included. Health was operationalized using the Positive Health framework, encompassing 6 dimensions: bodily functions, mental functions and perception, existential dimension, quality of life, social and societal participation, and daily functioning. The quality of included studies was assessed using the Mixed Methods Appraisal Tool. Results Sixteen studies were included of good to excellent quality. Compared to closed NHs, freedom of movement in semiopen and open NHs may have a positive influence on bodily functions, mental functions and perception, quality of life, and social and societal participation. The influence on daily functioning and on the existential dimension remains unclear. Discussion and Implications Freedom of movement of NH residents with dementia is often studied as part of a larger context in which other factors may contribute to health benefits. More research is therefore needed to unravel the underlying mechanisms of the positive influence of freedom of movement on health

Acute and long-lasting effects of oxytocin in cortico-limbic circuits: consequences for fear recall and extinction.

The extinction of conditioned fear responses entrains the formation of safe new memories to decrease those behavioral responses. The knowledge in neuronal mechanisms of extinction is fundamental in the treatment of anxiety and fear disorders. Interestingly, the use of pharmacological compounds that reduce anxiety and fear has been shown as a potent co-adjuvant in extinction therapy. However, the efficiency and mechanisms by which pharmacological compounds promote extinction of fear memories remains still largely unknown and would benefit from a validation based on functional neuronal circuits, and the neurotransmitters that modulate them. From this perspective, oxytocin receptor signaling, which has been shown in cortical and limbic areas to modulate numerous functions (Eliava et al. Neuron 89(6):1291-1304, 2016), among them fear and anxiety circuits, and to enhance the salience of social stimuli (Stoop Neuron 76(1):142-59, 2012), may offer an interesting perspective. Experiments in animals and humans suggest that oxytocin could be a promising pharmacological agent at adjusting memory consolidation to boost fear extinction. Additionally, it is possible that long-term changes in endogenous oxytocin signaling can also play a role in reducing expression of fear at different brain targets. In this review, we summarize the effects reported for oxytocin in cortico-limbic circuits and on fear behavior that are of relevance for the modulation and potential extinction of fear memories

Reduced TCR-dependent activation through citrullination of a T-cell epitope enhances Th17 development by disruption of the STAT3/5 balance

Citrullination is a post-translational modification of arginine that commonly occurs in inflammatory tissues. Because T-cell receptor (TCR) signal quantity and quality can regulate T-cell differentiation, citrullination within a T-cell epitope has potential implications for T-cell effector function. Here, we investigated how citrullination of an immunedominant T-cell epitope affected Th17 development. Murine na¨ıve CD4+ T cells with a transgenic TCR recognising p89-103 of the G1 domain of aggrecan (agg) were co-cultured with syngeneic bone marrow-derived dendritic cells (BMDC) presenting the native or citrullinated peptides. In the presence of pro-Th17 cytokines, the peptide citrullinated on residue 93 (R93Cit) significantly enhanced Th17 development whilst impairing the Th2 response, compared to the native peptide. T cells responding to R93Cit produced less IL-2, expressed lower levels of the IL-2 receptor subunit CD25, and showed reduced STAT5 phosphorylation, whilst STAT3 activation was unaltered. IL-2 blockade in native p89-103-primed T cells enhanced the phosphorylated STAT3/STAT5 ratio, and concomitantly enhanced Th17 development. Our data illustrate how a post-translational modification of a TCR contact point may promote Th17 development by altering the balance between STAT5 and STAT3 activation in responding T cells, and provide new insight into how protein citrullination may influence effector Th-cell development in inflammatory disorders

Safety risks among frail older people living at home in the Netherlands:A cross‐sectional study in a routine primary care sample

Frail older people face a range of problems and risks that could undermine their ability to live safely at home. A comprehensive overview of these risks, from a multidimensional perspective, is currently lacking. This study aims to examine the prevalence of risks in multiple domains of life among frail older people living at home. We used cross‐sectional data from 824 people aged 65 years and older, who received a comprehensive geriatric assessment (the interRAI Home Care [interRAI‐HC]) between 2014 and 2018, as part of routine care from 25 general practices in the region of West‐Friesland, the Netherlands. The interRAI‐HC identifies amenable risks related to people's clinical conditions, functioning, lifestyle and behaviour, and social and physical environment. Descriptive statistics were used to examine population characteristics (age, gender, marital status, living arrangements and presence of chronic conditions) and prevalence of risks. Most common risks were related to people's clinical conditions (i.e cardio‐respiratory health, urinary incontinence, pain), functioning (i.e. limitations in instrumental activities of daily living and mood) and social environment (i.e. limitations in informal care and social functioning). More than 80% of frail older people faced multiple risks, and often on multiple domains of life simultaneously. People experiencing multiple risks per person, and on multiple domains simultaneously, were more often widowed and living alone. The multidimensional character of risks among frail older people living at home implies that an integrated approach to care, comprising both health and social care, is necessary. Insight in the prevalence of these risks can give direction to care allocation decisions

Mannitol transport and mannitol dehydrogenase activities are coordinated in olea europaea under salt and osmotic stresses

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Plant and Cell Physiology following peer review. The definitive publisher-authenticated version is available online at http://pcp.oxfordjournals.org/cgi/content/abstract/pcr121? ijkey=6orgUM5fkIjedYn&keytype=refThe intracellular accumulation of organic compatible solutes functioning as osmoprotectants, such as polyols, is an important response mechanism of several plants to drought and salinity. In Olea europaea a mannitol transport system (OeMaT1) was previously characterised as a key player in plant response to salinity. In the present study, heterotrophic sink models, such as olive cell suspensions and fruit tissues, and source leaves were used for analytical, biochemical and molecular studies. The kinetic parameters of mannitol dehydrogenase (MTD) determined in mannitol-growing cells, at 25 °C and pH 9.0, were as follows: Km, 54.5 mM mannitol and Vmax, 0.47 μmol h-1 mg-1 protein. The corresponding cDNA was cloned and named OeMTD1. OeMTD1 expression was correlated with MTD activity, OeMaT1 expression and carrier-mediated mannitol transport, in mannitol- and sucrose-growing cells. Furthermore, sucrosegrowing cells displayed only residual OeMTD activity, even though high levels of OeMTD1 transcription were observed. There is evidence OeMTD is regulated at both transcriptional and post-transcriptional levels. MTD activity and OeMTD1 expression were repressed after Na+, K+ and PEG treatments, both in mannitol- and sucrose-growing cells. In contrast, salt and drought significantly increased mannitol transport activity and OeMaT1 expression. Altogether, these studies support that olive tree copes with salinity and drought by coordinating mannitol transport with intracellular metabolism.This work was supported by the Portuguese Foundation for Science and Technology (FCT) (research project ref. PTDC/AGR-ALI/100636/2008; to A. Conde, grant ref. SFRH/BD/47699/2008; to C. Conde, grant ref. SFRH/BPD/34998/2007; to P. Silvagrant ref. SFRH/BD/13460/2003)

Molecular determinants of treatment response in human germ cell tumors

PURPOSE: Germ cell tumors (GCTs) are highly sensitive to cisplatin-based chemotherapy. This feature is unexplained, as is the intrinsic chemotherapy resistance of mature teratomas and the resistant phenotype of a minority of refractory GCTs. Various cellular pathways may influence the efficacy of chemotherapy. Their impact has not been investigated in a comprehensive study of tumor samples from clinically defined subgroups of GCT patients. EXPERIMENTAL DESIGN: We investigated proteins involved in regulation of apoptosis (p53, BAX, BCL-2, and BCL-X(L)), cell cycle control [p21 and retinoblastoma protein (RB)], and drug export and inactivation [P-glycoprotein, multidrug resistance-associated protein (MRP) 1, MRP2, breast cancer resistance protein, lung resistance protein, metallothionein, and glutathione S-transferase pi] immunohistochemically in samples of unselected GCT patients (n = 20), patients with advanced metastatic disease in continuous remission after first-line chemotherapy (n = 12), and chemotherapy-refractory patients (n = 24). Mature teratoma components (n = 10) within tumor samples from all groups were analyzed separately. The apoptotic index was studied by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. RESULTS: Invasive GCTs of all groups showed a correlation between wild-type p53 and apoptotic index (r(s) = 0.66; P < 0.001). The levels of the antiapoptotic proteins BCL-2 and BCL-X(L) were generally low. p21 was hardly detectable and did not correlate with p53 (r(s) = 0.29; P = 0.07). No significant differences among the three patient groups were identified regarding any of the investigated parameters (all Ps were >0.08), even though only individual samples from chemotherapy-resistant cases showed a strong staining for MRP2 and GSTpi. In contrast to other components, mature teratomas showed an intense p21 and RB staining and were mostly positive for MRP2, lung resistance protein, and GSTpi. CONCLUSIONS: Our results indicate a multifactorial basis for the chemosensitivity of GCTs with lack of transporters for cisplatin, of antiapoptotic BCL-2 family members, of p21 induction by p53, and of RB and an intact apoptotic cascade downstream of p53. These findings suggest a preference for apoptosis over cell cycle arrest after up-regulation of p53. None of the examined parameters offers a general explanation for the chemotherapy-resistant phenotype of refractory tumors. The up-regulation of various factors interfering with chemotherapy efficacy and ability for a p21-induced cell cycle arrest may explain the intrinsic chemotherapy resistance of mature teratomas

The Academic Collaborative Center Older Adults:A description of co-creation between science, care practice and education with the aim to contribute to person-centered care for older adult

Long-term care for older adults is in transition. Organizations offering long-term care for older adults are expected to provide person-centered care (PCC) in a complex context, with older adults aging in place and participating in society for as long as possible, staff shortages and the slow adoption of technological solutions. To address these challenges, these organizations increasingly use scientific knowledge to evaluate and innovate long-term care. This paper describes how co-creation, in the sense of close, intensive, and equivalent collaboration between science, care practice, and education, is a key factor in the success of improving long-term care for older adults. Such co-creation is central in the Academic Collaborative Center (ACC) Older Adults of Tilburg University. In this ACC, Tilburg University has joined forces with ten organizations that provide care for older adults and CZ zorgkantoor to create both scientific knowledge and societal impact in order to improve the quality of person-centered care for older adults. In the Netherlands, a “zorgkantoor” arranges long-term (residential) care on behalf of the national government. A zorgkantoor makes agreements on cost and quality with care providers and helps people that are in need of care to decide what the best possible option in their situation is. The CZ zorgkantoor arranges the long-term (residential) care in the south and southwest of the Netherlands. This paper describes how we create scientific knowledge to contribute to the knowledge base of PCC for older adults by conducting social scientific research in which the perspectives of older adults are central. Subsequently, we show how we create societal impact by facilitating and stimulating the use of our scientific knowledge in daily care practice. In the closing section, our ambitions for the future are discussed