Uncovering the role of G9a modulatory landscape promoting neuronal plasticity and neuroprotection in Alzheimer's disease

Epigenetic alterations are a fundamental pathological hallmark of Alzheimer’s disease (AD). Herein, we uncover the unknown G9a modulation pathways involved in AD, showing the upregulation of G9a and H3K9me2 in the brains of AD patients. Likewise, treatment with a G9a inhibitor in SAMP8 mice reversed the high levels of H3K9me2 and rescued the cognitive decline. Interestingly, a transcriptional profile analysis revealed induction of neuronal plasticity and a reduction of oxidative stress and neuroinflammation; the latter being also validated in cell cultures. Furthermore, an exploratory H3K9me2 ChIP-seq analysis demonstrated that during G9a inhibition treatment, the H3K9me2 mark is enriched at the promoter of genes associated with neural functions. Lastly, we showed in Caenorhabditis elegans (C. elegans) AD transgenic strains, similar epigenetic modifications and modulated pathways were altered with increased β-amyloid levels, which were reverted by the set-25 (in C. elegans is similar to the mammalian G9a protein) knockout, including the cognitive impairment. Therefore, our findings confirm that RNAi suppression of set-25 or pharmacological G9a inhibition promotes a positive outcome in AD, being a promising therapeutic strategy.

The Effect of Landscape Features Implemented in Egyptian Parks on Satisfying the Human Needs and Well-being

Recently, parks have been recognized as one of the main contributors in the strategic objectives of urban projects, since they provide job opportunities, place attractiveness, increase the real estate market and property values, tourist development, increase the since of social belonging between the residents, improving the public health and the quality of the residents’ life. The presented research is aiming to investigate the effect of Landscape features on the quality of life (QOL) inside Egyptian parks. This study has been inspired by early theorists like “Maslow” and other theorists who have followed Maslow’s footsteps. They analysed and measured the concept of quality of life (QOL)into two well-known terms “human needs” and “well-being”. The study explores the impact of landscape features towards “human needs and well-being”. Lately, Egypt is suffering from inflation and economic crisis which affect the Egyptians life style. Most of the Egyptian society is living a stressful life; this study will examine whether the Egyptian parks help Egyptians as an escape way where all the negative vibes are going to meet with nature resulting in a positive outcome. This research used qualitative investigation method to measure the impact of implementing landscape features in Egyptian parks on enhancing the quality of the Egyptian life by measuring the (QOL) with regards to “human needs and well-being”. The presented research investigated the impact of landscape elements implemented in Al-Azhar Park and Family Park on “human needs and well-being”. That shall pave the way to investors, policymakers, architecture and civil practitioners to realize the potentials of designing and constructing parks in Egyptian urban environment, as an efficient tool to improve the quality of Egyptian life.

Ethnic translation studies as a new translation boarderland / frontier

Статья посвящена анализу некоторых изменений, происходящих в предметном поле современного переводоведения и связанных с появлением новых объектов перевода на практике и их теоретического осмысления. Случаи расширения категориальной парадигмы науки о переводе рассматриваются в контексте основных социокультурных процессов (глобализации и глокализации), поскольку ключевыми объектами рассматриваемого неовида перевода являются этнотексты, принадлежащие культурам коренных народов Сибири. Этнотексты представляют собой традиционные хранилища культурной информации и памяти уникальных этносов, некоторые из которых испытывают значительное влияние унификации, что нередко приводит к нивелированию их культурных и языковых особенностей. В настоящем исследовании предпринята попытка использования для рассмотрения проблематики декодирования информации этнотекстов методологического инструмента, ставшего в последнее время популярным в гуманитарном дискурсе – фронтира. Символическое понимание фронтира применимо к обозначению и рассмотрению в научном (переводоведческом в данном исследовании) дискурсе встречи старого и нового, изученного и неизученного, понятного и непонятного, однозначного и неоднозначного. В зоне фронтира информационная энтропия возрастает, что требует её преодоления и что в конечном счете может обеспечить дальнейшее развитие науки о переводе. Ставшая в XXI веке актуальной проблематика перевода этнотекстов отнесена в настоящей работе к новой фронтирной зоне переводоведения, в рамках которого еще предстоит решить вопросы определения механизмов изучения текстов, созданных первоначально на языках коренных народов, в зеркале этноперевода. Выделение этнопереводовения как самостоятельной области переводоведения может способствовать созданию новых возможностей для знакомства представителей «других» культур мира с уникальными языками и культурами, некоторые из которых находятся под угрозой исчезновения. Другая важная задача этноперевода определяется в отношении его использования для ревитализации и потенциальному возрождению языков коренных народов Сибири, сохранению их культурной идентичности и обеспечению культурного и языкового разнообразия современного мира, что может стать положительным исходомтекущего процесса глокализации. Некоторые вопросы формирующегося в настоящий момент этнопереводоведения рассмотрены на примере опыта перевода этнотекстов коренных народов Красноярского края и Республики Саха (Якутия). The article is devoted to the analysis of some changes taking place in the subject field of modern Translation Studies and related to the emergence of new translation objects in practice and their theoretical consideration. The cases of the categorical paradigm of the science of translation expansion are discussed in the context of the main socio-cultural processes (globalization and glocalization), since the key objects of the considered neo-type of translation are ethnic texts belonging to the cultures of the indigenous peoples of Siberia. Ethnic texts are traditional repositories of cultural information and memory of unique ethnic groups, some of which are significantly influenced by unification, which often leads to the leveling of their cultural and linguistic characteristics. In this study, an attempt is made to use a methodological tool that has recently become popular in the humanitarian discourse to consider the problems of decoding information of ethnic texts – a frontier. The symbolic interpretation of a frontier is applicable to the designation and consideration in the scholarly (Translation Studies in the present research) discourse of the meeting of the old and the new, the studied and the unexplored, the understandable and the incomprehensible, the definite and the ambiguous. In the frontier zone, information entropy increases, which requires overcoming it and ultimately can ensure the further development of the science of translation. The problems of ethnic texts translation, which have become relevant in the 21st century, are attributed in the present paper to the new frontier zone of Translation Studies, within the framework of which the issues of determining the mechanisms for studying texts originally created in the languages of indigenous peoples in the mirror of ethnic translation have yet to be resolved. The identification of ethnic translation as an independent field of Translation Studies can contribute to the creation of new opportunities for “other” cultures of the world representatives to get acquainted with unique languages and cultures, some of which are endangered. Another important task of ethnic translation is defined in relation to its use for the revitalization and potential revival of the languages of the indigenous peoples of Siberia, the preservation of their cultural identity and ensuring the cultural and linguistic diversity of the modern world, which can become a positive outcome of the current glocalization process. Some issues of the currently emerging Ethnic Translation Studies are considered on the example of the experience of translating the ethnic texts of the indigenous peoples of Krasnoyarsk Krai and the Sakha Republic (Yakutia).

Attachment and mentalization as predictors of outcome in family therapy for adolescent anorexia nervosa

Anorexia nervosa-focussed family therapy (FT-AN) is the first-line treatment for adolescent anorexia nervosa (AN), but the predictors of poor treatment response are not well understood. The main aim of this study was to investigate the role of attachment and mentalization in predicting treatment outcome. The secondary aims of the study were to investigate therapeutic alliance at 1 month as a predictor of outcome, and to test the associations between alliance and baseline attachment and mentalization. 192 adolescents with AN and their parents were recruited as they began family therapy in out-patient specialist eating disorder services. Self-report measures of attachment, mentalization, and emotion regulation were completed at the start of treatment by adolescent patients and one of their parents. Self-reported alliance scores were collected at one month. Higher scores on the Certainty Scale of the Reflective Functioning Questionnaire, completed by parents, which indicate over-certainty about mental states, were the strongest predictor of poor outcome (Odds Ratio: 0.42, CI: 0.20–0.87). Similarly, for adolescents, higher Lack of Clarity scores on the Difficulties in Emotion Regulation Scale, representing being unclear about one’s feelings, were predictive of positive treatment outcome (OR: 1.10, CI: 1.00–1.21). Higher alliance scores at 1 month predicted positive outcome, and were associated with attachment security and mentalization. These novel findings suggest that, particularly in parents, a tendency towards excessive certainty about mental states in others may predict poor outcome in FT-AN. Further research is warranted to replicate the finding and characterise families at risk of poor outcome.

Place-based approaches to improve health and development outcomes in young children: A scoping review

This scoping review examines the strength of evidence for the effectiveness of public policy-led place-based initiatives designed to improve outcomes for disadvantaged children, their families and the communities in which they live. Study designs and methods for evaluating such place-based initiatives were assessed, along with the contexts in which initiatives were implemented and evaluated. Thirty-two reports relating to 12 initiatives were included. Eleven initiatives used a quasi-experimental evaluation to assess impact, although there were considerable design variations within this. The remaining initiative used a pre- and post- evaluation design. Place-based initiatives by definition aim to improve multiple and interrelated outcomes. We examined initiatives to determine what outcomes were measured and coded them within the five domains of pregnancy and birth, child, parent, family and community. Across the 83 outcomes reported in the 11 studies with a comparison group, 30 (36.4%) demonstrated a positive outcome, and all but one initiative demonstrated a positive outcome in at least one outcome measure. Of the six studies that examined outcomes more than once post baseline, 10 from 38 outcomes (26.3%) demonstrated positive sustained results. Many initiatives were affected by external factors such as policy and funding changes, with unknown impact on their effectiveness. Despite the growth of place-based initiatives to improve outcomes for disadvantaged children, the evidence for their effectiveness remains inconclusive.

Sedation-Induced Burst Suppression Predicts Positive Outcome Following Traumatic Brain Injury

While electroencephalogram (EEG) burst-suppression is often induced therapeutically using sedatives in the intensive care unit (ICU), there is hitherto no evidence with respect to its association to outcome in moderate-to-severe neurological patients. We examined the relationship between sedation-induced burst-suppression (SIBS) and outcome at hospital discharge and at 6-month follow up in patients surviving moderate-to-severe traumatic brain injury (TBI). For each of 32 patients recovering from coma after moderate-to-severe TBI, we measured the EEG burst suppression ratio (BSR) during periods of low responsiveness as assessed with the Glasgow Coma Scale (GCS). The maximum BSR was then used to predict the Glasgow Outcome Scale extended (GOSe) at discharge and at 6 months post-injury. A multi-model inference approach was used to assess the combination of predictors that best fit the outcome data. We found that BSR was positively associated with outcomes at 6 months (P = 0.022) but did not predict outcomes at discharge. A mediation analysis found no evidence that BSR mediates the effects of barbiturates or propofol on outcomes. Our results provide initial observational evidence that burst suppression may be neuroprotective in acute patients with TBI etiologies. SIBS may thus be useful in the ICU as a prognostic biomarker.

Systemic Treatment of Immune-Mediated Keratoconjunctivitis Sicca with Allogeneic Stem Cells Improves the Schirmer Tear Test Score in a Canine Spontaneous Model of Disease

Keratoconjunctivitis sicca (KCS) is characterized by ocular discomfort, conjunctival hyperaemia, and corneal scarring, causing reduced aqueous tear production that can be measured using the standard Schirmer tear test (STT). Canine adipose tissue-derived MSCs (cATMSCs) have been proposed as treatment due to their anti-inflammatory effect, by releasing cytokines and immunomodulatory soluble factors. Purpose: The aim of this study was to evaluate the effect of the systemic administration of cATMSCs on tear production in dogs with immune-mediated KCS, compared to classical Cyclosporine A (CsA) treatment. Methods: Twenty-eight client-owned dogs with spontaneous KCS were allocated in the experimental group (n = 14, treated with systemic cATMSCs or control group (n = 14, treated with CsA). SST values increased significantly at days 15 (p = 0.002), 45 (p = 0.042) and 180 (p = 0.005) with no observed side-effects in the experimental group. Eyes with an initial STT value of 11–14 mm/min maintained significant improvement at day 180, needing only artificial tears as treatment. Eyes with an initial STT value <11 mm/min needed cyclosporin treatment at day 45, so follow-up was stopped. Control animals treated with CsA did not improve their STT at day 180. Results and Conclusions: Systemic allogeneic cATMSCs application appeared to be a feasible and effective therapy with positive outcome in dogs with initial STT between 11–14 mm/min, with a significant improvement in tear production. The STT increment was maintained for at least 180 days, without needing additional medication, thus suggesting it could constitute an alternative therapy to classical immunosuppressive treatments.

Management of intractable chronic cough during awake craniotomy: illustrative case

BACKGROUND Chronic cough is a common but challenging clinical condition that can adversely affect the safety of awake surgical endeavors such as awake craniotomy (AC). This case lesson highlighted a patient with severe refractory chronic cough undergoing AC for resection of a recurrent left frontal, insula, anterior temporal anaplastic ependymoma of the eloquent cortex. OBSERVATIONS The patient was successfully managed using a multifaceted medical treatment regimen combined with preoperative and intraoperative cough suppression therapy with a speech-language pathologist. The patient coughed only once intraoperatively and had a positive outcome. LESSONS Chronic cough is often multifactorial and requires a multifaceted treatment approach. Despite this challenge, select patients can successfully be navigated through AC with appropriate treatment for their condition. A review of neurogenic cough and modern treatments, which were used in this patient and would be helpful to neurologists or neurosurgeons, are also discussed.

Sectoral Allocation of Foreign Aids and Poverty Alleviation in Nigeria, 2010-2020

The study was necessitated by the high rate of poverty in Nigeria regardless of the foreign aids inflow into the country from 2010 to 2020. Whereas the country received foreign aids which could have resulted in poverty alleviation within the period of this study, she antithetically witnessed increase in poverty rate to the extent that the World Bank in May 2018 reported that Nigeria had emerged poverty capital of the world. According to the National Bureau of Statistics’ report, over 82.9 million persons, representing about 40.1 percent of the total population, were considered poor by national standards as at 2019. The poverty challenge inspite of the foreign aids inflow into Nigeria therefore necessitated the question on how sectoral allocation of foreign aids contributed to poverty alleviation in Nigeria from 2010 to 2020. Anchored on the Big Push Theory, the study adopted ex-post facto research design and documentary method for data collection. Qualitative descriptive method was used for data analysis. Among other things, the study found out that sectoral allocation of foreign aid resources did not contribute to poverty alleviation in Nigeria from 2010 to 2020 as those sectors critical for poverty alleviation did not receive massive investments. On the contrary, the foreign aids were split among numerous (consumption) sub-heads which rendered the aids incapable of contributing to poverty alleviation in the country. In view of the findings, the study therefore recommended the need to channel future foreign aids inflow into projects with high capital returns or the productive sectors of the economy in order to achieve a positive outcome on poverty alleviation.