Impact of Tyrosine Kinase Inhibitors (TKIs) on Growth in Children and Adolescents with Chronic Myeloid Leukemia: A Systematic Review.

BACKGROUND: Chronic Myeloid Leukemia (CML) is a rare myeloproliferative disease in childhood. Treatment in CML includes Tyrosine Kinase Inhibitors (TKI's), which inhibit the cytoplasmic kinase BCR/ABL. Tyrosine kinases play a key role in the secretion of growth hormone and insulin-like growth factor1 (IGF-1). OBJECTIVE: The aim of this systematic review was to study the effect of TKIs on the growth of children and adolescents with CML. METHODS: English-language publications were searched in the PubMed/Cochrane library/Google Scholar databases (2002-2023), and retrieved studies were assessed according to PRISMA-Statement and Newcastle- Ottawa-scale. RESULTS: The search strategy yielded 1066 articles. After applying the inclusion/exclusion criteria, 941 were excluded based on title screening and 111 on abstract review. The systematic review included 14 articles (11 retrospective observational studies/3 clinical trials). Twelve studies reported data on the prevalence of growth disorders after the administration of 1st generation TKIs (imatinib). Two studies reported a negative effect of 2nd generation TKIs (dasatinib/nilotinib) on physical growth. Four studies recorded a decrease in height z-score after treatment compared to baseline. Two 1st-generation TKIs studies reported data on children's final height; one reported restoration of final height to normal after the onset of puberty, despite initial slowing, and the final height was lower than mid-parental target height. Serum IGF-1 levels were reported in 2 studies to be within normal range, while in 3 studies, a significant decrease was documented. Considerable study heterogeneity was observed related to dosage/duration of treatment/disease phase/stage of puberty/ethnicity. CONCLUSION: A negative effect of TKIs on the growth and final height of children was noted.

The Impact of Outdoor in Nature Mindfulness on the Mental Well-being of Children and Adolescents. A Mental Health and Cross-cultural Approach.

Background: Mindfulness, originating from ancient meditation practices, has garnered substantial scientific interest in recent decades due to its potential to enhance various aspects of well-being. The rise of scientific interest in mindfulness has led to the development of Mindfulness-Based Stress Reduction (MBSR) and other mindfulness-based interventions (MBIs), which have demonstrated positive effects on stress reduction, emotional regulation, and cognitive flexibility. Objective: This study aimed to explore the characteristics and applications of mindfulness, investigate its impact on mental health, and assess the potential benefits of combining mindfulness with nature-based interventions in promoting the well-being of children and adolescents. Methods: This review draws from existing literature, scholarly articles, and empirical studies related to mindfulness, nature exposure, and their effects on mental health. Results: The results highlight the manifold benefits of mindfulness in different populations, including health professionals, patients, children, adolescents, and the general public. Mindfulness practice has been associated with notable reductions in stress, anxiety, and depression, and has shown positive effects on brain plasticity and cognitive functioning. Furthermore, the integration of mindfulness with exposure to natural environments holds potential for enhanced stress reduction and cognitive restoration. Conclusion: The findings underscore the potential of mindfulness as a cost-effective and accessible intervention to promote mental health across diverse age groups and settings. Further research should explore the specific mechanisms and long-term effects of this integrated approach to optimize its benefits.

Neurocognitive and psycho-emotional profile of children with disabilities.

OBJECTIVE: Neurocognitive deficits in attention, short-term memory, and sequential information processing are present in children with a variety of disabilities, whereas language and visuospatial abilities vary. METHOD: We compared the performance of 59 children (mean age, 15 years) with learning disabilities (n = 18), Down syndrome (n = 21), and intellectual disabilities (n = 20). A series of neuropsychological tests were used to evaluate the neurocognitive processes of memory, attention, visuospatial perception, and executive function. To better understand what emotions they experience, we assessed emotions like anxiety, depression, and positive and negative mood. RESULTS: The performance of children with Down syndrome was statistically significantly different from that of other groups, indicating lower performance (p = 0.001). In comparison to other groups, children with Down syndrome performed significantly worse across all cognitive domains. Additionally, there were no statistically significant differences between groups and low emotional functioning scores across the board for all children. People with DS frequently have distinctive neurocognitive and neurobehavioral profiles that appear during particular developmental phases and have many distinct strengths and weaknesses that should be respected as they mature over the course of their lives. The current findings have substantial consequences for interventions that are focused on achieving the best results.

Psychometric Properties of the Body-Mind-Spirit Wellness Behavior and Characteristic Inventory for the Greek Population.

The Body-Mind-Spirit Wellness Behavior and Characteristic Inventory (BMS-WBCI) is a free-of-charge wellness tool with good psychometric properties, widely used mainly in studies assessing quality of life and healthy lifestyle habits. This certain tool is based on the Hettler's (1980) model and has been validated for use with students aged 18-36. The purpose of this study was to adapt the BMS-WBCI in the Greek language and at the same time to validate it for use in the general population. This study included 520 participants aged 16-75 (M = 39.86, SD = 10.5), who were recruited from the Greek population using the snowball procedure. The BMS-WBCI was adapted into Greek language, following a multiple forward-and-backward translation protocol. Confirmatory Factor Analysis (CFA) was used to validate the overall construct of the Greek BMS-WBCI. The final solution was a three-factor model with 38 items, after removing the items B1, B8, B9, M11, M24, and S43. This final model demonstrated an acceptable to good fit, presenting higher goodness-of-fit indices (CFI = 0.91, TLI = 0.90) and lower badness-of-fit indices (χ2/653 = 2.29, p < 0.001, RMSEA = 0.05, SRMR = 0.06). All items in the hypothesized model exhibited statistically significant standardized factor loadings (p < 0.001), with loadings consistently above 0.40. A very good internal consistency was found using the composite reliability measures (Body 0.86, Mind 0.95, Spirit 0.94). Further analysis indicated a good convergent validity (average variance extracted values: Body 50.5%, Mind 50.7%, Spirit 54.9%). The results indicated adequate discriminant validity, as all square roots of average variance extracted were higher than the correlation between construct items. In conclusion, this psychometric evaluation of the BMS-WBCI adds to the evidence supporting its use in the Greek language, not only in students, but also in the general population.

What Do Cancer Surgery and orthopedic Surgery Elderly Patients Have in Common? A Long-term Postoperative Cognitive Dysfunction in Orthopedic and Cancer Patients Original Research.

Objectives-background: Postoperative cognitive dysfunction (POCD) involves decline in several cognitive domains after surgery and is particularly common after cardiac surgery, while also common among other types of surgery. Given the potential effects of such cognitive dysfunction on the quality of life, it is important to study it in multiple populations in order to limit its occurrence. Study design: We present the long-term neuropsychological outcome of 200 patients, 100 of whom had orthopedic surgery and 100 oncological surgery. Methods: We administered a series of neuropsychological tests assessing attention, complex scanning, verbal working memory, executive functioning, short-term and long-term memory, and visuospatial perception before surgery, prior to discharge, at 3-month follow-up and 6 years after surgery. We compared the performance of these patients to normative datasets. Results: Despite equivalent levels of pre-surgery performance between patients, oncology patients exceeded their preoperative neurocognitive levels, suggesting less postoperative cognitive dysfunction in orthopedic patients overall, in all neuropsychological domains at a 6-year follow-up, except short-term retention. In contrast, orthopedic patients showed no improvement, and, instead, showed some cognitive decline, which remained consistent over time. Conclusions: Our findings highlight the critical role of the type of surgery utilized in the development of POCD and have implications for clinical management and patients' quality of life in the very long term. Health policy professionals should be aware that patients' low POCD may persist in the long term, and this is useful from a clinician's point of view.

Neuropsychological Consequences of Massive Trauma: Implications and Clinical Interventions.

Traumatic events, especially massive trauma resulting from catastrophic incidents, wars, or severe abuse can elicit significant neuropsychological alterations, with profound implications for cognitive, emotional, and behavioral functioning. This mini-review delineates the primary neural changes post-trauma and underscores the importance of timely neuropsychological and clinical interventions. Specific brain regions, including the amygdala and prefrontal cortex, undergo physiological changes that can lead to memory impairments, attention deficits, and emotional disturbances. PTSD, a commonly diagnosed condition post-trauma, exemplifies the intricate relationship between trauma and memory processing. Furthermore, the concept of neuroplasticity, the brain's inherent ability to adapt and rewire, offers hope for recovery. Current clinical interventions, such as cognitive behavioral therapy, mindfulness practices, and biofeedback, leverage this neuroplastic potential to foster healing. The review underscores the vital importance of early intervention to mitigate long-term neuropsychological impacts, emphasizing the role of timely and targeted clinical interventions. The synthesis of this knowledge is crucial for clinicians, allowing for informed therapeutic approaches that holistically address both the physiological and psychological dimensions of trauma.

Self-Assessment of Health Professionals' Cultural Competence: Knowledge, Skills, and Mental Health Concepts for Optimal Health Care.

Current research often refers to cultural competence to improve health care delivery. In addition, it focuses on the cultural uniqueness of each health service user for optimal personalized care. This study aimed to collect self-assessment data from health professionals regarding their cultural competence and to identify their development needs. A mixed methods design was adopted using the Cultural Competence Self-assessment Checklist of the Central Vancouver Island Multicultural Society. This was translated into Greek, validated, and then shared with health professionals in Cyprus. Subsequently, a semi-structured interview guide was designed and utilized. This was structured in exactly the same question categories as the questionnaire. Data collection took place between October 2021 and May 2022, and convenience sampling was used to recruit 499 health scientists in Cyprus. The sample comprised doctors, nurses, psychologists, midwives, social workers, and physiotherapists. Subsequently, 62 interviews were conducted with participants from the same specialties. The results showed that (compared to other health professionals) nurses and psychologists are more sensitive to issues of cultural competence. It would appear that the more socially oriented sciences had better-prepared healthcare staff to manage diversity in context. However, there is a gap between knowledge and skills when comparing doctors to nurses; they seem to be more skilled and willing to intervene actively in cases of racist behavior or problem-solving. In conclusion, participants identified the importance of their cultural competence; they also realized the importance of optimal planning of personalized health care. There is a significant need for continuous and specialized cultural competence training for all health professions.

Morphosyntactic abilities in young children with Down syndrome: Evidence from the Greek language.

Down syndrome is the most common genetic syndrome of intellectual disabilities with a distinct linguistic profile. Language research so far has come mainly from the English language, a language with different syntax and morphology from many other languages, including Greek, indicating a paucity of research findings in the Greek language. Given the rich morphology and distinct syntactic characteristics of the Greek language, the present study evaluated the performance of children with Down syndrome (N = 45) who are native Greek speakers in syntax and morphology and compared it with the performance of children with typical development (N = 45) matched for chronological age. The paper also analysed the items of each task in terms of the performance of the two groups in subject-verb agreement, noun conversion from singular to plural, and verb conversion from present to past and future tenses. All children were tested in four subscales of a standardized test, including morphosyntactic comprehension, morphosyntactic completion and articulation (parts 1 and 2). The results showed that children with Down syndrome lag behind in syntax and morphology compared with children of typical development and present difficulties in specific aspects of morphology and syntax inherent in the Greek language. WHAT THIS PAPER ADDS: What is already known on this subject Morphosyntactic skills are severely impaired in Down syndrome, and research so far has come mainly from the English language, a language with different syntax and morphology from many other languages. What this paper adds to existing knowledge This research adds more information about morphosyntactic skills in children with Down syndrome compared with typically developing children in the Greek language, a language with rich morphology and syntax. What are the potential or actual clinical implications of this work? Children with Down syndrome face difficulties in morphosyntactic skills in the Greek language, especially in subject-verb agreement and in converting nouns from singular to plural.

Ageing and Down syndrome: Neurocognitive characteristics and pharmacological treatment.

Individuals with Down Syndrome (DS) are commonly characterized by unique neurocognitive and neurobehavioural profiles that emerge within specific stages in the developmental continuum. A plethora of studies have confirmed DS's relationship to premature aging and subsequent cognitive decline. Due to having three copies of the amyloid precursor protein (APP) gene which results in amyloid-beta plaque deposition, the cognitive decline often resembles the decline observed in Alzheimer's disease. More specifically, as individuals with DS mature in age (>40) they experience a dramatic increase in difficulties in several cognitive domains, such as language, visuo-spatial abilities, executive functions, working memory, etc. Especially, frontal functions are reported to show an inverse correlation with age. In contrast to the pronounced and well-described neuropsychological deficits, psychiatric symptoms presented by this patient category are not uniform. Mental health disturbances commonly include general anxiety, obsessive-compulsive or oppositional/aggressive behaviors, depression and sleep disorders, as well as self-injury and behavior belonging to autistic spectrum disorders. Therefore, the purpose of the present review is twofold. Our first goal is to depict the cognitive and behavioural phenotype of adults with DS and our second goal is to review the current treatment options available for the behavioral and psychological symptoms, with an emphasis put on the quality of evidence available through meta-analyses and appraising critically the anecdotal treatment often applied. We also present a review on the psychotropic medication, especially acetylcholinesterase inhibitors, that can potentially slow the progression of cognitive decline of those patients. Finally, novel therapeutic strategies, psychological interventions and future diagnostic and therapeutic challenges are discussed.

Glucosinolate biosynthesis in Eruca sativa.

Glucosinolates (GSLs) are a highly important group of secondary metabolites in the Caparalles order, both due to their significance in plant-biome interactions and to their chemoprotective properties. This study identified genes involved in all steps of aliphatic and indolic GSL biosynthesis in Eruca sativa, a cultivated plant closely related to Arabidopsis thaliana with agronomic and nutritional value. The impact of nitrogen (N) and sulfur (S) availability on GSL biosynthetic pathways at a transcriptional level, and on the final GSL content of plant leaf and root tissues, was investigated. N and S supply had a significant and interactive effect on the GSL content of leaves, in a structure-specific and tissue-dependent manner; the metabolites levels were significantly correlated with the relative expression of the genes involved in their biosynthesis. A more complex effect was observed in roots, where aliphatic and indolic GSLs and related biosynthetic genes responded differently to the various nutritional treatments suggesting that nitrogen and sulfur availability are important factors that control plant GSL content at a transcriptional level. The biological activity of extracts derived from these plants grown under the specific nutritional schemes was examined. N and S availability were found to significantly affect the cytotoxicity of E. sativa extracts on human cancer cells, supporting the notion that carefully designed nutritional schemes can promote the accumulation of chemoprotective substances in edible plants.

Towards Elucidating Carnosic Acid Biosynthesis in Lamiaceae: Functional Characterization of the Three First Steps of the Pathway in Salvia fruticosa and Rosmarinus officinalis.

Carnosic acid (CA) is a phenolic diterpene with anti-tumour, anti-diabetic, antibacterial and neuroprotective properties that is produced by a number of species from several genera of the Lamiaceae family, including Salvia fruticosa (Cretan sage) and Rosmarinus officinalis (Rosemary). To elucidate CA biosynthesis, glandular trichome transcriptome data of S. fruticosa were mined for terpene synthase genes. Two putative diterpene synthase genes, namely SfCPS and SfKSL, showing similarities to copalyl diphosphate synthase and kaurene synthase-like genes, respectively, were isolated and functionally characterized. Recombinant expression in Escherichia coli followed by in vitro enzyme activity assays confirmed that SfCPS is a copalyl diphosphate synthase. Coupling of SfCPS with SfKSL, both in vitro and in yeast, resulted in the synthesis miltiradiene, as confirmed by 1D and 2D NMR analyses (1H, 13C, DEPT, COSY H-H, HMQC and HMBC). Coupled transient in vivo assays of SfCPS and SfKSL in Nicotiana benthamiana further confirmed production of miltiradiene in planta. To elucidate the subsequent biosynthetic step, RNA-Seq data of S. fruticosa and R. officinalis were searched for cytochrome P450 (CYP) encoding genes potentially involved in the synthesis of the first phenolic compound in the CA pathway, ferruginol. Three candidate genes were selected, SfFS, RoFS1 and RoFS2. Using yeast and N. benthamiana expression systems, all three where confirmed to be coding for ferruginol synthases, thus revealing the enzymatic activities responsible for the first three steps leading to CA in two Lamiaceae genera.

A metabolic gene cluster in Lotus japonicus discloses novel enzyme functions and products in triterpene biosynthesis.

Genes for triterpene biosynthetic pathways exist as metabolic gene clusters in oat and Arabidopsis thaliana plants. We characterized the presence of an analogous gene cluster in the model legume Lotus japonicus. In the genomic regions flanking the oxidosqualene cyclase AMY2 gene, genes for two different classes of cytochrome P450 and a gene predicted to encode a reductase were identified. Functional characterization of the cluster genes was pursued by heterologous expression in Nicotiana benthamiana. The gene expression pattern was studied under different developmental and environmental conditions. The physiological role of the gene cluster in nodulation and plant development was studied in knockdown experiments. A novel triterpene structure, dihydrolupeol, was produced by AMY2. A new plant cytochrome P450, CYP71D353, which catalyses the formation of 20-hydroxybetulinic acid in a sequential three-step oxidation of 20-hydroxylupeol was characterized. The genes within the cluster are highly co-expressed during root and nodule development, in hormone-treated plants and under various environmental stresses. A transcriptional gene silencing mechanism that appears to be involved in the regulation of the cluster genes was also revealed. A tightly co-regulated cluster of functionally related genes is involved in legume triterpene biosynthesis, with a possible role in plant development.