Explore the vast range of titles available.

Over the last 20 years, the effectiveness of positive psychology interventions for the development of the well-being of children and adolescents and the moderation of high levels of anxiety and depression in this population has been largely demonstrated. Emphasis has been placed on the promotion of well-being and prevention of mental health problems in the school context in order to foster, through positive psychology, the cognitive and socio-emotional development of primary and secondary students, e.g., by strengthening positive relationships, positive emotions, character strengths, optimism, and hope. However, little is known about the impact of these interventions on young children. This systematic review aims at examining the effects of positive psychology interventions on the well-being of early childhood children (<6 years old), both in the preschool education context with educators or teachers and also in the family context with parents. Several electronic databases were searched, and the findings systematically reviewed and reported by the PRISMA guidelines. Very few studies met the inclusion criteria (n = 3), highlighting the need for further research in this area. Indeed, all of the selected studies demonstrated the importance of positive psychology interventions with young children to promote positive aspects of development, such as gratitude, positive emotions, life satisfaction, accomplishment, positive relationship, or self-esteem. Limitations in the field are discussed.

Numerous studies have shown that youth with behavioral disorders (BD) present an increased risk for developing severe and persistent antisocial behaviors in adulthood. Retrospective research notes that not all children and adolescents follow a negative trajectory and explains this heterogeneity in particular by the severity of CU traits. Our study examines how these traits affect the functioning of children and adolescents with BD. Method: A systematic literature review conducted through various databases and using different keywords made it possible to analyze 52 studies published from 2015 to 2020 that measured the bidirectional effects of CU traits on the functioning of young. Results: Out of the 52 studies, 47 analyzed links between CU traits and neurobiological or mental health, 20 examined family and school contexts, eight focused on social adjustment, 10 on social interactions and 19 measured links with cognitive functioning, especially executive functions. Conclusion: Consistent with previous recommendations in the field, our findings emphasize the importance of assessing the presence of UC traits in early childhood to prevent the emergence of comorbid disorders and to target multimodal (early) interventions to influence the life trajectories of youth with high CU traits.

The variant spectrum and the phenotype of X-linked Kabuki syndrome type 2 (KS2) are poorly understood. Genetic and clinical details of new and published individuals with pathogenic KDM6A variants were compiled and analyzed. Sixty-one distinct pathogenic KDM6A variants (50 truncating, 11 missense) from 80 patients (34 males, 46 females) were identified. Missense variants clustered in the TRP 2, 3, 7 and Jmj-C domains. Truncating variants were significantly more likely to be de novo. Thirteen individuals had maternally inherited variants and one had a paternally inherited variant. Neonatal feeding difficulties, hypoglycemia, postnatal growth retardation, poor weight gain, motor delay, intellectual disability (ID), microcephaly, congenital heart anomalies, palate defects, renal malformations, strabismus, hearing loss, recurrent infections, hyperinsulinism, seizures, joint hypermobility, and gastroesophageal reflux were frequent clinical findings. Facial features of over a third of patients were not typical for KS. Males were significantly more likely to be born prematurely, have shorter stature, and severe developmental delay/ID. We expand the KDM6A variant spectrum and delineate the KS2 phenotype. We demonstrate that the variability of the KS2 phenotypic depends on sex and the variant type. We also highlight the overlaps and differences between the phenotypes of KS2 and KS1.

BackgroundHeterozygous copy number variants (CNVs) or sequence variants in the contactin-associated protein 2 gene CNTNAP2 have been discussed as risk factors for a wide spectrum of neurodevelopmental and neuropsychiatric disorders. Bi-allelic aberrations in this gene are causative for an autosomal-recessive disorder with epilepsy, severe intellectual disability (ID) and cortical dysplasia (CDFES). As the number of reported individuals is still limited, we aimed at a further characterisation of the full mutational and clinical spectrum.MethodsTargeted sequencing, chromosomal microarray analysis or multigene panel sequencing was performed in individuals with severe ID and epilepsy.ResultsWe identified homozygous mutations, compound heterozygous CNVs or CNVs and mutations in CNTNAP2 in eight individuals from six unrelated families. All aberrations were inherited from healthy, heterozygous parents and are predicted to be deleterious for protein function. Epilepsy occurred in all affected individuals with onset in the first 3.5 years of life. Further common aspects were ID (severe in 6/8), regression of speech development (5/8) and behavioural anomalies (7/8). Interestingly, cognitive impairment in one of two affected brothers was, in comparison, relatively mild with good speech and simple writing abilities. Cortical dysplasia that was previously reported in CDFES was not present in MRIs of six individuals and only suspected in one.ConclusionsBy identifying novel homozygous or compound heterozygous, deleterious CNVs and mutations in eight individuals from six unrelated families with moderate-to-severe ID, early onset epilepsy and behavioural anomalies, we considerably broaden the mutational and clinical spectrum associated with bi-allelic aberrations in CNTNAP2.

Background: Vitamin D3 fortified food may improve serum vitamin D level, suggesting that the prevention of adverse consequences of hypovitaminosis D is possible with food fortification. The aim of this randomized controlled trial (RCT) was to examine the effects of vitamin D and calcium fortified yogurt on spatiotemporal gait parameters, cognitive performance, handgrip strength, and serum 25OHD levels in healthy older females. Methods: Forty older community-dwelling females were recruited in a single-blind, randomized, controlled, superiority clinical trial in two parallel groups (20 participants in the intervention group and 20 in the control group) with intent-to-treat. The intervention group took fortified yogurts daily (i.e., 400 UI of vitamin D3 and 800 mg calcium) for 3 months. The non-fortified yogurts contained similar proteins, carbohydrates and lipids, as well as a lower dose of calcium (300 mg) and no vitamin D3 supplementation. Spatiotemporal gait parameters (mean value and coefficient of variation) were assessed using a computerized walkway. Handgrip strength was measured with hydraulic dynamometers. Cognitive performances, including global cognitive functioning assessed with the Mini Mental Status Examination (MMSE) were recorded. All the outcomes were assessed at baseline and at the end of follow-up. The primary outcome was the coefficient of variation of stride time. Results: The intervention group maintained its global cognitive performance and serum 25OHD concentrations, whereas these outcomes decreased (i.e., worst performance) in the control group. The changes in the MMSE score (p = 0.022) and serum 25OHD concentrations were different (p ≤ 0.001) with better values reported in the intervention group compared to the control group. There was no significant change in gait parameters (p ≥ 0.518) and handgrip strength (p ≥ 0.600). Conclusions: Fortified yogurts with vitamin D (i.e., 200 IU) and calcium (i.e., 400 mg) twice a day maintained global cognitive performance and vitamin D status in older females, but not gait performances, signifying that they mainly prevent hypovitaminosis D-related extra-skeletal disorders.

Acceleration of bone remodelling increases the risk of fragility fractures. The objective of the present study was to explore in elderly women whether a vitamin D and Ca-fortified dairy product providing about 17–25 % of the recommended intakes in vitamin D, Ca and proteins would reduce secondary hyperparathyroidism and bone remodelling in a way that may attenuate age-related bone loss in the long term. Thirty-seven institutionalised women, aged 84·8 (sd 8·1) years, with low serum 25-hydroxyvitamin D (5·5 (sd 1·7) ng/ml) were enrolled into a multicentre open trial to consume during 1 month two servings of soft plain cheese made of semi-skimmed milk providing daily 686 kJ (164 kcal), 2·5 μg vitamin D, 302 mg Ca and 14·2 g proteins. The primary endpoint was the change in serum carboxy terminal cross-linked telopeptide of type I collagen (CTX), selected as a marker of bone resorption. Thirty-five subjects remained compliant. Mean serum changes were: 25-hydroyvitamin D, +14·5 % (P = 0·0051); parathyroid hormone (PTH), − 12·3 % (P = 0·0011); CTX, − 7·5 % (P = 0·01); tartrate-resistant acid phosphatase isoform 5b (TRAP 5b), − 9·9 % (P < 0·0001); albumin, +6·2 % (P < 0·0001); insulin-like growth factor-I (IGF-I),+16·9 % (P < 0·0001); osteocalcin, +8·3 % (P = 0·0166); amino-terminal propeptide of type 1 procollagen (P1NP),+19·3 % (P = 0·0031). The present open trial suggests that fortified soft plain cheese consumed by elderly women with vitamin D insufficiency can reduce bone resorption markers by positively influencing Ca and protein economy, as expressed by decreased PTH and increased IGF-I, respectively. The rise in the bone formation marker P1NP could be explained by a protein-mediated increase in IGF-I. Thus, such a dietary intervention might uncouple, at least transiently, bone resorption from bone formation and thereby attenuate age-related bone loss.

NF-κB is known to exert a cytoprotective action against TNF-α-induced apoptosis. To study the role of NF-κB in various TNF-α-treated epithelial cell lines, we generated stable transfectants overexpressing a mutated unresponsive form of the IκBα inhibitor (MT cells). As NF-κB prevented TNF-α-induced apoptosis in various epithelial cancer cell lines, we searched for NF-κB target gene products responsible for this difference of sensitivity. We observed an increased Bcl-XL expression level in OVCAR-3 cells compared with OVCAR-3 cells expressing a mutated IκBα inhibitor (MT cells). Induction of the antioxidant enzyme MnSOD was detected only in TNF-α-treated OVCAR, MCF7A/Z and HCT116 cells but not in MT cells. Moreover, reactive oxygen species were involved in TNF-α-induced apoptosis, as various antioxidants partially protected these cells from apoptosis. At last, transfection of the MnSOD cDNA in MT cells, which do not express this protein after TNF-α stimulation, partially restored resistance to TNF-α-induced cell death, as observed by clonogenic assays. However, transfection of the Bcl-XL cDNA did not induce any protective effect. Therefore, MnSOD expression is induced by NF-κB in epithelial cancer cells in response to TNF-α, and is at least partially responsible for their resistance to TNF-α-induced apoptosis, presumably through the clearance of death-inducing ROS.

The oncoprotein HER-2/neu is a prosurvival factor and its overexpression has been correlated with adverse prognosis in breast cancers. High levels of the cyclooxygenase-2 (COX-2), a proinflammatory and antiapoptotic enzyme, were detected in HER-2-positive tumors and this observation was linked to an HER-2-mediated induction of COX-2 gene transcription. Here, we report that COX-2 expression, and synthesis of its major enzymatic product, PGE2, leads in turn to an enhanced HER-2 expression. Moreover, COX-2 enzymatic inhibition dramatically reduced HER-2 protein levels, efficiently increased the cancer cells sensitility to chemotherapeutic treatment and acted in synergy with HER-2 inhibitor, trastuzumab. Therefore, we propose an original model where HER-2 and COX-2 transcriptionally regulate each other in a positive loop.

Key Clinical Message Germline loss‐of‐function GNAS mutations are associated with multiple phenotypes, depending on the parental origin of the mutant allele. Here, we describe an infantile lethal form of atypical pseudohypoparathyroidism type 1a or 1c with severe Albright's hereditary osteodystrophy phenotype, underlying the extremely variable expressivity of this syndrome. Germline loss‐of‐function GNAS mutations are associated with multiple phenotypes, depending on the parental origin of the mutant allele. Here, we describe an infantile lethal form of atypical pseudohypoparathyroidism type 1a or 1c with severe Albright's hereditary osteodystrophy phenotype, underlying the extremely variable expressivity of this syndrome.

Background: Participation in quality controls, also called external quality assessment (EQA) schemes, is required for the ISO15189 accreditation of the Medical Centers of Human Genetics. However, directives on the minimal frequency of participation in genetic quality control schemes are lacking or too heterogeneous, with a possible impact on health care quality. Objective: The aim of this project is to develop Belgian guidelines on the frequency of participation in quality controls for genetic testing in the context of rare diseases. Methods: A group of experts analyzed 90 EQA schemes offered by accredited providers and focused on analyses used for the diagnosis of rare diseases. On that basis, the experts developed practical recommendations about the minimal frequencies of participation of the Medical Centers of Human Genetics in quality controls and how to deal with poor performances and change management. These guidelines were submitted to the Belgian Accreditation Body and then reviewed and approved by the Belgian College of Human Genetics and Rare Diseases and by the National Institute for Health and Disability Insurance. Results: The guidelines offer a decisional algorithm for the minimal frequency of participation in human genetics EQA schemes. This algorithm has been developed taking into account the scopes of the EQA schemes, the levels of experience, and the annual volumes of the Centers of Human Genetics in the performance of the tests considered. They include three key principles: (1) the recommended annual assessment of all genetic techniques and technological platforms, if possible through EQAs covering the technique, genotyping, and clinical interpretation; (2) the triennial assessment of the genotyping and interpretation of specific germline mutations and pharmacogenomics analyses; and (3) the documentation of actions undertaken in the case of poor performances and the participation to quality control the following year. The use of a Bayesian statistical model has been proposed to help the Centers of Human Genetics to determine the theoretical number of tests that should be annually performed to achieve a certain threshold of performance (eg, a maximal error rate of 1%). Besides, the guidelines insist on the role and responsibility of the national public health authorities in the follow-up of the quality of analyses performed by the Medical Centers of Human Genetics and in demonstrating the cost-effectiveness and rationalization of participation frequency in these quality controls. Conclusions: These guidelines have been developed based on the analysis of a large panel of EQA schemes and data collected from the Belgian Medical Centers of Human Genetics. They are applicable to other countries and will facilitate and improve the quality management and financing systems of the Medical Centers of Human Genetics.