Congenital metabolic bone disorders as a cause of bone fragility

Bone fragility is a pathological condition caused by altered homeostasis of the mineralized bone mass with deterioration of the microarchitecture of the bone tissue, which results in a reduction of bone strength and an increased risk of fracture, even in the absence of high-impact trauma. The most common cause of bone fragility is primary osteoporosis in the elderly. However, bone fragility can manifest at any age, within the context of a wide spectrum of congenital rare bone metabolic diseases in which the inherited genetic defect alters correct bone modeling and remodeling at different points and aspects of bone synthesis and/or bone resorption, leading to defective bone tissue highly prone to long bone bowing, stress fractures and pseudofractures, and/or fragility fractures. To date, over 100 different Mendelian-inherited metabolic bone disorders have been identified and included in the OMIM database, associated with germinal heterozygote, compound heterozygote, or homozygote mutations, affecting over 80 different genes involved in the regulation of bone and mineral metabolism. This manuscript reviews clinical bone phenotypes, and the associated bone fragility in rare congenital metabolic bone disorders, following a disease taxonomic classification based on deranged bone metabolic activity

Bayesian modelling captures inter-individual differences in social belief computations in the putamen and insula

Computational models of social learning and decision-making provide mechanistic tools to investigate the neural mechanisms that are involved in understanding other people. While most studies employ explicit instructions to learn from social cues, everyday life is characterized by the spontaneous use of such signals (e.g., the gaze of others) to infer on internal states such as intentions. To investigate the neural mechanisms of the impact of gaze cues on learning and decision-making, we acquired behavioural and fMRI data from 50 participants performing a probabilistic task, in which cards with varying winning probabilities had to be chosen. In addition, the task included a computer-generated face that gazed towards one of these cards providing implicit advice. Participants\u2019 individual belief trajectories were inferred using a hierarchical Gaussian filter (HGF) and used as predictors in a linear model of neuronal activation. During learning, social prediction errors were correlated with activity in inferior frontal gyrus and insula. During decision-making, the belief about the accuracy of the social cue was correlated with activity in inferior temporal gyrus, putamen and pallidum while the putamen and insula showed activity as a function of individual differences in weighting the social cue during decision-making. Our findings demonstrate that model-based fMRI can give insight into the behavioural and neural aspects of spontaneous social cue integration in learning and decision-making. They provide evidence for a mechanistic involvement of specific components of the basal ganglia in subserving these processes

Light Ion Accelerating Line (L3IA): Test Experiment at ILIL-PW

The construction of a novel Laser driven Light Ions Acceleration Line(L3IA) is progressing rapidly towards the operation, following the recent upgrade of the ILIL-PW laser facility. The Line was designed following the pilot experimental activity carried out earlier at the same facility to define design parameters and to identify main components including target control and diagnostic equipment, also in combination with the numerical simulations for the optimization of laser and target parameters. A preliminary set of data was acquired following the successful commissioning of the laser system >100 TW upgrade. Data include output from a range of different ion detectors and optical diagnostics installed for qualification of the laser-target interaction. An overview of the results is given along with a description of the relevant upgraded laser facility and features.Comment: 6 pages, 7 figures, 18 references, presented at the EAAC 201

Ribosomal selection of mRNAs with degenerate initiation triplets

To assess the influence of degenerate initiation triplets on mRNA recruitment by ribosomes, five mRNAs identical but for their start codon (AUG, GUG, UUG, AUU and AUA) were offered to a limiting amount of ribosomes, alone or in competition with an identical AUGmRNA bearing a mutation conferring different electrophoretic mobility to the product. Translational efficiency and competitiveness of test mRNAs toward this AUGmRNA were determined quantifying the relative amounts of the electrophoretically separated wt and mutated products synthesized in vitro and found to be influenced to different extents by the nature of their initiation triplet and by parameters such as temperature and nutrient availability in the medium. The behaviors of AUAmRNA, UUGmRNA and AUGmRNA were the same between 20 and 40°C whereas the GUG and AUUmRNAs were less active and competed poorly with the AUGmRNA, especially at low temperature. Nutrient limitation and preferential inhibition by ppGpp severely affected activity and competitiveness of all mRNAs bearing non-AUG starts, the UUGmRNA being the least affected. Overall, our data indicate that beyond these effects exclusively due to the degenerate start codons within an optimized translational initiation region, an important role is played by the context in which the rare start codons are present

Physical activity, sedentary behaviour and screen time among youths with Down syndrome during the COVID-19 pandemic

Background: The COVID-19-related restrictions hampered habitual physical activity (PA), particularly affecting the more vulnerable, such as people with Down syndrome (DS). The study aimed to investigate changes in PA, sedentary behaviour (SB) and screen time (ST) of youths with DS, before, during and after the restrictions, also in relation to parental PA levels. Methods: A cross-sectional design with a retrospective assessment of variables for the before and during restrictions periods was adopted. Parents of youths with DS completed an online questionnaire. Sociodemographic aspects, weekly PA levels and youths' daily SB and ST were investigated, referring to three time-points: before the pandemic, during the restrictions and the restrictions-easing phase. Results: A total of 57 parents voluntarily participated in the study, proxy-reporting on their child (male = 41, female = 16, age = 21.4 ± 7.7 years). A repeated measures multivariate analysis of variance showed negative effects of restrictions (P < 0.05) on PA levels, SB and ST, independently from sociodemographic characteristics. In the restrictions-easing phase, PA levels did not return to before the pandemic values (P < 0.05). A positive correlation between parents and their child's PA was detected before the pandemic (r = 0.38; P < 0.01), no longer reported in the restrictions-easing phase. Conclusions: The findings showed the negative impact of restrictions on youths with DS lifestyle. Moreover, the importance of addressing the needs of the disabled community including the whole family is highlighted

MicroRNAs as potential biomarkers in pituitary adenomas

Pituitary adenomas (PAs) are one of the most common lesions of intracranial neoplasms, occurring in approximately 15% of the general population. They are typically benign, although some adenomas show aggressive behavior, exhibiting rapid growth, drug resistance, and invasion of surrounding tissues. Despite ongoing improvements in diagnostic and therapeutic strategies, late first diagnosis is common, and patients with PAs are prone to relapse. Therefore, earlier diagnosis and prevention of recurrence are of importance to improve patient care. MicroRNAs (miRNAs) are short non-coding single stranded RNAs that regulate gene expression at the post-transcriptional level. An increasing number of studies indicate that a deregulation of their expression patterns is related with pituitary tumorigenesis, suggesting that these small molecules could play a critical role in contributing to tumorigenesis and the onset of these tumors by acting either as oncosuppressors or as oncogenes, depending on the biological context. This paper provides an overview of miRNAs involved in PA tumorigenesis, which might serve as novel potential diagnostic and prognostic non-invasive biomarkers, and for the future development of miRNA-based therapeutic strategies for PAs

Aging time affects color stability and sensory properties of ground beef patties adjusted

Palatability traits of flavor, juiciness, and tenderness are associated with consumer satisfaction. Although grinding offers an opportunity to mechanically minimize differences in tenderness, muscle source and product quality may still affect the sensory properties of ground beef. The objective of this study was to determine the effects of two quality grades (Premium Choice and Select) and vacuum storage aging time (7, 21, and 42 days) before processing on ground beef patty display color from chuck roll and knuckle subprimals combined to obtain a common percentage of fat