Sustained correction of hippocampal neurogenic and cognitive deficits after a brief treatment by Nutlin-3 in a mouse model of Fragile X Syndrome

Background: Fragile X syndrome (FXS), the most prevalent inherited intellectual disability and one of the most common monogenic form of autism, is caused by a loss of FMRP translational regulator 1 (FMR1). We have previously shown that FMR1 represses the levels and activities of ubiquitin ligase MDM2 in young adult FMR1-deficient mice and treatment by a MDM2 inhibitor Nutlin-3 rescues both hippocampal neurogenic and cognitive deficits in FMR1-deficient mice when analyzed shortly after the administration. However, it is unknown whether Nutlin-3 treatment can have long-lasting therapeutic effects. Methods: We treated 2-month-old young adult FMR1-deficient mice with Nutlin-3 for 10 days and then assessed the persistent effect of Nutlin-3 on both cognitive functions and adult neurogenesis when mice were 6-month-old mature adults. To investigate the mechanisms underlying persistent effects of Nutlin-3, we analyzed proliferation and differentiation of neural stem cells isolated from these mice and assessed the transcriptome of the hippocampal tissues of treated mice. Results: We found that transient treatment with Nutlin-3 of 2-month-old young adult FMR1-deficient mice prevents the emergence of neurogenic and cognitive deficits in mature adult FXS mice at 6-month of age. We further found that the long-lasting restoration of neurogenesis and cognitive function might not be mediated by changing intrinsic properties of adult neural stem cells. Transcriptomic analysis of the hippocampal tissue demonstrated that transient Nultin-3 treatment leads to significant expression changes in genes related to extracellular matrix, secreted factors, and cell membrane proteins in FMR1-deficient hippocampus.

Musical and Gymnastic Education in the Republic

Chapter 6 examines Plato’s account of moral education in the Republic. It argues that musical and gymnastic training in the Kallipolis primarily aim at shaping the spirited part of the soul through social, political, and cultural influences and practices. In particular, music aims to make spirit gentle and instill in it the right emotional habits toward moral and immoral people, actions, and objects in the world. Gymnastics, meanwhile, aims to invigorate it and make it “strong” enough to act as reason’s “ally” effectively. Music and gymnastics also have important effects on reason and appetite as well, however. Music exercises reason and prepares it for its proper function in the souls of mature adults, and gymnastic training promotes necessary appetites while eliminating or preventing unnecessary ones.

Open Reduction and Internal Fixation of a Pediatric Talar Body Fracture using a Medial Malleolar Osteotomy – A Case Report

Introduction:Talus fracture injuries are rare and most literature pertains to fractures in skeletally mature adults. It is unusual for pediatric talus fractures to be treated operatively and is normally treated with immobilization. The location of the talus fracture required a medial malleolar osteotomy to facilitate exposure and reduction, which was fixed with temporary smooth K-wires. The authors were unable to identify a previous description of this technique in the literature. Case Report:An 11-year-old female was referred to our hospital due to polytraumatic injuries sustained in a roll-over MVC. A displaced fracture of the talus body was present. Due to the fracture location, a medial malleolar osteotomy was required for exposure. An open reduction and internal fixation was performed using subchondral minifragment screws under general anesthesia. The patient healed uneventfully, regained a normal gait and full, pain-free range of motion. Conclusions:Medial malleolar osteotomy with smooth K-wire fixation appears to be a safe method for gaining access to the talus when required for reduction and/or fixation of pediatric talus fractures. Keywords:Adolescent, talus fracture, osteotomy.

Absolute Temperature Thresholds for Detection of Skin Wetness and Dampness on the Hand and their Variation with Sex and Age

The human body has dedicated receptors for sensing temperature and touch, but not wetness. How then is wetness perceived? To test if wetness perception arises from the sensory integration of touch and temperature, and to quantify its measurement in humans, we designed a wetness perception monitor (WPM) which enabled variation of temperature at the fingertips of participants while measuring the pressure exerted on a test surface in the controlled environment of a moisture-free chamber. Thirty randomly selected adults (18+ years) were tested for their perception of dampness/wetness using the WPM. Our data suggest that humans perceive dampness and wetness at average temperatures of 22 ± 0.4°C and 18 ± 0.5°C, respectively, and these sensations are extinguished at temperatures below 16 ± 1°C. Measurements were obtained at an average tactile pressure of 1.5 ± 0.3 kPa. Young adults (18–35 years) sensed wetness at significantly higher temperatures than middle-aged adults (36–55 years) or mature adults (56+ years), who sensed wetness at similar temperatures. We found a surprising sex difference in wetness perception, with females sensing wetness at higher temperatures than males. When the data were screened for outliers, we found that participants whose readings were outside normal ranges, self-reported sensory deficits suggesting that wetness perception could potentially be used as a noninvasive biomarker.

State of Drosophila melanogaster Ovaries after a Full Cycle of Gametogenesis under Microgravity Modeling: Cellular Respiration and the Content of Cytoskeletal Proteins

The effect of weightlessness on gametogenesis and the functional state of female germ cells are still poorly understood. We studied the ovaries of Drosophila melanogaster, the full development cycle of which (from zygote to sexually mature adults) passed under simulated microgravity by a random positioning machine. The rate of cellular respiration was studied by polarography as a parameter reflecting the functional state of mitochondria. The content of cytoskeletal proteins and histones was determined using Western blotting. The relative content of mRNA was determined using qRT-PCR. The results obtained indicated an increase in the rate of cellular respiration under simulated microgravity conditions during the full cycle of gametogenesis in Drosophila melanogaster due to complex I of the respiratory chain. In addition, an increase in the contents of actin cytoskeleton components was observed against the background of an increase in the mRNA content of the cytoskeleton’s encoding genes. Moreover, we observed an increase in the relative content of histone H3 acetylated at Lys9 and Lys27, which may explain the increase in the expression of cytoskeletal genes. In conclusion, the formation of an adaptive pattern of functioning of the Drosophila melanogaster ovaries that developed under simulated microgravity includes structural and functional changes and epigenetic regulation.

Adolescents and young adults

Adolescents and young adults (AYAs) receiving palliative care form a distinct group with physical, emotional, psychological, and social needs that are significantly different from those of either children or mature adults. In this chapter, we focus on the unique needs of AYAs and the transition to adulthood in the context of living with a life-limiting condition (LLC) or life-threatening illness (LTI). For all our patients, the experiences and principles on which their adult identity is formed will be very different from those of their peers. The task for professionals is to deliver palliative care while supporting and respecting a transition to adulthood that may never be completed.

Correlation of grip and knee extension strength in mature adults

BACKROUND AND OBJECTIVE: Grip and knee strength are commonly measured but controversy exists as to whether either is a proxy for the other. The purpose of this meta-analysis was to summarize the correlation between the 2 variables. METHODS: Relevant literature was sought using PubMed, Google, and a hand search. Information on populations, measurements, and correlations were extracted. Correlational data were subjected to meta-analysis. RESULTS: Results from 17 studies were consolidated. The summary correlation between grip and knee extension strength was 0.64 with 95% CI of 0.57 to 0.71. Data were highly heterogeneous but did not show publication bias. CONCLUSION: The correlation between the grip and knee extension strength is good. However, it is not good enough to justify using either as a proxy for the other.

Morphology and sexual dimorphism of living mature adults of Amphiduros fuscescens (Marenzeller, 1875) (Annelida, Hesionidae, Amphidurine), first reported for the Iberian Peninsula

To date, the genus Amphiduros (Annelida: Hesionidae: Amphidurine) is considered as monotypic. Its single species, Amphiduros fuscescens (Marenzeller, 1875), is well characterised by lacking proboscideal papillae and emerging acicular chaetae, as well as by having three antennae, eight pairs of tentacular cirri and inflated dorsal cirri with characteristic alternating length and colour (transparent, with median orange band and white tips) in live animals. Three specimens, one male and two females, were found below boulders at 5–7 m depth in Punta Santa Anna, Blanes and Cala Maset, Sant Feliu de Guixols (Catalan Sea, NW Mediterranean, Iberian Peninsula). Our finding allowed us to describe different, unreported morphological traits and lead us to support the existence of sexual dimorphism (in terms of colouring, cirri morphology and distribution of sexual products along the body). Despite A. fuscescens having been previously reported from the Atlantic and the Mediterranean (particularly in SE French coasts), the specimens from Blanes represent the first record of the species from the Iberian Peninsula. In addition, our molecular results strongly support that Amphiduros pacificus Hartman, 1961 from California (currently synonymised with A. fuscescens) requires to be re-described and reinstalled as a valid species. In turn, our morphological observations support suggesting all other non-Mediterranean reports of A. fuscescens, including the species still under synonymy (i.e. Amphidrornus izukai Hessle, 1925 and Amphidromus setosus Hessle, 1925) as likely being a cryptic species complex whose the taxonomic status requires further assessment.