Search

Human prenatal skin is populated by innate immune cells, including macrophages, but whether they act solely in immunity or have additional functions in morphogenesis is unclear. Here we assembled a comprehensive multi-omics reference atlas of prenatal human skin (7-17 post-conception weeks), combining single-cell and spatial transcriptomics data, to characterize the microanatomical tissue niches of the skin. This atlas revealed that crosstalk between non-immune and immune cells underpins the formation of hair follicles, is implicated in scarless wound healing and is crucial for skin angiogenesis. We systematically compared a hair-bearing skin organoid (SkO) model derived from human embryonic stem cells and induced pluripotent stem cells to prenatal and adult skin1. The SkO model closely recapitulated in vivo skin epidermal and dermal cell types during hair follicle development and expression of genes implicated in the pathogenesis of genetic hair and skin disorders. However, the SkO model lacked immune cells and had markedly reduced endothelial cell heterogeneity and quantity. Our in vivo prenatal skin cell atlas indicated that macrophages and macrophage-derived growth factors have a role in driving endothelial development. Indeed, vascular network remodelling was enhanced following transfer of autologous macrophages derived from induced pluripotent stem cells into SkO cultures. Innate immune cells are therefore key players in skin morphogenesis beyond their conventional role in immunity, a function they achieve through crosstalk with non-immune cells.

Human embryonic bone and joint formation is determined by coordinated differentiation of progenitors in the nascent skeleton. The cell states, epigenetic processes and key regulatory factors that underlie lineage commitment of these cells remain elusive. Here we applied paired transcriptional and epigenetic profiling of approximately 336,000 nucleus droplets and spatial transcriptomics to establish a multi-omic atlas of human embryonic joint and cranium development between 5 and 11 weeks after conception. Using combined modelling of transcriptional and epigenetic data, we characterized regionally distinct limb and cranial osteoprogenitor trajectories across the embryonic skeleton and further described regulatory networks that govern intramembranous and endochondral ossification. Spatial localization of cell clusters in our in situ sequencing data using a new tool, ISS-Patcher, revealed mechanisms of progenitor zonation during bone and joint formation. Through trajectory analysis, we predicted potential non-canonical cellular origins for human chondrocytes from Schwann cells. We also introduce SNP2Cell, a tool to link cell-type-specific regulatory networks to polygenic traits such as osteoarthritis. Using osteolineage trajectories characterized here, we simulated in silico perturbations of genes that cause monogenic craniosynostosis and implicate potential cell states and disease mechanisms. This work forms a detailed and dynamic regulatory atlas of bone and cartilage maturation and advances our fundamental understanding of cell-fate determination in human skeletal development.

The contribution of motor efficiency to the maintenance of psychological well-being in cognitively impaired older individuals is still insufficiently examined. This investigation primarily intended to evaluate whether muscular strength mediates the relationship between different facets of psychological well-being (i.e., personal satisfaction, emotional competence, coping), negative mood, and central executive efficiency through the Clock-Drawing, Trail-Making (Part A), and verbal fluency tests. Furthermore, the impact of cognitive decline on self-reported psychological well-being and depression was explored, using the handgrip strength (HGS) measure as a covariate. One hundred and nineteen older participants, 44 males and 75 females, aged 63 years and older (M.sub.age = 77.7 years, SD = 5.6 years), completed a battery of tests assessing executive functions, HGS, depression, and psychological well-being. Significant low to moderate associations were found between distinct executive functions, HGS, psychological well-being, and depression. In addition, personal satisfaction did not correlate with any measure of executive functions, the clock-drawing score was associated only with coping index, and self-reported depression correlated only with the Trail-Making Test score. Moreover, a series of mediation analyses documented that executive functions (primarily assessing verbal fluency and motor speed) and HGS explained approximately 20-46% of the variance in perceived psychological well-being and depression. Finally, more cognitively impaired participants reported worse total psychological well-being, emotional competence, and coping. In conclusion, motor proficiency mediates the relationship between selective measures of executive functions and perceived psychological well-being and depression in cognitively impaired individuals., Author(s): Maria Chiara Fastame [sup.1] , Ilaria Mulas [sup.2] , Valeria Putzu [sup.3] , Gesuina Asoni [sup.3] , Daniela Viale [sup.3] , Irene Mameli [sup.3] , Massimiliano Pau [sup.2] Author [...]

The term "Activities of Daily Living" (ADLs) refers to a set of fundamental tasks (i.e., toileting, bathing, personal care, eating, grooming, and getting dressed) considered necessary for living and being autonomous in everyday life. Although in the clinical setting ADLs efficiency is a marker to diagnose dementia, limited evidence on the mechanism implicating muscular function and cognitive alterations in ADLs skills in late adulthood exists. This study primarily intended to determine the extent to which executive functions mediate between muscular strength, as assessed through handgrip strength (HGS) measurement, and ADLs skills of older community-dwellers. A further goal was to explore the impact of gender and cognitive status on ADLs and HGS scores, using education as a covariate. Three hundred and thirty-four older participants, 199 females and 135 males (Mage = 77.5 years, SD = 5.6 years, age range = 63–93 years) completed a battery of tests assessing ADLs, HGS, and executive functions. The results showed that 34–56% of the variance in the ADLs condition was explained by HGS and executive functioning. Furthermore, cognitively healthy participants exhibited better ADLs skills, whereas cognitively impaired individuals, both males and females, exhibited poorer HGS efficiency. In conclusion, in clinical settings, the concurrent evaluation of ADLs skills, motor, and higher-order cognitive processes should be encouraged to detect individuals needing a person-tailored intervention to boost their quality of life. [ABSTRACT FROM AUTHOR]

In clinical practice, different drawing tests are used for the assessment of cognitive efficiency in the geriatric population. However, so far, the contribution of motor skills to drawing performance has not been sufficiently examined in the late adult life span. This study was aimed at disentangling the role played by motor functioning in three well-known drawing tests that in the clinical field are commonly used to detect some signs of cognitive impairment of older individuals. One hundred and forty-nine community dwellers (Mage = 77.4 years, SD = 5.9 years) completed a battery of tests assessing global cognitive efficiency, drawing skills (i.e., Clock Drawing, Visuo-spatial Drawing ACE-R, Copy Figures Tests), handgrip muscular strength (HGS), and functional mobility (assessed through the Timed-Up-and-Go test). Significant relationships were found among those measures. Moreover, handgrip strength and functional mobility explained 12–19% of the variance in each drawing condition. Finally, participants exhibiting poorer HGS performed worse the drawing tasks and were successively recognized as cognitively deteriorated. In conclusion, these findings highlight that motor skills can significantly impact the assessment of cognitive efficiency in late adulthood. Therefore, in clinical practice, the concurrent assessment of basic motor functions (in terms of muscular strength and functional mobility) and cognitive efficiency of the geriatric population at risk for cognitive decline should be encouraged. [ABSTRACT FROM AUTHOR]

A body of studies suggests that coping resources may represent a protective factor against functional and cognitive losses associated with advanced ageing. This study intended to examine the contributions of global cognition, functional mobility, and muscular strength on self-reported coping strategies in late adulthood. One hundred and thirty-seven community-based older individuals (Mage = 77.2 years, SD = 5.8 years, age range: 63–92 years), 48 males and 89 females with and without signs of cognitive decline completed a battery of tools assessing global cognitive function, problem-focused coping, muscular strength (assessed by handgrip strength, HGS) and functional mobility (assessed using the instrumented Timed-Up-and-Go test). Significant associations were found between problem-focused coping, global cognitive function, HGS, functional mobility parameters, age, and education. Moreover, when the effects of education and gender were controlled for, HGS, functional mobility, and global cognitive function scores accounted for 44% of the variance in coping. In clinical practice, the use of functional mobility and muscular strength measures to screen the physical health of older individuals should be encouraged. [ABSTRACT FROM AUTHOR]

The effect of migration on perceived mental health has not been examined in older migrants after their return to their places of origin. This study was mainly aimed at evaluating the perceived mental health of older people who experienced migration and permanent resident peers living in the Sardinian Blue Zone (i.e. one of the four areas of exceptional longevity in the world). Forty‐eight community‐based older participants (32 males and 16 females) with and without a migration experience were recruited in two villages of the Sardinian Blue Zone and completed a battery of self‐report inventories assessing psychological well‐being, negative mood, and ego resilience. Older individuals who experienced migration reported higher ego resilience and exhibited greater resources used to manage positive emotionality (i.e. openness to life experiences). Moreover, compared to the normative data, both the groups reported higher psychological well‐being and fewer depressive symptoms. Finally, no significant associations were found between the length of migration and each mental health index. In conclusion, resilience seems to represent a psychological trait that helps to manage stressful events and contributes to the preservation of perceived mental health in late adulthood. [ABSTRACT FROM AUTHOR]

Objectives: The main aim of this study was to examine the impact of age-related changes on mental health, metacognitive, and motor functioning in late adulthood, while controlling for the effect of gender. Additionally, this investigation intended to study the association between motor efficiency indexes and self-reported psychological well-being, depression and cognitive failures over a period of 24 months.Design: Prospective longitudinal study: post hoc analysis.Participants: Ninety-one community-dwelling older participants (mean age = 78.7 years, SD = 5.6) were recruited in a rural village of the Sardinian Blue Zone - an area of exceptional longevity located in the central-eastern region of Sardinia, an Italian island in the Mediterranean Sea.Measurements: All respondents completed a battery of tests and questionnaires assessing motor and general cognitive efficiency, self-reported psychological well-being, negative affect, and cognitive failures.Results: The adoption of a multilevel modeling approach highlighted the significative impact of time on psychological well-being, as well as on mobility parameters like gait speed and cadence, while controlling for the gender effect. Overall, psychological well-being and motor swing significantly increase at follow-up, whereas the further above-mentioned measures decreased after 24 months. Moreover, compared to the national cut-off, at baseline and follow-up, participants reported higher perceived emotional well-being. Finally, significant relationships between motor scores and self-reported mental health and metacognitive measures were found both at baseline and follow-up.Conclusions: The maintenance of motor efficiency and preserved mental health seems to contribute to the successful aging of older people living in the Sardinian Blue Zone. [ABSTRACT FROM AUTHOR]

Aim: The main purpose of the present study was to verify the feasibility of wearable inertial sensors (IMUs) in a clinical setting to screen gait and functional mobility in Italian older persons. In particular, we intended to verify the capability of IMUs to discriminate individuals with and without cognitive impairments and assess the existence of significant correlations between mobility parameters extracted by processing trunk accelerations and cognitive status. Methods: This is a cross-sectional study performed on 213 adults aged over 65 years (mean age 77.0 ± 5.4; 62% female) who underwent cognitive assessment (through Addenbrooke's Cognitive Examination Revised, ACE-R) instrumental gait analysis and the Timed Up and Go (TUG) test carried out using a wearable IMU located in the lower back. Results: Individuals with cognitive impairments exhibit a peculiar gait pattern, characterized by significant reduction of speed (− 34% vs. healthy individuals), stride length (− 28%), cadence (− 9%), and increase in double support duration (+ 11%). Slight, but significant changes in stance and swing phase duration were also detected. Poorer performances in presence of cognitive impairment were observed in terms of functional mobility as overall and sub-phase TUG times resulted significantly higher with respect to healthy individuals (overall time, + 38%, sub-phases times ranging from + 22 to + 34%), although with some difference associated with age. The severity of mobility alterations was found moderately to strongly correlated with the ACE-R score (Spearman's rho = 0.58 vs. gait speed, 0.54 vs. stride length, 0.66 vs. overall TUG time). Conclusion: The findings obtained in the present study suggest that wearable IMUs appear to be an effective solution for the clinical assessment of mobility parameters of older persons screened for cognitive impairments within a clinical setting. They may represent a useful tool for the clinician in verifying the effectiveness of interventions to alleviate the impact of mobility limitations on daily life in cognitively impaired individuals. [ABSTRACT FROM AUTHOR]