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Cellular crosstalk is an essential process influenced by numerous factors, including secreted vesicles that transfer nucleic acids, lipids, and proteins between cells. Extracellular vesicles (EVs) have been the center of many studies focusing on neurodegenerative disorders, but whether EVs display cell-type-specific features for cellular crosstalk during neurodevelopment is unknown. Here, using human-induced pluripotent stem cell-derived cerebral organoids, neural progenitors, neurons, and astrocytes, we identify heterogeneity in EV protein content and dynamics in a cell-type-specific and time-dependent manner. Our results support the trafficking of key molecules via EVs in neurodevelopment, such as the transcription factor YAP1, and their localization to differing cell compartments depending on the EV recipient cell type. This study sheds new light on the biology of EVs during human brain development. [Display omitted] • Revealed the proteomic heterogeneity of EVs secreted by neural cells and COs • Neural cells present different EV uptake mechanisms • EVs traffic molecular cues relevant in brain development • EV treatment leads to transcriptional changes and increased proliferation Forero et al. highlight heterogeneity in the protein content of EVs secreted by neural cells and cerebral organoids. Their findings show that neural cells present different EV uptake mechanisms and that EV treatment exerts transcriptional changes and an increase in proliferation in NPCs. [ABSTRACT FROM AUTHOR]

This review highlights genes, proteins and subcellular mechanisms, recently shown to influence cortical neuronal migration. A current view on mechanisms which become disrupted in a diverse array of migration disorders is presented. The microtubule (MT) cytoskeleton is a major player in migrating neurons. Recently, variable impacts on MTs have been revealed in different cell compartments. Thus there are a multiplicity of effects involving centrosomal, microtubule-associated, as well as motor proteins. However, other causative factors also emerge, illuminating cortical neuronal migration research. These include disruptions of the actin cytoskeleton, the extracellular matrix, different adhesion molecules and signaling pathways, especially revealed in disorders such as periventricular heterotopia. These recent advances often involve the use of human in vitro models as well as model organisms. Focusing on cell-type specific knockouts and knockins, as well as generating omics and functional data, all seem critical for an integrated view on neuronal migration dysfunction. [ABSTRACT FROM AUTHOR]

Estimation errors associated with bioelectric impedance evaluation may affect the accuracy of body composition and its prognostic value. We evaluated the prognostic value of a new body composition parameter (Nutrigram®) obtained from bioimpedance vectorial analysis-derived body cell mass and its association with nutritional and functional status. Data of Italian and German cancer patients observed prospectively until death were used. Multivariable models (adjusted for age, gender, hydration status, performance status, and disease's stage) were built in both cohorts to assess the association between body composition outcome parameters (low fat-free mass [FFM], <15 [females] and <17 [males] kg/m2; low standardized phase angle [SPA], <−1.65; low Nutrigram®, <510 [females] and <660 [males] mg/24 h/m) and 1-year all-cause mortality, low body mass index (BMI; <20 [<70 years] and <22 [≥70 years] kg/m2), clinically significant weight loss (WL; ≥10% in 6 months) and low handgrip strength (HG; <20 [females] and <30 [males] kg). Low Nutrigram® was independently associated with mortality in both Italian (HR = 1.84 [95%CI, 1.18–2.86]; P = 0.007) and German cohorts (HR = 1.52 [95%CI, 1.17–2.07]; P = 0.008). Low FFMI and low SPA did not predict survival in the German cohort. In patients with low Nutrigram®, worse nutritional and functional status were observed in both study populations. Performance of models addressing the study endpoints showed substantial consistency with both cohorts, particularly of those including low Nutrigram®. We validated a new prognostic body composition parameter, which is easier to interpret than standard nutritional parameters and may be useful for identifying cancer patients at nutritional risk, requiring early nutritional support. [ABSTRACT FROM AUTHOR]

Summary Background & aims Old persons are more likely to suffer from malnutrition, which may result in higher dependency in activities of daily living. We aimed to provide a quantitative synthesis of prevalence data on malnutrition and its risk as assessed by the Mini Nutritional Assessment across different healthcare settings. The association between nutritional status and setting-related level of dependence was also investigated. Methods Non-interventional studies published as full-text articles in English up to 31th December 2014 were searched for in PubMed and by reviewing references of eligible articles. Meta-analysis and meta-regression of potential sources of heterogeneity were conducted. Results A total of 240 studies/795 citations – providing 258 setting-specific prevalence estimates (113,967 subjects) - fulfilled inclusion criteria for meta-analysis. Prevalence of malnutrition differed significantly across the healthcare settings considered: community, 3.1% (95%CI, 2.3–3.8); outpatients, 6.0% (95%CI, 4.6–7.5); home-care services, 8.7% (95%CI, 5.8–11.7); hospital, 22.0% (95%CI, 18.9–22.5); nursing homes, 17.5% (95%CI, 14.3–20.6); long-term care, 28.7% (95%CI, 21.4–36.0); rehabilitation/sub-acute care, 29.4% (95%CI, 21.7–36.9). For every setting significant heterogeneity in individual study results was observed ( I 2 ≥80%, P < 0.001) and meta-regression showed that study quality was the most important determinant. Finally, meta-regression of all the studies included showed that both malnutrition and its risk were directly associated with the setting-related level of dependence (P < 0.001). However, despite multiple adjustments, residual heterogeneity remained high. Conclusion We provided updated estimates of malnutrition and its risk in different healthcare settings. Although the level of dependence appears to be an important determinant, heterogeneity in individual study results remained substantially unexplained. The cause–effect relationship between nutritional status and level of dependence deserves further investigation. [ABSTRACT FROM AUTHOR]

Summary Background & aims Nutritional derangements are common in elderly patients, but how nutritional risk affects outcome in this subset of hospital inpatients deserves further investigation. We evaluated the impact of nutritional risk on length of stay (LOS) and in-hospital weight loss (WL) in elderly patients (>65yrs). Methods Nutritional risk was assessed by the Geriatric Nutritional Risk Index (GNRI) in a prospective multicentre hospital-based cohort study. The outcomes were LOS and in-hospital WL. Results In the whole sample ( N = 667), the prevalence of high (GNRI < 92) and mild (GNRI: 92–98) nutritional risk were 33% and 25%, respectively. Patients with a high nutritional risk were more likely (OR = 1.89; 95%CI: 1.22–2.92) to stay longer in hospital (fourth quartile, LOS ≥ 20 days) compared to those without. Other factors associated with prolonged LOS were cancer diagnosis (OR = 2.52; 95%CI: 1.69–3.75), the presence of comorbidities (OR = 1.24; 95%CI: 1.11–1.40) and surgical setting (OR = 1.65; 95%CI: 1.10–2.47). In-hospital WL ≥ 5% was recorded in 75 ambulant patients from a representative subgroup ( N = 583). It was independently associated with prolonged LOS (OR = 1.80; 95%CI: 1.03–3.06) and was more frequent among cancer patients (OR = 1.88; 95%CI: 1.09–3.24), in patients with a high nutritional risk (OR = 2.23; 95%CI: 1.20–4.14) or those admitted to surgical units (OR = 1.77; 95%CI: 1.02–3.05). Conclusions Nutritional risk assessed by the GNRI on admission, predicts LOS and in-hospital WL in elderly patients. [ABSTRACT FROM AUTHOR]

Adult stem cells are typically dependent on their specific niche environment, here we discuss to which extent this is applicable in the embryonic cortex. During development, signals regulating both proliferation and differentiation are derived from local sources within the stem and progenitor cell zone of the cerebral cortex as well as from extrinsic sources, such as the meninges, blood vessels and the cerebrospinal fluid. However, neural stem cells isolated as single cells in vitro self-renew and progress through a normal sequence of lineage decisions in the absence of the above signals. Taking these data together we propose a concept of intrinsic specification of the major lineage decisions with environmental niche signals influencing quantitative aspects, such as numbers of stem cells and timing of lineage progression, which are the parameters affected during brain evolution. [Copyright &y& Elsevier]

Summary The mammalian neocortex has undergone remarkable changes through evolution. A consequence of such rapid evolutionary events could be a trade-off that has rendered the brain susceptible to certain neurodevelopmental and neuropsychiatric conditions. We analyzed the exomes of 65 patients with the structural brain malformation periventricular nodular heterotopia (PH). De novo coding variants were observed in excess in genes defining a transcriptomic signature of basal radial glia, a cell type linked to brain evolution. In addition, we located two variants in human isoforms of two genes that have no ortholog in mice. Modulating the levels of one of these isoforms for the gene PLEKHG6 demonstrated its role in regulating neuroprogenitor differentiation and neuronal migration via RhoA, with phenotypic recapitulation of PH in human cerebral organoids. This suggests that this PLEKHG6 isoform is an example of a primate-specific genomic element supporting brain development. Graphical Abstract Highlights • Excess variants within basal radial glia transcriptomic signatures in cases of PH • PLEKHG6 primate-specific isoform mutated in a case of PH functions via RhoA • PLEKHG6 isoforms regulate features of neurogenesis • Modulation of the PLEKHG6 primate isoform reproduces features of PH in organoids O'Neill et al. show that variants in patients with PH are enriched within genes that define basal radial glia transcriptomic signatures and provide mechanistic evidence that a primate-specific isoform of one gene, mutated in a patient with PH, regulates neurogenesis. [ABSTRACT FROM AUTHOR]