By combining physical activity and exposure to nature,
can provide additional health benefits compared to physical activity alone. Immersive Virtual Environments (IVE) have emerged as a potentially ...valuable supplement to environmental and behavioral research, and might also provide new approaches to green exercise promotion. However, it is unknown to what extent green exercise in IVE can provide psychophysiological responses similar to those experienced in real natural environments. In this study, 26 healthy adults underwent three experimental conditions: nature walk, sitting-IVE, and treadmill-IVE. The nature walk took place on a paved trail along a large river. In the IVE conditions, the participants wore a head-mounted display with headphones reproducing a 360° video and audio of the nature walk, either sitting on a chair or walking on a manually driven treadmill. Measurements included environmental perceptions (presence and perceived environmental restorativeness - PER), physical engagement (walking speed, heart rate, and perceived exertion), and affective responses (enjoyment and affect). Additionally, qualitative information was collected through open-ended questions. The participants rated the IVEs with satisfactory levels of 'being there' and 'sense of reality,' but also reported discomforts such as 'flatness,' 'movement lag' and 'cyber sickness.' With equivalent heart rate and walking speed, participants reported higher perceived exertion in the IVEs than in the nature walk. The nature walk was associated with high enjoyment and enhanced affect. However, despite equivalent ratings of PER in the nature walk and in the IVEs, the latter were perceived as less enjoyable and gave rise to a poorer affect. Presence and PER did not differ between the two IVEs, although in the treadmill-IVE the negative affective responses had slightly smaller magnitude than in the sitting-IVE. In both the IVEs, the negative affective responses were mainly associated with cyber sickness, whereas PER was positively associated with enjoyment. From the qualitative analysis, it emerged that poor postural control and lack of a holistic sensory experience can also hinder immersion in the IVE. The results indicate that IVE technology might in future be a useful instrument in green exercise research and promotion, but only if image quality and cyber sickness can be addressed.
Transplanted neural stem/precursor cells possess peculiar therapeutic plasticity and can simultaneously instruct several therapeutic mechanisms in addition to cell replacement. Here, we interrogated ...the therapeutic plasticity of neural stem/precursor cells after their focal implantation in the severely contused spinal cord. We injected syngeneic neural stem/precursor cells at the proximal and distal ends of the contused mouse spinal cord and analysed locomotor functions and relevant secondary pathological events in the mice, cell fate of transplanted neural stem/precursor cells, and gene expression and inflammatory cell infiltration at the injured site. We used two different doses of neural stem/precursor cells and two treatment schedules, either subacute (7 days) or early chronic (21 days) neural stem/precursor cell transplantation after the induction of experimental thoracic severe spinal cord injury. Only the subacute transplant of neural stem/precursor cells enhanced the recovery of locomotor functions of mice with spinal cord injury. Transplanted neural stem/precursor cells survived undifferentiated at the level of the peri-lesion environment and established contacts with endogenous phagocytes via cellular-junctional coupling. This was associated with significant modulation of the expression levels of important inflammatory cell transcripts in vivo. Transplanted neural stem/precursor cells skewed the inflammatory cell infiltrate at the injured site by reducing the proportion of 'classically-activated' (M1-like) macrophages, while promoting the healing of the injured cord. We here identify a precise window of opportunity for the treatment of complex spinal cord injuries with therapeutically plastic somatic stem cells, and suggest that neural stem/precursor cells have the ability to re-programme the local inflammatory cell microenvironment from a 'hostile' to an 'instructive' role, thus facilitating the healing or regeneration past the lesion.
Recent evidence suggests that neural stem/precursor cells (NPCs) promote recovery in animal models with delayed neuronal death via a number of indirect bystander effects. A comprehensive knowledge of ...how transplanted NPCs exert their therapeutic effects is still lacking. Here, we investigated the effects of a delayed transplantation of adult syngenic NPCs—injected intravenously 72 h after transient middle cerebral artery occlusion—on neurological recovery, histopathology and gene expression. NPC-transplanted mice showed a significantly improved recovery from 18 days post-transplantation (dpt) onwards, which persisted throughout the study. A small percentage of injected NPCs accumulated in the brain, integrating mainly in the infarct boundary zone, where most of the NPCs remained undifferentiated up to 30 dpt. Histopathological analysis revealed a hitherto unreported very delayed neuroprotective effect of NPCs, becoming evident at 10 and 30 dpt. Tissue survival was associated with downregulation of markers of inflammation, glial scar formation and neuronal apoptotic death at both mRNA and protein levels. Our data highlight the relevance of very delayed degenerative processes in the stroke brain that are intimately associated with inflammatory and glial responses. These processes may efficaciously be antagonized by (stem) cell-based strategies at time-points far beyond established therapeutic windows for pharmacological neuroprotection.
Objective
Transplanted neural stem/precursor cells (NPCs) display peculiar therapeutic plasticity in vivo. Although the replacement of cells was first expected as the prime therapeutic mechanism of ...stem cells in regenerative medicine, it is now clear that transplanted NPCs simultaneously instruct several therapeutic mechanisms, among which replacement of cells might not necessarily prevail. A comprehensive understanding of the mechanism(s) by which NPCs exert their therapeutic plasticity is lacking. This study was designed as a preclinical approach to test the feasibility of human NPC transplantation in an outbreed nonhuman primate experimental autoimmune encephalomyelitis (EAE) model approximating the clinical and complex neuropathological situation of human multiple sclerosis (MS) more closely than EAE in the standard laboratory rodent.
Methods
We examined the safety and efficacy of the intravenous (IV) and intrathecal (IT) administration of human NPCs in common marmosets affected by human myelin oligodendrocyte glycoprotein 1‐125–induced EAE. Treatment commenced upon the occurrence of detectable brain lesions on a 4.7T spectrometer.
Results
EAE marmosets injected IV or IT with NPCs accumulated lower disability and displayed increased survival, as compared with sham‐treated controls. Transplanted NPCs persisted within the host central nervous system (CNS), but were also found in draining lymph nodes, for up to 3 months after transplantation and exhibited remarkable immune regulatory capacity in vitro.
Interpretation
Herein, we provide the first evidence that human CNS stem cells ameliorate EAE in nonhuman primates without overt side effects. Immune regulation (rather than neural differentiation) is suggested as the major putative mechanism by which NPCs ameliorate EAE in vivo. Our findings represent a critical step toward the clinical use of human NPCs in MS. Ann Neurol 2009;66:343–354
Subpolar Mode Waters (SPMW) in the eastern North Atlantic subpolar gyre are investigated with hydrographic and Lagrangian data (surface drifters and isopycnal floats). Historical hydrographic data ...show that SPMWs are surface water masses with nearly uniform properties, confined between the ocean surface and the permanent pycnocline. SPMWs represented by densities 27.3σθ, 27.4σθ, and 27.5σθ are present in the eastern subpolar gyre and are influenced by the topography and the regional circulation. Construction of an absolute surface stream function from surface drifters shows that SPMWs are found along the mean path of each of the several branches of the North Atlantic Current (NAC) and their density increases gradually downstream. The Rockall Trough branch of the NAC carries 27.3σθ, 27.4σθ, and 27.5σθ SPMW toward the Iceland‐Faroe Front. In the Iceland Basin, the Subarctic Front along the western flank of the Rockall Plateau carries a similar sequence of SPMW. The western side of the Central Iceland Basin branch of the NAC, on the other hand, veers westward and joins the East Reykjanes Ridge Current, feeding the 27.5σθ SPMW on the Reykjanes Ridge. The separation among the various NAC branches most likely explains the different properties that characterize the 27.5σθ SPMW found on the Reykjanes Ridge and on the Iceland‐Faroe Ridge. Since the branches of the NAC have a dominant northeastward direction, the newly observed distribution of SPMW combined with the new stream function calculation modify the original hypothesis of McCartney and Talley (1982) of a smooth cyclonic pathway for SPMW advection and density increase around the subpolar gyre.
The adult brain retains over life endogenous neural stem/precursor cells (eNPCs) within the subventricular zone (SVZ). Whether or not these cells exert physiological functions is still unclear. In ...the present work, we provide evidence that SVZ-eNPCs tune structural, electrophysiological, and behavioural aspects of striatal function via secretion of insulin-like growth factor binding protein-like 1 (IGFBPL1). In mice, selective ablation of SVZ-eNPCs or selective abrogation of IGFBPL1 determined an impairment of striatal medium spiny neuron morphology, a higher failure rate in GABAergic transmission mediated by fast-spiking interneurons, and striatum-related behavioural dysfunctions. We also found IGFBPL1 expression in the human SVZ, foetal and induced-pluripotent stem cell-derived NPCs. Finally, we found a significant correlation between SVZ damage, reduction of striatum volume, and impairment of information processing speed in neurological patients. Our results highlight the physiological role of adult SVZ-eNPCs in supporting cognitive functions by regulating striatal neuronal activity.
Endogenous neural stem/precursor cells (NPCs) are considered a functional reservoir for promoting tissue homeostasis and repair after injury, therefore regenerative strategies that mobilize these ...cells have recently been proposed. Despite evidence of increased neurogenesis upon acute inflammatory insults (e.g. ischaemic stroke), the plasticity of the endogenous brain stem cell compartment in chronic CNS inflammatory disorders remains poorly characterized. Here we show that persistent brain inflammation, induced by immune cells targeting myelin, extensively alters the proliferative and migratory properties of subventricular zone (SVZ)-resident NPCs in vivo leading to significant accumulation of non-migratory neuroblasts within the SVZ germinal niche. In parallel, we demonstrate a quantitative reduction of the putative brain stem cells proliferation in the SVZ during persistent brain inflammation, which is completely reversed after in vitro culture of the isolated NPCs. Together, these data indicate that the inflamed brain microenvironment sustains a non cell-autonomous dysfunction of the endogenous CNS stem cell compartment and challenge the potential efficacy of proposed therapies aimed at mobilizing endogenous precursors in chronic inflammatory brain disorders.
In response to the COVID-19 health emergency, mass media widely spread guidelines to stop the virus transmission, leading to an excessive and unaware use of detergents and disinfectants. In Italy and ...in other countries this tendency caused a significant increase of exposures to these products in 2020. Evaluating data collected by the Italian Pavia Poison Centre (PPC), this study intends to examine the relationship between the COVID-19 lockdown and the variations of exposures to specific product categories possibly associated to the containment measures implemented. Simultaneously, this work shows the effectiveness of the European Product Categorisation System (EuPCS) in surveillance activities of dangerous chemicals.
Exposure cases managed by the PPC during March-May 2020 (lockdown) and during the same months of 2017-2018-2019 were compared. Differences in categorical variables were tested with the Chi-square test. The level of significance was set at Alpha = .05. The study included all EuPCS groups but specifically focused on cleaners, detergents, biocides and cosmetics.
During the lockdown, calls from private citizens showed a highly significant increase (+ 11.5%, p < .001) and occupational exposures decreased (- 11.7%, p = .011). Among Cleaners, exposures to Bleaches slightly increased while Drain cleaning products went through a significant reduction (- 13.9%, p = .035). A highly significant increase of exposures to Disinfectants was observed (+ 7.7%, p = .007), particularly to those for surfaces (+ 6.8%, p = .039). Regarding Cosmetics, both handwashing soaps and gel products significantly increased (respectively: + 25.0, p = .016 and + 9.7%, p = .028). Among children 1-5 years, the statistical significance is reached with exposures to Dishwashing detergents (+ 13.1%, p = .032), handwashing soaps (+ 28.6%, p = .014) and handwashing gel products (+ 16.8%, p = .010). Contrarily, Liquid Laundry Detergent Capsules decreased in a highly significant manner (- 25%; p = .001). The general severity of exposures showed a highly significant decrease (Moderate: - 10.1%, p = .0002).
This study investigated the relationship between the COVID-19 lockdown and the variations of exposures to some product categories related to the containment measures. The results obtained support any action to be taken by Competent Authorities to implement measures for a safer use of cleaners/disinfectants. This paper shows the benefit in applying the EuPCS to categorize products according to their intended use, though an extension of this system to products not covered by CLP Regulation may be a further advantage.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Spinal cord injury (SCI) is a devastating condition mainly deriving from a traumatic damage of the spinal cord (SC). Immune cells and endogenous SC-neural stem cells (SC-NSCs) play a critical role in ...wound healing processes, although both are ineffective to completely restore tissue functioning. The role of SC-NSCs in SCI and, in particular, whether such cells can interplay with the immune response are poorly investigated issues, although mechanisms governing such interactions might open new avenues to develop novel therapeutic approaches.
We used two transgenic mouse lines to trace as well as to kill SC-NSCs in mice receiving SCI. We used Nestin CreERT2 mice to trace SC-NSCs descendants in the spinal cord of mice subjected to SCI. While mice carrying the suicide gene thymidine kinase (TK) along with the GFP reporter, under the control of the Nestin promoter regions (Nestin
mice) were used to label and selectively kill SC-NSCs.
We found that SC-NSCs are capable to self-activate after SCI. In addition, a significant worsening of clinical and pathological features of SCI was observed in the Nestin
mice, upon selective ablation of SC-NSCs before the injury induction. Finally, mice lacking in SC-NSCs and receiving SCI displayed reduced levels of different neurotrophic factors in the SC and significantly higher number of M1-like myeloid cells.
Our data show that SC-NSCs undergo cell proliferation in response to traumatic spinal cord injury. Mice lacking SC-NSCs display overt microglia activation and exaggerate expression of pro-inflammatory cytokines. The absence of SC-NSCs impaired functional recovery as well as neuronal and oligodendrocyte cell survival. Collectively our data indicate that SC-NSCs can interact with microglia/macrophages modulating their activation/responses and that such interaction is importantly involved in mechanisms leading tissue recovery.
The processes that lead to the transformation and origin of the eastern North Atlantic Subpolar Mode Waters (SPMW) are investigated from observational data using an extended Walin framework. Air‐sea ...flux data from the National Oceanography Center, Southampton (NOCS), and hydrographic data from the A24 cruise collected during the World Ocean Circulation Experiment (WOCE) are used to estimate the contribution of diapycnal and isopycnal fluxes to the density classes that include SPMW. Surface diapycnal volume flux is the dominant source of waters in the SPMW density. In the North Atlantic subpolar gyre the diapycnal volume flux occurs along the main branches of the North Atlantic Current (NAC) and it has an average transport of 14 ± 6.5 Sv, with a maximum of 21.5 Sv across the 27.35σθ isopycnal. The regional distribution of the diapycnal flux on isopycnal surfaces is computed to identify the areas with the largest diapycnal flux. These regions coincide with the location of SPMW based on potential vorticity. The surface diapycnal flux is associated with obduction and subduction through the permanent pycnocline. Therefore, the water involved in the transformation of SPMWs is continuously exchanged with the ocean interior. In addition, we suggest that subduction is not associated with smooth advection from the mixed layer to the ocean interior, but is water mass loss entrainment into the deep overflows of the subpolar gyre. The isopycnal component of the SPMW throughput is estimated from the geostrophic transport across the A24 section from Greenland to Scotland and is 10% to 40% of the diapycnal flux.
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