Current treatments for tendon injuries often fail to fully restore joint biomechanics leading to the recurrence of symptoms, and thus resulting in a significant health problem with a relevant social ...impact worldwide. Cell-based approaches involving the use of stem cells might enable tailoring a successful tendon regeneration outcome. As growth factors (GFs) powerfully regulate the cell biological response, their exogenous addition can further stimulate stem cells into the tenogenic lineage, which might eventually depend on stem cells source. In the present study we investigate the tenogenic differentiation potential of human- amniotic fluid stem cells (hAFSCs) and adipose-derived stem cells (hASCs) with several GFs associated to tendon development and healing; namely, EGF, bFGF, PDGF-BB and TGF-β1. Stem cells response to biochemical stimuli was studied by screening of tendon-related genes (collagen type I, III, decorin, tenascin C and scleraxis) and proteins found in tendon extracellular matrix (ECM) (Collagen I, III, and Tenascin C). Despite the fact that GFs did not seem to influence the synthesis of tendon ECM proteins, EGF and bFGF influenced the expression of tendon-related genes in hAFSCs, while EGF and PDGF-BB stimulated the genetic expression in hASCs. Overall results on cellular alignment morphology, immunolocalization and PCR analysis indicated that both stem cell source can be biochemically induced towards tenogenic commitment, validating the potential of hASCs and hAFSCs for tendon regeneration strategies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tendon tissue engineering strategies that recreate the biophysical and biochemical native microenvironment have a greater potential to achieve regeneration. Here, we developed tendon biomimetic ...scaffolds using mechanically competent yarns of poly-ε-caprolactone, chitosan, and cellulose nanocrystals to recreate the inherent tendon hierarchy from a nano-to-macro scale. These were then coated with tropoelastin (TROPO) through polydopamine (PDA) linking, to mimic the native extracellular matrix (ECM) composition and elasticity. Both PDA and TROPO coatings decreased surface stiffness without masking the underlying substrate. We found that human adipose-derived stem cells (hASCs) seeded onto these TROPO biomimetic scaffolds more rapidly acquired their spindle-shape morphology and high aspect ratio characteristic of tenocytes. Immunocytochemistry shows that the PDA and TROPO-coated surfaces boosted differentiation of hASCs toward the tenogenic lineage, with sustained expression of the tendon-related markers scleraxis and tenomodulin up to 21 days of culture. Furthermore, these surfaces enabled the deposition of a tendon-like ECM, supported by the expression of collagens type I and III, tenascin, and decorin. Gene expression analysis revealed a downregulation of osteogenic and fibrosis markers in the presence of TROPO when compared with the control groups, suggesting proper ECM deposition. Remarkably, differentiated cells exposed to TROPO acquired an elastogenic profile due to the evident elastin synthesis and deposition, contributing to the formation of a more mimetic matrix in comparison with the PDA-coated and uncoated conditions. In summary, our biomimetic substrates combining biophysical and biological cues modulate stem cell behavior potentiating their long-term tenogenic commitment and the production of an elastin-rich ECM.
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IJS, KILJ, NUK, PNG, UL, UM
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Tendons are powerful 3D biomechanically structures combining a few cells in an intrincated and highly hierarchical niche environment. When tendon homeostasis is compromised, ...restoration of functionality upon injury is limited and requires alternatives to current augmentation or replacement strategies. Cell sheet technologies are a powerful tool for the fabrication of living extracellular-rich patches towards regeneration of tenotopic defects. Thus, we originally propose the development of magnetically responsive tenogenic patches through magnetic cell sheet (magCSs) technology that enable the remote control upon implantation of the tendon-mimicking constructs. A Tenomodulin positive (TNMD+) subpopulation of cells sorted from a crude population of human adipose stem cells (hASCs) previously identified as being prone to tenogenesis was selected for the magCSs patch construction. We investigated the stability, the cellular co-location of the iron oxide nanoparticles (MNPs), as well as the morphology and mechanical properties of the developed magCSs. Moreover, the expression of tendon markers and collagenous tendon-like matrix were further assessed under the actuation of an external magnetic field.
Overall, this study confirms the potential to bioengineer tendon patches using a magnetic cell sheet construction with magnetic responsiveness, good mechanoelastic properties and a tenogenic prone stem cell population envisioning cell-based functional therapies towards tendon regeneration.
The concept of magnetic force-based tissue engineering may assist the development of innovative solutions to treat tendon (or other tissues) disorders upon remote control of biological processes as cell migration or differentiation. Herein, we originally fabricated magnetic responsive cell sheets (magCSs) with a Tenomodulin positive subpopulation of adipose tissue derived stem cells identified to commit to the tenogenic lineage. To the best of authors knowledge, this is the first time a tendon oriented strategy resorting on magCSsis reported. Moreover, the promising role of tenogenic living constructs fabricated as magnetically responsive ECM-rich patches is highlighted, envisioning the stimulation of endogenous regenerative mechanisms. Altogether, these findings contribute to future stem cell studies and their translation toward tendon therapies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Understanding how irrigation is used across agricultural landscapes is essential to support efforts to grow more food while reducing pressures on limited freshwater resources. However, to date, few ...studies have analyzed the underlying spatial and temporal variability in farmers' individual water use decisions at a landscape scale. We compare estimates of irrigation water requirements derived using state-of-the-art remote sensing models with metered abstraction records for 1400 fields over a 13 year period in the US state of Nebraska, one of the world's most intensively irrigated agricultural regions. We show that farmers' observed water use decisions often diverge significantly from biophysical estimates of crop irrigation requirements. In particular, our findings are consistent with widespread use of water conservation practices by farmers in drought years as an adaptive response to rising irrigation costs and regulatory water supply constraints in these years. We also demonstrate that, in any individual year, farmers observed water use exhibits large field-to-field variability, which cannot be explained fully by differences in weather, soil type, crop choice, or technology. Our results highlight the value of using both in situ monitoring and remote sensing to evaluate farmers' individual water use behavior and understand likely responses to future changes in climate or water policy. Moreover, our findings also demonstrate potential challenges for current efforts in developed and developing countries to apply model-based approaches for field-level water use accounting and enforcement of irrigation water rights.
Purpose
Most MR spectroscopy (MRS) pulse sequences rely on broadband excitation with water saturation and typically focus on upfield signals. By contrast, the downfield spectrum, which contains many ...potentially useful resonances, is typically not targeted because conventional water‐suppressed techniques indirectly saturate the labile protons through exchange. Relaxation‐enhanced MRS (RE‐MRS) uses frequency‐selective excitation while actively avoiding bulk water perturbation, thereby enabling high‐quality downfield spectroscopy. However, RE‐MRS typically requires very long (typically >40 ms) echo times (TEs) due to its localization module, which inevitably decreases sensitivity and filters shorter T2 components. Here, we overcome this limitation by combining RE‐MRS and image selected in vivo spectroscopy (ISIS) localization, abbreviated iRE‐MRS, which in turn allows very short TEs (5 ms using our hardware).
Methods
Experiments were performed in vitro for validation as well as and in in vivo rat brains at 9.4T.
Results
The new iRE‐MRS methodology was validated in phantoms where good performance was noted. When the downfield spectrum was investigated at short TEs in in vivo rat brains, iRE‐MRS provided very high sensitivity; the ensuing downfield spectra encompassed numerous broad peaks, as well as a broad baseline. All downfield spectral peaks were highly attenuated by increasing TEs as well as by applying water saturation, although to different extent. The signal ratios also varied between TEs, suggesting that exchange rates are different among the downfield signals.
Conclusions
Short‐TE iRE 1H downfield MRS opens new directions in the investigation of in vivo downfield metabolites and their role on healthy and disease processes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The present work has explored bioactive glass nanoparticles (BGNPs) and developed strontium-doped nanoparticles (BGNPsSr), envisioning orthopedic strategies compatible with vascularization. The ...nanoparticles were synthesized by the sol–gel method, achieving a diameter of 55 nm for BGNPs and 75 nm for BGNPsSr, and the inclusion of strontium caused no structural alteration. The nanoparticles exhibited high cytocompatibility for human umbilical vein endothelial cells (HUVECs) and SaOS-2. Additionally, the incorporation of strontium emphasized the tubule networking behavior of HUVECs. Our results demonstrate that the nanoparticle dissolution products encouraged the osteogenic differentiation of human adipose stem cells as it favored the expression of key genes and proteins associated with osteogenic lineage. This effect was markedly enhanced for BGNPsSr, which could prompt stem cell osteogenic differentiation without the typical osteogenic inducers. This study not only supports the hypothesis that BGNPs might play a significant role in osteogenic commitment but also highlights that the designed BGNPsSr is a valuable tool for stem cell “tune-up” in bone tissue engineering applications.
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IJS, KILJ, NUK, PNG, UL, UM
Carbapenem-resistant Enterobacteriaceae (CRE), especially those that produce Klebsiella pneumoniae carbapenemase (KPC) and are associated with colistin resistance, pose a severe health threat due to ...the limited treatment options.
To describe two outbreaks of KPC-producing K. pneumoniae in an adult intensive care unit (AICU) in Brazil. In May 2015, 14 patients had colistin-susceptible KPC-producing strains (ColS-KPC), and in July 2015, nine patients had colistin-resistant KPC-producing strains (ColR-KPC).
Between September 2014 and August 2015, we performed surveillance at a university hospital and all CRE were tested for blaKPC genes. Clonality was investigated by pulsed-field gel electrophoresis. Resistance to colistin was confirmed by broth microdilution method. Consumption of carbapenems and colistin was expressed as defined daily doses.
In all, 111 patients with CRE were identified during the surveillance period; K. pneumoniae was the major isolate (77.13%). The two outbreaks were identified when infection rates (KPC per 1000 patient-days) exceeded the background level. Rates of carbapenem and colistin consumption were high. Control measures (bedside alcohol gel, contact precautions, regular rectal swabs) did not curtail the outbreaks. Mortality rates were 42.9% and 44.4% for ColS-KPC- and ColR-KPC-infected patients, respectively. After the death of four infected patients with ColR-KPC, the unit was closed to new admissions.
Our experience demonstrates the serious risks presented by KPC, and especially ColR-KPC, in Brazilian AICUs. Selective pressure from excessive antibiotic use and transmission on healthcare workers' hands were likely the major factors in transmission.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
ASTEP 400, the main instrument of the ASTEP (Antarctica Search for Transiting ExoPlanets) programme, is a 40 cm telescope, designed to withstand the harsh conditions in Antarctica, achieving a ...photometric accuracy of a fraction of millimagnitude on hourly time-scales for planet-hosting southern bright (R ∼ 12 mag) stars. We review the performances of this instrument, describe its operating conditions, and present results from the analysis of observations obtained during its first three years (2010–2012) of operation, before its repatriation in 2014. During this time, we observed a total of 22 stellar fields (1° × 1° field of view). Each field, in which we measured stars up to magnitude R = 18 mag, was observed continuously during ∼7 to ∼30 d. More than 200 000 frames were recorded and 310 000 stars processed, using an implementation of the optimal image subtraction photometry algorithm. We found 43 planetary transit candidates. 20 of these candidates were observed using spectroscopic follow-ups including four targets classified as good planet candidates. Our results demonstrate that accurate near-continuous photometric observations are achievable from the Concordia station at Dome C in Antarctica, even if we were not able to reach the nominal photometric precision of the instrument. We conducted a correlation analysis between the rms noise and a large number of external parameters and found that source of the ∼1 mmag correlated noise is not obvious and does not depend on a single parameter. However, our analysis provided some hints and guidance to increase the photometric accuracy of the instrument. These improvements should equip any future telescope operating in Antarctica.
The basal ganglia are thought to contribute to decision-making and motor control. These functions are critically dependent on timing information, which can be extracted from the evolving state of ...neural populations in their main input structure, the striatum. However, it is debated whether striatal activity underlies latent, dynamic decision processes or kinematics of overt movement. Here, we measured the impact of temperature on striatal population activity and the behavior of rats, and compared the observed effects with neural activity and behavior collected in multiple versions of a temporal categorization task. Cooling caused dilation, and warming contraction, of both neural activity and patterns of judgment in time, mimicking endogenous decision-related variability in striatal activity. However, temperature did not similarly affect movement kinematics. These data provide compelling evidence that the timecourse of evolving striatal activity dictates the speed of a latent process that is used to guide choices, but not continuous motor control. More broadly, they establish temporal scaling of population activity as a likely neural basis for variability in timing behavior.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
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