Co-transplantation of Human Embryonic Stem Cell-derived Neural Progenitors and Schwann Cells in a Rat Spinal Cord Contusion Injury Model Elicits a Distinct Neurogenesis and Functional Recovery

Co-transplantation of neural progenitors (NPs) with Schwann cells (SCs) might be a way to overcome low rate of neuronal differentiation of NPs following transplantation in spinal cord injury (SCI) and the improvement of locomotor recovery. In this study, we initially generated NPs from human embryonic stem cells (hESCs) and investigated their potential for neuronal differentiation and functional recovery when co-cultured with SCs in vitro and co-transplanted in a rat acute model of contused SCI. Co-cultivation results revealed that the presence of SCs provided a consistent status for hESC-NPs and recharged their neural differentiation toward a predominantly neuronal fate. Following transplantation, a significant functional recovery was observed in all engrafted groups (NPs, SCs, NPs+SCs) relative to the vehicle and control groups. We also observed that animals receiving co-transplants established a better state as assessed with the BBB functional test. Immunohistofluorescence evaluation five weeks after transplantation showed invigorated neuronal differentiation and limited proliferation in the co-transplanted group when compared to the individual hESC-NPs grafted group. These findings have demonstrated that the co-transplantation of SCs with hESC-NPs could offer a synergistic effect, promoting neuronal differentiation and functional recovery

Assessment of left ventricular diastolic function in children after successful repair of aortic coarctation

The purpose of the study was an assessment of left ventricular diastolic function in children after the successful repair of aortic coarctation (CoA). The prospective study concerned 32 pediatric patients after the CoA surgery. Tissue Doppler imaging parameters including strain and strain rate and the conventional echocardiographic indexes were analyzed in patients and healthy controls. Analysis of mitral annulus velocities, E–E′ ratio, strain, and strain rate of left ventricular mid-cavity segments and conventional indexes of mitral inflow showed the worsening of left ventricular diastolic mechanics in the study group compared to healthy controls. The E/E′ ratio was significantly higher in the study group compared to the control group (8.30 ± 3.24 vs. 6.95 ± 1.36; p < 0.05). The early diastolic strain rate to late diastolic strain rate ratio as well as early to late diastolic strain ratio of the left ventricular mid-cavity segments were significantly lower in the study group compared to healthy controls (1.81 ± 0.63 vs. 3.74 ± 1.53; p < 0.001 and 1.20 ± 0.49 vs. 3.41 ± 1.26; p < 0.001). No differences of the pulmonary venous flow parameters between those two groups were observed. The left ventricular diastolic mechanics in hypertensive patients after CoA repair did not differ from normotensive subjects. Hypertensive and normotensive children after surgical repair of CoA are found to have worsening of the left ventricular diastolic mechanics suggesting the impairment of the active myocardial relaxation

The changing material around (2060) Chiron from an occultation on 2022 December 15

We could accurately predict the shadow path and successfully observe an occultation of a bright star by Chiron on 2022 December 15. The Kottamia Astronomical Observatory in Egypt did not detect the occultation by the solid body, but we detected three extinction features in the light curve that had symmetrical counterparts with respect to the central time of the occultation. One of the features is broad and shallow, whereas the other two features are sharper with a maximum extinction of $\sim$25$\%$ at the achieved spatial resolution of 19 km per data point. From the Wise observatory in Israel, we detected the occultation caused by the main body and several extinction features surrounding the body. When all the secondary features are plotted in the sky plane we find that they can be caused by a broad $\sim$580 km disk with concentrations at radii of 325 \pm 16 km and 423 \pm 11 km surrounding Chiron. At least one of these structures appears to be outside the Roche limit. The ecliptic coordinates of the pole of the disk are $\lambda$ = 151$^\circ~\pm$ 8$^\circ$ and $\beta$ = 18$^\circ~\pm$ 11$^\circ$, in agreement with previous results. We also show our long-term photometry indicating that Chiron had suffered a brightness outburst of at least 0.6 mag between March and September 2021 and that Chiron was still somewhat brighter at the occultation date than at its nominal pre-outburst phase. The outermost extinction features might be consistent with a bound or temporarily bound structure associated with the brightness increase. However, the nature of the brightness outburst is unclear, and it is also unclear whether the dust or ice released in the outburst could be feeding a putative ring structure or if it emanated from it.Comment: 6 pages, 4, figure

Schwann-Spheres Derived from Injured Peripheral Nerves in Adult Mice - Their In Vitro Characterization and Therapeutic Potential

Multipotent somatic stem cells have been identified in various adult tissues. However, the stem/progenitor cells of the peripheral nerves have been isolated only from fetal tissues. Here, we isolated Schwann-cell precursors/immature Schwann cells from the injured peripheral nerves of adult mice using a floating culture technique that we call “Schwann-spheres." The Schwann-spheres were derived from de-differentiated mature Schwann cells harvested 24 hours to 6 weeks after peripheral nerve injury. They had extensive self-renewal and differentiation capabilities. They strongly expressed the immature-Schwann-cell marker p75, and differentiated only into the Schwann-cell lineage. The spheres showed enhanced myelin formation and neurite growth compared to mature Schwann cells in vitro. Mature Schwann cells have been considered a promising candidate for cell-transplantation therapies to repair the damaged nervous system, whereas these “Schwann-spheres" would provide a more potential autologous cell source for such transplantation

Ready for O4 II: GRANDMA Observations of Swift GRBs during eight-weeks of Spring 2022

We present a campaign designed to train the GRANDMA network and its infrastructure to follow up on transient alerts and detect their early afterglows. In preparation for O4 II campaign, we focused on GRB alerts as they are expected to be an electromagnetic counterpart of gravitational-wave events. Our goal was to improve our response to the alerts and start prompt observations as soon as possible to better prepare the GRANDMA network for the fourth observational run of LIGO-Virgo-Kagra (which started at the end of May 2023), and future missions such as SM. To receive, manage and send out observational plans to our partner telescopes we set up dedicated infrastructure and a rota of follow-up adcates were organized to guarantee round-the-clock assistance to our telescope teams. To ensure a great number of observations, we focused on Swift GRBs whose localization errors were generally smaller than the GRANDMA telescopes' field of view. This allowed us to bypass the transient identification process and focus on the reaction time and efficiency of the network. During 'Ready for O4 II', 11 Swift/INTEGRAL GRB triggers were selected, nine fields had been observed, and three afterglows were detected (GRB 220403B, GRB 220427A, GRB 220514A), with 17 GRANDMA telescopes and 17 amateur astronomers from the citizen science project Kilonova-Catcher. Here we highlight the GRB 220427A analysis where our long-term follow-up of the host galaxy allowed us to obtain a photometric redshift of $z=0.82\pm0.09$, its lightcurve elution, fit the decay slope of the afterglows, and study the properties of the host galaxy

GRANDMA and HXMT Observations of GRB 221009A -- the Standard-Luminosity Afterglow of a Hyper-Luminous Gamma-Ray Burst

GRB 221009A is the brightest Gamma-Ray Burst (GRB) detected in more than 50 years of study. In this paper, we present observations in the X-ray and optical domains after the GRB obtained by the GRANDMA Collaboration (which includes observations from more than 30 professional and amateur telescopes) and the Insight-HXMT Collaboration. We study the optical afterglow with empirical fitting from GRANDMA+HXMT data, augmented with data from the literature up to 60 days. We then model numerically, using a Bayesian approach, the GRANDMA and HXMT-LE afterglow observations, that we augment with Swift-XRT and additional optical/NIR observations reported in the literature. We find that the GRB afterglow, extinguished by a large dust column, is most likely behind a combination of a large Milky-Way dust column combined with moderate low-metallicity dust in the host galaxy. Using the GRANDMA+HXMT-LE+XRT dataset, we find that the simplest model, where the observed afterglow is produced by synchrotron radiation at the forward external shock during the deceleration of a top-hat relativistic jet by a uniform medium, fits the multi-wavelength observations only moderately well, with a tension between the observed temporal and spectral evolution. This tension is confirmed when using the extended dataset. We find that the consideration of a jet structure (Gaussian or power-law), the inclusion of synchrotron self-Compton emission, or the presence of an underlying supernova do not improve the predictions, showing that the modelling of GRB22109A will require going beyond the most standard GRB afterglow model. Placed in the global context of GRB optical afterglows, we find the afterglow of GRB 221009A is luminous but not extraordinarily so, highlighting that some aspects of this GRB do not deviate from the global known sample despite its extreme energetics and the peculiar afterglow evolution.Comment: Accepted to ApJL for the special issue, 37 pages, 23 pages main text, 6 tables, 13 figure

The GRANDMA network in preparation for the fourth gravitational-wave observing run

GRANDMA is a world-wide collaboration with the primary scientific goal ofstudying gravitational-wave sources, discovering their electromagneticcounterparts and characterizing their emission. GRANDMA involves astronomers,astrophysicists, gravitational-wave physicists, and theorists. GRANDMA is now atruly global network of telescopes, with (so far) 30 telescopes in bothhemispheres. It incorporates a citizen science programme (Kilonova-Catcher)which constitutes an opportunity to spread the interest in time-domainastronomy. The telescope network is an heterogeneous set of already-existingobserving facilities that operate coordinated as a single observatory. Withinthe network there are wide-field imagers that can observe large areas of thesky to search for optical counterparts, narrow-field instruments that dotargeted searches within a predefined list of host-galaxy candidates, andlarger telescopes that are devoted to characterization and follow-up of theidentified counterparts. Here we present an overview of GRANDMA after the thirdobserving run of the LIGO/VIRGO gravitational-wave observatories in $2019-2020$and its ongoing preparation for the forthcoming fourth observational campaign(O4). Additionally, we review the potential of GRANDMA for the discovery andfollow-up of other types of astronomical transients.<br

Embryonic Stem Cell-Derived L1 Overexpressing Neural Aggregates Enhance Recovery after Spinal Cord Injury in Mice

An obstacle to early stem cell transplantation into the acutely injured spinal cord is poor survival of transplanted cells. Transplantation of embryonic stem cells as substrate adherent embryonic stem cell-derived neural aggregates (SENAs) consisting mainly of neurons and radial glial cells has been shown to enhance survival of grafted cells in the injured mouse brain. In the attempt to promote the beneficial function of these SENAs, murine embryonic stem cells constitutively overexpressing the neural cell adhesion molecule L1 which favors axonal growth and survival of grafted and imperiled cells in the inhibitory environment of the adult mammalian central nervous system were differentiated into SENAs and transplanted into the spinal cord three days after compression lesion. Mice transplanted with L1 overexpressing SENAs showed improved locomotor function when compared to mice injected with wild-type SENAs. L1 overexpressing SENAs showed an increased number of surviving cells, enhanced neuronal differentiation and reduced glial differentiation after transplantation when compared to SENAs not engineered to overexpress L1. Furthermore, L1 overexpressing SENAs rescued imperiled host motoneurons and parvalbumin-positive interneurons and increased numbers of catecholaminergic nerve fibers distal to the lesion. In addition to encouraging the use of embryonic stem cells for early therapy after spinal cord injury L1 overexpression in the microenvironment of the lesioned spinal cord is a novel finding in its functions that would make it more attractive for pre-clinical studies in spinal cord regeneration and most likely other diseases of the nervous system

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially