Experimental Treatments for Spinal Cord Injury: What you Should Know

Experiencing a spinal cord injury (SCI) is extremely distressing, both physically and psychologically, and throws people into a complex, unfamiliar world of medical procedures, terminology, and decision making. You may have already had surgery to stabilize the spinal column and reduce the possibility of further damage. You are understandably distressed about the functions you may have lost below the level of spinal injury. You wish to recover any lost abilities as soon as possible. You, your family, or friends may have searched the Internet for treatments and cures

Neighborhood Environment and Poor Maternal Glycemic Control-Associated Complications of Gestational Diabetes Mellitus

INTRODUCTION: Risk of complications due to gestational diabetes mellitus is increasing in the U.S., particularly among individuals from racial minorities. Research has focused largely on clinical interventions to prevent complications, rarely on individuals\u27 residential environments. This retrospective cohort study aims to examine the association between individuals\u27 neighborhoods and complications of gestational diabetes mellitus. METHODS: Demographic and clinical data were extracted from electronic health records and linked to American Community Survey data from the U.S. Census Bureau for 2,047 individuals who had 2,164 deliveries in 2014-2018. Data were analyzed in 2021-2022 using Wilcoxon rank sum test and chi-square test for bivariate analyses and logistic regression for analysis of independent effects. All census tract-based variables used in the model were dichotomized at the median. RESULTS: Bivariate analysis showed that the average percentage of adults earning CONCLUSIONS: Clinical interventions in concert with environmental changes could contribute to preventing maternal and neonatal complications of gestational diabetes mellitus

Antibody recognizing 4-sulfated chondroitin sulfate proteoglycans restores memory in tauopathy-induced neurodegeneration

Chondroitin sulfate proteoglycans (CSPGs) are the main active component of perineuronal nets (PNNs). Digestion of the glycosaminoglycan chains of CSPGs with chondroitinase ABC or transgenic attenuation of PNNs leads to prolongation of object recognition memory and activation of various forms of plasticity in the adult central nervous system. The inhibitory properties of the CSPGs depend on the pattern of sulfation of their glycosaminoglycans, with chondroitin 4-sulfate (C4S) being the most inhibitory form. In this study, we tested a number of candidates for functional blocking of C4S, leading to selection of an antibody, Cat316, which specifically recognizes C4S and blocks its inhibitory effects on axon growth. It also partly blocks binding of semaphorin 3A to PNNs and attenuates PNN formation. We asked whether injection of Cat316 into the perirhinal cortex would have the same effects on memory as chondroitinase ABC treatment. We found that masking C4S with the Cat316 antibody extended long-term object recognition memory in normal wild-type mice to 24 hours, similarly to chondroitinase or transgenic PNN attenuation. We then tested Cat316 for restoration of memory in a neurodegeneration model. Mice expressing tau with the P301S mutation showed profound loss of object recognition memory at 4 months of age. Injection of Cat316 into the perirhinal cortex normalized object recognition at 3 hours in P301S mice. These data indicate that Cat316 binding to C4S in the extracellular matrix can restore plasticity and memory in the same way as chondroitinase ABC digestion. Our results suggest that antibodies to C4S could be a useful therapeutic to restore memory function in neurodegenerative disorders.This work was supported by the ERC advanced grant ECM Neuro (294502), by a fellowship to SY from Alzheimer's Research UK (ARUK-RF2016A-1), and by the NIHR Cambridge Biomedical Research Centre

Astrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression.

The role of remote astrocyte (AC) reaction to central or peripheral axonal insult is not clearly understood. Here we use a transgenic approach to compare the direct influence of normal with diminished AC reactivity on neuronal integrity and synapse recovery following extracranial facial nerve transection in mice. Our model allows straightforward interpretations of AC-neuron signalling by reducing confounding effects imposed by inflammatory cells. We show direct evidence that perineuronal reactive ACs play a major role in maintaining neuronal circuitry following distant axotomy. We reveal a novel function of astrocytic signal transducer and activator of transcription-3 (STAT3). STAT3 regulates perineuronal astrocytic process formation and re-expression of a synaptogenic molecule, thrombospondin-1 (TSP-1), apart from supporting neuronal integrity. We demonstrate that, through this new pathway, TSP-1 is responsible for the remote AC-mediated recovery of excitatory synapses onto axotomized motor neurons in adult mice. These data provide new targets for neuroprotective therapies via optimizing AC-driven plasticity.This is the final version. It was first published in Nature Communications here: http://www.nature.com/ncomms/2014/140711/ncomms5294/abs/ncomms5294.html

How does the radio enhancement of broad absorption line quasars relate to colour and accretion rate?

The origin of radio emission in different populations of radio-quiet quasars is relatively unknown, but recent work has uncovered various drivers of increased radio-detection fraction. In this work, we pull together three known factors: optical colour (g - i), C IV distance (a proxy for L/LEdd), and whether or not the quasar contains broad absorption lines (BALQSOs) which signify an outflow. We use SDSS (Sloan Digital Sky Survey) DR14 spectra along with the LOFAR Two Metre Sky Survey Data Release 2 and find that each of these properties have an independent effect. BALQSOs are marginally more likely to be radio-detected than non-BALQSOs at similar colours and L/LEdd, moderate reddening significantly increases the radio-detection fraction and the radio detection increases with L/LEdd above a threshold for all populations. We test a widely used simple model for radio wind shock emission and calculate energetic efficiencies that would be required to reproduce the observed radio properties. We discuss interpretations of these results concerning radio-quiet quasars more generally. We suggest that radio emission in BALQSOs is connected to a different physical origin than the general quasar population since they show different radio properties independent of colour and C IV distance

6-Sulphated Chondroitins Have a Positive Influence on Axonal Regeneration

Chondroitin sulphate proteoglycans (CSPGs) upregulated in the glial scar inhibit axon regeneration via their sulphated glycosaminoglycans (GAGs). Chondroitin 6-sulphotransferase-1 (C6ST-1) is upregulated after injury leading to an increase in 6-sulphated GAG. In this study, we ask if this increase in 6-sulphated GAG is responsible for the increased inhibition within the glial scar, or whether it represents a partial reversion to the permissive embryonic state dominated by 6-sulphated glycosaminoglycans (GAGs). Using C6ST-1 knockout mice (KO), we studied post-injury changes in chondroitin sulphotransferase (CSST) expression and the effect of chondroitin 6-sulphates on both central and peripheral axon regeneration. After CNS injury, wild-type animals (WT) showed an increase in mRNA for C6ST-1, C6ST-2 and C4ST-1, but KO did not upregulate any CSSTs. After PNS injury, while WT upregulated C6ST-1, KO showed an upregulation of C6ST-2. We examined regeneration of nigrostriatal axons, which demonstrate mild spontaneous axon regeneration in the WT. KO showed many fewer regenerating axons and more axonal retraction than WT. However, in the PNS, repair of the median and ulnar nerves led to similar and normal levels of axon regeneration in both WT and KO. Functional tests on plasticity after the repair also showed no evidence of enhanced plasticity in the KO. Our results suggest that the upregulation of 6-sulphated GAG after injury makes the extracellular matrix more permissive for axon regeneration, and that the balance of different CSs in the microenvironment around the lesion site is an important factor in determining the outcome of nervous system injury

An interferometric SETI observation of Kepler-111 b

DATA AVAILABILITY : Data underlying this article are publicly available in the EVN Data Archive at JIVE at www.jive.eu/select -experiment and can be accessed with project codes RSG12 and RSW02. The e -MERLIN data and reduced EVN data will be shared on reasonable request to the corresponding author.This work has made use of data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC, https://www.cosmos.esa.int/web/gaia/dpac/consortium).The application of very long baseline interferometry (VLBI) to the search for extraterrestrial intelligence (SETI) has been limited to date, despite the technique offering many advantages o v er traditional single-dish SETI observations. In order to further develop interferometry for SETI, we used the European VLBI network (EVN) at 21 cm to observe potential secondary phase calibrators in the Kepler field. Unfortunately, no secondary calibrators were detected. Ho we ver, a VLBA primary calibrator in the field, J1926 + 4441, offset only ∼1.88 arcmin from a nearby exoplanet Kepler-111 b, was correlated with high temporal ( 0 . 25 s ) and spectral ( 16384 ×488 Hz channels ) resolution. During the analysis of the high-resolution data, we identified a spectral feature that was present in both the auto and cross-correlation data with a central frequency of 1420.424 ±0.0002 MHz and a width of 0.25 MHz. We demonstrate that the feature in the cross-correlations is an artefact in the data, associated with a significant increase in each telescope’s noise figure due to the presence of H I in the beam. This would typically go unnoticed in data correlated with standard spectral resolution. We flag (excluded from the subsequent analysis) these channels and phase rotate the data to the location of Kepler-111 b aided by the Gaia catalogue and search for signals with SNR > 7 . At the time of our observations, we detect no transmitters with an equivalent isotropically radiated power 4 ×10 15 W.A Newton Fund project, DARA (Development in Africa with Radio Astronomy), the European Commission Horizon 2020, Research and Innovation Programme.https://academic.oup.com/mnrasam2024PhysicsNon

Myelin-associated Glycoprotein Interacts with Neurons via a Sialic Acid Binding Site at ARG118 and a Distinct Neurite Inhibition Site

Inhibitory components in myelin are largely responsible for the lack of regeneration in the mammalian CNS. Myelin-associated glycoprotein (MAG), a sialic acid binding protein and a component of myelin, is a potent inhibitor of neurite outgrowth from a variety of neurons both in vitro and in vivo. Here, we show that MAG's sialic acid binding site is distinct from its neurite inhibitory activity. Alone, sialic acid–dependent binding of MAG to neurons is insufficient to effect inhibition of axonal growth. Thus, while soluble MAG-Fc (MAG extracellular domain fused to Fc), a truncated form of MAG-Fc missing Ig-domains 4 and 5, MAG(d1-3)-Fc, and another sialic acid binding protein, sialoadhesin, each bind to neurons in a sialic acid– dependent manner, only full-length MAG-Fc inhibits neurite outgrowth. These results suggest that a second site must exist on MAG which elicits this response. Consistent with this model, mutation of arginine 118 (R118) in MAG to either alanine or aspartate abolishes its sialic acid–dependent binding. However, when expressed at the surface of either CHO or Schwann cells, R118-mutated MAG retains the ability to inhibit axonal outgrowth. Hence, MAG has two recognition sites for neurons, the sialic acid binding site at R118 and a distinct inhibition site which is absent from the first three Ig domains

A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression

Background Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain. Methods We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients’ treatment assignments. Results Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and the psychotherapy group, as compared with 73 percent in the combined-treatment group (P Conclusions Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone