Methamphetamine Inhibits the Glucose Uptake by Human Neurons and Astrocytes: Stabilization by Acetyl-L-Carnitine

Methamphetamine (METH), an addictive psycho-stimulant drug exerts euphoric effects on users and abusers. It is also known to cause cognitive impairment and neurotoxicity. Here, we hypothesized that METH exposure impairs the glucose uptake and metabolism in human neurons and astrocytes. Deprivation of glucose is expected to cause neurotoxicity and neuronal degeneration due to depletion of energy. We found that METH exposure inhibited the glucose uptake by neurons and astrocytes, in which neurons were more sensitive to METH than astrocytes in primary culture. Adaptability of these cells to fatty acid oxidation as an alternative source of energy during glucose limitation appeared to regulate this differential sensitivity. Decrease in neuronal glucose uptake by METH was associated with reduction of glucose transporter protein-3 (GLUT3). Surprisingly, METH exposure showed biphasic effects on astrocytic glucose uptake, in which 20 µM increased the uptake while 200 µM inhibited glucose uptake. Dual effects of METH on glucose uptake were paralleled to changes in the expression of astrocytic glucose transporter protein-1 (GLUT1). The adaptive nature of astrocyte to mitochondrial β-oxidation of fatty acid appeared to contribute the survival of astrocytes during METH-induced glucose deprivation. This differential adaptive nature of neurons and astrocytes also governed the differential sensitivity to the toxicity of METH in these brain cells. The effect of acetyl-L-carnitine for enhanced production of ATP from fatty oxidation in glucose-free culture condition validated the adaptive nature of neurons and astrocytes. These findings suggest that deprivation of glucose-derived energy may contribute to neurotoxicity of METH abusers

Anopheles gambiae Antiviral Immune Response to Systemic O'nyong-nyong Infection

Mosquito-borne viral diseases are found across the globe and are responsible for numerous severe human infections. In order to develop novel methods for prevention and treatment of these diseases, detailed understanding of the biology of viral infection and transmission is required. Little is known about invertebrate responses to infection in mosquito hosts. In this study we used a model system of Anopheles gambiae mosquitoes and O'nyong-nyong virus to study mosquito immune responses to infection. We examined the global transcriptional responses of A. gambiae to viral infection of the mosquito blood equivalent (the hemolymph) identifying a number of genes with immune functions that are switched on or off in response to infection, including complement-like proteins that circulate in the mosquito hemolymph. The switching on of these genes combined with co-infection experiments with malaria parasites suggests that viral infection inhibits the melanisation pathway. Through silencing the function of a selection of viral responsive genes, we identified four genes that have roles in A. gambiae anti-viral immunity; two putative recognition receptors (a galectin and an MD2-like receptor); two effector lysozymes. These molecules have previously non-described roles in antiviral immunity, and suggest uncharacterised mechanisms for targeting viral infection in A. gambiae mosquitoes

The Curious Case of ASASSN-20hx: A Slowly Evolving, UV- and X-Ray-Luminous, Ambiguous Nuclear Transient

We present observations of ASASSN-20hx, a nearby ambiguous nuclear transient (ANT) discovered in NGC 6297 by the All-Sky Automated Survey for Supernovae (ASAS-SN). We observed ASASSN-20hx from -30 to 275 days relative to the peak UV/optical emission using high-cadence, multiwavelength spectroscopy and photometry. From Transiting Exoplanet Survey Satellite data, we determine that the ANT began to brighten on 2020 June 22.8 with a linear rise in flux for at least the first week. ASASSN-20hx peaked in the UV/optical 30 days later on 2020 July 22.8 (MJD = 59052.8) at a bolometric luminosity of L = (3.15 ± 0.04) × 1043 erg s-1. The subsequent decline is slower than any TDE observed to date and consistent with many other ANTs. Compared to an archival X-ray detection, the X-ray luminosity of ASASSN-20hx increased by an order of magnitude to L x ∼1.5 × 1042 erg s-1 and then slowly declined over time. The X-ray emission is well fit by a power law with a photon index of "∼2.3-2.6. Both the optical and near-infrared spectra of ASASSN-20hx lack emission lines, unusual for any known class of nuclear transient. While ASASSN-20hx has some characteristics seen in both tidal disruption events and active galactic nuclei, it cannot be definitively classified with current data

The controversy of patellar resurfacing in total knee arthroplasty: Ibisne in medio tutissimus?

Early arthroplasty designs were associated with a high level of anterior knee pain as they failed to cater for the patello-femoral joint. Patellar resurfacing was heralded as the saviour safeguarding patient satisfaction and success but opinion on its necessity has since deeply divided the scientific community and has become synonymous to topics of religion or politics. Opponents of resurfacing contend that the native patella provides better patellar tracking, improved clinical function, and avoids implant-related complications, whilst proponents argue that patients have less pain, are overall more satisfied, and avert the need for secondary resurfacing. The question remains whether complications associated with patellar resurfacing including those arising from future component revision outweigh the somewhat increased incidence of anterior knee pain recorded in unresurfaced patients. The current scientific literature, which is often affected by methodological limitations and observer bias, remains confusing as it provides evidence in support of both sides of the argument, whilst blinded satisfaction studies comparing resurfaced and non-resurfaced knees generally reveal equivalent results. Even national arthroplasty register data show wide variations in the proportion of patellar resurfacing between countries that cannot be explained by cultural differences alone. Advocates who always resurface or never resurface indiscriminately expose the patella to a random choice. Selective resurfacing offers a compromise by providing a decision algorithm based on a propensity for improved clinical success, whilst avoiding potential complications associated with unnecessary resurfacing. Evidence regarding the validity of selection criteria, however, is missing, and the decision when to resurface is often based on intuitive reasoning. Our lack of understanding why, irrespective of pre-operative symptoms and patellar resurfacing, some patients may suffer pain following TKA and others may not have so far stifled our efforts to make the strategy of selective resurfacing succeed. We should hence devote our efforts in defining predictive criteria and indicators that will enable us to reliably identify those individuals who might benefit from a resurfacing procedure. Level of evidence V

The mass and galaxy distribution around SZ-selected clusters

We present measurements of the radial profiles of the mass and galaxy number density around Sunyaev–Zel’dovich (SZ)-selected clusters using both weak lensing and galaxy counts. The clusters are selected from the Atacama Cosmology Telescope Data Release 5 and the galaxies from the Dark Energy Survey Year 3 data set. With signal-to-noise ratio of 62 (45) for galaxy (weak lensing) profiles over scales of about 0.2–20 h−1 Mpc, these are the highest precision measurements for SZ-selected clusters to date. Because SZ selection closely approximates mass selection, these measurements enable several tests of theoretical models of the mass and light distribution around clusters. Our main findings are: (1) The splashback feature is detected at a consistent location in both the mass and galaxy profiles and its location is consistent with predictions of cold dark matter N-body simulations. (2) The full mass profile is also consistent with the simulations. (3) The shapes of the galaxy and lensing profiles are remarkably similar for our sample over the entire range of scales, from well inside the cluster halo to the quasilinear regime. We measure the dependence of the profile shapes on the galaxy sample, redshift, and cluster mass. We extend the Diemer & Kravtsov model for the cluster profiles to the linear regime using perturbation theory and show that it provides a good match to the measured profiles. We also compare the measured profiles to predictions of the standard halo model and simulations that include hydrodynamics. Applications of these results to cluster mass estimation, cosmology, and astrophysics are discussed

The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study

BackgroundThere are few reports of new functional impairment following critical illness from COVID-19. We aimed to describe the incidence of death or new disability, functional impairment and changes in health-related quality of life of patients after COVID-19 critical illness at 6 months.MethodsIn a nationally representative, multicenter, prospective cohort study of COVID-19 critical illness, we determined the prevalence of death or new disability at 6 months, the primary outcome. We measured mortality, new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2.0 12L (WHODAS) and health status with the EQ5D-5LTM.ResultsOf 274 eligible patients, 212 were enrolled from 30 hospitals. The median age was 61 (51–70) years, and 124 (58.5%) patients were male. At 6 months, 43/160 (26.9%) patients died and 42/108 (38.9%) responding survivors reported new disability. Compared to pre-illness, the WHODAS percentage score worsened (mean difference (MD), 10.40% [95% CI 7.06–13.77]; p TM utility score (MD, − 0.19 [− 0.28 to − 0.10]; p ConclusionsAt six months after COVID-19 critical illness, death and new disability was substantial. Over a third of survivors had new disability, which was widespread across all areas of functioning