Narrative Review of Nimesulide in Adults: Current Scenario

Nimesulide, a nonsteroidal anti-inflammatory drug (NSAID), has been used as an effective treatment regimen for patients aged >12 years for fever, acute pain, acute tendinitis, osteoarthritis and dysmenorrhea. It is reported to be a superior antipyretic and anti-inflammatory drug than paracetamol and aspirin, respectively, and is equal to any of the NSAIDs alone in terms of analgesia. This paper reviews the current scenario of nimesulide in adult patients, concerning clinical evidence, use in special population and expert opinion. Overall, in comparison to other NSAIDs, including coxibs, nimesulide has a promising overall efficacy, safety and tolerability profile, as well as a satisfactory benefit/risk evaluation

A fast radio burst associated with a Galactic magnetar

Since their discovery in 2007, much effort has been devoted to uncovering the sources of the extragalactic, millisecond-duration fast radio bursts (FRBs). A class of neutron star known as magnetars is a leading candidate source of FRBs. Magnetars have surface magnetic fields in excess of $10^{14}$ G, the decay of which powers a range of high-energy phenomena. Here we present the discovery of a millisecond-duration radio burst from the Galactic magnetar SGR 1935+2154, with a fluence of $1.5\pm 0.3$ Mega-Jansky milliseconds. This event, termed ST 200428A(=FRB 200428), was detected on 28 April 2020 by the STARE2 radio array in the 1281--1468\,MHz band. The isotropic-equivalent energy released in ST 200428A is $4\times10^{3}$ times greater than in any Galactic radio burst previously observed on similar timescales. ST 200428A is just 40 times less energetic than the weakest extragalactic FRB observed to date, and is arguably drawn from the same population as the observed FRB sample. The coincidence of ST 200428A with an X-ray burst favours emission models developed for FRBs that describe synchrotron masers or electromagnetic pulses powered by magnetar bursts and giant flares. The discovery of ST 200428A implies that active magnetars like SGR 1935+2154 can produce FRBs at extragalactic distances. The high volumetric rate of events like ST 200428A motivates dedicated searches for similar bursts from nearby galaxies.Comment: 23 pages, 7 figures, 2 tables. Submitted to Natur

STARE2: Detecting Fast Radio Bursts in the Milky Way

There are several unexplored regions of the short-duration radio transient phase space. One such unexplored region is the luminosity gap between giant pulses (from pulsars) and cosmologically located fast radio bursts (FRBs). The Survey for Transient Astronomical Radio Emission 2 (STARE2) is a search for such transients out to 7 Mpc. STARE2 has a field of view of 3.6 steradians and is sensitive to 1 millisecond transients above ~300 kJy. With a two-station system we have detected and localized a solar burst, demonstrating that the pilot system is capable of detecting short duration radio transients. We found no convincing non-solar transients with duration between 65 μs and 34 ms in 200 days of observing, limiting with 95% confidence the all-sky rate of transients above ~300 kJy to <40 sky⁻¹ yr⁻¹. If the luminosity function of FRBs could be extrapolated down to 300 kJy for a distance of 10 kpc, then one would expect the rate to be ~2 sky⁻¹ yr⁻¹

STARE2: Detecting Fast Radio Bursts in the Milky Way

There are several unexplored regions of the short-duration radio transient phase space. One such unexplored region is the luminosity gap between giant pulses (from pulsars) and cosmologically located fast radio bursts (FRBs). The Survey for Transient Astronomical Radio Emission 2 (STARE2) is a search for such transients out to 7 Mpc. STARE2 has a field of view of 3.6 steradians and is sensitive to 1 millisecond transients above ~300 kJy. With a two-station system we have detected and localized a solar burst, demonstrating that the pilot system is capable of detecting short duration radio transients. We found no convincing non-solar transients with duration between 65 μs and 34 ms in 200 days of observing, limiting with 95% confidence the all-sky rate of transients above ~300 kJy to <40 sky⁻¹ yr⁻¹. If the luminosity function of FRBs could be extrapolated down to 300 kJy for a distance of 10 kpc, then one would expect the rate to be ~2 sky⁻¹ yr⁻¹

Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice

Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness, and airway remodeling. Epidemiologic data reveal that the prevalence of allergic sensitization and associated diseases has increased in the twentieth century. This has been hypothesized to be partly due to reduced contact with microbial organisms (the hygiene hypothesis) in industrialized society. Airway epithelial cells, once considered a static physical barrier between the body and the external world, are now widely recognized as immunologically active cells that can initiate, maintain, and restrain inflammatory responses, such as those that mediate allergic disease. Airway epithelial cells can sense allergens via expression of myriad Toll-like receptors (TLRs) and other pattern-recognition receptors. We sought to determine whether the innate immune response stimulated by a combination of Pam2CSK4 (“Pam2”, TLR2/6 ligand) and a class C oligodeoxynucleotide ODN362 (“ODN”, TLR9 ligand), when delivered together by aerosol (“Pam2ODN”), can modulate the allergic immune response to allergens. Treatment with Pam2ODN 7 days before sensitization to House Dust Mite (HDM) extract resulted in a strong reduction in eosinophilic and lymphocytic inflammation. This Pam2ODN immunomodulatory effect was also seen using Ovalbumin (OVA) and A. oryzae (Ao) mouse models. The immunomodulatory effect was observed as much as 30 days before sensitization to HDM, but ineffective just 2 days after sensitization, suggesting that Pam2ODN immunomodulation lowers the allergic responsiveness of the lung, and reduces the likelihood of inappropriate sensitization to aeroallergens. Furthermore, Pam2 and ODN cooperated synergistically suggesting that this treatment is superior to any single agonist in the setting of allergen immunotherapy

A Molecularly Engineered Antiviral Banana Lectin Inhibits Fusion and is Efficacious Against Influenza Virus Infection in Vivo

There is a strong need for a new broad-spectrum antiinfluenza therapeutic, as vaccination and existing treatments are only moderately effective. We previously engineered a lectin, H84T banana lectin (H84T), to retain broad-spectrum activity against multiple influenza strains, including pandemic and avian, while largely eliminating the potentially harmful mitogenicity of the parent compound. The amino acid mutation at position 84 from histidine to threonine minimizes the mitogenicity of the wild-type lectin while maintaining antiinfluenza activity in vitro. We now report that in a lethal mouse model H84T is indeed nonmitogenic, and both early and delayed therapeutic administration of H84T intraperitoneally are highly protective, as is H84T administered subcutaneously. Mechanistically, attachment, which we anticipated to be inhibited by H84T, was only somewhat decreased by the lectin. Instead, H84T is internalized into the late endosomal/lysosomal compartment and inhibits virus–endosome fusion. These studies reveal that H84T is efficacious against influenza virus in vivo, and that the loss of mitogenicity seen previously in tissue culture is also seen in vivo, underscoring the potential utility of H84T as a broad-spectrum antiinfluenza agent

AT2018cow: a luminous millimeter transient

We present detailed submillimeter- through centimeter-wave observations of the extraordinary extragalactic transient AT2018cow. The apparent characteristics—the high radio luminosity, the rise and long-lived emission plateau at millimeter bands, and the sub-relativistic velocity—have no precedent. A basic interpretation of the data suggests E_k ≳ 4 x 10^(48) erg coupled to a fast but sub-relativistic (ν ≈ 0.13c) shock in a dense (n_e ≈ 3 x 10^5 cm^(-3)) medium. We find that the X-ray emission is not naturally explained by an extension of the radio-submm synchrotron spectrum, nor by inverse Compton scattering of the dominant blackbody UV/optical/IR photons by energetic electrons within the forward shock. By Δt ≈ 20 days, the X-ray emission shows spectral softening and erratic inter-day variability. Taken together, we are led to invoke an additional source of X-ray emission: the central engine of the event. Regardless of the nature of this central engine, this source heralds a new class of energetic transients shocking a dense medium, which at early times are most readily observed at millimeter wavelengths

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands