A prospective open-label randomized comparative study in Alzheimer’s disease between two commonly used drugs in coastal Indian population

Background: Currently, therapy for Alzheimer’s disease (AD) is only symptomatic. Only two classes of drugs are approved by the United States Food and Drug Administration. Our study aimed at comparing efficacy and safety of memantine and donepezil in moderate to severe AD patients.Methods: Totally, 22 patients with moderate to severe AD were randomized into the 2 arms of the study. The study was divided into an initial 4 weeks for determination of onset of efficacy and subsequent 28 weeks of the treatment phase. Onset of efficacy and response was defined as >20% and >50% reduction in the mean total score of functional dementia scale (FDS) and clinical global impression scale (CGIS) from baseline to the study end, respectively.Results: Onset of efficacy on FDS and CGIS was 16.7% (mean-time 61.25 days) and 80% (mean-time 36 days) with memantine and donepezil, respectively. Response was 89.3% and 40% with memantine and Donepezil, respectively. Total reduction in FDS and CGIS score of from baseline to the study end was 39.50, 40.00, and 25.60, 27.20 with memantine and donepezil, respectively. Tolerability was 86.33% and 20% with memantine and donepezil, respectively. Anorexia, muscle cramps, constipation, headache, and insomnia, were the common side-effects and self-limiting. Safety was 100% in both groups.Conclusions: Onset of efficacy was faster with donepezil seen at 2 weeks. Response, improvement in CGIS, FDS, and tolerability were better seen with memantine at 40 weeks. Thus, in similar clinical settings, memantine can be preferred

Emergence of Severe Acute Respiratory Syndrome (SARS) COVID-19 and approach of AYUSH systems of medicine towards its prevention and management

SARS-CoV-2/novel coronavirus is a fresh virus strain that was first detected in the city of Wuhan located at Hubei province of China in December, 2019. Within a couple of months the virus has spread rapidly to different geographical regions through human transmission leading to serious disease burden worldwide. Although research is under progress to develop effective vaccine and drugs for the disease, a unified approach between conventional and traditional medicine system may prove to be beneficial in early prevention and management of the disease. Joint efforts are being put up at global scientific community level to enhance the research on advancement of meticulous diagnostics, antiviral measures and finally leading to development of an effective vaccine against the novel coronavirus. Some basic and safe measures from AYUSH systems of medicine have also been advocated for prophylaxis and treatment of COVID-19 which can be used independently or with integrated approach. The rationale of this review paper is to provide the details regarding disease spectrum, modes of transmission, social & economic consequences, and role of AYUSH systems of medicine in prevention and management of COVID-19. Based on the signs and symptoms of COVID-19, list of herbs and drugs of AYUSH systems of medicine were also searched and are being reported here

Thickness and width of the menisci of adult knee joint: a descriptive cross-sectional observational study in cadavers [version 2; peer review: 2 approved]

Background The goal was to determine the thickness and width of the knee joint meniscus at their different regions. The objective was to compare the dimensions at these regions and over the right- and left-sided specimens. Methods The present study included 50 adult cadaveric knee joints, and 100 menisci (50 medial menisci and 50 lateral menisci) were studied. The meniscus was distributed into anterior, middle and posterior parts. Thickness and width at the mid-point of these three parts were determined by using the Vernier caliper. Results The breadth of the medial meniscus was 8.38 ± 1.64 mm, 7.68 ± 1.92 mm and 13.93 ± 2.69 mm at the anterior, middle and posterior one-third regions. Same measurements for the lateral menisci at these regions were 9.84 ± 1.78 mm, 8.82 ± 2.01 mm and 10.18 ± 2.23 mm, respectively. The thickness of the medial meniscus was 4.49 ± 0.78 mm, 4.07 ± 0.81 mm and 4.79 ± 0.93 mm at these regions. The lateral meniscus thickness was 3.82 ± 0.69 mm, 4.43 ± 0.98 mm and 4.36 ± 0.8 mm, respectively. Conclusion It is believed that this data is enlightening to the arthroscopic surgeon during the meniscus transplantation either by using synthetic material or allograft as the proper sizing of the meniscus is important to prevent complications due to inaccurate sizing

Daksha: On Alert for High Energy Transients

We present Daksha, a proposed high energy transients mission for the study of electromagnetic counterparts of gravitational wave sources, and gamma ray bursts. Daksha will comprise of two satellites in low earth equatorial orbits, on opposite sides of earth. Each satellite will carry three types of detectors to cover the entire sky in an energy range from 1 keV to >1 MeV. Any transients detected on-board will be announced publicly within minutes of discovery. All photon data will be downloaded in ground station passes to obtain source positions, spectra, and light curves. In addition, Daksha will address a wide range of science cases including monitoring X-ray pulsars, studies of magnetars, solar flares, searches for fast radio burst counterparts, routine monitoring of bright persistent high energy sources, terrestrial gamma-ray flashes, and probing primordial black hole abundances through lensing. In this paper, we discuss the technical capabilities of Daksha, while the detailed science case is discussed in a separate paper.Comment: 9 pages, 3 figures, 1 table. Additional information about the mission is available at https://www.dakshasat.in

Science with the Daksha High Energy Transients Mission

We present the science case for the proposed Daksha high energy transients mission. Daksha will comprise of two satellites covering the entire sky from 1~keV to $>1$~MeV. The primary objectives of the mission are to discover and characterize electromagnetic counterparts to gravitational wave source; and to study Gamma Ray Bursts (GRBs). Daksha is a versatile all-sky monitor that can address a wide variety of science cases. With its broadband spectral response, high sensitivity, and continuous all-sky coverage, it will discover fainter and rarer sources than any other existing or proposed mission. Daksha can make key strides in GRB research with polarization studies, prompt soft spectroscopy, and fine time-resolved spectral studies. Daksha will provide continuous monitoring of X-ray pulsars. It will detect magnetar outbursts and high energy counterparts to Fast Radio Bursts. Using Earth occultation to measure source fluxes, the two satellites together will obtain daily flux measurements of bright hard X-ray sources including active galactic nuclei, X-ray binaries, and slow transients like Novae. Correlation studies between the two satellites can be used to probe primordial black holes through lensing. Daksha will have a set of detectors continuously pointing towards the Sun, providing excellent hard X-ray monitoring data. Closer to home, the high sensitivity and time resolution of Daksha can be leveraged for the characterization of Terrestrial Gamma-ray Flashes.Comment: 19 pages, 7 figures. Submitted to ApJ. More details about the mission at https://www.dakshasat.in

A gravitational-wave standard siren measurement of the Hubble constant

On 17 August 2017, the Advanced LIGO 1 and Virgo 2 detectors observed the gravitational-wave event GW170817-a strong signal from the merger of a binary neutron-star system 3 . Less than two seconds after the merger, a γ-ray burst (GRB 170817A) was detected within a region of the sky consistent with the LIGO-Virgo-derived location of the gravitational-wave source 4-6 . This sky region was subsequently observed by optical astronomy facilities 7 , resulting in the identification 8-13 of an optical transient signal within about ten arcseconds of the galaxy NGC 4993. This detection of GW170817 in both gravitational waves and electromagnetic waves represents the first 'multi-messenger' astronomical observation. Such observations enable GW170817 to be used as a 'standard siren' 14-18 (meaning that the absolute distance to the source can be determined directly from the gravitational-wave measurements) to measure the Hubble constant. This quantity represents the local expansion rate of the Universe, sets the overall scale of the Universe and is of fundamental importance to cosmology. Here we report a measurement of the Hubble constant that combines the distance to the source inferred purely from the gravitational-wave signal with the recession velocity inferred from measurements of the redshift using the electromagnetic data. In contrast to previous measurements, ours does not require the use of a cosmic 'distance ladder' 19 : the gravitational-wave analysis can be used to estimate the luminosity distance out to cosmological scales directly, without the use of intermediate astronomical distance measurements. We determine the Hubble constant to be about 70 kilometres per second per megaparsec. This value is consistent with existing measurements 20,21 , while being completely independent of them. Additional standard siren measurements from future gravitationalwave sources will enable the Hubble constant to be constrained to high precision

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

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management