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

Optogenetic Delay of Status Epilepticus Onset in an In Vivo Rodent Epilepsy Model

Epilepsy is a devastating disease, currently treated with medications, surgery or electrical stimulation. None of these approaches is totally effective and our ability to control seizures remains limited and complicated by frequent side effects. The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats. Hippocampal pyramidal neurons were transduced in vivo with a virus carrying an enhanced halorhodopsin (eNpHR), a yellow light activated chloride pump, and acute seizure progression was then monitored behaviorally and electrophysiologically in the presence and absence of illumination delivered via an optical fiber. Inhibition of those neurons with illumination prior to seizure onset significantly delayed electrographic and behavioral initiation of status epilepticus, and altered the dynamics of ictal activity development. These results reveal an essential role of hippocampal excitatory neurons in this model of ictogenesis and illustrate the power of optogenetic approaches for elucidation of seizure mechanisms. This early success in controlling seizures also suggests future therapeutic avenues

RNA recognition by Npl3p reveals U2 snRNA-binding compatible with a chaperone role during splicing

The conserved SR-like protein Npl3 promotes splicing of diverse pre-mRNAs. However, the RNA sequence(s) recognized by the RNA Recognition Motifs (RRM1 & RRM2) of Npl3 during the splicing reaction remain elusive. Here, we developed a split-iCRAC approach in yeast to uncover the consensus sequence bound to each RRM. High-resolution NMR structures show that RRM2 recognizes a 5´-GNGG-3´ motif leading to an unusual mille-feuille topology. These structures also reveal how RRM1 preferentially interacts with a CC-dinucleotide upstream of this motif, and how the inter-RRM linker and the region C-terminal to RRM2 contribute to cooperative RNA-binding. Structure-guided functional studies show that Npl3 genetically interacts with U2 snRNP specific factors and we provide evidence that Npl3 melts U2 snRNA stem-loop I, a prerequisite for U2/U6 duplex formation within the catalytic center of the B$^{act}$ spliceosomal complex. Thus, our findings suggest an unanticipated RNA chaperoning role for Npl3 during spliceosome active site formation

Green Synthesis of Silver Nanoparticles using Litsea glutinosa L. Leaves and Stem Extracts and their Antibacterial Efficacy

The present study explores the green approach for the preparation of silver nanoparticles (AgNPs) through the reduction of silver nitrate by the cell-free stem and leaf aqueous extracts of Litsea glutinosa (L.glutinosa) and its potential antibacterial activity. The analytical instruments include scanning electron microscopy, Fourier transforms infrared spectroscopy, UV-visible spectroscopy, and X-ray diffraction spectroscopy confirmed the synthesis of smaller, uniformly spherical AgNPs (10-40 nm). The average crystalline size of prepared AgNPs produced by L. glutinosa leaf extract was found to be 19 mm. From UV-visible spectral analysis, the maximum absorbance peak appeared at 444 nm for leaf extract AgNPs different from stem extract AgNPs (422 nm), which are found to be specific for AgNPs. The L.glutinosa stem extract-assisted AgNPs have shown significant antibacterial activity against Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative) in comparison to Gentamycin. Hence, the AgNPs obtained by green synthesis can be therapeutically explored against bacterial infections

Widespread fear of dengue transmission but poor practices of dengue prevention : A study in the slums of Delhi, India

Background This study has been conducted to throw light on the knowledge and practices related to dengue fever among the poor population living in Delhi's slums. Materials A household survey was conducted in 2013 among 3,350 households. The households were stratified by a number of variables related to socio-economic status and health events such as hospitalisation. The data collection was completed through face-to-face interviews conducted with the help of 25 field investigators. Results About 8% of the households had at least one diagnosed dengue case. In comparison to the population surveyed, teenagers (15-19 years) and adults (30-34 years) were more affected whereas children under four years of age were underrepresented. Housewives are more affected by dengue (24%) compared to their share of the population surveyed (17%). Despite the fact that 77% of the respondents are worried about mosquitoes, only 43% of them monitor environment to avoid the presence of breeding sites. Conclusion One cannot exclude the possibility that though young children under the age of four years are exposed to the virus, either their cases were asymptomatic or family members infected during this period had potentially more serious symptoms leading to hospitalisation. This result could thus be explained by budget-related health choices made by this population which do not favour small children. Educational programs should target housewives to improve their impact, as they are the ones mostly responsible for water storage and cleanliness of the house and its neighbourhood. Even with a dengue experience and potentially an acute perception of the risk and its factors, a proper management of environmental conditions is lacking. This along with the fact that word-of-mouth is the main source of information quoted should be a message for municipality health workers to give door-to-door information on how to prevent breeding sites and dengue infection

Has the Rajiv Aarogyasri Community Health Insurance Scheme of Andhra Pradesh Addressed the Educational Divide in Accessing Health Care?

Background Equity of access to healthcare remains a major challenge with families continuing to face financial and non-financial barriers to services. Lack of education has been shown to be a key risk factor for 'catastrophic' health expenditure (CHE), in many countries including India. Consequently, ways to address the education divide need to be explored. We aimed to assess whether the innovative state-funded Rajiv Aarogyasri Community Health Insurance Scheme of Andhra Pradesh state launched in 2007, has achieved equity of access to hospital inpatient care among households with varying levels of education. Methods We used the National Sample Survey Organization 2004 survey as our baseline and the same survey design to collect post-intervention data from 8623 households in the state in 2012. Two outcomes, hospitalisation and CHE for inpatient care, were estimated using education as a measure of socio-economic status and transforming levels of education into ridit scores. We derived relative indices of inequality by regressing the outcome measures on education, transformed as a ridit score, using logistic regression models with appropriate weights and accounting for the complex survey design. Findings Between 2004 and 2012, there was a 39% reduction in the likelihood of the most educated person being hospitalised compared to the least educated, with reductions observed in all households as well as those that had used the Aarogyasri. For CHE the inequality disappeared in 2012 in both groups. Sub-group analyses by economic status, social groups and rural-urban residence showed a decrease in relative indices of inequality in most groups. Nevertheless, inequalities in hospitalisation and CHE persisted across most groups. Conclusion During the time of the Aarogyasri scheme implementation inequalities in access to hospital care were substantially reduced but not eliminated across the education divide. Universal access to education and schemes such as Aarogyasri have the synergistic potential to achieve equity of access to healthcare

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

ICAR: endoscopic skull‐base surgery

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