Direct activation of KCC2 arrests benzodiazepine refractory status epilepticus and limits the subsequent neuronal injury in mice

Hyperpolarizing GABAAR currents, the unitary events that underlie synaptic inhibition, are dependent upon efficient Cl− extrusion, a process that is facilitated by the neuronal specific K+/Cl− co-transporter KCC2. Its activity is also a determinant of the anticonvulsant efficacy of the canonical GABAAR-positive allosteric: benzodiazepines (BDZs). Compromised KCC2 activity is implicated in the pathophysiology of status epilepticus (SE), a medical emergency that rapidly becomes refractory to BDZ (BDZ-RSE). Here, we have identified small molecules that directly bind to and activate KCC2, which leads to reduced neuronal Cl− accumulation and excitability. KCC2 activation does not induce any overt effects on behavior but prevents the development of and terminates ongoing BDZ-RSE. In addition, KCC2 activation reduces neuronal cell death following BDZ-RSE. Collectively, these findings demonstrate that KCC2 activation is a promising strategy to terminate BDZ-resistant seizures and limit the associated neuronal injury

Valuing Visitor Access to Forested Areas and Exploring Willingness to Pay for Forest Conservation and Restoration Financethe Case of Small Island Developing State of Mauritius

Small island developing states share as common constraints their small size, geographical dispersion, greater vulnerability to rapid and drastic environmental change, and limited administrative and technical resources. Within these, they have to cater for urban and agricultural areas, as well as enough natural landscape for ecosystem services. Funding for conservation of forest ecosystems on these islands has received relatively less attention and national park systems are chronically underfunded. We used Mauritius as a case study to investigate the willingness to pay for conservation of state and privately owned forests. It is part of a biodiversity hotspot with highly threatened forest ecosystems, but has known some conservation successes. We designed and administered survey based contingent valuation approach to estimate the willingness to pay entry fees to visit forest areas across the island. Study results suggest international and domestic tourists have a mean willingness to pay of USD 7.73 and USD 3.74 respectively, for conservation. These values represent amounts visitors are willing to pay every time they visit a public or private forested site. Results show that mid-level supervisory roles positively influence willingness to pay values. Results also show that people aged 50 and above, not having any supervisory role, married with one child or less, tend to have lower willingness to pay for conservation

Effect of atorvastatin and rosuvastatin on 25-hydroxy vitamin d levels in newly diagnosed South Indian dyslipidemic subjects: A randomized, open-label, single center study

Background: Statins are one of the mainstay treatment modality for the people suffering from dyslipidemia. Statins reduce the cholesterol bio-synthesis by ß-hydroxy-ß-methyl glutaryl Co-A (HMG-CoA) reductase inhibition which is rate-limiting enzyme. It also affects the Vit-D levels as metabolism of cholecalciferol and cholesterol are interrelated. Objectives: Effect of atorvastatin/ rosuvastatin on 25-hydroxy Vitamin-D (25OHD) concentrations among subjects with newly diagnosed dyslipidemia. Materials and Methods: Prospective randomized, open-label, parallel group study. Lipid and 25OHD levels are measured at baseline and end of 6 months after statin treatment. One group received atorvastatin and another study group received rosuvastatin for 6 months. Results: Mean 25OHD concentrations are 32.0±4.7, 31.7±4.8 and 32.9±4.9 in the control, atorvastatin and rosuvastatin groups respectively. Both atorvastatin and rosuvastatin groups, except TGs, all the lipid parameters and 25OHD has showed significant difference (<0.001) from baseline to end-line repeated parameters. All the study participants were well tolerated and no one discontinued the drug due to drug-related adverse reactions. Conclusion: Participants with atorvastatin treated group showed significant reduction in 25OHD concentrations. In addition, 25OHD concentrations are dependent on statin efficacy