J. Neurochem. (2010) 115, 537–549.
Japanese encephalitis virus (JEV), the leading cause of acute encephalitis in South‐East Asia is a neurotropic virus infecting various CNS cell types. Most ...Flaviviruses including JEV get internalised into cells by receptor‐mediated endocytosis, which involve clathrin and membrane cholesterol. The cholesterol‐enriched membrane microdomains referred to as lipid rafts act as portals for virus entry in a number of enveloped viruses, including Flavivirus. However, the precise role played by membrane lipid rafts in JEV internalisation into neural stem cells is still unknown. We have established neural stem/progenitor cells and C17.2 cell line as models of productive JEV infection. Increase in membrane fluidity and clustering of viral envelope proteins in lipid rafts was observed in early time points of infection. Localisation of non‐structural proteins to rafts at later infection stages was also observed. Co‐localisation of JEV glycoprotein with Cholera toxin B confirmed that JEV internalisation occurs in a lipid‐raft dependent manner. Though JEV entry is raft dependent, however, there is requirement of functional clathrin during endocytosis inside the cells. Besides virus entry, the lipid rafts act as signalling platforms for Src tyrosine kinases and result in activation of phosphoinositìde 3′‐kinase/Akt signalling during early JEV infection. Disruption of lipid raft formation by cholesterol depletion using Methyl β‐cyclodextrin, reduced JEV RNA levels and production of infectious virus particles as well as impaired phosphoinositìde 3′‐kinase/Akt signalling during initial infection. Overall, our results implicate the importance of host membrane lipid rafts in JEV entry and life cycle, besides maintaining survival of neural stem/progenitor cells during early infection.
Objective
To estimate dementia's incremental cost to the traditional Medicare program.
Data Sources
Health and Retirement Study (HRS) survey‐linked Medicare part A and B claims from 1991 to 2012.
...Study Design
We compared Medicare expenditures for 60 months following a claims‐based dementia diagnosis to those for a randomly selected, matched comparison group.
Data Collection/Extraction Methods
We used a cost estimator that accounts for differential survival between individuals with and without dementia and decomposes incremental costs into survival and cost intensity components.
Principal Findings
Dementia's five‐year incremental cost to the traditional Medicare program is approximately $15 700 per patient, nearly half of which is incurred in the first year after diagnosis. Shorter survival with dementia mitigates the incremental cost by about $2650. Increased costs for individuals with dementia were driven by more intensive use of Medicare part A covered services. The incremental cost of dementia was about $7850 higher for females than for males because of sex‐specific differential mortality associated with dementia.
Conclusions
Dementia's cost to the traditional Medicare program is significant. Interventions that target early identification of dementia and preventable inpatient and post‐acute care services could produce substantial savings.
Japanese encephalitis virus (JEV) is one of the major neurotropic viral infections that is known to dysregulate the homeostasis of neural stem/progenitor cells (NSPCs) and depletes the stem cell ...pool. NSPCs are multipotent stem cell population of the central nervous system (CNS) which are known to play an important role in the repair of the CNS during insults/injury caused by several factors such as ischemia, neurological disorders, CNS infections, and so on. Viruses have evolved to utilize host factors for their own benefit and during JEV infection, host factors, including the non-coding RNAs such as miRNAs, are reported to be affected, thereby cellular processes regulated by the miRNAs exhibit perturbed functionality. Previous studies from our laboratory have demonstrated the role of JEV infection in dysregulating the function of neural stem cells (NSCs) by altering the cell fate and depleting the stem cell pool leading to a decline in stem cell function in CNS repair mechanism post-infection. JEV-induced alteration in miRNA expression in the NSCs is one of the major interest to us. In prior studies, we have observed an altered expression pattern of certain miRNAs following JEV infection. In this study, we have validated the role of JEV infection in NSCs in altering the expression of miR-9-5p, which is a known regulator of neurogenesis in NSCs. Furthermore, we have validated the interaction of this miRNA with its target, Onecut2 (OC2), in primary NSCs utilizing miRNA mimic and inhibitor transfection experiments. Our findings indicate a possible role of JEV mediated dysregulated interaction between miR-9-5p and its putative target OC2 in NSPCs.
MicroRNAs have emerged as key disease pathogenic markers and potential therapeutic targets. In this study, we solidify this concept by studying a key miRNA, miR-9-5p, in Japanese encephalitis virus infection of neural stem/progenitor cells. miRNA target Onecut2 has a possible role in stem cell pool biology. Here, we show a possible mechanistic axis worth investing in neurotropic viral biology.
Objective:
To determine the extent to which counting observation stays changes hospital performance on 30-day readmission measures.
Methods:
This was a retrospective study of inpatient admissions and ...observation stays among fee-for-service Medicare enrollees in 2017. We generated 3 specifications of 30-day risk-standardized readmissions measures: the hospital-wide readmission (HWR) measure utilized by the Centers for Medicare and Medicaid Services, which captures inpatient readmissions within 30 days of inpatient discharge; an expanded HWR measure, which captures any unplanned hospitalization (inpatient admission or observation stay) within 30 days of inpatient discharge; an all-hospitalization readmission (AHR) measure, which captures any unplanned hospitalization following any hospital discharge (observation stays are included in both the numerator and denominator of the measure). Estimated excess readmissions for hospitals were compared across the 3 measures. High performers were defined as those with a lower-than-expected number of readmissions whereas low performers had higher-than-expected or excess readmissions. Multivariable logistic regression identified hospital characteristics associated with worse performance under the measures that included observation stays.
Results:
Our sample had 2586 hospitals with 5,749,779 hospitalizations. Observation stays ranged from 0% to 41.7% of total hospitalizations. Mean (SD) readmission rates were 16.6% (5.4) for the HWR, 18.5% (5.7) for the expanded HWR, and 17.9% (5.7) in the all-hospitalization readmission measure. Approximately 1 in 7 hospitals (14.9%) would switch from being classified as a high performer to a low performer or vice-versa if observation stays were fully included in the calculation of readmission rates. Safety-net hospitals and those with a higher propensity to use observation would perform significantly worse.
Conclusions:
Fully incorporating observation stays in readmission measures would substantially change performance in value-based programs for safety-net hospitals and hospitals with high rates of observation stays.
Japanese Encephalitis Virus (JEV) is a neurotropic virus that invades Central Nervous System (CNS) and causes severe neuroinflammation. Given the abundance and the position of astrocytes in the CNS, ...we speculate that they might play a critical role in the process of neuroinflammation. Unfortunately, the role of astrocytes in JEV-mediated neuroinflammation has long been understated. In this study, we have attempted to assess the role of astrocyte-mediated neuroinflammation upon JEV infection. Mouse model of JEV infection, generated by intraperitoneal injection, showed severe reactive astrogliosis. To further address our hypothesis, we employed immortalized astrocytic cell line (in vitro) and primary astrocyte-enriched culture (ex vivo) as experimental models. JEV infection in the astrocytes induces proinflammatory cytokines like MCP1/CCL2 and IL6 in both ex vivo and in vitro cultures as observed from the cytometric bead array analysis. A significantly altered cytokine profile was observed using PCR analysis in in vitro and ex vivo models upon infection, with respect to control, validating our previous results. We also show that there exists a major inconsistency in the viral replication kinetics, wherein the cell line showed a robust rate of replication whereas the primary astrocyte-enriched culture showed negligibly low number of plaques, underlining the importance of the selection of appropriate experimental model system. In conclusion, we claim that astrocytes significantly contribute to JEV-mediated neuroinflammation, despite not being a CNS immune cell.
We experimentally determined the magnitude of uranium isotopic fractionation induced by U(VI) reduction by metal reducing bacterial isolates. Our results indicate that microbial U(VI) reduction ...induces isotopic fractionation; heavier isotopes (i.e., 238U) partition into the solid U(IV) products. The magnitudes of isotopic fractionation (expressed as ε=1000‰*(α−1)) for 238U/235U were 0.68‰±0.05‰ and 0.99‰±0.12‰ for Geobacter sulfurreducens strain PCA and strain IFRC-N, respectively. The ε values for Anaeromyxobacter dehalogenans strain FRC-W, strain FRC-R5, a novel Shewanella isolate, and Desulfitobacterium sp. strain Viet1 were 0.72‰±0.15‰, 0.99‰±0.12‰, 0.96‰±0.16‰ and 0.86‰±0.06‰, respectively. Our results show that the maximum ε values of ∼1.0‰ were obtained with low biomass (∼107cells/mL) and low electron donor concentrations (∼500μM). These results provide an initial assessment of 238U/235U shifts induced by microbially-mediated U(VI) reduction, which is needed as 238U/235U data are increasingly applied as redox indicators in various geochemical settings.
Japanese encephalitis virus
, a neurotropic flavivirus, causes sporadic encephalitis with nearly 25% fatal case reports. JEV infects neural stem/progenitor cells (NSPCs) and decreases their ...proliferation. Statin, a commonly used class of cholesterol lowering drug, has been shown to possess potent anti-inflammatory and neuroprotective effects in acute brain injury and chronic neurodegenerative conditions. Here, we aimed to check the efficacy of atorvastatin in alleviating the symptoms of Japanese encephalitis (JE). Using BALB/c mouse model of JEV infection, we observed that atorvastatin effectively reduces viral load in the subventricular zone (SVZ) of infected pups and decreases the resultant cell death. Furthermore, atorvastatin abrogates microglial activation and production of proinflammatory cyto/chemokine production post JEV infection
in vivo.
It also reduced interferon-β response in the neurogenic environs. The neuroprotective role of atorvastatin is again evident from the rescued neurosphere size and decreased cell death
in vitro
. It has also been observed that upon atorvastatin administration, cell cycle regulatory proteins and cell survival proteins are also restored to their respective expression level as observed in uninfected animals. Thus the antiviral, immunomodulatory and neuroprotective roles of atorvastatin reflect in our experimental observations. Therefore, this drug broadens a path for future therapeutic measures against JEV infection.
Infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the Coronaviridae family and is a positive-sense single-stranded RNA virus originating from Wuhan, ...China, was declared a global public health emergency on 11 March 2020. SARS-CoV-2 infection in humans is characterized by symptoms such as fever and dyspnea accompanied by infrequent incidence of lymphopenia, gastrointestinal complications such as elevated hepatic aminotransferases, and diarrhea. Originating in bats, the SARS-CoV-2 virus has been transmitted to humans likely via an intermediate host that is yet to be discovered. Owing to the absence of any vaccines or definite anti-viral drugs alongside the greater mobility of people across the globe, international and national efforts in containing and treating SARS-CoV-2 infection are experiencing severe difficulties. In this review, we have provided a picture of SARS-CoV-2 epidemiological characteristics, the clinical symptoms experienced by patients of varying age groups, the molecular virology of SARS-CoV-2, and the treatment regimens currently employed for fighting SARS-CoV-2 infection as well as their outcomes.
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