Proximity labeling proteomics reveals Kv1.3 potassium channel immune interactors in microglia.

Microglia are resident immune cells of the brain and regulate its inflammatory state. In neurodegenerative diseases, microglia transition from a homeostatic state to a state referred to as disease associated microglia (DAM). DAM express higher levels of proinflammatory signaling molecules, like STAT1 and TLR2, and show transitions in mitochondrial activity toward a more glycolytic response. Inhibition of Kv1.3 decreases the proinflammatory signature of DAM, though how Kv1.3 influences the response is unknown. Our goal was to identify the potential proteins interacting with Kv1.3 during transition to DAM. We utilized TurboID, a biotin ligase, fused to Kv1.3 to evaluate potential interacting proteins with Kv1.3 via mass spectrometry in BV-2 microglia following TLR4-mediated activation. Electrophysiology, western blotting, and flow cytometry were used to evaluate Kv1.3 channel presence and TurboID biotinylation activity. We hypothesized that Kv1.3 contains domain-specific interactors that vary during a TLR4-induced inflammatory response, some of which are dependent on the PDZ-binding domain on the C-terminus. We determined that the N-terminus of Kv1.3 is responsible for trafficking Kv1.3 to the cell surface and mitochondria (e.g. NUDC, TIMM50). Whereas, the C-terminus interacts with immune signaling proteins in an LPS-induced inflammatory response (e.g. STAT1, TLR2, and C3). There are 70 proteins that rely on the C-terminal PDZ-binding domain to interact with Kv1.3 (e.g. ND3, Snx3, and Sun1). Furthermore, we used Kv1.3 blockade to verify functional coupling between Kv1.3 and interferon-mediated STAT1 activation. Overall, we highlight that the Kv1.3 potassium channel functions beyond conducting the outward flux of potassium ions in an inflammatory context and that Kv1.3 modulates the activity of key immune signaling proteins, such as STAT1 and C3.

Antiviral Approaches against Influenza Virus.

Preventing and controlling influenza virus infection remains a global public health challenge, as it causes seasonal epidemics to unexpected pandemics. These infections are responsible for high morbidity, mortality, and substantial economic impact. Vaccines are the prophylaxis mainstay in the fight against influenza. However, vaccination fails to confer complete protection due to inadequate vaccination coverages, vaccine shortages, and mismatches with circulating strains. Antivirals represent an important prophylactic and therapeutic measure to reduce influenza-associated morbidity and mortality, particularly in high-risk populations. Here, we review current FDA-approved influenza antivirals with their mechanisms of action, and different viral- and host-directed influenza antiviral approaches, including immunomodulatory interventions in clinical development. Furthermore, we also illustrate the potential utility of machine learning in developing next-generation antivirals against influenza.

Common Mutation in the HFE Gene Modifies Recovery After Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is characterized by bleeding into the brain parenchyma. During an ICH, iron released from the breakdown of hemoglobin creates a cytotoxic environment in the brain through increased oxidative stress. Interestingly, the loss of iron homeostasis is associated with the pathological process of other neurological diseases. However, we have previously shown that the H63D mutation in the homeostatic iron regulatory (HFE) gene, prevalent in 28% of the White population in the United States, acts as a disease modifier by limiting oxidative stress. The following study aims to examine the effects of the murine homolog, H67D HFE, on ICH. METHODS: An autologous blood infusion model was utilized to create an ICH in the right striatum of H67D and wild-type mice. The motor recovery of each animal was assessed by rotarod. Neurodegeneration was measured using fluorojade-B and mitochondrial damage was assessed by immunofluorescent numbers of CytC+ (cytochrome C) neurons and CytC+ astrocytes. Finally, the molecular antioxidant response to ICH was quantified by measuring Nrf2 (nuclear factor-erythroid 2 related factor), GPX4 (glutathione peroxidase 4), and FTH1 (H-ferritin) levels in the ICH-affected and nonaffected hemispheres via immunoblotting. RESULTS: At 3 days post-ICH, H67D mice demonstrated enhanced performance on rotarod compared with wild-type animals despite no differences in lesion size. Additionally, H67D mice displayed higher levels of Nrf2, GPX4, and FTH1 in the ICH-affected hemisphere; however, these levels were not different in the contralateral, non-ICH-affected hemisphere. Furthermore, H67D mice showed decreased degenerated neurons, CytC+ Neurons, and CytC+ astrocytes in the perihematomal area. CONCLUSIONS: Our data suggest that the H67D mutation induces a robust antioxidant response 3 days following ICH through Nrf2, GPX4, and FTH1 activation. This activation could explain the decrease in degenerated neurons, CytC+ neurons, and CytC+ astrocytes in the perihematomal region, leading to the improved motor recovery. Based on this study, further investigation into the mechanisms of this neuroprotective response and the effects of the H63D HFE mutation in a population of patients with ICH is warranted.

Acute Low Dose Naltrexone Increases ß-Endorphin and Promotes Neuronal Recovery Following Hypoxia-Ischemic Stroke in Type-2 Diabetic Mice.

Diabetic patients experience significant mortality and poor recovery following ischemic stroke. Our clinical and basic science studies demonstrate an overall immune suppression in the periphery of diabetic stroke patients, as well as within the central nervous system (CNS) of type-2 diabetic mice following hypoxia-ischemia (HI). Low doses of naltrexone (LDN) improved clinical outcomes in many autoimmune diseases by acting on opioid receptors to release ß-endorphin which in turn balances inflammatory cytokines and modulates the opioid growth factor (OGF)-opioid growth factor receptor (OGFr) pathway. We hypothesized that in our model of diabetic mice, LDN treatment will induce the release of ß-endorphin and improve CNS response by promoting neuronal recovery post HI. To test this hypothesis, we induced HI in 10 week old male db/db and db/ + mice, collected tissue at 24 and 72 h post HI, and measured OGF levels in plasma and brain tissue. The infarct size and number of OGF + neurons in the motor cortex, caudate and hippocampus (CA3) were measured. Following HI, db/db mice had significant increases in brain OGF expression, increased infarct size and neurological deficits, and loss of OGFr + neurons in several different brain regions. In the second experiment, we injected LDN (1 mg/kg) intraperitoneally into db/db and db/ + mice at 4, 24, and 48 h post HI, and collected brain tissue and blood at 72 h. Acute LDN treatment increased ß-endorphin and OGF levels in plasma and promoted neuronal recovery in db/db mice compared to phosphate buffer saline (PBS)-treated diabetic mice suggesting a protective or regenerative effect of LDN.

Surgical Matricectomy Versus Phenolization in the Treatment of Ingrown Toenails: A Randomized Controlled Trial.

BACKGROUND: Treatment of ingrown toenail includes various nonsurgical and surgical treatments. However, there is no consensus on the ideal first-choice treatment. OBJECTIVE: To compare phenolization versus surgical matricectomy (SM) after lateral nail plate avulsion in terms of efficacy, recurrence rates, postoperative outcomes, and cosmesis. METHODS: The authors enrolled 45 consenting patients and randomized them into 2 groups (Group 1 = phenolization and Group 2 = SM) using stratified block randomization and followed them up at 1 week, 1 month, and 6 months. RESULTS: The median percentage improvement in pain visual analog scale (VAS) score was comparable between the 2 groups ( p = 0.793). The mean photo VAS showed significant improvement in Group 1 at 1 week ( p = 0.00) and 1 month ( p = 0.02) but not at 6 months ( p = 0.44). The median number of days for pain relief ( p = 0.169), for healing ( p = 0.192), and for resuming work ( p = 0.136) were not significantly different between the 2 groups. The time required to regain normal morphology was significantly longer in Group 2 ( p = 0.006). None of the patients in either group presented with recurrence at 6 months and 1 year. The authors observed failure of treatment in 1 patient in Group 2. CONCLUSION: Both procedures were equally efficacious, had minimal complications, and showed no recurrence at 6 months and 1 year.

Human Innate Lymphoid Cells in Influenza Infection and Vaccination.

Influenza is a highly contagious respiratory virus that causes mild to severe respiratory illness, as well as death, and remains a serious threat to human health. Annual vaccination is the most cost-effective way to control influenza; however, the vaccine does not provide protection against emerging strains with epidemic and pandemic potential. Several antivirals have been developed to treat influenza but there is a rapid emergence of antiviral resistant strains. Therefore, there is an urgent need to understand the virus and its interactions with the host immune system so that novel strategies can be developed for prophylactic and therapeutic interventions. Innate lymphoid cells (ILCs), a family of immune cells present in the peripheral circulation and in mucosal tissues, play an important role in regulation of tissue homeostasis, inflammation, and immunity. This review examines the current understanding and therapeutic potential of ILCs during influenza virus infection in humans.

Seroprevalence of anti SARS-CoV-2 IgG antibodies among adults in Jammu district, India: A community-based study.

Background & objectives: Serology testing is essential for immunological surveillance in the population. This serosurvey was conducted to ascertain the cumulative population immunity against SARS-CoV-2 among adults in Jammu district and to understand the association of seropositivity with sociodemographic and clinical correlates. Methods: On September 30 and October 1, 2020, a household survey was done in 20 villages/wards chosen from 10 health blocks in district Jammu, India. Demographic, clinical and exposure information was collected from 2000 adults. Serum samples were screened for IgG antibodies using COVID Kavach MERILISA kit. Tests of association were used to identify risk factors associated with IgG positivity. Crude odds ratio with 95 per cent confidence intervals (CIs) was calculated during univariate analysis followed by logistic regression. Results: Overall adjusted seroprevalence for SARS-CoV-2 was 8.8 per cent (95% CI: 8.78-8.82); it varied from 4.1 per cent in Chauki choura to 16.7 per cent Pallanwalla across 10 blocks in the district. Seropositivity was observed to be comparatively higher in 41-50 and 61-70 yr age groups, among males and in rural areas. Fever, sore throat, cough, dyspnoea, myalgias, anosmia, ageusia, fatigue, seizures, history of exposure, medical consultation, hospitalization and missing work showed significant association with seropositivity on univariate analysis. On logistic regression, only sore throat, myalgia and missing work showed significant adjusted odds of IgG positivity. Extrapolation to adult population suggested that exposure to SARS-CoV-2 was 14.4 times higher than reported cases, translating into Infection fatality rate of 0.08 per cent. Interpretation & conclusions: Since a major part of population was immunologically naive, all efforts to contain COVID-19 need to be vigorously followed while these baseline results provide an important yardstick to monitor the trends of COVID-19 and guide locally appropriate control strategies in the region.

Transcriptomics of Parental Care in the Hypothalamic-Septal Region of Female Zebra Finch Brain.

(1) Background: The objective of this study was to uncover genomic causes of parental care. Since birds do not lactate and, therefore, do not show the gene expressional changes required for lactation, we investigate gene expression associated with parenting in caring and non-caring females in an avian species, the small passerine bird zebra finch (Taeniopygia guttata). Here, we compare expression patterns in the hypothalamic-septal region since, previously, we showed that this area is activated in parenting females. (2) Methods: Transcriptome sequencing was first applied in a dissected part of the zebra finch brain related to taking care of the nestlings as compared to a control group of social pairs without nestlings. (3) Results: We found genes differentially expressed between caring and non-caring females. When introducing a log2fold change threshold of 1.5, 13 annotated genes were significantly upregulated in breeding pairs, while 39 annotated genes were downregulated. Significant enrichments of dopamine and acetylcholine biosynthetic processes were identified among upregulated pathways, while pro-opiomelanocortin and thyroid hormone pathways were downregulated, suggesting the importance of these systems in parental care. Network analysis further suggested neuro-immunological changes in mothers. (4) Conclusions: The results confirm the roles of several hypothesized major pathways in parental care, whereas novel pathways are also proposed.

Loss of smarcad1a accelerates tumorigenesis of malignant peripheral nerve sheath tumors in zebrafish.

Malignant peripheral nerve sheath tumors (MPNSTs) are a type of sarcoma that generally originates from Schwann cells. The prognosis for this type of malignancy is relatively poor due to complicated genetic alterations and the lack of specific targeted therapy. Chromosome fragment 4q22-23 is frequently deleted in MPNSTs and other human tumors, suggesting tumor suppressor genes may reside in this region. Here, we provide evidence that SMARCAD1, a known chromatin remodeler, is a novel tumor suppressor gene located in 4q22-23. We identified two human homologous smarcad1 genes (smarcad1a and smarcad1b) in zebrafish, and both genes share overlapping expression patterns during embryonic development. We demonstrated that two smarcad1a loss-of-function mutants, sa1299 and p403, can accelerate MPNST tumorigenesis in the tp53 mutant background, suggesting smarcad1a is a bona fide tumor suppressor gene for MPNSTs. Moreover, we found that DNA double-strand break (DSB) repair might be compromised in both mutants compared to wildtype zebrafish, as indicated by pH2AX, a DNA DSB marker. In addition, both SMARCAD1 gene knockdown and overexpression in human cells were able to inhibit tumor growth and displayed similar DSB repair responses, suggesting proper SMARCAD1 gene expression level or gene dosage is critical for cell growth. Given that mutations of SMARCAD1 sensitize cells to poly ADP ribose polymerase inhibitors in yeast and the human U2OS osteosarcoma cell line, the identification of SMARCAD1 as a novel tumor suppressor gene might contribute to the development of new cancer therapies for MPNSTs.

Status of Rho kinase inhibitors in glaucoma therapeutics-an overview.

Medical management remains the cornerstone of glaucoma management despite advances in the surgical or laser procedures. After a leap of almost two decades of the advent of prostaglandin analogues, recently a new class of drug, Rho kinase (ROCK) inhibitors, has come to limelight because of their varied therapeutic potential in different clinical conditions of eye, especially glaucoma. Their efficacy of lowering intraocular pressure (IOP) by virtue of an entirely different mechanism of decreasing outflow resistance has ignited a series of clinical trials evaluating their potential as monotherapy or as adjunct to existing antiglaucoma medications, and three of them ripasudil, netarsudil and roclatan have even been approved for clinical use in the recent past. There are evidences suggesting their beneficial effects in glaucoma patients even via non-IOP-dependent mechanisms like neuroprotection by improving blood flow to the optic nerve and increasing ganglion cell survival. They can even act as antifibrotic agents and reduce bleb scarring after glaucoma surgery. Hence, their effective role in glaucomatous optic neuropathy is multifaceted primary being improved drainage through the conventional pathway. On the other hand, certain local adverse effects like conjunctival hyperaemia have been reported in substantial proportion of patients, while some others like blepharitis, subconjunctival haemorrhages and cornea verticillata constitute less common side effects. The purpose of this review is to summarize the discovery, evolution and recent update of clinical trials on Rho kinase inhibitors as antiglaucoma medicine and to delineate their role in existing management protocol.

Microbial Journey: Mount Everest to Mars.

A rigorous exploration of microbial diversity has revealed its presence on Earth, deep oceans, and vast space. The presence of microbial life in diverse environmental conditions, ranging from moderate to extreme temperature, pH, salinity, oxygen, radiations, and altitudes, has provided the necessary impetus to search for them by extending the limits of their habitats. Microbiology started as a distinct science in the mid-nineteenth century and has provided inputs for the betterment of mankind during the last 150 years. As beneficial microbes are assets and pathogens are detrimental, studying both have its own merits. Scientists are nowadays working on illustrating the microbial dynamics in Earth's subsurface, deep sea, and polar regions. In addition to studying the role of microbes in the environment, the microbe-host interactions in humans, animals and plants are also unearthing newer insights that can help us to improve the health of the host by modulating the microbiota. Microbes have the potential to remediate persistent organic pollutants. Antimicrobial resistance which is a serious concern can also be tackled only after monitoring the spread of resistant microbes using disciplines of genomics and metagenomics The cognizance of microbiology has reached the top of the world. Space Missions are now looking for signs of life on the planets (specifically Mars), the Moon and beyond them. Among the most potent pieces of evidence to support the existence of life is to look for microbial, plant, and animal fossils. There is also an urgent need to deliberate and communicate these findings to layman and policymakers that would help them to take an adequate decision for better health and the environment around us. Here, we present a glimpse of recent advancements by scientists from around the world, exploring and exploiting microbial diversity.

Tunable phonon-plasmon hybridization in α-MoO3-graphene based van der Waals heterostructures.

The plasmon-phonon hybridization behavior between anisotropic phonon polaritons (APhP) of orthorhombic phase Molybdenum Trioxide (α - MoO3) and the plasmon-polaritons of Graphene layer - forming a van der Waals (vdW) heterostructure is investigated theoretically in this paper. It is found that in-plane APhP shows strong interaction with graphene plasmons lying in their close vicinity, leading to large Rabi splitting. Anisotropic behavior of biaxial MoO3 shows the polarization-dependent response with strong anti-crossing behavior at 0.55 eV and 0.3 eV of graphene's Fermi potential for [100] and [001] crystalline directions, respectively. Numerical results reveal unusual electric field confinement for the two arms of enhanced hybrid modes: the first being confined in the graphene layer representing plasmonic-like behavior. The second shows volume confined zigzag pattern in hyperbolic MoO3. It is also found that the various plasmon-phonon hybridized modes could be wavelength tuned, simply by varying the Fermi potential of the graphene layer. The coupling response of the hybrid structure is studied analytically using the coupled oscillator model. Furthermore, we also infer upon the coupling strength and frequency splitting between the two layers with respect to their structural parameters and interlayer spacing. Our work will provide an insight into the active tunable property of hybrid van der Waals (vdW) structure for their potential application in sensors, detectors, directional spontaneous emission, as well as for the tunable control of the propagating polaritons in fields of flat dispersion where strong localization of photons can be achieved, popularly known as the flatband optics.

Tunable Van der Waal's optical metasurfaces (VOMs) for biosensing of multiple analytes.

Van der Waal's heterostructure assembling low dimensional materials are the new paradigm in the field of nanophotonics. In this work, we theoretically investigate Van der Waal's optical metasurfaces consisting of graphene and hBN for the application of biosensing of multiple analytes in the mid-infrared (MIR) region. Phonon polaritons of hexagonal boron nitride (hBN) show an advantage over plasmon polaritons, as the phonon polaritons are lossless and possess high momentum and enhanced lifetime. The hybrid phonon mode produced at 6.78 µm in the mid-infrared (MIR) region with near-perfect absorption is used for surface-enhanced infrared absorption (SEIRA) based detection of organic analytes. Moreover, by adding the graphene layer, the device's overall resonance responses can be tuned, enabling it to identify multiple organic analytes-such as 4,4'-bis(N-carbazolyl)-1,1'-biphenyl (CBP) and nitrobenzene (Nb) [C6H5NO2], just by changing graphene's fermi potential (Ef). Owing to large wave vector of phonon polariton, the device has the capability to detect small amount of number of molecules (390 for CBP and 1990 for nitrobenzene), thus creating a highly sensitive optical biosensor.

A Nitronaphthalimide Probe for Fluorescence Imaging of Hypoxia in Cancer Cells.

The bioreductive enzymes typically upregulated in hypoxic tumor cells can be targeted for developing diagnostic and drug delivery applications. In this study, a new fluorescent probe 4-(6-nitro-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)benzaldehyde (NIB) based on a nitronaphthalimide skeleton that could respond to nitroreductase (NTR) overexpressed in hypoxic tumors is designed and its application in imaging tumor hypoxia is demonstrated. The docking studies revealed favourable interactions of NIB with the binding pocket of NTR-Escherichia coli. NIB, which is synthesized through a simple and single step imidation of 4-nitro-1,8-naphthalic anhydride displayed excellent reducible capacity under hypoxic conditions as evidenced from cyclic voltammetry investigations. The fluorescence measurements confirmed the formation of identical products (NIB-red) during chemical as well as NTR-aided enzymatic reduction in the presence of NADH. The potential fluorescence imaging of hypoxia based on NTR-mediated reduction of NIB is confirmed using in-vitro cell culture experiments using human breast cancer (MCF-7) cells, which displayed a significant change in the fluorescence colour and intensity at low NIB concentration within a short incubation period in hypoxic conditions.

Utility of high-frequency ultrasound in assessing cutaneous edema in venous ulcer patients.

BACKGROUND: High-frequency ultrasound (HFUS) using a 20 MHz probe is a non-invasive assessment tool. Its utility in dermatology for diagnosis of disease or for monitoring of treatment response in various dermatological conditions is still being explored. Edema secondary to venous hypertension is the main pathogenic factor in the development of venous leg ulcers. However, there is no objective method for assessment of degree of edema. In this study, we explore the utility of high-frequency ultrasound in assessing cutaneous edema and for monitoring its improvement with compression therapy among patients with venous ulcer. MATERIALS AND METHODS: Twenty patients with venous ulcer were enrolled in the study. Measurement of cutaneous edema was done at baseline and after 2 weeks of compression therapy in all patients. The 3 levels of measurement were dorsum of foot (low site, L1), 4 cm proximal to the medial malleolus (middle site, L2), and the medial aspect of the calf between the medial malleolus and the knee (upper site, L3). RESULTS: Baseline subepidermal low echogenic band (SLEB) measurements were 2.46 ± 0.69 mm, 2.94 ± 0.65 mm, and 2.66 ± 0.64 mm at L1, L2, and L3, respectively. There was a significant reduction in SLEB measurement after compression therapy ( p values 0.008, 0.002, and 0.003 at L1, L2, and L3, respectively). The mean percentage reduction in SLEB at level of medial malleolus (mid level - 29.61 ± 12.24) was higher than the other 2 sites (L1-22.45 ± 15.83 and L3 were 27.57 ± 12.34). CONCLUSION: Cutaneous ultrasound aids in accurate assessment of level and severity of edema. Hence, it can be utilized in trials to objectively assess the adequacy of treatment for patients with venous insufficiency.

Transcriptome Sequencing in the Preoptic Region of Rat Dams Reveals a Role of Androgen Receptor in the Control of Maternal Behavior.

(1) Background: Preoptic region of hypothalamus is responsible to control maternal behavior, which was hypothesized to be associated with gene expressional changes. (2) Methods: Transcriptome sequencing was first applied in the preoptic region of rat dams in comparison to a control group of mothers whose pups were taken away immediately after parturition and did not exhibit caring behavior 10 days later. (3) Results: Differentially expressed genes were found and validated by quantitative RT-PCR, among them NACHT and WD repeat domain containing 1 (Nwd1) is known to control androgen receptor (AR) protein levels. The distribution of Nwd1 mRNA and AR was similar in the preoptic area. Therefore, we focused on this steroid hormone receptor and found its reduced protein level in rat dams. To establish the function of AR in maternal behavior, its antagonist was administered intracerebroventricularly into mother rats and increased pup-directed behavior of the animals. (4) Conclusions: AR levels are suppressed in the preoptic area of mothers possibly mediated by altered Nwd1 expression in order to allow sustained high-level care for the pups. Thus, our study first implicated the AR in the control of maternal behaviors.

Lasers in Glaucoma: an Overview.

Lasers have been in use as a treatment modality of glaucoma for more than last four decades. Each passing year has added newer dimensions to the existing laser technologies enhancing their safety and efficacy profile. This has become possible due to continuous research and innovations with proper understanding of the mechanism of action of different variety of lasers as treatment options. Each category of glaucoma has different underlying pathologies. Adequate knowledge and understanding of indications, limitations and hazards of these laser procedures are must before their application for improvising outcome. Recent years have witnessed a revolution this field. A thorough literature search was conducted in PubMed, Medline, the Cochrane Library Database, EMBASE, and Scopus and Google Scholar until May 2020 using the keywords, and all the articles pertaining to the relevant topics were included in this review. Purpose of this review is to summarize the important laser procedures currently in use for managing glaucoma along with updating the readers with recent advances in laser technologies, their extended applications and also analyzing possible future implications.

Rapunzel Syndrome in a 3-Year-Old Boy: A Menace too Early to Present.

Rapunzel syndrome is a rare type of trichobezoar with an extension of the hair into the small bowel. Clinical presentation is deceptive and vague, ranging from asymptomatic abdominal mass to gastrointestinal perforation. There are only few cases reported in literature, with the youngest age being 3 years. We present the case of a 3-year-old male child presenting with Rapunzel syndrome and features of subacute intestinal obstruction.

Endovascular Stroke Therapy Trends From 2011 to 2017 Show Significant Improvement in Clinical and Economic Outcomes.

Background and Purpose- The purpose of this study was to evaluate trends in length of stay, discharge status, and costs among patients with acute ischemic stroke who underwent endovascular therapy (ET) between 2011 and 2017. Methods- Using a retrospective observational study design, acute ischemic stroke patients undergoing ET from 2011 to 2017 were identified in the Premier Healthcare Database. The Mann-Kendall trend test was performed to examine clinical and economic outcomes trends. Results- Among the 505 824 acute ischemic stroke patients, 11 811(2.3%) were treated with ET. Patients receiving ET had a significant increase in home discharge and a significant decrease in mortality (17.7% to 29.6%, P<0.01; 21.6% to 12.8%, P<0.01). There was a significant decline in length of stay from 11.7 days to 8.7 days ( P<0.01). Total index admission costs declined ≈17% from 2011 to 2017 ($50 516.5-$42 026.9, P<0.01). Conclusions- Clinical and economic indicators significantly improved for acute ischemic stroke patients undergoing ET from 2011 to 2017.

Influenza A virus neuraminidase protein interacts with Hsp90, to stabilize itself and enhance cell survival.

Neuraminidase protein (NA) of influenza A virus (IAV) is popularly known for its sialidase function to assist in the release of progeny virus. However, involvement of NA in other stages of the IAV life cycle also indicates its multifunctional nature and necessity to interact with other host proteins. Here, we report a host protein-heat shock protein 90 (Hsp90), as a novel interacting partner of IAV NA. A classical yeast two-hybrid screen was conducted to identify a new host interacting partner for NA and the interaction was further validated by coimmunoprecipitation from cells, transiently expressing both proteins and also from IAV-infected cells. Confocal imaging showed that both proteins colocalized in the cytoplasm in transfected host cells. Interestingly, increased levels of NA in the presence of Hsp90 was observed, which tends to decrease if adenosine triphosphatase activity of Hsp90 is inhibited using 17-N-allylamino-17-demethoxygeldanamycin (17AAG). This establishes viral NA as a client protein of host chaperone Hsp90 contributing toward NA's stability via the NA-Hsp90 interaction. This is the first report showing the interaction of NA with Hsp90 and its role in stabilizing viral NA thus preventing it from degradation. Enhanced cell survival in the presence of this interaction was also observed, thus suggesting the requirement of stable viral NA, post-IAV infection, for efficient virus production in infected mammalian cells.