Cutting nanodisks in graphene down to 20 nm in diameter.

A direct focused He+beam direct machining is presented to fabricate solid-state nano-disk at the surface of a graphene multilayer micro-flake deposited on an Au/Ti/sapphire surface. At irradiation doses larger than 5.0 × 1017ions cm-2and with a beam size well below 1 nm, graphene disks down to 20 nm in diameter have been machined with for nano-disk down to 50 nm in diameter, a central hole for preparing the positioning of a rotation axle. The local heat generated by this irradiation is inducing a partial graphene amorphization and deformation, leading to a complete graphene nano-disk vaporization at doses larger than 5 × 1018ions cm-2. A dry transfer printing technique followed by a graphene surface cleaning was used to transfer the nano-disks from its initial surface to a fresh and clean surface. Tapping mode atomic force micrograph have been recorded to follow the vaporization as a function of the He+dose to confirm the graphene solid-state nano-disk fabrication limit to about 20 nm with this process.

Does Condylar Morphology Affect Maxillary Repositioning in Bimaxillary Orthognathic Surgery?

This study aimed to measure the association between condylar morphology and a measure of the maxillary centroid following bimaxillary surgery using mandibular-dependent splints. The study included skeletal Class III and Class II malocclusion patients, excluding those with facial asymmetry. Based on computed tomography imaging patients were characterized into normal or abnormal temporomandibular joint (TMJ) groups. A computer-aided design/computer-aided manufacturing splints were fabricated to reposition the maxilla in Le Fort I osteotomy. The primary outcome measure was the absolute differences between the maxillary centroid's the planned and actual postoperative positions calculated by superimposing computed tomography scans. The secondary outcome was the measure of other variations in linear and angular maxilla discrepancies. The demographic covariates included the age and sex of the patients. The operative covariates consisted of the dentofacial deformity and the planned movement of the maxilla. Seventy patients with skeletal maxillofacial deformities were included for analysis: 44 patients in the normal and 26 in the abnormal TMJ group. The average maxillary misalignment was 1.04±0.48 mm in the normal and 1.53±0.63 mm in the abnormal TMJ group (P<0.001). A statistically significant relationship existed between the discrepancies of the maxillary centroid and dentofacial deformity (η=0.656, P<0.001). These findings suggest an increased propensity for maxillary malposition in skeletal Class II patients. Furthermore, condylar morphology is a significant prognostic factor influencing maxillary repositioning errors in bimaxillary surgery with mandibular-dependent splints.

Early intervention for perioperative hypertension in cataract surgery.

PURPOSE: Although perioperative blood-pressure control is important, especially for high-risk patients, no previous report has examined early monitoring of perioperative blood-pressure changes before cataract surgery. In this single-center, retrospective, observational study, we evaluated the early intervention for perioperative hypertension in cataract surgery with topical anesthesia. METHODS: Hospitalized patients who underwent phacoemulsification and intraocular-lens insertion and whose blood pressure was controlled using standardized management to start early monitoring and control (standardized group; 134 eyes of 134 patients) were compared to age- and sex-matched patients who underwent the same cataract surgery and whose blood pressure was controlled using conventional means (control group; 134 eyes of 134 patients). The perioperative blood pressure, pulse pressure, and heart rate were compared preoperatively, upon entering the operation room, and at the beginning, end, and after the operation. RESULTS: Although there was no difference before the operation, the changes in systolic pressure in the standardized group were significantly lower at the point of entering the operation room, at the beginning of the operation, and at the end of the operation (P = 0.003, < 0.001, and < 0.001, respectively). No significant difference was observed between etizolam and nicardipine use. CONCLUSION: Early monitoring and control of blood pressure in cataract surgery could effectively control perioperative hypertension without additional drug use and could be widely applied in the clinical setting.

Changes in the preoperative ocular surface flora with an increase in patient age: A surveillance analysis of bacterial diversity and resistance to fluoroquinolone.

PURPOSE: This study analyzed the relationship between patient age and the prevalence and fluoroquinolone susceptibility of gram-positive cocci from the ocular surface flora before ophthalmic surgery. METHODS: This surveillance study included scraped samples from the conjunctival sac of 8923 eyes of 5490 patients (70.0 ± 13.7 years) without ocular infection before ophthalmologic surgery between August 2018 and December 2020. A review of microbiological records regarding patient age was used to determine the number of isolates and gram-positive species obtained, as well as their fluoroquinolone susceptibility. Fluoroquinolone susceptibility was determined using the Clinical and Laboratory Standards Institute protocols of broth microdilution. Statistical analysis was performed using a generalized additive model and a log-linear model. RESULTS: In total, 9,894 bacterial isolates obtained from scraped samples from the patients were analyzed. The detected species were Staphylococcus epidermidis (31.0%), Staphylococcus aureus (6.1%), Staphylococcus lugdunensis (3.9%), Enterococcus faecalis (5.8%), Corynebacterium species (31.7%), and Cutibacterium acnes (7.5%) and others. The number of species isolated from the ocular surface was increased at the rate of 1.018 per 10 years of age (p < 0.0001). S. epidermidis, S. lugdunensis, E. faecalis, and Corynebacterium species were isolated more often with an increase in patient age. The levofloxacin resistance ratio of methicillin-sensitive S. epidermidis and Corynebacterium species increased at the rate of 1.204 and 1.087 respectively with a 10-year increase in age (both p < 0.0001). CONCLUSION: Gram-positive bacteria in the ocular surface flora (OSF) exhibited gradual changes in diversity and fluoroquinolone resistance with an increase in patient age. It is important to monitor the OSF of the patients before ophthalmologic surgery to prevent refractory ocular postoperative infection.

New Candidate Preservative in Ophthalmic Solution Instead of Benzalkonium Chloride: 1,3-Didecyl-2-methyl Imidazolium Chloride.

Benzalkonium chloride (BAC) is a useful preservative for ophthalmic solutions but has some disadvantageous effects on corneal epithelium, especially keratinocytes. Therefore, patients requiring the chronic administration of ophthalmic solutions may suffer from damage due to BAC, and ophthalmic solutions with a new preservative instead of BAC are desired. To resolve the above situation, we focused on 1,3-didecyl-2-methyl imidazolium chloride (DiMI). As a preservative for ophthalmic solutions, we evaluated the physical and chemical properties (absorption to a sterile filter, solubility, heat stress stability, and light/UV stress stability), and also the anti-microbial activity. The results indicated that DiMI was soluble enough to prepare ophthalmic solutions, and was stable under severe heat and light/UV conditions. In addition, the anti-microbial effect of DiMI as a preservative was considered to be stronger than BAC. Moreover, our in vitro toxicity tests suggested that DiMI is safer to humans than BAC. Considering the test results, DiMI may be an excellent candidate for a new preservative to replace BAC. If we can overcome manufacturing process issues (soluble time and flushing volume) and the insufficiency of toxicological information, DiMI may be widely adopted as a safe preservative, and immediately contribute to the increased well-being of all patients.

Difference in Anti-microbial Activity of Propan-1,3-diol and Propylene Glycol.

Propan-1,3-diol (PD) and propan-1,2-diol (propylene glycol, PG) are very similar compounds because their structures, safety data, and anti-microbial activities are almost the same. Actually, both compounds are made up of three carbon atoms and two hydroxyl groups. Regarding their safety, they do not have serious hazard data for animals, and LD50 values (in rats) of both are similar. As for the anti-microbial activity, minimum inhibitory concentration (MIC) values of both PD and PG are approximately 10% (v/v). In this study, we used the preservatives-effectiveness test (PET) to evaluate the anti-microbial activities of PD and PG, because both compounds are used in cosmetics as preservatives. The results indicated that PD was more effective as an anti-microbial agent compared with PG, and the effect of PD was marked against Escherichia coli and Pseudomonas aeruginosa. Scanning electron microscopy (SEM) images showed that the membrane of Escherichia coli was injured by PD and PG, but the damage by PD was more marked. The damage of the cell membrane may be the cause of high anti-microbial activity of PD in PET. These results suggest that PD has greater potential as a preservative, and PD should be recommended as an additive for food and medicine.

Endothelial dysfunction of the cornea after exposure to sprayed venom from hornets.

PURPOSE: Ocular injuries due to Hymenoptera venom are uncommon and most injuries occur on the ocular surface. We reported two rare cases of corneal endothelial damage caused by hornet venom that was sprayed, not injected, through stinging in the eye. OBSERVATIONS: Case 1: A 57-year-old male patient was injured when a hornet sprayed venom into his left eye. He was referred to our hospital because the edoema and epithelial erosion of the cornea persisted. The patient presented with bullous keratopathy, asymmetrical iris atrophy, irreversible mydriasis, and glaucoma. His cataract progressed, and his best-corrected visual acuity was 0.03. Cataract surgery was performed after anti-inflammatory treatment with steroids, and Descemet-stripping automated endothelial keratoplasty was performed 6 months later. The patient recovered well postoperatively: his best-corrected visual acuity improved to 1.0 and he continued his glaucoma treatment. Case 2: A 75-year-old male patient had damage to his corneal epithelium, severe conjunctivitis, and conjunctival edoema when sprayed hornet venom entered his left eye. At initial presentation, the corneal endothelial cell density had decreased to 1042 cells/mm2. The conjunctival sac was washed, and steroid and topical antibacterial instillations were administered. His best-corrected visual acuity improved from 0.07 at the initial visit to 0.5. However, the corneal opacification and glaucoma persisted, and 3 months later the corneal endothelial cell density decreased to 846 cells/mm2. CONCLUSIONS AND IMPORTANCE: Corneal injuries caused by sprayed hornet venom are rare; however, they can cause intense anterior chamber inflammation and severe, irreversible corneal endothelial damage. In such cases, prompt initial treatment, the administration of adequate anti-inflammatory medication, and careful evaluation of the corneal endothelium are required.

Prognosis and etiology of traumatic and non-traumatic corneal perforations in a tertiary referral hospital: a 30-year retrospective study.

PURPOSE: To clarify the prognosis of corneal perforation, we compared the etiology and characteristics of patients with traumatic and non-traumatic corneal perforations. METHODS: This retrospective observational study included patients treated for traumatic or non-traumatic corneal perforations at a single tertiary hospital from 1989 to 2019. The variables collected included the primary cause of corneal perforation, final best-corrected visual acuity (BCVA), and treatment administered. The initial treatment administered and treatment success rates were compared between the traumatic and non-traumatic groups. Multivariate linear regression analysis was performed to determine the predictors of final visual acuity. RESULTS: Ninety eyes of 90 patients (mean age, 61.1 ± 19.7 years) were included. Traumatic and non-traumatic corneal perforations occurred in 40 (44.4%) and 50 eyes (55.6%), respectively. Among non-traumatic causes, infection and autoimmune disease were the causes for corneal perforation in 18 (20.0%) and 12 eyes (13.3%), respectively. The success rate for the closure of the perforated site with the initial procedure was significantly higher in traumatic corneal perforations than in non-traumatic corneal perforations (90.0% and 72.2%, respectively; p = 0.038). Patients with traumatic corneal perforation had significantly better final BCVA than those with non-traumatic corneal perforation (0.71 ± 1.18 and 1.52 ± 1.12, respectively; p = 0.0016). On multivariate analysis, older age and non-traumatic corneal perforation were significantly related to the final lower BCVA (p < 0.001 and p = 0.029, respectively). CONCLUSION: Traumatic corneal perforation demonstrated a significantly better prognosis than non-traumatic corneal perforation. It is critical to consider the primary cause of corneal perforation to anticipate prognosis.

Long-term outcome in corneal endotheliitis with molecular detection of herpes simplex virus 1 and human herpes virus 6: a case report.

BACKGROUND: Human herpesvirus 6B (HHV-6B) is known to cause exanthema subitem and has been detected in various ocular diseases, including keratitis, uveitis, optic neuritis, and endophthalmitis; however, the long-term outcome after the reactivation of HHV-6B has not been well-addressed. Sugita et al. previously reported the concomitant presence of HHV-6B with herpes simplex virus-1 (HSV-1) in the aqueous fluid at the onset of corneal endotheliitis. We focused on the same patient with corneal endotheliitis, in whom both HSV-1 and HHV-6B sequences were observed, and reported the clinical course and long-term outcomes. CASE PRESENTATION: A 64-year-old woman was referred to our center for visual disturbances in the left eye. Her best-corrected visual acuity in the left eye was 0.5 and the left intraocular pressure was elevated to 33 mmHg. Mid-sized keratic precipitates and 2+ cells were observed in the anterior chamber with corneal endothelial edema and reduction of the corneal endothelial cell density to 1828 cells/mm2. The patient was diagnosed with corneal endotheliitis with increased intraocular pressure. Polymerase chain reaction analysis revealed the concomitant presence of both HSV-1 and HHV-6B sequences in the left aqueous fluid. After treatment with oral valacyclovir and topical betamethasone, her intraocular inflammation gradually improved and has not recurred at 12 years after corneal endotheliitis onset although corneal opacity remained. CONCLUSIONS: Reactivation of HHV-6B infection might be associated with HSV-1 corneal endotheliitis; however, no serious late sequelae occurred after appropriate treatment for HSV-1 infection in this immunocompetent host.

Study of Morphological Changes in the Inferior Turbinate After Le Fort I Osteotomy.

OBJECTIVE: There are cases in which patients complain of nasal obstruction after Le Fort I osteotomy, but the relationship with postoperative morphological changes in the nasal cavity, including the septum and inferior turbinate, is not clear. STUDY DESIGN: The authors evaluated the three-dimensional relationship of the morphological changes in the inferior turbinate before and after surgery in 84 patients who underwent Le Fort I osteotomy. Three classifications were made according to superior amount of maxillary movement at the base of nasal cavity. RESULTS: The high elevation group (4.0 mm or more) had 31 sides, the moderate elevation group had 93 sides, and the low elevation group (less than 2.0 mm) had 44 sides. The volume of inferior turbinate was 76.9 ± 12.8% of that before surgery in the high elevation group. The high- and moderate-elevation groups had significantly higher changes than the low elevation group, and the rate of contact between inferior turbinate and nasal cavity floor was 67.7%. CONCLUSIONS: After Le Fort I osteotomy, the volume of inferior turbinate tissue decreased in proportion to the amount of elevation of the maxilla. Although the soft tissue volume may be reduced due to adaptation of respiratory function, the inferior nasal passage was not completely ventilated in the high elevation group. If the elevation exceeds 4.0 mm counterclockwise with maxillary movement, it is necessary to consider the concomitant inferior turbinate resection because it may lead to nasal obstruction.

Age factor in the fluoroquinolone susceptibility of gram-positive cocci isolates from bacterial keratitis cases between 2008 and 2016.

PURPOSE: To determine the relationship between fluoroquinolone susceptibility of gram-positive cocci (GPC) isolated from patients with bacterial keratitis and the age of the patients or the date of onset. METHODS: Bacterial isolates were obtained from corneal lesions of patients with infectious keratitis treated between January 2008 and December 2016. The fluoroquinolone susceptibility of GPC was assessed, and a retrospective review of microbiological records was performed. Fluoroquinolone susceptibility was measured through broth microdilution in accordance with protocols of the Clinical and Laboratory Standards Institute. Statistical analysis was performed using a generalized estimating equation and cubic spline to determine the association between fluoroquinolone susceptibility of GPC isolated from corneal lesions and patient age. RESULTS: Of the 1200 bacterial isolates, 471 GPC were identified. They included Staphylococcus epidermidis (45.6%), other coagulase-negative Staphylococcus sp. (17.8%), and Staphylococcus aureus (18.3%). Levofloxacin susceptibility of GPC exhibited a negative relationship with age and had an odds ratio of 0.893 (95% confidence interval, 0.825-0.967) for every 10 years of age. A non-adjusted cubic spline curve was well correlated with year-adjusted data in a generalized additive model, and the levofloxacin susceptibility of GPC was initially stable but gradually declined after 40 years of age, before re-stabilizing again after 70 years of age. CONCLUSION: The fluoroquinolone susceptibility of GPC isolated from corneal lesions of infectious keratitis is high in children under 15 years of age and declines with an increase in age of patients using a generalized estimating equation and cubic spline.

Single-Carrier Transport in Graphene/hBN Superlattices.

Graphene/hexagonal boron nitride (hBN) moiré superlattices have attracted interest for use in the study of many-body effects and fractal physics in Dirac fermion systems. Many exotic transport properties have been intensively examined in such superlattices, but previous studies have not focused on single-carrier transport. The investigation of the single-carrier behavior in these superlattices would lead to an understanding of the transition of single-particle/correlated phenomena. Here, we show the single-carrier transport in a high-quality bilayer graphene/hBN superlattice-based quantum dot device. We demonstrate remarkable device controllability in the energy range near the charge neutrality point (CNP) and the hole-side satellite point. Under a perpendicular magnetic field, Coulomb oscillations disappear near the CNP, which could be a signature of the crossover between Coulomb blockade and quantum Hall regimes. Our results pave the way for exploring the relationship of single-electron transport and fractal quantum Hall effects with correlated phenomena in two-dimensional quantum materials.

Dielectric-Screening Reduction-Induced Large Transport Gap in Suspended Sub-10 nm Graphene Nanoribbon Functional Devices.

The predicted quasiparticle energy gap of more than 1 eV in sub-6 nm graphene nanoribbons (GNRs) is elusive, as it is strongly suppressed by the substrate dielectric screening. The number of techniques that can produce suspended high-quality and electrically contacted GNRs is small. The helium ion beam milling technique is capable of achieving sub-5 nm patterning; however, the functional device fabrication and the electrical characteristics are not yet reported. Here, the electrical transport measurement of suspended ≈6 nm wide mono- and bilayer GNR functional devices is reported, which are obtained through sub-nanometer resolution helium ion beam milling with controlled total helium ion budget. The transport gap opening of 0.16-0.8 eV is observed at room temperature. The measured transport gap of the different edge orientated GNRs is in good agreement with first-principles simulation results. The enhanced electron-electron interaction and reduced dielectric screening in the suspended quasi-1D GNRs and anti-ferromagnetic coupling between opposite edges in the zigzag GNRs substantiate the observed large transport gap.

Controlled fabrication of electrically contacted carbon nanoscrolls.

Carbon nanoscrolls (CNS) with their open ended morphology have recently attracted interest due to the potential application in gas capture, biosensors and interconnects. However, CNS currently suffer from the same issue that have hindered widespread integration of CNTs in sensors and devices: formation is done ex situ, and the tubes have to be placed with precision and reliability-a difficult task with low yield. Here, we demonstrate controlled in situ formation of electrically contacted CNS from suspended graphene nanoribbons with slight tensile stress. Formation probability depends on the length to width aspect ratio. Van der Waals interaction between the overlapping layers fixes the nanoscroll once formed. The stability of these CNSs is investigated by helium nano ion beam assisted in situ cutting. The loose stubs remain rolled and mostly suspended unless subject to a moderate helium dose corresponding to a damage rate of 4%-20%. One CNS stub remaining perfectly straight even after touching the SiO2 substrate allows estimation of the bending moment due to van der Waals force between the CNS and the substrate. The bending moment of 5400 eV is comparable to previous theoretical studies. The cut CNSs show long-term stability when not touching the substrate.

Clinical Manifestations and Prognostic Factors of Pneumocystis jirovecii Pneumonia without HIV.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PCP) can occur in HIV patients but also in those without HIV (non-HIV PCP) but with other causes of immunodeficiency including malignancy or rheumatic diseases. OBJECTIVE AND METHODS: To evaluate the clinical presentation and prognostic factors of non-HIV PCP, we retrospectively reviewed all patients diagnosed as having PCP without HIV at Kameda Medical Center, Chiba, Japan, from January 2005 until June 2012. For the purpose of examining a prognostic factor for non-HIV PCP with 30-day mortality, we compared the characteristics of patients, clinical symptoms, radiological images, Eastern Cooperative Oncology Group performance status (PS), and the time from the onset of respiratory symptoms to the start of therapy, in both survival and fatality groups. RESULTS: A total of 38 patients were eligible in this study. Twenty-five survived and 13 had died. The non-HIV PCP patients in the survivor group had a better PS and received anti-PCP therapy earlier than those in the nonsurvivor group. Rales upon auscultation and respiratory failure at initial visits were seen more frequently in the nonsurvivor group than in the survivor group. Lactate dehydrogenase and C-reactive protein values tended to be higher in the nonsurvivor group, but this was not statistically significant. Multivariate analyses using 5 variables showed that a poor PS of 2-4 was an independent risk factor for non-HIV PCP patients and resulted in death (odds ratio 15.24; 95% confidence interval 1.72-135.21). CONCLUSION: We suggest that poor PS is an independent risk factor in non-HIV PCP, and a patient's PS and disease activity may correlate with outcome.

Noninvasive vascular imaging of ruptured retinal arterial macroaneurysms by Doppler optical coherence tomography.

BACKGROUND: To describe Doppler optical coherence tomography (OCT) imaging of ruptured retinal arterial macroaneurysms (RAMs). METHODS: Four eyes of four patients with ruptured RAMs were prospectively studied. Vascular imaging was obtained using swept-source Doppler OCT, and compared with indocyanine green angiography images. RESULTS: En face projection of Doppler OCT images clearly showed RAMs at the corresponding locations of lesions in the indocyanine green angiography images. In Doppler OCT images, RAMs were located in the inner retina in three eyes and in the medium layer of the retina in one eye. In one eye, detection of RAMs by standard OCT was difficult because of the presence of inner retinal hemorrhage. In one eye, disappearance of blood flow after direct laser photocoagulation could be confirmed by Doppler OCT images. CONCLUSIONS: Doppler OCT imaging may potentially function as a noninvasive complementary procedure with indocyanine green angiography.

Establishment of a panel of in-house polyclonal antibodies for the diagnosis of enterovirus infections.

The aim of this study was to establish a reliable method of virus detection for the diagnosis of critical enterovirus infections such as acute infective encephalitis, encephalomyelitis and myocarditis. Because histopathological and immunohistochemical analyses of paraffin-embedded tissues play an important role in recognizing infectious agents in tissue samples, six in-house polyclonal antibodies raised against three representative enteroviruses using an indirect immunofluorescence assay and immunohistochemistry were examined. This panel of polyclonal antibodies recognized three serotypes of enterovirus. Two of the polyclonal antibodies were raised against denatured virus particles from enterovirus A71, one was raised against the recombinant VP1 protein of coxsackievirus B3, and the other for poliovirus type 1 were raised against denatured virus particles, the recombinant VP1 protein and peptide 2C. Western blot analysis revealed that each of these antibodies recognized the corresponding viral antigen and none cross-reacted with non-enteroviruses within the family Picornaviridae. However, all cross-reacted to some extent with the antigens derived from other serotypes of enterovirus. Indirect immunofluorescence assay and immunohistochemistry revealed that the virus capsid and non-structural proteins were localized in the cytoplasm of affected culture cells, and skeletal muscles and neurons in neonatal mice experimentally-infected with human enterovirus. The antibodies also recognized antigens derived from recent clinical isolates of enterovirus A71, coxsackievirus B3 and poliovirus. In addition, immunohistochemistry revealed that representative antibodies tested showed the same recognition pattern according to each serotype. Thus, the panel of in-house anti-enterovirus polyclonal antibodies described herein will be an important tool for the screening and pathological diagnosis for enterovirus infections, and may be useful for the classification of different enterovirus serotypes, including coxsackieviruses A and B, echoviruses, enterovirus A71 and poliovirus.

The insulin-like growth factor 1 receptor causes acquired resistance to erlotinib in lung cancer cells with the wild-type epidermal growth factor receptor.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy often provides a dramatic response in lung cancer patients with EGFR mutations. In addition, moderate clinical efficacy of the EGFR-TKI, erlotinib, has been shown in lung cancer patients with the wild-type EGFR. Numerous molecular mechanisms that cause acquired resistance to EGFR-TKIs have been identified in lung cancers with the EGFR mutations; however, few have been reported in lung cancers with the wild-type EGFR. We used H358 lung adenocarcinoma cells lacking EGFR mutations that showed modest sensitivity to erlotinib. The H358 cells acquired resistance to erlotinib via chronic exposure to the drug. The H358 erlotinib-resistant (ER) cells do not have a secondary EGFR mutation, neither MET gene amplification nor PTEN downregulation; these have been identified in lung cancers with the EGFR mutations. From comprehensive screening of receptor tyrosine kinase phosphorylation, we observed increased phosphorylation of insulin-like growth factor 1 receptor (IGF1R) in H358ER cells compared with parental H358 cells. H358ER cells responded to combined therapy with erlotinib and NVP-AEW541, an IGF1R-TKI. Our results indicate that IGF1R activation is a molecular mechanism that confers acquired resistance to erlotinib in lung cancers with the wild-type EGFR.

Encephalomyocarditis virus disrupts stress granules, the critical platform for triggering antiviral innate immune responses.

In response to stress, cells induce ribonucleoprotein aggregates, termed stress granules (SGs). SGs are transient loci containing translation-stalled mRNA, which is eventually degraded or recycled for translation. Infection of some viruses, including influenza A virus with a deletion of nonstructural protein 1 (IAVΔNS1), induces SG-like protein aggregates. Previously, we showed that IAVΔNS1-induced SGs are required for efficient induction of type I interferon (IFN). Here, we investigated SG formation by different viruses using green fluorescent protein (GFP)-tagged Ras-Gap SH3 domain binding protein 1 (GFP-G3BP1) as an SG probe. HeLa cells stably expressing GFP-G3BP1 were infected with different viruses, and GFP fluorescence was monitored live with time-lapse microscopy. SG formations by different viruses was classified into 4 different patterns: no SG formation, stable SG formation, transient SG formation, and alternate SG formation. We focused on encephalomyocarditis virus (EMCV) infection, which exhibited transient SG formation. We found that EMCV disrupts SGs by cleavage of G3BP1 at late stages of infection (>8 h) through a mechanism similar to that used by poliovirus. Expression of a G3BP1 mutant that is resistant to the cleavage conferred persistent formation of SGs as well as an enhanced induction of IFN and other cytokines at late stages of infection. Additionally, knockdown of endogenous G3BP1 blocked SG formation with an attenuated induction of IFN and potentiated viral replication. Taken together, our findings suggest a critical role of SGs as an antiviral platform and shed light on one of the mechanisms by which a virus interferes with host stress and subsequent antiviral responses.

Clinical features and outcomes of aspiration pneumonia compared with non-aspiration pneumonia: a retrospective cohort study.

Pneumonia is a leading cause of death among elderly patients. Although aspiration pneumonia (AP) commonly occurs with aging, its clinical features and outcomes are still uncertain. The aims of this study were to describe the clinical features and outcomes of AP and to assess whether presence of AP affects clinical outcomes in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP). We retrospectively analyzed patients with CAP and HCAP hospitalized in our institution in Japan from October 2010 to March 2012. We compared clinical features and outcomes between AP and non-AP, and investigated risk factors for recurrence of pneumonia and death. Of 214 consecutive patients, 100 (46.7%) were diagnosed as having aspiration pneumonia. These patients were older and had lower body mass index, more comorbidities, and poorer Eastern Cooperative Oncology Group performance status (ECOG PS) than the patients with non-AP. Patients with AP had more severe disease, required longer hospital stays, and had a frequent recurrence rate of pneumonia and higher mortality. In multivariate analyses, AP, age, and ECOG PS were related to recurrence of pneumonia, and the prognostic factors were CURB-65 score and ECOG PS. AP was not a significant indicator for prognosis but was the strongest risk factor for recurrence of pneumonia. Clinical background and outcomes including recurrence and mortality of AP were obviously different from those of non-AP; therefore AP should be considered as a distinct subtype of pneumonia, and it is important to prevent the recurrence of pneumonia in the patients with AP.