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We simulated 3 transmission modes, including close-contact, respiratory droplets and aerosol routes, in the laboratory. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be highly transmitted among naive human angiotensin-converting enzyme 2 (hACE2) mice via close contact because 7 of 13 naive hACE2 mice were SARS-CoV-2 antibody seropositive 14 days after being introduced into the same cage with 3 infected-hACE2 mice. For respiratory droplets, SARS-CoV-2 antibodies from 3 of 10 naive hACE2 mice showed seropositivity 14 days after introduction into the same cage with 3 infected-hACE2 mice, separated by grids. In addition, hACE2 mice cannot be experimentally infected via aerosol inoculation until continued up to 25 minutes with high viral concentrations., Severe acute respiratory syndrome coronavirus 2 can be highly transmitted among naive angiotensin-converting enzyme 2 mice via close-contact spreading by respiratory droplets. However, these mice cannot be experimentally infected through aerosol inoculation unless it is continued for 25 minutes with a high viral concentration.

Background: Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models. Methods: Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2, and then analyzed by clinical signs, viral replication, chest X-ray, histopathological changes and immune response. Results: Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages. Conclusion: SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection. Key words: pathogenicity; pneumonia; rhesus macaque model; SARS-CoV-2

The outbreak of Corona Virus Disease 2019 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) is highly transmitted. The potential extra-respiratory transmission routes remain uncertain. Five rhesus macaques were inoculated with 1×106 TCID50 of SARS-CoV-2 via conjunctival (CJ), intratracheal (IT), and intragastric (IG) routes, respectively. Remarkably, the CJ inoculated-macaques developed mild interstitial pneumonia and viral load was detectable in the conjunctival swabs at 1 days post-inoculation (dpi). Only via IT inoculation, viral load was detected in the anal swab at 1-7 dpi and macaque showed weight loss. However, viral load was undetectable after IG inoculation. Comparatively, viral load was higher in the nasolacrimal system but lesions of lung were relatively mild and local via CJ inoculation compared with that via IT inoculation, demonstrating distinct characteristics of virus dispersion. Both the two routes affected the alimentary tract. Therefore the clinicians need to protect eye while working with patients.

A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection.One Sentence SummaryNeutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days.

Polarity sensitivity has been an established key topic of linguistic research for more than half a century. The study of polarity phenomena can be extremely revealing about the internal structure of a language, as they usually involve an interaction at the interface between syntax, semantics and pragmatics. In the past, most attention was paid to negative polarity items. However, recent years have witnessed a growing interest in positive polarity items. As a continuation of this trend, this issue collects four papers dedicated to positive polarity items, which enrich the empirical domain with novel observations from different languages and appeal to diverse theoretical concepts such as scalarity and presupposition in their modeling of positive polarity. The results show that positive polarity is a distributional phenomenon that has different sources and most likely cannot be modeled in a unifying way, although there may be subsets of positive polarity items that allow unifying accounts.

Refractory and resistant hypertension is defined as hypertension that is uncontrolled despite the use of multiple antihypertensives. The aim of the present study is to evaluate the prevalence, both in young and elderly, and the pattern of left ventricular hypertrophy (LVH) in South-Eastern Chinese patients with refractory, resistant and non-resistant hypertension.A total of 1455 patients (age 60.3 ± 13.9, male 55.7%) with essential hypertension were recruited. Refractory hypertension was defined as uncontrolled blood pressure (systolic/diastolic, ≥140/90 mm Hg) on ≥5 antihypertensive drug classes. Resistant hypertension was defined as uncontrolled blood pressure (systolic/diastolic, ≥140/90 mm Hg) on 3 or140/90 mm Hg on ≥4 antihypertensive classes.Among the total population, 1273 (87.4%) patients were considered non-resistant hypertension; 170 (11.7%) with resistant hypertension and 12 (0.8%) with refractory hypertension. The prevalence of the three groups of hypertension were similar between patients age60 or ≥60. Patients with refractory hypertension had the most dilated LV dimension, greatest left ventricular mass index and highest prevalence of diastolic dysfunction than patients with resistant and non-resistant hypertension. In particular, all patients with refractory hypertension had either concentric or eccentric LVH.In South-Eastern Chinese patients, the prevalence of refractory and resistant hypertension was 0.8% and 11.7%, respectively. Furthermore, no difference was observed in the hypertensive patterns between patients age60 and ≥60. Importantly, patients with refractory hypertension had the worst LV remodeling with all suffering from either concentric or eccentric hypertrophy.

Indicative conditionals are known to have the semantic property of nonveridicality, that is, they do not entail the truth of the antecedent. In this paper, I argue that the nonveridicality property of indicative conditionals is elastic in that it can be affected by the choice of conditional connectives and negative polarity items. Two experiments are reported, one on German and the other on English. They show that in both languages, the presence of negative polarity items conveys a weakened speaker commitment towards the antecedent, although there is cross-linguistic variation concerning the effect of conditional connectives.

The concept of conditionality is central to human thought and action. Conditionals are thus a widely studied topic in cognitive science. The present paper introduces the main topics addressed in this special issue and aims to provide a non-exhaustive overview of the recent research on grammatical aspects of conditionals (i.e. morphosyntax, semantics and pragmatics) and conditional reasoning.

To investigate interference, and how to avoid it, by high-frequency electromagnetic fields (EMFs) of Global System for Mobile Communications (GSM) mobile phone with communication between cardiac rhythm management devices (CRMs) and programmers, a combined in vivo and in vitro testing was conducted. During in vivo testing, GSM mobile phones interfered with CRM-programmer communication in 33 of 65 subjects tested (50.8%). Losing ventricle sensing was representative in this study. In terms of clinical symptoms, only 4 subjects (0.6%) felt dizzy during testing. CRM-programmer communication recovered upon termination of mobile phone communication. During in vitro testing, electromagnetic interference by high-frequency (700–950 MHz) EMFs reproducibly occurred in duplicate testing in 18 of 20 CRMs (90%). During each interference, the pacing pulse signal on the programmer would suddenly disappear while the synchronous signal was normal on the amplifier-oscilloscope. Simulation analysis showed that interference by radiofrequency emitting devices with CRM-programmer communication may be attributed to factors including materials, excitation source distance, and implant depth. Results suggested that patients implanted with CRMs should not be restricted from using GSM mobile phones; however, CRMs should be kept away from high-frequency EMFs of GSM mobile phone during programming. Bioelectromagnetics. 36:367–376, 2015. © 2015 Wiley Periodicals, Inc.

Context.— Chromosome analysis on bone marrow or peripheral blood samples fails in a small proportion of attempts. A method that is more reliable, with similar or better resolution, would be a welcome addition to the armamentarium of the cytogenetics laboratory. Objective.— To develop a method similar to banded metaphase chromosome analysis that relies only on interphase nuclei. Design.— To label multiple targets in an equidistant fashion along the entire length of each chromosome, including landmark subtelomere and centromere regions. Each label so generated by using cloned bacterial artificial chromosome probes is molecularly distinct with unique spectral characteristics, so the number and position of the labels can be tracked to identify chromosome abnormalities. Results.— Interphase chromosome profiling (ICP) demonstrated results similar to conventional chromosome analysis and fluorescence in situ hybridization in 55 previously studied cases and obtained useful ICP chromosome analysis results on another 29 cases in which conventional methods failed. Conclusions.— ICP is a new and powerful method to karyotype peripheral blood and bone marrow aspirate preparations without reliance on metaphase chromosome preparations. It will be of particular value for cases with a failed conventional analysis or when a fast turnaround time is required.

Tricuspid regurgitation (TR) is common in patients referred for cardiac assessment. Nonetheless, current estimates of its prevalence and contributing factors are limited. The aim of the present study was to evaluate the prevalence and demographics of TR in patients referred for echocardiography assessment at two University-affiliated hospitals.A total of 6711 consecutive Chinese patients were recruited as part of the Chinese Valvular Heart Disease Study (CVATS).The most common valvular lesion was TR (54.7%), followed by mitral regurgitation (44.7%) and aortic regurgitation (26.5%). Clinically significant (moderate or severe) TR was identified in 8.4% with the proportion increased from 3.9% amongst those aged51 to 15.9% in those aged ≥81. Multivariable adjustment demonstrated that significant TR was associated with age, congenital heart disease, chronic obstructive pulmonary disease, left-sided valvular heart disease (VHD), impaired left ventricular ejection fraction50%, atrial fibrillation and pulmonary hypertension.Among all types of VHD, TR was the most common and was identified in over half of the subjects and clinically significant in 8.4%. These unique data provide contemporary clinical and epidemiological characteristics of TR in a large cohort of patients referred for cardiac assessment and confirm the increased burden of TR in the aged population.

Background Karyotype determination has a central role in the genetic workup of pregnancy loss, as aneuploidy (trisomy and monosomy) and polyploidy (triploidy and tetraploidy) are the cause in at least 50% of first trimester, 25% of second trimester, and 11% of third trimester miscarriages. There are several limitations with the current approaches of obtaining a karyotype using traditional cytogenetics, fluorescence in situ hybridization with a limited number of probes, and chromosomal microarray. These include culture failure, incomplete results, lower sensitivity, and longer reporting time. Methods To overcome current limitations, a novel molecular assay is developed with a Standard Resolution Interphase Chromosome Profiling probe set which is a variation of the recently developed High Resolution probe set. It generates a molecular karyotype that can detect all major changes commonly associated with pregnancy loss. Initial familiarization of signal patterns from the probe set was used, followed by validation of the method using 83 samples from miscarriages in a blind study from three different laboratories. Finally, the clinical utility of the method was tested on 291 clinical samples in two commercial reference laboratory settings on two different continents. Results The new molecular approach not only identified all the chromosome changes observed by current methods, but also significantly improved abnormality detection by characterizing derivative chromosomes and finding subtle subtelomeric rearrangements, balanced and unbalanced. All Robertsonian translocations were also detected. The abnormality rate was 54% on clinical samples from commercial laboratory 1 and 63% from laboratory 2. Conclusion The attributes of this method make it an ideal choice for the genetic workup of miscarriages, namely (1) near 100% successful results, (2) greater sensitivity than conventional chromosome analysis or FISH panels, (3) rapid reporting time, and (4) favorable comparisons with chromosomal microarray.

A non-dipper pattern of high blood pressure is associated with increased risk of organ damage and cardiovascular disease in patients with hypertension. The aim of the study was to evaluate the left ventricular (LV) remodeling and function and arterial stiffness in a dipper/non-dipper pattern of high blood pressure in patients with hypertension. A total of 183 hypertensive patients with no history of adverse cardiovascular events were divided into two groups based on 24 hours ambulatory blood pressure monitoring (ABPM): 66 patients with a dipper pattern and 117 patients with non-dipper pattern. Detailed transthoracic echocardiogram was performed and analyzed with advance speckle tracking 3-orthogonal direction strain analysis to assess LV systolic function and tissue Doppler-derived E/E′ for LV diastolic function assessment. Cardio ankle vascular index (CAVI) was used to evaluate arterial stiffness. Compared with patients with dipper hypertension, those with non-dipper hypertension had increased LV mass index, higher prevalence of eccentric and concentric LV hypertrophy, more impaired LV diastolic and systolic function and peripheral arterial stiffness. Multivariable analysis revealed that a non-dipper pattern was independently associated with LV systolic dysfunction evaluated by speckle tracking-derived strain analysis. In conclusion, a non-dipper pattern of hypertension is an independent risk factor for LV systolic dysfunction. Treatment that could reverse this non-dipper pattern may reduce cardiac damage in these patients.

In this paper, I argue that pragmatics plays a role in the (anti-)licensing of polarity items in addition to semantic notions such as downward monotonicity and anti-additivity. In the case of positive polarity items (PPIs), I argue that they can co-occur with the anti-additive quantifier no N if intonation or enriched context makes it a contrastive negation or denial. The anti-licensing fails due to a positive implicature (PI) that performs pragmatic licensing and it is to this PI that PPIs contribute their meaning. As for negative polarity items (NPIs), I focus on the case of only that is not straightforwardly downward monotonic but licenses NPIs. Following Horn (2002), I assume that only is semantically conjunctive and that it licenses NPIs by its exclusive entailment that is negative. In addition to Horn’s arguments, I provide further arguments with domain-widening NPIs such as any, ever and minimizers that it is not to the prejacent but to the exclusive entailment that they contribute their domain widening (Kadmon and Landman 1993) function. In other words, the problem of only for NPI theories does not lie in the notion of downward monotonicity but in the compact packaging of two propositions with different monotonicity properties in one single sentence.

Statin, as a 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor, has been shown to prevent atrial fibrillation (AF) due to its anti-inflammatory and antioxidant effects. However, it is still not known whether statin can improve autonomic remodeling to prevent AF. In the present study, using an in vivo rat myocardial infarction (MI) model, we aimed to test whether simvastatin can attenuate nerve sprouting and sympathetic hyperinnervation to prevent AF during the post-MI remodeling process. Our data demonstrate that simvastatin, delivered 3 days after MI for 4 wk, can result in significant decreases in plasma levels of both TNF-α (239 ± 23 pg/ml) and IL-1β (123 ± 11 pg/ml) compared with MI rats without therapy (TNF-α, 728 ± 57 pg/ml; IL-1β, 213 ± 21 pg/ml; P < 0.05), which, however, were still higher than sham-operated rats (TNF-α, 194 ± 20 pg/ml; IL-1β, 75 ± 8 pg/ml; P < 0.05). The similar pattern of changes in inflammation responses was also observed in TNF-α and IL-1β protein expression in the left atrium free wall. The suppressed inflammation responses were associated with reduced superoxide and malondialdehyde generation in the atrium. These changes account for decreases in neural growth factor expression at levels of both mRNA (1.2 ± 0.09 AU vs. MI group, 1.78 ± 0.16 AU) and protein (1.57 ± 0.17 AU vs. MI group, 2.24 ± 0.19 AU; P < 0.05), thus resulting in reduced nerve sprouting and sympathetic hyperinnervation. Accordingly, the rate adaptation of the atrial effective refractory period also recovered, leading to the decreased inducibility of AF. These data suggest that simvastatin administration after MI can prevent AF through reduced sympathetic hyperinnervation.

Pediatric follicular lymphoma shares morphologic similarities with the adult form of the disease but lacks other classic features of adult lymphoma, including t(14;18) translocation, BCL2 overexpression, and transformation to aggressive higher-grade lymphoma. Herein, we report a novel case in which a 5-year-old boy (ethnicity unknown) had follicular lymphoma, along with concurrent high-grade and clonally related disease that fulfilled all of the morphologic, immunophenotypic, and genetic criteria for Burkitt lymphoma, including a t(8;14) translocation involving the MYC gene. To our knowledge, this case is the first reported instance of transformation of follicular lymphoma of any sort into true Burkitt lymphoma and the first reported instance of acquisition of MYC abnormalities in pediatric follicular lymphoma.

A-FABP (adipocyte fatty acid-binding protein), one of the most abundant proteins in adipocytes, plays a key role in obesity-related insulin resistance, inflammation and atherosclerosis in animals. In the present study, we sought to investigate the association of A-FABP with HF (heart failure) in Chinese subjects. Serum A-FABP levels were measured in 252 HF patients and 261 age-, gender- and BMI (body mass index)-matched non-HF subjects. Echocardiography was performed on each patient. The severity of HF was determined by the NYHA (New York Heart Association) classification system. After adjustments for age, gender and BMI, serum A-FABP concentrations in patients with HF were significantly higher than in non-HF patients [11.17 (6.63–19.93) ng/ml compared with 5.67 (3.20–8.87) ng/ml; P

Rationale: Remote ischemic conditioning induced by repeated episodes of transient limb ischemia is a clinically applicable method for protecting the heart against injury at the time of reperfusion. Objective: To assess the effect of chronic, repeated, remote conditioning on infarct size and long-term remodeling after myocardial infarction. Methods and Results: Rats with ischemia/reperfusion injury received different protocols of remote limb conditioning. While a single early episode of remote ischemic conditioning during coronary occlusion (perconditioning) resulted in a decrease in infarct size on both day 4 and day 28, when it was repeated (postconditioning) intermittently (every 3 days) and intensively (every day), it was not associated with a further decrease in infarct size. However, the protection against adverse remodeling offered by a single episode of limb perconditioning was further enhanced by repeated remote postconditioning therapy in a dose-dependent manner. In separate experiments there was a dose-dependent improvement in survival at 84 days by Kaplan–Meier analysis. Conclusions: Whereas a single early episode of remote perconditioning reduces infarct size, repeated remote postconditioning further reduces adverse LV remodeling and improves survival in a dose-dependent fashion. These data may have clinical implications for the treatment of patients with evolving myocardial infarction.

In the Drosophila visual cascade, the transient receptor potential (TRP) calcium channel, phospholipase Cbeta (no-receptor-potential A), and an eye-specific isoform of protein kinase C (eye-PKC) comprise a multimolecular signaling complex via their interaction with the scaffold protein INAD. Previously, we showed that the interaction between INAD and eye-PKC is a prerequisite for deactivation of a light response, suggesting eye-PKC phosphorylates proteins in the complex. To identify substrates of eye-PKC, we immunoprecipitated the complex from head lysates using anti-INAD antibodies and performed in vitro kinase assays. Wild-type immunocomplexes incubated with [(32)P]ATP revealed phosphorylation of TRP and INAD. In contrast, immunocomplexes from inaC mutants missing eye-PKC, displayed no phosphorylation of TRP or INAD. We also investigated protein phosphatases that may be involved in the dephosphorylation of proteins in the complex. Dephosphorylation of TRP and INAD was partially suppressed by the protein phosphatase inhibitors okadaic acid, microcystin, and protein phosphatase inhibitor-2. These phosphatase activities were enriched in the cytosol of wild-type heads, but drastically reduced in extracts prepared from glass mutants, which lack photoreceptors. Our findings indicate that INAD functions as RACK (receptor for activated PKC), allowing eye-PKC to phosphorylate INAD and TRP. Furthermore, dephosphorylation of INAD and TRP is catalyzed by PP1/PP2A-like enzymes preferentially expressed in photoreceptor cells.

Reactive oxygen species (ROS) is generated by oxidative stress and plays an important role in various cardiac pathologies. The SIRT1 signaling pathway and mitochondrial biogenesis play essential roles in mediating the production of ROS. SIRT1 activated by resveratrol protects cardiomyocytes from oxidative stress, but the exact mechanisms by which SIRT1 prevents oxidative stress, and its relationship with mitochondrial biogenesis, remain unclear. In this study, it was observed that after stimulation with 50μMH2O2 for 6h, H9C2 cells produced excessive ROS and downregulated SIRT1. The mitochondrial protein NDUFA13 was also downregulated by ROS mediated by SIRT1. Resveratrol induced the expression of SIRT1 and mitochondrial genes NDUFA1, NDUFA2, NDUFA13 and Mn-SOD. However, the production of these genes was reversed by SIRT1 inhibitor nicotinamide. These results suggest that resveratrol inhibits ROS generation in cardiomyocytes via SIRT1 and mitochondrial biogenesis signaling pathways.

Hepatocellular carcinoma is the most common type of liver cancer. The risk of hepatocellular carcinoma for type 2 diabetic patients is greater than that for non-diabetic individuals although the mechanism is unclear. The cancer suppressor resveratrol inhibits cancer cell proliferation partly through the STAT3 signaling pathway. However, the effects of resveratrol on STAT3 in high glucose-exposed HepG2 cells and the role of SIRT1 are not clear to date. The aim of the present study was to investigate the effects of resveratrol on STAT3 and SIRT1 regarding the proliferation of high glucose-exposed HepG2 cells. HepG2 cells were cultured in DMEM containing glucose (2.8, 5.5 and 25 mM) and resveratrol (0, 10 and 100 µM). HepG2 cell proliferation and viability were analyzed by MTT assays. The levels of p-STAT3 and SIRT1 were analyzed by western blotting, and RT-PCR methods were used to detect the transcription levels of cyclin B1, cyclin D1, VEGF and MMP-9. SIRT1-specific short-interfering RNA was used to investigate the role of SIRT1 in p-STAT3 signaling. A high glucose concentration (25 mM) induced HepG2 cell proliferation. This effect was suppressed by resveratrol (100 µM), and the effect on the p-STAT3 signaling pathway was found to be SIRT1-dependent. Our findings may provide new insights into the mechanism by which resveratrol suppresses HepG2 cell proliferation under conditions of high glucose. Furthermore, this information may provide the basis for a novel therapeutic strategy for hepatocellular carcinoma patients suffering from either diabetes or hyperglycemia.

The grammar of negative polarity items is one of the challenges for linguistic theory. NPIs cross-cut all traditional categories in grammar and semantics, yet their distribution is by no means arbitrary. Theories of NPI licensing have been proposed in terms of syntax, semantics, and pragmatics - each with its own merits and problems. The volume comprises state-of-the-art studies and suggests an interpolation approach to NPI licensing.

This chapter moves to the distribution of EADVs in and beyond entailment-cancelling contexts. It shows that LCP/CI can provide a type-logical account for 'polarity sensitivity' of EADVs, that is, the observation that they tend not to occur in negation. Polarity sensitivity is one of the most popular topics in generative linguistics. The idea is that in the lexicon there are items that tend only to occur in negative contexts and items that tend only to occur in positive contexts. The former are called negative polarity items (NPIs), and the latter positive polarity items (PPIs). The chapter goes through the distributional facts about EADVs in detail, which show their anti-collocational behaviours in negation and semantically or pragmatically related contexts such as modals, questions, conditionals, neg-rasing and volitional predicates. In German, semantic scope usually reflects surface structure c-command relations, that is, syntactically. Throughout, the chapter takes German as the main object language.Keywords:EADVs; German; positive polarity items (PPIs); negative polarity items (NPIs)

Background— Operative mortality after left ventricular assist device (LVAD) implantation is heavily influenced by patient selection and the technical difficulty of surgery. However, how we treat our patients and LVAD setting may affect the patient outcome beyond this period. We postulated that the presence of echocardiographic variables 1 month after surgery suggesting appropriate degree of LV unloading and an adequate forward flow would be important in determining clinical outcomes after the initial successful LVAD implantation. Methods and Results— We retrospectively analyzed various variables in echocardiographic examinations performed 30 days after LVAD implant in 76 consecutive patients receiving continuous flow device for their association with a compound end point (90-day mortality, readmission for heart failure, or New York Heart Association class III or higher at the end of the 90-day period). The echocardiographic associations examined included estimated LVAD flow, with and without native LV contribution, interventricular septal position, the status of aortic valve opening, an estimated left atrial pressure (ELAP), the mitral flow E-wave deceleration time, and the ratio of deceleration time to E-wave velocity (mitral deceleration index [MDI]). Four patients died during the 30- to 90-day period, 6 patients were readmitted for heart failure, and 25 patients were considered to have New York Heart Association class III or higher at the end of the 90-day period. Variables associated with adverse outcome included increased ELAP (odds ratio, 1.30 [1.16–1.48]; P P =0.02) and decreased tricuspid lateral annulus velocity (odds ratio, 0.70 implantation [0.48–0.95]; P =0.02). A leftward deviation of interventricular septum was associated with a worse outcome (odds ratio, 3.03 implantation [1.21–13.3]; P =0.01). Conclusions— Mortality and heart failure after LVAD surgery appear to be predominantly determined by echocardiographic evidence of inefficient unloading of the left ventricle and persistence of right ventricular dysfunction. Increased estimated LA pressure and short MDI are associated with worse mid term outcome. Leftward deviation of the septum is associated with worse outcome as well.

Endoplasmic reticulum (ER) stress is activated during and contributes to ischemia-reperfusion (I/R) injury. Attenuation of ER stress-induced apoptosis protects the heart against I/R injury. Using apelin, a ligand used to activate the apelin APJ receptor, which is known to be cardioprotective, this study was designed to investigate 1) the time course of changes in I/R injury after ER stress; 2) whether apelin infusion protects the heart against I/R injury via modulation of ER stress-dependent apoptosis signaling pathways; and 3) how phosphatidylinositol 3-kinase (PI3K)/Akt, endothelial nitric oxide synthase (eNOS), AMP-activated protein kinase (AMPK), and ERK activation are involved in the protection offered by apelin treatment. The results showed that, using an in vivo rat I/R model induced by 30 min of ischemia followed by reperfusion, infarct size (IS) increased from 2 h of reperfusion (34.85 ± 2.14%) to 12 h of reperfusion (48.98 ± 3.35, P < 0.05), which was associated with an abrupt increase in ER stress-dependent apoptosis activation, as evidenced by increased CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, and JNK activation (CHOP: 2.49-fold increase, caspase-12: 2.09-fold increase, and JNK: 3.38-fold increase, P < 0.05, respectively). Administration of apelin at 1 μg/kg not only completely abolished the activation of ER stress-induced apoptosis signaling pathways at 2 h of reperfusion but also significantly attenuated time-related changes at 24 h of reperfusion. Using pharmacological inhibition, we also demonstrated that PI3K/Akt, AMPK, and ERK activation were involved in the protection against I/R injury via inhibition of ER stress-dependent apoptosis activation. In contrast, although eNOS activation played a role in decreasing IS at 2 h of reperfusion, it failed to modify either IS or ER stress-induced apoptosis signaling pathways at 24 h after reperfusion.

Ischemic postconditioning (PostC) and perconditioning (PerC) provide practical methods for protecting the heart against ischemia-reperfusion (I/R) injury, but their combined effects have not been studied in detail. Using an in vivo rat I/R model, we tested 1) whether additive effects were produced when local PostC was preceded by varying doses of remote PerC, and whether the optimal PostC+PerC regime is additive to local ischemic preconditioning (IPC), and 2) how combined PostC+PerC alters the activity of the reperfusion injury salvage kinase pathway. The optimal combination of PerC and PostC therapy was produced by PerC delivered with four cycles of 5 min of limb ischemia followed by 5-min reperfusion. This resulted in lower infarct size (22.56 ± 4.45%) compared with rats with PostC alone (29.39 ± 3.66%) and PerC alone (33.49 ± 5.81%) and complementary differences in the generation of reactive oxygen species and apoptotic signaling. However, this optimal combination of PostC+PerC resulted in protection similar to local IPC alone (18.8 ± 2.54%, P = 0.13), and when added to IPC there was no additional protection (19.62 ± 2.89%, P = 0.675). Akt and ERK1/2 phosphorylation was induced by PostC and PerC and maximally by combined PostC+PerC treatment, and protection was abolished by phosphatidylinositol 3-kinase or ERK1/2 inhibitors. This study shows that neither PostC nor a maximized “dose” of PerC leads to optimal kinase signaling or cardioprotection compared with IPC alone. However, combined PostC+PerC may result in complementary effects on kinase signaling to recapitulate the effects of local IPC. Finally, combined PostC+PerC is not additive to IPC, suggesting that each works via a common pathway.

Adverbs of comment (AOCs) such as sadly raise a question of subjective meaning, much like predicates of personal taste (fun, tasty), namely, to whom the speaker attributes the emotion or evaluation when there is no overt for-PP. I extend Lasersohn's (2005) and Stephenson's (2007) judge analysis for predicates of personal taste to AOCs. My proposal is that disagreement on one and the same proposition sad(p, a) expressed by these adverbs only arises when the hearer correctly resolves the argument of judge a (a constant) despite its absence in overt syntax, i.e. sad(p, a) vs. ¬sad(p, a). Otherwise, only mis- or incomprehension occurs where the speaker and the hearer actually express two different propositions on the same issue, i.e. sad(p, a) vs. ¬sad(p, b).

To investigate the long-term feasibility and stability of active-fixation pacing leads following amputation of right atrial appendage (RAA). Active-fixation leads were used in 85 consecutive sick sinus syndrome or high-grade atrioventricular block patients with (Group 1, n=22) or without (Group 2