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Conditionals in Mandarin can be expressed by conjunctive sentences with no overt conditional connective (Type 1: P, Q) or with a conditional connective (CC) in the antecedent (Type 2: CC P, Q) and/or a conditional particle (CP) in the consequent (Type 3: (CC) P, CP Q). In this paper, we focus on jiu-conditionals (Type 3) without CCs. We assume that jiu in Mandarin is ambiguous between jiu 1 (unstressed, nonexclusive, left associating) and jiu 2 (stressed, exclusive, right associating), and that jiu-conditionals involve jiu 1 without exclusive force. We argue against a conditional conjunction analysis of jiu-conditionals and for a scalar analysis of jiu in conditionals as well as in temporal or spatial use. Furthermore, we present what we believe is the first uniform pragmatic account of Mandarin conditional constructions across Types 1–3: it is the subjective (non)veridicality property of the first clause P that determines the reading of the sentence P, Q. If P is entailed or presupposed, we get a conjunctive reading; if P is not entailed or presupposed, that is, if it is nonveridical, we get a conditional reading. Devices triggering the conditional reading include CCs or negative polarity items in the antecedent, as well as the broader discourse context or world knowledge.

Antilocality effects provide strong evidence for expectation-based sentence parsing models. Previous discussion of the antilocality effect, however, largely focused on the argument-verb dependencies in verb-final constructions, for which a memory retrieval-based account has been argued to be equally adequate. To test whether the principles of expectation/memory-based accounts hold for a wider range of dependencies, we report on two self-paced reading experiments that compared two different determiners in German: the morphologically complex determiner

In the present review paper by members of the collaborative research center “Register: Language Users' Knowledge of Situational-Functional Variation” (CRC 1412), we assess the pervasiveness of register phenomena across different time periods, languages, modalities, and cultures. We define “register” as recurring variation in language use depending on the function of language and on the social situation. Informed by rich data, we aim to better understand and model the knowledge involved in situation- and function-based use of language register. In order to achieve this goal, we are using complementary methods and measures. In the review, we start by clarifying the concept of “register”, by reviewing the state of the art, and by setting out our methods and modeling goals. Against this background, we discuss three key challenges, two at the methodological level and one at the theoretical level: (1) To better uncover registers in text and spoken corpora, we propose changes to established analytical approaches. (2) To tease apart between-subject variability from the linguistic variability at issue (intra-individual situation-based register variability), we use within-subject designs and the modeling of individuals' social, language, and educational background. (3) We highlight a gap in cognitive modeling, viz. modeling the mental representations of register (processing), and present our first attempts at filling this gap. We argue that the targeted use of multiple complementary methods and measures supports investigating the pervasiveness of register phenomena and yields comprehensive insights into the cross-methodological robustness of register-related language variability. These comprehensive insights in turn provide a solid foundation for associated cognitive modeling.

The concept of bias is familiar to linguists primarily from the literature on questions. Following the work of Giannakidou and Mari (Truth and Veridicality in Grammar and Thought: Modality, Mood, and Propositional Attitudes, University of Chicago Press, Chicago, 2021), we assume “nonveridical equilibrium” (implying that p and ¬p as equal possibilities) to be the default for epistemic modals, questions and conditionals. The equilibrium of conditionals, as that of questions, can be manipulated to produce bias (i.e., reduced or higher speaker commitment). In this paper, we focus on three kinds of modal elements in German that create bias in conditionals and questions: the adverb wirklich ‘really’, the modal verb sollte ‘should’, and conditional connectives such as falls ‘if/in case’. We conducted two experiments collecting participants’ inference about speaker commitment in different manipulations, Experiment 1 on sollte/wirklich in ob-questions and wenn-conditionals, and Experiment 2 on sollte/wirklich in wenn/falls/V1-conditionals. Our findings are that both ob-questions and falls-conditionals express reduced speaker commitment about the modified (antecedent) proposition in comparison to wenn-conditionals, which did not differ from V1-conditionals. In addition, sollte/wirklich in the antecedent of conditionals both create negative bias about the antecedent proposition. Our studies are among the first that deal with bias in conditionals (in comparison to questions) and contribute to furthering our understanding of bias.

Both indicative and counterfactual conditionals are known to be licensing contexts for negative polarity items (NPIs). However, a recent theoretical account suggests that the licensing of attenuating NPIs like English all that in the conditional antecedent is sensitive to pragmatic differences between various types of conditionals. We conducted three behavioral experiments in order to test key predictions made by that proposal. In Experiment 1, we tested hypothetical indicative and counterfactual conditionals with the English NPI all that, finding that the NPI is degraded in the former compared to the latter. In Experiment 2, we compared hypothetical indicative conditionals and premise conditionals with the same NPI, again finding a degradation only for the former. Both results align with theoretically derived predictions purporting that hypothetical indicative conditionals are degraded due to their susceptibility to conditional perfection. Finally, Experiment 3 provides empirical evidence that comprehenders readily strengthen counterfactual conditionals to biconditionals, in line with theoretical analyses that assume that conditional perfection and counterfactual inferences are compatible. Their ability to still host attenuating NPIs in the conditional antecedent, by contrast, falls into place via the antiveridical inference to the falsity of the antecedent. Altogether, our study sheds light on the interplay between NPI licensing and the semantic and pragmatic properties of various types of conditionals. Moreover, it provides a novel perspective on the processing of different kinds of conditionals in context, in particular, with regard to their (non)veridicality properties.

Domestic cats, an important companion animal, can be infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This has aroused concern regarding the ability of domestic cats to spread the virus that causes coronavirus disease 2019. We systematically demonstrated the pathogenesis and transmissibility of SARS-CoV-2 in cats. Serial passaging of the virus between cats dramatically attenuated the viral transmissibility, likely owing to variations of the amino acids in the receptor-binding domain sites of angiotensin-converting enzyme 2 between humans and cats. These findings provide insight into the transmissibility of SARS-CoV-2 in cats and information for protecting the health of humans and cats.

Existing literature shows that readers and listeners rapidly adjust their expectations about likely discourse continuations through discourse markers, as well as through other linguistic and extra-linguistic cues. However, it is unclear whether (i) the facilitative effects of various (extra-)linguistic cues differ in quality and (ii) whether the effects interact with one another in any principled manner. We conducted two self-paced reading experiments on concessive constructions in German and English wherein optional lexical and/or contextual cues appeared ahead of the concessive discourse marker. The results demonstrate that readers can use both types of cues to anticipate the upcoming discourse relation. Our study thus provides novel evidence for expectation-driven accounts of discourse processing and elucidates the functions of discourse signals. Furthermore, the results also show that the role that a type of cues plays is subject to cross-linguistic variation.

Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It is unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.

In the literature on relative clauses (e. g. Alexiadou et al.2000: 4), it is occasionally observed that the German complex definite determiner d-jenige (roughly ‘the one’) must share company with a restrictive relative clause, in contrast to bare determiners der/die/das (Roehrs2006: 213–215; Gunkel2006; Gunkel2007). Previous works such as Sternefeld (2008: 378–379) and Blümel (2011) treat the relative clause as a complement of D to account for its mandatory occurrence. While such syntactic analyses have intuitive appeal, they pose problems for a compositional semantic analysis. The goal of this paper is twofold. First, we report on two rating studies providing empirical evidence for the obligatoriness of relative clauses in German DPs introduced by the complex determiner d-jenige. Secondly, following Simonenko (2014, 2015), we provide an analysis of the phenomenon at the syntax-semantics interface that captures familiar (Blümel2011) as well as novel related observations. Particularly, the analysis accounts for the facts that postnominal modifiers can figure in d-jenige-DPs and that the element can have anaphoric demonstrative pronominal uses.

The Omicron (B.1.1.529) SARS-COV-2 variant has raised serious concerns because of its unprecedented rapid rate of spreading and the fact that there are 36 mutations in the spike protein. Since the vaccine-induced neutralizing antibody targets are the spike protein, this may lead to the possibility of vaccine-induced humoral immunity escape.We measured the neutralizing activity in vitro for Omicron and compared this with wild type (WH-09) and Delta variants in human and monkey sera from different types of immunity. The monkey sera samples were collected at 1 and 3 months post three-dose inactivated (PiCoVacc) and recombinant protein (ZF2001) vaccination. Human sera were collected from 1 month post three-dose inactivated vaccination.In inactivated vaccine sera, at 1/3 months post three-dose, geometric mean titers (GMTs) of neutralization antibody (NAb) against the Omicron variant were 4.9/5.2-fold lower than those of the wild type. In recombinant protein vaccine sera, GMTs of NAb against Omicron were 15.7/8.9-fold lower than those of the wild type. In human sera, at 1 month post three-dose inactivated vaccination, GMTs of NAb against Omicron were 3.1-fold lower than those of the wild type.This study demonstrated that despite a reduction in neutralization titers, cross-neutralizing activity against Omicron and Delta variants was still observed after three doses of inactivated and recombinant protein vaccination.

In natural language conversations, speakers often communicate ‘if and only if’ when they say ‘if’. The reasons why in some circumstances, yet not all, conditionals receive a biconditional interpretation remain under investigation. Von Fintel (2001) proposed an account where the interpretation of a conditional (“if p, then q”) is predicted to depend on the focus of the conversation which may either lie on the conditions that make the consequent, q, true or on the consequences following when the antecedent, p, is true. To test this account, we present two novel behavioral experiments with non-text based stimuli that take advantage of participants’ intuitive understanding of physics. We find some supporting evidence for the tested account that is not conclusive but suggests that other aspects, like the nature of potential alternative causes for the consequent to become true (e.g., with or w/o the influence of an external variable), also play a role for the interpretation of the conditional.

This study primarily explored the role of paeonol in doxorubicin (DOX)-induced chronic heart failure (CHF), considering the cardioprotective effect of paeonol on an epirubicin-induced cardiac injury.DOX-induced CHF-modeled rats were treated with paeonol. Cardiac function and myocardial damage in rats were evaluated by using the multifunction instrument, and the histopathology, apoptosis, and the expression of miR-21-5p and S-phase kinase-associated protein 2 (SKP2) in myocardium were detected. The target gene of miR-21-5p was confirmed by a dual-luciferase reporter assay. After the required transfection or paeonol treatment, the viability, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) of the DOX-induced cardiomyocytes were determined. Reverse-transcription quantitative-PCR (RT-qPCR) and Western blot were performed to quantify the expressions of miR-21-5p, SKP2, and apoptosis-related factors.Paeonol improved cardiac function and also ameliorated the cardiac damage of CHF-modeled rats, where the downregulation of abnormally elevated myocardial damage markers, including brain natriuretic peptide, lactate dehydrogenase, renin, angiotensin II, aldosterone, and endothelin 1, was observed. Paeonol alleviated the histopathological injury and suppressed the apoptosis in CHF-modeled rats, inhibited miR-21-5p expression, and upregulated SKP2 expressionPaeonol shows a cardioprotective effect on DOX-induced CHF

The interpretation of conditionals is a long but ongoing debate in linguistics (cf. von Fintel 2007, 2011, 2012). In this paper, we focus on the meaning contribution of conditional connectives (CCs). According to Kratzer (1986, 1991), the English CC if has no semantics on its own and if-clauses are used to restrict modal or generic frequency operators. The restrictor analysis of conditionals and CCs has inspired many insightful follow-up studies through which it becomes clear that the interpretation of conditional sentences is subject to a process of semantic and pragmatic modulation. However, the role of CCs in the modulation process remains far from clear in the current literature, although CCs can influence the interpretation of conditional sentences in various ways. In this paper, we will argue with distributional observations and experimental evidence that Mandarin CCs can express different degrees of speaker commitment (Giannakidou and Mari 2015) towards the antecedent proposition, as non-at-issue meaning.

Numerical concepts are an integral part of everyday conversation and communication. Expressions relating to numbers in natural language can have precise or imprecise interpretations. While the precise interpretation most prominently appears in mathematical contexts, the imprecise interpretation seems to arise when numbers (as quantities) are applied to real world contexts (e.g., the rope is 50 m long). Earlier literature shows that the (im)precise interpretation can depend on different factors, e.g., the kind of approximator a numeral appears with (precise vs. imprecise, e.g., exactly vs. roughly) or the kind of numeral itself (round vs. non-round, e.g., 50 vs. 47). We report on a corpus-linguistic study and a rating experiment of English numerical expressions. The results confirm the effects of both factors and additionally an effect of the kind of unit (discrete vs. continuous, e.g., people vs. meters). This shows the contextual variability in the interpretation of numerical concepts in natural language.

It is impossible to talk about human cognition without talking about concepts—there simply is no human cognition without concepts. Concepts form an abstraction of reality that is central to the functioning of the human mind. Conceptual knowledge (of e.g., APPLE, LOVE and BEFORE) is crucial for us to categorize, understand, and reason about the world. Only equipped with concepts and words for them can we successfully communicate and carry out actions. But what exactly are concepts? How are concepts acquired? How does the human mind use concepts? In this introduction chapter, we elaborate on these questions (i.e., representation, learning, application), and provide summaries of the seven individual chapters in the volume, which from different scientific disciplines relate to one or the other of the questions.

Influenza A virus may circulate simultaneously with the SARS-CoV-2 virus, leading to more serious respiratory diseases during this winter. However, the influence of these viruses on disease outcome when both influenza A and SARS-CoV-2 are present in the host remains unclear. Using a mammalian model, sequential infection was performed in ferrets and in K18-hACE2 mice, with SARS-CoV-2 infection following H1N1. We found that co-infection with H1N1 and SARS-CoV-2 extended the duration of clinical manifestation of COVID-19, and enhanced pulmonary damage, but reduced viral shedding of throat swabs and viral loads in the lungs of ferrets. Moreover, mortality was increased in sequentially infected mice compared with single-infection mice. Compared with single-vaccine inoculation, co-inoculation of PiCoVacc (a SARS-CoV-2 vaccine) and the flu vaccine showed no significant differences in neutralizing antibody titers or virus-specific immune responses. Combined immunization effectively protected K18-hACE2 mice against both H1N1 and SARS-CoV-2 infection. Our findings indicated the development of systematic models of co-infection of H1N1 and SARS-CoV-2, which together notably enhanced pneumonia in ferrets and mice, as well as demonstrated that simultaneous vaccination against H1N1 and SARS-CoV-2 may be an effective prevention strategy for the coming winter.

Objectives Right ventricular (RV) failure occurring after left ventricular assist device (LVAD) implantation is associated with increased mortality. Purpose We sought to determine whether RV strain by echocardiography predicts outcomes following LVAD. Methods Consecutive patients who underwent continuous flow LVAD placement at our clinic between February 2007 and October 2018 were included. Patients with complex congenital heart disease and arrhythmogenic right ventricular cardiomyopathy were excluded. Baseline characteristics, pre-operative hemodynamic catheterization (1 week) transthoracic echocardiography (1 month) measurements were obtained from the medical record. Speckle tracking RV free wall longitudinal 2D strain was measured using TomTec Imaging System. Univariate and multivariable analysis performed to identify predictors of mortality following LVAD. Results The study group was comprised of 323 patients (mean age 60.8±11.5, 79.9% male) of which 256 had adequate image quality for RV strain. RV strain was impaired in most patients (mean −11.7±3.47). RV strain of −8.1% was identified as predictive of poor outcomes. RV strain did not correlate with other measures of RV dysfunction including pulmonary artery pulsatility index (PAPi) and RVFAC. After adjusting for PAPi, RA pressure, and clinical cumulative risk scores (Matthews, Kormos and Lietz-Miller) impaired RV free wall longitudinal strain (OR: 1.14; 95% CI: 1.01–1.29, p=0.025), tricuspid regurgitation (by vena contracta width (TRvc) (OR: 1.19; 95% CI: 1.05–1.36, p=:0.0021) and smaller LVEDD (OR: 0.95; 95% CI: 0.92–0.99, p:0.023) predicted 30-day all-cause mortality and RV failure. Decreased RV free wall strain also predicted peri-operative mortality (22.58% vs. 4.89%, p=0.0003) and prolonged inotropic support (247.0.±277.4 vs. 122.8±139.3, p=0.024). Conclusions RV free wall strain is a non-invasive independent predictor of 30-day adverse outcomes (RV failure or all-cause mortality) Routine measurement of RV free strain may identify those patients at highest risk for early and long term mortality following LVAD. Funding Acknowledgement Type of funding source: None

Aims Little is known about the relative importance of body volume and haemodynamic parameters in the development of worsening of renal function in acutely decompensated heart failure (ADHF). To study the relationship between haemodynamic parameters, body water content and worsening of renal function in patients with heart failure with reduced ejection fraction (HFrEF) hospitalised for ADHF. Methods and results This prospective observational study involved 51 consecutive patients with HFrEF (age: 73±14 years, male: 60%, left ventricular ejection fraction: 33.3%±9.9%) hospitalised for ADHF. Echocardiographic-determined haemodynamic parameters and body volume determined using a bioelectric impedance analyser were serially obtained. All patients received intravenous furosemide 160 mg/day for 3 days. There was a mean weight loss of 3.95±2.82 kg (p Conclusions Normal body volume and lower serum BNP on admission were associated with worsening of renal function in patients with HFrEF hospitalised for ADHF.

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.

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.