Recent studies into the global causes of severe diarrhoea in young children have identified the protozoan parasite Cryptosporidium as the second most important diarrhoeal pathogen after rotavirus. ...Diarrhoeal disease is estimated to be responsible for 10.5% of overall child mortality. Cryptosporidium is also an opportunistic pathogen in the contexts of human immunodeficiency virus (HIV)-caused AIDS and organ transplantation. There is no vaccine and only a single approved drug that provides no benefit for those in gravest danger: malnourished children and immunocompromised patients. Cryptosporidiosis drug and vaccine development is limited by the poor tractability of the parasite, which includes a lack of systems for continuous culture, facile animal models, and molecular genetic tools. Here we describe an experimental framework to genetically modify this important human pathogen. We established and optimized transfection of C. parvum sporozoites in tissue culture. To isolate stable transgenics we developed a mouse model that delivers sporozoites directly into the intestine, a Cryptosporidium clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system, and in vivo selection for aminoglycoside resistance. We derived reporter parasites suitable for in vitro and in vivo drug screening, and we evaluated the basis of drug susceptibility by gene knockout. We anticipate that the ability to genetically engineer this parasite will be transformative for Cryptosporidium research. Genetic reporters will provide quantitative correlates for disease, cure and protection, and the role of parasite genes in these processes is now open to rigorous investigation.
Contemporary realities of global population movement increasingly bring to the fore the challenge of quality and equitable health provision across language barriers. While this linguistic challenge ...is not unique to immigration contexts and is likewise shared by health systems responding to the needs of aboriginal peoples and other historical linguistic minorities, the expanding multilingual landscape of receiving societies renders this challenge even more critical, owing to limited or even non‐existing familiarity of modern and often monolingual health systems with the particular needs of new linguistic minorities. The centrality of language to health beliefs, attitudes, practices, cultural scripts, and conceptual frameworks emphasizes its pivotal role in the healthcare process, and consequently in the adverse effects of treatment that is language‐insensitive and unaware. Such an attitude on the part of medical authorities risks considerable epistemic injustice in the form of a (mis)judgement of patients’ intelligence, credibility, and rationality based on the language that they speak and the manner in which they speak it, consequently impacting the quality and equity of care provided. This danger, I argue, may be effectively countered by fostering among the participants in the healthcare process a sense of epistemic humility through greater metalinguistic awareness. Outlining a range of operative steps that can be used to facilitate this. I argue that the reality of language barriers in the healthcare process, while not entirely eliminable, may nevertheless be successfully addressed, in order to mitigate the challenge of quality and equitable healthcare provision in multilingual societies.
Abstract
Background
Type 2 diabetes mellitus (DM) is a risk factor for cardiovascular diseases and is common among patients undergoing coronary artery bypass grafting (CABG) surgery. The main ...objective of our study was to investigate the impact of DM type 2, and its treatment subgroups, on short- and long-term mortality in patients with acute coronary syndrome (ACS) who undergo CABG.
Methods
The study included 1307 patients enrolled from the biennial Acute Coronary Syndrome Israeli Survey between 2000 and 2016, who were hospitalized for ACS and underwent CABG. Of them, 527 (40%) patients were with and 780 (60%) were without DM.
Results
Compared with the non-diabetic group, the diabetic group of patients comprised more women and had more comorbidities such as hypertension, dyslipidemia, renal impairment, peripheral vascular disease and prior ischemic heart disease. Overall 30-day mortality rate was similar between DM and non-DM patients (4.2% vs. 4%, p = 0.976). Ten-year mortality rate was higher in DM compared with non-diabetic patients (26.6% vs. 17.7%, log-rank p < 0.001), and higher in the subgroup of insulin-treated patients compared to non-insulin treated patients (31.5% vs. 25.6%, log-rank p = 0.019). Multivariable analysis showed that DM increased the mortality hazard by 1.61-fold, and insulin treatment among the diabetic patients increased the mortality hazard by 1.57-fold.
Conclusions
While type 2 DM did not influence the in-hospital mortality hazard, we showed that the presence of DM among patients with ACS referred to CABG, is a powerful risk factor for long-term mortality, especially when insulin was included in the diabetic treatment strategy.
Abstract
Background
To compare the outcomes of diabetic patients hospitalized with non-ST elevation myocardial infarction (NSTEMI) or unstable angina (UA) referred for revascularization by either ...coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in a real-life setting.
Methods
The study included 1987 patients with diabetes mellitus enrolled from the biennial Acute Coronary Syndrome Israeli Survey between 2000 and 2016, who were hospitalized for NSTEMI or UA, and underwent either PCI (N = 1652, 83%) or CABG (N = 335, 17%). Propensity score-matching analysis compared all-cause mortality in 200 pairs (1:1) who underwent revascularization by either PCI or CABG.
Results
Independent predictors for CABG referral included 3-vessel coronary artery disease (OR 4.9, 95% CI 3.6–6.8, p < 0.001), absence of on-site cardiac surgery (OR 1.4, 95% CI 1.1–1.9, p = 0.013), no previous PCI (OR 1.5, 95% CI 1.1–2.2, p = 0.024) or MI (OR 1.7, 95% CI 1.2–2.6, p = 0.002). While at 2 years of follow-up, survival analysis revealed no differences in mortality risk between the surgical and percutaneous revascularization groups (log-rank p = 0.996), after 2 years CABG was associated with a significant survival benefit (HR 1.53, 95% CI 1.07–2.21; p = 0.021). Comparison of the propensity score matching pairs also revealed a consistent long-term advantage toward CABG (log-rank p = 0.031).
Conclusions
In a real-life setting, revascularization by CABG of diabetic patients hospitalized with NSTEMI/UA is associated with better long-term outcomes. Prospective randomized studies are warranted in order to provide more effective recommendations in future guidelines.
The boundary problem in political theory concerns the question of the constitution of the demos, and the principle(s) and/or mechanism(s) that may be permissibly used for its demarcation. But what ...are the linguistic terms in which such demarcation acts should take place? I contend that the boundary problem is nested within a linguistic boundary problem, and that a normative consideration on the constitution of the demos cannot avoid the need to address the question of its linguistic constitution, particularly on the part of 'talk-centric' deliberative approaches to democratic citizenship and inclusion. I argue that conceptualising the demos in pre-linguistic, non-linguistic or otherwise linguistically-unaware terms has substantive and adverse implications for its legitimacy claims. I conclude the interrogation of the boundary problem and its linguistic variant by proposing a shift from an abstracted notion of communicative rationality, towards a more situated communicative linguistic and political culture, grounded in linguistic epistemic humility.
Abstract
Public debates on linguistic integration as a socially desired outcome often share a prevailing sentiment that newcomers ought to “learn the language.” But the intensity of that sentiment is ...rarely accompanied by an equally robust understanding of what, precisely, it means in practice. This results in a notion of linguistic integration with an inbuilt tension between a seemingly pragmatic and commonsensical appearance, on the one hand, and a minimal action‐guidance capacity, on the other hand. This paper explores this intriguing tension, and it identifies three moral and practical challenges that this challenge presents to the normative theorizing of the practical ethics of linguistic integration: (1) a predicament of arbitrary treatment; (2) the interpersonal structure of social and linguistic learning; and (3) the affective dimension of linguistic integration.
Heart transplantation (HT) in patients with prior cardiovascular implantable electronic devices (CIEDs) is becoming more common, in parallel with the increased use of CIEDs for patients with advanced ...heart failure. Complete removal of CIED components during HT is not always feasible, and it is thus surprising that the literature addressing the implications of retained CIED components is limited. Indeed, there are neither guidelines nor consensus regarding the need for removal of these CIED fragments. This issue is nonetheless becoming important in light of the increase in the percentage of HT candidates having CIEDs, on the one hand, and newer therapeutic immunosuppressive protocols with higher bacterial infection potential, on the other. Thus, with the aim to study the implications of retained CIED fragments as a step towards establishing a therapeutic approach for the unique population of HT recipients with CIED remnants, we present here a case series of HT patients with retained CIED fragments who developed complications of infections together with a review of the available literature.
Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). Reduced cardiovascular mortality and morbidity have been reported in non-HT ...patients treated with metformin. Given the high prevalence of type 2 diabetes mellitus (T2DM) in HT patients, we investigated the association between metformin therapy and cardiovascular outcomes after HT.
The study population comprised 103 DM patients who had undergone HT between 1994 and 2018 and were prospectively followed-up. We excluded from the study patients with type 1 diabetes mellitus. Fifty-five HT patients (53%) in the cohort were treated with metformin. Clinical data were recorded on prospectively designed forms. The primary outcomes included CAV, survival, and the combined end-point of CAV or cardiovascular mortality.
Kaplan-Meier survival analysis showed that the CAV rate at 20 years of follow-up was lower in DM patients treated with metformin than in those who were not (30 vs. 65%; log-rank p = 0.044). Similarly, the combined risk of CAV or cardiovascular mortality was lower in the metformin-treated patients than in those not receiving metformin (32 vs. 68%; log rank p = 0.01). Consistently, multivariate analysis adjusted for age and comorbidities showed that metformin therapy was independently associated with a significant 90% reduction (95% confidence interval 0.02-0.46, p = 0.003) in the risk for the development of CAV, and a 91% reduction (95% confidence interval 0.02-0.42; p = 0.003) in the risk for CAV or cardiovascular mortality.
In diabetic HT patients, metformin therapy is independently associated with a significant reduction in the long-term risk for CAV and the combined end-point of CAV or cardiovascular mortality after HT.
Solidarity and/in Language Peled, Yael
Global justice (Downer, A.C.T.),
01/2024, Letnik:
14, Številka:
1
Journal Article
Recenzirano
The notion of solidarity can be said to be premised on shared intention and joint action, particularly when oriented towards questions of social and political justice. Yet conceptions of solidary ...relations remain surprisingly thin on language, and the ethics of the linguistic practices and mechanisms through which individuals formulate a sufficiently meaningful backdrop necessary for shared intention and joint action. My aim in this article, therefore, is to begin filling this gap, in the form of a general normative account that identifies the multilayered interrelations between solidarity and language, and examines their moral and practical implications. I begin with a brief overview of solidarity and language in the context of normative debates on bounded political communities. I then proceed to offer a more critical account of solidarity and linguistic difference, challenging some of the assumptions underlying its present understanding in that literature. In order to highlight and illustrate that critique, I explore its relevance to the highly political and often overlooked question of solidarity and language loss. I conclude with a brief reflection on the field of political theory and philosophy, asking what theoretical, conceptual and methodological insights may be gained from a closer attention to the language of solidarity in the theoretical and practical pursuit of justice.
•Long-term mortality after acute coronary syndrome strongly correlates with left ventricular ejection fraction (LVEF).•The prevalence of reduced LVEF decreases over time.•In recent years mortality ...rates dropped for reduced LVEF and did not change for preserved LVEF.
Our aim was to investigate trends in prognosis among survivors of acute coronary syndrome according to left ventricular ejection fraction during a 16-year period.
Data were derived from the Acute Coronary Syndrome Israeli Survey during the years 2000–2016. Patients aged 18 years and older were included in the analysis (N=11,725). Patients were classified into two groups based on their left ventricular ejection fraction: preserved (≥50%) and reduced (<50%) and also according to their acute coronary syndrome onset (2000–2006 early period vs. 2008–2016 late period). Endpoints were all-cause mortality rates at one and three years after the index event.
Preserved left ventricular ejection fraction was present in 5047/11,725 (43%) of patients. As expected, patients with preserved left ventricular ejection fraction had lower 1 and 3-year mortality rates as compared with reduced left ventricular ejection fraction regardless of the acute coronary syndrome period onset (6% vs. 19%, p<0.001). Nevertheless, in the late period the prevalence of reduced left ventricular ejection fraction decreased significantly, becoming equal to preserved left ventricular ejection fraction 2761 (50.5%) vs. 2713 (49.5%) respectively, p=0.3. Moreover, prognosis during the late period as compared with the early period was improved only in patients with reduced left ventricular ejection fraction (HR 0.79; 95% CI 0.70–0.89, p=0.0001).
The prevalence of reduced left ventricular ejection fraction has decreased and prognosis has improved during the past several years but is still much worse than the prognosis of preserved left ventricular ejection fraction.
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