Notes

Solving the particular Cost Delocalization Problem regarding Density Practical Concept.
Elevated lipoprotein(a) (Lp[a]) and family history (FHx) of coronary heart disease (CHD) are individually associated with cardiovascular risk, and Lp(a) is commonly measured in those with FHx.

The aim of this study was to determine independent and joint associations of Lp(a) and FHx with atherosclerotic cardiovascular disease (ASCVD) and CHD among asymptomatic subjects.

Plasma Lp(a) was measured and FHx was ascertained in 2 cohorts. Elevated Lp(a) was defined as the highest race-specific quintile. Cytidine 5′-triphosphate solubility dmso Independent and joint associations of Lp(a) and FHx with cardiovascular risk were determined using Cox regression models adjusted for cardiovascular risk factors.

Among 12,149 ARIC (Atherosclerosis Risk In Communities) participants (54 years, 56% women, 23% black, 44% with FHx), 3,114 ASCVD events were observed during 21 years of follow-up. FHx and elevated Lp(a) were independently associated with ASCVD (hazard ratio [HR] 1.17; 95% confidence interval [CI] 1.09 to 1.26, and HR 1.25; 95%CI 1.12 to 1.40, respectively), and no Lp(a)-by-FHx interaction was noted (p=0.75). Compared with subjects without FHx and nonelevated Lp(a), those with either elevated Lp(a) or FHx were at a higher ASCVD risk, while those with both had the highest risk (HR 1.43; 95%CI 1.27 to 1.62). Similar findings were observed for CHD risk in ARIC, in analyses stratified by premature FHx, and in an independent cohort, the DHS (Dallas Heart Study). Presence of both elevated Lp(a) and FHx resulted in greater improvement in ASCVD and CHD risk reclassification and discrimination indexes than either marker alone.

Elevated plasma Lp(a) and FHx have independent and additive joint associations with cardiovascular risk and may be useful concurrently for guiding primary prevention therapy decisions.
Elevated plasma Lp(a) and FHx have independent and additive joint associations with cardiovascular risk and may be useful concurrently for guiding primary prevention therapy decisions.
It is estimated that 5% of patients with sarcoidosis have clinically manifest cardiac involvement, although autopsy and imaging studies suggest a significantly higher prevalence of cardiac involvement. There is a paucity of contemporary data on the risk of adverse cardiac outcomes, particularly heart failure (HF), in patients with sarcoidosis.

The purpose of this study was to examine the long-term risk of HF and other adverse cardiac outcomes in patients with sarcoidosis compared with matched control subjects.

In this cohort study, all patients age≥18 years with newly diagnosed sarcoidosis (1996 to 2016) were identified through Danish nationwide registries and matched 14 by age, sex, and comorbidities with control subjects from the background population without sarcoidosis.

Of the 12,042 patients diagnosed with sarcoidosis, 11,834 patients were matched with 47,336 subjects from the background population (median age 42.8 years [25th to 75th percentile 33.1 to 55.8 years], 54.3% men). The median follow-h matched control subjects.
Patients with sarcoidosis had a higher associated risk of HF and other adverse cardiac outcomes compared with matched control subjects.Preeclampsia is the archetype of a spectrum of clinical disorders related to abnormal placental development or function, characterized by placental histological lesions. Among those lesions, decidual vasculopathy is a term used to describe lesions of maternal spiral arteries, which are encountered on placental examination in about half of the women with preeclampsia. The morphological features of the lesions include perivascular lymphocytic infiltration, fibrinoid necrosis and foam cell incorporation within the vessel wall. Due to the resemblance of the latter characteristic to atherosclerosis, they are alternatively termed acute atherosis. Decidual vasculopathy correlates with worse maternal and neonatal outcomes, as well as placental pathology. In this article, we review the available literature on decidual vasculopathy and address the pitfalls in histological analysis of the lesions, including the varying definitions of the lesions and sample collection methods. We also discuss the current evidence on the etiology of the lesions and propose a novel hypothesis linking the three etiological pathways to the formation of decidual vasculopathy and, ultimately, the emergence of the heterogeneous group of placental dysfunction disorders, known as the great obstetric syndromes.
In the placenta, the (pro)renin receptor (ATP6AP2) is localised to the syncytiotrophoblast. ATP6AP2 can activate the placental renin-angiotensin system (RAS), producing Angiotensin II (Ang II) which, acting via the angiotensin II type 1 receptor (AGTR1), is important for placental development and function. ATP6AP2 can also independently stimulate intracellular signalling pathways known to regulate trophoblast syncytialisation. We proposed that ATP6AP2 plays a role in trophoblast syncytialisation.

Primary trophoblast cells were isolated from human placentae and transfected with an ATP6AP2 siRNA, a negative control siRNA or vehicle and allowed to spontaneously syncytialise. Syncytialisation was determined by secretion of human chorionic gonadotrophin (hCG) and by decreased CDH1 (E-cadherin) levels. Expression of RAS mRNAs and proteins were measured by qPCR and immunoblotting, respectively.

Primary trophoblast cells spontaneously syncytialised in culture. Syncytialisation did not affect ATP6AP2 mRNA or proanism via which the RAS was activated. Therefore, syncytialisation of primary trophoblasts may involve hCG-induced RAS activation and downstream activation of signalling pathways and growth factors, which can be stimulated via the interaction of Ang II with AGTR1. Nevertheless, it appears that the (pro)renin receptor is not involved.
We use an in-vitro human fetal membrane (FM) explant-based model to study inflammation-induced FM weakening, a prerequisite for PPROM. In this system, GMCSF is a critical intermediate, both necessary and sufficient for TNFα and thrombin induced FM weakening. α-Lipoic-acid (LA) blocks TNFα and thrombin, as well as GMCSF-induced weakening. Recently, we reported LA concomitantly blocks GMCSF-induction of MMPs 2, 9 and 10 and inhibition of TIMPs 1-3. The aim of this study was to show that LA blocks GMCSF-induced increases in additional proteases and reductions in additional protease inhibitors.

FM fragments were cultured±LA and then±GMCSF. In other experiments, weak versus strong, fresh FM were cultured without additions. Fragments were strength tested and media analyzed by multiplex protein ELISA for proteases and protease inhibitors.

GMCSF induced FM weakening and concomitantly increased several Proteases (Cathepsin-S, Proteinase-3, Elastase-2) and decreased several protease inhibitors (NGAL, Cystatin-C, HE4 and Thrombospondin1).
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