001 for both). Patients with a history of malignancy had higher rates of post-TAVI pacemaker implantation (p less then 0.001), otherwise periprocedural complication rates were similar to those without. Using a multivariate logistic regression model to adjust for confounding factors, a history of malignancy was predictive of decreased odds of death in patients underwent TAVI (OR 0.67, 95% CI, 0.60 to 0.76, p less then 0.001) and higher odds of pacemaker implantation (OR 1.14, 95% CI, 1.09 to 1.19, p less then 0.001). In conclusion, with time the proportion of TAVI patients with a history of malignancy trended upward. Despite a greater prevalence of previous tobacco use and major depressive disorder, patients with a history of malignancy had TAVI safely with a low in-hospital all-cause mortality, yet greater cost of hospitalization and more frequent implantation of pacemaker devices.Systolic and diastolic hypertension independently predict the risk of adverse cardiovascular events. It remains unclear how systolic pressure, diastolic pressure, and other patient characteristics influence the initial diagnosis of hypertension. Here, we use a cohort of 146,816 adults in a large healthcare system to examine how elevated systolic and/or diastolic blood pressure measurements influence initial diagnosis of hypertension and how other patient characteristics influence the diagnosis. Thirty-four percent of the cohort were diagnosed with hypertension within 1 year. In multivariable logistic regression of the diagnosis of hypertension, controlling for covariates, isolated systolic hypertensive measures (odds ratio [OR] 0.42 [95% confidence interval CI 0.41 to 0.43]) and isolated diastolic hypertensive measures (OR 0.32 [95% CI 0.31 to 0.33]) were less likely to lead to hypertension diagnosis when compared with combined hypertensive measures. Higher levels of systolic blood pressure had a greater impact on hypertension diagnosis (OR 1.77 [95% CI 1.75 to 1.79] per Z-score) than did higher levels of diastolic blood pressure (OR 1.34 [95% CI 1.32 to 1.36] per Z-score). Older age, non-white race/ethnicity, and medical comorbidities all predicted the establishment of a diagnosis of hypertension. Isolated systolic and isolated diastolic hypertension are underdiagnosed in clinical practice, and several patient-centered factors also strongly influence whether a diagnosis is made. In conclusion, our findings uncover a care gap that can be closed with increased attention to the independent influence of systolic and diastolic hypertension and the various patient-centered factors that may impact hypertension diagnosis.The efficacy and safety of prolonged (>1-year) dual antiplatelet therapy (DAPT) duration in high-risk patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) remain unknown. All patients undergoing PCI at Fuwai hospital between January 2013 and December 2013 were prospectively enrolled into the Fuwai PCI registry. A total of 3,696 high-risk diabetics patients with at least one additional atherothrombotic risk factor were screened for inclusion. The primary efficacy outcome was the composite of all-cause mortality, myocardial infarction, or stroke. The median follow-up duration was 887 days. 69.8% of DM patients were on DAPT at 1 year without discontinuation. Based on multivariate Cox regression model and inverse probability of treatment weighting (IPTW) analysis, long-term (>1-year) DAPT reduced the risk of primary efficacy outcome (1.7% vs 4.1%; adjusted hazard ratio [adjHR] 0.382, 95% confidence interval [CI] 0.252 to 0.577; IPTW-HR 0.362 [0.241 to 0.542]), as well as cardiovascular death and definite/probable stent thrombosis, compared with short-course (≤1-year) DAPT. Risk of the safety end point of clinically relevant bleeding (adjHR 0.920 [0.467 to 1.816]; IPTW-HR 0.969 [0.486 to 1.932]) was comparable between longer DAPT and shorter DAPT. A lower number of net clinical benefit adverse outcomes was observed with >1-year DAPT versus ≤1-year DAPT (adjHR 0.471 [0.331 to 0.671]; IPTW-HR 0.462 [0.327 to 0.652]), which appeared increasingly favorable in those with multiple atherothrombotic risk characteristics. In high-risk patients with DM receiving PCI who were event free at 1 year, DAPT prolongation resulted in significant reduction in the risk of ischemic events not offset by increase of clinically meaningful bleeding events, thereby achieving a net clinical benefit. Extending DAPT beyond the period mandated by guidelines seems reasonable in high-risk DM patients not deemed at high bleeding risk.It is well recognized that patients with diabetes mellitus (DM) and multivessel coronary artery disease (MVD) undergoing percutaneous coronary intervention (PCI) have poorer long-term outcomes compared with those undergoing coronary artery bypass grafting. However, the relative impact of DM status and extent of coronary artery disease on long term mortality in patients undergoing PCI is unknown. We sought to compare patients with DM undergoing PCI for single and multivessel disease to their non-DM counterparts. Overall, 34,690 consecutive patients undergoing PCI from the Melbourne Interventional Group registry (2005 to 2017) were included (mean age 64.5 ± 12 years, 76.6% male). Our cohort was stratified by the presence of DM and extent of CAD (DM-SVD [single-vessel disease] [n = 2,669], DM-MVD [n = 6,118], no-DM-SVD [n = 10,993], no-DM-MVD [n = 14,910]). DM-SVD and no-DM-MVD cohorts demonstrated comparable baseline cardiovascular risk profiles, although the no-DM-MVD cohort had higher rates of prior myocardial infarction, while the DM-SVD cohort had a higher proportion of patients with renal impairment. Over a median follow-up of 4.8 (IQR 2.0 to 8.2) years, 6,031 (17.5%) patients died. Using the no-DM-SVD group as the reference category, adjusted risk of mortality was highest in the MVD-DM cohort (HR 1.90; 95% CI 1.71 to 2.09). Similar adjusted risk of long-term mortality was observed in the DM-SVD (HR 1.32, 95%CI 1.15 to 1.51) and no-DM-MVD (HR 1.30, 95%CI 1.20 to 1.40) groups. In conclusion, we found that the long-term mortality of patients with DM and SVD undergoing PCI was the risk equivalent of non-DM patients with MVD.Intravascular brachytherapy (VBT) is an effective and safe treatment option for recurrent drug-eluting stent (DES) in-stent restenosis (ISR). However, the optimal therapy for patients with failed VBT is not well-defined. In this study, we sought to evaluate the optimal treatment strategy for patients after a failed VBT. Patients with recurrent ISR after an initial unsuccessful VBT were identified from our percutaneous coronary intervention database. Patients were divided into 2 cohorts (standard treatment with DES or balloon angioplasty versus repeat VBT). Baseline characteristics and clinical outcomes during follow-up were extracted. A total of 279 patients underwent PCI after an initial unsuccessful VBT at our institution. Of those, 215 (77%) patients underwent standard treatment with balloon angioplasty with or without DES, and 64 (33%) underwent balloon angioplasty followed by repeat VBT. The mean age of the cohort was 64±11 years. Overall, 71% were men, 47% had diabetes, and 22% had heart failure. The majority (64%) presented with unstable angina. The groups had similar baseline characteristics. The rate of major adverse cardiovascular events (defined as all-cause mortality, myocardial infarction, or target vessel revascularization) was significantly lower in the repeat VBT group at 1 year (31% vs 14%, p = 0.03), 2 years (51% vs 31%, p = 0.03), and 3 years (57% vs 41%, p = 0.08). Target lesion revascularization and target vessel revascularization were consistently lower in the repeat VBT group at all follow-up intervals than in the standard treatment group. Treatment of recalcitrant ISR following an initial failed VBT is associated with a high MACE rate at 3-year follow-up. Repeat VBT is safe and effective and should be considered as the preferred strategy.Centriole amplification in multiciliated cells occurs in a pseudo-cell cycle regulated process that typically utilizes a poorly characterized molecularly dense structure called the deuterosome. We identified the centrosomal protein Cep70 as a novel deuterosome-associated protein that forms a complex with other deuterosome proteins, CCDC78 and Deup1. Cep70 dynamically associates with deuterosomes during centriole amplification in the ciliated epithelia of Xenopus embryos. Cep70 is not found in nascent deuterosomes prior to amplification. However, it becomes localized at deuterosomes at the onset of centriole biogenesis and remains there after the completion of centriole amplification. Deuterosome localization requires a conserved C-terminal „Cep70” motif. Depletion of Cep70 using morpholino oligos or CRISPR/Cas9 editing in F0 embryos leads to a severe decrease in centriole formation in both endogenous MCCs, as well as ectopically induced MCCs. Consistent with a decrease in centrioles, endogenous MCCs have defects in the process of radial intercalation. We propose that Cep70 represents a novel regulator of centriole biogenesis in MCCs.

Symptoms and morbidities associated with obstructive sleep apnea (OSA) vary across individuals and are not predicted by the apnea-hypopnea index (AHI). Respiratory event duration is a heritable trait associated with mortality that may further characterize OSA.

We evaluated how hypopnea and apnea durations in non-rapid eye movement (NREM) sleep vary across demographic groups and quantified their associations with physiological traits (loop gain, arousal threshold, circulatory delay, pharyngeal collapsibility).

Data were analyzed from 1546 participants from the Multi-Ethnic Study of Atherosclerosis with an AHI ≥5. Physiological traits were derived using a validated model fit to the polysomnographic airflow signal. Multiple linear regression models were used to evaluate associations of event duration with demographic and physiological factors.

Participants had a mean age ±SD of 68.9 ±9.2 years, mean NREM hypopnea duration of 21.73 ±5.60 and mean NREM apnea duration of 23.87 ±7.44 seconds. In adjusted analyses, shorter events were associated with younger age, female sex, higher body mass index (p <0.01, all) and Black race (p <0.05). Longer events were associated with Asian race (p<0.01). Shorter event durations were associated with lower circulatory delay (2.53 ±0.13s, p<0.01), lower arousal threshold (1.39 ±0.15s, p<0.01), reduced collapsibility (-0.71 ±0.16s, p<0.01), and higher loop gain (-0.27 ±0.11s, p<0.05) per SD change. Adjustment for physiological traits attenuated age, sex, and obesity associations and eliminated racial differences in event duration.

Average event duration varies across population groups and provides information on ventilatory features and airway collapsibility not captured by the AHI.

Average event duration varies across population groups and provides information on ventilatory features and airway collapsibility not captured by the AHI.Purpose The plural is one of the first grammatical morphemes acquired by English-speaking children with normal hearing (NH). Yet, those with hearing loss show delays in both plural comprehension and production. However, little is known about the effects of unilateral hearing loss (UHL) on children’s acquisition of the plural, where children’s ability to perceive fricatives (e.g., the /s/ in cats ) can be compromised. This study therefore tested whether children with UHL were able to identify the grammatical number of newly heard words, both singular and plural. Method Eleven 3- to 5-year-olds with UHL participated in a novel word two-alternative forced choice task presented on an iPad. Their results were compared to those of 129 NH 3- to 5-year-olds. During the task, children had to choose whether an auditorily presented novel word was singular (e.g., tep, koss) or plural (e.g., teps, kosses) by touching the appropriate novel picture. Results Like their NH peers, children with UHL demonstrated comprehension of novel singulars.