Optimal Medical Therapy Following Transcatheter Aortic Valve Implantation.

Limited data exist on optimal medical therapy post-transcatheter aortic valve implantation (TAVI) for late cardiovascular events prevention. We aimed to evaluate the benefits of beta-blocker (BB), renin-angiotensin system inhibitor (RASi), and their combination on outcomes following successful TAVI. In a consecutive cohort of 1,684 patients with severe aortic stenosis undergoing TAVI, the status of BB and RASi treatment at discharge was collected, and patients were classified into 4 groups: no-treatment, BB alone, RASi alone, and combination groups. The primary outcome was a composite of all-cause mortality and rehospitalization for heart failure (HHF) at 2-year. There were 415 (25%), 462 (27%), 349 (21%), and 458 (27%) patients in no-treatment, BB alone, RASi alone, and combination groups, respectively. The primary outcome was lower in RASi alone (21%; adjusted hazard ratio [HR]adj: 0.58; 95% confidence interval [CI]: 0.42 to 0.81) and combination (22%; HRadj: 0.53; 95% CI: 0.39 to 0.72) groups than in no-treatment group (34%) but no significant difference between RASi alone and combination groups (HRadj: 1.14; 95% CI: 0.80 to 1.62). The primary outcome results were maintained in a sensitivity analysis of patients with reduced left ventricular systolic function. Furthermore, RASi treatment was an independent predictor of 2-year all-cause mortality (HRadj: 0.68; 95% CI: 0.51 to 0.90), while that was not observed in BB therapy (HRadj: 0.94; 95% CI: 0.71 to 1.25). In conclusion, post-TAVI treatment with RASi, but not with BB, was associated with lower all-cause mortality and HHF at 2-year. The combination of RASi and BB did not add an incremental reduction in the primary outcome over RASi alone.

E-Liquid Containing a Mixture of Coconut, Vanilla, and Cookie Flavors Causes Cellular Senescence and Dysregulated Repair in Pulmonary Fibroblasts: Implications on Premature Aging.

Electronic cigarette (e-cig) usage has risen dramatically worldwide over the past decade. While they are touted as a safe alternative to cigarettes, recent studies indicate that high levels of nicotine and flavoring chemicals present in e-cigs may still cause adverse health effects. We hypothesized that an e-liquid containing a mixture of tobacco, coconut, vanilla, and cookie flavors would induce senescence and disrupt wound healing processes in pulmonary fibroblasts. To test this hypothesis, we exposed pulmonary fibroblasts (HFL-1) to e-liquid at varying doses and assessed cytotoxicity, inflammation, senescence, and myofibroblast differentiation. We found that e-liquid exposure caused cytotoxicity, which was accompanied by an increase in IL-8 release in the conditioned media. E-liquid exposure resulted in elevated senescence-associated beta-galactosidase (SA-ß-gal) activity. Transforming growth factor-ß1 (TGF-ß1) induced myofibroblast differentiation was inhibited by e-liquid exposure, resulting in decreased α-smooth muscle actin and fibronectin protein levels. Together, our data suggest that an e-liquid containing a mixture of flavors induces inflammation, senescence and dysregulated wound healing responses.

Chemical Constituents Involved in E-Cigarette, or Vaping Product Use-Associated Lung Injury (EVALI).

The Centers for Disease Control declared e-cigarette, or vaping, product use-associated lung injury (EVALI) a national outbreak due to the high incidence of emergency department admissions and deaths. We have identified chemical constituents in e-cig counterfeit cartridges and compared these to medical-grade and CBD containing cartridges. Apart from vitamin E acetate (VEA) and tetrahydrocannabinol (THC), other potential toxicants were identified including solvent-derived hydrocarbons, silicon conjugated compounds, various terpenes, pesticides/plasticizers/polycaprolactones, and metals. This study provides additional insights into the chemicals associated with EVALI cartridges and thus may contribute to the underlying disease mechanism of acute lung injury.

E-cigarette flavored pods induce inflammation, epithelial barrier dysfunction, and DNA damage in lung epithelial cells and monocytes.

E-cigarette flavored pods are increasing in use among young adults. Although marketed as a safer alternative to conventional cigarettes, the health effects of e-cigarette flavored pods are unknown. We hypothesized that e-cigarette flavored pods would cause oxidative stress, barrier dysfunction, and an inflammatory response in monocytes and lung epithelial cells. JUUL pod flavors (Fruit Medley, Virginia Tobacco, Cool Mint, Crème Brulee, Cool Cucumber, Mango, and Classic Menthol) and similar pod flavors (Just Mango-Strawberry Coconut and Caffé Latte) were tested. These pod flavors generated significant amounts of acellular ROS and induced significant mitochondrial superoxide production in bronchial epithelial cells (16-HBE). Lung epithelial cells (16-HBE, BEAS-2B) and monocytes (U937) exposed to various pod aerosols resulted in increased inflammatory mediators, such as IL-8 or PGE2. JUUL pod flavors, Crème Brulee and Cool Cucumber, caused epithelial barrier dysfunction in 16-HBE cells. Moreover, tested flavors also showed DNA damage upon exposure in monocytes. We determined the chemical constituents present in various flavors. Our data suggest that these constituents in flavored pods induce oxidative stress, inflammation, epithelial barrier dysfunction, and DNA damage in lung cells. These data provide insights into the regulation of e-cigarette flavored pods, as well as constituents in these flavors.

New and Emerging Evidence on the Use of Second-Generation Direct Acting Antivirals for the Treatment of Hepatitis C Virus in Renal Impairment.

Due to the intimate relationship between liver and kidney disease in hepatitis C virus (HCV) infection, treatment options for HCV-positive patients at any stage of chronic kidney disease (CKD) are essential. The availability of second-generation, direct-acting antiviral (DAA) combinations has allowed for the advent of interferon-sparing treatment regimens with shorter durations and minimal side effects. While many of the second-generation DAAs are principally metabolized by the hepatic system, dosing in severe renal impairment (creatinine clearance [CrCl] <30 mL/min) or dialysis has remained questionable due to limited experience. New evidence regarding the use of these agents in renal impairment continues to become available, as real-world experience with these treatment regimens is reported. Simeprevir, ledipasvir, paritaprevir, ombitasvir, dasabuvir, and daclatasvir have data to suggest safety in end-stage renal disease. While safety and efficacy with sofosbuvir remains uncertain, data are now available to support utilizing a dose adjustment when glomerular filtration rates are <30 mL/min. Upcoming regimens grazoprevir/elbasvir and daclatasvir/asunaprevir/beclavubir may provide further options for patients with advanced kidney disease, and ongoing studies will continue to provide guidance for this unique patient population. This article will review the currently available literature, including the newest emerging evidence, on the use of second-generation DAAs in CKD stages 3 to 5 and dialysis.

Lacosamide Induced Psychosis: Case Report, Review of Differential Diagnosis and Relevant Pharmacokinetics.

Lacosamide (LCM) is an antiepileptic medication used as an adjunctive treatment for partial seizures. Psychosis associated with LCM use is a rarely documented phenomenon, which may be difficult to detect in the context of the often complicated clinical presentation of epilepsy. We report the development of psychosis in a young woman after the use of LCM, which subsequently resolved with its discontinuation. The possible differential diagnosis and pharmacokinetic nuances are discussed. This is the first case report of LCM-induced psychosis in the United States.

Exploring the associations between microRNA expression profiles and environmental pollutants in human placenta from the National Children's Study (NCS).

The placenta is the principal regulator of the in utero environment, and disruptions to this environment can result in adverse offspring health outcomes. To better characterize the impact of in utero perturbations, we assessed the influence of known environmental pollutants on the expression of microRNA (miRNA) in placental samples collected from the National Children's Study (NCS) Vanguard birth cohort. This study analyzed the expression of 654 miRNAs in 110 term placentas. Environmental pollutants measured in these placentas included dichlorodiphenyldichloroethylene (DDE), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd). A moderated t-test was used to identify a panel of differentially expressed miRNAs, which were further analyzed using generalized linear models. We observed 112 miRNAs consistently expressed in >70% of the samples. Consistent with the literature, miRNAs located within the imprinted placenta-specific C19MC cluster, specifically mir-517a, mir-517c, mir-522, and mir-23a, are among the top expressed miRNA in our study. We observed a positive association between PBDE 209 and miR-188-5p and an inverse association between PBDE 99 and let-7c. Both PCBs and Cd were positively associated with miR-1537 expression level. In addition, multiple let-7 family members were downregulated with increasing levels of Hg and Pb. We did not observe DDE or BPA levels to be associated with placental miRNA expression. This is the first birth cohort study linking environmental pollutants and placental expression of miRNAs. Our results suggest that placental miRNA profiles may signal in utero exposures to environmental chemicals.

Evidence of histidine and aspartic acid phosphorylation in human prostate cancer cells.

We have developed a method to identify previously undetected histidine and aspartic acid phosphorylations in a human prostate cancer progression model. A phosphoproteome of our cell line model is presented, with correlation of modified protein expression between the three states of cancer: non-tumorigenic, tumorigenic, and metastatic cells. With the described interaction proteins potentially phosphorylated by NM23-H1, cellular responses to motility and conformational change stimuli would be achievable. We detect 20 novel histidine-phosphorylated (pHis) and 80 novel aspartic acid-phosphorylated (pAsp) proteins with diverse functions, such as metabolism, protein folding, and motility. Our data indicate that pHis and pAsp are much more prevalent than previously appreciated and may provide insight into the role of NM23-H1 and signaling events that are critical for metastasis. Using the described method for detecting histidine and aspartic acid phosphorylations and our prostate cancer progression cell system, the potential function of NM23-H1 in suppressing metastasis with a two-component regulation system is discussed.

Myocardial perfusion imaging laboratory efficiency with the use of regadenoson compared to adenosine and dipyridamole.

OBJECTIVE: Adenosine, dipyridamole, and regadenoson are pharmacologic stress agents used in myocardial perfusion imaging (MPI), to diagnose and monitor coronary artery disease. Clinical studies suggest that regadenoson has pharmacologic properties that simplify the MPI procedure through availability to a wider range of patients and easier administrative requirements. This study assesses the operational advantages and laboratory efficiency associated with the use of regadenoson compared to adenosine and dipyridamole. METHODS: A web-based survey of 141 nuclear medicine technologists working in US-based cardiovascular imaging laboratories from June-July 2009. MAIN OUTCOME MEASURES: Descriptive statistics measured the adenosine, dipyridamole, and regadenoson cohorts. Bivariate analyses compared the overall and staff-specific time to conduct an MPI test. The site-specific sub-groups were defined by hospital vs non-hospital setting, hours of operation, number of SPECT cameras, and number of full-time equivalent staff, including nurses, nuclear technologists, physicians, and nurse practitioners/physician assistants. RESULTS: The total time to conduct an MPI test was shortest with regadenoson 156 (46) min compared to adenosine and dipyridamole 182 (63) and 191 (61) min, respectively. Time from regadenoson administration to the start of the imaging session, including dose calculation and infusion time, was 14.2 min less than adenosine, and 12.0 min less than dipyridamole. The time to manage adverse events was shortest if it occurred with regadenoson compared to adenosine and dipyridamole, with minor exceptions. Due to the nature of survey implementation, possible recall bias may limit the results. Some differences in procedures times may be attributable to differences in laboratories' protocols. CONCLUSIONS: Overall time savings and time savings stratified by operational ability (number of staff, number of SPECT cameras, hours of operation) translate to a more efficient utilization of laboratory resources when using regadenoson compared to adenosine and dipyridamole. Regadenoson is the most efficient pharmacologic stress agent compared to adenosine and dipyridamole.

Worry about terror among young adults living in ongoing security uncertainty.

The aim of the current study was to investigate worry about terror as a mediating variable, with the exogenous variables being media viewing, differentiation of self, and trait anxiety, and the endogenous variables being somatic symptoms and perceptions of security-related stress. Participants were divided into two groups by age/academic level: 248 high school students and 191 university students. A pathway correlation model was used to investigate worry about terror as a mediating variable. The central finding was that worry about terror was a significant mediating variable in the relationship between the extent of media viewing following terror events and the level of perception of security-related stress. That is, young people who said they worried a lot reported a high level of stress relating to the terror events they saw covered in the media. In addition, trait anxiety was found to have an effect on stress perception only via the level of worry about terror. This means that high levels of stress are not experienced by all highly trait-anxious people, but only by those who suffer from higher levels of worry about terror.

Assessing achievement and maintenance of glycemic control by patients initiating basal insulin.

OBJECTIVE: Describe characteristics of diabetic patients who initiated basal insulin and assess their glycemic control. RESEARCH DESIGN AND METHODS: Physician encounters in the General Electric EMR Database (2005-2010) were assessed for patients with type II diabetes (T2DM) who initiated basal insulin between February 2006 and August 2009, with initiation defined as no prescription record of insulin in prior 15 months. Patients were followed for an average 2.5 years after insulin initiation. The proportion and time to achieving HbA1c ≤ 7% ('goal') were assessed. Among patients who reached goal, the proportion and time to HbA1c increasing above 7% were analyzed. Cox proportional hazard models were estimated to identify predictors of HbA1c goal achievement and goal sustainability. RESULTS: Basal insulin initiators with T2DM (n = 13,373) were on average 60 years old, 50.5% were females, and 59.5% had HbA1c > 8%; 5840 (44%) patients reached goal within one year and 7699 (58%) reached goal during the ∼2.5-year follow-up. Being older, white or male, lower baseline HbA1c values, and no OAD use before insulin initiation were associated with significantly higher rates of reaching goal. Among patients who reached goal, 57.6% could not sustain the goal. Being Hispanic, higher baseline HbA1c values, and baseline OAD use were associated with significantly lower rates of goal sustainment. CONCLUSION: A high proportion of T2DM patients did not have adequate glycemic control after initiating basal insulin. Various factors existing prior to insulin initiation were related to successful treatment of T2DM. Further research on how to improve glycemic control is encouraged.

Introducing a brief measure of cultural and religious identification in American Jewish identity.

The authors conducted 3 studies to develop and investigate the psychometric properties of the American Jewish Identity Scales (AJIS), a brief self-report measure that assesses cultural identification and religious identification. Study 1 assessed the content validity of the item pool using an expert panel. In Study 2, 1,884 Jewish adults completed the initial AJIS and various measures of ethnic identity, collective self-esteem, and religiosity. Using confirmatory factor analyses, the authors selected and cross-validated 33 items that loaded highly and differentially on the 2 theorized latent factors. Study 3 assessed the AJIS's short-term stability and its relation to social desirability. Tests of reliability and construct validity provided initial psychometric support for the measure and confirmed the theorized primary salience of cultural identification. Participants reported significantly more private than public collective self-esteem, and the most Jewish-identified participants reported greater private self-esteem, acculturative stress, and perceived discrimination than did their more assimilated counterparts.

History of past sexual abuse in married observant Jewish women.

OBJECTIVE: The authors examined instances of past sexual abuse and related demographic characteristics in the self-reports of a select group of married observant Jewish women. METHODS: Orthodox Jewish married women (N=380) ages 19 to 58 responded to advertisements asking them to complete an anonymous questionnaire about sexual experiences, including sexual abuse. RESULTS: Sexual abuse was reported by 26% of the respondents surveyed, with 16% reporting abuse occurring by the age of 13. More ultra-Orthodox Jews reported abuse than modern-Orthodox Jews. Women who were raised observant reported significantly less childhood sexual abuse than those who became observant later in life. Sexual abuse was associated with increased treatment-seeking for depression, marital counseling, or other emotional or psychological problems. CONCLUSION: While observant Jewish women live in a culture defined by a high degree of adherence to specific laws of conduct, including rules designed to regulate sexual contact, sexual abuse of various types still exists among them.

Processing sentence context in women with schizotypal personality disorder: an ERP study.

Accumulating evidence suggests that schizophrenic patients do not use context efficiently. Also, studies suggest similarities in clinical and cognitive profiles between schizophrenic and schizotypal personality disorder (SPD) individuals, and epidemiological studies point to a genetic link between the two disorders. This study examined electrophysiological correlates of processing sentence context in a group of SPD women in a classical N400 sentence paradigm. The study assessed if the dysfunction in context use found previously in schizophrenia and male SPD also exists in female SPD. We tested 17 SPD and 16 matched normal control women. The results suggest the presence of abnormality in context use in female SPD similar to that previously reported for male schizophrenic and SPD individuals, but of lesser degree of severity. In SPD women, relative to their comparison group, a more negative N400 was found only to auditory congruent sentences.

A novel fast optical switch based on two cascaded Terahertz Optical Asymmetric Demultiplexers (TOAD).

A novel optical switch based on cascading two terahertz optical asymmetric demultiplexers (TOAD) is presented. By utilizing the sharp edge of the asymmetric TOAD switching window profile, two TOAD switching windows are overlapped to produce a narrower aggregate switching window, not limited by the pulse propagation time in the SOA of the TOAD. Simulations of the cascaded TOAD switching window show relatively constant window amplitude for different window sizes. Experimental results on cascading two TOADs, each with a switching window of 8ps, but with the SOA on opposite sides of the fiber loop, show a minimum switching window of 2.7ps.