Implementing change in the care of the complex cardiac patient.

PURPOSE OF REVIEW: Development of advanced and minimally invasive surgical procedures is providing treatment opportunities to older and higher risk patients. This has also led to highly specialized physicians and a need for better communication and planning with the patients and within the care team. RECENT FINDINGS: In the field of cardiac surgery, the heart team model has been advocated and implemented as a vehicle to optimize decision making prior to procedure, care during the procedure and in the recovery process. The goal is to provide a treatment path that prioritizes the patient's goals and to anticipate and minimize complications. SUMMARY: In this review, we discuss the concepts of shared decision making (SDM) and implementation science in the context of the complex cardiac patient. We also review the most recent evidence for their use in cardiac surgery. We argue that a team model not only bridges knowledge gaps but provides a multidisciplinary environment for the practice of SDM and implementation of evidence-based practices. Be believe this will provide patients with a better experience as they navigate their care and improve their medical outcomes as well.

Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic development.

The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45. Our data provide proof-of-concept that stabilization of PTP1B in an inactive, oxidized conformation by small molecules can promote insulin and leptin signaling. This work illustrates a novel paradigm for inhibiting the signaling function of PTP1B that may be exploited for therapeutic intervention in diabetes and obesity.

Smoking and Smoking Cessation During Pregnancy. An Analysis of a Hospital Based Cohort of Women in Romania.

Perinatal smoking is associated with a wide range of negative reproductive and pregnancy outcomes. The aim of the current study was to examine the prevalence and characteristics of women who report smoking prenatally and quit during pregnancy in a large sample of Romanian women. Understanding which women are more likely to quit will contribute to public health knowledge that will help more women stop smoking prior to or during pregnancy and prevent relapse postpartum. This cross-sectional analysis was conducted based on cross-sectional data collected between May 2012 and April 2015 as part of a cohort study of pregnancy implemented in six clinical settings in central Romania (N = 2370). Approximately 28 % of the sample reported smoking in the 6 months prior to learning they were pregnant. Half of the women who reported smoking 6 months before learning of their pregnancy, also reported that they stopped smoking by the time of the interview. Overall, tobacco consumption decreased from a sample mode of 10 cigarettes/day (range: 1-30) before pregnancy, to a sample mode of 5 cigarettes/day (range: 1-25) at the time of the interview. Women who quit had a higher socioeconomic position, were more likely to live in urban areas, partnered, primigravid, nulliparous, and reported lower anxiety and more social support. The combination of a socioeconomic gradient, less anxiety, and more social support suggests that efforts should be increased to target lower income, less educated, multigravid, and multiparous women and to develop programs that heighten social support and alleviate anxiety.

Maternal smoking during pregnancy and birth outcomes in a sample of Romanian women.

Smoking during pregnancy is causally associated with reduced birth weight and is strongly related to preterm birth. Smoking cessation in early pregnancy seems to reduce these risks, although the research evidence is limited. In a sample of Romanian women, differences in birth outcomes were assessed between non-smokers and women who continued to smoke during pregnancy and non-smokers and women who stopped smok- ing when they found out about the pregnancy. Pregnant women were recruited in two urban clinics (N= 474). A baseline questionnaire collected information on their smoking status, depressive symptoms, stress, demographics, and other characteristics at recruitment. The women reported the newborn weight and birth term by phone in the first weeks following birth. Descriptive statistics and multivariate regressions were used to ana- lyze the relationship between smoking status during pregnancy and birth outcomes. Over 61% (N = 290) women were non-smokers, 15% (N= 72) smoked during pregnancy, and 24% (N= 112) quit smoking when they found out about the pregnancy. Compared to non-smokers, continuous smokers delivered babies 165 grams lighter (95% CI -313, -17). Women who stopped smoking when they ascertained the pregnancy had higher odds of delivering a newborn who was small for gestational age compared to non-smokers (OR= 2.16, 95% CI 1.05, 4.43). Elevated maternal stress was associated with reduced birth weight (-113 grams, 95% CI -213, -11), and higher odds of a preterm birth (OR=2.8, 95% CI 1.17, 6.76). In a predominantly urban sample of Romanian women, continuous maternal smoking during pregnancy was a risk factor for restricted foetal growth. Smoking cessation when the pregnancy was ascertained did not seem to reduce this risk. Smoking prevention efforts should therefore begin before pregnancy and should integrate psychological components, addressing maternal stress in particular.

Defining informal payments in healthcare: a systematic review.

OBJECTIVES: To explore the literature for the definitions of informal payments in healthcare and critically analyze the proposed definitions. This will serve in the process of getting to a coherent definition of informal payments, which will further support acknowledging and addressing them globally. METHODS: A search strategy was developed to identify papers addressing informal payments on PubMed, ScienceDirect, Econlit, EconPapers and Google Scholar. RESULTS: 2225 papers were identified after a first search. 61 papers were included in the systematic review. Out of all definitions provided, we selected three definitions as being original. All other definitions either cite these definitions or do not provide new insight into the topic of informal payments. Although informal payments have been nominated by various terms over the years, there is a tendency in recent years towards an agreement to use this singular term. Definitions differ in terms of the relation of informal payments with other informal activities, their legality and the motivation behind them. CONCLUSIONS: The variety of forms which informal payments may take makes it difficult to define them in a comprehensive manner. However, we identified a definition that could serve as a beginning in this process. More effort is needed to build on it and get to a commonly accepted and shared definition of informal payments.

Risk factors associated with nicotine dependence in a sample of Romanian pregnant smokers.

OBJECTIVES: To fill the gap in assessing nicotine dependence during pregnancy in an unexplored population in Central and Eastern Europe and to analyze the associations of maternal characteristics and prenatal risk factors with moderate-heavy nicotine dependence among pregnant smokers. STUDY DESIGN: A questionnaire was applied to pregnant smokers in Romania to assess nicotine dependence and other related risks poorly documented in Central and Eastern Europe. The response rate was >80% and the valid sample included 137 pregnant smokers. Descriptive statistics and logistic regressions were used to assess nicotine dependence and to analyze the associations of maternal characteristic and prenatal risk factors with moderate-heavy nicotine dependence. RESULTS: Approximately 43% of the pregnant smokers in our sample (59 of 137) had moderate to heavy nicotine dependence. Depressive symptoms were associated with moderate-heavy nicotine dependence among pregnant smokers (OR=3.07, p<0.05). Women carrying an unwanted pregnancy had higher odds of moderate-heavy nicotine dependence (OR=2.59, p<0.05) compared to other pregnant women. High stress, lack of social support, and socioeconomic status were not associated with nicotine dependence. CONCLUSIONS: A large proportion of women had moderate-heavy nicotine dependence in a sample of Romanian pregnant smokers. The more dependent pregnant smokers were more likely to have depressive symptoms. Prenatal care should include brief nicotine dependence assessments and mental health screening and referrals for pregnant women who smoke. Special and intensive efforts, including psychosocial components, may be needed for the nicotine dependent pregnant smokers.

Smoking during pregnancy and associated risk factors in a sample of Romanian women.

BACKGROUND: Smoking during pregnancy is one of the most modifiable risk factor for poor birth outcomes. This study assesses the prevalence and correlates of smoking during pregnancy. METHODS: A questionnaire was applied to pregnant women in two urban clinics in Romania to assess smoking prevalence, attitudes and knowledge about smoking, and other risks poorly documented in Romania, such as depressive symptoms, stress and social support. The response rate was >80% and the valid sample comprised of 916 women. Descriptive statistics and logistic regressions were used to estimate the prevalence of smoking and other risk factors and to identify correlates of smoking during pregnancy. RESULTS: Approximately 15% of the women continued smoking during pregnancy, and 26% of all women said they smoked prior to pregnancy, but quit upon finding out they were pregnant. Depressive symptoms and stress were not associated with smoking during pregnancy. Women with no social support had higher odds of continued smoking vs. non-smoking (OR = 2.3, P < 0.01), and vs. quitting (OR = 2.3, P < 0.05). Roma women had 5.2 times the odds (P < 0.01) of continued smoking vs. non-smoking. Lack of awareness about the benefits of quitting smoking and about the risks of smoking light cigarettes were associated with continued smoking during pregnancy. CONCLUSIONS: Smoking was common in a sample of Romanian pregnant women. Smoking cessation programs in Romania should include components to raise the awareness about the risks of smoking during pregnancy and the benefits of quitting at any time during pregnancy. More targeted interventions are needed in Roma communities.

High-frequency canonical Wnt activation in multiple sarcoma subtypes drives proliferation through a TCF/ß-catenin target gene, CDC25A.

Wnt canonical signaling is critical for normal development as well as homeostasis of several epithelial tissues, and constitutive activation of this pathway is commonly observed in carcinomas. We show here that 50% of human sarcomas (n = 45) and 65% of sarcoma cell lines (n = 23) of diverse histological subtypes exhibit upregulated autocrine canonical Wnt signaling. Furthermore, in Wnt autocrine cell lines, we identify alterations including overexpression or gene amplification of Wnt ligands and/or LRP5/6 coreceptors and epigenetic silencing of different cell surface Wnt antagonists. Mutations in adenomatous polyposis coli (APC) gene were observed in two nonautocrine Wnt-positive sarcoma cell lines. Finally, downregulation of the activated Wnt pathway inhibited sarcoma cell proliferation both in vitro and in vivo by a mechanism involving the downregulation of CDC25A.

Influence of glutathione and its derivatives on fibrin polymerization.

A complex relationship exists between reduced, oxidized, and nitrosated glutathione (GSH, GSSG, and GSNO, respectively). Although previous studies have demonstrated S-nitrosoglutathione (GSNO) has potent antiplatelet efficacy, little work has examined the role of GSNO and related species on subsequent aspects of coagulation (e.g., fibrin polymerization). Herein, the effects of GSH, GSSG, and GSNO on the entire process of fibrin polymerization are described. Relative to normal fibrinogen, the addition of GSH, GSSG, or GSNO leads to prolonged lag times, slower rates of protofibril lateral aggregation and the formation of clots with lower final turbidities. Dose-dependent studies indicate the influence of GSH on fibrin formation is a function of both GSH and fibrinogen concentration. Studies with Aalpha251 recombinant fibrinogen (lacking alphaC regions) showed GSH had no influence on its polymerization, suggesting the glutathione species interact within the alphaC region of fibrinogen.

Surface-dependent fibrinopeptide A accessibility to thrombin.

Fibrinogen adsorption and more recently fibrin formation at interfaces has been reported to depend on surface properties of the underlying substrate. To provide insight into the surface-dependent mechanism of fibrinopeptide A (FpA) release and fibrin formation, the accessibility and susceptibility of FpA to thrombin-catalyzed fibrinopeptide cleavage were examined using polyclonal anti-FpA IgG binding and surface plasmon resonance (SPR). The amount of accessible FpA on adsorbed fibrinogen was significantly influenced by surface properties of the underlying substrate (methyl- and carboxyl-terminated self-assembled monolayers). Roughly 2.7 times more FpA was available on fibrinogen adsorbed at the hydrophobic vs. negatively charged surface. Upon exposure of adsorbed fibrinogen to thrombin, 100% of the available FpA was enzymatically cleaved at both surfaces, indicating that the extent of FpA release and fibrin formation is a function of the surface-dependent FpA availability. The results presented herein suggest negatively charged surfaces impair FpA accessibility, and therefore lead to reduced FpA release and subsequent fibrin formation. As such, negatively charged surfaces may be useful in minimizing surface-induced thrombosis initiated via fibrin formation thereby aiding in the development of more biocompatible blood-contacting devices.