Pregnancy, Genetic Risk and Congenital Heart Disease

An increasing number of women with congenital heart disease (CHD) are reaching childbearing age and are considering pregnancy. Pregnancy is tolerated well in most of these women with unoperated, or repaired cardiac lesions; however, the risk is increased considerably in certain situations such as pulmonary hypertension, severe valvular stenosis, pulmonary atresia, mechanical prosthetic valves, with Fontan type circulation, in Marfan syndrome and other aortopathy. Counseling prior to pregnancy in CHD also involves discussion of genetic testing, possibility of transmission to the child, management during pregnancy including preimplantation genetic testing, and recommendations regarding fetal echocardiography. All medications including anticoagulation options if needed should be carefully reviewed prior to pregnancy due to maternal and fetal risks. If needed, cardiac surgery or balloon valvuloplasty can be carried out with an increased risk to mother and fetus. Overall, pregnancy in CHD is feasible in most patients with good maternal and fetal outcome. High risk pregnancy patients with CHD have to be counseled by a multidisciplinary team including cardiologists, obstetricians and anesthesiologists at a tertiary care center

Oral Glutamine Supplement Reduces Subjective Fatigue Ratings during Repeated Bouts of Firefighting Simulations

Wildland firefighting requires repetitive (e.g., consecutive work shifts) physical work in dangerous conditions (e.g., heat and pollution). Workers commonly enter these environments in a nonacclimated state, leading to fatigue and heightened injury risk. Strategies to improve tolerance to these stressors are lacking. Purpose: To determine if glutamine ingestion prior to and after consecutive days of firefighting simulations in the heat attenuates subjective ratings of fatigue, and evaluate if results were supported by glutamine-induced upregulation of biological stress responses. Methods: Participants (5 male, 3 female) ingested glutamine (0.15 g/kg/day) or a placebo before and after two consecutive days (separated by 24 h) of firefighter simulations in a heated chamber (35 degrees C, 35% humidity). Perceived fatigue and biological stress were measured pre-, post-, and 4 h postexercise in each trial. Results: Subjective fatigue was reduced pre-exercise on Day 2 in the glutamine group (p \u3c 0.05). Peripheral mononuclear cell expression of heat shock protein 70 (HSP70) and serum antioxidants were elevated at 4 h postexercise on Day 1 in the glutamine trial (p \u3c 0.05). Conclusions: Ingestion of glutamine before and after repeated firefighter simulations in the heat resulted in reduced subjective fatigue on Day 2, which may be a result of the upregulation of biological stress systems (antioxidants, HSPs). This response may support recovery and improve work performance

Prevalence and determinants of SHS exposure in public and private areas after the 2010 smoke-free legislation in Greece

<div><p>The objective of the present survey was to assess the extent and socio-economic determinants of population exposure to secondhand smoke (SHS) in Greece in 2011. The national household survey Hellas Health IV was conducted in October 2011. SHS exposure was based on self-reported exposure within home, workplace and public places. Thirty-three per cent of the respondents reported living in a smoke-free home. Smokers (<i>p </i><<i> </i>0.001) and single individuals (<i>p </i><<i> </i>0.017) were less likely to prohibit smoking at home. SHS exposure at work, in restaurants and in bars/clubs/cafes was frequently mentioned by 41.6, 84.2 and 90.5%, respectively. SHS exposure in a bar/club/cafe was noted more among single individuals (<i>p </i>=<i> </i>0.004) and those aged 18–34<i> </i>years (<i>p </i>=<i> </i>0.007). Inhabitants of rural areas were more likely to report someone smoking indoors in all the above venues. Public health education and effective enforcement of the nationwide smoke-free legislation are imperative.</p></div

Petition for Writ of Certiorari, Kosilek v. O\u27Brien

Jennifer Levi, on behalf of Gay & Lesbian Advocates & Defenders, was one of the Authors of the Petition for Writ of Certiorari, filed in the Supreme Court of the United States on behalf of the Petitioner, Michelle Kosilek, in Kosilek v. O\u27Brien. Questions presented to the Court by the Petitioner were 1.) whether appellate courts must parse “ques­tions that present elements both factual and legal” into their factual and legal components, so that all factual findings can be reviewed for clear error, or whether, as the First Circuit ruled, they may review such questions as a whole along a “continuum” of deference, where the degree of deference given to the district court is of “variable exactitude,” and 2.) whether the Eighth Amendment prohibits prison officials from denying necessary medical treatment to a prisoner for non-medical reasons, such as security concerns

Equity and the financial costs of informal caregiving in palliative care: a critical debate.

BACKGROUND: Informal caregivers represent the foundation of the palliative care workforce and are the main providers of end of life care. Financial pressures are among the most serious concerns for many carers and the financial burden of end of life caregiving can be substantial. METHODS: The aim of this critical debate paper was to review and critique some of the key evidence on the financial costs of informal caregiving and describe how these costs represent an equity issue in palliative care. RESULTS: The financial costs of informal caregiving at the end of life can be significant and include carer time costs, out of pocket costs and employment related costs. Financial burden is associated with a range of negative outcomes for both patient and carer. Evidence suggests that the financial costs of caring are not distributed equitably. Sources of inequity are reflective of those influencing access to specialist palliative care and include diagnosis (cancer vs non-cancer), socio-economic status, gender, cultural and ethnic identity, and employment status. Effects of intersectionality and the cumulative effect of multiple risk factors are also a consideration. CONCLUSIONS: Various groups of informal end of life carers are systematically disadvantaged financially. Addressing these, and other, determinants of end of life care is central to a public health approach to palliative care that fully recognises the value of carers. Further research exploring these areas of inequity in more depth and gaining a more detailed understanding of what influences financial burden is required to take the next steps towards meeting this aspiration. We will address the conclusions and recommendations we have made in this paper through the work of our recently established European Association of Palliative Care (EAPC) Taskforce on the financial costs of family caregiving

Reply to Lipworth et al.

We thank Dr. Lipworth and colleagues for their interest in our work published recently in the Journal (1). They rightly point out that the biology of asthma attacks is more complex than blood eosinophils alone and that corticosteroids have a wide range of other potentially relevant antiinflammatory effects. However, local treatment with inhaled corticosteroids (ICS) is usually the mainstay of patients with frequent eosinophilic exacerbations, and therefore in the great majority of patients, the key question is what oral corticosteroids (OCS) add to ICS in an acute attack (2) and whether this effect is seen with benralizumab. We suggest that depletion of circulating eosinophils is the only effect OCS are likely to have that are not shared with ICS (3)

Pathologic gene network rewiring implicates PPP1R3A as a central regulator in pressure overload heart failure

Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvest 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtain genome-wide genotyping and gene expression measurements for a subset of 313. We build failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions, and highlights metabolic pathway regulation associated with increased cardiomyocyte size and perturbed respiratory metabolism. Mice lacking PPP1R3A are protected against pressure-overload heart failure. We present a global gene interaction map of the human heart failure transition, identify previously unreported cardiac eQTLs, and demonstrate the discovery potential of disease-specific networks through the description of PPP1R3A as a central regulator in heart failure

Threats of common method variance in student assessment of instruction instruments

Purpose – The purpose of this paper is to demonstrate that common method variance, specifically single-source bias, threatens the validity of a university-created student assessment of instructor instrument, suggesting that decisions made from these assessments are inherently flawed or skewed. Single-source bias leads to generalizations about assessments that might influence the ability of raters to separate multiple behaviors of an instructor. Design/methodology/approach – Exploratory factor analysis, nested confirmatory factor analysis and within-and-between analysis are used to assess a university-developed, proprietary student assessment of instructor instrument to determine whether a hypothesized factor structure is identifiable. The instrument was developed over a three-year period by a university-mandated committee. Findings – Findings suggest that common method variance, specifically single-source bias, resulted in the inability to identify hypothesized constructs statistically. Additional information is needed to identify valid instruments and an effective collection method for assessment. Practical implications – Institutions are not guaranteed valid or useful instruments even if they invest significant time and resources to produce one. Without accurate instrumentation, there is insufficient information to assess constructs for teaching excellence. More valid measurement criteria can result from using multiple methods, altering collection times and educating students to distinguish multiple traits and behaviors of individual instructors more accurately. Originality/value – This paper documents the three-year development of a university-wide student assessment of instructor instrument and carries development through to examining the psychometric properties and appropriateness of using this instrument to evaluate instructors

Comparison of Molecular Phenotypes of Ductal Carcinoma In Situ and Invasive Breast Cancer

Introduction: At least four major categories of invasive breast cancer that are associated with different clinical outcomes have been identified by gene expression profiling: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and basal-like. However, the prevalence of these phenotypes among cases of ductal carcinoma in situ (DCIS) has not been previously evaluated in detail. The purpose of this study was to compare the prevalence of these distinct molecular subtypes among cases of DCIS and invasive breast cancer. Methods: We constructed tissue microarrays (TMAs) from breast cancers that developed in 2897 women enrolled in the Nurses' Health Study (1976 to 1996). TMA slides were immunostained for oestrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR). Using these immunostain results, cases were grouped into molecularly defined subtypes. Results: The prevalence of the distinct molecular phenotypes differed significantly between DCIS (n = 272) and invasive breast cancers (n = 2249). The luminal A phenotype was significantly more frequent among invasive cancers (73.4%) than among DCIS lesions (62.5%) (p = 0.0002). In contrast, luminal B and HER2 molecular phenotypes were both more frequent among DCIS (13.2% and 13.6%, respectively) as compared with invasive tumours (5.2% and 5.7%, respectively) (p < 0.0001). The basal-like phenotype was more frequent among the invasive cancers (10.9%) than DCIS (7.7%), although this difference was not statistically significant (p = 0.15). High-grade DCIS and invasive tumours were more likely to be HER2 type and basal-like than low- or intermediate-grade lesions. Among invasive tumours, basal-like and HER2 type tumours were more likely to be more than 2 cm in size, high-grade and have nodal involvement compared with luminal A tumours. Conclusion: The major molecular phenotypes previously identified among invasive breast cancers were also identified among cases of DCIS. However, the prevalence of the luminal A, luminal B and HER2 phenotypes differed significantly between DCIS and invasive breast cancers