Adverse Perinatal Outcomes and Postpartum Multi-Systemic Dysregulation: Adding Vitamin D Deficiency to the Allostatic Load Index.

Background Allostatic load (AL) is an index of multi-system physiological "wear-and-tear," operationalizing emergent chronic disease risk and predicting morbidity and mortality. AL has been proposed as an organizing framework for studying pregnancy outcomes and additional AL biomarkers for the study of maternal health would be valuable. Objectives To test whether adverse perinatal outcomes are associated with postpartum AL and if including vitamin D deficiency (serum 25(OH)D < 20 ng/ml) as an additional marker of postpartum AL increases the association.

Observers in the Medical Setting.

Requests for observation experiences are common in the emergency department and other medical settings. There is little guidance in the literature or in professional societies' polices about who should be granted this privilege. This article reviews the ethical and legal issues that should be taken into account when one decides whether to allow observers in the medical setting.

Chronic Stress and C-Reactive Protein in Mothers During the First Postpartum Year.

Objective: Elevated levels of C-reactive protein (CRP) are associated with increased risk of cardiovascular and metabolic disease. The current study tested associations between psychosocial stress and CRP in a large sample of women during the first postpartum year.

Methods: We analyzed data collected by the five-site Community Child Health Network study, which studied a predominately poor population.

and Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function.

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (: 111,666; : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (, , and ; <3.

Review: Found in Translation: International Initiatives Pursuing Interleukin-1 Blockade for Treatment of Acute Kawasaki Disease.

The decision to move forward with three clinical trials of IL-1 blockade for treatment of acute Kawasaki disease is a case study in translational science. These trials were born on the one hand from transcriptome studies of host response during the acute disease coupled with animal model investigations of key immune signaling pathways and, on the other hand, out of clinical desperation to intervene in patients with severe inflammation in the setting of acute Kawasaki disease. The convergence of laboratory science and clinical observations led to the clinical trials described here and serves as a model for how such observations can be translated into new therapies.

Prescription Drug Monitoring Programs: Ethical Issues in the Emergency Department.

Prescription drug monitoring programs are statewide databases available to clinicians to track prescriptions of controlled medications. These programs may provide valuable information to assess the history and use of controlled substances and contribute to clinical decisionmaking in the emergency department (ED). The widespread availability of the programs raises important ethical issues about beneficence, nonmaleficence, respect for persons, justice, confidentiality, veracity, and physician autonomy.

Law Enforcement and Emergency Medicine: An Ethical Analysis.

Emergency physicians frequently interact with law enforcement officers and patients in their custody. As always, the emergency physician's primary professional responsibility is to promote patient welfare, and his or her first duty is to the patient. Emergency physicians should treat criminals, suspects, and prisoners with the same respect and attention they afford other patients while ensuring the safety of staff, visitors, and other patients.

Ocular indicators of Alzheimer's: exploring disease in the retina.

Although historically perceived as a disorder confined to the brain, our understanding of Alzheimer's disease (AD) has expanded to include extra-cerebral manifestation, with mounting evidence of abnormalities in the eye. Among ocular tissues, the retina, a developmental outgrowth of the brain, is marked by an array of pathologies in patients suffering from AD, including nerve fiber layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. While the hallmark pathological signs of AD, amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFT) comprising hyperphosphorylated tau (pTau) protein, have long been described in the brain, identification of these characteristic biomarkers in the retina has only recently been reported.

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.

Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.

Interpregnancy Interval and Childbirth Outcomes in California, 2007-2009.

Objectives The goals of interconception care are to optimize women's health and encourage adequate spacing between pregnancies. Our study calculated trends in interpregnancy interval (IPI) patterns and measured the association of differing intervals with birth outcomes in California. Methods Women with "non-first birth" deliveries in California hospitals from 2007 to 2009 were identified in a linked birth certificate and patient discharge dataset and divided into three IPI birth categories: <6, 6-17, and 18-50 months.

Interrelationship of Primary Virus Replication, Level of Latency, and Time to Reactivation in the Trigeminal Ganglia of Latently Infected Mice.

Unlabelled: We sought to determine the possibility of an interrelationship between primary virus replication in the eye, the level of viral DNA in the trigeminal ganglia (TG) during latency, and the amount of virus reactivation following ocular herpes simplex virus type 1 (HSV-1) infection. Mice were infected with virulent (McKrae) or avirulent (KOS and RE) strains of HSV-1, and virus titers in the eyes and TG during primary infection, level of viral gB DNA in TG on day 28 postinfection (p.i.

Exome genotyping arrays to identify rare and low frequency variants associated with epithelial ovarian cancer risk.

Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from the international Ovarian Cancer Association Consortium (OCAC). Pooled association analyses were conducted at the variant and gene level for 98,543 variants directly genotyped through two exome genotyping projects.

Rationale and study design for a phase I/IIa trial of anakinra in children with Kawasaki disease and early coronary artery abnormalities (the ANAKID trial).

Background: Although Kawasaki disease (KD) is the most common cause of acquired heart disease in children and may result in coronary artery aneurysms (CAA) with an attendant risk of myocardial infarction, there is no recommended therapy to halt progression of arterial wall damage and prevent aneurysm formation in the acute phase of the vasculitis. While intravenous immunoglobulin (IVIG) reduces the risk of CAA, up to 20% of KD patients are IVIG resistant and have a higher risk for developing CAA. The IL-1 pro-inflammatory pathway is upregulated in children with acute KD and plays a critical role in the experimental animal model of KD.

Association Between Menopausal Estrogen-Only Therapy and Ovarian Carcinoma Risk.

Objective: To describe the association between postmenopausal estrogen-only therapy use and risk of ovarian carcinoma, specifically with regard to disease histotype and duration and timing of use.

Methods: We conducted a pooled analysis of 906 women with ovarian carcinoma and 1,220 women in a control group; all 2,126 women included reported having had a hysterectomy. Ten population-based case-control studies participating in the Ovarian Cancer Association Consortium, an international consortium whose goal is to combine data from many studies with similar methods so reliable assessments of risk factors can be determined, were included.

Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer.

Background: While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC).

Methods: The primary patient set (Set 1) included 14 independent EOC studies (4,293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1,744 patients) and 114,620 variants.

Infection and Inflammatory Diseases.

, an obligate intracellular bacterial pathogen, has long been investigated as a potential developmental or exacerbating factor in various pathologies. Its unique lifestyle and ability to disseminate throughout the host while persisting in relative safety from the immune response has placed this obligate intracellular pathogen in the crosshairs as a potentially mitigating factor in chronic inflammatory diseases. Many animal model and human correlative studies have been performed to confirm or deny a role for infection in these disorders.

Long-Term Risk Assessment After the Performance of Stress Myocardial Perfusion Imaging.

Stress-rest myocardial perfusion imaging (MPI) is a potent method for assessing the presence and magnitude of inducible myocardial ischemia. Stress MPI currently faces increased scrutiny for its therapeutic effectiveness because of the emergence of other competing means for assessing clinical risk. New data have examined the usefulness stress-rest-MPI as a predictor for long-term clinical outcomes, in contrast to its traditional role for assessing short-term cardiovascular risk.

Sex and Ethnic Differences in the Association of Obesity With Risk of Hepatocellular Carcinoma.

Background & Aims: Obesity is associated with increased risk for hepatocellular carcinoma (HCC), but the risk associated with obesity may vary by sex or ethnicity. We examined whether the association of body mass index (BMI) with HCC incidence, as well as correlations of BMI with total, visceral, and hepatic adiposity, differs among ethnic groups.

Methods: We collected data from the Multiethnic Cohort Study, a population-based prospective cohort study of more than 215,000 men and women from Hawaii and California that was assembled from 1993 through 1996.

Variation in childbirth services in California: a cross-sectional survey of childbirth hospitals.

Objective: The objective of the study was to describe the resources and activities associated with childbirth services.

Study Design: We adapted models for assessing the quality of healthcare to generate a conceptual framework hypothesizing that childbirth hospital resources and activities contributed to maternal and neonatal outcomes. We used this framework to guide development of a survey, which we administered by telephone to hospital labor and delivery nurse managers in California.

Cross-sectional survey of California childbirth hospitals: implications for defining maternal levels of risk-appropriate care.

Objective: Measures of maternal mortality and severe maternal morbidity have risen in the United States, sparking national interest regarding hospitals' ability to provide maternal risk-appropriate care. We examined the extent to which hospitals could be classified by increasingly sophisticated maternal levels of care.

Study Design: We performed a cross-sectional survey to identify hospital-specific resources and classify hospitals by criteria for basic, intermediate, and regional maternal levels of care in all nonmilitary childbirth hospitals in California.

Effect of endurance and/or strength training on muscle fiber size, oxidative capacity, and capillarity in hemodialysis patients.

We previously reported reduced limb muscle fiber succinate dehydrogenase (SDH) activity and capillarity density and increased cross-sectional areas (CSAs) of all fiber types in maintenance hemodialysis (MHD) patients compared with matched controls that may contribute to their effort intolerance and muscle weakness. This study evaluated whether endurance training (ET), strength training (ST), or their combination (EST) alters these metabolic and morphometric aberrations as a mechanism for functional improvement. Five groups were evaluated: 1) controls; 2) MHD/no training; 3) MHD/ET; 4) MHD/ST; and 5) MHD/EST.