Citations

ObjectiveTo examine associations between circulating levels of the bone‐derived protein osteocalcin (OC) and type 2 diabetes (T2D) risk in Latino children and adults.MethodsSerum OC was measured in 136 children and 531 adults who had the following T2D risk factors assessed, body mass index (BMI), Hemoglobin A1c (HbA1c), fasting and 2‐hour glucose during an oral glucose tolerance test.ResultsOC was significantly higher in children than adults (209.0 ± 12.1 vs. 41.0 ± 0.9 ng/ml, p<0.0001). In adults, OC was inversely associated (all p<0.001) with BMI (r=‐0.2), HbA1c (r=‐0.2), fasting glucose (r=‐0.16), and 2‐hour glucose (r=‐0.21), while there were no significant associations in children. There was a stepwise decrease in OC with increasing dysglycemia in adults, normoglycemic (44.1 ± 1.3 ng/ml), prediabetic (39.3 ± 1.3 ng/ml), and T2D (31.8 ± 1.2 ng/ml), (p<0.0001), whereas there were no differences between normal and prediabetic youth (195.7 ± 16.1 vs. 194.7 ± 25.8 ng/ml, p=0.3).ConclusionsOC was inversely associated with T2D risk in Latino adults; however, this pattern was not observed in children. Am. J. Hum. Biol. 27:859–861, 2015. © 2015 Wiley Periodicals, Inc.

Background and Purpose— The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Methods— Using METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic and 1592 total stroke cases) from COMPASS, and tested genetic variants with P <10 −6 for validation in METASTROKE, a consortium of ischemic stroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. Results— The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613; P =3.9×10 −8 ) in African Americans. Nominal associations ( P <10 −6 ) for total or ischemic stroke were observed for 18 variants in or near genes implicated in cell cycle/mRNA presplicing ( PTPRG , CDC5L ), platelet function ( HPS4 ), blood–brain barrier permeability ( CLDN17 ), immune response ( ELTD1, WDFY4 , and IL1F10-IL1RN ), and histone modification ( HDAC9 ). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 ( P =0.03), and 1p31.1 ( P =0.018). Four of 7 previously reported ischemic stroke loci ( PITX2, HDAC9, CDKN2A/CDKN2B , and ZFHX3 ) were nominally associated ( P <0.05) with stroke in COMPASS. Conclusions— We identified a novel genetic variant associated with total stroke in African Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations.

Nearly 2 centuries have passed since the use of intravenous fluid became a foundational component of clinical practice. Despite a steady stream of published investigations on the topic, questions surrounding the choice, dose, timing, targets, and cost-effectiveness of various fluid options remain insufficiently answered. In recent years, 2 of the most debated topics reference the role of albumin in acute care and the safety of normal saline. Although albumin has a place in therapy for specific patient populations, its high cost relative to other fluids makes it a less desirable option for hospitals and health systems with escalating formulary scrutiny. Pharmacists bear responsibility for reconciling this disparity and supporting the rational use of albumin in acute care through a careful evaluation of recently published literature. In parallel, it has become clear that crystalloids should no longer be considered a homogenous class of fluids. The past reliance on normal saline has been questioned due to recent findings of renal dysfunction attributable to the solution's supraphysiologic chloride concentration. These safety concerns with 0.9% sodium chloride may result in a practice shift toward more routine use of “balanced crystalloids,” such as lactated Ringer's or Plasma-Lyte, that mimic the composition of extracellular fluid. The purpose of this review is to summarize the evidence regarding these 2 important fluid controversies that are likely to affect hospital pharmacists in the coming decades — the evidence-based use of human albumin and the rising role of balanced salt solutions in clinical practice.

Abstract Neuropsychiatric symptoms (NPS) are common in dementia and in predementia syndromes such as mild cognitive impairment (MCI). NPS in MCI confer a greater risk for conversion to dementia in comparison to MCI patients without NPS. NPS in older adults with normal cognition also confers a greater risk of cognitive decline in comparison to older adults without NPS. Mild behavioral impairment (MBI) has been proposed as a diagnostic construct aimed to identify patients with an increased risk of developing dementia, but who may or may not have cognitive symptoms. We propose criteria that include MCI in the MBI framework, in contrast to prior definitions of MBI. Although MBI and MCI can co‐occur, we suggest that they are different and that both portend a higher risk of dementia. These MBI criteria extend the previous literature in this area and will serve as a template for validation of the MBI construct from epidemiologic, neurobiological, treatment, and prevention perspectives.

SUMMARYThis comprehensive review outlines the impact of military-relevant respiratory infections, with special attention to recruit training environments, influenza pandemics in 1918 to 1919 and 2009 to 2010, and peacetime operations and conflicts in the past 25 years. Outbreaks and epidemiologic investigations of viral and bacterial infections among high-risk groups are presented, including (i) experience by recruits at training centers, (ii) impact on advanced trainees in special settings, (iii) morbidity sustained by shipboard personnel at sea, and (iv) experience of deployed personnel. Utilizing a pathogen-by-pathogen approach, we examine (i) epidemiology, (ii) impact in terms of morbidity and operational readiness, (iii) clinical presentation and outbreak potential, (iv) diagnostic modalities, (v) treatment approaches, and (vi) vaccine and other control measures. We also outline military-specific initiatives in (i) surveillance, (ii) vaccine development and policy, (iii) novel influenza and coronavirus diagnostic test development and surveillance methods, (iv) influenza virus transmission and severity prediction modeling efforts, and (v) evaluation and implementation of nonvaccine, nonpharmacologic interventions.

Background The International Classification of Headache Disorders provides criteria for the diagnosis and subclassification of migraine. Since there is no objective gold standard by which to test these diagnostic criteria, the criteria are based on the consensus opinion of content experts. Accurate migraine classifiers consisting of brain structural measures could serve as an objective gold standard by which to test and revise diagnostic criteria. The objectives of this study were to utilize magnetic resonance imaging measures of brain structure for constructing classifiers: (1) that accurately identify individuals as having chronic vs episodic migraine vs being a healthy control; and (2) that test the currently used threshold of 15 headache days/month for differentiating chronic migraine from episodic migraine. Methods Study participants underwent magnetic resonance imaging for determination of regional cortical thickness, cortical surface area, and volume. Principal components analysis combined structural measurements into principal components accounting for 85% of variability in brain structure. Models consisting of these principal components were developed to achieve the classification objectives. Tenfold cross validation assessed classification accuracy within each of the 10 runs, with data from 90% of participants randomly selected for classifier development and data from the remaining 10% of participants used to test classification performance. Headache frequency thresholds ranging from 5‐15 headache days/month were evaluated to determine the threshold allowing for the most accurate subclassification of individuals into lower and higher frequency subgroups. Results Participants were 66 migraineurs and 54 healthy controls, 75.8% female, with an average age of 36 +/− 11 years. Average classifier accuracies were: (1) 68% for migraine (episodic + chronic) vs healthy controls; (2) 67.2% for episodic migraine vs healthy controls; (3) 86.3% for chronic migraine vs healthy controls; and (4) 84.2% for chronic migraine vs episodic migraine. The classifiers contained principal components consisting of several structural measures, commonly including the temporal pole, anterior cingulate cortex, superior temporal lobe, entorhinal cortex, medial orbital frontal gyrus, and pars triangularis. A threshold of 15 headache days/month allowed for the most accurate subclassification of migraineurs into lower frequency and higher frequency subgroups. Conclusions Classifiers consisting of cortical surface area, cortical thickness, and regional volumes were highly accurate for determining if individuals have chronic migraine. Furthermore, results provide objective support for the current use of 15 headache days/month as a threshold for dividing migraineurs into lower frequency (ie, episodic migraine) and higher frequency (ie, chronic migraine) subgroups.

Background— The molecular underpinnings of hypoplastic left heart are poorly understood. Staged surgical palliation has dramatically improved survival, yet eventual failure of the systemic right ventricle necessitates cardiac transplantation in a subset of patients. We sought to identify genetic determinants of hypoplastic left heart with latent right ventricular dysfunction in individuals with a Fontan circulation. Methods and Results— Evaluation of cardiac structure and function by echocardiography in patients with hypoplastic left heart and their first-degree relatives identified 5 individuals with right ventricular ejection fraction ≤40% after Fontan operation. Whole genome sequencing was performed on DNA from 21 family members, filtering for genetic variants with allele frequency <1% predicted to alter protein structure or expression. Secondary family-based filtering for de novo and recessive variants revealed rare inherited missense mutations on both paternal and maternal alleles of MYH6 , encoding myosin heavy chain 6, in 2 patients who developed right ventricular dysfunction 3 to 11 years postoperatively. Parents and siblings who were heterozygous carriers had normal echocardiograms. Protein modeling of the 4 highly conserved amino acid substitutions, residing in both head and tail domains, predicted perturbation of protein structure and function. Conclusions— In contrast to dominant MYH6 mutations with variable penetrance identified in other congenital heart defects and dilated cardiomyopathy, this study reveals compound heterozygosity for recessive MYH6 mutations in patients with hypoplastic left heart and reduced systemic right ventricular ejection fraction. These findings implicate a shared molecular basis for the developmental arrest and latent myopathy of left and right ventricles, respectively.