Prostaglandin-Induced Resorption of the Adult Rat Calvarium

Prostaglandin E1-containing solutions injected under the skin overlying the calvarium of adult rats produced a visible resorptive lesion within the bone in seven days. The resorptive process was characterized by fibrous replacement of bone matrix and by increased vascularity. Inflammatory cells were not apparent.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67319/2/10.1177_00220345740530032601.pd

Strategies for the evolution of sex

We find that the hypothesis made by Jan, Stauffer and Moseley [Theory in Biosc., 119, 166 (2000)] for the evolution of sex, namely a strategy devised to escape extinction due to too many deleterious mutations, is sufficient but not necessary for the successful evolution of a steady state population of sexual individuals within a finite population. Simply allowing for a finite probability for conversion to sex in each generation also gives rise to a stable sexual population, in the presence of an upper limit on the number of deleterious mutations per individual. For large values of this probability, we find a phase transition to an intermittent, multi-stable regime. On the other hand, in the limit of extremely slow drive, another transition takes place to a different steady state distribution, with fewer deleterious mutations within the asexual population.Comment: RevTeX, 11 pages, multicolumn, including 12 figure

Chikungunya Virus and Central Nervous System Infections in Children, India

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus best known for causing fever, rash, arthralgia, and occasional neurologic disease. By using real-time reverse transcription–PCR, we detected CHIKV in plasma samples of 8 (14%) of 58 children with suspected central nervous system infection in Bellary, India. CHIKV was also detected in the cerebrospinal fluid of 3 children

Predicting Risk in Patients Hospitalized for Acute Decompensated Heart Failure and Preserved Ejection Fraction: The Atherosclerosis Risk in Communities Study Heart Failure Community Surveillance

Background Risk-prediction models specifically for hospitalized heart failure with preserved ejection fraction are lacking. Methods and Results We analyzed data from the ARIC (Atherosclerosis Risk in Communities) Study Heart Failure Community Surveillance to create and validate a risk score predicting mortality in patients ≥55 years of age admitted with acute decompensated heart failure with preserved ejection fraction (ejection fraction ≥50%). A modified version of the risk-prediction model for acute heart failure developed from patients in the EFFECT (Enhanced Feedback for Effective Cardiac Treatment) study was used as a composite predictor of 28-day and 1-year mortalities and evaluated together with other potential predictors in a stepwise logistic regression. The derivation sample consisted of 1852 hospitalizations from 2005 to 2011 (mean age, 77 years; 65% women; 74% white). Risk scores were created from the identified predictors and validated in hospitalizations from 2012 to 2013 (n=821). Mortality in the derivation and validation sample was 11% and 8% at 28 days and 34% and 31% at 1 year. The modified EFFECT score, including age, systolic blood pressure, blood urea nitrogen, sodium, cerebrovascular disease, chronic obstructive pulmonary disease, and hemoglobin, was a powerful predictor of mortality. Another important predictor for both 28-day and 1-year mortalities was hypoxia. The risk scores were well calibrated and had good discrimination in the derivation sample (area under the curve: 0.76 for 28-day and 0.72 for 1-year mortalities) and validation sample (area under the curve: 0.73 and 0.71, respectively). Conclusions Mortality after acute decompensation in patients with heart failure with preserved ejection fraction is high, with one third of patients dying within a year. A prediction tool may allow for greater discrimination of the highest risk patients. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005131

Heart failure risk across the spectrum of ankle-brachial index: The ARIC study (Atherosclerosis RiskIn Communities)

The aim of this study was to describe the relationship between ankle brachial index (ABI) and the risk for heart failure (HF). Background: The ABI is a simple, noninvasive measure associated with atherosclerotic cardiovascular disease and death; however, the relationship between ABI and risk for HF is less well characterized. Methods: Between 1987 and 1989 in the ARIC (Atherosclerosis Risk In Communities) study, an oscillometric device was used to measure blood pressure in a single upper and randomly chosen lower extremity to determine the ABI. Incident HF events were defined by the first hospitalization with an International Classification of Diseases, Ninth Revision, code of 428.x through 2008. The risk for HF was assessed across the ABI range using restricted cubic splines and Cox proportional hazards models. Results: ABI was available in 13,150 participants free from prevalent HF. Over a mean 17.7 years of follow-up, 1,809 incident HF events occurred. After adjustment for traditional HF risk factors, prevalent coronary heart disease, subclinical carotid atherosclerosis, and interim myocardial infarction, compared with an ABI of 1.01 to 1.40, participants with ABIs≤0.90 were at increased risk for HF (hazard ratio: 1.40; 95% confidence interval: 1.12 to 1.74), as were participants with ABIs of 0.91 to 1.00 (hazard ratio: 1.36; 95% confidence interval: 1.17 to 1.59). Conclusions: In a middle-age community cohort, an ABI≤1.00 was significantly associated with an increased risk for HF, independent of traditional HF risk factors, prevalent coronary heart disease, carotid atherosclerosis, and interim myocardial infarction. Low ABI may reflect not only overt atherosclerosis but also pathologic processes in the development of HF beyond epicardial atherosclerotic disease and myocardial infarction alone. A low ABI, as a simple, noninvasive measure, may be a risk marker for HF

Predictors of mortality by sex and race in heart failure with preserved ejection fraction: Aric community surveillance study

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure hospitalizations, with limited data on predictors of mortality by sex and race. We evaluated for differences in predictors of all-cause mortality by sex and race among hospitalized patients with HFpEF in the ARIC (Atherosclerosis Risk in Communities) Community Surveillance Study. METHODS AND RESULTS: Adjudicated HFpEF hospitalization events from 2005 to 2013 were analyzed from the ARIC Community Surveillance Study, comprising 4 US communities. Comparisons between clinical characteristics and mortality at 1 year were made by sex and race. Of 4335 adjudicated acute decompensated heart failure cases, 1892 cases (weighted n=8987) were categorized as HFpEF. Men had an increased risk of 1-year mortality compared with women in adjusted analysis (hazard ratio [HR], 1.27; 95% CI, 1.06–1.52 [P=0.01]). Black participants had lower mortality compared with White participants in unadjusted and adjusted analyses (HR, 0.79; 95% CI, 0.64–0.97 [P=0.02]). Age, heart rate, worsening renal function, and low hemoglobin were associated with increased mortality in all subgroups. Higher body mass index was associated with improved survival in men, with borderline interaction by sex. Higher blood pressure was associated with improved survival among all groups, with significant interaction by race. CONCLUSIONS: In a diverse HFpEF population, men had worse survival compared with women, and Black participants had improved survival compared with White participants. Age, heart rate, and worsening renal function were associated with increased mortality across all subgroups; high blood pressure was associated with decreased mortality with interaction by race. These insights into sex-and race-based differences in predictors of mortality may help strategize targeted management of HFpEF

Whole exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association

Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum-stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle’s loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or CAKUT in VACTERL association

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies

Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. Objective: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. Method: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. Results: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing >= 60 g/d with = 25 g/d with Conclusion: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation

Prior dengue virus exposure shapes T Cell immunity to Zika Virus in humans

While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether pre-existing dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with Tetravalent Dengue Attenuated Vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors, but declines in DENV pre-exposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells form DENV pre-exposed donors selectively up-regulated granzyme B and PD1, as compared to DENV-naïve donors. Finally, we discovered that ZIKV structural proteins (E, prM and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins