Evaluating a Telephone and Home Blood Pressure Monitoring Intervention to Improve Blood Pressure Control and Self-Care Behaviors in Adults with Low-Socioeconomic Status.

Hypertension (HTN) affects nearly 75 million in the United States, and percentages increase with low socioeconomic status (SES) due to poor access to, and quality of, care, and poor self-care behaviors. Federally Qualified Health Centers (FQHCs) employ evidence-based strategies, such as telehealth interventions, to improve blood pressure (BP) control in under-resourced communities, yet a southeastern FQHC could achieve a BP control rate of only 27.6%, well below the Health People 2020 goal of 61.2%. This pilot project used a pre/post, matched-cohort design to evaluate the effect of a telehealth intervention on BP control and self-care behaviors. Secondary outcomes included self-efficacy and perceived stress. Frequency and percentage, Wilcoxon signed-rank, and McNemar tests were used for statistical analysis of results from a convenience sample of 27 participants. Baseline HTN management guidance that incorporated home blood pressure monitoring (HBPM) was reinforced through telephone counseling every two weeks. Although BP control was not achieved, average scores for systolic and diastolic blood pressures decreased significantly: 13 mm Hg (p = 0.0136) and 5 mm Hg (p = 0.0095), respectively. Statistically significant differences were also seen in select self-care behaviors. Greater BP reduction aligned with higher self-efficacy scores and call engagement. Overall, telephone counseling and HBPM were feasible and effective in reducing BP and increasing self-care behaviors. The inability to control BP may be attributable to under-recognition of stress, lack of medication adherence/reconciliation, and underutilization of guideline-based prescribing recommendations. Findings elucidate the potential effectiveness of a sustainable telehealth intervention to improve BP in low-SES populations.

Amino acids induce high seed-specific expression driven by a soybean (Glycine max) glycinin seed storage protein promoter.

KEY MESSAGE: We characterize GFP expression driven by a soybean glycinin promoter in transgenic soybean. We demonstrate specific amino acid-mediated induction of this promoter in developing soybean seeds in vitro. In plants, gene expression is primarily regulated by promoter regions which are located upstream of gene coding sequences. Promoters allow transcription in certain tissues and respond to environmental stimuli as well as other inductive phenomena. In soybean, seed storage proteins (SSPs) accumulate during seed development and account for most of the monetary and nutritional value of this crop. To better study the regulatory functions of a SSP promoter, we developed a cotyledon culture system where media and media addenda were evaluated for their effects on cotyledon development and promoter activity. Stably transformed soybean events containing a glycinin SSP promoter regulating the green fluorescent protein (GFP) were generated. Promoter activity, as visualized by GFP expression, was only observed in developing in planta seeds and in vitro-cultured isolated embryos and cotyledons from developing seeds when specific media addenda were included. Asparagine, proline, and especially glutamine induced glycinin promoter activity in cultured cotyledons from developing seeds. Other amino acids did not induce the glycinin promoter. Here, we report, for the first time, induction of a reintroduced glycinin SSP promoter by specific amino acids in cotyledon tissues during seed development.

Transient Transformation Using Particle Bombardment for Gene Expression Analysis.

Transient transformation or transient expression results in rapid and fleeting gene expression. This approach is often used as a first-tier screening tool for evaluation of components that affect gene expression. Here, we describe the use of particle bombardment of lima bean cotyledons with constructs containing the green fluorescent protein (gfp) coding region for evaluation of promoter components that influence gene expression. Although this approach is conceptually quite simple, this lima bean transient expression system may not work well, if our methods and notes are not carefully read and followed. Our laboratory has successfully optimized this method over the past 10 years, resulting in a transient expression system, which works like no other that we have seen.

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

BACKGROUND: Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. METHODS: We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. RESULTS: We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10-7) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. IMPACT: A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR.

Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients.

Here we perform the first genome-wide association study (GWAS) of multiple myeloma (MM) survival. In a meta-analysis of 306 MM patients treated at UCSF and 239 patients treated at the Mayo clinic, we find a significant association between SNPs near the gene FOPNL on chromosome 16p13 and survival (rs72773978; P=6 × 10(-10)). Patients with the minor allele are at increased risk for mortality (HR: 2.65; 95% CI: 1.94-3.58) relative to patients homozygous for the major allele. We replicate the association in the IMMEnSE cohort including 772 patients, and a University of Utah cohort including 318 patients (rs72773978 P=0.044). Using publicly available data, we find that the minor allele was associated with increased expression of FOPNL and increased expression of FOPNL was associated with higher expression of centrosomal genes and with shorter survival. Polymorphisms at the FOPNL locus are associated with survival among MM patients.

Acidosis decreases c-Myc oncogene expression in human lymphoma cells: a role for the proton-sensing G protein-coupled receptor TDAG8.

Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65) is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partially rescues c-Myc expression, respectively. Acidic pH alone is insufficient to reduce c-Myc expression, as it does not decrease c-Myc in H1299 lung cancer cells expressing very low levels of pH-sensing G protein-coupled receptors (GPCRs). Instead, c-Myc is slightly increased by acidosis in H1299 cells, but this increase is completely inhibited by ectopic overexpression of TDAG8. Interestingly, TDAG8 expression is decreased by more than 50% in human lymphoma samples in comparison to non-tumorous lymph nodes and spleens, suggesting a potential tumor suppressor function of TDAG8 in lymphoma. Collectively, our results identify a novel mechanism of c-Myc regulation by acidosis in the tumor microenvironment and indicate that modulation of TDAG8 and related pH-sensing receptor pathways may be exploited as a new approach to inhibit Myc expression.

Feline eosinophilic keratoconjunctivitis: a retrospective study of 45 cases (56 eyes).

The medical records of 45 cases (56 eyes) of feline eosinophilic keratoconjunctivitis (EKC) diagnosed between 2005 and 2011 were reviewed. Cats were included if a clinical diagnosis of EKC was recorded and eosinophils were found on corneal cytology. Median age at presentation was 5 years (interquartiles 5-9 years) for both males and females. Domestic shorthair was the predominant breed, accounting for 77.8% of the cats. The condition was unilateral in 75.6% of cases, with the superotemporal quadrant of the cornea the most frequently affected position (76.8% of eyes). A history of corneal ulceration was recorded in 37.8% of cases, and corneal ulcers were present at or before diagnosis in 66.7% of the cats. Eosinophils were found in 92.0% of conjunctival scrapings. We performed polymerase chain reaction (PCR) for feline herpesvirus type 1 (FHV-1) for 33/45 cats. Viral DNA was detected in 54.5% of these cats. FHV-1 DNA was detected by PCR in 66.7% of cats with a history and/or presence of a corneal ulcer at first presentation, which is significantly more than those with no corneal ulcer at any time (22.2% FHV-1 DNA detected). Our findings suggest that a corneal ulcer can be present prior to the development of eosinophilic keratitis. Further studies are mandatory to explore the role that FHV-1 could play in EKC-associated corneal ulceration.

Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT).

Total white blood cell (WBC) and neutrophil counts are lower among individuals of African descent due to the common African-derived "null" variant of the Duffy Antigen Receptor for Chemokines (DARC) gene. Additional common genetic polymorphisms were recently associated with total WBC and WBC sub-type levels in European and Japanese populations. No additional loci that account for WBC variability have been identified in African Americans. In order to address this, we performed a large genome-wide association study (GWAS) of total WBC and cell subtype counts in 16,388 African-American participants from 7 population-based cohorts available in the Continental Origins and Genetic Epidemiology Network. In addition to the DARC locus on chromosome 1q23, we identified two other regions (chromosomes 4q13 and 16q22) associated with WBC in African Americans (P<2.5×10(-8)). The lead SNP (rs9131) on chromosome 4q13 is located in the CXCL2 gene, which encodes a chemotactic cytokine for polymorphonuclear leukocytes. Independent evidence of the novel CXCL2 association with WBC was present in 3,551 Hispanic Americans, 14,767 Japanese, and 19,509 European Americans. The index SNP (rs12149261) on chromosome 16q22 associated with WBC count is located in a large inter-chromosomal segmental duplication encompassing part of the hydrocephalus inducing homolog (HYDIN) gene. We demonstrate that the chromosome 16q22 association finding is most likely due to a genotyping artifact as a consequence of sequence similarity between duplicated regions on chromosomes 16q22 and 1q21. Among the WBC loci recently identified in European or Japanese populations, replication was observed in our African-American meta-analysis for rs445 of CDK6 on chromosome 7q21 and rs4065321 of PSMD3-CSF3 region on chromosome 17q21. In summary, the CXCL2, CDK6, and PSMD3-CSF3 regions are associated with WBC count in African American and other populations. We also demonstrate that large inter-chromosomal duplications can result in false positive associations in GWAS.

Ocular thelaziosis in dogs, France.

During 2005-2008, veterinary practitioners reported ocular infection by Thelazia spp. nematodes in 115 dogs and 2 cats in southwestern France. Most cases were detected in Dordogne, particularly in 3 counties with numerous strawberry farms, which may favor development of the fruit fly vector. Animal thelaziosis may lead to emergence of human cases.

Analysis of close stable homolog juxtaposition during meiosis in mutants of Saccharomyces cerevisiae.

A unique aspect of meiosis is the segregation of homologous chromosomes at the meiosis I division. The pairing of homologous chromosomes is a critical aspect of meiotic prophase I that aids proper disjunction at anaphase I. We have used a site-specific recombination assay in Saccharomyces cerevisiae to examine allelic interaction levels during meiosis in a series of mutants defective in recombination, chromatin structure, or intracellular movement. Red1, a component of the chromosome axis, and Mnd1, a chromosome-binding protein that facilitates interhomolog interaction, are critical for achieving high levels of allelic interaction. Homologous recombination factors (Sae2, Rdh54, Rad54, Rad55, Rad51, Sgs1) aid in varying degrees in promoting allelic interactions, while the Srs2 helicase appears to play no appreciable role. Ris1 (a SWI2/SNF2 related protein) and Dot1 (a histone methyltransferase) appear to play minor roles. Surprisingly, factors involved in microtubule-mediated intracellular movement (Tub3, Dhc1, and Mlp2) appear to play no appreciable role in homolog juxtaposition, unlike their counterparts in fission yeast. Taken together, these results support the notion that meiotic recombination plays a major role in the high levels of homolog interaction observed during budding yeast meiosis.

[Epidemiological, clinical, echo-doppler characteristics of mitral valve endocardiosis in Cavalier King Charles in France: a retrospective study of 451 cases (1995 to 2003)]. / Caractéristiques épidémiologiques, cliniques, écho-doppler de l'endocardiose mitrale chez le Cavalier King Charles en France: étude retrospective de 451 cas (1995 à 2003).

A study performed on 451 Cavalier King Charles showed that 40.6% of dogs had a left apical systolic heart murmur, whose prevalence increased with age (> 11-year-old, 100%), but was not different between males and females. Mitral valve endocardiosis represented 93.3% of the ultrasonographic abnormalities.

Close, stable homolog juxtaposition during meiosis in budding yeast is dependent on meiotic recombination, occurs independently of synapsis, and is distinct from DSB-independent pairing contacts.

A site-specific recombination system that probes the relative probabilities that pairs of chromosomal loci collide with one another in living cells of budding yeast was used to explore the relative contributions of pairing, recombination, synaptonemal complex formation, and telomere clustering to the close juxtaposition of homologous chromosome pairs during meiosis. The level of Cre-mediated recombination between a pair of loxP sites located at an allelic position on homologous chromosomes was 13-fold greater than that between a pair of loxP sites located at ectopic positions on nonhomologous chromosomes. Mutations affecting meiotic recombination initiation and the processing of DNA double-strand breaks (DSBs) into single-end invasions (SEIs) reduced the levels of allelic Cre-mediated recombination levels by three- to sixfold. The severity of Cre/loxP phenotypes is presented in contrast to relatively weak DSB-independent pairing defects as assayed using fluorescence in situ hybridization for these mutants. Mutations affecting synaptonemal complex (SC) formation or crossover control gave wild-type levels of allelic Cre-mediated recombination. A delay in attaining maximum levels of allelic Cre-mediated recombination was observed for a mutant defective in telomere clustering. None of the mutants affected ectopic levels of recombination. These data suggest that stable, close homolog juxtaposition in yeast is distinct from pre-DSB pairing interactions, requires both DSB and SEI formation, but does not depend on crossovers or SC.