Analysis of Hypertension Control Rates Among Participants in the Georgia Hypertension Management and Outreach Program

Background: This study utilized health department electronic medical records retrospectively to evaluate hypertension control rates achieved by the Georgia Hypertension Management and Outreach Program (HMOP), an education, screening, and treatment control program that provides services, including blood pressure screening and assessment, referral to physicians, counseling, educational material, disease case management, and treatment. Methods: Hypertension control rates after at least 6 months of study participation were determined for patients participating in the program for at least 6 months between 2010 and 2014, and for African American and uninsured subgroups. Results: The overall hypertension control rate was 61.1%, above the 2012 national average of 51.8%. The control rates for African Americans and the uninsured were 58.9% and 62%, respectively, compared to 41.7% and 28.7% nationally. Conclusions: Although potential bias sources in the use of retrospectively obtained electronic medical records should be considered, this analysis suggests that the Georgia HMOP provides substantial improvements in hypertension control for a population of patients with otherwise poor control. Key words: hypertension, blood pressure, cardiovascular diseases, African Americans, medically uninsure

Dissociation of Automatic and Strategic Lexical-semantics: Functional Magnetic Resonance Imaging Evidence for Differing Roles of Multiple Frontotemporal Regions

Behavioral research has demonstrated three major components of the lexical-semantic processing system: automatic activation of semantic representations, strategic retrieval of semantic representations, and inhibition of competitors. However, these component processes are inherently conflated in explicit lexical-semantic decision tasks typically used in functional magnetic resonance imaging (fMRI) research. Here, we combine the logic of behavioral priming studies and the neurophysiological phenomenon of fMRI priming to dissociate the neural bases of automatic and strategic lexical-semantic processes across a series of three studies. A single lexical decision task was used in all studies, with stimulus onset asynchrony or linguistic relationship between prime and target being manipulated. Study 1 demonstrated automatic semantic priming in the left mid-fusiform gyrus (mid-FFG) and strategic semantic priming in five regions: left middle temporal gyrus (MTG), bilateral anterior cingulate, anterior left inferior prefrontal cortex (aLIPC), and posterior LIPC (pLIPC). These priming effects were explored in more detail in two subsequent studies. Study 2 replicated the automatic priming effect in mid-FFG and demonstrated that automatic priming in this region is preferential for the semantic domain. Study 3 demonstrated a neural dissociation in regions contributing to the strategic semantic priming effect. Strategic semantic facilitation was observed in the aLIPC and MTG, whereas strategic semantic inhibition was observed in the pLIPC and anterior cingulate. These studies provide reproducible evidence for a neural dissociation between three well established components of the lexical-semantic processing system

CRIg-expressing peritoneal macrophages are associated with disease severity in patients with cirrhosis and ascites

Infections are an important cause of morbidity and mortality in patients with decompensated cirrhosis and ascites. Hypothesizing that innate immune dysfunction contributes to susceptibility to infection, we assessed ascitic fluid macrophage phenotype and function. The expression of complement receptor of the immunoglobulin superfamily (CRIg) and CCR2 defined two phenotypically and functionally distinct peritoneal macrophage subpopulations. The proportion of CRIg(hi) macrophages differed between patients and in the same patient over time, and a high proportion of CRIg(hi) macrophages was associated with reduced disease severity (model for end-stage liver disease) score. As compared with CRIg(lo) macrophages, CRIg(hi) macrophages were highly phagocytic and displayed enhanced antimicrobial effector activity. Transcriptional profiling by RNA sequencing and comparison with human macrophage and murine peritoneal macrophage expression signatures highlighted similarities among CRIg(hi) cells, human macrophages, and mouse F4/80(hi) resident peritoneal macrophages and among CRIg(lo) macrophages, human monocytes, and mouse F4/80lo monocyte-derived peritoneal macrophages. These data suggest that CRIg(hi) and CRIg(lo) macrophages may represent a tissue-resident population and a monocytederived population, respectively. In conclusion, ascites fluid macrophage subset distribution and phagocytic capacity is highly variable among patients with chronic liver disease. Regulating the numbers and/or functions of these macrophage populations could provide therapeutic opportunities in cirrhotic patients

A Very Sensitive 21cm Survey for Galactic High-Velocity HI

Very sensitive HI 21cm observations have been made in 860 directions at dec >= -43deg in search of weak, Galactic, high-velocity HI emission lines at moderate and high Galactic latitudes. One-third of the observations were made toward extragalactic objects. The median 4-sigma detection level is NHI = 8x10^{17} cm^-2 over the 21' telescope beam. High-velocity HI emission is detected in 37% of the directions; about half of the lines could not have been seen in previous surveys. The median FWHM of detected lines is 30.3 km/s. High- velocity HI lines are seen down to the sensitivity limit of the survey implying that there are likely lines at still lower values of NHI. The weakest lines have a kinematics and distribution on the sky similar to that of the strong lines, and thus do not appear to be a new population. Most of the emission originates from objects which are extended over several degrees; few appear to be compact sources. At least 75%, and possibly as many as 90%, of the lines are associated with one of the major high-velocity complexes. The Magellanic Stream extends at least 10 deg to higher Galactic latitude than previously thought and is more extended in longitude as well. Although there are many lines with low column density, their numbers do not increase as rapidly as NHI^-1, so most of the HI mass in the high-velocity cloud phenomenon likely resides in the more prominent clouds. The bright HI features may be mere clumps within larger structures, and not independent objects.Comment: 88 pages includes 22 figures Accepted for Publication in ApJ Suppl. June 200

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction in Tauopathy

Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression. In this study, we treated early stage tau transgenic mice with a multi-target kinase inhibitor to identify novel substrates that contribute to cognitive impairment and exhibit therapeutic potential. Drug treatment significantly ameliorated brain atrophy and cognitive function as determined by behavioral testing and a sensitive imaging technique called manganese-enhanced magnetic resonance imaging (MEMRI) with quantitative R1 mapping. Surprisingly, these benefits occurred despite unchanged hyperphosphorylated tau levels. To elucidate the mechanism behind these improved cognitive outcomes, we performed quantitative proteomics to determine the altered protein network during this early stage in tauopathy and compare this model with the human Alzheimer’s disease (AD) proteome. We identified a cluster of preserved pathways shared with human tauopathy with striking potential for broad multi-target kinase intervention. We further report high confidence candidate proteins as novel therapeutically relevant targets for the treatment of tauopathy. Proteomics data are available via ProteomeXchange with identifier PXD023562

Core Outcomes for Colorectal Cancer Surgery: A Consensus Study

Background: Colorectal cancer (CRC) is a major cause of worldwide morbidity and mortality. Surgical treatment is common, and there is a great need to improve the delivery of such care. The gold standard for evaluating surgery is within well-designed randomized controlled trials (RCTs); however, the impact of RCTs is diminished by a lack of coordinated outcome measurement and reporting. A solution to these issues is to develop an agreed standard “core” set of outcomes to be measured in all trials to facilitate cross-study comparisons, meta-analysis, and minimize outcome reporting bias. This study defines a core outcome set for CRC surgery. Methods and Findings: The scope of this COS includes clinical effectiveness trials of surgical interventions for colorectal cancer. Excluded were nonsurgical oncological interventions. Potential outcomes of importance to patients and professionals were identified through systematic literature reviews and patient interviews. All outcomes were transcribed verbatim and categorized into domains by two independent researchers. This informed a questionnaire survey that asked stakeholders (patients and professionals) from United Kingdom CRC centers to rate the importance of each domain. Respondents were resurveyed following group feedback (Delphi methods). Outcomes rated as less important were discarded after each survey round according to predefined criteria, and remaining outcomes were considered at three consensus meetings; two involving international professionals and a separate one with patients. A modified nominal group technique was used to gain the final consensus. Data sources identified 1,216 outcomes of CRC surgery that informed a 91 domain questionnaire. First round questionnaires were returned from 63 out of 81 (78%) centers, including 90 professionals, and 97 out of 267 (35%) patients. Second round response rates were high for all stakeholders (>80%). Analysis of responses lead to 45 and 23 outcome domains being retained after the first and second surveys, respectively. Consensus meetings generated agreement on a 12 domain COS. This constituted five perioperative outcome domains (including anastomotic leak), four quality of life outcome domains (including fecal urgency and incontinence), and three oncological outcome domains (including long-term survival). Conclusion: This study used robust consensus methodology to develop a core outcome set for use in colorectal cancer surgical trials. It is now necessary to validate the use of this set in research practice

Using focus groups to design systems science models that promote oral health equity

Background While the US population overall has experienced improvements in oral health over the past 60 years, oral diseases remain among the most common chronic conditions across the life course. Further, lack of access to oral health care contributes to profound and enduring oral health inequities worldwide. Vulnerable and underserved populations who commonly lack access to oral health care include racial/ethnic minority older adults living in urban environments. The aim of this study was to use a systematic approach to explicate cause and effect relationships in creating a causal map, a type of concept map in which the links between nodes represent causality or influence. Methods To improve our mental models of the real world and devise strategies to promote oral health equity, methods including system dynamics, agent-based modeling, geographic information science, and social network simulation have been leveraged by the research team. The practice of systems science modeling is situated amidst an ongoing modeling process of observing the real world, formulating mental models of how it works, setting decision rules to guide behavior, and from these heuristics, making decisions that in turn affect the state of the real world. Qualitative data were obtained from focus groups conducted with community-dwelling older adults who self-identify as African American, Dominican, or Puerto Rican to elicit their lived experiences in accessing oral health care in their northern Manhattan neighborhoods. Results The findings of this study support the multi-dimensional and multi-level perspective of access to oral health care and affirm a theorized discrepancy in fit between available dental providers and patients. The lack of information about oral health at the community level may be compromising the use and quality of oral health care among racial/ethnic minority older adults. Conclusions Well-informed community members may fill critical roles in oral health promotion, as they are viewed as highly credible sources of information and recommendations for dental providers. The next phase of this research will involve incorporating the knowledge gained from this study into simulation models that will be used to explore alternative paths toward improving oral health and health care for racial/ethnic minority older adults

Pathogenic variants in glutamyl-tRNAGln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.

Mitochondrial protein synthesis requires charging mt-tRNAs with their cognate amino acids by mitochondrial aminoacyl-tRNA synthetases, with the exception of glutaminyl mt-tRNA (mt-tRNAGln). mt-tRNAGln is indirectly charged by a transamidation reaction involving the GatCAB aminoacyl-tRNA amidotransferase complex. Defects involving the mitochondrial protein synthesis machinery cause a broad spectrum of disorders, with often fatal outcome. Here, we describe nine patients from five families with genetic defects in a GatCAB complex subunit, including QRSL1, GATB, and GATC, each showing a lethal metabolic cardiomyopathy syndrome. Functional studies reveal combined respiratory chain enzyme deficiencies and mitochondrial dysfunction. Aminoacylation of mt-tRNAGln and mitochondrial protein translation are deficient in patients' fibroblasts cultured in the absence of glutamine but restore in high glutamine. Lentiviral rescue experiments and modeling in S. cerevisiae homologs confirm pathogenicity. Our study completes a decade of investigations on mitochondrial aminoacylation disorders, starting with DARS2 and ending with the GatCAB complex