The role of atrial natriuretic peptide to attenuate inflammation in a mouse skin wound and individually perfused rat mesenteric microvessels.

We tested the hypothesis that the anti-inflammatory actions of atrial natriuretic peptide (ANP) result from the modulation of leukocyte adhesion to inflamed endothelium and not solely ANP ligation of endothelial receptors to stabilize endothelial barrier function. We measured vascular permeability to albumin and accumulation of fluorescent neutrophils in a full-thickness skin wound on the flank of LysM-EGFP mice 24 h after formation. Vascular permeability in individually perfused rat mesenteric microvessels was also measured after leukocytes were washed out of the vessel lumen. Thrombin increased albumin permeability and increased the accumulation of neutrophils. The thrombin-induced inflammatory responses were attenuated by pretreating the wound with ANP (30 min). During pretreatment ANP did not lower permeability, but transiently increased baseline albumin permeability concomitant with the reduction in neutrophil accumulation. ANP did not attenuate acute increases in permeability to histamine and bradykinin in individually perfused rat microvessels. The hypothesis that anti-inflammatory actions of ANP depend solely on endothelial responses that stabilize the endothelial barrier is not supported by our results in either individually perfused microvessels in the absence of circulating leukocytes or the more chronic skin wound model. Our results conform to the alternate hypothesis that ANP modulates the interaction of leukocytes with the inflamed microvascular wall of the 24 h wound. Taken together with our previous observations that ANP reduces deformability of neutrophils and their strength of attachment, rolling, and transvascular migration, these observations provide the basis for additional investigations of ANP as an anti-inflammatory agent to modulate leukocyte-endothelial cell interactions

A review of studies of adherence with antihypertensive drugs using prescription databases

Poor adherence with antihypertensive therapies is a major factor in the low rates of blood pressure control among people with hypertension. Patient adherence is influenced by a large number of interacting factors but their exact impact is not well understood, partly because it is difficult to measure adherence. Longitudinal prescription data can be used as a measure of drug supply and are particularly useful to identify interruptions and changes of treatment. Obtaining a medicine does not ensure its use; however, it has been established that continuous collection of prescription medications is a useful marker of adherence. We found 20 studies published in the last 10 years that used large prescription databases to investigate adherence with antihypertensive therapies. These were assessed in terms of patient selection, the definition of the adherence outcome(s), and statistical modeling. There was large variation between studies, limiting their comparability. Particular methodological problems included: the failure to identify an inception cohort, which ensures baseline comparability, in four studies; the exclusion of patients who could not be followed up, which results in a selection bias, in 17 studies; failure to validate outcome definitions; and failure to model the discrete-time structure of the data in all the studies we examined. Although the data give repeated measurements on patients, none of the studies attempted to model patient-level variability. Studies of such observational data have inherent limitations, but their potential has not been fully realized in the modeling of adherence with antihypertensive drugs. Many of the studies we reviewed found high rates of nonadherence to antihypertensive therapies despite differences in populations and methods used. Adherence rates from one database ranged from 34% to 78% at 1 year. Some studies found women had better adherence than men, while others found the reverse. Novel approaches to analyzing data from such databases are required to use the information available appropriately and avoid the problems of bias

The cultural capitalists: notes on the ongoing reconfiguration of trafficking culture in Asia

Most analysis of the international flows of the illicit art market has described a global situation in which a postcolonial legacy of acquisition and collection exploits cultural heritage by pulling it westwards towards major international trade nodes in the USA and Europe. As the locus of consumptive global economic power shifts, however, these traditional flows are pulled in other directions: notably for the present commentary, towards and within Asia

The Student Movement Volume 105 Issue 11: Together We Can: Celebrating Women\u27s History Month

NEWS Andrews Symphony Orchestra and Featured Soloists Perform at Young Artist Celebration: Part II, Jenae Rogers WEAUU Continues to Provide Creative Events during Women\u27s History Month, Caralynn Chan Week of Prayer Covers the Theme Love is Life , Terika Williams PULSE Improving by 1 Percent: Atomic Habits Book Review, Jessica Rim International Women\u27s Month: Lessons From My Mother, Wambui Karanja Spring Birding, Interview by Masy Domecillo HUMANS AU\u27s Favorite Spring Activities, Interviewed by Fitz-Earl McKenzie II WEAAU Executive Officers Interview, Interviewed by Abigail Lee Women in Science, English, Math, and More!, Interviewed by Terika Williams ARTS & ENTERTAINMENT Over the Moon , Hannah Cruse Contemporary Young Women Making an Impact: Kaela McFadden The Importance of Female Art & Creativity, Alannah Tjhartra IDEAS Billie and Gender Binaries, Alyssa Henriquez The Equality Act and Transgender Existence, Adoniah Simon The Importance of a Woman, Evin N. Musgrove THE LAST WORD Master Your Mindset, Cultivate Your Creativity, Megan Napodhttps://digitalcommons.andrews.edu/sm-105/1015/thumbnail.jp

The Student Movement Volume 105 Issue 4: Students Destress in AUSA\u27s Nest

NEWS AU Adelante Club Hosts Vespers, Joelle Kim AUSA Hosts The Nest, Amanda Cho The Gazebo Reopens with GetFood App, Taylor Uphus PULSE Cultural Hispanic Catchphrases, Wambui Karanja Keep Calm and Breathing On (Yourself), Jessica Rim Meet & Make: Reflections, Masy Domecillo HUMANS Event Planning With Malachi Regis, Interviewed by Fitz-Earl McKenzie II Interview with Michael Nixon: Vice President for Diversity & Inclusion, Interviewed by Abigail Lee Meet Professor Pedro Navia, Interviewed by Pearl Parker Torian Hill, Interviewed by TJ Hunter ARTS & ENTERTAINMENT Hispanic Artist Feature: Felix Gillett, Megan Napod Música para el Alma or Music for the Soul, Hannah Cruse Signal Boost, Alannah Tjhatra IDEAS An Defense Against Burnout: Why Meaning Matters, Adoniah Simon Remembering RBG: Part Two, Lyle Goulbourne THE LAST WORD How Does it Change Us?, Daniel Selfhttps://digitalcommons.andrews.edu/sm-105/1004/thumbnail.jp

The Student Movement Volume 105 Issue 9: Celebrating the Caribbean Impact on Black History

NEWS AUSA and BSCF Host The Dating Game, Caralynn Chan Honors Agape Worship Celebrates Beverly Matiko\u27s Service, Terika Williams The Andrews University Wind Symphony Performs Stage & Screen Concert, Jenae Rogers PULSE Black History Month: Favorite Media, Interviews by Alec Bofetiado Black History Month: The Modern Heritage of Culture, Wambui Karanja Lunar New Year: A Reflection, Jessica Rim The Slump, Masy Domecillo HUMANS February Freshman Spotlight, Alyssa Henriquez Senior Spotlight: Brandi Seawood, Interviewed by Celeste Richardson Updates on 2020-21 Graduation Ceremony, Interviewed by Fitz-Earl McKenzie II ARTS & ENTERTAINMENT Black Artists I Recommend, Hannah Cruse Creative Spotlight: Be of Good Cheer with Itumeleng Gabasiane, Interviewed by Megan Napod Tesla, To the Moon!, Joshua Deonarine IDEAS Harlem Jazz and Louis Armstrong: His Life and Impact, Sion Kim How to be a Black Community Ally, Kavya Mohanram The Plans and Hopes of the Biden Administration, Lyle Goulbourne THE LAST WORD The Mountain, The Tree and You, Adoniah Simonhttps://digitalcommons.andrews.edu/sm-105/1012/thumbnail.jp

Development and content validity of a patient reported outcomes measure to assess symptoms of major depressive disorder

<p>Abstract</p> <p>Background</p> <p>Although many symptoms of Major Depressive Disorder (MDD) are assessed through patient-report, there are currently no patient-reported outcome (PRO) instruments that incorporate documented evidence of patient input in PRO instrument development. A review of existing PROs used in MDD suggested the need to conduct qualitative research with patients with MDD to better understand their experience of MDD and develop an evaluative instrument with content validity. The aim of this study was to develop a disease-specific questionnaire to assess symptoms important and relevant to adult MDD patients.</p> <p>Methods</p> <p>The questionnaire development involved qualitative interviews for concept elicitation, instrument development, and cognitive interviews to support content validity. For concept elicitation, ten MDD severity-specific focus group interviews with thirty-eight patients having clinician-confirmed diagnoses of MDD were conducted in January 2009. A semi-structured discussion guide was used to elicit patients' spontaneous descriptions of MDD symptoms. Verbatim transcripts of focus groups were coded and analyzed to develop a conceptual framework to describe MDD. A PRO instrument was developed by operationalizing concepts elicited in the conceptual framework. Cognitive interviews were carried out in patients (n = 20) to refine and test the content validity of the instrument in terms of item relevance and comprehension, instructions, recall period, and response categories.</p> <p>Results</p> <p>Concept elicitation focus groups identified thirty-five unique concepts falling into several domains: i) emotional, ii) cognitive, iii) motivation, iv) work, v) sleep, vi) appetite, vii) social, viii) activities of daily living, ix) tired/fatigue, x) body pain, and xi) suicidality. Concept saturation, the point at which no new relevant information emerges in later interviews, was achieved for each of the concepts. Based on the qualitative findings, the PRO instrument developed had 15 daily and 20 weekly items. The cognitive interviews confirmed that the instructions, item content, and response scales were understood by the patients.</p> <p>Conclusions</p> <p>Rigorous qualitative research resulted in the development of a PRO measure for MDD with supported content validity. The MDD PRO can assist in understanding and assessing MDD symptoms from patients' perspectives as well as evaluating treatment benefit of new targeted therapies.</p

Stochastic Pharmacokinetic-Pharmacodynamic Modeling for Assessing the Systemic Health Risk of Perfluorooctanoate (PFOA)

A phase 1 dose-escalation trial assessed the chemotherapeutic potential of ammonium perfluorooctanoate (APFO). Forty-nine primarily solid-tumor cancer patients who failed standard therapy received weekly APFO doses (50mg-1200mg) for six-weeks. Clinical chemistries and plasma PFOA (anionic APFO) were measured pre-dose and weekly thereafter. Several clinical measures including total cholesterol, high-density lipoproteins (HDL), thyroid stimulating hormone (TSH), and free thyroxine (fT4), relative to PFOA concentrations, were examined by: standard statistical analyses using general estimating equations (GEE) and a probabilistic analysis using probability distribution functions (pdf) at various PFOA concentrations; and a two-compartment pharmacokinetic/pharmacodynamic (PK/PD) model to directly estimate mean changes. Based on the GEE, the average rates of change in total cholesterol and fT4 associated with increasing PFOA were approximately -1.2x10−3mmol/L/μM and 2.8x10−3pmol/L/μM, respectively. The PK/PD model predicted more closely the trends observed in the data as well as the pdfs of biomarkers. A decline in total cholesterol was observed, with a clear transition in shape and range of the pdfs, manifested by the maximum value of the Kullback-Leibler (KL) divergence, that occurred at plasma PFOA between 420 and 565 μM (175,000–230,000 ng/mL). HDL was unchanged. An increase in fT4 was observed at a higher PFOA transition point, albeit TSH was unchanged. Our findings are consistent with some animal models and may motivate re-examination of the epidemiological studies to PFOA at levels several orders of magnitude lower than this study. These observational studies have reported contrary associations, but currently understood biology does not support the existence of such conflicting effects