Selective loss of resident macrophage-derived insulin-like growth factor-1 abolishes adaptive cardiac growth to stress.

Hypertension affects one-third of the world's population, leading to cardiac dysfunction that is modulated by resident and recruited immune cells. Cardiomyocyte growth and increased cardiac mass are essential to withstand hypertensive stress; however, whether immune cells are involved in this compensatory cardioprotective process is unclear. In normotensive animals, single-cell transcriptomics of fate-mapped self-renewing cardiac resident macrophages (RMs) revealed transcriptionally diverse cell states with a core repertoire of reparative gene programs, including high expression of insulin-like growth factor-1 (Igf1). Hypertension drove selective in situ proliferation and transcriptional activation of some cardiac RM states, directly correlating with increased cardiomyocyte growth. During hypertension, inducible ablation of RMs or selective deletion of RM-derived Igf1 prevented adaptive cardiomyocyte growth, and cardiac mass failed to increase, which led to cardiac dysfunction. Single-cell transcriptomics identified a conserved IGF1-expressing macrophage subpopulation in human cardiomyopathy. Here we defined the absolute requirement of RM-produced IGF-1 in cardiac adaptation to hypertension.

Dissecting and Visualizing the Functional Diversity of Cardiac Macrophages.

Cardiac macrophages represent a functionally diverse population of cells involved in cardiac homeostasis, repair, and remodeling. With recent advancements in single-cell technologies, it is possible to elucidate specific macrophage subsets based on transcriptional signatures and cell surface protein expression to gain a deep understanding of macrophage diversity in the heart. The use of fate-mapping technologies and parabiosis studies have provided insight into the ontogeny and dynamics of macrophages identifying subsets derived from embryonic and adult definitive hematopoietic progenitors that include tissue-resident and bone marrow monocyte-derived macrophages, respectively. Within the heart, these subsets have distinct tissue niches and functional roles in the setting of homeostasis and disease, with cardiac resident macrophages representing a protective cell population while bone marrow monocyte-derived cardiac macrophages have a context-dependent effect, triggering both proinflammatory tissue injury, but also promoting reparative functions. With the increased understanding of the clinical relevance of cardiac macrophage subsets, there has been an increasing need to detect and measure cardiac macrophage compositions in living animals and patients. New molecular tracers compatible with positron emission tomography/computerized tomography and positron emission tomography/ magnetic resonance imaging have enabled investigators to noninvasively and serially visualize cardiac macrophage subsets within the heart to define associations with disease and measure treatment responses. Today, advancements within this thriving field are poised to fuel an era of clinical translation.

Reproductive male partner testing when the female is identified to be a genetic disease carrier.

OBJECTIVE: To quantify carrier testing uptake rates for male partners of women found to be a carrier(s) for autosomal recessive conditions and to understand reasons for declining testing (uptake rate). METHODS: A retrospective chart review of 513 female patients seen at Rutgers-Robert Wood Johnson Medical School found to be carriers through expanded carrier screening (ECS) panels. The aims of this study were to determine how often their male partner chose testing, reasons for declining and the type of methodology chosen for their screening. RESULTS: Male partner uptake rate was 77%. We identified that the most significant barrier to male partner testing is female patients not following up on their own carrier screening results, thus missing the opportunity for partner testing. When male partners were provided options for testing, the most reported reason for declining is the belief it would have no impact on pregnancy management (20%). A carrier couple rate of 8.3% was identified of partners tested. CONCLUSION: Despite a relatively high male testing uptake rate, a quarter of carrier females did not proceed with testing their partner. To ascertain fetal risk, results for both parents is necessary. Pretest counseling should stress need for potential male partner follow-up testing.

In Vivo Biosynthesis of Inorganic Nanomaterials Using Eukaryotes-A Review.

Bionanotechnology, the use of biological resources to produce novel, valuable nanomaterials, has witnessed tremendous developments over the past two decades. This eco-friendly and sustainable approach enables the synthesis of numerous, diverse types of useful nanomaterials for many medical, commercial, and scientific applications. Countless reviews describing the biosynthesis of nanomaterials have been published. However, to the best of our knowledge, no review has been exclusively focused on the in vivo biosynthesis of inorganic nanomaterials. Therefore, the present review is dedicated to filling this gap by describing the many different facets of the in vivo biosynthesis of nanoparticles (NPs) using living eukaryotic cells and organisms-more specifically, live plants and living biomass of several species of microalgae, yeast, fungus, mammalian cells, and animals. It also highlights the strengths and weaknesses of the synthesis methodologies and the NP characteristics, bio-applications, and proposed synthesis mechanisms. This comprehensive review also brings attention to enabling a better understanding between the living organisms themselves and the synthesis conditions that allow their exploitation as nanobiotechnological production platforms as these might serve as a robust resource to boost and expand the bio-production and use of desirable, functional inorganic nanomaterials.

A Mechanistic View of the Light-Induced Synthesis of Silver Nanoparticles Using Extracellular Polymeric Substances of Chlamydomonas reinhardtii.

In the current study, extracellular polymeric substances (EPS) of Chlamydomonas reinhardtii and photon energy biosynthetically converted Ag+ to silver nanoparticles (AgNPs). The reaction mechanism began with the non-photon-dependent adsorption of Ag+ to EPS biomolecules. An electron from the EPS biomolecules was then donated to reduce Ag+ to Ag0, while a simultaneous release of H+ acidified the reaction mixture. The acidification of the media and production rate of AgNPs increased with increasing light intensity, indicating the light-dependent nature of the AgNP synthesis process. In addition, the extent of Ag+ disappearance from the aqueous phase and the AgNP production rate were both dependent on the quantity of EPS in the reaction mixture, indicating Ag+ adsorption to EPS as an important step in AgNP production. Following the reaction, stabilization of the NPs took place as a function of EPS concentration. The shifts in the intensities and positions of the functional groups, detected by Fourier-transform infrared spectroscopy (FTIR), indicated the potential functional groups in the EPS that reduced Ag+, capped Ag0, and produced stable AgNPs. Based on these findings, a hypothetic three-step, EPS-mediated biosynthesis mechanism, which includes a light-independent adsorption of Ag+, a light-dependent reduction of Ag+ to Ag0, and an EPS concentration-dependent stabilization of Ag0 to AgNPs, has been proposed.

Travel time and attrition from VHA care among women veterans: how far is too far?

BACKGROUND: Travel time, an access barrier, may contribute to attrition of women veterans from Veterans Health Administration (VHA) care. OBJECTIVE: We examined whether travel time influences attrition: (a) among women veterans overall, (b) among new versus established patients, and (c) among rural versus urban patients. RESEARCH DESIGN: This retrospective cohort study used logistic regression to estimate the association between drive time and attrition, overall and for new/established and rural/urban patients. SUBJECTS: In total, 266,301 women veteran VHA outpatients in the Fiscal year 2009. MEASURES: An "attriter" did not return for VHA care during the second through third years after her first 2009 visit (T0). Drive time (log minutes) was between the patient's residence and her regular source of VHA care. "New" patients had no VHA visits within 3 years before T0. Models included age, service-connected disability, health status, and utilization as covariates. RESULTS: Overall, longer drive times were associated with higher odds of attrition: drive time adjusted odds ratio=1.11 (99% confidence interval, 1.09-1.14). The relationship between drive time and attrition was stronger among new patients but was not modified by rurality. CONCLUSIONS: Attrition among women veterans is sensitive to longer drive time. Linking new patients to VHA services designed to reduce distance barriers (telemedicine, community-based clinics, mobile clinics) may reduce attrition among women new to VHA.

Prevalence, risk, and correlates of posttraumatic stress disorder across ethnic and racial minority groups in the United States.

OBJECTIVES: We assess whether posttraumatic stress disorder (PTSD) varies in prevalence, diagnostic criteria endorsement, and type and frequency of potentially traumatic events (PTEs) among a nationally representative US sample of 5071 non-Latino whites, 3264 Latinos, 2178 Asians, 4249 African Americans, and 1476 Afro-Caribbeans. METHODS: PTSD and other psychiatric disorders were evaluated using the World Mental Health-Composite International Diagnostic Interview (WMH-CIDI) in a national household sample that oversampled ethnic/racial minorities (n=16,238) but was weighted to produce results representative of the general population. RESULTS: Asians have lower prevalence rates of probable lifetime PTSD, whereas African Americans have higher rates as compared with non-Latino whites, even after adjusting for type and number of exposures to traumatic events, and for sociodemographic, clinical, and social support factors. Afro-Caribbeans and Latinos seem to demonstrate similar risk to non-Latino whites, adjusting for these same covariates. Higher rates of probable PTSD exhibited by African Americans and lower rates for Asians, as compared with non-Latino whites, do not appear related to differential symptom endorsement, differences in risk or protective factors, or differences in types and frequencies of PTEs across groups. CONCLUSIONS: There appears to be marked differences in conditional risk of probable PTSD across ethnic/racial groups. Questions remain about what explains risk of probable PTSD. Several factors that might account for these differences are discussed, as well as the clinical implications of our findings. Uncertainty of the PTSD diagnostic assessment for Latinos and Asians requires further evaluation.

The Past and Present of Breast Cancer Resources: A Re-evaluation of the Quality of Online Resources After Eight Years.

Background and objective The internet has become a major resource of information for cancer patients. However, the quality of these resources is variable, and a better understanding is needed to guide physicians as to how to best support patients in their online searches. We previously evaluated the quality of online breast cancer resources in 2011. Nearly a decade later, we aimed to assess the present quality of online breast cancer-related information and to compare our current analysis with data collected in 2011. Methods A list of 100 breast cancer websites was systematically compiled using meta-search engines Yippy and Dogpile and the search engine Google using the search term "breast cancer". Content accuracy and quality markers, including authorship, attribu-tion, currency, site organization, and readability were assessed by using a previously validated standardized rating tool. Results were analyzed using descriptive statistics and Fisher's exact test. The same strategy was used in both 2011 and 2019. Results When comparing 2011 data to the current one, 27% of websites had been updated in the previous two years in 2011 compared to 65% in 2019 (p<0.00001). Both data sets remained similar in terms of website disclosures and objectivity. Only 30% of websites analyzed in 2019 used two or more reliable sources, while 63% had no reliable sources or no sources cited. From 2011 to 2019, resources with readability above grade 12 increased from 4% to 30% (p<0.0001), while websites offering educational support rose from 8% to 35% (p<0.0001). In 2019, treatment and etiology/risk factors were the most accurately covered areas (64% and 63% of websites, respectively). In 2011, 63% of websites were found to be globally accurate. Prognosis coverage increased from 18% to 33% from 2011 to 2019 (p=0.02). In 2019, survivorship was also evaluated and found to be covered in only 24% of resources. Conclusion Over the past eight years, there have been variable changes in the quality of online breast cancer resources. Promisingly, websites are being updated more frequently and the educational support offered is expanding. Furthermore, there has been significant improvement in the coverage of prognosis, although this requires further progress. Unfortunately, websites are becoming increasingly challenging to understand for the average patient, and coverage of survivorship is lacking. Our study provides vital information to healthcare providers on these trends in online breast cancer resources and how to best support patients in their internet searches.

Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia.

PURPOSE: Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes. METHODS: This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up. RESULTS: Between January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57-1.40). There were no significant differences in secondary outcomes or complications. CONCLUSIONS: In patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.

Childhood trauma and psychiatric disorders as correlates of school dropout in a national sample of young adults.

The effect of childhood trauma, psychiatric diagnoses, and mental health services on school dropout among U.S.-born and immigrant youth is examined using data from the Collaborative Psychiatric Epidemiology Surveys, a nationally representative probability sample of African Americans, Afro-Caribbeans, Asians, Latinos, and non-Latino Whites, including 2,532 young adults, aged 21-29. The dropout prevalence rate was 16% overall, with variation by childhood trauma, childhood psychiatric diagnosis, race/ethnicity, and nativity. Childhood substance and conduct disorders mediated the relation between trauma and school dropout. Likelihood of dropout was decreased for Asians, and increased for African Americans and Latinos, compared to non-Latino Whites as a function of psychiatric disorders and trauma. Timing of U.S. immigration during adolescence increased risk of dropout.

Use and quality of mental health services for Haitian youth.

OBJECTIVE: To describe the mental health service use of Haitian, African-American, and non-Latino White youth in a community mental health setting. Groups are compared on adherence to treatment guidelines for attention-deficit/hyperactivity disorder (ADHD) and depressive disorders. DESIGN: Retrospective review of outpatient mental health charts (n = 252) from five community sites in an urban area of the Northeastern United States. We recorded the total number and treatment type of sessions during the first six months of treatment. Guideline-adherent treatments were compared and predicted after controlling for clinical need. RESULTS: Most Haitian and African-American youth stopped treatment by six months, with the majority attending less than eight sessions. One third of Haitian and African-American patients attended just one session. Haitian patients who presented with less severe symptoms and dysfunction were more likely to have single-session treatments. Guideline-adherent treatment for ADHD and depression was less likely for Haitians. Older patients were more likely to receive adequate depression treatment. Haitian youth were relatively underinsured, had more family separations documented, and received Adjustment Disorder diagnoses more often. CONCLUSIONS: Haitian youth use outpatient mental health services in similar proportion to African-American youth and at lower rates than White youth. Guideline-adherent treatment for ADHD and depression is limited by low retention in care for Black youth. Low insurance coverage is likely an important contributor to reduced use of services, especially for Haitians. These findings are discussed in the context of providing culturally sensitive mental health care to diverse communities.

Using the angle-dependent resonances of molded plasmonic crystals to improve the sensitivities of biosensors.

This paper describes how angle-dependent resonances from molded plasmonic crystals can be used to improve real-time biosensing. First, an inexpensive and massively parallel approach to create single-use, two-dimensional metal nanopyramidal gratings was developed. Second, although constant in bulk dielectric environments, the sensitivities (resonance wavelength shift and resonance width) of plasmonic crystals to adsorbed molecular layers of varying thickness were found to depend on incident excitation angle. Third, protein binding at dilute concentrations of protein was carried out at an angle that optimized the signal to noise of our plasmonic sensing platform. This angle-dependent sensitivity, which is intrinsic to grating-based sensors, is a critical parameter that can assist in maximizing signal to noise.

Professional knowledge creation in the hospital sector: a qualitative study in Taiwan.

This paper aims to develop a professional knowledge creation model for the hospital sector. For this purpose, we qualitatively explore the determinants and process of knowledge creation in the hospital sector. Drawing from organization theory, we develop a hospital's professional knowledge creation model and develop three propositions first. We further explore the theoretical model at organization level by case study in Taiwan. The findings suggest that the hospital's professional knowledge creation is influenced by knowledge stock, social ties and isomorphic pressures as propositions argued. However, hospitals' attempts to keep aligned with their highly institutionalized environments may pay more attention to both existing knowledge stock and the process of professional knowledge creation for their survival. Finally, it is hoped that the significances of this study will contribute to the development of hypotheses in the future quantitative study for building a generalized knowledge creation model for the hospital organization.

Lessons learned from the clinical reappraisal study of the Composite International Diagnostic Interview with Latinos.

Given recent adaptations of the World Health Organization's World Mental Health Composite International Diagnostic Interview (WMH-CIDI), new methodological studies are needed to evaluate the concordance of CIDI diagnoses with clinical diagnostic interviews. This paper summarizes lessons learned from a clinical reappraisal study done with US Latinos. We compare CIDI diagnoses with independent clinical diagnosis using the World Mental Health Structured Clinical Interview for DSM-IV (WMH-SCID 2000). Three sub-samples stratified by diagnostic status (CIDI positive, CIDI negative, or CIDI sub-threshold for a disorder) based on nine disorders were randomly selected for a telephone re-interview using the SCID. We calculated sensitivity, specificity, and weight-adjusted Cohen's kappa. Weighted 12 month prevalence estimates of the SCID are slightly higher than those of the CIDI for generalized anxiety disorder, alcohol abuse/dependence, and drug abuse/dependence. For Latinos, CIDI-SCID concordance at the aggregate disorder level is comparable, albeit lower, to other published reports. The CIDI does very well identifying negative cases and classifying disorders at the aggregate level. Good concordance was also found for major depressive episode and panic disorder. Yet, our data suggests that the CIDI presents problems for assessing post-traumatic stress disorder (PTSD) and generalized anxiety disorder (GAD). Recommendations on how to improve future versions of the CIDI for Latinos are offered.

Pathways and correlates connecting Latinos' mental health with exposure to the United States.

OBJECTIVES: We examined potential pathways by which time in the United States may relate to differences in the predicted probability of past-year psychiatric disorder among Latino immigrants as compared with US-born Latinos. METHODS: We estimated predicted probabilities of psychiatric disorder for US-born and immigrant groups with varying time in the United States, adjusting for different combinations of covariates. We examined 6 pathways by which time in the United States could be associated with psychiatric disorders. RESULTS: Increased time in the United States is associated with higher risk of psychiatric disorders among Latino immigrants. After adjustment for covariates, differences in psychiatric disorder rates between US-born and immigrant Latinos disappear. Discrimination and family cultural conflict appear to play a significant role in the association between time in the United States and the likelihood of developing psychiatric disorders. CONCLUSIONS: Increased perceived discrimination and family cultural conflict are pathways by which acculturation might relate to deterioration of mental health for immigrants. Future studies assessing how these implicit pathways evolve as contact with US culture increases may help to identify strategies for ensuring maintenance of mental health for Latino immigrants.

Nested Markov compliance class model in the presence of time-varying noncompliance.

SUMMARY: We consider a Markov structure for partially unobserved time-varying compliance classes in the Imbens-Rubin (1997, The Annals of Statistics 25, 305-327) compliance model framework. The context is a longitudinal randomized intervention study where subjects are randomized once at baseline, outcomes and patient adherence are measured at multiple follow-ups, and patient adherence to their randomized treatment could vary over time. We propose a nested latent compliance class model where we use time-invariant subject-specific compliance principal strata to summarize longitudinal trends of subject-specific time-varying compliance patterns. The principal strata are formed using Markov models that relate current compliance behavior to compliance history. Treatment effects are estimated as intent-to-treat effects within the compliance principal strata.

The effects of trust in physician on self-efficacy, adherence and diabetes outcomes.

Trust in physicians has been associated with a range of patient behaviors. However, previous research has not focused on the mechanisms by which trust affects health outcomes and mostly has made use of self-rated health. This study tested a theoretical model of variables influencing the relations of trust to both objective and self-rated health. We hypothesized that patients who trust their physicians more were likely to have stronger self-efficacy and outcome expectations. We expected this, in turn, to be associated with better treatment adherence and objective health outcomes. In addition, we hypothesized that highly trusting patients would be more likely to report better health status through enhanced self-efficacy. Data for this research came from a sample of 480 adult patients with type 2 diabetes in Taiwan. Patients completed measures of trust, self-efficacy, outcome expectations, adherence, and the SF-12 health survey. Objective outcomes, including body mass index, glycosylated hemoglobin, blood lipid, and diabetes-related complications, were assessed by follow-up chart review. The structural equation analyses which were implemented by LISREL VIII resulted in a proper solution that exhibited adequate fit. All hypothesized paths were statistically significant and in the predicted directions. The mediation roles of self-efficacy and outcome expectations were further confirmed by the results of structural equation modeling and bootstrap analyses. In the multivariate regression, although the relations of patient trust to blood lipid and self-rated health were confirmed, the direct link of trust to glycosylated hemoglobin was only significant in the bivariate model. This study clarifies the association of trust with different types of health outcomes and provides the empirical evidence that trust in physicians is associated with both self-rated health and therapeutic response. However, a more longitudinal study design is necessary to precisely determine both the strength and causality of these relationships.

The effect of a primary care practice-based depression intervention on mortality in older adults: a randomized trial.

BACKGROUND: Few studies have tested the effects of a depression intervention on the risk for death associated with depression. OBJECTIVE: To test whether an intervention to improve depression care can modify the risk for death. DESIGN: Practice-based, randomized, controlled trial. SETTING: 20 primary care practices in New York, New York, and Philadelphia and Pittsburgh, Pennsylvania. PATIENTS: 1226 randomly sampled patients identified through a 2-stage, age-stratified (60 to 74 years and > or =75 years) depression screening. INTERVENTION: Depression care manager working with primary care physicians to provide algorithm-based care. MEASUREMENTS: Depression status based on clinical interview and vital status at 5 years by using the National Death Index. RESULTS: At baseline, 396 patients met criteria for major depression and 203 patients met criteria for clinically significant minor depression. After a median follow-up of 52.8 months, 223 patients died. Patients with depression in intervention practices were less likely to have died than those in usual care practices (adjusted hazard ratio, 0.67 [95% CI, 0.44 to 1.00]). Risk for death was reduced in patients with major depression (adjusted hazard ratio, 0.55 [CI, 0.36 to 0.84]) but not in patients with clinically significant minor depression (adjusted hazard ratio, 0.97 [CI, 0.49 to 1.92]). The benefit seemed to be almost entirely attributable to a reduction in deaths due to cancer. LIMITATIONS: The mechanism for an effect on deaths due to cancer is unclear. Depression status, cause of death, and vital status might have been misclassified. CONCLUSIONS: Older primary care patients with major depression in practices that implemented depression care management were less likely to die over a 5-year period than were patients with major depression in usual care practices. The effect seemed to be limited to deaths due to cancer. The mechanism for such an effect is unclear and warrants further investigation. ClinicalTrials.gov registration number: NCT00000367.

How missing information in diagnosis can lead to disparities in the clinical encounter.

Previous studies have documented diagnostic bias and noted that its reduction could eliminate misdiagnosis and improve mental health service delivery. Few studies have investigated clinicians' methods of obtaining and using information during the initial clinical encounter. We describe a study examining contributions to clinician bias during diagnostic assessment of ethnic/racial minority patients. A total of 129 mental health intakes were videotaped, involving 47 mental health clinicians from 8 primarily safety-net clinics. Videos were coded by another clinician using an information checklist, blind to the diagnoses provided by the original clinician. We found high levels of concordance between clinicians for substance-related disorders, low levels for depressive disorders, and anxiety disorders except panic. Most clinicians rely on patients' mention of depression, anxiety, or substance use to identify disorders, without assessing specific criteria. With limited diagnostic information, clinicians can optimize the clinical intake time to establish rapport with patients. We found Latino ethnicity to be a modifying factor of the association between symptom reports and likelihood of a depression diagnosis. Differential discussion of symptom areas, depending on patient ethnicity, may lead to differential diagnosis and increased likelihood of diagnostic bias.