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.

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.

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.

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.

Establishing a data monitoring committee for clinical trials.

SUMMARY: A data monitoring committee (DMC) is a group of clinicians and biostatisticians appointed by study sponsors who provide independent assessment of the safety, scientific validity and integrity of clinical trials. In the United States, the Food and Drug Administration requires the formation of DMC in all trials that assess new interventions. DMC are also strongly recommended in other clinical studies that have substantial safety issues, that have double-blind treatment assignment or that are expected to have a major impact on clinical practice. They are important in clinical research in psychiatry because they provide an added layer of protection for the vulnerable populations that are often enrolled in such studies. This report describes the role, formation and operation of DMC.

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.

Consequences of radial artery harvest: results of a prospective, randomized, multicenter trial.

IMPORTANCE: To date, no study has defined the consequences of radial artery harvest based on a large number of patients in a prospective randomized trial. OBJECTIVE: To compare pain at the harvest site and functional changes associated with harvesting the radial artery vs saphenous vein for coronary artery bypass grafting. DESIGN, SETTING, AND PARTICIPANTS: This study compares the consequences of radial artery harvest with saphenous vein harvest in patients undergoing elective coronary artery bypass grafting procedures in Veterans Affairs hospitals. MAIN OUTCOMES AND MEASURES: Eleven hospitals screened 6148 patients, of whom 751 were included in this trial. We analyzed 2 variables: pain at the harvest site as measured on a scale of 0 to 100 (least to most painful) and hand performance testing. Patients included in this analysis had radial artery only (n = 80) or saphenous vein only (n = 337) harvest. Pain score, grip strength, and dexterity were measured before surgery and at 3 and 12 months after surgery. We adjusted for pain scores of the nonharvested extremity, age, whether the patient underwent endoscopic vein harvesting, and comorbid health conditions (smoking history, type 2 diabetes mellitus, hypertension, and heart failure). RESULTS: There was a significant difference in change of pain score at 3 months from the preoperative baseline between radial artery and saphenous vein groups after adjusting for covariates (P < .001) but not at 12 months (P = .07). No significant changes occurred in grip strength or dexterity from preoperative baseline to 3 and 12 months after surgery (P > .05). CONCLUSIONS AND RELEVANCE: The radial artery group reported significantly more pain than the saphenous vein group 3 months after surgery; however, similar levels of pain were observed in both groups at 12 months after surgery. Grip strength and manual dexterity were not changed by radial artery harvesting at 3 and 12 months.

Patient-clinician ethnic concordance and communication in mental health intake visits.

OBJECTIVE: This study examines how communication patterns vary across racial and ethnic patient-clinician dyads in mental health intake sessions and its relation to continuance in treatment, defined as attending the next scheduled appointment. METHODS: Observational study of communication patterns among ethnically/racially concordant and discordant patient-clinician dyads. Primary analysis included 93 patients with 38 clinicians in race/ethnic concordant and discordant dyads. Communication was coded using the Roter Interaction Analysis System (RIAS) and the Working Alliance Inventory Observer (WAI-O) bond scale; continuance in care was derived from chart reviews. RESULTS: Latino concordant dyad patients were more verbally dominant (p<.05), engaged in more patient-centered communication (p<.05) and scored higher on the (WAI-O) bond scale (all p<.05) than other groups. Latino patients had higher continuance rates than other patients in models that adjusted for non-communication variables. When communication, global affect, and therapeutic process variables were adjusted for, differences were reversed and white dyad patients had higher continuance in care rates than other dyad patients. CONCLUSION: Communication patterns seem to explain the role of ethnic concordance for continuance in care. PRACTICE IMPLICATIONS: Improve intercultural communication in cross cultural encounters appears significant for retaining minorities in care.

What factors are associated with myopia in young adults? A survey study in Taiwan Military Conscripts.

PURPOSE: We investigated the independent impact of potential risk factors on myopia in young adults. METHODS: A survey study was conducted with male military conscripts aged 18 to 24 years between February 2010 and March 2011 in Taiwan. The participants were examined using non-cycloplegic autorefraction and biometry. The participants provided data about potential risk factors, including age, parental myopia, education, near work, outdoor activity, and urbanization. Myopia was defined as the mean spherical equivalent of the right eye of ≤ 0.5 diopters (D). RESULTS: Among 5145 eligible participants, 5048 (98.11%) had refraction and questionnaire data available; 2316 (45.88%) of these received axial length examination. The prevalence of myopia was 86.1% with a mean refractive error of -3.66 D (SD = 2.73) and an axial length of 25.40 mm (SD = 1.38). Older age, having myopic parents, higher education level, more time spent reading, nearer reading distance, less outdoor activity, and higher urbanization level were associated with myopia and longer axial length. More computer use was related to longer axial length. All risk factors associated with myopia also were predictors of high myopia (≤ -6.0 D), with the exception of outdoor activity. Finally, an interaction analysis showed shorter axial length was associated with more time spent outdoors only at high urbanization level. CONCLUSIONS: Older age, parental myopia, higher education level, more near work, less outdoor activity, and higher urbanization level were independent predictors of myopia. These data provided evidence to the multifactorial nature of myopia in young men in Taiwan.

Diagnostic validity across racial and ethnic groups in the assessment of adolescent DSM-IV disorders.

We examine differential validity of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnoses assessed by the fully-structured Composite International Diagnostic Interview Version 3.0 (CIDI) among Latino, non-Latino Black, and non-Latino White adolescents in comparison to gold standard diagnoses derived from the Schedule for Affective Disorders and Schizophrenia for School-age Children (K-SADS). Results are based on the National Comorbidity Survey Replication Adolescent Supplement, a national US survey of adolescent mental health. Clinicians re-interviewed 347 adolescent/parent dyads with the K-SADS. Sensitivity and/or specificity of CIDI diagnoses varied significantly by ethnicity/race for four of ten disorders. Modifications to algorithms sometimes reduced bias in prevalence estimates, but at the cost of reducing individual-level concordance. These findings document the importance of assessing fully-structured diagnostic instruments for differential accuracy in ethnic/racial subgroups.

Role of referrals in mental health service disparities for racial and ethnic minority youth.

OBJECTIVE: To investigate racial/ethnic differences in teachers' and other adults' identification and/or encouragement of parents to seek treatment for psychiatric problems in their children and to evaluate if and whether identification/encouragement is associated with service use. METHOD: Data on identification/encouragement to seek treatment for externalizing disorders (i.e., attention-deficit/hyperactivity disorder, oppositional-defiant disorder, and/or conduct disorder) and internalizing disorders (i.e., major depressive episode/dysthymia and/or separation anxiety disorder) and services used were obtained for 6,112 adolescents (13-17 years of age) in the National Comorbidity Survey Adolescent Supplement. Racial/ethnic differences were examined for Latinos, non-Latino blacks, and non-Latino whites. RESULTS: There were few racial/ethnic differences in rates of youth identification/encouragement and how identification/encouragement related to service use. Only non-Latino black youth with low severity internalizing disorders were less likely to be identified/encouraged to seek services compared with non-Latino white youth with the same characteristics (odds ratio [OR] = 0.4, 95% confidence interval [CI] = [0.2-0.7]). Identification/encouragement increased the likelihood of seeking services for externalizing and internalizing disorders for all youth. However, compared with their non-Latino white counterparts, non-Latino black youth who met criteria for internalizing disorders appeared less likely to have used any services (OR = 0.4, 95%, CI = 0.2-0.7), after adjusting for identification/encouragement, clinical, and sociodemographic characteristics. Non-Latino black youth with internalizing disorders and without identification/encouragement were less likely to use the specialty care sector than their non-Latino white counterparts. CONCLUSIONS: In this study of a nationally representative sample of adolescents, almost no ethnic/racial differences in identification/encouragement were found. However, identification/encouragement may increase service use for all youth.

The impact of insurance coverage in diminishing racial and ethnic disparities in behavioral health services.

OBJECTIVE: To estimate whether racial/ethnic behavioral health service disparities are likely to be reduced through insurance expansion coverage expected through the Affordable Health Care Act. DATA SOURCES: Pooled data from the nationally representative NIMH Collaborative Psychiatric Epidemiological Studies (2001-2003). STUDY DESIGN: We employ a novel reweighting method to estimate service disparities in the presence and absence of insurance coverage. DATA COLLECTION: Access to care was assessed by whether any behavioral health treatment was received in the past year. Need was determined by presence of prior year psychiatric disorder, psychiatric diagnoses, physical comorbidities, gender, and age. PRINCIPAL FINDINGS: Improving patient education and availability of community clinics, combined with insurance coverage reduces service disparities across racial/ethnic groups.However, even with expanded insurance coverage, approximately 10 percent fewer African Americans with need for behavioral health services are likely to receive services compared to non-Latino whites while Latinos show no measurable disparity. CONCLUSIONS: Expansion of insurance coverage might have different effects for racial/ethnic groups, requiring additional interventions to reduce disparities for all groups.

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.