No effect of acute exposure to coarse particulate matter air pollution in a rural location on high-density lipoprotein function.

CONTEXT: High-density lipoprotein (HDL) particles perform numerous vascular-protective functions. Animal studies demonstrate that exposure to fine or ultrafine particulate matter (PM) can promote HDL dysfunction. However, the impact of PM on humans remains unknown. OBJECTIVE: We aimed to determine the effect of exposure to coarse concentrated ambient particles (CAP) on several metrics of HDL function in healthy humans. METHODS: Thirty-two adults (25.9 ± 6.6 years) were exposed to coarse CAP [76.2 ± 51.5 µg·m(-3)] in a rural location and filtered air (FA) for 2 h in a randomized double-blind crossover study. Venous blood collected 2- and 20-h post-exposures was measured for HDL-mediated efflux of [(3)H]-cholesterol from cells and 20-h exposures for HDL anti-oxidant capacity by a fluorescent assay and paraoxonase activity. The changes [median (first, third quartiles)] between exposures among 29 subjects with available results were compared by matched Wilcoxon tests. RESULTS: HDL-mediated cholesterol efflux capacity did not differ between exposures at either time point [16.60% (15.17, 19.19) 2-h post-CAP versus 17.56% (13.43, 20.98) post-FA, p = 0.768 and 14.90% (12.47, 19.15) 20-h post-CAP versus 17.75% (13.22, 23.95) post-FA, p = 0.216]. HOI [0.26 (0.24, 0.35) versus 0.28 (0.25, 0.40), p = 0.198] and paraoxonase activity [0.54 (0.39, 0.82) versus 0.60 µmol·min(-1 )ml plasma(-1) (0.40, 0.85), p = 0.137] did not differ 20-h post-CAP versus FA, respectively. CONCLUSIONS: Brief inhalation of coarse PM from a rural location did not acutely impair several facets of HDL functionality. Whether coarse PM derived from urban sites, fine particles or longer term PM exposures can promote HDL dysfunction warrant future investigations.

The effect of acute exposure to coarse particulate matter air pollution in a rural location on circulating endothelial progenitor cells: results from a randomized controlled study.

CONTEXT: Fine particulate matter (PM) air pollution has been associated with alterations in circulating endothelial progenitor cell (EPC) levels, which may be one mechanism whereby exposures promote cardiovascular diseases. However, the impact of coarse PM on EPCs is unknown. OBJECTIVE: We aimed to determine the effect of acute exposure to coarse concentrated ambient particles (CAP) on circulating EPC levels. METHODS: Thirty-two adults (25.9 ± 6.6 years) were exposed to coarse CAP (76.2 ± 51.5 µg m(-3)) in a rural location and filtered air (FA) for 2 h in a randomized double-blind crossover study. Peripheral venous blood was collected 2 and 20 h post-exposures for circulating EPC (n = 21), white blood cell (n = 24) and vascular endothelial growth factor (VEGF) (n = 16-19) levels. The changes between exposures were compared by matched Wilcoxon signed-rank tests. RESULTS: Circulating EPC levels were elevated 2 [108.29 (6.24-249.71) EPC mL(-1); median (25th-75th percentiles), p = 0.052] and 20 h [106.86 (52.91-278.35) EPC mL(-1), p = 0.008] post-CAP exposure compared to the same time points following FA [38.47 (0.00-84.83) and 50.16 (0.00-104.79) EPC mL(-1)]. VEGF and white blood cell (WBC) levels did not differ between exposures. CONCLUSIONS: Brief inhalation of coarse PM from a rural location elicited an increase in EPCs that persisted for at least 20 h. The underlying mechanism responsible may reflect a systemic reaction to an acute "endothelial injury" and/or a circulating EPC response to sympathetic nervous system activation.

Antibiotic prescription patterns among US general dentists and periodontists.

BACKGROUND: In the absence of a full spectrum of evidence-based guidelines for the appropriate use of antimicrobial agents, dentists, including periodontists, remain a highly frequent antibiotic prescribing group. With the goal of understanding antibiotic prescribing practices, the authors surveyed a convenience sample of dental practitioners and periodontists to identify differences between the 2 cohorts and assess the factors that affect prescribing practices. METHODS: An institutional review board-approved 15-item survey was developed to capture antibiotic prescribing practices addressing the main research question, factors affecting systemic antibiotic prescription patterns, and prescription timing. The authors collaborated with the American Dental Association (ADA) and the American Academy of Periodontology (AAP) for survey dissemination. Responses were summarized using descriptive statistics. Multivariable models were developed to identify antibiotic prescription predictors. RESULTS: Overall, 32.4% of the participants prescribed systemic antibiotics with scaling and root planing. When comparing the 2 groups, the authors found that 46.4% and 18.7% of the AAP and ADA members, respectively, prescribed systemic antibiotics with scaling and root planing (P = .0001). The authors found a significant difference between the AAP and ADA groups in prescription timing (P = .01). The multivariable model revealed that practitioner sex (P = .03), AAP membership (P = .0001), and years of practitioner experience (P = .04) predicted antibiotic prescription practices. The geographic location, practice setting, and occupation type did not predict antibiotic prescription patterns. CONCLUSION: The authors found a lack of clarity related to prescription timing, factors determining prescription patterns, and selection of patient population who would benefit more from antibiotics. PRACTICAL IMPLICATIONS: This study confirmed a lack of clarity related to antibiotic prescription patterns in combination with nonsurgical periodontal treatment.

Impact of long-term administration of maralixibat on children with cholestasis secondary to Alagille syndrome.

There is growing interest in, but limited data about, intestinal bile acid transport inhibitors as treatment for cholestatic liver disease. The current analyses combine two similar randomized placebo-controlled trials with subsequent extension phases investigating the impact of maralixibat in children with severe cholestasis secondary to Alagille Syndrome (n = 57). The primary outcomes were measures of pruritus (ItchRO[Obs]) and clinician scratch scale (CSS), both increasing in severity from 0 to 4) and quality of life (QoL) (Parent PedsQL and Multidimensional Fatigue Scale module [MFS] scaled 0-100 with increased QoL) at week 48 of the extension phase relative to the baseline of the placebo-controlled trials (week 13). Secondary assessments included other clinical and biochemical parameters assessed in participants at week 72 or end of treatment (after week 48). At week 48, statistically and clinically significant least square mean (95% CI) improvements in pruritus and QoL were observed (ItchRO[Obs] -1.59 [-1.81, -1.36], CSS -1.36 [-1.67, -1.05], PedsQL +10.17 [4.48, 15.86], and multidimension fatigue [MFS] +13.97 [7.85, 20.08]). At week 48, serum bile acids, platelet count, and cholesterol decreased, whereas alanine aminotransferase (ALT) increased and total bilirubin (TB) and albumin were stable. Changes were durable at week 72 and end of treatment. There were no deaths; 2 participants underwent liver transplantation. Study drug was discontinued in 9 participants after treatment-emergent adverse events, 6 of which were events of increased ALT or TB. Conclusion: Maralixibat administration was associated with marked improvement in pruritus and QoL. Interpretation of these findings is complicated by the complex natural history of severe cholestasis in Alagille syndrome.

Lymphocyte subset abnormalities in early diffuse cutaneous systemic sclerosis.

BACKGROUND: Abnormalities in lymphocyte surface markers and functions have been described in systemic sclerosis (SSc), but conflicting results abound, and these studies often examined patients with heterogeneous disease duration, severity, clinical phenotype, and concurrent immunosuppressive agents. We studied a clinically homogeneous group of early diffuse cutaneous SSc patients not exposed to immunosuppressive drugs who were enrolled in a clinical trial and compared their immune parameters to healthy control subjects. METHODS: Lymphocyte subsets were enumerated by multi-parameter flow cytometry of peripheral blood mononuclear cells at baseline visit. Production of the cytokines IL-4 and IL-17 was measured by intracellular flow cytometry following T cell activation. RESULTS: SSc patients had increased percentages of CD4+ T cells but lower percentages of CD8+ T cells versus controls. The CD28-negative population was expanded in SSc, in the CD4 subset. Striking expansion of CD319+ T cells was noted among the CD4+ cells, in which they were barely detectable in healthy subjects. Frequencies of IL-4 producing cells did not differ between SSc and controls, but expansion of IL-17 producing cells was observed in SSc. A higher proportion of CD319+ cells produced cytokines, compared to other CD4+ cells. Numbers of activated T cells, regulatory T cells, and B cells were similar in SSc and control groups. Circulating follicular helper but not peripheral helper T cells were slightly expanded in SSc. CONCLUSION: In this carefully selected group of early diffuse cutaneous SSc patients, analysis of immune cell parameters has identified abnormalities that likely reflect disease pathogenesis and that are candidate biomarkers for sub-classification and targeted treatment. The CD4+CD319+ (SLAM-F7+) cells are cytotoxic and oligoclonal, were recently shown to be a dominant T cell population in perivascular lymphocytic infiltrates in SSc skin, actively secrete cytokines, and are emerging as a target for novel treatments of SSc.

Caregiver Health-Related Quality of Life, Burden, and Patient Outcomes in Ambulatory Advanced Heart Failure: A Report From REVIVAL.

Background Heart failure (HF) imposes significant burden on patients and caregivers. Longitudinal data on caregiver health-related quality of life (HRQOL) and burden in ambulatory advanced HF are limited. Methods and Results Ambulatory patients with advanced HF (n=400) and their participating caregivers (n=95) enrolled in REVIVAL (Registry Evaluation of Vital Information for VADs [Ventricular Assist Devices] in Ambulatory Life) were followed up for 24 months, or until patient death, left ventricular assist device implantation, heart transplantation, or loss to follow-up. Caregiver HRQOL (EuroQol Visual Analog Scale) and burden (Oberst Caregiving Burden Scale) did not change significantly from baseline to follow-up. At time of caregiver enrollment, better patient HRQOL by Kansas City Cardiomyopathy Questionnaire was associated with better caregiver HRQOL (P=0.007) and less burden by both time spent (P<0.0001) and difficulty (P=0.0007) of caregiving tasks. On longitudinal analyses adjusted for baseline values, better patient HRQOL (P=0.034) and being a married caregiver (P=0.016) were independently associated with better caregiver HRQOL. Patients with participating caregivers (versus without) were more likely to prefer left ventricular assist device therapy over time (odds ratio, 1.43; 95% CI, 1.03-1.99; P=0.034). Among patients with participating caregivers, those with nonmarried (versus married) caregivers were at higher composite risk of HF hospitalization, death, heart transplantation or left ventricular assist device implantation (hazard ratio, 2.99; 95% CI, 1.29-6.96; P=0.011). Conclusions Patient and caregiver characteristics may impact their HRQOL and other health outcomes over time. Understanding the patient-caregiver relationship may better inform medical decision making and outcomes in ambulatory advanced HF.

Quality of life and treatment preference for ventricular assist device therapy in ambulatory advanced heart failure: A report from the REVIVAL study.

BACKGROUND: The Registry Evaluation of Vital Information for Ventricular Assist Devices (VADs) in Ambulatory Life study is a prospective multicenter cohort of 400 ambulatory patients with advanced chronic systolic heart failure (HF). The aim of the study is to better understand disease trajectory and optimal timing of advanced HF therapies. We examined patient health-related quality of life (HRQOL) data collected at enrollment and their association with patient treatment preferences for VAD placement. METHODS: Baseline assessment of HRQOL included the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQol EQ-5D-3L Visual Analogue Scale (VAS), along with patient self-assessment of remaining life (PSARL). Descriptive statistics were used to present baseline HRQOL data and Spearman correlation tests to assess the association between KCCQ, VAS, and VAD treatment preference with patient clinical characteristics of interest. RESULTS: The median age was 60 years, 75% were male, and the median left ventricular ejection fraction was 20%. The median (25th percentile, 75th percentile), baseline KCCQ summary score was 64 (48, 78), VAS score 65 (50, 75), and PSARL 7 years (5, 10). There were statistically significant associations of baseline KCCQ and VAS with New York Heart Association class and Interagency Registry of Mechanically Assisted Circulatory Support profile (p < 0.005 for all comparisons). Baseline KCCQ and VAS revealed a modest association with PSARL (correlation = 0.45 and 0.35, respectively; p < 0.001), and many patients were overly optimistic about their expected survival. VAD treatment preference was associated with KCCQ scores (p < 0.031), but the absolute differences were small. VAD treatment preference was independent of other key clinical characteristics such as subject age, VAS, and PSARL. CONCLUSIONS: We found a lack of strong association between HRQOL and patient preference for VAD therapy. Better understanding of patients' perceptions of their illness and how this relates to HRQOL outcomes, clinician risk assessment, and patient decision-making is needed. This may in turn allow better guidance toward available HF therapies in this vulnerable population.

Ambulatory Advanced Heart Failure in Women: A Report From the REVIVAL Registry.

OBJECTIVES: This study sought to explore clinical characteristics and outcomes in women and men with ambulatory advanced heart failure (HF). BACKGROUND: Women have been underrepresented in studies of advanced HF and have an increased mortality on the transplant waiting list and early after mechanical circulatory support (MCS). An increased understanding of the differential burden of HF between women and men is required to inform the use of mechanical circulatory support in ambulatory advanced HF patients. METHODS: REVIVAL (Registry Evaluation for Vital Information on Ventricular Assist Devices in Ambulatory Life) is a prospective, observational study of 400 outpatients with chronic systolic HF, New York Heart Association functional class II to IV, and 1 additional high-risk feature. Clinical characteristics, quality of life, and functional capacity were compared between women and men, as was a primary composite endpoint of death, durable MCS, or urgent heart transplantation at 1 year. RESULTS: REVIVAL enrolled 99 women (25% of the cohort) who had similar age, ejection fraction, INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profiles, medication use, and willingness to consider MCS as the men enrolled; however, women reported significantly greater limitations in quality of life with respect to physical limitation, reduced 6-min walk distance, and more frequent symptoms of depression. Nevertheless, 1-year combined risk of death, durable MCS, or urgent transplantation did not differ between women and men (24% vs. 22%; p = 0.94). CONCLUSIONS: This study represents the largest report to date of women with ambulatory advanced HF receiving contemporary therapies. Systematic elicitation of patient-reported outcome measures uncovered an added burden of HF in women and may be an appropriate target of augmented support and intervention.

Reduction of personal PM2.5 exposure via indoor air filtration systems in Detroit: an intervention study.

The adverse health effects of fine particulate matter (PM < 2.5 µm in diameter [PM2.5]) air pollution are well-documented. There is a growing body of evidence that high-efficiency particulate arrestance (HEPA) filtration can reduce indoor PM2.5 concentrations and deliver some health benefits via the reduction of exposure to PM. However, few studies have tested the ability of portable air filtration systems to lower overall personal-level PM2.5 exposures. The Reducing Air Pollution in Detroit Intervention Study (RAPIDS) was designed to evaluate cardiovascular health benefits and personal PM2.5 exposure reductions via indoor portable air filtration systems among senior citizens in Detroit, Michigan. We evaluated the utility of two commercially available high-efficiency (HE: true-HEPA) and low-efficiency (LE: HEPA-type) indoor air filtration to reduce indoor PM2.5 concentrations and personal PM2.5 exposures for 40 participants in a double-blinded randomized crossover intervention. Each participant was subjected to three intervention scenarios: HE, LE, or no filter (control) of three consecutive days each, during which personal, indoor, and outdoor PM2.5 concentrations were measured daily. For mean indoor PM2.5 concentrations, we observed 60 and 52% reductions using HE and LE filters, respectively, relative to no filtration. Personal PM2.5 exposures were reduced by 53 and 31% using HE and LE filters, respectively, when compared with the control scenario. To our knowledge, this is the first indoor air filtration intervention study to examine the effectiveness of both HE and LE filters in reducing personal PM2.5 exposures.

Preventing Early Renal Loss in Diabetes (PERL) Study: A Randomized Double-Blinded Trial of Allopurinol-Rationale, Design, and Baseline Data.

OBJECTIVE: Higher serum uric acid (SUA) is associated with diabetic kidney disease (DKD). Preventing Early Renal Loss in Diabetes (PERL) evaluates whether lowering SUA with allopurinol slows glomerular filtration rate (GFR) loss in people with type 1 diabetes (T1D) and mild to moderate DKD. We present the PERL rationale, design, and baseline characteristics. RESEARCH DESIGN AND METHODS: This double-blind, placebo-controlled, multicenter trial randomized 530 participants with T1D, estimated GFR (eGFR) of 40-99.9 mL/min/1.73 m2, SUA ≥4.5 m/dL, and micro- to macroalbuminuric DKD or normoalbuminuria with declining kidney function (NDKF) (defined as historical eGFR decline ≥3 mL/min/1.73 m2/year) to allopurinol or placebo. The primary outcome is baseline-adjusted iohexol GFR (iGFR) after 3 years of treatment plus a 2-month washout period. RESULTS: Participants are 66% male and 84% white. At baseline, median age was 52 years and diabetes duration was 35 years, 93% of participants had hypertension, and 90% were treated with renin-angiotensin system inhibitors (median blood pressure 127/71 mmHg). Median HbA1c was 8%, SUA 5.9 mg/dL, iGFR 68 mL/min/1.73 m2, and historical eGFR slope -3.5 mL/min/1.73 m2/year. Compared with participants with albuminuria (n = 419), those with NDKF (n = 94) were significantly older (56 vs. 52 years), had lower HbA1c (7.7 vs. 8.1%) and SUA (5.4 vs. 6.0 mg/dL), and had higher eGFR (82 vs. 74 mL/min/1.73 m2) and historical eGFR loss (-4.7 vs. -2.5 mL/min/1.73 m2/year). These differences persisted when comparing groups with similar rates of historical eGFR loss. CONCLUSIONS: PERL will determine the effect of allopurinol on mild to moderate DKD in T1D, with or without albuminuria. Participants with normoalbuminuria and rapid GFR loss manifested many DKD risk factors of those with albuminuria, but with less severity.

Effect of Portable Air Filtration Systems on Personal Exposure to Fine Particulate Matter and Blood Pressure Among Residents in a Low-Income Senior Facility: A Randomized Clinical Trial.

Importance: Fine particulate matter (smaller than 2.5 µm) (PM2.5) air pollution is a major global risk factor for cardiovascular (CV) morbidity and mortality. Few studies have tested the benefits of portable air filtration systems in urban settings in the United States. Objective: To investigate the effectiveness of air filtration at reducing personal exposures to PM2.5 and mitigating related CV health effects among older adults in a typical US urban location. Design, Setting, and Participants: This randomized, double-blind crossover intervention study was conducted from October 21, 2014, through November 4, 2016, in a low-income senior residential building in Detroit, Michigan. Forty nonsmoking older adults were enrolled, with daily CV health outcome and PM2.5 exposure measurements. Interventions: Participants were exposed to the following three 3-day scenarios separated by 1-week washout periods: unfiltered air (sham filtration), low-efficiency (LE) high-efficiency particulate arrestance (HEPA)-type filtered air, and high-efficiency (HE) true-HEPA filtered air using filtration systems in their bedroom and living room. Main Outcomes and Measures: The primary outcome was brachial blood pressure (BP). Secondary outcomes included aortic hemodynamics, pulse-wave velocity, and heart rate variability. Exposures to PM2.5 were measured in the participants' residences and by personal monitoring. Results: The 40 participants had a mean (SD) age of 67 (8) years (62% men). Personal PM2.5 exposures were significantly reduced by air filtration from a mean (SD) of 15.5 (10.9) µg/m3 with sham filtration to 10.9 (7.4) µg/m3 with LE fitration and 7.4 (3.3) µg/m3 with HE filtration. Compared with sham filtration, any filtration for 3 days decreased brachial systolic and diastolic BP by 3.2 mm Hg (95% CI, -6.1 to -0.2 mm Hg) and 1.5 mm Hg (95% CI, -3.3 to 0.2 mm Hg), respectively. A continuous decrease occurred in systolic and diastolic BP during the 3-day period of LE filtration, with a mean of 3.4 mm Hg (95% CI, -6.8 to -0.1 mm Hg) and 2.2 mm Hg (95% CI, -4.2 to -0.3 mm Hg), respectively. For HE filtration, systolic and diastolic BP decreased by 2.9 mm Hg (95% CI, -6.2 to 0.5 mm Hg) and 0.8 mm Hg (95% CI, -2.8 to 1.2 mm Hg), respectively. Most secondary outcomes were not significantly improved. Conclusions and Relevance: Results of this study showed that short-term use of portable air filtration systems reduced personal PM2.5 exposures and systolic BP among older adults living in a typical US urban location. The use of these relatively inexpensive systems is potentially cardioprotective against PM2.5 exposures and warrants further research. Trial Registration: ClinicalTrials.gov identifier: NCT03334565.

A Collaborative, Network-Based Approach to Advance Women's Depression Research in the United States: Preliminary Findings.

OBJECTIVE: Translation of women's mental health research has yet to impact overall prevalence and burden of Mood Disorders in the United States. The lack of standard measures and methodological coordination across studies has contributed to the slow impact of research on outcomes. The primary aims of this project were to demonstrate the process by which multiple investigators, sites, and settings administered a standard women's mental health questionnaire within a new Women's Depression Network. Information on the prevalence of mental health and service use across sites is provided. METHODS: A standard women's mental health questionnaire was developed and administered across seven different women's health sites in the United States. Validated measures of depression and anxiety were included (Patient Health Questionnaire Depression Scale [PHQ-9] and Generalized Anxiety Disorder Scale [GAD-7]). Administration of the questionnaire was embedded into existing clinical or research activities at each site. RESULTS: Data from 1,316 women were collected from seven sites over 12 months. A total of 14% and 15% of the women scored at or above the cutoff on the PHQ-9 and GAD-7 respectively. Just over half of the women screening positive for either depression or anxiety reported current treatment use. CONCLUSIONS: Findings suggest that coordination and administration of a standard women's mental health questionnaire is feasible across multiple settings and sites. Results highlight a low percentage of treatment use across various settings. The infrastructure developed for this study sets the stage for hypothesis-driven studies that can facilitate coordinated, network-based research that has the potential to accelerate advances in the field.

Inflammation, Active Fibroplasia, and End-stage Fibrosis in 172 Biliary Atresia Remnants Correlate Poorly With Age at Kasai Portoenterostomy, Visceral Heterotaxy, and Outcome.

Published histologic studies of the hilar plate or entire biliary remnant at the time of Kasai portoenterostomy (KHPE) have not provided deep insight into the pathogenesis of biliary atresia, relation to age at surgery, prognosis or the basis for successful drainage. We report detailed histologic findings in 172 centrally reviewed biliary remnants with an average of 6 sections per subject. Active lesions were classified as either necroinflammatory (rare/clustered in a few subjects) or active concentric fibroplasia with or without inflammation (common). Inactive lesions showed bland replacement by collagen and fibrous cords with little or no inflammation. Heterogeneity was common within a given remnant; however, relatively homogenous histologic patterns, defined as 3 or more inactive or active levels in the hepatic ducts levels, characterized most remnants. Homogeneity did not correlate with age at KHPE, presence/absence of congenital anomalies at laparotomy indicative of heterotaxy and outcome. Remnants from youngest subjects were more likely than older subjects to be homogenously inactive suggesting significantly earlier onset in the youngest subset. Conversely remnants from the oldest subjects were often homogenously active suggesting later onset or slower progression. More data are needed in remnants from subjects <30 days old at KHPE and in those with visceral anomalies. Prevalence of partially preserved epithelium in active fibroplastic biliary atresia lesions at all ages suggests that epithelial regression or injury may not be a primary event or that reepithelialization is already underway at the time of KHPE. We hypothesize that outcome after KHPE results from competition between active fibroplasia and reepithelialization of retained, collapsed but not obliterated lumens. The driver of active fibroplasia is unknown.

A naturalistic, multi-site study of repetitive transcranial magnetic stimulation therapy for depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) was approved in 2008 in the United States, and there are relatively few studies describing its use in regular clinical practice since approval. METHODS: From April 2011 to October 2014, ten sites within the National Network of Depression Centers (NNDC) provided data on 62 evaluable patients with a depressive episode. Treatment was determined naturalistically. Response was assessed by the Quick Inventory of Depressive Symptoms, Self-Report (QIDS-SR) as the primary outcome, and the Patient Health Questionnaire-9 (PHQ-9) and the clinician-rated Clinical Global Impression (CGI) as secondary depression measures. RESULTS: Enrolled patients exhibited significant treatment resistance, with 70.2% reporting more than 4 prior depressive episodes. Most patients received treatment with standard parameters (10Hz over the left dorsolateral prefrontal cortex), although 22.6% of the patients received 1 or 5Hz stimulation at some point. Over 6 weeks of treatment, response and remission rates were 29.4% and 5.9%, respectively, for the QIDS-SR; 39.2% and 15.7%, respectively, for the PHQ-9; and 50.9% and 17.9%, respectively, for the CGI. Moderator analyses revealed no effect of prior depressive episodes, history of ECT or gender, although early life stress predicted a better response to rTMS therapy. LIMITATIONS: The study was an open-label, registry trial, with relatively coarse clinical data, reflecting practice only in academic, depression-specialty centers. Because of the relatively small size and heterogeneity of the sample, type 2 errors are possible and positive findings are in need of replication. CONCLUSION: rTMS demonstrates effectiveness in clinical practice within the NNDC, although remission rates appear slightly lower in comparison with other recent naturalistic studies.

Acute increase in blood pressure during inhalation of coarse particulate matter air pollution from an urban location.

Particulate matter (PM) air pollution is a leading global risk factor for cardiovascular mortality. Although exposure to fine PM <2.5 µm raises arterial blood pressure (BP), few studies have evaluated the impact of coarse PM which differs in size (2.5-10 µm), sources, and chemistry. Twenty-nine healthy adults (30.4 ± 8.2 years) underwent a randomized double-blind crossover study involving 2-hour exposures to concentrated ambient coarse PM (164.2 ± 80.4 µg/m(3)) at an urban location (Dearborn, Michigan) versus filtered air. Cardiovascular outcomes were measured during, immediately, and 2 hours after exposures. Both systolic (1.9 mm Hg; 95% confidence interval: 0.96, 2.8; P < .001) and diastolic (1.9 mm Hg; 95% confidence interval: 1.1, 2.7; P < .001) BP levels were higher throughout coarse PM compared with filtered air exposures by mixed-model analyses. Heart rate variability, endothelial function, and arterial compliance were not significantly affected. Brief exposure to coarse PM in an urban environment raises arterial BP. These findings add mechanistic support to the contention that coarse PM may be capable of promoting cardiovascular events.

Key Histopathologic Features of Liver Biopsies That Distinguish Biliary Atresia From Other Causes of Infantile Cholestasis and Their Correlation With Outcome: A Multicenter Study.

The liver biopsy guides diagnostic investigation and therapy in infants with undiagnosed cholestasis. Histologic features in the liver may also have prognostic value in the patient with biliary atresia (BA). We assessed the relative value of histologic features in 227 liver needle biopsies in discriminating between BA and other cholestatic disorders in infants enrolled in a prospective Childhood Liver Disease Research Network (ChiLDReN) cohort study by correlating histology with clinical findings in infants with and without BA. In addition, we reviewed 316 liver biopsies from clinically proven BA cases and correlated histologic features with total serum bilirubin 6 months after hepatoportoenterostomy (the Kasai procedure, HPE) and transplant-free survival up to 6 years. Review pathologists were blinded to clinical information except age. Semiquantitative scoring of 26 discrete histologic features was based on consensus. Bile plugs in portal bile ducts/ductules, moderate to marked ductular reaction, and portal stromal edema had the largest odds ratio for predicting BA versus non-BA by logistic regression analysis. The diagnostic accuracy of the needle biopsy was estimated to be 90.1% (95% confidence interval [CI]: 85.2%, 94.9%), whereas sensitivity and specificity for a diagnosis of BA are 88.4% (95% CI: 81.4, 93.5) and 92.7% (95% CI: 84.8, 97.3), respectively. No histologic features were associated with an elevated serum bilirubin 6 months after HPE, although it (an elevated serum bilirubin) was associated with an older age at HPE. Higher stages of fibrosis, a ductal plate configuration, moderate to marked bile duct injury, an older age at HPE, and an elevated international normalized ratio were independently associated with a higher risk of transplantation.

The characteristics of coarse particulate matter air pollution associated with alterations in blood pressure and heart rate during controlled exposures.

Although fine particulate matter (PM) air pollution <2.5 µm in aerodynamic diameter (PM2.5) is a leading cause of global morbidity and mortality, the potential health effects of coarse PM (2.5-10 µm in aerodynamic diameter; PM10-2.5) remain less clearly understood. We aimed to elucidate the components within coarse PM most likely responsible for mediating these hemodynamic alterations. Thirty-two healthy adults (25.9 ± 6.6 years) were exposed to concentrated ambient coarse PM (CAP) (76.2 ± 51.5 µg/m(3)) and filtered air (FA) for 2 h in a rural location in a randomized double-blind crossover study. The particle constituents (24 individual elements, organic and elemental carbon) were analyzed from filter samples and associated with the blood pressure (BP) and heart rate (HR) changes occurring throughout CAP and FA exposures in mixed model analyses. Total coarse PM mass along with most of the measured elements were positively associated with similar degrees of elevations in both systolic BP and HR. Conversely, total PM mass was unrelated, whereas only two elements (Cu and Mo) were positively associated with and Zn was inversely related to diastolic BP changes during exposures. Inhalation of coarse PM from a rural location rapidly elevates systolic BP and HR in a concentration-responsive manner, whereas the particulate composition does not appear to be an important determinant of these responses. Conversely, exposure to certain PM elements may be necessary to trigger a concomitant increase in diastolic BP. These findings suggest that particulate mass may be an adequate metric of exposure to predict some, but not all, hemodynamic alterations induced by coarse PM mass.

Cardiovascular depression in rats exposed to inhaled particulate matter and ozone: effects of diet-induced metabolic syndrome.

BACKGROUND: High ambient levels of ozone (O3) and fine particulate matter (PM2.5) are associated with cardiovascular morbidity and mortality, especially in people with preexisting cardiopulmonary diseases. Enhanced susceptibility to the toxicity of air pollutants may include individuals with metabolic syndrome (MetS). OBJECTIVE: We tested the hypothesis that cardiovascular responses to O3 and PM2.5 will be enhanced in rats with diet-induced MetS. METHODS: Male Sprague-Dawley rats were fed a high-fructose diet (HFrD) to induce MetS and then exposed to O3, concentrated ambient PM2.5, or the combination of O3 plus PM2.5 for 9 days. Data related to heart rate (HR), HR variability (HRV), and blood pressure (BP) were collected. RESULTS: Consistent with MetS, HFrD rats were hypertensive and insulin resistant, and had elevated fasting levels of blood glucose and triglycerides. Decreases in HR and BP, which were found in all exposure groups, were greater and more persistent in HFrD rats compared with those fed a normal diet (ND). Coexposure to O3 plus PM2.5 induced acute drops in HR and BP in all rats, but only ND rats adapted after 2 days. HFrD rats had little exposure-related changes in HRV, whereas ND rats had increased HRV during O3 exposure, modest decreases with PM2.5, and dramatic decreases during O3 plus PM2.5 coexposures. CONCLUSIONS: Cardiovascular depression in O3- and PM2.5-exposed rats was enhanced and prolonged in rats with HFrD-induced MetS. These results in rodents suggest that people with MetS may be prone to similar exaggerated BP and HR responses to inhaled air pollutants.

Long-term exposure to concentrated ambient PM2.5 increases mouse blood pressure through abnormal activation of the sympathetic nervous system: a role for hypothalamic inflammation.

BACKGROUND: Exposure to particulate matter≤2.5 µm in diameter (PM2.5) increases blood pressure (BP) in humans and animal models. Abnormal activation of the sympathetic nervous system may have a role in the acute BP response to PM2.5 exposure. The mechanisms responsible for sympathetic nervous system activation and its role in chronic sustenance of hypertension in response to PM2.5 exposure are currently unknown. OBJECTIVES: We investigated whether central nervous system inflammation may be implicated in chronic PM2.5 exposure-induced increases in BP and sympathetic nervous system activation. METHODS: C57BL/6J mice were exposed to concentrated ambient PM2.5 (CAPs) for 6 months, and we analyzed BP using radioactive telemetric transmitters. We assessed sympathetic tone by measuring low-frequency BP variability (LF-BPV) and urinary norepinephrine excretion. We also tested the effects of acute pharmacologic inhibitors of the sympathetic nervous system and parasympathetic nervous system. RESULTS: Long-term CAPs exposure significantly increased basal BP, paralleled by increases in LF-BPV and urinary norepinephrine excretion. The increased basal BP was attenuated by the centrally acting α2a agonist guanfacine, suggesting a role of increased sympathetic tone in CAPs exposure-induced hypertension. The increase in sympathetic tone was accompanied by an inflammatory response in the arcuate nucleus of the hypothalamus, evidenced by increased expression of pro-inflammatory genes and inhibitor kappaB kinase (IKK)/nuclear factor-kappaB (NF-κB) pathway activation. CONCLUSION: Long-term CAPs exposure increases BP through sympathetic nervous system activation, which may involve hypothalamic inflammation.