Low dose inflammatory potential of silica particles in human-derived THP-1 macrophage cell culture studies - Mechanism and effects of particle size and iron.

Silica and iron are major constituents in ambient particulate matter, and iron is a common impurity in many engineered nanomaterials. The purpose of this work was to determine the pro-inflammatory and other biological effects and mechanism of particle size and iron presence under low dose, non-cytotoxic conditions that are likely to approximate actual exposure levels, in contrast with higher dose studies in which cytotoxicity occurs. Specifically, human-derived THP-1 macrophages were exposed to 1 μg/ml of pristine and iron-coated 50 nm and 2 μm engineered silica nanoparticles. Particles were first characterized for size, size distribution, surface area, iron concentration, phase and aggregation in cell culture media. Then, biological assays were conducted to determine a non-lethal dose used in subsequent experiments. Superoxide production, lipid peroxidation, and increased pro-inflammatory cytokine (TNF-α and IL-1β) mRNA expression were measured as a function of particle size and iron presence. Smaller particle size and the presence of iron increased superoxide production, lipid peroxidation, and the induction of pro-inflammatory cytokine mRNA expression. Separate addition of an iron-chelator, a scavenger of superoxide and hydrogen peroxide, and an inhibitor of phosphatidylcholine specific phospholipase C (PC-PLC), suppressed the increase in cytokine mRNA expression. Furthermore, free iron itself showed none of the aforementioned effects. The results highlight the importance of particle size and iron in lung inflammation for both natural and engineered nanomaterials, under low dose, non-toxic conditions, and support the role of an oxidant, lipid peroxidation and PC-PLC dependent inflammatory mechanism

A Therapist-guided Smartphone App for Major Depression in Young Adults: A Randomized Clinical Trial

Background: Meru Health Program (MHP) is a therapist-guided, 8-week intervention for depression delivered via smartphone. The aim was to test its efficacy in patients with clinical depression in a Finnish university student health service. Methods: Patients (n=124, women 72.6%, mean age 25y) were stratified based on antidepressant status, and randomized into intervention group receiving MHP plus treatment as usual (TAU), and control group receiving TAU only. Depression, measured by the Patient Health Questionnaire-9 (PHQ-9) scale, was the primary outcome. After baseline (T0), follow-ups were at mid-intervention (T4), immediately post-intervention (T8); 3 months (T20), and 6 months (T32) post-intervention. Results: The intervention group and control group did not have significant differences in depression outcomes throughout end of treatment and follow-up. Among secondary outcomes, increase in resilience (d=0.32, p=0.03) and mindfulness (d=0.57, p=0.002), and reduction in perceived stress (d=-0.52, p=0.008) were greater in MHP+TAU versus TAU at T32; no differences were found in anxiety, sleep disturbances, and quality of life between groups. Post-hoc comparisons of patients on antidepressants showed significantly greater reduction in depression at T32 for MHP+TAU versus TAU (d=-0.73, p=0.01); patients not on antidepressants showed no between-group differences. Limitations: Limitations include unknown characteristics of TAU, potential bias from patients and providers not being blinded to treatment group, and failure to specify examination of differences by antidepressant status in the protocol. Conclusions: Most outcomes, including depression, did not significantly differ between MHP+TAU and TAU. Exploratory analysis revealed intervention effect at the end of the 6-month follow-up among patients on antidepressant medication.Background: Meru Health Program (MHP) is a therapist-guided, 8-week intervention for depression delivered via smartphone. The aim was to test its efficacy in patients with clinical depression in a Finnish university student health service.& nbsp; Methods: Patients (n=124, women 72.6%, mean age 25y) were stratified based on antidepressant status, and randomized into intervention group receiving MHP plus treatment as usual (TAU), and control group receiving TAU only. Depression, measured by the Patient Health Questionnaire-9 (PHQ-9) scale, was the primary outcome. After baseline (T0), follow-ups were at mid-intervention (T4), immediately post-intervention (T8); 3 months (T20), and 6 months (T32) post-intervention.& nbsp; Results: The intervention group and control group did not have significant differences in depression outcomes throughout end of treatment and follow-up. Among secondary outcomes, increase in resilience (d=0.32, p=0.03) and mindfulness (d=0.57, p=0.002), and reduction in perceived stress (d=-0.52, p=0.008) were greater in MHP+TAU versus TAU at T32; no differences were found in anxiety, sleep disturbances, and quality of life between groups. Post-hoc comparisons of patients on antidepressants showed significantly greater reduction in depression at T32 for MHP+TAU versus TAU (d=-0.73, p=0.01); patients not on antidepressants showed no between-group differences.& nbsp; Limitations: Limitations include unknown characteristics of TAU, potential bias from patients and providers not being blinded to treatment group, and failure to specify examination of differences by antidepressant status in the protocol.& nbsp; & nbsp;Conclusions: Most outcomes, including depression, did not significantly differ between MHP+TAU and TAU. Exploratory analysis revealed intervention effect at the end of the 6-month follow-up among patients on anti-depressant medication.Peer reviewe

Long-Term Outcomes of a Therapist-Supported, Smartphone-Based Intervention for Elevated Symptoms of Depression and Anxiety : Quasiexperimental, Pre-Postintervention Study

Background: Depression is one of the most common mental health disorders and severely impacts one's physical, psychological, and social functioning. To address access barriers to care, we developed Ascend-a smartphone-delivered, therapist-supported, 8-week intervention based on several evidence-based psychological treatments for depression and anxiety. A previous feasibility study with 102 adults with elevated depression reported that Ascend is associated with a postintervention reduction in depression symptoms. Objective: We aimed to examine whether Ascend is associated with a reduction in symptoms of anxiety, and importantly, whether reductions in symptoms of depression and anxiety are maintained up to 12-months postintervention. Methods: We assessed whether the previously reported, end-of-treatment improvements seen in the 102 adults with elevated symptoms of depression extended up to 12 months posttreatment for depression symptoms (measured by the Patient Health Questionnaire-9 [PHQ-9]) and up to 6 months posttreatment for anxiety symptoms (added to the intervention later and measured using the Generalized Anxiety Disorder-7 [GAD-7] scale). We used linear mixed effects models with Tukey contrasts to compare time points and reported intention-to-treat statistics with a sensitivity analysis. Results: The intervention was associated with reductions in symptoms of depression that were maintained 12 months after the program (6.67-point reduction in PHQ-9 score, 95% CI 5.59-7.75; P= 10) reported clinically significant improvement at the 12-month follow-up (at least 50% reduction in PHQ-9 score and postprogram score Conclusions: There is limited evidence on whether outcomes associated with smartphone-based interventions for common mental health problems are maintained posttreatment. Participants who enrolled in Ascend experienced clinically significant reductions in symptoms of depression and anxiety that were maintained for up to 1 year and 6 months after the intervention, respectively. Future randomized trials are warranted to test Ascend as a scalable solution to the treatment of depression and anxiety.Peer reviewe

Delayed Nrf2-regulated antioxidant gene induction in response to silica nanoparticles.

Silica nanoparticles with iron on their surface cause the production of oxidants and stimulate an inflammatory response in macrophages. Nuclear factor erythroid-derived 2 - like factor 2 (Nrf2) signaling and its regulated antioxidant genes play critical roles in maintaining redox homeostasis. In this study we investigated the regulation of four representative Nrf2-regulated antioxidant genes; i.e., glutamate cysteine ligase (GCL) catalytic subunit (GCLC), GCL modifier subunit (GCLM), heme oxygenase 1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO-1), by iron-coated silica nanoparticles (SiO2-Fe) in human THP-1 macrophages. We found that the expression of these four antioxidant genes was modified by SiO2-Fe in a time-dependent manner. At 6h, their expression was unchanged except for GCLC, which was reduced compared with controls. At 18h, the expression of these antioxidant genes was significantly increased compared with controls. In contrast, the Nrf2 activator sulforaphane induced all antioxidant genes at as early as 3h. The nuclear translocation of Nrf2 occurred later than that for NF-κB p65 protein and the induction of proinflammatory cytokines (TNFα and IL-1β). NF-κB inhibitor SN50 prevented the reduction of GCLC at 6h and abolished the induction of antioxidant genes at 18h by SiO2-Fe, but did not affect the basal and sulforaphane-induced expression of antioxidant genes, suggesting that NF-κB signaling plays a key role in the induction of Nrf2-mediated genes in response to SiO2-Fe. Consistently, SN50 inhibited the nuclear translocation of Nrf2 caused by SiO2-Fe. In addition, Nrf2 silencing decreased the basal and SiO2-induced expression of the four reprehensive antioxidant genes. Taken together, these data indicated that SiO2-Fe induced a delayed response of Nrf2-regulated antioxidant genes, likely through NF-κB-Nrf2 interactions

Feasibility and Efficacy of the Addition of Heart Rate Variability Biofeedback to a Remote Digital Health Intervention for Depression

A rise in the prevalence of depression underscores the need for accessible and effective interventions. The objectives of this study were to determine if the addition of a treatment component showing promise in treating depression, heart rate variability-biofeedback (HRV-B), to our original smartphone-based, 8-week digital intervention was feasible and whether patients in the HRV-B ("enhanced") intervention were more likely to experience clinically significant improvements in depressive symptoms than patients in our original ("standard") intervention. We used a quasi-experimental, non-equivalent (matched) groups design to compare changes in symptoms of depression in the enhanced group (n = 48) to historical outcome data from the standard group (n = 48). Patients in the enhanced group completed a total average of 3.86 h of HRV-B practice across 25.8 sessions, and were more likely to report a clinically significant improvement in depressive symptom score post-intervention than participants in the standard group, even after adjusting for differences in demographics and engagement between groups (adjusted OR 3.44, 95% CI [1.28-9.26], P = .015). Our findings suggest that adding HRV-B to an app-based, smartphone-delivered, remote intervention for depression is feasible and may enhance treatment outcomes.Peer reviewe

Screening for Major Depressive Disorder in Children and Adolescents: A Systematic Review for the U.S. Preventive Services Task Force

BACKGROUND: Major depressive disorder (MDD) is common among children and adolescents and is associated with functional impairment and suicide. PURPOSE: To update the 2009 U.S. Preventive Services Task Force (USPSTF) systematic review on screening for and treatment of MDD in children and adolescents in primary care settings. DATA SOURCES: Several electronic searches (May 2007 to February 2015) and searches of reference lists of published literature. STUDY SELECTION: Trials and recent systematic reviews of treatment, test-retest studies of screening, and trials and large cohort studies for harms. DATA EXTRACTION: Data were abstracted by 1 investigator and checked by another; 2 investigators independently assessed study quality. DATA SYNTHESIS: Limited evidence from 5 studies showed that such tools as the Beck Depression Inventory and Patient Health Questionnaire for Adolescents had reasonable accuracy for identifying MDD among adolescents in primary care settings. Six trials evaluated treatment. Several individual fair- and good-quality studies of fluoxetine, combined fluoxetine and cognitive behavioral therapy, escitalopram, and collaborative care demonstrated benefits of treatment among adolescents, with no associated harms. LIMITATION: The review included only English-language studies, narrow inclusion criteria focused only on MDD, high thresholds for quality, potential publication bias, limited data on harms, and sparse evidence on long-term outcomes of screening and treatment among children younger than 12 years. CONCLUSION: No evidence was found of a direct link between screening children and adolescents for MDD in primary care or similar settings and depression or other health-related outcomes. Evidence showed that some screening tools are accurate and some treatments are beneficial among adolescents (but not younger children), with no evidence of associated harms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality

A therapist-guided smartphone app for major depression in young adults: A randomized clinical trial

Background: Meru Health Program (MHP) is a therapist-guided, 8-week intervention for depression delivered via smartphone. The aim was to test its efficacy in patients with clinical depression in a Finnish university student health service. Methods: Patients (n=124, women 72.6%, mean age 25y) were stratified based on antidepressant status, and randomized into intervention group receiving MHP plus treatment as usual (TAU), and control group receiving TAU only. Depression, measured by the Patient Health Questionnaire-9 (PHQ-9) scale, was the primary outcome. After baseline (T0), follow-ups were at mid-intervention (T4), immediately post-intervention (T8); 3 months (T20), and 6 months (T32) post-intervention. Results: The intervention group and control group did not have significant differences in depression outcomes throughout end of treatment and follow-up. Among secondary outcomes, increase in resilience (d=0.32, p=0.03) and mindfulness (d=0.57, p=0.002), and reduction in perceived stress (d=-0.52, p=0.008) were greater in MHP+TAU versus TAU at T32; no differences were found in anxiety, sleep disturbances, and quality of life between groups. Post-hoc comparisons of patients on antidepressants showed significantly greater reduction in depression at T32 for MHP+TAU versus TAU (d=-0.73, p=0.01); patients not on antidepressants showed no between-group differences. Limitations: Limitations include unknown characteristics of TAU, potential bias from patients and providers not being blinded to treatment group, and failure to specify examination of differences by antidepressant status in the protocol. Conclusions: Most outcomes, including depression, did not significantly differ between MHP+TAU and TAU. Exploratory analysis revealed intervention effect at the end of the 6-month follow-up among patients on anti-depressant medication.</p

Helicobacter pylori and cancer among adults in Uganda

Data from Africa on infection with Helicobacter pylori (H. pylori) are sparse. Therefore, as part of an epidemiological study of cancer in Uganda, we investigated the prevalence and determinants of antibodies against H. pylori among 854 people with different cancer types and benign tumours. Patients were recruited from hospitals in Kampala, Uganda, interviewed about various demographic and lifestyle factors and tested for antibodies against H. pylori. In all patients combined, excluding those with stomach cancer (which has been associated with H. pylori infection), the prevalence of antibodies was 87% (723/833) overall, but declined with increasing age (p = 0.02) and was lower among people who were HIV seropositive compared to seronegative (p <0.001). Otherwise, there were few consistent epidemiological associations. Among those with stomach cancer, 18/21 (86%) had anti-H. pylori antibodies (odds ratio 0.8, 95% confidence intervals 0.2–2.9, p = 0.7; estimated using all other patients as controls, with adjustment for age, sex and HIV serostatus). No other cancer site or type was significantly associated with anti-H. pylori antibodies. The prevalence of H. pylori reported here is broadly in accord with results from other developing countries, although the determinants of infection and its' role in the aetiology of gastric cancer in Uganda remain unclear

Change and Exchange: Economies of Literature and Knowledge in Early Modern Europe

The introductory essay outlines the way in which Change and Exchange places literature, and, in a wider sense, imaginative practice, at the centre of early modern economic knowledge. Probing the affinity between economic and metaphorical experience in terms of the transactional processes of change and exchange, it sets up the parameters within which the essays in the volume collectively forge a language to grasp early modern economic phenomena and their epistemic dimensions. It prepares the reader for the stimulating combination of materials that the book presents: the range of generic contexts engendered by emergent economic practices, structures of feeling and modes of knowing made available by new economic relations, and economies of transformation in discursive domains that are distinct from ‘economics’ as we understand it but cognate in their intuition of change and exchange as shaping agents

Quality improvement, implementation, and dissemination strategies to improve mental health care for children and adolescents: a systematic review

Abstract Background Some outcomes for children with mental health problems remain suboptimal because of poor access to care and the failure of systems and providers to adopt established quality improvement strategies and interventions with proven effectiveness. This review had three goals: (1) assess the effectiveness of quality improvement, implementation, and dissemination strategies intended to improve the mental health care of children and adolescents; (2) examine harms associated with these strategies; and (3) determine whether effectiveness or harms differ for subgroups based on system, organizational, practitioner, or patient characteristics. Methods Sources included MEDLINE®, the Cochrane Library, PsycINFO, and CINAHL, from database inception through February 17, 2017. Additional sources included gray literature, additional studies from reference lists, and technical experts. Two reviewers selected relevant randomized controlled trials (RCTs) and observational studies, extracted data, and assessed risk of bias. Dual analysis, synthesis, and grading of the strength of evidence for each outcome followed for studies meeting inclusion criteria. We also used qualitative comparative analysis to examine relationships between combinations of strategy components and improvements in outcomes. Results We identified 18 strategies described in 19 studies. Eleven strategies significantly improved at least one measure of intermediate outcomes, final health outcomes, or resource use. Moderate strength of evidence (from one RCT) supported using provider financial incentives such as pay for performance to improve the competence with which practitioners can implement evidence-based practices (EBPs). We found inconsistent evidence involving strategies with educational meetings, materials, and outreach; programs appeared to be successful in combination with reminders or providing practitioners with newly collected clinical information. We also found low strength of evidence for no benefit for initiatives that included only educational materials or meetings (or both), or only educational materials and outreach components. Evidence was insufficient to draw conclusions on harms and moderators of interventions. Conclusions Several strategies can improve both intermediate and final health outcomes and resource use. This complex and heterogeneous body of evidence does not permit us to have a high degree of confidence about the efficacy of any one strategy because we generally found only a single study testing each strategy. Trial registration PROSPERO, CRD42015024759