Nonprofessional Peer Support to Improve Mental Health: Randomized Trial of a Scalable Web-Based Peer Counseling Course

Background: Millions of people worldwide are underserved by the mental health care system. Indeed, most mental health problems go untreated, often because of resource constraints (eg, limited provider availability and cost) or lack of interest or faith in professional help. Furthermore, subclinical symptoms and chronic stress in the absence of a mental illness diagnosis often go unaddressed, despite their substantial health impact. Innovative and scalable treatment delivery methods are needed to supplement traditional therapies to fill these gaps in the mental health care system. Objective: This study aims to investigate whether a self-guided web-based course can teach pairs of nonprofessional peers to deliver psychological support to each other. Methods: In this experimental study, a community sample of 30 dyads (60 participants, mostly friends), many of whom presented with mild to moderate psychological distress, were recruited to complete a web-based counseling skills course. Dyads were randomized to either immediate or delayed access to training. Before and after training, dyads were recorded taking turns discussing stressors. Participants’ skills in the helper role were assessed before and after taking the course: the first author and a team of trained research assistants coded recordings for the presence of specific counseling behaviors. When in the client role, participants rated the session on helpfulness in resolving their stressors and supportiveness of their peers. We hypothesized that participants would increase the use of skills taught by the course and decrease the use of skills discouraged by the course, would increase their overall adherence to the guidelines taught in the course, and would perceive posttraining counseling sessions as more helpful and their peers as more supportive. Results: The course had large effects on most helper-role speech behaviors: helpers decreased total speaking time, used more restatements, made fewer efforts to influence the speaker, and decreased self-focused and off-topic utterances (ds=0.8-1.6). When rating the portion of the session in which they served as clients, participants indicated that they made more progress in addressing their stressors during posttraining counseling sessions compared with pretraining sessions (d=1.1), but they did not report substantive changes in feelings of closeness and supportiveness of their peers (d=0.3). Conclusions: The results provide proof of concept that nonprofessionals can learn basic counseling skills from a scalable web-based course. The course serves as a promising model for the development of web-based counseling skills training, which could provide accessible mental health support to some of those underserved by traditional psychotherapy

Synergistic Induction of Apoptosis in Primary B-CLL Cells after Treatment with Recombinant Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Histone Deacetylase Inhibitors

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is currently being investigated as a therapeutic agent for a variety of malignancies, as it triggers apoptosis specifically in transformed cells. However, TRAIL use as a stand alone therapeutic is hampered by the fact that many primary tumor cells are resistant to TRAIL-mediated apoptosis. Here, we investigated the extent to which pretreatment of TRAIL-resistant primary B-cell chronic lymphocytic leukemia (B-CLL) cells with histone deacetylase inhibitors (HDACis) could render them susceptible to killing by TRAIL. We found that HDAC inhibition in B-CLL cells led to increased TRAIL receptor expression, increased caspase activation, decreased expression of antiapoptotic regulators such as Bcl-2, and ultimately, enhanced TRAIL-induced apoptosis. Importantly, untransformed peripheral blood mononuclear cells remained largely resistant to TRAIL, even in the presence of HDACis. These results suggest that combination therapies using HDAC inhibition and TRAIL could prove beneficial for the treatment of B-CLL

Eradication of Metastatic Renal Cell Carcinoma after Adenovirus-Encoded TNF-Related Apoptosis-Inducing Ligand (TRAIL)/CpG Immunotherapy

Despite evidence that antitumor immunity can be protective against renal cell carcinoma (RCC), few patients respond objectively to immunotherapy and the disease is fatal once metastases develop. We asked to what extent combinatorial immunotherapy with Adenovirus-encoded murine TNF-related apoptosis-inducing ligand (Ad5mTRAIL) plus CpG oligonucleotide, given at the primary tumor site, would prove efficacious against metastatic murine RCC. To quantitate primary renal and metastatic tumor growth in mice, we developed a luciferase-expressing Renca cell line, and monitored tumor burdens via bioluminescent imaging. Orthotopic tumor challenge gave rise to aggressive primary tumors and lung metastases that were detectable by day 7. Intra-renal administration of Ad5mTRAIL+CpG on day 7 led to an influx of effector phenotype CD4 and CD8 T cells into the kidney by day 12 and regression of established primary renal tumors. Intra-renal immunotherapy also led to systemic immune responses characterized by splenomegaly, elevated serum IgG levels, increased CD4 and CD8 T cell infiltration into the lungs, and elimination of metastatic lung tumors. Tumor regression was primarily dependent upon CD8 T cells and resulted in prolonged survival of treated mice. Thus, local administration of Ad5mTRAIL+CpG at the primary tumor site can initiate CD8-dependent systemic immunity that is sufficient to cause regression of metastatic lung tumors. A similar approach may prove beneficial for patients with metastatic RCC

Activation of PPARγ in Myeloid Cells Promotes Lung Cancer Progression and Metastasis

Activation of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits growth of cancer cells including non-small cell lung cancer (NSCLC). Clinically, use of thiazolidinediones, which are pharmacological activators of PPARγ is associated with a lower risk of developing lung cancer. However, the role of this pathway in lung cancer metastasis has not been examined well. The systemic effect of pioglitazone was examined in two models of lung cancer metastasis in immune-competent mice. In an orthotopic model, murine lung cancer cells implanted into the lungs of syngeneic mice metastasized to the liver and brain. As a second model, cancer cells injected subcutaneously metastasized to the lung. In both models systemic administration of pioglitazone increased the rate of metastasis. Examination of tissues from the orthotopic model demonstrated increased numbers of arginase I-positive macrophages in tumors from pioglitazone-treated animals. In co-culture experiments of cancer cells with bone marrow-derived macrophages, pioglitazone promoted arginase I expression in macrophages and this was dependent on the expression of PPARγ in the macrophages. To assess the contribution of PPARγ in macrophages to cancer progression, experiments were performed in bone marrow-transplanted animals receiving bone marrow from Lys-M-Cre+/PPARγflox/flox mice, in which PPARγ is deleted specifically in myeloid cells (PPARγ-Macneg), or control PPARγflox/flox mice. In both models, mice receiving PPARγ-Macneg bone marrow had a marked decrease in secondary tumors which was not significantly altered by treatment with pioglitazone. This was associated with decreased numbers of arginase I-positive cells in the lung. These data support a model in which activation of PPARγ may have opposing effects on tumor progression, with anti-tumorigenic effects on cancer cells, but pro-tumorigenic effects on cells of the microenvironment, specifically myeloid cells

Comprehensive Analysis Reveals Dynamic and Evolutionary Plasticity of Rab GTPases and Membrane Traffic in Tetrahymena thermophila

Cellular sophistication is not exclusive to multicellular organisms, and unicellular eukaryotes can resemble differentiated animal cells in their complex network of membrane-bound structures. These comparisons can be illuminated by genome-wide surveys of key gene families. We report a systematic analysis of Rabs in a complex unicellular Ciliate, including gene prediction and phylogenetic clustering, expression profiling based on public data, and Green Fluorescent Protein (GFP) tagging. Rabs are monomeric GTPases that regulate membrane traffic. Because Rabs act as compartment-specific determinants, the number of Rabs in an organism reflects intracellular complexity. The Tetrahymena Rab family is similar in size to that in humans and includes both expansions in conserved Rab clades as well as many divergent Rabs. Importantly, more than 90% of Rabs are expressed concurrently in growing cells, while only a small subset appears specialized for other conditions. By localizing most Rabs in living cells, we could assign the majority to specific compartments. These results validated most phylogenetic assignments, but also indicated that some sequence-conserved Rabs were co-opted for novel functions. Our survey uncovered a rare example of a nuclear Rab and substantiated the existence of a previously unrecognized core Rab clade in eukaryotes. Strikingly, several functionally conserved pathways or structures were found to be associated entirely with divergent Rabs. These pathways may have permitted rapid evolution of the associated Rabs or may have arisen independently in diverse lineages and then converged. Thus, characterizing entire gene families can provide insight into the evolutionary flexibility of fundamental cellular pathways

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations

Inverse association between changes in energetic cost of walking and vertical accelerations in non-metastatic breast cancer survivors

Purpose: With accelerometry, the utility to detect changes in physical activity are predicated on the assumption that walking energetics and gait mechanics do not change. The present work examined associations between changes (∆) in walking energetics, exercise self-efficacy, and several accelerometer-derived metrics. Methods Secondary analyses were performed among a sub-sample ($n$ = 29) of breast cancer survivors participating in a larger randomized trial. During 4 min of treadmill walking (0.89 m s$^{−1}$, 0% grade), indirect calorimetry quantified steady-state energy expenditure (EE), wherein, participants were fitted with a heart rate monitor and hip-worn triaxial accelerometer. Exercise self-efficacy was measured using a 9-item questionnaire, while vector magnitude (VM) and individual planes (e.g., mediolateral, vertical, and anteroposterior) of the movement were extracted for data analyses. Evaluations were made at baseline and after 3 months. Results From baseline to 3 months, the energetic cost of walking (kcals min$^{−1}$) significantly decreased by an average of  − 5.1% ($p$ = 0.001; $d$ = 0.46). Conversely, VM significantly increased ($p$ = 0.007; $d$ = 0.53), exclusively due to greater vertical accelerations (acc) (+ 5.7 ± 7.8 acc; $p$ = 0.001; $d$ = 0.69). Changes in vertical accelerations were inversely and positively associated with ∆walking EE ($r$ = − 0.37; $p$ = 0.047) and ∆exercise self-efficacy ($r$ = 0.39; $p$ = 0.034), respectively. Conclusion: Hip-worn accelerometers do not appear well-suited to correctly detect changes in ease of walking as evidenced by reduced energetic cost. Further research should determine if a divergence between measured EE and vertical accelerations could contribute to erroneous inferences in free-living physical activity

A Flexible Curriculum for Computer Science Undergraduate Major

This paper describes an innovative approach to establish a CS curriculum, aiming flexibility and minimization of the time spent in the classrooms. This approach has been developed at the Paulista State University - Unesp - at S ao Jos e do Rio Preto, and is producing very interesting results. The load reduction is achieved through a series of fundamental core and breadth courses that precede depth courses in specific areas. The flexibility comes as a side effect of the depth courses, which can be adapted without any changes in the core courses. In the following pages we fully describe our motivations, actions and results