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AZT has induced a macrocytic anemia in AIDS patients on long term AZT therapy. It is generally assumed that DNA elongation is stopped by the insertion of AZT into the chain in place of thymidine thus preventing the phosphate hydroxyl linkages and therefore suppresses hemopoietic progenitor cell proliferation in an early stage of differentiation. CBA/Ca male mice started on AZT 0.75 mg/ml H2O at 84 days of age and kept on it for 687 days when dosage reduced to 0.5 mg/ml H2O for a group, another group removed from AZT to see recovery, and third group remained on 0.75 mg. At 687 days mice that had been on 0.75 mg had average platelet counts of 2.5 x 106. Histological examination on 9 of 10 mice with such thrombocytopenia showed changes compatible with myelodysplastic syndrome (MDS). A variety of histological patterns was observed. There were two cases of hypocellular myelodysplasia, two cases of hypersegmented myelodysplastic granulocytosis, two cases of hypercellular marrow with abnormal megakaryocytes with bizarre nuclei, one case of megakaryocytic myelosis associated with a hyperplastic marrow, dysmyelopoiesis and a hypocellular marrow and two cases of myelodysplasia with dyserythropoiesis, hemosiderosis and a hypocellular marrow. Above mentioned AZT incorporation may have induced an ineffective hemopoiesis in the primitive hemopoietic progenitor cells, which is known to be seen commonly in the myelodysplastic syndrome. [ABSTRACT FROM AUTHOR]

Dropout from psychotherapy is common and can have negative effects for patients, providers, and researchers. A better understanding of when and why patients stop treatment early, as well as actionable factors contributing to dropout, has the potential to prevent it. Here, we examined dropout from a large randomized controlled trial of transdiagnostic versus single-diagnosis cognitive-behavioral treatment (CBT) for patients with anxiety disorders (n = 179; Barlow et al., 2017). We aimed to characterize the timing of and reasons for dropout and test whether participants who dropped out had different symptom trajectories than those who completed treatment. Results indicated that overall, the greatest risk of dropout was prior to the first treatment session. In single-diagnosis CBT, dropout risk was particularly elevated before the first session and after other early sessions, whereas in transdiagnostic CBT, dropout risk was low and stable before and during treatment. Participants most often dropped out due to failure to comply with study procedures or dissatisfaction with or desiring alternative treatment. Results from multilevel models showed that trajectories of anxiety symptoms did not significantly differ between dropouts and completers. These findings suggest that there may be specific time windows for targeted and timely interventions to prevent dropout from CBT., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: Treatment utilization for psychiatric illness is low, perhaps influenced by limited consumer knowledge of evidence-based psychological treatments (EBPTs). To inform consumer-directed dissemination efforts, we characterized preferences, beliefs, and knowledge about specific EBPTs (cognitive behavioral therapy [CBT], dialectical behavior therapy [DBT], and acceptance and commitment therapy [ACT]); and examined potential sociodemographic and treatment history correlates., Method: Before receiving treatment at a psychiatric partial hospital, patients (n = 249) completed the Psychological Treatment Consumer Questionnaire., Results: Most (75%) patients felt responsible for being aware of psychotherapy options and that it was important to receive research-supported psychotherapy (80%), but were split on whether research (42%) or their provider's recommendation (58%) carried greater decisional weight. Most (93%) patients had heard of CBT (93%) and DBT (71%), but not ACT (35%). Prior exposure to these EBPTs increased the likelihood of recommending them to others., Conclusions: Findings support initiatives to enhance consumer familiarity with these EBPTs and inform dissemination efforts., (© 2019 Wiley Periodicals, Inc.)

Cognitive-behavioral prevention programs have demonstrated efficacy in reducing subclinical symptoms of anxiety and depression, and there is some evidence to suggest that they can lower the risk of future disorder onset. However, existing interventions tend to be relatively lengthy and target specific disorders or problem areas, both of which limit their potential for widespread dissemination. To address these limitations, we aimed to develop a single-session, transdiagnostic preventive intervention based on the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders for young adults at risk for developing anxiety and/or depressive disorders within a college setting. Results from this proof-of-concept study indicated that the intervention was viewed as highly satisfactory and acceptable. The intervention also was successful at delivering adaptive emotion management skills in its 2-hr workshop format. Future studies evaluating the efficacy of this novel transdiagnostic, emotion-focused prevention program are warranted.

Importance: Transdiagnostic interventions have been developed to address barriers to the dissemination of evidence-based psychological treatments, but only a few preliminary studies have compared these approaches with existing evidence-based psychological treatments., Objective: To determine whether the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) is at least as efficacious as single-disorder protocols (SDPs) in the treatment of anxiety disorders., Design, Setting, and Participants: From June 23, 2011, to March 5, 2015, a total of 223 patients at an outpatient treatment center with a principal diagnosis of panic disorder with or without agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, or social anxiety disorder were randomly assigned by principal diagnosis to the UP, an SDP, or a waitlist control condition. Patients received up to 16 sessions of the UP or an SDP for 16 to 21 weeks. Outcomes were assessed at baseline, after treatment, and at 6-month follow-up. Analysis in this equivalence trial was based on intention to treat., Interventions: The UP or SDPs., Main Outcomes and Measures: Blinded evaluations of principal diagnosis clinical severity rating were used to evaluate an a priori hypothesis of equivalence between the UP and SDPs., Results: Among the 223 patients (124 women and 99 men; mean [SD] age, 31.1 [11.0] years), 88 were randomized to receive the UP, 91 to receive an SDP, and 44 to the waitlist control condition. Patients were more likely to complete treatment with the UP than with SDPs (odds ratio, 3.11; 95% CI, 1.44-6.74). Both the UP (Cohen d, -0.93; 95% CI, -1.29 to -0.57) and SDPs (Cohen d, -1.08; 95% CI, -1.43 to -0.73) were superior to the waitlist control condition at acute outcome. Reductions in clinical severity rating from baseline to the end of treatment (β, 0.25; 95% CI, -0.26 to 0.75) and from baseline to the 6-month follow-up (β, 0.16; 95% CI, -0.39 to 0.70) indicated statistical equivalence between the UP and SDPs., Conclusions and Relevance: The UP produces symptom reduction equivalent to criterion standard evidence-based psychological treatments for anxiety disorders with less attrition. Thus, it may be possible to use 1 protocol instead of multiple SDPs to more efficiently treat the most commonly occurring anxiety and depressive disorders., Trial Registration: clinicaltrials.gov Identifier: NCT01243606.

The Unified Protocol (UP) for the Transdiagnostic Treatment of Emotional Disorders is a cognitive-behavioral intervention designed to treat the range of anxiety, depressive, and related disorders. Thus far, the UP treatment modules have only been studied when they are delivered in their entirety and presented in a standard sequence. To personalize the presentation of the UP modules for a given patient's presentation (e.g., providing the modules in a varied order, dropping irrelevant modules), it is first necessary to establish that each module leads to change in the skill it is designed to promote, and that these changes can occur in the absence of the other modules. Using a multiple baseline design in accordance with the single-case reporting guidelines in behavioral interventions (SCRIBE), eight patients with heterogeneous emotional disorders were randomly assigned to a 1- or 3-week baseline assessment phase followed by four sessions of one of four UP modules (psychoeducation, emotional awareness, cognitive flexibility, and countering emotional behaviors). Results provide preliminary support for the notion that each UP module under study leads to change in its associated skill in the absence of the other modules (five of eight patients demonstrated reliable change in the module-specific skill). In addition, exploratory analyses suggest that the emotion awareness training and cognitive flexibility modules appeared to exhibit change specific to their associated skills, psychoeducation, and countering emotional behaviors demonstrated somewhat more broad-based change across skills.

Research in psychopathology has identified psychological processes that are relevant across a range of Diagnostic and Statistical Manual (DSM) mental disorders, and these efforts have begun to produce treatment principles and protocols that can be applied transdiagnostically. However, review of recent work suggests that there has been great variability in conceptions of the term "transdiagnostic" in the treatment development literature. We believe that there is value in arriving at a common understanding of the term "transdiagnostic." The purpose of the current paper is to outline three principal ways in which the term "transdiagnostic" is currently used, to delineate treatment approaches that fall into these three categories, and to consider potential advantages and disadvantages of each approach., (Copyright © 2016. Published by Elsevier Ltd.)

The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) has demonstrated promising results among patients with heterogeneous anxiety and comorbid depressive disorders when delivered on an individual basis, but greater efficiencies may be achieved with group-based applications. The aim of the present study was to provide a preliminary exploration of the UP when delivered in a group format. Among diagnostically diverse patients (N = 11), the UP group treatment resulted in moderate to strong effects on anxiety and depressive symptoms, functional impairment, quality of life, and emotion regulation skills, as well as good acceptability and overall satisfaction ratings from patients. Three clinical cases are presented in detail to illustrate the group-based UP delivery, followed by a critical discussion of associated challenges and proposed guidelines for group administration, as well as directions for future research., (© The Author(s) 2014.)

Objective: The aim of this study is to conduct a preliminary examination of long-term outcomes on a broad range of affective disorder symptoms treated with a newly developed intervention: The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP)., Method: Maintenance of treatment gains at long-term follow-up (LTFU) were explored in patients (N=15, mean age=32.27; 60% female) who completed a clinical trial of the UP., Results: Treatment gains observed at 6-month follow-up (6MFU) on measures of clinical severity, general symptoms of depression and anxiety, and a measure of symptom interference in daily functioning were largely maintained 12months later (at an average of 18months posttreatment), and any significant changes from 6MFU to LTFU reflected small increases in symptoms that remained, on average, in the subclinical range., Conclusions: These findings provide the first initial support for the durability of broad treatment gains following transdiagnostic treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In this article, we provide a fresh perspective on the developmental origins of neuroticism--a dimension of temperament marked by elevated stress reactivity resulting in the frequent experience of negative emotions. This negative affectivity is accompanied by a pervasive perception that the world is a dangerous and threatening place, along with beliefs about one's inability to manage or cope with challenging events. Historically, neuroticism has been viewed as a stable, genetically based trait. However, recent understanding of ongoing gene-environment interactions that occur throughout the life span suggests there may be a more complex and dynamic etiology. Thus, the purpose of this article is to offer a theory for understanding the development of neuroticism that integrates genetic, neurobiological, and environmental contributions to this trait. Given the strong correlation between neuroticism and the development of negative health outcomes--most notably, the full range of anxiety and mood disorders--an enhanced understanding of how neuroticism originates has implications for the treatment and prevention of a broad range of pathologies and, perhaps, even for the prevention of neuroticism itself., (© The Author(s) 2014.)

Background and Objectives: There has been a recent proliferation of research evaluating the efficacy of mindfulness as a clinical intervention. However, there is still little known about trait mindfulness, or how trait mindfulness interacts with maladaptive emotion regulation strategies. The current study further explores the effect of trait mindfulness on emotion regulation, as well as whether specific factors of trait mindfulness are uniquely associated with subjective and autonomic reactivity to stress., Methods: Forty-eight healthy male participants were trained in the use of the suppression strategy and then instructed to suppress their responses to the inhalation of a 15% CO2-enriched air mixture for 90 s while their subjective distress and heart rate were recorded., Results: After controlling for anxiety-related variables, the ability to provide descriptions of observed experiences predicted less heart rate reactivity to CO2 inhalation, while skillfulness at restricting attention to the present moment was uniquely predictive of less subjective distress. The tendency to attend to bodily or sensory stimuli predicted greater distress during CO2 inhalation., Limitations: The inclusion of only healthy males limits the generalizability of study findings. Also, the sample size was relatively small., Conclusions: These findings suggest that factors associated with trait mindfulness predict less stress reactivity and distress while engaging in suppression above and beyond other variables that have been shown to predict anxious responding. The implications for emotion and clinical research are discussed., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Intravenous drug use (IDU) remains a prominent pathway of HIV transmission in the United States, though little is known about modifiable factors influencing quality of life among IDUs. The goal of this study was to evaluate the influence of psychological variables (e.g., depression and anxiety) on health-related quality of life among HIV-positive individuals with a history of IDU who were enrolled in outpatient treatment for opioid dependence., Method: 108 HIV-positive individuals with a history of IDU and participating in current outpatient treatment for opiate dependence who were screened for participation in a depression and adherence study reported sociodemographic data, depressive and anxiety symptoms, and health-related quality of life (HRQoL; Multidimensional Health Assessment using the ACTG-SF 21)., Results: Multiple regression models controlling for disease stage and background characteristics identified significant negative relationships between General Health Perception and Functioning without Pain for anxiety and depression, and between Role Functioning and Physical Functioning for anxiety. CD4 cell count was significantly related to Physical Functioning only., Conclusions: Results indicate that distress (both depression and anxiety) contribute significantly to variation in HRQoL over and above the effects of disease variables. Effective depression and anxiety treatment may result in improved overall functioning.

Enormous progress in the field of clinical science has been made over the past 50 years, with advances in our understanding of psychopathology and more sophisticated research methodology leading to the development of more efficacious psychological treatments for a variety of behavioral disorders. Despite these advances, the public health impact of well-established psychological treatments is less than it should be. After an overview of the current status of the field, we identify barriers that must be overcome to maximize the public health impact and propose that to breach these barriers we must (a) augment the efficacy of treatments, (b) broaden the impact of treatments across diagnoses to include temperamental variables, (c) attend more closely to mechanisms of action of treatments, and (d) learn the best methods for disseminating and implementing psychological interventions. We conclude by proposing new directions in both research and clinical practice to accomplish these goals.

Objective: Depression and substance use, the most common comorbidities with HIV, are both associated with poor treatment adherence. Injection drug users comprise a substantial portion of individuals with HIV in the United States and globally. The present study tested cognitive behavioral therapy for adherence and depression (CBT-AD) in patients with HIV and depression in active substance abuse treatment for injection drug use., Method: This is a 2-arm, randomized controlled trial (N = 89) comparing CBT-AD with enhanced treatment as usual (ETAU). Analyses were conducted for two time-frames: (a) baseline to post-treatment and (b) post-treatment to follow-up at 3 and 6 months after intervention discontinuation., Results: At post-treatment, the CBT-AD condition showed significantly greater improvement than ETAU in MEMS (electronic pill cap) based adherence, γslope = 0.8873, t(86) = 2.38, p = .02; dGMA-raw = 0.64, and depression, assessed by blinded assessor: Mongomery-Asberg Depression Rating Scale, F(1, 79) = 6.52, p < .01, d = 0.55; clinical global impression, F(1, 79) = 14.77, p < .001, d = 0.85. After treatment discontinuation, depression gains were maintained, but adherence gains were not. Viral load did not differ across condition; however, the CBT-AD condition had significant improvements in CD4 cell counts over time compared with ETAU, γslope = 2.09, t(76) = 2.20, p = .03, dGMA-raw = 0.60., Conclusions: In patients managing multiple challenges including HIV, depression, substance dependence, and adherence, CBT-AD is a useful way to integrate treatment of depression with an adherence intervention. Continued adherence counseling is likely needed, however, to maintain or augment adherence gains in this population.

Childhood sexual abuse (CSA) is related to poorer health outcomes, associated with increased risk for HIV acquisition, and prevalent among HIV risk groups. Links between CSA and health behavior are an important health concern. We examined the relationship between CSA and transmission risk behavior and medication adherence in 119 HIV-infected individuals with an injection drug use history. 47% reported CSA, with no gender difference. Individuals who experienced CSA were more likely to report sexual HIV transmission risk behavior in the past 6 months, more sexual partners, use of heroin in the past 30 days, and worse adherence to HIV medication than those who did not. These findings confirm that rates of CSA are high in this population, and suggest that a history of CSA may place people managing both HIV and opioid dependence at increased risk for HIV transmission, poor adherence to medication, and vulnerability to substance use relapse.

The frequency of mood and anxiety disorders is elevated among individuals with a history of intravenous drug abuse and among those with human immunodeficiency virus (HIV), and these disorders are associated with continued substance use despite treatment. The present study examined rates of mood and anxiety disorders, and recent heroin use, among HIV-infected and HIV-noninfected patients receiving methadone maintenance therapy. Participants were 160 (80 HIV-infected, 80 HIV-noninfected) methadone patients. Clinician-administered, semistructured interviews were used to identify unipolar and bipolar depression, and four major anxiety disorders (panic disorder with agoraphobia [PDA], generalized anxiety disorder [GAD], post-traumatic stress disorder [PTSD], and social anxiety disorder [SAD]). Toxicology screens and self-reporting were used to assess heroin, cocaine, marijuana, and alcohol use over the past month. The entire sample met criteria for at least one psychiatric disorder other than substance dependence. Substantial proportions of participants met criteria for major depressive disorder (55.6%), bipolar I, bipolar II, or cyclothymia (6.4%), PDA (34.4%), GAD (22.5%), SAD (16.9%), and PTSD (34.4%). A greater proportion of HIV-infected participants met criteria for SAD (χ 2 = 5.03), and a greater proportion of HIV-noninfected participants met criteria for GAD (χ 2 = 5.39, P < 0.01). About 14% of participants continued to use heroin over the past month, a significantly greater proportion of whom were HIV-infected. In adjusted analyses, none of the mood or anxiety disorders emerged as significant predictors of recent heroin use, but being HIV-infected did. This study highlights the high rate of psychopathology and continued heroin use despite substance abuse treatment, and underscores the need for interventions that help mitigate these problems among methadone patients.

Because of increasing evidence of heterogeneity in the hematopoietic stem cell compartments, the radiosensitivity of spleen colony-forming units (CFU-S) was reevaluated to ascertain whether the classical single exponential curve for a graded dose of radiation is applicable at higher doses of radiation, 400-600 cGy. Bone marrow cells (BMC) removed from mice immediately after death under anesthesia were irradiated in vitro. Great care was taken to exclude anoxic effects during irradiation and to avoid any possible effects in the recipient mice from injection of excessive numbers of BMC. By estimating the number of cells to be injected to produce numbers of colonies within the evaluation range of the assay, we obtained a radiation survival curve that appeared to have a multiphasic concave shape; the D0 value for the 400-600 cGy range was estimated to be about 275 cGy, whereas the D0 for the lower doses was 95 cGy, the same value as previously reported. The reason a single exponential survival curve was previously obtained after graded doses of radiation is discussed, and a comparison of those results with the present data from in vitro radiation is made. Lacking experimental evidence, we speculate that the major factor that determines the slope of the survival curve is the degree to which the stem cells are in their normal hematopoietic environment during the irradiation. The probable existence of a fraction surviving after an exposure to 600 cGy, estimated by the limiting dilution assay, was about 1 per 2 x 10(6) BMC. Such radio-insensitive CFU-S appear to be primitive CFU-S, which can contribute materially to the long-term survival of lethally irradiated bone marrow recipients.