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The poem "Vision" by D. Foy is presented. First Line: What if all humanity's nightmare; Last Line: uh, the vestiges of dreams?

The poem "The Vermin and the Stars" by D. Foy is presented. First Line: Fog moon, mud moon, Last Line: but sweetness...

Relationships among pretrauma risk factors (e.g., family instability, childhood antisocial behavior), war-zone stressors (e.g., combat, perceived threat), posttrauma resilience-recovery variables (e.g., hardiness, social support), and posttraumatic stress disorder (PTSD) symptom severity were examined. Data from a national sample of 432 female and 1,200 male veterans were analyzed using structural equation modeling. For both genders, direct links to PTSD from pretrauma, war-zone, and posttrauma variable categories were found; several direct associations between pretrauma and posttrauma variables were documented. Although war-zone stressors appeared preeminent for PTSD in men, posttrauma resilience-recovery variables were more salient for women. Researchers, policymakers, and clinicians are urged to take a broad view on trauma and its sequelae, especially regarding possible multiple exposures over time and the depletion and availability of important resources. [ABSTRACT FROM AUTHOR]

Purpose: Between 30 and 68% of patients prematurely discontinue their antidepressant treatment, posing significant risks to patient safety and healthcare outcomes. Online healthcare forums have the potential to offer a rich and unique source of data, revealing dimensions of antidepressant discontinuation that may not be captured by conventional data sources., Methods: We analyzed 891 patient narratives from the online healthcare forum, "askapatient.com," utilizing content analysis to create PsyRisk-a corpus highlighting the risk factors associated with antidepressant discontinuation. Leveraging PsyRisk, alongside PsyTAR [a publicly available corpus of adverse drug reactions (ADRs) related to antidepressants], we developed a machine learning-driven algorithm for proactive identification of patients at risk of abrupt antidepressant discontinuation., Results: From the analyzed 891 patients, 232 reported antidepressant discontinuation. Among these patients, 92% experienced ADRs, and 72% found these reactions distressful, negatively affecting their daily activities. Approximately 26% of patients perceived the antidepressants as ineffective. Most reported ADRs were physiological (61%, 411/673), followed by cognitive (30%, 197/673), and psychological (28%, 188/673) ADRs. In our study, we employed a nested cross-validation strategy with an outer 5-fold cross-validation for model selection, and an inner 5-fold cross-validation for hyperparameter tuning. The performance of our risk identification algorithm, as assessed through this robust validation technique, yielded an AUC-ROC of 90.77 and an F1-score of 83.33. The most significant contributors to abrupt discontinuation were high perceived distress from ADRs and perceived ineffectiveness of the antidepressants., Conclusion: The risk factors identified and the risk identification algorithm developed in this study have substantial potential for clinical application. They could assist healthcare professionals in identifying and managing patients with depression who are at risk of prematurely discontinuing their antidepressant treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor LW declared a shared affiliation with author DF at the time of the review. The reviewer LT declared a shared affiliation with the authors MK and TP at the time of the review., (Copyright © 2023 Zolnour, Eldredge, Faiola, Yaghoobzadeh, Khani, Foy, Topaz, Kharrazi, Fung, Fontelo, Davoudi, Tabaie, Breitinger, Oesterle, Rouhizadeh, Zonnor, Moen, Patrick and Zolnoori.)

Multiple myeloma remains an incurable plasma cell malignancy despite the rapidly evolving treatment landscape. Chimeric antigen receptor T cells targeted against BCMA have recently shown great promise in relapsed refractory multiple myeloma; however, all patients ultimately still progress from their disease. Lack of CAR T-cell persistence, impaired T-cell fitness in autologous CAR T-cell products and the presence of an immunosuppressive bone marrow (BM) microenvironment are contributory factors to treatment failure. We generated anti-BCMA CAR T cells from healthy donors (HD) and patients with multiple myeloma at different stages of disease to compare their T-cell profile, fitness, and cytotoxic activity in preclinical studies. We also used an ex vivo assay with multiple myeloma BM biopsies from distinct genomic subgroups to test the efficacy of HD-derived CAR T cells in a clinically relevant model. HD volunteers showed increased T-cell counts, higher CD4/CD8 ratio, and expanded naïve T-cell population compared with patients with multiple myeloma. After anti-BCMA CAR T-cell production, patients with relapsed multiple myeloma had lower frequencies of CAR + T cells, decreased central memory phenotype, and increased checkpoint inhibitory markers compared with HD-derived products, which compromised their expansion and cytotoxicity against multiple myeloma cells in vitro . Importantly, HD-derived CAR T cells efficiently killed primary multiple myeloma cells within the BM microenvironment of different multiple myeloma genomic subgroups and their cytotoxic activity could be boosted with gamma secretase inhibitors. In conclusion, allogeneic anti-BCMA CAR T cells are a potential therapeutic strategy for patients with relapsed multiple myeloma and should be further developed in the clinic., Significance: Multiple myeloma is an incurable cancer of the plasma cells. A new therapy with anti-BCMA CAR T cells - the patient's own T cells genetically engineered to find and kill myeloma cancer cells - has shown encouraging results. Unfortunately, patients still relapse. In this study, we propose to use T cells from HD volunteers, which have a stronger T-cell fitness, higher cancer killing capacity, and are ready to be administered when needed., Competing Interests: A.M. Metelo reports grants from Allogene Therapeutics during the conduct of the study. A. Jozwik reports grants from Allogene during the conduct of the study and grants from Servier outside the submitted work. C. Graham reports grants from Allogene during the conduct of the study; grants from Servier outside the submitted work. M. Streetly reports personal fees from Bristol Myers Squibb / Celgene, personal fees from Janssen-Cilag, and personal fees from EuSa Pharma outside the submitted work. T. Bentley reports non-financial support and other from Allogene Therapeutics, Inc during the conduct of the study. B. Boldajipour reports personal fees from Pfizer, personal fees from Kite Pharma, and personal fees from Lyell Immunopharma outside the submitted work; in addition, B. Boldajipour has a patent to US10294304B2 issued. C. Sommer reports other from Allogene Therapeutics, Inc. outside the submitted work; in addition, C. Sommer has a patent to US Provisional Application Nos.: 62/962,014 and 63/117,281 pending. B. Sasu is an employee and receives stocks and salary from Allogene Therapeutics. R. Benjamin reports grants from Allogene Therapeutics during the conduct of the study. No disclosures were reported by the other authors., (© 2022 The Authors; Published by the American Association for Cancer Research.)

Introduction: Enhanced recovery programmes for hip and knee arthroplasty surgery have been shown to decrease length of stay and improve patient outcomes in the elective setting. There are limited studies looking at pre-operative patient education alone and its role, however, more recent studies have demonstrated that it can help reduce length of stay and health care costs. The elective orthopaedic unit at Tullamore Hospital was the first unit in the Irish public health system to have a joint school, pre-operative, educational session, and the aim of this study was to assess our patient understanding of this session to ensure a sustained, high level of patient care, quality assurance and educational standards., Methods: A sample size of n = 51 was calculated to adequately power the study. Final sample size was 57. Data was collected across four joint school sessions. Patients were asked to complete a questionnaire before and after the session., Results: Twenty-seven male (47.3%) and 30 female (52.7%) patients completed the surveys. Mean age overall was 64.5 years. All survey questions except those related to anaesthesia and physiotherapy showed a statistically significant improvement after the joint school session. A total knowledge score was calculated and revealed a statistically significant difference between pre- and post-joint school survey answering (P value < 0.001)., Conclusion: Our joint school, pre-operative educational session remains a very effective way of delivering content to patients regarding their surgery. Continuous auditing is paramount to its success and there is potential scope for web-based learning as an adjunct to this validated session.

Background: People donating blood more than twice annually are at risk of developing iron deficiency. Little is known about the iron status of dogs enrolled in blood donor programs., Hypothesis: Dogs donating blood ≥6 times annually will show evidence of iron deficiency based on their reticulocyte indices., Animals: Thirteen dogs enrolled in a blood donor program donating ≥6 times over the preceding 12 months and 20 healthy nondonor control dogs., Methods: Prospective observational study. Mature red blood cell (RBC) indices, reticulocyte indices, serum iron, serum ferritin, and total iron-binding capacity (TIBC) were compared between groups., Results: Packed cell volume (median 47%, range 40-52%, P < .01), hematocrit (median 46.4%, range 40.3-52.5%, P < .01), and reticulocyte count (median 16,000/μL, range 9,000-38,000/μL, P < .01) were significantly lower in the blood donor dogs. No statistically significant differences were noted in the mature RBC indices between groups. Both reticulocyte mean corpuscular volume (median 88.8 fL, range 83.4-95.5 fL, P = .03) and reticulocyte hemoglobin content (median 24.6 pg, range 23.1-26.6 pg, P < .01) were significantly lower in the blood donor group. Serum iron and ferritin were similar between groups; however, TIBC was significantly higher in the control group (median 403 μg/dL, range 225-493 μg/dL, P = .02)., Conclusions: The findings in dogs donating ≥6 times annually suggest the presence of iron-deficient erythropoiesis in this population., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.)

Unlabelled: Moral injury is an emerging construct related to negative consequences associated with war-zone stressors that transgress military veterans' deeply held values/beliefs. Given the newness of the construct, there is a need for instrumentation that might assess morally injurious experiences (MIEs) in this population. Drawing on a community sample of 131 Iraq and/or Afghanistan Veterans and clinical sample of 82 returning Veterans, we conducted an initial psychometric evaluation of the newly developed Moral Injury Questionnaire-Military version (MIQ-M)-a 20-item self-report measure for assessing MIEs. Possibly due to low rates of reporting, an item assessing sexual trauma did not yield favourable psychometric properties and was excluded from analyses. Veterans in the clinical sample endorsed significantly higher scores across MIQ-M items. Factor analytic results for the final 19 items supported a unidimensional structure, and convergent validity analyses revealed that higher scores (indicative of more MIEs) were correlated with greater general combat exposure, impairments in work/social functioning, posttraumatic stress and depression in the community sample. In addition, when controlling for demographics, deployment-related factors and exposure to life threat stressors associated with combat, tests of incremental validity indicated that MIQ-M scores were also uniquely linked with suicide risk and other mental health outcomes. These findings provide preliminary evidence for the validity of the MIQ-M and support the applicability of this measure for further research and clinical work with Veterans., Key Practitioner Message: Military service can confront service members with experiences that undermine their core sense of humanity and violate global values and beliefs. These types of experiences increase the risk for posttraumatic maladjustment in this population, even when accounting for rates of exposure to life threat traumas. Moral injury is an emerging construct to more fully capture the many possible psychological, ethical, and spiritual/existential challenges among persons who served in modern wars and other trauma-exposed professional groups. There is currently a need for psychometrically sound instrumentation for assessing morally injurious experiences (MIEs). The Moral Injury Questionnaire - Military Version (MIQ-M) was developed to provide a tool for assessing possible MIEs among military populations. This study provides preliminary evidence of the validity - including factorial, concurrent, and incremental - and clinical utility of the MIQ-M for further applications in clinical and research contexts., (Copyright © 2013 John Wiley & Sons, Ltd.)

Helping professionals working to alleviate the effects of violence and injustice can confront morally injurious experiences (MIE) that violate deeply held moral values/beliefs, placing them at risk for burnout and trauma-related problems (e.g., posttraumatic stress disorder [PTSD]). Focusing on 257 teachers from educational departments throughout El Salvador, we incorporated structural equation modeling (SEM) to examine (1) whether exposure to MIEs for this population (e.g., betrayal, witnessing harm to an innocent student) are directly linked with higher PTSD symptomatology and work-related burnout and (2) whether MIEs contribute to these outcomes via meaning made of trauma. SEM results revealed that MIEs were in fact uniquely linked with PTSD symptoms and burnout, above and beyond rates of direct victimization and demographic factors. In addition, greater MIEs were indirectly linked with study outcomes via the extent to which teachers were able to make meaning of their identified stressors. These findings support the importance of screening for MIEs among helping professionals and also suggest that meaning making could serve as a central mediating factor for how MIEs contribute to trauma-related problems among persons working to promote peace and justice in the world., ((c) 2015 APA, all rights reserved).)

Background: Serum and urine Blastomyces antigen concentrations can be used to diagnose blastomycosis in dogs., Objectives: Blastomyces antigen concentrations correlate with clinical remission in dogs during antifungal treatment, and detect disease relapse after treatment discontinuation., Animals: 21 dogs with newly diagnosed blastomycosis monitored until clinical remission (Treatment Phase), and 27 dogs monitored over 1 year from the time of antifungal discontinuation or until clinical relapse (After Treatment Phase)., Methods: Prospective study. Dogs were monitored monthly during treatment and every 3 months after treatment discontinuation, with a complete history, physical exam, chest radiographs, and ocular exam. Urine and serum Blastomyces antigen concentrations were measured at each visit using a quantitative enzyme immunoassay., Results: At enrollment in the Treatment Phase, Blastomyces antigen was positive in all 21 urine samples (100% sensitivity; 95% CI 85-100%), and in 18 of 20 serum samples (90% sensitivity; 95% CI 70-97%). At 2-4 months of treatment, urine antigen was more sensitive for clinically detectable disease (82%; CI 60-94%) than serum antigen (18%; CI 6-41%). The sensitivity of the urine test for clinical relapse was 71% (CI 36-92%), with close to 100% specificity (CI 84-100%) during after treatment surveillance in this population., Conclusions: Urine Blastomyces antigen testing has high sensitivity for active disease at the time of diagnosis and during treatment, and moderate sensitivity but high specificity for clinical relapse. Urine testing should be useful at the time of diagnosis, when treatment discontinuation is being considered, and anytime there is poor clinical response or suspicion of relapse., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)

One institution's registered nurse preceptor training curriculum was revised to include preceptors' input to ensure their learning needs were being met. A descriptive study design was used to answer the following research questions: (a) what knowledge, skills, and attitudes do nurses believe they need to have to be a preceptor; (b) when, in the course of their development, do preceptors believe they need this information; and (c) in what manner(s) do preceptors prefer to learn this information? Thirteen topics that preceptors believed were important were identified. The results of this study were used to successfully revise the preceptor training curriculum.

Background: The diagnosis of intestinal lymphangiectasia (IL) has been associated with characteristic duodenal mucosal changes. However, the sensitivity and specificity of the endoscopic duodenal mucosal appearance for the diagnosis of IL are not reported., Hypothesis/objectives: To evaluate the utility of endoscopic images of the duodenum for diagnosis of IL. Endoscopic appearance of the duodenal mucosal might predict histopathologic diagnosis of IL with a high degree of sensitivity and specificity., Animals: 51 dogs that underwent upper gastrointestinal (GI) endoscopy and endoscopic biopsies., Methods: Retrospective review of images acquired during endoscopy. Dogs were included if adequate biopsies were obtained during upper GI endoscopy and digital images were saved during the procedure. Images were assessed for the presence and severity of IL. Using histopathology as the gold standard, the sensitivity and specificity of endoscopy for diagnosing IL were calculated., Results: Intestinal lymphangiectasia (IL) was diagnosed in 25/51 dogs. Gross endoscopic appearance of the duodenal mucosa had a sensitivity and specificity (95% confidence interval) of 68% (46%, 84%) and 42% (24%, 63%), respectively for diagnosis of IL. Endoscopic images in cases with lymphopenia, hypocholesterolemia, and hypoalbuminemia had a sensitivity of 80%., Conclusions and Clinical Importance: Endoscopic duodenal mucosa appearance alone lacks specificity and has only a moderate sensitivity for diagnosis of IL. Evaluation of biomarkers associated with PLE improved the sensitivity; however, poor specificity for diagnosis of IL supports the need for histopathologic confirmation., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Background: International humanitarian aid workers providing care in emergencies are subjected to numerous chronic and traumatic stressors., Objectives: To examine consequences of such experiences on aid workers' mental health and how the impact is influenced by moderating variables., Methodology: We conducted a longitudinal study in a sample of international non-governmental organizations. Study outcomes included anxiety, depression, burnout, and life and job satisfaction. We performed bivariate regression analyses at three time points. We fitted generalized estimating equation multivariable regression models for the longitudinal analyses., Results: Study participants from 19 NGOs were assessed at three time points: 212 participated at pre-deployment; 169 (80%) post-deployment; and 154 (73%) within 3-6 months after deployment. Prior to deployment, 12 (3.8%) participants reported anxiety symptoms, compared to 20 (11.8%) at post-deployment (p = 0.0027); 22 (10.4%) reported depression symptoms, compared to 33 (19.5%) at post-deployment (p = 0.0117) and 31 (20.1%) at follow-up (p = .00083). History of mental illness (adjusted odds ratio [AOR] 4.2; 95% confidence interval [CI] 1.45-12.50) contributed to an increased risk for anxiety. The experience of extraordinary stress was a contributor to increased risk for burnout depersonalization (AOR 1.5; 95% CI 1.17-1.83). Higher levels of chronic stress exposure during deployment were contributors to an increased risk for depression (AOR 1.1; 95% CI 1.02-1.20) comparing post- versus pre-deployment, and increased risk for burnout emotional exhaustion (AOR 1.1; 95% CI 1.04-1.19). Social support was associated with lower levels of depression (AOR 0.9; 95% CI 0.84-0.95), psychological distress (AOR = 0.9; [CI] 0.85-0.97), burnout lack of personal accomplishment (AOR 0.95; 95% CI 0.91-0.98), and greater life satisfaction (p = 0.0213)., Conclusions: When recruiting and preparing aid workers for deployment, organizations should consider history of mental illness and take steps to decrease chronic stressors, and strengthen social support networks.

Objective: To demonstrate the noninferiority of a telemedicine modality, videoteleconferencing, compared to traditional in-person service delivery of a group psychotherapy intervention for rural combat veterans with posttraumatic stress disorder (PTSD)., Method: A randomized controlled noninferiority trial of 125 male veterans with PTSD (according to DSM criteria on the Clinician-Administered PTSD Scale) and anger difficulties was conducted at 3 Veterans Affairs outpatient clinics. Participants were randomly assigned to receive anger management therapy delivered in a group setting with the therapist either in-person (n = 64) or via videoteleconferencing (n = 61). Participants were assessed at baseline, midtreatment (3 weeks), posttreatment (6 weeks), and 3 and 6 months posttreatment. The primary clinical outcome was reduction of anger difficulties, as measured by the anger expression and trait anger subscales of the State-Trait Anger Expression Inventory-2 (STAXI-2) and by the Novaco Anger Scale total score (NAS-T). Data were collected from August 2005 to October 2008., Results: Participants in both groups showed significant and clinically meaningful reductions in anger symptoms, with posttreatment and 3 and 6 months posttreatment effect sizes ranging from .12 to .63. Using a noninferiority margin of 2 points for STAXI-2 subscales anger expression and trait anger and 4 points for NAS-T outcomes, participants in the videoteleconferencing condition demonstrated a reduction in anger symptoms similar ("non-inferior") to symptom reductions in the in-person groups. Additionally, no significant between-group differences were found on process variables, including attrition, adherence, satisfaction, and treatment expectancy. Participants in the in-person condition reported significantly higher group therapy alliance., Conclusions: Clinical and process outcomes indicate delivering cognitive-behavioral group treatment for PTSD-related anger problems via videoteleconferencing is an effective and feasible way to increase access to evidence-based care for veterans residing in rural or remote locations., ((c) Copyright 2010 Physicians Postgraduate Press, Inc.)

This article serves as a quick reference for metabolic alkalosis. Guidelines for analysis and causes, signs, and a stepwise approach are presented.

Heart failure is the most common reason for hospital admission in the United States. All nurses, regardless of their specialty, should be familiar with this clinical syndrome. This column describes the pathophysiology and treatment of heart failure.

Investigations of how individuals with schizophrenia differ from non-patients in their responses to stressful life events are subject to the criticism that any between-group differences might merely reflect differences in the types of stressful events that each group experiences. This report presents new analyses of data collected from schizophrenia patients (n=96), bipolar disorder patients (n=18), and healthy controls (n=18) immediately after the Northridge Earthquake that struck Southern California in 1994, a natural experiment that confronted all groups with the same stressful event. Participants completed the Impact of Events Scale (IES; [Horowitz, M.J., Wilner, N., Alvarez, W., 1979. Impact of Events Scale. A measure of subjective stress. Psychosomatic Medicine 41, 209-218]) at 1 week and 5 weeks post-earthquake. At the 5-week follow-up, measures of coping, social support, and self-esteem were also completed. Both patient groups reported higher IES avoidance symptoms than controls immediately after the earthquake. The schizophrenia group also reported lower approach coping, self-esteem, and social support than controls, with the bipolar group reporting intermediate levels. Within the schizophrenia group, higher levels of avoidance coping predicted higher residual stress symptoms at follow-up. Results support the validity of prior reports of altered responses to stressful life events in schizophrenia and demonstrate the clinical relevance of individual differences in coping among affected individuals.

The Mixed-Lineage Leukemia (MLL) gene encodes a Trithorax-related chromatin-modifying protooncogene that positively regulates Hox genes. In addition to their well-characterized roles in axial patterning, Trithorax and Polycomb family proteins perform less-understood functions in vertebrate hematopoiesis. To define the role of MLL in the development of the hematopoietic system, we examined the potential of cells lacking MLL. Mll-deficient cells could not develop into lymphocytes in adult RAG-2 chimeric animals. Similarly, in vitro differentiation of B cells required MLL. In chimeric embryos, Mll-deficient cells failed to contribute to fetal liver hematopoietic stem cell/progenitor populations. Moreover, we show that aorta-gonad-mesonephros (AGM) cells from Mll-deficient embryos lacked hematopoietic stem cell (HSC) activity despite their ability to generate hematopoietic progeny in vitro. These results demonstrate an intrinsic requirement for MLL in definitive hematopoiesis, where it is essential for the generation of HSCs in the embryo.

V(D)J recombination is targeted by short recombination signal (RS) sequences that are relatively conserved but exhibit natural sequence variations. To evaluate the potential of RS sequence variations to determine the primary and peripheral TCRbeta repertoire, we generated mice containing specific replacement of the endogenous Vbeta14 RS with the 3'Dbeta1 RS (Vbeta14/3'DbetaRS). These mice exhibited a dramatic increase in Vbeta14(+) thymocyte numbers at the expense of thymocytes expressing other Vbetas. In addition, the percentage of peripheral Vbeta14(+) alphabeta T lymphocytes was similarly increased. Strikingly, this altered Vbeta repertoire resulted predominantly from a higher relative level of primary Vbeta14/3'DbetaRS rearrangement to DbetaJbeta complexes, despite the ability of the 3'Dbeta1 RS to break B12/23 restriction and allow direct rearrangement of Vbeta14/3'DbetaRS to Jbeta segments.

Radiosensitive severe combined immune deficiency in humans results from mutations in Artemis, a protein which, when coupled with DNA-dependent protein kinase catalytic subunit (DNA-PKcs), possesses DNA hairpin-opening activity in vitro. Here, we report that Artemis-deficient mice have an overall phenotype similar to that of DNA-PKcs-deficient mice-including severe combined immunodeficiency associated with defects in opening and joining V(D)J coding hairpin ends and increased cellular ionizing radiation sensitivity. While these findings strongly support the notion that Artemis functions with DNA-PKcs in a subset of NHEJ functions, differences between Artemis- and DNA-PKcs-deficient phenotypes, most notably decreased fidelity of V(D)J signal sequence joining in DNA-PKcs-deficient but not Artemis-deficient fibroblasts, suggest additional functions for DNA-PKcs. Finally, Artemis deficiency leads to chromosomal instability in fibroblasts, demonstrating that Artemis functions as a genomic caretaker.

This study examined the influence of bomb-related television viewing in the context of physical and emotional exposure on posttraumatic stress symptoms--intrusion, avoidance, and arousal--in middle school students following the 1995 Oklahoma City bombing. Over 2,000 middle school students in Oklahoma City were surveyed 7 weeks after the incident. The primary outcome measures were the total posttraumatic stress symptom score and symptom cluster scores at the time of assessment. Bomb-related television viewing in the aftermath of the disaster was extensive. Both emotional and television exposure were associated with posttraumatic stress at 7 weeks. Among children with no physical or emotional exposure, the degree of television exposure was directly related to posttraumatic stress symptomatology. These findings suggest that television viewing in the aftermath of a disaster may make a small contribution to subsequent posttraumatic stress symptomatology in children or that increased television viewing may be a sign of current distress and that it should be monitored. Future research should examine further whether early symptoms predict increased television viewing and/or whether television viewing predicts subsequent symptoms.

Leukocyte capture and rolling are mediated by selectins expressed on leukocytes (L-selectin) and the vascular endothelium (P- and E-selectin). To investigate the role of core 2 beta1-6-N-glucosaminyltransferase (C2GlcNAcT-I) for synthesis of functional selectin ligands in vivo, leukocyte rolling flux and velocity were studied in venules of untreated and tumor necrosis factor-alpha (TNFalpha)-pretreated autoperfused cremaster muscles of C2GlcNAcT-I-deficient (core 2(-/-)) and littermate control mice. In untreated core 2(-/-) mice, leukocyte rolling was dramatically reduced with markedly increased rolling velocities (81 +/- 4 microm/s vs 44 +/- 3 microm/s). The reduced rolling in core 2(-/-) mice was due mainly to severely impaired binding of P-selectin to P-selectin glycoprotein ligand-1 (PSGL-1). Some rolling remained after blocking PSGL-1 in controls but not in core 2(-/-) mice. In TNFalpha-pretreated mice, rolling was markedly reduced in core 2(-/-) mice owing to impaired P-selectin- and E-selectin-mediated rolling. Rolling velocities in core 2(-/-) mice treated with an E-selectin-blocking monoclonal antibody (59 +/- 4 microm/s) were significantly higher than in controls (14 +/- 1 microm/s), which provides further evidence for the severe impairment in P-selectin-mediated rolling. In conclusion, P-selectin ligands including PSGL-1 are largely C2GlcNAcT-I dependent. In addition, E-selectin-mediated rolling in vivo is partially dependent on the targeted C2GlcNAcT-I. (Blood. 2001;97:3812-3819)

Endothelial surface expression of P-selectin and subsequent leukocyte rolling in venules can be induced by mast cell-derived histamine and binding of thrombin to protease-activated receptor-1 (PAR1). We hypothesized that activation of endothelial PAR2 by mast cell tryptase or other proteases also contributes to inflammatory responses. Leukocyte rolling flux and rolling velocity were assessed by intravital microscopy of the cremaster muscles of wild-type mice following perivenular micropipette injections of a control (LSIGRL) or PAR2-activating (SLIGRL) oligopeptide. Injection of SLIGRL increased mean rolling leukocyte flux fraction from 34 +/- 11 to 71 +/- 24% (p < 0.05) and decreased mean rolling velocity from 63 +/- 29 to 32 +/- 2 micrometer/s (p < 0.05). No significant changes occurred with control peptide injection. To further evaluate the role of PAR2 in inflammatory responses, PAR2-deficient mice were generated by gene targeting and homologous recombination. Perivenular injections of SLIGRL resulted in only a small increase in rolling leukocyte flux fraction (from 21 +/- 8 to 30 +/- 2%) and no change in rolling velocity. Leukocyte rolling after surgical trauma was assessed in 9 PAR2-deficient and 12 wild-type mice. Early (0-15 min) after surgical trauma, the mean leukocyte rolling flux fraction was lower (10 +/- 3 vs 30 +/- 6%, p < 0.05) and mean rolling velocity was higher (67 +/- 46 vs 52 +/- 36 micrometer/s, p < 0.01) in PAR2-deficient compared with control mice. The defect in leukocyte rolling in PAR2-deficient mice did not persist past 30 min following surgical trauma. These results indicate that activation of PAR2 produces microvascular inflammation by rapid induction of P-selectin-mediated leukocyte rolling. In the absence of PAR2, the onset of inflammation is delayed.

The leukocyte integrins LFA-1 and Mac-1 bind to endothelial intercellular adhesion molecule-1 (ICAM-1). Leukocyte adhesion induced by micropipette injection of formylmethionylleucylphenylalanine (fMLP) or macrophage inflammatory protein 2 (MIP-2) next to a venule in the exteriorized mouse cremaster muscle was almost completely blocked after intravenous injection of the ICAM-1 mAb YN-1. In contrast, after 2-h pretreatment with TNF-alpha, leukocyte adhesion induced in postcapillary venules by fMLP or MIP-2 was not blocked by the ICAM-1 mAb. Leukocyte adhesion was significantly reduced by mAb GAME-46 to CD18 even after TNF-alpha treatment. We conclude that ICAM-1 is necessary for neutrophil adhesion to unstimulated endothelium, but not for adhesion to cytokine-stimulated endothelium. Although ICAM-1 is expressed at high levels after TNF-alpha, ICAM-1 either is not functional or is redundant with other endothelial ligands for beta(2) integrins., (Copyright 2000 Academic Press.)

The standard management of primary lower limb varicosities (stripping of the long saphenous vein (LSV) with avulsion of the varicosities) is based on the assumption that the disease originates from primary valvular insufficiency and incompetent perforating veins. It has recently been suggested that the LSV may be spared in patients with superficial varicosities without incompetence of this vein, i.e., early disease. However, pre-operative identification of suitable patients for conservative surgery has proved difficult. In this study, we employed selective duplex scanning in cases with primary varicosity in whom sapheno-femoral and sapheno-popliteal incompetence had been excluded both clinically and with the hand-held Doppler (52 limbs [10% of new referrals]). We found that the varicosities in these limbs were of 3 types: (a) those arising independent of superficial vein incompetence (Type 1); (b) those associated with segmental LSV incompetence (Type 2); (c) those in whom incompetence of the sapheno-femoral junction and LSV was missed (Type 3). We therefore suggest that long saphenous varicosity may progress from Type 1 through to Type 3 with each type representing an increase in severity of the disease. We suggest that selective use of duplex scanning will assist in identifying those patients with early stages of the disease who can then be treated effectively with LSV-sparing surgery.

Primary lower limb varicosities classically arise from incompetence of the junction of the superficial and the deep venous systems with retrograde flow into the saphenous veins. However, some patients with superficial varicosities have no demonstrable incompetence of the saphenofemoral or saphenopopliteal junctions. In this study, we examined 52 limbs with primary varicose disease in whom saphenofemoral and saphenopopliteal incompetence had been excluded (clinically and with the hand-held Doppler) using a duplex ultrasound scan. Seventeen (33%) of the limbs had superficial varicosities despite normal long and short saphenous veins. The varicosities in 12 of these legs originated from groin veins, while those in the remaining 5 limbs communicated directly with normal deep veins. In this latter group of limbs, the superficial varicosities were found on the lateral aspect of the thighs only. Primary varicosities arising from normal deep venous systems have not been previously described, and are relatively rare (1.0% of patients referred to our clinic). As this complex venular anatomy was only detected on duplex scanning, we conclude that this study provides further evidence of the need for this imaging modality in patients with varicose disease of uncertain origin and/or those with an unusual distribution of superficial varicosities.

Objective: This clinical assessment was designed to identify middle and high school students in need of formal evaluation for posttraumatic response symptoms following the 1995 bombing of the Alfred P. Murrah Federal Building in Oklahoma City., Method: A clinical needs assessment instrument was developed and administered to grade 6 through 12 students 7 weeks after the bombing (N = 3,218)., Results: More than 40% of the students reported knowing someone injured, and more than one-third reported knowing someone killed in the blast. Posttraumatic stress symptoms at 7 weeks significantly correlated with gender, exposure through knowing someone injured or killed, and bomb-related television viewing., Conclusions: This study documents the intensity of community exposure to the bombing and the lingering symptoms of stress. The assessment was used in planning for clinical service delivery, training professional responders, and supporting funding requests.

This study tested a family-based skills-building intervention in veterans with chronic combat-related posttraumatic stress disorder (PTSD). Veterans and a family member were randomly assigned to 1 of 3 conditions: (a) waiting list, (b) 18 sessions of twice-weekly exposure therapy, or (c) 18 sessions of twice-weekly exposure therapy followed by 16 sessions of behavioral family therapy (BFT). Participation in exposure therapy reduced PTSD positive symptoms (e.g., reexperiencing and hyperarousal) but not PTSD negative symptoms. Positive symptom gains were maintained at 6-month follow-up. However, participation in BFT had no additional impact on PTSD symptoms.

This research assessed the lifetime prevalence of traumatic events and current posttraumatic stress disorder (PTSD) in 275 patients with severe mental illness (e.g., schizophrenia and bipolar disorder) receiving public mental health services in Concord and Manchester, New Hampshire, and Baltimore, Maryland. Lifetime exposure to traumatic events was high, with 98% of the sample reporting exposure to at least 1 traumatic event. The rate of PTSD in our sample was 43%, but only 3 of 119 patients with PTSD (2%) had this diagnosis in their charts. PTSD was predicted most strongly by the number of different types of trauma, followed by childhood sexual abuse. The findings suggest that PTSD is a common comorbid disorder in severe mental illness that is frequently overlooked in mental health settings.

Objectives: To compare the findings of continuous wave Doppler (CWD) with duplex ultrasound in the assessment of primary and uncomplicated varicose veins, and to determine how their relative roles might be best applied., Materials and Methods: One hundred consecutive limbs were studied in 73 patients with primary (no previous surgery) and uncomplicated (no significant skin change) varicose veins. CWD was employed by a single observer; followed by duplex scanning performed "blind" and independently., Results: There were 87 limbs with long saphenous incompetence on duplex; all but four of which were correctly identified by CWD, by which technique there were no false positives. (Sensitivity 95%, specificity 100%.) There were 21 limbs with short saphenous incompetence on duplex, all but two of which were recognised on CWD. However, CWD incorrectly diagnosed reflux at the saphenopopliteal junction in five limbs (false positives) with what was, in fact, segmental reflux in the long saphenous trunk on duplex (sensitivity 90%, specificity 93%.) This would have led to inappropriate exploration of the saphenopopliteal junction had surgery proceeded without checking with duplex., Conclusions: CWD is adequate for long saphenous incompetence. All "reflux" demonstrated on CWD in the popliteal fossa (about 25% of cases) should be checked by duplex. If this policy had been followed, all the patients in this study would have undergone the correct procedure. The only "errors" would have been missing coexistent short saphenous incompetence in two limbs undergoing appropriate long saphenous exploration.

This study compared symptoms of posttraumatic stress disorder (PTSD) in a group of 45 adult women in outpatient treatment for childhood sexual abuse (CSA) and a group of 31 women who reported no CSA. The comparison group consisted of women in outpatient treatment for problems in their committed relationships with male living partners. This research also investigated the traumatic impact of dual abuse (both childhood sexual and physical abuse). Standardized assessment instruments were used to measure PTSD, CSA, and childhood physical abuse (CPA). Results indicated that 86.7% of the CSA group met criteria for current PTSD in accordance with the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised; American Psychiatric Association, 1987), compared with 19.4% of the relationship distress group, providing support for CSA as an etiological agent for PTSD. In addition, 89% of the CSA survivors reported CPA. Multivariate analysis revealed that both CSA and CPA exposure variables accounted for a significant portion of the variance in PTSD symptoms in the CSA group.