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Introduction: Nurse turnover has accelerated during the COVID-19 pandemic. Nurse refusal of mandated vaccines contributes to understaffing and affects patient health outcomes. The purposes of this study were to describe (1) nurse reasons for COVID-19 vaccine decisions and (2) the relationship between vaccine status and nurse characteristics., Methods: This cross-sectional descriptive study employed a survey of US nurses who worked in nursing during the COVID-19 pandemic. The survey included a free-text question about COVID-19 vaccine uptake rationale, self-reported vaccine acceptance/refusal, and demographic data., Results: Of the 1682 participants, 11.2% refused the COVID-19 vaccine. Higher education level was correlated with greater vaccine acceptance rates ( P  < 0.001). Themes for vaccine rationale included safeguarding well-being, trust in the science, coercion to vaccinate, perceived immunity, and concern about preexisting health conditions., Conclusions: The risks of COVID-19 vaccine mandates may be greater than the potential benefits given the potential for compounding workforce attrition during a nursing staffing crisis. Further research is needed to outline the relationships between vaccine education, advocacy, and vaccine uptake among nurses., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)

Objectives: The aim of this study was to assess the prevalence of use of objective voice measurements (OVM), instrumentation, and factors that may impact OVM outcomes, such as setting and implementation to clarify current practice. Doing so should clarify the impact of OVM research on patient care., Methods: A 12-question, one-time anonymous survey using the Research Electronic Data Capture tool was distributed during January 2023 to laryngologists in the United States identified through membership in The Voice Foundation (TVF) or previous participation in a TVF symposium., Results: A total of 101 responses to 418 emails yielded a response rate of 24.2%. Seventeen point eight percentage (N = 18) were in private practice, 63.4% (N = 64) were in academic settings, and 18.8% (N = 19) were classified as mixed private and academic. Common OVMs used were fundamental frequency 95.12% (N = 78), maximum phonation time 90.24% (N = 74), noise-to-harmonic ratio 71.95% (N = 59), jitter 71.95% (N = 59), and shimmer 70.73% (N = 58). Common equipment and software used Pentax Multi-Dimensional Voice Program 42.68% (N = 35), Pentax Computerized Speech Lab Model 4500B 37.80% (N = 31), and Pentax Visi-Pitch, Model 3950C 23.17% (N = 19), PRAAT 21.95% (N = 18), OperaVOX 4.88% (N = 4), VoceVista 3.66% (N = 3). Fifty one point two percentage (N = 42) stated that they used OVMs with the majority of their patients, most commonly for the assessment of treatment effectiveness (84.1%, N = 69), documentation (78.0%, N = 64), research (70.7%, N = 58), and/or diagnosis (61.0%, N = 50). Ninety point two percentage (N = 74) stated that OVMs were used during initial evaluation of patients., Conclusion: This study estimates of the prevalence of OVM use among laryngologists in the United States. There appears to be sufficient consistency among laryngology centers to permit comparison of results between centers, although additional research is needed. Future OVM research should compare measurements and equipment commonly used by laryngologists to define further the generalizability of results., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Study Objective: The purpose of this quality improvement study was to reduce nonemergent visits to the emergency department attendance within a multistate Veterans Health Affairs network., Methods: Telephone triage protocols were developed and implemented for registered nurse staff to triage selected calls to a same-day telephonic or video virtual visit with a provider (physician or nurse practitioner). Calls, registered nurse triage dispositions, and provider visit dispositions were tracked for 3 months., Results: There were 1606 calls referred by registered nurses for provider visits. Of these, 192 were initially triaged as emergency department dispositions. Of these, 57.3% of calls that would have been referred to the emergency department were resolved via the virtual visit. Thirty-eight percent fewer calls were referred to the emergency department following licensed independent provider visit compared to the registered nurse triage., Conclusion: Telephone triage services augmented by virtual provider visits may reduce emergency department disposition rates, resulting in fewer nonemergent patient presentations to the emergency department and reducing unnecessary emergency department overcrowding. Reducing nonemergent attendance to emergency departments can improve outcomes for patients with emergent dispositions., (Copyright © 2023. Published by Elsevier Inc.)

The purpose of this mixed-method study was to understand the relationships between work-related burnout (WRB), compassion fatigue (CF), and intention to leave the nursing profession. The Job Demands-Resources model was used to predict intention to leave as a function of WRB, CF, and caring for COVID-19 patients in a sample of 1299 US nurses. Greater WRB and CF scores were associated with intention to leave the profession. Contrary to prior research, working with COVID-19 patients was associated with greater intention to stay in nursing. Personal finances may represent the rationale for nurses to choose to stay nurses despite burnout., (2022 by Elsevier Inc. All rights reserved.)

Objective: To describe the lived experience of nursing staff and nurse leaders working in COVID-19 devoted units (intensive care or medical unit) prior to vaccine availability., Research Design: Qualitative phenomenological design with a focus group approach., Methods: The study team recruited a convenience sample of nursing staff (nurses, and nursing assistants/nurse technicians) and nurse leaders (managers, assistant nurse managers, clinical nurse specialists, and nurse educators) at an academic medical center in the midwestern United States. Focus groups and individual interviews were conducted to encourage participants to describe their (1) experiences as nursing professionals, (2) coping strategies, and (3) perspectives about supportive resources. Moral distress was measured with the moral distress thermometer and qualitative data were analyzed with Giorgi-style phenomenology., Results: We conducted 10 in-person focus groups and five one-on-one interviews ( n   =  44). Seven themes emerged: (1) the reality of COVID-19: we are sprinting in a marathon; (2) acute/critical care nurse leaders experience unique burdens; (3) acute/critical care staff nurses experience unique burdens; (4) meaning of our lived experience; (5) what helped us during the pandemic; (6) what hurt us during the pandemic; and (7) we are not okay. Participants reported a moderate level of moral distress ( M   =  5.26 SD   =  2.31). They emphasized that peer support was preferred over other types of support offered by the healthcare organization. Participants expressed positive feedback about the focus group experience and commented that group processing validated their experiences and helped them "feel heard.", Conclusion: These findings affirm the need for trauma-informed care and grief support for nurses, interventions that increase meaning in work, and efforts to enhance primary palliative communication skills. Study findings can inform efforts to tailor existing interventions and develop new, more comprehensive resources to meet the psychosocial needs of nursing staff and nurse leaders practicing during a pandemic., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Nurse duty of care, the balance between nursing occupational obligations to provide care, the personal costs for providing such care, and the reward for providing care, has been significantly altered by the COVID-19 pandemic. ICU nurses are increasingly burdened with higher personal costs to fulfill their jobs, but little additional reward for continuing to provide care., Objectives: The purpose of this study was to examine the impact of the COVID-19 pandemic on the duty of care balance among ICU nurses who manage COVID-19 patients., Design: This was a descriptive qualitative study using semi-structured interviews., Methods: Nurses were recruited for a parent study on ICU nursing during COVID-19; this is a secondary analysis of the interviews that took place during the parent study. Content analysis was utilized to identify themes from interview transcripts., Results: Thirteen nurses participated in interviews. Nurses reported betrayal at perceived breeches in their duty of care agreement by their employers, the general public, and national health authorities. They described alterations to previous standards of care such as significantly increased workloads, worsening understaffing, and changes to patient care expectations that were implemented for reasons other than betterment of patient care. Nurses reported they felt a moral obligation to provide care, however they experienced disempowerment and burnout that affected them both in and out of the workplace., Conclusion: The COVID-19 pandemic has affected several aspects of the duty of care balance, resulting in a duty of care balance that is inequitable to nurses. Imbalance in the effort, risks, and rewards for nursing professionals may contribute to nurse burnout., Relevance to Clinical Practice: This research highlights the need for healthcare administrators to consider resource allocation, nurse appreciation, and commensurate compensation for professional nurses., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Tumorigenesis and metastasis have deep connections to inflammation and inflammatory cytokines, but the mechanisms underlying these relationships are poorly understood. Leukemia Inhibitory Factor (LIF) and its receptor (LIFR), part of the interleukin-6 (IL-6) cytokine family, make up one such ill-defined piece of the puzzle connecting inflammation to cancer. Although other members of the IL-6 family have been shown to be involved in the metastasis of multiple types of cancer, the role of LIF and LIFR has been challenging to determine. Described by others in the past as enigmatic and paradoxical, LIF and LIFR are expressed in a diverse array of cells in the body, and the narrative surrounding them in cancer-related processes has been vague, and at times even contradictory. Despite this, recent insights into their functional roles in cancer have highlighted interesting patterns that may allude to a broader understanding of LIF and LIFR within tumor growth and metastasis. This review will discuss in depth the signaling pathways activated by LIF and LIFR specifically in the context of cancer-the purpose being to summarize recent literature concerning the downstream effects of LIF/LIFR signaling in a variety of cancer-related circumstances in an effort to begin teasing out the intricate web of contradictions that have made this pair so challenging to define., 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., (Copyright © 2021 Christianson, Oxford and Jorcyk.)

Objective: To determine relationships between age of men with potential male factor infertility and sperm chromatin structure assay (SCSA) measures of sperm DNA fragmentation (SDF) and high DNA stainable sperm (HDS), and to compare these data with those obtained from healthy donor men without reproductive issues., Design: Retrospective study., Setting: Infertility clinics and diagnostic laboratory., Patients: A total of 25,445 men attending infertility clinics. Donors were 87 men working at Lawrence Livermore National Laboratory., Intervention: None., Main Outcome Measures: SCSA measures (% DNA fragmentation index (DFI), X DFI, SD DFI, and %HDS) of men aged 21-80 years., Results: In the study population, advancing paternal age was associated with increased sperm DNA fragmentation (SDF) scored as increased percentage of sperm in semen ejaculates with measurable DNA strand breaks (%DFI). The slope of increase in %DFI prior to age 41.6 years was 0.39, which increased after age 41.6 to more than double at a slope of 0.86. These changes in DNA/chromatin in more than 25,000 aging men attending infertility clinics are similar to those seen over the same age span (20-80 years) in 87 nonpatient, healthy men without reproductive issues. For the age group 20-50 years, there was no major significant difference in %DFI between patients and donor men. According to a logistic regression model, the estimated probability is that, for example, a 40-year-old and a 50-year-old man have a 20% and 40% chance, respectively, to have a pathological DFI ≥25% by age factor alone. The condensation of sperm chromatin in patients increased with age in a linear fashion, from a mean of 12.2 %HDS at age 20-25 to a mean of 7.9 %HDS at age 60-65. Patients had a greater %HDS than donors across all ages., Conclusions: The great heterogeneity of both DFI and HDS values at a specific age prevents the automatic translation of age into an index of DNA fragmentation. However, it reinforces the idea that both DFI and HDS evaluation can play a role in detecting potential male infertility in cases that are not resolved by routine testing and in cases of multiple miscarriages. DFI and HDS data can help clinicians to predict a man's fertility potential, to consider corrective therapeutic approaches, as well as to assess the risk to the offspring's health., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The ability of an individual to reduce the intensity, duration or frequency of a stressor is a critical determinant of the consequences of that stressor on physiology and behavior. To expand our understanding of the brain networks engaged during controllable and uncontrollable stress and to identify sex differences, we used functional connectivity analyses of the immediate early gene product Fos in male and female rats exposed to either controllable or uncontrollable tail shocks. Twenty-eight regions of interest (ROI) were selected from the structures previously evinced to be responsible for stress response, action-outcome learning, or sexual dimorphism. We found that connectivity across these structures was strongest in female rats without control while weaker connectivity was evident in male rats with control over stress. Interestingly, this pattern correlates with known behavioral sex differences where stressor controllability leads to resilience in male but not female rats. Graph theoretical analysis identified several structures important to networks under specific conditions. In sum, the findings suggest that control over stress reshapes functional connectivity., (© 2020 The Authors.)

Neural activity within the ventromedial prefrontal cortex (vmPFC) is a critical determinant of stressor-induced anxiety. Pharmacological activation of the vmPFC during stress protects against stress-induced social anxiety suggesting that altering the excitatory/inhibitory (E/I) tone in the vmPFC may promote stress resilience. E/I balance is maintained, in part, by endogenous cannabinoid (eCB) signaling with the calcium dependent retrograde release of 2-arachidonoylglycerol (2-AG) suppressing presynaptic neurotransmitter release. We hypothesized that raising 2-AG levels, via inhibition of its degradation enzyme monoacylglycerol lipase (MAGL) with KML29, would shift vmPFC E/I balance and promote resilience. In acute slice experiments, bath application of KML29 (100 nM) augmented evoked excitatory neurotransmission as evidenced by a left-shift in fEPSP I/O curve, and decreased sIPSC amplitude. In whole-cell recordings, KML29 increased resting membrane potential but reduced the after depolarization, bursting rate, membrane time constant and slow after hyperpolarization. Intra-vmPFC administration of KML29 (200ng/0.5μL/hemisphere) prior to inescapable stress (IS) exposure (25, 5s tail shocks) prevented stress induced anxiety as measured by juvenile social exploration 24 h after stressor exposure. Conversely, systemic administration of KML29 (40 mg/kg, i.p.) 2 h before IS exacerbated stress induced anxiety. MAGL inhibition in the vmPFC may promote resilience by augmenting the output of neurons that project to brainstem and limbic structures that mediate stress responses., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Endometriosis is a female disease which is defined as the presence of ectopic endometrial tissue and is dependent on estrogen for its survival in these ectopic locations. Expression of the ribosomal protein large P1 (RPLP1) is associated with cell proliferation and invasion in several pathologies, but a role in the pathophysiology of endometriosis has not been explored. In this study, we aimed to evaluate the expression and function of RPLP1 with respect to endometriosis pathophysiology. RPLP1 protein was localised by immunohistochemistry (IHC) in eutopic and ectopic tissue from 28 subjects with confirmed endometriosis and from 20 women without signs or symptoms of the disease, while transcript levels were evaluated by qRT-PCR in 77 endometriotic lesions and 55 matched eutopic endometrial biopsies, and protein expression was evaluated using western blotting in 20 of these matched samples. To evaluate the mechanism for enhanced lesion expression of RPLP1, an experimental murine model of endometriosis was used and RPLP1 expression was localized using IHC. In vitro studies using an endometriosis cell line coupled with shRNA knockdown was used to demonstrate its role in cell survival. Expression of RPLP1 mRNA and protein were significantly higher in ectopic lesion tissue compared to paired eutopic endometrium and immunohistochemical localisation revealed predominant localisation to epithelial cells. This pattern of lesion RPLP1 was recapitulated in mice with experimentally induced endometriosis. Stable knockdown of RPLP1 protein resulted in a significant decrease in cell survival in vitro. These studies reveal that RPLP1 is associated with cell proliferation and/or survival and may play a role in the pathophysiology of endometriosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Oncolytic viruses represent an emerging approach to cancer therapy. However, better understanding of their interaction with the host cancer cell and approaches to enhance their efficacy are needed. Here, we investigate the effect of chemically induced endoplasmic reticulum (ER) stress on the activity of the chimeric group B adenovirus Enadenotucirev, its closely related parental virus Ad11p, and the archetypal group C oncolytic adenovirus Ad5. We show that treatment of colorectal and ovarian cancer cell lines with thapsigargin or ionomycin caused an influx of Ca 2+ , leading to an upregulation in E1A transcript and protein levels. Increased E1A protein levels, in turn, increased levels of expression of the E2B viral DNA polymerase, genome replication, late viral protein expression, infectious virus particle production, and cell killing during Enadenotucirev and Ad11p, but not Ad5, infection. This effect was not due to the induction of ER stress, but rather the influx of extracellular Ca 2+ and consequent increase in protein kinase C activity. These results underscore the importance of Ca 2+ homeostasis during adenoviral infection, indicate a signaling pathway between protein kinase C and E1A, and raise the possibility of using Ca 2+ flux-modulating agents in the manufacture and potentiation of oncolytic virotherapies., (© 2019 The Authors.)

Firefighters' work responsibilities involve strenuous physical activity and exposure to extremely stressful situations. The purpose of this research study was to describe the physical activity, stress, and culture promoting or inhibiting a healthy work environment. A descriptive qualitative study design was used with a convenience sample of firefighters from an urban Midwestern public fire service. Respondents participated in focus groups from which data were audio recorded, transcribed verbatim, and analyzed using Colaizzi's phenomenological method. Themes derived from the data were Stressors Affecting Physical Health, Barriers to Physical Health, Facilitators of Physical Health, and Motivators for Physical Health. Future research is needed to test interventions based on the study findings., (© 2015 The Author(s).)

Acquiring additional education and certifications can transform occupational health nurses into leaders who can enhance the workplace., (Copyright 2014, SLACK Incorporated.)

Objective: Examine the factors that are associated with awareness of physician quality information (PQI) among older people with one or more chronic illnesses and the implications for Medicare., Data Sources/study Setting: Random digit-dial survey of adults with one or more chronic illnesses., Research Design: Structural equation modeling to examine factors related to awareness of PQI., Results: Awareness of PQI is low (13 percent), but comparable to findings in general population surveys. Age, race, education, and self-reported health status are associated with PQI awareness. Trust in the Internet as a source of health care information and not trusting one's physician as a source of information both are associated with a greater likelihood of being aware of PQI. Patients with high levels of activation have greater trust in physicians as information sources, but this is not associated with awareness, nor is degree of satisfaction with their care experience., Conclusions: Awareness of PQI among older persons with chronic illnesses is relatively low across all socio-economic and demographic subgroups. Changes in population characteristics over time are unlikely to improve awareness in this population, nor are changes in patient activation or satisfaction with care. Medicare would need a broad-based effort if it wishes to raise PQI awareness among Medicare beneficiaries in the near term. Before undertaking resource-intensive efforts to increase awareness, Medicare may want to consider what level of awareness actually is needed to accomplish the overall objective for PQI transparency, which is raising the quality of care received by beneficiaries. It may be that relatively low levels of awareness are sufficient.

Early life stress can permanently alter functioning of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the stress response and influences the perception of pain. Chronic pelvic pain patients commonly report having experienced childhood neglect or abuse, which increases the likelihood of presenting with comorbid chronic pain and/or mood disorders. Animal models of neonatal stress commonly display enhanced anxiety-like behaviors, colorectal hypersensitivity, and disruption of proper neuro-immune interactions in adulthood. Here, we tested the hypothesis that early life stress impacts vaginal sensitivity by exposing mice to neonatal maternal separation (NMS) for 3h/day during the first two (NMS14) or three (NMS21) postnatal weeks. As adults, female mice underwent vaginal balloon distension (VBD), which was also considered an acute stress. Before or after VBD, mice were assessed for anxiety-like behavior, hindpaw sensitivity, and changes in gene and protein expression related to HPA axis function and regulation. NMS21 mice displayed significantly increased vaginal sensitivity compared to naïve mice, as well as significantly reduced anxiety-like behavior at baseline, which was heightened following VBD. NMS21 mice exhibited significant thermal and mechanical hindpaw hypersensitivity at baseline and following VBD. NMS14 mice displayed no change in anxiety-like behavior and only exhibited significantly increased hindpaw mechanical and thermal sensitivity following VBD. Centrally, a significant decrease in negative regulation of the HPA axis was observed in the hypothalamus and hippocampus of NMS21 mice. Peripherally, NMS and VBD affected the expression of inflammatory mediators in the vagina and bladder. Corticotropin-releasing factor (CRF) receptor and transient receptor potential (TRP) channel protein expression was also significantly, and differentially, affected in vagina, bladder, and colon by both NMS and VBD. Together these data indicate that NMS affects both central and peripheral aspects of the HPA axis, which may drive changes in vaginal sensitivity and the development of comorbid chronic pain and mood disorders., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

Mammalian pain-related sensory neurons are derived from TrkA lineage neurons located in the dorsal root ganglion. These neurons project to peripheral targets throughout the body, which can be divided into superficial and deep tissues. Here, we find that the transcription factor Runx1 is required for the development of many epidermis-projecting TrkA lineage neurons. Accordingly, knockout of Runx1 leads to the selective loss of sensory innervation to the epidermis, whereas deep tissue innervation and two types of deep tissue pain are unaffected. Within these cutaneous neurons, Runx1 suppresses a large molecular program normally associated with sensory neurons that innervate deep tissues, such as muscle and visceral organs. Ectopic expression of Runx1 in these deep sensory neurons causes a loss of this molecular program and marked deficits in deep tissue pain. Thus, this study provides insight into a genetic program controlling the segregation of cutaneous versus deep tissue pain pathways., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Improving the quality and efficiency of chronic disease care is an important goal., Objective: To test whether patients with chronic disease working with lay "care guides" would achieve more evidence-based goals than those receiving usual care., Design: Parallel-group randomized trial, stratified by clinic and conducted from July 2010 to April 2012. Patients were assigned in a 2:1 ratio to a care guide or usual care. Patients, providers, and persons assessing outcomes were not blinded to treatment assignment. (ClinicalTrials.gov: NCT01156974)., Setting: 6 primary care clinics in Minnesota., Patients: Adults with hypertension, diabetes, or heart failure., Intervention: 2135 patients were given disease-specific information about standard care goals and asked to work toward goals for 1 year, with or without the help of a care guide. Care guides were 12 laypersons who received brief training about these diseases and behavior change., Measurements: The primary end point for each patient was change in percentage of goals met 1 year after enrollment., Results: The percentage of goals met increased in both the care guide and usual care groups (changes from baseline, 10.0% and 3.9%, respectively). Patients with care guides achieved more goals than usual care patients (82.6% vs. 79.1%; odds ratio, 1.31 [95% CI, 1.16 to 1.47]; P < 0.001); reduced unmet goals by 30.1% compared with 12.6% for usual care patients; and improved more than usual care patients in meeting several individual goals, including not using tobacco. Estimated cost was $286 per patient per year., Limitations: Providers' usual care may have been influenced by contact with care guides. Last available data in the electronic health record were used to assess end points., Conclusion: Adding care guides to the primary care team can improve care for some patients with chronic disease at low cost.

Objectives: To measure the effect of electronic medical records (EMRs) on a publicly reported composite measure indicating optimal diabetes care (ODC) rates in ambulatory settings., Study Design: Data from Minnesota Community Measurement on 557 clinics were used, including information on ODC, EMR adoption, and clinic characteristics., Methods: A difference-in-differences strategy was used to estimate the impact of EMR adoption on patient outcomes while controlling for observed and unobserved clinic characteristics. Results were compared with a cross-sectional analysis of the same data., Results: EMRs had no observable effect on ODC for the average clinic during the first 2 years postadoption. EMRs may, however, generate modest (+4 percentage point) ODC increases for clinics in large, multisite practices. Cross-sectional analysis likely overestimates the effect of EMRs on quality., Conclusions: There is little evidence that EMR adoption improves diabetes care during the first 2 years postadoption. This is notable as diabetes is a condition for which information technology has the potential to improve care management. The results suggest that policy makers should not expect public sector EMR investments to yield significant short-term improvements in publicly reported measures.

Uncontrollable stress can interfere with instrumental learning and induce anxiety in humans and rodents. While evidence supports a role for serotonin (5-HT) and serotonin 2C receptors (5-HT(2C)R) in the behavioral consequences of uncontrollable stress, the specific sites of action are unknown. These experiments sought to delineate the role of 5-HT and 5-HT(2C)R in the dorsal striatum (DS) and the lateral/basolateral amygdala (BLA) in the expression of stress-induced instrumental escape deficits and exaggerated fear, as these structures are critical to instrumental learning and fear behaviors. Using in vivo microdialysis, we first demonstrated that prior uncontrollable, but not controllable, stress sensitizes extracellular 5-HT in the dorsal striatum, a result that parallels prior work in the BLA. Additionally, rats were implanted with bi-lateral cannula in either the DS or the BLA and exposed to uncontrollable tail shock stress. One day later, rats were injected with 5-HT(2C)R antagonist (SB242084) and fear and instrumental learning behaviors were assessed in a shuttle box. Separately, groups of non-stressed rats received an intra-DS or an intra-BLA injection of the 5-HT(2C)R agonist (CP809101) and behavior was observed. Intra-DS injections of the 5-HT(2C)R antagonist prior to fear/escape tests completely blocked the stress-induced interference with instrumental escape learning; a partial block was observed when injections were in the BLA. Antagonist administration in either region did not influence stress-induced fear behavior. In the absence of prior stress, intra-DS administration of the 5-HT(2C)R agonist was sufficient to interfere with escape behavior without enhancing fear, while intra-BLA administration of the 5-HT(2C)R agonist increased fear behavior but had no effect on escape learning. Results reveal a novel role of the 5-HT(2C)R in the DS in the expression of instrumental escape deficits produced by uncontrollable stress and demonstrate that the involvement of 5-HT(2C)R activation in stress-induced behaviors is regionally specific., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

Mitochondrial fatty acid oxidation provides an important energy source for cellular metabolism, and decreased mitochondrial fatty acid oxidation has been implicated in the pathogenesis of type 2 diabetes. Paradoxically, mice with an inherited deficiency of the mitochondrial fatty acid oxidation enzyme, very long-chain acyl-CoA dehydrogenase (VLCAD), were protected from high-fat diet-induced obesity and liver and muscle insulin resistance. This was associated with reduced intracellular diacylglycerol content and decreased activity of liver protein kinase Cvarepsilon and muscle protein kinase Ctheta. The increased insulin sensitivity in the VLCAD(-/-) mice were protected from diet-induced obesity and insulin resistance due to chronic activation of AMPK and PPARalpha, resulting in increased fatty acid oxidation and decreased intramyocellular and hepatocellular diacylglycerol content.

Safflower ( Carthamus tinctorius L.) is currently being developed as a platform for the production of novel proteins. Methods for detecting and quantifying transgenic safflower are needed to ensure seed quality and to monitor for its adventitious presence. We developed and compared three methods of assaying for transgenic safflower presence in conventional seedlots: field bioassays, enzyme-linked immunosorbent assays (ELISA), and quantitative polymerase chain reaction (Q-PCR). Limits for reliable quantification for both ELISA and Q-PCR are approximately 0.1%, although levels at least as low as 0.02% can be detected by Q-PCR. Levels of quantification for the field bioassay are limited only by space and resources available. Multiple sampling methods to detect and quantify transgenic safflower presence at levels lower than 0.1% were used on field collected samples from a pollen outcrossing experiment to quantify the adventitious presence of transgenic safflower. Taking into account the potential utility and relative advantages or disadvantages of each detection method, it is recommended that the initial testing for the adventitious presence of transgenic seed be carried out using an antibody-based test if available and that Q-PCR-based assays to quantify transgenic proportion be used when it is necessary to identify specific transgenic constructs or if antibody-based assays are not readily available.

Fear conditioning and fear extinction play key roles in the development and treatment of anxiety-related disorders, yet there is little information concerning experiential variables that modulate these processes. Here we examined the impact of exposure to a stressor in a different environment on subsequent fear conditioning and extinction, and whether the degree of behavioral control that the subject has over the stressor is of importance. Rats received a session of either escapable (controllable) tail shock (ES), yoked inescapable (uncontrollable) tail shock (IS), or control treatment (home cage, HC) 7 days before fear conditioning in which a tone and foot shock were paired. Conditioning was measured 24 h later. In a second experiment rats received ES, IS or HC 24 h after contextual fear conditioning. Extinction then occurred every day beginning 7 days later until a criterion was reached. Spontaneous recovery of fear was assessed 14 days after extinction. IS potentiated fear conditioning when given before fear conditioning, and potentiated fear responding during extinction when given after conditioning. Importantly, ES potently interfered with later fear conditioning, decreased fear responding during fear extinction, and prevented spontaneous recovery of fear. Additionally, we examined if the activation of the ventral medial prefrontal cortex (mPFCv) by ES is critical for the protective effects of ES on later fear conditioning. Inactivation of the mPFCv with muscimol at the time of the initial experience with control prevented ES-induced reductions in later contextual and auditory fear conditioning. Finally, we explored if the protective effects of ES extended to an unconditioned fear stimulus, ferret odor. Unlike conditioned fear, prior ES increased the fear response to ferret odor to the same degree as did IS.

Human diabetic patients often lose touch and vibratory sensations, but to date, most studies on diabetes-induced sensory nerve degeneration have focused on epidermal C-fibers. Here, we explored the effects of diabetes on cutaneous myelinated fibers in relation to the behavioral responses to tactile stimuli from diabetic mice. Weekly behavioral testing began prior to streptozotocin (STZ) administration and continued until 8 weeks, at which time myelinated fiber innervation was examined in the footpad by immunohistochemistry using antiserum to neurofilament heavy chain (NF-H) and myelin basic protein (MBP). Diabetic mice developed reduced behavioral responses to non-noxious (monofilaments) and noxious (pinprick) stimuli. In addition, diabetic mice displayed a 50% reduction in NF-H-positive myelinated innervation of the dermal footpad compared with non-diabetic mice. To test whether two neurotrophins nerve growth factor (NGF) and/or neurotrophin-3 (NT-3) known to support myelinated cutaneous fibers could influence myelinated innervation, diabetic mice were treated intrathecally for 2 weeks with NGF, NT-3, NGF and NT-3. Neurotrophin-treated mice were then compared with diabetic mice treated with insulin for 2 weeks. NGF and insulin treatment both increased paw withdrawal to mechanical stimulation in diabetic mice, whereas NT-3 or a combination of NGF and NT-3 failed to alter paw withdrawal responses. Surprisingly, all treatments significantly increased myelinated innervation compared with control-treated diabetic mice, demonstrating that myelinated cutaneous fibers damaged by hyperglycemia respond to intrathecal administration of neurotrophins. Moreover, NT-3 treatment increased epidermal Merkel cell numbers associated with nerve fibers, consistent with increased numbers of NT-3-responsive slowly adapting A-fibers. These studies suggest that myelinated fiber loss may contribute as significantly as unmyelinated epidermal loss in diabetic neuropathy, and the contradiction between neurotrophin-induced increases in dermal innervation and behavior emphasizes the need for multiple approaches to accurately assess sensory improvements in diabetic neuropathy.

Animal models of stress-induced depression have identified a bimodal reactivity to stress, namely 'resilience' and 'vulnerability.' Possible corresponding differences in endocrine and immunological responses between these groups have not been delineated. Male Sprague-Dawley rats were divided into three groups: stress (n=25), confined controls (n=7), and home cage controls (n=7). Stress rats were exposed to 80, 5-s inescapable cold water swim trials (15 degrees C). Twenty-four hours later, the stress rats were tested on an instrumental swim escape test (SET) but now they had access to an omnidirectional lever that terminated the stress. Immediately after the SET, trunk blood was collected to assay for serum corticosterone (CORT), and spleens were removed and natural killer cell activity (NKCA) and concanavalin A (CON-A) induced lymphocyte proliferation determined. Subjects in the stress treatment group were divided into distinct 'resilient' and 'vulnerable' categories by a median split for average escape latencies across the last 25 trials of the SET. Stress rats secreted more CORT than controls and vulnerable rats secreted greater levels than resilient rats. NKCA was greatest in control rats, and was decreased in the stress rats although the resilient and the vulnerable groups did not differ. Conversely, CON-A-induced lymphocyte proliferation was greatest in stress rats, vulnerable rats exhibiting more proliferation than resilient rats, but both were greater than both control groups. Stress animals were hypothermic throughout the swim stress procedures but exhibited a stress-induced fever following the initial swim trials. The observed differences may have important predictive and theoretical utility for vulnerable and resilient profiles.

We examine the factors that lead employees to search for health plan quality information and the effect of such information on the decision to switch plans. Extending Hirshleifer and Riley's model [Hirshleifer, J., Riley, J.G., 1979. The analytics of uncertainty and information--an expositional survey. Journal of Economic Literature 17 (December (4)), 1375-1421] of the economics of information, we develop a two-equation model of quality information awareness and switching behavior. We estimate the model using data from a random sample of 651 single employees from 16 firms that are members of the Buyers Health Care Action Group, a health care purchasing coalition in the Minneapolis-St. Paul region. Our empirical results do not support either a link between quality information and switching behavior, or between perceived health plan satisfaction and switching. We do, however, find that switching is influenced by changes in premiums and whether an individual has an existing relationship with a health care provider.

Previous studies in our laboratories found that isolectin B(4)(IB(4))-positive polymodal nociceptors in the mouse do not express transient receptor potential vanilloid 1 (TRPV1), nor does deletion of TRPV1 compromise the ability of these afferents to detect thermal stimuli. Considering that IB(4)-positive afferents account for over 70% of cutaneous nociceptors and that 30-50% of all mouse primary afferents express TRPV1, it is highly likely that many TRPV1-positive fibers project to non-cutaneous structures. To investigate this issue, Alexa Fluor-conjugated wheat germ agglutinin (WGA) or IB(4) was injected into the nerves innervating quadriceps muscle (femoral) or hindlimb skin (saphenous) of male C57Bl/6 mice. Similarly, Alexa Fluor-conjugated cholera toxin-beta was injected subserosally into the distal colon. Spinal ganglia at the appropriate level (L2-3 for saphenous and femoral nerves; L6 for colon) were processed for TRPV1, calcitonin gene-related peptide (CGRP), neurofilament heavy chain (NHF) and IB(4) visualization and examined on a confocal microscope. Colon afferents contained the highest percentage of both TRPV1- and CGRP-positive neurons, followed by femoral (WGA) and saphenous afferents (WGA and IB(4)). In contrast, NHF staining was more prevalent among femoral afferents, followed by saphenous (WGA) and colon afferents. IB(4) binding was observed in very few colon or saphenous (WGA) afferents, with no femoral afferents binding or transporting IB(4). Considering that the largest percentages of TRPV1-positive neurons observed in this study were within visceral and muscle afferent populations (neurons that typically are not subject to noxious temperatures), these results suggest that TRPV1 may not function primarily as a temperature sensor but rather as a detector of protons, vanilloid compounds or through interactions with other membrane proteins.

Blackleg disease of crucifers, caused by the fungus Leptosphaeria maculans, is a major concern to oilseed rape producers worldwide. Brassica species containing the B genome have high levels of resistance to blackleg. Brassica juncea F2 and first-backcross (B1) populations segregating for resistance to a PG2 isolate of L. maculans were created. Segregation for resistance to L. maculans in these populations suggested that resistance was controlled by two independent genes, one dominant and one recessive in nature. A map of the B. juncea genome was constructed using segregation in the F2 population of a combination of restriction fragment length polymorphism (RFLP) and microsatel lite markers. The B. juncea map consisted of 325 loci and was aligned with previous maps of the Brassica A and B genomes. The gene controlling dominant resistance to L. maculans was positioned on linkage group J13 based on segregation for resistance in the F2 population. This position was confirmed in the B1 population in which the resistance gene was definitively mapped in the interval flanked by pN199RV and sB31143F. The provisional location of the recessive gene controlling resistance to L. maculans on linkage group J18 was identified using a subset of informative F2 individuals.

Bacterial IIC introns are a newly recognized subclass of group II introns whose ribozyme properties have not been characterized in detail. IIC introns are typically located downstream of transcriptional terminator motifs (inverted repeat followed by T's) or other inverted repeats in bacterial genomes. Here we have characterized the self-splicing activity of a IIC intron, B.h.I1, from Bacillus halodurans. B.h.I1 self-splices in vitro through hydrolysis to produce linear intron, but interestingly, additional unexpected products were formed that were highly dependent on ionic conditions. These products were determined to represent alternative splicing events at the 5' junction and cleavages throughout the RNA transcript. The alternative splicing and cleavage events occurred at cryptic splice sites containing stem-loop and IBS1 motifs, suggesting that the 5' exon is recognized by both elements. These results provide the first example of a group II intron that uses 5' splice sites nonadjacent to the ribozyme structure. Furthermore, the data suggest that IIC introns differ from IIA and IIB introns with respect to 5' exon definition, and that the terminator stem-loop substitutes in part for the missing IBS2-EBS2 (intron and exon binding sites 2) interaction.

Pain and discomfort are the leading cause for consultative visits to gastroenterologists. Acute pain should be considered a symptom of an underlying disease, thereby serving a physiologically important function. However, many patients experience chronic pain in the absence of potentially harmful stimuli or disorders, turning pain into the primary problem rather than a symptom. Vagal and spinal afferents both contribute to the sensory component of the gut-brain axis. Current evidence suggests that they convey different elements of the complex sensory experience. Spinal afferents play a key role in the discriminatory dimension, while vagal input primarily affects the strong emotional and autonomic reactions to noxious visceral stimuli. Drugs, surgical and non-pharmacological treatments can target these pathways and provide therapeutic options for patients with chronic visceral pain syndromes.

More than half of all Americans receive health insurance coverage through an employer. The rising costs and escalating complexity of health insurance has led many employers to embark on extensive employee education campaigns. In 2002, 1,365 randomly selected employees from 16 Buyers Health Care Action Group firms in the Minneapolis region were surveyed to evaluate their awareness of employer-provided health plan quality information and the extent to which this information influences their enrollment decisions. The study found mixed evidence with respect to the value of employer communication. On one hand, employer communication does not significantly increase the probability that an employee responded correctly to the pharmacy benefit question posed in the survey. However, employer communication has a large effect on the awareness of quality information. How well those campaigns work, and by extension how well employees are informed about the health benefits decisions they make, is a key issue in health care today.

Group A Streptococcus (GAS) colonizes the oropharynx and damaged skin. To cause local infection or severe invasive syndromes the bacteria must gain access into deeper tissues. Host cell death may facilitate this process. GAS internalization has been identified to induce apoptosis. We now report an alternate mechanism of GAS-mediated apoptosis of primary human keratinocytes, initiated by extracellular GAS and involving dysregulation of intracellular calcium to produce endoplasmic reticulum stress. Two bacterial virulence factors are required for effective induction of apoptosis by extracellular GAS: (i) hyaluronic acid capsule that inhibits bacterial internalization and (ii) secreted cytolysin, streptolysin O (SLO), that forms transmembrane pores that permit extracellular calcium influx into the cytosol. Induction of keratinocyte apoptosis by wild-type GAS was accompanied by cell detachment and loss of epithelial integrity, a phenomenon not observed with GAS deficient in capsule or SLO. We propose that cell signalling initiated by extracellular GAS compromises the epithelial barrier by inducing premature keratinocyte differentiation and apoptosis, thereby facilitating GAS invasion of deeper tissues.

This paper examines differences in availability, use, and perceived usefulness of disease management programs as reported by generalist and specialist physicians functioning as primary care providers in health plans. Implications of these differences are discussed in terms of the three types of purchasers: private insurers, Medicare, and Medicaid. The design is a cross-sectional mail and telephone mixed-mode survey. The data come from 23 health plans in five states (Florida, New York, Colorado, Pennsylvania, and Washington), including six metropolitan areas: Seattle, New York City, Miami, Pittsburgh, Philadelphia, and Denver. The study participants are 1,244 generalist and specialist physicians who contracted with health plans as primary care providers. They were drawn from a 2001 mail and telephone survey of 2,105 generalist and 1,693 specialist physicians serving commercial, Medicaid, and Medicare patients. Physician responses about use of disease management for their patients in the health plan and how useful they thought it was were regressed on physician, physician organization, and physician-health plan relationship characteristics. While generalist physicians are likely to report having disease management programs available and using them, specialists vary greatly in their response to the disease management programs. In contrast to physicians associated with commercial plans, implementation of disease management programs among physicians associated with Medicaid plans varied across states. Primary care providers trained in generalist areas of practice are more likely than specialists functioning as primary care providers to report that disease management programs are available and to use them. They also find them more useful than do specialists.

Our paper draws lessons for policymakers from twelve communities as we identify the power and limits of general market-based strategies for improving the efficiency of health systems. The vision of market forces driving our system toward efficiency attracted politicians, policy analysts, and practitioners in the 1990s. Today some policy advocates profess even more faith in unfettered market forces. Market participants in the twelve communities in the Community Tracking Study, however, have become doubtful, and our analysis confirms the logic of their pessimism. Major barriers to efficient market outcomes exist amid growing willingness to consider renewed government interventions.

Presenilin 1 (PS1) and presenilin 2 play a critical role in the gamma-secretase processing of amyloid precursor protein (APP) and Notch1. Here, we investigate maturation and intracellular trafficking of APP and other membrane proteins in cells expressing an experimental PS1 deletion mutant (deltaM1,2). Stable expression of deltaM1,2 impairs gamma-secretase processing of Notch1 and delays Abeta secretion. Kinetic studies show enhanced O-glycosylation and sialylation of holo-APP and marked accumulation of APP COOH-terminal fragments (CTFs). Surface biotinylation, live staining, and trafficking studies show increased surface accumulation of holo-APP and CTFs in deltaM1,2 cells resulting from enhanced surface delivery of newly synthesized APP. Expression of a loss-of-function PS1 mutant (D385A) or incubation of cells with gamma-secretase inhibitors also increases surface levels of holo-APP and CTFs. In contrast to APP, glycosylation and surface accumulation of another type I membrane protein, nicastrin, are markedly reduced in deltaM1,2 cells. Finally, expression of deltaM1,2 results in the increased assembly and surface expression of nicotinic acetylcholine receptors, illustrating that PS1's influence on protein trafficking extends beyond APP and other type I membrane protein substrates of gamma-secretase. Collectively, our findings provide evidence that PS1 regulates the glycosylation and intracellular trafficking of APP and select membrane proteins.

Policymakers are concerned that some rural hospitals have suffered significant losses under the Balanced Budget Act (BBA) of 1997 and that access to inpatient and emergency care may be at risk. This article projects that the median total profit margin for rural hospitals will fall from 4 percent in 1997 to between 2.5 and 3.7 percent after the BBA, Balanced Budget Refinement Act (BBRA) of 1999, and Benefits Improvement and Protection Act (BIPA) of 2000 are fully implemented in 2004. The Critical Access Hospital (CAH) Program is expected to prevent reductions in inpatient and outpatient prospective payments from causing an increase in rural hospital closures.

In the spring of 1996, the Minnesota Health Partnership (MHP) received a demonstration grant from the Robert Wood Johnson Foundation Workers Compensation Health Initiative to pilot a model of health care that was designed to combine the best practices of general health and workers' compensation medical care. This paper outlines the genesis of the MHP, and the relationship of its Coordinated Health Care and Disability Prevention model to traditional managed care and 24-h care models. In order to effectively implement disability prevention principles within a primary care clinical setting, it is essential to increase health care provider awareness that the disability relating to a specific impairment can be positively impacted by specific clinical strategies. The basis and specifics of these strategies are also discussed. Plans for the evaluation of this model will also be described.

This paper presents the first empirical analysis of a 1997 initiative of the Buyers Health Care Action Group (BHCAG) known as Choice Plus. This initiative entailed direct contracts with provider-controlled delivery systems; annual care system bidding; public reports of consumer satisfaction and quality; uniform benefits; and risk-adjusted payment. After case-mix adjustment, hospital costs decreased, ambulatory care costs rose modestly, and pharmacy costs increased substantially. Process-oriented quality indicators were stable or improved. The BHCAG employer-to-provider direct contracting and consumer choice model appeared to perform reasonably well in containing costs, without measurable adverse effects on quality.

Objective: To investigate consumers' use of report cards that provide information on service quality and satisfaction at the provider group level., Data Sources: In 1998 we conducted a telephone survey of randomly selected employees in firms aligned with the Buyers Health Care Action Group (BHCAG) in the Minneapolis-St. Paul market., Study Design: Univariate probit models were used to determine report card utilization, perceived helpfulness of the report card, and ease of selecting a provider group. The characteristics used in the models included health status, age, gender, education, residency, job tenure, marital status, presence of dependent children, household income, and whether consumers changed provider groups., Data Collection: Our sample consists of survey responses from 996 single individuals (a response rate of 91 percent) and 913 families (a response rate of 96 percent). The survey was supplemented with data obtained directly from employers aligned with BHCAG., Principle Findings: Consumers who changed to a new provider group are more likely to use report card information and find it helpful, consumers employed in large firms are less likely to use the report card, and families who use information from their own health care experiences are less likely to find the report card helpful. In addition, individuals who changed to a new provider group are more likely to find the selection decision difficult., Conclusion: The findings show that health care consumers are using satisfaction and service-quality information provided by their employers.

Organized delivery systems are becoming an increasingly important component of urban health care markets and are expanding their influence in rural areas as well. They also are developing new linkages with rural providers. This article, based on the experiences of 20 diverse organizations, identifies and describes the strategies being used by urban systems to redefine linkages with rural hospitals and, particularly, physicians.

This study examines the use of information by employees in the Buyers Health Care Action Group, a purchasing coalition of large employers in Minneapolis. BHCAG employers contract directly with multiple health-care provider systems and attempt to inform employees about those choices. Shortly after the close of the 1998 open-enrollment period, a survey of 927 BHCAG employees with single-coverage health insurance was conducted. Seventy-six percent of the employees relied on information from their employer when selecting their current care system. Use of information from the employer was positively related to education and years of residence in the Twin Cities. Previous experience with doctors and hospitals in the care system also was a common information source. Older and low-income workers were more likely to use information from advertisements. The survey results suggest that employers can predict which information sources their employees will use.

The Buyers Health Care Action Group (BHCAG) in the Twin Cities has implemented a new purchasing initiative that offers employees a choice among care systems with nonoverlapping networks of primary care providers. These systems offer a standardized benefit package, submit annual bids, and are paid on a risk-adjusted basis. Employees are provided with information on quality and other differences among systems, and most have financial incentives to choose lower-cost systems. Generally, providers have responded favorably to direct contracting and to risk-adjusted payments but have concerns about the risk-adjustment mechanism used and, more importantly, the strength of employers' commitment to the purchasing model.

Unsedated transnasal esophagogastroduodenoscopy (EGD) is a unique approach to viewing the gastrointestinal tract. A significant portion of the expense and complications of conventional EGD is related to the use of conscious sedation. Transnasal EGD can be performed with a topical anesthetic alone and can be safely executed in inpatient and outpatient settings.

Background: We evaluated an upper respiratory infection (URI) clinical guideline to determine if it would favorably affect the quality and cost of care in a health maintenance organization., Methods: Patients with URI symptoms contacting 4 primary care practices before and after guideline implementation were compared to ascertain what proportion of all patients with respiratory symptoms were eligible for treatment in accordance with the URI guideline; what proportion of eligible patients were managed without an office visit; and what proportion of eligible patients were treated with antibiotics, before and after guideline implementation., Results: A total of 3163 patients with respiratory symptoms were identified. Of these, 59% (n = 1880) had disqualifying symptoms or comorbid conditions for URI guideline care, and 28% (n = 1290) received disqualifying diagnoses on the day of first contact, leaving 13% (n = 408) who received a diagnosis of URI and were eligible for care in accordance with the guideline. Among this group of patients, the proportion who received guideline-recommended initial telephone care was 45% preguideline and 47% postguideline (chi2 = 0.40; P = .82). Likelihood of a subsequent office visit increased from pre- to postguideline (chi2 = 17.1; P <.01), although the majority of patients had no further diagnoses other than URI. Antibiotic use for the initial URI diagnosis declined from 24% preguideline to 16% postguideline (chi2 = 3.97; P = .046), but antibiotic use during 21-day follow-up did not change (F = 0.46, P = .66). The mean cost of initial care was $37.80 preguideline and $36.20 postguideline (P >.05)., Conclusions: Only 13% of primary care patients with respiratory symptoms were eligible for URI guideline care. Among eligible patients, use of the guideline failed to decrease clinic visits, decrease antibiotic use during a 21-day period, or reduce cost of care to the health plan.

The health maintenance organization (HMO) industry has undergone a wave of national consolidations in recent years. The most notable among these were between United HealthCare and MetraHealth (1995), PacifiCare Health Systems and FHP International (1996), Aetna Life and Casualty and U.S. Healthcare (1996), and Aetna and Prudential's health care unit (1999). This paper examines HMO consolidation from 1994 to 1997, looking first at concentration at the national level and then at the consequences of national consolidations for local markets. Whereas earlier mergers may have caused only a small increase in the type of local market concentration that may increase prices, later and currently proposed mergers may be motivated by considerations of increasing local market concentration. However, the concentration-increasing effect of national mergers was offset by the concentration-decreasing effect of HMO entry and growth. The analyses suggest that antitrust policy still has a role to play in ensuring that HMO markets remain open to new entry and in evaluating the effect of national mergers on local market concentration.

This study examines the impact of a mental health carve-out, the Utah Prepaid Mental Health Plan (UPMHP), on use of outpatient mental health services by Medicaid beneficiaries with schizophrenia. Data were collected through interviews with the same group of Medicaid schizophrenic beneficiaries. A pre/post comparison with a contemporaneous control group examined the impact of the program on type of outpatient services used by beneficiaries. The results indicate a greater reliance on medically-oriented outpatient mental health services in treatment of beneficiaries under the UPMHP. Medicaid beneficiaries with schizophrenia in the UPMHP group received relatively fewer day treatment visits, but relatively more medication visits and individual therapy visits over the first 3 1/2 years of the program.

We tested the hypothesis that health maintenance organizations (HMOs) increase their commercial premiums when Medicare pays less. Such a linkage would be taken as evidence of "cost shifting." Other studies have tested the cost-shifting hypothesis among health care providers, but this is the first to examine the HMO industry. Our data consisted of annual observations on all HMOs that operated in the United States between 1990 and 1995 and had a Medicare risk contract. A comparison group of HMOs that had no Medicare contract during that period also was analyzed. The main finding from this study is that HMOs have not shifted costs from Medicare to commercial premiums. This results supports the skeptical consensus that is developing toward the cost-shifting hypothesis. Additional findings include the negative effects of competition and for-profit status on HMOs' commercial premiums.

Employers can play an important role in shaping community health care systems through their direct efforts to institute system change, their negotiations with health plans, and their decisions concerning the structure of health benefits for their employees. This paper describes recent employer initiatives in all three of these areas, using data collected from interview respondents in the twelve communities that are part of the Community Tracking Study being carried out by the Center for Studying Health System Change. During the recent period of relative health premium stability, employers have responded to employees' concerns about managed care by favoring looser, less structured managed care plans offering broader networks of providers or out-of-network options.