Optical projection tomography reveals dynamics of HEV growth after immunization with protein plus CFA and features shared with HEVs in acute autoinflammatory lymphadenopathy

The vascular-stromal compartment of lymph nodes is important for lymph node function, and high endothelial venules (HEVs) play a critical role in controlling the entry of recirculating lymphocytes. In autoimmune and autoinflammatory diseases, lymph node swelling is often accompanied by apparent HEV expansion and, potentially, targeting HEV expansion could be used therapeutically to limit autoimmunity. In previous studies using mostly flow cytometry analysis, we defined three differentially regulated phases of lymph node vascular-stromal growth: initiation, expansion, and the re-establishment of vascular quiescence and stabilization. In this study, we use optical projection tomography to better understand the morphologic aspects of HEV growth upon immunization with ovalbumin/CFA (OVA/CFA). We find HEV elongation as well as modest arborization during the initiation phase, increased arborization during the expansion phase, and, finally, vessel narrowing during the re-establishment of vascular quiescence and stabilization. We also examine acutely enlarged autoinflammatory lymph nodes induced by regulatory T cell depletion and show that HEVs are expanded and morphologically similar to the expanded HEVs in OVA/CFA-stimulated lymph nodes. These results reinforce the idea of differentially regulated, distinct phases of vascular-stromal growth after immunization and suggest that insights gained from studying immunization-induced lymph node vascular growth may help to understand how the lymph node vascular-stromal compartment could be therapeutically targeted in autoimmune and autoinflammatory diseases.

State-Level Pharmaceutical Assistance Programs for the Elderly: A national survey.

In order to put Pennsylvania's Pharmaceutical Assistance Contract for the Elderly (PACE) Program in a national context, a nationwide mail survey and telephone follow-up to each of the 58 State Unit Directors on Aging in the United States and its territories identified 10 programs. The results reported in this article are specific to the seven state-level pharmaceutical assistance programs which were in operation during the fiscal year 1984-85. In general, the programs varied on select program characteristics and on their efforts to address major policy issues. Data from the non-program states indicated support, legislative efforts, and a high interest in fiscal concerns. The findings reflect a lack of program uniformity and have implications for program development and implementation. Suggestions on how to identify the "optimum" or best combination of program and policy options are discussed.

Self-efficacy as a predictor of outcome after residential treatment programs for alcohol dependence: simply ask the patient one question!

Self-efficacy has been identified as one of the most consistent variables that predict the outcome of alcohol treatment. However, many previous studies in this field failed to control for other important predictors (e.g., dependences severity, psychiatric symptoms, and treatment goal). Our study's first goal was to evaluate the predictive value of self-efficacy when most other relevant variables were statistically controlled. The second goal was to compare the predictive values of self-efficacy assessed with the Situational Confidence Questionnaire (SCQ), and general self-efficacy assessed with a single question.

Sorting through the garbage can: under what conditions do governments adopt policy programs?

The paper aims at explaining the adoption of policy programs. We use the garbage can model of organizational choice as our theoretical framework and complement it with the institutional setting of administrative decision-making in order to understand the complex causation of policy program adoption. Institutions distribute decision power by rules and routines and coin actor identities and their interpretations of situations. We therefore expect institutions to play a role when a policy window opens. We explore the configurative explanations for program adoption in a systematic comparison of the adoption of new alcohol policy programs in the Swiss cantons employing Qualitative Comparative Analysis. The most important conditions are the organizational elements of the administrative structure decisive for the coupling of the streams. The results imply that classic bureaucratic structures are better suited to put policies into practice than limited government.

Comparison of genetic gains per year for carcass traits among breeding programs in the Japanese Brown and the Japanese Black cattle

The breeding program for beef cattle in Japan has changed dramatically over 4 decades. Visual judging was done initially, but progeny testing in test stations began in 1968. In the 1980s, the genetic evaluation program using field records, so-called on-farm progeny testing, was first adopted in Oita, Hyogo, and Kumamoto prefectures. In this study, genetic trends for carcass traits in these 3 Wagyu populations were estimated, and genetic gains per year were compared among the 3 different beef cattle breeding programs. The field carcass records used were collected between 1988 and 2003. The traits analyzed were carcass weight, LM area, rib thickness, s.c. fat thickness, and beef marbling standard number. The average breeding values of reproducing dams born the same year were used to estimate the genetic trends for the carcass traits. For comparison of the 3 breeding programs, birth years of the dams were divided into 3 periods reflecting each program. Positive genetic trends for beef marbling standard number were clearly shown in all populations. The genetic gains per year for all carcass traits were significantly enhanced by adopting the on-farm progeny testing program. These results indicate that the on-farm progeny testing program with BLUP is a very powerful approach for genetic improvement of carcass traits in Japanese Wagyu beef cattle.

Substance use disorder treatment programs in Switzerland and the USA: Program characteristics and 1-year outcomes

AIM: This study compared matched samples of substance use disorder (SUD) patients in Swiss and United States (US) residential treatment programs and examined the relationship of program characteristics to patients' substance use and psychosocial functioning at a 1-year follow-up. DESIGN AND SETTING: The study used a prospective, naturalistic design and a sample of 10 public programs in the German-speaking part of Switzerland and 15 US public treatment programs. PARTICIPANTS: A total of 358 male patients in Swiss programs were matched on age, marital status and education with 358 male patients in US programs. A total of 160 Swiss and 329 US patient care staff members also participated. MEASUREMENT: Patients completed comparable inventories at admission, discharge and 1-year follow-up to assess their substance use and psychological functioning and receipt of continuing care. Staff members reported on program characteristics and their beliefs about substance use. FINDINGS: Compared to Swiss patients, US patients had more severe substance use and psychological problems at intake and although they did not differ on abstinence and remission at follow-up, had somewhat poorer outcomes in other areas of functioning. Swiss programs were longer and included more individual treatment sessions; US programs included more group sessions and were more oriented toward a disease model of treatment. Overall, length of program, treatment intensity and 12-step orientation were associated with better 1-year outcomes for patients in both Swiss and US programs. CONCLUSIONS: The sample of Swiss and US programs studied here differed in patient and treatment characteristics; however, in general, there were comparable associations between program characteristics and patients' 1-year outcomes. These findings suggest that associations between treatment processes and patients' outcomes may generalize from one cultural context to another.

Delays in childhood immunization in a conflict area: a study from Sierra Leone during civil war

ABSTRACT: BACKGROUND: Sierra Leone has undergone a decade of civil war from 1991 to 2001. From this period few data on immunization coverage are available, and conflict-related delays in immunization according to the Expanded Programme on Immunization (EPI) schedule have not been investigated. We aimed to study delays in childhood immunization in the context of civil war in a Sierra Leonean community. METHODS: We conducted an immunization survey in Kissy Mess-Mess in the Greater Freetown area in 1998/99 using a two-stage sampling method. Based on immunization cards and verbal history we collected data on immunization for tuberculosis, diphtheria, tetanus, pertussis, polio, and measles by age group (0-8/9-11/12-23/24-35 months). We studied differences between age groups and explored temporal associations with war-related hostilities taking place in the community. RESULTS: We included 286 children who received 1690 vaccine doses; card retention was 87%. In 243 children (85%, 95% confidence interval (CI): 80-89%) immunization was up-to-date. In 161 of these children (56%, 95%CI: 50-62%) full age-appropriate immunization was achieved; in 82 (29%, 95%CI: 24-34%) immunization was not appropriate for age. In the remaining 43 children immunization was partial in 37 (13%, 95%CI: 9-17) and absent in 6 (2%, 95%CI: 1-5). Immunization status varied across age groups. In children aged 9-11 months the proportion with age-inappropriate (delayed) immunization was higher than in other age groups suggesting an association with war-related hostilities in the community. CONCLUSION: Only about half of children under three years received full age-appropriate immunization. In children born during a period of increased hostilities, immunization was mostly inappropriate for age, but recommended immunizations were not completely abandoned. Missing or delayed immunization represents an additional threat to the health of children living in conflict areas.

Immunization of Macaca fascicularis against experimental periodontitis using a vaccine containing cysteine proteases purified from Porphyromonas gingivalis

INTRODUCTION: Periodontitis is a common infectious disease to which Porphyromonas gingivalis has been closely linked, in which the attachment tissues of the teeth and their alveolar bone housing are destroyed. We conducted a study to determine if immunization using a purified antigen could alter the onset and progression of the disease. METHODS: Using the ligature-induced model of periodontitis in Macaca fascicularis, we immunized five animals with cysteine protease purified from P. gingivalis and used an additional five animals as controls. Alveolar bone loss was measured by digital subtraction radiography. RESULTS: Immunization induced high titers of specific immunoglobuin G serum antibodies that were opsonic. Total bacterial load, levels of P. gingivalis in subgingival plaque and levels of prostaglandin E(2) in gingival crevicular fluid were significantly reduced. Onset and progression of alveolar bone loss was inhibited by approximately 50%. No manifestations of toxicity were observed. CONCLUSIONS: Immunization using a purified protein antigen from P. gingivalis inhibits alveolar bone destruction in a ligature-induced periodontitis model in M. fascicularis.

Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation

A key energy-saving adaptation to chronic hypoxia that enables cardiomyocytes to withstand severe ischemic insults is hibernation, i.e., a reversible arrest of contractile function. Whereas hibernating cardiomyocytes represent the critical reserve of dysfunctional cells that can be potentially rescued, a lack of a suitable animal model has hampered insights on this medically important condition. We developed a transgenic mouse system for conditional induction of long-term hibernation and a system to rescue hibernating cardiomyocytes at will. Via myocardium-specific induction (and, in turn, deinduction) of a VEGF-sequestering soluble receptor, we show that VEGF is indispensable for adjusting the coronary vasculature to match increased oxygen consumption and exploit this finding to generate a hypoperfused heart. Importantly, ensuing ischemia is tunable to a level at which large cohorts of cardiomyocytes are driven to enter a hibernation mode, without cardiac cell death. Relieving the VEGF blockade even months later resulted in rapid revascularization and full recovery of contractile function. Furthermore, we show that left ventricular remodeling associated with hibernation is also fully reversible. The unique opportunity to uncouple hibernation from other ischemic heart phenotypes (e.g., infarction) was used to determine the genetic program of hibernation; uncovering hypoxia-inducible factor target genes associated with metabolic adjustments and induced expression of several cardioprotective genes. Autophagy, specifically self-digestion of mitochondria, was identified as a key prosurvival mechanism in hibernating cardiomyocytes. This system may lend itself for examining the potential utility of treatments to rescue dysfunctional cardiomyocytes and reverse maladaptive remodeling.