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1.
Aging Ment Health ; 28(10): 1351-1356, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38533723

RESUMEN

OBJECTIVES: This study sought to (1) identify the percentage of high-risk substance use or substance use disorder (SUD) and (2) examine the factors associated with high-risk substance use or SUD in adults aged 50 years and older receiving mental health treatment with a primary delirium or dementia diagnosis. METHOD: This study used 7 years (2013-2019) of national administrative data on community mental health center patients aged 50 years and older with a primary delirium or dementia diagnosis receiving treatment in the United States (U.S.). To examine factors associated with the dependent variable (high-risk substance use or SUD), a multivariable binary logistic regression model was utilized. RESULTS: The sample included 77,509 individuals who were mostly aged 65 years and older (69.7%), and did not have co-occurring high-risk substance use or SUD (90.1%). Receiving treatment in a U.S. region other than the Northeast, being younger, male, not non-Hispanic White, and having multiple mental health diagnoses had greater odds of co-occurring high-risk substance use or SUD. CONCLUSION: One in ten persons in this sample having high-risk substance use or SUD highlights the clinical necessity for screening and subsequent treatment for co-occurring high-risk substance use among persons receiving treatment for a neurocognitive disorder.


Asunto(s)
Trastornos Relacionados con Sustancias , Humanos , Masculino , Femenino , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/terapia , Anciano , Persona de Mediana Edad , Estados Unidos/epidemiología , Anciano de 80 o más Años , Demencia/epidemiología , Demencia/terapia , Trastornos Neurocognitivos/epidemiología , Trastornos Neurocognitivos/terapia , Comorbilidad
2.
BMC Palliat Care ; 22(1): 105, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37496001

RESUMEN

BACKGROUND: Palliative care is an effective model of care focused on maximizing quality of life and relieving the suffering of people with serious illnesses, including dementia. Evidence shows that many people receiving care in nursing homes are eligible for and would benefit from palliative care services. Yet, palliative care is not consistently available in nursing home settings. There is a need to test pragmatic strategies to implement palliative care programs in nursing homes. METHODS/DESIGN: The UPLIFT-AD (Utilizing Palliative Leaders in Facilities to Transform care for people with Alzheimer's Disease) study is a pragmatic stepped wedge trial in 16 nursing homes in Maryland and Indiana, testing the effectiveness of the intervention while assessing its implementation. The proposed intervention is a palliative care program, including 1) training at least two facility staff as Palliative Care Leads, 2) training for all staff in general principles of palliative care, 3) structured screening for palliative care needs, and 4) on-site specialty palliative care consultations for a one-year intervention period. All residents with at least moderate cognitive impairment, present in the facility for at least 30 days, and not on hospice at baseline are considered eligible. Opt-out consent is obtained from legal decision-makers. Outcome assessments measuring symptoms and quality of care are obtained from staff and family proxy respondents at four time points: pre-implementation (baseline), six months after implementation, at 12 months (conclusion of implementation), and six months after the end of implementation. Palliative care attitudes and practices are assessed through surveys of frontline nursing home staff both pre- and post-implementation. Qualitative and quantitative implementation data, including fidelity assessments and interviews with Palliative Care Leads, are also collected. The study will follow the Declaration of Helsinki. DISCUSSION: This trial assesses the implementation and effectiveness of a robust palliative care intervention for residents with moderate-to-advanced cognitive impairment in 16 diverse nursing homes. The intervention represents an innovative, pragmatic approach that includes both internal capacity-building of frontline nursing home staff, and support from external palliative care specialty consultants. TRIAL REGISTRATION: The project is registered on ClinicalTrials.gov: NCT04520698.


Asunto(s)
Enfermedad de Alzheimer , Demencia , Humanos , Enfermedad de Alzheimer/terapia , Casas de Salud , Cuidados Paliativos/métodos , Calidad de Vida
3.
J Aging Soc Policy ; : 1-18, 2023 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-37348205

RESUMEN

Medical aid in dying refers to policies that allow terminally ill patients to seek assistance from their medical providers to obtain medications to hasten death. In this paper, we used a 7-point policy analysis model to examine the diversity of medical aid in dying policies that exist in jurisdictions (states and territories) in the U.S. and the implications of these policies for suffering at end of life. As of this writing, these practices are available in 12 jurisdictions, including 11 states and the District of Columbia. Legalization has occurred via statutory approaches in 10 jurisdictions and permissive approaches in two jurisdictions. We discuss the structures of these laws, the requirements for participation, and the limitations created by having jurisdiction-specific policies on such broad, bioethical issues. Existing laws appear to relieve suffering in patients at end of life. Jurisdictional differences create barriers to comprehensive expansion but provide insights into practice in different contexts.

4.
Omega (Westport) ; 86(4): 1235-1253, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33823699

RESUMEN

Although the Medicare Hospice Benefit mandates that hospices offer bereavement support services to families for at least 1 year following the death of a patient, it does not stipulate which services they should offer. As a result, little is known about what bereavement support services hospices provide, especially on a national scale. The current study recruited a national sample of hospice representatives who responded to an open-ended question that asked, "What types of bereavement support services does your hospice provide to families?" Seventy-six viable responses were recorded and content analyzed. Four overarching domains emerged: (a) timing of support, (b) providers of support, (c) targets of support, and (d) formats of support. Other notable findings included the underutilization of bereavement support services and the utility of informal support formats. These findings present implications for future study regarding which specific aspects of hospice bereavement support services are most beneficial to bereaved families.


Asunto(s)
Aflicción , Cuidados Paliativos al Final de la Vida , Hospitales para Enfermos Terminales , Anciano , Humanos , Estados Unidos , Medicare , Pesar
5.
Death Stud ; 46(3): 728-737, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-32615057

RESUMEN

The relationship between health care utilization and death anxiety in older adults is underexplored. This secondary analysis of the 2012 Health and Retirement Study examined health care utilization as a predictor of death anxiety in a nationally representative sample of American older adults (N = 3,960). Hierarchical binary logistic regression results revealed that overnight hospitalization, overnight nursing home placement, and outpatient visit were all statistically significant predictors of death anxiety. Outpatient visit was the strongest health care utilization predictor in the model. Increased end-of-life training for providers may improve patient-provider communication and alleviate patients' death anxiety. Future research should explore the directionality between study variables.


Asunto(s)
Hospitalización , Aceptación de la Atención de Salud , Anciano , Ansiedad , Humanos , Casas de Salud , Estados Unidos
6.
J Immunol ; 188(1): 77-84, 2012 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-22116826

RESUMEN

Nutrition is a critical but poorly understood determinant of immunity. There is abundant epidemiological evidence linking protein malnutrition to impaired vaccine efficacy and increased susceptibility to infections; yet, the role of dietary protein in immune memory homeostasis remains poorly understood. In this study, we show that protein-energy malnutrition induced in mice by low-protein (LP) feeding has a detrimental impact on CD8 memory. Relative to adequate protein (AP)-fed controls, LP feeding in lymphocytic choriomeningitis virus (LCMV)-immune mice resulted in a 2-fold decrease in LCMV-specific CD8 memory T cells. Adoptive transfer of memory cells, labeled with a division tracking dye, from AP mice into naive LP or AP mice demonstrated that protein-energy malnutrition caused profound defects in homeostatic proliferation. Remarkably, this defect occurred despite the lymphopenic environment in LP hosts. Whereas Ag-specific memory cells in LP and AP hosts were phenotypically similar, memory cells in LP hosts were markedly less responsive to polyinosinic-polycytidylic acid-induced acute proliferative signals. Furthermore, upon recall, memory cells in LP hosts displayed reduced proliferation and protection from challenge with LCMV-clone 13, resulting in impaired viral clearance in the liver. The findings show a metabolic requirement of dietary protein in sustaining functional CD8 memory and suggest that interventions to optimize dietary protein intake may improve vaccine efficacy in malnourished individuals.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Proteínas en la Dieta , Memoria Inmunológica , Deficiencia de Proteína/inmunología , Animales , Linfocitos T CD8-positivos/patología , Linfocitos T CD8-positivos/virología , Proliferación Celular , Femenino , Coriomeningitis Linfocítica/inmunología , Coriomeningitis Linfocítica/patología , Coriomeningitis Linfocítica/virología , Virus de la Coriomeningitis Linfocítica/inmunología , Ratones , Ratones Transgénicos , Deficiencia de Proteína/genética , Deficiencia de Proteína/patología , Deficiencia de Proteína/virología
7.
Palliat Med Rep ; 5(1): 162-170, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38665226

RESUMEN

Introduction: The Effective Management of Pain by Overcoming Worries to Enable Relief (EMPOWER) intervention is an evidence-supported approach for addressing barriers to pain management (e.g., patient/family concerns about addiction) at the end of life. Such barriers appear more pronounced among Spanish-speaking individuals. This study aimed to (1) translate EMPOWER materials into Spanish, (2) disseminate materials to hospices with ≥25% Hispanic patients, and (3) survey hospices about the use and usefulness of materials. Methods: We back translated EMPOWER materials with harmonization, then disseminated materials to 242 hospices. Thereafter, we used a semistructured survey to assess use and usefulness of EMPOWER materials using univariate statistics and content analysis. Results: Thirty-eight hospice representatives responded (participation rate = 15.7%). Respondents were primarily non-White (55.3%) and Hispanic (60.5%). Nealy half (47.4%) were nurses. A majority (81.6%) indicated they currently employ ≥1 full-time English-Spanish bilingual team member. Among those who reported receiving the EMPOWER materials (n = 29), 58.6% indicated they-or another staff member-used them with patients or families. Using a single-item rating (0 = not useful to 10 = very useful), respondents evaluated the English EMPOWER materials' usefulness as 7.6 (standard deviation [SD] = 1.4) and Spanish materials as 8.4 (SD = 1.4). Most (62.1%) indicated they would likely use EMPOWER materials in the future. Conclusion: Thematic findings suggest EMPOWER reinforces clinical education, promotes discussion about pain management, and helps address culturally specific barriers to care. EMPOWER appears to be a useful, easy to use, and promising intervention that can be implemented among both English- and Spanish-speaking populations.

8.
J Appl Gerontol ; : 7334648241265183, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39030730

RESUMEN

This study examined the psychometric properties of the eight-item Hospice Philosophy Scale (HPS-8) through confirmatory factor analysis; differential item functioning by age, gender, race, and professional discipline; and internal consistency reliability. We administered the HPS-8 to a national convenience sample of 471 interdisciplinary hospice clinicians. Confirmatory factor analysis results supported a one-factor model with an error correlation between two similarly worded items, χ2(19) = 48.38, p < .001 (RMSEA = .06, SRMR = .03, CFI = .98, TLI = .97). "Multiple indicators, multiple causes" model results indicated differential item functioning by age, race, and/or professional discipline on five items. However, subsequent uncorrected and differential item functioning-corrected models detected no statistically significant HPS-8 mean differences by grouping variables. Composite reliability results (CR = .82) demonstrated acceptable internal consistency reliability. Our results support the HPS-8 as a valid and reliable measure of attitudes toward the hospice philosophy of care in hospice clinicians.

9.
Palliat Med Rep ; 5(1): 238-246, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39044760

RESUMEN

Background: Nearly half of more than 1.7 million older Americans who receive hospice care each year have a primary or comorbid diagnosis of dementia. Pain is often undertreated in this patient population owing to myriad factors, including unmet informational needs among family caregivers. Objective: We sought to inform the adaptation of a pain education intervention for hospice family caregivers to the context of dementia by eliciting feedback on the educational content covered in adapted intervention materials. Design: We conducted a multimethod, formative research study to inform the adaptation of an existing, evidence-based intervention. Setting/Subjects: The study included a purposively recruited sample (n = 33) of hospice professionals (n = 18) and family caregivers (n = 15) from across the United States. Measurements: Participants quantitatively rated the importance of each of the eight pain concerns presented in the adapted intervention materials (1 = not important to 3 = very important) and provided qualitative feedback via Zoom interview on the acceptability, clinical accuracy, and potential benefits of the adapted content. We analyzed quantitative data via descriptive statistics and qualitative data via content analysis. Results: Participants rated the adapted educational content as highly important (rangemean = 2.56-3.00), particularly regarding concerns about caregivers' pain assessment, communicating with the hospice team about pain, and addressing misinformation regarding pain medication outcomes. Participants also provided suggestions to strengthen specific educational messages to improve comprehension and uptake. Conclusions: Findings support the continued development and testing of the adapted intervention.

10.
J Pain Symptom Manage ; 65(2): 133-142, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36328176

RESUMEN

CONTEXT: Various contextual factors surrounding hospice care have reinforced the need for scholars to pursue practice-relevant research questions. Although priority-setting is a primary approach to streamline such efforts, research appears yet to have conducted priority-setting with hospice professionals. OBJECTIVE: To describe the areas of needed research and clinical focus voiced by a national probability sample of US hospice agency representatives. METHODS: A national probability sample of 600 hospice agencies proportionately stratified by state and profit status was surveyed. At the end of the survey, participants indicated whether or not they were willing to answer two additional open-ended questions. These two questions requested participants' input on areas of needed attention related to (1) research topics and (2) unmet needs for patients and families. Responses were content analyzed. RESULTS: A total of 317 surveys were completed (response rate = 61.8%). Viable responses were recorded by 129 participants responding to at least one item. Content analysis generated the following five categories (and various subcategories): earlier access to hospice, education (outside physicians, patients and families, public), policy barriers to hospice enrollment (hospice eligibility and reimbursement, gaps in insurance coverage), effects of policy restrictions on hospice care (reimbursement for care, pain management, clinician issues), and improving the provision of in-home hospice care (community resources, supports for caregivers, supports for when caregiver assistance is inadequate, needs already are being met). CONCLUSION: These findings presented by hospice agency representatives reflect directions for research and clinical development. Efforts are needed to cohere professional- and patient-reported areas of needed attention.


Asunto(s)
Servicios de Atención de Salud a Domicilio , Cuidados Paliativos al Final de la Vida , Hospitales para Enfermos Terminales , Humanos , Manejo del Dolor , Cuidadores/educación , Investigación Cualitativa
11.
Bio Protoc ; 13(20): e4859, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37900101

RESUMEN

Strawberries are delicious and nutritious fruits that are widely cultivated and consumed around the world, either fresh or in various products such as jam, juice, and ice cream. Botrytis cinerea is a fungal pathogen that causes gray mold disease on many crops, including strawberries. Disease monitoring is an important aspect for growing commercial crops like strawberry because there is an urgent need to develop effective strategies to control this destructive gray mold disease. In this protocol, we provide an important tool to monitor the gray mold fungal infection progression in different developmental stages of strawberry. There are different types of inoculation assays for B. cinerea on strawberry plants, such as in vitro (in/on a culture medium) or in vivo (in a living plant). In vivo inoculation assays can be performed at early, middle, and late stages of strawberry development. Here, we describe three methods for in vivo inoculation assays of B. cinerea on strawberry plants. For early-stage strawberry plants, we modified the traditional fungal disc inoculation method to apply to fungal infection on strawberry leaves. For middle-stage strawberry plants, we developed the flower infection assay by dropping fungal conidia onto flowers. For late-stage strawberry plants, we tracked the survival rate of strawberry fruits after fungal conidia infection. This protocol has been successfully used in both lab and greenhouse conditions. It can be applied to other flowering plants or non-model species with appropriate modifications. Key features • Fungal disc inoculation on early-stage strawberry leaves. • Fungal conidia inoculation on middle-stage strawberry flowers. • Disease rating for late-stage strawberry fruits. • This protocol is applicable to the other flowering plants with appropriate modifications.

12.
J Appl Gerontol ; 42(7): 1611-1619, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36703571

RESUMEN

This study explored nursing home social services directors' interest in pursuing trauma-informed care (TIC) training, and individual and organizational characteristics associated with their interest. Data from the 2019 National Nursing Home Social Services Directors Survey, a national cross-sectional survey, were used. Measures sought information on participants' interest in TIC training, sociodemographic characteristics, and characteristics of employing nursing homes. Descriptive statistics and multivariate binary logistic regression analyses were used. Of the 924 respondents, 880 (95.2%) were included in the analysis. Most (71.7%) expressed high interest in TIC training. Younger age, fewer years of nursing home social services experience, being degreed and licensed in social work, and being a person of color were associated with greater odds of high interest in TIC training. Neither nursing home ownership nor social services staffing ratio was significantly associated with interest in TIC training. As policy requires TIC in nursing homes, these findings present a first step towards understanding implementation.


Asunto(s)
Casas de Salud , Servicio Social , Humanos , Estudios Transversales , Encuestas y Cuestionarios , Servicio Social/educación , Instituciones de Cuidados Especializados de Enfermería
13.
Health Soc Care Community ; 30(6): e5527-e5538, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36039906

RESUMEN

Social isolation is a well-established determinant of late-life well-being, and it may be particularly relevant for older adults in Puerto Rico following Hurricane María. The abbreviated Lubben Social Network Scale (LSNS-6) is a widely used measure of social isolation, but it has not been validated with Spanish-speaking older adults. The objectives of this study were to (1) assess the psychometric properties of a Spanish-language LSNS-6 and (2) examine its association with self-rated health (SRH) and psychological sense of community (PSOC). Data came from face-to-face survey interviews with a nonprobability sample of 154 community-dwelling older adults in Puerto Rico 2 years after Hurricane María. We assessed the LSNS-6's internal consistency reliability and convergent validity. We then conducted structural equational modelling consisting of (1) a measurement model using confirmatory factor analysis to test the factor structure of the LSNS-6 and (2) a structural model using path analysis to examine the direct effect of social isolation on SRH and to test the role of PSOC as a mediator in this relationship. The LSNS-6 demonstrated acceptable internal consistency reliability (α = 0.74) and convergent validity, r(151) = -0.33, p < 0.001. A correlated two-factor model (Family and Friends) provided the best fit (comparative fit index = 0.986, Tucker-Lewis index = 0.975, root mean square error of approximation = 0.082, standardised root mean squared residual = 0.033). Path model results show the Friends factor was negatively associated with SRH (ß = -0.31, p = 0.045), whilst the Family factor was nonsignificant. The Friends factor had a statistically significant indirect effect on SRH through PSOC (ß = 0.08, 95% CI [0.01, 0.29]). Our findings provide insight into the effect of social isolation on health amongst older adults in Puerto Rico and highlight the potential role of PSOC for assessment and intervention with older adults in post-disaster settings.


Asunto(s)
Red Social , Humanos , Anciano , Reproducibilidad de los Resultados , Puerto Rico , Psicometría , Encuestas y Cuestionarios
14.
Dementia (London) ; 21(2): 701-721, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34872364

RESUMEN

INTRODUCTION: The number of people with dementia has been increasing. Evidence shows that over 16 million family caregivers provide unpaid care for people with dementia. However, family caregivers experience several challenges throughout their caregiving role, including that of social isolation. Although social isolation in people with dementia has been well documented, social isolation in their family caregivers has not received as much scholarly attention. This scoping review sought to address this dearth of research through the following research question: "What are themes, concepts, or constructs that describe social isolation of family caregivers for people living with dementia?". METHOD: An electronic search was conducted in PubMed, PsycInfo, and Scopus, using the following Boolean search phrase: dementia AND "social isolation" AND (caregiver OR carers). Content analysis was conducted to identify relevant themes. FINDINGS: The initial search yielded 301 studies. Through screening processes, 13 studies were eligible for review. Based on a synthesis of evidence, five themes emerged from the data: disease progression, psychological state, social networks, social supports, and technology. DISCUSSION: This review demonstrates that caregiving is related to social isolation in family caregivers of people living with dementia. The experience of social isolation was related to the progression of dementia, psychological states, and lack of supports. In contrast, social supports, social networks, and using technology may reduce social isolation. Identifying themes provides policy and practice implications, such as using information and communication technology to create and redefine social networks.


Asunto(s)
Cuidadores , Demencia , Comunicación , Familia , Humanos , Aislamiento Social , Apoyo Social
15.
Palliat Med Rep ; 3(1): 123-131, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36059907

RESUMEN

Background: Improving rates of advance care planning (ACP) and advance directive completion is a recognized goal of health care in the United States. No prior study has examined the efficacy of standardized patient (SP)-based student interprofessional ACP trainings. Objectives: The present study aims to evaluate an interprofessional approach to ACP education using SP encounters. Design: We designed a pre-post evaluation of an innovative interprofessional ACP training curriculum using multimodal adult learning techniques to test the effects of completing ACP discussions with SPs. Three surveys (pre-training T1, post-training T2, and post-clinical encounter T3) evaluated student knowledge, Communication Self-Efficacy (CSES), ACP self-efficacy, and interprofessional teamwork (using SPICE-R2). Setting/Subjects: Students from the schools of medicine, nursing, and social work attended three training modules and two SP encounters focused on ACP. Measurements/Results: During academic year 2018-2019, 36 students participated in the training at University of Maryland. Results demonstrated statistically significant improvements in ACP self-efficacy, M T1 = 2.9 (standard deviation [SD]T1 = 0.61) compared with M T3 = 3.9 (SDT3 = 0.51), p < 0.001, and CSES, M T1 = 4.6 (SDT1 = 1.35) versus M T3 = 7.3 (SDT3 = 0.51), p < 0.001, from T1 to T3. There was a medium-to-large improvement in knowledge from an average score of 4.3 (SD = 1.0) at T1 to an average score of 5.5 (SD = 1.4) at T2, p = 0.005, d = 0.67. Conclusions: Our interprofessional training module and SP encounter was successful in improving medical, social work, and nursing students' self-reported communication skills and knowledge regarding ACP.

16.
J Exp Med ; 195(12): 1541-8, 2002 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-12070282

RESUMEN

The generation and efficient maintenance of antigen-specific memory T cells is essential for long-lasting immunological protection. In this study, we examined the role of interleukin (IL)-15 in the generation and maintenance of virus-specific memory CD8 T cells using mice deficient in either IL-15 or the IL-15 receptor alpha chain. Both cytokine- and receptor-deficient mice made potent primary CD8 T cell responses to infection with lymphocytic choriomeningitis virus (LCMV), effectively cleared the virus and generated a pool of antigen-specific memory CD8 T cells that were phenotypically and functionally similar to memory CD8 T cells present in IL-15(+/+) mice. However, longitudinal analysis revealed a slow attrition of virus-specific memory CD8 T cells in the absence of IL-15 signals. This loss of CD8 T cells was due to a severe defect in the proliferative renewal of antigen-specific memory CD8 T cells in IL-15(-/-) mice. Taken together, these results show that IL-15 is not essential for the generation of memory CD8 T cells, but is required for homeostatic proliferation to maintain populations of memory cells over long periods of time.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , División Celular/fisiología , Memoria Inmunológica/fisiología , Interleucina-15/fisiología , Virus/inmunología , Animales , Linfocitos T CD8-positivos/citología , Femenino , Homeostasis/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
17.
Infect Immun ; 76(10): 4564-73, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18694965

RESUMEN

Previous studies have shown that mucosal application of interleukin-12 (IL-12) can stimulate elevated secretory immunoglobulin A (IgA) responses. Since possible exposure to plague is via Yersinia pestis-laden aerosols that results in pneumonic plague, arming both the mucosal and systemic immune systems may offer an added benefit for protective immunity. Two bicistronic plasmids were constructed that encoded the protective plague epitopes, capsular antigen (F1-Ag) and virulence antigen (V-Ag) as a F1-V fusion protein but differed in the amounts of IL-12 produced. When applied nasally, serum IgG and mucosal IgA anti-F1-Ag and anti-V-Ag titers were detectable beginning at week 6 after three weekly doses, and recombinant F1-Ag boosts were required to elevate the F1-Ag-specific antibody (Ab) titers. Following pneumonic challenge, the best efficacy was obtained in mice primed with IL-12(Low)/F1-V vaccine with 80% survival compared to mice immunized with IL-12(Low)/F1, IL-12(Low)/V, or IL-12(Low) vector DNA vaccines. Improved expression of IL-12 resulted in lost efficacy when using the IL-12(High)/F1-V DNA vaccine. Despite differences in the amount of IL-12 produced by the two F1-V DNA vaccines, Ab responses and Th cell responses to F1- and V-Ags were similar. These results show that IL-12 can be used as a molecular adjuvant to enhance protective immunity against pneumonic plague, but in a dose-dependent fashion.


Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas Bacterianas/inmunología , Interleucina-12/inmunología , Vacuna contra la Peste/inmunología , Peste/prevención & control , Proteínas Citotóxicas Formadoras de Poros/inmunología , Vacunas de ADN/inmunología , Administración Intranasal , Animales , Anticuerpos Antibacterianos/análisis , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Citocinas/metabolismo , Femenino , Inmunidad Mucosa , Inmunización Secundaria , Inmunoglobulina A/análisis , Inmunoglobulina G/sangre , Interleucina-12/genética , Linfocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Vacuna contra la Peste/administración & dosificación , Vacuna contra la Peste/genética , Plásmidos , Proteínas Citotóxicas Formadoras de Poros/genética , Bazo/inmunología , Análisis de Supervivencia , Vacunas de ADN/administración & dosificación , Vacunas de ADN/genética
18.
Biotechnol Prog ; 22(1): 225-32, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16454514

RESUMEN

Surfactant-induced unfolding is a significant degradation pathway for detergent enzymes. This study examines the kinetics of surfactant-induced unfolding for endoglucanase III, a detergent cellulase, under conditions of varying pH, temperature, ionic strength, surfactant type, and surfactant concentration. Interactions between protein and surfactant monomer are shown to play a key role in determining the kinetics of the unfolding process. We demonstrate that the unfolding rate can be slowed by (1) modifying protein charge and/or pH conditions to create electrostatic repulsion of ionic surfactants and (2) reducing the amount of monomeric ionic surfactant available for interaction with the enzyme (i.e., by lowering the critical micelle concentration). Additionally, our results illustrate that there is a poor correlation between thermodynamic stability in buffer (DeltaG(unfolding)) and resistance to surfactant-induced unfolding.


Asunto(s)
Celulasa/química , Pliegue de Proteína , Tensoactivos/química , Bacterias/enzimología , Celulasa/metabolismo , Electroforesis en Gel de Poliacrilamida , Concentración de Iones de Hidrógeno , Cinética , Compuestos de Amonio Cuaternario/química , Dodecil Sulfato de Sodio/química , Termodinámica
19.
Biotechnol Prog ; 21(2): 568-74, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15801800

RESUMEN

Novel attrition-resistant and spherical enzyme granules encapsulating active subtilisin were formed by emulsification of 2% alginate sol loaded with active enzyme, instantaneous gelation triggered through in situ release of Ca(2+) (internal gelation), particle separation, and finally acetone extractive drying. Granular subtilisin was highly active, readily dispersible, and mechanically robust. This technique serves as a new and attractive alternative to established enzyme granulation processes, such as fluid bed coating, extrusion followed by marumerization, drum granulation, or prilling, for use in industrial enzyme applications such as detergents, textile manufacturing, and food processing. The formulation and encapsulation conditions were optimized to maximize the resistance of the granule to compression and impact forces, consistent with enzyme release and particle dispersion in detergent solutions. Well characterized alginates, with specified guluronic/mannuronic acid (G/M) content and molecular weight, were used in the formulation. The characteristics of the resulting microspheres, including their size and distribution, morphology, shrinkage, compression resistance, impact strength, solubility and encapsulation yield, were examined. Spherical dry granules were formulated with a mean diameter of 500 microm with particle sizes ranging from 300 to 800 microm. Dry alginate granules were discrete, spherical, and glossy white and exhibited impact strength, compression resistance, and solubility difference dependent on composition. Reduced starch levels, high alginate concentration, low alginate molecular weight, and use of high guluronate alginates resulted in the lowest dust level and highest compression resistance. Subtilisin mass yields were approximately 50%, and specific activity yields ranged from 60% to 100%. A formulation consisting of 3% SG150 alginate, 10% starch, 10% TiO(2), and 1% CaCO(3) provided granules appropriate for use in detergent application.


Asunto(s)
Alginatos/química , Subtilisina/química , Hidrogeles , Ensayo de Materiales , Microesferas
20.
Biotechnol Prog ; 21(6): 1716-23, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16321056

RESUMEN

Detergent proteases and amylases generally bind Ca(2+) ions. These bound ions enhance enzyme stability, reducing the rates of degradative reactions such as unfolding and proteolysis. Thus, surfactant aggregates, such as micelles, affect protease and amylase stability indirectly, by competing with the enzymes for Ca(2+) ions. Dissociation constants for Ca(2+) interactions with anionic surfactant micelles are in the 10(-3) to 10(-2) M range. These interactions are weak relative to enzyme-Ca(2+) interactions (K(d) of order 10(-6) M). However, surfactant is typically present at much higher concentration than enzyme, and it is the Ca(2+)-micelle equilibrium that largely determines the amount of free Ca(2+) available for binding to enzymes. The problem of surfactant-mediated Ca(2+) removal from enzymes can be avoided by adding calcium to a detergent formulation in an amount such that the concentration of free Ca(2+) is around 10(-5)M.


Asunto(s)
Estabilidad de Enzimas , Bacillus/enzimología , Biotecnología , Calcio , Celulasa/química , Detergentes , Técnicas In Vitro , Micelas , Pliegue de Proteína , Dodecil Sulfato de Sodio , Soluciones , Subtilisinas/química , Tensoactivos , Trichoderma/enzimología , alfa-Amilasas/química
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