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1.
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.

2.
Aging Ment Health ; : 1-6, 2024 Mar 27.
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.

3.
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.

4.
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
5.
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.

6.
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
7.
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
8.
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
9.
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.

10.
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
11.
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
12.
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
13.
J Leukoc Biol ; 92(2): 375-87, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22636321

RESUMEN

Human brucellosis exhibits diverse pathological manifestations that can affect almost any organ. In particular, osteoarticular complications are the most common focal manifestation of brucellosis and occur in 40-80% of patients. In immunocompetent mice, Brucella replication is generally restricted to the spleen, liver, and to a lesser extent, LNs, thereby limiting their use for study of focal inflammation often found in brucellosis. Here, we report that nasal, oral, or peritoneal infection of IFN-γ(-/-) mice with WT Brucella melitensis or Brucella abortus results in joint and periarticular tissue inflammation. Histological analysis of the affected joints revealed inflammatory infiltrates and debris within the joint space colocalizing with Brucella antigen. Osteoarthritis, necrosis, periarticular soft tissue inflammation, and substantial brucellae burdens were observed. Oral rifampicin was effective in clearing infection and halting further progression of focal inflammation from infected IFN-γ(-/-) mice, although some symptoms and swelling remained. Elevated IL-1 ß, but not TNF-α, IL-6, or IL-17, was detected in joint homogenates from infected IFN-γ(-/-) mice. Whereas more susceptible to systemic infection, IL-1R(-/-) mice depleted of IFN-γ were more resistant to focal inflammation than WT mice similarly depleted of IFN-γ. Collectively, these results show IFN-γ(-/-) mice represent a potential model for study of focal inflammation attributed to Brucella infection and will allow evaluation of intervention strategies targeting IL-1, IL-1R, or other inflammatory mediators, with the potential to complement antibiotic-based therapies.


Asunto(s)
Brucelosis/inmunología , Dermatitis/inmunología , Mediadores de Inflamación/fisiología , Interferón gamma/deficiencia , Interleucina-1/fisiología , Miositis/inmunología , Animales , Brucelosis/genética , Brucelosis/microbiología , Células Cultivadas , Dermatitis/genética , Dermatitis/microbiología , Modelos Animales de Enfermedad , Humanos , Inflamación/inmunología , Inflamación/microbiología , Inflamación/patología , Interferón gamma/fisiología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Miositis/genética , Miositis/microbiología , Conejos
14.
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
15.
Vaccine ; 28(18): 3219-30, 2010 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-20197132

RESUMEN

The chemokine, lymphotactin (LTN), was tested as a molecular adjuvant using bicistronic DNA vaccines encoding the protective Yersinia capsular (F1) antigen and virulence antigen (V-Ag) as a F1-V fusion protein. The LTN-encoding F1-V or V-Ag vaccines were given by the intranasal (i.n.) or intramuscular (i.m.) routes, and although serum IgG and mucosal IgA antibodies (Abs) were induced, F1-Ag boosts were required for robust anti-F1-Ag Abs. Optimal efficacy against pneumonic plague was obtained in mice i.m.-, not i.n.-immunized with these DNA vaccines. These vaccines stimulated elevated Ag-specific Ab-forming cells and mixed Th cell responses, with Th17 cells markedly enhanced by i.m. immunization. These results show that LTN can be used as a molecular adjuvant to enhance protective immunity against plague.


Asunto(s)
Vacuna contra la Peste/administración & dosificación , Vacuna contra la Peste/inmunología , Peste/prevención & control , Vacunas de ADN/administración & dosificación , Vacunas de ADN/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/genética , Administración Intranasal , Animales , Anticuerpos Antibacterianos/análisis , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/genética , Antígenos Bacterianos/inmunología , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Femenino , Inmunidad Mucosa , Inmunización Secundaria/métodos , Inmunoglobulina A/análisis , Inmunoglobulina G/sangre , Inyecciones Intramusculares , Linfocinas/administración & dosificación , Linfocinas/genética , Ratones , Ratones Endogámicos BALB C , Peste/inmunología , Vacuna contra la Peste/genética , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Citotóxicas Formadoras de Poros/inmunología , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Sialoglicoproteínas/administración & dosificación , Sialoglicoproteínas/genética , Análisis de Supervivencia , Vacunas de ADN/genética , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología
16.
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
17.
J Invest Dermatol ; 128(9): 2225-31, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18337829

RESUMEN

A key cell type of the resident skin immune system is the dendritic cell (DC), which in normal skin is located in two distinct microanatomical compartments: Langerhans cells (LCs), mainly in the epidermis, and dermal DCs (DDCs), in the dermis. Here, the lineage of DDCs was investigated using monoclonal antibodies and immunohistology. We provide evidence that "DDC" comprise at least two major phenotypic populations of dendritic-appearing cells, immature DC expressing CD1, CD11c and CD208; and macrophages expressing CD209, CD206, CD163, and CD68. These data suggest that dermal dendritic-appearing macrophages comprise a novel part of the innate immune response in the resident skin immune system.


Asunto(s)
Antígenos CD1/metabolismo , Moléculas de Adhesión Celular/metabolismo , Células de Langerhans/citología , Células de Langerhans/inmunología , Lectinas Tipo C/metabolismo , Macrófagos/citología , Macrófagos/inmunología , Receptores de Superficie Celular/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biopsia , Antígeno CD11c/metabolismo , Humanos , Inmunohistoquímica , Receptor de Manosa , Lectinas de Unión a Manosa/metabolismo , Microscopía Confocal , Piel/inmunología , Piel/patología
18.
J Immunol ; 178(2): 1059-67, 2007 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-17202369

RESUMEN

The gut provides a large area for immunization enabling the development of mucosal and systemic Ab responses. To test whether the protective Ags to Yersinia pestis can be orally delivered, the Y. pestis caf1 operon, encoding the F1-Ag and virulence Ag (V-Ag) were cloned into attenuated Salmonella vaccine vectors. F1-Ag expression was controlled under a promoter from the caf1 operon; two different promoters (P), PtetA in pV3, PphoP in pV4, as well as a chimera of the two in pV55 were tested. F1-Ag was amply expressed; the chimera in the pV55 showed the best V-Ag expression. Oral immunization with Salmonella-F1 elicited elevated secretory (S)-IgA and serum IgG titers, and Salmonella-V-Ag(pV55) elicited much greater S-IgA and serum IgG Ab titers than Salmonella-V-Ag(pV3) or Salmonella-V-Ag(pV4). Hence, a new Salmonella vaccine, Salmonella-(F1+V)Ags, made with a single plasmid containing the caf1 operon and the chimeric promoter for V-Ag allowed the simultaneous expression of F1 capsule and V-Ag. Salmonella-(F1+V)Ags elicited elevated Ab titers similar to their monotypic derivatives. For bubonic plague, mice dosed with Salmonella-(F1+V)Ags and Salmonella-F1-Ag showed similar efficacy (>83% survival) against approximately 1000 LD(50) Y. pestis. For pneumonic plague, immunized mice required immunity to both F1- and V-Ags because the mice vaccinated with Salmonella-(F1+V)Ags protected against 100 LD(50) Y. pestis. These results show that a single Salmonella vaccine can deliver both F1- and V-Ags to effect both systemic and mucosal immune protection against Y. pestis.


Asunto(s)
Antígenos Bacterianos/inmunología , Peste/inmunología , Infecciones por Salmonella/inmunología , Infecciones por Salmonella/prevención & control , Vacunas contra la Salmonella/inmunología , Salmonella/inmunología , Yersinia pestis/inmunología , Administración Oral , Animales , Anticuerpos/inmunología , Antígenos Bacterianos/genética , Inmunogenética , Ratones , Ratones Endogámicos BALB C , Membrana Mucosa/inmunología , Peste/prevención & control , Salmonella/genética , Vacunas contra la Salmonella/administración & dosificación , Tasa de Supervivencia , Yersiniosis
19.
20.
Infect Immun ; 74(7): 3874-9, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16790759

RESUMEN

znuA is known to be an important factor for survival and normal growth under low Zn(2+) concentrations for Escherichia coli, Haemophilus spp., Neisseria gonorrhoeae, and Pasteurella multocida. We hypothesized that the znuA gene present in Brucella melitensis 16 M would be similar to znuA in B. abortus and questioned whether it may also be an important factor for growth and virulence of Brucella abortus. Using the B. melitensis 16 M genome sequence, primers were designed to construct a B. abortus deletion mutant. A znuA knockout mutation in B. abortus 2308 (DeltaznuA) was constructed and found to be lethal in low-Zn(2+) medium. When used to infect macrophages, DeltaznuA B. abortus showed minimal growth. Further study with DeltaznuA B. abortus showed that its virulence in BALB/c mice was attenuated, and most of the bacteria were cleared from the spleen within 8 weeks. Protection studies confirmed the DeltaznuA mutant as a potential live vaccine, since protection against wild-type B. abortus 2308 challenge was as effective as that obtained with the RB51 or S19 vaccine strain.


Asunto(s)
Brucella abortus/genética , Brucella abortus/inmunología , Brucelosis/prevención & control , Eliminación de Gen , Factores de Virulencia/genética , Animales , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/genética , Vacunas Bacterianas/inmunología , Brucella abortus/crecimiento & desarrollo , Brucella abortus/patogenicidad , Brucelosis/inmunología , Brucelosis/microbiología , Línea Celular , Femenino , Macrófagos/inmunología , Macrófagos/microbiología , Ratones , Ratones Endogámicos BALB C , Factores de Virulencia/aislamiento & purificación , Zinc/metabolismo
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