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OBJECTIVES: The convergence of socially engaged art and innovative health care was a key focus of Space and Place in End-of-Life Care, a Swedish transdisciplinary research project (2017-2020). For this project, researchers created, facilitated, and documented a range of socially engaged art and innovative healthcare practices during their exploration of the end of life in the context of Stockholm elder care residential settings. STUDY DESIGN: Formulated as a year-long transdisciplinary research residency, two or more art, design, and/or innovative healthcare researchers met in a Stockholm residential elder care home on a weekly basis to observe and encounter people and place and interact, converse, produce, and exchange knowledge in collaboration with the residents, carers, management, friends, family members, and other researchers. METHODS: Researchers engaged in a weekly transdisciplinary research residency in a Stockholm elder care residence to encounter and interact with the people, space and place of the study setting, and learn from and contribute to the residential home. The scientific researchers engaged in a community-based participatory action research project that utilized interviews, photo-elicitation processes, and community round table discussions. This happened in dialogue with the artistic residency process, wherein the artists collaborated with the inhabitants, staff, and visitors of the residential elder care home to produce a series of socially engaged events, experiences, and artifacts, one of which was the participatory art event, the Handfestival that is the case study of this article. RESULTS: The weekly artistic residency for the Space and Place in End-of-Life Care project resulted in the Handfestival, a participatory art event exploring hands, touch and conversation generated by researchers from the fields of art, design, innovative health and elder care in collaboration with residents, staff and family of a Swedish elder care residence. The Handfestival is a model on the intersection between socially engaged art practices and innovative health care approaches and demonstrates how elder care residences and public health agencies could engage in regular, creative, and relational activities for the participation of inhabitants in healthcare settings. CONCLUSIONS: Socially engaged and participatory art practices increase levels of social engagement and promote a greater sense of interconnectivity within health care settings. As such, the Handfestival participatory event reveals the potential for the convergence of art and health via social practice, modeling a way to develop, orchestrate and disseminate events, experiences, and/or artifacts as health services that public health agencies can and should deliver, but might find challenging to imagine and manifest.
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Cuidado Terminal , Anciano , Cuidadores , Comunicación , Investigación Participativa Basada en la Comunidad , Familia , HumanosRESUMEN
BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised concern for the health of immunocompromised individuals, who are potentially at higher risk of more severe infection and poorer outcomes. As a large London transplant center serving a diverse patient population, we report the outcomes of SARS-CoV-2 infection in our cohort of 2848 kidney and/or pancreas transplant patients. METHODS: Data were obtained retrospectively for all transplant patients who attended hospital during the peak of the pandemic and had a positive nasopharyngeal SARS-CoV-2 test. RESULTS: Sixty-six patients were found to be positive for SARS-CoV-2. Twenty percent were treated as outpatients, 59% were admitted to the general ward, and 21% required intensive care. Treatment consisted of reduced immunosuppression, antibiotics for pneumonia or sepsis, and other supportive treatments. Within our cohort, 12 patients died (18%), with an overall mortality of 0.4%. Predictive risk factors for COVID-19 severity were explored. CONCLUSIONS: Severe disease was associated with lower hemoglobin prior to COVID-19 diagnosis and lower lymphocyte count at the time of diagnosis but not age, sex, ethnicity, or preexisting comorbidities. Lower glomerular filtration rate and higher C-reactive protein were associated with more severe disease. Despite no use of hydroxychloroquine, azithromycin, antiviral, or immunomodulatory medications, our mortality rate (kidney and pancreas transplant patients) is similar to current international rates.
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COVID-19/epidemiología , Huésped Inmunocomprometido/inmunología , Trasplante de Riñón/efectos adversos , Trasplante de Páncreas/efectos adversos , Complicaciones Posoperatorias/epidemiología , SARS-CoV-2/inmunología , Adulto , Anciano , COVID-19/inmunología , COVID-19/virología , Comorbilidad , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Terapia de Inmunosupresión/efectos adversos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/virología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Reino Unido/epidemiologíaRESUMEN
The label 'post-truth' signals for many a troubling turn away from principles of enlightened government. The word 'post', moreover, implies a past when things were radically different and whose loss should be universally mourned. In this paper, we argue that this framing of 'post-truth' is flawed because it is ahistorical and ignores the co-production of knowledge and norms in political contexts. Debates about public facts are necessarily debates about social meanings, rooted in realities that are subjectively experienced as all-encompassing and complete, even when they are partial and contingent. Facts used in policy are normative in four ways: They are embedded in prior choices of which experiential realities matter, produced through processes that reflect institutionalized public values, arbiters of which issues are open to democratic contestation and deliberation, and vehicles through which polities imagine their collective futures. To restore truth to its rightful place in democracy, governments should be held accountable for explaining who generated public facts, in response to which sets of concerns, and with what opportunities for deliberation and closure.
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Decepción , Democracia , Política , Política PúblicaRESUMEN
BACKGROUND: Psoriasis is an inflammatory long-term condition involving comorbidities, unhealthy lifestyle and significant life impact. Patients' understanding of psoriasis is limited and support lacking. The Common-Sense Model of Self-Regulation of Health and Illness emphasizes the role of illness and treatment beliefs on coping and self-management. New 'Pso Well® ' patient materials informed by the model, addressed psoriasis as a long-term condition, medication management and lifestyle behaviours. OBJECTIVES: To investigate whether Pso Well® materials (i) broaden understanding of psoriasis without increasing anxiety; (ii) are acceptable; and (iii) comprise features that appear to effect change. METHODS: The Revised Illness Perceptions Questionnaire (IPQ-R modified) and the Hospital Anxiety and Depression Scale (HADS) were administered in patients before and after intervention. Numerical rating scales assessed perceptions of change in understanding and anxiety resulting from engagement with the materials. Qualitative interviews explored acceptability and perceived 'active ingredients'. RESULTS: Fifty-five patients completed pre- and postintervention questionnaires (56% female; median age 59 years). Postintervention, a large effect size was indicated in two IPQ-R domains - illness coherence [t(55) = -3·48, P = 0·001 (two-tailed), η2 = 0·19] and personal control [t(55) = -2·98, P = 0·004 (two-tailed), η2 = 0·14] - and a medium effect in one, treatment control [t(55) = -2·08, P = 0·042 (two-tailed), η2 = 0·08]. HADS scores did not change. For numerical rating scales, 80% of participants reported increased understanding of psoriasis and none reported increased anxiety. Interviews with 19 patients indicated the materials were acceptable and usable. Factors reported to broaden understanding and promote engagement with self-management included linking of related disease aspects, personally relevant content and high-quality design. CONCLUSIONS: High-quality, theory-based psoriasis materials are acceptable to patients and can improve understanding and sense of control without increasing anxiety.
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Comprensión , Psoriasis/psicología , Adulto , Anciano , Ansiedad/etiología , Estudios de Factibilidad , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Percepción , Psoriasis/terapia , Escalas de Valoración Psiquiátrica , Autocuidado/métodos , Autoimagen , Encuestas y CuestionariosRESUMEN
Designing modern vaccine adjuvants depends on understanding the cellular and molecular events that connect innate and adaptive immune responses. The synthetic TLR4 agonist glycopyranosyl lipid adjuvant (GLA) formulated in a squalene-in-water emulsion (GLA-SE) augments both cellular and humoral immune responses to vaccine Ags. This adjuvant is currently included in several vaccines undergoing clinical evaluation including those for tuberculosis, leishmaniasis, and influenza. Delineation of the mechanisms of adjuvant activity will enable more informative evaluation of clinical trials. Early after injection, GLA-SE induces substantially more Ag-specific B cells, higher serum Ab titers, and greater numbers of T follicular helper (TFH) and Th1 cells than alum, the SE alone, or GLA without SE. GLA-SE augments Ag-specific B cell differentiation into germinal center and memory precursor B cells as well as preplasmablasts that rapidly secrete Abs. CD169+ SIGNR1+ subcapsular medullary macrophages are the primary cells to take up GLA-SE after immunization and are critical for the innate immune responses, including rapid IL-18 production, induced by GLA-SE. Depletion of subcapsular macrophages (SCMÑ) or abrogation of IL-18 signaling dramatically impairs the Ag-specific B cell and Ab responses augmented by GLA-SE. Depletion of SCMÑ also drastically reduces the Th1 but not the TFH response. Thus the GLA-SE adjuvant operates through interaction with IL-18-producing SCMÑ for the rapid induction of B cell expansion and differentiation, Ab secretion, and Th1 responses, whereas augmentation of TFH numbers by GLA-SE is independent of SCMÑ.
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Adyuvantes Inmunológicos/farmacología , Linfocitos B/inmunología , Diferenciación Celular/efectos de los fármacos , Glucósidos/farmacología , Interleucina-18/inmunología , Lípido A/farmacología , Ganglios Linfáticos/inmunología , Macrófagos/inmunología , Receptor Toll-Like 4/agonistas , Animales , Linfocitos B/citología , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/inmunología , Diferenciación Celular/inmunología , Femenino , Glucósidos/farmacocinética , Interleucina-18/genética , Subunidad alfa del Receptor de Interleucina-18/genética , Subunidad alfa del Receptor de Interleucina-18/inmunología , Lectinas Tipo C/genética , Lectinas Tipo C/inmunología , Lípido A/farmacocinética , Ganglios Linfáticos/citología , Macrófagos/citología , Ratones , Ratones Noqueados , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/inmunología , Lectina 1 Similar a Ig de Unión al Ácido Siálico/genética , Lectina 1 Similar a Ig de Unión al Ácido Siálico/inmunología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Transducción de Señal/inmunología , Células TH1/citología , Células TH1/inmunología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/inmunologíaRESUMEN
We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell-related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group-namely, the tolerant recipients-were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS-independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross-validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management.
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Biomarcadores/metabolismo , Rechazo de Injerto/diagnóstico , Supervivencia de Injerto/inmunología , Tolerancia Inmunológica/inmunología , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Adulto , Anciano , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Linfocitos B/metabolismo , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/etiología , Rechazo de Injerto/metabolismo , Supervivencia de Injerto/efectos de los fármacos , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Studies assessing cardiovascular disease (CVD) risk factors in patients with psoriasis have been limited by selection bias, inappropriate controls or a reliance on data collected for clinical reasons. OBJECTIVES: To investigate whether screening for CVD risk factors in patients with psoriasis in primary care augments the known prevalence of CVD risk factors in a cross-sectional study. METHODS: Patients listed as having psoriasis in primary care were recruited, screened and risk assessed by QRISK2. RESULTS: In total, 287 patients attended (mean age 53 years, 57% women, 94% white British, 22% severe disease, 33% self-reported psoriatic arthritis). The proportion with known and screen-detected (previously unknown) risk factors was as follows: hypertension 35% known and 13% screen-detected; hypercholesterolaemia 32% and 37%; diabetes 6·6% and 3·1% and chronic kidney disease 1·1% and 4·5%. At least one screen-detected risk factor was found in 48% and two or more risk factors were found in 21% of patients. One in three patients (37%) not previously known to be at high risk were found to have a high (> 10%) 10-year CVD risk. Among the participants receiving treatment for known CVD risk factors, nearly half had suboptimal levels for blood pressure (46%) and cholesterol (46%). CONCLUSIONS: Cardiovascular risk factor screening of primary care-based adults with psoriasis identified a high proportion of patients (i) at high CVD risk, (ii) with screen-detected risk factors and (iii) with suboptimally managed known risk factors. These findings need to be considered alongside reports that detected limited responses of clinicians to identified risk factors before universal CVD screening can be recommended.
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Enfermedades Cardiovasculares/prevención & control , Psoriasis/complicaciones , Artritis Psoriásica/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios Transversales , Complicaciones de la Diabetes/complicaciones , Inglaterra/epidemiología , Femenino , Humanos , Hipercolesterolemia/complicaciones , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Prevalencia , Insuficiencia Renal Crónica/complicaciones , Factores de Riesgo , AutoinformeRESUMEN
Pythiosis is an infection caused by the aquatic oomycete Pythium insidiosum. Commonly known as 'swamp cancer' in veterinary pathology, pythiosis is now considered an emerging human disease associated with significant morbidity and mortality. However, because clinical information is limited, many healthcare providers, including dermatologists, are unfamiliar with this diagnosis. To increase awareness of this life-threatening infection, a case of cutaneous pythiosis is presented. We describe a middle-aged man with acute myeloid leukaemia who presented with necrotizing haemorrhagic plaques on his thighs after a weekend of freshwater boating. Histological examination of a biopsy specimen showed invasive fungal hyphae associated with dense perivascular inflammation and vessel damage. Diagnostic testing on tissue culture revealed growth of P. insidiosum. Despite multiple debridements and antifungal therapy, the patient died within 2 weeks of presentation. There are four clinical presentations reported in human pythiosis. Pythium insidiosum infection should be considered in any patient with a suggestive exposure history and fungal elements found on histological examination or in culture. Identification of the organism can be difficult, so polymerase chain reaction and serological assays can be useful in making a diagnosis. To improve clinical outcomes, early combination therapy with antifungals and surgery is needed.
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Dermatomicosis/diagnóstico , Pitiosis/diagnóstico , Enfermedades Cutáneas Parasitarias/diagnóstico , Adulto , Diagnóstico Diferencial , Resultado Fatal , Fiebre de Origen Desconocido/parasitología , Humanos , Masculino , MusloRESUMEN
The synthetic TLR4 agonist glucopyranosyl lipid adjuvant (GLA) is a potent Th1-response-inducing adjuvant when formulated in a squalene oil-in-water emulsion (SE). While the innate signals triggered by TLR4 engagement are well studied, the contribution of SE remains unclear. To better understand the effect of SE on the adjuvant properties of GLA-SE, we compared the innate and adaptive immune responses elicited by immunization with different formulations: GLA without oil, SE alone or the combination, GLA-SE, in mice. Within the innate response to adjuvants, only GLA-SE displayed features of inflammasome activation, evidenced by early IL-18 secretion and IFN-γ production in memory CD8(+) T cells and neutrophils. Such early IFN-γ production was ablated in caspase-1/11(-/-) mice and in IL-18R1(-/-) mice. Furthermore, caspase-1/11 and IL-18 were also required for full Th1 CD4(+) T-cell induction via GLA-SE. Thus, we demonstrate that IL-18 and caspase-1/11 are components of the response to immunization with the TLR4 agonist/squalene oil-in-water based adjuvant, GLA-SE, providing implications for other adjuvants that combine oils with TLR agonists.
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Adyuvantes Inmunológicos/administración & dosificación , Caspasa 1/inmunología , Caspasas/inmunología , Interferón gamma/inmunología , Interleucina-18/inmunología , Escualeno/administración & dosificación , Receptor Toll-Like 4/agonistas , Inmunidad Adaptativa/efectos de los fármacos , Adyuvantes Inmunológicos/síntesis química , Animales , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Caspasa 1/genética , Caspasas/genética , Caspasas Iniciadoras , Emulsiones , Femenino , Expresión Génica , Inmunidad Innata/efectos de los fármacos , Inmunización , Memoria Inmunológica , Inflamasomas/efectos de los fármacos , Interferón gamma/biosíntesis , Interleucina-18/biosíntesis , Lípidos/administración & dosificación , Lípidos/síntesis química , Lípidos/inmunología , Ratones , Ratones Noqueados , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Receptores de Interleucina-18/genética , Receptores de Interleucina-18/inmunología , Escualeno/química , Escualeno/inmunología , Células TH1/citología , Células TH1/efectos de los fármacos , Células TH1/inmunología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/inmunologíaRESUMEN
Studies were conducted to assess glacial acetic acid (GAA) with various host plant volatiles (HPVs) and the sex pheromone, (E,E)-8, 10-dodecadien-1-ol, of codling moth, Cydia pomonella (L), as lures in traps for tortricid pests that often co-occur in tree fruits in the western United States. In addition to codling moth, field trapping studies were conducted with oriental fruit moth, Grapholita molesta (Busck), obliquebanded leafroller Choristoneura rosaceana (Harris), the leafroller Pandemis pyrusana Kearfott, and the eyespotted budmoth, Spilonota ocellana (Denis and Schiffermüller). HPVs included ethyl (E,Z)-2,4-decadienoate (pear ester), (E)-4,8-dimethyl-1,3,7-nonatriene, butyl hexanoate, (E)-ß-ocimene, (E)-ß-farnesene, and farnesol. Three types of GAA co-lures differing in a 10-fold range in weekly evaporation rates were tested. The evaporation rate of GAA co-lures was an important factor affecting moth catches. The highest rate tested captured fewer codling moth but more leafrollers and eyespotted budmoth. GAA co-lures caught both sexes of each species. The field life of butyl hexanoate and (E)-ß-ocimene lures were much shorter than pear ester or sex pheromone lures. Adding GAA to pear ester or to (E)-ß-ocimene significantly increased the catches of only codling moth or oriental fruit moth, respectively. Combining pear ester or (E)-ß-ocimene with GAA did not affect the catch of either species compared with the single more attractive HPV. Adding HPVs to GAA did not increase the catches of either leafroller species or eyespotted budmoth. Traps baited with pear ester, sex pheromone, and GAA for monitoring codling moth were also effective in classifying pest pressure of both leafroller species within orchards.
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Ácido Acético/farmacología , Agricultura/métodos , Frutas/parasitología , Control de Insectos/métodos , Mariposas Nocturnas/fisiología , Manejo de Especímenes/métodos , Árboles/parasitología , Ácido Acético/química , Animales , Cromatografía de Gases , Oregon , Feromonas/química , Feromonas/farmacología , Especificidad de la Especie , Compuestos Orgánicos Volátiles/química , Compuestos Orgánicos Volátiles/farmacología , WashingtónRESUMEN
It has been demonstrated that sonic energy can be harnessed to enhance convection in Galvanic cells during cyclic voltammetry; however, the practical value of this approach is limited due to the lack of open volumes for convection patterns to develop in most batteries. This study evaluates the ability of ultrasonic waves to enhance diffusion in membrane separators commonly used in sandwich-architecture batteries. Studies include the measuring of open-circuit performance curves to interpret performances in terms of reductions in concentration overpotentials. The use of a 40 kHz sonicator bath can consistently increase the voltage of the battery and reduce overpotential losses up to 30%. This work demonstrates and quantifies battery enhancement due to enhanced diffusion made possible with ultrasonic energy.
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Suministros de Energía Eléctrica , Sonicación , Difusión , ElectroquímicaRESUMEN
Since the introduction of highly active antiretroviral therapy (HAART) in 1996, mortality in patients with human immunodeficiency virus (HIV) infection has decreased markedly. As a result, morbidity from other chronic conditions such as kidney, liver and heart disease is increasing. This is in part as a natural consequence of ageing, and in part due to the higher risk of solid organ failure in these individuals. This higher risk is related to the co-morbidities associated with HIV infection and to the metabolic consequences of drug therapy. Kidney disease is an important cause of morbidity and mortality in patients with HIV infection and encompasses a range of clinical presentations including acute kidney injury, chronic kidney disease (CKD), and end-stage kidney disease. Black race is the most important predictor of kidney disease in HIV-infected persons due to both genetic and modifiable causes. HIVassociated nephropathy (HIVAN) is caused by viral infection of the renal epithelium and, although decreasing in incidence, remains the most common cause of CKD in HIV-infected persons. In addition to HIVAN, a wide spectrum of other histopathological presentations, many of which are immune complex-mediated, is increasingly recognised. Clinicians who treat these patients should be aware of the nephrotoxic potential of several commonly used medications, particularly antiviral agents, and also the need to dose-adjust medication in renal impairment. The increased life expectancy of patients with HIV and end-stage kidney disease has meant that kidney transplantation is increasingly an option. Results from carefully conducted prospective studies are promising, at least in the short term.
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Antirretrovirales/efectos adversos , Infecciones por VIH/complicaciones , Enfermedades Renales/etiología , Lesión Renal Aguda/etiología , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Población Negra , Infecciones por VIH/tratamiento farmacológico , Humanos , Enfermedades Renales/etnología , Enfermedades Renales/terapia , Diálisis RenalRESUMEN
Vaccination with an isolated antigen is frequently not sufficient to elicit a protective immune response. The addition of adjuvants to the antigen can increase the magnitude and breadth of the response generated, but quantification of this increase as a function of adjuvant has been intractable. We have directly determined the variation of the immunoglobulin G variable-chain repertoire of an entire organism as a function of vaccination. Using the well-established Plasmodium vivax antigen, PvRII, and massively parallel sequencing, we showed that the use of a Toll-like receptor (TLR) agonist in the vaccine formulation increased the diversity of the variable region sequences in comparison to the use of an oil-in-water emulsion adjuvant alone. Moreover, increased variable domain diversity in response to the use of TLR agonist-based adjuvants correlated with improved antigen neutralization. The use of TLR agonists also broadened the range of polymorphic variants against which these antibodies could be effective. In addition, a peptide microarray demonstrated that inclusion of adjuvants changed the profile of linear epitopes from PvRII that were recognized by serum from immunized animals. The results of these studies have broad implications for vaccine design--they may enable tailored adjuvants that elicit the broad spectrum of antibodies required to neutralize drifted and polymorphic pathogen strains as well as provide a method for rapid determination of correlates of adjuvant-induced humoral immunity.
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Anticuerpos Antiprotozoarios/inmunología , Vacunas contra la Malaria/inmunología , Receptores Toll-Like/inmunología , Adyuvantes Inmunológicos , Secuencia de Aminoácidos , Animales , Anticuerpos Antiprotozoarios/química , Formación de Anticuerpos/inmunología , ADN Complementario/genética , Epítopos/inmunología , Inmunización , Región Variable de Inmunoglobulina/química , Región Variable de Inmunoglobulina/inmunología , Ratones , Ratones Endogámicos BALB C , Péptidos/inmunologíaRESUMEN
Therapy of intracellular pathogens can be complicated by drug toxicity, drug resistance, and the need for prolonged treatment regimens. One approach that has shown promise is immunotherapy. Leishmaniasis, a vector-borne disease ranked among the six most important tropical infectious diseases by the World Health Organization, has been treated clinically with crude or defined vaccine preparations or cytokines, such as IFN-gamma and GM-CSF, in combination with chemotherapy. We have attempted to develop an improved and defined immunotherapeutic using a mouse model of cutaneous leishmaniasis. We hypothesized that immunotherapy may be improved by using TLR synergy to enhance the parasite-specific immune response. We formulated L110f, a well-established Leishmania poly-protein vaccine candidate, in conjunction with either monophosphoryl lipid A, a TLR4 agonist, or CpG, a TLR9 agonist, or a combination of these, and evaluated anti-Leishmania immune responses in absence or presence of active disease. Only mice treated with L110f plus monophosphoryl lipid A-CpG were able to induce a strong effective T cell response during disease and subsequently cured lesions and reduced parasite burden when compared with mice treated with L110f and either single adjuvant. Our data help to define a correlate of protection during active infection and indicate TLR synergy to be a potentially valuable tool in treating intracellular infections.
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Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/terapia , Receptores Toll-Like/fisiología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Antígenos Bacterianos/administración & dosificación , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/metabolismo , Células Cultivadas , Proteínas del Citoesqueleto/fisiología , Quimioterapia Combinada , Femenino , Interleucina-12/biosíntesis , Leishmaniasis Cutánea/microbiología , Lípido A/administración & dosificación , Lípido A/análogos & derivados , Lipopolisacáridos/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Oligodesoxirribonucleótidos/administración & dosificación , Pirina , Receptores Toll-Like/agonistasRESUMEN
The application of a microencapsulated (MEC) sex pheromone formulation (Checkmate CM-F) for codling moth, Cydia pomonella (L.), in low volume, concentrated sprays was evaluated in a series of small plot and grower trials in apple, Malus domestica Borkhausen, and pear, Pyrus communis L. Preliminary tests found that MEC sprays applied at 172-207 kilopascals in 12-23 liters/ha deposited the highest density of microcapsules per leaf. The addition of a latex sicker did not increase the deposition of microcapsules. Small plot tests in 2004 compared the effectiveness of two low-volume sprayers against a standard high-volume spray (926 liters/ha) applied at 1,379 kilopascals. Moth catches and fruit injury were significantly lower in plots treated with the low-volume sprays compared with plots treated with the standard sprayer. These results suggest that concentrating the MEC formulation increases the deposition of microcapsules and improves its effectiveness. Larger trials were conducted with a low-volume sprayer in 4-ha plots within commercial apple (2005-2006) and pear orchards (2005) paired with similar plots treated with hand-applied pheromone dispensers. Levels of fruit injury were not significantly different between pheromone treatments in any of the three tests. Moth catches, however, were significantly higher in the MEC- versus the dispenser-treated apple plots in 2005. No difference was found in the fruit injury levels in MEC-treated apple orchards in 2005 caused by irrigation method, but moth catches were significantly higher in overhead versus undertree orchards. The advantages and current limitations of using MEC sex pheromone sprays to supplement current grower's management strategies for codling moth is discussed.
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Control de Insectos/métodos , Mariposas Nocturnas , Atractivos Sexuales , Animales , Composición de Medicamentos , Frutas/fisiología , Control de Insectos/instrumentación , Malus/fisiología , Pyrus/fisiologíaRESUMEN
(E,Z) -2,4-decadienoate (pear ester) is a larval kairomone for the codling moth, Cydia pomonella (L.) (Lepidoptera: Tortricidae). Orchard studies were conducted in 2005 and 2006 in apple, Malus domestica Borkhausen, and pear, Pyrus communis L., to evaluate a 5% active ingredient (AI), microencapsulated formulation of pear ester (PE-MEC) as an insecticidal additive for the codling moth granulovirus (CpGV). Although CpGV applied at 5-15-d intervals at commercial rates (2.2 X 10(12)-10(13) granules per ha) killed the majority (82-94%) of larvae found inside infested fruit, it did not eliminate significant damage, i.e., 30-92% fruit injury at harvest versus 51-82% in controls. PE-MEC treatments had significant but inconsistent results in our tests. In apple (mixed cultivars), PE-MEC (3.7-4.7 g [AI] /ha) plus CpGV reduced the percentage of fruit injured during the second but not the first larval generation, compared with CpGV alone, but there no was no additional population reduction (live larvae collected from infested fruit and tree bands). In 'Bartlett' pear, PE-MEC (3.7 g [AI] /ha) plus CpGV significantly increased larval mortality and reduced deep fruit entries at harvest over CpGV alone in 2006, but similar improvements were not observed in 2005 when a lower rate (1.5 g [AI] /ha) was tested. Surprisingly, compared with untreated controls, the PE-MEC formulation alone also reduced fruit injury (mid-season in Bartlett) and larval survivorship inside infested fruit at harvest (2006 apple tests and both years in Bartlett). Although pear ester seems amenable as a kairomonal adjuvant for use with insecticides, our inconsistent data with CpGV in apple and pear suggest practical improvements in formulation and application strategies (e.g., to optimize and maintain attractive release rates) are needed.
Asunto(s)
Decanoatos/farmacología , Granulovirus/fisiología , Mariposas Nocturnas/efectos de los fármacos , Control Biológico de Vectores , Feromonas/farmacología , Pyrus/química , Animales , Decanoatos/aislamiento & purificación , Conducta Alimentaria/efectos de los fármacos , Malus/parasitología , Mariposas Nocturnas/fisiología , Mariposas Nocturnas/virología , Feromonas/aislamiento & purificación , Pyrus/parasitologíaRESUMEN
Corticosteroids have been the most widely used immunosuppressive agents since the first clinical transplantation in the 1950s. There are few studies of late steroid withdrawal in renal transplantation and none have prospectively assessed bone mineral density (BMD). The study aim was to assess the impact of corticosteroid withdrawal, in stable renal transplant recipients, on BMD and bone turnover. BMD, osteocalcin (OC) and cross-linked telopeptide of type I collagen (CTx) were measured in 92 patients randomized into a trial of steroid withdrawal. Patients with functioning renal transplants for more than 1 year with a serum creatinine below 200 micromol/L entered the trial. All patients were on triple immunosuppression (Cyclosporin microemulsion, Azathioprine and prednisolone), corticosteroids were withdrawn at 1 mg/month. BMD was measured twice annually with serum CTx and OC. One year following withdrawal of glucocorticoids there was no significant difference in creatinine. BMD increased in the withdrawal group (2.54% per year L1-L4, p < 0.01), there was a slight reduction in the control group. Mean OC increased from 5.3 to 12.2 ng/mL (p < 0.05) in the withdrawal group, but was unchanged in the controls. No change was seen in CTx. Corticosteroid withdrawal in renal transplant recipients results in an increase in BMD with a corresponding increase in serum OC.
Asunto(s)
Corticoesteroides/uso terapéutico , Densidad Ósea , Desarrollo Óseo , Trasplante de Riñón/fisiología , Absorciometría de Fotón , Corticoesteroides/efectos adversos , Adulto , Biomarcadores/sangre , Colágeno Tipo I/sangre , Creatinina/metabolismo , Esquema de Medicación , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Osteocalcina/sangre , Péptidos/sangre , Valores de Referencia , Factores de TiempoRESUMEN
O câncer renal é uma moléstia onde a cura é obtida essencialmente através de tratamento cirúrgico em estágios iniciais. A nefroctomia radical pode ser realizada por via aberta ou laparoscópica, sendo que a última associa as vantagens de procedimentos minimamente invasivos. Neste artigo os autores realizam uma revisão extensa da literatura para comparar os resultados da nefrectomia radical aberta (NRA) versus nefrectomia radical laparoscópica (NRL).
Asunto(s)
Humanos , Riñón , Neoplasias Renales , Nefrectomía , LaparoscopíaRESUMEN
BACKGROUND: Interprofessional education (IPE) is a novel teaching and learning initiative where students of more than one health profession learn interactively together. However, despite its potential for improving interprofessional relationships, there is little information regarding the participation of student dietitians in IPE. The aim of this paper was to consider the reaction of student dietitians to an IPE course in order to stimulate debate between dietitians regarding the issues relating to IPE. METHODS: Student dietitians participated in an IPE course consisting of seven sessions on communication and ethics in health care together with students of medicine and nursing. Student dietitians completed an evaluation questionnaire following each session that surveyed their reaction to the session using both a Likert scale and free-text comments. RESULTS: Twenty-six student dietitians completed the IPE course. All sessions were rated positively for interest value (P < or = 0.14), learning experience (P < or = 0.036) and value for clinical practice (P < or = 0.05). The limited number of free-text comments indicated some positive experiences regarding interprofessional learning, teaching content and teaching strategy. CONCLUSIONS: This is one of very few evaluations to describe the reaction of student dietitians to IPE. Student dietitians had largely positive reactions to the IPE course. Further research is required to evaluate whether these positive reactions were a direct consequence of the inclusion of students from other health professions and whether these translate into positive effects on learning, behaviour and results. The opportunities for the dietetic profession posed by students' involvement in IPE are discussed.
Asunto(s)
Dietética/educación , Educación de Pregrado en Medicina/métodos , Comunicación Interdisciplinaria , Relaciones Interprofesionales , Estudiantes/psicología , Adulto , Femenino , Humanos , Masculino , Grupo de Atención al Paciente , Encuestas y Cuestionarios , EnseñanzaRESUMEN
The case of a man with progressive breathlessness and pulmonary infiltration caused by AL amyloidosis associated with multiple myeloma is presented. There was a marked peripheral eosinophilia, which has not previously been described with amyloidosis.