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The case of a giant thoracic desmoid tumour in a 44-year-old woman, who presented two years following a breast reconstruction with a latissimus dorsi (LD) flap and implant, is reported. Clinical findings included a rapidly growing, painless mass. Computed tomography (CT) suggested skin and intercostal soft tissue invasion. The tumour was resected en bloc with the LD muscle, implant capsule and underlying rib segments. The resultant thoracic and abdominal wall defects were reconstructed with Dualmesh® and polypropylene meshes respectively. There was no evidence of recurrence at thirty-six months follow-up.
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Fibromatosis Agresiva/diagnóstico por imagen , Mamoplastia/efectos adversos , Complicaciones Posoperatorias/diagnóstico por imagen , Músculos Superficiales de la Espalda/trasplante , Pared Abdominal/patología , Pared Abdominal/cirugía , Adulto , Femenino , Fibromatosis Agresiva/patología , Fibromatosis Agresiva/cirugía , Humanos , Mamoplastia/métodos , Invasividad Neoplásica , Complicaciones Posoperatorias/patología , Complicaciones Posoperatorias/cirugía , Piel/patología , Colgajos Quirúrgicos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Despite the critical role of immunoglobulin E (IgE) in allergy, circulating IgE+ B cells are scarce. Here, we describe in patients with allergic rhinitis B cells with a memory phenotype responding to a prototypic aeroallergen. METHODS: Fifteen allergic rhinitis patients with grass pollen allergy and 13 control subjects were examined. Blood mononuclear cells stained with carboxyfluorescein diacetate succinimidyl ester (CFSE) were cultured with Bahia grass pollen. Proliferation and phenotype were assessed by multicolour flow cytometry. RESULTS: In blood of allergic rhinitis patients with high serum IgE to grass pollen, most IgE(hi) cells were CD123+ HLA-DR(-) basophils, with IgE for the major pollen allergen (Pas n 1). Both B and T cells from pollen-allergic donors showed higher proliferation to grass pollen than nonallergic donors (P = 0.002, and 0.010, respectively), whereas responses to vaccine antigens and mitogen did not differ between groups. Allergen-driven B cells that divided rapidly (CD19(mid) CD3(-) CFSE(lo) ) showed higher CD27 (P = 0.008) and lower CD19 (P = 0.004) and CD20 (P = 0.004) expression than B cells that were slow to respond to allergen (CD19(hi) CD3(-) CFSE(mid) ). Moreover, rapidly dividing allergen-driven B cells (CD19(mid) CFSE(lo) CD27(hi) ) showed higher expression of the plasmablast marker CD38 compared with B cells (CD19(hi) CFSE(mid) CD27(lo) ) that were slow to divide. CONCLUSION: Patients with pollen allergy but not control donors have a population of circulating allergen-specific B cells with the phenotype and functional properties of adaptive memory B-cell responses. These cells could provide precursors for allergen-specific IgE production upon allergen re-exposure.
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Alérgenos/inmunología , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Inmunoglobulina E/inmunología , Memoria Inmunológica , Rinitis Alérgica/inmunología , Rinitis Alérgica/metabolismo , Adulto , Alérgenos/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/metabolismo , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Fenotipo , Poaceae/efectos adversos , Polen/inmunología , Unión Proteica/inmunología , Rinitis Alérgica/diagnóstico , Rinitis Alérgica Estacional/diagnóstico , Rinitis Alérgica Estacional/inmunología , Rinitis Alérgica Estacional/metabolismo , Adulto JovenRESUMEN
In the same way that individuals' risk perceptions can influence how they behave toward risks, how organizational members make sense of risk controls is an important influence on how they apply and maintain such controls. In this article, we describe an analysis of sensemaking about the control of risk in offshore hydrocarbons production, an industry that continues to produce disasters of societal significance. A field study of 80 interviews was conducted in five offshore oil and gas companies and the agency that regulates them. The interviews were analyzed using qualitative template analysis. This provided a categorization of the many ways of acting through which informants made sense of the risk control task, and indicated that the organizations placed substantially different emphases on different ways of acting. Nevertheless, this sensemaking fell into two broad classes: that which tended to limit or be pessimistic about organizational controls, and that which tended to extend or be optimistic about organizational controls. All the participating organizations collectively placed a balanced emphasis on these two classes. We argue that this balanced sensemaking is an adaptation rather than a deliberate choice, but that it is an important element of controlling risk in its own right.
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A 'Bare Below the Elbows' (BBTE) dress code policy has been introduced by the majority of NHS trusts in the UK. The aim of this Irish study was to evaluate the impact of an educational intervention on perception of medical attire. The study was carried out in two centres: a tertiary referral centre (Beaumont Hospital) and a district hospital (MRH, Portlaoise). Two questionnaires, incorporating photographic evaluation of appropriate attire for consultants and junior doctors, were completed pre and post BBTE education. One hundred and five patients participated. Analysis pre BBTE education indicated patients considered formal attire and white coats most appropriate for consultants and junior doctors respectively. Post-intervention analysis revealed a significant reduction in the popularity of both (p <0.001), with scrubs and smart casual attire gaining significant support in both cohorts (p <0.001). Our findings demonstrated that patient opinion on medical attire is malleable. The support of such a policy may be achieved if patients are informed that the aim is to reduce the spread of healthcare-associated infections.
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Vestuario , Médicos , Estudios Transversales , Codo , Femenino , Hospitales Generales , Humanos , Irlanda , Masculino , Política Organizacional , Relaciones Médico-Paciente , Encuestas y Cuestionarios , Atención Terciaria de SaludRESUMEN
Monitoring the presence of commensal and pathogenic respiratory microorganisms is of critical global importance. However, community-based surveillance is difficult because nasopharyngeal swabs are uncomfortable and painful for a wide age range of participants. We designed a methodology for minimally invasive self-sampling at home and assessed its use for longitudinal monitoring of the oral, nasal and hand microbiota of adults and children within families. Healthy families with two adults and up to three children, living in and near Liverpool, United Kingdom, self-collected saliva, nasal lining fluid using synthetic absorptive matrices and hand swabs at home every two weeks for six months. Questionnaires were used to collect demographic and epidemiological data and assess feasibility and acceptability. Participants were invited to take part in an exit interview. Thirty-three families completed the study. Sampling using our approach was acceptable to 25/33 (76%) families, as sampling was fast (76%), easy (76%) and painless (60%). Saliva and hand sampling was acceptable to all participants of any age, whereas nasal sampling was accepted mostly by adults and children older than 5 years. Multi-niche self-sampling at home can be used by adults and children for longitudinal surveillance of respiratory microorganisms, providing key data for design of future studies.
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Microbiota , Nariz , Adulto , Niño , Humanos , Preescolar , Encuestas y Cuestionarios , Manejo de Especímenes/métodos , SalivaRESUMEN
Patterns of somatic mutation in IgE genes from allergic individuals have been a focus of study for many years, but IgE sequences have never been reported from parasitized individuals. To study the role of antigen selection in the evolution of the anti-parasite response, we therefore generated 118 IgE sequences from donors living in Papua New Guinea (PNG), an area of endemic parasitism. For comparison, we also generated IgG1, IgG2, IgG3 and IgG4 sequences from these donors, as well as IgG1 sequences from Australian donors. IgE sequences had, on average, 23.0 mutations. PNG IgG sequences had average mutation levels that varied from 17.7 (IgG3) to 27.1 (IgG4). Mean mutation levels correlated significantly with the position of their genes in the constant region gene locus (IgG3 < IgG1 < IgG2 < IgG4). Interestingly, given the heavy, life-long antigen burden experienced by PNG villagers, average mutation levels in IgG sequences were little different to that seen in Australian IgG1 sequences (19.2). Patterns of mutation provide clear evidence of antigen selection in many IgG sequences. The percentage of IgG sequences that showed significant accumulations of replacement mutations in the complementarity determining regions ranged from 22% of IgG3 sequences to 39% of IgG2 sequences. By contrast, only 12% of IgE sequences had such evidence of antigen selection, and this was significantly less than in PNG IgG1, IgG2 and IgG4 subclass sequences (P < 0.01). The anti-parasite IgE response therefore has the reduced evidence of antigen selection that has previously been reported in studies of IgE sequences from allergic individuals.
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Antígenos Helmínticos/inmunología , Helmintiasis/inmunología , Helmintos/inmunología , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Adulto , Animales , Variación Antigénica/genética , Variación Antigénica/inmunología , Antígenos Helmínticos/genética , Secuencia de Bases , Regiones Determinantes de Complementariedad/genética , Regiones Determinantes de Complementariedad/inmunología , Biología Computacional/métodos , Helmintiasis/parasitología , Helmintos/genética , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/genética , Inmunoglobulina G/sangre , Inmunoglobulina G/genética , Persona de Mediana Edad , Modelos Inmunológicos , Datos de Secuencia Molecular , Mutación/inmunología , Papúa Nueva Guinea , Polimorfismo de Nucleótido Simple , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Población Rural , Alineación de Secuencia , Adulto JovenRESUMEN
PURPOSE: When Carl Langer described the aberrant axillary arch in 1846 its relevance in sentinel node biopsy (SNB) surgery could not have been contemplated. The authors define an incidence and elucidate relevance of the arch in SNB of the axilla. METHODS: A review of a database for breast and melanoma axillary SNB was carried out. The sample was 1 year at Princess Margaret Hospital, Toronto. RESULTS: Of 319 axillary SNB, 3 (0.9%) had axillary arches noted. Two were in the melanoma group (n = 59) and one in the breast (n = 260). Interestingly one arch case had an ipsilateral 'idiopathic' axillary vein thrombosis as a child. CONCLUSIONS: The authors see no reason to deviate from the practice of division of the arch at the highest level when recognised at SNB. This would abrogate the risk of concealed nodes and possible future neurovascular compression.
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Axila/anatomía & histología , Biopsia del Ganglio Linfático Centinela , Adulto , Axila/cirugía , Neoplasias de la Mama/patología , Femenino , Humanos , Metástasis Linfática/diagnóstico por imagen , Masculino , Melanoma/patología , Persona de Mediana Edad , Estudios Prospectivos , Cintigrafía , Radiofármacos , Azufre Coloidal Tecnecio Tc 99mRESUMEN
OBJECTIVE: Ovine footrot is a contagious bacterial disease that reduces meat and wool production and can trigger on-farm quarantine in New South Wales. Field diagnosis is based on the prevalence and severity of foot lesions, environmental conditions and flock history. The study evaluated whether a PCR assay or gelatin gel test for virulence in Dichelobacter nodosus isolated from hoof material could aid in the clinical diagnosis of virulent footrot. METHODS: A quantitative polymerase chain reaction (qPCR) used for diagnosis of virulent footrot in some Australian states was evaluated on 218 hoof swabs taken from 44 sheep flocks from 36 NSW properties, quantifying both the aprV2 positive and aprB2 positive acidic protease genotypes of D. nodosus. DESIGN: The same flocks/swabs were used to evaluate test agreement between the aprV2/B2 qPCR and the gelatin gel test, and a multiple logistic regression was used to identify factors critical for field diagnosis of virulent footrot. RESULTS: Only fair to moderate agreement (kappa test) and significant disagreement (McNemar's) was shown between the gelatin gel test and the ratio of aprV2 positive to total D. nodosus. The proportion of aprV2 positive D. nodosus was not significantly different between foot lesions scores of increasing severity. Field diagnosis of virulent footrot was best explained by the prevalence of score 4 and 5 lesions, wet and warm environmental conditions, and recent footrot diagnosis. CONCLUSION: Although the apr2 gene could differentiate between benign and virulent strains of D. nodosus, the apr2 qPCR was of minimal use for field diagnosis of virulent footrot, where disease expression relies on host genetics, immunity and environmental conditions.
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Dichelobacter nodosus , Panadizo Interdigital , Enfermedades de las Ovejas , Animales , Australia , Nueva Gales del Sur , Péptido Hidrolasas , Ovinos , VirulenciaRESUMEN
Africanized drone honey bees (Apis mellifera) migrate into European honey-bee colonies in large numbers, but Africanized colonies only rarely host drones from other colonies. This migration leads to a strong mating advantage for Africanized bees since it both inhibits European drone production and enhances Africanized drone production.
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Africanized and European honey bee (Apis mellifera) populations showed quantitative differences in colony defensive behavior. Africanized bees responded faster and in much larger numbers than European honey bees and produced 8.2 and 5.9 times as many stings during two different experiments. Times to react to alarming stimuli were negatively correlated with the number of bees responding and to the total number of stings. The number of bees responding was significantly correlated to the total number of stings only for the Africanized population.
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Partial genome segments of a begomovirus were previously amplified from Wissadula amplissima exhibiting yellow-mosaic and leaf-curl symptoms in the parish of St. Thomas, Jamaica and this isolate assigned to a tentative begomovirus species, Wissadula golden mosaic St. Thomas virus. To clone the complete genome of this isolate of Wissadula golden mosaic St. Thomas virus, abutting primers were designed to PCR amplify its full-length DNA-A and DNA-B components. Sequence analysis of the complete begomovirus genome obtained, confirmed that it belongs to a distinct begomovirus species and this isolate was named Wissadula golden mosaic St. Thomas virus-[Jamaica:Albion:2005] (WGMSTV-[JM:Alb:05]). The genome of WGMSTV-[JM:Alb:05] is organized similar to that of other bipartite Western Hemisphere begomoviruses. Phylogenetic analyses placed the genome components of WGMSTV-[JM:Alb:05] in the Abutilon mosaic virus clade and showed that the DNA-A component is most closely related to four begomovirus species from Cuba, Tobacco leaf curl Cuba virus, Tobacco leaf rugose virus, Tobacco mottle leaf curl virus, and Tomato yellow distortion leaf virus. The putative Rep-binding-site motif in the common region of WGMSTV-[JM:Alb:05] was observed to be identical to that of Chino del tomate virus-Tomato [Mexico:Sinaloa:1983], Sida yellow mosaic Yucatan virus-[Mexico:Yucatan:2005], and Tomato leaf curl Sinaloa virus-[Nicaragua:Santa Lucia], suggesting that WGMSTV-[JM:Alb:05] is capable of forming viable pseudo-recombinants with these begomoviruses, but not with other members of the Abutilon mosaic virus clade. Biolistic inoculation of test plant species with partial dimers of the WGMSTV-[JM:Alb:05] DNA-A and DNA-B components showed that the virus was infectious to Nicotiana benthamiana and W. amplissima and the cultivated species Phaseolus vulgaris (kidney bean) and Lycopersicon esculentum (tomato). Infected W. amplissima plants developed symptoms similar to symptoms observed under field conditions, confirming that this virus is a causal agent of Wissadula yellow mosaic disease in W. amplissima.
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Begomovirus/clasificación , Begomovirus/crecimiento & desarrollo , Malvaceae/virología , Secuencia de Bases , Begomovirus/genética , Begomovirus/aislamiento & purificación , Análisis por Conglomerados , Cartilla de ADN/genética , ADN Viral/química , ADN Viral/genética , Orden Génico , Genes Virales , Genoma Viral , Jamaica , Solanum lycopersicum/virología , Datos de Secuencia Molecular , Phaseolus/virología , Filogenia , Reacción en Cadena de la Polimerasa/métodos , Análisis de Secuencia de ADN , Homología de Secuencia , Sintenía , Nicotiana/virologíaRESUMEN
Endometrioma formation is an uncommon complication of caesarean sections. Frequently the diagnosis is delayed, due to a failure to include it in the differential diagnosis for an abdominal wall mass. The case of a thirty-six year-old female, presenting with the classical triad of a mass and cyclical pain arising in a caesarean section scar, is reported. Wide excision was performed via a transverse lower abdominal ellipse, similar to that used for abdominoplasty. The involved rectus muscle was excised and the abdominal wall was reconstructed using polypropylene mesh. An abdominoplasty-like approach affords clear margins for large caesarean section scar endometriomas thus reducing the recurrence risk. Abdominal wall reconstruction may be required for extensive lesions.
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Pared Abdominal , Cesárea/efectos adversos , Cicatriz/etiología , Cicatriz/patología , Endometriosis/etiología , Endometriosis/cirugía , Adulto , Cicatriz/cirugía , Endometriosis/patología , Femenino , HumanosRESUMEN
Widespread use of Pneumococcal Conjugate Vaccines (PCV) has reduced vaccine-type nasopharyngeal colonisation and invasive pneumococcal disease. In a double-blind, randomised controlled trial using the Experimental Human Pneumococcal Challenge (EHPC) model, PCV-13 (Prevenar-13) conferred 78% protection against colonisation acquisition and reduced bacterial intensity (AUC) as measured by classical culture. We used a multiplex qPCR assay targeting lytA and pneumococcal serotype 6A/B cpsA genes to re-assess the colonisation status of the same volunteers. Increase in detection of low-density colonisation resulted in reduced PCV efficacy against colonisation acquisition (29%), compared to classical culture (83%). For experimentally colonised volunteers, PCV had a pronounced effect on decreasing colonisation density. These results obtained in adults suggest that the success of PCV vaccination could primarily be mediated by the control of colonisation density. Studies assessing the impact of pneumococcal vaccines should allow for density measurements in their design.
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Vacunas Neumococicas/uso terapéutico , Vacunación/métodos , Vacunas Conjugadas/uso terapéutico , Adolescente , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/prevención & control , Streptococcus pneumoniae/inmunología , Streptococcus pneumoniae/patogenicidad , Adulto JovenRESUMEN
An experimental challenge model was developed to demonstrate Lawsonia intracellularis colonization and reproduction of proliferative enteropathy (PE) in naïve weaner pigs. Groups of pigs were orally dosed with between 10(10) and 10(5)L. intracellularis extracted from haemorrhagic PE affected mucosa. Pigs were monitored for clinical signs and intestinal lesions of PE and evidence of bacterial colonization by serology and faecal polymerase chain reaction (PCR). One group of challenged pigs were necropsied after 21 days to confirm the reproduction of PE. L. intracellularis colonization and seroconversion was delayed in pigs dosed with lower numbers of L. intracellularis. When faecal shedding of L. intracellularis ceased to be detected in all of the challenged pigs, they were re-dosed orally with approximately 10(10)L. intracellularis and monitored for evidence of re-colonization and clinical disease. This study demonstrated that pigs previously challenged with L. intracellularis were protected from re-colonization and clinical disease on subsequent exposure 10 weeks later, regardless of the initial dose of L. intracellularis.
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Infecciones por Desulfovibrionaceae/veterinaria , Enfermedades Intestinales/veterinaria , Lawsonia (Bacteria)/patogenicidad , Enfermedades de los Porcinos/microbiología , Enfermedades de los Porcinos/prevención & control , Administración Oral , Animales , Anticuerpos Antibacterianos/sangre , Colon/patología , Infecciones por Desulfovibrionaceae/microbiología , Infecciones por Desulfovibrionaceae/prevención & control , Heces/microbiología , Femenino , Íleon/patología , Inmunización/métodos , Inmunización/veterinaria , Enfermedades Intestinales/microbiología , Enfermedades Intestinales/prevención & control , Lawsonia (Bacteria)/crecimiento & desarrollo , Lawsonia (Bacteria)/inmunología , Masculino , Distribución Aleatoria , Porcinos , Enfermedades de los Porcinos/patología , Factores de Tiempo , Vacunación/veterinariaRESUMEN
Pulmonary infections in the returned traveller are a common presentation. A wide variety of infections may present with pulmonary symptoms. It is important for clinicians to differentiate the cause of these symptoms. The risk of contracting certain travel-related pulmonary diseases depends on travel destination, length of stay, activities undertaken and co-morbidities. Some pathogens are found worldwide, whilst others are related to specific locations. This review article will discuss the approach to diagnosing and treating pulmonary infections in the returned traveller.
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BACKGROUND: The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood-brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). MATERIALS AND METHODS: The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. RESULTS: Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P<0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. CONCLUSION: CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic.
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Neoplasias Encefálicas/tratamiento farmacológico , Convección , Sistemas de Liberación de Medicamentos , Glioma/tratamiento farmacológico , Ácidos Hidroxámicos/uso terapéutico , Indoles/uso terapéutico , Micelas , Nanopartículas/química , Poloxámero/química , Animales , Muerte Celular , Línea Celular Tumoral , Supervivencia Celular , Modelos Animales de Enfermedad , Técnica del Anticuerpo Fluorescente , Humanos , Ácidos Hidroxámicos/administración & dosificación , Indoles/administración & dosificación , Panobinostat , Ratas Endogámicas F344 , Ratas Wistar , Análisis de SupervivenciaRESUMEN
The ability of pneumococcal conjugate vaccine (PCV) to decrease transmission by blocking the acquisition of colonization has been attributed to herd immunity. We describe the role of mucosal immunoglobulin G (IgG) to capsular polysaccharide (CPS) in mediating protection from carriage, translating our findings from a murine model to humans. We used a flow cytometric assay to quantify antibody-mediated agglutination demonstrating that hyperimmune sera generated against an unencapsulated mutant was poorly agglutinating. Passive immunization with this antiserum was ineffective to block acquisition of colonization compared to agglutinating antisera raised against the encapsulated parent strain. In the human challenge model, samples were collected from PCV and control-vaccinated adults. In PCV-vaccinated subjects, IgG levels to CPS were increased in serum and nasal wash (NW). IgG to the inoculated strain CPS dropped in NW samples after inoculation suggesting its sequestration by colonizing pneumococci. In post-vaccination NW samples pneumococci were heavily agglutinated compared with pre-vaccination samples in subjects protected against carriage. Our results indicate that pneumococcal agglutination mediated by CPS-specific antibodies is a key mechanism of protection against acquisition of carriage. Capsule may be the only vaccine target that can elicit strong agglutinating antibody responses, leading to protection against carriage acquisition and generation of herd immunity.
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Aglutinación , Anticuerpos Antibacterianos/metabolismo , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Adolescente , Adulto , Animales , Cápsulas Bacterianas/inmunología , Portador Sano , Femenino , Humanos , Inmunización Pasiva , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Infecciones Neumocócicas/prevención & control , Vacunación , Vacunas Conjugadas , Adulto JovenRESUMEN
We describe the ability of a short-chain amphiphilic block copolymer to self-assemble to form an artificial supramolecular light-harvesting system. Specifically, we demonstrate that the 2.5 kDa, poly(ethylene oxide)-block-poly(butadiene) (PEO-b-PBD), exhibits sufficient morphological flexibility as a membrane material and enables generation of mimics of three-dimensional chlorosomes as well as supported membrane bilayers containing energy acceptors. This overall architecture replicates green bacterial light-harvesting function whereby these assemblies exhibit long-range order and three-dimensional morphology similar to native chlorosomes and are capable of energy transfer internally and to external acceptors, located in a supporting biomimetic polymer membrane. Unlike native green bacterial systems that use multiple lipids as a matrix to generate the appropriate environment for chlorosome assembly and function, the described system matrix is comprised entirely of a single polymer amphiphile. This work demonstrates the potential of short-chain amphiphilic block copolymers in generating self-assembled, bio-mimetic membrane architectures, and in doing so, generates scalable, spatial-energetic landscapes for photonic applications. Finally, the results presented provide evidence of minimal requirements to induce chlorosome-like organization and function.
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Materiales Biomiméticos , Luz , Polímeros/química , Butadienos/química , Chloroflexus/fisiología , Elastómeros/química , Transferencia de Energía , Polietilenglicoles/químicaRESUMEN
Increased nasopharyngeal colonization density has been associated with pneumonia. We used experimental human pneumococcal carriage to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. A total of 101 healthy subjects were screened for respiratory virus before pneumococcal intranasal challenge. Virus was associated with increased odds of colonization (75% virus positive became colonized vs. 46% virus-negative subjects; P=0.02). Nasal Factor H (FH) levels were increased in virus-positive subjects and were associated with increased colonization density. Using an in vitro epithelial model we explored the impact of increased mucosal FH in the context of coinfection. Epithelial inflammation and FH binding resulted in increased pneumococcal adherence to the epithelium. Binding was partially blocked by antibodies targeting the FH-binding protein Pneumococcal surface protein C (PspC). PspC epitope mapping revealed individuals lacked antibodies against the FH binding region. We propose that FH binding to PspC in vivo masks this binding site, enabling FH to facilitate pneumococcal/epithelial attachment during viral infection despite the presence of anti-PspC antibodies. We propose that a PspC-based vaccine lacking binding to FH could reduce pneumococcal colonization, and may have enhanced protection in those with underlying viral infection.