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BACKGROUND: There is no standard of care for ≥ 3rd-line treatment of metastatic pancreatic adenocarcinoma (PDAC). CBP501 is a novel calmodulin-binding peptide that has been shown to enhance the influx of platinum agents into tumor cells and tumor immunogenicity. This study aimed to (1) confirm efficacy of CBP501/cisplatin/nivolumab for metastatic PDAC observed in a previous phase 1 study, (2) identify combinations that yield 35% 3-month progression-free survival rate (3MPFS) and (3) define the contribution of CBP501 to the effects of combination therapy. METHODS: CBP501 16 or 25 mg/m2 (CBP(16) or CBP(25)) was combined with 60 mg/m2 cisplatin (CDDP) and 240 mg nivolumab (nivo), administered at 3-week intervals. Patients were randomized 1:1:1:1 to (1) CBP(25)/CDDP/nivo, (2) CBP(16)/CDDP/nivo, (3) CBP(25)/CDDP and (4) CDDP/nivo, with randomization stratified by ECOG PS and liver metastases. A Fleming two-stage design was used, yielding a one-sided type I error rate of 2.5% and 80% power when the true 3MPFS is 35%. RESULTS: Among 36 patients, 3MPFS was 44.4% in arms 1 and 2, 11.1% in arm 3% and 33.3% in arm 4. Two patients achieved a partial response in arm 1 (ORR 22.2%; none in other arms). Median PFS and OS were 2.4, 2.1, 1.5 and 1.5 months and 6.3, 5.3, 3.7 and 4.9 months, respectively. Overall, all treatment combinations were well tolerated. Most treatment-related adverse events were grade 1-2. CONCLUSIONS: The combination CBP(25)/(16)/CDDP/nivo demonstrated promising signs of efficacy and a manageable safety profile for the treatment of advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT04953962.
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Adenocarcinoma , Neoplasias Pancreáticas , Fragmentos de Peptídeos , Fosfatases cdc25 , Humanos , Cisplatino , Adenocarcinoma/patologia , Nivolumabe/efeitos adversos , Neoplasias Pancreáticas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
IMPORTANCE: Intracellular calcium signaling plays an important role in the resistance and adaptation to stresses encountered by fungal pathogens within the host. This study reports the optimization of the GCaMP fluorescent calcium reporter for live-cell imaging of dynamic calcium responses in single cells of the pathogen, Candida albicans, for the first time. Exposure to membrane, osmotic or oxidative stress generated both specific changes in single cell intracellular calcium spiking and longer calcium transients across the population. Repeated treatments showed that calcium dynamics become unaffected by some stresses but not others, consistent with known cell adaptation mechanisms. By expressing GCaMP in mutant strains and tracking the viability of individual cells over time, the relative contributions of key signaling pathways to calcium flux, stress adaptation, and cell death were demonstrated. This reporter, therefore, permits the study of calcium dynamics, homeostasis, and signaling in C. albicans at a previously unattainable level of detail.
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Candida albicans , Proteínas Fúngicas , Candida albicans/genética , Candida albicans/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Cálcio/metabolismo , Transdução de Sinais , Estresse OxidativoRESUMO
BACKGROUND: A multi-cancer early detection (MCED) test used to complement existing screening could increase the number of cancers detected through population screening, potentially improving clinical outcomes. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was a prospective, case-controlled, observational study and demonstrated that a blood-based MCED test utilizing cell-free DNA (cfDNA) sequencing in combination with machine learning could detect cancer signals across multiple cancer types and predict cancer signal origin (CSO) with high accuracy. The objective of this third and final CCGA substudy was to validate an MCED test version further refined for use as a screening tool. PATIENTS AND METHODS: This pre-specified substudy included 4077 participants in an independent validation set (cancer: n = 2823; non-cancer: n = 1254, non-cancer status confirmed at year-one follow-up). Specificity, sensitivity, and CSO prediction accuracy were measured. RESULTS: Specificity for cancer signal detection was 99.5% [95% confidence interval (CI): 99.0% to 99.8%]. Overall sensitivity for cancer signal detection was 51.5% (49.6% to 53.3%); sensitivity increased with stage [stage I: 16.8% (14.5% to 19.5%), stage II: 40.4% (36.8% to 44.1%), stage III: 77.0% (73.4% to 80.3%), stage IV: 90.1% (87.5% to 92.2%)]. Stage I-III sensitivity was 67.6% (64.4% to 70.6%) in 12 pre-specified cancers that account for approximately two-thirds of annual USA cancer deaths and was 40.7% (38.7% to 42.9%) in all cancers. Cancer signals were detected across >50 cancer types. Overall accuracy of CSO prediction in true positives was 88.7% (87.0% to 90.2%). CONCLUSION: In this pre-specified, large-scale, clinical validation substudy, the MCED test demonstrated high specificity and accuracy of CSO prediction and detected cancer signals across a wide diversity of cancers. These results support the feasibility of this blood-based MCED test as a complement to existing single-cancer screening tests. CLINICAL TRIAL NUMBER: NCT02889978.
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Detecção Precoce de Câncer , Neoplasias , Biomarcadores Tumorais/genética , Metilação de DNA , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Oncogenes , Estudos ProspectivosRESUMO
AIMS: To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. METHODS: Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8,
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Antidepressivos , Depressão , Adulto , Antidepressivos/uso terapêutico , Ansiedade , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estado Civil , PrognósticoRESUMO
Detection of gastrointestinal nematodes (GIN) as both a qualitative and quantitative test is highly desirable. Methods such as multiplex and qPCR are capable of providing such results, but can be laborious and expensive. This paper presents a rapid, low-cost method of preparing GIN egg from faecal samples that produces DNA suitable for PCR analysis. We also describe a set of primers that are suitable for single-tube multiplex PCR.
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DNA de Helmintos/isolamento & purificação , Fezes/parasitologia , Nematoides/classificação , Infecções por Nematoides/veterinária , Parasitologia/métodos , Reação em Cadeia da Polimerase , Animais , Primers do DNA , Trato Gastrointestinal/parasitologia , Reação em Cadeia da Polimerase Multiplex , Nematoides/genética , Nematoides/isolamento & purificação , Infecções por Nematoides/parasitologia , Óvulo , Ovinos , Doenças dos Ovinos/parasitologiaAssuntos
COVID-19/epidemiologia , COVID-19/prevenção & controle , Infecção Hospitalar , Controle de Infecções/métodos , Equipamento de Proteção Individual , COVID-19/transmissão , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/transmissão , Infecção Hospitalar/virologia , Pessoal de Saúde , Humanos , SARS-CoV-2 , Tropanos , Reino Unido/epidemiologiaRESUMO
AIM: To explore nurses' and physicians' experiences with diabetes consultations in general and the use of dialogue tools in the Diabetes Patient-Related Outcome Measures (DiaPROM) pilot trial. METHODS: We used a qualitative explorative design by conducting semi-structured in-depth interviews with five nurses and nine physicians engaged in the DiaPROM pilot trial. The pilot trial aimed to test an intervention utilizing the patient-reported Problem Areas In Diabetes (PAID) scale and person-centred communication skills as dialogue tools in clinical consultations with adults with type 1 diabetes. We used thematic analysis to analyse the data. RESULTS: We generated three themes (each including two subthemes) from the analysis of participants' experiences: (1) 'Conflicting demands and priorities' (subthemes: 'Balancing guideline recommendations with patients' main concerns' and 'Experiencing that patients need more support to disclose their emotional concerns'); (2) 'Insights about using dialogue tools' (subthemes: 'The benefits and challenges of using the PAID as a dialogue tool' and 'Communication techniques are helpful'); and (3) 'Facilitating new interventions is challenging' (subthemes: 'Unclear roles and responsibilities in the multidisciplinary teamwork' and 'The capacity sets the limit, not the willingness'). CONCLUSIONS: Our findings indicate that the physicians and nurses experienced substantial challenges related to time and resources in the use of dialogue tools to support people's emotional concerns in clinical diabetes consultations. Thus, there is a need for healthcare organizations to adjust priorities to focus on the emotional burden of diabetes if the multidisciplinary diabetes teams are to successfully integrate psychosocial support into routine diabetes care.
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Atitude do Pessoal de Saúde , Diabetes Mellitus Tipo 1/terapia , Enfermeiras e Enfermeiros/normas , Médicos/normas , Pesquisa Qualitativa , Encaminhamento e Consulta/normas , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Estudos RetrospectivosRESUMO
The hurricane is no stranger to longtime residents of Florida's east coast. In 1979, after about 15 years of local inactivity, Hurricane David made landfall in West Palm Beach. Thirteen years later and 100 miles south, category 5 Hurricane Andrew caused catastrophic damage when it hit the city of Homestead in the Miami-Dade area. In 2004, the counties along the east coast of central Florida were hit by 2 devastating hurricanes, Frances and Jeanne, that made landfall at Sewall's Point just 20 days apart. The very next year, Hurricane Wilma made landfall near Everglades City as a Category 3 storm. After a decade of relief, a glancing blow from Hurricane Matthew struck in 2016, only to be followed by the extremely devastating Hurricane Irma just 1 year later. Each of these hurricanes caused significant property damage and mosquito problems for the Florida residents affected by these storms. In 1997, the Indian River Mosquito Control District (IRMCD) developed a hurricane preparedness plan outlining the appropriate action to be taken depending on the severity of the approaching storm. The IRMCD has also learned to negotiate the intricacies of the Federal Emergency Management Agency's reimbursement program, thus reducing the financial impact to the District. This paper provides an overview of how IRMCD has prepared, reacted, and followed-up with the seemingly constant parade of hurricanes that have threatened and affected the east coast over time.
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Defesa Civil/organização & administração , Tempestades Ciclônicas , Controle de Mosquitos/organização & administração , FloridaRESUMO
BACKGROUND: Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HSPC) causes multi-lineage myelosuppression. Trilaciclib is an intravenous CDK4/6 inhibitor in development to proactively preserve HSPC and immune system function during chemotherapy (myelopreservation). Preclinically, trilaciclib transiently maintains HSPC in G1 arrest and protects them from chemotherapy damage, leading to faster hematopoietic recovery and enhanced antitumor immunity. PATIENTS AND METHODS: This was a phase Ib (open-label, dose-finding) and phase II (randomized, double-blind placebo-controlled) study of the safety, efficacy and PK of trilaciclib in combination with etoposide/carboplatin (E/P) therapy for treatment-naive extensive-stage small-cell lung cancer patients. Patients received trilaciclib or placebo before E/P on days 1-3 of each cycle. Select end points were prespecified to assess the effect of trilaciclib on myelosuppression and antitumor efficacy. RESULTS: A total of 122 patients were enrolled, with 19 patients in part 1 and 75 patients in part 2 receiving study drug. Improvements were seen with trilaciclib in neutrophil, RBC (red blood cell) and lymphocyte measures. Safety on trilaciclib+E/P was improved with fewer ≥G3 adverse events (AEs) in trilaciclib (50%) versus placebo (83.8%), primarily due to less hematological toxicity. No trilaciclib-related ≥G3 AEs occurred. Antitumor efficacy assessment for trilaciclib versus placebo, respectively, showed: ORR (66.7% versus 56.8%, P = 0.3831); median PFS [6.2 versus 5.0 m; hazard ratio (HR) 0.71; P = 0.1695]; and OS (10.9 versus 10.6 m; HR 0.87; P = 0.6107). CONCLUSION: Trilaciclib demonstrated an improvement in the patient's tolerability of chemotherapy as shown by myelopreservation across multiple hematopoietic lineages resulting in fewer supportive care interventions and dose reductions, improved safety profile, and no detriment to antitumor efficacy. These data demonstrate strong proof-of-concept for trilaciclib's myelopreservation benefits. CLINICAL TRAIL NUMBER: NCT02499770.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Células Mieloides/efeitos dos fármacos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/secundário , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Método Duplo-Cego , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Prognóstico , Pirimidinas/administração & dosagem , Pirróis/administração & dosagem , Carcinoma de Pequenas Células do Pulmão/enzimologia , Carcinoma de Pequenas Células do Pulmão/patologia , Taxa de Sobrevida , Distribuição TecidualRESUMO
Gastrointestinal nematode (GIN) infections cause millions of dollars of economic loss annually. Increasing cases of anthelmintic resistance have resulted in calls for restricted drug use and implementation of sustainable management practices to slow the rate of resistance. The limited uptake of available management systems and advice has sparked multiple surveys into the psychology and behaviours preventing uptake. These surveys have looked mainly at the farmers, the majority of whom have reported they rely on the advice of their local veterinarian or suppliers for treatment and management. However, there is little research into the psychology of veterinarians and people performing animal health testing on this topic. In the current study, a short survey of people performing faecal egg counts on animals was conducted. The survey focused on identifying areas for improving diagnosis to encourage uptake, and found other areas of interest worth further investigation. Respondents most frequently named manual labour as the main contributor to the cost of testing (65% of respondents) with analysis (42%) and sample preparation (32%) being the main contributors to time. In the survey comments, there was little consistency or commonality in the issues raised. The disparity between onsite and laboratory testers is an area worth investigation, particularly into how to co-ordinate behaviour and advice between proactive farmers and parasitology/veterinary services. Further investigation could provide better insight into how to encourage and maintain sustainable practices on farms.
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Técnicos em Manejo de Animais/psicologia , Atitude , Gastroenteropatias/veterinária , Infecções por Nematoides/veterinária , Contagem de Ovos de Parasitas/psicologia , Contagem de Ovos de Parasitas/veterinária , Criação de Animais Domésticos/economia , Criação de Animais Domésticos/métodos , Animais , Anti-Helmínticos/economia , Anti-Helmínticos/uso terapêutico , Austrália , Fazendeiros/psicologia , Fazendas , Gastroenteropatias/diagnóstico , Gastroenteropatias/parasitologia , Infecções por Nematoides/diagnóstico , Inquéritos e QuestionáriosRESUMO
The aims of this review were to compare planning for both mosquito control and land use in east-central Florida, USA, and in New South Wales, Queensland, and the Northern Territory, Australia. Saltwater mosquito production in mangroves and salt marsh is the predominant mosquito control concern in all the areas. Urban encroachment towards saltwater mosquito habitats is a problem in both Florida and Australia. In east-central Florida and the Northern Territory, mosquito control is supported by comprehensive source reduction programs, whereas in Queensland and New South Wales, larviciding is the main method of control. The long-term control by source reduction programs reduces vulnerability to mosquito issues as population encroaches towards wetlands, whereas larviciding programs have to respond repeatedly as problems arise. Problems from urban encroachment are exacerbated if mosquito control and land-use planning are not integrated. Further, urban planning that is not informed by mosquito management can lead to increased mosquito problems by inadvertent design or allowing residential development close to mosquito habitats. This increases the need for mosquito control and related resourcing. At the regional level of governance, Florida and the Northern Territory generally have greater integration between planning for development and mosquito control than at the local government level in New South Wales and Queensland, where there is a lack of integration between mosquito agencies and planners. It is concluded that coordination of planning and mosquito control is more effective at higher government levels than at local levels, which have less connectivity between management areas and/or insufficient resources. The lesson is that collaboration can assist in avoiding or resolving conflicts.
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Ecossistema , Controle de Mosquitos/métodos , Austrália , Florida , Controle de Mosquitos/instrumentação , Controle de Mosquitos/estatística & dados numéricosRESUMO
BACKGROUND: Exposure to new stressors places college students at increased risk for developing mental health problems. Preventive interventions aimed at enhancing resilience have the potential to improve mental health and well-being in college students and internet-delivery may improve access to these interventions. However, few studies have evaluated the efficacy of online interventions for resilience in college students. The present study seeks to assess the feasibility [initial efficacy and acceptability] of a newly developed internet-delivered intervention for resilience provided with human or automated support, in a sample of college students. METHOD: A pilot randomised controlled trial including three groups: 1) an intervention group with human support; 2) an intervention group with automated support; and 3) a waiting list control group. The intervention, Space for Resilience, is based on positive psychology and consists of seven modules, delivered over a period of eight weeks. Primary outcomes measures will include the Connor-Davidson Resilience Scale (CD-RISC) and the Pemberton Happiness Index (PHI). Secondary outcomes measures will include the Brief Resilience Scale (BRS), the Patient Health Questionnaire - 4 items (PHQ-4), the Rosenberg Self-Esteem Scale (RSES), and the Perceived Stress Scale - 4 items (PSS-4). Acceptability will be examined using the Satisfaction with Treatment (SAT) questionnaire. Analysis will be conducted on an intention-to-treat basis. DISCUSSION: The study seeks to establish the initial efficacy and acceptability of an internet-delivered intervention for resilience with human support and automated support. Apart from determining the impact of the intervention on acceptability and effectiveness, this study will be a first to explore more clearly the relative benefits of different support modes.
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OBJECTIVE: To determine the scope and quality of evidence on the effectiveness of community-based nutrition interventions to promote oral health and restore healthy body weight in school-aged refugee children. BASIC RESEARCH DESIGN: Scoping review using a systematic approach. MAIN OUTCOME MEASURES: Oral health and body weight. RESULTS: Four primary studies, two evaluation studies and one systematic review met the inclusion criteria. No nutrition interventions or reviews to promote oral health in school-aged refugee children were found. There is limited weak evidence for the effectiveness of community-based nutrition interventions to restore healthy body weight in refugee settings. A systematic review also reported weak evidence of correction of child body weight as a result of community-based nutrition interventions in refugee camps. CONCLUSION: This scoping review found no community-based nutrition interventions for school-aged refugee children to promote oral health and restore healthy body weight. There is limited and weak evidence for the effectiveness of community-based nutrition interventions to restore healthy body weight in refugee settings. There is a need to conduct an early phase study to develop and co-produce community-based nutrition interventions to promote oral health and healthy body weight for children residing in long-term refugee situations and to investigate the feasibility for their implementation.
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Peso Corporal , Assistência Odontológica para Crianças , Promoção da Saúde , Distúrbios Nutricionais/prevenção & controle , Saúde Bucal , Refugiados , Criança , HumanosRESUMO
Background: Colorectal Cancer Canada, in partnership with a Scientific Advisory Committee, is developing a Canadian Patient Group Pathway to Accessing Cancer Clinical Trials ("Pathway"). A central element of the Pathway is presented here-namely, a set of recommendations and tools aimed at each stakeholder group. Methods: A summary of the peer-reviewed and grey literature informed discussions at a meeting, held in June 2017, in which a cross-section of stakeholders reached consensus on the potential roles of patient groups in the cancer clinical trials process, barriers to accessing cancer clinical trials, best practice models for patient-group integration, and a process for developing the Pathway. Canadian recommendations and tools were subsequently developed by a small working group and reviewed by the Scientific Advisory Committee. Results: The major output of the consensus conference was agreement that the Clinical Trials Transformation Initiative (ctti) model, successfully applied in the United States, could be adapted to create a Canadian Pathway. Two main differences between the Canadian and American cancer clinical research environments were highlighted: the effects of global decision-making and systems of regulatory and funding approvals. The working group modified the ctti model to incorporate those aspects and to reflect Canadian stakeholder organizations and how they currently interact with patient groups. Conclusions: Developing and implementing a Canadian Pathway that incorporates the concepts of multi-stakeholder collaboration and the inclusion of patient groups as equal partners is expected to generate significant benefits for all stakeholders. The next steps to bring forward a proposed Pathway will involve engaging the broader cancer research community. Clinical trial sponsors will be encouraged to adopt a Charter recognizing the importance of including patient groups, and to support the training of patient groups through an independent body to ensure quality research partners. Integration of patient groups into the process of developing "real world" evidence will be advanced by a further consensus meeting being organized by Colorectal Cancer Canada for 6-7 November 2018.
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Ensaios Clínicos como Assunto , Procedimentos Clínicos , Pesquisa Biomédica , Canadá , Estudos Transversais , Tomada de Decisões , Diretrizes para o Planejamento em Saúde , Humanos , Modelos TeóricosRESUMO
BACKGROUND: Subsets of patients with severe asthma remain symptomatic despite prolonged, high-dose glucocorticoid therapy. We hypothesized that the clinical glucocorticoid sensitivity of these asthmatics is reflected in differences in peripheral blood dendritic cell subsets. OBJECTIVE: To compare peripheral blood leucocyte populations using flow cytometry at baseline and after 2 weeks of systemic glucocorticoid (steroid) treatment to identify immunological differences between steroid-sensitive (SS) and steroid-resistant (SR) asthmatics. METHODS: Adult severe asthmatics (SS n = 12; SR n = 23) were assessed for their response to 2 weeks of therapy with oral prednisolone. Peripheral blood was obtained before and after therapy and stained for lymphocyte (CD3, CD19, CD4, CD8 and Foxp3) and dendritic cell markers (Lineage negative [CD3, CD14, CD16, CD19, CD20, CD56], HLA-DR+, CD304, CD11c, ILT3 and CD86). RESULTS: A higher median frequency of myeloid DCs (mDCs) but not plasmacytoid DCs (pDCs) was observed in the blood of SR as compared to SS asthmatics (P = .03). Glucocorticoid therapy significantly increased median B cell, but not T cell numbers in both cohorts, with a trend for increased numbers of Foxp3+ Tregs in SS (P = .07), but not SR subjects. Oral prednisolone therapy significantly reduced the median numbers and frequencies of total DCs and pDCs in both SS and SR asthmatics. Interestingly, the expression of HLA-DR and ILT3 was also reduced on pDCs in all patients. In contrast, therapy increased the median frequency of mDCs in SS, but reduced it in SR asthmatics. CONCLUSIONS: Myeloid DC frequency is elevated in SR compared with SS asthmatics, and mDC shows a differential response to oral prednisolone therapy.
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Antígenos CD/imunologia , Células Dendríticas/imunologia , Glucocorticoides/administração & dosagem , Prednisolona/administração & dosagem , Linfócitos T/imunologia , Administração Oral , Adulto , Asma/tratamento farmacológico , Asma/imunologia , Asma/patologia , Células Dendríticas/patologia , Feminino , Citometria de Fluxo , Humanos , Masculino , Linfócitos T/patologiaRESUMO
Mechanistic understanding of the control of vesicle motion from within a secretory cell to the site of exocytosis remains incomplete. In this work, we have used total internal reflection (TIRF) microscopy to examine the mobility of secretory vesicles at the plasma membrane. Under resting conditions, we found vesicles showed little lateral mobility. Anchoring of vesicles in this membrane proximal compartment could be disrupted with latrunculin A, indicating an apparent actin dependent process. A candidate intermediary between vesicles and the actin skeleton is the actin binding protein scinderin. Co-transfection of an shRNA construct against scinderin blocked secretion, and also increased the mobility of vesicles in the membrane-proximal section of the cell, indicating a dual role for scinderin in secretion; tethering vesicles to the cytoskeleton, as well as liberating them following stimulation through the previously described calcium dependent actin severing activity. Analysis of lipid dependence indicates that scinderin exhibits calcium dependent binding to phosphatidyl-inositol monophosphate, providing a possible mechanism for vesicle binding.
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Exocitose/fisiologia , Gelsolina/metabolismo , Vesículas Secretórias/metabolismo , Animais , Células PC12 , RatosRESUMO
To commission dental services for vulnerable (special care) patient groups effectively, consistently and fairly an evidence base is needed of the costs involved. The simplified Case Mixed Tool (sCMT) can assess treatment mode complexity for these patient groups. OBJECTIVE: To determine if the sCMT can be used to identify costs of service provision. CLINICAL SETTING: Patients (n=495) attending the Sussex Community NHS Trust Special Care Dental Service for care were assessed using the sCMT. MAIN MEASURES: sCMT score and costs (staffing, laboratory fees, etc.) besides patient age, whether a new patient and use of general anaesthetic/intravenous sedation. METHOD: Statistical analysis (adjusted linear regression modelling) compared sCMT score and costs then sensitivity analyses of the costings to age, being a new patient and sedation use were undertaken. Regression tables were produced to present estimates of service costs. RESULTS: Costs increased with sCMT total scale and single item values in a predictable manner in all analyses except for 'cooperation'. Costs increased with the use of IV sedation; with each rising level of the sCMT, and with complexity in every sCMT category, except cooperation. CONCLUSION: Costs increased with increase in complexity of treatment mode as measured by sCMT scores. Measures such as the sCMT can provide predictions of the resource allocations required when commissioning special care dental services.
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Serviços Contratados , Custos e Análise de Custo , Assistência Odontológica/economia , Grupos Diagnósticos Relacionados , Humanos , Reino UnidoRESUMO
There is a need for an alternative approach for health promotion prisons since previous work has indicated that health education, while improving health knowledge, does not result in behaviour change. Evidence has suggested that a health coaching assists in this regard. However, the question remained whether this approach would be appropriate and possible in prisons? This paper presents the public health strategies used to work in partnership with prison management to address challenges and accept opportunities as a health coaching intervention protocol was developed for oral health and wellbeing in the prison setting.
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Educação em Saúde Bucal/métodos , Promoção da Saúde , Saúde Bucal , Prisioneiros , Educação em Saúde Bucal/organização & administração , Promoção da Saúde/métodos , Promoção da Saúde/organização & administração , Humanos , EscóciaRESUMO
Numerous non-neoplastic and neoplastic conditions manifest with distinctive features in blood. Although automated complete blood count (CBC) data are essential, CBC information alone is insufficient for diagnosis. Consequently, morphologic review of blood smears is still relevant in the era of sophisticated automated analyzer systems. Pathologist interpretation of the peripheral blood smear, in conjunction with CBC and clinical information, can provide rapid diagnostic information and guide cost-effective targeted laboratory testing. Pathologist review of blood smears can be used to diagnose cases in which the clinical findings are misleading or nonspecific. Here, we discuss a selection of cases in which the pathologist examination of the blood smear can aid in rapid and accurate diagnosis and guide appropriate treatment. Exemplary non-neoplastic disorders with distinctive morphologic blood features of RBC, neutrophils, monocytes, and lymphocytes will be highlighted. The differential diagnostic considerations in blood smears with RBC destruction will be presented, expanding beyond microangiopathic hemolytic anemia. Lymphocyte morphologic assessment guides differential diagnosis including the identification of rare germline disorders. In each case presented, the integration of morphologic features guided additional testing with confirmation of the diagnosis. Peripheral blood smear review is timely and cost effective, even in an era of sophisticated automated laboratory testing.