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1.
Br J Cancer ; 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38704477

RESUMEN

The COVID-19 pandemic brought unplanned service disruption for breast cancer diagnostic, treatment and support services. This scoping review describes these changes and their impact in the UK and the Republic of Ireland based on studies published between January 2020 and August 2023. Thirty-four of 569 papers were included. Data were extracted and results thematically organized. Findings include fewer new cases; stage shift (fewer early- and more late-stage disease); and changes to healthcare organization, breast screening and treatment. Examples are accepting fewer referrals, applying stricter referral criteria and relying more on virtual consultations and multi-disciplinary meetings. Screening service programs paused during the pandemic before enacting risk-based phased restarts with longer appointment times to accommodate reduced staffing numbers and enhanced infection-control regimes. Treatments shifted from predominantly conventional to hypofractionated radiotherapy, fewer surgical procedures and increased use of bridging endocrine therapy. The long-term impact of such changes are unknown so definitive guidelines for future emergencies are not yet available. Cancer registries, with their large sample sizes and population coverage, are well placed to monitor changes to stage and survival despite difficulties obtaining definitive staging during diagnosis because surgery and pathological assessments are delayed. Multisite longitudinal studies can also provide guidance for future disaster preparedness.

2.
Nat Microbiol ; 9(5): 1244-1255, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38649414

RESUMEN

Carbapenem-resistant Acinetobacter baumannii infections have limited treatment options. Synthesis, transport and placement of lipopolysaccharide or lipooligosaccharide (LOS) in the outer membrane of Gram-negative bacteria are important for bacterial virulence and survival. Here we describe the cerastecins, inhibitors of the A. baumannii transporter MsbA, an LOS flippase. These molecules are potent and bactericidal against A. baumannii, including clinical carbapenem-resistant Acinetobacter baumannii isolates. Using cryo-electron microscopy and biochemical analysis, we show that the cerastecins adopt a serpentine configuration in the central vault of the MsbA dimer, stalling the enzyme and uncoupling ATP hydrolysis from substrate flipping. A derivative with optimized potency and pharmacokinetic properties showed efficacy in murine models of bloodstream or pulmonary A. baumannii infection. While resistance development is inevitable, targeting a clinically unexploited mechanism avoids existing antibiotic resistance mechanisms. Although clinical validation of LOS transport remains undetermined, the cerastecins may open a path to narrow-spectrum treatment modalities for important nosocomial infections.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Proteínas Bacterianas , Lipopolisacáridos , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/metabolismo , Lipopolisacáridos/metabolismo , Animales , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/tratamiento farmacológico , Ratones , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Transporte Biológico , Pruebas de Sensibilidad Microbiana , Humanos , Microscopía por Crioelectrón , Carbapenémicos/farmacología , Carbapenémicos/metabolismo , Modelos Animales de Enfermedad , Femenino , Transportadoras de Casetes de Unión a ATP
3.
Int J Cancer ; 154(10): 1731-1744, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38268160

RESUMEN

The COVID-19 pandemic had a major impact on cancer patients and services but has been difficult to quantify. We examined how the entire cancer pathway-from incidence, presentation, diagnosis, stage, treatment and survival-was affected in Northern Ireland during April-December 2020 compared to equivalent 2018-2019 periods using retrospective, observational cancer registry data from the Northern Ireland Cancer Registry (NICR). There were 6748 cancer cases in April-December 2020 and an average 7724 patients in April-December 2018-2019. Incident cases decreased by 13% (almost 1000). Significant differences were found across age cohorts and deprivation quintiles, with reductions greatest for younger people (<55 years; 19% decrease) and less deprived (22% decrease). A higher proportion had emergency admission (16%-to-20%) with lower proportions diagnosed pathologically (85%-to-83%). There was a significant stage shift, with lower proportions of early stage (29%-to-25%) and higher late-stage (21%-to-23%). Lower proportions received surgery (41%-to-38%) and radiotherapy (24%-to-22%) with a higher proportion not receiving treatment (29%-to-33%). One-year observed-survival decreased from 73.7% to 69.8% and 1-year net-survival decreased from 76.1% to 72.9%, with differences driven by five tumours; Lung (40.3%-to-35.0%), Head-and-Neck (77.4%-to-68.4%), Oesophageal (53.5%-to-42.3%), Lymphoma (81.1%-to-75.2%) and Uterine cancer (87.4%-to-80.4%). Our study reveals profound adverse impact of COVID-19 on the entire cancer patient pathway, with 13% fewer cases, greater emergency admissions and significant stage-shift from early to more advanced-stage disease. There was major treatment impact with lower rates of surgery and radiotherapy and higher proportions receiving no treatment. There were significant reductions in 1-year survival. Our study will support service recovery and protect cancer services in future pandemics or disruptions.


Asunto(s)
COVID-19 , Neoplasias , Humanos , Persona de Mediana Edad , Incidencia , Irlanda del Norte , Estudios Retrospectivos , Pandemias , COVID-19/epidemiología , Neoplasias/epidemiología , Prueba de COVID-19
4.
BMC Cancer ; 23(1): 700, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37495980

RESUMEN

BACKGROUND: The COVID-19 pandemic was managed in Aotearoa New Zealand (NZ) by a COVID-19 elimination policy, involving border closure and an initial national lockdown. This was different to most other countries including Northern Ireland (NI) and the Netherlands (NED). We quantify the effect of these policies on the diagnosis of three major cancers, comparing NZ with these two European countries. METHOD: Data from NED, NZ and NI population-based cancer registries were used to assess trends in all pathologically diagnosed (PD) lung, breast, and colorectal cancers from March to December 2020 (pandemic period) and compared to the similar pre-pandemic period (2017-2019). Trend data were also collated on COVID-19 cases and deaths per 100,000 in each population. RESULTS: Comparing the pre-pandemic period to the pandemic period there were statistically significant reductions in numbers of lung (↓23%) and colorectal (↓15%) PD cancers in NI and numbers of breast (↓18%) and colorectal cancer (↓18.5%) diagnosed in the NED. In NZ there was no significant change in the number of lung (↑10%) or breast cancers (↑0.2%) but a statistically significant increase in numbers of colorectal cancer diagnosed (↑5%). CONCLUSION: The impact of COVID-19 on cancer services was mitigated in NZ as services continued as usual reflecting minimal healthcare disruption and protected cancer services linked with the elimination approach adopted. The reduction in PD cases diagnosed in NED and NI were linked with higher COVID-19 rates and reflect societal restrictions which resulted in delayed patient presentation to primary and secondary care, disruption to screening and healthcare services as a result of COVID-19 infections on staff and the need to shift intensive care to COVID-19 patients. Reductions in PD cancers in NI and the NED and in particularly lung cancers in NI, highlight the need for targeted public health campaigns to identify and treat 'missing' patients. Protecting cancer services should be a priority in any future pandemic or systemic healthcare system disruption.


Asunto(s)
Neoplasias de la Mama , COVID-19 , Neoplasias Colorrectales , Neoplasias Pulmonares , Países Bajos/epidemiología , Nueva Zelanda/epidemiología , Irlanda del Norte/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Humanos , Sistema de Registros , Pandemias , Masculino , Femenino
5.
BMC Cancer ; 22(1): 850, 2022 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-35927617

RESUMEN

BACKGROUND: The pandemic disrupted society and health services through lockdowns and resource reallocation to care for COVID-19 patients. Reductions in numbers of cancer patients having surgery, being diagnosed pathologically or via 2-week wait, and screening programs pauses have been described. The effect on emergency presentation, which represents an acute episode with poor outcomes, has not been investigated. This study explored the pandemic's impact on emergency hospital admissions for cancer patients in a UK region. METHODS: Hospital discharge data for cancer patients in Northern Ireland, which included route to admission, were analysed for the pandemic era in 2020 compared to averages for March to December 2017-2019, focusing on volume and route of emergency admissions by demography and tumour site. FINDINGS: Compared with the pre-pandemic era, the number of cancer emergency admissions fell by 12·3% in 2020. Emergency admissions for cancer were significantly reduced when COVID-19 levels were highest (- 18·5% in April and - 16.8% in October). Females (- 15·8%), urban residents (- 13·2%), and age groups 0 to 49 and 65-74 years old (- 17%) experienced the largest decreases as did those with haematological (- 14·7%), brain and CNS (- 27·9%), and lung cancers(- 14·3%). Significant reductions in referrals from outpatient departments (- 51%) and primary care (- 43%) (p < 0·001) were counterbalanced by admissions from other routes including confirmed or suspected COVID-19 infection (increase 83·6%). INTERPRETATION: Reductions in emergency admissions, and pathologically diagnosed cancers, as reported by the Northern Ireland Cancer Registry (NICR), indicate undiagnosed patients in the community which has implications for future workloads and survival. Data suggest undiagnosed cases may be higher for haematological, brain and CNS, and lung cancers and among females. Efforts should be made to encourage people with symptoms to present for diagnosis or reassurance. FUNDING: The NICR is funded by the Public Health Agency of Northern Ireland. This work was supported by Macmillan Cancer Support and uses data collected by health services as part of their care and support functions.


Asunto(s)
COVID-19 , Neoplasias Pulmonares , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Femenino , Hospitales , Humanos , Pandemias , Reino Unido/epidemiología
6.
BMC Health Serv Res ; 22(1): 46, 2022 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-35000599

RESUMEN

BACKGROUND: The aim of this work was to develop a National Evaluation Framework to facilitate the standardization of delivery, quality, reporting, and evaluation of diabetes education and support programs delivered throughout Australia through the National Diabetes Services Scheme (NDSS). The NDSS is funded by the Australian Government, and provides access to diabetes information, education, support, and subsidized product across diverse settings in each state and territory of Australia through seven independent service-providers. This article reports the approach undertaken to develop the Framework. METHODS: A participatory approach was undertaken, focused on adopting nationally consistent outcomes and indicators, nominating objectives and measurement tools, specifying evaluation processes, and developing quality standards. Existing programs were classified based on related, overarching indicators enabling the adoption of a tiered system of evaluation. RESULTS: Two outcomes (i.e., improved clinical, reduced cost) and four indicators (i.e., improved knowledge and understanding, self-management, self-determination, psychosocial adjustment) were adopted from the Eigenmann and Colagiuri national consensus position statement for diabetes education. This allowed for the identification of objectives (i.e., improved empowerment, reduced distress, autonomy supportive program delivery, consumer satisfaction) and related measurement instruments. Programs were categorized as comprehensive, topic-specific, or basic education, with comprehensive programs allocated to receive the highest-level of evaluation. Eight quality standards were developed, with existing programs tested against those standards. Based on the results of testing, two comprehensive (OzDAFNE for people with type 1 diabetes, DESMOND for people with type 2 diabetes), and eight topic-specific (CarbSmart, ShopSmart, MonitorSmart, FootSmart, MedSmart, Living with Insulin, Insulin Pump Workshop, Ready Set Go - Let's Move) structured diabetes self-management education and support programs were nominated for national delivery. CONCLUSIONS: The National Evaluation Framework has facilitated consistency of program quality, delivery, and evaluation of programs delivered by multiple service providers across diverse contexts. The Framework could be applied by other service providers who facilitate multiple diabetes education and support programs and could be adapted for use in other chronic disease populations where education and support are indicated.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Educación en Enfermería , Automanejo , Australia , Humanos
7.
Nat Commun ; 12(1): 6546, 2021 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-34764270

RESUMEN

Acute myeloid leukemia (AML) is a malignancy of immature progenitor cells. AML differentiation therapies trigger leukemia maturation and can induce remission, but relapse is prevalent and its cellular origin is unclear. Here we describe high resolution analysis of differentiation therapy response and relapse in a mouse AML model. Triggering leukemia differentiation in this model invariably produces two phenotypically distinct mature myeloid lineages in vivo. Leukemia-derived neutrophils dominate the initial wave of leukemia differentiation but clear rapidly and do not contribute to residual disease. In contrast, a therapy-induced population of mature AML-derived eosinophil-like cells persists during remission, often in extramedullary organs. Using genetic approaches we show that restricting therapy-induced leukemia maturation to the short-lived neutrophil lineage markedly reduces relapse rates and can yield cure. These results indicate that relapse can originate from therapy-resistant mature AML cells, and suggest differentiation therapy combined with targeted eradication of mature leukemia-derived lineages may improve disease outcome.


Asunto(s)
Leucemia Mieloide Aguda/metabolismo , Neoplasia Residual/metabolismo , Diferenciación Celular , Humanos , Leucemia Mieloide Aguda/genética , Neoplasia Residual/genética
9.
Blood ; 136(8): 957-973, 2020 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-32369597

RESUMEN

Modulators of epithelial-to-mesenchymal transition (EMT) have recently emerged as novel players in the field of leukemia biology. The mechanisms by which EMT modulators contribute to leukemia pathogenesis, however, remain to be elucidated. Here we show that overexpression of SNAI1, a key modulator of EMT, is a pathologically relevant event in human acute myeloid leukemia (AML) that contributes to impaired differentiation, enhanced self-renewal, and proliferation of immature myeloid cells. We demonstrate that ectopic expression of Snai1 in hematopoietic cells predisposes mice to AML development. This effect is mediated by interaction with the histone demethylase KDM1A/LSD1. Our data shed new light on the role of SNAI1 in leukemia development and identify a novel mechanism of LSD1 corruption in cancer. This is particularly pertinent given the current interest surrounding the use of LSD1 inhibitors in the treatment of multiple different malignancies, including AML.


Asunto(s)
Transformación Celular Neoplásica , Transición Epitelial-Mesenquimal/genética , Histona Demetilasas/metabolismo , Leucemia Mieloide Aguda/patología , Factores de Transcripción de la Familia Snail/fisiología , Animales , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Células HEK293 , Células HL-60 , Histona Demetilasas/genética , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Ratones , Ratones Transgénicos , Unión Proteica , Factores de Transcripción de la Familia Snail/genética , Factores de Transcripción de la Familia Snail/metabolismo
10.
J Dent ; 93: 103276, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31927031

RESUMEN

OBJECTIVES: The aim of this birth cohort study was to identify concurrent associations between early childhood caries and putative risk and protective factors. METHODS: Data were collected in seven waves over five years. The study outcome measure, d3-6mfs, was modelled in a set of sequential negative binomial regressions that introduced the variables in steps starting from health determinants most distal to the child and ending with the more proximal ones. The goodness of fit of each model at each step was tested using the quasi-likelihood under independence model criterion (QIC). A final model included all significant factors identified in the sequential modelling. Bacterial composition of the child's saliva was determined by 16S RNA gene sequencing. RESULTS: Overall, 467 children (48.6 % female) participated, of whom 419 (89.7 %) had at least one follow-up visit after baseline. Of the 419 children included in the analyses, 133 (31.7 %) had their saliva samples sequenced for microbiomic determination. Independent protectors of surface cavitation included water fluoridation, and older age of mothers. Risk for d3-6mfs was significantly higher among children whose mothers were current smokers (IRR 3.29, 95 % CI 1.09-9.88, p = 0.034), children who went to bed with a bottle (IRR 2.67, 95-6.88, p = 0.041) and whose saliva sample sequencing over time showed higher percentages of Streptococcus mutans (IRR 1.39, 95 % CI 1.11-1.74, p = 0.005). Model fit was mostly improved by child's proximal variables. Household and mother covariates did not substantially improve model fit. CONCLUSION: This analysis highlights the relevance and importance of child-proximal risk factors in childhood dental cavitation. CLINICAL SIGNIFICANCE: The study findings inform clinical decision making for the management of early childhood caries at both the individual and population level. At an individual and family level these risk factors should be incorporated into caries risk assessment tools for more precise identification of risk and evidence-informed interventions by health professionals.


Asunto(s)
Caries Dental/diagnóstico , Anciano , Australia/epidemiología , Niño , Preescolar , Estudios de Cohortes , Caries Dental/epidemiología , Femenino , Humanos , Masculino , Madres , Streptococcus mutans
11.
J Dent ; 91: 103225, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31693918

RESUMEN

OBJECTIVES: To determine if chewing gum containing casein phosphopeptide stabilised amorphous calcium phosphate (CPP-ACP) promoted an increase in the abundance of Streptococcus sanguinis and other species associated with dental health in supragingival plaque in a clinical study. MATERIALS AND METHODS: Nineteen participants were recruited for a three-leg cross-over, randomised, controlled clinical trial. Participants chewed a sugar-free gum with or without CPP-ACP six times daily for 20 min over two weeks. The study also involved no gum chewing (no gum) for the same two week period. Participants were randomly assigned to one of the test gums or no gum for each intervention period. Participants abstained from oral hygiene and had washout periods of two weeks between intervention periods. After each intervention period, supragingival plaque was collected and analysed for bacterial composition by sequencing the V4 variable region of the 16S rRNA gene. Data were analysed using a linear mixed model. RESULTS: The CPP-ACP gum intervention produced a significant (p < 0.01) increase in the proportions of S. sanguinis (112%), as well as the commensal species Rothia dentocariosa (127%), Corynebacterium durum (80%) and Streptococcus mitis (55%) when compared with the no gum intervention. All the species that were promoted by the CPP-ACP gum are known to possess one or both of the alkali-producing enzymes arginine deiminase and nitrate reductase. CONCLUSION: This clinical study demonstrated that chewing a sugar-free gum containing CPP-ACP promoted prebiosis by significantly increasing the proportion of S. sanguinis and other health-associated bacterial species in supragingival plaque. CLINICAL SIGNIFICANCE: Regular chewing of CPP-ACP sugar-free gum increases the proportions of health-associated commensal species in supragingival plaque to promote prebiosis and oral homeostasis.


Asunto(s)
Caseínas/farmacología , Goma de Mascar , Esmalte Dental/efectos de los fármacos , Placa Dental/metabolismo , Prebióticos , Estudios Cruzados , Esmalte Dental/metabolismo , Placa Dental/tratamiento farmacológico , Humanos , ARN Ribosómico 16S , Streptococcus , Streptococcus sanguis , Azúcares/efectos adversos , Remineralización Dental
12.
Br J Nurs ; 28(10): S15-S20, 2019 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-31116603

RESUMEN

Since 2005, when the first patients outside of a clinical trial were treated with trastuzumab at The Christie NHS Foundation Trust, a nurse-led service has been developed to facilitate and support a safe treatment pathway for patients. There have been significant developments in the number of patients treated, the mode of administration of the drug and patient choice regarding the location of treatment delivery. This article focuses on the change from intravenous to subcutaneous administration, considering patient experience and choice, particularly in light of the advent of biosimilar drugs, which will necessitate a return to the intravenous route. The relative costs of intravenous and subcutaneous administration are illustrated and the results of a patient survey presented, indicating a strong preference for subcutaneous trastuzumab.


Asunto(s)
Administración Intravenosa/economía , Antineoplásicos Inmunológicos/administración & dosificación , Inyecciones Subcutáneas/economía , Prioridad del Paciente/estadística & datos numéricos , Trastuzumab/administración & dosificación , Antineoplásicos Inmunológicos/economía , Encuestas de Atención de la Salud , Humanos , Pautas de la Práctica en Enfermería , Medicina Estatal/organización & administración , Trastuzumab/economía , Reino Unido
14.
Front Microbiol ; 8: 48, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28184216

RESUMEN

Porphyromonas gingivalis is a keystone pathogen of chronic periodontitis. The virulence of P. gingivalis is reported to be strain related and there are currently a number of strain typing schemes based on variation in capsular polysaccharide, the major and minor fimbriae and adhesin domains of Lys-gingipain (Kgp), amongst other surface proteins. P. gingivalis can exchange chromosomal DNA between strains by natural competence and conjugation. The aim of this study was to determine the genetic variability of P. gingivalis strains sourced from international locations over a 25-year period and to determine if variability in surface virulence factors has a phylogenetic basis. Whole genome sequencing was performed on 13 strains and comparison made to 10 previously sequenced strains. A single nucleotide polymorphism-based phylogenetic analysis demonstrated a shallow tri-lobed phylogeny. There was a high level of reticulation in the phylogenetic network, demonstrating extensive horizontal gene transfer between the strains. Two highly conserved variants of the catalytic domain of the major virulence factor the Kgp proteinase (KgpcatI and KgpcatII) were found. There were three variants of the fourth Kgp C-terminal cleaved adhesin domain. Specific variants of the cell surface proteins FimA, FimCDE, MfaI, RagAB, Tpr, and PrtT were also identified. The occurrence of all these variants in the P. gingivalis strains formed a mosaic that was not related to the SNP-based phylogeny. In conclusion P. gingivalis uses domain rearrangements and genetic exchange to generate diversity in specific surface virulence factors.

15.
Infect Immun ; 84(9): 2575-85, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27354442

RESUMEN

Periodontitis is a significant problem in companion animals, and yet little is known about the disease-associated microbiota. A major virulence factor for the human periodontal pathogen Porphyromonas gingivalis is the lysyl- and arginyl-specific proteolytic activity of the gingipains. We screened several Porphyromonas species isolated from companion animals-P. asaccharolytica, P. circumdentaria, P. endodontalis, P. levii, P. gulae, P. macacae, P. catoniae, and P. salivosa-for Lys- and Arg-specific proteolytic activity and compared the epithelial and macrophage responses and induction of alveolar bone resorption of the protease active species to that of Porphyromonas gingivalis Only P. gulae exhibited Lys-and Arg-specific proteolytic activity. The genes encoding the gingipains (RgpA/B and Kgp) were identified in the P. gulae strain ATCC 51700 and all publicly available 12 draft genomes of P. gulae strains. P. gulae ATCC 51700 induced levels of alveolar bone resorption in an animal model of periodontitis similar to those in P. gingivalis W50 and exhibited a higher capacity for autoaggregation and binding to oral epithelial cells with induction of apoptosis. Macrophages (RAW 264.7) were found to phagocytose P. gulae ATCC 51700 and the fimbriated P. gingivalis ATCC 33277 at similar levels. In response to P. gulae ATCC 51700, macrophages secreted higher levels of cytokines than those induced by P. gingivalis ATCC 33277 but lower than those induced by P. gingivalis W50, except for the interleukin-6 response. Our results indicate that P. gulae exhibits virulence characteristics similar to those of the human periodontal pathogen P. gingivalis and therefore may play a key role in the development of periodontitis in companion animals.


Asunto(s)
Periodontitis/microbiología , Porphyromonas gingivalis/inmunología , Porphyromonas gingivalis/patogenicidad , Porphyromonas/inmunología , Porphyromonas/patogenicidad , Factores de Virulencia/inmunología , Virulencia/inmunología , Pérdida de Hueso Alveolar/inmunología , Pérdida de Hueso Alveolar/microbiología , Animales , Infecciones por Bacteroidaceae/inmunología , Infecciones por Bacteroidaceae/microbiología , Línea Celular , Modelos Animales de Enfermedad , Células Epiteliales/inmunología , Células Epiteliales/microbiología , Femenino , Humanos , Interleucina-6/inmunología , Macrófagos/inmunología , Macrófagos/microbiología , Ratones , Ratones Endogámicos BALB C
16.
BMJ Support Palliat Care ; 5(4): 328-34, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26586678

RESUMEN

BACKGROUND: Within the UK, general practitioners (GPs) are required to maintain a register of palliative patients under their care. The term 'palliative' when applied to patients encompasses a highly heterogeneous population with varying meanings amongst health professionals. We explored GPs views of what defines a palliative care patient in the context of identifying clinical service needs. METHODS: Audiotaped semi-structured interviews were conducted with GPs to explore how they identify patients requiring inclusion on a palliative care register. Thematic analysis was undertaken and emerging themes identified. RESULTS: Major themes suggested GPs found it difficult to define the palliative care patient. The decision to include a patient on the palliative care register was made as a multidisciplinary team. Patients not identified as 'palliative' were often discussed unofficially if care requirements were significant or prognosis uncertain. The needs of patients with non-malignant disease were considered equal to those with cancer but the challenges of identifying such patients greater. More emphasis was placed on intensity of care required than prognosis. Inclusion on a register triggered greater professional input and was considered beneficial to patient care. CONCLUSIONS: No definition of the palliative care patient exists in working practice and without one there is a risk that some patients with palliative needs will not receive the necessary support, while others may access valuable resources before time. Achieving health policy targets which require identification of palliative patients will continue to be a challenge until a workable and reliable definition of the term 'palliative' is agreed upon.

17.
Genom Data ; 5: 167-8, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26484248

RESUMEN

Porphyromonas gingivalis is a Gram-negative anaerobic bacterium that has an absolute requirement for iron which it transports from the host as heme and/or Fe(2 +). Iron transport must be regulated to prevent toxic effects from excess metal in the cell. P. gingivalis has one ferric uptake regulator (Fur) orthologue encoded in its genome called Har, which would be expected to regulate the transport and usage of iron within this bacterium. As a gene regulator, inactivation of Har should result in changes in gene expression of several genes compared to the wild-type. This dataset (GEO accession number GSE37099) provides information on expression levels of genes in P. gingivalis in the absence of Har. Surprisingly, these genes do not relate to iron homeostasis.

18.
PLoS Pathog ; 11(9): e1005152, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26340749

RESUMEN

The type IX secretion system (T9SS) of Porphyromonas gingivalis secretes proteins possessing a conserved C-terminal domain (CTD) to the cell surface. The C-terminal signal is essential for these proteins to translocate across the outer membrane via the T9SS. On the surface the CTD of these proteins is cleaved prior to extensive glycosylation. It is believed that the modification on these CTD proteins is anionic lipopolysaccharide (A-LPS), which enables the attachment of CTD proteins to the cell surface. However, the exact site of modification and the mechanism of attachment of CTD proteins to the cell surface are unknown. In this study we characterized two wbaP (PG1964) mutants that did not synthesise A-LPS and accumulated CTD proteins in the clarified culture fluid (CCF). The CTDs of the CTD proteins in the CCF were cleaved suggesting normal secretion, however, the CTD proteins were not glycosylated. Mass spectrometric analysis of CTD proteins purified from the CCF of the wbaP mutants revealed the presence of various peptide/amino acid modifications from the growth medium at the C-terminus of the mature CTD proteins. This suggested that modification occurs at the C-terminus of T9SS substrates in the wild type P. gingivalis. This was confirmed by analysis of CTD proteins from wild type, where a 648 Da linker was identified to be attached at the C-terminus of mature CTD proteins. Importantly, treatment with proteinase K released the 648 Da linker from the CTD proteins demonstrating a peptide bond between the C-terminus and the modification. Together, this is suggestive of a mechanism similar to sortase A for the cleavage and modification/attachment of CTD proteins in P. gingivalis. PG0026 has been recognized as the CTD signal peptidase and is now proposed to be the sortase-like protein in P. gingivalis. To our knowledge, this is the first biochemical evidence suggesting a sortase-like mechanism in Gram-negative bacteria.


Asunto(s)
Aminoaciltransferasas/metabolismo , Proteínas Bacterianas/metabolismo , Sistemas de Secreción Bacterianos/metabolismo , Cisteína Endopeptidasas/metabolismo , Porphyromonas gingivalis/fisiología , Procesamiento Proteico-Postraduccional , Aminoaciltransferasas/química , Aminoaciltransferasas/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Cisteína Endopeptidasas/química , Cisteína Endopeptidasas/genética , Endopeptidasa K , Eliminación de Gen , Peso Molecular , Mutación , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Mapeo Peptídico , Porphyromonas gingivalis/enzimología , Señales de Clasificación de Proteína , Estructura Terciaria de Proteína , Proteolisis , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo
19.
PLoS One ; 9(11): e111168, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25375181

RESUMEN

Porphyromonas gingivalis is a Gram-negative pathogen associated with the biofilm-mediated disease chronic periodontitis. P. gingivalis biofilm formation is dependent on environmental heme for which P. gingivalis has an obligate requirement as it is unable to synthesize protoporphyrin IX de novo, hence P. gingivalis transports iron and heme liberated from the human host. Homeostasis of a variety of transition metal ions is often mediated in Gram-negative bacteria at the transcriptional level by members of the Ferric Uptake Regulator (Fur) superfamily. P. gingivalis has a single predicted Fur superfamily orthologue which we have designated Har (heme associated regulator). Recombinant Har formed dimers in the presence of Zn2+ and bound one hemin molecule per monomer with high affinity (Kd of 0.23 µM). The binding of hemin resulted in conformational changes of Zn(II)Har and residue 97Cys was involved in hemin binding as part of a predicted -97C-98P-99L- hemin binding motif. The expression of 35 genes was down-regulated and 9 up-regulated in a Har mutant (ECR455) relative to wild-type. Twenty six of the down-regulated genes were previously found to be up-regulated in P. gingivalis grown as a biofilm and 11 were up-regulated under hemin limitation. A truncated Zn(II)Har bound the promoter region of dnaA (PGN_0001), one of the up-regulated genes in the ECR455 mutant. This binding decreased as hemin concentration increased which was consistent with gene expression being regulated by hemin availability. ECR455 formed significantly less biofilm than the wild-type and unlike wild-type biofilm formation was independent of hemin availability. P. gingivalis possesses a hemin-binding Fur orthologue that regulates hemin-dependent biofilm formation.


Asunto(s)
Proteínas Bacterianas/metabolismo , Biopelículas/crecimiento & desarrollo , ADN Bacteriano/metabolismo , Hemina/metabolismo , Porphyromonas gingivalis/metabolismo , Proteínas Represoras/metabolismo , Proteínas Bacterianas/genética , Transporte Biológico , ADN Bacteriano/genética , Hemo/metabolismo , Porphyromonas gingivalis/genética , Proteínas Represoras/genética
20.
Br J Nurs ; 23(8): 427-32, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24763298

RESUMEN

BACKGROUND: Menopausal symptoms are commonly experienced in women treated for breast cancer. This project aimed to identify the types and prevalence of menopausal symptoms women experience and assess how well such symptoms are managed by means of a clinical audit. The authors also wanted to identify whether patients and health professionals require further education in this area to enhance patients' quality of life. METHOD: A pilot audit was initially undertaken. Twenty women were recruited from medical and clinical oncology clinics spanning a 2-week period. The main audit was conducted over a 3-week period (19 March 2012 to 6 April 2012). A total of 215 patients were surveyed from 11 consultant-led and 1 nurse-led clinic per week. A menopause rating scale (MRS) developed by Heinemann et al (2003) was used to assess the types and severity of symptoms. RESULTS: Findings from the main audit provided preliminary evidence that certain breast cancer treatments can cause either the early onset of menopausal symptoms in pre-menopausal women or the return or aggravation of menopausal symptoms in peri-menopausal or post-menopausal women. This indicated that, for many women, symptoms are inadequately managed and supported. DISCUSSION: A more detailed exploratory study of the management of menopausal symptoms is needed. Health professionals should consider discussing such symptoms when patients start treatment and assess these symptoms at follow-up appointments to identify potential interventions.


Asunto(s)
Neoplasias de la Mama/enfermería , Sofocos/enfermería , Menopausia , Auditoría de Enfermería , Enfermería Oncológica/métodos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/terapia , Femenino , Sofocos/etiología , Sofocos/terapia , Humanos , Persona de Mediana Edad , Enfermería Oncológica/normas
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