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1.
Eur Arch Otorhinolaryngol ; 278(7): 2225-2228, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32869160

RESUMEN

BACKGROUND AND AIMS: Squamous cell carcinoma (SCC) of the temporal bone is a rare malignancy accounting for only 0.2% of head and neck cancers. There is currently no clear consensus on staging or common approach to management. It is the aim of this work to provide the readers with a review of the current literature on this malignancy. METHODS: A literature review was performed identifying 16 case series with patient numbers ranging from 12 to 124. A total of 708 patients were included in this review, 67% presented with advanced disease. 578 cases were managed operatively with lateral temporal bone resection, some underwent local resection alone in early stage disease. In all studies radiation therapy was used as an adjunct to some degree. RESULTS: More than half of studies reported 100% either 2-, 3- or 5-year survival for T1 and T2 disease with no nodal involvement. Survival correlated with disease stage and in five studies SCC differentiation was found to be a significant prognostic factor. Post-operative radiotherapy was found to improve survival in only one study. CONCLUSIONS: Temporal bone SCC is a readily treatable malignancy in early stage disease, however late stage disease has a poor prognosis. Differentiation of the SCC and stage of disease at presentation appear to have the greatest influence on 5-year survival rates. Further work is required in both the identification of early stage disease and in the treatment of later T3 and T4 lesions.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Humanos , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Hueso Temporal/patología
3.
Genet Sel Evol ; 48(1): 86, 2016 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-27832740

RESUMEN

BACKGROUND: Accurate genomic analyses are predicated upon access to accurate genotype input data. The objective of this study was to quantify the reproducibility of genotype data that are generated from the same genotype platform and from different genotyping platforms. METHODS: Genotypes based on 51,121 single nucleotide polymorphisms (SNPs) for 84 animals that were each genotyped on Illumina and Affymetrix platforms and for another 25 animals that were each genotyped twice on the same Illumina platform were compared. Genotypes based on 11,323 SNPs for an additional 21 animals that were genotyped on two different Illumina platforms by two different service providers were also compared. Reproducibility of the results was measured as the correlation between allele counts and as genotype and allele concordance rates. RESULTS: A mean within-animal correlation of 0.9996 was found between allele counts in the 25 duplicate samples that were genotyped on the same Illumina platform and varied from 0.9963 to 1.0000 per animal. The mean (minimum, maximum) genotype and allele concordance rates per animal between the 25 duplicate samples were equal to 0.9996 (0.9968, 1.0000) and 0.9993 (0.9937, 1.0000), respectively. The concordance rate between the two different Illumina platforms was also near 1. A mean within-animal correlation of 0.9738 was found between genotypes that were generated on the Illumina and Affymetrix platforms and varied from 0.9505 to 0.9812 per animal. The mean (minimum, maximum) within-animal genotype and allele concordance rates between the Illumina and Affymetrix platforms were equal to 0.9711 (0.9418, 0.9798) and 0.9845 (0.9695, 0.9889), respectively. The genotype concordance rate across all genotypes increased from 0.9711 to 0.9949 when the SNPs used were restricted to those with three high-resolution genotype clusters which represented 75.2% of the called genotypes. CONCLUSIONS AND IMPLICATIONS: Our results suggest that, regardless of the genotype platform or service provider, high genotype concordance rates are achieved especially if they are restricted to high-quality extracted DNA and SNPs that result in high-quality genotypes.


Asunto(s)
Técnicas de Genotipaje/instrumentación , Análisis de Secuencia por Matrices de Oligonucleótidos/instrumentación , Polimorfismo de Nucleótido Simple , Ovinos/genética , Animales , ADN/genética , ADN/aislamiento & purificación , Genotipo , Reproducibilidad de los Resultados
4.
Paediatr Anaesth ; 25(4): 346-62, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25684039

RESUMEN

BACKGROUND: Most airway problems in children are identified in advance; however, unanticipated difficulties can arise and may result in serious complications. Training for these sporadic events can be difficult. We identified the need for a structured guideline to improve clinical decision making in the acute situation and also to provide a guide for teaching. OBJECTIVE: Guidelines for airway management in adults are widely used; however, none have been previously devised for national use in children. We aimed to develop guidelines for the management of the unanticipated difficult pediatric airway for use by anesthetists working in the nonspecialist pediatric setting. METHOD: We reviewed available guidelines used in individual hospitals. We also reviewed research into airway management in children and graded papers for the level of evidence according to agreed criteria. A Delphi panel comprising 27 independent consultant anesthetists considered the steps of the acute airway management guidelines to reach consensus on the best interventions to use and the order in which to use them. If following the literature review and Delphi feedback, there was insufficient evidence or lack of consensus, regarding inclusion of a particular point; this was reviewed by a Second Specialist Group comprising 10 pediatric anesthetists. RESULTS: Using the Delphi group's deliberations and feedback from the Second Specialist Group, we developed three guidelines for the acute airway management of children aged 1-8 years. CONCLUSIONS: This paper provides the background, available evidence base, and justification for each step in the resultant guidelines and gives a rationale for their use.


Asunto(s)
Manejo de la Vía Aérea/métodos , Complicaciones Intraoperatorias/terapia , Adolescente , Manejo de la Vía Aérea/instrumentación , Niño , Preescolar , Consenso , Técnica Delphi , Humanos , Lactante , Intubación Intratraqueal/efectos adversos , Intubación Intratraqueal/métodos , Máscaras Laríngeas/efectos adversos , Oxígeno/sangre , Posicionamiento del Paciente , Gastropatías/etiología , Traqueostomía
5.
Front Pediatr ; 11: 1264286, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37908966

RESUMEN

Introduction: Though the nature of breastfeeding is critical, scant information is available on how the action of the milk transfer from mother to infant is regulated in humans, where the points of dysfunction are, and what can be done to optimize breastfeeding outcomes. While better therapeutic strategies are needed, before they can be devised, a basic scientific understanding of the biomechanical mechanisms that regulate human milk transfer from breast to stomach must first be identified, defined, and understood. Methods: Combining systems biology and systems medicine into a conceptual framework, using engineering design principles, this work investigates the use of biosensors to characterize human milk flow from the breast to the infant's stomach to identify points of regulation. This exploratory study used this framework to characterize Maternal/Infant Lactation physioKinetics (MILK) utilizing a Biosensor ARray (BAR) as a data collection method. Results: Participants tolerated the MILKBAR well during data collection. Changes in breast turgor and temperature were significant and related to the volume of milk transferred from the breast. The total milk volume transferred was evaluated in relation to contact force, oral pressure, and jaw movement. Contact force was correlated with milk flow. Oral pressure appears to be a redundant measure and reflective of jaw movements. Discussion: Nipple and breast turgor, jaw movement, and swallowing were associated with the mass of milk transferred to the infant's stomach. More investigation is needed to better quantify the mass of milk transferred in relation to each variable and understand how each variable regulates milk transfer.

6.
J Neurol Surg B Skull Base ; 84(4): 307-319, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37405239

RESUMEN

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p = 0.036). Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

8.
Int J Health Care Qual Assur ; 25(2): 145-9, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22455179

RESUMEN

PURPOSE: The purpose of this paper is to determine head and neck cancer patients' perspective of their follow-up regime and to suggest ways in which these perspectives can be incorporated into current practice. DESIGN/METHODOLOGY/APPROACH: This is a prospective survey-based study. A total of 263 patients consecutively attending a head and neck cancer clinic completed a survey about their experience of the follow-up process in the post-treatment period between January 2009 and October 2009. FINDINGS: The paper finds that, of the patients, 67 per cent (n = 176) felt that the clinic met the goals they hoped would be achieved during their visit; 84 per cent (n = 221) felt that their follow-up visits were too frequent. In total 60 per cent (n = 159) were booked to see both an allied health professional and the attending clinician. Of these, 84 per cent (n = 134/159) felt that issues addressed at follow-up with the clinician duplicated those addressed by the allied healthcare professionals. When asked about their opinion of a less intensive follow-up system based on patients reporting problems and requesting appointments, 73 per cent (n = 192) favoured it. When asked who they would like to contact first in such a system, most patients (n = 118, 45 per cent) stated a clinical nurse specialist. PRACTICAL IMPLICATIONS: Current follow-up regimes may be too prescriptive in their approach without taking patient perspective into consideration. Patients felt that being seen intensively for the first year, then having visits tapered off over the next two years and finally being seen according to symptoms thereafter to be appropriate and felt that this represented an overall better system. ORIGINALITY/VALUE: These data suggest the need for a more patient-focused, individualised approach to follow-up in head and neck cancer.


Asunto(s)
Neoplasias de Cabeza y Cuello/psicología , Cuidados a Largo Plazo/organización & administración , Satisfacción del Paciente/estadística & datos numéricos , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/terapia , Encuestas de Atención de la Salud , Humanos , Londres , Cuidados a Largo Plazo/normas
9.
Behav Sci (Basel) ; 12(2)2022 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-35200278

RESUMEN

Increased digitisation of day-to-day activities was occurring prior to the COVID-19 pandemic. The pandemic only accelerated the virtual shift, making web accessibility an urgent issue, especially for marginalised populations. Despite decades of work to develop, refine, and implement web accessibility standards, people with cognitive disabilities regularly experience many barriers to web accessibility. To inform ongoing work to improve web accessibility for people with cognitive disabilities, a systematic review was conducted. The main question guiding this review is: what are the state-of-the-art of interventions that support web accessibility for citizens, 9 years of age and up, living with cognitive impairment? A set of 50 search strings were entered into three academic databases: SCOPUS, ProQuest, and Web of Science. Systematic screening procedures narrowed the search returns to a total of 45 included papers. A data analysis revealed themes associated with the lived experiences of people with cognitive disabilities, tools for improving web accessibility, and methodological best practices for involving people with cognitive disabilities in research. These findings have immediate implications for ongoing research and the development of meaningful solutions to the problem of web accessibility for people with cognitive disabilities.

10.
Eur J Cancer ; 162: 221-236, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34980502

RESUMEN

INTRODUCTION: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy. METHODS: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763). RESULTS: Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD). CONCLUSIONS: This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.


Asunto(s)
Estesioneuroblastoma Olfatorio , Neuroblastoma , Neoplasias Nasales , Estesioneuroblastoma Olfatorio/patología , Estesioneuroblastoma Olfatorio/terapia , Humanos , Cavidad Nasal/metabolismo , Cavidad Nasal/patología , Neuroblastoma/patología , Neoplasias Nasales/radioterapia , Tomografía de Emisión de Positrones , Radioisótopos , Cintigrafía , Receptores de Somatostatina/metabolismo , Estudios Retrospectivos
11.
J Surg Case Rep ; 2021(12): rjab530, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34909167

RESUMEN

Eagle's syndrome refers to a group of characteristic symptoms affecting the oropharynx and neck that are caused by regional compression of structures due to a calcified stylohyoid ligament or an elongated styloid process. Of its two types, the former type is more common than the latter, but carotid artery dissection as a result of an elongated styloid is exceptionally rare. Following an extensive literature review, we present a case of carotid artery dissection causing multiple strokes secondary to direct compression from an elongated styloid process. Managed surgically through excision of the elongated styloid and post-operative rehabilitation, the patient recovered well and was discharged on anti-thrombotic medication, preventing further potentially detrimental attacks.

12.
Lancet Neurol ; 20(9): 709-720, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34418398

RESUMEN

BACKGROUND: Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis. METHODS: This randomised, double-blind, placebo-controlled, parallel-group, phase 2a trial (CCMR One) recruited patients with relapsing-remitting multiple sclerosis from two centres in the UK. Eligible participants were aged 18-50 years and had been receiving dimethyl fumarate for at least 6 months. Via a web-based system run by an independent statistician, participants were randomly assigned (1:1), by probability-weighted minimisation using four binary factors, to receive 300 mg/m2 of body surface area per day of oral bexarotene or oral placebo for 6 months. Participants, investigators, and outcome assessors were masked to treatment allocation. MRI scans were done at baseline and at 6 months. The primary safety outcome was the number of adverse events and withdrawals attributable to bexarotene. The primary efficacy outcome was the patient-level change in mean lesional magnetisation transfer ratio between baseline and month 6 for lesions that had a baseline magnetisation transfer ratio less than the within-patient median. We analysed the primary safety outcome in the safety population, which comprised participants who received at least one dose of their allocated treatment. We analysed the primary efficacy outcome in the intention-to-treat population, which comprised all patients who completed the study. This study is registered in the ISRCTN Registry, 14265371, and has been completed. FINDINGS: Between Jan 17, 2017, and May 17, 2019, 52 participants were randomly assigned to receive either bexarotene (n=26) or placebo (n=26). Participants who received bexarotene had a higher mean number of adverse events (6·12 [SD 3·09]; 159 events in total) than did participants who received placebo (1·63 [SD 1·50]; 39 events in total). All bexarotene-treated participants had at least one adverse event, which included central hypothyroidism (n=26 vs none on placebo), hypertriglyceridaemia (n=24 vs none on placebo), rash (n=13 vs one on placebo), and neutropenia (n=10 vs none on placebo). Five (19%) participants on bexarotene and two (8%) on placebo discontinued the study drug due to adverse events. One episode of cholecystitis in a placebo-treated participant was the only serious adverse event. The change in mean lesional magnetisation transfer ratio was not different between the bexarotene group (0·25 percentage units [pu; SD 0·98]) and the placebo group (0·09 pu [0·84]; adjusted bexarotene-placebo difference 0·16 pu, 95% CI -0·39 to 0·71; p=0·55). INTERPRETATION: We do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. However, statistically significant effects were seen in some exploratory MRI and electrophysiological analyses, suggesting that other retinoid X receptor agonists might have small biological effects that could be investigated in further studies. FUNDING: Multiple Sclerosis Society of the United Kingdom.


Asunto(s)
Bexaroteno/farmacología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud , Remielinización/efectos de los fármacos , Receptores X Retinoide/agonistas , Adulto , Bexaroteno/administración & dosificación , Bexaroteno/efectos adversos , Método Doble Ciego , Potenciales Evocados Visuales/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/fisiopatología
14.
Cochrane Database Syst Rev ; (2): CD004708, 2009 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-19370605

RESUMEN

BACKGROUND: Psychosexual dysfunction (sexual difficulties not directly due to physical factors) is known to be a common complication of treatment for gynaecological cancer. It has a considerable impact on quality of life (QoL) for the increasing number of women who are survivors of gynaecological cancer. OBJECTIVES: To determine the effectiveness of interventions for psychosexual dysfunction in women who have been treated for gynaecological malignancy (cancer of uterine cervix, uterine corpus, ovary, vulva). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, up to October 2008), MEDLINE (1950 to October 2008), EMBASE (1982 to October 2008), CINAHL (1980 to October 2008) and PsycINFO (1806 to October 2008). We hand searched reference lists from eligible trials. SELECTION CRITERIA: We selected all randomized controlled trials (RCTs) of a medical or psychological intervention to prevent or treat psychosexual dysfunction in adult women previously treated for gynaecological cancer. DATA COLLECTION AND ANALYSIS: We selected five studies for inclusion in this review and analysed any outcome data relating to resumption of sexual intercourse, DSM-IV diagnoses or validated scales of sexual functioning. Sensitivity analysis was performed where possible. MAIN RESULTS: The review included data from 5 studies, comprising a total of 413 patients, examining 5 different interventions. One trial suggested a short-term benefit for the use of vaginal Dienoestrol in women after pelvic radiotherapy (NNT = 4). Another trial suggested a short-term benefit for one regime of low dose-rate brachytherapy over another but this modality is not in widespread use. Studies of a Clinical Nurse Specialist intervention, Psychoeducational Group Therapy and a Couple-Coping intervention, did not show any significant benefit. All the studies were of poor methodological quality. AUTHORS' CONCLUSIONS: There is no convincing evidence to support the use of any interventions for psychosexual dysfunction in women treated for gynaecological cancer. There is a need for more studies of high methodological quality.


Asunto(s)
Neoplasias de los Genitales Femeninos/terapia , Disfunciones Sexuales Psicológicas/terapia , Braquiterapia , Estrógenos/uso terapéutico , Femenino , Neoplasias de los Genitales Femeninos/psicología , Humanos , Educación del Paciente como Asunto , Psicoterapia/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Disfunciones Sexuales Psicológicas/etiología
16.
Front Genet ; 9: 84, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29599798

RESUMEN

A major use of genetic data is parentage verification and identification as inaccurate pedigrees negatively affect genetic gain. Since 2012 the international standard for single nucleotide polymorphism (SNP) verification in Bos taurus cattle has been the ISAG SNP panels. While these ISAG panels provide an increased level of parentage accuracy over microsatellite markers (MS), they can validate the wrong parent at ≤1% misconcordance rate levels, indicating that more SNP are needed if a more accurate pedigree is required. With rapidly increasing numbers of cattle being genotyped in Ireland that represent 61 B. taurus breeds from a wide range of farm types: beef/dairy, AI/pedigree/commercial, purebred/crossbred, and large to small herd size the Irish Cattle Breeding Federation (ICBF) analyzed different SNP densities to determine that at a minimum ≥500 SNP are needed to consistently predict only one set of parents at a ≤1% misconcordance rate. For parentage validation and prediction ICBF uses 800 SNP (ICBF800) selected based on SNP clustering quality, ISAG200 inclusion, call rate (CR), and minor allele frequency (MAF) in the Irish cattle population. Large datasets require sample and SNP quality control (QC). Most publications only deal with SNP QC via CR, MAF, parent-progeny conflicts, and Hardy-Weinberg deviation, but not sample QC. We report here parentage, SNP QC, and a genomic sample QC pipelines to deal with the unique challenges of >1 million genotypes from a national herd such as SNP genotype errors from mis-tagging of animals, lab errors, farm errors, and multiple other issues that can arise. We divide the pipeline into two parts: a Genotype QC and an Animal QC pipeline. The Genotype QC identifies samples with low call rate, missing or mixed genotype classes (no BB genotype or ABTG alleles present), and low genotype frequencies. The Animal QC handles situations where the genotype might not belong to the listed individual by identifying: >1 non-matching genotypes per animal, SNP duplicates, sex and breed prediction mismatches, parentage and progeny validation results, and other situations. The Animal QC pipeline make use of ICBF800 SNP set where appropriate to identify errors in a computationally efficient yet still highly accurate method.

17.
Sci Rep ; 8(1): 14550, 2018 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-30266917

RESUMEN

Left ventricular myocardial fibrosis in patients with aortic stenosis (AS) confers worse prognosis. Plasma osteoprotegerin (OPG), a cytokine from the TNF receptor family, correlates with the degree of valve calcification in AS, reflecting the activity of the tissue RANKL/RANK/OPG (receptor activator of nuclear factor κΒ ligand/RANK/osteoprotegerin) axis, and is associated with poorer outcomes in AS. Its association with myocardial fibrosis is unknown. We hypothesised that OPG levels would reflect the extent of myocardial fibrosis in AS. We included 110 consecutive patients with AS who had undergone late-gadolinium contrast enhanced cardiovascular magnetic resonance (LGE-CMR). Patients were characterised according to pattern of fibrosis (no fibrosis, midwall fibrosis, or chronic myocardial infarction fibrosis). Serum OPG was measured with ELISA and compared between groups defined by valve stenosis severity. Some 36 patients had no fibrosis, 38 had midwall fibrosis, and 36 had chronic infarction. Patients with midwall fibrosis did not have higher levels of OPG compared to those without fibrosis (6.78 vs. 5.25 pmol/L, p = 0.12). There was no difference between those with midwall or chronic myocardial infarction fibrosis (6.78 vs. 6.97 pmol/L, p = 0.27). However, OPG levels in patients with chronic myocardial infarction fibrosis were significantly higher than those without fibrosis (p = 0.005).


Asunto(s)
Estenosis de la Válvula Aórtica/sangre , Infarto del Miocardio/sangre , Miocardio/patología , Osteoprotegerina/sangre , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/patología , Femenino , Fibrosis , Ventrículos Cardíacos/patología , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/patología
18.
Oral Oncol ; 83: 32-37, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30098776

RESUMEN

OBJECTIVES: p16INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven. MATERIALS AND METHODS: We integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project. Samples were queried for alterations in CDKN2A, and other pathway genes to investigate possible drivers of p16 expression. RESULTS: While p16 levels as measured by RPPA were significantly different by HPV status, there were multiple HPV (-) samples with similar expression levels of p16 to HPV (+) samples, particularly at non-oropharyngeal subsites. In many cases, p16 overexpression in HPV (-) tumors could not be explained by mutation or amplification of CDKN2A or by RB1 mutation. Instead, we observed enrichment for inactivating mutations in the histone H3 lysine 36 methyltransferase, NSD1 in HPV (-)/p16-high tumors. CONCLUSIONS: RPPA data suggest high p16 protein expression in many HPV (-) non-oropharyngeal HNSCCs, limiting its potential utility as an HPV biomarker outside of the oropharynx. HPV-independent overexpression of wild-type p16 in non-oropharyngeal HNSCC may be linked to global deregulation of chromatin state by inactivating mutations in NSD1.


Asunto(s)
Alphapapillomavirus/aislamiento & purificación , Biomarcadores de Tumor/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Alphapapillomavirus/metabolismo , Estudios de Cohortes , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Fase G1 , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/virología , Humanos , Mutación , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/virología , Fase S , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Regulación hacia Arriba
19.
Sci Rep ; 7(1): 12287, 2017 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-28947819

RESUMEN

Bovine fertility remains a critical issue underpinning the sustainability of the agricultural sector. Phenotypic records collected on >7,000 bulls used in artificial insemination (AI) were used to identify 160 reliable and divergently fertile bulls for a dual strategy of targeted sequencing (TS) of fertility-related ß-defensin genes and whole exome sequencing (WES). A haplotype spanning multiple ß-defensin genes and containing 94 SNPs was significantly associated with fertility and functional analysis confirmed that sperm from bulls possessing the haplotype showed significantly enhanced binding to oviductal epithelium. WES of all exons in the genome in 24 bulls of high and low fertility identified 484 additional SNPs significantly associated with fertility. After validation, the most significantly associated SNP was located in the FOXJ3 gene, a transcription factor which regulates sperm function in mice. This study represents the first comprehensive characterisation of genetic variation in bovine ß-defensin genes and functional analysis supports a role for ß-defensins in regulating bull sperm function. This first application of WES in AI bulls with divergent fertility phenotypes has identified a novel role for the transcription factor FOXJ3 in the regulation of bull fertility. Validated genetic variants associated with bull fertility could prove useful for improving reproductive outcomes in cattle.


Asunto(s)
Cruzamiento/métodos , Secuenciación del Exoma/métodos , Fertilidad/genética , Inseminación Artificial/veterinaria , beta-Defensinas/genética , Crianza de Animales Domésticos/métodos , Animales , Biomarcadores , Bovinos , Femenino , Factores de Transcripción Forkhead/genética , Inseminación Artificial/métodos , Masculino , Polimorfismo de Nucleótido Simple , Espermatozoides/fisiología
20.
PLoS One ; 12(7): e0181077, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28704465

RESUMEN

BACKGROUND: Aortic stenosis is the most common age-related valvular pathology. Patients with aortic stenosis and myocardial fibrosis have worse outcome but the underlying mechanism is unclear. Lipoprotein(a) is associated with adverse cardiovascular risk and is elevated in patients with aortic stenosis. Although mechanistic pathways could link Lipoprotein(a) with myocardial fibrosis, whether the two are related has not been previously explored. In this study, we investigated whether elevated Lipoprotein(a) was associated with the presence of myocardial replacement fibrosis. METHODS: A total of 110 patients with mild, moderate and severe aortic stenosis were assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance to identify fibrosis. Mann Whitney U tests were used to assess for evidence of an association between Lp(a) and the presence or absence of myocardial fibrosis and aortic stenosis severity and compared to controls. Univariable and multivariable linear regression analysis were undertaken to identify possible predictors of Lp(a). RESULTS: Thirty-six patients (32.7%) had no LGE enhancement, 38 (34.6%) had midwall enhancement suggestive of midwall fibrosis and 36 (32.7%) patients had subendocardial myocardial fibrosis, typical of infarction. The aortic stenosis patients had higher Lp(a) values than controls, however, there was no significant difference between the Lp(a) level in mild, moderate or severe aortic stenosis. No association was observed between midwall or infarction pattern fibrosis and Lipoprotein(a), in the mild/moderate stenosis (p = 0.91) or severe stenosis patients (p = 0.42). CONCLUSION: There is no evidence to suggest that higher Lipoprotein(a) leads to increased myocardial midwall or infarction pattern fibrosis in patients with aortic stenosis.


Asunto(s)
Estenosis de la Válvula Aórtica/diagnóstico por imagen , Lipoproteína(a)/metabolismo , Imagen por Resonancia Cinemagnética/métodos , Miocardio/patología , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/metabolismo , Femenino , Gadolinio DTPA/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
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