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1.
Echo Res Pract ; 11(1): 7, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38424646

RESUMEN

INTRODUCTION: Athletic training can result in electrical and structural changes of the right ventricle that may mimic phenotypical features of arrhythmogenic right ventricular cardiomyopathy (ARVC), such as T-wave inversion and right heart dilatation. An erroneous interpretation may have consequences ranging from false reassurance in an athlete vulnerable to cardiac arrhythmias, to unnecessary sports restriction in a healthy individual. The primary aim of this study was to define normal RV dimension reference ranges for academy adolescent footballers of different ethnicities. Secondary aims include analysis of potential overlap between this adolescent group with ARVC criteria and comparison with normal adult ranges. RESULTS: Electrocardiographic (ECG) and echocardiographic data of 1087 academy male footballers aged between 13 and 18 years old (mean age 16.0 ± 0.5 years), attending mandatory cardiac screening were analysed. Ethnicity was categorised as white (n = 826), black (African/Caribbean; n = 166) and mixed-race (one parent white and one parent black; n = 95). Arrhythmogenic right ventricular cardiomyopathy major criteria for T-wave inversion was seen in 3.3% of the cohort. This was more prevalent in black footballers (12%) when compared to mixed race footballers (6.3%) or white footballers (1%), P < 0.05. Up to 59% of the cohort exceeded adult reference ranges for some of the right ventricular parameters, although values were similar to those seen in adult footballers. There were no differences in right ventricular dimensions between ethnicities. In particular, the right ventricular outflow tract diameter would fulfil major criteria for ARVC dimension in 12% of footballers. Overall, 0.2% of the cohort would fulfil diagnosis for 'definite' arrhythmogenic right ventricular cardiomyopathy and 2.2% would fulfil diagnosis for 'borderline' arrhythmogenic right ventricular cardiomyopathy for RV dimensions and ECG changes. This was seen more frequently in black footballers (9.9%) than mixed race footballers (3.9%) or white footballer (0.6%), P < 0.05. Among athletes meeting definite or borderline arrhythmogenic right ventricular cardiomyopathy criteria, no cardiomyopathy was identified after comprehensive clinical assessment, including with cardiac magnetic resonance imaging, exercise testing, ambulatory electrocardiograms and familial evaluation. CONCLUSION: Right heart sizes in excess of accepted adult ranges occurred in as many as one in two adolescent footballers. Structural adaptations in conjunction with anterior T-wave inversion may raise concern for ARVC, highlighting the need for evaluation in expert settings.

2.
Clin Radiol ; 78(12): e941-e949, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37788968

RESUMEN

AIM: To investigate how magnetic resonance imaging (MRI) examinations are protocolled in tertiary paediatric neuroradiology centres around the UK for some of the more common presentations encountered in paediatric neuroradiology, and to identify any variations of note. MATERIALS AND METHODS: All 19 UK tertiary paediatric neuroradiology centres registered with the British Society of Neuroradiologists-Paediatric Group were contacted and asked if they could provide a copy of their standard MRI protocols. Twelve responded (63%) and 10 of the more common presentations were selected and the standard acquired sequences obtained at each participating centre were compared. Where available the collated protocols were also compared against current published guidance. RESULTS: The basic sequences carried out by centres around the UK are similar; however, there are lots of variations overall. The only standardised protocol currently being implemented nationally in paediatric imaging is that for brain tumours. Otherwise, chosen protocols are generally dependent on the preferences and technical capabilities of individual centres. Suggested published protocols also exist for non-accidental injury (NAI), multiple sclerosis, epilepsy, and head and neck imaging. CONCLUSIONS: The differences in MRI protocolling depend in part on technical capabilities and in part on the experience and preferences of the paediatric neuroradiologists at each centre. For most presentations, there is no consensus as to what constitutes the perfect protocol. The present results will be useful for specialist centres who may wish to review their current protocols, and for more generalist centres to use as a reference to guide their MRI protocolling.


Asunto(s)
Neoplasias Encefálicas , Hospitales Pediátricos , Niño , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Centros de Atención Terciaria , Reino Unido
3.
Nat Commun ; 13(1): 6975, 2022 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-36379931

RESUMEN

Histone methylation is an important post-translational modification that plays a crucial role in regulating cellular functions, and its dysregulation is implicated in cancer and developmental defects. Therefore, systematic characterization of histone methylation is necessary to elucidate complex biological processes, identify biomarkers, and ultimately, enable drug discovery. Studying histone methylation relies on the use of antibodies, but these suffer from lot-to-lot variation, are costly, and cannot be used in live cells. Chromatin-modification reader domains are potential affinity reagents for methylated histones, but their application is limited by their modest affinities. We used phage display to identify key residues that greatly enhance the affinities of Cbx chromodomains for methylated histone marks and develop a general strategy for enhancing the affinity of chromodomains of the human Cbx protein family. Our strategy allows us to develop powerful probes for genome-wide binding analysis and live-cell imaging. Furthermore, we use optimized chromodomains to develop extremely potent CRISPR-based repressors for tailored gene silencing. Our results highlight the power of engineered chromodomains for analyzing protein interaction networks involving chromatin and represent a modular platform for efficient gene silencing.


Asunto(s)
Histonas , Lisina , Humanos , Metilación , Histonas/metabolismo , Lisina/metabolismo , Procesamiento Proteico-Postraduccional , Cromatina/genética
5.
J Hosp Infect ; 126: 93-102, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35562072

RESUMEN

BACKGROUND: Healthcare-associated infections (HAIs) are not present on admission but are contracted while a patient is undergoing hospital treatment. While the prevalence of HAIs, and their causes and treatments have been researched in various contexts to date, patients' perspectives of contracting and living with the consequences of an HAI remain under-researched. OBJECTIVE: To explore patients' experiences of having an HAI. METHODS: A qualitative phenomenological study that drew on data from semi-structured interviews was conducted in order to explore the lived experiences of patients who had recently contracted an HAI while in hospital. Participants were recruited from two Australian hospitals in 2019 and 2021. Telephone interviews were conducted with 10 participants by two research team members, and transcripts from these interviews were analysed qualitatively using a thematic coding process to identify the patients' perspectives of contracting an HAI. RESULTS: The participants had a range of different HAIs. The participants described how the experience of having an HAI can be very isolating and distressing from the patient's perspective, with life-long implications. This contributes to understanding of the way in which patients are impacted emotionally and mentally as a result of contracting an HAI. CONCLUSION: There is a need for improved, person-centred communication about the source, treatment and prognosis of HAIs. The findings from this study indicate the importance of considering patients' voices in their own health care.


Asunto(s)
Infección Hospitalaria , Australia/epidemiología , Comunicación , Infección Hospitalaria/epidemiología , Atención a la Salud , Hospitales , Humanos , Investigación Cualitativa
6.
Toxicol In Vitro ; 69: 104997, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32896591

RESUMEN

Electronic nicotine delivery systems (ENDS) are a rapidly growing global market advertised as a safer alternative to combustible cigarettes. However, comprehensive investigations of END aerosol physicochemical and toxicological properties have not been fully explored across brands to assess relative safety. In this study, we evaluated aerosols collected from three ENDS - Juul Fruit Medley (5% nicotine), Logic Power (2.4% nicotine), and Mistic (1.8% nicotine). ENDS aerosols were generated using standard machine puffing regimen and collected with a novel fluoropolymer condensation trap. Triple quadrupole-inductively coupled plasma-mass determined the presence of heavy metals in collected aerosols. The toxicological effects of ENDS aerosols on normal human bronchial epithelial cells (NHBE) were investigated using cellular viability, reactive oxygen species, oxidative stress assays, along with DNA damage assessments using the CometChip©. Results indicated the total metal concentrations within collected ENDS aerosols were higher for Mistic and Logic compared to Juul. Logic Power aerosols elicited higher reactive oxygen species levels than Mistic and Juul in NHBE after 24-h exposure. Similar dose-dependent reductions of cellular viability and total glutathione were found for each exposure. However, Logic and Juul aerosols caused greater single stranded DNA damage compared to Mistic. Our study indicates that regardless of brand, ENDS aerosols are toxic to upper airway epithelial cells and may pose a potential respiratory hazard to occasional and frequent users.


Asunto(s)
Bronquios/citología , Cigarrillo Electrónico a Vapor/toxicidad , Sistemas Electrónicos de Liberación de Nicotina , Células Epiteliales/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Daño del ADN , Cigarrillo Electrónico a Vapor/análisis , Células Epiteliales/metabolismo , Humanos , Metales Pesados/análisis , Metales Pesados/toxicidad , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
7.
Inhal Toxicol ; 31(9-10): 357-367, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31779509

RESUMEN

Objective: The aerosolization of common nano-enabled consumer products such as cosmetics has significantly increased engineered nanoparticle inhalation risks. While several studies have investigated the impact of cosmetic dermal exposures, inhalation hazards of aerosolized cosmetics are much less known but could pose considerable harm to users due to potential co-exposure of nanoparticles and other product components.Materials and Methods: In this study, we developed a fully automated aerosol generation system to examine the aerosol properties of four aerosolized nano-enabled cosmetics using real-time monitoring and sampling instrumentation. Physicochemical characterization of aerosols was conducted using scanning electron microscopy coupled with energy dispersive x-ray spectroscopy (SEM-EDX). Characterization and calibration of animal exposure pods coupled to the system were also performed by measuring and comparing particle concentrations between pods.Results and Discussion: Results show peak emissions are shade dependent and varied between 12,000-22,000 particles/cm3 with modal diameters ranging from 36 nm-1.3 µm. SEM-EDX analysis determined that the original products and collected aerosols have similar morphological features consisting of micron-sized particles decorated with nanoparticles and crystalline structures. Mean total particle concentration in pods at 5 and 10 mg/m3 target levels were 2.22E + 05 #/cm3 and 4.33E + 05 #/cm3, respectively, with <10% variability between pods.Conclusions: The fully automated exposure platform described herein provides reproducible aerosol generation, conforms to recommended guidelines on chemical testing, and therefore is suitable for future in vivo toxicological assessments to examine potential respiratory hazards of aerosolized nano-enabled consumer products.


Asunto(s)
Aerosoles/química , Cosméticos/química , Exposición por Inhalación , Nanoestructuras/química , Pruebas de Toxicidad/instrumentación , Pruebas de Toxicidad/métodos , Humanos
8.
Leukemia ; 32(4): 882-889, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29089643

RESUMEN

Despite advances in our understanding of the molecular basis for particular subtypes of acute myeloid leukemia (AML), effective therapy remains a challenge for many individuals suffering from this disease. A significant proportion of both pediatric and adult AML patients cannot be cured and since the upper limits of chemotherapy intensification have been reached, there is an urgent need for novel therapeutic approaches. The transcription factor c-MYB has been shown to play a central role in the development and progression of AML driven by several different oncogenes, including mixed lineage leukemia (MLL)-fusion genes. Here, we have used a c-MYB gene expression signature from MLL-rearranged AML to probe the Connectivity Map database and identified mebendazole as a c-MYB targeting drug. Mebendazole induces c-MYB degradation via the proteasome by interfering with the heat shock protein 70 (HSP70) chaperone system. Transient exposure to mebendazole is sufficient to inhibit colony formation by AML cells, but not normal cord blood-derived cells. Furthermore, mebendazole is effective at impairing AML progression in vivo in mouse xenotransplantation experiments. In the context of widespread human use of mebendazole, our data indicate that mebendazole-induced c-MYB degradation represents a safe and novel therapeutic approach for AML.


Asunto(s)
Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Mebendazol/farmacología , Proteolisis/efectos de los fármacos , Proteínas Proto-Oncogénicas c-myb/metabolismo , Animales , Niño , Femenino , Humanos , Lactante , Masculino , Ratones , Oncogenes/efectos de los fármacos , Complejo de la Endopetidasa Proteasomal/metabolismo
9.
J Anim Sci ; 95(10): 4260-4273, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29108061

RESUMEN

Genetic correlations between 29 wool production and quality traits and 25 meat quality and nutritional value traits were estimated for Merino sheep from an Information Nucleus (IN). Genetic correlations among the meat quality and nutritional value traits are also reported. The IN comprised 8 flocks linked genetically and managed across a range of sheep production environments in Australia. The wool traits included over 5,000 yearling and 3,700 adult records for fleece weight, fiber diameter, staple length, staple strength, fiber diameter variation, scoured wool color, and visual scores for breech and body wrinkle. The meat quality traits were measured on samples from the and included over 1,200 records from progeny of over 170 sires for intramuscular fat (IMF), shear force of meat aged for 5 d (SF5), 24 h postmortem pH (pHLL; also measured in the , pHST), fresh and retail meat color and meat nutritional value traits such as iron and zinc levels, and long-chain omega-3 and omega-6 polyunsaturated fatty acid levels. Estimated heritabilities for IMF, SF5, pHLL, pHST, retail meat color lightness (), myoglobin, iron, zinc and across the range of long-chain fatty acids were 0.58 ± 0.11, 0.10 ± 0.09, 0.15 ± 0.07, 0.20 ± 0.10, 0.59 ± 0.15, 0.31 ± 0.09, 0.20 ± 0.09, 0.11 ± 0.09, and range of 0.00 (eicosapentaenoic, docosapentaenoic, and arachidonic acids) to 0.14 ± 0.07 (linoleic acid), respectively. The genetic correlations between the wool production and meat quality traits were low to negligible and indicate that wool breeding programs will have little or no effect on meat quality. There were moderately favorable genetic correlations between important yearling wool production traits and the omega-3 fatty acids that were reduced for corresponding adult wool production traits, but these correlations are unlikely to be important in wool/meat breeding programs because they have high SE, and the omega-3 traits have little or no genetic variance. Significant genetic correlations among the meat quality traits included IMF with SF5 (-0.76 ± 0.24), fresh meat color * (0.50 ± 0.18), and zinc (0.41 ± 0.19). Selection to increase IMF will improve meat tenderness and color which may address some of the issues with Merino meat quality. These estimated parameters allow Merino breeders to combine wool and meat objectives without compromising meat quality.


Asunto(s)
Carne/normas , Ovinos/genética , Lana/normas , Animales , Australia , Peso Corporal/genética , Cruzamiento , Color , Ácidos Grasos/análisis , Femenino , Hierro/análisis , Masculino , Valor Nutritivo/genética , Fenotipo , Ovinos/fisiología , Zinc/análisis
11.
J Anim Sci ; 95(6): 2385-2398, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28727038

RESUMEN

Genetic correlations between 29 wool production and quality traits and 14 whole carcass measures and carcass component traits were estimated from the Information Nucleus of 8 flocks managed across a range of Australian sheep production environments and genetically linked. Wool data were from over 5,000 Merino progeny born over 5 yr, whereas carcass data were from over 1,200 wether progeny of over 176 sires, slaughtered at about 21 kg carcass weight, on average. Wool traits included yearling and adult records for wool weight, fiber diameter, fiber diameter variation, staple strength, scoured color, and visual scores for breech and body wrinkle. Whole carcass measures included HCW, dressing percentage (DP), and various measures of fat depth and eye muscle dimensions. Carcass components were obtained by dissection, and lean meat yield (LMY) was predicted. Heritability estimates for whole carcass measures ranged from 0.12 ± 0.08 to 0.35 ± 0.10 and ranged from 0.17 ± 0.10 to 0.46 ± 0.10 for carcass dissection traits, with no evidence of important genotype × environment interactions. Genetic correlations indicated that selection for increased clean wool weight will result in reduced carcass fat (-0.17 to -0.34) and DP (-0.48 ± 0.15), with little effect on carcass muscle. Selection for lower fiber diameter will reduce HCW (-0.48 ± 0.15) as well as carcass fat (0.14 to 0.27) and muscle (0.21 to 0.50). There were high genetic correlations between live animal measures of fat and muscle depth and the carcass traits (generally greater than 0.5 in size). Selection to increase HCW (and DP) will result in sheep with fewer wrinkles on the body (-0.57 ± 0.10) and barer breeches (-0.74 ± 0.12, favorable), with minor deterioration in scoured wool color (reduced brightness and increased yellowness). Selection for reduced fat will also result in sheep with fewer body wrinkles (-0.42 to -0.79). Increasing LMY in Merinos through selection would result in a large reduction in carcass fat and DP (-0.66 to -0.84), with a smaller increase in carcass muscle and some increase in wool weight and wrinkles. Although no major antagonisms are apparent between the wool and carcass traits, developing selection indexes for dual-purpose wool and meat breeding objectives will require accurate estimates of genetic parameters to ensure that unfavorable relationships are suitably considered. The findings will aid development of dual-purpose wool and meat breeding objectives.


Asunto(s)
Ovinos/genética , Lana/crecimiento & desarrollo , Animales , Australia , Peso Corporal , Cruzamiento , Color , Femenino , Genotipo , Masculino , Fenotipo , Carne Roja , Ovinos/crecimiento & desarrollo
12.
Int J Immunogenet ; 43(6): 404-412, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27870355

RESUMEN

The EBMT risk score is an established tool successfully used in the prognosis of survival post-HSCT and is applicable for a range of haematological disorders. One of its main advantages is that score generation involves summation of clinical parameters that are available pretransplant. However, the EBMT risk score is recognized as not being optimal. Previous analyses, involving patients with various diagnoses, have shown that non-HLA gene polymorphisms influence outcome after allogeneic HSCT. This study is novel as it focuses only on patients having acute leukaemia (N = 458) and attempts to demonstrate how non-HLA gene polymorphisms can be added to the EBMT risk score in a Cox regression model to improve prognostic ability for overall survival. The results of the study found that three genetic factors improved EBMT risk score. The presence of MAL (rs8177374) allele T in the patient, absence of glucocorticoid receptor haplotype (consisting of rs6198, rs33389 and rs33388) ACT in the patient and absence of heat-shock protein 70-hom (+2437) (rs2227956) allele C in the patient were associated with decreased survival time. When compared to the EBMT risk score, the scores combining EBMT risk score with the genetic factors had an improved correlation with clinical outcome and better separation of risk groups. A bootstrapping technique, involving repeated testing of a model using multiple validation sets, also revealed that the newly proposed model had improved predictive value when compared to the EBMT risk score alone. Results support the view that non-HLA polymorphisms could be useful for pretransplant clinical assessment and provide evidence that polymorphisms in the recipient genotype may influence incoming donor cells, suppressing the initiation of the graft versus leukaemia effect and reducing survival.


Asunto(s)
Enfermedad Injerto contra Huésped/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia/genética , Leucemia/inmunología , Adulto , Femenino , Genómica , Genotipo , Proteínas HSP70 de Choque Térmico/genética , Haplotipos/genética , Prueba de Histocompatibilidad , Humanos , Leucemia/patología , Leucemia/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Trasplante Homólogo/efectos adversos
14.
Hum Reprod ; 31(3): 582-90, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26762315

RESUMEN

STUDY QUESTION: Does age of the sperm donor have an effect on reproductive outcomes (live birth rate and miscarriage occurrence) of donor insemination or in vitro fertilization treatment using donated sperm? SUMMARY ANSWER: Live birth and miscarriage occurrence in assisted reproduction treatment using donor sperms was not found to be affected by the age of sperm donors up to 45 years old. WHAT IS ALREADY KNOWN: Literature on the effect of sperm donor age on outcome of medically assisted reproduction is scarce. Most researchers agree that semen parameters deteriorate with increasing paternal age. However, there is no substantial evidence to suggest that this deterioration adversely affects the reproductive outcomes in couples undergoing medically assisted reproduction. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study analysed 46 078 first donor insemination treatments and fresh in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using donated sperm from 1991 to 2012. PARTICIPANTS/ DURATION/METHODS: The first fresh donor insemination and IVF/ICSI treatment cycles (46 078 treatment cycles) using donated sperm from the long-term anonymized data registry from 1991 to 2012 of the HFEA, the UK regulator, were analysed by the binary logistic modelling technique for association between sperm donor age and reproductive outcomes (live birth occurrence and miscarriage occurrence). The statistical package SPSS (version 21) was used for analysis and results were considered to be statistically significant if the P-value was <0.05. MAIN RESULTS AND THE ROLE OF CHANCE: Of 46 078 women, 84.6% (N = 38 974) underwent donor insemination treatment and the remainder, 15.4% (N = 7104), had IVF/ICSI treatment with donor sperm. The live birth occurrence decreased with increasing female age in both treatment groups; In the donor insemination treatment group, it was 11.1% in 18-34 year old women, 8.3% in 35-37 year old women and 4.7% in 38-50 year old women. The corresponding figures in the IVF/ICSI treatment group were 28.9, 22.0 and 12.9% respectively. In each of these subgroups, no evidence of declining likelihood of live birth with increasing sperm donor age was found (P > 0.05). The miscarriage occurrence (i.e. number of miscarriages per 100 women commencing treatment) was 1.3% in 18-34 year old women, 1.9% in 35-37 year old women and 1.9% in 38-50 year old women undergoing donor insemination treatment. In the sperm donation IVF/ICSI treatment group, these figures were 5.7, 8.4 and 6.8% respectively. The results were not suggestive of any unfavourable effect of advancing sperm donor age on the odds of miscarriage occurrence (P > 0.05). LIMITATIONS, REASONS FOR CAUTION: As sperm donors are a select population based on good semen indices, the generalization of results to the paternal population at large may not be possible. Although the study subgroups were controlled for female age, treatment modality and effect of previous treatment cycles, adjustments for certain potential compounding factors, such as smoking status, BMI of women and stimulation protocol used in IVF/ICSI treatment cycles, were not possible. WIDER IMPLICATIONS OF THE FINDINGS: Live birth and miscarriage occurrence following assisted reproduction weren't adversely affected by increasing sperm donor age up to 45 years. In view of the increasing demand for donor sperm, further studies may be required to ascertain the safe upper age limit for sperm donors. STUDY FUNDING/COMPETING INTERESTS: No funding was received from any individual or funding agency. NG was on a Commonwealth Scholarship for the duration of the study. The authors do not have any conflicts of interest to declare.


Asunto(s)
Inseminación Artificial Heteróloga , Nacimiento Vivo , Espermatozoides , Donantes de Tejidos , Aborto Espontáneo/epidemiología , Adulto , Factores de Edad , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
15.
Bone Marrow Transplant ; 50(12): 1563-71, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26367225

RESUMEN

Graft versus host disease (GVHD) is a major complication of haematopoietic SCT (HSCT). A number of inflammatory cytokines/chemokines are implicated in GVHD and have been identified in numerous single centre studies as potential biomarkers for acute and/or chronic GVHD. In this study, we analysed candidate inflammatory biomarkers (B-cell activating factor (BAFF), interleukin 33 (IL-33), CXCL10 and CXCL11) in a two-centre study. Biomarkers were evaluated pre-transplant and at serial time points post transplant in acute and chronic GVHD patient sera with time-matched control samples from patients without GVHD. Further validation was performed using the human skin explant assay, clinical GVHD biopsies and mRNA expression analysis. BAFF was significantly increased pre-transplant. BAFF, IL-33, CXCL10 and CXCL11 showed increased levels in acute GVHD patient sera and high protein expression in grades II-III of the in vitro skin explant graft versus host reaction (GVHR) group. BAFF, CXCL10 and CXCL11 also showed increased mRNA expression levels in clinical biopsies compared with the no/low-grade GVHD group. BAFF, CXCL10 and CXCL11 levels were increased in chronic GVHD patient sera. The results identify BAFF and CXCL10 as predictive biomarkers for acute GVHD and BAFF, CXCL10 and CXCL11 as useful diagnostic biomarkers for acute GVHD and chronic GVHD.


Asunto(s)
Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/diagnóstico , Trasplante de Células Madre Hematopoyéticas , Enfermedad Aguda , Aloinjertos , Biomarcadores/sangre , Enfermedad Crónica , Citocinas , Femenino , Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/terapia , Humanos , Masculino
16.
Bone Marrow Transplant ; 50(11): 1445-52, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26214138

RESUMEN

Previous studies of non-histocompatibility leukocyte antigen (HLA) gene single-nucleotide polymorphisms (SNPs) on subgroups of patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) revealed an association with transplant outcome. This study further evaluated the association of non-HLA polymorphisms with overall survival in a cohort of 762 HSCT patients using data on 26 polymorphisms in 16 non-HLA genes. When viewed in addition to an already established clinical risk score (EBMT-score), three polymorphisms: rs8177374 in the gene for MyD88-adapter-like (MAL; P=0.026), rs9340799 in the oestrogen receptor gene (ESR; P=0.003) and rs1800795 in interleukin-6 (IL-6; P=0.007) were found to be associated with reduced overall survival, whereas the haplo-genotype (ACC/ACC) in IL-10 was protective (P=0.02). The addition of these non-HLA polymorphisms in a Cox regression model alongside the EBMT-score improved discrimination between risk groups and increased the level of prediction compared with the EBMT-score alone (gain in prediction capability for EBMT-genetic-score 10.8%). Results also demonstrated how changes in clinical practice through time have altered the effects of non-HLA analysis. The study illustrates the significance of non-HLA genotyping prior to HSCT and the importance of further investigation into non-HLA gene polymorphisms in risk prediction.


Asunto(s)
Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/mortalidad , Polimorfismo de Nucleótido Simple , Medición de Riesgo/métodos , Adolescente , Adulto , Anciano , Aloinjertos , Causas de Muerte , Niño , Receptor alfa de Estrógeno/genética , Femenino , Estudios de Seguimiento , Genotipo , Enfermedad Injerto contra Huésped/mortalidad , Haplotipos , Neoplasias Hematológicas/mortalidad , Histocompatibilidad , Humanos , Infecciones/mortalidad , Interleucina-10/genética , Interleucina-6/genética , Estimación de Kaplan-Meier , Masculino , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Insuficiencia Multiorgánica/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Receptores de Interleucina-1/genética , Acondicionamiento Pretrasplante/efectos adversos , Resultado del Tratamiento
17.
Meat Sci ; 96(2 Pt B): 1016-24, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24084607

RESUMEN

Genetic parameters were estimated for a range of meat quality traits recorded on Australian lamb meat. Data were collected from Merino and crossbred progeny of Merino, terminal and maternal meat breed sires of the Information Nucleus programme. Lambs born between 2007 and 2010 (n=8968) were slaughtered, these being the progeny of 372 sires and 5309 dams. Meat quality traits were found generally to be of moderate heritability (estimates between 0.15 and 0.30 for measures of meat tenderness, meat colour, polyunsaturated fat content, mineral content and muscle oxidative capacity), with notable exceptions of intramuscular fat (0.48), ultimate pH (0.08) and fresh meat colour a* (0.08) and b* (0.10) values. Genetic correlations between hot carcass weight and the meat quality traits were low. The genetic correlation between intramuscular fat and shear force was high (-0.62). Several measures of meat quality (fresh meat redness, retail meat redness, retail oxy/met value and iron content) appear to have potential for inclusion in meat sheep breeding objectives.


Asunto(s)
Cruzamiento , Dieta , Carne/análisis , Fenotipo , Oveja Doméstica/genética , Tejido Adiposo/metabolismo , Animales , Australia , Peso Corporal/genética , Color , Grasas de la Dieta/metabolismo , Ácidos Grasos Insaturados/genética , Ácidos Grasos Insaturados/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Hierro/metabolismo , Carne/normas , Minerales/metabolismo , Valor Nutritivo , Oxidación-Reducción , Estrés Mecánico
18.
Meat Sci ; 96(2 Pt B): 1076-87, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23968666

RESUMEN

The impact of selecting for lean meat yield using breeding values for increased eye muscle depth (PEMD) and decreased fat depth (PFAT) on the consumer acceptance of lamb meat was evaluated. Consumer sensory scores (tenderness, juiciness, flavour, odour, overall liking) were obtained for the longissimus lumborum (loin) and semimembranosus (topside) muscles of 1471 lambs. On average loin samples were more acceptable for consumers. Sensory scores increased with higher IMF levels, with lower shear force levels, and when animals were younger and less muscular. Increasing PEMD decreased tenderness, overall liking and flavour scores in both muscles, and decreasing PFAT reduced tenderness within the loin samples only. This negative impact of PEMD and PFAT is not solely driven through the phenotypic impact of IMF and shear force on sensory scores. Our results confirm the growing concerns that selecting for lean meat yield would reduce consumer eating quality, and highlight that careful monitoring of selection programmes is needed to maintain lamb eating quality.


Asunto(s)
Tejido Adiposo/metabolismo , Adiposidad/genética , Cruzamiento , Carne/análisis , Músculos/metabolismo , Estrés Mecánico , Gusto , Animales , Australia , Comportamiento del Consumidor , Dieta , Humanos , Masculino , Carne/normas , Músculos Paraespinales/metabolismo , Fenotipo , Oveja Doméstica/genética
19.
J AOAC Int ; 93(2): 622-7, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20480910

RESUMEN

An AOAC collaborative study was conducted to evaluate an affinity LC procedure for measuring immunoglobulin G (IgG) in selected dairy powders. The powders were extracted with 0.15 M sodium chloride solution and the pH was adjusted to 4.6 to precipitate caseins, which would otherwise lead to an overestimation of IgG. The analyte was then bound to a commercially available Protein G affinity cartridge and selectively eluted with a glycine buffer at pH 2.5. Detection was at 280 nm and quantification was made against a calibration curve prepared from bovine serum IgG. The samples analyzed included the likely matrixes for which this assay will find commercial use, namely, high- and low-protein-content colostrum powders, tablets containing colostrum powder, and some IgG-containing dairy powders; milk protein isolate, whey protein concentrate, and skim milk powder. Eleven laboratories provided data for the study and assayed blind duplicates of six materials. The repeatability RSD values ranged from 2.1 to 4.2% and the reproducibility RSD values ranged from 6.4 to 18.5%. The Protein G method with casein removal has adequate reproducibility for measuring IgG in colostrum-derived powders that are traded on the basis of IgG content as a colostral marker.


Asunto(s)
Técnicas de Química Analítica , Cromatografía Liquida/métodos , Calostro/metabolismo , Inmunoglobulina G/análisis , Leche/metabolismo , Proteínas del Tejido Nervioso/química , Animales , Biomarcadores , Calibración , Bovinos , Concentración de Iones de Hidrógeno , Inmunoglobulina G/química , Polvos , Reproducibilidad de los Resultados , Factores de Tiempo
20.
Meat Sci ; 81(1): 188-95, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22063981

RESUMEN

The use of alternating frequencies during stimulation can increase stimulation response of a medium voltage electrical stimulation unit (MVS) by increasing the rate of pH decline. Various combinations of frequency modulation were tested in experiment 1 to determine the treatment resulting in the greatest stimulation response; the lowest initial pH, fastest rate of pH decline, highest temperature at pH 6 and the highest number of carcasses with a pH of 6 by 25(o)C and the treatment achieving the highest number of carcasses in the pH temp window (temperature at pH 6 between 18-25(o)C). The objective meat quality of these treatments compared to an unstimulated treatment was tested in experiment 2. Modulating the frequency (Hz) across the 6 segmented electrodes of the MVS by 10, 15, 25, 10, 15, 25Hz (Treatment 6, using a pulse width: 2.5ms, current: 1A) resulted in the greatest stimulation response. This treatment may be suitable for abattoirs that hot bone sheepmeat and require fast pH declines to ensure minimal cold shortening of meat. However, this treatment did not result in the tenderer meat despite the higher stimulation response. This treatment may have induced a greater number of contractions overall and therefore a greater pH decline response but resulted in less myofibrillar disruption compared to the other treatments due to a concomitant decreased force of contraction thus reducing potential tenderisation. Maintaining a constant frequency of 15Hz (Treatment 1; pulse width: 2.5ms, current: 1A) resulted in a higher number of carcasses in the pH temp window required (temperature at pH 6 between 18-25(o)C) in part A (P<0.05) and in addition to the higher tenderness levels this treatment may be more appropriate to satisfy the overall demands of abattoirs using these systems. This paper has also demonstrated electrical stimulation results in tenderer meat compared to unstimulated meat even after 30d of ageing (2.53±0.4 compared to 2.85±0.1 for the loin (M. longissimus thoracis et lumborum) (P<0.01) possibly due to a protective benefit of stimulation on meat tenderness. Overall, no detrimental effects of modulating frequency were observed on drip loss or retail colour display despite a greater rate of colour change observed with the modulated frequency treatment and the longer aged product.

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