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1.
Clin Radiol ; 78(12): e941-e949, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37788968

RESUMO

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.


Assuntos
Neoplasias Encefálicas , Hospitais Pediátricos , Criança , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Centros de Atenção Terciária , Reino Unido
2.
Inhal Toxicol ; 31(9-10): 357-367, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31779509

RESUMO

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.


Assuntos
Aerossóis/química , Cosméticos/química , Exposição por Inalação , Nanoestruturas/química , Testes de Toxicidade/instrumentação , Testes de Toxicidade/métodos , Humanos
3.
Hum Reprod ; 31(3): 582-90, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26762315

RESUMO

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.


Assuntos
Inseminação Artificial Heteróloga , Nascido Vivo , Espermatozoides , Doadores de Tecidos , Aborto Espontâneo/epidemiologia , Adulto , Fatores Etários , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
4.
Int J Immunogenet ; 43(6): 404-412, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27870355

RESUMO

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.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/genética , Leucemia/imunologia , Adulto , Feminino , Genômica , Genótipo , Proteínas de Choque Térmico HSP70/genética , Haplótipos/genética , Teste de Histocompatibilidade , Humanos , Leucemia/patologia , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Transplante Homólogo/efeitos adversos
5.
Echo Res Pract ; 11(1): 7, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424646

RESUMO

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.

6.
J Hosp Infect ; 126: 93-102, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35562072

RESUMO

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.


Assuntos
Infecção Hospitalar , Austrália/epidemiologia , Comunicação , Infecção Hospitalar/epidemiologia , Atenção à Saúde , Hospitais , Humanos , Pesquisa Qualitativa
7.
Nat Commun ; 13(1): 6975, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36379931

RESUMO

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.


Assuntos
Histonas , Lisina , Humanos , Metilação , Histonas/metabolismo , Lisina/metabolismo , Processamento de Proteína Pós-Traducional , Cromatina/genética
8.
J AOAC Int ; 93(2): 622-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20480910

RESUMO

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.


Assuntos
Técnicas de Química Analítica , Cromatografia Líquida/métodos , Colostro/metabolismo , Imunoglobulina G/análise , Leite/metabolismo , Proteínas do Tecido Nervoso/química , Animais , Biomarcadores , Calibragem , Bovinos , Concentração de Íons de Hidrogênio , Imunoglobulina G/química , Pós , Reprodutibilidade dos Testes , Fatores de Tempo
9.
Toxicol In Vitro ; 69: 104997, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32896591

RESUMO

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.


Assuntos
Brônquios/citologia , Vapor do Cigarro Eletrônico/toxicidade , Sistemas Eletrônicos de Liberação de Nicotina , Células Epiteliais/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Vapor do Cigarro Eletrônico/análise , Células Epiteliais/metabolismo , Humanos , Metais Pesados/análise , Metais Pesados/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
10.
Meat Sci ; 81(1): 285-93, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22063997

RESUMO

Fifty merino wethers (liveweight range from 44 to 81kg, average of 58.6kg) were lot fed for 42d and scanned through a dual X-ray absorptiometry (DXA) as both a live animal and whole carcass (carcass weight range from 15 to 32kg, average of 22.9kg) producing measures of total tissue, lean, fat and bone content. The carcasses were subsequently boned out into saleable cuts and the weights and yield of boned out muscle, fat and bone recorded. The relationship between chemical lean (protein+water) was highly correlated with DXA carcass lean (r(2)=0.90, RSD=0.674kg) and moderately with DXA live lean (r(2)=0.72, RSD=1.05kg). The relationship between the chemical fat was moderately correlated with DXA carcass fat (r(2)=0.86, RSD=0.42kg) and DXA live fat (r(2)=0.70, RSD=0.71kg). DXA carcass and live animal bone was not well correlated with chemical ash (both r(2)=0.38, RSD=0.3). DXA carcass lean was moderately well predicted from DXA live lean with the inclusion of bodyweight in the regression (r(2)=0.82, RSD=0.87kg). DXA carcass fat was well predicted from DXA live fat (r(2)=0.86, RSD=0.54kg). DXA carcass lean and DXA carcass fat with the inclusion of carcass weight in the regression significantly predicted boned out muscle (r(2)=0.97, RSD=0.32kg) and fat weight, respectively (r(2)=0.92, RSD=0.34kg). The use of DXA live lean and DXA live fat with the inclusion of bodyweight to predict boned out muscle (r(2)=0.83, RSD=0.75kg) and fat (r(2)=0.86, RSD=0.46kg) weight, respectively, was moderate. The use of DXA carcass and live lean and fat to predict boned out muscle and fat yield was not correlated as weight. The future for the DXA will exist in the determination of body composition in live animals and carcasses in research experiments but there is potential for the DXA to be used as an online carcass grading system.

11.
Meat Sci ; 81(1): 188-95, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22063981

RESUMO

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.

12.
Am J Med Genet A ; 146A(17): 2252-7, 2008 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-18671281

RESUMO

Fraser syndrome (FS) is an autosomal recessive malformation disorder characterized by cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract. FS is considered to be the human equivalent of the murine blebbing mutants: in the mouse mutations at five loci cause a phenotype that is comparable to FS in humans, and thus far mutations in two syntenic human genes, FRAS1 and FREM2, have been identified to cause FS. Here we present the molecular analysis of 48 FS patients from 18 consanguineous and 15 nonconsanguineous families. Linkage analysis in consanguineous families indicated possible linkage to FRAS1 and FREM2 in 60% of the cases. Mutation analysis identified 11 new mutations in FRAS1 and one FREM2 mutation. Manifestations of these patients and previously reported cases with an FRAS1 mutation were compared to cases without detectable FRAS1 mutations to study genotype-phenotype correlations. Although our data suggest that patients with an FRAS1 mutation have more frequently skull ossification defects and low insertion of the umbilical cord, these differences are not statistically significant. Mutations were identified in only 43% of the cases suggesting that other genes syntenic to murine genes causing blebbing may be responsible for FS as well.


Assuntos
Proteínas da Matriz Extracelular/genética , Pálpebras/anormalidades , Ligação Genética , Sindactilia/genética , Anormalidades Múltiplas/genética , Consanguinidade , Análise Mutacional de DNA , Genótipo , Humanos , Fenótipo , Síndrome
13.
Meat Sci ; 79(2): 344-54, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22062763

RESUMO

The carcass and eating quality of sheep grazing a saltbush dominant saline pasture system or on a 'control' dry pasture, stubble plot both supplemented with barley for 14 weeks was investigated (Experiment 1, 50 (2×25) 6 month merino lamb wethers and Experiment 2, 50 (2×25) 18 month old merino hogget wethers). Treatment had no significant effect on eating quality attributes (P>0.05). Saltbush grazed sheep in both experiments had a significantly (P<0.01) lower carcass fat and significantly higher lean (P<0.01) content than the control grazed sheep. This is a positive finding as fat denudation is a significant cost to processors. The long term consumption of saltbush and barley prior to slaughter did increase muscle fluid content (P<0.05) but did not result in a decreased carcass weight loss at slaughter due to confounding changes in body composition. Grazing saltbush resulted in increased urine weight (P<0.001) and decreased urine concentration (P<0.05) at slaughter indicating an improved hydration status at slaughter. However both experiments demonstrated sub-optimal liveweight gains indicating that saltbush with a barley supplement can still be effectively used as a maintenance ration without compromising carcass and eating quality.

14.
Leukemia ; 32(4): 882-889, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29089643

RESUMO

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.


Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Mebendazol/farmacologia , Proteólise/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myb/metabolismo , Animais , Criança , Feminino , Humanos , Lactente , Masculino , Camundongos , Oncogenes/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo
16.
J Anim Sci ; 95(10): 4260-4273, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29108061

RESUMO

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.


Assuntos
Carne/normas , Ovinos/genética , Lã/normas , Animais , Austrália , Peso Corporal/genética , Cruzamento , Cor , Ácidos Graxos/análise , Feminino , Ferro/análise , Masculino , Valor Nutritivo/genética , Fenótipo , Ovinos/fisiologia , Zinco/análise
17.
J Anim Sci ; 95(6): 2385-2398, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28727038

RESUMO

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.


Assuntos
Ovinos/genética , Lã/crescimento & desenvolvimento , Animais , Austrália , Peso Corporal , Cruzamento , Cor , Feminino , Genótipo , Masculino , Fenótipo , Carne Vermelha , Ovinos/crescimento & desenvolvimento
18.
Seizure ; 15(3): 184-9, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16488630

RESUMO

OBJECTIVE: To investigate whether electroencephalogram (EEG) requests at St George's Hospital (SGH) are being made according to clinical guideline recommendations. METHODS: A retrospective audit at a regional neurology and neurosurgery referral centre, also serving a district population. All adult National Health Service patients undergoing standard EEG between 1st November 2003 and 31st January 2004, for whom the request originated within the hospital, were identified. Data was collected from each subject's case notes, request form and EEG report and compared to predetermined criteria. RESULTS: Fifty sets of notes from ninety patients meeting the inclusion criteria were available for review. Twenty-six percent of requests were considered 'inappropriate', with respect to clinical guidelines, of which 92% were for 'funny turns' where there appeared to be insufficient clinical evidence to justify the request. The EEG contributed to diagnosis or management in only 22% of cases, all of which had been appropriately requested. Neurologists/epileptologists appeared better than non-specialists in terms of appropriateness of referrals, though the numbers were too small to reach significance (p = 0.173, Fisher's exact). Forty-two percent of all patients, and less than 10% of outpatients, had their EEG within the guideline target wait of 4 weeks. CONCLUSIONS: Over a quarter of EEG referrals are not being made in accordance with guidelines, mainly because of the misconception that an EEG can confirm or exclude a diagnosis of epilepsy in patients with "funny turns". In addition, less than 10% of out patient requests are being met within 4 weeks. Strategies to maximise service utilisation are discussed.


Assuntos
Eletroencefalografia/estatística & dados numéricos , Procedimentos Desnecessários , Revisão da Utilização de Recursos de Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais de Distrito/estatística & dados numéricos , Hospitais Gerais/estatística & dados numéricos , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Reino Unido
19.
Biochim Biophys Acta ; 1112(2): 259-65, 1992 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-1457457

RESUMO

Previous work has shown that bovine prothrombin fragment 1 binds to supported planar membranes composed of phosphatidylcholine and phosphatidylserine in a Ca(2+)-specific manner (Tendian et al. (1991) Biochemistry 30, 10991; Pearce et al. (1992) Biochemistry 31, 5983-5995). In the present work, fluorescence pattern photobleaching recovery has been used to examine the effect of membrane-bound fragment 1 on the translational diffusion coefficients of two fluorescent phospholipids in fluid-like phosphatidylserine/phosphatidylcholine Langmuir-Blodgett monolayers. The results show that saturating concentrations of fragment 1, in the presence of Ca2+, reduce the diffusion coefficient of nitrobenzoxadiazolyl-conjugated phosphatidylserine (NBD-PS) and nitrobenzoxadiazolyl-conjugated phosphatidylcholine (NBD-PC) by factors of approximately four and two, respectively. Ca2+ or fragment 1 alone do not have a statistically significant effect on NBD-PS or NBD-PC diffusion. In addition, a nonspecific protein (ovalbumin) does not change the diffusion coefficients of the fluorescent phospholipids either in the absence or presence of Ca2+. The fractions of the fluorescent phospholipids that are laterally mobile are approximately 0.9 for all samples. These results are interpreted with several models for possible mechanisms by which extrinsically bound proteins might retard phospholipid diffusion in membranes.


Assuntos
4-Cloro-7-nitrobenzofurazano/análogos & derivados , Membranas Artificiais , Fragmentos de Peptídeos/farmacologia , Fosfatidilcolinas/metabolismo , Fosfatidilserinas/metabolismo , Precursores de Proteínas/farmacologia , Protrombina/farmacologia , 4-Cloro-7-nitrobenzofurazano/metabolismo , Animais , Cálcio/farmacologia , Bovinos , Difusão , Ácido Edético/farmacologia , Microscopia de Fluorescência , Ovalbumina/farmacologia , Fotoquímica
20.
Arch Intern Med ; 152(4): 750-6, 1992 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1558432

RESUMO

BACKGROUND: Ambulatory blood pressures (BPs) have generally been reported to be lower than office blood pressures, but population-based data are lacking. METHODS: To better characterize ambulatory and office BP relationships, we explored the interrelationships of BPs measured in the office by mercury sphygmomanometry, 24-hour ambulatory BP measured with a portable device, and echocardiographic left ventricular mass in a random sample of 50 men aged 51 to 72 years drawn from a much larger pool. Office BP was based on the mean of 10 measurements performed over five visits. RESULTS: Among all participants, mean 24-hour ambulatory and mean office BPs were highly correlated: r (systolic/diastolic) = .90/.79; and both mean 24-hour and mean awake ambulatory BPs were significantly higher than mean office BPs. For the subsample not receiving antihypertensive therapy, mean ambulatory and office BPs were similar in terms of their associations with Penn left ventricular mass index (LVMI). No association between BP and left ventricular mass was observed among the subjects receiving antihypertensive medication. CONCLUSIONS: We conclude that a single session of 24-hour ambulatory BP monitoring is unlikely to improve the determination of usual BP in older white men beyond that achievable with BP carefully measured over five separate office visits; and that white coat hypertension is rare in this population.


Assuntos
Assistência Ambulatorial , Determinação da Pressão Arterial/métodos , Hipertensão/epidemiologia , Consultórios Médicos , Idoso , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Minnesota , Ultrassonografia
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