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1.
Regul Toxicol Pharmacol ; 147: 105571, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244664

RESUMO

The World Health Organization (WHO) assesses potential health risks of dioxin-like compounds using Toxic Equivalency Factors (TEFs). This study systematically updated the relative potency (REP) database underlying the 2005 WHO TEFs and applied advanced methods for quantitative integration of study quality and dose-response. Data obtained from fifty-one publications more than doubled the size of the previous REP database (∼1300 datasets). REP quality and relevance for these data was assessed via application of a consensus-based weighting framework. Using Bayesian dose-response modeling, available data were modeled to produce standardized dose/concentration-response Hill curves. Study quality and REP data were synthesized via Bayesian meta-analysis to integrate dose/concentration-response data, author-calculated REPs and benchmark ratios. The output is a prediction of the most likely relationship between each congener and its reference as model-predicted TEF uncertainty distributions, or the 'best estimate TEF' (BE-TEF). The resulting weighted BE-TEFs were similar to the 2005 TEFs, though provide more information to inform selection of TEF values as well as to provide risk assessors and managers with information needed to quantitatively characterize uncertainty around TEF values. Collectively, these efforts produce an updated REP database and an objective, reproducible approach to support development of TEF values based on all available data.


Assuntos
Dioxinas , Bifenilos Policlorados , Animais , Dioxinas/toxicidade , Teorema de Bayes , Mamíferos
2.
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
3.
Osteoporos Int ; 33(6): 1347-1355, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35088102

RESUMO

In this retrospective cohort study, men and women with eating disorders (n = 8867) had higher risk of injurious falls and hip fractures than age, sex, and county-matched controls (n = 88670). INTRODUCTION: Eating disorders have been associated with decreased bone mineral density and increased fracture risk, but the association with fall injuries without fracture has not previously been investigated. Furthermore, fracture risk in men with eating disorders has been insufficiently studied. METHODS: In the present study, 8867 patients (9.4% men) with a diagnosed eating disorders and 88670 age-, sex-, and county-matched controls were investigated. RESULTS: The mean (standard deviation) age of the patients and controls was 41.6 (13.7) years and the follow-up time 9.6 (5.2, 14.4) years (median, interquartile range) for patients and 10.1 (5.5, 14.2) years for controls. The proportions of injurious falls without fracture (17.3% vs. 9.0%) and of hip fracture (1.6% vs. 0.7%) were substantially greater in patients with an eating disorder than in their corresponding population controls. In an unadjusted Cox proportional hazards model, individuals with an eating disorder had a higher risk of injurious falls without fracture (Hazard ratio (HR) 95% confidence interval (CI): 2.07 (1.96-2.18), and hip fracture (HR 2.30 (1.92-2.75)) than the risk observed in the controls. The HR for any investigated outcome associated with an eating disorder did not differ by sex or age (interaction term p > 0.10). The risk of injurious falls without fracture and hip fracture was increased in both women (HR 2.07 (1.95-2.19) and HR 2.41 (1.98-2.93), respectively) and men (HR 2.09 (1.76-2.49) and HR 1.84(1.12-3.02), respectively), with an eating disorder. CONCLUSION: The risk of injurious falls without fracture and of hip fracture is increased in both women and men with eating disorders, indicating measures to prevent both falls and fractures are important in these patients, regardless of age and sex.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Fraturas do Quadril , Densidade Óssea , Criança , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Suécia/epidemiologia
4.
Clin Exp Dermatol ; 47(1): 37-42, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34160837

RESUMO

BACKGROUND: Skin conditions have a large emotional, psychological and psychiatric impact on the individual. The All-Party Parliamentary Group on Skin (APPGS) commissioned a qualitative survey to further explore this relationship alongside the experiences of those accessing services in relation to these difficulties in the UK. AIM: To examine the experiences of UK individuals living with a skin condition, and their views of seeking and receiving psychological treatment. This survey formed part of the evidence collected in the preparation of the APPGS Mental Health and Skin Disease report. METHODS: A free-text electronic survey was widely distributed by professional bodies and skin-related charities. Responses were analysed using descriptive thematic analysis and descriptive statistics. Data for each question were classified and labelled, leading to the development of a coding frame. Inter-rater reliability was assessed using Cohen kappa statistic. RESULTS: In total, 544 participants (84% female) completed the survey. The majority of respondents had inflammatory skin diseases such as eczema (43%) or psoriasis (33%). The thematic analysis revealed five key themes associated with impact on mood; impact of intimacy; impact on activities of daily living; lack of recognition from others of the impact; and lack of accessible services. CONCLUSION: The survey demonstrates that there is an urgent need to improve both awareness of the impact that skin conditions can have, and for the provision of psychological services to address this impact.


Assuntos
Acessibilidade aos Serviços de Saúde , Sistemas de Apoio Psicossocial , Dermatopatias/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Autorrelato , Dermatopatias/terapia , Reino Unido
5.
Adv Exp Med Biol ; 1354: 299-314, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34807448

RESUMO

Dairy and beef cattle make a vital contribution to global nutrition, and since their domestication, they have been continuously exposed to natural and artificial selection to improve production characteristics. The technologies of transgenesis and gene editing used in cattle are responsible for generating news characteristics in bovine breeding, such as alteration of nutritional components of milk and meat enhancing human health benefits, disease resistance decreasing production costs and offering safe products for human food, as well as the recombinant protein production of biomedical significance. Different methodologies have been used to generate transgenic cattle as bioreactors. These methods include the microinjection of vectors in pronuclear, oocyte or zygote, sperm-mediate transgenesis, and somatic cell nuclear transfer. Gene editing has been applied to eliminate unwanted genes related to human and animal health, such as allergy, infection, or disease, and to insert transgenes into specific sites in the host genome. Methodologies for the generation of genetically modified cattle are laborious and not very efficient. However, in the last 30 years, transgenic animals were produced using many biotechnological tools. The result of these modifications includes (1) the change of nutritional components, including proteins, amino acids and lipids for human nutrition; (2) the removal allergic proteins milk; (3) the production of cows resistant to disease; or (4) the production of essential proteins used in biomedicine (biomedical proteins) in milk and blood plasma. The genetic modification of cattle is a powerful tool for biotechnology. It allows for the generation of new or modified products and functionality that are not currently available in this species.


Assuntos
Leite , Técnicas de Transferência Nuclear , Animais , Animais Geneticamente Modificados , Reatores Biológicos , Biotecnologia , Bovinos , Feminino
6.
Haemophilia ; 24 Suppl 6: 87-94, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29878652

RESUMO

INTRODUCTION: Information from the genes encoding factor VIII (F8) and IX (F9) is used in reproductive planning and to inform inhibitor formation, bleeding severity and response to therapies. Advances in technology and our understanding of the human genome now allows more comprehensive methods to study genomic variation and its impact on haemophilia. AIMS: The My Life Our Future (MLOF) programme was begun in 2012 to provide genetic analysis and to expand research in haemophilia through a research repository. METHODS: MLOF enrolled haemophilia A and B patients followed at haemophilia treatment centers in the U.S., including, since 2015, known and potential genetic carriers. Initial F8 and F9 DNA analysis was performed utilizing a next generation sequencing approach which allowed simultaneous detection of F8 inversions and other variants. Candidate variants were confirmed using a second method and multiplex ligation-dependent probe amplification was used to detect structural variants. RESULTS: The initial phase of MLOF completed enrollment in December 2017 with 11,356 patients, genetic carriers, and potential carriers enrolled. In the 9453 subjects in whom analysis is complete, 687 unique previously unreported variants were found. Simultaneous sequencing of the F8 and F9 genes resulted in identification of non-deleterious variants previously reported as causative in haemophilia. DNA from 5141 MLOF subjects has undergone whole genome sequencing through the NHLBI TOPMed programme of the U.S. NIH. CONCLUSION: MLOF has provided genetic information for patients and their families to help inform clinical care and has established a repository of data and biospecimens to further advance haemophilia research.


Assuntos
Genótipo , Hemofilia A/genética , Fenótipo , Sequenciamento Completo do Genoma/métodos , Hemofilia A/diagnóstico , Humanos , Prognóstico
7.
Cereb Cortex ; 27(3): 2403-2417, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-27095824

RESUMO

Control of goal-directed tasks is putatively carried out via the cinguloopercular (CO) and frontoparietal (FP) systems. However, it remains unclear whether these systems show dissociable moment-to-moment processing during distinct stages of a trial. Here, we characterize dynamics in the CO and FP networks in a meta-analysis of 5 decision-making tasks using fMRI, with a specialized "slow reveal" paradigm which allows us to measure the temporal characteristics of trial responses. We find that activations in left FP, right FP, and CO systems form separate clusters, pointing to distinct roles in decision-making. Left FP shows early "accumulator-like" responses, suggesting a role in pre-decision processing. CO has a late onset and transient response linked to the decision event, suggesting a role in performance reporting. The majority of right FP regions show late onsets with prolonged responses, suggesting a role in post-recognition processing. These findings expand upon past models, arguing that the CO and FP systems relate to distinct stages of processing within a trial. Furthermore, the findings provide evidence for a heterogeneous profile in the FP network, with left and right FP taking on specialized roles. This evidence informs our understanding of how distinct control networks may coordinate moment-to-moment components of complex actions.


Assuntos
Encéfalo/fisiologia , Tomada de Decisões/fisiologia , Mapeamento Encefálico , Função Executiva/fisiologia , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/fisiologia
8.
Int J Obes (Lond) ; 41(1): 149-158, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27773938

RESUMO

BACKGROUND: Consumption of dietary fat is one of the key factors leading to obesity. High-fat diet (HFD)-induced obesity is characterized by induction of inflammation in the hypothalamus; however, the temporal regulation of proinflammatory markers and their impact on hypothalamic appetite-regulating neuropeptide Y/agouti-related peptide (NPY/AgRP) neurons remains undefined. METHODS: Mice were injected with an acute lipid infusion for 24 h or fed a HFD over 8-20 weeks. Characterized mouse NPY/AgRP hypothalamic cell lines were used for in vitro experimentation. Immunohistochemistry in brain slices or quantitative real-time PCR in cell lines, was performed to determine changes in the expression of key inflammatory markers and neuropeptides. RESULTS: Hypothalamic inflammation, indicated by tumor necrosis factor (TNF)-α expression and astrocytosis in the arcuate nucleus, was evident following acute lipid infusion. HFD for 8 weeks suppressed TNF-α, while significantly increasing heat-shock protein 70 and ciliary neurotrophic factor, both neuroprotective components. HFD for 20 weeks induced TNF-α expression in NPY/AgRP neurons, suggesting a detrimental temporal regulatory mechanism. Using NPY/AgRP hypothalamic cell lines, we found that palmitate provoked a mixed inflammatory response on a panel of inflammatory and endoplasmic reticulum (ER) stress genes, whereas TNF-α significantly upregulated IκBα, nuclear factor (NF)-κB and interleukin-6 mRNA levels. Palmitate and TNF-α exposure predominantly induced NPY mRNA levels. Utilizing an I kappa B kinase ß (IKKß) inhibitor, we demonstrated that these effects potentially occur via the inflammatory IKKß/NF-κB pathway. CONCLUSIONS: These findings indicate that acute lipid and chronic HFD feeding in vivo, as well as acute palmitate and TNF-α exposure in vitro, induce markers of inflammation or ER stress in the hypothalamic appetite-stimulating NPY/AgRP neurons over time, which may contribute to a dramatic alteration in NPY/AgRP content or expression. Acute and chronic HFD feeding in vivo temporally regulates arcuate TNF-α expression with reactive astrocytosis, which suggests a time-dependent neurotrophic or neurotoxic role of lipids.


Assuntos
Apetite/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Hipotálamo/patologia , Inflamação/induzido quimicamente , Neurônios/efeitos dos fármacos , Neuropeptídeo Y/metabolismo , Palmitatos/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Núcleo Arqueado do Hipotálamo/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hipotálamo/efeitos dos fármacos , Inflamação/patologia , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Obesidade/patologia
9.
Mol Hum Reprod ; 23(4): 248-256, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-27418669

RESUMO

The in vitro production of livestock embryos is central to several areas of animal biotechnology. Further, the use of in vitro embryo manipulation is expanding as new applications emerge. ARTs find direct applications in increasing genetic quality of livestock, producing transgenic animals, cloning, artificial insemination, reducing disease transmission, preserving endangered germplasm, producing chimeric animals for disease research, and treating infertility. Whereas new techniques such as nuclear transfer and intracytoplasmic sperm injection are now commonly used, basic embryo culture procedures remain the limiting step to the development of these techniques. Research over the past 2 decades focusing on improving the culture medium has greatly improved in vitro development of embryos. However, cleavage rates and viability of these embryos is reduced compared with in vivo indicating that present in vitro systems are still not optimal. Furthermore, the methods of handling mammalian oocytes and embryos have changed little in recent decades. While pipetting techniques have served embryology well in the past, advanced handling and manipulation technologies will be required to efficiently implement and commercialize the basic biological advances made in recent years. Microfluidic systems can be used to handle gametes, mature oocytes, culture embryos, and perform other basic procedures in a microenvironment that more closely mimic in vivo conditions. The use of microfluidic technologies to fabricate microscale devices has being investigated to overcome this obstacle. In this review, we summarize the development and testing of microfabricated fluidic systems with feature sizes similar to the diameter of an embryo for in vitro production of pre-implantation mammalian embryos.


Assuntos
Técnicas de Cultura Embrionária/métodos , Desenvolvimento Embrionário/fisiologia , Técnicas Analíticas Microfluídicas/métodos , Microfluídica/métodos , Animais , Animais Geneticamente Modificados , Conservação dos Recursos Naturais/métodos , Meios de Cultura/química , Meios de Cultura/farmacologia , Embrião de Mamíferos , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Gado , Camundongos , Microfluídica/instrumentação , Técnicas de Transferência Nuclear/instrumentação , Injeções de Esperma Intracitoplásmicas/instrumentação , Injeções de Esperma Intracitoplásmicas/métodos
10.
Reprod Fertil Dev ; 29(6): 1144-1154, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27166082

RESUMO

The aim of the present study was to evaluate the effect of anti-Müllerian hormone (AMH), with and without FSH, on the in vitro development of isolated caprine preantral follicles, as well as follicular steroid production and mRNA levels of AMH, hormone receptors (AMH and FSH), CYP19A1 (cytochrome P450, family 19, subfamily A, polypeptide 1), CYP17 (cytochrome P450, family 17, subfamily A, polypeptide 1), HSD3B (3-beta-hydroxysteroid dehydrogenase) and Myc (myelocytomatosis oncogene). Isolated secondary follicles were cultured in minimum essential medium alpha (α-MEM+) alone or supplemented with 50ng mL-1 AMH and/or 100ng mL-1 FSH added sequentially on different days of culture. Follicles were cultured for a total of 18 days, with different media during the first (Days 0-9) and second (Days 10-18) halves of the culture period, resulting in six treatment groups, as follows: α-MEM+/α-MEM+, FSH/FSH, AMH/AMH, AMH+FSH/AMH+FSH, AMH/FSH, and FSH/AMH. Follicle development was evaluated on the basis of follicular growth, oocyte maturation and steroid secretion. There was a decrease in follicular growth rate in the AMH, AMH+FSH and AMH/FSH treatment groups compared with α-MEM+ and FSH treatment groups (P<0.05). However, the different culture conditions had no effect on rates of meiotic resumption and steroid secretion (P>0.05). Moreover, follicles cultured in the presence of FSH had lower levels of AMH receptor type II (AMHRII) mRNA compared with non-cultured control (freshly isolated follicles), and the AMH and AMH/FSH treatment groups. In conclusion, AMH reduces the follicular growth rate of isolated goat preantral follicles in vitro without affecting follicular survival.


Assuntos
Hormônio Antimülleriano/metabolismo , Hormônio Foliculoestimulante/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Oogênese , Folículo Ovariano/metabolismo , Receptores do FSH/agonistas , Receptores de Peptídeos/agonistas , Receptores de Fatores de Crescimento Transformadores beta/agonistas , Matadouros , Animais , Hormônio Antimülleriano/genética , Hormônio Antimülleriano/farmacologia , Brasil , Bovinos , Proliferação de Células/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cruzamentos Genéticos , Estradiol/metabolismo , Feminino , Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Cabras , Humanos , Oogênese/efeitos dos fármacos , Folículo Ovariano/citologia , Folículo Ovariano/efeitos dos fármacos , Progesterona/metabolismo , Receptores do FSH/genética , Receptores do FSH/metabolismo , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Testosterona/metabolismo , Técnicas de Cultura de Tecidos
13.
Am J Transplant ; 15(3): 650-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25648766

RESUMO

We conducted a review of patients undergoing heart transplantation (HT) at our institution for amyloid cardiomyopathy (ACM) between 2008 and 2013. Complete follow-up was available for all patients. Nineteen patients with ACM underwent HT during the study period, accounting for 9.4% of all HT performed at our institution during this period. Amyloid subtype was light chain (AL) in 9 patients and transthyretin (ATTR) in 10 (2 wild-type, 7 familial, 1 unknown). Eight of nine patients with AL amyloidosis began chemotherapy prior to HT, six have resumed chemotherapy since HT, and five have undergone autologous stem cell transplantation. Most recent free light chain levels in AL patients decreased by a median of 85% from peak values. Only one patient developed recurrent graft amyloidosis, occurring at 3.5 years post-HT and asymptomatic. After a median follow-up of 380 days, 17 (89.5%) patients are alive. To our knowledge, this is the largest single-center series reported of ACM patients undergoing HT in the modern era. Our results suggest that acceptable outcomes following HT can be achieved in the short-to-intermediate term and that this is a feasible option for end-stage ACM with careful patient selection and aggressive control of amyloidogenic light chains in AL patients.


Assuntos
Amiloidose/complicações , Cardiomiopatias/cirurgia , Transplante de Coração , Resultado do Tratamento , Idoso , Cardiomiopatias/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Diabetes Obes Metab ; 17(10): 1003-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26095311

RESUMO

Increasing evidence points to the cytotoxicity of islet amyloid polypeptide (IAPP) aggregates as a major contributor to the loss of ß-cell mass in type 2 diabetes. Prevention of IAPP formation represents a potential treatment to increase ß-cell survival and function. The IAPP inhibitory peptide, D-ANFLVH, has been previously shown to prevent islet amyloid accumulation in cultured human islets. To assess its activity in vivo, D-ANFLVH was administered by intraperitoneal injection into a human IAPP transgenic mouse model, which replicates type 2 diabetes islet amyloid pathology. The peptide was a potent inhibitor of islet amyloid deposition, resulting in reduced islet cell apoptosis and preservation of ß-cell area leading to improved glucose tolerance. These findings provide support for a key role of islet amyloid in ß-cell survival and validate the application of anti-amyloid compounds as therapeutic strategies to maintain normal insulin secretion in patients with type 2 diabetes.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Homeostase/efeitos dos fármacos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Modelos Animais de Doenças , Células Secretoras de Insulina/efeitos dos fármacos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/uso terapêutico , Ilhotas Pancreáticas/efeitos dos fármacos , Camundongos , Camundongos Transgênicos
15.
J Phys Chem A ; 119(19): 4358-72, 2015 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-25345526

RESUMO

Ice nucleation on mineral dust particles is known to be an important process in the atmosphere. To accurately implement ice nucleation on mineral dust particles in atmospheric simulations, a suitable theory or scheme is desirable to describe laboratory freezing data in atmospheric models. In the following, we investigated ice nucleation by supermicron mineral dust particles [kaolinite and Arizona Test Dust (ATD)] in the immersion mode. The median freezing temperature for ATD was measured to be approximately -30 °C compared with approximately -36 °C for kaolinite. The freezing results were then used to test four different schemes previously used to describe ice nucleation in atmospheric models. In terms of ability to fit the data (quantified by calculating the reduced chi-squared values), the following order was found for ATD (from best to worst): active site, pdf-α, deterministic, single-α. For kaolinite, the following order was found (from best to worst): active site, deterministic, pdf-α, single-α. The variation in the predicted median freezing temperature per decade change in the cooling rate for each of the schemes was also compared with experimental results from other studies. The deterministic model predicts the median freezing temperature to be independent of cooling rate, while experimental results show a weak dependence on cooling rate. The single-α, pdf-α, and active site schemes all agree with the experimental results within roughly a factor of 2. On the basis of our results and previous results where different schemes were tested, the active site scheme is recommended for describing the freezing of ATD and kaolinite particles. We also used our ice nucleation results to determine the ice nucleation active site (INAS) density for the supermicron dust particles tested. Using the data, we show that the INAS densities of supermicron kaolinite and ATD particles studied here are smaller than the INAS densities of submicron kaolinite and ATD particles previously reported in the literature.

16.
J Occup Environ Hyg ; 12 Suppl 1: S7-17, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26252067

RESUMO

Virtually no occupational exposure standards specify the level of risk for the prescribed exposure, and most occupational exposure limits are not based on quantitative risk assessment (QRA) at all. Wider use of QRA could improve understanding of occupational risks while increasing focus on identifying exposure concentrations conferring acceptably low levels of risk to workers. Exposure-response modeling between a defined hazard and the biological response of interest is necessary to provide a quantitative foundation for risk-based occupational exposure limits; and there has been considerable work devoted to establishing reliable methods quantifying the exposure-response relationship including methods of extrapolation below the observed responses. We review several exposure-response modeling methods available for QRA, and demonstrate their utility with simulated data sets.


Assuntos
Exposição Ocupacional/história , Saúde Ocupacional/história , Medição de Risco/métodos , Métodos Epidemiológicos , História do Século XX , Humanos , Modelos Estatísticos , Nível de Efeito Adverso não Observado , Exposição Ocupacional/normas , Saúde Ocupacional/normas
17.
Clin Endocrinol (Oxf) ; 81(2): 294-305, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24593684

RESUMO

OBJECTIVE: To measure a profile of hormones in a group of elite athletes. Increasing awareness of the widespread use of hormones as performance-enhancing agents focusses attention on what may be considered as normal in this unusual group. DESIGN: Blood samples were obtained from 813 volunteer elite athletes from a cross-section of 15 sporting categories. An endocrine profile was measured on a subset of 693. PARTICIPANTS: Volunteer elite athletes. Samples were drawn within two hours of an event at a major national or international competition. MEASUREMENTS: Demographics and hormone profiles were obtained on 454 male and 239 female elite athletes. RESULTS: Hormone profiles showed significant differences in 19 of the 24 measured variables between sexes and between all of the 15 sporting disciplines in men and 11 out of 24 in women. 16.5% of men had low testosterone levels, whereas 13.7% of women had high levels with complete overlap between the sexes. Women had a lean body mass 85% that of men - sufficient to account for sex differences in performance. There were highly significant correlations between many of the measured hormones. CONCLUSIONS: Hormone profiles from elite athletes differ from usual reference ranges. Individual results are dependent on a number of factors including age, gender and physique. Differences in profiles between sports suggest that an individual's profile may contribute to his/her proficiency in a particular sport. The IOC definition of a woman as one who has a 'normal' testosterone level is untenable.


Assuntos
Atletas , Sistema Endócrino/metabolismo , Hormônios/sangue , Esportes/fisiologia , Adulto , Estudos Transversais , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hidrocortisona/sangue , Hormônio Luteinizante/sangue , Masculino , Prolactina/sangue , Receptores de Superfície Celular/sangue , Testosterona/sangue , Tireotropina/sangue , Tri-Iodotironina/sangue , Adulto Jovem
18.
Diabetologia ; 56(9): 2010-20, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23783352

RESUMO

AIMS/HYPOTHESIS: Sirtuin 1 (SIRT1) has emerged as a key metabolic regulator of glucose homeostasis and insulin secretion. Enhanced SIRT1 activity has been shown to be protective against diabetes, although the mechanisms remain largely unknown. The aim of this study was to determine how SIRT1 regulates insulin secretion in the pancreatic beta cell. METHODS: Pancreatic beta cell-specific Sirt1 deletion was induced by tamoxifen injection in 9-week-old Pdx1CreER:floxSirt1 mice (Sirt1BKO). Controls were injected with vehicle. Mice were assessed metabolically via glucose challenge, insulin tolerance tests and physical variables. In parallel, Sirt1 short interfering RNA-treated MIN6 cells (SIRT1KD) and isolated Sirt1BKO islets were used to investigate the effect of SIRT1 inactivation on insulin secretion and gene expression. RESULTS: OGTTs showed impaired glucose disposal in Sirt1BKO mice due to insufficient insulin secretion. Isolated Sirt1BKO islets and SIRT1KD MIN6 cells also exhibited impaired glucose-stimulated insulin secretion. Subsequent analyses revealed impaired α-ketoisocaproic acid-induced insulin secretion and attenuated glucose-induced Ca(2+) influx, but normal insulin granule exocytosis in Sirt1BKO beta cells. Microarray studies revealed a large cluster of mitochondria-related genes, the expression of which was dysregulated in SIRT1KD MIN6 cells. Upon further analysis, we demonstrated an explicit defect in mitochondrial function: the inability to couple nutrient metabolism to mitochondrial membrane hyperpolarisation and reduced oxygen consumption rates. CONCLUSIONS/INTERPRETATION: Taken together, these findings indicate that in beta cells the deacetylase SIRT1 regulates the expression of specific mitochondria-related genes that control metabolic coupling, and that a decrease in beta cell Sirt1 expression impairs glucose sensing and insulin secretion.


Assuntos
Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Sirtuína 1/metabolismo , Animais , Western Blotting , Feminino , Imuno-Histoquímica , Masculino , Potencial da Membrana Mitocondrial/fisiologia , Camundongos , Microscopia Eletrônica de Transmissão , Reação em Cadeia da Polimerase em Tempo Real , Sirtuína 1/genética
19.
Insect Mol Biol ; 22(5): 562-73, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23889463

RESUMO

Vitellogenin (Vg) is best known as a yolk protein precursor. Vg also functions to regulate behavioural maturation in adult honey bee workers, but the underlying molecular mechanisms by which it exerts this novel effect are largely unknown. We used abdominal vitellogenin (vg) knockdown with RNA interference (RNAi) and brain transcriptomic profiling to gain insights into how Vg influences honey bee behavioural maturation. We found that vg knockdown caused extensive gene expression changes in the bee brain, with much of this transcriptional response involving changes in central biological functions such as energy metabolism. vg knockdown targeted many of the same genes that show natural, maturation-related differences, but the direction of change for the genes in these two contrasts was not correlated. By contrast, vg knockdown targeted many of the same genes that are regulated by juvenile hormone (JH) and there was a significant correlation for the direction of change for the genes in these two contrasts. These results indicate that the tight coregulatory relationship that exists between JH and Vg in the regulation of honey bee behavioural maturation is manifest at the genomic level and suggest that these two physiological factors act through common pathways to regulate brain gene expression and behaviour.


Assuntos
Abelhas/genética , Comportamento Animal , Química Encefálica/genética , Proteínas de Insetos/deficiência , Vitelogeninas/deficiência , Animais , Abelhas/metabolismo , Dieta , Feminino , Regulação da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Hormônios Juvenis/deficiência , Hormônios Juvenis/genética , Hormônios Juvenis/metabolismo , Masculino , Vias Neurais/metabolismo , Vias Neurais/fisiologia , Interferência de RNA , Vitelogeninas/genética , Vitelogeninas/metabolismo
20.
J Environ Manage ; 128: 594-601, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23845952

RESUMO

Aspen Plus(®) based simulation models have been developed to design a pyrolysis process for on-site production and utilization of pyrolysis oil from equine waste at the Equine Rehabilitation Center at Morrisville State College (MSC). The results indicate that utilization of all the available waste from the site's 41 horses requires a 6 oven dry metric ton per day (ODMTPD) pyrolysis system but it will require a 15 ODMTPD system for waste generated by an additional 150 horses at the expanded area including the College and its vicinity. For this a dual fluidized bed combustion reduction integrated pyrolysis system (CRIPS) developed at USDA's Agricultural Research Service (ARS) was identified as the technology of choice for pyrolysis oil production. The Aspen Plus(®) model was further used to consider the combustion of the produced pyrolysis oil (bio-oil) in the existing boilers that generate hot water for space heating at the Equine Center. The model results show the potential for both the equine facility and the College to displace diesel fuel (fossil) with renewable pyrolysis oil and alleviate a costly waste disposal problem. We predict that all the heat required to operate the pyrolyzer could be supplied by non-condensable gas and about 40% of the biochar co-produced with bio-oil. Techno-economic Analysis shows neither design is economical at current market conditions; however the 15 ODMTPD CRIPS design would break even when diesel prices reach $11.40/gal. This can be further improved to $7.50/gal if the design capacity is maintained at 6 ODMTPD but operated at 4950 h per annum.


Assuntos
Modelos Econômicos , Gerenciamento de Resíduos/métodos , Animais , Análise Custo-Benefício , Desenho de Equipamento , Calefação , Cavalos , Modelos Teóricos , New York , Óleos , Gerenciamento de Resíduos/economia , Gerenciamento de Resíduos/instrumentação
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