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1.
Mamm Genome ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837040

RESUMO

Hypercholesterolemia raises the risk for cardiovascular complications and overall health. Hypercholesterolemia is common, affecting 10% of the general population of the US, and heritable. Most individuals with hypercholesterolemia have a polygenic predisposition to the condition. Previously we identified a quantitative trait locus, Tachol1, linked to hypercholesterolemia on mouse chromosome 1 (Chr1) in a cross between C57BL/6J (B6) and TALLYHO/JngJ (TH) mice, a polygenic model for human obesity, type 2 diabetes and hyperlipidemia. Subsequently, using congenic mice that carry a TH-derived genomic segment of Chr1 on a B6 background, we demonstrated that the distal segment of Chr1, where Tachol1 maps, is necessary to cause hypercholesterolemia, as well as diet-induced obesity. In this study, we generated overlapping subcongenic lines to the distal segment of congenic region and characterized subcongenic mice carrying the smallest TH region of Tachol1, ~ 16.2 Mb in size (B6.TH-Chr1-16.2 Mb). Both male and female B6.TH-Chr1-16.2 Mb mice showed a significantly increased plasma total cholesterol levels compared to B6 on both chow and high fat (HF) diet. B6.TH-Chr1-16.2 Mb mice also had greater fat mass than B6 on HF diet, without increasing food intake. The gene and protein expression levels of absent in melanoma 2 (Aim2) gene were significantly upregulated in B6.TH-Chr1-16.2 Mb mice compared to B6. In summary, we confirmed the effect of Tachol1 on hypercholesterolemia and diet-induced obesity using subcongenic analysis.

2.
Metab Eng ; 80: 142-150, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37739158

RESUMO

We have developed an electrical-biological hybrid system wherein an engineered microorganism consumes electrocatalytically produced formate from CO2 to supplement the bioproduction of isobutanol, a valuable fuel chemical. Biological CO2 sequestration is notoriously slow compared to electrochemical CO2 reduction, while electrochemical methods struggle to generate carbon-carbon bonds which readily form in biological systems. A hybrid system provides a promising method for combining the benefits of both biology and electrochemistry. Previously, Escherichia coli was engineered to assimilate formate and CO2 in central metabolism using the reductive glycine pathway. In this work, we have shown that chemical production in E. coli can benefit from single carbon substrates when equipped with the RGP. By installing the RGP and the isobutanol biosynthetic pathway into E. coli and by further genetic modifications, we have generated a strain of E. coli that can consume formate and produce isobutanol at a yield of >100% of theoretical maximum from glucose. Our results demonstrate that carbon produced from electrocatalytically reduced CO2 can bolster chemical production in E. coli. This study shows that E. coli can be engineered towards carbon efficient methods of chemical production.


Assuntos
Carbono , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Formiatos/metabolismo , Engenharia Metabólica/métodos
3.
Metab Eng ; 79: 118-129, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37499856

RESUMO

Cyanobacteria are attracting increasing attention as a photosynthetic chassis organism for diverse biochemical production, however, photoautotrophic production remains inefficient. Photomixotrophy, a method where sugar is used to supplement baseline autotrophic metabolism in photosynthetic hosts, is becoming increasingly popular for enhancing sustainable bioproduction with multiple input energy streams. In this study, the commercially relevant diacid, succinate, was produced photomixotrophically. Succinate is an important industrial chemical that can be used for the production of a wide array of products, from pharmaceuticals to biopolymers. In this system, the substrate, glucose, is transported by a proton symporter and the product, succinate, is hypothesized to be transported by another proton symporter, but in the opposite direction. Thus, low pH is required for the import of glucose and high pH is required for the export of succinate. Succinate production was initiated in a pH 7 medium containing bicarbonate. Glucose was efficiently imported at around neutral pH. Utilization of bicarbonate by CO2 fixation raised the pH of the medium. As succinate, a diacid, was produced, the pH of the medium dropped. By repeating this cycle with additional pH adjustment, those contradictory requirements for transport were overcome. pH affects a variety of biological factors and by cycling from high pH to neutral pH processes such as CO2 fixation rates and CO2 solubility can vary. In this study the engineered strains produced succinate during fluctuating pH conditions, achieving a titer of 5.0 g L-1 after 10 days under shake flask conditions. These results demonstrate the potential for photomixotrophic production as a viable option for the large-scale production of succinate.


Assuntos
Ácido Succínico , Simportadores , Ácido Succínico/metabolismo , Dióxido de Carbono/metabolismo , Prótons , Bicarbonatos/metabolismo , Engenharia Metabólica/métodos , Succinatos/metabolismo , Glucose/metabolismo , Concentração de Íons de Hidrogênio
4.
Nano Lett ; 21(14): 6163-6170, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34259523

RESUMO

The use of solid-state electrolyte may be necessary to enable safe, high-energy-density Li metal anodes for next-generation energy storage systems. However, the inhomogeneous local current densities during long-term cycling result in instability and detachment of the Li anode from the electrolyte, which greatly hinders practical application. In this study, we report a new approach to maintain a stable Li metal | electrolyte interface by depositing an amorphous carbon nanocoating on garnet-type solid-state electrolyte. The carbon nanocoating provides both electron and ion conducting capability, which helps to homogenize the lithium metal stripping and plating processes. After coating, we find the Li metal/garnet interface displays stable cycling at 3 mA/cm2 for more than 500 h, demonstrating the interface's outstanding electro-chemomechanical stability. This work suggests amorphous carbon coatings may be a promising strategy for achieving stable Li metal | electrolyte interfaces and reliable Li metal batteries.

5.
N Engl J Med ; 379(22): 2122-2130, 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30485780

RESUMO

BACKGROUND: Younger children in a school grade cohort may be more likely to receive a diagnosis of attention deficit-hyperactivity disorder (ADHD) than their older peers because of age-based variation in behavior that may be attributed to ADHD rather than to the younger age of the children. Most U.S. states have arbitrary age cutoffs for entry into public school. Therefore, within the same grade, children with birthdays close to the cutoff date can differ in age by nearly 1 year. METHODS: We used data from 2007 through 2015 from a large insurance database to compare the rate of ADHD diagnosis among children born in August with that among children born in September in states with and states without the requirement that children be 5 years old by September 1 for enrollment in kindergarten. ADHD diagnosis was determined on the basis of diagnosis codes from the International Classification of Diseases, 9th Revision. We also used prescription records to compare ADHD treatment between children born in August and children born in September in states with and states without the cutoff date of September 1. RESULTS: The study population included 407,846 children in all U.S. states who were born in the period from 2007 through 2009 and were followed through December 2015. The rate of claims-based ADHD diagnosis among children in states with a September 1 cutoff was 85.1 per 10,000 children (309 cases among 36,319 children; 95% confidence interval [CI], 75.6 to 94.2) among those born in August and 63.6 per 10,000 children (225 cases among 35,353 children; 95% CI, 55.4 to 71.9) among those born in September, an absolute difference of 21.5 per 10,000 children (95% CI, 8.8 to 34.0); the corresponding difference in states without the September 1 cutoff was 8.9 per 10,000 children (95% CI, -14.9 to 20.8). The rate of ADHD treatment was 52.9 per 10,000 children (192 of 36,319 children; 95% CI, 45.4 to 60.3) among those born in August and 40.4 per 10,000 children (143 of 35,353 children; 95% CI, 33.8 to 47.1) among those born in September, an absolute difference of 12.5 per 10,000 children (95% CI, 2.43 to 22.4). These differences were not observed for other month-to-month comparisons, nor were they observed in states with non-September cutoff dates for starting kindergarten. In addition, in states with a September 1 cutoff, no significant differences between August-born and September-born children were observed in rates of asthma, diabetes, or obesity. CONCLUSIONS: Rates of diagnosis and treatment of ADHD are higher among children born in August than among children born in September in states with a September 1 cutoff for kindergarten entry. (Funded by the National Institutes of Health.).


Assuntos
Fatores Etários , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estudantes , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Pré-Escolar , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Doenças não Transmissíveis/epidemiologia , Estados Unidos/epidemiologia
6.
Plant Dis ; 105(4): 1101-1107, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32880532

RESUMO

Potential resistance to the guava root-knot nematode, Meloidogyne enterolobii, in 91 selected sweetpotato (Ipomoea batatas [L.] Lam.) genotypes was evaluated in six greenhouse experiments. Ten thousand eggs of M. enterolobii were inoculated on each sweetpotato genotype grown in a 3:1 sand to soil mixture. Sixty days after inoculation, the percentage of total roots with nematode-induced galls was determined, and nematode eggs were extracted from roots. Significant differences (P < 0.001) between sweetpotato genotypes were found in all six tests for gall rating, total eggs, and eggs per gram of root. Resistant sweetpotato genotypes were calculated as final eggs per root system divided by the initial inoculum, where Pf/Pi < 1 (reproduction factor; final egg count divided by initial inoculum of 10,000 eggs), and statistical mean separations were confirmed by Fisher's least significant difference t test. Our results indicated that 19 out of 91 tested sweetpotato genotypes were resistant to M. enterolobii. Some of the susceptible genotypes included 'Covington,' 'Beauregard,' 'NCDM04-001', and 'Hernandez.' Some of the resistant sweetpotato genotypes included 'Tanzania,' 'Murasaki-29,' 'Bwanjule,' 'Dimbuka-Bukulula,' 'Jewel,' and 'Centennial.' Most of the 19 resistant sweetpotato genotypes supported almost no M. enterolobii reproduction, with <20 eggs/g root of M. enterolobii. A number of segregants from a 'Tanzania' × 'Beauregard' cross demonstrated strong resistance to M. enterolobii observed in the 'Tanzania' parent. In collaboration with North Carolina State University sweetpotato breeding program, several genotypes evaluated in these tests are being used to incorporate the observed resistance to M. enterolobii into commercial sweetpotato cultivars.


Assuntos
Ipomoea batatas , Tylenchoidea , Animais , Genótipo , North Carolina , Melhoramento Vegetal , Tanzânia , Tylenchoidea/genética
7.
J Radiol Prot ; 41(2)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33784644

RESUMO

The PODIUM project aims to provide real-time assessments of occupationally exposed workers by tracking their motion and combining this with a simulation of the radiation field. The present work describes the approach that would be taken in mixed neutron-gamma fields, and details the methods for generating and applying an effective dose rate map; the required fluence to effective dose conversion coefficients at intercardinal angles are also presented. A proof-of-concept of the approach is demonstrated using a simple simulated workplace field within a calibration laboratory, with corroborative comparisons made against survey instrument measurements generally confirming good agreement. Simulated tracking of an individual within the facility was performed, recording a 1.25µSv total effective dose and accounting for dose rates as low as 0.5 nSv h-1, which is much lower than anything that could be accurately measured by physical neutron dosemeters in such a field.


Assuntos
Exposição Ocupacional , Monitoramento de Radiação , Proteção Radiológica , Calibragem , Humanos , Nêutrons , Exposição Ocupacional/análise , Doses de Radiação
8.
J Radiol Prot ; 41(1)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33406511

RESUMO

Working Group (WG) 6 'Computational Dosimetry' of the European Radiation Dosimetry Group promotes good practice in the application of computational methods for radiation dosimetry in radiation protection and the medical use of ionising radiation. Its cross-sectional activities within the association cover a large range of current topics in radiation dosimetry, including more fundamental studies of radiation effects in complex systems. In addition, WG 6 also performs scientific research and development as well as knowledge transfer activities, such as training courses. Monte Carlo techniques, including the use of anthropomorphic and other numerical phantoms based on voxelised geometrical models, play a strong part in the activities pursued in WG 6. However, other aspects and techniques, such as neutron spectra unfolding, have an important role as well. A number of intercomparison exercises have been carried out in the past to provide information on the accuracy with which computational methods are applied and whether best practice is being followed. Within the exercises that are still ongoing, the focus has changed towards assessing the uncertainty that can be achieved with these computational methods. Furthermore, the future strategy of WG 6 also includes an extension of the scope toward experimental benchmark activities and evaluation of cross-sections and algorithms, with the vision of establishing a gold standard for Monte Carlo methods used in medical and radiobiological applications.


Assuntos
Proteção Radiológica , Radiometria , Estudos Transversais , Método de Monte Carlo , Nêutrons , Doses de Radiação
9.
Ann Emerg Med ; 76(5): 615-620, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33097121

RESUMO

STUDY OBJECTIVE: The change in reimbursement rates for emergency physician services has yet to be quantified. We attempted to fill this knowledge gap by evaluating the monetary trends in Medicare reimbursement rates over the last 20 years for the most common emergency medicine services. METHODS: We obtained commonly used Current Procedural Terminology (CPT) codes in emergency medicine from the American College of Emergency Physicians website. We queried the Physician Fee Schedule Look-Up Tool from the Centers for Medicare & Medicaid Services for each of the included CPT codes, and we extracted reimbursement data. We adjusted all monetary data for inflation to 2020 US dollars by using changes to the United States consumer price index. Both the average annual and the total percentage change in reimbursement were calculated on the basis of these adjusted trends for all included services. RESULTS: Reimbursement by Medicare for the services decreased by an average of 29.13% from 2000 to 2020 after adjusting for inflation. There was a stable decline in adjusted reimbursement rates throughout the study period, with an average decrease of 1.61% each year. The largest decrease was seen for laceration repairs up to 7.5 cm, with reimbursement rates for all 4 relevant CPT codes decreasing by more than 60%. CONCLUSION: When adjusted for inflation, Medicare reimbursement declined by an average of 29% over the last 20 years for the 20 most common emergency medicine services. Knowledge of these trends is essential to address current controversies in emergency medicine billing adequately and advocate for sustainable payment system reform.


Assuntos
Medicina de Emergência/economia , Reembolso de Seguro de Saúde/tendências , Medicare/tendências , Médicos/economia , Medicina de Emergência/tendências , Medicare/economia , Médicos/tendências , Estados Unidos
10.
Nano Lett ; 18(6): 3926-3933, 2018 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-29787678

RESUMO

Solid-state electrolytes (SSEs) have been widely considered as enabling materials for the practical application of lithium metal anodes. However, many problems inhibit the widespread application of solid state batteries, including the growth of lithium dendrites, high interfacial resistance, and the inability to operate at high current density. In this study, we report a three-dimensional (3D) mixed electron/ion conducting framework (3D-MCF) based on a porous-dense-porous trilayer garnet electrolyte structure created via tape casting to facilitate the use of a 3D solid state lithium metal anode. The 3D-MCF was achieved by a conformal coating of carbon nanotubes (CNTs) on the porous garnet structure, creating a composite mixed electron/ion conductor that acts as a 3D host for the lithium metal. The lithium metal was introduced into the 3D-MCF via slow electrochemical deposition, forming a 3D lithium metal anode. The slow lithiation leads to improved contact between the lithium metal anode and garnet electrolyte, resulting in a low resistance of 25 Ω cm2. Additionally, due to the continuous CNT coating and its seamless contact with the garnet we observed highly uniform lithium deposition behavior in the porous garnet structure. With the same local current density, the high surface area of the porous garnet framework leads to a higher overall areal current density for stable lithium deposition. An elevated current density of 1 mA/cm2 based on the geometric area of the cell was demonstrated for continuous lithium cycling in symmetric lithium cells. For battery operation of the trilayer structure, the lithium can be cycled between the 3D-MCF on one side and the cathode infused into the porous structure on the opposite side. The 3D-MCF created by the porous garnet structure and conformal CNT coating provides a promising direction toward new designs in solid-state lithium metal batteries.

11.
J Environ Manage ; 247: 849-866, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31349180

RESUMO

The review encompasses the development of municipal wastewater treatment process using MBBR from early stages, established application, and recent advancements. An overview of main drivers leading to the MBBR technology development over its early stage is discussed. Biocarriers types and features together with biofilm development and role of extracellular polymeric substances (EPS) are presented, ultimately, addressing the challenge in decreasing startup time required for full operation. Furthermore, the review investigates the state of the art of MBBR technology for nutrient removal (i.e., COD and BOD, nitrogen and phosphorus) through process functionality and configuration of established (e.g., IFAS) and under development (e.g. PN/A) applications. Reactor operational characteristics such as filling fractions, mixing properties, dissolved oxygen requirements, and loading rates are presented and related to full scale examples. Current literature discussing the most recent studies on MBBR capability in reduction and removal of chemicals of emerging concern (CEC) released is presented. Ultimately, high rate carbon and nitrogen removal through A/B stage process are examined in its main operational parameters and its application towards energy neutrality suggesting novel MBBR application to further reduce energy requirements and plant footprint.


Assuntos
Biofilmes , Águas Residuárias , Reatores Biológicos , Nitrogênio , Esgotos , Eliminação de Resíduos Líquidos
12.
J Radiol Prot ; 39(2): 399-421, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30716724

RESUMO

The International Commission on Radiation Units and Measurements is considering revising the definitions of the operational dose quantities used for personal monitoring. This paper investigates the impacts of the proposed changes on the Public Health England two-element ß/γ personal thermoluminescence dosemeter (TLD), in terms of its energy and angle dependences of responses for both skin and whole-body dose assessments. In general, the photon response of the skin element would be unaffected by the proposal, though technical issues may arise during calibration. For body photon doses, the current TLD design still produces acceptable response characteristics in some circumstances, but in general it will need to be redesigned to better match the requirements of the new operational quantity; to that end, a simple adaption is demonstrated that might provide a partial solution. For electron/beta exposures, matching the combined responses of both the body and skin elements to the dose quantities may be more challenging. The performance criteria against which dosemeters are judged may also need to be revised to reflect the proposed change.


Assuntos
Partículas beta , Raios gama , Exposição Ocupacional/análise , Imagens de Fantasmas , Doses de Radiação , Dosímetros de Radiação , Monitoramento de Radiação , Inglaterra , Humanos , Dosímetros de Radiação/normas , Monitoramento de Radiação/instrumentação
13.
J Radiol Prot ; 39(4): R37-R50, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307030

RESUMO

This paper provides a summary of the Education and Training (E&T) activities that have been developed and organised by the European Radiation Dosimetry Group (EURADOS) in recent years and in the case of Training Courses over the last decade. These E&T actions include short duration Training Courses on well-established topics organised within the activity of EURADOS Working Groups (WGs), or one-day events integrated in the EURADOS Annual Meeting (workshops, winter schools, the intercomparison participants' sessions and the learning network, among others). Moreover, EURADOS has recently established a Young Scientist Grant and a Young Scientist Award. The Grant supports young scientists by encouraging them to perform research projects at other laboratories of the EURADOS network. The Award is given in recognition of excellent work developed within the WGs' work programme. Additionally, EURADOS supports the dissemination of knowledge in radiation dosimetry by promoting and endorsing conferences such as the individual monitoring (IM) series, the neutron and ion dosimetry symposia (NEUDOS) and contributions to E&T sessions at specific events.

14.
J Anat ; 232(5): 824-835, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29460315

RESUMO

Sealed osteons are unusual variants of secondary osteons that have received little attention, especially in non-human bones. Sealed osteons are characterized by central canals that are plugged with bone tissue. As with other variants of secondary osteons (e.g. drifting, dumbbell, multi-canal), understanding how and why sealed osteons form can shed light on the mechanisms that regulate normal bone remodeling and how this process can be perturbed with aging and some diseases. In a recent microscopic evaluation of human tibiae obtained after traumatic amputations, 4-5% of the osteons were sealed. It is suggested that this high prevalence reflects occasional localized microscopic ischemia from normal osteonal remodeling; hence sealed osteons are implicated in human skeletal fragility. Therefore, osteon prevalence would be expected to correlate with the bone remodeling seen with aging; for example, showing positive relationships between sealed osteons and the population density of typical secondary osteons (OPD). We evaluated the prevalence of partially sealed (80-99% sealed) and fully sealed osteons with respect to age and variations in OPD in 10 adult human femora (34-71 years) and in various non-human appendicular bones of mature animals that were not of advanced age, including deer calcanei, equine radii and equine third metacarpals. An additional sample of 10 bilateral human femora with unilateral non-cemented total hip replacements (F,+HR) and non-implanted contralateral femora (F,-HR) were evaluated (10 patients; 52-94 years). In non-human bones, sealed + partially sealed osteons were rare (~0.1%) even when having relatively high OPD. When considering sealed + partially sealed osteons in femora from patients without any HR, results showed that 1.6% of the osteons were sealed or partially sealed, which was much lower than anticipated, but this is 10- to 20-fold more than in any of the non-human bones. Additionally, in all bones, sealed + partially sealed osteons were significantly smaller than typical secondary osteons (mean diameters: 125 vs. 272 µm; P < 0.005). In the patients with HR, the percentage of sealed + partially sealed osteons: (i) did not correlate with age, (ii) showed no significant difference between F,-HR and F,+HR (1.9 vs. 2.1%; P = 0.2), and (iii) was positively correlated with OPD (r = 0.67, P = 0.001), which differs from the very weak or lack of correlations in the non-human bones and the other human femur sample. The lack of an age-related relationship, in addition to the very low prevalence of sealed + partially sealed osteons are inconsistent with the idea that they contribute to reduced bone quality seen in aging humans. The small size of sealed and partially sealed osteons, regardless of species affiliation, suggests that they represent closing cones at the termini of some osteons. Available evidence suggests that osteons of primates might have a greater capacity for branching that is associated with closing cones, which might explain the 10-20 times higher prevalence of sealed + partially sealed osteons in the human bones examined in this study.


Assuntos
Fêmur/anatomia & histologia , Ósteon/anatomia & histologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Variação Anatômica , Animais , Cervos , Feminino , Prótese de Quadril , Cavalos , Humanos , Masculino , Pessoa de Meia-Idade
15.
J Radiol Prot ; 38(2): 688-701, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29424365

RESUMO

The ICRU is considering revising the definition of ambient dose equivalent. This paper investigates the impacts of the proposed change on four designs of neutron survey instrument, the GNU, HSREM, LB6411 and Studsvik 2202D, in terms of their respective energy dependences of response and their performances in realistic workplace fields. In some circumstances the current designs of instrument still produce acceptable characteristics, but in general they may need to be re-optimized to better match the requirements of the new operational quantity; to that end, a simple retrofit solution for the GNU is demonstrated. The performance criteria against which instruments are judged may also need to be revised to reflect the proposed change.


Assuntos
Nêutrons , Doses de Radiação , Radiometria/instrumentação
16.
Ir Med J ; 111(5): 758, 2018 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-30379053

RESUMO

Failed surgical mitral valve repair using an annuloplasty ring has traditionally been treated with surgical valve replacement or repair1. For patients at high risk for repeat open heart surgery, placement of a trans-catheter aortic valve (i.e., TAVI valve) within the mitral ring (i.e., Mitral-Valve-in-Ring, MViR) has emerged as a novel alternative treatment strategy2-5 . We describe our experience of a failed mitral valve repair that was successfully treated with a TAVI valve delivered via the trans-septal approach, and summarise the data relating to this emerging treatment strategy.


Assuntos
Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral/cirurgia , Substituição da Valva Aórtica Transcateter , Feminino , Humanos , Pessoa de Meia-Idade , Falha de Tratamento
17.
EMBO Rep ; 16(10): 1334-57, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26265008

RESUMO

In embryonic stem cells (ESCs), gene regulatory networks (GRNs) coordinate gene expression to maintain ESC identity; however, the complete repertoire of factors regulating the ESC state is not fully understood. Our previous temporal microarray analysis of ESC commitment identified the E3 ubiquitin ligase protein Makorin-1 (MKRN1) as a potential novel component of the ESC GRN. Here, using multilayered systems-level analyses, we compiled a MKRN1-centered interactome in undifferentiated ESCs at the proteomic and ribonomic level. Proteomic analyses in undifferentiated ESCs revealed that MKRN1 associates with RNA-binding proteins, and ensuing RIP-chip analysis determined that MKRN1 associates with mRNAs encoding functionally related proteins including proteins that function during cellular stress. Subsequent biological validation identified MKRN1 as a novel stress granule-resident protein, although MKRN1 is not required for stress granule formation, or survival of unstressed ESCs. Thus, our unbiased systems-level analyses support a role for the E3 ligase MKRN1 as a ribonucleoprotein within the ESC GRN.


Assuntos
Células-Tronco Embrionárias/fisiologia , Redes Reguladoras de Genes/genética , Proteínas do Tecido Nervoso/genética , Ribonucleoproteínas/genética , Animais , Citoplasma/metabolismo , Genômica , Camundongos , Proteínas do Tecido Nervoso/química , Proteômica , RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Ribonucleoproteínas/química , Ubiquitina-Proteína Ligases/metabolismo
18.
Ir Med J ; 109(1): 347-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26904794

RESUMO

Testicular pain is a common presentation in the emergency department. The cause includes a wide array of differentials. This report highlights a case of thrombosis of the pampiniform plexus as a rare cause of testicular pain. Doppler ultrasound should be the first line investigation. Symptomatic relief with anti-inflammatory medication should be sufficient for management.


Assuntos
Dor/etiologia , Testículo/irrigação sanguínea , Trombose Venosa/complicações , Humanos , Masculino , Cordão Espermático/diagnóstico por imagem , Testículo/diagnóstico por imagem , Ultrassonografia Doppler , Trombose Venosa/diagnóstico por imagem , Adulto Jovem
19.
Thorax ; 70(3): 251-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25586938

RESUMO

INTRODUCTION: Patients with COPD commonly exhibit pursed-lip breathing during exercise, a strategy that, by increasing intrinsic positive end-expiratory pressure, may optimise lung mechanics and exercise tolerance. A similar role for laryngeal narrowing in modulating exercise airways resistance and the respiratory cycle volume-time course is postulated, yet remains unstudied in COPD. The aim of this study was to assess the characteristics of laryngeal narrowing and its role in exercise intolerance and dynamic hyperinflation in COPD. METHODS: We studied 19 patients (n=8 mild-moderate; n=11 severe COPD) and healthy age and sex matched controls (n=11). Baseline physiological characteristics and clinical status were assessed prior to an incremental maximal cardiopulmonary exercise test with continuous laryngoscopy. Laryngeal narrowing measures were calculated at the glottic and supra-glottic aperture at rest and peak exercise. RESULTS: At rest, expiratory laryngeal narrowing was pronounced at the glottic level in patients and related to FEV1 in the whole cohort (r=-0.71, p<0.001) and patients alone (r=-0.53, p=0.018). During exercise, glottic narrowing was inversely related to peak ventilation in all subjects (r=-0.55, p=0.0015) and patients (r=-0.71, p<0.001) and peak exercise tidal volume (r=-0.58, p=0.0062 and r=-0.55, p=0.0076, respectively). Exercise glottic narrowing was also inversely related to peak oxygen uptake (% predicted) in all subjects (r=-0.65, p<0.001) and patients considered alone (r=-0.58, p=0.014). Exercise inspiratory duty cycle was related to exercise glottic narrowing for all subjects (r=-0.69, p<0.001) and patients (r=-0.62, p<0.001). CONCLUSIONS: Dynamic laryngeal narrowing during expiration is prevalent in patients with COPD and is related to disease severity, respiratory duty cycle and exercise capacity.


Assuntos
Expiração/fisiologia , Glote/fisiopatologia , Inalação/fisiologia , Respiração por Pressão Positiva Intrínseca/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resistência das Vias Respiratórias , Estudos de Casos e Controles , Teste de Esforço , Tolerância ao Exercício , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Ventilação Pulmonar , Volume de Ventilação Pulmonar
20.
Ir Med J ; 108(4): 123-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26016308

RESUMO

Epistaxis affects up to 60% of people. The basic first aid management of epistaxis is clearly stated in the literature and guidelines. Anecdotal evidence would suggest that these principles are not understood by patients and are not being conveyed to patients by their doctors. The aim was to assess current knowledge of epistaxis first aid management and identify the principle source of education in epistaxis control. This was a single centre cross-sectional study. The study population included those presenting to otolaryngology outpatients with epistaxis. 20 patients participated in this study over a 7 month period. Five (25%) patients did not use compression during an episode of epistaxis. Nine (60%) patients that used the compression technique failed to compress the lower one-third of the nose. Only two (10%) of patients identified their GP as having taught them first aid for epistaxis. Knowledge of epistaxis management is poor. Education regarding the basic principles of first aid for epistaxis may reduce morbidity and unnecessary consultations from health professionals.


Assuntos
Epistaxe/prevenção & controle , Primeiros Socorros/métodos , Técnicas Hemostáticas , Educação de Pacientes como Assunto , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , Humanos , Lactente , Pessoa de Meia-Idade , Pressão , Adulto Jovem
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