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1.
Cell ; 152(5): 1051-64, 2013 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-23452853

RESUMO

Endosomal protein trafficking is an essential cellular process that is deregulated in several diseases and targeted by pathogens. Here, we describe a role for ubiquitination in this process. We find that the E3 RING ubiquitin ligase, MAGE-L2-TRIM27, localizes to endosomes through interactions with the retromer complex. Knockdown of MAGE-L2-TRIM27 or the Ube2O E2 ubiquitin-conjugating enzyme significantly impaired retromer-mediated transport. We further demonstrate that MAGE-L2-TRIM27 ubiquitin ligase activity is required for nucleation of endosomal F-actin by the WASH regulatory complex, a known regulator of retromer-mediated transport. Mechanistic studies showed that MAGE-L2-TRIM27 facilitates K63-linked ubiquitination of WASH K220. Significantly, disruption of WASH ubiquitination impaired endosomal F-actin nucleation and retromer-dependent transport. These findings provide a cellular and molecular function for MAGE-L2-TRIM27 in retrograde transport, including an unappreciated role of K63-linked ubiquitination and identification of an activating signal of the WASH regulatory complex.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Complexos Multiproteicos/metabolismo , Proteínas Nucleares/metabolismo , Transporte Proteico , Proteínas/metabolismo , Actinas/metabolismo , Proteínas de Ligação a DNA/genética , Endossomos/metabolismo , Técnicas de Silenciamento de Genes , Complexo de Golgi/metabolismo , Humanos , Proteínas dos Microfilamentos/metabolismo , Proteínas Nucleares/genética , Proteínas/genética , Interferência de RNA , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitinação
2.
Ann Surg ; 275(3): 617-620, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32511125

RESUMO

OBJECTIVE: To describe the quality of operative performance feedback using evaluation tools commonly used by general surgery residency training programs. SUMMARY OF BACKGROUND DATA: The majority of surgical training programs administer an evaluation through which faculty members may rate and comment on trainee operative performance at the end of the rotation (EOR). Many programs have also implemented the system for improving and measuring procedural learning (SIMPL), a workplace-based assessment tool with which faculty can rate and comment on a trainee's operative performance immediately after a case. It is unknown how the quality of narrative operative performance feedback delivered with these tools compares. METHODS: The authors collected EOR evaluations and SIMPL narrative comments on trainees' operative performance from 3 university-based surgery training programs during the 2016-2017 academic year. Two surgeon raters categorized comments relating to operative skills as being specific or general and as encouraging and/or corrective. Comments were then classified as effective, mediocre, ineffective, or irrelevant. The frequencies with which comments were rated as effective were compared using Chi-square analysis. RESULTS: The authors analyzed a total of 600 comments. 10.7% of EOR and 58.3% of SIMPL operative performance evaluation comments were deemed effective (P < 0.0001). CONCLUSIONS: Evaluators give significantly higher quality operative performance feedback when using workplace-based assessment tools rather than EOR evaluations.


Assuntos
Competência Clínica , Feedback Formativo , Cirurgia Geral/educação , Internato e Residência , Procedimentos Cirúrgicos Operatórios/educação , Procedimentos Cirúrgicos Operatórios/normas , Humanos , Estudos Retrospectivos
3.
Genet Sel Evol ; 52(1): 2, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000665

RESUMO

BACKGROUND: Linear type traits, which reflect the muscular characteristics of an animal, could provide insight into how, in some cases, morphologically very different animals can yield the same carcass weight. Such variability may contribute to differences in the overall value of the carcass since primal cuts vary greatly in price; such variability may also hinder successful genome-based association studies. Therefore, the objective of our study was to identify genomic regions that are associated with five muscularity linear type traits and to determine if these significant regions are common across five different breeds. Analyses were carried out using linear mixed models on imputed whole-genome sequence data in each of the five breeds, separately. Then, the results of the within-breed analyses were used to conduct an across-breed meta-analysis per trait. RESULTS: We identified many quantitative trait loci (QTL) that are located across the whole genome and associated with each trait in each breed. The only commonality among the breeds and traits was a large-effect pleiotropic QTL on BTA2 that contained the MSTN gene, which was associated with all traits in the Charolais and Limousin breeds. Other plausible candidate genes were identified for muscularity traits including PDE1A, PPP1R1C and multiple collagen and HOXD genes. In addition, associated (gene ontology) GO terms and KEGG pathways tended to differ between breeds and between traits especially in the numerically smaller populations of Angus, Hereford, and Simmental breeds. Most of the SNPs that were associated with any of the traits were intergenic or intronic SNPs located within regulatory regions of the genome. CONCLUSIONS: The commonality between the Charolais and Limousin breeds indicates that the genetic architecture of the muscularity traits may be similar in these breeds due to their similar origins. Conversely, there were vast differences in the QTL associated with muscularity in Angus, Hereford, and Simmental. Knowledge of these differences in genetic architecture between breeds is useful to develop accurate genomic prediction equations that can operate effectively across breeds. Overall, the associated QTL differed according to trait, which suggests that breeding for a morphologically different (e.g. longer and wider versus shorter and smaller) more efficient animal may become possible in the future.


Assuntos
Bovinos/genética , Músculo Esquelético/química , Carne Vermelha/análise , Animais , Cruzamento , Bovinos/classificação , Bovinos/crescimento & desenvolvimento , Bovinos/fisiologia , Feminino , Genômica , Modelos Lineares , Masculino , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Sequenciamento Completo do Genoma
4.
Genet Sel Evol ; 52(1): 51, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32842956

RESUMO

BACKGROUND: Temperament traits are of high importance across species. In humans, temperament or personality traits correlate with psychological traits and psychiatric disorders. In cattle, they impact animal welfare, product quality and human safety, and are therefore of direct commercial importance. We hypothesized that genetic factors that contribute to variation in temperament among individuals within a species will be shared between humans and cattle. Using imputed whole-genome sequence data from 9223 beef cattle from three cohorts, a series of genome-wide association studies was undertaken on cattle flight time, a temperament phenotype measured as the time taken for an animal to cover a short-fixed distance after release from an enclosure. We also investigated the association of cattle temperament with polymorphisms in bovine orthologs of risk genes for neuroticism, schizophrenia, autism spectrum disorders (ASD), and developmental delay disorders in humans. RESULTS: Variants with the strongest associations were located in the bovine orthologous region that is involved in several behavioural and cognitive disorders in humans. These variants were also partially validated in independent cattle cohorts. Genes in these regions (BARHL2, NDN, SNRPN, MAGEL2, ABCA12, KIFAP3, TOPAZ1, FZD3, UBE3A, and GABRA5) were enriched for the GO term neuron migration and were differentially expressed in brain and pituitary tissues in humans. Moreover, variants within 100 kb of ASD susceptibility genes were associated with cattle temperament and explained 6.5% of the total additive genetic variance in the largest cattle cohort. The ASD genes with the most significant associations were GABRB3 and CUL3. Using the same 100 kb window, a weak association was found with polymorphisms in schizophrenia risk genes and no association with polymorphisms in neuroticism and developmental delay disorders risk genes. CONCLUSIONS: Our analysis showed that genes identified in a meta-analysis of cattle temperament contribute to neuron development functions and are differentially expressed in human brain tissues. Furthermore, some ASD susceptibility genes are associated with cattle temperament. These findings provide evidence that genetic control of temperament might be shared between humans and cattle and highlight the potential for future analyses to leverage results between species.


Assuntos
Transtorno do Espectro Autista/genética , Comportamento Animal , Bovinos/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Temperamento , Animais , Encéfalo/metabolismo , Bovinos/psicologia , Proteínas Culina/genética , Estudo de Associação Genômica Ampla , Humanos , Hipófise/metabolismo , Receptores de GABA-A/genética , Esquizofrenia/genética
6.
Jt Comm J Qual Patient Saf ; 45(2): 131-143, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30172662

RESUMO

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal death, and its rate and severity have been increasing. Oxytocin is widely recommended for PPH prophylaxis, but consensus is lacking on the dose or duration, leading to disparate and subjective practices. In this study, clinical outcomes were compared before and after introduction of a quality measure: a standardized oxytocin protocol for PPH prophylaxis. METHODS: A retrospective cohort study was conducted of postpartum women ≥24 weeks' gestation delivered from 2010 to 2015. Women were grouped according to delivery pre-protocol (PREP) or post-protocol (POSTP) then subgrouped by specified criteria indicating low risk for PPH. The protocol was standardized for all POSTP women: 60 units of oxytocin over 5.25 hours postdelivery. The primary outcome was a composite: defined treatment for hemorrhage or uterine atony. RESULTS: Of 16,811 women included, 46.3% were PREP (n = 7,791), and 53.7% were POSTP (n = 9,020). A total of 2,315 subjects (13.8%) met low risk for PPH criteria. The primary outcome rate was lower after protocol introduction for all subjects (7.0% vs. 4.6%; p <0.001) and low-risk subset women (3.8% vs. 1.4%; p <0.001). Delivery after protocol introduction was associated with a decreased risk of the primary outcome among all subjects women (adjusted odds ratio [AOR], 0.63; 95% confidence interval [CI] = 0.55-0.72) and low-risk subset women (AOR, 0.33; 95% CI = 0.19-0.57). CONCLUSION: Standardized, higher-dose postpartum oxytocin may be associated with less PPH treatment in this cohort. These findings support standardization and set the stage for a randomized controlled trial.


Assuntos
Ocitócicos/administração & dosagem , Ocitocina/administração & dosagem , Hemorragia Pós-Parto/prevenção & controle , Adolescente , Adulto , Protocolos Clínicos , Feminino , Humanos , Qualidade da Assistência à Saúde , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
7.
Mol Cell ; 39(6): 963-74, 2010 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-20864041

RESUMO

The melanoma antigen (MAGE) family consists of more than 60 genes, many of which are cancer-testis antigens that are highly expressed in cancer and play a critical role in tumorigenesis. However, the biochemical and cellular functions of this enigmatic family of proteins have remained elusive. Here, we identify really interesting new gene (RING) domain proteins as binding partners for MAGE family proteins. Multiple MAGE family proteins bind E3 RING ubiquitin ligases with specificity. The crystal structure of one of these MAGE-RING complexes, MAGE-G1-NSE1, reveals structural insights into MAGE family proteins and their interaction with E3 RING ubiquitin ligases. Biochemical and cellular assays demonstrate that MAGE proteins enhance the ubiquitin ligase activity of RING domain proteins. For example, MAGE-C2-TRIM28 is shown to target p53 for degradation in a proteasome-dependent manner, consistent with its tumorigenic functions. These findings define a biochemical and cellular function for the MAGE protein family.


Assuntos
Antígenos Específicos de Melanoma/metabolismo , Domínios RING Finger , Ubiquitina-Proteína Ligases/metabolismo , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Biocatálise , Proteínas de Transporte/química , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Cristalografia por Raios X , Citoplasma/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Antígenos Específicos de Melanoma/química , Antígenos Específicos de Melanoma/genética , Modelos Moleculares , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Ligação Proteica/fisiologia , Domínios e Motivos de Interação entre Proteínas/fisiologia , Estrutura Quaternária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transfecção , Proteína 28 com Motivo Tripartido , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
8.
Graefes Arch Clin Exp Ophthalmol ; 256(5): 879-884, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29532171

RESUMO

AIM: The aim of this study is to determine whether there is any difference in the quality of life of patients with a blind eye with long-term silicone oil compared to without. METHOD: Patients with either long-term silicone oil in situ (N = 17), defined as a period greater than 6 months duration with no plan for future removal, or those with a phthisical, non oil-filled eye were identified (N = 13). Two validated questionnaires (NEI VFQ-25 and the FACE-Q) that cover indicators for visual function, pain and cosmesis were sent to all patients in the two cohorts. RESULTS: There was no significant difference found in quality of life outcomes between the two groups in terms of visual function, pain or cosmesis. CONCLUSION: The results of this study support a holistic approach to the consent process before vitreoretinal surgery. Patients that may need to undergo multiple vitreoretinal procedures, where the endstage result is a long-term silicone oil fill, should be informed that their functional outcome may be similar to having no surgical intervention.


Assuntos
Cegueira/psicologia , Olho/patologia , Qualidade de Vida/psicologia , Descolamento Retiniano/psicologia , Óleos de Silicone/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia/psicologia , Tamponamento Interno , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Descolamento Retiniano/cirurgia , Perfil de Impacto da Doença , Inquéritos e Questionários , Acuidade Visual/fisiologia , Vitrectomia , Cirurgia Vitreorretiniana
9.
Biochemistry ; 56(42): 5698-5711, 2017 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-28956599

RESUMO

The genome of Bacillus subtilis strain 168 contains the mother cell metabolic gene (mmg) operon that encodes homologues from the methylcitric acid cycle. We showed that the three genes, mmgDE and yqiQ(mmgF), provide three of the five steps of the methylcitric acid cycle. We also showed that the fourth step can be supplied by citB (aconitase), and we suggest that the fifth missing step, the propionyl-CoA synthetase, is probably skipped because the ß-oxidation of methyl-branched fatty acids by the enzymes encoded by mmgABC should produce propionyl-CoA. We also noted interesting enzymology for MmgD and MmgE. First, MmgD is a bifunctional citrate synthase/2-methylcitrate synthase with 2.3-fold higher activity as a 2-methylcitrate synthase. This enzyme catalyzes the formation of either (2S,3R)- or (2R,3S)-2-methylcitrate, but reports of 2-methylcitrate synthases from other species indicated that they produced the (2S,3S) isomer. However, we showed that MmgD and PrpC (from Escherichia coli) in fact produce the same stereoisomer. Second, the MmgE enzyme is not a stereospecific 2-methylcitrate dehydratase because it can dehydrate at least two of the four diastereomers of 2-methylcitrate to yield either (E)-2-methylaconitate or (Z)-2-methylaconitate. We also showed for the first time that the E. coli homologue PrpD exhibited the same lack of stereospecificity. However, the physiological pathways proceed via (Z)-2-methylaconitate, which served as the substrate for the citB enzyme in the synthesis of 2-methylisocitrate. We completed our characterization of this pathway by showing that the 2-methylisocitrate produced by CitB is converted to pyruvate and succinate by the enzyme YqiQ(MmgF).


Assuntos
Bacillus subtilis/metabolismo , Citratos/metabolismo , Óperon/fisiologia , Oxo-Ácido-Liases/metabolismo , Bacillus subtilis/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Hidroliases/genética , Hidroliases/metabolismo , Oxirredução , Oxo-Ácido-Liases/genética , Estereoisomerismo
10.
J Neuroophthalmol ; 34(4): 366-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24705257

RESUMO

A 19-year-old man reported bilateral peripheral visual field loss, hemeralopia, and photophobia. Examination and testing was in keeping with peripheral cone dystrophy. This rare entity is discussed.


Assuntos
Retinose Pigmentar/diagnóstico , Campos Visuais/fisiologia , Humanos , Masculino , Fotofobia/etiologia , Retinose Pigmentar/complicações , Transtornos da Visão/etiologia , Testes de Campo Visual , Adulto Jovem
11.
BMJ Case Rep ; 17(4)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38670565

RESUMO

We report the case of a woman in her 50s who presented headaches, blurred vision, diplopia and loss of peripheral vision. She was treated for normal tension glaucoma based on optic nerve cupping prior to the development of diplopia. Records demonstrated visual field constriction over 4 months despite well-controlled intraocular pressures. Examination revealed decreased visual acuity and visual field constriction. The multifocal electroretinogram was abnormal. After a thorough review of her medical and family history, a concern for cancer-associated retinopathy developed. Blood samples were positive for antiretinal antibodies against 23 kDA and 46 kDA proteins. Cancer screening was recommended as the aetiology for retinopathy was unknown and revealed a left breast lump. Following lumpectomy with adjuvant chemoradiation, her visual acuity normalised and visual field defects completely resolved. This case serves to provide an example that distant systemic symptoms may be a manifestation of the underlying malignancy and the importance of clinical suspicion with prompt evaluation.


Assuntos
Neoplasias da Mama , Eletrorretinografia , Humanos , Feminino , Neoplasias da Mama/complicações , Pessoa de Meia-Idade , Síndromes Paraneoplásicas Oculares/diagnóstico , Doenças Retinianas/etiologia , Doenças Retinianas/diagnóstico , Campos Visuais , Transtornos da Visão/etiologia , Transtornos da Visão/diagnóstico , Acuidade Visual
12.
BMJ Open ; 14(3): e078388, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553054

RESUMO

OBJECTIVES: This study aimed to explore how the unprecedented stressors associated with the COVID-19 pandemic may have contributed to heightened levels of depression and anxiety among pregnant Indigenous persons, and identify protective individual-level factors. DESIGN: The current study used a mixed-methods design including standardised questionnaires and open-ended response questions. Using hierarchical regression models, we examined the extent to which COVID-19-related factors of service disruption (ie, changes to prenatal care, changes to birth plans and social support) were associated with mental well-being. Further, through qualitative analyses of open-ended questions, we examined the coping strategies used by pregnant Indigenous persons in response to the pandemic. SETTING: Participants responded to an online questionnaire consisting of standardised measures from 2020 to 2021. PARTICIPANTS: The study included 336 self-identifying Indigenous pregnant persons in Canada. RESULTS: Descriptive results revealed elevated rates of clinically relevant depression (52.7%) and anxiety (62.5%) symptoms among this population. 76.8% of participants reported prenatal care service disruptions, including appointment cancellations. Thematic analyses identified coping themes of staying informed, social and/or cultural connections and activities, and internal mental well-being strategies. Disruptions to services and decreased quality of prenatal care negatively impacted mental well-being of Indigenous pregnant persons during the COVID-19 pandemic. CONCLUSIONS: Given the potential for mental well-being challenges to persist and long-term effects of perinatal distress, it is important to examine the quality of care that pregnant individuals receive. Service providers should advance policies and practices that promote relationship quality and health system engagement as key factors linked to well-being during the perinatal period for Indigenous persons.


Assuntos
COVID-19 , Pandemias , Feminino , Gravidez , Humanos , COVID-19/epidemiologia , Canadá/epidemiologia , Apoio Social , Cuidado Pré-Natal
13.
BMJ Open ; 14(4): e073639, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38631839

RESUMO

INTRODUCTION: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments. METHODS AND ANALYSIS: This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk. TRIAL REGISTRATION NUMBER: ISRCTN96296121.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/terapia , Doença de Crohn/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Medicina de Precisão , Estudos Prospectivos , Qualidade de Vida
14.
Emerg Med J ; 30(6): 444-6, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22764169

RESUMO

OBJECTIVE: Bell's palsy is a non-life threatening disorder with important functional and psychosocial effects. While recent research has shown significant benefit from treatment with steroids in adults, there have been no conclusive studies demonstrating benefit in children. This study set out to explore the medium term resolution of symptoms in Bell's palsy presenting to the emergency department (ED). PATIENTS AND METHODS: This was a retrospective cohort study of children attending an Irish paediatric ED with a diagnosis of Bell's palsy. Patients were identified via the ED database. The primary outcome measure was resolution at follow-up call (6-18 months after presentation). Secondary outcome measures were ED treatment, imaging and time to resolution of symptoms. RESULTS: There were 48 presentations, involving 45 patients. Left and right-sided palsies were equally represented. Of these, 16 (33%) received prednisolone. MRI was performed in five cases (10%), four were normal and one did not change management. In follow-up telephone contact, of 35 presentations, 28 (80%, 95% CI 63% to 91%) had complete resolution, six (17%, 95% CI 7% to 34%) partial resolution to variable degrees and one patient showed no improvement. Of the 13 patients who had received prednisolone, nine (69%, 95% CI 39% to 91%) had complete resolution; of the 22 patients who were not treated with prednisolone 19 (86%, 95% CI 65% to 97%) had complete resolution (p=0.22). CONCLUSIONS: The majority of children with Bell's palsy have complete resolution of the facial weakness. Steroid use is highly variable and warrants a placebo controlled randomised trial.


Assuntos
Paralisia de Bell/terapia , Serviços Médicos de Emergência/estatística & dados numéricos , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Criança , Estudos de Coortes , Seguimentos , Humanos , Irlanda , Imageamento por Ressonância Magnética , Debilidade Muscular/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
15.
Eur J Ophthalmol ; 33(1): 223-229, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35369780

RESUMO

INTRODUCTION: Performing cataract surgery in the setting of only one seeing-eye has significant benefits but also potential negative consequences for both patient and surgeon. This study investigates the surgical outcomes in patients undergoing cataract surgery on their only seeing-eye. METHODS: A retrospective analysis was conducted in a single tertiary centre of all adult patients who had undergone cataract surgery on their only eye, where the fellow eye had a vision of 1.0 LogMAR or worse. Complication rates and visual outcomes were compared against data from the National Ophthalmology Database (NOD) Audit. RESULTS: 918 patients underwent cataract surgery on their only seeing-eye and had their postoperative visual acuity recorded. The overall unadjusted complication rate was 4.0% (versus 2.5% from NOD data) with the rate of posterior capsule rupture (PCR) being 1.9% (versus 1.14% from NOD data). 72.5% (versus 91.5% from NOD data) of patients attained a post-operative visual acuity of 0.3 LogMAR or better. The grade of surgeon performing the surgery did not have a statistically significant effect on the risk of complications. DISCUSSION: In this cohort of only-eye patients undergoing cataract surgery, there was a small increased risk of operative complications including an increased, unadjusted risk of PCR, and fewer eyes achieved 0.3 LogMAR vision post-operatively compared to the NOD audit data. Grade of surgeon did not have an impact on the complication rate, indicating that with appropriate supervision, trainee surgeons may gain experience in only-eye surgery without additional risk to the patient. Further multicentre studies are recommended to assess reproducibility across units.


Assuntos
Extração de Catarata , Catarata , Oftalmologia , Adulto , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Extração de Catarata/efeitos adversos , Catarata/etiologia , Resultado do Tratamento
16.
Biology (Basel) ; 12(2)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36829502

RESUMO

The burrowing crustacean decapod Nephrops norvegicus is a significant species in European Atlantic and Mediterranean fisheries. Research over the decades has mainly focused on behavioral and physiological aspects related to the burrowing lifestyle, since animals can only be captured by trawls when engaged in emergence on the seabed. Here, we performed a global bibliographic survey of all the scientific literature retrieved in SCOPUS since 1965, and terminology maps were produced with the VOSviewer software to reveal established and emerging research areas. We produced three term-map plots: term clustering, term citation, and term year. The term clustering network showed three clusters: fishery performance, assessment, and management; biological cycles in growth, reproduction, and behavior; and finally, physiology and ecotoxicology, including food products. The term citation map showed that intense research is developed on ecotoxicology and fishery management. Finally, the term year map showed that the species was first studied in its morphological and physiological aspects and more recently in relation to fishery and as a food resource. Taken together, the results indicate scarce knowledge on how burrowing behavior and its environmental control can alter stock assessment, because of the poor use of current and advanced monitoring technologies.

17.
Patient ; 16(1): 67-76, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36169919

RESUMO

OVERVIEW: This paper describes stakeholder involvement and formative qualitative research in the creation of health state descriptions (HSDs) or vignettes for low-risk thyroid cancer. The aim of this project was to engage stakeholders in the contribution of a novel set of HSDs, an important first step in the process of assessing value in thyroid cancer health states. METHODS: We draw upon formative, descriptive qualitative methods, following a multi-stage framework of data collection. We conducted individual semi-structured interviews, cognitive interviews, and focus groups with thyroid cancer patients, community providers, academic subspecialists, and participants with no thyroid cancer diagnosis (N = 31). The HSDs went through several iterations over the course of a year, in collaboration with a highly engaged community advisory board, laying the groundwork for HSDs that are comprehensible, comparable, and appropriate for stated-preference research. FINDINGS: Thyroid cancer survivors compared their experiences with those described in the HSDs. Feedback included concern for the emotional well-being of study participants who would be reading them. Providers were attuned to the need for clinical accuracy and made suggestions to reflect their clinical experience, including for patients with complications or disease progression. The pilot participants with no thyroid cancer were particularly valuable in promoting the need to simplify language and maximize readability. DISCUSSION: Stakeholder engagement was critical to being responsive to feedback as the iterations were refined and presented. Continuous engagement and consultation with multiple sources strengthened the HSDs. A secondary outcome from this project is that stakeholders expressed interest in adapting the HSDs into decision aids for people newly diagnosed with low-risk thyroid cancer.


Assuntos
Neoplasias , Participação dos Interessados , Humanos , Pesquisa Qualitativa , Grupos Focais
18.
Am J Pathol ; 178(2): 935-44, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21281824

RESUMO

Chronic limb ischemia, a complication commonly observed in conjunction with cardiovascular disease, is characterized by insufficient neovascularization despite the up-regulation of pro-angiogenic mediators. One hypothesis is that ischemia induces inhibitory signals that circumvent the normal capillary growth response. FoxO transcription factors exert anti-proliferative and pro-apoptotic effects on many cell types. We studied the regulation of FoxO1 protein in ischemic rat skeletal muscle following iliac artery ligation and in cultured endothelial cells. We found that FoxO1 expression was increased in capillaries within ischemic muscles compared with those from rats that underwent a sham operation. This finding correlated with increased expression of p27(Kip1) and reduced expression of Cyclin D1. Phosphorylated Akt was reduced concurrently with the increase in FoxO1 protein. In skeletal muscle endothelial cells, nutrient stress as well as lack of shear stress stabilized FoxO1 protein, whereas shear stress induced FoxO1 degradation. Endogenous FoxO1 co-precipitated with the E3 ubiquitin ligase murine double minute-2 (Mdm2) in endothelial cells, and this interaction varied in direct relation to the extent of Akt and Mdm2 phosphorylation. Moreover, ischemic muscles had a decreased level of Mdm2 phosphorylation and a reduced interaction between Mdm2 and FoxO1. Our results provide novel evidence that the Akt-Mdm2 pathway acts to regulate endothelial cell FoxO1 expression and illustrate a potential mechanism underlying the pathophysiological up-regulation of FoxO1 under ischemic conditions.


Assuntos
Inibidores da Angiogênese/metabolismo , Células Endoteliais/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Isquemia/metabolismo , Músculos/irrigação sanguínea , Músculos/patologia , Proteínas do Tecido Nervoso/metabolismo , Animais , Capilares/metabolismo , Capilares/patologia , Ciclo Celular , Hipóxia Celular , Células Cultivadas , Células Endoteliais/enzimologia , Células Endoteliais/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Membro Posterior/irrigação sanguínea , Membro Posterior/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isquemia/patologia , Masculino , Músculos/metabolismo , Estresse Oxidativo , Fosforilação , Ligação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Estresse Mecânico , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
Transl Anim Sci ; 6(2): txac038, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35529043

RESUMO

The breeding of sport horses to compete in the Olympic disciplines of show jumping, eventing, and dressage is fast becoming a global industry with the increased use of reproductive technologies, including artificial insemination and embryo transfer. Reproductive technologies have facilitated the dissemination of genetics from elite horses across multiple countries and breeds as breeders are no longer limited by location. Due to this increased level of crossbreeding, there is an increased need for estimated breeding values (EBVs) for sport horse performance that can be compared across breeds and countries. However, the implementation of across-breed or across-country genetic evaluations has been limited by the differences in each studbook's individual breeding programs and genetic evaluations. Consequently, the aim of this review was to compare the genetic evaluations for show jumping of sport horse studbooks worldwide. The top sport horse studbooks in the world according to the World Breeding Federation for Sport Horses Studbook Rankings 2019 were contacted by email to request information on their current breeding programs and genetic evaluations. Twenty-six of the 51 studbooks contacted replied to this request but only 18 of these studbooks conducted their own genetic evaluations or were part of a larger genetic evaluation in their country of origin. The other eight studbooks were not involved in genetic evaluations at present but expressed an interest in the implementation of such in the future. Overall, many differences were identified among the genetic evaluations of each studbook or each country. The definition of show jumping performance differed within each evaluation and the methods and models utilized also differed. Despite some stallions and mares being registered in multiple studbooks or having progeny in multiple studbooks, these differences make comparison of EBVs across studbooks difficult. Further transparency and collaboration of sport horse studbooks with organizations such as Interstallion, will be essential to facilitate any future implementation of international genetic evaluations for show jumping performance.

20.
J Intensive Care Soc ; 23(2): 177-182, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35615227

RESUMO

With the declaration of coronavirus 2019 (COVID-19) as a pandemic, intensive care units across the globe began to prepare for large numbers of patients. For many years, UK Intensive Care Units (ICUs) have been at high capacity, while facing staffing shortages. In order to prepare for the predicted increased work caring for large numbers with COVID-19, staff were redeployed from other clinical areas to help. Many of these staff had no previous ICU experience. In this article, we share our experiences redeploying medical staff from an extensive range of backgrounds, and how we utilised those staff to maximise use of their existing skills, together with reflections from a variety of redeployed staff members.

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