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1.
Nature ; 593(7857): 74-82, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953415

RESUMO

The land ice contribution to global mean sea level rise has not yet been predicted1 using ice sheet and glacier models for the latest set of socio-economic scenarios, nor using coordinated exploration of uncertainties arising from the various computer models involved. Two recent international projects generated a large suite of projections using multiple models2-8, but primarily used previous-generation scenarios9 and climate models10, and could not fully explore known uncertainties. Here we estimate probability distributions for these projections under the new scenarios11,12 using statistical emulation of the ice sheet and glacier models. We find that limiting global warming to 1.5 degrees Celsius would halve the land ice contribution to twenty-first-century sea level rise, relative to current emissions pledges. The median decreases from 25 to 13 centimetres sea level equivalent (SLE) by 2100, with glaciers responsible for half the sea level contribution. The projected Antarctic contribution does not show a clear response to the emissions scenario, owing to uncertainties in the competing processes of increasing ice loss and snowfall accumulation in a warming climate. However, under risk-averse (pessimistic) assumptions, Antarctic ice loss could be five times higher, increasing the median land ice contribution to 42 centimetres SLE under current policies and pledges, with the 95th percentile projection exceeding half a metre even under 1.5 degrees Celsius warming. This would severely limit the possibility of mitigating future coastal flooding. Given this large range (between 13 centimetres SLE using the main projections under 1.5 degrees Celsius warming and 42 centimetres SLE using risk-averse projections under current pledges), adaptation planning for twenty-first-century sea level rise must account for a factor-of-three uncertainty in the land ice contribution until climate policies and the Antarctic response are further constrained.

2.
Nature ; 580(7802): E4, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32269337

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

3.
Nature ; 573(7774): 408-411, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31534245

RESUMO

The combustion of fossil fuels produces emissions of the long-lived greenhouse gas carbon dioxide and of short-lived pollutants, including sulfur dioxide, that contribute to the formation of atmospheric aerosols1. Atmospheric aerosols can cool the climate, masking some of the warming effect that results from the emission of greenhouse gases1. However, aerosol particulates are highly toxic when inhaled, leading to millions of premature deaths per year2,3. The phasing out of unabated fossil-fuel combustion will therefore provide health benefits, but will also reduce the extent to which the warming induced by greenhouse gases is masked by aerosols. Because aerosol levels respond much more rapidly to changes in emissions relative to carbon dioxide, large near-term increases in the magnitude and rate of climate warming are predicted in many idealized studies that typically assume an instantaneous removal of all anthropogenic or fossil-fuel-related emissions1,4-9. Here we show that more realistic modelling scenarios do not produce a substantial near-term increase in either the magnitude or the rate of warming, and in fact can lead to a decrease in warming rates within two decades of the start of the fossil-fuel phase-out. Accounting for the time required to transform power generation, industry and transportation leads to gradually increasing and largely offsetting climate impacts of carbon dioxide and sulfur dioxide, with the rate of warming further slowed by reductions in fossil-methane emissions. Our results indicate that even the most aggressive plausible transition to a clean-energy society provides benefits for climate change mitigation and air quality at essentially all decadal to centennial timescales.


Assuntos
Poluição do Ar/análise , Política Ambiental , Combustíveis Fósseis , Modelos Teóricos , Atmosfera , Mudança Climática , Política Ambiental/legislação & jurisprudência , Política Ambiental/tendências
4.
Nature ; 571(7765): 335-342, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31316194

RESUMO

Research reported during the past decade has shown that global warming is roughly proportional to the total amount of carbon dioxide released into the atmosphere. This makes it possible to estimate the remaining carbon budget: the total amount of anthropogenic carbon dioxide that can still be emitted into the atmosphere while holding the global average temperature increase to the limit set by the Paris Agreement. However, a wide range of estimates for the remaining carbon budget has been reported, reducing the effectiveness of the remaining carbon budget as a means of setting emission reduction targets that are consistent with the Paris Agreement. Here we present a framework that enables us to track estimates of the remaining carbon budget and to understand how these estimates can improve over time as scientific knowledge advances. We propose that application of this framework may help to reconcile differences between estimates of the remaining carbon budget and may provide a basis for reducing uncertainty in the range of future estimates.


Assuntos
Atmosfera/química , Dióxido de Carbono/análise , Aquecimento Global/prevenção & controle , Aquecimento Global/estatística & dados numéricos , Objetivos , Modelos Teóricos , Temperatura , Planeta Terra , Política Ambiental/legislação & jurisprudência , Retroalimentação , Aquecimento Global/legislação & jurisprudência , Atividades Humanas/legislação & jurisprudência , Cooperação Internacional/legislação & jurisprudência , Paris , Reprodutibilidade dos Testes , Fatores de Tempo , Incerteza
5.
Proc Natl Acad Sci U S A ; 119(34): e2206131119, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35969735

RESUMO

Split air conditioners (ACs) are the most used appliance for space cooling worldwide. The phase-down of refrigerants with high global warming potential (GWP) prescribed by the Kigali Amendment to the Montreal Protocol has triggered a major effort to find less harmful alternative refrigerants. HFC-32 is currently the most common refrigerant to replace HFC-410A in split ACs. The GWP of HFC-32 is about one-third that of HFC-410A but still considerably higher than that of a growing number of nonfluorinated alternatives like propane with a GWP of <1, which have recently become commercially available for split ACs. Here, we show that a switch to propane as an energy-efficient and commercially available low-GWP alternative in split ACs could avoid 0.09 (0.06 to 0.12) °C increase in global temperature by the end of the century. This is significantly more than the 0.03 (0.02 to 0.05) °C avoided warming from a complete switch to HFC-32 in split ACs.


Assuntos
Poluentes Atmosféricos/análise , Aquecimento Global , Hidrocarbonetos Fluorados/análise , Propano , Desenvolvimento Sustentável , Temperatura
6.
J Lipid Res ; 64(4): 100351, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36868360

RESUMO

Sphingosine 1-phosphate lyase (SGPL1) insufficiency (SPLIS) is a syndrome which presents with adrenal insufficiency, steroid-resistant nephrotic syndrome, hypothyroidism, neurological disease, and ichthyosis. Where a skin phenotype is reported, 94% had abnormalities such as ichthyosis, acanthosis, and hyperpigmentation. To elucidate the disease mechanism and the role SGPL1 plays in the skin barrier we established clustered regularly interspaced short palindromic repeats-Cas9 SGPL1 KO and a lentiviral-induced SGPL1 overexpression (OE) in telomerase reverse-transcriptase immortalised human keratinocytes (N/TERT-1) and thereafter organotypic skin equivalents. Loss of SGPL1 caused an accumulation of S1P, sphingosine, and ceramides, while its overexpression caused a reduction of these species. RNAseq analysis showed perturbations in sphingolipid pathway genes, particularly in SGPL1_KO, and our gene set enrichment analysis revealed polar opposite differential gene expression between SGPL1_KO and _OE in keratinocyte differentiation and Ca2+ signaling genesets. SGPL1_KO upregulated differentiation markers, while SGPL1_OE upregulated basal and proliferative markers. The advanced differentiation of SGPL1_KO was confirmed by 3D organotypic models that also presented with a thickened and retained stratum corneum and a breakdown of E-cadherin junctions. We conclude that SPLIS associated ichthyosis is a multifaceted disease caused possibly by sphingolipid imbalance and excessive S1P signaling, leading to increased differentiation and an imbalance of the lipid lamellae throughout the epidermis.


Assuntos
Ictiose , Esfingolipídeos , Humanos , Cálcio/metabolismo , Aldeído Liases/genética , Aldeído Liases/metabolismo , Lisofosfolipídeos/metabolismo , Esfingosina/genética , Esfingosina/metabolismo , Ictiose/genética
7.
Cereb Cortex ; 33(2): 316-329, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-35212373

RESUMO

The male preponderance in autism spectrum disorder (ASD) led to the hypothesis that aspects of female biology are protective against ASD. Females with ASD (ASD-F) report more compensatory behaviors (i.e. "camouflaging") to overcome ASD-related social differences, which may be a mechanism of protection. No studies have examined sex-related brain pathways supporting camouflaging in ASD-F, despite its potential to inform mechanisms underlying the ASD sex bias. We used functional connectivity (FC) to investigate "sex-atypical" and "sex-typical" FC patterns linked to camouflaging in adults with ASD and examined multimodal coherence of findings via structural connectometry. Exploratory associations with cognitive/emotional functioning examined the adaptive nature of FC patterns. We found (i) "sex-atypical" FC patterns linked to camouflaging in the hypothalamus and precuneus and (ii) "sex-typical" patterns in the right anterior cingulate and anterior parahippocampus. Higher hypothalamic FC with a limbic reward cluster also correlated with better cognitive control/emotion recognition. Structural connectometry validated FC results with consistent brain pathways/effect patterns implicated in ASD-F. In summary, "male-typical" and "female-typical" brain connectivity patterns support camouflaging in ASD-F in circuits implicated in reward, emotion, and memory retrieval. "Sex-atypical" results are consistent with fetal steroidogenic/neuroinflammatory hypotheses. However, female genetics/biology may contribute to "female-typical" patterns implicated in camouflaging.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Masculino , Adulto , Humanos , Feminino , Transtorno do Espectro Autista/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Vias Neurais/diagnóstico por imagem
8.
Glob Chang Biol ; 28(2): 349-361, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34558764

RESUMO

Anthropogenic activity is changing Earth's climate and ecosystems in ways that are potentially dangerous and disruptive to humans. Greenhouse gas concentrations in the atmosphere continue to rise, ensuring that these changes will be felt for centuries beyond 2100, the current benchmark for projection. Estimating the effects of past, current, and potential future emissions to only 2100 is therefore short-sighted. Critical problems for food production and climate-forced human migration are projected to arise well before 2100, raising questions regarding the habitability of some regions of the Earth after the turn of the century. To highlight the need for more distant horizon scanning, we model climate change to 2500 under a suite of emission scenarios and quantify associated projections of crop viability and heat stress. Together, our projections show global climate impacts increase significantly after 2100 without rapid mitigation. As a result, we argue that projections of climate and its effects on human well-being and associated governance and policy must be framed beyond 2100.


Assuntos
Mudança Climática , Gases de Efeito Estufa , Efeitos Antropogênicos , Atmosfera , Ecossistema , Humanos
9.
BMC Med Educ ; 22(1): 171, 2022 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-35279153

RESUMO

BACKGROUND: Point-of-care ultrasound (POCUS) graduate medical education is expanding across many specialties, but a lack of trained faculty is a common barrier. Even well-designed faculty development programs struggle with retention, yet little is known about the experiences of practicing physicians learning POCUS. Our objective is to explore the experiences of clinician-educators as they integrate POCUS into their clinical and teaching practices to help inform curriculum design. METHODS: Qualitative study using instrumental case study design to analyze interview data from 18 internal medicine clinician-educators at 3 academic health centers. Interviewees were recruited by program directors at each site to include participants with a range of POCUS use patterns. Interviews took place from July-August 2019. RESULTS: Analysis yielded 6 themes: teaching performance, patient care, curriculum needs, workflow and access, administrative support, and professional engagement. Participants felt POCUS enhanced their teaching skills, clinical decision making, and engagement with patients. The themes highlighted the importance of longitudinal supervision and feedback, streamlined integration of POCUS into clinical workflow, and administrative support of time and resources. Interviewees reported learning and teaching POCUS helped combat burn-out and enhance their sense of professional engagement. CONCLUSIONS: Learning POCUS as a practicing clinician-educator is a complicated endeavor that must take into account mastery of psychomotor skills, existing practice habits, and local institutional concerns. Based upon the themes generated from this study, we make recommendations to help guide POCUS faculty development curriculum design. Although this study focused on internists, the findings are likely generalizable to other specialties with growing interest in POCUS education.


Assuntos
Motivação , Sistemas Automatizados de Assistência Junto ao Leito , Docentes , Humanos , Medicina Interna/educação , Ultrassonografia
10.
J Gen Intern Med ; 35(10): 3081-3086, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32779142

RESUMO

BACKGROUND: Point-of-care ultrasound (POCUS) training is growing across internal medicine graduate medical education, but lack of trained faculty is a barrier to many programs. Interprofessional education (IPE) may offer a solution but must overcome potential biases of trainees. AIM: To evaluate the impact of an interprofessional POCUS training on residents' attitudes towards interprofessional learning and stereotypes. SETTING: Midwestern health sciences university. PARTICIPANTS: Diagnostic medical sonography (DMS) students (n = 13) served as teachers for first-year internal medicine residents (IMR) (n = 49). PROGRAM DESCRIPTION: DMS students participated in a train-the-trainer session to learn teaching strategies via case-based simulation, then coached IMR to acquire images of the kidneys, bladder, and aorta on live models. PROGRAM EVALUATION: Mixed-methods evaluation, including pre-/post-surveys and focus group interviews. The survey response rate was 100% (49/49 IMR). Composite survey scores evaluating residents' attitudes towards IPE and stereotyping of sonographers improved significantly following the intervention. Qualitative analysis of focus group interviews yielded four themes: enhanced respect for other disciplines, implications for future practice, increased confidence of DMS students, and interest in future IPE opportunities. DISCUSSION: Interprofessional POCUS education can improve residents' perceptions towards IPE, increase their level of respect for sonographers, and motivate interest in future interprofessional collaboration.


Assuntos
Internato e Residência , Estudantes de Medicina , Atitude do Pessoal de Saúde , Humanos , Relações Interprofissionais , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia
11.
J Gen Intern Med ; 34(5): 754-757, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30993610

RESUMO

In the context of internal medicine, "triage" is a newly popularized term that refers to constellation of activities related to determining the most appropriate disposition plans for patients, including assessing patients for admissions into the inpatient medicine service. The physician or "triagist" plays a critical role in the transition of care from the outpatient to the inpatient settings, yet little literature exists addressing this particular transition. The importance of this set of responsibilities has evolved over time as health systems become increasingly complex to navigate for physicians and patients. With the emphasis on hospital efficiency metrics such as emergency department throughput and appropriateness of admissions, this type of systems-based thinking is a necessary skill for practicing contemporary inpatient medicine. We believe that triaging admissions is a critical transition in the care continuum and represents an entrustable professional activity that integrates skills across multiple Accreditation Council for Graduate Medical Education (ACGME) competencies that internal medicine residents must master. Specific curricular competencies that address the domains of provider, system, and patient will deliver a solid foundation to fill a gap in skills and knowledge for the triagist role in IM residency training.


Assuntos
Medicina Interna/educação , Admissão do Paciente , Triagem/métodos , Médicos Hospitalares/organização & administração , Humanos , Internato e Residência/organização & administração , Papel do Médico
12.
BMC Med Educ ; 18(1): 321, 2018 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-30591050

RESUMO

BACKGROUND: Point-of-care-ultrasound (POCUS) training is expanding in undergraduate and graduate medical education, but lack of trained faculty is a major barrier. Two strategies that may help mitigate this obstacle are interprofessional education (IPE) and near-peer teaching. The objective of this study was to evaluate a POCUS course in which diagnostic medical sonography (DMS) students served as near-peer teachers for internal medicine residents (IMR) learning to perform abdominal sonography. METHODS: Prior to the IPE workshop, DMS students participated in a train-the-trainer session to practice teaching and communication skills via case-based simulation. DMS students then coached first-year IMR to perform POCUS examinations of the kidney, bladder, and gallbladder on live models. A mixed-methods evaluation of the interprofessional workshop included an objective structured clinical exam (OSCE), course evaluation, and qualitative analysis of focus group interviews. RESULTS: Twenty-four of 24 (100%) IMR completed the OSCE, averaging 97.7/107 points (91.3%) (SD 5.2). Course evaluations from IMR and DMS students were globally positive. Twenty three of 24 residents (96%) and 6/6 DMS students (100%) participated in focus group interviews. Qualitative analysis identified themes related to the learning environment, scanning technique, and suggestions for improvement. IMR felt the interprofessional training fostered a positive learning environment and that the experience complimented traditional faculty-led workshops. Both groups noted the importance of establishing mutual understanding of expectations and suggested future workshops have more dedicated time for DMS student demonstration of scanning technique. CONCLUSION: An interprofessional, near-peer workshop was an effective strategy for teaching POCUS to IMR. This approach may allow broader adoption of POCUS in medical education, especially when faculty expertise is limited.


Assuntos
Medicina Interna/educação , Sistemas Automatizados de Assistência Junto ao Leito , Ensino , Ultrassonografia , Abdome/diagnóstico por imagem , Educação Médica/métodos , Humanos , Grupo Associado , Estudantes de Medicina
13.
J Gen Intern Med ; 31(5): 576-81, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26194641

RESUMO

We present a case of chikungunya virus (CHIKV) in a 39-year-old female who developed an acute febrile illness marked by polyarthralgia and rash after returning from Saint Lucia. This epidemic-prone pathogen is increasingly likely to be encountered by primary care and hospital physicians in the coming months. The virus was first locally transmitted in the Caribbean in December 2013 and has since spread to 44 countries and 47 US states, affecting a suspected 1.2 million people. A mosquito-borne virus, CHIKV causes a severe and symmetric polyarthralgia that can relapse for months to years, creating debilitating illness and profound socioeconomic consequences. Current treatment is limited to supportive measures, which are dependent on nonsteroidal anti-inflammatory drugs. Research into immunomodulatory agents, antiviral therapies, and vaccines is ongoing. Prevention remains key in slowing the spread of disease. Patient education should focus on personal protective measures, such as insect repellant and remaining indoors, while public health departments should implement strategies to control vector breeding grounds. Given the possibility of relapsing and debilitating disease, general internists should consider CHIKV in the differential diagnosis of a returning traveler with acute onset of fever, polyarthralgia, and rash.


Assuntos
Febre de Chikungunya/diagnóstico , Adulto , Artralgia/virologia , Febre de Chikungunya/complicações , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/terapia , Diagnóstico Diferencial , Feminino , Febre/virologia , Humanos , Viagem
14.
J Gen Intern Med ; 31(12): 1490-1495, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27629784

RESUMO

BACKGROUND: Medical residents are routinely entrusted with transitions of care, yet little is known about the duration or content of their perceived responsibility for patients they discharge from the hospital. OBJECTIVE: To examine the duration and content of internal medicine residents' perceived responsibility for patients they discharge from the hospital. The secondary objective was to determine whether specific individual experiences and characteristics correlate with perceived responsibility. DESIGN: Multi-site, cross-sectional 24-question survey delivered via email or paper-based form. PARTICIPANTS: Internal medicine residents (post-graduate years 1-3) at nine university and community-based internal medicine training programs in the United States. MAIN MEASURES: Perceived responsibility for patients after discharge as measured by a previously developed single-item tool for duration of responsibility and novel domain-specific questions assessing attitudes towards specific transition of care behaviors. KEY RESULTS: Of 817 residents surveyed, 469 responded (57.4 %). One quarter of residents (26.1 %) indicated that their responsibility for patients ended at discharge, while 19.3 % reported perceived responsibility extending beyond 2 weeks. Perceived duration of responsibility did not correlate with level of training (P = 0.57), program type (P = 0.28), career path (P = 0.12), or presence of burnout (P = 0.59). The majority of residents indicated they were responsible for six of eight transitional care tasks (85.1-99.3 % strongly agree or agree). Approximately half of residents (57 %) indicated that it was their responsibility to directly contact patients' primary care providers at discharge. and 21.6 % indicated that it was their responsibility to ensure that patients attended their follow-up appointments. CONCLUSIONS: Internal medicine residents demonstrate variability in perceived duration of responsibility for recently discharged patients. Neither the duration nor the content of residents' perceived responsibility was consistently associated with level of training, program type, career path, or burnout, suggesting there may be unmeasured factors such as professional role modeling that shape these perceptions.


Assuntos
Atitude do Pessoal de Saúde , Medicina Interna/tendências , Internato e Residência/tendências , Alta do Paciente/tendências , Inquéritos e Questionários , Estudos Transversais , Feminino , Humanos , Medicina Interna/métodos , Internato e Residência/métodos , Masculino , Estados Unidos/epidemiologia
15.
Skinmed ; 14(1): 68-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27072737

RESUMO

A previously healthy 35-year-old Caucasian woman presented with abrupt onset of erythematous, mildly pruritic plaques surrounding the majority of the nevi present on her neck, chest, back, and upper and lower extremities. She denied history of any recent systemic illnesses and was not taking any medications. On further questioning, the patient reported a recent episode of recurrent herpes labialis 2 weeks prior. The patient has a Fitzpatrick type I skin type with more than 100 brown and reddish brown pigmented macules and papules over her entire body. Plaques ranged in size from 0.4 cm to 1.5 cm depending on the size of the corresponding nevus. The patient's skin was examined in its entirety, and there were no lesions suspicious for melanoma. Two biopsies were performed from the patient's back: one from the nevus itself and another from the surrounding erythematous plaque. The nevocentric erythematous plaques were visible for approximately 1 week at which time they gradually disappeared without treatment. As these areas improved, the patient noticed targetoid lesions on the dorsal hands without associated nevi. Two weeks later, the targetoid lesions had spontaneously resolved.


Assuntos
Eritema Multiforme/patologia , Herpes Labial/complicações , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Adulto , Eritema Multiforme/virologia , Feminino , Humanos , Melanoma , Remissão Espontânea , Neoplasias Cutâneas/virologia
16.
J Cell Sci ; 126(Pt 6): 1366-80, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23418353

RESUMO

Activation of the epidermal growth factor receptor (EGFR) results in internalization and ubiquitin-dependent endosomal sorting, leading to lysosomal degradation. Here we describe the role of the RING-finger-domain-containing protein RNF126 and the related protein, Rabring7 in EGFR endosomal sorting. We demonstrate that RNF126 specifies K48-linked chains with UbcH5b and also functions with Ubc13/Uev1a to form K63-linked chains in vitro. RNF126 and Rabring7 associate with the EGFR through a ubiquitin-binding zinc finger domain and both E3 ubiquitin ligases promote ubiquitylation of EGFR. In the absence of c-Cbl or in cells expressing Cbl-70Z, the binding of RNF126 and Rabring7 to the EGFR is reduced, suggesting that RNF126 and Rabring7 function downstream of c-Cbl. In HeLa cells depleted of either RNF126 or Rabring7 the EGFR is retained in a late endocytic compartment and is inefficiently degraded. In addition, depletion of RNF126 or Rabring7 destabilizes ESCRT-II and reduces the number of multivesicular bodies formed after EGF stimulation. We also show that the depletion of Rabring7 attenuates the degradation of MET and that both RNF126 and Rabring7 regulate the sorting of CXCR4 from an early endocytic compartment. Together these data suggest that RNF126 and Rabring7 play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors.


Assuntos
Endossomos/metabolismo , Receptores ErbB/metabolismo , Fibroblastos/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Técnicas de Silenciamento de Genes , Engenharia Genética , Células HeLa , Humanos , Camundongos , Mutação/genética , Transporte Proteico , Proteólise , Proteínas Proto-Oncogênicas c-cbl/genética , Proteínas Proto-Oncogênicas c-cbl/metabolismo , RNA Interferente Pequeno/genética , Receptores CXCR4/metabolismo , Transgenes/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo
17.
Exp Cell Res ; 320(2): 219-32, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24275455

RESUMO

The ubiquitin proteasome system is central to the regulation of a number of intracellular sorting pathways in mammalian cells including quality control at the endoplasmic reticulum and the internalization and endosomal sorting of cell surface receptors. Here we describe that RNF126, an E3 ubiquitin ligase, is involved in the sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR). In cells transiently depleted of RNF126, the CI-MPR is dispersed into Rab4 positive endosomes and the efficiency of retrograde sorting is delayed. Furthermore, the stable knockdown of RNF126 leads to the lysosomal degradation of CI-MPR and missorting of cathepsin D. RNF126 specifically regulates the sorting of the CI-MPR as other cargo that follow the retrograde sorting route including the cholera toxin, furin and TGN38 are unaffected in the absence of RNF126. Lastly we show that the RING finger domain of RNF126 is required to rescue the decrease in CI-MPR levels, suggesting that the ubiquitin ligase activity of RNF126 is required for CI-MPR sorting. Together, our data indicate that the ubiquitin ligase RNF126 has a role in the retrograde sorting of the CI-MPR.


Assuntos
Receptor IGF Tipo 2/metabolismo , Ubiquitina-Proteína Ligases/fisiologia , Toxina da Cólera/metabolismo , Endocitose/efeitos dos fármacos , Endocitose/genética , Endossomos/efeitos dos fármacos , Endossomos/metabolismo , Furina/metabolismo , Células HEK293 , Células HeLa , Humanos , Glicoproteínas de Membrana/metabolismo , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/genética , RNA Interferente Pequeno/farmacologia , Ubiquitina-Proteína Ligases/antagonistas & inibidores
18.
BMC Med Educ ; 14: 191, 2014 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-25227271

RESUMO

BACKGROUND: There is an increasing prevalence of diabetes. Doctors in training, irrespective of specialty, will have patients with diabetes under their care. The aim of this further evaluation of the TOPDOC Diabetes Study data was to identify if there was any variation in confidence in managing diabetes depending on the geographical location of trainees and career aspirations. METHODS: An online national survey using a pre-validated questionnaire was administered to trainee doctors. A 4-point confidence rating scale was used to rate confidence in managing aspects of diabetes care and a 6-point scale used to quantify how often trainees would contribute to the management of patients with diabetes. Responses were grouped depending on which UK country trainees were based and their intended career choice. RESULTS: Trainees in Northern Ireland reported being less confident in IGT diagnosis, use of IV insulin and peri-operative management and were less likely to adjust oral treatment, contact specialist, educate lifestyle, and optimise treatment. Trainees in Scotland were less likely to contact a specialist, but more likely to educate on lifestyle, change insulin, and offer follow-up advice. In Northern Ireland, Undergraduate (UG) and Postgraduate (PG) training in diagnosis was felt less adequate, PG training in emergencies less adequate, and reporting of need for further training higher. Trainees in Wales felt UG training to be inadequate. In Scotland more trainees felt UG training in diagnosis and optimising treatment was inadequate. Physicians were more likely to report confidence in managing patients with diabetes and to engage in different aspects of diabetes care. Aspiring physicians were less likely to feel the need for more training in diabetes care; however a clear majority still felt they needed more training in all aspects of care. CONCLUSIONS: Doctors in training have poor confidence levels dealing with diabetes related care issues. Although there is variability between different groups of trainees according to geographical location and career aspirations, this is a UK wide issue. There should be a UK wide standardised approach to improving training for junior doctors in diabetes care with local training guided by specific needs.


Assuntos
Diabetes Mellitus/terapia , Educação Médica/normas , Competência Clínica/estatística & dados numéricos , Coleta de Dados , Diabetes Mellitus/diagnóstico , Educação Médica/métodos , Humanos , Avaliação das Necessidades , Médicos/psicologia , Médicos/normas , Inquéritos e Questionários , Reino Unido
19.
J Autism Dev Disord ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536637

RESUMO

PURPOSE:  Most assessment tools used to diagnose and characterize autism spectrum disorder (ASD) were developed for in-person administration. The coronavirus disease 2019 (COVID-19) pandemic resulted in the need to adapt traditional assessment tools for online administration with only minimal evidence to support validity of such practices. METHODS: The current exploratory study compared scores from online administration of the Kaufman Brief Intelligence Test, Second Edition (KBIT-2) during the pandemic to scores derived from follow-up testing using traditional in-person administration. Participants were 47 children and adolescents (M age = 9.48 years, SD = 4.06; 68.10% male) who participated in a telehealth diagnostic evaluation for ASD that included online administration of the KBIT-2. Participants were invited to complete the KBIT-2 a second time during an in-person study visit. RESULTS: Pearson's correlation coefficients suggested acceptable to good reliability between online and in-person administration. Although most participants' online and in-person scores were within one standard deviation of each other, results suggested statistically significant differences between scores derived from the two modalities. Additionally, 19-26% of participants (depending on domain examined) had scores that differed by more than one standard deviation. Notably, all but one of these participants was under the age of 12 years. CONCLUSION: Findings suggest that online administration of the KBIT-2 is likely appropriate for older children and adolescents with ASD. However, additional research is needed to test online administration of intellectual assessments for children with ASD.

20.
Vaccine ; 42(4): 937-944, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38245390

RESUMO

Increased risks associated with Coronavirus disease 2019 (COVID-19) among individuals with autism spectrum disorder (ASD) combined with previous reports of heightened vaccine hesitancy among parents of children with ASD indicate the need for a better understanding of attitudes and behaviors related to COVID-19 vaccines among the ASD community. This study is the first to our knowledge to use a mixed-methods approach to understand attitudes toward COVID-19 vaccines among parents of children with ASD and autistic adults. Participants were 135 members of the ASD community residing in the state of Arizona (99 parents of children with ASD and 36 autistic adults) who responded to the third (Spring 2021) and fourth (Summer 2021) time points of a larger longitudinal online survey. Quantitative findings indicated that autistic adults had slightly more favorable attitudes toward COVID-19 vaccines than parents, and attitudes in both subsamples became more positive over time. However, both parents and autistic adults reported COVID-19 vaccine uptake that was consistent with or better than the general population at both time points. Thematic analysis of responses to open-ended questions identified five themes that characterized factors that contributed to participants' decisions about COVID-19 vaccinations, including: (1) Desiring a Return to Normalcy, (2) Protection of Self and Others, (3) Previous Experience with COVID-19 (4) Science and Medical Professionals,and (5) Skepticism Regarding Safety, Effectiveness, and Need. Current findings combined with emerging literature paint a relatively optimistic picture about COVID-19 vaccine acceptance in the ASD community.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , COVID-19 , Criança , Adulto , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Pais
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