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1.
J Cell Physiol ; 232(9): 2407-2417, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28158906

RESUMO

Alkaptonuria (AKU) is a rare inherited disease resulting from a deficiency of the enzyme homogentisate 1,2-dioxygenase which leads to the accumulation of homogentisic acid (HGA). AKU is characterized by severe cartilage degeneration, similar to that observed in osteoarthritis. Previous studies suggest that AKU is associated with alterations in cytoskeletal organization which could modulate primary cilia structure/function. This study investigated whether AKU is associated with changes in chondrocyte primary cilia and associated Hedgehog signaling which mediates cartilage degradation in osteoarthritis. Human articular chondrocytes were obtained from healthy and AKU donors. Additionally, healthy chondrocytes were treated with HGA to replicate AKU pathology (+HGA). Diseased cells exhibited shorter cilia with length reductions of 36% and 16% in AKU and +HGA chondrocytes respectively, when compared to healthy controls. Both AKU and +HGA chondrocytes demonstrated disruption of the usual cilia length regulation by actin contractility. Furthermore, the proportion of cilia with axoneme breaks and bulbous tips was increased in AKU chondrocytes consistent with defective regulation of ciliary trafficking. Distribution of the Hedgehog-related protein Arl13b along the ciliary axoneme was altered such that its localization was increased at the distal tip in AKU and +HGA chondrocytes. These changes in cilia structure/trafficking in AKU and +HGA chondrocytes were associated with a complete inability to activate Hedgehog signaling in response to exogenous ligand. Thus, we suggest that altered responsiveness to Hedgehog, as a consequence of cilia dysfunction, may be a contributing factor in the development of arthropathy highlighting the cilium as a novel target in AKU.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Alcaptonúria/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Proteínas Hedgehog/metabolismo , Transdução de Sinais , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/patologia , Alcaptonúria/genética , Alcaptonúria/patologia , Cartilagem Articular/patologia , Estudos de Casos e Controles , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Cílios/metabolismo , Cílios/patologia , Proteínas Hedgehog/genética , Ácido Homogentísico/farmacologia , Humanos , Ligantes , Receptor Patched-1/genética , Receptor Patched-1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo
2.
Pflugers Arch ; 467(11): 2337-49, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25724933

RESUMO

Classical work in squid axon reports resting membrane potential is independent of temperature, but our findings suggest that this is not the case for axons in mammalian optic nerve. Refractory period duration changes over 10 times between 37 °C and room temperature, and afterpotential polarity is also acutely temperature sensitive, inconsistent with changes in temperature impacting nerve function only through altered rates of ion channel gating kinetics. Our evidence suggests that the membrane potential is enhanced by warming, an effect reduced by exposure to ouabain. The temperature dependence can be explained if axonal Na(+)/K(+) ATPase continuously expels Na(+) ions that enter axons largely electroneutrally, thereby adding a substantial electrogenic component to the membrane potential. Block of the Na(+) transporter NKCC1 with bumetanide increases refractoriness, like depolarization, indicating that this is a probable route by which Na(+) enters, raising the expectation that the rate of electroneutral Na(+) influx increases with temperature and suggesting a temperature-dependent transmembrane Na(+) cycle that contributes to membrane potential.


Assuntos
Axônios/fisiologia , Fenômenos Eletrofisiológicos/fisiologia , Potenciais da Membrana/fisiologia , Nervo Óptico/fisiologia , Animais , Bumetanida/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ouabaína/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Wistar , Período Refratário Eletrofisiológico/fisiologia , Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/metabolismo , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Temperatura
3.
Br J Hosp Med (Lond) ; 84(2): 1-12, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36848161

RESUMO

BACKGROUND/AIMS: The workload of orthopaedic trainees is rapidly increasing at the expense of training. Trainees are expected to assimilate large quantities of information efficiently. This prospective cohort study explores the learning styles, resource preferences and educational needs of aspiring orthopaedic trainees. METHOD: A 21-item questionnaire was distributed to delegates of an orthopaedic teaching series. Data were obtained pertaining to demographics, visual, aural, read/write and kinaesthetic learning styles, study materials used and teaching exposure. RESULTS: Participants had a strong preference for visual (48.0%) and kinaesthetic (43.0%) learning modalities. Most participants prepared for written exams using online question banks (85.9%), clinical exams using question banks (37.5%) and discussion with colleagues (27.3%), and surgical procedures intraoperatively (43.8%). Only 12.4% of participants felt the teaching they received was consistently adapted to their visual, aural, read/write or kinaesthetic learning preference. CONCLUSIONS: The surgical landscape is rapidly changing. It is vital that trainers take into consideration how budding orthopaedic surgeons learn and make the relevant accommodations, to ensure optimal learning.


Assuntos
Cirurgiões Ortopédicos , Humanos , Estudos Prospectivos , Aprendizagem , Emoções , Reino Unido
4.
Br J Hosp Med (Lond) ; 83(9): 1-12, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36193925

RESUMO

BACKGROUND/AIMS: This study aimed to explore definitions of diversity, and views and attitudes towards diversity in healthcare among future generations of surgical trainees. METHODS: This was a prospective, cohort study via an online questionnaire during a virtual, nationwide surgical course, targeted at aspiring surgeons. RESULTS: Out of 202 participants, 166 met the inclusion criteria. Participants' definitions of diversity most frequently included race, gender and ethnicity, with fewer than 50.0% recognising pregnancy, communication style or political preference in their definition. Of the respondents, 56.0% (93/166) believed that the surgical community did not do enough to encourage diversity. The rising cost of training, lack of diverse role models and dated ideologies were identified as barriers to achieving greater diversity within surgery. CONCLUSIONS: Important components of diversity continue to be under-recognised. Surgery must maximise diversity to attract, support and motivate the next generation of surgeons, for the benefit of the health service and the populations it serves.


Assuntos
Cirurgiões , Estudos de Coortes , Humanos , Estudos Prospectivos , Inquéritos e Questionários
5.
Br J Hosp Med (Lond) ; 83(11): 1-10, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36454064

RESUMO

BACKGROUND/AIMS: An orthopaedic department requires good teamwork and communication to function. This is undermined by bullying and harassment, which may affect the victim's health and career. METHODS: A 26-item questionnaire was sent to all delegates who registered for a free orthopaedic webinar teaching series via email and social media. This study includes the responses from all those who had worked in a UK orthopaedic department. RESULTS: There were 168 respondents from varying backgrounds; 17.9% had experienced bullying or harassment in their orthopaedic department, while 36.3% had witnessed it. Women and people from ethnic minority backgrounds suffered 10.2% and 6.9% higher rates of bullying than their male or white counterparts respectively. CONCLUSIONS: The results demonstrate that despite attempts to reduce bullying in orthopaedics, it remains prevalent, and particularly affects women and those from ethnic minority backgrounds. Orthopaedic departments must adapt to reflect changes in society.


Assuntos
Bullying , Ortopedia , Feminino , Masculino , Humanos , Etnicidade , Grupos Minoritários , Inquéritos e Questionários , Reino Unido
6.
Br J Hosp Med (Lond) ; 83(12): 1-15, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36594776

RESUMO

AIMS/BACKGROUND: This study aims to identify and analyse the factors that influence or discourage junior doctors in the UK and across the world from wanting to pursue a career in orthopaedics. METHODS: A prospective, cohort study was carried out via an online questionnaire targeted at aspiring orthopaedic surgeons. RESULTS: A total of 654 respondents met inclusion criteria; 370 (56.6%) were UK-based and 284 (43.4%) were based abroad. The practical and technical nature of orthopaedics was the biggest influencing factor globally. UK respondents were notably more concerned by the financial impact of training (49%) followed by poor work-life balance (36%). Themes from the comments section revealed concern regarding gender bias and a lack of diverse role models within orthopaedics. CONCLUSIONS: Reducing the cost and length of training, diversification of role models, removal of bias and increasing positive early experiences may help to encourage people of all backgrounds to pursue a career in orthopaedic surgery.


Assuntos
Cirurgiões Ortopédicos , Humanos , Masculino , Feminino , Estudos de Coortes , Escolha da Profissão , Estudos Prospectivos , Sexismo , Inquéritos e Questionários
7.
Br J Hosp Med (Lond) ; 82(11): 1-9, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34817262

RESUMO

BACKGROUND: In recent years, the number of people pursuing a surgical career in the UK has decreased. The COVID-19 pandemic has led to the cancellation of surgical placements for medical students and has affected surgical education. This study evaluates the perceptions and impact of a 1-day virtual surgical conference for medical students considering pursuing a surgical career. METHODS: All delegates of the 2021 Barts and The London International Surgical Conference were invited to participate in two online surveys pre- and post-conference. Data were collected and analysed to evaluate delegates' reasons for attending the conference, and attitudes towards virtual conferences and a surgical career before and after the conference. RESULTS: Out of 132 participants, 106 (80.3%) completed both the pre- and post-conference surveys. Clinical students showed a statistically significant difference in interest in pursuing a surgical career after the conference than before (P=0.03), unlike pre-clinical students (P=0.12). Post-conference, 43 (40.6%) preferred a virtual to a face-to-face conference, which was a slight increase from 40 (37.7%) pre-conference, while 73 (68.9%) and 80 (75.5%) participants favoured virtual talks and presentations respectively. In contrast, only 12 (11.3%) and 21 (19.8%) students preferred workshops and networking virtually. Furthermore, delegates liked the global accessibility and environmentally-friendly nature of virtual conferences but found they can be less engaging and be disrupted by a poor internet connection. CONCLUSIONS: Virtual surgical conferences have many benefits and can help encourage medical students towards a surgical career. They could help bridge the surgical educational gap in medical school during these unprecedented times. Virtual conferences, which have a broader and more inclusive reach, could be an important complement to conventional conferences after the pandemic.


Assuntos
COVID-19 , Estudantes de Medicina , Humanos , Pandemias , SARS-CoV-2 , Faculdades de Medicina
8.
Ann Med Surg (Lond) ; 28: 38-44, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29744051

RESUMO

INTRODUCTION: The Academic Surgical Collaborative (ASC) is a trainee research collaborative (TRC) formed in the UK in October 2014. Three years on, the achievements are presented along with advice for emerging and established TRCs. Methods: A retrospective review of internal, member-maintained ASC records was conducted. Membership numbers, PubMed indexed publications, presentations and prizes awarded were all calculated over time. Google Scholar was used to calculate citations per ASC publication. An online survey was distributed to members to ascertain member satisfaction. RESULTS: With 62 active members (predominantly medical students) the ASC has published 33 PubMed indexed papers over three years, with a mean of 21 citations per paper (SD 89, range 0-491). 54 presentations have been delivered and eight prizes have been awarded for ASC research projects. 60% of ASC members believe the ASC delivers research that improves patient care. Key learning points for the ASC have been the use of a set of resources distributed to new members, the value of regular meetings, close mentoring throughout research projects to develop the skills of junior researchers, encouragement for junior members to present at conferences, and an ongoing focus on research conduct and improving evidence based medicine. CONCLUSIONS: The ASC has fulfilled many of its goals set out at its inception. The ASCs subsequent aims are to enhance existing research training for junior members, advances in the field of core outcome development and also multi-collaborative research.

9.
Clin Teach ; 14(1): 32-36, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26749221

RESUMO

BACKGROUND: Recent reports have shown that in the UK there has been a decrease in interest towards pursuing a surgical career, whereas early exposure to surgery may increase interest. We aimed to assess the effect of a 1-day medical school surgical conference in encouraging attendees to pursue a surgical career. METHODS: All attendees of the 2014 Barts and The London National Undergraduate Surgical conference were invited to participate in an online survey. Data were collected and analysed to evaluate students' reasons for attending the conference, and attitudes to careers in surgery before and after the conference. RESULTS: Of 229 students, 130 (56.8%) completed the survey. Year-12 high-school and preclinical medical students showed a statistically significant difference in interest in pursuing a surgical career after the conference than before it (p = 0.0002 and p = 0.0027, respectively), but clinical medical students demonstrated no such change. CONCLUSION: Attendance at surgical conferences designed for medical students can significantly increase the desire of high-school students and preclinical medical students to pursue a surgical career, but may not have the same effect for clinical medical students. Surgical conferences may act as an effective means of recruiting students towards choosing a surgical career for a certain subset of students.


Assuntos
Cirurgia Geral/educação , Estudantes de Medicina/psicologia , Escolha da Profissão , Congressos como Assunto , Feminino , Humanos , Masculino , Inquéritos e Questionários , Reino Unido
10.
Int J Surg ; 44: 215-222, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28625821

RESUMO

BACKGROUND: In 2013, the Declaration of Helsinki changed to mandate that all research studies involving human subjects, rather than just clinical trials alone, must have a protocol registered in a publicly accessible database prior to the enrolment of the first patient. The objective of this work was to assess the number of research studies involving human participants published in leading journals of plastic surgery that had either published a protocol or registered a protocol with a publicly accessible database. MATERIALS AND METHODS: This systematic review examined all research articles involving human participants published in Plastic and Reconstructive Surgery, The Journal of Plastic Reconstructive and Aesthetic Surgery and The Annals of Plastic Surgery from 1st April 2014-31st March 2015. The primary outcome measure was whether each study had either published or registered a protocol with any mainstream registry database. ClinicalTrials.gov, the International Standard Randomized Control Trial Number (ISRCTN) registry, the WHO (World Health Organisation) International Clinical Trials Registry Platform, The Cochrane Collaboration, the Research Registry, PROSPERO and PubMed were all reviewed. RESULTS: Of 595 included articles, the most common study designs were case series (n = 185, 31.1%). There were 24 randomized controlled trials (RCTs, 4.0%). A total of 24 studies had a protocol registered (4.0%). The most common database to register a protocol was with ClinicalTrials.gov (n = 17). The study design that most commonly had a registered protocol was the RCT (n = 8 of 24, 33.3% of RCTs). Three studies published a protocol in a journal (0.6%). CONCLUSION: Publication or registration of protocols for recent studies involving human participants in major plastic surgery journals is low. There is considerable scope to improve this and guidance is provided.


Assuntos
Protocolos Clínicos/normas , Publicações/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Sistema de Registros/normas , Cirurgia Plástica/normas , Humanos , Procedimentos de Cirurgia Plástica , Projetos de Pesquisa
11.
Int J Surg ; 30: 169-72, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27112835

RESUMO

BACKGROUND: Journals are an important conduit for the publication of research. However, the reporting quality of research has been shown to be lacking. We sought to determine if reporting quality could be improved by mandating compliance with the relevant reporting guidelines during the submission process to a single surgical journal. METHODS: The policy above was implemented in the International Journal of Surgery (IJS) in March 2013. This involved requiring all authors submitting observational studies, randomised controlled trials (RCTs) and systematic reviews to submit completed STROBE, CONSORT and PRISMA Statement checklists respectively along with their paper, making them available to the editor and peer-reviewers. Articles were analysed in three distinct periods from 2012 to 2014, before and after guideline implementation by two independent teams. RESULTS: Our results show that overall STROBE compliance following implementation of the policy increased by a statistically significant 12% (68%-77%, p = 0.00018). Similarly CONSORT compliance increased (50%-70%) as did PRISMA compliance (48%-76%). The items that improved the most were those providing detail on study design, outcome definitions as well as measurement, how patients and quantitative variables were handled during the analyses and discussing limitations and detailing potential sources of bias. CONCLUSION: Implementing a policy mandating the submission of a completed reporting guideline checklist for observational studies, RCTs and systematic reviews can increase compliance. We advocate this measure for other journals and for other study types.


Assuntos
Guias como Assunto/normas , Notificação de Abuso , Editoração/normas , Pesquisa Biomédica/normas , Estudos Clínicos como Assunto/normas , Fidelidade a Diretrizes/normas , Humanos , Publicações/normas , Projetos de Pesquisa/normas
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