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1.
Prev Med Rep ; 43: 102781, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38975283

RESUMO

Objective: No standardised approach exists to provide advice after urgent suspected cancer (USC) referral when cancer is not found. This study aimed to assess preferences and acceptability of receiving advice after USC referral related to: 1) managing ongoing symptoms, 2) responding to early symptoms of other cancers, 3) cancer screening, 4) reducing risks of future cancer. Methods: 2,541 patients from two English NHS Trusts were mailed a survey 1-3 months after having no cancer found following urgent suspected gastrointestinal or head and neck cancer referral. Participants were asked about: willingness to receive advice; prospective acceptability; preferences related to mode, timing and who should provide advice; and previous advice receipt. Results: 406 patients responded (16.0%) with 397 in the final analyses. Few participants had previously received advice, yet most were willing to. Willingness varied by type of advice: fewer were willing to receive advice about early symptoms of other cancers (88.9%) than advice related to ongoing symptoms (94.3%). Acceptability was relatively high for all advice types. Reducing the risk of future cancer advice was more acceptable. Acceptability was lower in those from ethnic minority groups, and with lower levels of education. Most participants preferred to receive advice from a doctor; with results or soon after; either face to face or via the telephone. Conclusions: There is a potential unmet need for advice after USC referral when no cancer is found. Equitable intervention design should focus on increasing acceptability for people from ethnic minority groups and those with lower levels of education.

2.
Med Decis Making ; : 272989X241254828, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828503

RESUMO

BACKGROUND: A risk-stratified breast screening program could offer low-risk women less screening than is currently offered by the National Health Service. The acceptability of this approach may be enhanced if it corresponds to UK women's screening preferences and values. OBJECTIVES: To elicit and quantify preferences for low-risk screening options. METHODS: Women aged 40 to 70 y with no history of breast cancer took part in an online discrete choice experiment. We generated 32 hypothetical low-risk screening programs defined by 5 attributes (start age, end age, screening interval, risk of dying from breast cancer, and risk of overdiagnosis), the levels of which were systematically varied between the programs. Respondents were presented with 8 choice sets and asked to choose between 2 screening alternatives or no screening. Preference data were analyzed using conditional logit regression models. The relative importance of attributes and the mean predicted probability of choosing each program were estimated. RESULTS: Participants (N = 502) preferred all screening programs over no screening. An older starting age of screening, younger end age of screening, longer intervals between screening, and increased risk of dying had a negative impact on support for screening programs (P < 0.01). Although the risk of overdiagnosis was of low relative importance, a decreased risk of this harm had a small positive impact on screening choices. The mean predicted probabilities that risk-adapted screening programs would be supported relative to current guidelines were low (range, 0.18 to 0.52). CONCLUSIONS: A deintensified screening pathway for women at low risk of breast cancer, especially one that recommends a later screening start age, would run counter to women's breast screening preferences. Further research is needed to enhance the acceptability of offering less screening to those at low risk of breast cancer. HIGHLIGHTS: Risk-based breast screening may involve the deintensification of screening for women at low risk of breast cancer.Low-risk screening pathways run counter to women's screening preferences and values.Longer screening intervals may be preferable to a later start age.Work is needed to enhance the acceptability of a low-risk screening pathway.

3.
JMIR Cancer ; 10: e52577, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767941

RESUMO

This viewpoint paper considers the authors' perspectives on the potential role of smartphones, wearables, and other technologies in the diagnosis of cancer. We believe that these technologies could be valuable additions in the pursuit of early cancer diagnosis, as they offer solutions to the timely detection of signals or symptoms and monitoring of subtle changes in behavior that may otherwise be missed. In addition to signal detection, technologies could assist symptom interpretation and guide and facilitate access to health care. This paper aims to provide an overview of the scientific rationale as to why these technologies could be valuable for early cancer detection, as well as outline the next steps for research and development to drive investigation into the potential for smartphones and wearables in this context and optimize implementation. We draw attention to potential barriers to successful implementation, including the difficulty of the development of signals and sensors with sufficient utility and accuracy through robust research with the target group. There are regulatory challenges; the potential for innovations to exacerbate inequalities; and questions surrounding acceptability, uptake, and correct use by the intended target group and health care practitioners. Finally, there is potential for unintended consequences on individuals and health care services including unnecessary anxiety, increased symptom burden, overinvestigation, and inappropriate use of health care resources.

4.
Br J Gen Pract ; 74(743): e387-e392, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38684377

RESUMO

BACKGROUND: Cancer incidence increases with age, so some clinical guidelines include patient age as one of the criteria used to decide whether a patient should be referred through the urgent suspected cancer (USC) pathway. Little is known about how strictly GPs adhere to these age criteria and what factors might influence their referral decisions for younger patients. AIM: To understand GPs' clinical decision making for younger patients with concerning symptoms who do not meet the age criteria for USC referral. DESIGN AND SETTING: Qualitative study using in-depth, semi-structured interviews with GPs working in surgeries across England. METHOD: Participants (n = 23) were asked to recall consultations with younger patients with cancer symptoms, describe factors influencing their clinical decisions, and discuss their overall attitude to age thresholds in cancer referral guidelines. A thematic analysis guided by the Framework approach was used to identify recurring themes. RESULTS: GPs' decision making regarding younger patients was influenced by several factors, including personal experiences, patients' views and behaviour, level of clinical concern, and ability to bypass system constraints. GPs weighted potential benefits and harms of a referral outside guidelines both on the patient and the health system. If clinical concern was high, GPs used their knowledge of local systems to ensure patients were investigated promptly even when not meeting the age criteria. CONCLUSION: While most GPs interpret age criteria flexibly and follow their own judgement and experience when making clinical decisions regarding younger patients, system constraints may be a barrier to timely investigation.


Assuntos
Clínicos Gerais , Neoplasias , Pesquisa Qualitativa , Encaminhamento e Consulta , Humanos , Masculino , Feminino , Neoplasias/psicologia , Clínicos Gerais/psicologia , Adulto , Inglaterra , Pessoa de Meia-Idade , Tomada de Decisão Clínica , Fatores Etários , Atitude do Pessoal de Saúde , Padrões de Prática Médica , Medicina Geral , Entrevistas como Assunto
5.
Mol Ther Methods Clin Dev ; 32(2): 101234, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38558569

RESUMO

Gene therapies and associated technologies are transforming biomedical research and enabling novel therapeutic options for patients living with debilitating and incurable genetic disorders. The vector system based on recombinant adeno-associated viral vectors (AAVs) has shown great promise in recent clinical trials for genetic diseases of multiple organs, such as the liver and the nervous system. Despite recent successes toward the development of novel bioengineered AAV variants for improved transduction of primary human tissues and cells, vectors that can efficiently transduce human Schwann cells (hSCs) have yet to be identified. Here, we report the application of the functional transduction-RNA selection method in primary hSCs for the development of AAV variants for specific and efficient transgene delivery to hSCs. The two identified capsid variants, Pep2hSC1 and Pep2hSC2, show conserved potency for delivery across various in vitro, in vivo, and ex vivo models of hSCs. These novel AAV capsids will serve as valuable research tools, forming the basis for therapeutic solutions for both SC-related disorders or peripheral nervous system injury.

6.
Mol Ther ; 32(3): 818-836, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38297833

RESUMO

Directed evolution of natural AAV9 using peptide display libraries have been widely used in the search for an optimal recombinant AAV (rAAV) for transgene delivery across the blood-brain barrier (BBB) to the CNS following intravenous ( IV) injection. In this study, we used a different approach by creating a shuffled rAAV capsid library based on parental AAV serotypes 1 through 12. Following selection in mice, 3 novel variants closely related to AAV1, AAV-BBB6, AAV-BBB28, and AAV-BBB31, emerged as top candidates. In direct comparisons with AAV9, our novel variants demonstrated an over 270-fold improvement in CNS transduction and exhibited a clear bias toward neuronal cells. Intriguingly, our AAV-BBB variants relied on the LY6A cellular receptor for CNS entry, similar to AAV9 peptide variants AAV-PHP.eB and AAV.CAP-B10, despite the different bioengineering methods used and parental backgrounds. The variants also showed reduced transduction of both mouse liver and human primary hepatocytes in vivo. To increase clinical translatability, we enhanced the immune escape properties of our new variants by introducing additional modifications based on rational design. Overall, our study highlights the potential of AAV1-like vectors for efficient CNS transduction with reduced liver tropism, offering promising prospects for CNS gene therapies.


Assuntos
Barreira Hematoencefálica , Terapia Genética , Humanos , Animais , Camundongos , Terapia Genética/métodos , Capsídeo , Fígado , Peptídeos/genética , Dependovirus , Vetores Genéticos/genética , Transdução Genética
7.
Sports Med Open ; 10(1): 10, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38240903

RESUMO

BACKGROUND: Climbing is an intricate sport composed of various disciplines, holds, styles, distances between holds, and levels of difficulty. In highly skilled climbers the potential for further strength-specific adaptations to increase performance may be marginal in elite climbers. With an eye on the upcoming 2024 Paris Olympics, more climbers are trying to maximize performance and improve training strategies. The relationships between muscular strength and climbing performance, as well as the role of strength in injury prevention, remain to be fully elucidated. This narrative review seeks to discuss the current literature regarding the effect of resistance training in improving maximal strength, muscle hypertrophy, muscular power, and local muscular endurance on climbing performance, and as a strategy to prevent injuries. MAIN BODY: Since sport climbing requires exerting forces against gravity to maintain grip and move the body along the route, it is generally accepted that a climber`s absolute and relative muscular strength are important for climbing performance. Performance characteristics of forearm flexor muscles (hang-time on ledge, force output, rate of force development, and oxidative capacity) discriminate between climbing performance level, climbing styles, and between climbers and non-climbers. Strength of the hand and wrist flexors, shoulders and upper limbs has gained much attention in the scientific literature, and it has been suggested that both general and specific strength training should be part of a climber`s training program. Furthermore, the ability to generate sub-maximal force in different work-rest ratios has proved useful, in examining finger flexor endurance capacity while trying to mimic real-world climbing demands. Importantly, fingers and shoulders are the most frequent injury locations in climbing. Due to the high mechanical stress and load on the finger flexors, fingerboard and campus board training should be limited in lower-graded climbers. Coaches should address, acknowledge, and screen for amenorrhea and disordered eating in climbers. CONCLUSION: Structured low-volume high-resistance training, twice per week hanging from small ledges or a fingerboard, is a feasible approach for climbers. The current injury prevention training aims to increase the level of performance through building tolerance to performance-relevant load exposure and promoting this approach in the climbing field.

8.
Lancet Oncol ; 24(11): 1242-1251, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37922929

RESUMO

BACKGROUND: Following referral for investigation of urgent suspected cancer within the English National Health Service referral system, 7% of referred individuals are diagnosed with cancer. This study aimed to investigate the risk of cancer occurrence within 1-5 years of finding no cancer following an urgent suspected cancer referral. METHODS: This national cohort study used urgent suspected cancer referral data for England from the Cancer Waiting Times dataset and linked it with cancer diagnosis data from the National Cancer Registration dataset. Data were extracted for the eight most commonly referred to urgent suspected cancer referral pathways (breast, gynaecological, head and neck, lower and upper gastrointestinal, lung, skin, and urological) for the period April 1, 2013, to March 31, 2014, with 5-year follow-up for individuals with no cancer diagnosis within 1 year of referral. The primary objective was to investigate the occurrence and type of subsequent cancer in years 1-5 following an urgent suspected cancer referral when no cancer was initially found, both overall and for each of the eight referral pathways. The numbers of subsequent cancers were compared with expected cancer incidence in years 1-5 following referral, using standardised incidence ratios (SIRs) based on matched age-gender distributions of expected cancer incidence in England for the same time period. The analysis was repeated, stratifying by referral group, and by calculating the absolute and expected rate of all cancers and of the same individual cancer as the initial referral. FINDINGS: Among 1·18 million referrals without a cancer diagnosis in years 0-1, there were 63 112 subsequent cancers diagnosed 1-5 years post-referral, giving an absolute rate of 1338 (95% CI 1327-1348) cancers per 100 000 referrals per year (1038 [1027-1050] in females, 1888 [1867-1909] in males), compared with an expected rate of 1054 (1045-1064) cancers per 100 000 referrals per year (SIR 1·27 [95% CI 1·26-1·28]). The absolute rate of any subsequent cancer diagnosis 1-5 years after referral was lowest following suspected breast cancer referral (746 [728-763] cancers per 100 000 referrals per year) and highest following suspected urological (2110 [2070-2150]) or lung cancer (1835 [1767-1906]) referral. For diagnosis of the same cancer as the initial referral pathway, the highest absolute rates were for the urological and lung pathways (1011 [984-1039] and 638 [598-680] cancers per 100 000 referrals per year, respectively). The highest relative risks of subsequent diagnosis of the same cancer as the initial referral pathway were for the head and neck pathway (SIR 3·49 [95% CI 3·22-3·78]) and lung pathway (3·00 [2·82-3·20]). INTERPRETATION: Cancer risk was higher than expected in the 5 years following an urgent suspected cancer referral. The potential for targeted interventions, such as proactive monitoring, safety-netting, and cancer awareness or risk reduction initiatives should be investigated. FUNDING: Cancer Research UK.


Assuntos
Neoplasias Pulmonares , Medicina Estatal , Masculino , Feminino , Humanos , Estudos de Coortes , Risco , Inglaterra/epidemiologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Encaminhamento e Consulta
9.
Mol Ther Methods Clin Dev ; 30: 459-473, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37674904

RESUMO

Recombinant adeno-associated viruses (rAAVs) have emerged as one of the most promising gene therapy vectors that have been successfully used in pre-clinical models of heart disease. However, this has not translated well to humans due to species differences in rAAV transduction efficiency. As a result, the search for human cardiotropic capsids is a major contemporary challenge. We used a capsid-shuffled rAAV library to perform directed evolution in human iPSC-derived cardiomyocytes (hiPSC-CMs). Five candidates emerged, with four presenting high sequence identity to AAV6, while a fifth divergent variant was related to AAV3b. Functional analysis of the variants was performed in vitro using hiPSC-CMs, cardiac organoids, human cardiac slices, non-human primate and porcine cardiac slices, as well as mouse heart and liver in vivo. We showed that cell entry was not the best predictor of transgene expression efficiency. The novel variant rAAV.KK04 was the best-performing vector in human-based screening platforms, exceeding the benchmark rAAV6. None of the novel capsids demonstrate a significant transduction of liver in vivo. The range of experimental models used revealed the value of testing for tropism differences under the conditions of human specificity, bona fide, myocardium and cell type of interest.

10.
BMJ Open ; 13(8): e076661, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620257

RESUMO

INTRODUCTION: Just under half of patients with obstructive sleep apnoea (OSA) also have gastro-oesophageal reflux disease (GORD). These conditions appear to be inter-related and continual positive airway pressure (CPAP) therapy, the gold standard treatment for OSA to prevent airway collapse, has been shown to reduce GORD. As the impact of mandibular advancement devices, a second-line therapy for OSA, on GORD has yet to be investigated, a feasibility study is needed prior to a definitive trial. METHODS: This will be a single-centre, single-blinded, tertiary-care based, interdisciplinary, parallel randomised controlled study. Potential OSA participants presenting to the sleep department will be pre-screened for GORD using validated questionnaires, consented and invited to receive simultaneous home sleep and oesophageal pH monitoring. Those with confirmed OSA and GORD (n=44) will be randomly allocated to receive either CPAP (n=22) or MAD therapy (n=22). Following successful titration and 3 weeks customisation period, participants will repeat the simultaneous sleep and oesophageal pH monitoring while wearing the device. The number of patients screened for recruitment, drop-out rates, patient feedback of the study protocol, costs of interventions and clinical information to inform a definitive study design will be investigated. ETHICS AND DISSEMINATION: Health Research Authority approval has been obtained from the Nottingham 2 Research Ethics Committee, ref:22/EM/0157 and the trial has been registered on ISRCTN (https://doi.org/10.1186/ISRCTN16013232). Definitive findings about the feasibility of doing 24 hour pH oesophageal monitoring while doing a home sleep study will be disseminated via clinical and research networks facilitating valuable insights into the simultaneous management of both conditions. TRIAL REGISTRATION NUMBER: ISRCTN Reg No: 16013232.


Assuntos
Refluxo Gastroesofágico , Apneia Obstrutiva do Sono , Humanos , Estudos de Viabilidade , Placas Oclusais , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/terapia , Apneia Obstrutiva do Sono/terapia , Sono , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Br J Gen Pract ; 73(733): e597-e604, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37365009

RESUMO

BACKGROUND: Cancer is predominantly a disease of older adults. To date there has been little research on the experiences of older adults or their views on the diagnostic pathway. AIM: To gain an improved understanding of the views and experiences of older adults on all aspects of cancer investigation. DESIGN AND SETTING: This was a qualitative study using semi-structured interviews with patients aged ≥70 years. Patients were recruited from primary care in West Yorkshire, UK. METHOD: Data were analysed using a thematic framework analysis. RESULTS: The themes identified in participants' accounts included the patients' process of decision making, the value of having a diagnosis, the patients' experience of cancer investigations, and the impact of the COVID-19 pandemic on the diagnostic pathway. Older adults in this study indicated a clear preference for having clarity on the cause of symptoms and the diagnosis, even in the face of unpleasant investigations. Patients suggested they wanted to be involved in the decision process. CONCLUSION: Older adults who present to primary care with symptoms suggestive of cancer may accept diagnostic testing solely for the benefit of knowing the diagnosis. There was a clear patient preference that referrals and investigations for cancer symptoms should not be deferred or delayed based on age or subjective assessments of frailty. Shared decision making and being involved in the decision-making process are important to patients, regardless of age.


Assuntos
COVID-19 , Neoplasias , Humanos , Idoso , Pandemias , COVID-19/diagnóstico , Neoplasias/diagnóstico , Pesquisa Qualitativa , Atenção Primária à Saúde , Tomada de Decisões
12.
Patient Educ Couns ; 112: 107757, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37099888

RESUMO

OBJECTIVE: This study investigated perspectives of healthcare professionals (HCPs) on the feasibility of giving additional support to patients after cancer is not found following urgent referral. We sought to understand key facilitators or barriers to offering such support. METHODS: A convenience sample of primary and secondary care healthcare professionals (n = 36) participated in semi-structured interviews. Interviews were transcribed verbatim and analysed using Framework Analysis, inductively and deductively, guided by the Theoretical Domains Framework. RESULTS: HCPs indicated that support should be offered if proven to be efficacious. It needs to avoid potential negative consequences such as patient anxiety and information overload. HCPs were more hesitant about whether support could feasibly be offered, due to resource restrictions and perceived remit of the urgent pathway for suspected cancer. CONCLUSION: HCP support after discharge from urgent cancer referral pathways needs to be resource efficient, developed in collaboration with patients and should have proven efficacy. Development of brief interventions for delivery by a range of staff, and use of technology could mitigate barriers to implementation. PRACTICE IMPLICATIONS: Changes to discharge procedures to provide information, endorsement or direction to services could offer much needed support. Additional support would need to overcome logistical challenges and address limited capacity.


Assuntos
Detecção Precoce de Câncer , Neoplasias , Humanos , Estudos de Viabilidade , Pesquisa Qualitativa , Pessoal de Saúde , Neoplasias/diagnóstico , Neoplasias/prevenção & controle , Encaminhamento e Consulta
13.
Hum Gene Ther ; 34(7-8): 273-288, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36927149

RESUMO

The liver is a prime target for in vivo gene therapies using recombinant adeno-associated viral vectors. Multiple clinical trials have been undertaken for this target in the past 15 years; however, we are still to see market approval of the first liver-targeted adeno-associated virus (AAV)-based gene therapy. Inefficient expression of the therapeutic transgene, vector-induced liver toxicity and capsid, and/or transgene-mediated immune responses reported at high vector doses are the main challenges to date. One of the contributing factors to the insufficient clinical outcomes, despite highly encouraging preclinical data, is the lack of robust, biologically and clinically predictive preclinical models. To this end, this study reports findings of a functional evaluation of 6 AAV vectors in 12 preclinical models of the human liver, with the aim to uncover which combination of models is the most relevant for the identification of AAV capsid variant for safe and efficient transgene delivery to primary human hepatocytes. The results, generated by studies in models ranging from immortalized cells, iPSC-derived and primary hepatocytes, and primary human hepatic organoids to in vivo models, increased our understanding of the strengths and weaknesses of each system. This should allow the development of novel gene therapies targeting the human liver.


Assuntos
Dependovirus , Fígado , Humanos , Dependovirus/genética , Fígado/metabolismo , Terapia Genética/métodos , Hepatócitos/metabolismo , Proteínas do Capsídeo/metabolismo , Tropismo , Vetores Genéticos/genética
14.
J Adv Nurs ; 79(7): 2484-2501, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36805610

RESUMO

AIMS: To explore and describe registered nurses' perceptions and experiences of work well-being extending from what inspired them to join the healthcare organization, what created a great day at work for them, through to what may have supported them to stay. DESIGN: Qualitative descriptive study. METHODS: Thirty-nine Australian nurses who resigned in 2021 from two metropolitan healthcare organizations in Victoria were interviewed in 2022, each for 30-60 min. The semi-structured interview transcripts were transcribed verbatim and analysed inductively and thematically. RESULTS: Four themes were constructed for each of the key research questions. Inspiration to join the organizations transpired through organizational reputation, recruitment experiences, right position and right time, fit and feel. A great day at work was created through relationships with colleagues, experiences with managers, adequate resourcing and delivering quality care. Factors contributing to nurses resigning included COVID-19, uncertainty of role, workload and rostering, and finally, not feeling supported, respected and valued. Factors that may have supported the nurses to stay included flexible work patterns and opportunities, improved workplace relationships, workload management and support, and supportive systems and environments. Cutting across these themes were five threads: (1) relationships, (2) communication, (3) a desire to learn and develop, (4) work-life balance and (5) providing quality patient care. CONCLUSIONS: Novel ways of working and supporting individuals, teams and organizations are needed to maintain and sustain nurses. The nurses' inspiration, what created a great day at work, and support needed to stay highlighted the importance of workplace initiatives to build nursing career pathways, provide equitable opportunities for professional development, workload and roster flexibility and implement professional relationship-enhancing actions to foster authentic civility. IMPACT: This study contributes an in-depth exploration of the perceptions and experiences of nurses who resigned from two healthcare organizations and provides a description of (1) what inspired these nurses to initially join the organization, (2) what they perceived created a great day at work for them, (3) the factors contributing to their resignation and (4) what may have supported them to stay. The reasons nurses resign from an organization were identified as complex and multi-factorial, with opportunities for promoting nursing career pathways, addressing equity in opportunities and implementing professional relationship-enhancing actions. These contributions add both context and opportunity to strengthen organizational initiatives to attract, sustain and retain nurses.


Assuntos
COVID-19 , Enfermeiras e Enfermeiros , Humanos , Austrália , Pesquisa Qualitativa , Qualidade da Assistência à Saúde , Local de Trabalho
16.
Mol Ther Methods Clin Dev ; 28: 220-237, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36700121

RESUMO

Recent clinical successes have intensified interest in using adeno-associated virus (AAV) vectors for therapeutic gene delivery. The liver is a key clinical target, given its critical physiological functions and involvement in a wide range of genetic diseases. In the present study, we first investigated the validity of a liver xenograft mouse model repopulated with primary hepatocytes using single-nucleus RNA sequencing (sn-RNA-seq) by studying the transcriptomic profile of human hepatocytes pre- and post-engraftment. Complementary immunofluorescence analyses performed in highly engrafted animals confirmed that the human hepatocytes organize and present appropriate patterns of zone-dependent enzyme expression in this model. Next, we tested a set of rationally designed HSPG de-targeted AAV-LK03 variants for relative transduction performance in human hepatocytes. We used immunofluorescence, next-generation sequencing, and single-nucleus transcriptomics data from highly engrafted FRG mice to demonstrate that the optimally HSPG de-targeted AAV-LK03 displayed a significantly improved lobular transduction profile in this model.

17.
Community Dent Oral Epidemiol ; 51(5): 887-895, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35964230

RESUMO

OBJECTIVES: Dentists and other members of the dental team could raise awareness by talking about oral cancer during routine dental check-ups. A communication guide has been developed to facilitate this. However, it has been suggested that discussions about oral cancer may raise patients' anxiety and this has been documented by dentists as a barrier to having these conversations. The current research aimed to investigate implementation of the communication guide and its impact on the dental patient. METHODS: A consecutive-case sample of adult dental patients attending primary dental care for a routine NHS check-up at one dental practice were invited to take part in the study via letter prior to their appointment. Consultations of participating patients (n = 77) were audio-recorded. Before and after their appointment, patients were asked to rate their current anxiety via the six-item version of Spielberger's State-Trait Anxiety Inventory. Audio recordings of each consultation were reviewed by two raters to determine the extent to which the dentist covered the topics recommended in the communication guide. RESULTS: The dentist informed all patients that they were being checked for oral cancer, spoke about signs and symptoms, and discussed risk factors. However, they rarely recommended where help should be sought or addressed barriers to seeking help. Discussions took an average of 95 s. The extent to which oral cancer was discussed did not correlate with patients' post-appointment anxiety. Patients made positive or neutral responses to the discussions. The few questions that were asked were easily addressed. CONCLUSIONS: As findings are based on one dentist working at one practice, generalization of these results should be cautious. The study indicated that using an evidence-based guide to talk about oral cancer did not appear to raise patients' anxiety in this practice population. This could help to increase awareness of oral cancer in the endeavour to facilitate early cancer diagnosis.


Assuntos
Neoplasias Bucais , Adulto , Humanos , Neoplasias Bucais/diagnóstico , Comunicação , Fatores de Risco , Ansiedade , Assistência Odontológica , Odontólogos
19.
Sports Med Open ; 8(1): 73, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35670925

RESUMO

Attempts to better understand the relationship between training and competition load and injury in football are essential for helping to understand adaptation to training programmes, assessing fatigue and recovery, and minimising the risk of injury and illness. To this end, technological advancements have enabled the collection of multiple points of data for use in analysis and injury prediction. The full breadth of available data has, however, only recently begun to be explored using suitable statistical methods. Advances in automatic and interactive data analysis with the help of machine learning are now being used to better establish the intricacies of the player load and injury relationship. In this article, we examine this recent research, describing the analyses and algorithms used, reporting the key findings, and comparing model fit. To date, the vast array of variables used in analysis as proxy indicators of player load, alongside differences in approach to key aspects of data treatment-such as response to data imbalance, model fitting, and a lack of multi-season data-limit a systematic evaluation of findings and the drawing of a unified conclusion. If, however, the limitations of current studies can be addressed, machine learning has much to offer the field and could in future provide solutions to the training load and injury paradox through enhanced and systematic analysis of athlete data.

20.
Front Physiol ; 13: 899078, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35733996

RESUMO

The aims of this study were to compare power output during a bench press throw (BPT) executed with (BPTbounce) and without (BPT) the barbell bounce technique, and examine the effect of cueing different barbell descent velocities on BPT power output in resistance-trained males. In total, 27 males (age 23.1 ± 2.1 years; body mass 79.4 ± 7.4 kg; height 178.8 ± 5.5 cm; and 4.6 ± 1.9 years of resistance training experience) were recruited and attended one familiarization session and two experimental sessions (EXP 1 and EXP 2). The force-velocity profile during maximal BPT and BPTbounce (randomized order) under different loads (30-60 kg) was established (EXP 1), and the effect of varying external barbell descent velocity cues "slow, medium, and as fast as possible" (i.e., "fast") on the power output for each technique (BPT and BPTbounce) was examined (EXP 2). Comparing two BPT techniques (EXP 1), BPTbounce demonstrated 7.9-14.1% greater average power (p ≤ 0.001, ES = 0.48-0.90), 6.5-12.1% greater average velocity (p ≤ 0.001, ES = 0.48-0.91), and 11.9-31.3% shorter time to peak power (p ≤ 0.001-0.05, ES = 0.33-0.83) across the loads 30-60 kg than BPT. The cueing condition "fast" (EXP 2) resulted in greater power outcomes for both BPT and BPTbounce than "slow." No statistically significant differences in any of the power outcomes were observed between "medium" and "slow" cuing conditions for BPT (p = 0.097-1.000), whereas BPTbounce demonstrated increased average power and velocity under the "medium" cuing condition, compared to "slow" (p = 0.006-0.007, ES = 0.25-0.28). No statistically significant differences were observed in barbell throw height comparing BPT and BPTbounce under each cuing condition (p = 0.225-1.000). Overall, results indicate that both bouncing the barbell and emphasizing barbell descent velocity be considered to improve upper body power in athlete and non-athlete resistance-training programs.

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