Measuring and increasing rates of self-isolation in the context of COVID-19: a systematic review with narrative synthesis.

OBJECTIVES: This study aimed to investigate (1) definitions of self-isolation used during the COVID-19 pandemic; (2) measures used to quantify adherence and their reliability, validity, and acceptability; (3) rates of self-isolation adherence; and (4) factors associated with adherence. STUDY DESIGN: This was a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Synthesis Without Meta-analysis (PRISMA) guidelines (PROSPERO record CRD42022377820). METHODS: MEDLINE, PsycINFO, Embase, Web of Science, PsyArXiv, medRxiv, and grey literature sources were searched (1 January 2020 to 13 December 2022) using terms related to COVID-19, isolation, and adherence. Studies were included if they contained original, quantitative data of self-isolation adherence during the COVID-19 pandemic. We extracted definitions of self-isolation, measures used to quantify adherence, adherence rates, and factors associated with adherence. RESULTS: We included 45 studies. Self-isolation was inconsistently defined. Four studies did not use self-report measures. Of 41 studies using self-report, one reported reliability; another gave indirect evidence for the lack of validity of the measure. Rates of adherence to self-isolation for studies with only some concerns of bias were 51%-86% for COVID-19 cases, 78%-94% for contacts, and 16% for people with COVID-19-like symptoms. There was little evidence that self-isolation adherence was associated with sociodemographic or psychological factors. CONCLUSIONS: There was no consensus in defining, operationalising, or measuring self-isolation, resulting in significant risk of bias in included studies. Future definitions of self-isolation should state behaviours to be enacted and duration. People recommended to self-isolate should be given support. Public health campaigns should aim to increase perceived effectiveness of self-isolation and promote accurate information about susceptibility to infection.

COVID-19 survey burden for health care workers: literature review and audit.

OBJECTIVES: Concerns have been raised about the quantity and quality of research conducted during the COVID-19 pandemic, particularly related to the mental health and wellbeing of health care workers (HCWs). For understanding the volume, source, methodological rigour and degree of overlap in COVID-19, studies were conducted among HCWs in the United Kingdom (UK). STUDY DESIGN: Mixed methods approach, literature review and audit. METHODS: First, a literature review of published research studies and second, an audit of studies HCWs have been invited to complete. For the literature review, we searched Medline, PsycINFO and Nexis, webpages of three medical organisations (Royal Society of Medicine, Royal College of Nursing and British Medical Association), and the YouGov website. For the audit, a non-random purposive sample of six HCWs from different London NHS Trusts reviewed email, WhatsApp and SMS messages they received for study invitations. RESULTS: The literature review identified 27 studies; the audit identified 70 study invitations. Studies identified by the literature review were largely of poor methodological rigour: only eight studies (30%) provided response rate, one study (4%) reported having ethical approval, and one study (4%) reported funding details. There was substantial overlap in the topics measured. In the audit, volunteers received a median of 12 invitations. The largest number of study invitations were for national surveys (n = 23), followed by local surveys (n = 16) and research surveys (n = 8). CONCLUSION: HCWs have been asked to complete numerous surveys that frequently have methodological shortcomings and overlapping aims. Many studies do not follow scientific good-practice and generate questionable, non-generalisable results.

Tiered restrictions for COVID-19 in England: knowledge, motivation and self-reported behaviour.

OBJECTIVES: To test whether public knowledge and confidence in one's understanding of the local restrictions, motivation to adhere to local restrictions, and self-reported behaviour (going out for exercise, to work, socially) differed according to tier level. STUDY DESIGN: Cross-sectional, nationally representative, online survey of 1728 participants living in England (data collection: 26 to 28 October 2020). METHODS: We conducted logistic regression analyses to investigate whether knowledge of restrictions, confidence in knowledge of restrictions, motivation to adhere to restrictions, and self-reported behaviour were associated with personal characteristics and tier. RESULTS: Between 81% (tier 2) and 89% (tier 3) of participants correctly identified which tier they lived in. Knowledge of specific restrictions was variable. 73% were confident that they understood which tier was in place in their local area, whereas 71% were confident they understood the guidance in their local area. Confidence was associated with being older and living in a less deprived area. 73% were motivated to adhere to restrictions in their local area. Motivation was associated with being female and older. People living in tiers with greater restrictions were less likely to report going out to meet people from another household socially; reported rates of going out for exercise and for work did not differ. CONCLUSIONS: Although recognition of local tier level was high, knowledge of specific guidance for tiers was variable. There was some indication that nuanced guidance (e.g. behaviour allowed in some settings but not others) was more poorly understood than guidance which was absolute (i.e. behaviour is either allowed or not allowed).

COVID-19 vaccination acceptability in the UK at the start of the vaccination programme: a nationally representative cross-sectional survey (CoVAccS - wave 2).

OBJECTIVES: Investigate factors associated with the intention to have the COVID-19 vaccination following initiation of the UK national vaccination programme. STUDY DESIGN: An online cross-sectional survey completed by 1500 adults (13th-15th January 2021). METHODS: Linear regression analyses were used to investigate associations between intention to be vaccinated for COVID-19 and sociodemographic factors, previous influenza vaccination, attitudes and beliefs about COVID-19 and COVID-19 vaccination and vaccination in general. Participants' main reasons for likely vaccination (non-)uptake were also solicited. RESULTS: 73.5% of participants (95% CI 71.2%, 75.7%) reported being likely to be vaccinated against COVID-19, 17.3% (95% CI 15.4%, 19.3%) were unsure, and 9.3% (95% CI 7.9%, 10.8%) reported being unlikely to be vaccinated. The full regression model explained 69.8% of the variance in intention. Intention was associated with: having been/intending to be vaccinated for influenza last winter/this winter; stronger beliefs about social acceptability of a COVID-19 vaccine; the perceived need for vaccination; adequacy of information about the vaccine; and weaker beliefs that the vaccine is unsafe. Beliefs that only those at serious risk of illness should be vaccinated and that the vaccines are just a means for manufacturers to make money were negatively associated with vaccination intention. CONCLUSIONS: Most participants reported being likely to get the COVID-19 vaccination. COVID-19 vaccination attitudes and beliefs are a crucial factor underpinning vaccine intention. Continued engagement with the public with a focus on the importance and safety of vaccination is recommended.

Learning about COVID-19 across borders: public health information and adherence among international travellers to the UK.

OBJECTIVE: Public health control measures at borders have long been central to national strategies for the prevention and containment of infectious diseases. Travel was inevitably associated with the rapid global transmission of COVID-19. In the UK, public health authorities tried to reduce the risks of travel-associated spread by providing public health information at ports of entry. This study investigates risk assessment processes, decision-making and adherence to official advice among international travellers, to provide evidence for future policy on the provision of public health information to facilitate safer international travel. STUDY DESIGN: This study is a qualitative study evaluation. METHOD: International air passengers arriving at the London Heathrow Airport on scheduled flights from China and Singapore were approached for interview after consenting to contact in completed surveys. Semi-structured interviews were conducted by telephone, using two topic guides to explore views of official public health information and self-isolation. Interview transcripts were coded and analysed thematically. RESULTS: Participants regarded official advice from Public Health England as adequate at the time, despite observing differences with intervention measures implemented in their countries of departure. Most participants also described adopting precautionary measures, including self-isolation and the use of face coverings that went beyond official advice, but reported adherence to guidance on contacting health authorities was more variable. Adherence to the official guidance was informed by the perceived salience of specific transmission possibilities and containment measures assessed in relation to participants' local social and institutional environments. CONCLUSION: Analysis of study findings demonstrates that international air travellers' responses to public health advice constitute a proactive process of risk assessment and rationalised decision-making to guide preventive action. This process incorporates consideration of the current living situation, trust in information sources, correspondence with cultural logics and willingness to accept potential risk to self and significant others. Our findings concerning international passengers' understanding of, and compliance with, official advice and mitigation measures provide valuable evidence to inform future policy and generate recommendations on the presentation of public health information to facilitate safer international travel. Access to a central source of regularly updated official information would help minimise confusion between different national guidelines. Greater attention to the differentiated information needs of diverse groups in creating future public-facing guidance would help to minimise the uncertainties generated by the receipt of generic information.

Parental perceptions of COVID-19-like illness in their children.

OBJECTIVES: The objective of the study is to explore parents' perceptions of COVID-19-like symptoms in their child and attitudes towards isolating from others in the household when unwell. STUDY DESIGN: The study used qualitative, semistructured interviews. METHODS: The study involved thirty semistructured telephone interviews with parents of children between 4 and 18 years. Thirty semistructured telephone interviews with parents of children between 4 and 18 years. RESULTS: We found four themes relating to symptom attribution ('normalising symptoms', 'err on the side of caution', 'experience of temperature', 'symptoms not normal for us'). In general, parents were more likely to attribute symptoms to COVID-19 if a temperature was present or the symptoms were perceived as 'unusual' for their family. Four themes relating to self-isolation ('difficult to prevent contact with children', 'isolation would be no different to lockdown life', 'ability to get food and supplies', 'limited space'). Parents believed they would find isolation within the household difficult or impossible if they had dependent children, had limited space or could not shop for groceries. CONCLUSIONS: The findings highlight complexities in symptom perception, attribution and household isolation. We suggest that they can be overcome by (a) providing better guidance on what symptoms require action, (b) providing guidance as to how to prevent infection within the household and (c) by supporting families with grocery shopping through a potential second or third wave.

Factors associated with non-essential workplace attendance during the COVID-19 pandemic in the UK in early 2021: evidence from cross-sectional surveys.

OBJECTIVES: Working from home where possible is important in reducing the spread of COVID-19. In early 2021, a quarter of people in England who believed they could work entirely from home reported attending their workplace. To inform interventions to reduce this, this study examined associated factors. STUDY DESIGN: Data from the ongoing COVID-19 Rapid Survey of Adherence to Interventions and Responses survey series of nationally representative samples of people in the UK aged 16+ years in January-February 2021 were used. METHODS: The study sample was 1422 respondents who reported that they could work completely from home. The outcome measure was self-reported workplace attendance at least once during the preceding week. Factors of interest were analysed in three blocks: 1) sociodemographic variables, 2) variables relating to respondents' circumstances and 3) psychological variables. RESULTS: 26.8% (95% confidence interval [CI] = 24.5%-29.1%) of respondents reported having attended their workplace at least once in the preceding week. Sociodemographic variables and living circumstances significantly independently predicted non-essential workplace attendance: male gender (odds ratio [OR] = 1.85, 95% CI = 1.33-2.58); dependent children in the household (OR = 1.65, 95% CI = 1.17-2.32); financial hardship (OR = 1.14, 95% CI = 1.08-1.21); lower socio-economic grade (C2DE; OR = 1.65, 95% CI = 1.19-2.53); working in sectors such as health or social care (OR = 4.18, 95% CI = 2.56-6.81), education and childcare (OR = 2.45, 95% CI = 1.45-4.14) and key public service (OR = 3.78, 95% CI = 1.83-7.81) and having been vaccinated (OR = 2.08, 95% CI = 1.33-3.24). CONCLUSIONS: Non-essential workplace attendance in the UK in early 2021 during the COVID-19 pandemic was significantly independently associated with a range of sociodemographic variables and personal circumstances. Having been vaccinated, financial hardship, socio-economic grade C2DE, having a dependent child at home and working in certain key sectors were associated with higher likelihood of workplace attendance.

Do members of the public think they should use lateral flow tests (LFT) or polymerase chain reaction (PCR) tests when they have COVID-19-like symptoms? The COVID-19 Rapid Survey of Adherence to Interventions and Responses study.

OBJECTIVES: This study aimed to investigate public use of lateral flow tests (LFT) and polymerase chain reaction (PCR) tests when experiencing key COVID-19 symptoms. STUDY DESIGN: In this study, data from two waves of a cross-sectional nationally representative online survey (data collected 1 and 2 June, and 14 and 15 June 2021; n = 3665 adults aged ≥18 years living in England or Scotland) were used. METHODS: We report data investigating which type of test, if any, the public think Government guidance asks people to use if they have COVID-19 symptoms. In people with key COVID-19 symptoms (high temperature / fever; new, continuous cough; loss of sense of smell; loss of taste), we also describe the uptake of testing, if any. RESULTS: Ten percent of respondents thought Government guidance stated that they should take an LFT if symptomatic, whereas 18% of people thought that they should take a PCR test; 60% of people thought they should take both types of test (12% did not select either option). In people who were symptomatic, 32% reported taking a test to confirm whether they had COVID-19. Of these, 53% reported taking a PCR test and 44% reported taking an LFT. CONCLUSIONS: Despite Government guidance stating that anyone with key COVID-19 symptoms should complete a PCR test, a significant percentage of the population use LFT tests when symptomatic. Communications should emphasise the superiority of, and need for, PCR tests in people with symptoms.

Public health information on COVID-19 for international travellers: lessons learned from a mixed-method evaluation.

OBJECTIVES: In the containment phase of the response to the COVID-19 outbreak, Public Health England (PHE) delivered advice to travellers arriving at major UK ports. We aimed to rapidly evaluate the impact and effectiveness of these communication materials for passengers in the early stages of the pandemic. STUDY DESIGN: The study design used is the mixed-methods evaluation. METHODS: A questionnaire survey and follow-up interviews with passengers arriving at London Heathrow Airport on scheduled flights from China and Singapore. The survey assessed passengers' knowledge of symptoms, actions to take, and attitudes towards PHE COVID-19 public health information; interviews explored their views of official public health information and self-isolation. RESULTS: One hundred and twenty-one passengers participated in the survey and 15 in follow-up interviews. Eighty three percentage of surveyed passengers correctly identified all three COVID-19 associated symptoms listed in PHE information at that time. Most could identify the recommended actions and found the advice understandable and trustworthy. Interviews revealed that passengers shared concerns about the lack of wider official action, and that passengers' knowledge had been acquired elsewhere as much from PHE. Respondents also noted their own agency in choosing to self-isolate, partially as a self-protective measure. CONCLUSION: PHE COVID-19 public health information was perceived as clear and acceptable, but we found that passengers acquired knowledge from various sources and they saw the provision of information alone on arrival as an insufficient official response. Our study provides fresh insights into the importance of taking greater account of diverse information sources and of the need for public assurance in creating public health information materials to address global health threats.

How to improve adherence with quarantine: rapid review of the evidence.

OBJECTIVES: The December 2019 outbreak of coronavirus has once again thrown the vexed issue of quarantine into the spotlight, with many countries asking their citizens to 'self-isolate' if they have potentially come into contact with the infection. However, adhering to quarantine is difficult. Decisions on how to apply quarantine should be based on the best available evidence to increase the likelihood of people adhering to protocols. We conducted a rapid review to identify factors associated with adherence to quarantine during infectious disease outbreaks. STUDY DESIGN: The study design is a rapid evidence review. METHODS: We searched Medline, PsycINFO and Web of Science for published literature on the reasons for and factors associated with adherence to quarantine during an infectious disease outbreak. RESULTS: We found 3163 articles and included 14 in the review. Adherence to quarantine ranged from as little as 0 up to 92.8%. The main factors which influenced or were associated with adherence decisions were the knowledge people had about the disease and quarantine procedure, social norms, perceived benefits of quarantine and perceived risk of the disease, as well as practical issues such as running out of supplies or the financial consequences of being out of work. CONCLUSIONS: People vary in their adherence to quarantine during infectious disease outbreaks. To improve this, public health officials should provide a timely, clear rationale for quarantine and information about protocols; emphasise social norms to encourage this altruistic behaviour; increase the perceived benefit that engaging in quarantine will have on public health; and ensure that sufficient supplies of food, medication and other essentials are provided.

Factors associated with adherence to self-isolation and lockdown measures in the UK: a cross-sectional survey.

OBJECTIVES: To investigate factors associated with adherence to self-isolation and lockdown measures due to COVID-19 in the UK. STUDY DESIGN: Online cross-sectional survey. METHODS: Data were collected between 6th and 7th May 2020. A total of 2240 participants living in the UK aged 18 years or older were recruited from YouGov's online research panel. RESULTS: A total of 217 people (9.7%) reported that they or someone in their household had symptoms of COVID-19 (cough or high temperature/fever) in the last 7 days. Of these people, 75.1% had left the home in the last 24 h (defined as non-adherent). Men were more likely to be non-adherent, as were people who were less worried about COVID-19, and who perceived a smaller risk of catching COVID-19. Adherence was associated with having received help from someone outside your household. Results should be taken with caution as there was no evidence for associations when controlling for multiple analyses. Of people reporting no symptoms in the household, 24.5% had gone out shopping for non-essentials in the last week (defined as non-adherent). Factors associated with non-adherence and with a higher total number of outings in the last week included decreased perceived effectiveness of government 'lockdown' measures, decreased perceived severity of COVID-19 and decreased estimates of how many other people were following lockdown rules. Having received help was associated with better adherence. CONCLUSIONS: Adherence to self-isolation is poor. As we move into a new phase of contact tracing and self-isolation, it is essential that adherence is improved. Communications should aim to increase knowledge about actions to take when symptomatic or if you have been in contact with a possible COVID-19 case. They should also emphasise the risk of catching and spreading COVID-19 when out and about and the effectiveness of preventative measures. Using volunteer networks effectively to support people in isolation may promote adherence.

Making biodiversity-friendly cocoa pay: combining yield, certification, and REDD for shade management.

The twin United Nations' Millennium Development Goals of biodiversity preservation and poverty reduction both strongly depend on actions in the tropics. In particular, traditional agroforestry could be critical to both biological conservation and human livelihoods in human-altered rainforest areas. However, traditional agroforestry is rapidly disappearing, because the system itself is economically precarious, and because the forest trees that shade traditional crops are now perceived to be overly detrimental to agricultural yield. Here, we show a case where the commonly used agroforestry shade metric, canopy cover, would indeed suggest complete removal of shade trees to maximize yield, with strongly negative biodiversity and climate implications. However, a yield over 50% higher was achievable if approximately 100 shade trees per hectare were planted in a spatially organized fashion, a win-win for biodiversity and the smallholder. The higher yield option was detected by optimizing simultaneously for canopy cover, and a second shade metric, neighboring tree density, which was designed to better capture the yield value of ecological services flowing from forest trees. Nevertheless, even a 50% yield increase may prove insufficient to stop farmers converting away from traditional agroforestry. To further increase agroforestry rents, we apply our results to the design of a sustainable certification (eco-labelling) scheme for cocoa-based products in a biodiversity hotspot, and consider their implications for the use of the United Nations REDD (reducing emissions from deforestation and forest degradation) program in agroforestry systems. Combining yield boost, certification, and REDD has the potential to incentivize eco-friendly agroforestry and lift smallholders out of poverty, simultaneously.

Risk for transmission of Naegleria fowleri from solid organ transplantation.

Primary amebic meningoencephalitis (PAM) caused by the free-living ameba (FLA) Naegleria fowleri is a rare but rapidly fatal disease of the central nervous system (CNS) affecting predominantly young, previously healthy persons. No effective chemotherapeutic prophylaxis or treatment has been identified. Recently, three transplant-associated clusters of encephalitis caused by another FLA, Balamuthia mandrillaris, have occurred, prompting questions regarding the suitability of extra-CNS solid organ transplantation from donors with PAM. During 1995-2012, 21 transplant recipients of solid organs donated by five patients with fatal cases of PAM were reported in the United States. None of the recipients developed PAM, and several recipients tested negative for N. fowleri by serology. However, historical PAM case reports and animal experiments with N. fowleri, combined with new postmortem findings from four patients with PAM, suggest that extra-CNS dissemination of N. fowleri can occur and might pose a risk for disease transmission via transplantation. The risks of transplantation with an organ possibly harboring N. fowleri should be carefully weighed for each individual recipient against the potentially greater risk of delaying transplantation while waiting for another suitable organ. In this article, we present a case series and review existing data to inform such risk assessments.

Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis.

Erythrokeratodermia variabilis (EKV, OMIM 133200) is an autosomal dominant genodermatosis with considerable intra- and interfamilial variability. It has a disfiguring phenotype characterized by the independent occurrence of two morphologic features: transient figurate red patches and localized or generalized hyperkeratosis. Both features can be triggered by external factors such as trauma to the skin. After initial linkage to the RH locus on 1p, EKV was mapped to an interval of 2.6 cM on 1p34-p35, and a candidate gene (GJA4) encoding the gap junction protein alpha-4 (connexin 31, Cx31) was excluded by sequence analysis. Evidence in mouse suggesting that the EKV region harbours a cluster of epidermally expressed connexin genes led us to characterize the human homologues of GJB3 (encoding Cx31) and GJB5 (encoding Cx31.1). GJB3, GJB5 and GJA4 were localized to a 1.1-Mb YAC in the candidate interval. We detected heterozygous missense mutations in GJB3 in four EKV families leading to substitution of a conserved glycine by charged residues (G12R and G12D), or change of a cysteine (C86S). These mutations are predicted to interfere with normal Cx31 structure and function, possibly due to a dominant inhibitory effect. Our results implicate Cx31 in the pathogenesis of EKV, and provide evidence that intercellular communication mediated by Cx31 is crucial for epidermal differentiation and response to external factors.

Delivery of multipotent adult progenitor cells via a functionalized plasma polymerized surface accelerates healing of murine diabetic wounds.

Introduction: Stem cell therapies have been investigated as potential treatment modalities for chronic wounds however there has been limited success to date. Multipotent Adult Progenitor Cells (MAPCs©) have been identified as having potential as an allogenic stem cell product due to their high population doubling number and their characteristic dampening of T-cell proliferation. This helps to prevent autoimmunity and graft/cell rejection. Methods: We have developed a dressing, consisting of medical grade silicone coated with a heptylamine plasma polymer, which supports the growth and transfer of MAPCs to skin. To determine if the dressing can deliver functional stem cells into diabetic wounds, they were loaded with MAPCs and then placed over excisional wounds in both normal and diabetic mice. Results and discussion: Accelerated healing was observed in both the normal and diabetic wounds with wound gape being significantly smaller at day 3 when compared to controls. Wound analysis showed that treatment with the MAPC dressings dampened the inflammatory response with reduced numbers of neutrophils and macrophages observed. Additionally, an increase in pro-angiogenic VEGF and CD31 positive endothelial cells was observed indicating improved new blood vessel formation. The MAPC dressings had no effect on fibrosis with collagen I and III being equally affected in both control and treated wounds. Overall, the functionalized MAPC dressings improve healing responses particularly in diabetic mice with impaired healing responses and therefore, show potential for development as an advanced therapeutic approach for the treatment of chronic diabetic wounds.

Transanal endoscopic microsurgery for rectal carcinoids: the largest reported United States experience.

AIM: Rectal carcinoids are often inadequately resected by snare excision during colonoscopy. Transanal endoscopic microsurgery is a minimally invasive procedure with low morbidity that offers full-thickness excision with a low rate of negative margins. It presents an excellent alternative to radical surgery for mid and proximally located lesions. We report the largest United States (US) experience in the use of transanal endoscopic microsurgery for rectal carcinoids. METHOD: Data of patients who had undergone transanal endoscopic microsurgery for rectal carcinoids were prospectively collected and retrospectively analyzed. Patient and tumour characteristics, operative and perioperative details, as well as oncological outcomes were reviewed. RESULTS: Over a 12-year period, 24 patients underwent transanal endoscopic microsurgery for rectal carcinoids. Of these, six (25%) were primary surgical resections and 18 (75%) were performed after incomplete snare excisions during colonoscopy. Three (17%) patients who underwent full-thickness resection after snare excision had residual tumour on histopathological examination. Negative margins were obtained in all cases. No recurrences were noted. CONCLUSION: Transanal endoscopic microsurgery is effective and safe for the surgical resection of rectal carcinoids<2 cm in diameter, with typical features and located more than 5 cm from the anal verge. Transanal endoscopic microsurgery can be used for primary resection or for resection after incomplete colonoscopic snare excision.

The effects of high-intensity functional training on cardiometabolic risk factors and exercise enjoyment in men and women with metabolic syndrome: study protocol for a randomized, 12-week, dose-response trial.

BACKGROUND: Individuals with metabolic syndrome (MetS) are at a greater risk for developing atherosclerotic cardiovascular disease (ASCVD) than those without MetS, due to underlying endothelial dysfunction, dyslipidemia, and insulin resistance. Exercise is an effective primary and secondary prevention strategy for MetS; however, less than 25% of adults meet the minimum stated public recommendations. Barriers often identified are lack of enjoyment and lack of time. High-intensity functional training (HIFT), a time-efficient modality of exercise, has shown some potential to elicit positive affectivity and elicit increased fitness and improved glucose metabolism. However, the effects of HIFT on dyslipidemia and endothelial dysfunction have not been explored nor have the effects been explored in a population with MetS. Additionally, no studies have investigated the minimal dose of HIFT per week to see clinically meaningful changes in cardiometabolic health. The purpose of this study is to (1) determine the dose-response effect of HIFT on blood lipids, insulin resistance, and endothelial function and (2) determine the dose-response effect of HIFT on body composition, fitness, and perceived enjoyment and intention to continue the exercise. METHODS/DESIGN: In this randomized, dose-response trial, participants will undergo a 12-week HIFT intervention of either 1 day/week, 2 days/week, or 3 days/week of supervised, progressive exercise. Outcomes assessed at baseline and post-intervention will be multiple cardiometabolic markers, and fitness. Additionally, the participant's affective response will be measured after the intervention. DISCUSSION: The findings of this research will provide evidence on the minimal dose of HIFT per week to see clinically meaningful improvements in the risk factors of MetS, as well as whether this modality is likely to mitigate the barriers to exercise. If an effective dose of HIFT per week is determined and if this modality is perceived positively, it may provide exercise specialists and health care providers a tool to prevent and treat MetS. TRIAL REGISTRATION: ClinicalTrials.gov NCT05001126 . August 11, 2021.

Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor.

Although insulin-like growth factor 1 (IGF-1) has been associated with retinopathy, proof of a direct relationship has been lacking. Here we show that an IGF-1 receptor antagonist suppresses retinal neovascularization in vivo, and infer that interactions between IGF-1 and the IGF-1 receptor are necessary for induction of maximal neovascularization by vascular endothelial growth factor (VEGF). IGF-1 receptor regulation of VEGF action is mediated at least in part through control of VEGF activation of p44/42 mitogen-activated protein kinase, establishing a hierarchical relationship between IGF-1 and VEGF receptors. These findings establish an essential role for IGF-1 in angiogenesis and demonstrate a new target for control of retinopathy. They also explain why diabetic retinopathy initially increases with the onset of insulin treatment. IGF-1 levels, low in untreated diabetes, rise with insulin therapy, permitting VEGF-induced retinopathy.