The Development of a Multi-Modal Cancer Rehabilitation (Including Prehabilitation) Service in Sheffield, UK: Designing the Active Together Service.

Cancer patients undergoing major interventions face numerous challenges, including the adverse effects of cancer and the side effects of treatment. Cancer rehabilitation is vital in ensuring cancer patients have the support they need to maximise treatment outcomes and minimise treatment-related side effects and symptoms. The Active Together service is a multi-modal rehabilitation service designed to address critical support gaps for cancer patients. The service is located and provided in Sheffield, UK, an area with higher cancer incidence and mortality rates than the national average. The service aligns with local and regional cancer care objectives and aims to improve the clinical and quality-of-life outcomes of cancer patients by using lifestyle behaviour-change techniques to address their physical, nutritional, and psychological needs. This paper describes the design and initial implementation of the Active Together service, highlighting its potential to support and benefit cancer patients.

International consensus is needed on a core outcome set to advance the evidence of best practice in cancer prehabilitation services and research.

Prehabilitation aims to optimise patients' physical and psychological status before treatment. The types of outcomes measured to assess the impact of prehabilitation interventions vary across clinical research and service evaluation, limiting the ability to compare between studies and services and to pool data. An international workshop involving academic and clinical experts in cancer prehabilitation was convened in May 2022 at Sheffield Hallam University's Advanced Wellbeing Research Centre, England. The workshop substantiated calls for a core outcome set to advance knowledge and understanding of best practice in cancer prehabilitation and to develop national and international databases to assess outcomes at a population level.

Lichen Sclerosus and Sexual Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: Lichen sclerosus (LS) is a common autoimmune dermatological condition that is often under-diagnosed in women and has been documented to affect quality of life and sexual function. AIM: To determine the prevalence of sexual dysfunction among women with vulvar lichen sclerosus. METHODS: The authors conducted a systematic review and meta-analysis of the existing research on LS and sexual function in database including PubMed using search terms: lichen sclerosus OR vulvar lichen sclerosus OR vulvar lichen sclerosus et atrophicus OR kraurosis vulvae) AND (sexual function OR sexual functions OR sexual disorder OR sexual disorders OR sexual activity OR sexual activities OR sexual dysfunction OR sexual dysfunctions OR dyspareunia OR vaginismus). OUTCOMES: Nearly 60% of women with lichen sclerosus suffer from sexual dysfunction. RESULTS: Two hundred and ten studies were initially identified. Twenty-six articles met inclusion criteria and 3 were excluded as they did not relate to sexual function, were regarding a surgical or medical intervention and sexual dysfunction and one was a review article. Therefore, 23 studies were included in the final analysis resulting in a cumulative 486 participants with LS with 208 patients experiencing any kind of sexual dysfunction. Meta-analysis presented prevalence of sexual dysfunction among LS patients as 59% (95% CI: 48 - 70%). Dyspareunia or generalized pain with intercourse was the most commonly reported type of dysfunction. CLINICAL IMPLICATIONS: Discussing sexual concerns with women with LS could empower them to seek treatment. STRENGTHS AND LIMITATIONS: Few articles met criteria for inclusion. CONCLUSION: A large proportion of women with LS experience sexual dysfunction. More research is needed, especially that which includes biopsy-proven LS and validated tools on sexual function. Pope R, Lee MH, Myers A, et al. Lichen Sclerosus and Sexual Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2022;19:1616-1624.

Physical activity promotion by GPs: a cross-sectional survey in England.

BACKGROUND: Physical activity (PA) contributes to the prevention and management of many health conditions. Primary care practitioners have an important role to play in supporting people to be physically active. AIM: This study had the following three aims: 1) to explore GPs' awareness and knowledge of the PA guidelines; 2) to assess GPs' confidence in promoting PA; and 3) to explore factors that influence PA promotion among GPs. DESIGN & SETTING: Cross-sectional survey, using secondary analysis. METHOD: UK-based GPs were invited to take part in an online survey in January 2021. Demographic questions were followed by nine multiple choice questions. Categorical data were analysed using descriptive statistics, and open-ended data were analysed using content analysis and inductive coding. RESULTS: In total, 839 GPs based in England completed the survey. Most GP responders (98.9%) believed that PA was important, yet only 35.7% reported being at least 'somewhat familiar' with current PA guidance. Despite this, 74.1% of GPs reported feeling confident raising the topic of PA with their patients. Barriers included lack of time, perceptions of patient attitude and risk, language issues, and COVID-19. Key facilitators were identified and 'Couch to 5k' and the 'parkrun practice' initiatives were the most widely used support tools. CONCLUSION: GPs value PA yet well-known barriers exist to embedding promotion into primary care. As primary care reconfigures, there is an opportunity to embed PA into systems, services, and processes.

Free-Living Energy Balance Behaviors Are Associated With Greater Weight Loss During a Weight Loss Program.

Introduction: Free-living movement (physical activity [PA] and sedentary behavior [SB]) and eating behaviors (energy intake [EI] and food choice) affect energy balance and therefore have the potential to influence weight loss (WL). This study explored whether free-living movement and/or eating behaviors measured early (week 3) in a 14-week WL programme or their change during the intervention are associated with WL in women. Methods: In the study, 80 women (M ± SD age: 42.0 ± 12.4 years) with overweight or obesity [body mass index (BMI): 34.08 ± 3.62 kg/m2] completed a 14 week WL program focused primarily on diet (commercial or self-led). Body mass (BM) was measured at baseline, and again during week 2 and 14 along with body composition. Free-living movement (SenseWear Armband) and eating behavior (weighed food diaries) were measured for 1 week during week 3 and 12. Hierarchical multiple regression analyses examined whether early and early-late change in free-living movement and eating behavior were associated with WL. The differences in behavior between clinically significant weight losers (CWL; ≥5% WL) and non-clinically significant weight losers (NWL; ≤ 3% WL) were compared. Results: The energy density of food consumed [ß = 0.45, p < 0.001] and vigorous PA [ß = -0.30, p < 0.001] early in the intervention (regression model 1) and early-late change in light PA [ß = -0.81 p < 0.001], moderate PA [ß = -1.17 p < 0.001], vigorous PA [ß = -0.49, p < 0.001], total energy expenditure (EE) [ß = 1.84, p < 0.001], and energy density of food consumed [ß = 0.27, p = 0.01] (regression model 2) significantly predicted percentage change in BM. Early in the intervention, CWL consumed less energy dense foods than NWL [p = 0.03]. CWL showed a small but significant increase in vigorous PA, whereas NWL showed a slight decrease in PA [p = 0.04]. Conclusion: Both early and early-late change in free-living movement and eating behaviors during a 14 week WL program are predictors of WL. These findings demonstrate that specific behaviors that contribute to greater EE (e.g., vigorous PA) and lower EI (e.g., less energy-dense foods) are related to greater WL outcomes. Interventions targeting these behaviors can be expected to increase the effectiveness of WL programs.

The Active Hospital pilot: A qualitative study exploring the implementation of a Trust-wide Sport and Exercise Medicine-led physical activity intervention.

BACKGROUND: In 2017 Public Health England and Sport England commissioned a Consultant-led Sport and Exercise Medicine (SEM) pilot to test the feasibility and acceptability of embedding physical activity interventions in secondary care clinical pathways. The aim of this paper is to report qualitative findings exploring the experience of healthcare professionals (HCPs) and patients involved in the Active Hospital pilot. METHODS: Qualitative data was collected by semi-structured interviews with Active Hospital pilot SEM Consultants, and staff and patients involved in three clinical pathways. Interviews with SEM Consultants explored the experience of developing and implementing the pilot. Interviews with staff and patients explored the experience of delivering and receiving Active Hospital interventions. Data were analysed thematically. RESULTS: Interviews identified the importance of the Active Hospital pilot being Consultant-led for the following reasons; i) having trusting relationships with decision makers, ii) having sufficient influence to effect change, iii) identifying champions within the system, and iv) being adaptable to change and ensuring the programme fits within the wider strategic frameworks. HCPs emphasised the importance of the Active Hospital interventions fitting easily within existing work practices, the need for staff training and to tailor interventions for individual patient needs. The Active Hospital pilot was well received by patients, however a lack of dedicated resource and capacity to deliver the intervention was highlighted as a challenge by both patients and HCPs. CONCLUSION: The SEM Consultants' ability to navigate the political climate of a large National Health Service (NHS) Trust with competing agendas and limited resource was valuable. The interventions were well received and a valued addition to usual clinical care. However, implementation and ongoing delivery of the pilot encountered challenges including lack of capacity within the system and delays with recruiting to the delivery teams in each pathway.

Susceptibility to increased high energy dense sweet and savoury food intake in response to the COVID-19 lockdown: The role of craving control and acceptance coping strategies.

Emerging evidence indicates that for some people, the COVID-19 lockdowns are a time of high risk for increased food intake. A clearer understanding of which individuals are most at risk of over-eating during the lockdown period is needed to inform interventions that promote healthy diets and prevent weight gain during lockdowns. An online survey collected during the COVID-19 lockdown (total n = 875; analysed n = 588; 33.4 ± 12.6 years; 82% UK-based; mostly white, educated, and not home schooling) investigated reported changes to the amount consumed and changes to intake of high energy dense (HED) sweet and savoury foods. The study also assessed which eating behaviour traits predicted a reported increase of HED sweet and savoury foods and tested whether coping responses moderated this relationship. Results showed that 48% of participants reported increased food intake in response to the COVID-19 lockdown. There was large individual variability in reported changes and lower craving control was the strongest predictor of increased HED sweet and savoury food intake. Low cognitive restraint also predicted greater increases in HED sweet snacks and HED savoury meal foods. Food responsiveness, enjoyment of food, emotional undereating, emotional overeating and satiety responsiveness were not significant predictors of changes to HED sweet and savoury food intake. High scores on acceptance coping responses attenuated the conditional effects of craving control on HED sweet snack intake. Consistent with previous findings, the current research suggests that low craving control is a risk factor for increased snack food intake during lockdown and may therefore represent a target for intervention.

Effectiveness of clinical training on improving essential newborn care practices in Bossaso, Somalia: a pre and postintervention study.

BACKGROUND: Increasingly, neonatal mortality is concentrated in settings of conflict and political instability. To promote evidence-based practices, an interagency collaboration developed the Newborn Health in Humanitarian Settings: Field Guide. The essential newborn care component of the Field Guide was operationalized with the use of an intervention package encompassing the training of health workers, newborn kit provisions and the installation of a newborn register. METHODS: We conducted a quasi-experimental prepost study to test the effectiveness of the intervention package on the composite outcome of essential newborn care from August 2016 to December 2018 in Bossaso, Somalia. Data from the observation of essential newborn care practices, evaluation of providers' knowledge and skills, postnatal interviews, and qualitative information were analyzed. Differences in two-proportion z-tests were used to estimate change in essential newborn care practices. A generalized estimating equation was applied to account for clustering of practice at the health facility level. RESULTS: Among the 690 pregnant women in labor who sought care at the health facilities, 89.9% (n = 620) were eligible for inclusion, 84.7% (n = 525) were enrolled, and newborn outcomes were ascertained in 79.8% (n = 419). Providers' knowledge improved from pre to posttraining, with a mean difference in score of + 11.9% (95% CI: 7.2, 16.6, p-value < 0.001) and from posttraining to 18-months after training with a mean difference of + 10.9% (95% CI: 4.7, 17.0, p-value < 0.001). The proportion of newborns who received two or more essential newborn care practices (skin-to-skin contact, early breastfeeding, and dry cord care) improved from 19.9% (95% CI: 4.9, 39.7) to 94.7% (95% CI: 87.7, 100.0). In the adjusted model that accounted for clustering at health facilities, the odds of receiving two or more essential newborn practices was 64.5 (95% CI: 15.8, 262.6, p-value < 0.001) postintervention compared to preintervention. Predischarge education offered to mothers on breastfeeding 16.5% (95% CI: 11.8, 21.1) vs 44.2% (95% CI: 38.2, 50.3) and newborn illness danger signs 9.1% (95% CI: 5.4, 12.7) vs 5.0% (95% CI: 2.4, 7.7) remained suboptimal. CONCLUSIONS: The intervention package was feasible and effective in improving essential newborn care. Knowledge and skills gained after training were mostly retained at the 18-month follow-up.

Association between keratoconus disease severity and repeatability in measurements of parameters for the assessment of progressive disease.

BACKGROUND: Progressive keratoconus can lead to severely impaired vision, but there is currently no consensus on the definition of progressive disease. Errors in the measurement of the parameters commonly used to establish progressive disease were evaluated in an attempt to determine the limits at which a true change in the values can be detected. The possible association between measurement error and disease severity was also investigated to evaluate the need for limits based on disease severity. METHODS: Sixty-one eyes were studied in 61 patients with keratoconus. Four replicate measurements were made in each patient using a Scheimpflug-based tomographic system (denoted the PC) and an auto-keratometer (denoted the AK). The repeatability coefficient, i.e., the level below which differences between two measurements are found in 95% of paired observations, was calculated. Patients were further divided into three groups based on disease severity (parameter magnitude). RESULTS: Increasing magnitude of all the keratometric parameters investigated was significantly associated with increasing measurement errors, and thus worse repeatability. The maximum keratometry value (Kmax) was the least repeatable parameter (1.23 D, 95% CI 1.11-1.35 D) and showed the strongest association between parameter magnitude and measurement error. The repeatability coefficient ranged between 0.32 and 1.62 D, depending on disease severity. The most repeatable parameter was the flattest central keratometry value (K1), measured with the PC (0.51 D, 95% CI 0.46-0.56 D) and the AK (0.54 D, 95% CI 0.48-0.59 D). K1 showed the weakest association between parameter magnitude and measurement error. The repeatability coefficient for K1 ranged between 0.40 and 0.54 D when using the PC, and between 0.34 and 0.70 D when using the AK in the three groups. CONCLUSIONS: The association between the magnitude of the keratometric parameters and their measurement errors suggests that limits should be based on disease severity to ensure reliable detection of progressive keratoconus. Further studies are, however, required.

Women with a low-satiety phenotype show impaired appetite control and greater resistance to weight loss.

This trial compared weight loss outcomes over 14 weeks in women showing low- or high-satiety responsiveness (low- or high-satiety phenotype (LSP, HSP)) measured by a standardised protocol. Food preferences and energy intake (EI) after low and high energy-density (LED, HED) meals were also assessed. Ninety-six women (n 52 analysed; 41·24 (SD 12·54) years; 34·02 (sd 3·58) kg/m2) engaged in one of two weight loss programmes underwent LED and HED laboratory test days during weeks 3 and 12. Preferences for LED and HED food (Leeds Food Preference Questionnaire) and ad libitum evening meal and snack EI were assessed in response to equienergetic LED and HED breakfasts and lunches. Weekly questionnaires assessed control over eating and ease of adherence to the programme. Satiety quotients based on subjective fullness ratings post LED and HED breakfasts determined LSP (n 26) and HSP (n 26) by tertile splits. Results showed that the LSP lost less weight and had smaller reductions in waist circumference compared with HSP. The LSP showed greater preferences for HED foods, and under HED conditions, consumed more snacks (kJ) compared with HSP. Snack EI did not differ under LED conditions. LSP reported less control over eating and reported more difficulty with programme adherence. In conclusion, low-satiety responsiveness is detrimental for weight loss. LED meals can improve self-regulation of EI in the LSP, which may be beneficial for longer-term weight control.

Structured, aerobic exercise reduces fat mass and is partially compensated through energy intake but not energy expenditure in women.

BACKGROUND: Exercise-induced weight loss is often less than expected and highly variable in men and women. Behavioural compensation for the exercise-induced energy deficit could be through energy intake (EI), non-exercise physical activity (NEPA) or sedentary behaviour (SB). We investigated this issue in women. METHODS: Twenty-four overweight [body mass index (BMI) M = 27.9 kg/m2, SD = 2.7] women [age M = 33.1 years, SD = 11.7] completed 12-weeks of supervised exercise (5×500kcal per week) in a non-randomised, pre-post intervention study. Body mass (BM), waist circumference (WC), body composition, resting metabolic rate (RMR), total daily EI, individual meals, appetite sensations and appetite-related peptides were measured at baseline (week 0) and post-intervention (week 12). Free-living physical activity (PA) and SB were measured (SenseWear) at baseline, week 1 and 10 of the exercise intervention, and at post-intervention (week 13). RESULTS: Following the 12-week exercise intervention BM [p = .04], BMI [p = .035], WC [p < .001] and fat mass (FM) [p = .003] were significantly reduced, and fat-free mass (FFM) significantly increased [p = .003]. Total [p = .028], ad libitum [p = .03] and snack box EI [p = .048] were significantly increased and this was accompanied by an increase in hunger [p = .01] and a decrease in fullness [p = .03] before meals. The peptides did not explain changes in appetite [p > .05]. There was no compensatory reduction in NEPA [p > .05] and no increase in SB, rather there was a decrease in SB during the exercise intervention [p = .03]. CONCLUSIONS: Twelve-weeks of supervised aerobic exercise resulted in a significant reduction in FM and an increase in FFM. Exercise increased hunger and EI which only partially compensated for the increase in energy expenditure. There was no evidence for a compensatory reduction in NEPA or an increase in SB. Dietary intervention, as an adjunct to exercise, may offset the compensatory increase in EI and result in a greater reduction in BM. TRIAL REGISTRATION: Our trial was retrospectively registered on the International Standard Randomised Controlled Trials Registry (ISRCTN78021668, 27th September 2016) and can be found here: https://doi.org/10.1186/ISRCTN78021668.

Facilitators and barriers in implementing the Minimum Initial Services Package (MISP) for reproductive health in Nepal post-earthquake.

BACKGROUND: Following the Nepal earthquake in April 2015, UNFPA estimated that 1.4 million women of reproductive age were affected, with approximately 93,000 pregnant and 28,000 at risk of sexual violence. A set of priority reproductive health (RH) actions, the Minimum Initial Services Package (MISP), was initiated by government, international and local actors. The purpose of this study was to identify the facilitators and barriers affecting the implementation of priority RH services in two districts. METHODS: In September 2015, a mixed methods study design was used in Kathmandu and Sindhupalchowk districts to assess the implementation of the priority RH services five months post-earthquake. Data collection activities included 32 focus group discussions with male and female participants aged 18-49; 26 key informant interviews with RH, gender-based violence (GBV), and human immunodeficiency virus (HIV) experts; and 17 health facility assessments. RESULTS: The implementation of priority RH services was achieved in both districts. In Kathmandu implementation of emergency RH services started within days of the earthquake. Facilitating factors for successful implementation included disaster preparedness; leadership and commitment among national, international, and district level actors; resource mobilization; strong national level coordination; existing reproductive and child health services and community outreach programs; and supply chain management. Barriers included inadequate MISP training for RH coordinators and managers; weak communication between national and district level stakeholders; inadequate staffing; under-resourced and fewer facilities in rural areas; limited attention given to local GBV and HIV organizations; low availability of clinical management of rape services; and low awareness of GBV services and benefits of timely care. CONCLUSION: Ensuring RH is included in emergency preparedness and immediate response efforts and is continued through the transition to comprehensive care is critical for national governments and humanitarian response agencies. The MISP for RH remains a critical component of response efforts, and the humanitarian community should consider these learnings in future emergency response.

Disentangling the relationship between sedentariness and obesity: Activity intensity, but not sitting posture, is associated with adiposity in women.

BACKGROUND: The relationship between free-living sedentary behaviour (SB) and obesity is unclear. Studies may arrive at disparate conclusions because of inconsistencies and limitations when defining and measuring free-living SB. The aim of this cross-sectional study was to examine whether the relationship between SB and adiposity differed depending on the way SB was operationally defined and objectively measured. METHODS: Sixty-three female participants aged 37.1 years (SD = 13.6) with a body mass index (BMI) of 29.6 kg/m2 (SD = 4.7) had their body composition measured (BodPod, Concord, CA) then were continuously monitored for 5-7 days with the SenseWear Armband (SWA; sleep and activity intensity) and the activPAL (AP; posture). Data from both activity monitors were analysed separately and integrated resulting in a third measure of SB (activity intensity and posture; SEDINT). SB outputs were compared according to week or weekend day averages then correlated against body composition parameters after adjusting for moderate-to-vigorous physical activity (MVPA). RESULTS: SEDSWA resulted in the most sedentary time 11.74 h/day (SD = 1.60), followed by SEDAP 10.16 h/day (SD = 1.75) and SEDINT 9.10 h/day (SD = 1.67). There was a significant positive association between SEDSWA and body mass [r(61) = 0.29, p = .02], BMI [r (61) = 0.33, p = .009] and fat mass [r(61) = 0.32, p = .01]. SEDAP and SEDINT were not associated with any of the indices of adiposity. Correlations between SB and adiposity were non-significant when controlling for MVPA. CONCLUSIONS: The relationship between SB and adiposity differed depending on how SB was operationally defined and measured, and was dependent on MVPA. The definition of SB based on a sitting posture (SEDAP) was not strongly related to body fat, whereas the accumulation of any behaviour (sitting or standing) with an intensity of <1.5 METs (SEDSWA) (offset by the presence of MVPA) was positively associated with indices of adiposity. These data suggest that the postural element of SB (sitting) is not sufficient for the accumulation of adiposity, rather activities requiring low EE (<1.5 METs) and the absence of MVPA, regardless of posture, are associated with higher fat mass.

A novel integrative procedure for identifying and integrating three-dimensions of objectively measured free-living sedentary behaviour.

BACKGROUND: The widely accepted definition of sedentary behaviour [SB] refers to any waking behaviour characterized by an energy expenditure ≤1.5 metabolic equivalents [METs] while in a sitting or reclining posture. At present, there is no single field-based device which objectively measures sleep, posture and activity intensity simultaneously. The aim of this study was to develop a novel integrative procedure [INT] to combine information from two validated activity monitors on sleep, activity intensity and posture, the three key dimensions of SB. METHODS: Participants in this analysis were initially recruited from a series of three studies conducted between December 2014 and June 2016 at the University of Leeds. Sixty-three female participants aged 37.1 (13.6) years with a body mass index of 29.6 (4.7) kg/m2 were continuously monitored for 5-7 days with the SenseWear Armband [SWA] (sleep and activity intensity) and the activPAL [AP] (posture). Data from both activity monitors were analysed separately and integrated resulting in three measures of sedentary time. Differences in Sedentary time between the three measurement methods were assessed as well as how well the three measures correlated. RESULTS: The three measures of sedentary time were positively correlated, with the weakest relationship between SEDSWA (awake and <1.5 METs) and SEDAP (awake and sitting/lying posture) [r(61) = .37,p = .003], followed by SEDSWA and SEDINT (awake, <1.5 METs and sitting/lying posture) [r(61) = .58,p < .001], and the strongest relationship was between SEDAP and SEDINT [r(61) = .91,p < .001]. There was a significant difference between the three measures of sedentary time [F(1.18,73.15) = 104.70,p < .001]. Post-hoc tests revealed all three methods differed significantly from each other [p < .001]. SEDSWA resulted in the most sedentary time 11.74 (1.60) hours/day, followed by SEDAP 10.16 (1.75) hours/day, and SEDINT 9.10 (1.67) hours/day. Weekday and weekend day sedentary time did not differ for any of the measurement methods [p = .04-.25]. CONCLUSION: Information from two validated activity monitors was combined to obtain an objective measure of free-living SB based on posture and activity intensity during waking hours. The amount of sedentary time accumulated varied according to the definition of SB and its measurement. The novel data integration and processing procedures presented in this paper represents an opportunity to investigate whether different components of SB are differentially related to health end points.

Associations among sedentary and active behaviours, body fat and appetite dysregulation: investigating the myth of physical inactivity and obesity.

BACKGROUND: There is considerable disagreement about the association between free-living physical activity (PA) and sedentary behaviour and obesity. Moreover studies frequently do not include measures that could mediate between PA and adiposity. The present study used a validated instrument for continuous tracking of sedentary and active behaviours as part of habitual daily living, together with measures of energy expenditure, body composition and appetite dysregulation. This cross-sectional study tested the relationship between inactivity and obesity. METHODS: 71 participants (81.7% women) aged 37.4 years (±14) with a body mass index of 29.9 kg/m2 (±5.2) were continuously monitored for 6-7 days to track free-living PA (light 1.5-3 metabolic equivalents (METs), moderate 3-6 METs and vigorous >6 METs) and sedentary behaviour (<1.5 METs) with the SenseWear Armband. Additional measures included body composition, waist circumference, cardiovascular fitness, total and resting energy expenditure, and various health markers. Appetite control was assessed by validated eating behaviour questionnaires. RESULTS: Sedentary behaviour (11.06±1.72 h/day) was positively correlated with fat mass (r=0.50, p<0.001) and waist circumference (r=-0.65, p<0.001). Moderate-to-vigorous PA was negatively associated with fat mass (r=-0.72, p<0.001) and remained significantly correlated with adiposity after controlling for sedentary behaviour. Activity energy expenditure was positively associated with the level of PA and negatively associated with fat mass. Disinhibition and binge eating behaviours were positively associated with fat mass (r=0.58 and 0.47, respectively, p<0.001). CONCLUSIONS: This study demonstrated clear associations among objective measures of PA (and sedentary behaviour), energy expenditure, adiposity and appetite control. The data indicate strong links between physical inactivity and obesity. This relationship is likely to be bidirectional.

Mechanisms responsible for homeostatic appetite control: theoretical advances and practical implications.

INTRODUCTION: Homeostatic appetite control is part of a psychobiological system that has evolved to maintain an adequate supply of nutrients for growth and maintenance. The system links the physiological needs for energy with the behaviour that satisfies these needs (feeding), and is shaped by excitatory and inhibitory signals. Owing to rapid shifts in the food environment, homeostatic appetite control is not well adapted for modern-day human functioning. Areas covered: Homeostatic appetite control has two divisions. Tonic processes exert stable and enduring influences, with signals arising from bodily tissues and metabolism. Episodic processes fluctuate rapidly and are related to nutrient ingestion and the composition of foods consumed. Research in these areas incorporates potent endocrine signals that can influence behaviour. Expert commentary: The regulation of adipose tissue, and its impact on appetite (energy) homeostasis, has been heavily researched. More recently however, it has been demonstrated that fat-free mass has the potential to act as a tonic driver of food intake. A challenging issue is to determine how the post-prandial action of episodic satiety hormones and gastrointestinal mechanisms can effectively brake the metabolic drive to eat, in order to keep food intake under control and prevent a positive energy balance and fat accumulation.

Retinal function and morphology in the rabbit eye after intravitreal injection of the TNF alpha inhibitor adalimumab.

AIM: To study the effects of the tumor necrosis factor alpha inhibitor adalimumab on rabbit retina after injection into the vitreous body. METHODS: Forty-eight rabbits of mixed strain (9-12 months old, weighing ≈ 3.5 kg) were randomized into four groups. Adalimumab was injected at one of two concentrations (1.25 mg or 2.5 mg) into the eyes of two groups, and balanced salt solution into the eyes of the third group. The fourth group acted as controls. Full-field electroretinography (ffERG) was performed before injection and 1 and 6 weeks post-injection. At 6 weeks post-injection the rabbits were euthanized and the sectioned retinas were studied. Retinal histology was studied with hematoxylin-eosin staining. Immunohistochemical analysis was performed on rods, cones, rod bipolar cells, horizontal cells, amacrine cells and Müller cells. RESULTS: No significant difference in ffERG amplitudes or implicit times was observed between the four groups at any time point. Histological and immunohistochemical findings were similar in all groups. CONCLUSIONS: Injection of adalimumab into the vitreous body of healthy rabbits, at doses up to 2.5 mg, does not appear to be toxic to the rabbit retina.

Intravitreal injection of triamcinolone acetonide into healthy rabbit eyes alters retinal function and morphology.

AIM: To study the effects of intravitreally injected triamcinolone acetonide (TA) and/or its preservative benzyl alcohol (BA) in healthy rabbit retina. METHODS: Forty-eight rabbits (aged 4 months, body weight ≈3 kg) were randomized into four groups (n = 12). They were examined with electroretinography (ERG) prior to drug exposure, and then injected intravitreally with a combination of TA and BA, TA without BA, BA alone or a balanced saline solution (BSS). The electroretinograms were assessed 1 week and 7 weeks post-injection. The rabbits were euthanized and the sectioned retinas were studied. Immunohistochemical analysis was performed on rods, cones, rod bipolar cells, horizontal cells, amacrine cells and Müller cells. RESULTS: Rabbits injected with BA showed a significantly lower rod-mediated b-wave amplitude than the controls 1 week after injection. TA-injected rabbits demonstrated significantly higher a- and b-wave amplitudes in the total retinal response than the controls 1 week post-injection. The rabbits injected with TA + BA demonstrated a significantly higher b-wave amplitude in the total retinal response than the controls 1 week after injection. The significantly higher a-wave amplitude in the total retinal response remained in the TA-injected rabbits 7 weeks after injection. Immunohistochemistry revealed that protein kinase C alpha (PKC α) was down-regulated in both the perikarya and the axons of bipolar cells in histological sections from rabbit retina injected with TA + BA, BA and TA. CONCLUSIONS: Intravitreal injection of the preservative BA reduces the isolated rod-mediated retinal response in the rabbit, transiently and selectively. Intravitreal injection of TA increases the total retinal response in the rabbit up to seven weeks after injection. The effects observed are not only limited to retinal function, but also include changes in the expression of PKC α in rod bipolar cells, indicating drug-related interference with normal retinal physiology in the healthy rabbit eye.

Retinal function and morphology in rabbit after intravitreal injection of VEGF inhibitors.

PURPOSE/AIM: To explore changes in morphology and function in the rabbit retina after intravitreal high-dose injection of three commonly used VEGF inhibitors. MATERIALS AND METHODS: Forty-eight rabbits of mixed strain (6 months of age, body weight ≈ 3 kg) were randomized into four groups (n = 12). They were examined with full-field electroretinography (ERG) and with multifocal electroretinography (mf ERG) prior to drug exposure. The rabbits were then injected intravitreally with bevacizumab, ranibizumab, pegaptanib, or with a balanced saline solution. The dose of VEGF inhibitor was chosen to achieve a vitreous concentration approximately three times higher than the one clinically used in the adult human eye. ERG was then performed 8 weeks postinjection, and mf ERG 9 weeks postinjection. After 9 weeks, the rabbits were sacrificed and the sectioned retina was studied. Immunohistochemical analysis was performed of rods, cones, rod bipolar cells, horizontal cells, and amacrine cells. RESULTS: Rabbits injected with VEGF inhibitors all showed significantly lower amplitude of the dark-adapted b-wave rod-mediated response to dim light, compared to the rabbits injected with BSS. The a wave (reflecting photoreceptor function) in the response to single flash white light was however not affected. Immunohistochemistry revealed a significant reduction in PKC labeling of rod bipolar cells in pegaptanib and ranibizumab injected eyes whereas bevacizumab injected eyes displayed normal PKC labeling. No apparent morphological change was seen with markers for remaining retinal cells. CONCLUSIONS: Our results indicate that the use of high-dose intravitreal VEGF inhibitors in the rabbit eye affects rod-mediated retinal function and PKC expression in rod bipolars cells for at least 9 weeks after drug administration. The three VEGF inhibitors influence the retina slightly differently. These results are important for the understanding of drug action and when devising therapeutical strategies in new areas such as retinopathy of prematurity where vitreous volume is significantly lower compared to the adult eye.