Citizen involvement in COVID-19 contact tracing with digital tools: a qualitative study to explore citizens' perspectives and needs.

BACKGROUND: Contact tracing (CT) is a key strategy when dealing with outbreaks of infectious diseases such as COVID-19. The scale of the COVID-19 pandemic has often left public health professionals (PHPs), who are responsible for the execution of CT, unable to keep up with the rapid and largescale spread of the virus. To enhance or support its execution, and potentially lower the workload for PHPs, citizens may be more actively involved in CT-tasks that are commonly executed by PHPs (referred to as 'self-led CT'). There is limited insight into citizens' perspectives on and needs for self-led CT for COVID-19. This study aims to explore the perspectives and needs of Dutch citizens on taking more responsibilities in the execution of CT for COVID-19, potentially through the use of digital tools. METHODS: An exploratory qualitative study was performed, in which online semi-structured interviews were conducted. Questions were based on the Reasoned Action Approach and Health Belief Model. Interviews were audio-recorded and transcribed verbatim. A thematic analysis was conducted to identify citizens' perspectives and needs to participate in self-led CT. RESULTS: We conducted 27 interviews with Dutch citizens. Seven main themes were identified from the interviews: 1) 'Citizens' perspectives on self-led CT are influenced by prior experiences with regular CT', 2) 'Citizens' felt responsibilities and the perceived responsibilities of the PHS in CT shape their perspectives on self-led CT', 3) 'Anticipated impacts of self-led CT on the CT-process', 4) 'Citizens' attitude towards the application of self-led CT depends on their own perceived skills and the willingness and skills of others', 5) 'Shame and social stigma may hamper participation in self-led CT', 6) 'Concerns about privacy and data security: a barrier for self-led CT', and 7) 'Citizens' perspectives and anticipated needs for the implementation and application of self-led CT in practice'. CONCLUSIONS: Most interviewees hold a positive attitude towards self-led CT and using digital tools for this purpose. However, their intention for self-led CT may depend on various factors, such as prior experiences with regular CT, and their perceived self-efficacy to participate. Perspectives and needs of citizens should be considered for the future implementation of self-led CT in practice.

Effects of providing tailored information about e-cigarettes in a digital smoking cessation intervention: randomized controlled trial.

The effectiveness of e-cigarettes in smoking cessation is under debate. Informing smokers who are motivated to quit smoking about e-cigarettes may help them to make an informed decision about their use for smoking cessation, which, however, may also lead to unintended effects such as less quitting. This experimental study assessed the influence of providing tailored information about e-cigarettes in a web-based tailored smoking cessation intervention on participants' decision-making and smoking behavior. Adult smokers (N = 331) were randomized into a personalized eHealth intervention on (i) smoking cessation (control condition) or (ii) smoking cessation and information about e-cigarettes (intervention condition). Directly postintervention, participants in the intervention condition had more knowledge about e-cigarettes than participants in the control condition. Attitudes toward e-cigarettes were more positive among intervention participants than control participants, but the differences in attitude were less pronounced than the differences in knowledge and not consistent across items. At a 6-month follow-up, no between-condition differences were observed in the use of e-cigarettes as a smoking cessation method, the number of tobacco cigarettes smoked in the past 7 days, or other smoking outcomes.

Dutch public health professionals' perspectives and needs regarding citizen involvement in COVID-19 contact tracing through digital support tools: an exploratory qualitative study.

BACKGROUND: Contact tracing (CT) is an important, but resource-intensive tool to control outbreaks of communicable diseases. Under pandemic circumstances, public health services may not have sufficient resources at their disposal to effectively facilitate CT. This may be addressed by giving cases and their contact persons more autonomy and responsibility in the execution of CT by public health professionals, through digital contact tracing support tools (DCTS-tools). However, the application of this approach has not yet been systematically investigated from the perspective of public health practice. Therefore, we investigated public health professionals' perspectives and needs regarding involving cases and contact persons in CT for COVID-19 through DCTS-tools. METHODS: Between October 2020 and February 2021, we conducted online semi-structured interviews (N = 17) with Dutch public health professionals to explore their perspectives and needs regarding the involvement of cases and contact persons in CT for COVID-19 through DCTS-tools, in the contact identification, notification, and monitoring stages of the CT-process. Interviews were audio recorded and transcribed verbatim. A thematic analysis was performed. RESULTS: Four main themes related to Dutch public health professionals' perspectives and needs regarding involving cases and contact persons in CT for COVID-19 through DCTS-tools emerged from the data: 'Distinct characteristics of CT with DCTS-tools'; 'Anticipated benefits and challenges of CT for COVID-19 with DCTS- tools'; 'Circumstances in CT for COVID-19 that permit or constrain the application of DCTS-tools'; and 'Public health professionals' needs regarding the development and application of DCTS-tools for CT'. Public health professionals seem to have a positive attitude towards involving cases and contact persons through DCTS-tools. Public health professionals' (positive) attitudes seem conditional on the circumstances under which CT is performed, and the fulfilment of their needs in the development and application of DCTS-tools. CONCLUSIONS: Dutch public health professionals seem positive towards involving cases and contact persons in CT for COVID-19 through DCTS-tools. Through adequate implementation of DCTS-tools in the CT-process, anticipated challenges can be overcome. Future research should investigate the perspectives and needs of cases and contact persons regarding DCTS-tools, and the application of DCTS-tools in practice.

Optimizing decision-making among childcare staff on fever and common infections: cluster randomized controlled trial.

BACKGROUND: Children 0-4 years attending childcare are more prone to acquire infections than home-cared children. Childcare illness absenteeism due to fever is mostly driven by fear towards fever in childcare staff and parents. This may cause high childcare absenteeism, healthcare service use, and work absenteeism in parents. This study evaluates a multicomponent intervention targeting determinants of decision-making among childcare staff on illness absenteeism due to fever and common infections. METHODS: The multicomponent intervention was developed based on the Intervention Mapping approach and consisted of (i) an educational session, (ii) a decision tool, (iii) an information booklet and (iv) an online video. The intervention was evaluated in a cluster randomized controlled trial in Southern Netherlands. Nine centres received the intervention and nine provided childcare-as-usual. Primary outcome measure was the percentage of illness absenteeism on cluster level, defined as number of childcare days absent due to illness on total of registered childcare contract days in a 12-week period. Secondary outcome measures included intended behaviour, attitude, risk perception, knowledge and self-efficacy of childcare staff. Outcomes were analyzed using linear mixed models accounting for clustering. Knowledge was descriptively analysed. RESULTS: Overall illness absenteeism was comparable in intervention (2.95%) and control group (2.52%). Secondary outcomes showed significant improvements in intervention group regarding intended behaviour, two of three attitude dimensions. Knowledge increased compared with control but no differences regarding self-efficacy. CONCLUSION: The intervention was not effective in reducing illness absenteeism. However, the intervention improved determinants of decision-making such as intended behaviour, attitude, and knowledge on fever. TRIAL REGISTRATION: NTR6402 (registered on 21 April 2017).

Strength exercises during physical education classes in secondary schools improve body composition: a cluster randomized controlled trial.

BACKGROUND: Metabolic health in people with obesity is determined by body composition. In this study, we examined the influence of a combined strength exercise and motivational programme -embedded in the school curriculum- on adolescents body composition and daily physical activity. METHODS: A total of 695 adolescents (11-15y) from nine Dutch secondary schools participated in a one year cluster randomised controlled trial (RCT). In the intervention schools, physical education teachers were instructed to spend 15-30 min of all physical education lessons (2× per week) on strength exercises. Monthly motivational lessons were given to stimulate students to be more physically active. Control schools followed their usual curriculum. The primary outcome measure was body composition assessed by the deuterium dilution technique. Daily physical activity and sedentary behaviour measured by accelerometry served as a secondary outcome. RESULTS: After 1 year, a 1.6% fat mass difference was found in favour of the intervention group (p = .007). This reflected a 0.9 kg difference in fat free mass (intervention>control; p = .041) and 0.7 kg difference in fat mass (intervention

Prevention of tick bites: an evaluation of a smartphone app.

BACKGROUND: Lyme borreliosis (LB) is the most common reported tick-borne infection in Europe, and involves transmission of Borrelia by ticks. As long as a vaccine is not available and effective measures for controlling tick populations are insufficient, LB control is focused on preventive measures to avoid tick bites. To inform citizens about the risk of ticks, motivate them to check for tick bites, and encourage them to remove any attached tick as quickly as possible, a mobile app called 'Tekenbeet' (Dutch for 'tick bite') was developed and released. The aim of this study was to evaluate the usage and user satisfaction of the 'Tekenbeet' app and to investigate whether it affects users' knowledge, perceived severity, perceived susceptibility, self-efficacy, response efficacy, current behavior and intention to comply with preventive measures. METHODS: Usage of the app was evaluated with data obtained from Google Analytics. A survey among the Dutch general adult population with two data collection periods evaluated the usage, user satisfaction and its influence on abovementioned outcomes. RESULTS: Data obtained from Google Analytics showed the app was downloaded almost 40,000 in the 20 months following the launch. The 'tick radar' and 'tick diary' screens were viewed most often. In addition, a total of 554 respondents completed an online survey. The mean user satisfaction score was 7.44 (on a scale of 1-10) and 90.9% of respondents would recommend the app to others. On average, survey respondents who downloaded the app (n = 243) recorded significantly more often higher knowledge scores (OR 3.37; 95% CI 2.02-5.09) and had a higher intention to comply with preventive measures (OR 2.47; 95% CI 1.22-5.85) compared to respondents who did not download the app (n = 311). CONCLUSIONS: The 'Tekenbeet' app is a frequently used and well-appreciated educational tool to increase public knowledge of ticks and tick bites. It also helps to improve the user's intention to apply preventive measures. The use of smartphones and apps is now commonplace in the Netherlands; the 'Tekenbeet' app feeds into this trend and thereby offers a modern day alternative to established formats such as an information leaflet and information provision on the Internet.

Designing more engaging computer-tailored physical activity behaviour change interventions for breast cancer survivors: lessons from the iMove More for Life study.

BACKGROUND: Participating in regular physical activity is a recommended cancer recovery strategy for breast cancer survivors. However, tailored support services are not widely available and most survivors are insufficiently active to obtain health benefits. Delivering tailored programs via the Internet offers one promising approach. However, recent evaluations of such programs suggest that major improvements are needed to ensure programs meet the needs of users and are delivered in an engaging way. Understanding participants' experiences with current programs can help to inform the next generation of systems. PURPOSE: The purposes of this study are to explore breast cancer survivor's perspectives of and experiences using a novel computer-tailored intervention and to describe recommendations for future iterations. METHODS: Qualitative data from a sub-sample of iMove More for Life study participants were analysed thematically to identify key themes. Participants long-term goals for participating in the program were explored by analysing open-ended data extracted from action plans completed during the intervention (n = 370). Participants negative and positive perceptions of the website and recommendations for improvement were explored using data extracted from open-ended survey items collected at the immediate intervention follow-up (n = 156). RESULTS: The majority of participants reported multi-faceted goals, consisting of two or more outcomes they hoped to achieve within a year. While clear themes were identified (e.g. 'being satisfied with body weight'), there was considerable variability in the scope of the goal (e.g. desired weight loss ranged from 2 to 30 kg). Participants' perceptions of the website were mixed, but clear indications were provided of how intervention content and structure could be improved. CONCLUSIONS: This study provides insight into how to better accommodate breast cancer survivors in the future and ultimately design more engaging computer-tailored interventions.

Optimising decision making on illness absenteeism due to fever and common infections within childcare centres: development of a multicomponent intervention and study protocol of a cluster randomised controlled trial.

BACKGROUND: Evidence has shown that children 0-4 year-old attending childcare are prone to acquire infections compared to children cared for at home, with fever being the most common symptom. Illness absenteeism due to fever and common infections is substantial and mostly driven by unrealistic concerns and negative attitude towards fever of both childcare staff and parents, resulting in illness absenteeism from childcare, work absenteeism among parents and healthcare service use. The objective of this study is to optimise decision making among childcare staff on illness absenteeism due to fever and common infections in childcare. Underlying determinants of behavioural change were targeted by means of a multicomponent intervention. METHODS: A multicomponent intervention was developed to improve decision making, using the stepwise approach of Intervention Mapping, and in close collaboration with stakeholders and experts. The intervention consisted of 1) a two-hour educational session on fever among childcare staff; 2) an online video for childcare staff and parents emphasising key information of the educational session; 3) a decision tool for childcare staff and parents in the format of a traffic light system to estimate the severity of illness and corresponding advices for childcare staff and parents; 4) an information booklet regarding childhood fever, common infections, and self-management strategies for childcare staff and parents. The multicomponent intervention will be evaluated in a cluster randomised trial with a 12-week follow-up period and absenteeism due to illness (defined as the percentage of childcare days absent due to illness on the total of childcare days during a 12-week period) as primary outcome measure. Secondary outcome measures are: incidence rate and duration of illness episodes, knowledge, attitude, self-efficacy, and risk perception on fever and common infections of childcare staff and parents, healthcare service use in general and paracetamol use, and work absenteeism of parents. DISCUSSION: This study aims to develop a multicomponent intervention and to evaluate to what extent illness absenteeism due to fever and common infections can be affected by implementing a multicomponent intervention addressing decision making and underlying determinants among childcare staff and parents of children attending daycare. TRIAL REGISTRATION: NTR6402 (registered on 21-apr-2017).

Education on tick bite and Lyme borreliosis prevention, aimed at schoolchildren in the Netherlands: comparing the effects of an online educational video game versus a leaflet or no intervention.

BACKGROUND: Lyme disease or Lyme borreliosis (LB) is the most common tick-borne disease both in the United States and Europe. Children, in particular, are at high risk of contracting LB. Since child-specific educational tools on ticks, tick bites and LB are lacking, we developed an online educational video game. In this study, we compared the effectiveness of an online educational video game versus a newly developed leaflet aimed to improve prevention of tick bites and LB among Dutch schoolchildren. METHODS: A total of 887 children, aged 9-13 years and attending the two final years of primary schooling, were recruited from 25 primary schools in June and July 2012. They were assigned through cluster randomization to one of three intervention groups: 'game' (22.4%), 'leaflet' (35.6%) or 'control' (41.9%). Prior to and directly following intervention, the children were asked to complete a short questionnaire. The main outcome measures were knowledge, perception (perceived susceptibility and importance) and preventive behavior in relation to tick bites and LB. Generalized linear mixed models were used to analyze the data. RESULTS: In the game group, the leaflet group and the control group, knowledge about ticks and tick bites improved significantly. The game was also an effective tool for improving preventive behavior; the frequency of checking for ticks increased significantly. However, there were no significant differences in knowledge improvement between the interventions. The game outperformed the leaflet in terms of improving preventive behavior, whereas the frequency of tick checks increased significantly. But this frequency didn't increase more than in the control group. CONCLUSIONS: The positive knowledge effects observed in the control group suggests the presence of a mere measurement effect related to completion of the questionnaire. The game did not outperform the leaflet or control group on all outcome measures. Therefore, the game may be of value as a complementary role, in addition to other media, in child-specific public health education programs on ticks and LB. This trial was retrospectively registered on October 21, 2016 (trial registration number: ISRCTN15142369).

Does NAD(P)H oxidase-derived H2O2 participate in hypotonicity-induced insulin release by activating VRAC in ß-cells?

NAD(P)H oxidase (NOX)-derived H(2)O(2) was recently proposed to act, in several cells, as the signal mediating the activation of volume-regulated anion channels (VRAC) under a variety of physiological conditions. The present study aims at investigating whether a similar situation prevails in insulin-secreting BRIN-BD11 and rat ß-cells. Exogenous H(2)O(2) (100 to 200 µM) at basal glucose concentration (1.1 to 2.8 mM) stimulated insulin secretion. The inhibitor of VRAC, 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) inhibited the secretory response to exogenous H(2)O(2). In patch clamp experiments, exogenous H(2)O(2) was observed to stimulate NPPB-sensitive anion channel activity, which induced cell membrane depolarization. Exposure of the BRIN-BD11 cells to a hypotonic medium caused a detectable increase in intracellular level of reactive oxygen species (ROS) that was abolished by diphenyleneiodonium chloride (DPI), a universal NOX inhibitor. NOX inhibitors such as DPI and plumbagin nearly totally inhibited insulin release provoked by exposure of the BRIN-BD11 cells to a hypotonic medium. Preincubation with two other drugs also abolished hypotonicity-induced insulin release and reduced basal insulin output: 1) N-acetyl-L-cysteine (NAC), a glutathione precursor that serves as general antioxidant and 2) betulinic acid a compound that almost totally abolished NOX4 expression. As NPPB, each of these inhibitors (DPI, plumbagin, preincubation with NAC or betulinic acid) strongly reduced the volume regulatory decrease observed following a hypotonic shock, providing an independent proof that VRAC activation is mediated by H(2)O(2). Taken together, these data suggest that NOX-derived H(2)O(2) plays a key role in the insulin secretory response of BRIN-BD11 and native ß-cells to extracellular hypotonicity.

Functional role of aquaglyceroporin 7 expression in the pancreatic beta-cell line BRIN-BD11.

Both mouse and rat pancreatic islet beta-cells were recently found to express aquaglyceroporin 7 (AQP7). In the present study, the expression and role of AQP7 in the function of BRIN-BD11 cells were investigated. AQP7 mRNA and protein were detected by RT-PCR and Western blot analysis, respectively. In an isoosmolar medium, the net uptake of [2-(3)H]glycerol displayed an exponential time course reaching an equilibrium plateau value close to its extracellular concentration. Within 2 min of incubation in a hypotonic medium (caused by a 50 mM decrease in NaCl concentration), the [2-(3)H]glycerol uptake averaged 143.2 +/- 3.8% (n = 24; P < 0.001) of its control value in isotonic medium, declining thereafter consistently with previously demonstrated volume regulatory decrease. When isoosmolarity was restored by the addition of 100 mM urea to the hypotonic medium, [2-(3)H]glycerol uptake remained higher (112.1 +/- 2.8%, n = 24; P < 0.001) than its matched control under isotonic conditions, indicating rapid entry of urea and water. Insulin release by BRIN-BD11 cells was 3 times higher in hypotonic than in isotonic medium. When glycerol (100 mM) or urea (100 mM) were incorporated in the hypotonic medium, the insulin release remained significantly higher than that found in the control isotonic medium, averaging respectively 120.2 +/- 4.2 and 107.0 +/- 3.8% of the paired value recorded in the hypotonic medium. These findings document the rapid entry of glycerol and urea in BRIN-BD11 cells, likely mediated by AQP7.

Systematic review of interventions aimed at reducing hookah pipe use: Implications for practitioners and clinicians.

BACKGROUND: Globally, tobacco ranks as one of the major risk factors for death, disease and disability. While strong measures have been implemented to reduce cigarette use, there are alternative ways to smoke tobacco, such as the hookah pipe. Hookah pipe use appears to pose a significant public health concern and has serious short- and long-term health consequences for users and those exposed to second-hand smoke. To date, few studies have reviewed hookah pipe interventions beyond the efficacy-based paradigm. OBJECTIVES: To systematically review interventions aimed at reducing hookah pipe use through the RE-AIM framework (reach, efficacy, adoption, implementation and maintenance of results) in order to provide a practical means of evaluating interventions. METHODS: A systematic review spanning 12 databases identified studies aimed at reducing hookah pipe use. All methodological types of intervention studies that were peer reviewed and in the English language were considered for inclusion. The quality of each study was assessed. Ten studies were deemed eligible. For each study, data were extracted using the RE-AIM framework. RESULTS: All studies focused solely on the smoker, and their recruitment strategies were described. Eight studies reported meeting their objectives. Overall, the studies presented limited information regarding adoption success. The interventions were mainly supportive, educational or counselling sessions. Only five studies reported on the maintenance of results post intervention. CONCLUSIONS: Interventions focusing on reducing hookah pipe use are limited. Counselling and educational support sessions seem to be the most feasible and potentially successful approaches for intervention.

Complexity of Organ Donation Registration: Determinants of Registration Behavior Among Lower-educated Adolescents.

BACKGROUND: Registration rates are low for organ donation among lower educated adolescents in The Netherlands. This could be improved by preparing them for making a decision regarding donation when they become 18 years old. To do so, more insight is needed into their beliefs about organ donation and registration. METHODS: A cross-sectional quantitative study was conducted among students in intermediate vocational education schools. Data were gathered my means of self-administrated questionnaires. The outcome measurements included current registration status, being an organ donor, intention to register, and intention to become a donor. Correlation coefficients were used to assess the strength of associations between beliefs and each of the 4 outcome measurements. RESULTS: A total of 405 participants (mean age, 18.86 years) were included, of whom 26.6% had already registered a decision. Most beliefs showed a significant correlation with one or more of the outcomes. In general, the correlations were of small to medium size and participants scored around the middle of the scales on the beliefs. CONCLUSION: Means and correlations need to be combined to gain insight into the importance of certain beliefs for future interventions. However, it is plausible that, in addition to these explicit beliefs, implicit factors play a role in registration behavior. This could be explored in future research. Results could support intervention development for increasing registration rates.

Can you elaborate on that? Addressing participants' need for cognition in computer-tailored health behavior interventions.

Computer-tailored interventions, which deliver health messages adjusted based on characteristics of the message recipient, can effectively improve a range of health behaviours. Typically, the content of the message is tailored to user demographics, health behaviours and social cognitive factors (e.g., intentions, attitudes, self-efficacy, perceived social support) to increase message relevance, and thus the extent to which the message is read, considered and translated into attitude and behaviour change. Some researchers have suggested that the efficacy of computer-tailored interventions may be further enhanced by adapting messages to suit recipients' need for cognition (NFC) - a personality trait describing how individuals tend to process information. However, the likely impact of doing so, especially when tailored in conjunction with other variables, requires further consideration. It is possible that intervention effects may be reduced in some circumstances due to interactions with other variables (e.g., perceived relevance) that also influence information processing. From a practical point of view, it is also necessary to consider how to optimally operationalise and measure NFC if it is to be a useful tailoring variable. This paper aims to facilitate further research in this area by critically examining these issues based on relevant theories and existing evidence.

How do different delivery schedules of tailored web-based physical activity advice for breast cancer survivors influence intervention use and efficacy?

PURPOSE: The purpose of the study is to investigate the impact of differing delivery schedules of computer-tailored physical activity modules on engagement and physical activity behaviour change in a web-based intervention targeting breast cancer survivors. METHODS: Insufficiently active breast cancer survivors (n = 492) were randomly assigned to receive one of the following intervention schedules over 12 weeks: a three-module intervention delivered monthly, a three-module intervention delivered weekly or a single module intervention. Engagement with the website (number of logins, time on site, modules viewed, action plans completed) was measured using tracking software. Other outcomes (website acceptability, physical activity behaviour) were assessed using online surveys. Physical activity outcomes were analysed using regression models for both study completers and when applying intention-to-treat (using multiple imputation). RESULTS: Completers allocated to the monthly module group rated the intervention higher (b = 2.2 95 % CI = 0.02-4.53) on acceptability and had higher levels of resistance-training (IRR = 1.88, 95 % CI = 1.16-3.04) than those in the single module group. When accounting for missing data, these differences were no longer significant. The completion of at least two action plans was higher among those allocated to the monthly module group compared to those in the weekly module group (53 vs 40 %, p = 0.02); though the completion of at least two modules was higher in the weekly module group compared to the monthly module group (60 vs 46 %; p = 0.01). There were no other significant between group differences observed. CONCLUSION: This study provides preliminary evidence that web-based computer-tailored interventions can be used to increase physical activity among breast cancer survivors. Further, there were some outcome differences based on how the tailored modules were delivered, with the most favourable outcomes observed in the monthly delivery group. IMPLICATIONS FOR CANCER SURVIVORS: This study will be useful for informing the design of future web-based interventions targeting breast cancer survivors.

Increasing fruit and vegetable intake among children: comparing long-term effects of a free distribution and a multicomponent program.

The aim of this study was to evaluate and compare the effectiveness of two primary school-based interventions on children's fruit and vegetable (F&V) consumption on the long term (2 years after the start of the interventions). Six primary schools were recruited and randomly assigned to (i) a daily free distribution program for the whole school or (ii) a multicomponent program consisting of a classroom curriculum and parental involvement (without free F&V), and six schools served as controls. Follow-up measurements were conducted at the end of the intervention (Follow-up I) and 1 year later (Follow-up II). Random coefficient analyses for longitudinal data showed that the effects of both interventions did not differ between the two follow-up measurements. The results showed similar effects for the free distribution program and the multicomponent program in increasing children's fruit consumption over time (respectively, 7.2 and 15.2 g day(-1)). The distribution program also increased children's vegetable consumption over time (3.25 g day(-1)), even after repeating the analyses using a pessimistic scenario. Despite the large dropout and its consequences for generalizability of our results, the distribution program is considered as the preferred intervention of the two, and implementation on a larger scale should be investigated.

Hypotonic cell swelling stimulates permeability to cAMP in a rat colonic cell line.

This study characterized the membrane permeability to cAMP in a cell line derived from the rat colon (CC531(mdr+)) by comparison of fluxes of 3H-cAMP, 3H-8-bromo-cAMP, 3H-taurine, 3H-adenosine and 3H-5'AMP under various experimental conditions including cell membrane depolarization and hypotonic cell swelling. Cell volume was modified by changing the osmolality and composition of the extracellular medium. Incubation in iso- and hypotonic KCl media induced graded increases in cell volume and stable activation of volume-sensitive channels that was reflected in an increased efflux of 3H-taurine. Incubation in hypotonic KCl solution also enhanced the efflux of 3H-8-Br-cAMP (a non-hydrolysable analogue of cAMP). Both the efflux of 3H-taurine and of 3H-8-Br-cAMP were inhibited by 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB, 100 microM) suggesting the involvement of volume-sensitive anion channels. To gain further insight into the route mediating cAMP permeability, the uptakes of 3H-cAMP, 3H-8-Br-cAMP and 3H-taurine were determined over short (5-min) periods. Uptakes of these substrates demonstrated close similarities: comparable increases were observed that correlated with the increases in cell volume in iso- and hypoosmotic KCl media; they were inhibited strongly by NPPB (100 microM) and metabolic inhibitors (deoxyglucose, 20 mM together with the mitochondrial uncoupler carbonylcyanide p-(trifluoromethoxy)phenylhydrazone, FCCP, 10 microM) while barely reduced by dipyridamole (100 microM) and they were not affected by adenosine (1 mM). In contrast, the uptakes of 3H-adenosine and 3H-5'AMP had strikingly different properties; they were insensitive to cell swelling; barely inhibited by NPPB (100 microM) and metabolic inhibitors (deoxyglucose and FCCP) while strongly reduced by dipyridamole (100 micro M). Unlike the uptakes of 3H-cAMP, 3H-8-Br-cAMP and 3H-taurine, the uptakes of 3H-adenosine and 3H-5'AMP were reduced in Na(+)-free media, suggesting the presence in this cell line of two different adenosine carriers, one sodium-dependent and one sodium-independent. Taken together the present data show that in this rat colonic cell line, cAMP permeability is increased by cell swelling in hypotonic KCl medium and inhibited by NPPB and metabolic inhibitors. The similarity of these characteristics to those of taurine permeability suggests the involvement of a volume-sensitive anion pathway.