Developing symptom-specific dietary leaflets to address radiotherapy side effects using an eDelphi method.

INTRODUCTION: Patients suffering from head and neck (HN) cancer undergoing Radiotherapy (RT) suffer from various debilitating side effects that greatly hinder their eating ability. This leads to patients having a poor nutritional status causing weight loss. This study aimed to assess if an e-Delphi method variation allowed efficiently developing dietary advice leaflets addressing these side effects and achieving a consensus among healthcare professionals. METHODS: An e-Delphi style approach was used. Six participants representing the professions working with HN patients were asked to give feedback on four symptom-specific dietary leaflets. These leaflets were designed based on a previous extensive literature review. After each round, the participants' suggested changes were applied. Before applying major changes to the leaflet, the participants were asked to vote if they agreed with each major change. RESULTS: Overall consensus was reached after three rounds since all participants voted "highly likely" to use it in their clinical practice. Most suggestions by the participants agreed with the existing literature. The only change (accepted as a result of voting) that contradicted the literature was concerning sugar intake. CONCLUSION: The participants reached consensus and developed leaflets that were based on literature recommendations for use for patients that, in their opinion, were acceptable for clinical use. This e-Delphi variation proved to be efficient to achieve consensus among healthcare professionals regarding patient information tools. IMPLICATIONS FOR PRACTICE: This eDelphi method is an efficient and effective way to revise and achieve consensus regarding the development of patient information material.

Acute sub-diaphragmatic anterior vagus nerve stimulation increases peripheral glucose uptake in anaesthetized rats.

The sub-diaphragmatic vagus innervates various organs involved in the control of glucose homeostasis including the liver, pancreas and the intestines. In the current study, we investigated the effect of acute electrical stimulation of the anterior trunk of the sub-diaphragmatic vagus on glucose fluxes in anaesthetized adult male rats. After overnight fast, rats underwent either vagus nerve stimulation (VNS+, n = 11; rectangular pulses at 5 Hz, 1.5 mA, 1 msec pulse width) or sham stimulation (VNS-; n = 11) for 120 min under isoflurane anesthesia. Before stimulation, the rats received an i.v. bolus of 1 mL/kg of a sterilized aqueous solution containing 125 mg/mL of D-[6,6-2H2] glucose. Endogenous glucose production (EGP) and glucose clearance rate (GCR) were calculated by kinetic analysis from the wash-out of injected D-[6,6-2H2]glucose from the circulation. VNS+ resulted in lower glucose levels compared to the VNS- group (p < 0.05), with similar insulin levels. EGP was similar in both groups, but the GCR was higher in the VNS+ group compared to the VNS- group (p < 0.001). Circulating levels of the sympathetic transmitter norepinephrine were reduced by VNS+ relative to VNS- treatment (p < 0.01). It is concluded that acute anterior sub-diaphragmatic VNS causes stimulation of peripheral glucose uptake, while plasma insulin levels remained similar, and this is associated with lower activity of the sympathetic nervous system.

Nutrient dynamics of 12 Sphagnum species during establishment on a rewetted bog.

Peatland degradation through drainage and peat extraction have detrimental environmental and societal consequences. Rewetting is an option to restore lost ecosystem functions, such as carbon storage, biodiversity and nutrient sequestration. Peat mosses (Sphagnum) are the most important peat-forming species in bogs. Most Sphagnum species occur in nutrient-poor habitats; however, high growth rates have been reported in artificial nutrient-rich conditions with optimal water supply. Here, we demonstrate the differences in nutrient dynamics of 12 Sphagnum species during their establishment in a 1-year field experiment at a Sphagnum paludiculture area in Germany. The 12 species are categorized into three groups (slower-, medium- and fast-growing). Establishment of peat mosses is facilitated by constant supply of nutrient-rich, low pH, and low alkalinity surface water. Our study shows that slower-growing species (S. papillosum, S. magellancium, S. fuscum, S. rubellum, S. austinii; often forming hummocks) displayed signs of nutrient imbalance. These species accumulated higher amounts of N, P, K and Ca in their capitula, and had an elevated stem N:K quotient (>3). Additionally, this group sequestered less C and K per m2 than the fast and medium-growing species (S. denticulatum, S. fallax, S. riparium, S. fimbriatum, S. squarrosum, S. palustre, S. centrale). Lower lawn thickness may have amplified negative effects of flooding in the slower-growing species. We conclude that nutrient dynamics and carbon/nutrient sequestration rates are species-specific. For bog restoration, generating ecosystem services or choosing suitable donor material for Sphagnum paludiculture, it is crucial to consider their compatibility with prevailing environmental conditions.

Sphagnum bleaching: Bicarbonate 'toxicity' and tolerance for seven Sphagnum species.

Growth and functioning of Sphagnum mosses are closely linked to water level and chemistry. Sphagnum mosses occur in wet, generally acidic conditions, and when buffered, alkaline water is known to negatively impact Sphagnum. The effects of time, dose and species-specific responses of buffered, alkaline water on Sphagnum are largely unknown. We investigated the effects of bicarbonate and calcium on the survival, growth and physiological functioning of seven Sphagnum species occurring in contrasting environments, from raised bogs to (rich) fens. Mosses were submerged in different concentrations of bicarbonate and calcium solutions for 10 weeks under climate-controlled circumstances. After 2 weeks, all species exposed to the high bicarbonate treatment (2.0 mM) showed severe potassium leakage and swift discoloration. In contrast, species showed differential responses to the intermediate bicarbonate treatment (0.8 mM), some with a later onset of potassium leakage. S. squarrosum, S. teres & S. contortum generally persisted the longest, with all species dying after 6 to 10 weeks. Calcium alone, in contrast, negatively affected S. squarrosum, S. teres & S. contortum, causing discoloration and potassium leakage. Our study shows enrichment with bicarbonate, but not calcium, is detrimental for most Sphagnum species tested. A mechanistic model was developed that is consistent with dose and duration dependence and the species specificity. Future conservation and restoration measures for Sphagnum-dominated habitats and Sphagnum farming (cultivation, production and harvest of Sphagnum moss biomass) should limit flooding with bicarbonate-rich waters while investigating new management options, like acidifying surface waters to lower bicarbonate levels.

Ileal transposition: A non-restrictive bariatric surgical procedure that reduces body fat and increases ingestion-related energy expenditure.

BACKGROUND: Ileal Transposition (IT) was developed as a model to study body weight reduction without the restrictive or malabsorptive aspects of other bariatric surgeries, but the exact mechanisms of the alterations in body weight after IT are not completely understood. OBJECTIVE: To provide a detailed description of the surgical procedure of IT, and describe its effect on energy balance parameters. METHODS: Adult male Lewis rats underwent either IT (IT+) or sham (IT-) surgery. Following surgery body weight and energy intake were monitored. After attaining weight stability (> 30 days), energy expenditure and its components were assessed using indirect calorimetry at a day of fasting, limited intake, and ad libitum intake. At the end of the study body composition analysis was performed. RESULTS: IT+ resulted in transiently reduced energy intake, increased ingestion-related energy expenditure (IEE) and decreased body and adipose tissue weight when compared to IT-. At weight stability, neither energy budget (i.e., energy intake - energy expenditure), nor energy efficiency was different in IT+ rats compared to IT-. CONCLUSION: Our data show that the primary cause of weight reduction following IT+ is a transient reduction in energy intake. If the increased IEE is related to a higher level of satiety, compensatory feeding to bridge body weight difference between IT+ and IT- rats is less likely to occur.

Home alone: a systematic review and meta-analysis on the effects of individual housing on body weight, food intake and visceral fat mass in rodents.

Rats and mice are widely used to study environmental effects on psychological and metabolic health. Study designs differ widely and are often characterized by varying (social) housing conditions. In itself, housing has a profound influence on physiology and behaviour of rodents, affecting energy balance and sustainable metabolic health. However, evidence for potential long-term consequences of individual versus social housing on body weight and metabolic phenotype is inconsistent. We conducted a systematic literature review and meta-analyses assessing effects of individual versus social housing of rats and mice, living under well-accepted laboratory conditions, on measures of metabolic health, including body weight, food intake and visceral adipose tissue mass. Seventy-one studies were included in this review; 59 were included in the meta-analysis. Whilst housing did not affect body weight, both food intake and visceral adipose tissue mass were significantly higher in individually compared with socially housed animals. A combination of emotional stress and lack of social thermoregulation likely contributed to these effects. Increased awareness of consequences and improved specifications of housing conditions are necessary to accurately evaluate efficacy of drugs, diets or other interventions on metabolic and other health outcomes because housing conditions are rarely considered as possible moderators of reported outcomes.

Reducing dietary intake of linoleic acid of mouse dams during lactation increases offspring brain n-3 LCPUFA content.

Omega (n-)3 and n-6 long chain polyunsaturated fatty acids (LCPUFA) accumulation in the infant brain after birth is strongly driven by dietary supply of n-3 and n-6 LCPUFAs and their C18 precursors through breast milk or infant formula. n-3 LCPUFA accretion is associated with positive effects on neurodevelopmental outcome whereas high n-6 LCPUFA accumulation is considered disadvantageous. Maternal diet is crucial for breast milk fatty acid composition. Unfortunately, global increases in linoleic acid (C18:2n-6; LA) intake have dramatically increased n-6 LCPUFA and reduced n-3 LCPUFA availability for breastfed infants. We investigated the effects of reducing maternal dietary LA, or increasing n-3 LCPUFA, during lactation on milk and offspring brain fatty acids in mice. Offspring brain n-3 LCPUFA was higher following both interventions, although effects were mediated by different mechanisms. Because of competitive interactions between n-3 and n-6 fatty acids, lowering maternal LA intake may support neurodevelopment in breastfed infants.

Organ Donation After Euthanasia: A Dutch Practical Manual.

Many physicians and patients do not realize that it is legally and medically possible to donate organs after euthanasia. The combination of euthanasia and organ donation is not a common practice, often limited by the patient's underlying pathology, but nevertheless has been performed >40 times in Belgium and the Netherlands since 2005. In anticipation of patients' requests for organ donation after euthanasia and contributing to awareness of the possibility of this combination among general practitioners and medical specialists, the Maastricht University Medical Center and the Erasmus University Medical Center Rotterdam have developed a multidisciplinary practical manual in which the organizational steps regarding this combined procedure are described and explained. This practical manual lists the various criteria to fulfill and the rules and regulations the different stakeholders involved need to comply with to meet all due diligence requirements. Although an ethicist was involved in writing this paper, this report is not specifically meant to comprehensively address the ethical issues surrounding the topic. This paper is focused on the operational aspects of the protocol.

A new high-quality set of singly ((2) H) and doubly ((2) H and (18) O) stable isotope labeled reference waters for biomedical and other isotope-labeled research.

RATIONALE: Research using water with enriched levels of the rare stable isotopes of hydrogen and/or oxygen requires well-characterized enriched reference waters. The International Atomic Energy Agency (IAEA) did have such reference waters available, but these are now exhausted. New reference waters thus had to be produced in sufficient quantity, and higher characterization quality was desired. METHODS: The reference waters have been prepared gravimetrically from three parent waters: natural water, pure (2) H water and highly (18) O-enriched water. These parent waters have been thoroughly assessed for their full isotopic compositions. To ensure the integrity and correctness of the gravimetric procedure, validation measurements have been carried out on the isotopic composition of the produced reference waters by two of our laboratories. These measurements corroborate the values obtained on the basis of gravimetric data. RESULTS: Two new sets of three reference waters enriched in the stable isotopes have been produced and certified: one set of singly labeled waters, only enriched in (2) H, and another set of Doubly Labeled Waters, enriched in both (2) H and (18) O. They cover δ(2) H and δ(18) O values in the range of 800-16000 ‰ and 100-2000 ‰, respectively. The process has led to highly accurate isotopic values for these waters. CONCLUSIONS: These reference waters are now available (called IAEA-604 to IAEA-609). They will be valuable as reference materials for all fields using isotope labeling of water, most prominently, but not exclusively, biomedical research (body composition analyses, metabolic rate measurements). The two waters with the lowest enrichments will also be useful as anchor values for isotope measurements around the natural range.

Avoidance of activity and limitations in activities in patients with osteoarthritis of the hip or knee: a 5 year follow-up study on the mediating role of reduced muscle strength.

OBJECTIVE: To evaluate the mediating role of reduced muscle strength in the relationship between avoidance of activity and limitations in activities in patients with knee or hip osteoarthritis (OA). METHODS: A longitudinal cohort study with 5 years follow-up was conducted. Patients with knee or hip OA (n = 288) were recruited at rehabilitation centers and hospitals. Self-reported and performance based limitations in activities, avoidance of activity and muscle strength were assessed at baseline, 1, 2, 3 and 5 years follow-up. Generalized Estimating Equations (GEE) analyses were used to evaluate mediation. RESULTS: In patients with knee OA, reduced knee extensor muscle strength mediated the relationship between avoidance of activity and limitations in activities. In patients with hip OA reduced hip abductor muscle strength mediates the relationship between avoidance of activity and limitations in activities. CONCLUSION: The results of this longitudinal study support the theory that avoidance of activity leads to deterioration of muscle strength and consequently to more limitations in activities in patients with knee and hip OA.

Doubly Labelled Water analysis: preparation, memory correction, calibration and quality assurance for δ2H and δ18O measurements over four orders of magnitudes.

RATIONALE: The Doubly Labelled Water (DLW) method is an established way of determining the metabolic rate in humans and animals, with the advantage that the subjects need not be confined. The method, however, needs accurate determination of both the δ(2)H and the δ(18)O isotope values over a wide range of enrichments. METHODS: In this paper we describe a number of crucial steps in the process of isotope determination in body fluids. These steps include micro-distillation, correction of the measurements for sample-to-sample memory and calibration of the isotope scales over many orders of magnitudes. In contrast to several published protocols and guidelines, we also take highly enriched samples into account, as they are required for studying the metabolic rate of birds and small mammals. For our isotope scale calibration, we made a set of gravimetrically prepared, double labelled waters with known isotope values. Our quality assurance includes a scheme for easy calculation of the error propagation, leading to a reliable estimate of the analytical error in the metabolic rate. RESULTS: Our memory correction algorithm assumes the existence of three water "pools" that have different sizes and exchange rates with the injected samples. We show that the method can correct even huge memory signals, without the need for "true" values. CONCLUSIONS: With the presented building blocks, we show how to assure a reliable and accurate isotope analysis for the DLW method, both for human and for animal applications. Although our measurements have been performed using isotope ratio mass spectrometry, most of the procedures are also useful for laser spectrometry.

Taekwondo training improves balance in volunteers over 40.

Balance deteriorates with age, and may eventually lead to falling accidents which may threaten independent living. As Taekwondo contains various highly dynamic movement patterns, Taekwondo practice may sustain or improve balance. Therefore, in 24 middle-aged healthy volunteers (40-71 year) we investigated effects of age-adapted Taekwondo training of 1 h a week during 1 year on various balance parameters, such as: motor orientation ability (primary outcome measure), postural and static balance test, single leg stance, one leg hop test, and a questionnaire. Motor orientation ability significantly increased in favor of the antero-posterior direction with a difference of 0.62° toward anterior compared to pre-training measurement, when participants corrected the tilted platform rather toward the posterior direction; female gender being an independent outcome predictor. On postural balance measurements sway path improved in all 19 participants, with a median of 9.3 mm/s (range 0.71-45.86), and sway area in 15 participants with 4.2 mm(2)/s (range 17.39-1.22). Static balance improved with an average of 5.34 s for the right leg, and with almost 4 s for the left. Median single leg stance duration increased in 17 participants with 5 s (range 1-16), and in 13 participants with 8 s (range 1-18). The average one leg hop test distance increased (not statistically significant) with 9.5 cm. The questionnaire reported a better "ability to maintain balance" in 16. In conclusion, our data suggest that age-adapted Taekwondo training improves various aspects of balance control in healthy people over the age of 40.

Metabolic consequences of chronic sleep restriction in rats: changes in body weight regulation and energy expenditure.

Epidemiological studies have shown an association between short or disrupted sleep and an increased risk to develop obesity. In animal studies, however, sleep restriction leads to an attenuation of weight gain that cannot be explained by changes in energy intake. In the present study, we assessed whether the attenuated weight gain under conditions of restricted sleep is a consequence of an overall increase in energy expenditure. Adult male rats were subjected to a schedule of chronic sleep restriction (SR) for 8 days with a 4h window of unrestricted rest per day. Electroencephalogram and electromyogram recordings were performed to quantify the effect of the sleep restriction schedule on sleep-wake patterns. In a separate experiment, we measured sleep restriction-induced changes in body weight, food intake, and regulatory hormones such as glucose, insulin, leptin and corticosterone. To investigate whether a change in energy expenditure underlies the attenuation of weight gain, energy expenditure was measured by the doubly labeled water method from day 5 until day 8 of the SR protocol. Results show a clear attenuation of weight gain during sleep restriction but no change in food intake. Baseline plasma glucose, insulin and leptin levels are decreased after sleep restriction which presumably reflects the nutritional status of the rats. The daily energy expenditure during SR was significantly increased compared to control rats. Together, we conclude that the attenuation of body weight gain in sleep restricted rats is explained by an overall increase in energy expenditure together with an unaltered energy intake.

The course of limitations in activities over 5 years in patients with knee and hip osteoarthritis with moderate functional limitations: risk factors for future functional decline.

OBJECTIVE: To describe the course of limitations in activities over 5 years follow-up and identify predictors of future limitations in activities in elderly patients with osteoarthritis (OA) of the hip or knee with moderate functional limitations. METHOD: A longitudinal cohort study with 5 years follow-up was conducted. Patients (n=288) were recruited at rehabilitation centers and hospitals. The main outcome measures were self-reported and performance-based limitations in activities. Prognostic factors were demographic and clinical data, body functions, comorbidity, cognitive functioning, avoidance of activity and social support. Measurements were conducted at baseline, 1, 2, 3 and 5 years follow-up. RESULTS: Both in patients with knee and hip OA, the course of limitations in activities remained fairly stable over a period of 5 years. Avoidance of activity, increased pain, more comorbidity, a higher age, a longer disease duration, a reduced muscle strength and range of joint motion at baseline predicted more future limitations in activities in patients with knee OA. In patients with hip OA, avoidance of activity, increased pain, more comorbidity, a higher age, a higher educational level and a reduced range of motion at baseline predicted more future limitations in activities. CONCLUSIONS: The course of limitations in activities remains fairly stable over a period of 5 years in elderly patients with hip or knee OA. However, at individual level there is considerable variation. Predictors of more future limitations in activities include avoidance of activity, increased pain, higher morbidity count, reduced range of motion, and a higher age.

Nutrient additions in pristine Patagonian Sphagnum bog vegetation: can phosphorus addition alleviate (the effects of) increased nitrogen loads.

Sphagnum-bog ecosystems have a limited capability to retain carbon and nutrients when subjected to increased nitrogen (N) deposition. Although it has been proposed that phosphorus (P) can dilute negative effects of nitrogen by increasing biomass production of Sphagnum mosses, it is still unclear whether P-addition can alleviate physiological N-stress in Sphagnum plants. A 3-year fertilisation experiment was conducted in lawns of a pristine Sphagnum magellanicum bog in Patagonia, where competing vascular plants were practically absent. Background wet deposition of nitrogen was low (≈ 0.1-0.2 g · N · m(-2) · year(-1)). Nitrogen (4 g · N · m(-2) · year(-1)) and phosphorus (1 g · P · m(-2) · year(-1)) were applied, separately and in combination, six times during the growing season. P-addition substantially increased biomass production of Sphagnum. Nitrogen and phosphorus changed the morphology of Sphagnum mosses by enhancing height increment, but lowering moss stem density. In contrast to expectations, phosphorus failed to alleviate physiological stress imposed by excess nitrogen (e.g. amino acid accumulation, N-saturation and decline in photosynthetic rates). We conclude that despite improving growth conditions by P-addition, Sphagnum-bog ecosystems remain highly susceptible to nitrogen additions. Increased susceptibility to desiccation by nutrients may even worsen the negative effects of excess nitrogen especially in windy climates like in Patagonia.

Perinatal polyunstaurated fatty acids supplementation causes alterations in fuel homeostasis in adult male rats but does not offer resistance against STZ-induced diabetes.

Maternal factors can have major imprinting effects on homeostatic mechanisms in the developing fetus and newborn. Here we studied whether supplemented perinatal polyunsaturated fatty acids (PUFAs) influence energy balance and fuel homeostasis later in life. Between day 10 after conception and day 10 after delivery, female rats were subjected to chow enriched with 10% fish-oil (FO-rich). Fish oil contains high concentrations of n-3 biosynthesis endpoint products, which may have caused the increased membrane phospholipid incorporation (particularly derived from the long-chain 20 +:n-3 PUFAs) in 10-day old pup brains. Adult male offspring of FO-rich fed rats had reduced body weight (- 20%) at 3 months, and had lower levels of plasma leptin (- 54%), insulin (- 41%), triglycerides (- 65%), and lactate (- 46%) than controls. All differences between groups were lost 48 h after streptozotocin (STZ) treatment. At 4.5 months of age, body weights of FO-rich were still lower (- 6%) than controls, but were associated with increased food intake, and increased insulin sensitivity (following intraperitoneal injection) to lower blood glucose levels relative to controls. We concluded that perinatal FO supplementation has lasting effects on body weight homeostasis and fuel metabolism in male offspring, but does not offer resistance against STZ-induced diabetes.

Stress revisited: a critical evaluation of the stress concept.

With the steadily increasing number of publications in the field of stress research it has become evident that the conventional usage of the stress concept bears considerable problems. The use of the term 'stress' to conditions ranging from even the mildest challenging stimulation to severely aversive conditions, is in our view inappropriate. Review of the literature reveals that the physiological 'stress' response to appetitive, rewarding stimuli that are often not considered to be stressors can be as large as the response to negative stimuli. Analysis of the physiological response during exercise supports the view that the magnitude of the neuroendocrine response reflects the metabolic and physiological demands required for behavioural activity. We propose that the term 'stress' should be restricted to conditions where an environmental demand exceeds the natural regulatory capacity of an organism, in particular situations that include unpredictability and uncontrollability. Physiologically, stress seems to be characterized by either the absence of an anticipatory response (unpredictable) or a reduced recovery (uncontrollable) of the neuroendocrine reaction. The consequences of this restricted definition for stress research and the interpretation of results in terms of the adaptive and/or maladaptive nature of the response are discussed.

Norovirus disease associated with excess mortality and use of statins: a retrospective cohort study of an outbreak following a pilgrimage to Lourdes.

Although norovirus infection is generally known to be a mild disease, there is some evidence for severe outcome. An outbreak in a Dutch psychiatric institution, originating from pilgrims returning from Lourdes (France), provided an opportunity for performing a retrospective cohort study in order to identify risk factors for norovirus disease and excess mortality. Relative risks (RR) including 95% confidence intervals (CI) showed that attending the pilgrimage (RR 2·0, 95% CI 1·4-3·0) and age >70 (RR 1·7, 95% CI 1·2-2·2) were risk factors for symptomatic infection. In a subset of patients, for whom more detailed information was available, the use of statins was associated with norovirus disease when adjusted for underlying condition (adjusted odds ratio 3·9, 95% CI 1·2-13·0). Mortality was higher in cases infected during the pilgrimage compared to other residents (RR 20·9, 95% CI 4·7-93·8). Norovirus disease can lead to severe outcome. The newly identified risk of statins for contracting norovirus disease may have considerable consequences for the Western world and needs prospective confirmation.