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There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.

Objectives Secondary prevention of rheumatoid arthritis (RA) is generally considered potentially impactful because the entire RA population is believed to experience a symptomatic ‘pre-RA’ phase. We wondered whether this dogma is correct. Therefore we investigated an inception cohort of patients with newly diagnosed RA and studied among them patients who did and did not present with preceding arthralgia at risk for RA.Methods Consecutively diagnosed patients with RA between 2012 and 2022 were studied (n=699). These patients had either directly presented with clinically apparent arthritis, or had first presented with clinically suspect arthralgia (CSA). Clinical characteristics at symptom onset and RA diagnosis were compared. Whether certain characteristics frequently occurred together was studied using a K-means algorithm after dimension reduction with partial least squares discriminant analysis. To validate that groups differed in long-term outcomes, sustained disease-modifying anti-rheumatic drug-free remission (SDFR) of the groups was studied during a median follow-up of 5.3 years.Results Patients with RA who had first presented with CSA were younger, more often had a gradual symptom onset and were more often anti-citrullinated protein antibodies (ACPA)-positive. Studying characteristics at symptom onset and RA diagnosis revealed four patient clusters, of which two clusters included almost all patients with a preceding CSA phase. Patients in these two clusters (55% of RA population) were younger, had a gradual symptom onset, longer symptom duration and were more frequently ACPA-positive. Patients with RA in these clusters achieved SDFR less often (HR 0.51 (95% CI 0.37 to 0.68)) than the patients with RA in the two clusters where preceding CSA was infrequent/absent.Conclusion These data suggest the notion that the entire RA population has an identifiable symptomatic risk stage should be refuted. This may impact on the scope of preventive interventions targeting the symptomatic risk phase.

Background Conventional radiographs of hands and feet are used to depict structural damage in rheumatoid arthritis (RA). This is also commonly done in clinical practice in symptomatic patients at risk for RA (clinically suspect arthralgia (CSA)), but its rationale is unclear. We aimed to investigate the prevalence of radiographic erosive disease in patients with CSA and its progression over time.Methods Patients with symptomatic arthralgia of the Leiden CSA cohort were studied during 2-year follow-up or until development of inflammatory arthritis (IA). Erosive disease was defined according to the radiologist, or according to the RA-specific erosive definition in light of the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2010 RA criteria. Serial radiographs were evaluated according to the Sharp van der Heijde Scoring method (SHS) and radiographic erosive progression was determined. Additionally, it was evaluated if baseline erosive disease associated with IA development. Analyses were stratified for anticitrullinated protein antibody status.Results 1497 radiographs of hands and feet of 749 patients with CSA were studied. Median SHS-erosion score at baseline was 0 (IQR 0–1). RA-specific erosive disease was present in 1.7% according to the radiologist, and 2.5% according to the ACR/EULAR criteria. No patients with CSA progressed ≥5 SHS-erosion points during follow-up. Erosive disease at CSA onset was not associated with IA development (HR 0.98 (95% CI 0.40 to 2.44)).Conclusions At CSA onset, radiographic erosive disease is rare. In addition, it is rarely progressive within the CSA phase and not predictive for IA development. Therefore, for clinical practice, routinely made radiographs of hands and feet (such as regularly done at RA diagnosis) can be omitted in the at-risk stage of arthralgia.

IntroductionSperm cryopreservation is a valuable technique for storing valuable canine genetics. However, little is known concerning the fate of frozen sperm stored in a sperm bank. This study aimed to characterize dogs presented for sperm cryopreservation and describe the use and popularity of frozen sperm in the Netherlands and Belgium over recent years.MethodsMedical records from dogs presented for sperm cryopreservation between January 1, 2014 and December 31, 2022 at two different freezing centers were reviewed retrospectively. Imported frozen sperm was excluded due to lack of usage information. Each sperm cryopreservation was considered a single event, and data were collected separately for each cryopreserved sample.ResultsA total of 3,090 ejaculates from 1,040 males of 157 different breeds were included and investigated using exploratory data analysis. The findings showed a steady rise in the popularity of sperm cryopreservation, with annual growth rates ranging from 8.4 to 41.9%. The majority of dogs (88.5%) were between 1 and 9 years old at the time of sperm cryopreservation, with nearly one-third aged 2–4 years. Most dogs were collected for sperm cryopreservation once (62.8%) or twice (21.6%). Sperm banks were used for both short- and long-term storage needs, and 6.83% of ejaculates were eventually discarded. The primary use of froze sperm was for international shipment, while 21.8% was used locally for artificial insemination. Depending on the year of cryopreservation, between 44.1 and 79.6% of frozen ejaculates remained unused or only partially used at the time of data collection.DiscussionThe results of this study provides the first comprehensive analysis of the use and popularity of frozen sperm among dog breeders in Belgium and the Netherlands and suggest a change in breeding practices in recent years. The percentage of breeders resorting to sperm cryopreservation and the extent of frozen sperm use in current breeding strategies remain to be defined in future studies.

Objectives To investigate whether a combination of general health (Visual Analogue Scale (VAS)), Health Assessment Questionnaire-Disability Index (HAQ-DI), pain (VAS/Numerical Rating Scale (NRS)), quality of life (EQ-5D), fatigue (VAS/NRS) and presenteeism (0%–100% productivity loss) could aid as a screening tool to detect active disease in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA).Methods RA patients from the tREACH trial and TARA trial (n=683) and PsA patients from the DEPAR cohort (n=525) were included. The association of a deterioration in the aforementioned patient-reported outcome measure (PROM) scores between two consecutive visits and having active disease was assessed. Active disease was defined as a change from disease activity score (DAS) ≤2.4 to DAS >2.4 in RA or Disease Activity Index in Psoriatic Arthritis (DAPSA) ≤14 to DAPSA >14 in PsA. The area under the curve (AUC) of the sum score of deteriorated PROMs was evaluated.Results 4594 RA and 1154 PsA visits were evaluated and active disease occurred in 358 (8%) RA and 177 (15%) PsA visits. In both RA and PsA, a deterioration in general health (VAS), HAQ-DI, EQ-5D and pain (VAS/NRS) was significantly associated with active disease. The combination of these PROMs showed acceptable to excellent discriminative ability (RA AUC=0.76, PsA AUC=0.85). If a cut-point of ≥1 deteriorated PROMs is used, 40% of the visits in which RA patients have remission or low disease activity are correctly specified (specificity of 40%), while 10% of visits with active disease are overlooked (sensitivity of 90%). In PsA, these percentages are 41% and 4%, respectively.Conclusion A combination of general health, HAQ-DI, EQ-5D and pain could aid as a screening tool for active disease in patients with RA and PsA. These data could help facilitate remote monitoring of RA and PsA patients in the future.Trial registration numbers ISRCTN26791028, NTR2754.

Objectives Although joint swelling is traditionally interpreted as synovitis, recent imaging studies showed that there is also inflammation of tenosynovium and intermetatarsal bursae in the forefoot. We aimed to increase our understanding of differences and similarities regarding forefoot involvement between ACPA-positive and ACPA-negative rheumatoid arthritis (RA) at diagnosis. Therefore, we (1) compared metatarsophalangeal (MTP) joint counts, walking disabilities and inflamed tissues between ACPA groups and (2) studied associations of joint swelling/tenderness and walking disabilities with underlying inflamed tissues within ACPA groups.Methods 171 ACPA-positive and 203 ACPA-negative consecutively diagnosed patients with RA had a physical joint examination (swollen joint count-66/tender joint count-68), filled a Health Assessment Questionnaire including the domain walking and underwent MRI of the MTP joints at diagnosis. Synovitis, tenosynovitis, osteitis and intermetatarsal bursitis (IMB) were assessed. Findings in age-matched healthy controls were applied to define abnormalities on MRI.Results While ACPA-negative RA patients had more swollen joints (mean SJC 8 vs 6 in ACPA-positives, p=0.003), the number of swollen MTP joints was similar (mean 1 in both groups); walking disabilities were also equally common (49% vs 53%). In contrast, inflamed tissues were all more prevalent in ACPA-positive compared with ACPA-negative RA. Within ACPA-positive RA, IMB was associated independently with MTP-joint swelling (OR 2.6, 95% CI 1.4 to 5.0) and tenderness (OR 3.0, 95% CI 1.8 to 5.0). While in ACPA-negatives, synovitis was associated independently with MTP-joint swelling (OR 2.8, 95% CI 1.4 to 5.8) and tenderness (OR 2.5, 95% CI 1.3 to 4.8). Tenosynovitis contributed most to walking disabilities.Conclusions Although the forefoot of ACPA-positives and ACPA-negatives share clinical similarities at diagnosis, there are differences in underlying inflamed tissues. This reinforces that ACPA-positive and ACPA-negative RA are different entities.

Helping university students develop productive views of what characterizes good scientific research and scientific knowledge is an important objective of science education. However, many studies show that students’ views of the nature of science (NOS) do not become more informed or even become less informed after learning activities that engage students in scientific practice. This could mean that the way we teach students to conduct scientific research might unintentionally strengthen or bring about uninformed views of NOS. In this article, we argue that scientific discourse (how language is used in science) might play a role in this relation between learning scientific inquiry and uninformed views of NOS. We argue that there could be implicit notions relating to NOS underlying scientific discourse that uninformed readers might translate to uninformed views of NOS. We call these implicit notions underlying scientific language use “epistemological notions.” In this article, we further define this construct of epistemological notions, contrast it with explicit views of NOS and other related constructs, explain how we think epistemological notions might affect explicit views of NOS, and present a framework we developed to characterize them in scientific language use. It is a descriptive and interpretative analysis framework which combines, optimizes, and extends several text analysis methods, discourse analysis, and reflexive thematic analysis. We provide a guide to use the framework and point out quality criteria. We finish by advocating the framework for educational researchers interested in developing instructional interventions during which learning about science is combined with explicit reflection on NOS. Identifying epistemological notions in scientific language use could provide starting points for these activities by making explicit the translation from NOS understanding to scientific practice and vice versa.

Obesity is caused by a prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes is debated3,4. Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.

Abstract Background Research on childhood adversity and psychopathology has begun investigating the dimension of timing, however the results have been contradictory depending on the study population, outcome and how adverse life events (ALEs) were operationalized. Additionally, studies so far typically focus only on a narrow range of psychiatric diagnoses or symptoms. The current cross-sectional study aimed to examine the association between timing, type and chronicity of ALEs and adolescent mental health problems. Methods Adolescents from a population-based cohort oversampled on emotional and behavioral problems (mean age 14.8; range 12–17, N = 861) were included in the current analysis. Primary caregivers were interviewed on what ALEs adolescents experienced. ALEs were defined in two ways: (1) broad operationalization, including school difficulties, parental divorce, and family sickness; and (2) physically threatening abuse only, including physical and sexual violence. After looking at lifetime ALEs, we turned to chronicity, timing and sex differences. We focused on overall psychiatric symptoms as well as specific domains of emotional and behavioral problems, assessed using the Youth Self Report (YSR) and psychotic experiences assessed using the Prodromal Questionnaire-16 (PQ-16). A series of linear models adjusted for sociodemographic and parental factors were used. Results Lifetime ALEs were associated with all types of psychopathology, with relatively bigger effect sizes for broad than for physical ALEs. The latter associations were found to be more robust to unmeasured confounding. The 9–12 age period of experiencing both broad and physical ALE’s was most saliently associated with any psychopathology. Girls were more at risk after experiencing any ALEs, especially if the adversity was chronic or ALEs took place after the age of 12. Conclusions Broad as well as physical ALEs are associated with psychopathology, especially ALEs experienced during the 9–12 age period. Physical ALEs may be more useful in investigating specific etiological factors than broad ALEs. Sex differences may not emerge in lifetime measures of ALEs, but can be important for chronic and later childhood adversity.

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lacks access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5604 people from the ages of 8 days to 96 years from 23 countries using isotope-tracking (2H) methods. Age, body size, and composition were significantly associated with WT, as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People who lived in countries with a low human development index (HDI) had higher WT than people in high-HDI countries. On the basis of this extensive dataset, we provide equations to predict human WT in relation to anthropometric, economic, and environmental factors.

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved sex differences in the degree of interindividual variation in energy expenditure. We found that, even when statistically comparing males and females of the same age, height, and body composition, there is much more variation in total, activity, and basal energy expenditure among males. However, with aging, variation in total energy expenditure decreases, and because this happens more rapidly in males, the magnitude of greater male variation, though still large, is attenuated in older age groups. Considerably greater male variation in both total and activity energy expenditure could be explained by greater male variation in levels of daily activity. The considerably greater male variation in basal energy expenditure is remarkable and may be explained, at least in part, by greater male variation in the size of energy-demanding organs. If energy expenditure is a trait that is of indirect interest to females when choosing a sexual partner, this would suggest that energy expenditure is under sexual selection. However, we present a novel energetics model demonstrating that it is also possible that females have been under stabilizing selection pressure for an intermediate basal energy expenditure to maximize energy available for reproduction.

Abstract Background Patients with advanced cancer who no longer have standard treatment options available may decide to participate in early phase clinical trials (i.e. experimental treatments with uncertain outcomes). Shared decision-making (SDM) models help to understand considerations that influence patients’ decision. Discussion of patient values is essential to SDM, but such communication is often limited in this context and may require new interventions. The OnVaCT intervention, consisting of a preparatory online value clarification tool (OnVaCT) for patients and communication training for oncologists, was previously developed to support SDM. This study aimed to qualitatively explore associations between patient values that are discussed between patients and oncologists during consultations about potential participation in early phase clinical trials before and after implementation of the OnVaCT intervention. Methods This study is part of a prospective multicentre nonrandomized controlled clinical trial and had a between-subjects design: pre-intervention patients received usual care, while post-intervention patients additionally received the OnVaCT. Oncologists participated in the communication training between study phases. Patients’ initial consultation on potential early phase clinical trial participation was recorded and transcribed verbatim. Applying a directed approach, two independent coders analysed the transcripts using an initial codebook based on previous studies. Steps of continuous evaluation and revision were repeated until data saturation was reached. Results Data saturation was reached after 32 patient-oncologist consultations (i.e. 17 pre-intervention and 15 post-intervention). The analysis revealed the values: hope, perseverance, quality or quantity of life, risk tolerance, trust in the healthcare system/professionals, autonomy, social adherence, altruism, corporeality, acceptance of one’s fate, and humanity. Patients in the pre-intervention phase tended to express values briefly and spontaneously. Oncologists acknowledged the importance of patients’ values, but generally only gave ‘contrasting’ examples of why some accept and others refuse to participate in trials. In the post-intervention phase, many oncologists referred to the OnVaCT and/or asked follow-up questions, while patients used longer phrases that combined multiple values, sometimes clearly indicating their weighing. Conclusions While all values were recognized in both study phases, our results have highlighted the different communication patterns around patient values in SDM for potential early phase clinical trial participation before and after implementation of the OnVaCT intervention. This study therefore provides a first (qualitative) indication that the OnVaCT intervention may support patients and oncologists in discussing their values. Trial registration Netherlands Trial Registry: NL7335, registered on July 17, 2018.

Abstract Background Obese RA patients have higher disease activity scores (DAS). Previous research showed that obese RA patients have higher tender joint count (TJC) and VAS general health. However, it remains unclear whether DAS components measuring local and systemic inflammation (swollen joint count (SJC), CRP) are increased and if this is present in the total RA population or confined to an ACPA subgroup. As ACPA is suggested to enhance inflammatory responses, we hypothesized that the association of obesity with SJC and CRP is present especially in ACPA-positive RA. We therefore studied associations of obesity with courses of DAS components in ACPA subgroups. Methods We studied 649 RA patients (291 ACPA-positive), included in the Leiden Early Arthritis Clinic. Five-year courses of DAS44 and DAS44 components (SJC—44, TJC—53, CRP, VAS (0–100)) were compared between RA patients with normal weight (BMI 18.5–24.9), overweight (25.0–29.9), and obesity (≥ 30.0), stratified for ACPA. Linear/Poisson mixed models with a knot at 4 months were used. Results Obese RA patients had + 0.32 higher DAS compared to normal weight during the 5-year follow-up. In ACPA-positive RA, obese patients had + 0.43 (95% CI: 0.22, 0.64) higher DAS, whereas in ACPA-negative RA, this difference was smaller and not statistically significant: + 0.19 (95% CI: − 0.01, 0.38). In ACPA-positive RA, all DAS components were significantly higher in obese patients compared to normal weight: SJC + 60% (IRR1.60; 95% CI: 1.18, 2.16), CRP + 3.7 mg/L (95% CI:0.95, 6.53), TJC + 55% (IRR1.55; 95% CI:1.15, 2.10), and VAS + 9 (95% CI: 4.0, 14.2). ACPA-negative obese RA patients tended to have higher TJC (IRR1.22; 95% CI: 0.96, 1.55) and VAS (β4.3; 95% CI: − 0.4, 9.0), while SJC (IRR1.07; 95% CI:0.85, 1.33) and CRP (β0.24; 95% CI: − 1.29, 3.32) were unaffected. Conclusion The association of obesity with a worse DAS course is mainly present in ACPA-positive RA; especially SJC and CRP levels remain higher in ACPA-positive RA patients with obesity but not ACPA-negative RA patients. This is the first demonstration that obesity influences the disease course of ACPA-positive and ACPA-negative RA differently.

Anne Lise Meulenbroek,1 Ewout W Steyerberg,2 Ties L Janssen,1 Stefanie R van Mil,1 Miriam C Faes,3 Lijckle van der Laan1,4 1Department of Surgery, Amphia Hospital, Breda, the Netherlands; 2Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands; 3Department of Geriatrics, Amphia Hospital, Breda, the Netherlands; 4Department of Cardiovascular Sciences, Research Group of Vascular Surgery, KU Leuven, Leuven, BelgiumCorrespondence: Anne Lise Meulenbroek, Department of Surgery, Amphia Hospital, Molengracht 21, Breda, 4818 CK, the Netherlands, Tel +31 76 595 3157, Fax +31 76 595 3818, Email AMeulenbroek1@amphia.nlObjective: Delirium is a common and serious postoperative complication in elderly patients undergoing abdominal aortic aneurysm (AAA) repair and is associated with a variety of adverse outcomes. Multimodal prehabilitation aims to identify and minimize potential risk factors for delirium and improve overall health. The aim of this study is to investigate the effect of multimodal prehabilitation on delirium incidence in elderly patients undergoing elective repair for AAA.Methods: A single-centre cohort analysis was performed in the Netherlands for patients aged ≥ 70 years, undergoing elective repair for AAA (open surgery and endovascular aortic repair). Prehabilitation was gradually introduced between 2016 and 2019 and offered as standard care from 2019. The program was constructed to optimize overall health and included delirium risk assessment, home-based tailor-made exercises by a physical therapist, nutritional optimization by a dietician, iron infusion in case of anaemia and a comprehensive geriatric assessment by a geriatrician in case of frailty. The primary outcome was incidence of delirium within 30 days after surgery.Results: A total of 81 control and 123 prehabilitation patients were included. A reduction in incidence of delirium was found (11.1% in the control group to 4.9% in the prehabilitation group), with too small numbers to reach statistical significance (p=0.09). Also, patients in the prehabilitation group had a small, non-significant decreased length of hospital stay (4 days) compared to the control group (5 days) (p=0.07).Conclusion: Although no significant differences were found, we carefully conclude that this study provides some support for implementing multimodal prehabilitation for delirium prevention in elderly patients undergoing AAA repair. Further research with larger cohorts is necessary to identify and select patients that would most benefit from prehabilitation.Plain Language Summary: Delirium is a common complication in elderly patients after undergoing abdominal aortic aneurysm (AAA) repair. Delirium is associated with a prolonged hospital-stay, decreased quality of life and increased mortality. To prevent delirium it is important to identify possible risk factors and assess the patients’ overall fitness. This is best done preoperatively, since the patient is not yet recovering from a major surgery. This is called “prehabilitation”.In this study, we investigated the effect of multimodal prehabilitation in patients undergoing surgery for an AAA. The program consists of:Individual delirium risk-assessment,Personalized home-based tailor-made exercises,Nutritional optimization,Iron infusion in case of anaemia, andA comprehensive geriatric assessment by a geriatrician in case of frailty.Eighty-one control and 123 prehabilitation patients were included. A reduction in incidence of delirium was found (11.1% control to 4.9% prehabilitation), with too small numbers to reach statistical significance (p=0.09). Also, patients in the prehabilitation group had a small, non-significant decreased length of stay (4 days) compared to the control group (5 days) (p=0.07).Prehabilitation may be effective in preventing delirium in elderly patients undergoing AAA repair. Further research is necessary to identify and select patients that would most benefit from prehabilitation.Keywords: aneurysm of the abdominal aorta, prehabilitation, preoperative rehabilitation, delirium, delirium/prevention and control

Abstract Background After myocardial infarction, the lost myocardium is replaced by fibrotic tissue, eventually progressively leading to myocardial dysfunction. Direct reprogramming of fibroblasts into cardiomyocytes via the forced overexpression of cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) offers a promising strategy for cardiac repair. The limited reprogramming efficiency of this approach, however, remains a significant challenge. Methods We screened seven factors capable of improving direct cardiac reprogramming of both mice and human fibroblasts by evaluating small molecules known to be involved in cardiomyocyte differentiation or promoting human-induced pluripotent stem cell reprogramming. Results We found that vitamin C (VitC) significantly increased cardiac reprogramming efficiency when added to GMT-overexpressing fibroblasts from human and mice in 2D and 3D model. We observed a significant increase in reactive oxygen species (ROS) generation in human and mice fibroblasts upon Doxy induction, and ROS generation was subsequently reduced upon VitC treatment, associated with increased reprogramming efficiency. However, upon treatment with dehydroascorbic acid, a structural analog of VitC but lacking antioxidant properties, no difference in reprogramming efficiency was observed, suggesting that the effect of VitC in enhancing cardiac reprogramming is partly dependent of its antioxidant properties. Conclusions Our findings demonstrate that VitC supplementation significantly enhances the efficiency of cardiac reprogramming, partially by suppressing ROS production in the presence of GMT. Graphical abstract

Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (-10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p

Introduction In the Netherlands, bariatric surgery in adolescents is currently only allowed in the context of scientific research. Besides this, there was no clinical pathway for bariatric surgery in adolescents. In this paper, the development of a comprehensive clinical pathway for bariatric surgery in adolescents with severe obesity in the is described. Methods The clinical pathway for bariatric surgery in adolescents consists of an eligibility assessment as well as comprehensive peri- and postoperative care. Regarding the eligibility assessment, the adolescents need to be identified by their attending pediatricians and afterwards be evaluated by specialized pediatric obesity units. If the provided treatment is considered to be insufficiently effective, the adolescent will anonymously be evaluated by a national board. This is an additional diligence procedure specifically established for bariatric surgery in adolescents. The national board consists of independent experts regarding adolescent bariatric surgery, and evaluates whether the adolescents meet the criteria defined by the national professional associations. The final step is an assessment by a multidisciplinary team for adolescent bariatric surgery. The various disciplines (pediatrician, bariatric surgeon, psychologist, dietician) evaluate whether an adolescent is eligible for bariatric surgery. In this decision-making process, it is crucial to assess whether the adolescent is expected to adhere to postoperative behavioral changes and follow-up. When an adolescent is deemed eligible for bariatric surgery, he or she will receive preoperative counselling by a bariatric surgeon to decide on the type of bariatric procedure (Roux-en-Y gastric bypass or sleeve gastrectomy). Postoperative care consists of intensive guidance by the multidisciplinary team for adolescent bariatric surgery. In this guidance, several regular appointments are included and additional care will be provided based on the needs of the adolescent and his or her family. Furthermore, the multidisciplinary lifestyle intervention, in which the adolescents participated before bariatric surgery, continues in coordination with the multidisciplinary team for adolescent bariatric surgery, and this ensures long-term counselling and follow-up. Conclusion The implementation of bariatric surgery as an integral part of a comprehensive treatment for adolescents with severe obesity requires the development of a clinical pathway with a variety of disciplines.

Objectives Rheumatoid arthritis (RA) mainly affects small joints. Despite the mechanical function of joints, the role of mechanical stress in the development of arthritis is insufficiently understood. We hypothesised that mechanical stress/physical strain is a risk factor for joint inflammation in RA. Therefore, we studied work-related physical strain in subjects with clinically suspected arthralgia (CSA) as a risk factor for the presence of imaging-detected subclinical joint inflammation and the development of clinical arthritis/RA.Methods In 501 CSA patients and 155 symptom-free persons’ occupation-related physical strain was quantified using the International Standard Classification of Occupations. Contrast-enhanced hand-MRIs were made and evaluated for joint inflammation (sum of synovitis/tenosynovitis/osteitis). CSA patients were followed on RA development. Age relationship was studied using an interaction term of physical strain with age.Results The degree of physical strain in CSA is associated with the severity of joint inflammation, independent of educational-level/BMI/smoking (interaction physical strain-age p=0.007; indicating a stronger association with increasing age). Physical strain is associated with higher tenosynovitis scores, in particular. In symptom-free persons, physical strain was not associated with imaging-detected joint inflammation. Higher degrees of physical strain also associated with higher risks for RA development in an age-dependent manner (HR=1.20 (1.06–1.37)/10-year increase in age), independent of educational-level/BMI/smoking. This association was partly mediated by an effect via subclinical joint inflammation.Conclusions Work-related physical strain increases the risk of subclinical joint inflammation and of developing RA. The age relationship suggests an effect of long-term stress or that tenosynovium is more sensitive to stress at older age. Together, the data indicate that mechanical stress contributes to the development of arthritis in RA.