Assessing the Immunomodulatory Effect of Size on the Uptake and Immunogenicity of Influenza- and Hepatitis B Subunit Vaccines In Vitro

Viral subunit vaccines are a safer and more tolerable alternative to whole inactivated virus vaccines. However, they often come with limited efficacy, necessitating the use of adjuvants. Using free and particle-bound viral antigens, we assessed whether size affects the uptake of those antigens by human monocyte-derived dendritic cells (Mo-DCs) and whether differences in uptake affect their capacity to stimulate cytokine production by T cells. To this end, influenza antigens and hepatitis B surface antigen (HBsAg) were covalently conjugated to polystyrene particles of 500 nm and 3 μm. Cellular uptake of the antigens, either unconjugated or conjugated, and their capacity to stimulate T cells within a population of human peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry. Conjugation of both antigens to particles significantly increased their uptake by Mo-DCs. Moreover, both the 500 nm and 3 μm influenza conjugates induced significantly higher numbers of cytokine-producing CD4+ T cells and induced increased production of the pro-inflammatory cytokines IFNγ and TNFα. In contrast, conjugation of HBsAg to particles did not notably affect the T cell response. In conclusion, conjugation of antigen to 500 nm and 3 μm particles leads to increased antigen uptake by human Mo-DCs, although the capacity of such conjugates to induce T cell stimulation likely depends on the immunological status of the PBMC donor

Best packing of rods into boxes

AbstractWe determine the maximum number of 1 × 1 x … × 1 × n rods which will fit inside an arbitrary d-dimensional rectangular box, on condition that they be packed parallel to the edges of the box

Comparing the efficacy of a web-assisted calprotectin-based treatment algorithm (IBD-live) with usual practices in teenagers with inflammatory bowel disease:study protocol for a randomized controlled trial

Background: To prevent clinical relapse in teenagers with inflammatory bowel disease (IBD) there is a need to monitor disease activity continuously. Timely optimisation of medical treatment may nip a preclinical relapse in the bud and change the natural course of IBD. Traditionally, disease monitoring is done during scheduled visits, but this is when most teenagers report full control. IBD care could be more efficient if patients were seen at times of clinical need. This study aims to examine the effectiveness of a web-assisted calprotectin-based treatment algorithm (IBD-live) compared with usual practices in teenagers with IBD. Methods/design: A randomized trial of web-based disease monitoring versus usual care is conducted at 10 Dutch IBD care centers. We plan to recruit 180 patients between 10-and 19-years old with quiescent IBD at baseline. Teenagers assigned to IBD-live will use the flarometer -an automatic cumulation of disease activity and fecal calprotectin measurements-to estimate probability of relapse. In case the flarometer indicates high risk the patient requires treatment intensification in accordance with national guidelines; low risk means that maintenance therapy is unchanged; and intermediate risk requires optimisation of drug adherence. Patients assigned to usual practice get the best accepted medical care with regular health checks. Primary outcome is the frequency of relapse at 52 weeks of follow-up. The diagnosis of relapse is based on a clinical activity index score >10 points necessitating remission induction therapy. Secondary outcomes include quality of life and cost-effectiveness. Discussion: Web-assisted monitoring of disease activity with rapid access for those with acute relapse may allow teenagers to develop skills that are required of adult patients (including communication and self-determination). Similar monitoring systems have been introduced for teenagers with asthma and diabetes, with a positive effect on disease control, but the intervention has not been evaluated in teenagers with IBD. A randomized trial in adult patients with ulcerative colitis showed that a web-assisted treatment algorithm is feasible, safe and cost-effective. Results of the current trial are expected to have important implications for teenagers with IBD that incurs substantial health burdens and economic costs

Gallstone disease in severely obese children participating in a lifestyle intervention programme

Background: besity is a risk factor for gallstone development in children and adolescents. However, the exact risk factors that determine which obese paediatric patients develop gallstones have not been identified yet. Particularly, no data are available on the risks related to lifestyle interventions in these patients. Design:: In this prospective cohort study 407 children and adolescents (age 8-18 years) with severe obesity (SDS-BMI >2.3 with comorbidity or SDS-BMI >3.0) participated in a lifestyle intervention programme during six months. Abdominal ultrasonography for the presence of gallstones, anthropometric measurements and biochemistry were evaluated before start and at the end of the lifestyle intervention. Results: 14 out of 388 children (3.7%) had gallstones before lifestyle intervention. Those children with gallstones were more severely obese (P = 0.029*), with higher obesity related parameters. A history of two or more weight loss attempts seemed to increase the risk compared to less weight loss attempts. During lifestyle intervention 17 children developed gallstones (5.9%). The degree of weight loss and improvement in its related anthropometric parameters all correlated with the risk of developing gallstones. Gallstones were only observed in those losing more than 10% of initial body weight and the risk increased sharply when losing more than 25% of initial weight. In multivariate analysis only weight loss was independently correlated. 29 (93%) children with gallstones remained asymptomatic and in 8 (25%) children gallstones dissolved during follow-up. Conclusion: The risk of gallstones in obese children and adolescents before and during life style intervention is mainly related to the degree of obesity and the degree of weight loss. Other factors did not correlate in this study. Complications of gallstones were rare.

Avoid Endoscopy in Children With Suspected Inflammatory Bowel Disease Who Have Normal Calprotectin Levels

In children with suspected inflammatory bowel disease, adding calprotectin stool testing to the screening strategy has been recommended to distinguish organic from nonorganic disease. In this cohort study with historical controls, we could not confirm that screening with stool calprotectin improves the diagnostic yield (ratio inflammatory bowel disease-positive endoscopies and total number of endoscopies); however, in patients with normal fecal calprotectin levels

Gallstone disease in severely obese children participating in a lifestyle intervention program: incidence and risk factors

INTRODUCTION: Cholelithiasis is increasingly encountered in childhood and adolescence due to the rise in obesity. As in adults, weight loss is presumed to be an important risk factor for cholelithiasis in children, but this has not been studied. METHODS: In a prospective observational cohort study we evaluated the presence of gallstones in 288 severely obese children and adolescents (mean age 14.1±2.4 years, body mass index (BMI) z-score 3.39±0.37) before and after participating in a 6-month lifestyle intervention program. RESULTS: During the lifestyle intervention, 17/288 children (5.9%) developed gallstones. Gallstones were only observed in those losing >10% of initial body weight and the prevalence was highest in those losing >25% of weight. In multivariate analysis change in BMI z-score (odds ratio (OR) 3.26 (per 0.5 s.d. decrease); 95% CI:1.60-6.65) and baseline BMI z-score (OR 2.32 (per 0.5 s.d.); 95% CI: 1.16-4.70) were independently correlated with the development of gallstones. Sex, family history, OAC use, puberty and biochemistry were not predictive in this cohort. During post-treatment follow-up (range 0.4-7.8 years) cholecystectomy was performed in 22% of those with cholelithiasis. No serious complications due to gallstones occurred. CONCLUSION: The risk of developing gallstones in obese children and adolescents during a lifestyle intervention is limited and mainly related to the degree of weight loss and initial body weight

Home-based guided hypnotherapy for children with functional abdominal pain and irritable bowel syndrome in primary care: study protocol for a randomised controlled trial

Introduction Children often present to primary care with functional abdominal pain (FAP) or irritable bowel syndrome (IBS), and around half still have abdominal complaints 1 year later. Hypnotherapy is an evidence-based treatment that is used in specialist care, but it lacks evidence in primary care. This study will investigate the (cost) effectiveness of home-based guided hypnotherapy for children with FAP or IBS in primary care.Methods and analysis We report the design of a pragmatic randomised controlled trial among children aged 7–17 years, diagnosed with FAP or IBS by their general practitioner (GP), with assessments over 12 months. The control group will receive care as usual (CAU) by their GP (eg, communication, education and reassurance), while the intervention group will receive CAU plus 3 months of home-based guided hypnotherapy via a website. The primary outcome will be the proportion of children with adequate relief from abdominal pain/discomfort at 12 months, analysed on an intention-to-treat basis. Secondary outcomes will include the adequacy of pain relief at 3 and 6 months, pain/discomfort severity, pain frequency and intensity, daily functioning and impact on function, anxiety and depression, pain beliefs, sleep disturbances, school absence, somatisation, and healthcare use and costs. We must include 200 children to determine a 20% difference in those with adequate relief (55% control vs 75% intervention).Ethics and dissemination The Medical Ethics Review Committee of the University Medical Center Groningen, the Netherlands, approved this study (METc2020/237). The results will be disseminated to patients, GPs and other stakeholders via email, a dedicated website, peer-reviewed publications and presentations at national and international conferences. We plan to collaborate with the Dutch Society of GPs to implement the results in clinical practice.Trial registration number NCT05636358