The effects of combined glucosamine sulfate and chondroitin sulfate supplements on condylar cartilage remodeling during functional appliance therapy. A Micro-CT study.

Glucosamine and chondroitin sulphate supplementation is used to prevent the degeneration of articular surfaces and also to enhance repair and regeneration of cartilage. The ability for adaptation of condylar cartilage to mandibular forward positioning is what constitutes the fundamental rationale for orthodontic functional therapy, which partially contributes to the correction of jaw discrepancies in growing Skeletal II mandibular retrusive patients. The purpose of this study was to qualitatively and quantitatively analyse the effect of Glucosamine sulphate (GS) and Chondroitin sulphate (CS) supplementation on condylar remodeling with functional appliance therapy in rats. One hundred and forty 3-week-old female Sprague-Dawley rats were randomly divided into 4 groups consisting of; baseline controls, supplementation only, functional appliances only and those receiving both supplements and functional appliances. Supplements were preloaded for a period of 2 weeks prior to the placement of functional appliances at five weeks of age. The animals were sacrificed at days 0, 7 and 21 after appliance placement. The appliances were removed in the remaining experimental animals on day 21 with sacrifice on day 28 to analyse post growth modification changes. Condylar samples were then soaked in 0.2 M Gadolinium Chloride (GdCl3) (aq) for 6 days and analyzed using micro-computed tomography (μCT) for morphological characteristics and linear and volumetric measurements of the mandibular condyle. The results demonstrated supplement therapy increased the volume of cartilage with and without functional appliance therapy. Functional appliance therapy alone resulted in increases in cartilage volume over untreated animals, with peak volume increases occurring by day 7 of appliance wear followed with decreases as endochondral ossification ensued. Supplement therapy was found to enhance the normal biological response to functional appliance therapy in the rat model

Burden and Rates of Treatment and Control of Cardiovascular Disease Risk Factors in Obesity: The Framingham Heart Study

OBJECTIVE— Obesity is associated with an increased risk for cardiovascular disease (CVD). We sought to determine rates of treatment and control of CVD risk factors among normal weight, overweight, and obese individuals in a community-based cohort

Blended intensive programs in higher education: collaborative innovation for global health challenges

Blended intensive programs (BIP) in higher education combine short-term mobility with online collaboration (BIP, 2024) to foster innovative learning and teaching methods. These initiatives facilitate joint curricular development for students, academics, and staff in Higher Education Institutions (HEI) and empower students to create innovative solutions for global health issues. Eight institutions from six countries developed a BIP to enhance students' understanding of global health and social challenges. The two-month program, involving 12 teachers and 35 students, was divided into an online session and an in-person week. The course covered migration, non-communicable diseases, climate change, and economic impacts on global health, emphasizing the Sustainable Development Goals. By the course's end, participants gained insights into global health complexities and the need for collaborative innovation. An online questionnaire surveyed participants, collecting both quantitative data and qualitative feedback, providing a comprehensive overview of their experiences and learning outcomes. Survey responses were mainly positive (n=25). Most participants felt the program increased their awareness of global issues, the importance of societal participation, and their profession's role in addressing them. However, some found certain lectures and activities less relevant, indicating areas for improvement.N/

Cluster analysis of functional independence in community-dwelling older people

Background: The concept of Functional Independence (FI), defined as ‘functioning physically safe and independent from other persons, within one’s context”, plays an important role in maintaining the functional ability to enable well-being in older age. FI is a dynamic and complex concept covering four clinical outcomes: physical capacity, empowerment, coping flexibility, and health literacy. As the level of FI differs widely between older adults, healthcare professionals must gain insight into how to best support older people in maintaining their level of FI in a personalized manner. Insight into subgroups of FI could be a first step in providing personalized support This study aims to identify clinically relevant, distinct subgroups of FI in Dutch community-dwelling older people and subsequently describe them according to individual characteristics. Results: One hundred fifty-three community-dwelling older persons were included for participation. Cluster analysis identified four distinctive clusters: (1) Performers – Well-informed; this subgroup is physically strong, well-informed and educated, independent, non-falling, with limited reflective coping style. (2) Performers – Achievers: physically strong people with a limited coping style and health literacy level. (3) The reliant- Good Coper representing physically somewhat limited people with sufficient coping styles who receive professional help. (4) The reliant – Receivers: physically limited people with insufficient coping styles who receive professional help. These subgroups showed significant differences in demographic characteristics and clinical FI outcomes. Conclusions: Community-dwelling older persons can be allocated to four distinct and clinically relevant subgroups based on their level of FI. This subgrouping provides insight into the complex holistic concept of FI by pointing out for each subgroup which FI domain is affected. This way, it helps to better target interventions to prevent the decline of FI in the community-dwelling older population

Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques

Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [I-123], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT) imaging that effectively targets atherosclerotic lesions in mice

A nationwide assessment of hepatocellular adenoma resection:Indications and pathological discordance

Hepatocellular adenomas (HCAs) are benign liver tumors associated with bleeding or malignant transformation. Data on the indication for surgery are scarce. We analyzed indications and outcome of patients operated for HCAs 50 mm (52%), suspicion of (pre)malignancy (28%), and (previous) bleeding (5.1%). No difference was observed in HCA-subtype distribution between small and large tumors. Ninety-six (43%) patients had a postoperative change in diagnosis. Independent risk factors for change in diagnosis were tumor size <50 mm (adjusted odds ratio [aOR], 3.4; p < 0.01), male sex (aOR, 3.7; p = 0.03), and lack of hepatobiliary contrast-enhanced magnetic resonance imaging (CE-MRI) (aOR, 1.8; p = 0.04). Resection for small (suspected) HCAs was mainly indicated by suspicion of (pre)malignancy, whereas for large (suspected) HCAs, tumor size was the most prevalent indication. Male sex, tumor size <50 mm, and lack of hepatobiliary CE-MRI were independent risk factors for postoperative change in tumor diagnosis

Volume–outcome relationship of liver surgery: a nationwide analysis

Background: Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit. Methods: This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien–Dindo grade IIIA or higher) and 30-day or in-hospital mortality. Results: A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20–69) procedures. Overall major morbidity and mortality rates were 11·2 and 2·0 per cent respectively. The mortality rate was 1·9 per cent after resection for colorectal liver metastases (CRLMs), 1·2 per cent for non-CRLMs, 0·4 per cent for benign tumours, 4·9 per cent for hepatocellular carcinoma and 10·3 per cent for biliary tumours. Higher-volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events. Conclusion: Hospital volume and postoperative outcomes were not associated

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program ‘iTHER’

iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program ‘iTHER’

iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival