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Precision approaches towards diabetes prevention:towards a clustering approach with more phenotypical granularity
No full textMilk Protein Glycation Compromises Postprandial Lysine Bioavailability but Does Not Modulate Postprandial Muscle Protein Synthesis Rates In Vivo in Males:A Double-blind, Randomized Parallel Trial
No full textBackground: Industrial processing and storage of milk products can strongly increase protein glycation level. Previously, we have reported that a high protein glycation level impairs protein digestion, thereby compromising lysine bioavailability. The lower postprandial lysine availability may restrict the anabolic properties of a high glycated protein. Objectives: The objective of this study was to assess the impact of milk protein glycation on postprandial plasma amino acid availability and subsequent postprandial muscle protein synthesis rates during recovery from a single bout of resistance-type exercise. Methods: Forty-five recreationally active, healthy young males participated in this double-blinded, randomized parallel study. After performing a single bout of whole-body resistance-type exercise, subjects ingested 20 g milk protein with either a low (4%; LOW-GLYC) or high (47%; HIGH-GLYC) glycation level or a noncaloric placebo (PLA). Continuous intravenous infusion of L-[ring- 13C 6]-phenylalanine was combined with the collection of blood and muscle tissue samples during a 6-h postprandial period to assess plasma amino acid concentrations and muscle protein synthesis rates. Results: Protein ingestion increased plasma total and essential amino acid concentrations compared with placebo (time × treatment interaction: P < 0.001), with no differences between the low and high glycated milk protein. Plasma lysine availability, assessed over the full 6 h postprandial period, was substantially lower following ingestion of the protein with the high versus low glycation level (−5 ± 7 compared with 10 ± 9 mmol · L -1 · 360 min, respectively, P < 0.001). Postprandial muscle protein synthesis rates did not differ between treatments (0.059 ± 0.016, 0.061 ± 0.012, and 0.061 ± 0.018 % · h -1, in LOW-GLYC, HIGH-GLYC and PLA, respectively, P = 0.939). Conclusions: Ingestion of protein with a higher glycation level attenuates postprandial plasma lysine availability. Milk protein glycation does not modulate postprandial muscle protein synthesis rates during recovery from resistance exercise in healthy, young males. This trial was registered at the Dutch Trial Register as NL8690; https://onderzoekmetmensen.nl/nl/trial/49398.</p
Guidelines for developing and integrating 360-degree video in healthcare education
No full textThe rapid growth of immersive virtual reality (VR) has gained widespread global attention in the field of education. In higher education within healthcare, VR has already been widely explored and employed. One specific form of virtual reality, 360-degree video, is regarded as a more user-friendly, realistic, and cost-effective alternative to other VR modalities, providing an immersive experience that requires less complex technology while still offering a high level of engagement in educational contexts. A 360-degree video is relatively easy to produce and can be seamlessly integrated into educational settings, serving a versatile and accessible tool for enhancing interactive learning experiences across various healthcare disciplines. We developed and integrated ten 360-degree videos, designed for viewing through head-mounted displays, to enhance educational practices in healthcare at Maastricht University, the Netherlands. In this article, we share guidelines for developing and integrating 360-degree videos into undergraduate and graduate healthcare programs, drawing on insights from our own experiences
Cancer prognosis and treatment results in patients with PTEN Hamartoma Tumour Syndrome (PHTS)-a European cohort study
No full textBACKGROUND: PTEN hamartoma tumour syndrome (PHTS) patients have a high hereditary risk of cancer, especially breast (BC), endometrial (EC), and thyroid cancer (TC). However, the prognosis of PHTS-related cancers is unknown. METHODS: This European cohort study included adult PHTS patients with data from medical files, registries, and/or questionnaires. Overall survival (OS) was assessed using Kaplan-Meier analyses and were compared with sporadic cancer and the general population using standardized mortality (SMR) and relative survival rates (RSR). Survival bias was addressed using left-truncation. RESULTS: Overall, 147 BC patients were included. The 10y-OS was 77% (95%CI = 66-90), decreasing with increasing stage from 90% (95%CI = 73-100) for stage 0 to 0% (95%CI = 0-0) for stage IV. BC relative survival was comparable to sporadic BC in the first two years (2y-RSR = 1.1; 95%CI = 1.1-1.1) and increasing thereafter (5y-RSR = 1.7; 95%CI = 1.6-1.7). For TC (N = 56) and EC (N = 35), 10y-OS was 87% (95%CI = 74-100) and 64% (95%CI = 38-100), respectively. Overall and cancer-specific mortality in female PHTS patients exceeded general population rates (SMR = 3.7; 95%CI = 2.6-5.0 and SMR = 2.7; 95%CI = 1.6-4.4). CONCLUSIONS: The prognosis of PHTS-related cancers was comparable to the general population. The higher overall mortality in PHTS patients is presumably related to their higher cancer incidence. These findings, and the high survival observed in early-stage cancer, emphasise the importance of recognising PHTS early to facilitate cancer surveillance
Optimal follow-up strategy using high-risk human papillomavirus testing and cytology after conservative treatment for cervical adenocarcinoma in situ
No full textBackground: After treatment for cervical adenocarcinoma in situ, patients remain a risk for recurrent adenocarcinoma in situ, cervical intraepithelial grade 3, or cervical cancer. Objective: This study aimed to determine the optimal follow-up strategy for high-risk human papillomavirus and cytology testing in conservatively treated patients with adenocarcinoma in situ. Study Design: Patients were selected from a nationwide, retrospective cohort that included pathology reports from the Dutch Nationwide Pathology Databank (Palga) and survival data from the Central Bureau for Genealogy for patients conservatively treated for adenocarcinoma in situ between 1990 and 2021. The main outcome was the 5-year cumulative incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer stratified by single and consecutive human papillomavirus test and/or cytology results at 6, 12, 18, and 24 months. Results: A total of 3411 patients were eligible for analysis. High-risk human papillomavirus test and/or cytology results in the first 5 years of follow-up were available in 3312 of 3411 patients (97.1%), including 5207 high-risk human papillomavirus test results of 1928 patients and 13,369 cytology results of 3306 patients. Up to 5 years after a single high-risk human papillomavirus test at 6 months after treatment, the incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer was lower among high-risk human papillomavirus–negative patients (2.3%; 95% confidence interval, 0.8–3.7) compared with high-risk human papillomavirus–positive patients (20.1%; 95% confidence interval, 14.2–25.5). Patients with normal cytology results 6 months after treatment for adenocarcinoma in situ had a lower incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer (3%; 95% confidence interval, 2.2–3.8) compared with patients with low-grade (5.9%; 95% confidence interval, 3.4–8.4) or high-grade cytology (52.1%; 95% confidence interval, 42.7–59.9). The 5-year cumulative incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer among patients testing negative for high-risk human papillomavirus consecutively at 6 and 12, 6 and 18, and 6 and 24 months was 0.6% (95% confidence interval, 0–1.8), 1.1% (95% confidence interval, 0–3.4), and 0% (95% confidence interval not applicable), respectively. Similarly, for patients with consecutive normal cotest results (high-risk human papillomavirus–negative with normal or low-grade cytology) at 6 and 12, 6 and 18, and 6 and 24 months, the 5-year cumulative incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer was 0.6% (95% confidence interval, 0–1.8), 1.2% (95% confidence interval, 0–3.5), and 0% (95% confidence interval not applicable), respectively. Conclusion: After 2 consecutive negative high-risk human papillomavirus or normal cotests within 2 years after conservative adenocarcinoma in situ treatment, the risk of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer is low, and it seems acceptable to refer patients back to the national cervical cancer screening program, if applicable.</p
Enhanced risk stratification for stage II colorectal cancer using deep learning-based CT classifier and pathological markers to optimize adjuvant therapy decision
No full textBackground: Current risk stratification for stage II colorectal cancer (CRC) has limited accuracy in identifying patients who would benefit from adjuvant chemotherapy, leading to potential overtreatment or undertreatment. We aimed to develop a more precise risk stratification system by integrating artificial intelligence-based imaging analysis with pathological markers. Patients and methods: We analyzed 2992 stage II CRC patients from 12 centers. A deep learning classifier (Swin Transformer Assisted Risk-stratification for CRC, STAR-CRC) was developed using multi-planar computed tomography (CT) images from 1587 patients (training : internal validation = 7 : 3) and validated in 1405 patients from eight independent centers, which stratified patients into low-, uncertain-, and high-risk groups. To further refine the uncertain-risk group, a composite score based on pathological markers (pT4 stage, number of lymph nodes sampled, perineural invasion, and lymphovascular invasion) was applied, forming the Intelligent Risk Integration System for stage II Colorectal Cancer (IRIS-CRC). IRIS-CRC was compared against the guideline-based risk stratification system (GRSS-CRC) for prediction performance and validated in the validation dataset. Results: IRIS-CRC stratified patients into four prognostic groups with distinct 3-year disease-free survival rates (≥95%, 95%-75%, 75%-55%, ≤55%). Upon external validation, compared with GRSS-CRC, IRIS-CRC downstaged 27.1% of high-risk patients into the favorable group, and upstaged 6.5% of low-risk patients into the very poor prognosis group who might require more aggressive treatment. In the GRSS-CRC intermediate-risk group of the external validation dataset, IRIS-CRC reclassified 40.1% as favorable prognosis and 7.0% as very poor prognosis. IRIS-CRC’s performance maintained generalizability in both chemotherapy and non-chemotherapy cohorts. Conclusions: IRIS-CRC offers a more precise and personalized risk assessment than current guideline-based risk factors, potentially sparing low-risk patients from unnecessary adjuvant chemotherapy while identifying high-risk individuals for more aggressive treatment. This novel approach holds promise for improving clinical decision-making and outcomes in stage II CRC.</p
Frequent vocalizations and deep brain stimulation-responsive hyperkinesia in a striatal disinhibition rat model for Tourette syndrome
No full textBackground The lack of a rodent model for both motor and phonic tics hinders research on deep brain stimulation (DBS) for refractory Tourette syndrome (TS). Striatal disinhibition with a gamma-aminobutyric acid A antagonist (bicuculline) was previously shown to induce hyperkinesia and vocalizations in monkeys, indicating its potential as a TS model. In rats, however, only hyperkinesia was validated, prompting us to investigate whether they can also develop abnormal vocalizations and whether both conditions respond to thalamic DBS. Methods Rats underwent surgical implantation of a unilateral guide cannula targeting the caudate putamen (CPu) or nucleus accumbens (NAc). Additionally, they were implanted with an ipsilateral stimulation electrode targeting the border between the central medial (CM) and ventrolateral (VL) thalamic nuclei. Motor changes and ultrasound vocalizations were recorded and characterized offline. Results CPu bicuculline elicited arrhythmic shoulder jerks that tend to appear in fading bursts and sporadically alternate with sustained generalized hyperextension. Nucleus accumbens bicuculline elicited similar hyperkinesia, but at a much lower dose to prevent convulsions. DBS of CM/VL, but not adjacent regions, attenuated hyperkinesia with lower intensity showing stronger effects. In addition, bicuculline in NAc, but not CPu, elicited nonsensical vocalizations. However, the effect of CM/VL DBS on vocalizations remained inconclusive. Conclusions Hyperkinesia temporal features, co-development with vocalizations, and responsiveness to CM/VL DBS suggest striatal disinhibition may serve as a TS rat model. However, other movement disorders with vocal complications cannot be excluded, given the challenge of validating key tic indicators in animals, such as premonitory urge and suppressibility.</p
Response to the letter on "Comprehensive geriatric assessment in nonhospitalized settings"
No full textCritically ill patients undergoing interhospital transportation:a prospective multicentre cohort study in the Euregio Meuse-Rhine
No full textOBJECTIVE: The principal aim of this study was to investigate differences in the characteristics and physiological parameters of critically ill patients who underwent interhospital transportation. DESIGN: Prospective observational cohort study. SETTING: Multicentre study within the Euregio Meuse-Rhine, including Dutch and German hospitals. PATIENTS: A representative sample of critically ill adult patients who underwent interhospital transport accompanied by a physician was included. INTERVENTIONS: None. TRANSPORTATION COHORT DESCRIPTION: Data on patient characteristics, transport logistics, interventions and adverse events were recorded using an online questionnaire. The cohort was divided into Dutch and German subsets and further stratified based on the transportation modality. Descriptive statistics were utilised to present the cohort characteristics. RESULTS: Dutch patients (89%) were mainly transported by mobile intensive care unit (MICU). For the present investigation, in Germany, the Intensivtransportwagen was included in this MICU category, whereas German patients (48%) were mainly transported by intensive care ambulance (ICA). An intensivist accompanied most transports in the Netherlands, whereas various specialists transported patients in Germany. Interventions were primarily performed in the MICU for Dutch patients and in the ICA for German patients. Adverse events were reported in 5% of the cases. CONCLUSIONS: These comprehensive data provide insights into the transportation differences of critically ill patients. This serves as a foundation for future investigations concerning the quality and efficacy of interhospital transportation. TRIAL REGISTRATION NUMBER: This study was registered in the Dutch National Trial Registration (NTR4937)
Growing gains? Financial scalability of the Dutch defence industry by private equity
No full textThis chapter presents the results of our research into the potential for financial scalability of the defence industry caused by the increase in investments in this industry, specifically by Private Equity (PE) firms. It investigates the following questions: (1) to what extent does the Dutch defence industry use private equity as a source of business capital; and (2) what are the effects of the use of private equity in the growth of the companies involved? To this end, we analyse current financial statements of the defence industry in the Netherlands. Based on a comprehensive dataset we determine if and how much, PE firms invest in national defence corporations, as an indicator for scalability in the defence industry. Results show that the involvement of private equity in the Dutch defence industry is still rather small; however when PE is applied, companies seem to benefit from the financial injections of PE, showing higher amounts of average total assets and higher average revenues and profits. This indicates potential for financial scalability