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Article ; Online: Deep versus moderate neuromuscular blockade during total hip arthroplasty to improve postoperative quality of recovery and immune function: protocol for a randomised controlled study.

Bijkerk, Veerle / Visser, Jetze / Jacobs, Lotte M C / Keijzer, Christiaan / Warlé, Michiel C

2023 Volume 13, Issue 8, Page(s) e073537

Abstract: Introduction: There is accumulating evidence that deep neuromuscular blockade (NMB) improves intraoperative surgical conditions during laparoscopic surgery. Studies investigating the effects of deep NMB in open surgery are scarce. In theory, by limiting ...

Abstract	Introduction: There is accumulating evidence that deep neuromuscular blockade (NMB) improves intraoperative surgical conditions during laparoscopic surgery. Studies investigating the effects of deep NMB in open surgery are scarce. In theory, by limiting surgical damage through deeper muscle relaxation, postoperative inflammation and concomitant immune suppression can be reduced. Therefore, this study will investigate the effects of deep NMB during total hip arthroplasty, which demands a relatively large exposure of the hip joint through and in between muscles. Methods and analysis: This study is a monocentre blinded randomised controlled trial in 100 patients undergoing total hip arthroplasty under general anaesthesia. Patients will be randomised in a 1:1 fashion to an intervention group of intraoperative deep NMB (a post-tetanic count of 1-2) or a control group receiving moderate NMB (a train-of-four count of 1-2). NMB will be achieved by continuous or bolus administration of rocuronium, respectively. The primary endpoint is the quality of recovery at postoperative day 1 measured by the Quality of Recovery-40 Questionnaire, analysed by Analysis of Variance. The secondary endpoint is postoperative innate immune function, measured by Ethics and dissemination: Ethical approval for this study was granted by the Medical Ethics Committee 'METC Oost-Nederland' (reference number 2022-15754). Informed consent will be obtained prior to study participation. Study results will be published in an international peer-reviewed journal. Trial registration numbers: ClinicalTrials.gov Registry (NCT05562999) and EudraCT Registry (2022-002451-19).
MeSH term(s)	Humans ; Neuromuscular Blockade ; Arthroplasty, Replacement, Hip ; Anesthetics ; Neuromuscular Diseases ; Immunity ; Randomized Controlled Trials as Topic
Chemical Substances	Anesthetics
Language	English
Publishing date	2023-08-28
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-073537
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Article ; Online: Design of OSMI-4 Analogs Using Scaffold Hopping: Investigating the Importance of the Uridine Mimic in the Binding of OGT Inhibitors.

Balsollier, Cyril / Tomašič, Tihomir / Yasini, Daniel / Bijkerk, Simon / Anderluh, Marko / Pieters, Roland J

ChemMedChem

2023 Volume 18, Issue 8, Page(s) e202300001

Abstract: β-N-Acetylglucosamine transferase (OGT) inhibition is considered an important topic in medicinal chemistry. The involvement of O-GlcNAcylation in several important biological pathways is pointing to OGT as a potential therapeutic target. The field of OGT ...

Abstract	β-N-Acetylglucosamine transferase (OGT) inhibition is considered an important topic in medicinal chemistry. The involvement of O-GlcNAcylation in several important biological pathways is pointing to OGT as a potential therapeutic target. The field of OGT inhibitors drastically changed after the discovery of the 7-quinolone-4-carboxamide scaffold and its optimization to the first nanomolar OGT inhibitor: OSMI-4. While OSMI-4 is still the most potent inhibitor reported to date, its physicochemical properties are limiting its use as a potential drug candidate as well as a biological tool. In this study, we have introduced a simple modification (elongation) of the peptide part of OSMI-4 that limits the unwanted cyclisation during OSMI-4 synthesis while retaining OGT inhibitory potency. Secondly, we have kept this modified peptide unchanged while incorporating new sulfonamide UDP mimics to try to improve binding of newly designed OGT inhibitors in the UDP-binding site. With the use of computational methods, a small library of OSMI-4 derivatives was designed, prepared and evaluated that provided information about the OGT binding pocket and its specificity toward quinolone-4-carboxamides.
MeSH term(s)	Acetylglucosamine/chemistry ; Acetylglucosamine/metabolism ; Binding Sites ; Uridine ; Uridine Diphosphate ; N-Acetylglucosaminyltransferases/metabolism
Chemical Substances	Acetylglucosamine (V956696549) ; Uridine (WHI7HQ7H85) ; Uridine Diphosphate (58-98-0) ; N-Acetylglucosaminyltransferases (EC 2.4.1.-)
Language	English
Publishing date	2023-03-02
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2218496-X
ISSN	1860-7187 ; 1860-7179
ISSN (online)	1860-7187
ISSN	1860-7179
DOI	10.1002/cmdc.202300001
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Zs.A 6280: Show issues

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Article ; Online: Branched-chain amino acid levels are inversely associated with incident and prevalent chronic kidney disease in people with type 2 diabetes.

de Klerk, Juliette A / Bijkerk, Roel / Beulens, Joline W J / van Zonneveld, Anton Jan / Muilwijk, Mirte / Harms, Peter P / Blom, Marieke T / 't Hart, Leendert M / Slieker, Roderick C

Diabetes, obesity & metabolism

2024 Volume 26, Issue 5, Page(s) 1706–1713

Abstract: Aim: To investigate the association of plasma metabolites with incident and prevalent chronic kidney disease (CKD) in people with type 2 diabetes and establish whether this association is causal.: Materials and methods: The Hoorn Diabetes Care System ...

Abstract	Aim: To investigate the association of plasma metabolites with incident and prevalent chronic kidney disease (CKD) in people with type 2 diabetes and establish whether this association is causal. Materials and methods: The Hoorn Diabetes Care System cohort is a large prospective cohort consisting of individuals with type 2 diabetes from the northwest part of the Netherlands. In this cohort we assessed the association of baseline plasma levels of 172 metabolites with incident (N Results: Elevated levels of total and individual branched-chain amino acids (BCAAs)-valine, leucine and isoleucine-were associated with an increased risk of incident CKD, but with reduced odds of prevalent CKD, where BMI was identified as an effect modifier. The observed inverse effects were replicated in the UK Biobank. Mendelian randomization analysis did not provide evidence for a causal relationship between BCAAs and prevalent CKD. Conclusions: Our study shows the intricate relationship between plasma BCAA levels and CKD in individuals with type 2 diabetes. While an association exists, its manifestation varies based on disease status and BMI, with no definitive evidence supporting a causal link between BCAAs and prevalent CKD.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/epidemiology ; Risk Factors ; Prospective Studies ; Amino Acids, Branched-Chain/adverse effects ; Amino Acids, Branched-Chain/metabolism ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/chemically induced
Chemical Substances	Amino Acids, Branched-Chain
Language	English
Publishing date	2024-02-01
Publishing country	England
Document type	Journal Article
ZDB-ID	1454944-x
ISSN	1463-1326 ; 1462-8902
ISSN (online)	1463-1326
ISSN	1462-8902
DOI	10.1111/dom.15475
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Article: Survey on Colostrum Management by Dairy Farmers in the Netherlands.

Robbers, Lisa / Bijkerk, Hannes J C / Koets, Ad P / Benedictus, Lindert / Nielen, Mirjam / Jorritsma, Ruurd

Frontiers in veterinary science

2021 Volume 8, Page(s) 656391

Abstract: Colostrum feeding is essential for the transfer of passive immunity and health of newborn calves. Information on current colostrum management practices to reduce calf morbidity and mortality is important but lacking for Dutch dairy herds. We therefore ... ...

Abstract	Colostrum feeding is essential for the transfer of passive immunity and health of newborn calves. Information on current colostrum management practices to reduce calf morbidity and mortality is important but lacking for Dutch dairy herds. We therefore conducted a survey to investigate colostrum management strategies on Dutch dairy farms. The survey was specifically focused on the most recently born calf and was returned by 107 respondents (response rate of 13.4%). The mean amount of colostrum fed at first feeding was 2.9 liters. Overall, 79% of farmers provided the calf with at least 6 liters of colostrum in up to three feedings. The majority of respondents (84%) claimed to provide the calf with colostrum for the first time within 2 h post-partum. Using ordinal logistic regression and Wilcoxon rank sum test, we found no differences in time to first colostrum feeding or total amount of colostrum fed between bull calves and heifer calves, respectively. Ordinal logistic regression showed no significant differences in time to first colostrum feeding or time between calving and removing the calf from the dam between AMS and conventional milking herds. Two sample
Language	English
Publishing date	2021-04-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2021.656391
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Article ; Online: Discovery of two non-UDP-mimic inhibitors of O-GlcNAc transferase by screening a DNA-encoded library.

Balsollier, Cyril / Bijkerk, Simon / de Smit, Arjan / van Eekelen, Kevin / Bozovičar, Krištof / Husstege, Dirk / Tomašič, Tihomir / Anderluh, Marko / Pieters, Roland J

Bioorganic chemistry

2024 Volume 147, Page(s) 107321

Abstract: Finding potent inhibitors of O-GlcNAc transferase (OGT) has proven to be a challenge, especially because the diversity of published inhibitors is low. The large majority of available OGT inhibitors are uridine-based or uridine-like compounds that mimic ... ...

Abstract	Finding potent inhibitors of O-GlcNAc transferase (OGT) has proven to be a challenge, especially because the diversity of published inhibitors is low. The large majority of available OGT inhibitors are uridine-based or uridine-like compounds that mimic the main interactions of glycosyl donor UDP-GlcNAc with the enzyme. Until recently, screening of DNA-encoded libraries for discovering hits against protein targets was dedicated to a few laboratories around the world, but has become accessible to wider public with the recent launch of the DELopen platform. Here we report the results and follow-up of a DNA-encoded library screening by using the DELopen platform. This led to the discovery of two new hits with structural features not resembling UDP. Small focused libraries bearing those two scaffolds were made, leading to low micromolar inhibition of OGT and elucidation of their structure-activity relationship.
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	120080-x
ISSN	1090-2120 ; 0045-2068
ISSN (online)	1090-2120
ISSN	0045-2068
DOI	10.1016/j.bioorg.2024.107321
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Zs.A 4207: Show issues

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Article ; Online: Altered blood gene expression in the obesity-related type 2 diabetes cluster may be causally involved in lipid metabolism: a Mendelian randomisation study.

de Klerk, Juliette A / Beulens, Joline W J / Mei, Hailiang / Bijkerk, Roel / van Zonneveld, Anton Jan / Koivula, Robert W / Elders, Petra J M / 't Hart, Leen M / Slieker, Roderick C

Diabetologia

2023 Volume 66, Issue 6, Page(s) 1057–1070

Abstract: Aims/hypothesis: The aim of this study was to identify differentially expressed long non-coding RNAs (lncRNAs) and mRNAs in whole blood of people with type 2 diabetes across five different clusters: severe insulin-deficient diabetes (SIDD), severe ... ...

Abstract	Aims/hypothesis: The aim of this study was to identify differentially expressed long non-coding RNAs (lncRNAs) and mRNAs in whole blood of people with type 2 diabetes across five different clusters: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), mild diabetes (MD) and mild diabetes with high HDL-cholesterol (MDH). This was to increase our understanding of different molecular mechanisms underlying the five putative clusters of type 2 diabetes. Methods: Participants in the Hoorn Diabetes Care System (DCS) cohort were clustered based on age, BMI, HbA Results: Eleven lncRNAs and 175 mRNAs were differentially expressed in the MOD cluster, the lncRNA AL354696.2 was upregulated in the SIDD cluster and GPR15 mRNA was downregulated in the MDH cluster. mRNAs and lncRNAs that were differentially expressed in the MOD cluster were correlated among each other. Six lncRNAs and 120 mRNAs validated in the IMI DIRECT study. Using two-sample Mendelian randomisation, we found 52 mRNAs to have a causal effect on anthropometric traits (n=23) and lipid metabolism traits (n=10). GPR146 showed a causal effect on plasma HDL-cholesterol levels (p = 2×10 Conclusions/interpretation: Multiple lncRNAs and mRNAs were found to be differentially expressed among clusters and particularly in the MOD cluster. mRNAs in the MOD cluster showed a possible causal effect on anthropometric traits, lipid metabolism traits and blood cell fractions. Together, our results show that individuals in the MOD cluster show aberrant RNA expression of genes that have a suggested causal role on multiple diabetes-relevant traits.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/genetics ; Lipid Metabolism/genetics ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Genome-Wide Association Study ; Cholesterol, HDL ; Gene Expression ; Insulins ; Obesity/complications ; Obesity/genetics ; Receptors, Peptide/genetics ; Receptors, Peptide/metabolism ; Receptors, G-Protein-Coupled/metabolism
Chemical Substances	RNA, Long Noncoding ; Cholesterol, HDL ; Insulins ; GPR15 protein, human ; Receptors, Peptide ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2023-02-24
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-023-05886-8
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Article ; Online: The effect of administering preprocedural VITamin K on the international normalized ratio in patients anticoagulated with ACEnocoumarol (VITKACE-study).

Bijkerk, Stella / Lourens, Harm J / Mares, Wout G N / van Kampen, Corine A / van der Veen, Maurits J / Adriaansen, Henk J / Ponfoort, Erik D / Festen, Barbara / Westendorp, G Wouter / Rovers, Jörgen M P / Groot, Gerie M C / Bootsma, Hans-Peter R / Amelung, Linde M / Bins, Sander / Velders, Gerjo / Bemelmans, Remy H H

Journal of thrombosis and haemostasis : JTH

2024

Abstract: Background: The effect of the vitamin K antagonist (VKA) acenocoumarol on coagulation needs to be reversed when patients undergo an invasive procedure with considerable bleeding risk. A strategy to achieve this is administering oral vitamin K before a ... ...

Abstract	Background: The effect of the vitamin K antagonist (VKA) acenocoumarol on coagulation needs to be reversed when patients undergo an invasive procedure with considerable bleeding risk. A strategy to achieve this is administering oral vitamin K before a procedure while continuing acenocoumarol. Objectives: To assess the effect on periprocedural International Normalized Ratio (INR)-values and safety using oral vitamin K as anticoagulant reversal method. Methods: In this prospective cohort study, consecutive patients using acenocoumarol undergoing elective procedures between 2019 and 2022 were included. According to standard-of-care in our hospital, patients took 10 mg oral vitamin K 36-48 hours before the procedure while continuing their normal use of acenocoumarol. Effectiveness to lower INR <1.8 preprocedural was assessed. Bleeding and thrombotic complications within 30 days after the procedure were assessed. Periprocedural course of INR was monitored by collecting additional blood samples. Results: 74 patients were included for analysis. On the day of the procedure, an adequate INR <1.8 was achieved in 99% of patients. One clinically relevant non-major bleeding complication and no thrombotic complications were observed during the first 30 days after the procedure. INR gradually restored to therapeutic level during the days after the procedure. Conclusions: Using oral vitamin K while patients continue acenocoumarol intake is an effective way to adequately lower INR before an invasive procedure. Low amount of bleeding complications and absence of thromboembolic complications suggest that this is a safe strategy. The INR-values returned gradually to therapeutic range after the procedure, probably contributing to the observed low bleeding rate.
Language	English
Publishing date	2024-04-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2024.03.016
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Article: Adsorption and Dissociation of CO

Pachecka, M / Sturm, J M / Lee, C J / Bijkerk, F

The journal of physical chemistry. C, Nanomaterials and interfaces

2017 Volume 121, Issue 12, Page(s) 6729–6735

Abstract: The adsorption and dissociation of carbon dioxide on a Ru(0001) single crystal surface was investigated by reflection-absorption infrared spectroscopy (RAIRS) and temperature-programmed desorption (TPD) spectroscopy for ... ...

Abstract	The adsorption and dissociation of carbon dioxide on a Ru(0001) single crystal surface was investigated by reflection-absorption infrared spectroscopy (RAIRS) and temperature-programmed desorption (TPD) spectroscopy for CO
Language	English
Publishing date	2017-03-03
Publishing country	United States
Document type	Journal Article
ISSN	1932-7447
ISSN	1932-7447
DOI	10.1021/acs.jpcc.7b00021
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Article ; Online: Survey on Colostrum Management by Dairy Farmers in the Netherlands

Robbers, Lisa / Bijkerk, Hannes J.C. / Koets, Ad P. / Benedictus, Lindert / Nielen, Mirjam / Jorritsma, Ruurd

Frontiers in Veterinary Science

2021 Volume 8

Abstract	Colostrum feeding is essential for the transfer of passive immunity and health of newborn calves. Information on current colostrum management practices to reduce calf morbidity and mortality is important but lacking for Dutch dairy herds. We therefore conducted a survey to investigate colostrum management strategies on Dutch dairy farms. The survey was specifically focused on the most recently born calf and was returned by 107 respondents (response rate of 13.4%). The mean amount of colostrum fed at first feeding was 2.9 liters. Overall, 79% of farmers provided the calf with at least 6 liters of colostrum in up to three feedings. The majority of respondents (84%) claimed to provide the calf with colostrum for the first time within 2 h post-partum. Using ordinal logistic regression and Wilcoxon rank sum test, we found no differences in time to first colostrum feeding or total amount of colostrum fed between bull calves and heifer calves, respectively. Ordinal logistic regression showed no significant differences in time to first colostrum feeding or time between calving and removing the calf from the dam between AMS and conventional milking herds. Two sample T-test comparing the total volume of colostrum showed no significant difference between AMS and conventional milking herds. Time of day at which a calf was born affected both volume fed at first colostrum feeding and time until first colostrum feeding. Calves born between 00.00 and 06.00 were significantly at risk of receiving the first colostrum later as compared to calves born at other times. Calves born in the evening received on average a lower amount of colostrum at first feeding. Survey results on colostrum management on most Dutch dairy farms are in agreement with the advice to feed as soon as possible after parturition and to provide at least 6 liters within 24 h of age. The current study points at time of calving as a potential risk factor for sub-optimal colostrum feeding. Further research is necessary to determine the consequences of this ...
Keywords	calf feeding ; colostrum ; colostrum management ; dairy farm ; survey
Subject code	630
Language	English
Publishing country	nl
Document type	Article ; Online
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
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Article ; Online: Evidence for transfer of maternal antigen specific cellular immunity against Mycobacterium avium ssp. paratuberculosis via colostrum in a goat twin model.

Robbers, L / van de Mheen, R / Benedictus, L / Jorritsma, R / Nielen, M / Bijkerk, H J C / van der Grein, S G / Ravesloot, L / Koets, A P

Veterinary immunology and immunopathology

2022 Volume 246, Page(s) 110402

Abstract: Colostrum intake is one of the most important factors in neonatal health in ruminants, mainly because of its unique immunological properties. Both in practice as well as in research, the attention of lactogenic immunity is focused on the importance of ... ...

Abstract	Colostrum intake is one of the most important factors in neonatal health in ruminants, mainly because of its unique immunological properties. Both in practice as well as in research, the attention of lactogenic immunity is focused on the importance of colostral antibodies and less attention is given to the functional role of maternal cells in colostrum. Here we study the transfer of maternal leukocytes via colostrum and the functionality in goat kids. In experiment 1, twenty twin pairs of goat kids from dams previously immunized with an inactivated Mycobacterium avium subsp. paratuberculosis (MAP) vaccine were fed maternal colostrum from their dam (kid 1) or pasteurized and frozen/thawed bovine colostrum (kid 2). The presence of cell mediated immune response (CMIR) against Mycobacterium avium antigens in the kids was assessed using intradermal skin testing with PPD-A tuberculin. Linear mixed effect models showed an increase in skin thickness in response to intradermal PPD-A injection in maternal colostrum fed kids compared to bovine colostrum fed kids. After intradermal PPD-A application, serum concentration of MAP specific antibodies increased in kids fed maternal colostrum, indicating antigen specific activation of the adaptive immune system. We did not detect a similar increase in antibodies in the kids fed bovine colostrum. In experiment 2, a more reductionistic approach was applied to specifically study the effects of the transfer of maternal colostral leukocytes on CMIR in goat kids. Similar to experiment 1, twin kids from MAP immunized dams were randomly divided over two groups. The experimental group received colostrum replacer supplemented with fluorescently labelled colostral cells of the dam and the control group received colostrum replacer only. No difference in skin response following intradermal PPD-A injection was observed between both groups of kids. Histologic examination of the skin at the intradermal injection site did not show fluorescently labelled cells. In conclusion, in our initial experiment we observed an antigen specific CMIR in goat kids fed fresh colostrum with colostral leukocytes from vaccinated dams. The lack of a DTH response in kids fed colostrum replacer supplemented with maternal colostrum derived leukocytes indicated that the complete colostral matrix is probably required for colostrum leukocytes to transfer across the intestinal epithelial barrier and modulate the neonatal immune response. In line with earlier studies, our results indicate that caprine maternal leukocytes present in colostrum can functionally contribute to the newborns' early adaptive immune responses adding to the importance of colostrum feeding in ruminant neonates.
MeSH term(s)	Animals ; Animals, Newborn ; Cattle ; Colostrum ; Female ; Goat Diseases/prevention & control ; Goats ; Immunity, Cellular ; Mycobacterium avium subsp. paratuberculosis ; Paratuberculosis ; Pregnancy
Language	English
Publishing date	2022-02-16
Publishing country	Netherlands
Document type	Journal Article ; Randomized Controlled Trial, Veterinary
ZDB-ID	754160-0
ISSN	1873-2534 ; 0165-2427
ISSN (online)	1873-2534
ISSN	0165-2427
DOI	10.1016/j.vetimm.2022.110402
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