Afscheid van de uitstrijk?

Afscheidsrede Prof. dr. Theo Helmerhorst Hoogleraar vrouwenziekten en verloskunde Erasmus MC Uitgesproken op 9 december 201

Pharmaceutically modified subtilisins withstand acidic conditions and effectively degrade gluten in vivo

Detoxification of gluten immunogenic epitopes is a promising strategy for the treatment of celiac disease. Our previous studies have shown that these epitopes can be degraded in vitro by subtilisin enzymes derived from Rothia mucilaginosa, a natural microbial colonizer of the oral cavity. The challenge is that the enzyme is not optimally active under acidic conditions as encountered in the stomach. We therefore aimed to protect and maintain subtilisin-A enzyme activity by exploring two pharmaceutical modification techniques: PEGylation and Polylactic glycolic acid (PLGA) microencapsulation. PEGylation of subtilisin-A (Sub-A) was performed by attaching methoxypolyethylene glycol (mPEG, 5 kDa). The PEGylation protected subtilisin-A from autolysis at neutral pH. The PEGylated Sub-A (Sub-A-mPEG) was further encapsulated by PLGA. The microencapsulated Sub-A-mPEG-PLGA showed significantly increased protection against acid exposure in vitro. In vivo, gluten immunogenic epitopes were decreased by 60% in the stomach of mice fed with chow containing Sub-A-mPEG-PLGA (0.2mg Sub-A/ g chow) (n=9) compared to 31.9 % in mice fed with chow containing unmodified Sub-A (n=9). These results show that the developed pharmaceutical modification can protect Sub-A from auto-digestion as well as from acid inactivation, thus rendering the enzyme more effective for applications in vivo.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522598/Published versio

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Cognitive coping, goal adjustment, and depressive and anxiety symptoms in people undergoing infertility treatment:a prospective study

The relationships between cognitive coping strategies, goal adjustment, and symptoms of depression and anxiety were studied in people with fertility problems. Both cross-sectional and prospective relationships were studied in a sample of 313 patients attending an infertility clinic. Self-report questionnaires were filled out at home. Positive refocusing, rumination and catastrophizing, and goal reengagement were related to symptoms of depression and anxiety. When looking at the long-term effects, rumination and catastrophizing were also related to emotional problems nine months later. These findings suggest that intervention programs should focus on cognitive coping strategies and goal-based processe

Discovery of a Novel and Rich Source of Gluten-Degrading Microbial Enzymes in the Oral Cavity

BACKGROUND. Celiac disease is a T cell mediated-inflammatory enteropathy caused by the ingestion of gluten in genetically predisposed individuals carrying HLA-DQ2 or HLA-DQ8. The immunogenic gliadin epitopes, containing multiple glutamine and proline residues, are largely resistant to degradation by gastric and intestinal proteases. Salivary microorganisms however exhibit glutamine endoprotease activity, discovered towards glutamine- and proline-rich salivary proteins. The aim was to explore if gliadins can serve as substrates for oral microbial enzymes. METHODOLOGY/PRINCIPAL FINDINGS. Proteolytic activity in suspended dental plaque was studied towards a) gliadin-derived paranitroanilide(pNA)-linked synthetic enzyme substrates b) a mixture of natural gliadins and c) synthetic highly immunogenic gliadin peptides (33-mer of a2-gliadin and 26-mer of ?-gliadin). In addition, gliadin zymography was conducted to obtain the approximate molecular weights and pH activity profiles of the gliadin-degrading oral enzymes and liquid iso-electric focusing was performed to establish overall enzyme iso-electric points. Plaque bacteria efficiently hydrolyzed Z-YPQ-pNA, Z-QQP-pNA, Z-PPF-pNA and Z-PFP-pNA, with Z-YPQ-pNA being most rapidly cleaved. Gliadin immunogenic domains were extensively degraded in the presence of oral bacteria. Gliadin zymography revealed that prominent enzymes exhibit molecular weights >70 kD and are active over a broad pH range from 3 to 10. Liquid iso-electric focusing indicated that most gliadin-degrading enzymes are acidic in nature with iso-electric points between 2.5 and 4.0. CONCLUSIONS/SIGNIFICANCE. This is the first reported evidence for gluten-degrading microorganisms associated with the upper gastro-intestinal tract. Such microorganisms may play a hitherto unappreciated role in the digestion of dietary gluten and thus protection from celiac disease in subjects at risk.National Institutes of Health (AI087803, DE18132, DK073254, AI078385, DE05672, DE7652

A systematic review of reliability and objective criterion-related validity of physical activity questionnaires.

Physical inactivity is one of the four leading risk factors for global mortality. Accurate measurement of physical activity (PA) and in particular by physical activity questionnaires (PAQs) remains a challenge. The aim of this paper is to provide an updated systematic review of the reliability and validity characteristics of existing and more recently developed PAQs and to quantitatively compare the performance between existing and newly developed PAQs.A literature search of electronic databases was performed for studies assessing reliability and validity data of PAQs using an objective criterion measurement of PA between January 1997 and December 2011. Articles meeting the inclusion criteria were screened and data were extracted to provide a systematic overview of measurement properties. Due to differences in reported outcomes and criterion methods a quantitative meta-analysis was not possible.In total, 31 studies testing 34 newly developed PAQs, and 65 studies examining 96 existing PAQs were included. Very few PAQs showed good results on both reliability and validity. Median reliability correlation coefficients were 0.62-0.71 for existing, and 0.74-0.76 for new PAQs. Median validity coefficients ranged from 0.30-0.39 for existing, and from 0.25-0.41 for new PAQs.Although the majority of PAQs appear to have acceptable reliability, the validity is moderate at best. Newly developed PAQs do not appear to perform substantially better than existing PAQs in terms of reliability and validity. Future PAQ studies should include measures of absolute validity and the error structure of the instrument.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Changes in coercive parenting and child externalizing behavior across COVID-19 and the moderating role of parent-child attachment relationship quality

Research indicates increases in coercive parenting towards children and increases in child externalizing behavior during COVID-19 as compared to the pre-pandemic period. In this preregistered study, we extended previous knowledge by investigating to what extent, and under what conditions, changes in coercive parenting and child externalizing behavior are interrelated. Ninety-five mothers and fathers of children (of age 3 prior to the pandemic) reported on coercive parenting and child externalizing behavior before and during the pandemic, and trained assistants observed the quality of mother-child and father-child attachment relationship prior to the pandemic. We employed latent change score modeling to test the extent to which changes in maternal and paternal coercive parenting and changes in child externalizing behavior across the pre-pandemic period and the onset of the first COVID-19 lockdown are interrelated. Moreover, we tested whether these linkages are moderated by changes in the other parent’s coercive parenting and the quality of parent-child attachment relationship. Specifically, we tested the moderation by mother-child (fatherchild) attachment relationship quality in the relation between changes in mothers’ (fathers’) coercive parenting and changes in child externalizing behavior. We found that changes in mothers’, but not fathers’ coercive parenting were positively associated with changes in child externalizing behavior. We found no moderation by changes in the other parent’s parenting or by parent-child attachment relationship quality. Our findings provide support for the transactional processes underlying mothers’ and children’s behavior in the context of non-normative stressful conditions. We recommend incorporating evidence-based (parenting) support for mothers, fathers, and young children in prevention strategies and recovery tools employed during and after future lockdowns and non-normative stressful events

Dose–response between frequency of interruption of sedentary time and fasting glucose, the dawn phenomenon and night-time glucose in Type 2 diabetes

Aim: To explore the dose-response between frequency of interruption of sedentary time and basal glucose (fasting glucose, the dawn phenomenon and night-time glucose) in Type 2 diabetes. Methods: In a randomized three-treatment, two-period balanced incomplete block trial, 12 people with Type 2 diabetes (age, 60.0 +/- 3.2 years; BMI, 30.2 +/- 1.4 kg/m(2)) completed two of three conditions: sitting for 7 h interrupted every 60 min (Condition 1), 30 min (Condition 2), and 15 min (Condition 3) by 3-min light-intensity walking breaks. The activPAL3 and FreeStyle Libre were used to assess physical activity/sedentary behaviour and continuous glucose profile. Standardized meals were provided, and changes in basal glucose of the nights and early mornings before and after treatment conditions were calculated (mean +/- SE). Results: After treatment conditions, fasting glucose and duration of the dawn phenomenon were lower for Condition 3 (-1.0 +/- 0.2 mmol/l, P < 0.02; -3.1 +/- 1.3 h, P = 0.004) compared with Condition 1 (-0.1 +/- 0.2 mmol/l; 1.9 +/- 1.2 h). The magnitude of the dawn phenomenon was reduced in Condition 3 (-0.6 +/- 0.4 mmol/l, P = 0.041) compared with Condition 2 (0.6 +/- 0.3 mmol/l). Night-time glycaemic variability (coefficient of variation) was reduced in Condition 3 (-9.7 +/- 3.9%) relative to Condition 2 (6.1 +/- 4.8%, P < 0.03) and Condition 1 (2.5 +/- 1.8%, P = 0.02). There was no change in night-time mean glucose. Conclusions: Frequent interruptions of prolonged sitting with 3 min of light-intensity walking breaks every 15 min improves fasting glucose, the dawn phenomenon and night-time glycaemic variability, and this might be a simple therapeutic intervention to improve glucose control. Clinicaltrials.gov Identifier: NCT0273899