België ontsnapt niet aan het 'rabbit hemorrhagic disease virus-2'

Since 2016, an extensive spread of RHDV2, a virus variant of the classical rabbit hemorrhagic disease virus (RHDV) is ongoing in the Belgian rabbit population. Both variants of the virus usually cause acute death without prior symptoms. Vaccination against both variants of the virus is possible. In Belgium, only a vaccine protecting against the classical RHDV has been registered. On their own responsibility, veterinarians are allowed to import a vaccine protecting against RHDV2 that is registered in another EU member state, in accordance with the so-called legislative waterfall-system. The current epidemiological situation warrants preventive vaccination of rabbits against RHD. It should be noted that myxomatosis is currently rather neglected in view of the increased attention for the RHDV2 spread. Myxomatosis also still causes a high mortality in both wild and domesticated rabbits. Veterinarians should correctly inform the public about the two important viral diseases in rabbits and the possibilities for prevention

Assessment of aberrant DNA methylation two years after paediatric critical illness:a pre-planned secondary analysis of the international PEPaNIC trial

Critically ill children requiring intensive care suffer from impaired physical/neurocognitive development 2 y later, partially preventable by omitting early use of parenteral nutrition (early-PN) in the paediatric intensive-care-unit (PICU). Altered methylation of DNA from peripheral blood during PICU-stay provided a molecular basis hereof. Whether DNA-methylation of former PICU patients, assessed 2 y after critical illness, is different from that of healthy children remained unknown. In a pre-planned secondary analysis of the PEPaNIC-RCT (clinicaltrials.gov-NCT01536275) 2-year follow-up, we assessed buccal-mucosal DNA-methylation (Infinium-HumanMethylation-EPIC-BeadChip) of former PICU-patients (N = 406 early-PN; N = 414 late-PN) and matched healthy children (N = 392). CpG-sites differentially methylated between groups were identified with multivariable linear regression and differentially methylated DNA-regions via clustering of differentially methylated CpG-sites using kernel-estimates. Analyses were adjusted for technical variation and baseline risk factors, and corrected for multiple testing (false-discovery-rate <0.05). Differentially methylated genes were functionally annotated (KEGG-pathway database), and allocated to three classes depending on involvement in physical/neurocognitive development, critical illness and intensive medical care, or pre-PICU-admission disorders. As compared with matched healthy children, former PICU-patients showed significantly different DNA-methylation at 4047 CpG-sites (2186 genes) and 494 DNA-regions (468 genes), with most CpG-sites being hypomethylated (90.3%) and with an average absolute 2% effect-size, irrespective of timing of PN initiation. Of the differentially methylated KEGG-pathways, 41.2% were related to physical/neurocognitive development, 32.8% to critical illness and intensive medical care and 26.0% to pre-PICU-admission disorders. Two years after critical illness in children, buccal-mucosal DNA showed abnormal methylation of CpG-sites and DNA-regions located in pathways known to be important for physical/neurocognitive development

Impact of critical illness and withholding of early parenteral nutrition in the pediatric intensive care unit on long-term physical performance of children:a 4-year follow-up of the PEPaNIC randomized controlled trial

Background: Many critically ill children face long-term developmental impairments. The PEPaNIC trial attributed part of the problems at the level of neurocognitive and emotional/behavioral development to early use of parenteral nutrition (early-PN) in the PICU, as compared with withholding it for 1 week (late-PN). Insight in long-term daily life physical functional capacity after critical illness is limited. Also, whether timing of initiating PN affects long-term physical function of these children remained unknown. Methods: This preplanned follow-up study of the multicenter PEPaNIC randomized controlled trial subjected 521 former critically ill children (253 early-PN, 268 late-PN) to quantitative physical function tests 4 years after PICU admission in Leuven or Rotterdam, in comparison with 346 age- and sex-matched healthy children. Tests included handgrip strength measurement, timed up-and-go test, 6-min walk test, and evaluation of everyday overall physical activity with an accelerometer. We compared these functional measures for the former critically ill and healthy children and for former critically ill children randomized to late-PN versus early-PN, with multivariable linear or logistic regression analyses adjusting for risk factors. Results: As compared with healthy children, former critically ill children showed less handgrip strength (p &lt; 0.0001), completed the timed up-and-go test more slowly (p &lt; 0.0001), walked a shorter distance in 6 min (p &lt; 0.0001) during which they experienced a larger drop in peripheral oxygen saturation (p ≤ 0.026), showed a lower energy expenditure (p ≤ 0.024), performed more light and less moderate physical activity (p ≤ 0.047), and walked fewer steps per day (p = 0.0074). Late-PN as compared with early-PN did not significantly affect these outcomes. Conclusions: Four years after PICU admission, former critically ill children showed worse physical performance as compared with healthy children, without impact of timing of supplemental PN in the PICU. This study provides further support for de-implementing the early use of PN in the PICU. Trial registration ClinicalTrials.gov, NCT01536275; registered on February 22, 2012.</p

Time course of altered DNA methylation evoked by critical illness and by early administration of parenteral nutrition in the paediatric ICU

Background: A genome-wide study identifed de novo DNA methylation alterations in leukocytes of children at paediatric intensive care unit (PICU) discharge, ofering a biological basis for their impaired long-term development. Early parenteral nutrition (early-PN) in PICU, compared with omitting PN in the frst week (late-PN), explained diferential methylation of 23% of the afected CpG-sites. We documented the time course of altered DNA methylation in PICU and the impact hereon of early nutritional management. Results: We selected 36 early-PN and 36 late-PN matched patients, and 42 matched healthy children. We quantifed DNA methylation on days 3, 5 and 7 for the 147 CpG-sites of which methylation was normal upon PICU admission in this subset and altered by critical illness at PICU discharge. Methylation in patients difered from healthy children for 64.6% of the 147 CpG-sites on day 3, for 72.8% on day 5 and for 90.5% on day 7 as revealed by ANOVA at each time point. Within-patients methylation time course analyses for each CpG-site identifed diferent patterns based on paired t test p value and direction of change. Rapid demethylation from admission to day 3 occurred for 76.2% of the CpG-sites, of which 67.9% remained equally demethylated or partially remethylated and 32.1% further demethylated beyond day 3. From admission to day 3, 19.7% of the CpG-sites became hypermethylated, of which, beyond day 3, 34.5% remained equally hypermethylated or partially demethylated again and 65.5% further hypermethylated. For 4.1% of the CpG-sites, changes only appeared beyond day 3. Finally, for the CpG-sites afected by early-PN on the last PICU day, earlier changes in DNA methylation were compared for early-PN and late-PN patients, revealing that 38.9% were already diferentially methylated by day 3, another 25.0% by day 5 and another 13.9% by day 7. Conclusions: Critical illness- and early-PN-induced changes in DNA methylation occurred mainly within 3 days. Most abnormalities were at least partially maintained or got worse with longer time in PICU. Interventions targeting aberrant DNA methylation changes should be initiated earl

Early Supplemental Parenteral Nutrition in Critically Ill Children: An Update

In critically ill children admitted to pediatric intensive care units (PICUs), enteral nutrition (EN) is often delayed due to gastrointestinal dysfunction or interrupted. Since a macronutrient deficit in these patients has been associated with adverse outcomes in observational studies, supplemental parenteral nutrition (PN) in PICUs has long been widely advised to meeting nutritional requirements. However, uncertainty of timing of initiation, optimal dose and composition of PN has led to a wide variation in previous guidelines and current clinical practices. The PEPaNIC (Early versus Late Parenteral Nutrition in the Pediatric ICU) randomized controlled trial recently showed that withholding PN in the first week in PICUs reduced incidence of new infections and accelerated recovery as compared with providing supplemental PN early (within 24 hours after PICU admission), irrespective of diagnosis, severity of illness, risk of malnutrition or age. The early withholding of amino acids in particular, which are powerful suppressors of intracellular quality control by autophagy, statistically explained this outcome benefit. Importantly, two years after PICU admission, not providing supplemental PN early in PICUs did not negatively affect mortality, growth or health status, and significantly improved neurocognitive development. These findings have an important impact on the recently issued guidelines for PN administration to critically ill children. In this review, we summarize the most recent literature that provides evidence on the implications for clinical practice with regard to the use of early supplemental PN in critically ill children.status: publishe

How painful was it? Retrospective overestimation of pain in high habitual symptom reporters

Background and aims: During a retrospective evaluation of a painful event, the initial somatic experience is dynamically reconstructed and susceptible to various distortions. Since elevated but unfounded symptom reporting is strongly associated with trait negative affectivity (NA), we investigated memory distortion in high and low habitual symptom reporters (scoring high and low for NA). We hypothesized that high symptom reporters (HSR) would show more distorted memory for pain than low symptom reporters (LSR). Methods: Healthy female students (N = 31; 13 HSR/18 LSR) participated in a cold pressor task. In a short trial, they submerged one hand in water at 12°C for 60s. In a long trial, they held their other hand in water at 12°C for 60s, with additional 60s in water at 14°C. The order of the two trials was counterbalanced across participants and groups. Pain ratings were collected at four times: (1) continuously during pain induction, (2) after each trial, (3) after the experiment, (4) after 2 weeks. Results: Continuous pain ratings during hand immersion were not different for both groups. However, significantly higher retrospective pain assessments were given by HSR compared to LSR, starting already at the first retrospective evaluation, i.e. right after the trial. Conclusions: These findings suggest that retrospective pain ratings are importantly biased, especially in HSR. Pain overestimation occurs directly after completion of the trial, showing that distortions in symptom memory may operate promptly.status: publishe

The E2F-regulated gene Chk1 is highly expressed in triple-negative estrogen receptor-/progesterone receptor-/HER-2- Breast carcinomas

We previously showed that checkpoint kinase 1 (Chk1) and Claspin, two DNA-damage checkpoint proteins, were down-regulated by 1,25-dihydroxyvitamin D(3), a known inhibitor of cell proliferation. In the present study, we aimed to investigate the transcriptional regulation of Chk1 and Claspin and to study their expression levels in human breast cancer tissue. Transient transfection experiments in MCF-7 breast cancer cells showed that promoter activities of Chk1 and Claspin were regulated by the E2F family of transcription factors. Subsequently, transcript levels of Chk1, Claspin, and E2F1 were determined by quantitative reverse transcriptase-PCR analysis in 103 primary invasive breast carcinomas and were compared with several clinicopathologic variables in breast cancer. A strong correlation was found between Chk1 and Claspin transcript levels. Transcript levels of Chk1, Claspin, and E2F1 were highest in histologic grade 3 tumors and in tumors in which the expression of estrogen receptor (ER) and progesterone receptor (PR) was lost. Moreover, Chk1 expression was significantly elevated in grade 3 breast carcinomas showing a triple-negative ER-/PR-/HER-2- phenotype compared with other grade 3 tumors. Further research is warranted to validate the use of Chk1 inhibitors in triple-negative breast carcinomas for which treatment strategies are limited at present.status: publishe

The E2F-regulated gene Chk1 is highly expressed in triple-negative estrogen receptor-/progesterone receptor-/HER-2-breast carcinomas

We previously showed that checkpoint kinase 1 (Chk1) and Claspin, two DNA-damage checkpoint proteins, were down-regulated by 1,25-dihydroxyvitamin D-3, a known inhibitor of cell proliferation. In the present study, we aimed to investigate the transcriptional regulation of Chk1 and Claspin and to study their expression levels in human breast cancer tissue. Transient transfection experiments in MCF-7 breast cancer cells showed that promoter activities of Chk1 and Claspin were regulated by the E2F family of transcription factors. Subsequently, transcript levels of Chk1, Claspin, and E2F1 were determined by quantitative reverse transcriptase-PCR analysis in 103 primary invasive breast carcinomas and were compared with several clinicopathologic variables in breast cancer. A strong correlation was found between Chk1 and Claspin transcript levels. Transcript levels of Chk1, Claspin, and E2F] were highest in histologic grade 3 tumors and in tumors in which the expression of estrogen receptor (ER) and progesterone receptor (PR) was lost. Moreover, Chk1 expression was significantly elevated in grade 3 breast carcinomas showing a triple-negative ER-/PR-/HER-2- phenotype compared with other grade 3 tumors. Further research is warranted to validate the use of Chk1 inhibitors in triple-negative breast carcinomas for which treatment strategies are limited at present