Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes : A systematic review and meta-analyses of animal studies

Funding Information: This work was supported by a ZonMw grant (MKMD project; ID 114024127 ) awarded to JO & AR, and a grant awarded to JH from the Donders Institute for Brain, Cognition and Behavior . Funding bodies had no role in study design, data collection, data analysis, data interpretation, or the writing of the report.Peer reviewedPublisher PD

Establishment of the New Particle Therapy Research Center (PARTREC) at UMCG Groningen

After 25 years of successful research in the nuclear and radiation physics domain, the KVI-CART research center in Groningen is upgraded and re-established as the PARticle Therapy REsearch Center (PARTREC). Using the superconducting cyclotron AGOR and being embedded within the University Medical Center Groningen, it operates in close collaboration with the Groningen Proton Therapy Center. PARTREC uniquely combines radiation physics, medical physics, biology and radiotherapy research with an R&D program to improve hadron therapy technology and advanced radiation therapy for cancer. A number of further upgrades, scheduled for completion in 2023, will establish a wide range of irradiation modalities, such as pencil beam scanning, shoot-through with high energy protons and SOBP for protons, helium and carbon ions. Delivery of spatial fractionation (GRID) and dose rates over 300 Gy/s (FLASH) are envisioned. In addition, PARTREC delivers a variety of ion beams and infrastructure for radiation hardness experiments conducted by scientific and commercial communities, and nuclear science research in collaboration with the Faculty of Science and Engineering of the University of Groningen

Weight loss and elevated gluconeogenesis from alanine in lung cancer patients

BACKGROUND: The role of gluconeogenesis from protein in the pathogenesis of weight loss in lung cancer is unclear. OBJECTIVE: Our aim was to study gluconeogenesis from alanine in lung cancer patients and to analyze its relation to the degree of weight loss. DESIGN: In this cross-sectional study, we used primed-constant infusions of [6,6-(2)H(2)]-D-glucose and [3-(13)C]-L-alanine to assess whole-body glucose and alanine turnover and gluconeogenesis from alanine in weight-losing (WL, n = 9) and weight-stable (WS, n = 10) lung cancer patients and healthy control (n = 15) subjects. RESULTS: Energy intake and plasma alanine concentrations did not differ significantly among the subject groups. Mean (+/-SEM) whole-body glucose production was significantly higher in WL than in WS and control subjects (0.74 +/- 0.06 compared with 0.55 +/- 0.04 and 0.51 +/- 0.04 mmol*kg(-)(1)*h(-)(1), respectively, P < 0.01). Alanine turnover was significantly elevated in WL compared with WS and control subjects (0.57 +/- 0.04 compared with 0.42 +/- 0.05 and 0.40 +/- 0.03 mmol*kg(-)(1)*h(-)(1), respectively, P < 0.01). Gluconeogenesis from alanine was significantly higher in WL than in WS and control subjects (0.47 +/- 0.04 compared with 0.31 +/- 0.04 and 0.29 +/- 0.04 mmol*kg(-)(1)*h(-)(1), respectively, P < 0.01). The degree of weight loss was positively correlated with glucose and alanine turnover and with gluconeogenesis from alanine (r = 0.45 for all, P < 0.01). CONCLUSIONS: Aberrant glucose and alanine metabolism occurred in WL lung cancer patients. These changes were related to the degree of weight loss and not to the presence of lung cancer per se

Waiting List Dynamics and Lung Transplantation Outcomes After Introduction of the Lung Allocation Score in The Netherlands

The Netherlands was the third country to adopt the lung allocation score (LAS) for national allocation of donor lungs in April 2014. Evaluations of the introduction of the LAS in the United States and Germany showed mainly beneficial effects, including increased survival after transplantation. Methods: Data for transplant candidates from 2010 to 2019 were retrieved from the Dutch Transplant Foundation database. Diagnosis categories and outcomes were compared between the periods before and after the introduction of the LAS. Time-dependent Cox regression and Fine-Gray analyses were performed to compare the chance for transplantation before and after introduction of the LAS. Results: The cohort comprised 1276 patients. After introduction of the LAS, the annual number of transplantations and waiting list mortality did not change. The proportion of patients on the waiting list and transplanted patients with pulmonary fibrosis increased (25%-37%, P < 0.001; 22%-39%, P < 0.001). The chance of transplantation increased significantly for patients with pulmonary fibrosis after introduction of the LAS (hazard ratio 1.9 [95% confidence interval 1.4-2.9]). Patients who died on the waiting list had an increased LAS compared to the time of placement on the waiting list, reflecting clinical deterioration. This was not the case in patients with chronic obstructive pulmonary disease (P < 0.001). Overall survival was similar after introduction of the LAS (5-y survival 68%, compared to 74% [P = 0.171]). Conclusions: After the introduction of the LAS in The Netherlands, an increased proportion of transplantations was performed for patients with pulmonary fibrosis. Overall survival after transplantation did not change

The effect of COVID-19 on transplant function and development of CLAD in lung transplant patients:A multicenter experience

Background : Concerns have been raised on the impact of coronavirus disease (COVID-19) on lung transplant (LTx) patients. The aim of this study was to evaluate the transplant function pre- and post-COVID-19 in LTx patients. Methods : Data were retrospectively collected from LTx patients with confirmed COVID-19 from all 3 Dutch transplant centers, between February 2020 and September 2021. Spirometry results were collected pre-COVID-19, 3- and 6-months post infection. Results : Seventy-four LTx patients were included. Forty-two (57%) patients were admitted, 19 (26%) to the intensive care unit (ICU). The in-hospital mortality was 20%. Twelve out of 19 ICU patients died (63%), a further 3 died on general wards. Patients with available spirometry (78% at 3 months, 65% at 6 months) showed a significant decline in mean forced expiratory volume in 1 second (FEV1) (ΔFEV1 138 ± 39 ml, p = 0.001), and forced vital capacity (FVC) (ΔFVC 233 ±74 ml, p = 0.000) 3 months post infection. Lung function improved slightly from 3 to 6 months after COVID-19 (ΔFEV1 24 ± 38 ml; ΔFVC 100 ± 46 ml), but remained significantly lower than pre-COVID-19 values (ΔFEV1 86 ml ± 36 ml, p = 0.021; ΔFVC 117 ± 35 ml, p = 0.012). FEV1/FVC was > 0.70. Conclusions: In LTx patients COVID-19 results in high mortality in hospitalized patients. Lung function declined 3 months after infection and gradually improved at 6 months, but remained significantly lower compared to pre-COVID-19 values. The more significant decline in FVC than in FEV1 and FEV1/FVC > 70%, suggested a more restrictive pattern

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted

Identification of Risk Factors for Dupilumab-associated OculaSurface Disease in Patients with Atopic Dermatitis

This study identified risk factors for the development of dupilumab-associated ocular surface disease in patients with moderate-to-severe atopic dermatitis in a large prospective daily practice cohort. Data from the Dutch BioDay Registry were used to assess the risk of developing dupilumab-associated ocular surface di-sease, by performing univariate and multivariate logistic regression analyses. A total of 469 patients were included, of which 152/469 (32.4%) developed dupi-lumab-associated ocular surface disease. Multivariate analysis showed a statistically significant association of the development of dupilumab-associated ocular surface disease with a history of any eye disease (his-tory of self-reported episodic acute allergic conjunctivitis excluded) combined with the use of ophthalmic medication at the start of dupilumab (odds ratio 5.16, 95% confidence interval 2.30–11.56, p < 0.001). In conclusion, a history of any eye disease (history of self-reported episodic acute allergic conjunctivitis ex-cluded) combined with the use of ophthalmic medication at baseline was associated with the development of dupilumab-associated ocular surface disease in patients with atopic dermatitis