Intrusions related to indirectly experienced events in clinical offspring of World War Two survivors

Negative events may not only linger on in the form of intrusive memories in the minds of those directly exposed but also in those who are only indirectly confronted with these events. The aim of the present study was to investigate if intrusions referring to indirectly experienced traumatic events do indeed occur, and to compare their frequency and characteristics to intrusions about directly experienced negative events. Participants (N = 98) were adult postwar offspring of World War Two survivors currently in treatment in one of two clinics specialized in the treatment of war victims. We examined the frequency and characteristics of intrusions about indirectly experienced (i.e., parent war-related) events and two types of directly (self-) experienced events: Self-experienced traumatic events and negative events related to participants' upbringing. Intrusions referring to indirectly experienced traumatic events did indeed occur. The frequency as well as other characteristics of these intrusions did not differ from those of both types of intrusions about directly experienced events. The similarities between intrusions related to different types of events emphasize the (re)constructive nature of memory. Our findings indicate that traumatic events not only affect those directly involved but may also continue to plague the next generation

Comparison of health behaviours between cancer survivors and the general population:a cross-sectional analysis of the Lifelines cohort

Purpose: To compare the differences in lifestyle behaviours between cancer survivors (CSs) and cancer-free participants in a large and representative population-based cohort. Methods: We included 115,257 adults from the Lifelines cohort. Cancer status was self-reported, and health behaviours were measured (e.g. body mass index [BMI]) or assessed by questionnaire (e.g. physical activity, smoking, alcohol consumption, sedentary behaviour and diet). The data were then categorised for logistic regression analysis, stratified and adjusted by sex and age (< 55 vs ≥ 55 years). Results: CSs (5473; 4.7%) were diagnosed 9 ± 8.5 years before data collection, were older (mean age 55.4 vs 44.4 years) and more often female (66.6% vs 33.4%) than the cancer-free participants. They were also more likely to be physically active and to have a better diet, and also less likely to be alcohol drinkers; but, were more likely to have a higher BMI, be former smokers and to be sedentary. After adjustment for sex and age, however, BMI was more likely to be normal, physical activity was more likely to be higher and smoking to be prevalent in CSs. Current smoking was also significantly higher among females and those aged < 55 years who were CSs than for those with no history of cancer. Conclusions: In this population-based cohort, CSs have health behaviour comparable to those without a cancer diagnosis. Implications for cancer survivors: Smoking cessation strategies should target all CSs, but efforts could yield greatest benefit if they target females and those younger than 55 years

Higher Programmatic Volume in Neonatal Heart Surgery Is Associated With Lower Early Mortality

BACKGROUND: The early results of congenital heart surgery in neonates remain a challenge. We sought to determine the nature of the association between annual center volume of neonatal cardiac surgery and operative mortality using a multicenter cohort. METHODS: The dataset consists of 27,556 neonatal procedures performed between 1999 and 2015 in 90 centers participating in the European Congenital Heart Surgeons Association database. Centers with mean annual volume load of six or more that submitted data for at least 3 consecutive years were included. World Bank annual gross national index per capita was utilized as an indicator of temporal national affluence. Multilevel logistic regression was used to create a model including the significant risk factors and to calculate odds ratios for operative mortality. Iterative modeling of the dataset incrementally excluding centers with lower annual caseload was used to identify the relationship between annual volume and mortality. RESULTS: In the model thus calculated including The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) mortality score, operative weight and age, noncardiac genetic anomalies, and annual volume of operations were independent risk factors for operative mortality in the analysis of the entire cohort. In the model containing these variables, annual gross national index and year of surgery were not significantly associated with mortality. In the iterative process, annual volume ceased to be a risk factor when units operating on fewer than 60 neonates annually were excluded. CONCLUSIONS: In neonatal congenital heart surgery, the risk of operative death decreased with the increase of volume load. The cutoff point in this cohort was a mean annual volume of 60 neonatal operations per year.info:eu-repo/semantics/publishedVersio

Impact of the NK Cell Receptor LIR-1 (ILT-2/CD85j/LILRB1) on Cytotoxicity against Multiple Myeloma

The role of different receptors in natural-killer- (NK-) cell-mediated cytotoxicity against multiple myeloma (MM) cells is unknown. We investigated if an enhancement of NK-cell-mediated cytotoxicity against MM could be reached by blocking of the inhibitory leukocyte immunoglobulin-like receptor 1 (LIR-1). Our investigations revealed high levels of LIR-1 expression not only on the NK cell line NK-92, but also on myeloma cells (MOLP-8, RPMI8226) as well as on a lymphoblastoid cell line (LBCL; IM-9). Subsequent cytotoxicity assays were designed to show the isolated effects of LIR-1 blocking on either the effector or the tumor side to rule out receptor-receptor interactions. Although NK-92 was shown to be capable of myeloma cell lysis, inhibition of LIR-1 on NK-92 did not enhance cytotoxicity. Targeting the receptor on MM and LBCL did not also alter NK-92-mediated lysis. We come to the conclusion that LIR-1 alone does not directly influence NK-cell-mediated cytotoxicity against myeloma. To our knowledge, this work provides the first investigation of the inhibitory capability of LIR-1 in NK-92-mediated cytotoxicity against MM and the first functional evaluation of LIR-1 on MM and LBCL

Vascular aging in long-term survivors of testicular cancer more than 20 years after treatment with cisplatin-based chemotherapy

Background: Late effects of cisplatin-based chemotherapy in testicular cancer survivors (TCS) include cardiovascular morbidity, but little data is available beyond 20 years. The objective was to assess vascular damage in very long-term TCS. Methods: TCS (treated with chemotherapy or orchiectomy only) and age-matched healthy controls were invited. Study assessment included vascular stiffness with ultrasound measurement of carotid-femoral pulse wave velocity (cf-PWV). Results: We included 127 TCS consisting of a chemotherapy group (70 patients) and an orchiectomy group (57 patients) along with 70 controls. Median follow-up was 28 years (range: 20–42). The cf-PWV (m/s) was higher in TCS than in controls (geometrical mean 8.05 (SD 1.23) vs. 7.60 (SD 1.21), p = 0.04). The cf-PWV was higher in the chemotherapy group than in the orchiectomy group (geometrical mean 8.39 (SD 1.22) vs. 7.61 (SD 1.21), p < 0.01). In the chemotherapy group cf-PWV increased more rapidly as a function of age compared to controls (regression coefficient b 7.59 × 10−3 vs. 4.04 × 10−3; p = 0.03). Conclusion: Very long-term TCS treated with cisplatin-based chemotherapy show increased vascular damage compatible with “accelerated vascular aging” and continue to be at risk for cardiovascular morbidity, thus supporting the need for intensive cardiovascular risk management. Clinical trial registration: The clinical trial registration number is NCT02572934

GlyT2+ Neurons in the Lateral Cerebellar Nucleus

The deep cerebellar nuclei (DCN) are a major hub in the cerebellar circuitry but the functional classification of their neurons is incomplete. We have previously characterized three cell groups in the lateral cerebellar nucleus: large non-GABAergic neurons and two groups of smaller neurons, one of which express green fluorescence protein (GFP) in a GAD67/GFP mouse line and is therefore GABAergic. However, as a substantial number of glycinergic and glycine/GABA co-expressing neurons have been described in the DCN, this classification needed to be refined by considering glycinergic neurons. To this end we took advantage of a glycine transporter isoform 2 (GlyT2)-eGFP mouse line that allows identification of GlyT2-expressing, presumably glycinergic neurons in living cerebellar slices and compared their electrophysiological properties with previously described DCN neuron populations. We found two electrophysiologically and morphologically distinct sets of GlyT2-expressing neurons in the lateral cerebellar nucleus. One of them showed electrophysiological similarity to the previously characterized GABAergic cell group. The second GlyT2+ cell population, however, differed from all other so far described neuron types in DCN in that the cells (1) are intrinsically silent in slices and only fire action potentials upon depolarizing current injection and (2) have a projecting axon that was often seen to leave the DCN and project in the direction of the cerebellar cortex. Presence of this so far undescribed DCN neuron population in the lateral nucleus suggests a direct inhibitory pathway from the DCN to the cerebellar cortex

Pharmacological Characterization of [3H]CHIBA-3007 Binding to Glycine Transporter 1 in the Rat Brain

Glycine transporter-1 (GlyT-1) in glial cells regulates extracellular levels of glycine, which acts as an obligatory co-agonist at the N-methyl-D-aspartate (NMDA) receptors in the brain. In the present study, we developed a novel radioligand, [3H]3-chloro-N-((S)-((R)-1-methylpiperidin-2-yl)(thiophen- 3-yl)methyl)-4- (trifluoromethyl)picolinamide ([3H]CHIBA-3007), for studying GlyT-1 in the brain. The presence of a single saturable high-affinity binding component for [3H]CHIBA-3007 binding to the rat brain membranes was detected. Scatchard analysis revealed an apparent equilibrium dissociation constant (Kd) of 1.61±0.16 nM and a maximal number of binding sites (Bmax) of 692.8±22.8 fmol/mg protein (mean ± SEM, n = 3). The specific binding of [3H]CHIBA-3007 was inhibited by a number of GlyT-1 inhibitors, such as CHIBA-3007, desmethyl-CHIBA-3007, CHIBA-3008, SSR504734, NFPS/ALX5407, LY2365109 and Org24598, consistent with the pharmacological profiles of GlyT-1 inhibitors. Interestingly, the potency of eight GlyT-1 inhibitors (CHIBA-3007, desmethyl-CHIBA-3007, NFPS/ALX5407, LY2365109, Org24598, SSR504734, sarcosine, and glycine) for blocking in vitro specific binding of [3H]CHIBA-3007 was significantly correlated with the potency of these inhibitors for inhibiting [14C]glycine uptake in the rat brain membranes. In contrast, the GlyT-2 inhibitor ALX1393 exhibited very weak for [3H]CHIBA-3007 binding. Furthermore, the regional distribution of [3H]CHIBA-3007 binding in the rat brain was similar to the previously reported distribution of GlyT-1. The present findings suggest that [3H]CHIBA-3007 would be a useful new radioligand for studying GlyT-1 in the brain