Desire for children among male survivors of childhood cancer: A DCCSS LATER study

Background

Knowledge of the desire for children among childhood cancer survivors (CCSs) is scarce. This study evaluated the desire for children in male CCSs in comparison with male siblings.

Methods

A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor Study LATER study: 1317 male CCSs and 407 male sibling controls completed a questionnaire addressing the desire for children. Logistic regression analyses were used to explore the independent association between survivorship status and the desire for children. Furthermore, additional analyses were performed to identify which cancer-related factors were associated with the desire for children in male CCSs.

Results

After adjustments for the age at assessment, the percentage of men who had a desire for children was significantly lower among CCSs compared with the siblings (74% vs. 82%; odds ratio [OR], 0.61; 95% CI, 0.46–0.82; p = .001). The association between survivorship status and the desire for children was attenuated after adjustments for marital status, level of education, and employment status (OR, 0.83; 95% CI, 0.61–1.14; p = .250). The percentage of men who had an unfulfilled desire for children remained significantly higher among CCSs compared with the siblings after adjustments for sociodemographic factors (25% vs. 7%; OR, 5.14; 95% CI, 2.48–10.64; p < .001).

Conclusions

The majority of male CCSs have a desire for children. The likelihood of having to deal with an unfulfilled desire for children is 5 times higher among CCSs compared with their siblings. This insight is important for understanding the needs and experienced problems of CCSs regarding family planning and fertility issues.     

Clinical evaluation of late outcomes in Dutch childhood cancer survivors: Methodology of the DCCSS LATER 2 study

Background

Childhood cancer survivors face late health problems; despite advances in research, details on risk remain unclear. We describe the methodological aspects of the Dutch Childhood Cancer Survivor Study (DCCSS) cross-sectional clinical study (LATER 2 study).

Procedure

From the multi-center DCCSS LATER cohort of 6165 five-year survivors diagnosed during 1963–2001, we invited 4735 eligible survivors in 2016, as well as siblings and parents of survivors. Gaps in evidence identified during development of surveillance guidelines were translated into clinical research questions for 16 outcome-specific subprojects. The regular care visit to the LATER outpatient clinic forms the backbone of outcome assessment complemented with research-defined measurements (physical examination, clinical tests, questionnaires). Furthermore, blood/saliva samples were taken for deoxyribonucleic acid (DNA) extraction.

Results

In total, 2519 (53.2%) survivors participated in the LATER 2 study. When comparing participants with nonparticipants, we observed that males, CNS survivors, and those treated with surgery only were less likely to participate. Of the participating survivors, 49.3% were female. Median time since childhood cancer diagnosis was 26.9 years (range 14.8–54.7 years) and median attained age was 34.4 years (range 15.4–66.6 years).

Conclusions

The high-quality data generated in the LATER 2 study will provide valuable insights into risks of and risk factors for clinical and physical and psychosocial health outcomes and factors for early recognition of those health outcomes in long-term childhood cancer survivors. This will contribute to fill in important gaps in knowledge and improve the quality of life and care for childhood cancer survivors.     

Characteristics of contralesional and ipsilesional saccades in hemianopic patients

In order to further our understanding of action-blindsight, four hemianopic patients suffering from visual field loss contralateral to a unilateral occipital lesion were compared to six healthy controls during a double task of verbally reported target detection and saccadic responses toward the target. Three oculomotor tasks were used: a fixation task (i.e., without saccade) and two saccade tasks (eliciting reflexive and voluntary saccades, using step and overlap 600 ms paradigms, respectively), in separate sessions. The visual target was briefly presented at two different eccentricities (5° and 8°), in the right or left visual hemifield. Blank trials were interleaved with target trials, and signal detection theory was applied. Despite their hemifield defect, hemianopic patients retained the ability to direct a saccade toward their contralesional hemifield, whereas verbal detection reports were at chance level. However, saccade parameters (latency and amplitude) were altered by the defect. Saccades to the contralesional hemifield exhibited longer latencies and shorter amplitudes compared to those of the healthy group, whereas only the latencies of reflexive saccades to the ipsilesional hemifield were altered. Furthermore, healthy participants showed the expected latency difference between reflexive and voluntary saccades, with the latter longer than the former. This difference was not found in three out of four patients in either hemifield. Our results show action-blindsight for saccades, but also show that unilateral occipital lesions have effects on saccade generation in both visual hemifields.     

Acute hypoxic exercise does not alter post-exercise iron metabolism in moderately trained endurance athletes

Purpose

This study measured the influence of acute hypoxic exercise on Interleukin-6 (IL-6), hepcidin, and iron biomarkers in athletes.

Methods

In a repeated measures design, 13 moderately trained endurance athletes performed 5 × 4 min intervals at 90 % of their peak oxygen consumption velocity (vVO_2peak) in both normoxic [NORM, fraction of inspired oxygen (F _IO₂) = 0.2093, 15.3 ± 1.7 km h^?1] and simulated hypoxic (HYP, F _IO₂ = 0.1450, 13.2 ± 1.5 km h^?1) conditions. Venous blood samples were obtained pre-, post-, and 3 h post-exercise, and analysed for serum hepcidin, IL-6, ferritin, iron, soluble transferrin receptor (sTfR), and transferrin saturation.

Results

Peak heart rate was significantly lower in HYP compared with NORM (p = 0.01); however, the rating of perceived exertion was similar between trials (p = 0.24). Ferritin (p = 0.02), transferrin (p = 0.03), and IL-6 (p = 0.01) significantly increased immediately post-exercise in both conditions, but returned to baseline 3 h later. Hepcidin levels significantly increased in both conditions 3 h post-exercise (p = 0.05), with no significant differences between trials. A significant treatment effect was observed between trials for sTfR (p = 0.01), but not iron and transferrin saturation.

Conclusion

Acute exercise in hypoxia did not influence post-exercise IL-6 production, hepcidin activity or iron metabolism compared with exercise at the same relative intensity in normoxia. Hence, acute exercise performed at the same relative intensity in hypoxia poses no further risk to an athlete’s iron status, as compared with exercise in normoxia.     

CT-guided injection technique into intervertebral discs in the ovine lumbar spine

Purpose

Disc injection to create intervertebral (IVD) disc degeneration (IVDD) has been reported in ovine models, but the techniques have not been thoroughly described. The current ex vivo study aimed to evaluate a computed tomography (CT)-guided injection technique into IVDs in the ovine lumbar spine.

Methods

Insertion of needles into the nucleus pulposus was assessed by gross anatomic dissection in two lumbar segments (group A), and injection of liquid within the disc was assessed by discography in six segments (group B).

Results

The pathway of the needle was simulated on computer after an initial CT scan, followed by control of the insertion process via a laser beam and monitoring scans. In group A, 20 insertions were assessed and 17 needles (85 %) were successfully positioned in the nucleus pulposus. In group B of 30 injections, the rate of success was 90 %.

Conclusions

The current study provides useful clinical information that will help surgeons working with an ovine model for research on IVDD. This model could also be useful to train less experienced surgeons or radiologists to disc injection. This CT-guided injection seems to offer several advantages such as ease of use, good success rate and safety to important nervous and vascular structures.     

Collective and single cell behavior in epithelial contact inhibition

Control of cell proliferation is a fundamental aspect of tissue physiology central to morphogenesis, wound healing, and cancer. Although many of the molecular genetic factors are now known, the system level regulation of growth is still poorly understood. A simple form of inhibition of cell proliferation is encountered in vitro in normally differentiating epithelial cell cultures and is known as "contact inhibition." The study presented here provides a quantitative characterization of contact inhibition dynamics on tissue-wide and single cell levels. Using long-term tracking of cultured Madin-Darby canine kidney cells we demonstrate that inhibition of cell division in a confluent monolayer follows inhibition of cell motility and sets in when mechanical constraint on local expansion causes divisions to reduce cell area. We quantify cell motility and cell cycle statistics in the low density confluent regime and their change across the transition to epithelial morphology which occurs with increasing cell density. We then study the dynamics of cell area distribution arising through reductive division, determine the average mitotic rate as a function of cell size, and demonstrate that complete arrest of mitosis occurs when cell area falls below a critical value. We also present a simple computational model of growth mechanics which captures all aspects of the observed behavior. Our measurements and analysis show that contact inhibition is a consequence of mechanical interaction and constraint rather than interfacial contact alone, and define quantitative phenotypes that can guide future studies of molecular mechanisms underlying contact inhibition.     

Internal model deficits impair joint action in children and adolescents with autism spectrum disorders

Qualitative differences in social interaction and communication are diagnostic hallmarks in autism spectrum disorders (ASD). The present study investigated the hypothesis that impaired social interaction in ASD reflects a deficit to internally model the behavior of a co-actor. Children and adolescents with ASD and matched controls performed a computerized bar-balancing task in a solo condition (S), and together with another individual in two joint action conditions (J2 and J4) in which they used either two or four hands to control the bar lift. Consistent with predictions derived from the ‘internal modelling hypothesis’, results from the J2 task indicated that ASD dyads were impaired in predicting the occurrence of their partner's response and failed to coordinate their actions in time. Furthermore, results from the J4 task showed that ASD participants used an adaptive strategy to disambiguate their responses from their partner's by regulating opposite sides of the bar during lifting. These findings provide empirical support of theories positing the existence of an internal modelling deficit in ASD. In addition, our findings suggest that impaired social reciprocal behavior and joint cooperative play exhibited by individuals with ASD may reflect behavioral adaptations to evade conflicting or ambiguous information in social settings.