Cancer is a disease of the elderly, and old age is its largest risk factor. With age, DNA damage accumulates continuously, increasing the chance of malignant transformation. The zebrafish has emerged as an important vertebrate model to study these processes. Key mechanisms such as DNA damage responses and cellular senescence can be studied in zebrafish throughout its life course. In addition, the zebrafish is becoming an important resource to study telomere biology in aging, regeneration and cancer. Here we review some of the tools and resources that zebrafish researchers have developed and discuss their potential use in the study of DNA damage, cancer and aging related diseases.

This experimental study compares the appropriateness of direct digital radiography (DDR) and ultrasonography at detecting soft-tissue wooden foreign bodies (FBs) in extremities.
Varying wooden FB splinters (2 mm, 5 mm and 10 mm) were inserted into eight porcine feet to simulate a patient presenting with a soft-tissue FB injury. Each of the FBs was placed in muscle distant, behind and near bone in the porcine feet. Control groups were used to check for false-positive diagnoses and, based on the presence of FBs; images were given a score depending on the level of visibility by the researcher.
A higher detection rate was achieved for all FBs in muscle distant from bone using ultrasound. All of the 2 mm and 5 mm wooden FBs were not detected using DDR. The sensitivity in detecting the FBs was 5.8% and 30% in DDR and ultrasound respectively.
Poor sensitivities and specificities were identified in this study. However, this study shows that ultrasound remains superior to DDR at identifying small foreign body objects. This study demonstrates that ultrasound can be a clinically effective tool for detecting suspected wooden FBs >5 mm in the foot and thus should be considered as the primary imaging modality of choice for referring clinicians.

Chemotherapy may exert immunomodulatory effects, thereby combining favorably with the immune checkpoint blockade. The pharmacodynamic effects of such combinations, and potential predictive biomarkers, remain unexplored.
To determine the safety, efficacy, and immunomodulatory effects of gemcitabine and cisplatin (GC) plus ipilimumab and explore the impact of somatic DNA damage response gene alterations on antitumor activity.
Multicenter single arm phase 2 study enrolling 36 chemotherapy-naïve patients with metastatic urothelial cancer. Peripheral blood flow cytometry was performed serially on all patients and whole exome sequencing of archival tumor tissue was performed on 28/36 patients.
Two cycles of GC followed by four cycles of GC plus ipilimumab.
The primary endpoint was 1-yr overall survival (OS). Secondary endpoints included safety, objective response rate, and progression-free survival.
Grade ≥3 adverse events occurred in 81% of patients, the majority of which were hematologic. The objective response rate was 69% and 1-yr OS was 61% (lower bound 90% confidence interval: 51%). On exploratory analysis, there were no significant changes in the composition and frequency of circulating immune cells after GC alone. However, there was a significant expansion of circulating CD4 cells with the addition of ipilimumab which correlated with improved survival. The response rate was significantly higher in patients with deleterious somatic DNA damage response mutations (sensitivity=47.6%, specificity=100%, positive predictive value=100%, and negative predictive value=38.9%). Limitations are related to the sample size and single-arm design.
GC+ipilimumab did not achieve the primary endpoint of a lower bound of the 90% confidence interval for 1-yr OS of >60%. However, within the context of a small single-arm trial, the results may inform current approaches combining chemotherapy plus immunotherapy from the standpoint of feasibility, appropriate cytotoxic backbones, and potential predictive biomarkers.
ClinicalTrials.gov NCT01524991.
Combining chemotherapy and immune checkpoint blockade in patients with metastatic urothelial cancer is feasible. Further studies are needed to refine optimal combinations and evaluate tests that might identify patients most likely to benefit.

Research has identified appetitive aggression, i.e., the perception of committed, violent acts as appealing, exciting and fascinating, as a common phenomenon within populations living in precarious and violent circumstances. Investigating demobilized soldiers in the Democratic Republic of Congo (DRC) demonstrated that violent offending is associated with appetitive aggression and not necessarily with symptoms of posttraumatic stress. In the present study, we sought to replicate these results in an independent and larger sample of demobilized soldiers from Burundi. As with the Congolese ex-combatants, random forest regression revealed that the number of lifetime perpetrated violent acts is the most important predictor of appetitive aggression and the number of lifetime experienced traumatic events is the main predictor for posttraumatic stress. Perpetrated violent acts with salient cues of hunting (pursuing the victim, the sight of blood, etc.) were most predictive for perceiving violent cues appealingly after demobilization. Moreover, the association of violent acts and appetitive aggression as well as traumatic events and posttraumatic stress remains strong even years after demobilization. Patterns of traumatic events and perpetrated acts as predictors for posttraumatic stress and appetitive aggression seem to be robust among different samples of ex-combatants who fought in civil wars. Psychotherapeutic interventions that address these complementary facets of combat-related disorders-namely, posttraumatic stress and appetitive aggression-are indispensable for a successful reintegration of those who fought in armed conflicts and to achieve a successful transition to peace.