Involvement of autophagy in melatonin‐induced cytotoxicity in glioma‐initiating cells

Glioblastoma‐initiating cells (GICs) represent a stem cell‐like subpopulation within malignant glioblastomas responsible for tumor development, progression, therapeutic resistance, and tumor relapse. Thus, eradication of this subpopulation is essential to achieve stable, long‐lasting remission. We have previously reported that melatonin decreases cell proliferation of glioblastoma cells both in vitro and in vivo and synergistically increases effectiveness of drugs in glioblastoma cells and also in GICs. In this study, we evaluated the effect of the indolamine alone in GICs and found that melatonin treatment reduces GICs proliferation and induces a decrease in self‐renewal and clonogenic ability accompanied by a reduction in the expression of stem cell markers. Moreover, our results also indicate that melatonin treatment, by modulating stem cell properties, induces cell death with ultrastructural features of autophagy. Thus, data reported here reinforce the therapeutic potential of melatonin as a treatment of malignant glioblastoma both by inhibiting tumor bulk proliferation or killing GICs, and simultaneously enhancing the effect of chemotherapy.     

Perioperative infliximab application has marginal effects on ischemia–reperfusion injury in experimental small bowel transplantation in rats

Purpose  

Ischemia-reperfusion injury leads to impaired smooth muscle function and inflammatory reactions after intestinal transplantation. In previous studies, infliximab has been shown to effectively protect allogenic intestinal grafts in the early phase after transplantation with resulting improved contractility. This study was designed to reveal protective effects of infliximab on ischemia–reperfusion injury in isogenic transplantation.     

Video head impulse in comparison to caloric testing in unilateral vestibular schwannoma

Conclusions: Although there was a statistically significant relationship between the results of the vHIT and the caloric test, the limited strength of this relationship suggests that, for unilateral vestibular schwannoma (UVS), caloric testing and vHIT may provide complementary information on vestibular function.

Objective: There is limited information that can be used to determine which of the video head impulse test (vHIT) and caloric test might be better used in the diagnosis and management of UVS. In this study, a group of participants with un-operated UVS was studied using both methods.

Methods: The subjects’ vestibular function was assessed using the vHIT and caloric testing. Tumour size was quantified using MRI and their balance disturbance assessed using the Jacobsen Dizziness Handicap Inventory (DHI).

Results: Twenty of 30 subjects had an abnormal canal paresis according to the Jongkees’ criterion (>?0.25); however, only 10/30 had an ipsilesional vHIT gain of <0.79. Canal paresis could be predicted from the ipsilesional and contralesional vHIT gains. Tumour size could also be predicted from the ipsilesional vHIT gain and canal paresis. However, DHI scores could not be predicted from the degree of canal paresis, vHIT gain, or the MRI measures.     

TAp73 depletion accelerates aging through metabolic dysregulation

Aging is associated with impaired scavenging of reactive oxygen species (ROS). Here, we show that TAp73, a p53 family member, protects against aging by regulating mitochondrial activity and preventing ROS accumulation. TAp73-null mice show more pronounced aging with increased oxidative damage and senescence. TAp73 deletion reduces cellular ATP levels, oxygen consumption, and mitochondrial complex IV activity, with increased ROS production and oxidative stress sensitivity. We show that the mitochondrial complex IV subunit cytochrome C oxidase subunit 4 (Cox4i1) is a direct TAp73 target and that Cox4i1 knockdown phenocopies the cellular senescence of TAp73-null cells. Results indicate that TAp73 affects mitochondrial respiration and ROS homeostasis, thus regulating aging.     

Circumcision Status and Time to Sexual Debut Among Youth in Sub-Saharan Africa: Evidence from Six Demographic and Health Surveys

This paper examines the relationship between circumcision status and timing of sexual debut among unmarried youth in Sub-Saharan Africa using Demographic and Health Surveys. Results from survival analysis indicate that the association between circumcision and timing of first sex is place and context specific. Compared to uncircumcised, circumcised men in Rwanda, Uganda and Namibia hasten sexual initiation, whilst circumcised youth in Ethiopia and Mali delayed sex initiation. In Togo however, we found parity in timing to sexual debut. Our multivariate results reveal that, knowledge of HIV/AIDS risk and educational level also feed into the association between circumcision and timing of sex initiation- implying that efforts to prevent new HIV infection through circumcision could benefit from a proper understanding of how diverse set of factors interact in specific contexts to shape youth’s decisions to initiate early sex.     

A systematic review of resource habitat taboos and human health outcomes in the context of global environmental change

The dependence of humans on the ecosystem services that natural resources provide is absolute. The need for social taboos as frameworks for governing natural resource abstraction is gaining widespread recognition especially within the context of climate change. However, the complex relationship between resource and habitat taboos (RHTs) and human health is not entirely understood. We conducted a systematic review of existing studies of the association between RHTs and human health outcomes, focusing on the best evidence available. We searched JSTOR, SocINDEX, Greenfile and Academic Search Complete databases from 1970 to July 2015; and also searched the reference lists of reviews and relevant articles. About 779 studies and data from 26 studies were eligible for the analysis. Only 9 out of 26 studies clearly linked RHTs to human health. Overall, nine taboos, spatial, temporal, gear, method, effort, catch, species-specific, life history and segment, were covered by the empirical studies. This systematic review provides new evidence of relationships between RHTs and human health outcomes. Several methodological limitations were identified in the empirical material. The findings suggest the need for context-specific conservation policies to reduce erosion of RHTs in order to sustain human health in the face of climate change.     

VISUAL PATHWAY TUMORS AND HYDROCEPHALUS

The authors evaluated the impact of hydrocephalus on the clinical picture of children with visua pathway tumor (VPT) with or without neurofibromatosis (NF).Charts of children with VPT treated in the authors' center since 1985 were retrospectively reviewed, and those with hydrocephalus were selected and summarized. Thirty-five children with VPT were found, of whom 20 had NF.Hydrocephalus was found in 4 children with NF (20% ) and in 5 without NF (33.3% ). In 6 ofthechildren, ventricular dilatation with signs of acute increased intracranial pressure already existed at the time of diagnosis and the hydrocephalus was shunted at this time. In the other 3 children, all with NF,the hydrocephalus resulted from slowly developing aqueductal stenosis, leading in 2 to severe visual acuity deterioration. The results suggest that in children with VPT and NF, hydrocephalus, and especially hydrocephalus resulting from aqueductal stenosis, is more frequent than in the general population of NF patients, and less frequent than in VPT patients without NF. The possibility of the indolent development of hydrocephalus should be borne in mind while following children with NF. The optic nerve, when already involved with a glioma, is more vulnerable to increased pressure. Thus, in children with VPT and NF, any ventricular dilatation should lead to a consideration of early shunting.     

Multimodal molecular 3D imaging for the tumoral volumetric distribution assessment of folate-based biosensors

The aim of this study was to characterize the in vivo volumetric distribution of three folate-based biosensors by different imaging modalities (X-ray, fluorescence, Cerenkov luminescence, and radioisotopic imaging) through the development of a tridimensional image reconstruction algorithm. The preclinical and multimodal Xtreme imaging system, with a Multimodal Animal Rotation System (MARS), was used to acquire bidimensional images, which were processed to obtain the tridimensional reconstruction. Images of mice at different times (biosensor distribution) were simultaneously obtained from the four imaging modalities. The filtered back projection and inverse Radon transformation were used as main image-processing techniques. The algorithm developed in Matlab was able to calculate the volumetric profiles of ^99mTc-Folate-Bombesin (radioisotopic image), ¹⁷⁷Lu-Folate-Bombesin (Cerenkov image), and FolateRSense? 680 (fluorescence image) in tumors and kidneys of mice, and no significant differences were detected in the volumetric quantifications among measurement techniques. The imaging tridimensional reconstruction algorithm can be easily extrapolated to different 2D acquisition-type images. This characteristic flexibility of the algorithm developed in this study is a remarkable advantage in comparison to similar reconstruction methods.