Elevated visual dependency in young adults after chemotherapy in childhood

Chemotherapy in childhood can result in long-term neurophysiological side-effects, which could extend to visual processing, specifically the degree to which a person relies on vision to determine vertical and horizontal (visual dependency). We investigated whether adults treated with chemotherapy in childhood experience elevated visual dependency compared to controls and whether any difference is associated with the age at which subjects were treated. Visual dependency was measured in 23 subjects (mean age 25.3 years) treated in childhood with chemotherapy (CTS) for malignant, solid, non-CNS tumors. We also stratified CTS into two groups: those treated before 12 years of age and those treated from 12 years of age and older. Results were compared to 25 healthy, age-matched controls. The subjective visual horizontal (SVH) and vertical (SVV) orientations was recorded by having subjects position an illuminated rod to their perceived horizontal and vertical with and without a surrounding frame tilted clockwise and counter-clockwise 20° from vertical. There was no significant difference in rod accuracy between any CTS groups and controls without a frame. However, when assessing visual dependency using a frame, CTS in general (p = 0.006) and especially CTS treated before 12 years of age (p = 0.001) tilted the rod significantly further in the direction of the frame compared to controls. Our findings suggest that chemotherapy treatment before 12 years of age is associated with elevated visual dependency compared to controls, implying a visual bias during spatial activities. Clinicians should be aware of symptoms such as visual vertigo in adults treated with chemotherapy in childhood

Contribution of limbic norepinephrine to cannabinoid-induced aversion

RATIONALE: The cannabinoid system has risen to the forefront in the development of novel treatments for a number of pathophysiological processes. However, significant side effects have been observed in clinical trials raising concerns regarding the potential clinical utility of cannabinoid-based agents. Understanding the neural circuits and neurochemical substrates impacted by cannabinoids will provide a better means of gaging their actions within the central nervous system that may contribute to the expression of unwanted side effects. OBJECTIVES: In the present study, we investigated whether norepinephrine (NE) in the limbic forebrain is a critical determinant of cannabinoid receptor agonist-induced aversion and anxiety in rats. METHODS: An immunotoxin lesion approach was combined with behavioral analysis using a place conditioning paradigm and the elevated zero maze. RESULTS: Our results show that the non-selective CB1/CB2 receptor agonist, WIN 55,212-2, produced a significant place aversion in rats. Further, NE in the nucleus accumbens was critical for WIN 55,212-2-induced aversion but did not affect anxiety-like behaviors. Depletion of NE from the bed nucleus of the stria terminalis was ineffective in altering WIN 55,212-2-induced aversion and anxiety. CONCLUSIONS: These results indicate that limbic, specifically accumbal, NE is required for cannabinoid-induced aversion but is not essential to cannabinoid-induced anxiety.This works was supported by PHS grant DA 020129. Ana Franky Carvalho was supported by the Portuguese Foundation for Science and Technology (SFRH/BD/33236/2007)

Longitudinal Study of the Dynamics of Vaginal Microflora during Two Consecutive Menstrual Cycles

Although the vaginal microflora (VMF) has been well studied, information on the fluctuation of the different bacterial species throughout the menstrual cycle and the information on events preceding the presence of disturbed VMF is still very limited. Documenting the dynamics of the VMF during the menstrual cycle might provide better insights. In this study, we assessed the presence of different Lactobacillus species in relation to the BV associated species during the menstrual cycle, assessed the influence of the menstrual cycle on the different categories of vaginal microflora and assessed possible causes, such as menstruation and sexual intercourse, of VMF disturbance. To our knowledge, this is the first longitudinal study in which swabs and Gram stains were available for each day of two consecutive menstrual cycles, whereby 8 grades of VMF were distinguished by Gram stain analysis, and whereby the swabs were cultured every 7(th) day and identification of the bacterial isolates was carried out with a molecular technique.status: publishe

Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

Cannabis is the most commonly used illicit drug among pregnant women. Since the endocannabinoid system plays a crucial role in brain development, maternal exposure to cannabis derivatives might result in long-lasting neurobehavioral abnormalities in the exposed offspring. It is difficult to detect these effects, and their underlying neurobiological mechanisms, in clinical cohorts, because of their intrinsic methodological and interpretative issues. The present paper reviews relevant rodent studies examining the long-term behavioral consequences of exposure to cannabinoid compounds during pregnancy and/or lactation. Maternal exposure to even low doses of cannabinoid compounds results in atypical locomotor activity, cognitive impairments, altered emotional behavior, and enhanced sensitivity to drugs of abuse in the adult rodent offspring. Some of the observed behavioral abnormalities might be related to alterations in stress hormone levels induced by maternal cannabis exposure. There is increasing evidence from animal studies showing that cannabinoid drugs are neuroteratogens which induce enduring neurobehavioral abnormalities in the exposed offspring. Several preclinical findings reviewed in this paper are in line with clinical studies reporting hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis. Conversely, genetic, environmental and social factors could also influence the neurobiological effects of early cannabis exposure in humans

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field