Effect of sodium arsenite on peripheral lymphocytes in vitro: individual susceptibility among a population exposed to arsenic through the drinking water

Arsenic (As) contamination in ground water has affected more than 19 countries. Approximately 36 million people in the Bengal delta alone are exposed to this toxicant via drinking water (>50 microg/l) and are at potential health risk. Chronic ingestion of As via drinking water is associated with occurrence of skin lesions, cancer and other arsenic-induced diseases in West Bengal, India. An in vitro cytogenetic study was performed utilizing chromosomal aberrations (CA) in lymphocytes treated with sodium arsenite (0-5 microM) in six symptomatic (having arsenic-related skin lesions) individuals, six age- and sex-matched As-exposed asymptomatic (no arsenic-related skin lesions) individuals and six control individuals with similar socio-economic status residing in non-affected districts of West Bengal with no evidence of As exposure. The mean As content in nails and hair was 9.61 and 5.23 microg/g in symptomatic, 3.48 and 2.17 microg/g in asymptomatic and 0.42 and 0.33 microg/g in the control individuals, respectively. The main aim of our study was to determine whether genotoxic effects differed in the lymphocytes of the control (no exposure to arsenic), asymptomatic and symptomatic individuals after in vitro treatment with sodium arsenite. Although both the exposed groups had chronic exposure to As through the drinking water, individuals with skin lesions accumulated more As in their nails and hair and excreted less in urine (127.80 versus 164.15 microg/l). The results show that sodium arsenite induced a significantly higher percentage of aberrant cells in the lymphocytes of control individuals than in the lymphocytes of both the exposed groups. Within the two exposed groups As induced higher incidences of CA in the symptomatic than the asymptomatic individuals. These results suggest that asymptomatic individuals have relatively lower sensitivity and susceptibility to induction of genetic damage by As compared with the symptomatic individuals.     

PEDIATRIC OBSESSIVE-COMPULSIVE DISORDER: A GUIDE TO ASSESSMENT AND TREATMENT

Obsessive-compulsive disorder (OCD) is an anxiety disorder characterized by recurrent or persistent thoughts, impulses, or images that are experienced as intrusive or distressing (obsessions), and repetitive behaviors or mental acts (compulsions) often performed in response to an obsession. Recent epidemiological studies have found lifetime prevalence of pediatric OCD to be approximately 1-4% in the USA. OCD begins before the age of 18 years for as many as 80% of cases and follows a chronic, unremitting course. Due to the distressing, time-consuming, and debilitating nature of OCD, impairments in academic, social, and family functioning are often substantial. Despite the relatively high prevalence rate of OCD, dissemination about effective assessment and treatment has lagged. Increasing the awareness of OCD symptoms and its treatment among nurses and other health professionals will enhance identification of children presenting with unrecognized or untreated symptoms of OCD and will stimulate appropriate referrals for treatment to improve children's psychological functioning and overall quality of life. This paper reviews the nature, etiology, assessment, and treatment of OCD, highlighting clinical implications for nurses involved in mental health care.     

Cardiac Genetic Predisposition in Sudden Infant Death Syndrome

Background

Sudden infant death syndrome (SIDS) is a leading cause of postneonatal mortality. Genetic heart diseases (GHDs) underlie some cases of SIDS.

Social norms and obesity prevalence: From cohort to system dynamics models

Group‐level obesity can be seen as an emergent property of a complex system, consisting of feedback loops between individual body weight perception, individual weight‐related behaviour and group‐level social norms (a product of group‐level ‘normal' body mass index (BMI) and sociocultural ‘ideal' BMI). As overweight becomes normal, the norm might be counteracting health awareness in shaping individual weight‐related behaviour. System dynamics modelling facilitates understanding and simulating this system's emergent behaviour. We constructed six system dynamics models (SDMs) based on an expert‐informed causal loop diagram and data from six sociocultural groups (Dutch, Moroccan and South‐Asian Surinamese men and women). The SDMs served to explore the effect of three scenarios on group‐level BMI: ‘what if' weight‐related behaviour were driven by (1) health awareness, (2) norms or (3) a combination of the two. Median BMI decreased approximately 50% and 30% less in scenarios 2 and 3, respectively, than in 1. In men, the drop in BMI was approximately two times larger in scenario 1 versus 3, whereas in women, the drop was approximately equal in these scenarios. This study indicates that the overweight norm in men holds group‐level BMI close to overweight despite health awareness. Since norms are counteracting health awareness less strongly in women, other drivers of obesity must be more relevant.     

Imaging tri-fusion multimodality reporter gene expression in living subjects

Imaging reporter gene expression in living subjects with various imaging modalities is a rapidly accelerating area of research. Applications of these technologies to cancer research, gene therapy, and transgenic models are rapidly expanding. We report construction and testing of several triple fusion reporter genes compatible with bioluminescence, fluorescence and positron emission tomography (PET) imaging. A triple fusion reporter vector harboring a bioluminescence synthetic Renilla luciferase (hrl) reporter gene, a reporter gene encoding the monomeric red fluorescence protein (mrfp1), and a mutant herpes simplex virus type 1 sr39 thymidine kinase [HSV1-truncated sr39tk (ttk); a PET reporter gene] was found to preserve the most activity for each protein component and was therefore investigated in detail. After validating the activities of all three proteins encoded by the fusion gene in cell culture, we imaged living mice bearing 293T cells transiently expressing the hrl-mrfp-ttk vector by microPET and using a highly sensitive cooled charge-coupled device camera compatible with both bioluminescence and fluorescence imaging. A lentiviral vector carrying the triple fusion reporter gene was constructed and used to isolate stable expressers by fluorescence-activated cell sorting. These stable 293T cells were further used to show good correlation (R(2) approximately 0.74-0.85) of signal from each component by imaging tumor xenografts in living mice with all three modalities. Furthermore, metastases of a human melanoma cell line (A375M) stably expressing the triple fusion were imaged by microPET and optical technologies over a 40-50-day time period in living mice. Imaging of reporter gene expression from single cells to living animals with the help of a single tri-fusion reporter gene will have the potential to accelerate translational cancer research.     

Dysregulation of arousal and amygdala-prefrontal systems in paranoid schizophrenia

OBJECTIVE: The authors investigated impaired differentiation of limbic-prefrontal systems by autonomic arousal in schizophrenia. It was predicted that paranoid patients would be distinguished by a disjunction of hyperarousal but reduced amygdala and medial prefrontal activity relative to both healthy comparison subjects and patients with nonparanoid schizophrenia. METHOD: Pictures depicting facial expressions of fear were presented to 27 schizophrenia patients (13 paranoid, 14 nonparanoid) and 22 matched healthy comparison subjects in an implicit perception task to evoke limbic activity. Simultaneous functional magnetic resonance imaging and skin conductance arousal recordings were acquired during presentation of faces expressing fear or neutral emotion. Responses to fear stimuli were further examined by contrasting those that were associated with a skin conductance response ("with arousal") and those that were not ("without arousal"). RESULTS: In the comparison subjects, arousal dissociated amygdala/medial prefrontal ("visceral") networks and hippocampus/lateral prefrontal ("context") networks for fear perception. Excessive arousal responses were elicited in the schizophrenia subjects, but there was an associated reduction in amygdala/medial prefrontal activity. This disjunction was pronounced in paranoid patients relative to both healthy subjects and nonparanoid patients. Paranoid patients also showed a relatively greater prefrontal deficit for "without-arousal" responses. CONCLUSIONS: This is the first study to reveal a functional disconnection in autonomic and central systems for processing threat-related signals in patients with paranoid schizophrenia. Paranoid cognition may reflect an internally generated cycle of misattribution regarding incoming fear signals due to a breakdown in the regulation of these systems.