Social influences on alcohol consumption by black and white males

Thirty-two black and 32 white male normal drinkers participated in a beer taste test either simultaneously (co-action condition) with a heavy drinking black or white experimental accomplice or white the accomplice completed an art rating task (control observer condition). Subjects in the co-action condition drank significantly more beer (p < .001) than subjects in the control observer condition, regardless of their race or the race of the accomplice. Subjects' post-experimental questionnaire answers indicated they did not perceive themselves to be in competition with the accomplice. The mechanism underlying the robust co-action facilitation effect on drinking, now demonstrated in several studies and extended to black males in the present study, remains unexplained.     

Radiation-guided drug delivery systems

A primary limiting factor for cancer treatment is normal tissue toxicity. Targeted cancer treatment can potentially maximize cancer cure and minimize normal tissue toxicity. Physical energy can be used to activate inert oncologic drugs. X-rays have an advantage over other forms of physical energy because tissue penetration and precise localization can be achieved. Radiation can be used to control drug delivery through radiation-inducible gene therapy. Radiation-guided drug delivery systems involve the targeting of immunoconjugates to radiation-inducible neoantigens induced by irradiation of neoplasms. Magnetic fields can compliment these technologies by drawing magnetic particles containing oncologic drugs toward an externally applied magnetic field. The field of targeted drug delivery by use of external radiation fields will ultimately bring new delivery systems into clinical trials. This review highlights radiation-guided cancer drug delivery systems, at preclinical and clinical stages of development, to tumors and tumor blood vessels.     

Morphology of human Fallopian tubes after infection with Mycoplasma genitalium and Mycoplasma hominis--in vitro organ culture study

BACKGROUND: Female infertility can be caused by scarring and occlusion of the Fallopian tubes. Sexually transmitted bacteria can damage the delicate epithelial layer of human Fallopian tubes (HFT). Genital mycoplasmas are associated with human reproductive failure. Yet, there is not enough evidence that mycoplasmas can cause tubal factor infertility. We analysed the effects of infections with Mycoplasma hominis and Mycoplasma genitalium on the HFT epithelium and compared them with the effects of infections with genital pathogens: Chlamydia trachomatis and Neisseria gonorrhoeae. METHODS: We used an in vitro model in which pieces of normal HFT were infected with different bacteria, and the outcome of the infections was analysed by scanning electron microscopy (SEM) and confocal microscopy. RESULTS: The presence of M. hominis did not cause any morphological changes of the epithelium of HFT. Noticeable changes in the morphology of the ciliated cells were observed in M. genitalium-infected tissue. Five days post-infection, the cilia were abnormally swollen and some of the ciliated cells fell off the epithelium. These effects could be inhibited by pre-incubation of M. genitalium with antibody directed against the C-terminal part of the adhesion protein MgPa before infection of HFT organ culture. CONCLUSION: We have shown that the presence of M. genitalium, but not M. hominis, in the HFT organ culture affected the epithelium and resulted in cilia damage. The effect of infection with M. genitalium on the HFT was, however, very moderate when compared with the extensive damage of the epithelium caused by N. gonorrhoeae or C. trachomatis.     

Coding variants identified in patients with diabetes alter PICK1 BAR domain function in insulin granule biogenesis

Bin/amphiphysin/Rvs (BAR) domains are positively charged crescent-shaped modules that mediate curvature of negatively charged lipid membranes during remodeling processes. The BAR domain proteins PICK1, ICA69, and the arfaptins have recently been demonstrated to coordinate the budding and formation of immature secretory granules (ISGs) at the trans-Golgi network. Here, we identify 4 coding variants in the PICK1 gene from a whole-exome screening of Danish patients with diabetes that each involve a change in positively charged residues in the PICK1 BAR domain. All 4 coding variants failed to rescue insulin content in INS-1E cells upon knock down of endogenous PICK1. Moreover, 2 variants showed dominant-negative properties. In vitro assays addressing BAR domain function suggested that the coding variants compromised BAR domain function but increased the capacity to cause fission of liposomes. Live confocal microscopy and super-resolution microscopy further revealed that PICK1 resides transiently on ISGs before egress via vesicular budding events. Interestingly, this egress of PICK1 was accelerated in the coding variants. We propose that PICK1 assists in or complements the removal of excess membrane and generic membrane trafficking proteins, and possibly also insulin, from ISGs during the maturation process; and that the coding variants may cause premature budding, possibly explaining their dominant-negative function.     

‘Avoidance Preening’, Displacement Behavior and Co-Dependency in Professional Team Sport: When Wants Become More Important Than Needs

An athlete’s body plays an important role in their performance and well-being. However, game-relevant skills are better determinants of success, compared with physical fitness, in technically-driven team sports. In the professional era, over utilization of resources, in pursuit of physical optimization, can detract from time spent on priorities. Athletes’ non-strategic, time-demanding focus on physical preparation/treatments resembles avian ‘avoidance preening’, whereby stressful situations trigger birds to excessively preen in place of more productive activities. The purpose of this commentary is to explore the behaviors of resource-rich professional teams and the roles of staff dedicated to optimizing physical performance, including circumstances that foster avoidance behavior and create the potential for practitioners to encourage co-dependent relationships with athletes. To cultivate healthy/productive environments, the following is recommended: I) recognition of non-productive avoidance behaviors; II) eschewing unjustified, fear promoting, pathoanatomical language; III) fostering collaborative approaches; IV) encouraging utilization of psychology services; V) recognizing that optimal physical function and feeling good is rarely the primary goal in professional team sports.Level of Evidence5     

Prevalence and correlates of common mental disorders among children and adolescents in Blantyre-Urban,Malawi

BackgroundThe high global prevalence of mental disorders justifies the need to quantify their burden in the sub-Saharan Africa where there is a dearth of information. These mental disorders are linked to different socio-demographic factors.ObjectiveTo determine the prevalence of, and factors associated with mental disorders among children and adolescents in Blantyre City, Malawi.MethodsChildren and adolescents aged 6 to 17 years were interviewed to determine their socio-demographic characteristics and assess their mental health status using the Strengths and Difficulties Questionnaire (SDQ) and Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Associations between mental disorders and socio-demographic characteristics were tested using Chi-square and logistic regression analysis.ResultsThe prevalence of symptoms of psychopathology on the SDQ was 7.3% (95%CI 4.8–10.5%) while for the K-SADS was 5.9% (95% CI 3.7%–8.9%). The prevalence of mental disorders across the age ranges of 6 to 12 years and 13 to 17 years was 5.4% and 7.9 % respectively. Males had a higher prevalence (7.1%) compared to females (4.7%). Conduct disorder was most prevalent (3.4%), followed by either type of ADHD-Attention Deficit Hyperactive Disorders (2.0%). Having a single parent (p<0.001), staying with a non-biological guardian (p<0.030), engaging in paid work (p<0.039), not attending school (p<0.019) and having teacher difficulties(p<0.028) were positively associated with a mental disorder.ConclusionThe socio-demographic factors associated with the risk of developing mental disorders may be important targets for mental health intervention programs.     

Diagnostic Applications of Ultrasmall Superparamagnetic Particles of Iron Oxide for Imaging Myocardial and Vascular Inflammation

Cardiac magnetic resonance (CMR) is at the forefront of noninvasive methods for the assessment of myocardial anatomy, function, and most importantly tissue characterization. The role of CMR is becoming even more significant with an increasing recognition that inflammation plays a major role for various myocardial diseases such as myocardial infarction, myocarditis, and takotsubo cardiomyopathy. Ultrasmall superparamagnetic particles of iron oxide (USPIO) are nanoparticles that are taken up by monocytes and macrophages accumulating at sites of inflammation. In this context, USPIO-enhanced CMR can provide valuable additional information regarding the cellular inflammatory component of myocardial and vascular diseases. Here, we will review the recent diagnostic applications of USPIO in terms of imaging myocardial and vascular inflammation, and highlight some of their future potential.     

Nicotine effects on learning in zebrafish: the role of dopaminergic systems

Rationale

Nicotine improves cognitive function in a number of animal models including rats, mice, monkeys, and recently, zebrafish. The zebrafish model allows higher throughput and ease in discovering mechanisms of cognitive improvement.

Materials and methods

To further characterize the neural bases of nicotine effects on learning in zebrafish, we determined changes in dopaminergic systems that accompany nicotine-enhanced learning.

Results

Nicotine improved learning and increased brain levels of dihydroxyphenylacetic acid (DOPAC), the primary dopamine metabolite. There was a significant correlation between choice accuracy and DOPAC levels. The nicotinic antagonist mecamylamine blocked the nicotine-induced increase in DOPAC concentrations, in line with our previous finding that mecamylamine reversed nicotine-induced learning improvement.

Conclusions

Dopamine systems are related to learning in zebrafish; nicotine exposure increases both learning rates and DOPAC levels; and nicotinic antagonist administration blocks nicotine-induced rises in DOPAC concentrations. Rapid cognitive assessment of drugs with zebrafish could serve as a useful screening tool for the development of new therapeutics for cognitive dysfunction.     

Zebrafish provide a sensitive model of persisting neurobehavioral effects of developmental chlorpyrifos exposure: Comparison with nicotine and pilocarpine effects and relationship to dopamine deficits

Chlorpyrifos (CPF) an organophosphate pesticide causes persisting behavioral dysfunction in rat models when exposure is during early development. In earlier work zebrafish were used as a complementary model to study mechanisms of CPF-induced neurotoxicity induced during early development. We found that developmental (first five days after fertilization) chlorpyrifos exposure significantly impaired learning in zebrafish. However, this testing was time and labor intensive. In the current study we tested the hypothesis that persisting effects of developmental chlorpyrifos could be detected with a brief automated assessment of startle response and that this behavioral index could be used to help determine the neurobehavioral mechanisms for persisting CPF effects. The swimming activity of adult zebrafish was assessed by a computerized video-tracking device after a sudden tap to the test arena. Ten consecutive trials (1/min) were run to determine startle response and its habituation. Additionally, habituation recovery trials were run at 8, 32 and 128 min after the end of the initial trial set. CPF-exposed fish showed a significantly (p < 0.025) greater overall startle response during the 10-trial session compared to controls (group sizes: Control N = 40, CPF N = 24). During the initial recovery period (8 min) CPF-exposed fish showed a significantly (p < 0.01) greater startle response compared to controls. To elucidate the contributions of nicotinic and muscarinic acetylcholine receptors to developmental CPF-mediated effects, the effects of developmental nicotine and pilocarpine exposure throughout the first five days after fertilization were determined. Developmental nicotine and pilocarpine exposure significantly increased startle response, though nicotine (group sizes: Control N = 32, 15 mM N = 12, 25 mM N = 20) was much more potent than pilocarpine (group sizes: Control N = 20, 100 µM N = 16, 1000 µM N = 12). Neither was as potent as CPF for developmental exposure increasing startle response in adulthood. Lastly, developmental CPF exposure decreased dopamine and serotonin levels and increased transmitter turnover in developing zebrafish larvae (N = 4 batches of 50 embryos/treatment). Only the decline in dopamine concentrations persisted into adulthood (group sizes: Control N = 14, CPF N = 13). This study shows that a quick automated test of startle can detect persisting neurobehavioral impairments caused by developmental exposure to CPF. This may be helpful in screening for persisting neurobehavioral defects from a variety of toxicants.     

Metallothionein in the central nervous system: Roles in protection, regeneration and cognition

Metallothionein (MT) is an enigmatic protein, and its physiological role remains a matter of intense study and debate 50 years after its discovery. This is particularly true of its function in the central nervous system (CNS), where the challenge remains to link its known biochemical properties of metal binding and free radical scavenging to the intricate workings of brain. In this compilation of four reports, first delivered at the 11th International Neurotoxicology Association (INA-11) Meeting, June 2007, the authors present the work of their laboratories, each of which gives an important insight into the actions of MT in the brain. What emerges is that MT has the potential to contribute to a variety of processes, including neuroprotection, regeneration, and even cognitive functions. In this article, the properties and CNS expression of MT are briefly reviewed before Dr Hidalgo describes his pioneering work using transgenic models of MT expression to demonstrate how this protein plays a major role in the defence of the CNS against neurodegenerative disorders and other CNS injuries. His group's work leads to two further questions, what are the mechanisms at the cellular level by which MT acts, and does this protein influence higher order issues of architecture and cognition? These topics are addressed in the second and third sections of this review by Dr West, and Dr Levin and Dr Eddins, respectively. Finally, Dr Aschner examines the ability of MT to protect against a specific toxicant, methylmercury, in the CNS.