Mice selectively bred for High and Low fear behavior show differences in the number of pMAPK (p44/42 ERK) expressing neurons in lateral amygdala following Pavlovian fear conditioning

Individual variability in the acquisition, consolidation and extinction of conditioned fear potentially contributes to the development of fear pathology including posttraumatic stress disorder (PTSD). Pavlovian fear conditioning is a key tool for the study of fundamental aspects of fear learning. Here, we used a selected mouse line of High and Low Pavlovian conditioned fear created from an advanced intercrossed line (AIL) in order to begin to identify the cellular basis of phenotypic divergence in Pavlovian fear conditioning. We investigated whether phosphorylated MAPK (p44/42 ERK/MAPK), a protein kinase required in the amygdala for the acquisition and consolidation of Pavlovian fear memory, is differentially expressed following Pavlovian fear learning in the High and Low fear lines. We found that following Pavlovian auditory fear conditioning, High and Low line mice differ in the number of pMAPK-expressing neurons in the dorsal sub nucleus of the lateral amygdala (LAd). In contrast, this difference was not detected in the ventral medial (LAvm) or ventral lateral (LAvl) amygdala sub nuclei or in control animals. We propose that this apparent increase in plasticity at a known locus of fear memory acquisition and consolidation relates to intrinsic differences between the two fear phenotypes. These data provide important insights into the micronetwork mechanisms encoding phenotypic differences in fear. Understanding the circuit level cellular and molecular mechanisms that underlie individual variability in fear learning is critical for the development of effective treatment of fear-related illnesses such as PTSD.

Expression Profiles of Mitochondrial Genes in the Frontal Cortex and the Caudate Nucleus of Developing Humans and Mice Selectively Bred for High and Low Fear

A growing body of evidence suggests that mitochondrial function may be important in brain development and psychiatric disorders. However, detailed expression profiles of those genes in human brain development and fear-related behavior remain unclear. Using microarray data available from the public domain and the Gene Ontology analysis, we identified the genes and the functional categories associated with chronological age in the prefrontal cortex (PFC) and the caudate nucleus (CN) of psychiatrically normal humans ranging in age from birth to 50 years. Among those, we found that a substantial number of genes in the PFC (115) and the CN (117) are associated with the GO term: mitochondrion (FDR qv <0.05). A greater number of the genes in the PFC (91%) than the genes in the CN (62%) showed a linear increase in expression during postnatal development. Using quantitative PCR, we validated the developmental expression pattern of four genes including monoamine oxidase B (MAOB), NADH dehydrogenase flavoprotein (NDUFV1), mitochondrial uncoupling protein 5 (SLC25A14) and tubulin beta-3 chain (TUBB3). In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in the PFC were comparable to the pattern observed in humans (p<0.05). However, mice selectively bred for high fear did not exhibit normal developmental changes of MAOB and TUBB3. These findings suggest that the genes associated with mitochondrial function in the PFC play a significant role in brain development and fear-related behavior.

Expression pattern of the cannabinoid receptor genes in the frontal cortex of mood disorder patients and mice selectively bred for high and low fear

Although the endocannabinoid system (ECS) has been implicated in brain development and various psychiatric disorders, precise mechanisms of the ECS on mood and anxiety disorders remain unclear. Here, we have investigated developmental and disease-related expression pattern of the cannabinoid receptor 1 (CB1) and the cannabinoid receptor 2 (CB2) genes in the dorsolateral prefrontal cortex (PFC) of humans. Using mice selectively bred for high and low fear, we further investigated potential association between fear memory and the cannabinoid receptor expression in the brain. The CB1, not the CB2, mRNA levels in the PFC gradually decrease during postnatal development ranging in age from birth to 50 years (r 2 > 0.6 & adj. p < 0.05). The CB1 levels in the PFC of major depression patients were higher when compared to the age-matched controls (adj. p < 0.05). In mice, the CB1, not the CB2, levels in the PFC were positively correlated with freezing behavior in classical fear conditioning (p < 0.05). These results suggest that the CB1 in the PFC may play a significant role in regulating mood and anxiety symptoms. Our study demonstrates the advantage of utilizing data from postmortem brain tissue and a mouse model of fear to enhance our understanding of the role of the cannabinoid receptors in mood and anxiety disorders

High energy states of gold and their importance in electrocatalytic processes at surfaces and interfaces

The ability of metals to store or trap considerable amounts of energy, and thus exist in a non-equilibrium or metastable state, is very well known in metallurgy; however, such behaviour, which is intimately connected with the defect character of metals, has been largely ignored in noble metal surface electrochemistry. Techniques for generating unusually high energy surface states for gold, and the unusual voltammetric responses of such states, are outlined. The surprisingly high (and complex) electrocatalytic activity of gold in aqueous media is attributed to the presence of a range of such non-equilibrium states as the vital entities at active sites on conventional gold surfaces. The possible relevance of these ideas to account for the remarkable catalytic activity of oxide-supported gold microparticles is briefly outlined.

Gold nanospikes formed through a simple electrochemical route with high electrocatalytic and surface enhanced Raman scattering activity

We demonstrate a simple electrochemical route to produce uniformly sized gold nanospikes without the need for a capping agent or prior modification of the electrode surface, which are predominantly oriented in the {111} crystal plane and exhibit promising electrocatalytic and SERS properties.

Hybrid antibacterial fabrics with extremely high aspect ratio Ag/AgTCNQ nanowires

This study reports the synthesis of extremely high aspect ratios (>3000) organic semiconductor nanowires of Ag–tetracyanoquinodimethane (AgTCNQ) on the surface of a flexible Ag fabric for the first time. These one-dimensional (1D) hybrid Ag/AgTCNQ nanostructures are attained by a facile, solution-based spontaneous reaction involving immersion of Ag fabrics in an acetonitrile solution of TCNQ. Further, it is discovered that these AgTCNQ nanowires show outstanding antibacterial performance against both Gram negative and Gram positive bacteria, which outperforms that of pristine Ag. The outcomes of this study also reflect upon a fundamentally important aspect that the antimicrobial performance of Ag-based nanomaterials may not necessarily be solely due to the amount of Ag+ ions leached from these nanomaterials, but that the nanomaterial itself may also play a direct role in the antimicrobial action. Notably, the applications of metal-organic semiconducting charge transfer complexes of metal-7,7,8,8-tetracyanoquinodimethane (TCNQ) have been predominantly restricted to electronic applications, except from our recent reports on their (photo)catalytic potential and the current case on antimicrobial prospects. This report on growth of these metal-TCNQ complexes on a fabric not only widens the window of these interesting materials for new biological applications, it also opens the possibilities for developing large-area flexible electronic devices by growing a range of metal-organic semiconducting materials directly on a fabric surface.

Validity of dietary questionnaires in Sri Lankan adults and the association of dietary intake with obesity

Traditionally, infectious diseases and under-nutrition have been considered major health problems in Sri Lanka with little attention paid to obesity and associated non-communicable diseases (NCDs). However, the recent Sri Lanka Diabetes and Cardiovascular Study (SLDCS) reported the epidemic level of obesity, diabetes and metabolic syndrome. Moreover, obesity-associated NCDs is the leading cause of death in Sri Lanka and there is an exponential increase in hospitalization due to NCDs adversely affecting the development of the country. Despite Sri Lanka having a very high prevalence of NCDs and associated mortality, little is known about the causative factors for this burden. It is widely believed that the global NCD epidemic is associated with recent lifestyle changes, especially dietary factors. In the absence of sufficient data on dietary habits in Sri Lanka, successful interventions to manage these serious health issues would not be possible. In view of the current situation the dietary survey was undertaken to assess the intakes of energy, macro-nutrients and selected other nutrients with respect to socio demographic characteristics and the nutritional status of Sri Lankan adults especially focusing on obesity. Another aim of this study was to develop and validate a culturally specific food frequency questionnaire (FFQ) to assess dietary risk factors of NCDs in Sri Lankan adults. Data were collected from a subset of the national SLDCS using a multi-stage, stratified, random sampling procedure (n=500). However, data collection in the SLDCS was affected by the prevailing civil war which resulted in no data being collected from Northern and Eastern provinces. To obtain a nationally representative sample, additional subjects (n=100) were later recruited from the two provinces using similar selection criteria. Ethical Approval for this study was obtained from the Ethical Review Committee, Faculty of Medicine, University of Colombo, Sri Lanka and informed consent was obtained from the subjects before data were collected. Dietary data were obtained using the 24-h Dietary Recall (24HDR) method. Subjects were asked to recall all foods and beverages, consumed over the previous 24-hour period. Respondents were probed for the types of foods and food preparation methods. For the FFQ validation study, a 7-day weight diet record (7-d WDR) was used as the reference method. All foods recorded in the 24 HDR were converted into grams and then intake of energy and nutrients were analysed using NutriSurvey 2007 (EBISpro, Germany) which was modified for Sri Lankan food recipes. Socio-demographic details and body weight perception were collected from interviewer-administrated questionnaire. BMI was calculated and overweight (BMI ≥23 kg.m-2), obesity (BMI ≥25 kg.m-2) and abdominal obesity (Men: WC ≥ 90 cm; Women: WC ≥ 80 cm) were categorized according to Asia-pacific anthropometric cut-offs. The SPSS v. 16 for Windows and Minitab v10 were used for statistical analysis purposes. From a total of 600 eligible subjects, 491 (81.8%) participated of whom 34.5% (n=169) were males. Subjects were well distributed among different socio-economic parameters. A total of 312 different food items were recorded and nutritionists grouped similar food items which resulted in a total of 178 items. After performing step-wise multiple regression, 93 foods explained 90% of the variance for total energy intake, carbohydrates, protein, total fat and dietary fibre. Finally, 90 food items and 12 photographs were selected. Seventy-seven subjects completed (response rate = 65%) the FFQ and 7-day WDR. Estimated mean energy intake (SD) from FFQ (1794±398 kcal) and 7DWR (1698±333 kcal, P<0.001) was significantly different due to a significant overestimation of carbohydrate (~10 g/d, P<0.001) and to some extent fat (~5 g/d, NS). Significant positive correlations were found between the FFQ and 7DWR for energy (r = 0.39), carbohydrate (r = 0.47), protein (r = 0.26), fat (r =0.17) and dietary fiber (r = 0.32). Bland-Altman graphs indicated fairly good agreement between methods with no relationship between bias and average intake of each nutrient examined. The findings from the nutrition survey showed on average, Sri Lankan adults consumed over 14 portions of starch/d; moreover, males consumed 5 more portions of cereal than females. Sri Lankan adults consumed on average 3.56 portions of added sugars/d. Moreover, mean daily intake of fruit (0.43) and vegetable (1.73) portions was well below minimum dietary recommendations (fruits 2 portions/d; vegetables 3 portions/d). The total fruit and vegetable intake was 2.16 portions/d. Daily consumption of meat or alternatives was 1.75 portions and the sum of meat and pulses was 2.78 portions/d. Starchy foods were consumed by all participants and over 88% met the minimum daily recommendations. Importantly, nearly 70% of adults exceeded the maximum daily recommendation for starch (11portions/d) and a considerable proportion consumed larger numbers of starch servings daily, particularly men. More than 12% of men consumed over 25 starch servings/d. In contrast to their starch consumption, participants reported very low intakes of other food groups. Only 11.6%, 2.1% and 3.5% of adults consumed the minimum daily recommended servings of vegetables, fruits, and fruits and vegetables combined, respectively. Six out of ten adult Sri Lankans sampled did not consume any fruits. Milk and dairy consumption was extremely low; over a third of the population did not consume any dairy products and less than 1% of adults consumed 2 portions of dairy/d. A quarter of Sri Lankans did not report consumption of meat and pulses. Regarding protein consumption, 36.2% attained the minimum Sri Lankan recommendation for protein; and significantly more men than women achieved the recommendation of ≥3 servings of meat or alternatives daily (men 42.6%, women 32.8%; P<0.05). Over 70% of energy was derived from carbohydrates (Male:72.8±6.4%, Female:73.9±6.7%), followed by fat (Male:19.9±6.1%, Female:18.5±5.7%) and proteins (Male:10.6±2.1%, Female:10.9±5.6%). The average intake of dietary fiber was 21.3 g/day and 16.3 g/day for males and females, respectively. There was a significant difference in nutritional intake related to ethnicities, areas of residence, education levels and BMI categories. Similarly, dietary diversity was significantly associated with several socio-economic parameters among Sri Lankan adults. Adults with BMI ≥25 kg.m-2 and abdominally obese Sri Lankan adults had the highest diet diversity values. Age-adjusted prevalence (95% confidence interval) of overweight, obesity, and abdominal obesity among Sri Lankan adults were 17.1% (13.8-20.7), 28.8% (24.8-33.1), and 30.8% (26.8-35.2), respectively. Men, compared with women, were less overweight, 14.2% (9.4-20.5) versus 18.5% (14.4-23.3), P = 0.03, less obese, 21.0% (14.9-27.7) versus 32.7% (27.6-38.2), P < .05; and less abdominally obese, 11.9% (7.4-17.8) versus 40.6% (35.1-46.2), P < .05. Although, prevalence of obesity has reached to epidemic level body weight misperception was common among Sri Lankan adults. Two-thirds of overweight males and 44.7% of females considered themselves as in "about right weight". Over one third of both male and female obese subjects perceived themselves as "about right weight" or "underweight". Nearly 32% of centrally obese men and women perceived that their waist circumference is about right. People who perceived overweight or very overweight (n = 154) only 63.6% tried to lose their body weight (n = 98), and quarter of adults seek advices from professionals (n = 39). A number of important conclusions can be drawn from this research project. Firstly, the newly developed FFQ is an acceptable tool for assessing the nutrient intake of Sri Lankans and will assist proper categorization of individuals by dietary exposure. Secondly, a substantial proportion of the Sri Lankan population does not consume a varied and balanced diet, which is suggestive of a close association between the nutrition-related NCDs in the country and unhealthy eating habits. Moreover, dietary diversity is positively associated with several socio-demographic characteristics and obesity among Sri Lankan adults. Lastly, although obesity is a major health issue among Sri Lankan adults, body weight misperception was common among underweight, healthy weight, overweight, and obese adults in Sri Lanka. Over 2/3 of overweight and 1/3 of obese Sri Lankan adults believe that they are in "right weight" or "under-weight" categories.

High seroprevalence of antibodies to varicella zoster virus in adult women in a tropical climate

OBJECTIVES To determine whether the seroprevalence of antibodies to varicella zoster virus (VZV) in adults is similar to that reported in tropical populations elsewhere. METHODS We measured the seroprevalence of VZV IgG antibodies, using an enzyme immunoassay (EIA) in women attending an antenatal clinic in an urban centre in tropical Australia. RESULTS The overall seroprevalence of VZV antibodies in 298 women was 92% (95% CI 88-95), with no difference between women who spent their childhoods in the tropics and colleagues. None of the overseas-born women was seronegative. CONCLUSION The seroprevalence of VZV antibodies in this tropical population in Australia is as high as that reported from temperate regions, suggesting that social and cultural factors and population mobility are more important determinants of age distribution of VZV immunity than tropical climate.

Identification of radiological alveolar pneumonia in children with high rates of hospitalized respiratory infections : Comparison of WHO-defined and pediatric pulmonologist diagnosis in the clinical context

Background A reliable standardized diagnosis of pneumonia in children has long been difficult to achieve. Clinical and radiological criteria have been developed by the World Health Organization (WHO), however, their generalizability to different populations is uncertain. We evaluated WHO defined chest radiograph (CXRs) confirmed alveolar pneumonia in the clinical context in Central Australian Aboriginal children, a high risk population, hospitalized with acute lower respiratory illness (ALRI). Methods CXRs in children (aged 1-60 months) hospitalized and treated with intravenous antibiotics for ALRI and enrolled in a randomized controlled trial (RCT) of Vitamin A/Zinc supplementation were matched with data collected during a population-based study of WHO-defined primary endpoint pneumonia (WHO-EPC). These CXRs were reread by a pediatric pulmonologist (PP) and classified as pneumonia-PP when alveolar changes were present. Sensitivities, specificities, positive and negative predictive values (PPV, NPV) for clinical presentations were compared between WHO-EPC and pneumonia-PP. Results Of the 147 episodes of hospitalized ALRI, WHO-EPC was significantly less commonly diagnosed in 40 (27.2%) compared to pneumonia-PP (difference 20.4%, 95% CI 9.6-31.2, P < 0.001). Clinical signs on admission were poor predictors for both pneumonia-PP and WHO-EPC; the sensitivities of clinical signs ranged from a high of 45% for tachypnea to 5% for fever + tachypnea + chest-indrawing. The PPV range was 40-20%, respectively. Higher PPVs were observed against the pediatric pulmonologist's diagnosis compared to WHO-EPC. Conclusions WHO-EPC underestimates alveolar consolidation in a clinical context. Its use in clinical practice or in research designed to inform clinical management in this population should be avoided. Pediatr Pulmonol. 2012; 47:386-392. (C) 2011 Wiley Periodicals, Inc.

Comparing outcomes of a school based injury prevention intervention for low-medium risk adolescents with high-risk adoelscents

High-risk adolescents are shown to jeopardise their future social and health functioning as well as placing themselves and others at immediate risk of harm. The challenge of “reaching” high-risk adolescents, who are often marginalised, is considerable. There is a positive relationship between age and risk taking behaviors during adolescence. This study examines outcomes (alcohol use, transport risk behaviors, violence) of a school based intervention (SPIY) by comparing low-medium risk adolescents with high-risk adolescents over a six month period.

A phase II study of the modulation of 5-fluorouracil and folinic acid with high-dose infusional hydroxyurea in metastatic colorectal carcinoma

Background: Hydroxyurea (HU), an inhibitor of ribonucleotide reductase, may potentiate the activity of 5-fluorouracil (5-FU) and folinic acid (FA) by reducing the deoxyribonucleotide pool available for DNA synthesis and repair. However as HU may inhibit the formation of 5-fluoro-2-deoxyuridine-5- monophosphate (FdUMP), one of the principal active metabolites of 5-FU, the scheduling of HU may be critical. In vitro experiments suggest that administration of HU following 5-FU, maintaining the concentration in the region of I mM for six or more hours, significantly enhances the efficacy of 5-FU. Patients and methods: 5-FU/FA was given as follows: days 1 and 2 - FA 250 mg/m 2 (max. 350 mg) over two hours followed by 5-FU 400 mg/m 2 by intravenous bolus (ivb) over 15 minutes and subsequently 5-FU 400 mg/m 2 infusion (ivi) over 22 hours. HU was administered on day 3 immediately after the 5-FU with 3 g ivb over 15 minutes followed by 12 g ivi over 12 hours. Results: Thirty patients were entered into the study. Median survival was nine months (range 1-51 + months). There were eight partial responses (28%, 95% CI: 13%-47%). The median duration of response was 6.5 (range 4-9 months). Grade 3-4 toxicities included neutropenia (grade 3 in eight patients and grade 4 in five), anaemia (grade 3 in one patient) and diarrhoea (grade 3 in two patients). Neutropenia was associated with pyrexia in two patients. Phlebitis at the infusion site occurred in five patients. The treatment was complicated by pulmonary embolism in one patient and deep venous thrombosis in another. Conclusion: HU administered in this schedule is well tolerated. Based on these results and those of other phase II studies, a randomised phase III study of 5-FU, FA and HU versus 5-FU and FA using the standard de Gramont schedule is recommended.

Submission to the inquiry into the high level of involvement of Indigenous juveniles and young adults in the criminal justice system

Introduction • The Australian Institute of Criminology (AIC) is Australia's national research and knowledge centre on crime and justice. • The Institute seeks to promote justice and reduce crime by undertaking and communicating evidence-based research to inform policy and practice. • The AIC is governed by the Criminology Research Act and has been in operation since 1973. • The AIC is pleased to have the opportunity to contribute to the Committee's Inquiry into the high level of involvement of Indigenous juveniles and young adults in the criminal justice system. • There is a great deal of evidence to demonstrate that Indigenous young people are significantly over-represented at every stage of the criminal justice system in Australia.

Lesion selection by melanoma high-risk consumers during skin self-examination using mobile teledermoscopy

Mobile teledermatoscopy (MTD) for the early detection of skin cancer uses smartphones with dermatoscope attachments to magnify, capture, and transfer images remotely.1 Using the asymmetry–color variation (AC) rule, consumers achieve dermoscopy sensitivity of 92.9% to 94.0% and specificity of 62.0% to 64.2% for melanoma.2 This pilot randomized trial assessed lesions of concern selected by consumers at high risk of melanoma using MTD plus the AC rule (intervention, n = 10) or the AC rule alone (control, n = 12) during skin self-examination (SSE). Also measured were lesion location patterns, lesions overlooked by participants, provisional clinical diagnoses, likelihood of malignant tumor, and participant pressure to excise lesions.