Cytochrome P450 (CYP) proteins compose a highly diverse superfamily found in all domains of life. These proteins are enzymes involved in metabolism of endogenous and exogenous compounds. In vertebrates, the CYP2 family is one of the largest, most diverse and plays an important role in mammalian drug metabolism. However, there are more than 20 vertebrate CYP2 subfamilies with uncertain evolution and fairly discrete subfamily composition within vertebrate classes, hindering extrapolation of knowledge across subfamilies. To better understand CYP2 diversity, a phylogenetic analysis of 196 CYP2 protein sequences from 16 species was performed using a maximum likelihood approach and Bayesian inference. The analyses included the CYP2 compliment from human, fugu, zebrafish, stickleback, medaka, cow, and dog genomes. Additional sequences were included from rabbit, marsupial, platypus, chicken, frog, and salmonid species. Three CYP2 sequences from the tunicate Ciona intestinalis were utilized as the outgroup. Results indicate a single ancestral vertebrate CYP2 gene and monophyly of all CYP2 subfamilies. Two subfamilies (CYP2R and CYP2U) pre-date vertebrate diversification, allowing direct comparison across vertebrate classes, while all other subfamilies originated during vertebrate diversification, often within specific vertebrate lineages. Analysis of site-specific evolution indicates that some substrate recognition sites (SRS) previously proposed for CYP genes do not have elevated rates of evolution, suggesting that these regions of the protein are not necessarily important in recognition of CYP2 substrates. Type II functional divergence analysis identified multiple residues in the active site of CYP2F, CYP2A, and CYP2B proteins that have undergone radical biochemical changes and may be functionally important.

OBJECTIVE

The aim is to present an overview of tumor markers other than CA-125 that have been proposed for use in the diagnosis of epithelial ovarian cancer and explore molecular studies which have been used to identify genomic and proteomic changes associated with this malignancy for possible future development of more sensitive tumor markers.

METHODS

A Medline search was conducted to review published articles from American and European studies from 1990 to 2010, related to tumor markers for ovarian cancer. Different methods such as genomic, proteomic and transcriptional profiling were used to identify new tumor markers for clinical use.

RESULTS

A few of the newer tumor markers alone have demonstrated equal or slightly higher sensitivity to CA-125. Improved sensitivity and specificity have been reported using these new markers combined with CA-125.

CONCLUSIONS

Addition of new tumor markers as a compliment to CA-125 were associated with higher sensitivity and detection rates than either marker alone. However, the low prevalence of ovarian cancer necessitates a higher level of sensitivity and specificity that has still not been achieved if these biomarkers are used for diagnosis and monitoring the disease progress as a result of low positive predictive value.

BACKGROUND

The use of repellent materials from plants against nuisance insects is common with great potential to compliment existing malaria control programmes and this requires evaluation in the field. Ocimum plant species, Ocimum suave (Willd) and O. kilimandscharicum (Guerke) materials and their essential oils extracted by steam distillation were evaluated in the field and experimental huts for repellence, exophily and feeding inhibition effects against three mosquito species, Anopheles arabiensis (Patton), An. gambiae ss (Giles) and Culex quinquefasciatus (Say). The protective effect of essential oils from Ocimum plants were compared with N, N-diethly-3- methylbenzamide (DEET), a standard synthetic repellent. Also, the protective effect of fumigation by burning of repellent plants; Ocimum suave, Ocimum kilimandscharicum, Azadirachta indica, Eucalyptus globules and Lantana camara were tested in experimental huts and selected local houses.

RESULTS

In the field, protection by Ocimum plants from mosquito bites was high and there was small variation among different mosquito species. Protection efficiency was 93.4%, 91.98% and 89.75% for An. arabiensis while for Cx. quinquefaciatus it was 91.30%, 88.65% and 90.50% for DEET, Ocimum suave and O. kilimandscharicum respectively. In the experimental hut, deterrence induced by burning of Ocimum and other plants ranged from 73.1.0% to 81.9% for An. arabiensis and 56.5% to 67.8% for Cx. quinquefaciatus, while feeding inhibition was 61.1% to 100% for An. arabiensis and 50% to 100% for Cx. quinquefaciatus. Evaluations under field conditions confirmed high protective efficacy, enhanced feeding inhibition and house entry inhibition (Deterrence).

CONCLUSIONS

This study shows the potential of Ocimum suave and Ocimum kilimandscharicum crude extracts and whole plants of Ocimum suave, Ocimum kilimandscharicum, Azadirachta indica, Eucalyptus globules and Lantana camara for use in protecting against human biting while the burning of plants reduces significantly the indoor resting mosquitoes.

The reinforcing effects and long-term consequences of cocaine self-administration have been associated with brain regions of the mesolimbic dopamine pathway, namely the nucleus accumbens (NAc). Studies of cocaine-induced biochemical adaptations in rodent models have advanced our knowledge; however, unbiased detailed assessments of intracellular alterations in the primate brain are scarce, yet essential, to develop a comprehensive understanding of cocaine addiction. To this end, two-dimensional difference in gel electrophoresis (2D-DIGE) was used to compare changes in cytosolic protein abundance in the NAc between rhesus monkeys self-administering cocaine and controls. Following image normalization, spots with significantly differential image intensities (P<0.05) were identified, excised, trypsin digested and analyzed by matrix-assisted laser-desorption ionization time-of-flight time-of-flight (MALDI-TOF-TOF). In total, 1098 spots were subjected to statistical analysis with 22 spots found to be differentially abundant of which 18 proteins were positively identified by mass spectrometry. In addition, approximately 1000 protein spots were constitutively expressed of which 21 proteins were positively identified by mass spectrometry. Increased levels of proteins in the cocaine-exposed monkeys include glial fibrillary acidic protein, syntaxin-binding protein 3, protein kinase C isoform, adenylate kinase isoenzyme 5 and mitochondrial-related proteins, whereas decreased levels of proteins included beta-soluble N-ethylmaleimide-sensitive factor attachment protein and neural and non-neural enolase. Using a complimentary proteomics approach, the differential expression of phosphorylated proteins in the cytosolic fraction of these subjects was examined. Two-dimensional gel electrophoresis (2DGE) was followed by gel staining with Pro-Q Diamond phosphoprotein gel stain, enabling differentiation of approximately 150 phosphoprotein spots between the groups. Following excision and trypsin digestions, MALDI-TOF-TOF was used to confirm the identity of 15 cocaine-altered phosphoproteins. Significant increased levels were detected for gamma-aminobutyric acid type A receptor-associated protein 1, 14-3-3 gamma-protein, glutathione S-transferase and brain-type aldolase, whereas significant decreases were observed for beta-actin, Rab GDP-dissociation inhibitor, guanine deaminase, peroxiredoxin 2 isoform b and several mitochondrial proteins. Results from these studies indicate coordinated dysregulation of proteins related to cell structure, signaling, metabolism and mitochondrial function. These data extend and compliment previous studies of cocaine-induced biochemical alterations in human postmortem brain tissue, using an animal model that closely recapitulates the human condition and provide new insight into the molecular basis of the disease and potential targets for pharmacotherapeutic intervention.

The development of ultrasound contrast agents has allowed for the evaluation of vascularity in digestive organs by contrast-enhanced endoscopic ultrasonography (EUS). Contrast-enhanced Doppler EUS and contrast-enhanced harmonic EUS (CH-EUS) have improved characterization of pancreatic tumors, lymph nodes, and gastrointestinal submucosal tumors and compliment EUS fine-needle aspiration (FNA) in identifying malignant tumors. Moreover, CH-EUS can be used to identify the target for EUS-guided FNA by clearly depicting the outline of the lesions.

BACKGROUND

Amongst a long list of health issues driving the disparity experienced by Indigenous Australians, cardiovascular disease (CVD) remains the primary target. It is the principal cause of death and of excess death among Indigenous people in Australia, and accounts for almost one-third of the life expectancy gap. Most attention has focused on the higher burden of traditional risk factors experienced by Indigenous people to explain CVD disparity. Far less attention has focused on the quality and outcomes of health system performance in explaining these differentials. The CASPA study was a retrospective, mixed-methods clinical registry and quality improvement program established in the NT of Australia, focused on the patterns, burdens, provision of care, experience of services, adverse outcomes and their determinants among 492 patients (214 Indigenous and 278 non-Indigenous).

RESULTS

Indigenous patients were significantly younger and more likely to have existing CVD risk factors and co-morbid chronic disease. During hospitalisation they received similar rates of evidence-based care with the exception of lower rates of diagnostic angiography (36.2% vs. 47.6%, p=0.012), lower rates of in-patient cardiac rehabilitation (8.9% vs. 15.3%, p=0.03) and lower prescription of discharge statin (44.8% vs. 57.8%, p=0.006). Indigenous patients were more likely to die during two years of follow-up (30% vs. 17.8%, p=0.002). Both Indigenous and non-Indigenous patients were similarly under-prescribed evidence based therapy after discharge. Exploratory qualitative examination of the experience of Indigenous patients in Alice Springs identified significant barriers to care across the continuum.

CONCLUSIONS

Improvements in the delivery of known effective therapies will make a significant impact on adverse outcomes in Indigenous and non-Indigenous patients alike. Comprehensive and sustained prospective data collection to compliment system reform is essential to improve outcomes and reduce disparity in CVD outcomes experienced by Indigenous Australians.

The spiral ganglion neurons (SGN) provide the afferent innervation of the hair cells in the organ of Corti and relay auditory information from the inner ear to the brain. Voltage-gated sodium channels (Na(V)) initiate and propagate action potentials that encode this sensory information but little is known regarding the subtypes expressed in these cells. We have used RT-PCR and immunohistochemistry to study the compliment and anatomical distribution of Na(V) channels in rodent SGN. Na(V)1.1, Na(V)1.6 and Na(V)1.7 were all detected at the mRNA level. Fluorescence or streptavidin-horseradish peroxidase immunohistochemistry extended these findings, demonstrating predominant localisation of Na(V)1.6 and Na(V)1.7 on SGN cell bodies and Na(V)1.1 on axonal processes. Dual labelling with peripherin demonstrated higher Na(V)1.6 and Na(V)1.7 expression on Type I rather than Type II neurons. These results provide evidence for selective expression and variations in the distribution of VGSC in the rodent SGN, which may guide further studies into afferent function in the auditory pathway and therapeutic approaches for diseases such as hearing loss and tinnitus.

BACKGROUND

Two lymphatic filariasis endemic communities Mampong and Hwida in Ghana have been regularly monitored for impact on transmission after annual mass drug administration (MDA) with albendazole and ivermectin. After six MDAs even though the ABR for Mampong was 55883/person/year and that of Hwida was 2494/person/year, they both had ATPs of 15.21 infective larvae/person/year. Interestingly the human microfilaraemia levels had reduced significantly from 14% to 0% at Mampong and 12% to 3% at Hwida. In an attempt to understand this anomaly, we collected mosquitoes over a 5-month period using human landing catches to determine the species composition, the number of cibarial teeth, the lengths and widths of the cibarium and the cibarial dome of the vector populations.

RESULTS

Out of 2553 mosquitoes caught at Mampong, 42.6% were An. gambiae s.l. All 280 identified further by PCR were An. gambiae s.s (275 M and 5 S molecular forms). At Hwida, 112 mosquitoes were obtained; 67 (59.8%) were An. gambiae s.l, comprised of 40 (59.7%) An. melas, 24 (35.8%) An. gambiae s.s (17 and 5 M and S molecular forms respectively) and 3 (4.5%) unidentified. The mean number of teeth for An. melas was 14.1 (median = 14, range = 12-15), An. gambiae s.s., 15.7 (median = 15, range = 13-19) M form 15.5 (median = 15 range = 13-19) and S form 16 (median = 16, range 15-17). The observed differences in teeth numbers were significantly different between An. melas and An. gambiae s.s (p = 0.004), and the M form (p = 0.032) and the S form (p = 0.002).

CONCLUSIONS

In this study, An. gambiae s.s was the main vector at Mampong and was found to possess significantly more cibarial teeth than An. melas, the principal vector at Hwida. We postulate that the different impact observed after 6 MDAs may be due to An. gambiae s.s exhibiting 'facilitation' at Mampong and at Hwida An. melas the main vector exhibits 'limitation'. Thus it may be necessary to compliment MDA with vector control to achieve interruption of transmission in areas where An. melas may exhibit limitation.

A rapid expansion of new scientific information and the introduction of new technology in operative and diagnostic medicine has marked the last several decades. Medical educators, because of and parallel to these developments, initiated a search for a more effective system of presenting core material to medical students. The new educational trends, although varying somewhat from one institution to another, concentrated on the following pedagogical shifts: 1) expansion of conceptual presentation of material at the expense of detail-oriented education; 2) amplification of an integrated approach, as opposed to subject-oriented instruction; 3) scheduling of elective courses to compliment required courses in the curriculum; and 4) institution of small group instruction (i.e., problem-based learning) to actively involve students in the educational process and to develop deductive reasoning based on clinical cases. The future pedagogical system in medical schools will most likely be a combination of "classical" presentation of material combined with concept-oriented, subject-integrated and small group instruction based on either hypothetical or real clinical cases. It is imperative for the success of the new curriculum, however, that certain criteria are satisfied: 1) reorganize basic science departments to determine course ownership; 2) establish a reward system for teaching faculty; and 3) establish new course objectives.

Data collectors play a vital role in producing scientific knowledge. They are also an important component in understanding the practice of bioethics. Yet, very little attention has been given to their everyday experiences or the context in which they are expected to undertake these tasks. This paper argues that while there has been extensive philosophical attention given to 'the what' and 'the why' in bioethics - what action is taken place and why - these should be considered along 'the who' - who are the individuals tasked with bioethics and what can their insights bring to macro-level and abstract discussions of bioethics. This paper will draw on the philosophical theories of Paul Ricoeur which compliments a sociological examination of data collectors experiences and use of their agency coupled with a concern for contextual and institutional factors in which they worked. In emphasising everyday experiences and contexts, I will argue that data collectors' practice of bioethics was shaped by their position at the frontline of face-to-face interactions with medical research participants and community members, alongside their own personal ethical values and motivations. Institutional interpretations of bioethics also imposed certain parameters on their bioethical practice but these were generally peripheral to their sense of obligation and the expectations conferred in witnessing the needs and suffering of those they encountered during their quotidian research duties. This paper will demonstrate that although the principle of autonomy has dominated discussions of bioethics and gaining informed consent seen as a central facet of ethical research by many research institutions, for data collectors this principle was seldom the most important marker of their ethical practice. Instead, data collectors were concerned with remedying the dilemmas they encountered through enacting their own interpretations of justice and beneficence and imposing their own agency on the circumstances they experienced. Their practice of bioethics demonstrates their contribution to the conduct of research and the shortcomings of an over-emphasis on autonomy.

It has become widely accepted that homeostatic and Hebbian plasticity mechanisms work hand in glove to refine neural circuit function. Nonetheless, our understanding of how these fundamentally distinct forms of plasticity compliment (and under some circumstances interfere with) each other remains rudimentary. Here, I describe some of the recent progress of the field, as well as some of the deep puzzles that remain. These include unravelling the spatial and temporal scales of different homeostatic and Hebbian mechanisms, determining which aspects of network function are under homeostatic control, and understanding when and how homeostatic and Hebbian mechanisms must be segregated within neural circuits to prevent interference.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'.

At relatively low cerebrospinal fluid (CSF) pressures, the majority of CSF drainage in 6- to 8-month-old sheep occurs through the cribriform plate into lymphatic vessels in the nasal submucosa. As CSF pressures are elevated, other absorption sites are recruited and these may include transport through arachnoid projections. To test for the transport of CSF directly into the venous sinus, the concentration of a tracer (131I-human serum albumin [HSA]) administered into the CSF compartment was measured in the confluence of the intracranial venous sinuses (torcular) and in the peripheral blood (inferior vena cava). CSF pressures were adjusted to favor absorption. Enrichment of the CSF tracer in the cranial venous system was most evident when the CSF-venous sinus pressure gradients were high. Peak concentration differences occurred 90 s after the CSF pressures were elevated. When pressure gradients approached 30 cm H(2)O, tracer concentrations in the torcular were approximately twofold higher than those observed in peripheral blood. The greatest concentration differences favoring the torcular were obtained when the CSF-venous sinus pressure gradients were elevated to high levels (20- to 40 cm H(2)O) and when CSF access to the paranasal lymphatics and CSF transport into the spinal subarachnoid compartment were prevented. In conjunction with previous studies, these results are compatible with the view that CSF absorption in the adult animal can occur directly into the cranial venous system. However, contrary to the established view, this pathway may represent a secondary system that is recruited to compliment lymphatic transport when global absorption capacity is stressed or compromised.

BACKGROUND

The anaerobic spirochaete Brachyspira pilosicoli causes enteric disease in avian, porcine and human hosts, amongst others. To date, the only available genome sequence of B. pilosicoli is that of strain 95/1000, a porcine isolate. In the first intra-species genome comparison within the Brachyspira genus, we report the whole genome sequence of B. pilosicoli B2904, an avian isolate, the incomplete genome sequence of B. pilosicoli WesB, a human isolate, and the comparisons with B. pilosicoli 95/1000. We also draw on incomplete genome sequences from three other Brachyspira species. Finally we report the first application of the high-throughput Biolog phenotype screening tool on the B. pilosicoli strains for detailed comparisons between genotype and phenotype.

RESULTS

Feature and sequence genome comparisons revealed a high degree of similarity between the three B. pilosicoli strains, although the genomes of B2904 and WesB were larger than that of 95/1000 (~2,765, 2.890 and 2.596 Mb, respectively). Genome rearrangements were observed which correlated largely with the positions of mobile genetic elements. Through comparison of the B2904 and WesB genomes with the 95/1000 genome, features that we propose are non-essential due to their absence from 95/1000 include a peptidase, glycine reductase complex components and transposases. Novel bacteriophages were detected in the newly-sequenced genomes, which appeared to have involvement in intra- and inter-species horizontal gene transfer. Phenotypic differences predicted from genome analysis, such as the lack of genes for glucuronate catabolism in 95/1000, were confirmed by phenotyping.

CONCLUSIONS

The availability of multiple B. pilosicoli genome sequences has allowed us to demonstrate the substantial genomic variation that exists between these strains, and provides an insight into genetic events that are shaping the species. In addition, phenotype screening allowed determination of how genotypic differences translated to phenotype. Further application of such comparisons will improve understanding of the metabolic capabilities of Brachyspira species.

BACKGROUND

(68)Ga-PET imaging is showing slow but steady progress when compared to (18)F-FDG PET. The advantage of in-house preparation of (68)Ga without necessity of a cyclotron, and the new generator configuration with future possibility of freeze-dried kits would make it a promising PET agent for the future.

METHODS

An exhaustive literature exploration was performed using the search engines High-Wire Press, Pubmed, Embase and library databases. Recent reviews on the subject and up-to-date studies on the topic were found that described the role of (68)Ga-PET imaging. Clinical experiences, including our own are described.

RESULTS

Recent resurgence in development of peptides labelled with radiometals, for diagnostic and therapeutic purposes, resulted in a new beginning for (68)Ga-PET imaging. Pre-clinical experience employing animal models and investigation of tracer kinetics/tumour uptake measurements using dynamic (68)Ga-PET have provided data regarding identification of Somatostatin receptors subtypes on many tumours. Present published experiences including our own support these and highlight current clinical utility of (68)Ga-PET imaging. (68)Ga-DOTATOC and (68)Ga-DOTANOC are the most prominent radiopharmaceuticals used nowadays.

CONCLUSIONS

(68)Ga-PET is employed in the management of neuroendocrine tumours and neural crest tumours (phaeochromocytoma and paraganglioma) with diagnostic and therapeutic implications where it compliments present radiologic and scintigraphic procedures. Diagnosis and radiotherapy treatment planning for meningiomas in pertinent clinical setting is another potential use of (68)Ga-PET. Limited studies have shown its utility in prostate cancer but further studies are contemplated. Therefore, current experience tends to open a new horizon for the clinical utility of (68)Ga-PET imaging in future.

Dendritic pruning and loss of synaptic contacts are early events in many neurodegenerative diseases. These effects are dynamic and seem to differ mechanistically from the cell death process. Cannabinoids modulate synaptic activity and afford protection in some neurotoxicity models. We investigated the effects of cannabinoids on activity-induced changes in the number of synapses between rat hippocampal neurons in culture. Morphology and synapses were visualized by confocal imaging of neurons expressing DsRed2 and postsynaptic density protein 95 (PSD95) fused to enhanced green fluorescent protein (GFP). Reducing the extracellular Mg2+ concentration to 0.1 mM for 4 h induced intense synaptic activity, which decreased the number of PSD95-GFP puncta by 45 +/- 13%. Synapse loss was an early event, required activation of N-methyl-D-aspartate receptors, and was mediated by the ubiquitin-proteasome pathway. The cannabinoid receptor full agonist WIN55,212-2 [(R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)-methyl] pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-napthalenyl)-methanone monomethanesulfonate] (EC(50) = 2.5 +/- 0.5 nM) and the partial agonist Delta(9)-tetrahydrocannabinol (THC; EC(50) = 9 +/- 3 nM) inhibited PSD loss in a manner reversed by the CB1 receptor antagonist rimonabant [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide]. The protection was mimicked by inhibition of presynaptic Ca2+ channels, and WIN55,212-2 did not prevent PSD loss elicited by direct application of glutamate, suggesting a presynaptic mechanism. Prolonged exposure to WIN55,212-2, but not THC, desensitized the protective effect. Treating cells that had undergone PSD loss with WIN55,212-2 reversed the loss and enabled recovery of a full compliment of synapses. The modulation of synaptic number by acute and prolonged exposure to cannabinoids may account for some of the effects of these drugs on the plasticity, survival, and function of neural networks.

FMRI analysis techniques can be broadly divided into model based and data driven techniques. The most widely used approach assumes an explicit temporal hemodynamic model based upon the experimental paradigm. Such an approach has proven very useful and powerful even though it is limited by the accuracy of the prespecified model. An alternative approach is to use data driven techniques like independent component analysis or fuzzy cluster analysis. These approaches have proven useful for exploratory analysis in a multivariate sense; however, they can present additional difficulties in the interpretation of the results. An alternative to these approaches is to take advantage of similarities in the patterns of the hemodynamics between participants [i.e., interparticipant correlation (IPC)]. This FMRI analysis technique enjoys the parsimony of the general linear model (GLM) but does not assume a specific FMRI time course. The technique consists of calculating voxel-wise correlations between participants resulting in IPC maps, which indicate the activated regions the participants have in common. We applied the IPC approach to data collected from healthy controls in an auditory oddball task. As expected, high inter-participant correlations were detected in auditory cortical regions in the temporal lobes where highest correlations were evident. In addition, areas that appear to be involved in the task were detected using IPC's but not the GLM regression. This technique, designed to have increased sensitivity to inter-subject correlations that are not necessarily task-related, may potentially be useful as a compliment to model-based approaches.

The purpose of this study was to examine the contributions of autonomous and controlled motives drawn from Self-Determination Theory (SDT; Intrinsic Motivation and Self-determination in Human Behavior. Plenum Press: New York, 1985; Handbook of Self-determination Research. University of Rochester Press: New York, 2002) towards predicting physical activity behaviours and outcome expectations in adult cancer survivors. Participants were cancer-survivors (N=220) and a non-cancer comparison cohort (N=220) who completed an adapted version of the Treatment Self-Regulation Questionnaire modified for physical activity behaviour (TSRQ-PA), an assessment of the number of minutes engaged in moderate-to-vigorous physical activity (MVPA) weekly, and the anticipated outcomes expected from regular physical activity (OE). Simultaneous multiple regression analyses indicated that autonomous motives was the dominant predictor of OEs across both cancer and non-cancer cohorts (R(2adj)=0.29-0.43), while MVPA was predicted by autonomous (beta's ranged from 0.21 to 0.34) and controlled (beta's ranged from -0.04 to -0.23) motives after controlling for demographic considerations. Cancer status (cancer versus no cancer) did not moderate the motivation-physical activity relationship. Collectively, these findings suggest that the distinction between autonomous and controlled motives is useful and compliments a growing body of evidence supporting SDT as a framework for understanding motivational processes in physical activity contexts with cancer survivors.

It has been suggested that proteases are involved in removal of damaged or obsolete proteins and/or that the activation of proteases could contribute to cataract formation. This review summarizes the properties of several recently studied lens endopeptidases including: trypsin-like protease, multicatalytic endopeptidase complex, membrane bound proteases, and calpain. Properties discussed include composition, substrate specificity, distribution, changes in activity during aging, and regulation. Additionally, properties of the lens ubiquitin conjugation system are reviewed. When possible, an attempt was made to relate these findings to whether the lens proteolytic activity was involved in clearing damaged proteins, or whether it could contribute to cataract formation. Clearing of damaged or obsolete lens proteins may involve the participation of several protease activities. Findings suggest that lens protease activities are lost at variable rates during aging, and differ in concentration between species. It was concluded that the consequence of proteolytic activity in the lens may depend closely on the compliment of proteolytic activities found. For instance, proteases causing only partial degradation of lens proteins may predominate in lenses undergoing cataract formation, while proteases assisting in the removal of partially degraded proteins are lost. The partially degraded lens proteins, as well as other denatured lens proteins, may then accumulate and lead to cataract formation.

BACKGROUND

Nipple-areolar complex (NAC) reconstruction and tattooing complete and compliment reconstruction of the breast mound. Patient satisfaction with NAC reconstruction and tattoo, independent from breast mound reconstruction is evaluated in this study.

METHODS

Patients who underwent nipple tattooing between January 2001 and June 2008 were sent a postal questionnaire retrospectively. Questions included those regarding reconstruction type, patient satisfaction with NAC reconstruction and tattoo outcome, and complications.

RESULTS

110 patients with completed questionnaires were included from the 172 patients who were invited. Median follow up time was 38.5 months (1-86). Eighty eight percent reported overall satisfaction with their NAC reconstruction. Seventy percent of patients were satisfied with their nipple tattoos. All procedures were done in a day case setting and eighty-nine patients reported no postoperative complications. The commonest causes for disappointment were lack of projection of the NAC reconstruction and fading of tattoos. Ninety-six percent of women stated that NAC reconstruction and tattooing were important to them, and 93% of the patients would undergo the procedures again.

CONCLUSIONS

We believe that NAC reconstruction is an important and integral part of breast reconstruction. This study should inform surgeons and patients regarding outcome, possible complications and the potential need and timing of further tattooing.

The authors provide an overview of the current state of knowledge with regards to the neurobiological mechanisms involved in normal and pathological anxiety. A brief review of the classification and cognitive psychology of anxiety is followed by a more in-depth look at the neuroanatomical and neurochemical processes and their relevance to our understanding of the modes of action of anxiolytic drugs. The serotonergic, noradrenergic, and gamma-aminobutyric acidergic systems are reviewed. The numerous physiological and pharmacological methods of anxiety provocation and the increasing importance of functional neuroimaging are also examined. The review provides an overview of the biology and basic pharmacology of anxiolytic drugs, and compliments the more clinically oriented companion review.

OBJECTIVE

Patients with mechanical heart valves must follow lifelong warfarin therapy. Warfarin, however, is a difficult drug to manage because it has a narrow therapeutic window and potentially serious side effects. Successful anticoagulation treatment is dependent upon the patient's knowledge of this drug; however, little is known regarding the determinants of such knowledge. Therefore, the purpose of this study was to determine the influence of both in-hospital teaching practices as well as socioeconomic status and demographic variables on patients' knowledge of warfarin therapy.

METHODS

A telephone survey was conducted among 100 patients 3 to 6 months after mechanical heart valve replacement. A previously validated 20-item questionnaire was used to measure the patient's knowledge of warfarin, its side effects, and vitamin K food sources. Demographic information, socioeconomic status data, and medical education information were also collected. Knowledge scores were compared using the Student t test or one-way analysis of variance. Variables with P < or = .2 on univariate analysis were entered in multiple stepwise regression analysis.

CONCLUSIONS

Sixty-one percent of participants had scores indicative of insufficient knowledge of warfarin therapy (score < or = 80%). Age was negatively related to warfarin knowledge scores (r = 0.27, P = .007). Patients with family incomes greater than $25,000, who had greater than a grade 8 education, and who were employed or self-employed had significantly higher warfarin knowledge scores (P = .007, P = .002, and P = .001, respectively). Gender, ethnicity, and warfarin therapy before surgery were not related to warfarin knowledge scores. Furthermore, none of the in-hospital teaching practices significantly influenced knowledge scores, whereas receiving postdischarge community counseling significantly improved knowledge scores (P = .001). Multivariate regression analysis revealed that understanding the concept of International Normalized Ratio, knowing the acronym, age, and receiving community counseling after discharge were the strongest predictors of warfarin knowledge. Accessing postdischarge counseling resulted in significantly improved warfarin knowledge scores. Because improved knowledge has been associated with improved compliance and control, our findings support the need to develop a comprehensive postdischarge education program or at least to ensure that patients have access to a community counselor to compliment the in-hospital education program.

The purpose of this study was to assess the effects of short-term sprint training on transient changes in monocarboxylate lactate transporter 1 (MCT1) and MCT4 protein and mRNA content. Seven moderately endurance-trained runners (mean +/- SE; age 27.7+/-2.9 years, body mass 81.1+/-5.9 kg, .VO(2max) 58.1+/-2.0 ml kg(-1) min(-1)) completed a .VO(2max) and a supramaximal running test to exhaustion (RTE) before and after a 6-week period of sprint training. The sprint training was progressive and consisted of 18 sessions of near maximal short duration (5-15 s) sprints to compliment the athlete's endurance training. Prior to the training period there was a significant (P<0.05) increase in MCT1, but not MCT4 protein, 2 h after the RTE. This occurred without any change in corresponding mRNA levels. After the training period, there was a significant increase in MCT1 protein but no significant change in the MCT4 isoform. Both MCT1 and MCT4 mRNA was significantly lower at rest and 2 h post-RTE after the completion of the training period. After the training period, there was a significant increase in the time to exhaustion and distance covered during the RTE. This study demonstrates that sprint training of this length and type results in an upregulation of MCT1 protein, but not MCT4 content. Additionally, this study shows conflicting adaptations in MCT1 and MCT4 protein and mRNA levels following training, which may indicate post-transcriptional regulation of MCT expression in human muscle.

BACKGROUND

α-Mangostin (α-MG) is the most representative xanthone isolated from the pericarp of mangosteen, possessing extensive biological activities and pharmacological properties, considered as an antineoplastic agent, antioxidant, anti-proliferation and induces apoptosis. Areas covered: The bioactivity and pharmacological properties of α-MG are being actively investigated by various industrial and academic institutions. The bioactivities of α-MG have been summarized in several previous reviews, which were worthy of high compliment. However, recently, many new literatures about the bioactivities of α-MG have been further reported from 2016 to 2017. Herein, the activities of α-MG are supplemented and summarized in this text. Expert opinion: As previously said, α-MG possesses good bioactivities pharmacological properties. More recently, it found that α-MG has the effect of maintaining cardiovascular system and gastrointestinal health and controlling free radical oxidation. Furthermore, α-MG has more applications in cosmetics, with the effects of anti-aging, anti-wrinkle, acne treatment, maintenance of skin lubrication. The application of α-MG in treating rheumatoid arthritis has been disclosed and the MG-loaded self-micro emulsion (MG-SME) was designed to improve its pharmacokinetic deficiencies. As mentioned above, α-MG can be a promising drug, also worthy of developing, and further research is crucial for the future application of α-MG.

Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo. Here, a method is presented to increase physiological availability of chemokines at the site of injury over a defined time-span and simultaneously control their release using biodegradable hydrogels. Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24 hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4 weeks. We demonstrate that the time-controlled release using Met-CCL5-FDH and CXCL12 (S4V)-SDH suppressed initial neutrophil infiltration, promoted neovascularization and reduced apoptosis in the infarcted myocardium. Thus, we were able to significantly preserve the cardiac function after MI. This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies.