Pb-PbOHCl Composite Nanowires Synthesized by Galvanic Deposition in Template.
In this paper, we report a detailed study on the synthesis of composite nanowires of Pb-PbOHCl via galvanic deposition into the pores of a membrane acting as a template. PbOHCl deposition quantitatively occurs as the solution pH exceeds the value of about 4.12. Simultaneously, owing to the galvanic coupling, electro-deposition of lead occurs, so composite nanowires were formed. The role of different parameters controlling the kinetic evolution of the process, such as oxygen bubbling, solution pH, surface area and type of sacrificial anode were investigated one at a time. The results suggest that every modification accelerating the alkalization of the solution inside the template pores favors growth of composite nanowires richer in PbOHCl. Alumina and polycarbonate membranes were investigated as template, and the best results were obtained for polycarbonate membrane, which can be easily removed by dissolution in CHCl₃ avoiding the collapse and successive loss of the nanowires.


Universal chemical gradient platforms using poly(methyl methacrylate) based on the biotin-streptavidin interaction for biological applications.
This article describes a simple method for the construction of a universal surface chemical gradient platform based on the biotin-streptavidin model. In this approach, surface chemical gradients were prepared in poly(methyl methacrylate) (PMMA), a biocompatible polymer, by a controlled hydrolysis procedure. The physicochemical properties of the resulting modified surfaces were extensively characterized. Chemical analysis carried out via time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS) showed the formation of a smooth, highly controllable carboxylic acid gradient of increasing concentration along the sample surface. Atomic force microscopy (AFM) and contact angle (CA) results indicate that, in contrast with most of the chemical gradient methods published in the literature, the chemical modification of the polymer surface barely affects its physical properties. The introduction of carboxylic acid functionality along the surface was then used for biomolecule anchoring. For this purpose, the surface was activated and derivatized first with biotin and finally with streptavidin (SAV) in a directed orientation fashion. The SAV gradient was qualitatively assessed by fluorescence microscopy analysis and quantified by surface plasmon resonance (SPR) in order to establish a quantitative relationship between SAV surface densities and the surface location. The usefulness of the fabrication method described for biological applications was tested by immobilizing biotinylated bradykinin onto the SAV gradient. This proof-of-concept application shows the effectiveness of the concentration range of the gradient because the effects of bradykinin on cell morphology were observed to increase gradually with increasing drug concentrations. The intrinsic characteristics of the fabricated gradient platform (absence of physicochemical modifications other than those due to the biomolecules included) allow us to attribute cell behavior unequivocally to the biomolecule surface density changes.


Development of a retinoic acid receptor-binding assay with rainbow trout tissue: characterization of retinoic acid binding, receptor tissue distribution, and developmental changes.
Retinoic acid (RA) regulates the transcription of various genes required for several essential functions in vertebrates through binding to two classes of nuclear receptors, the retinoic acid receptors (RAR) and retinoid X receptors (RXR). We investigated nuclear RA binding in tissues from rainbow trout using the radiolabeled all-trans and 9-cis isomers of RA. Specific binding (indicative of receptor binding) of both all-trans- and 9-cis-RA was found in all tissues tested, including the adult trout ovary, testis, gill, liver, kidney, blood, white muscle, and heart. The kinetics and absolute amount of RA binding were dependent on both the tissue and the isomer of RA used. All-trans-RA bound with high affinity (K(d) approximately 1.0-3.9 nM), and low capacity (B(max) approximately 75-484 fmol RA/mg protein), while 9-cis-RA bound with lower affinity (K(d) approximately 7-56 nM), but with a greater capacity (B(max) approximately 214-1076 fmol RA/mg protein). The B(max) results were used to estimate RAR and RXR levels and revealed that the gill possesses primarily RARs while the liver possesses primarily RXRs. The RAR-specific competitor TTNPB was able to effectively displace all-trans-[3H]RA in most tissues, and the RXR-specific competitor AGN 194204 was able to effectively displace 9-cis-[3H]RA. However, TTNPB and AGN 194204 could not displace all of the RA in the kidney and testis, suggesting the existence of another nuclear RA binding protein. Binding of all-trans- and 9-cis-RA was also found in developing trout embryos and fry. Kinetic analysis revealed that RAR levels predominated at the eyed-embryo stage, but decreased 87% by the swim-up fry stage, while RXR levels remained relatively constant over the same time period. These findings suggest that RA and its receptors may play a key role in early trout development. This study has provided a simple and rapid radioligand binding assay that can identify RAR and RXRs in trout tissues.


The influence of cochlear spectral processing on the timing and amplitude of the speech-evoked auditory brain stem response.
The speech-evoked auditory brain stem response (speech ABR) is widely considered to provide an index of the quality of neural temporal encoding in the central auditory pathway. The aim of the present study was to evaluate the extent to which the speech ABR is shaped by spectral processing in the cochlea. High-pass noise masking was used to record speech ABRs from delimited octave-wide frequency bands between 0.5 and 8 kHz in normal-hearing young adults. The latency of the frequency-delimited responses decreased from the lowest to the highest frequency band by up to 3.6 ms. The observed frequency-latency function was compatible with model predictions based on wave V of the click ABR. The frequency-delimited speech ABR amplitude was largest in the 2- to 4-kHz frequency band and decreased toward both higher and lower frequency bands despite the predominance of low-frequency energy in the speech stimulus. We argue that the frequency dependence of speech ABR latency and amplitude results from the decrease in cochlear filter width with decreasing frequency. The results suggest that the amplitude and latency of the speech ABR may reflect interindividual differences in cochlear, as well as central, processing. The high-pass noise-masking technique provides a useful tool for differentiating between peripheral and central effects on the speech ABR. It can be used for further elucidating the neural basis of the perceptual speech deficits that have been associated with individual differences in speech ABR characteristics.


Does neuromuscular taping influence hand kinesiology? A pilot study on Down's Syndrome.
This paper is a first attempt analysis of hand and upper limb proprioception coordination induced by NeuroMuscular Taping (NMT): application in a group of 5 participants with Down syndrome. The participants underwent a drawing test with motion capture system acquisition before and after NMT application. Specific and descriptive parameters were computed and analysed in order to quantify the differences. Results showed statistical differences between pre and post treatment sessions: the 5 participants with Down syndrome evidenced more reliance on proprioceptive signals in the post treatment session during the execution of the specific writing tasks. Based on the hypothesis that modifications in proprioception should alter motor pathway mapping of the motor cortex, Neuromuscular taping may play a role in the treatment of dysgraphia and improving hand coordination following CNS impairment, even though a small treatment group was chosen for this pilot study the results lead to further discussions concerning the role of different afferent signals in a pathological context.


The effect of silica on the degradation of organohalides in granular iron columns.
Dissolved silica species are naturally occurring, ubiquitous groundwater constituents with corrosion-inhibiting properties. Their influence on the performance and longevity of iron-based permeable reactive barriers for treatment of organohalides was investigated through long-term column studies using Connelly iron as the reactive medium. Addition of dissolved silica (0.5 mM) to the column feed solution led to a reduction in iron reactivity of 65% for trichloroethylene (TCE), 74% for 1,1,2-trichloroethane (1,1,2-TCA), and 93% for 1,1,1-trichloroethane (1,1,1-TCA), compared to columns operated under silica-free conditions. Even though silica adsorption was a gradual process, the inhibitory effect was evident within the first week, with subsequent decreases in reactivity over 288 days being relatively minor. Lower concentrations of dissolved silica species (0.2 mM) led to a lesser decrease (70%) in iron reactivity toward 1,1,1-TCA. The presence of dissolved silica species produced a shift in TCE product distribution toward the more highly chlorinated product cis-dichloroethylene (cis-DCE), although it did not appear to alter products originating from the trichloroethanes. The major corrosion products identified were magnetite (Fe3O4) or maghemite (gamma-Fe2O3) and carbonate green rust ([Fe4(2+)Fe(2)3+(OH)12][CO(3).2H2O]). Iron carbonate hydroxide (Fe(II)1.8Fe(III)0.2(OH)2.2CO3) was only found in the silica-free column, indicating that silica may hinder its formation. A comparison with columns operated under the same conditions, but using Master Builder iron as the reactive matrix, showed that Connelly iron is initially less reactive, but performs better than Master Builder iron over 288 days.


3,3'-diindolylmethane exerts antiproliferation and apoptosis induction by TRAF2-p38 axis in gastric cancer.
3,3'-diindolylmethane (DIM), an active phytochemical derivative extracted from cruciferous vegetables, possesses anticancer effects. However, the underlying anticancer mechanism of DIM in gastric cancer remains unknown. Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2), one of the signal transduction proteins, plays critical role in proliferation and apoptosis of human gastric cancer cells, but there are still lack of practical pharmacological modulators for potential clinical application. Here, we further explored the role of TRAF2 in inhibiting cell proliferation and inducing apoptosis by DIM in human gastric cancer BGC-823 and SGC-7901 cells. After treating BGC-823 and SGC-7901 cells with DIM for 24 h, cell proliferation, apoptosis and TRAF2-related protein were measured. Our findings showed that DIM inhibited the expressions of TRAF2, activated p-p38 and its downstream protein p-p53, which were paralleled with DIM-triggered cells proliferation, inhibition and apoptosis induction. These effects of DIM were reversed by TRAF2 overexpression or p38 mitogen-activated protein kinase (MAPK)-specific inhibitor (SB203580). Taken together, our data suggest that regulating TRAF2/p38 MAPK signaling pathway is essential for inhibiting gastric cancer proliferation and inducing apoptosis by DIM. These findings broaden the understanding of the pharmacological mechanism of DIM's action as a new modulator of TRAF2, and provide a new therapeutic target for human gastric cancer.


Intracellular pH regulation in detubulated frog skeletal muscle fibers.
Intracellular pH regulation was studied in semitendinosus muscle fibers from frog (Rana pipiens). Intracellular pH (pHi) was measured with recessed-tip glass microelectrodes and membrane potential with conventional microelectrodes. Fibers had their connections between the surface and transverse tubular membrane disrupted (detubulation) with the formamide shock technique. Fibers were approximately 80% detubulated as determined by the decrease in membrane capacitance and the loss of contractile capability. The initial rate of pHi recovery from acidification to approximately 6.8 (no CO2) was dependent on external buffering power, reaching a maximum of approximately 0.6 pH/h at 50 mM HEPES, indicating that the rate of pHi recovery in frog muscle is limited by the diffusion of buffer through an external "unstirred layer". In detubulated fibers, pHi recovery from acidification due to both the amiloride-sensitive Na+/H+ and the 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS)-sensitive (Na+ + HCO3-)/Cl- exchangers was nearly identical to recovery in fully tubulated fibers. This is consistent with these two pH recovery transporters being localized to the surface, and not the transverse tubular, membrane domain in frog skeletal muscle fibers.


A flexible microrobotic platform for handling microscale specimens of fibrous materials for microscopic studies.
One of the most challenging issues faced in handling specimens for microscopy, is avoiding artefacts and structural changes in the samples caused by human errors. In addition, specimen handling is a laborious and time-consuming task and requires skilful and experienced personnel. This paper introduces a flexible microrobotic platform for the handling of microscale specimens of fibrous materials for various microscopic studies such as scanning electron microscopy and nanotomography. The platform is capable of handling various fibres with diameters ranging from 10 to 1000 μm and lengths of 100 μm-15 mm, and mounting them on different types of specimen holders without damaging them. This tele-operated microrobotic platform minimizes human interaction with the samples, which is one of the main sources contributory to introducing artefacts into the specimens. The platform also grants a higher throughput and an improved success rate of specimen handling, when compared to the manual processes. The operator does not need extensive experience of microscale manipulation and only a short training period is sufficient to operate the platform. The requirement of easy configurability for various samples and sample holders is typical in the research and development of materials in this field. Therefore, one of the main criteria for the design of the microrobotic platform was the ability to adapt the platform to different specimen handling methods required for microscopic studies. To demonstrate this, three experiments are carried out using the microrobotic platform. In the first experiment, individual paper fibres are mounted successfully on scanning electron microscopy specimen holders for the in situ scanning electron microscopy diagonal compression test of paper fibres. The performance of the microrobotic platform is compared with a skilled laboratory worker performing the same experiment. In the second experiment, a strand of human hair and an individual paper fibre bond are mounted on a specimen holder for nanotomography studies. In the third experiment, individual paper fibre bonds with controlled crossing and vertical angles are made using the microrobotic platform. If an industrial application requires less flexibility but a higher speed when handling one type of sample to a specific holder, then the platform can be automated in the future.


Mining for viral fragments in methylation enriched sequencing data.
Most next generation sequencing experiments generate more data than is usable for the experimental set up. For example, methyl-CpG binding domain (MBD) affinity purification based sequencing is often used for DNA-methylation profiling, but up to 30% of the sequenced fragments cannot be mapped uniquely to the reference genome. Here we present and evaluate a methodology for the identification of viruses in these otherwise unused paired-end MBD-seq data. Viral detection is accomplished by mapping non-reference alignable reads to a comprehensive set of viral genomes. As viruses play an important role in epigenetics and cancer development, 92 (pre)malignant and benign samples, originating from two different collections of cervical samples and related cell lines, were used in this study. These samples include primary carcinomas (n = 22), low- and high-grade cervical intraepithelial neoplasia (CIN1 and CIN2/3 - n = 2/n = 30) and normal tissue (n = 20), as well as control samples (n = 17). Viruses that were detected include phages, adenoviruses, herpesviridae and HPV. HPV, which causes virtually all cervical cancers, was identified in 95% of the carcinomas, 100% of the CIN2/3 samples, both CIN1 samples and in 55% of the normal samples. Comparing the amount of mapped fragments on HPV for each HPV-infected sample yielded a significant difference between normal samples and carcinomas or CIN2/3 samples (adjusted p-values resp. <10(-5), <10(-5)), reflecting different viral loads and/or methylation degrees in non-normal samples. Fragments originating from different HPV types could be distinguished and were independently validated by PCR-based assays in 71% of the detections. In conclusion, although limited by the a priori knowledge of viral reference genome sequences, the proposed methodology can provide a first confined but substantial insight into the presence, concentration and types of methylated viral sequences in MBD-seq data at low additional cost.


A flicker paradigm for inducing change blindness reveals alcohol and cannabis information processing biases in social users.
To apply a new paradigm using transient changes to visual scenes to explore information processing biases relating to "social" levels of alcohol and cannabis use. Male and female student volunteers (n = 200) not self-reporting substance-related problems. Quiet testing areas throughout the university campus. A flicker paradigm, for inducing change blindness with lighter and heavier social users of alcohol (experiment 1, n= 100) and social users and non-users of cannabis (experiment 2, n= 100), explored the associations between habitual level of use and the latency to detection of a single substance-related or neutral change made to a scene of grouped substance-related and neutral objects. Alcohol use was measured as the number of units of the heaviest drinking day from the previous week; cannabis use as the number of months of use in previous 12. Change-detection latency comparisons were used to evaluate processing biases. In both experiments, (i) heavier social users detected substance-related changes quicker than lighter and non-users; (ii) lighter and non-users detected substance-neutral changes quicker than heavier users; (iii) heavier social users detected substance-related quicker than substance-neutral changes; and (iv) lighter and non-users detected substance-neutral changes quicker than substance-related changes. Alcohol and cannabis processing biases are found at levels of social use, have the potential to influence future consumption and for this reason merit further research.


Enhanced power production from microbial fuel cells with high cell density culture.
Improvement of power production in a microbial fuel cell (MFC) with a high cell density culture strategy was developed. By using high cell density culture, the voltage output and power density output of the MFC were enhanced about 0.6 and 1.6 times compared to the control, respectively. Further analysis showed that riboflavin concentration in the MFC was dramatically increased from 0.1 mg/L to 1.2 mg/L by high cell density culture. Moreover, the biofilm formation on the anode surface was significantly enhanced by this new strategy. The increased accumulation of electron shuttle (riboflavin) as well as enhanced biofilm formation contributed to the improvement in anodic electrochemical activity and these factors were the underlying mechanism for MFC performance improvement by high cell density culture. This work demonstrated that high cell density culture would be a simple and practical strategy for MFC manipulation.


Effects of reef proximity on the structure of fish assemblages of unconsolidated substrata.
Fish assemblages of unconsolidated sedimentary habitats on continental shelves are poorly described when compared to those of hard substrata. This lack of data restricts the objective management of these extensive benthic habitats. In the context of protecting representative areas of all community types, one important question is the nature of the transition from reefal to sedimentary fish assemblages. We addressed this question using Baited Remote Underwater Videos (BRUVs) to assess fish assemblages of sedimentary habitats at six distances from rocky reefs (0, 25, 50, 100, 200, and 400 m) at four sites in subtropical eastern Australia. Distance from reef was important in determining fish assemblage structure, and there was no overlap between reef sites and sedimentary sites 400 m from reef. While there was a gradient in assemblage structure at intermediate distances, this was not consistent across sites. All sites, however, supported a mixed 'halo' assemblage comprising both reef and sediment species at sampling stations close to reef. BRUVs used in conjunction with high-resolution bathymetric and backscatter spatial data can resolve differences in assemblage structure at small spatial scales (10s to 100s of metres), and has further application in unconsolidated habitats. Unless a 'reef halo' assemblage is being examined, a minimum of 200 m but preferably 400 m distance from any hard substrate is recommended when designing broader-scale assessments of fish assemblages of sedimentary habitats.


Helping or hindering: the role of nurse managers in the transfer of practice development learning.
This paper reports selected findings from a recent PhD study exploring how graduates from a BSc Specialist Nursing programme, with an NMC-approved Specialist Practitioner Qualification, engage in practice development during their subsequent careers. The UKCC (1998) defines specialist practice as requiring higher levels of judgement, discretion and decision-making, with leadership in clinical practice development forming a core dimension of this level of practice. However, there is little evidence in the published literature that describes or evaluates the practice development role of graduate specialist practitioners. This study applied a modified Glaserian approach to grounded theory methods. A preliminary descriptive survey questionnaire was posted to all graduates from the programme, response rate of 45% (n=102). From these respondents, theoretical sampling decisions directed the selection of 20 participants for interview, permitting data saturation. The grounded theory generated by this study discovered a basic social process labelled 'making a difference', whereby graduate specialist practitioners are increasingly able to impact in developing patient care at a strategic level by coming to own the identity of an expert practitioner (Currie, 2006). Contextual factors strongly influence the practitioner journey, with organizational position and other people presenting enabling or blocking conditions. The line manager plays a crucial role in helping or hindering graduate specialist practitioners to transfer their learning to the clinical setting and become active in practice development. Recommendations to enhance managerial support for the practice development role of graduate specialist practitioners are proposed. ADDING TO CURRENT KNOWLEDGE: This work adds to currently limited knowledge of the graduate specialist practitioners' role in the leadership of clinical practice development. In addition, the findings emphasize the potential influence of the workplace environment by analyzing organizational factors in the specific context of the graduate specialist practitioner attempting to develop practice.


National scale-up of zinc promotion in Nepal: results from a post-project population-based survey.
The World Health Organization and the United Nations Children's Fund recommend using a new oral rehydration solution (ORS) plus zinc supplementation for 10-14 days for the treatment of diarrhoea in children aged less than five years. The Social Marketing Plus for Diarrhoeal Disease Control: Point of Use Water Disinfection and Zinc Treatment (POUZN) project in Nepal was one of the first zinc-promotion projects to move beyond pilot efforts into a scaled-up programme with national-level reach. This study used data from a survey conducted in 26 districts in Nepal in 2008 to examine zinc-use behaviour, knowledge, and beliefs of caregivers of children aged less than six years, other diarrhoea-treatment practices, and recollection of project communication messages. The results of the survey indicated that, by six months following the onset of a zinc-promotion campaign, the majority (67.5%) of children (n=289), aged less than six years, with diarrhoea were treated with ORS, and 15.4% were treated with zinc. Over half (53.1%) of all caregivers (n=3,550) interviewed had heard about zinc products; most (97.1%) of those who had heard of zinc knew that zinc should be used for the treatment of diarrhoea. Zinc-related knowledge and behaviours were positively associated with recall of communication messages. Children whose caregivers recalled the mass-media message that zinc should be used for 10 days [odds ratio (OR)=2.02, 95% confidence interval (CI) 1.85-2.19] and whose caregivers perceived that zinc is easy to obtain (OR=1.76, 95% CI 1.49-2.09) were more likely to be treated with zinc for 10 days, along with ORS. The findings demonstrated that mass media play an important role in increasing caregivers' knowledge about zinc and encouraging trial and correct use. Future efforts should also focus on understanding the factors that motivate providers to continue recommending antibiotics and antidiarrhoeals instead of zinc. These findings are being used for informing the design and implementation of zinc programmes in other developing countries with a high prevalence of diarrhoea.


The impact of HIV/SRH service integration on workload: analysis from the Integra Initiative in two African settings.
There is growing interest in integration of HIV and sexual and reproductive health (SRH) services as a way to improve the efficiency of human resources (HR) for health in low- and middle-income countries. Although this is supported by a wealth of evidence on the acceptability and clinical effectiveness of service integration, there is little evidence on whether staff in general health services can easily absorb HIV services. We conducted a descriptive analysis of HR integration through task shifting/sharing and staff workload in the context of the Integra Initiative - a large-scale five-year evaluation of HIV/SRH integration. We describe the level, characteristics and changes in HR integration in the context of wider efforts to integrate HIV/SRH, and explore the impact of HR integration on staff workload. Improvements in the range of services provided by staff (HR integration) were more likely to be achieved in facilities which also improved other elements of integration. While there was no overall relationship between integration and workload at the facility level, HIV/SRH integration may be most influential on staff workload for provider-initiated HIV testing and counselling (PITC) and postnatal care (PNC) services, particularly where HIV care and treatment services are being supported with extra SRH/HIV staffing. Our findings therefore suggest that there may be potential for further efficiency gains through integration, but overall the pace of improvement is slow. This descriptive analysis explores the effect of HIV/SRH integration on staff workload through economies of scale and scope in high- and medium-HIV prevalence settings. We find some evidence to suggest that there is potential to improve productivity through integration, but, at the same time, significant challenges are being faced, with the pace of productivity gain slow. We recommend that efforts to implement integration are assessed in the broader context of HR planning to ensure that neither staff nor patients are negatively impacted by integration policy.


Olive mill wastewater treatment using a simple zeolite-based low-cost method.
Olive mill wastewater (OMW), a liquid by-product of the olive oil industry, represents a severe environmental problem owing to its high pollution load. In this study, successive columns containing different types of natural materials were investigated for their OMW treatment efficiency. Passing OMW through three columns of gravel, fine sand, and a mixture of acidified cotton and zeolite (weight:weight ratio of cotton:clinoptilolite of 2:1), followed by treatment with activated charcoal (AC) and lime, was the best treatment in terms of the quality of water obtained. This treatment decreased concentrations of [Formula: see text] , B, K, P, and total fat in OMW by mean percentages of 78.0, 92.4, 66.6, 48.3, and 93.3%, respectively. Furthermore, it decreased OMW turbidity and electric conductivity (EC) by 96.8 and 48.4%, respectively. Most contaminants were removed from the OMW in the cotton/clinoptilolite column owing to the high sorption affinity of clinoptilolite on its active sites. The AC was efficient for organic particle removal; meanwhile, lime was used to raise the pH of the treated OMW (TOMW) from 2.9 to 5.1. This simple method enables us to obtain environmentally friendly TOMW that can be safely used for irrigation.


Disparities in healthcare utilisation rates for Aboriginal and non-Aboriginal Albertan residents, 1997-2006: a population database study.
It is widely recognised that significant discrepancies exist between the health of indigenous and non-indigenous populations. Whilst the reasons are incompletely defined, one potential cause is that indigenous communities do not access healthcare to the same extent. We investigated healthcare utilisation rates in the Canadian Aboriginal population to elucidate the contribution of this fundamental social determinant for health to such disparities. Healthcare utilisation data over a nine-year period were analysed for a cohort of nearly two million individuals to determine the rates at which Aboriginal and non-Aboriginal populations utilised two specialties (Cardiology and Ophthalmology) in Alberta, Canada. Unadjusted and adjusted healthcare utilisation rates obtained by mixed linear and Poisson regressions, respectively, were compared amongst three population groups - federally registered Aboriginals, individuals receiving welfare, and other Albertans. Healthcare utilisation rates for Aboriginals were substantially lower than those of non-Aboriginals and welfare recipients at each time point and subspecialty studied [e.g. During 2005/06, unadjusted Cardiology utilisation rates were 0.28% (Aboriginal, n = 97,080), 0.93% (non-Aboriginal, n = 1,720,041) and 1.37% (Welfare, n = 52,514), p = <0.001]. The age distribution of the Aboriginal population was markedly different [2.7%≥65 years of age, non-Aboriginal 10.7%], and comparable utilisation rates were obtained after adjustment for fiscal year and estimated life expectancy [Cardiology: Incidence Rate Ratio 0.66, Ophthalmology: IRR 0.85]. The analysis revealed that Aboriginal people utilised subspecialty healthcare at a consistently lower rate than either comparatively economically disadvantaged groups or the general population. Notably, the differences were relatively invariant between the major provincial centres and over a nine year period. Addressing the causes of these discrepancies is essential for reducing marked health disparities, and so improving the health of Aboriginal people.


Elevation of the head during intensive care management in people with severe traumatic brain injury.
Traumatic brain injury (TBI) is a major public health problem and a fundamental cause of morbidity and mortality worldwide. The burden of TBI disproportionately affects low- and middle-income countries. Intracranial hypertension is the most frequent cause of death and disability in brain-injured people. Special interventions in the intensive care unit are required to minimise factors contributing to secondary brain injury after trauma. Therapeutic positioning of the head (different degrees of head-of-bed elevation (HBE)) has been proposed as a low cost and simple way of preventing secondary brain injury in these people. The aim of this review is to evaluate the evidence related to the clinical effects of different backrest positions of the head on important clinical outcomes or, if unavailable, relevant surrogate outcomes. To assess the clinical and physiological effects of HBE during intensive care management in people with severe TBI. We searched the following electronic databases from their inception up to March 2017: Cochrane Injuries' Specialised Register, CENTRAL, MEDLINE, Embase, three other databases and two clinical trials registers. The Cochrane Injuries' Information Specialist ran the searches. We selected all randomised controlled trials (RCTs) involving people with TBI who underwent different HBE or backrest positions. Studies may have had a parallel or cross-over design. We included adults and children over two years of age with severe TBI (Glasgow Coma Scale (GCS) less than 9). We excluded studies performed in children of less than two years of age because of their unfused skulls. We included any therapeutic HBE including supine (flat) or different degrees of head elevation with or without knee gatch or reverse Trendelenburg applied during the acute management of the TBI. Two review authors independently checked all titles and abstracts, excluding references that clearly didn't meet all selection criteria, and extracted data from selected studies on to a data extraction form specifically designed for this review. There were no cases of multiple reporting. Each review author independently evaluated risk of bias through assessing sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other sources of bias. We included three small studies with a cross-over design, involving a total of 20 participants (11 adults and 9 children), in this review. Our primary outcome was mortality, and there was one death by the time of follow-up 28 days after hospital admission. The trials did not measure the clinical secondary outcomes of quality of life, GCS, and disability. The included studies provided information only for the secondary outcomes intracranial pressure (ICP), cerebral perfusion pressure (CPP), and adverse effects.We were unable to pool the results as the data were either presented in different formats or no numerical data were provided. We included narrative interpretations of the available data.The overall risk of bias of the studies was unclear due to poor reporting of the methods. There was marked inconsistency across studies for the outcome of ICP and small sample sizes or wide confidence intervals for all outcomes. We therefore rated the quality of the evidence as very low for all outcomes and have not included the results of individual studies here. We do not have enough evidence to draw conclusions about the effect of HBE during intensive care management of people with TBI. The lack of consistency among studies, scarcity of data and the absence of evidence to show a correlation between physiological measurements such as ICP, CCP and clinical outcomes, mean that we are uncertain about the effects of HBE during intensive care management in people with severe TBI.Well-designed and larger trials that measure long-term clinical outcomes are needed to understand how and when different backrest positions can affect the management of severe TBI.


Serotonin receptor ligands and the treatment of obesity.
It was first established in the 1970s that the brain serotonin (5-HT) system was involved in the control of eating. Subsequent progress in the molecular pharmacology of 5-HT receptors, and the development of selective 5-HT receptor ligands, has clarified our understanding of the role of 5-HT in the regulation of ingestive behavior. Of the 14 5-HT receptor subtypes currently described, 5-HT1A, 5-HT1B and 5-HT2C receptors have been of principal interest in the regulation of food intake. This is largely due to the development of suitable agonists, antagonists and gene-knockout animals with which the role of these receptors can be elucidated. The recent development of selective ligands and knockout mice for other 5-HT receptors, including the 5-HT2B and 5-HT6 receptors, has also suggested a role for these receptor subtypes in eating behavior. Studies using such approaches should further our understanding of the role of serotonin in the regulation of feeding behavior and thus, may lead to the development of novel, safe, serotonin receptor ligands for the treatment of obesity.


Lead-iron phosphate glass: a stable storage medium for high-level nuclear waste.
Results are presented which show that lead-iron phosphate glasses are a promising new waste form for the safe immobilization of both high-level defense and high-level commercial radioactive waste. Relative to the borosilicate nuclear waste glasses that are currently the "reference" waste form for the long-term disposal of nuclear waste, lead-iron phosphate glasses have several distinct advantages: (i) an aqueous corrosion rate that is about 1000 times lower, (ii) a processing temperature that is 100 degrees to 250 degrees C lower, and (iii) a much lower melt viscosity in the temperature range from 800 degrees to 1000 degrees C. Most significantly, the lead-iron phosphate waste form can be processed using a technology similar to that developed for borosilicate nuclear waste glasses.


Predicting physical and chemical water properties from relationships with watershed soil characteristics.
The Surface Waters component of the Environmental Monitoring and Assessment Program (EMAPSW) was developed by the USEPA to evaluate the extent and condition of lakes and streams over national and regional scales. Realistically, chemical or physical water properties (WPs) such as acidity or turbidity can be field-sampled for only a small portion of all lakes and streams. However, soil characteristics (SCs) affect WPs and broad-scale soil survey data have become available in the State Soil Geographic Data Base (STATSGO). We developed models relating observed WPs to SCs to extrapolate the sampled WPs to a region, potentially reducing extensive monitoring needs. Our study region consisted of 13 northeastern and Mid-Atlantic states and contained 882 STATSGO soil map units. We used map units as the spatial component of WP analysis. The WPs were sampled in 721 randomly selected EMAPSW study sites. The watersheds of these sites represent 7.1% of the region's total area and spatially intersect 400 of its soil map units. Each intersected map unit was assigned the weighted average WPs from the corresponding watersheds. Conditional expectation models were used to extrapolate sampled WPs to 882 map units. The relative standard errors ranged from low for pH (0.8%), intermediate for total P (12.1%), and very high for chloride (54.8%). The high extrapolation errors indicate outlier conditions from natural, non-soil, or anthropogenic sources.


Deltoid muscle characteristics in wrestlers.
The purpose of the present study was to investigate the deltoid muscle characteristics of wrestlers. Nine Greco-Roman competitive male wrestlers (mean age 20.1+/-2.7 yrs, height 175+/-0.6 cm, weight 83.2+/-12.5 kg, years of training 7.6+/-2.7 yrs) participated in this study. Six male healthy sedentary students (mean age 21.2+/-0.9 yrs, height 180+/-0.3 cm, weight 80.1+/-9.4 kg) served as controls. Muscle fibre distribution, cross-sectional area (CSA), as well as satellite cells, myonuclei and capillary density per muscle fibre area were determined by immunohistochemistry. Myosin heavy chain MHC isoform composition of single fibres was determined with protein electrophoresis. Immunohistochemical analysis showed that muscle fibre distribution of the MHC I and IIA were significantly higher in wrestlers than in controls (p<0.05). Electrophoretic analysis of single fibres revealed a significantly higher proportion of fibres containing MHC I and IIC in wrestlers (p<0.05). The mean CSA of type IIA fibres and the number of myonuclei per type II was significantly higher in wrestlers (p<0.05). We also found that the number of satellite cells was 2.5 fold higher in wrestlers than in the control group. This study suggests that the observed muscle fibre profile in the deltoid of wrestlers may represent an adaptation based on the specific mechanical and biochemical demands of the long-term training in Greco-Roman wrestling.


Itinerant teaching: the inside story.
The number of students who are deaf or hard of hearing attending local neighborhood schools has increased steadily over the past 20 years (Holden-Pitt & Diaz, 1998). This increase has led to larger numbers of teachers serving these students as itinerant teachers. However, little research has been conducted to examine the efficacy of this model of service delivery (Brelje, 1992; Luckner & Miller, 1994). Qualitative research methods were used to investigate itinerant teachers' perceptions of their responsibilities, job satisfaction, and effectiveness. Individual interviews were conducted with 10 itinerant teachers. Participants reported they preferred working directly with students rather than consulting with general education teachers and families. They noted the primary advantages of working as an itinerant teacher were variety, autonomy, time for reflection, and the diversity of students with whom they worked. Some of the most significant disadvantages they cited were isolation, time and budget constraints, and the distances required to travel from school to school. Essential skills and challenges to being an effective itinerant teacher are identified, recommendations for future itinerant teachers are discussed, and suggestions for future research are presented.


Enterolithotomy for the treatment of large bowel obstruction secondary to gallstones.
We describe the case of an 81-year-old woman with large bowel-obstruction caused by an impacted gallstone. An 81-year-old, Caucasian, fully independent woman without significant comorbidities presented with absolute constipation, faecal vomiting and abdominal pain. Abdominal radiography revealed dilated small bowel, and a subsequent contrast CT demonstrated a 2.5 cm gallstone in the sigmoid colon. This is believed to have entered the transverse colon via a cholecyst-colonic fistula, and then migrated to a section of sigmoid colon affected by diverticular disease, where it became impacted. Two sigmoidoscopic removals were attempted but were unsuccessful as the gallstone's size prevented removal with an endoscopic basket. A laparotomy was performed and the stone extracted via a sigmoid enterotomy. No covering stoma was formed, and following 48 h on intensive trauma unit and a short ward-based stay for rehabilitation, the patient was discharged home and is currently doing well.


Oxidative Stress and Cardiovascular Dysfunction Associated with Cadmium Exposure: Beneficial Effects of Curcumin and Tetrahydrocurcumin.
Cadmium (Cd) is a non-essential heavy metal with high toxicity potential. Humans are exposed to Cd present in diet, polluted air, and cigarette smoke. Cd exposure has been associated with increased risk of chronic diseases, including hypertension, atherosclerosis, diabetes, and nephropathy, all of which could be attributable to dysfunctional endothelial and smooth muscle cells. Cd toxicity is correlated with increased reactive oxygen formation and depletion of antioxidants, resulting in an oxidative stress. Chelation of Cd has proved useful in the removal of the Cd burden. However, several chelating agents cause side effects in clinical usage. Recent studies have shown that the antioxidant compounds curcumin and tetrahydrocurcumin can alleviate vascular dysfunction and high blood pressure caused by Cd toxicity. In chronic Cd exposure, these antioxidants protect vascular endothelium by increasing nitric oxide (NO•) bioavailability and improving vascular function. Antioxidant activity against Cd intoxication results directly and/or indirectly through free radical scavenging, metal chelation, enhanced expression of the antioxidant defense system, regulation of inflammatory enzymes, increase in NO• bioavailability, and reduction of gastrointestinal absorption and tissue Cd accumulation. This review summarizes current knowledge of Cd-induced oxidative stress and cardiovascular dysfunction and a possible protective effect conferred by the antioxidants curcumin and tetrahydrocurcumin.


The Glycerate and Phosphorylated Pathways of Serine Synthesis in Plants: The Branches of Plant Glycolysis Linking Carbon and Nitrogen Metabolism.
Serine metabolism in plants has been studied mostly in relation to photorespiration where serine is formed from two molecules of glycine. However, two other pathways of serine formation operate in plants and represent the branches of glycolysis diverging at the level of 3-phosphoglyceric acid. One branch (the glycerate - serine pathway) is initiated in the cytosol and involves glycerate formation from 3-phosphoglycerate, while the other (the phosphorylated serine pathway) operates in plastids and forms phosphohydroxypyruvate as an intermediate. Serine formed in these pathways becomes a precursor of glycine, formate and glycolate accumulating in stress conditions. The pathways can be linked to GABA shunt via transamination reactions and via participation of the same reductase for both glyoxylate and succinic semialdehyde. In this review paper we present a hypothesis of the regulation of redox balance in stressed plant cells via participation of the reactions associated with glycerate and phosphorylated serine pathways. We consider these pathways as important processes linking carbon and nitrogen metabolism and maintaining cellular redox and energy levels in stress conditions.


Natural products against cancer: a comprehensive bibliometric study of the research projects, publications, patents and drugs.
To analyze multi-source data including awards, publications, patents and drugs, and try to draw the whole landscape of the research and development community in the area of natural products (NPs) against cancer. Awards, publications, patents and drugs data from National Institute of Health/Natural Science Foundation of China (NIH/NSFC), PubMed, Derwent Innovation Index and Cortellis were collected. Bibliometric methodologies and technology are used to investigate publications/patents/drugs, their contents and relationships. NIH and NSFC respectively demonstrated a stable and sustained expenditure growth in this area. The number of publications is continuously increasing. Yet the annual patent applications worldwide and FDA drug approvals were little changed or not obviously fluctuated in 2003-2013. USA and several Asia-pacific countries/territories are important contributing powers. We described the evolution of major research topics by those MeSH Major Topics indexed in PubMed with the largest growth range in three intervals, and analyzed hot research topics in the recent 10 years which include NPs or NPs derivatives, cell line/animal model, laboratory technologies and activation mechanisms. China published the most publications and received the most patent applications, but drug discovery performance is no better than USA and Japan. Research on anti-neoplastic structures and compounds originated from Chinese traditional medicine (TCM), medicinal plants, herbal medicine and marine NPs are major research topics in the recent 10 years. There still exits translational gap between basic research and drug discovery. Translational research should be undertaken to strengthen the applicability of NPs.


Laboratory Monitoring of Oral Vitamin K Anticoagulation.
Vitamin K antagonists (VKA) have been used for many years as effective anticoagulant therapy. The laboratory plays a crucial role in measuring the prothrombin time (PT) and calculating the international normalized ratio (INR). Each component of the calculation has the potential to increase error in the final result. This article discusses the laboratory aspects of monitoring VKA including sample requirements, PT, determination of the INR, point of care (POC) testing, external quality assurance/proficiency testing, and reversal strategies for VKA therapy. The implementation of the PT/INR reporting standard was a significant improvement in laboratory medicine. However, further room for improvement exists in the management of PT/INR testing, to clarify the role of POC testing and continue the harmonization process to ensure reliability and reproducibility of INR results.


Characterization of nitrogen mustard formamidopyrimidine adduct formation of bis(2-chloroethyl)ethylamine with calf thymus DNA and a human mammary cancer cell line.
A robust, quantitative ultraperformance liquid chromatography ion trap multistage scanning mass spectrometric (UPLC/MS(3)) method was established to characterize and measure five guanine adducts formed by reaction of the chemotherapeutic nitrogen mustard (NM) bis(2-chloroethyl)ethylamine with calf thymus (CT) DNA. In addition to the known N7-guanine (NM-G) adduct and its cross-link (G-NM-G), the ring-opened formamidopyrimidine (FapyG) monoadduct (NM-FapyG) and cross-links in which one (FapyG-NM-G) or both (FapyG-NM-FapyG) guanines underwent ring-opening to FapyG units were identified. Authentic standards of all adducts were synthesized and characterized by NMR and mass spectrometry. These adducts were quantified in CT DNA treated with NM (1 μM) as their deglycosylated bases. A two-stage neutral thermal hydrolysis was developed to mitigate the artifactual formation of ring-opened FapyG adducts involving hydrolysis of the cationic adduct at 37 °C, followed by hydrolysis of the FapyG adducts at 95 °C. The limit of quantification values ranged between 0.3 and 1.6 adducts per 10(7) DNA bases when the equivalent of 5 μg of DNA hydrolysate was assayed on column. The principal adduct formed was the G-NM-G cross-link, followed by the NM-G monoadduct; the FapyG-NM-G cross-link adduct; and the FapyG-NM-FapyG was below the limit of detection. The NM-FapyG adducts were formed in CT DNA at a level ∼20% that of the NM-G adduct. NM-FapyG has not been previously quanitified, and the FapyG-NM-G and FapyG-NM-FapyG adducts have not been previously characterized. Our validated analytical method was then applied to measure DNA adduct formation in the MDA-MB-231 mammary tumor cell line exposed to NM (100 μM) for 24 h. The major adduct formed was NM-G (970 adducts per 10(7) bases), followed by G-NM-G (240 adducts per 10(7) bases), NM-FapyG (180 adducts per 10(7) bases), and, last, the FapyG-NM-G cross-link adduct (6.0 adducts per 10(7) bases). These lesions are expected to contribute to NM-mediated toxicity and genotoxicity in vivo.


Two nucleophilic mutants of the Micromonospora viridifaciens sialidase operate with retention of configuration by two different mechanisms.
Mutants of the Micromonospora viridifaciens sialidase, Y370E and Y370F, are catalytically active retaining enzymes that operate by different mechanisms. Previous substitutions with smaller amino acids, including Y370D, yielded inverting sialidases. At least one water molecule can fit into the active-site cavity of this mutant and act as a nucleophile from the face opposite the leaving group (Biochemistry 2003, 42, 12 682). Thus, addition of a CH(2) unit (Asp versus Glu) changes the mechanism from inversion back to retention of configuration. Based on Brønsted beta(lg) values, it is proposed that the Y370E mutant reacts by a double-displacement mechanism (beta(lg) on k(cat)/K(m) -0.36+/-0.04) with Glu370 acting as the nucleophile. However, the Y370F mutant (beta(lg) on k(cat)/K(m) -0.79+/-0.12) reacts via a dissociative transition state. The crystal structure of the Y370F mutant complexed with 2-deoxy-2,3-dehydro-N-acetylneuraminic acid shows no significant active-site perturbation relative to the wild-type enzyme.


A qualitative exploration of the emotional wellbeing and support needs of new mothers from Afghanistan living in Melbourne, Australia.
The Afghan community is a priority population for many health and social services within the southeast region of Melbourne, which is home to the largest population of Afghanistan-born people within the state of Victoria. The majority of Afghan women arriving in Australia are of childbearing age, and evidence suggests that they are at increased risk of emotional challenges following birth as a result of the refugee and migration experience. This research aimed to explored the experiences of Afghan women living in Melbourne throughout pregnancy, birth, and early motherhood, and gain insight into the aspects of their experiences that they perceive as positively and negatively impacting their emotional wellbeing. This qualitative study collected data through two focus group discussions (conducted in Dari) and 10 in-depth interviews (conducted in Dari or English). Thirty-eight Afghanistan-born women aged 18 years and older, who recently migrated to Australia and have at least one Australian-born child, were purposively selected to participate. A trained bicultural worker assisted in recruitment, data collection and translation. Thematic analysis was performed, and findings were confirmed with a subgroup of participants prior to being included within reporting. Participants consistently discussed experiencing emotional challenges following birth, identifying symptoms commonly associated with postnatal depression. Women largely attributed this emotional state to separation from family and culture, leading to loneliness, isolation, and disconnection. Participants expressed resistance towards professional support due to cultural stigma associated with mental illness. Partner support was seen to be positive but difficult to negotiate. Religion, strong relationship with child, forming friendships, education, and utilising childcare were identified as positive influences on the emotional wellbeing of women. This study highlighted social and cultural factors contributing towards the emotional wellbeing of Afghan mothers. Findings confirm the need for innovative community-based models to support the mental health of Afghan women. This is particularly pertinent given the identified resistance towards discussing emotional wellbeing with healthcare professionals. Further research and investment is required in this area.


Prospective derivation of a clinical decision rule for thoracolumbar spine evaluation after blunt trauma: An American Association for the Surgery of Trauma Multi-Institutional Trials Group Study.
Unlike the cervical spine (C-spine), where National Emergency X-Radiography Utilization Study (NEXUS) and the Canadian C-spine Rules can be used, evidence-based thoracolumbar spine (TL-spine) clearance guidelines do not exist. The aim of this study was to develop a clinical decision rule for evaluating the TL-spine after injury. Adult (≥15 years) blunt trauma patients were prospectively enrolled at 13 US trauma centers (January 2012 to January 2014). Exclusion criteria included the following: C-spine injury with neurologic deficit, preexisting paraplegia/tetraplegia, and unevaluable examination. Remaining evaluable patients underwent TL-spine imaging and were followed up to discharge. The primary end point was a clinically significant TL-spine injury requiring TL-spine orthoses or surgical stabilization. Regression techniques were used to develop a clinical decision rule. Decision rule performance in identifying clinically significant fractures was tested. Of 12,479 patients screened, 3,065 (24.6%) met inclusion criteria (mean [SD] age, 43.5 [19.8] years [range, 15-103 years]; male sex, 66.3%; mean [SD] Injury Severity Score [ISS], 8.8 [7.5]). The majority underwent computed tomography (93.3%), 6.3% only plain films, and 0.2% magnetic resonance imaging exclusively. TL-spine injury was identified in 499 patients (16.3%), of which 264 (8.6%) were clinically significant (29.2% surgery, 70.8% TL-spine orthosis). The majority was AO Type A1 282 (56.5%), followed by 67 (13.4%) A3, 43 (8.6%) B2, and 32 (6.4%) A4 injuries. The predictive ability of clinical examination (pain, midline tenderness, deformity, neurologic deficit), age, and mechanism was examined; positive clinical examination finding resulted in a sensitivity of 78.4% and a specificity of 72.9%. Addition of age of 60 years or older and high-risk mechanism (fall, crush, motor vehicle crash with ejection/rollover, unenclosed vehicle crash, auto vs. pedestrian) increased sensitivity to 98.9% with specificity of 29.0% for clinically significant injuries and 100.0% sensitivity and 27.3% specificity for injuries requiring surgery. Clinical examination alone is insufficient for determining the need for imaging in evaluable patients at risk of TL-spine injury. Addition of age and high-risk mechanism results in a clinical decision-making rule with a sensitivity of 98.9% for clinically significant injuries. Diagnostic test, level III.


Decreased renal accumulation of aminoglycoside reflects defective receptor-mediated endocytosis in cystic fibrosis and Dent's disease.
The clinical use of aminoglycoside (AG) antibiotics is limited by their renal toxicity, which is caused by drug accumulation in proximal tubule (PT) cells. Clinical studies reported that renal clearance of AG is enhanced in cystic fibrosis (CF) patients, which might reflect the role of CFTR in PT cell endocytosis. In order to assess the role of chloride transporters on the renal handling of AG, we investigated gentamicin uptake and renal accumulation in mice lacking functional CFTR (Cftr ( ∆F/∆F)) or knock-out for the Cl(-)/H(+) exchanger ClC-5 (Clcn5 ( Y/- )). The latter represent a paradigm of PT dysfunction and defective receptor-mediated endocytosis. As compared with controls, Cftr ( ∆F/∆F) and Clcn5 ( Y/- ) mice showed a 15% to 85% decrease in gentamicin accumulation in the kidney, respectively, in absence of renal failure. Studies on primary cultures of Cftr ( ∆F/∆F) and Clcn5 ( Y/- ) mouse PT cells confirmed the reduction in gentamicin uptake, although colocalization with endosomes and lysosomes was maintained. Quantification of endocytosis in PT cells revealed that gentamicin, similar to albumin, preferentially binds to megalin. The functional loss of ClC-5 or CFTR was reflected by a decrease of the endocytic uptake of gentamicin, with a more pronounced effect in cells lacking ClC-5. These results support the concept that CFTR, as well as ClC-5, plays a relevant role in PT cell endocytosis. They also demonstrate that the functional loss of these two chloride transporters is associated with impaired uptake of AG in PT cells, reflected by a decreased renal accumulation of the drug.


A chick bioassay approach for determining the bioavailable choline concentration in normal and overheated soybean meal, canola meal and peanut meal.
Our objectives were to use a soy protein isolate (SPI) diet containing 2-amino-2-methyl-1-propanol, an inhibitor of choline biosynthesis, to determine the bioavailable choline content of normal and overheated soybean meal (SBM), canola meal (CM) and peanut meal (PM). In the first four experiments, it was determined that weight gain of chicks fed the basal diet would respond linearly (P < 0.05) to graded levels of crystalline choline and would not respond to betaine, and that when fortified with adequate choline, no weight gain or feed intake response would occur upon addition of 100 g/kg SBM, CM or PM to the basal diet. Furthermore, addition of crystalline amino acids simulating the amino acid composition of 100 g/kg SBM did not alter the utilization of crystalline choline. In Experiment 5, feeding graded doses of choline, SBM, CM or PM resulted in linear (P < 0.05) increases in weight gain. Multiple linear regression analysis indicated bioavailable choline concentrations of 1708, 1545 and 1203 mg/kg for SBM, CM and PM, respectively. In Experiment 6, no differences (P > 0.05) in bioavailable choline concentrations occurred between normal and overheated SBM, CM or PM, and the bioavailable choline concentration of normal SBM, CM and PM was 2002, 1464 and 1320 mg/kg, respectively. Average bioavailable choline levels were 83, 24 and 76% of analytically determined choline levels in SBM, CM and PM, respectively. Canola meal, although three times as rich in total choline as SBM, has less bioavailable choline than SBM. A substantial portion of choline in SBM, CM and PM is unavailable, and overheating does not appear to decrease the bioavailability of choline in these products.


Electrochemical Potential Derived from Atomic Cluster Structures.
Based on the atomic cluster structures and free electron approximation model, it is revealed that the electrochemical potential (ECP) for the system of interest is proportional to the reciprocal of atomic cluster radius squared, i.e., φ = k·(1/r(2)). Applied to elemental crystals, the correlation between atomic cluster radii and the ECP that we have predicted agrees well with the previously reported results. In addition, some other physicochemical properties associated with the ECP have also been found relevant to the atomic cluster radii of materials. Thus, the atomic cluster radii can be perceived as an effective characteristic parameter to measure the ECP and related properties of materials. Our results provide a better understanding of ECP directly from the atomic structures perspective.


Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy.
Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by loss of survival motor neuron (SMN) protein. While SMN restoration therapies are beneficial, they are not a cure. We aimed to identify potentially novel treatments to alleviate muscle pathology combining transcriptomics, proteomics, and perturbational data sets. This revealed potential drug candidates for repurposing in SMA. One of the candidates, harmine, was further investigated in cell and animal models, improving multiple disease phenotypes, including lifespan, weight, and key molecular networks in skeletal muscle. Our work highlights the potential of multiple and parallel data-driven approaches for the development of potentially novel treatments for use in combination with SMN restoration therapies.


Making classical ground-state spin computing fault-tolerant.
We examine a model of classical deterministic computing in which the ground state of the classical system is a spatial history of the computation. This model is relevant to quantum dot cellular automata as well as to recent universal adiabatic quantum computing constructions. In its most primitive form, systems constructed in this model cannot compute in an error-free manner when working at nonzero temperature. However, by exploiting a mapping between the partition function for this model and probabilistic classical circuits we are able to show that it is possible to make this model effectively error-free. We achieve this by using techniques in fault-tolerant classical computing and the result is that the system can compute effectively error-free if the temperature is below a critical temperature. We further link this model to computational complexity and show that a certain problem concerning finite temperature classical spin systems is complete for the complexity class Merlin-Arthur. This provides an interesting connection between the physical behavior of certain many-body spin systems and computational complexity.


Stage-dependent remodeling of the nuclear envelope and lamina during rabbit early embryonic development.
Utilizing 3D structured illumination microscopy, we investigated the quality and quantity of nuclear invaginations and the distribution of nuclear pores during rabbit early embryonic development and identified the exact time point of nucleoporin 153 (NUP153) association with chromatin during mitosis. Contrary to bovine early embryonic nuclei, featuring almost exclusively nuclear invaginations containing a small volume of cytoplasm, nuclei in rabbit early embryonic stages show additionally numerous invaginations containing a large volume of cytoplasm. Small-volume invaginations frequently emanated from large-volume nuclear invaginations but not vice versa, indicating a different underlying mechanism. Large- and small-volume nuclear envelope invaginations required the presence of chromatin, as they were restricted to chromatin-positive areas. The chromatin-free contact areas between nucleolar precursor bodies (NPBs) and large-volume invaginations were free of nuclear pores. Small-volume invaginations were not in contact with NPBs. The number of invaginations and isolated intranuclear vesicles per nucleus peaked at the 4-cell stage. At this stage, the nuclear surface showed highly concentrated clusters of nuclear pores surrounded by areas free of nuclear pores. Isolated intranuclear lamina vesicles were usually NUP153 negative. Cytoplasmic, randomly distributed NUP153-positive clusters were highly abundant at the zygote stage and decreased in number until they were almost absent at the 8-cell stage and later. These large NUP153 clusters may represent a maternally provided NUP153 deposit, but they were not visible as clusters during mitosis. Major genome activation at the 8- to 16-cell stage may mark the switch from a necessity for a deposit to on-demand production. NUP153 association with chromatin is initiated during metaphase before the initiation of the regeneration of the lamina. To our knowledge, the present study demonstrates for the first time major remodeling of the nuclear envelope and its underlying lamina during rabbit preimplantation development.


Derivation of snake venom gland organoids for in vitro venom production.
More than 400,000 people each year suffer adverse effects following bites from venomous snakes. However, snake venom is also a rich source of bioactive molecules with known or potential therapeutic applications. Manually 'milking' snakes is the most common method to obtain venom. Safer alternative methods to produce venom would facilitate the production of both antivenom and novel therapeutics. This protocol describes the generation, maintenance and selected applications of snake venom gland organoids. Snake venom gland organoids are 3D culture models that can be derived within days from embryonic or adult venom gland tissues from several snake species and can be maintained long-term (we have cultured some organoids for more than 2 years). We have successfully used the protocol with glands from late-stage embryos and recently deceased adult snakes. The cellular heterogeneity of the venom gland is maintained in the organoids, and cell type composition can be controlled through changes in media composition. We describe in detail how to derive and grow the organoids, how to dissociate them into single cells, and how to cryopreserve and differentiate them into toxin-producing organoids. We also provide guidance on useful downstream assays, specifically quantitative real-time PCR, bulk and single-cell RNA sequencing, immunofluorescence, immunohistochemistry, fluorescence in situ hybridization, scanning and transmission electron microscopy and genetic engineering. This stepwise protocol can be performed in any laboratory with tissue culture equipment and enables studies of venom production, differentiation and cellular heterogeneity.


Localization of adenylate cyclase in unfixed sections of cardiac muscle.
Previous investigators have shown that prefixation and lead staining completely inhibit the activity of adenylate cyclase. Lead has also been shown to stimulate the nonenzymatic hydrolysis of AMP-PMP (the substrate for adenylate cyclase) after 30 min incubation. The present studies were performed to determine if the omission of prefixation would provide a better method for localizing adenylate cyclase in cardiac muscle. These studies were also performed to determine the effect of short incubation on the lead-induced nonenzymatic hydrolysis of AMP-PNP. In prefixed sections the reaction product was diffusely localized over the section. However, in unfixed sections the reaction product appeared only on the sarcolemma and sarcotubule system. Results are presented showing that short incubation (i.e., 5 min) prevents the nonenzymatic hydrolysis of AMP-PMP by lead. In biochemical studies lead (10(-3) M) was shown to completely inhibit the activity of this enzyme. However, in the presence of 4 micrograms phosphatidylinositol, lead inhibition of this enzyme was reduced to 50% of the control value. Based on this observation, it is suggested that approximately 50% of adenylate cyclase is present in sections of cardiac muscle exposed to 2 x 10(-3) M lead, which is presumably enough activity for demonstration of adenylate cyclase activity.


Genetic Reagents for Making Split-GAL4 Lines in Drosophila.
The ability to reproducibly target expression of transgenes to small, defined subsets of cells is a key experimental tool for understanding many biological processes. The Drosophila nervous system contains thousands of distinct cell types and it has generally not been possible to limit expression to one or a few cell types when using a single segment of genomic DNA as an enhancer to drive expression. Intersectional methods, in which expression of the transgene only occurs where two different enhancers overlap in their expression patterns, can be used to achieve the desired specificity. This report describes a set of over 2800 transgenic lines for use with the split-GAL4 intersectional method.


Diagnostic criteria and symptom grading for delayed gastric conduit emptying after esophagectomy for cancer: international expert consensus based on a modified Delphi process.
Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air-fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process.


Renal transplantation from HLA-haploidentical living-related donors: the effects of donor-specific blood transfusions and different immunosuppressive regimens.
One-hundred-nine HLA-haploidentical living related renal transplants have been retrospectively analysed to compare the effect of donor-specific blood transfusion (DST) and different immunosuppressive regimens on graft survival and acute rejection. The recipients were divided into four groups according to the immunosuppressive therapy. Group 1 (n = 44): conventional therapy with posttransplant azathioprine (AZP) + methylprednisolone (MP). Group 2 (n = 25): pretransplant DST + posttransplant AZP + MP. Group 3 (n = 12): triple-drug therapy with posttransplant AZP + MP + cyclosporine (CS). Group 4 (n = 25): pretransplant DST + posttransplant AZP + MP + CS. The five-year actuarial survival rates for groups 1, 2, 3 and 4 were 48%, 73%, 79%, and 89%, respectively. The graft survival rate in group 3 was significantly (p less than 0.01) better than that in group 1. The transfusion effect was reduced, and appears as a 10% improvement in the graft survival in the cyclosporin era compared with a 25% improvement at pre-cyclosporin era. Furthermore, the incidence of the first rejection episode was decreased in recipients that received DST. The present study revealed that DST, as pretransplant conditioning has a definite impact on rejection-free long-term graft survival in HLA-haploidentical living-related kidney recipients and the most favorable outcome in such patients could be achieved by DST pretreatment in conjunction with posttransplant triple-drug therapy including cyclosporine.


Sirt6 enhances macrophage lipophagy and improves lipid metabolism disorder by regulating the Wnt1/β-catenin pathway in atherosclerosis.
Lipid metabolism disorders are considerably involved in the pathology of atherosclerosis; nevertheless, the fundamental mechanism is still largely unclear. This research sought to examine the function of lipophagy in lipid metabolism disorder-induced atherosclerosis and its fundamental mechanisms. Previously, Sirt6 has been reported to stimulate plaque stability by promoting macrophage autophagy. However, its role in macrophage lipophagy and its relationship with Wnt1 remains to be established. In this study, ApoE-/-: Sirt6-/- and ApoE-/-: Sirt6Tg mice were used and lipid droplets were analysed via transmission electron microscopy and Bodipy 493/503 staining in vitro. Atherosclerotic plaques in ApoE-/-: Sirt6-/- mice showed greater necrotic cores and lower stability score. Reconstitution of Sirt6 in atherosclerotic mice improved lipid metabolism disorder and prevented the progression of atherosclerosis. Furthermore, macrophages with Ac-LDL intervention showed more lipid droplets and increased expression of adipophilin and PLIN2. Reconstitution of Sirt6 recruited using SNF2H suppressed Wnt1 expression and improved lipid metabolism disorder by promoting lipophagy. In addition, downregulation of Sirt6 expression in Ac-LDL-treated macrophages inhibited lipid droplet degradation and stimulated foam cell formation. Innovative discoveries in the research revealed that atherosclerosis is caused by lipid metabolism disorders due to downregulated Sirt6 expression. Thus, modulating Sirt6's function in lipid metabolism might be a useful therapeutic approach for treating atherosclerosis.


Iris segmentation using an edge detector based on fuzzy sets theory and cellular learning automata.
Iris-based biometric systems identify individuals based on the characteristics of their iris, since they are proven to remain unique for a long time. An iris recognition system includes four phases, the most important of which is preprocessing in which the iris segmentation is performed. The accuracy of an iris biometric system critically depends on the segmentation system. In this paper, an iris segmentation system using edge detection techniques and Hough transforms is presented. The newly proposed edge detection system enhances the performance of the segmentation in a way that it performs much more efficiently than the other conventional iris segmentation methods.


Transient Cognitive Impairment and White Matter Hyperintensities in Severely Depressed Older Patients Treated With Electroconvulsive Therapy.
Although electroconvulsive therapy (ECT) is a safe and effective treatment for patients with severe late life depression (LLD), transient cognitive impairment can be a reason to discontinue the treatment. The aim of the current study was to evaluate the association between structural brain characteristics and general cognitive function during and after ECT. A total of 80 patients with LLD from the prospective naturalistic follow-up Mood Disorders in Elderly treated with Electroconvulsive Therapy study were examined. Magnetic resonance imaging scans were acquired before ECT. Overall brain morphology (white and grey matter) was evaluated using visual rating scales. Cognitive functioning before, during, and after ECT was measured using the Mini Mental State Examination (MMSE). A linear mixed-model analysis was performed to analyze the association between structural brain alterations and cognitive functioning over time. Patients with moderate to severe white matter hyperintensities (WMH) showed significantly lower MMSE scores than patients without severe WMH (F(1,75.54) = 5.42, p = 0.02) before, during, and post-ECT, however their trajectory of cognitive functioning was similar as no time × WMH interaction effect was observed (F(4,65.85) = 1.9, p = 0.25). Transient cognitive impairment was not associated with medial temporal or global cortical atrophy (MTA, GCA). All patients showed a significant drop in cognitive functioning during ECT, which however recovered above baseline levels post-ECT and remained stable until at least 6 months post-ECT, independently of severity of WMH, GCA, or MTA. Therefore, clinicians should not be reluctant to start or continue ECT in patients with severe structural brain alterations.


Improved residue contact prediction using support vector machines and a large feature set.
Predicting protein residue-residue contacts is an important 2D prediction task. It is useful for ab initio structure prediction and understanding protein folding. In spite of steady progress over the past decade, contact prediction remains still largely unsolved. Here we develop a new contact map predictor (SVMcon) that uses support vector machines to predict medium- and long-range contacts. SVMcon integrates profiles, secondary structure, relative solvent accessibility, contact potentials, and other useful features. On the same test data set, SVMcon's accuracy is 4% higher than the latest version of the CMAPpro contact map predictor. SVMcon recently participated in the seventh edition of the Critical Assessment of Techniques for Protein Structure Prediction (CASP7) experiment and was evaluated along with seven other contact map predictors. SVMcon was ranked as one of the top predictors, yielding the second best coverage and accuracy for contacts with sequence separation > or = 12 on 13 de novo domains. We describe SVMcon, a new contact map predictor that uses SVMs and a large set of informative features. SVMcon yields good performance on medium- to long-range contact predictions and can be modularly incorporated into a structure prediction pipeline.


Suicide in adolescents: using life charts to understand the suicidal process.
A greater understanding of the pathways which lead young people to take their lives is important in ensuring that prevention strategies and health service delivery are as effective as possible. In this study we examined the duration, development and characteristics of the suicidal process in young people who ultimately died by suicide. Life charts of psychological autopsy information from multiple informants were used to identify the suicidal process among 27 young people who died by suicide. Life charts were generated for 27 young people who died by suicide, of whom 93% (n=25) were male, with an average age at death of 20.9 years (SD=2.4). Three types of suicidal process were identified: Group I characterised by longstanding difficulties which spanned the developmental domains of home, school and peers. The suicidal process was longstanding, and included deliberate self-harm prior to their death and direct communication to friends and family about suicidal ideas and plans. The second group was characterised by evidence of an established psychiatric disorder. Two subgroups were identified, namely those individuals with a protracted suicidal process which lasted approximately 5-9 years, and those with a brief suicidal process lasting approximately one year. The third and smallest group was characterised by the emergence of the suicidal process as an acute response to life events among young people who appeared to have previously been functioning well, without apparent mental illness or known self-harm. However, two out of five in this group communicated specific suicidal intent in the weeks before their death. The suicidal process may emerge and disappear in the lives of young people. Repeated episodes of self-cutting by young men, against a backdrop of substance abuse, relationship difficulties, and mental health problems require further clinical attention.


Psychological capacity limitations according to Mini-ICF-APP are differently related with sick leave in patients from different professional fields.
Up to 29% of the working population suffer from (chronic) mental disorders and work disability. As different professions pose different psychological capacity demands, one core aspect for describing work disability is psychological capacity limitations. The distribution of capacity limitations in patients with chronic mental disorders (CMD) from different professional fields is unknown, as well as their relation with sick leave. Are there different work ability limitations in CMD patients working in different professions? 263 CMD patients from different professions were investigated cross-sectionally in a thorough medical and psychological assessment by a trained psychosomatic study physician. Besides CMD diagnostic (MINI) and subjective work ability limitations (IMET), an observer rating on capacity limitations was conducted with Mini-ICF-APP. No relevant differences in perceived work ability limitations were found between the professions. Differences of capacity limitations were better explained by psychopathology than by profession. But capacity limitations were differently related with sick leave in different professions and there are differences in sick leave duration. The variance of capacity limitations was explained by psychopathology. The variance of sick leave duration was explained by profession. Similar capacity limitations are associated differently with sick leave in different professions. Different professional fields may have different tolerances towards the same capacity limitations. Therefore, similar capacity limitations are more or less strongly associated with sick leave in different professions.


Orienteering in knowledge spaces: the hyperbolic geometry of Wikipedia Mathematics.
In this paper we show how the coupling of the notion of a network with directions with the adaptation of the four-point probe from materials testing gives rise to a natural geometry on such networks. This four-point probe geometry shares many of the properties of hyperbolic geometry wherein the network directions take the place of the sphere at infinity, enabling a navigation of the network in terms of pairs of directions: the geodesic through a pair of points is oriented from one direction to another direction, the pair of which are uniquely determined. We illustrate this in the interesting example of the pages of Wikipedia devoted to Mathematics, or "The MathWiki." The applicability of these ideas extends beyond Wikipedia to provide a natural framework for visual search and to prescribe a natural mode of navigation for any kind of "knowledge space" in which higher order concepts aggregate various instances of information. Other examples would include genre or author organization of cultural objects such as books, movies, documents or even merchandise in an online store.


Novel paclitaxel formulations solubilized by parenteral nutrition nanoemulsions for application against glioma cell lines.
The aim of this study is to investigate using nanoemulsion formulations as drug-delivery vehicles of paclitaxel (PX), a poor water-soluble anticancer drug. Two commercially available nanoemulsion fat formulations (Clinoleic 20% and Intralipid 20%) were loaded with PX and characterised based on their size, zeta potential, pH and loading efficiency. The effect of formulation on the cytotoxicity of PX was also evaluated using MTT assay. The droplet size of the Clinoleic emulsion increased from 254.1nm to 264.7nm when paclitaxel (6mg/ml) was loaded into the formulation, compared to the drug-free formulation. Similarly, the droplet size of Intralipid increased from 283.3 to 294.6nm on inclusion of 6mg/ml paclitaxel. The Polydispersity Indexes (PDIs) of all the nanoemulsion formulations (Clinoleic and Intralipid) were less than 0.2 irrespective of paclitaxel concentration indicating that all nanoemulsion formulations used were homogeneously sized. The pH range for the Clinoleic formulations (7.1-7.5) was slightly higher than that of the Intralipid formulations (6.5-6.9). The zeta potential of linoleic had a greater negative value than that of Intralipid. Loading efficiencies for paclitaxel were 70.4-80.2% and 44.2-57.4% for Clinoleic and Intralipid formulations, respectively. Clinoleic loaded with paclitaxel decreased the viability of U87-MG cell to 6.4±2.3%, compared to Intralipid loaded with paclitaxel (21.29±3.82%). Both nanoemulsions were less toxic to the normal glial cells (SVG-P12), decreasing the cell viability to 25-35%. This study suggests that nanoemulsions are useful and potentially applicable vehicles of paclitaxel for treatment of glioma.


Effects of Firing Variability on Network Structures with Spike-Timing-Dependent Plasticity.
Synaptic plasticity is believed to be the biological substrate underlying learning and memory. One of the most widespread forms of synaptic plasticity, spike-timing-dependent plasticity (STDP), uses the spike timing information of presynaptic and postsynaptic neurons to induce synaptic potentiation or depression. An open question is how STDP organizes the connectivity patterns in neuronal circuits. Previous studies have placed much emphasis on the role of firing rate in shaping connectivity patterns. Here, we go beyond the firing rate description to develop a self-consistent linear response theory that incorporates the information of both firing rate and firing variability. By decomposing the pairwise spike correlation into one component associated with local direct connections and the other associated with indirect connections, we identify two distinct regimes regarding the network structures learned through STDP. In one regime, the contribution of the direct-connection correlations dominates over that of the indirect-connection correlations in the learning dynamics; this gives rise to a network structure consistent with the firing rate description. In the other regime, the contribution of the indirect-connection correlations dominates in the learning dynamics, leading to a network structure different from the firing rate description. We demonstrate that the heterogeneity of firing variability across neuronal populations induces a temporally asymmetric structure of indirect-connection correlations. This temporally asymmetric structure underlies the emergence of the second regime. Our study provides a new perspective that emphasizes the role of high-order statistics of spiking activity in the spike-correlation-sensitive learning dynamics.


Optical analysis of a liquid-crystal switch system based on total internal reflection.
A complete methodology using matrix representations for describing light transmission and reflection at an interface between an isotropic medium with high refractive index and a uniaxial birefringent material where total internal reflection (TIR) could happen is described systematically. A new TIR-based liquid-crystal (LC) switch system is proposed and investigated in detail by using this analyzing method. The criteria of selection of critical parameters such as LC mixture, waveguide, and operation mode of the LC layer, etc., are discussed. Dependence of transmission on incident angle and dynamic characteristics under an electric field are given for different cell gaps. The results give detailed and useful guidance in the fabrication of the LC switch system.


Hairy transcriptional repression targets and cofactor recruitment in Drosophila.
Members of the widely conserved Hairy/Enhancer of split family of basic Helix-Loop-Helix repressors are essential for proper Drosophila and vertebrate development and are misregulated in many cancers. While a major step forward in understanding the molecular mechanism(s) surrounding Hairy-mediated repression was made with the identification of Groucho, Drosophila C-terminal binding protein (dCtBP), and Drosophila silent information regulator 2 (dSir2) as Hairy transcriptional cofactors, the identity of Hairy target genes and the rules governing cofactor recruitment are relatively unknown. We have used the chromatin profiling method DamID to perform a global and systematic search for direct transcriptional targets for Drosophila Hairy and the genomic recruitment sites for three of its cofactors: Groucho, dCtBP, and dSir2. Each of the proteins was tethered to Escherichia coli DNA adenine methyltransferase, permitting methylation proximal to in vivo binding sites in both Drosophila Kc cells and early embryos. This approach identified 40 novel genomic targets for Hairy in Kc cells, as well as 155 loci recruiting Groucho, 107 loci recruiting dSir2, and wide genomic binding of dCtBP to 496 loci. We also adapted DamID profiling such that we could use tightly gated collections of embryos (2-6 h) and found 20 Hairy targets related to early embryogenesis. As expected of direct targets, all of the putative Hairy target genes tested show Hairy-dependent expression and have conserved consensus C-box-containing sequences that are directly bound by Hairy in vitro. The distribution of Hairy targets in both the Kc cell and embryo DamID experiments corresponds to Hairy binding sites in vivo on polytene chromosomes. Similarly, the distributions of loci recruiting each of Hairy's cofactors are detected as cofactor binding sites in vivo on polytene chromosomes. We have identified 59 putative transcriptional targets of Hairy. In addition to finding putative targets for Hairy in segmentation, we find groups of targets suggesting roles for Hairy in cell cycle, cell growth, and morphogenesis, processes that must be coordinately regulated with pattern formation. Examining the recruitment of Hairy's three characterized cofactors to their putative target genes revealed that cofactor recruitment is context-dependent. While Groucho is frequently considered to be the primary Hairy cofactor, we find here that it is associated with only a minority of Hairy targets. The majority of Hairy targets are associated with the presence of a combination of dCtBP and dSir2. Thus, the DamID chromatin profiling technique provides a systematic means of identifying transcriptional target genes and of obtaining a global view of cofactor recruitment requirements during development.


Clinical holistic medicine: prevention through healthy lifestyle and quality of life.
Biomedical prevention of diseases seems very difficult, but we believe that holistic medicine offers a simple and seemingly efficient solution that is useful for both physicians and dentists in their clinics, with a focus on improvement of quality of life as an important supplement to improving their patients' lifestyles. Quality of life is improved when the patient's personal philosophy of life is adjusted in accordance with life and its fundamental purpose. The relevant concept of personal growth can be introduced to the motivated patient in the clinic, during the conversation with the dentist. To prevent health problems in the future, personal development must focus on improving the quality of life of the patient by: 1) increasing self insight to obtain knowledge and understanding of the purpose of life; 2) recovery of character to be the good person the patient really is; and 3) full expression of talent in private and professional life in order to be optimally valuable to the patient and others. It is also important to work on the ethics of the patient to prevent the patient from destroying personal relationships and harm others, because such deeds will almost always also damage the patient. Parallel to clinical work, we believe that dentists can make an impact on their patients and inspire an improvement in their quality of life. The dentist, who sees the patient at shorter intervals, can coach his patient and often efficiently help him/her to improve intimacy and personal relationships, consciousness of responsibility, and quality of life which might be highly beneficial for the patient's health.


Use of cardiac radionuclide imaging to identify patients at risk for arrhythmic sudden cardiac death.
Sudden cardiac death (SCD) accounts for about ½ of all cardiovascular deaths, in most cases the result of a lethal ventricular arrhythmia. Patients considered at risk are often treated with an implantable cardiac defibrillator (ICD), but current criteria for device use, based largely on left ventricular ejection fraction (LVEF), leads to many patients receiving ICDs that they do not use, and many others not receiving ICDs but who suffer SCD. Thus, better methods of identifying patients at risk for SCD are needed, and radionuclide imaging offers much potential. Recent work has focused on imaging of cardiac autonomic innervation. (123)I-mIBG, a norepinephrine analog, is the tracer most studied, and a variety of positron emission tomographic tracers are also under investigation. Radionuclide autonomic imaging may identify at-risk patients with ischemic coronary artery disease, particularly following myocardial infarction and in the setting of hibernating myocardium. Most studies have been done in the setting of congestive heart failure (CHF), with a recent large multicenter study of patients with advanced disease, typically at high risk of SCD, showing that (123)I-mIBG can identify a low risk subgroup with an extremely low incidence of lethal ventricular arrhythmias and cardiac death, therefore, perhaps not requiring an ICD. Cardiac neuronal imaging has been shown to be better predictive of lethal arrhythmias/cardiac death than LVEF and New York Heart Association class, as well as various ECG parameters. Autonomic imaging will likely play an important role in the advancement of cardiac molecular imaging.


American Indian women cancer survivors' perceptions and experiences with conventional and non-conventional mental health care for depressive symptoms.
Background: Despite cancer and depression being disproportionately high for American Indian and Alaska Native (AI/AN) women, such cancer survivors' help-seeking practices and perceptions related to depression are absent in extant research. A broader context of historical oppression has set the stage for unequal health outcomes and access to quality services. The purpose of this article was to explore AI women cancer survivors' experiences with conventional mental health services and informal and tribally-based assistance, as well as barriers related to mental health service utilization.Methods: A qualitative descriptive study methodology, with qualitative content analysis, was used to examine the experiences of AI women cancer survivors as they related to help-seeking experiences for depressive symptoms. The sample included 43 AI women cancer survivors (n = 14 breast cancer, n = 14 cervical cancer, and n = 15 colon and other types of cancer survivors).Results: Since receiving a cancer diagnosis, 26 (62%) participants indicated they had feelings of depression. Some participants (n = 13) described mixed perceptions of the mental health service system. Generally, participants viewed families and informal support systems as primary forms of assistance, whereas conventional services were reported as a supplementary or 'as needed' forms of support, particularly when the informal support system was lacking. Participants received help in the forms of psychotropic medications and psychotherapy, as well as help from family and AI-specific healing modalities (e.g. sweat lodges and healing ceremonies). Stigma and confidentiality concerns were primary barriers to utilizing conventional services as described by 12 (29%) participants.Discussion: Participants' help primarily came from family and tribally-based entities, with conventional mental health care being more salient when informal supports were lacking. The mixed perceptions espoused by participants may be related to a broader context of historical oppression; family and social support and tribally-based services may be protective factors for cancer survivors with depression.


Insulin-Like Growth Factor Binding Protein-4 as a Marker of Chronic Lupus Nephritis.
Kidney biopsy remains the mainstay of Lupus Nephritis (LN) diagnosis and prognostication. The objective of this study is to identify non-invasive biomarkers that closely parallel renal pathology in LN. Previous reports have demonstrated that serum Insulin-like growth factor binding protein 4 (IGFBP-4) was increased in diabetic nephropathy in both animal models and patients. We proceeded to assess if IGFBP4 could be associated with LN. We performed ELISA using the serum of 86 patients with LN. Normal healthy adults (N = 23) and patients with other glomerular diseases (N = 20) served as controls. Compared to the healthy controls or other glomerular disease controls, serum IGFBP-4 levels were significantly higher in the patients with LN. Serum IGFBP-4 did not correlate well with systemic lupus erythematosus disease activity index (SLEDAI), renal SLEDAI or proteinuria, but it did correlate with estimated glomerular filtration rate (R = 0.609, P < 0.0001). Interestingly, in 18 patients with proliferative LN whose blood samples were obtained at the time of renal biopsy, serum IGFBP-4 levels correlated strongly with the chronicity index of renal pathology (R = 0.713, P < 0.001). IGFBP-4 emerges a potential marker of lupus nephritis, reflective of renal pathology chronicity changes.