Psychiatric nursing in prison: the state of the art?
Psychiatric nursing in prisons has received criticism from within and outside the profession in recent years. In England and Wales this amongst other issues has prompted a review of forensic health care by the United Kingdom Central Council for Nursing, Midwifery & Health Visiting (UKCC). The status of forensic psychiatric nursing as a specialty has also been disputed in the literature and the role of nurses working in this field is seen by some to be more about social control than caring. These arguments are set in the present situation of increasing numbers of mentally ill individuals in the prison system and a crisis in the availability of beds in secure units, a situation that is paralleled throughout the western world. The standard expected of health care services in prisons is equivalence with the service the public receives from the National Health Service (NHS). The number of prisoners needing transfer to hospital has increased during the last decade, resulting in competition for a limited number of suitable beds. The effect on health care centres (HCCs) in English prisons is that they now must provide long-term care for seriously mentally ill prisoners. This paper outlines the development of British psychiatric services in prisons. It then describes the HCC in Her Majesty's prison (HMP) Belmarsh and reports on recent radical changes in the management structure of this service. The aim of these changes is to produce a clinical environment in which psychiatric nurses can deliver high quality care in an area beset with difficulties for clinicians and managers and to further progress towards the goal of equivalence. These advances have been achieved through a shift of emphasis in management structure that increases the number of clinical posts and minimizes administrative and security-based responsibilities held by clinical grades. We conclude that although external contracts are necessary, much can be achieved through internal review and changes in policy.


Antigenic and cellular heterogeneity of primary uveal malignant melanomas.
Monoclonal antibody (MAb) MAb8-1H, which identifies an ocular melanoma-associated antigen, and computer-assisted cytomorphometric analysis were used to investigate antigenic and cellular heterogeneity in four atypical cases of choroidal or ciliary body melanoma. The presence of one or more well-localized, morphologically distinct areas within each uveal melanoma, suggestive of multiple tumor cell populations, was observed by conventional light microscopy. In one choroidal melanoma with an unusual bilobed configuration, MAb8-1H bound only to the anterior lobe composed of spindle melanoma cells. In the other three cases, MAb8-1H bound selectively to discrete regions within the uveal melanoma corresponding to the well-localized, morphologically distinct areas seen by light microscopy. In each case, a computer was used to calculate the nuclear area of 50 tumor cells corresponding to the areas binding or not binding MAb8-1H. In three of the four cases examined, the differences in mean nuclear area between the discrete populations of tumor cells were statistically significant. Our results suggest that some uveal melanomas are composed of two or more discrete populations of tumor cells with regard to both expression of melanoma-associated antigens and cytomorphologic features.


Comparison of pharmaceutical properties of topical non-steroidal anti-inflammatory drug preparations on quality of life.
To compare the effects of different pharmaceutical properties of commercially available topical nonsteroidal antiinflammatory drugs (NSAIDs) on the quality of life, we administered a questionnaire to 65 healthy volunteers. We investigated five creams, five gels, and four solutions of topical NSAID preparations in this study. The survey was conducted to clarify the relationship of their answers and pharmaceutical properties of the topical NSAID preparations. Questions addressed spreadability, smell, viscosity, and comfort level of the topical NSAID preparations. Among the five creams, Napageln had lower spreadability, less smell, and greater viscosity than the other preparations. Because of its easy spreadability, weak smell, and low viscosity, the volunteers favored Sector cream among the cream preparations. Among the five gel preparations, Inteban had less spreadability, stronger smell, and higher viscosity than the other preparations. The volunteers favored Epatec over the other gel preparations. All four solutions had the odor of menthol and other artificial ingredients, except for Napageln. These findings indicate that information on the pharmaceutical properties of commercially available topical NSAID preparations will be helpful to physicians and pharmacists in conducting medical treatment and prescribing.


Ecological specificity of the metagenome in a set of lower termite species supports contribution of the microbiome to adaptation of the host.
Elucidating the interplay between hosts and their microbiomes in ecological adaptation has become a central theme in evolutionary biology. A textbook example of microbiome-mediated adaptation is the adaptation of lower termites to a wood-based diet, as they depend on their gut microbiome to digest wood. Lower termites have further adapted to different life types. Termites of the wood-dwelling life type never leave their nests and feed on a uniform diet. Termites of the foraging life type forage for food outside the nest and have access to other nutrients. Here we sought to investigate whether the microbiome that is involved in food substrate breakdown and nutrient acquisition might contribute to adaptation to these dietary differences. We reasoned that this should leave ecological imprints on the microbiome. We investigated the protist and bacterial microbiomes of a total of 29 replicate colonies from five termite species, covering both life types, using metagenomic shotgun sequencing. The microbiome of wood-dwelling species with a uniform wood diet was enriched for genes involved in lignocellulose degradation. Furthermore, metagenomic patterns suggest that the microbiome of wood-dwelling species relied primarily on direct fixation of atmospheric nitrogen, while the microbiome of foraging species entailed the necessary pathways to utilize nitrogen in the form of nitrate for example from soil. Our findings are consistent with the notion that the microbiome of wood-dwelling species bears an imprint of its specialization on degrading a uniform wood diet, while the microbiome of the foraging species might reflect its adaption to access growth limiting nutrients from more diverse sources. This supports the idea that specific subsets of functions encoded by the microbiome can contribute to host adaptation.


The effects of therapeutic exercise on the balance of women with knee osteoarthritis: a systematic review.
The objective of this review was to examine evidence regarding the effects of therapeutic exercise on the balance of women with knee osteoarthritis (OA). The search was conducted in Pubmed, Medline, Lilacs, SciELO, ISI web of knowledge, PEDro and the Cochrane Collaboration. We used the keywords: "knee", "balance", "women" and "rehabilitation" in combination with "osteoarthritis". We selected randomized controlled clinical trials published in English, Portuguese and Spanish over the last 10 years. To verify the methodological quality of selected clinical trials, the PEDro Scale was applied. A total of 20 studies were found in the electronic search. Of these, only 9 met the inclusion criteria and were analyzed in full. Eight of these 9 studies were classified as having high methodological quality on the PEDro Scale. Although the methods and interventions regarding balance varied widely in these studies, most found significant improvement in the balance of women with knee OA. Since the studies included in this systematic review were of high methodological quality, we can conclude that the therapeutic exercises they used improved the balance of women with knee OA.


Resolving the Structure of a Well-Ordered Hydroxyl Overlayer on In2O3(111): Nanomanipulation and Theory.
Changes in chemical and physical properties resulting from water adsorption play an important role in the characterization and performance of device-relevant materials. Studies of model oxides with well-characterized surfaces can provide detailed information that is vital for a general understanding of water-oxide interactions. In this work, we study single crystals of indium oxide, the prototypical transparent contact material that is heavily used in a wide range of applications and most prominently in optoelectronic technologies. Water adsorbs dissociatively already at temperatures as low as 100 K, as confirmed by scanning tunneling microscopy (STM), photoelectron spectroscopy, and density functional theory. This dissociation takes place on lattice sites of the defect-free surface. While the In2O3(111)-(1 × 1) surface offers four types of surface oxygen atoms (12 atoms per unit cell in total), water dissociation happens exclusively at one of them together with a neighboring pair of 5-fold coordinated In atoms. These O-In groups are symmetrically arranged around the 6-fold coordinated In atoms at the surface. At room temperature, the In2O3(111) surface thus saturates at three dissociated water molecules per unit cell, leading to a well-ordered hydroxylated surface with (1 × 1) symmetry, where the three water OWH groups plus the surface OSH groups are imaged together as one bright triangle in STM. Manipulations with the STM tip by means of voltage pulses preferentially remove the H atom of one surface OSH group per triangle. The change in contrast due to strong local band bending provides insights into the internal structure of these bright triangles. The experimental results are further confirmed by quantitative simulations of the STM image corrugation.


Elastic net-based framework for imaging mass spectrometry data biomarker selection and classification.
Imaging mass spectrometry (IMS) shows great potential for the rapid mapping of protein localization and for detecting of sizeable differences in protein expression. However, data processing remains challenging due to the difficulty of analyzing high dimensionality, the fact that the number of predictors is significantly larger than the number of observations, and the need to consider both spectral and spatial information in order to represent the advantage of IMS technology. Ideally one would like to efficiently analyze all acquired data to find trace features based on both spectral and spatial patterns. Therefore, biomarker selection from IMS data is a problem of global optimization. A recently developed regularization and variable selection method,elastic net (EN), produces a sparse model with admirable prediction accuracy and can be an effective tool for IMS data processing. In this paper, we incorporate a spatial penalty term into the EN model and develop anew tool for IMS data biomarker selection and classification. A comprehensive IMS data processing software package, called EN4IMS, is also presented. The results of applying our method to both simulated and real data show that the EN4IMS algorithm works efficiently and effectively for IMS data processing: producing a more precise listing of selected peaks, helping confirmation of new potential biomarkers discovery, and providing more accurate classification results.


Lymphoblast purine pathway enzymes in B-cell acute lymphoblastic leukemia.
Activities of enzymes of the purine metabolic pathway, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'-nucleotidase (5'-N), were investigated in the lymphoblasts of a patient with B-cell acute lymphoblastic leukemia. These lymphoblasts exhibited increased ADA activity and diminished activities of both PNP and 5'N' as compared to normal lymphocytes as well as non-T, non-B leukemia cells. This enzymatic pattern is identical to that which has been described in T-cell leukemic lymphoblasts and differs from that which has been observed in the malignant cells of undifferentiated B-cell lymphomas. These data suggest that there is biochemical heterogeneity within the spectrum of B-cell malignancies. Furthermore, inhibitors of ADA may be of use in those B-cell lymphoid neoplasms that exhibit increased ADA activity.


Repeated administration of AMPA or a metabotropic glutamate receptor agonist into the rat ventral tegmental area augments the subsequent behavioral hyperactivity induced by cocaine.
Glutamate receptors and their related second messengers in the ventral tegmental area (VTA) are known to play critical roles in the initiation of behavioral sensitization to cocaine. To evaluate the hypothesis that repeated intra-VTA microinjections of the ionotropic glutamate agonist, AMPA, or the metabotropic glutamate agonist, t-ACPD, augment the behavioral hyperactivity induced by a subsequent challenge injection of cocaine. In addition, the dependency of the t-ACPD effect on activation of the calcium/calmodulin-dependent kinases (CaM-Ks) was assessed. Male Sprague-Dawley rats received four once-daily microinjections of saline, AMPA, t-ACPD, or t-ACPD plus the CaM-KII inhibitor KN-93 directly into the VTA; locomotor activity was measured for 120 min after each of the daily treatments. One week after the 4 treatment days, all animals received a challenge injection of cocaine (15 mg/kg, IP) and behavioral activity was monitored for 120 min. Intra-VTA administration of t-ACPD increased behavioral activity only on the first 2 treatment days, an effect that was blocked by pre-treatment with KN-93. Administration of AMPA into the VTA, in contrast, produced behavioral hyperactivity that sensitized over the 4 treatment days. Following the cocaine challenge injection, there was an augmentation of cocaine-induced behavioral hyperactivity in the groups pretreated with AMPA or t-ACPD but not in the animals administered t-ACPD plus KN-93. These results indicate that repeated stimulation of AMPA or metabotropic glutamate receptors in the VTA mimics the initiation of behavioral sensitization to cocaine. The present findings also suggest that glutamate agonist-induced activation of CaM-KII in the VTA plays a critical role in the behavioral and neuronal plasticity induced by repeated cocaine injections.


Advancing Health Equity: An Innovative Program for Building Community Engagement in Research.
The Community Research Fellows (CRF) program seeks to mobilize New Haven residents with lower incomes or from communities of color who are educated and equipped to engage as equal partners in health research at Yale University. The training program combines curriculum-based information with 'on-the-ground' experience with Yale research projects, while building relationships between CRFs and researchers. The Community Alliance for Research and Engagement launched two consecutive cohorts of the program in 2018-2020. To assess the effect of the CRF program on participants' knowledge of the research process and confidence to engage in research and participants' satisfaction and perspectives on the program. The evaluation of the CRF program included four components: 1) Pre- and Post- Program Surveys to assess change in confidence and self-reported knowledge. 2) Curriculum Feedback Satisfaction Survey to gauge satisfaction and make program improvements after each training session. 3) Post-Program CRF Interviews to explore their CRF experiences. 4) Research Team Surveys to assess program satisfaction and areas for improvement. CRFs reported increased confidence and knowledge, personal and professional growth, and interest in community-engaged research. Overall, participants were very satisfied with each training module. The CRF program demonstrated that community members are well-suited, well-positioned, and eager to engage in and inform public health research. CRFs bring capacity and valuable perspective to research teams. The CRF training program offers an innovative approach to address power imbalances in research and to move towards more equitable community-university partnerships for improved health outcomes.


Diurnal changes and adaptation by the liver of hamsters to an atherogenic diet.
Studies were performed in freely feeding, male (F1B) Syrian hamsters fed a high-fat diet to determine the extent and manner of adaptation of the liver to diurnal changes in eating patterns and an increase in serum lipids. Serum cholesterol and triglycerides strongly paralleled changes in food consumption and were 40-50% greater during the 12-h dark period than the 12-h light period of the diurnal cycle. Hepatic cholesterol changes closely approximated changes in serum cholesterol (r = 0.916) due principally to changes in hepatic cholesteryl esters that were on average about 10-fold greater with the high-fat diet than with a chow diet. With the high-fat diet, hepatic cholesteryl esters were, however, extremely variable and were 40% greater at the mid-dark than at the mid-light period. With high fat there was also a marked increase in the secretion of very low density lipoproteins (VLDL) from the liver that were cholesteryl ester rich and closely paralleled the diurnal changes in hepatic cholesteryl esters (r = 0.911). In contrast, although with a high-fat diet biliary cholesterol secretion was increased, the increase in cholesterol in bile exhibited no diurnal pattern and with the high-fat diet was far less in magnitude than the increase of cholesterol in VLDL. Biliary cholesterol secretion is dependent on bile acid secretion. However, with the high-fat diet, neither the bile acid pool size nor bile acid secretion was increased compared with chow-fed controls. Moreover, with high fat at mid-dark period, bile acid secretion was significantly less than controls at mid-dark period. Thus in these hamsters a high-fat diet produced a marked increase in serum cholesterol that was distinctly diurnal and was compensated for by a diurnal increase in hepatic cholesteryl ester stores and the secretion of cholesteryl esters in VLDL. In contrast, cholesterol secretion in bile did not correspond to the fluctuating changes of cholesterol in the liver and was far less in magnitude than would be necessary to reduce a greatly expanded pool of hepatic cholesterol.


Spectrum of concepts associated with the term "biodiversity": a case study in a biodiversity hotspot in South America.
In most conservation programs that include public participation, the word "biodiversity" is used. However, many variables influence the public understanding of the term and determine what biodiversity means to local stakeholders. Those representations of the concept must be addressed and included in conservation actions. We asked 47 local stakeholders in a biosphere reserve (BR) located in a biodiversity hotspot in South America, for whom the conservation of biodiversity is not the main focus of interest, to explain how they understand the term "biodiversity." Twenty-two different definitions were provided, ranging from purely ecological concepts to the human dimension. Although the diversity of animals and plants was the most frequently mentioned concept, the variety of concepts that emerged suggested that more explicit examples of social constructions must be considered in public participatory projects and environmental education programs. Actors living in a close relationship with nature provide a greater diversity of elements in defining biodiversity, visualizing ecological but also instrumental values.


[Features of psychologic adaptation and prevalence of border mental disorders among cargo vehicle drivers].
Studying features of psychic adaptation in 148 cargo transport drivers, the authors revealed high risk of boundary psychic disorders. Occupational research defined emotional and informational load characteristic for drivers and leading to exhaustion of adaptation and compensatory mechanisms. Factor dispersion analysis helped to determine leading role of occupational length of service--risk factor and indicator of psychic dysadaptation.


Twenty percent of biopsy specimens from sun-exposed skin of normal young adults demonstrate positive immunofluorescence.
Fifty normal healthy adults, aged 18 to 41 years, without a history of systemic diseases, dermatoses, or photosensitivity and who were not receiving medication were studied. Paired 3-mm punch biopsy specimens were obtained from the sun-exposed and the non-sun-exposed skin. The data from the study revealed a bright continuous band of immunofluorescence (IF) along the dermoepidermal junction in 10 (20%) of 50 sun-exposed skin biopsy specimens, as compared with none from non-sun-exposed skin biopsy specimens with the use of polyvalent antisera. Fractionated monospecific immunoglobulin demonstrated a bright continuous band of IF composed of IgG alone in one patient, IgA alone in two patients, IgG and IgA in combination in two patients, and the combination of IgG, IgM, and IgA in five patients. There was a statistically significant increase in positive IF in men (seven of 15) vs women (three of 35). This information suggests that in the examination of a patient suspected of having lesions of cutaneous lupus erythematosus, positive IF from sun-exposed skin is nonspecific and adds little information to the clinical and histopathologic findings.


Sodium Dodecyl Sulfate-Dependent Disassembly and Reassembly of Soybean Lipophilic Protein Nanoparticles: An Environmentally Friendly Nanocarrier for Resveratrol.
The development of protein-based nanocarriers to improve the water solubility, stability, and bioavailability of hydrophobic or poorly soluble bioactive molecules has attracted increasing interest in the food and pharmaceutical industries. In this study, a network-like nanostructure of soybean lipophilic protein (LP) was obtained through sodium dodecyl sulfate (SDS)-dependent decomposition and recombination. This nanostructure served as an excellent nanocarrier for resveratrol (Res), a poorly soluble biologically active molecule. The structure of LP gradually decomposed into its independent subunits at SDS concentrations ≤5% (w/v). After the removal of SDS, the dissociated subunits partially reassembled into a fibrous network-like nanostructure in which the Res molecules were encapsulated, and they preferentially interacted with the hydrophobic subunits (α and α' subunits and the 24 kDa subunit) of the protein. This system exhibited a high encapsulation efficiency (95.93%), high water solubility (85.29%), extraordinary oxidation resistance (DPPH radical scavenging activity of 67.1%), and improved Res digestibility (78.7%).


Effects of penile fracture and its surgical treatment on psychosocial and sexual function.
The current therapy for penile fracture is immediate surgical repair, but sexual and psychosocial effects of the repair have been poorly investigated. We aimed to assess the impact of surgical correction of penile fracture on psychosocial status, sexual function, and erectile quality. Sixty-four patients classified into two subgroups according to follow-up: 2-24 months (Group 1), and longer than 24 months (Group 2), and 28 healthy men (Control group). The mean overall follow-up period was 39.1±32.7 months. The number of sexual intercourse origin was 44 (68.8%), the mean time interval from incident-to-surgery was 13.6±9.3 h. The mean sexual relationship score decreased during first year (P=0.001), and significant recovery was observed over 12-24 months. The mean overall relationship scores and the mean self-esteem scores of the study groups decreased until the end of the 24 months (P<0.05). The mean erectile function domains remained stable in all groups (P>0.05). The mean EHS scores were lower but the difference was not significant in the study groups (P>0.05). Penile fracture repair have no detrimental effect on sexual function, but psychogenic aspect may be adversely affected. This article concludes lower complication rates can be reached with immediate surgical correction of the penile fracture whereas psychogenic recovery might prolonged.


Insulin stimulates endogenous angiotensin II production via a mitogen-activated protein kinase pathway in vascular smooth muscle cells.
The present study was designed to determine the effects of insulin on cytosolic angiotensin II production and proliferation in cultured rat vascular smooth muscle cells. Vascular smooth muscle cells were incubated with insulin for 48 h. Cytosolic angiotensin I and II were determined by radioimmunoassays of purified cell homogenates. Angiotensin II was also detected by immunohistochemistry of intact cells. Cell proliferation was determined by pulse labeling with radiolabeled thymidine. Angiotensinogen mRNA expression was determined by slot-blot analysis. Insulin significantly increased cytosolic angiotensin II concentration in vascular smooth muscle cells. Lisinopril, omapatrilat and irbesartan inhibited this increase of angiotensin II, but had no effect on angiotensin I levels. Immunohistochemical staining confirmed the presence of angiotensin II in control and insulin-treated vascular smooth muscle cells. Insulin increased cell proliferation, and addition of lisinopril, omapatrilat or irbesartan inhibited this effect. Insulin also increased expression of angiotensinogen mRNA in cultured vascular smooth muscle cells, but PD98059, a mitogen-activated protein kinase inhibitor, prevented the rise in angiotensinogen expression. These results support the concept that insulin stimulates angiotensin II production in cultured vascular smooth muscle cells through a mitogen-activated, protein kinase-dependent pathway that might be a factor in the progression of atherosclerosis. Agents that block the renin-angiotensin system have direct protective effects, reducing vascular angiotensin II and growth of vascular smooth muscle cells and are thus of cardiovascular benefit.


[Mathematical model for study the reliability of organism function in extreme conditions of high altitude].
The health of a person and his capacity for work under conditions of high mountains in many respects is determined by the reliability of the function of physiological systems. Mathematical methods of both the reliability theory and mathematical simulation of basic functional systems are proposed to be used for investigating the reliability. It is shown that the most suitable reliability model for living systems is a chain model-a successive connection of links representing separate functional systems of organism. Besides, the weakest links determining the reliability of functioning of the whole organism under the extreme conditions of high mountains even for a healthy person are-respiration, blood circulation, thermoregulation and psychophysiological systems. Quantitative characteristics of the reliability of these systems are determined through the main indicators. The influence of non-sufficient contents of oxygen in respiration mixture, low atmospheric pressure, low temperatures of the environment are simulated by computer models of organism. An analyses of modeling data shows that moderate physical loading improves indicators of organisms adaptively to external conditions of high mountains and promotes the increasing of persons capacity for work and the reliability of his functioning.


[Phenotypic and genotypic methods for detecting multidrug resistance in Mycobacterium tuberculosis].
Expeditious charactization of drug susceptibility in Mycobacterium tuberculosis is difficult and, calls for the design and evaluation of faster, cheaper and more effective new techniques. The aim of the current study was to compare one genotypic and two phenotypic methods for rapid susceptibility detection of M. tuberculosis. Twenty-one M. tuberculosis strains were evaluated by phenotypic methodologies of oxidation and reduction of Alamar blue and MTT in the presence of streptomycin, isoniazid, rifampin and ethambutol. In all tests, the proportion method was applied as the comparison standard. By means of receiver operative characteristic (ROC) analysis, the performance, predictive values and threshold values for all drugs were determined. In addition, the performance of PCR and reverse line blot hybridization in establishing predictive values for sensitivity and resistance were compared in contingency tables. The susceptibility patterns established by colorimetric techniques were obtained after seven days of incubation. The performances of these tests were excellent for all drugs-the areas under curves were >0.9, 100% of sensitivity (S) and specificity (E) >80%. The genotypic method of RFLP oligotyping detected multidrug resistance with S of 100% and E of 93%. Conclusion. The results indicated that Alamar blue, MTT and RFLP methodologies are rapid and useful tools for characterizing multidrug resistance in M. tuberculosis, particularly for those patients with high risk of developing multidrug resistant tuberculosis.


Larval development of Myzostoma cirriferum (Myzostomida).
The larval development of Myzostoma cirriferum is described by means of SEM, TEM, and cLSM. It is similar to that of other myzostomids and includes three stages: the protrochophore, the trochophore, and the metatrochophore. The protrochophore is a ball-shaped larva present in culture from 18-48 h after egg laying. It has no internal organs and its body is made of three cell types: covering cells and ciliated cells that are external and surrounded by a cuticle, and resting cells that fill the blastocoel. The trochophore is a pear-shaped larva that develops 20-72 h after egg laying; the body includes the same three cell types as the previous stage. The metatrochophore is a pear-shaped larva that develops between 40 h and 14 days and is characterized by the presence of two bundles of four chaetae. When fully developed, the metatrochophore has a digestive system (made of a pharynx, an esophagus, and a blind digestive pouch), two pairs of protonephridia, and a nervous system composed of a supraesophageal ganglion, circumesophageal connectives, and dorsal and ventral nerves. Metamorphosis generally occurs 7 days after egg laying. At that time, the metatrochophore loses its chaetae and becomes pleated ventrally. This ultrastructural analysis suggests that chaetae and the five ventral longitudinal nerve cords of M. cirriferum metatrochophores are homologous structures to those observed in some polychaete trochophores. Coupled with recent phylogenetic analyses, where the Myzostomida are placed outside the Annelida, homologies between myzostomid and polychaete larvae support the view that a trochophore appeared early during the spiralian evolution.


The Relationship between Nociceptive Detection Thresholds and Pressure- and Electrical Pain Thresholds: An Explorative Study in Rheumatoid Arthritis Patients.
Recently, methods have been developed enabling the characterization of the nociceptive function at the detection threshold level by measuring nociceptive detection thresholds (NDTs), rather than at the level of the pain threshold via pain threshold (PT) measurements. Both NDT and PT measurements aim to characterize (parts of) the nociceptive system. To date it is unclear if, and if so to what extent, the two outcomes relate to one another. In this study, the primary aim is to explore the relationship between the two measures in patients with rheumatoid arthritis (RA). As secondary aim, we explore differences in NDT between these RA patients with age- and sex-matched healthy controls (HC) from a readily existing dataset. In total 46 RA patients have been recruited, whereby the pressure- (PPT; bilaterally at two locations) and electrical (EPT) pain threshold were evaluated, as well as the NDTs. Significant, positive correlations were found between the EPT and PPT (R=0.54-0.60), but not with the NDTs (R≤0.25). As compared to HC, higher NDTs were found in the RA group. As the presence of a statistically significant weak relationship can only be evaluated using a larger sample size, our results indicate that there is no moderate or stronger relation between PT and NDT outcomes. This implicates that the two outcomes are not strongly driven by the same (nociceptive) mechanism(s). Future research into NDTs and what factors and/or mechanisms affect the outcome, could yield relevant insights into how to use and interpret the results of this relatively new method.Clinical Relevance - The evaluation of nociceptive detection thresholds, in isolation or together with conventionally evaluated pain thresholds, might provide valuable and complementary insights into nociceptive (dis)function in man.


Pitfalls in genetic analysis of pheochromocytomas/paragangliomas-case report.
About 35% of patients with pheochromocytoma/paraganglioma carry a germline mutation in one of the 10 main susceptibility genes. The recent introduction of next-generation sequencing will allow the analysis of all these genes in one run. When positive, the analysis is generally unequivocal due to the association between a germline mutation and a concordant clinical presentation or positive family history. When genetic analysis reveals a novel mutation with no clinical correlates, particularly in the presence of a missense variant, the question arises whether the mutation is pathogenic or a rare polymorphism. We report the case of a 35-year-old patient operated for a pheochromocytoma who turned out to be a carrier of a novel SDHD (succinate dehydrogenase subunit D) missense mutation. With no positive family history or clinical correlates, we decided to perform additional analyses to test the clinical significance of the mutation. We performed in silico analysis, tissue loss of heterozygosity analysis, immunohistochemistry, Western blot analysis, SDH enzymatic assay, and measurement of the succinate/fumarate concentration ratio in the tumor tissue by tandem mass spectrometry. Although the in silico analysis gave contradictory results according to the different methods, all the other tests demonstrated that the SDH complex was conserved and normally active. We therefore came to the conclusion that the variant was a nonpathogenic polymorphism. Advancements in technology facilitate genetic analysis of patients with pheochromocytoma but also offer new challenges to the clinician who, in some cases, needs clinical correlates and/or functional tests to give significance to the results of the genetic assay.


Effects of acute Δ9-tetrahydrocannabinol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice.
Cannabis use is highly prevalent especially among people living with HIV (PLWH). Activation of the anti-inflammatory and neuroprotective endocannabinoid system by phytocannabinoids, i.e. Δ9-tetrahydrocannabinol (THC), has been proposed to reduce HIV symptoms. However, THC's effects on HIV-related memory deficits are unclear. Using HIV-1 Tat transgenic mice, the current study investigates acute THC effects on various behavioral outcomes and the endocannabinoid system. For the rodent tetrad model, THC doses (1, 3, 10 mg/kg) induced known antinociceptive effects, with Tat induction increasing antinociceptive THC effects at 3 and 10 mg/kg doses. Only minor or no effects were noted for acute THC on body temperature, locomotor activity, and coordination. Increased anxiety-like behavior was found for females compared to males, but acute THC had no effect on anxiety. Object recognition memory was diminished by acute THC in Tat(-) females but not Tat(+) females, without affecting males. The endocannabinoid system and related lipids were not affected by acute THC, except for THC-induced decreases in CB1R protein expression levels in the spinal cord of Tat(-) mice. Female sex and Tat induction was associated with elevated 2-AG, AEA, AA, CB1R, CB2R, FAAH and/or MAGL expression in various brain regions. Further, AEA levels in the prefrontal cortex of Tat(+) females were negatively associated with object recognition memory. Overall, findings indicate that acute THC exerts differential effects on antinociception and memory, dependent on sex and HIV Tat expression, potentially in relation to an altered endocannabinoid system, which may be of relevance in view of potential cannabis-based treatment options for PLWH.


Ultrasound molecular imaging contrast agent binding to both E- and P-selectin in different species.
Ultrasound molecular imaging is increasingly used in preclinical studies to measure the expression of vascular markers during inflammation process. In this context, a new ultrasound contrast agent functionalized with a recombinant P-selectin glycoprotein ligand-1 analogue (rPSGL-Ig) was developed (MBrPSGL-Ig). This agent was assayed in vitro and in vivo to evaluate its binding performance and potential to image expression of inflammatory markers E- and P-selectin. Performance of this newly developed agent was compared with that of antibody (MBAb) or sialyl Lewis X (MBsLe) containing microbubbles and with control microbubbles (MBC). The targeted ultrasound contrast agents were prepared by coupling biotin-conjugated ligands onto streptavidin-functionalized microbubbles. First, in vitro experiments were performed to measure the adhesion efficiency of these microbubble constructs under static or flow conditions (114 sec), on cell monolayer (human umbilical vein endothelial cells and bEnd.5), or coatings of E- or P-selectin of various animal species, respectively. Second, molecular imaging studies were performed in a rat inflammatory model 24 hours after intramuscular injection of lipopolysaccharide in the hind limb. Finally, immunohistochemistry staining of rat inflamed muscle tissue was performed to assess expression of E- and P-selectin. Microbubbles functionalized with rPSGL-Ig (MBrPSGL-Ig) displayed firm in vitro binding on the coating of both recombinant E- or P-selectin, with an efficiency similar to microbubbles comprising antibody specific for E-selectin (MBE) or P-selectin (MBP). In contrast, lower binding capacity was measured with MBsLe. At the surface of inflamed endothelial cells, MBrPSGL-Ig were able to interact specifically with E- and P-selectin. Binding specificity was demonstrated by performing blocking experiments with target-specific antibodies, resulting in an 80% to 95% decrease in binding. Ten minutes after microbubble injection, echo signal measured with MBrPSGL-Ig in the inflamed muscles was 20-fold higher compared with MBC. Moreover, the in vivo adhesion of MBrPSGL-Ig was 2- and 7-fold higher compared with P-selectin or E-selectin-specific microbubbles, respectively. Immunohistochemistry revealed a temporal coexpression of E- and P-selectin in the vascular bed of inflamed rat muscle 24 hours after lipopolysaccharide injection. The molecular imaging study demonstrates that MBrPSGL-Ig provide imaging signal higher than those measured with antibody or sialyl Lewis X containing microbubbles. These results suggest that MBrPSGL-Ig is a powerful agent to image the expression of both E- and P-selectin in the context of an inflammatory process.


Effects of patterns of walking training on metabolic health of untrained postmenopausal women.
High-intensity aerobic interval training (AIT) has been reported to be more effective than continuous aerobic training (CoAT) to improve metabolic health. The aim of our study was to investigate whether moderate-intensity AIT is more effective than CoAT on metabolic health when applied to a walking training program. Thirty-two postmenopausal women (55.37 ± 3.46 years) were investigated for body composition, plasma glucose, insulin, lipids, adiponectin, HOMA-IR, HOMA-AD, aerobic fitness, dietary habits, and spontaneous physical activity, and randomly assigned to one of two different walking training programs: CoAT or AIT. CoAT and AIT elicited the same physiological benefits, including: reduction of plasma glucose, insulin, HOMA-IR and HOMA-AD, and increase of plasma HDL-C, adiponectin, and aerobic fitness. An AIT scheme as part of an outdoor walking training program elicits the same physiological adaptations as a CoAT scheme, probably because walking does not promote exercise intensities that elicit greater effects.


Comparative genotyping of the Saccharomyces cerevisiae laboratory strains S288C and CEN.PK113-7D using oligonucleotide microarrays.
To analyse the reliability and accuracy of genotype analysis with high-density oligonucleotide microarrays, this method and other experimental approaches were used to analyse genomic DNA of two popular Saccharomyces cerevisiae laboratory strains. S288C was used for systematic sequencing of 'the' S. cerevisiae genome; CEN.PK113-7D is a popular strain for physiological studies and functional genomics. Random amplified polymorphic DNA, electrophoretic karyotyping and microarray analysis all indicated a high level of sequence similarity between the two strains. In the microarray analysis, as few as 288 (4.5%) of the ca. 6300 represented yeast genes were identified that yielded significantly different hybridisation intensities between the two strains. These could be classified as amplified, absent, or with sequence polymorphism in CEN.PK113-7D compared to S288C. A detailed analysis focused on the subset of 25 genes called absent in CEN.PK113-7D. Among these absent genes, 17 were clustered together on five chromosomes, mainly in subtelomeric regions. Thorough analysis of these regions by polymerase chain reaction (PCR) and restriction fragment length polymorphism confirmed the absence of these genes in CEN.PK113-7D. Surprisingly, three of these regions were not smaller in CEN.PK113-7D chromosomes, indicating that they may harbour unidentified and potentially new sequences. In addition, eight genes called absent by the microarrays were scattered over the chromosomes. Using diagnostic PCR most of these genes were actually found to be present in CEN.PK113-7D, but after sequencing were found to differ significantly at the DNA level from S288C, explaining the poor hybridisation to the arrays. Our results indicate that DNA microarrays are a powerful tool for determining genotypic similarity between different yeast strains. However, to obtain meaningful information at the individual gene level, this method should be backed up by additional techniques.


Protection by sterols against the cytotoxicity of syringomycin in the yeast Saccharomyces cerevisiae.
A brief exposure (ca 20 min) of the yeast Saccharomyces cerevisiae to the phytotoxin syringomycin was sufficient to kill the cell. The protective effect of sterols against this cytotoxicity of syringomycin was investigated. Syringomycin was much more toxic to growing cells than to stationary-phase cells. The cytotoxicity of syringomycin was reduced in an environment containing sterols. Cytotoxicity of syringomycin at 3 micrograms ml-1 (ca 2.5 microM) was completely abolished by the simultaneous presence of 10 microM-cholesterol in the medium. Cholesterol acetate had no protective effect. Ergosterol, sitosterol and stigmasterol also protected against syringomycin, but they were less effective than cholesterol. The protective effect of sterols against the action of syringomycin is consistent with our hypothesis that membrane ergosterol is a critical component for syringomycin-binding as suggested by recent genetic studies.


Non-surgical interventions for paediatric pes planus.
Paediatric pes planus ('flat feet') is a common childhood condition with a reported prevalence of 14%. Flat feet can result in pain and altered gait. No optimal strategy for non-surgical management of paediatric flat feet has been identified. To assess the effectiveness of non-surgical interventions for treatment of paediatric pes planus (flat feet). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL, Index to Theses, and Dissertation Abstracts (up to June 2009). All randomised and quasi-randomised trials of non-surgical interventions for paediatric pes planus were identified. The primary outcomes were pain reduction and adverse events; secondary outcomes included disability involving the foot, goniometric measurements, quality of life and patient comfort. Two authors independently extracted data and assessed the risk of bias of included trials. Three trials involving 305 children were included in this review. Due to clinical heterogeneity, data were not pooled. All trials had potential for bias. Data from one trial (40 children with juvenile arthritis and foot pain) indicated that use of custom-made orthoses compared with supportive shoes alone resulted in significantly greater reduction in pain intensity (mean difference (MD) -1.5 points on a 10-point visual analogue scale (VAS), 95% CI -2.8 to -0.2; number need to treat to benefit (NNTB) 3, 95% CI 2 to 23), and reduction in disability (measured using the disability subscale of the Foot Function Index on a 100mm scale (MD -18.65mm, 95% CI -34.42 to -2.68mm). The second trial of seven to 11 year old children with bilateral flat feet (n = 178) found no difference in the number of participants with foot pain between custom-made orthoses, prefabricated orthoses and the control group who received no treatment. A third trial of one to five year olds with bilateral flat feet (n=129) did not report pain at baseline but reported the subjective impression of pain reduction after wearing shoes. No adverse effects were reported in the three trials. The evidence from randomised controlled trials is currently too limited to draw definitive conclusions about the use of non-surgical interventions for paediatric pes planus. Future high quality trials are warranted in this field. Only limited interventions commonly used in practice have been studied and there is much debate over the treatment of symptomatic and asymptomatic pes planus.


Ferromagnetic Cr4PtGa17: A Half-Heusler-Type Compound with a Breathing Pyrochlore Lattice.
We describe the crystal structure and elementary magnetic properties of a previously unreported ternary intermetallic compound, Cr4PtGa17, which crystallizes in a rhombohedral unit cell in the noncentrosymmetric space group R3m. The crystal structure is closely related to those of XYZ half-Heusler compounds, where X, Y, and Z are reported to be single elements only, occupying three different face-centered-cubic sublattices. The new material, Cr4PtGa17, can be most straightforwardly illustrated by writing the formula as (PtGa2)(Cr4Ga14)Ga (X = PtGa2, Y = Cr4Ga14, Z = Ga); that is, the X and Y sites are occupied by clusters instead of single elements. The magnetic Cr occupies a breathing pyrochlore lattice. Ferromagnetic ordering is found below TC ∼ 61 K, by both neutron diffraction and magnetometer studies, with a small, saturated moment of ∼0.25 μB/Cr observed at 2 K, making Cr4PtGa17 the first ferromagnetically ordered material with a breathing pyrochlore lattice. A magnetoresistance of ∼140% was observed at 2 K. DFT calculations suggest that the material has a nearly half-metallic electronic structure. The new material, Cr4PtGa17, the first realization of both a half-Heusler-type structure and a breathing pyrochlore lattice, might pave a new way to achieve novel types of half-Heusler compounds.


Mitochondrial DNA variation and population structure of the island endemic Azorean bat (Nyctalus azoreum).
The Azorean bat Nyctalus azoreum is the only endemic mammal native to the remote archipelago of the Azores. It evolved from a continental ancestor related to the Leisler's bat Nyctalus leisleri and is considered threatened because of its restricted and highly fragmented distribution. We studied the genetic variability in 159 individuals from 14 colonies sampled throughout the archipelago. Sequences of the D-loop region revealed moderate but highly structured genetic variability. Half of the 15 distinct haplotypes were restricted to a single island, but the most common was found throughout the archipelago, suggesting a single colonization event followed by limited interisland female gene flow. All N. azoreum haplotypes were closely related and formed a star-like structure typical of expanded populations. The inferred age of demographic expansions was consistent with the arrival of founder animals during the Holocene, well before the first humans inhabited the Azores. Comparisons with a population of N. leisleri from continental Portugal confirmed not only that all N. azoreum lineages were unique to the archipelago, but also that the current levels of genetic diversity were surprisingly high for an insular species. Our data imply that the Azorean bat has a high conservation value. We argue that geographical patterns of genetic structuring indicate the existence of two management units.


Attachment representations of deaf adults.
The primary goal of this study was to examine the feasibility of using the Adult Attachment Interview (AAI) with 50 culturally Deaf adults. Modifications to the standard protocol included using a visual-spatial language (American Sign Language) rather than a spoken language (English), as well as coding and procedural variations from the standardized protocol. Results suggested that the adapted AAI interview and coding processes provided an effective assessment of the state of mind regarding the attachment of Deaf individuals. The expectation that Deaf participants would be less coherent in their AAI transcripts and therefore less likely than hearing individuals to be classified as Autonomous was not supported. The distribution of the classifications of this Deaf sample was not different from existing normative distributions. Moreover, there was no evidence that early separation from parents associated with attendance at a residential school for the Deaf resulted in attachment formations with residential counselors or teachers at the school.


The hybridization of glyceraldehyde 3-phosphate dehydrogenases from rabbit muscle and yeast. Kinetics and thermodynamics of the reaction and isolation of the hybrid.
A kinetic and thermodynamic study was made of the formation of the hybrid (R(2)Y(2)) glyceraldehyde 3-phosphate dehydrogenase from the yeast (Y(4)) and rabbit (R(4)) enzymes. The values of the thermodynamic parameters for the equilibrium between R(4), Y(4) and R(2)Y(2) suggest that the R(2)-R(2) and Y(2)-Y(2) interactions are similar. However, the failure to observe the RY(3) and R(3)Y hybrids is interpreted in terms of differences at the interfaces of the R-R and Y-Y interactions (the glyceraldehyde 3-phosphate dehydrogenase molecule being regarded as a dimer of dimers). The kinetics of formation of the R(2)Y(2) hybrid were studied and a model was proposed to account for the results. Best-fit values for the rate constants of the individual steps were evaluated by computer simulation, and the rate-limiting steps were identified as the dissociation of tetramers to dimers. It is proposed that the cleavage plane for dissociation of the tetramers corresponds to the region of low electron density through the centre of the molecule in the X-ray-crystallographic structure for human glyceraldehyde 3-phosphate dehydrogenase (Watson et al., 1972), which is probably the plane containing the Q and R axes in the lobster enzyme (Buehner et al., 1974). The R(2)Y(2) hybrid was isolated in milligram amounts by ion-exchange chromatography and its rate of reversion to the native enzyme was shown to be consistent with the kinetic model proposed from the hybrid-formation experiments.


Effects of Short- and Long-Term Aerobic-Strength Training and Determinants of Walking Speed in the Elderly.
Walking speed (WS) is an objective measure of physical capacity and a modifiable risk factor of morbidity and mortality in the elderly. In this study, we (i) determined effects of 3-month supervised aerobic-strength training on WS, muscle strength, and habitual physical activity; (ii) evaluated capacity of long-term (21 months) training to sustain higher WS; and (iii) identified determinants of WS in the elderly. Volunteers (F 48/M 14, 68.4 ± 7.1 years) completed either 3-month aerobic-strength (3 × 1 h/week, n = 48) or stretching (active control, n = 14) intervention (study A). Thirty-one individuals (F 24/M 7) from study A continued in supervised aerobic-strength training (2 × 1 h/week, 21 months) and 6 (F 5/M 1) became nonexercising controls. Three-month aerobic-strength training increased preferred and maximal WS (10-m walk test, p < 0.01), muscle strength (p < 0.01) and torque (p < 0.01) at knee extension, and 24-h habitual physical activity (p < 0.001), while stretching increased only preferred WS (p < 0.03). Effect of training on maximal WS was most prominent in individuals with baseline WS between 1.85 and 2.30 m·s-1. Maximal WS measured before intervention correlated negatively with age (r = -0.339, p = 0.007), but this correlation was weakened by the intervention (r = -0.238, p = 0.06). WS progressively increased within the first 9 months of aerobic-strength training (p < 0.001) and remained elevated during 21-month intervention (p < 0.01). Cerebellar gray matter volume (MRI) was positively associated with maximal (r = 0.54; p < 0.0001) but not preferred WS and explained >26% of its variability, while age had only minor effect. Supervised aerobic-strength training increased WS, strength, and dynamics of voluntary knee extension as well as habitual physical activity in older individuals. Favorable changes in WS were sustainable over the 21-month period by a lower dose of aerobic-strength training. Training effects on WS were not limited by age, and cerebellar cortex volume was the key determinant of WS.


Functional analysis of 30K proteins during silk gland degeneration by a caspase-dependent pathway in Bombyx.
The 30K proteins are involved with important functions in the growth and development of Bombyx mori. In this study, the synthesis and regulation of 30K proteins were examined during the degeneration of Bombyx silk glands. On day 3 of the fifth instar, the protein level of 30Kc19 was low, whereas the silk proteins were rapidly synthesized. However, synthesis and accumulation of the 30Kc19 protein significantly increased at the prepupal stage and on day 1 of the pupal stage. At this stage, the silk gland cells were filled with 30Kc19 and genomic DNA. Moreover, the transcript levels of the 30K-encoding genes, including 30Kc6, 30Kc12, 30Kc19 and 30Kc23 were up-regulated during the degeneration of the Bombyx silk glands. During the time that the levels of the 30Kc19 protein were significantly up-regulated, it is notable that the transcript levels of the BmAtg8, BmAtg6 and BmDronc genes dramatically increased to regulate the programmed cell death of this gland. On day 1 of the pupal stage, intense fragmentation of genomic DNA occurred in the silk gland cells, and the putative active form of caspase was detected in the cytoplasm, showing the complete degradation of the silk glands in one day. In conclusion, the 30K proteins are synthesized in high concentrations, while proteolysis mediates silk gland degeneration in Bombyx by a caspase-dependent pathway. We propose that the 30K proteins may be nutrients and energy vectors to be absorbed by the developing tissues of pupae or moths.


Mode of insertion of lipopolysaccharide into the outer membrane of escherichia coli.
A mutant of Escherichia coli that lacks uridine 5'-diphosphate galactose-4-epimerase makes lipopolysaccharide with less carbohydrate than the parent, unless galactose is present during growth. Carbohydrate is dense, and the outer membrane, which contains lipopolysaccharide, was found to be denser when isolated from cells grown with galactose then when galactose was omitted. Cells given galactose after growth in its absence rapidly formed dense regions within the outer membrane that disappeared when galactose was removed. These results indicate that lipopolysaccharide enters the outer membrane nonrandomly at a minimum of 10 to 22 discrete "insertion points." Isopycnic centrifugation provides a method for isolating these regions.


Can positive social exchanges buffer the detrimental effects of negative social exchanges? Age and gender differences.
Findings from existing research exploring whether positive social exchanges can help to offset (or 'buffer' against) the harmful effects of negative social exchanges on mental health have been inconsistent. This could be because the existing research is characterized by different approaches to studying various contexts of 'cross-domain' and 'within-domain' buffering, and/or because the nature of buffering effects varies according to sociodemographic characteristics that underlie different aspects of social network structure and function. The purpose of this study was to examine whether the buffering effects of global perceptions of positive exchanges on the link between global negative exchanges and mental health varied as a function of age and gender. We used a series of regressions in a sample of 556 Australian older adults (ages 55-94) to test for three-way interactions among gender, positive social exchanges, and negative social exchanges, as well as age and positive and negative social exchanges, in predicting mental health, controlling for years of education, partner status, and physical functioning. We found that positive exchanges buffered against negative exchanges for younger old adults, but not for older old adults, and for women, but not for men. Our findings are interpreted in light of research on individual differences in coping responses and interpersonal goals among late middle-aged and older adults. Our findings are in line with gerontological theories (e.g., socioemotional selectivity theory), and imply that an intervention aimed at using positive social exchanges as a means of coping with negative social exchanges might be more successful among particular populations (i.e., women, 'younger' old adults).


Effects of thalidomide and pentoxyphylline over local and remote organ injury after intestinal ischemia/reperfusion.
We investigated the effects of thalidomide alone or in combination with pentoxyphylline upon intestinal ischemia/reperfusion (I/R) injury in the rat. Twenty male Wistar rats were randomized into 5 groups: sham-operated (SHAM), control (CTL), thalidomide (400 mg/kg) treatment (THAL), pentoxyphylline (50 mg/kg) treatment and a combination group (THAL + POX). I/R was induced by clamping the superior mesenteric artery for 45 minutes, followed by 120 minutes of reperfusion. We measured serum concentrations of aspartate-aminotransferase (AST), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-alpha as well as lipid peroxidation and antioxidant status. Intestinal samples were morphologically analyzed, and dry to wet (W/D) ratios calculated in intestinal, lung and liver samples, as a measurement of tissue edema. Serum concentrations of AST, LDH, and TNF-alpha were increased after I/R in the CTL compared with the SHAM group (P < .05). Lipid peroxidation was also increased, and antioxidant capacity in serum, decreased (P < .05). The W/D ratio was elevated in all tissue samples as well (P < .05). Both thalidomide and pentoxyphylline effectively reduced AST, LDH, TNF-alpha, and lipid peroxidation levels, as well as attenuated tissue edema and intestinal injury induced by I/R (P < .05). Combination treatment showed only modest additive effects on lung W/D ratio and TNF-alpha levels. Both drugs protected the intestine, lungs, and liver against intestinal I/R injury, probably by inhibition of TNF-alpha and lipid peroxidation. However, combination treatment showed small, additive effects.


Comparative pelvic development of the axolotl (Ambystoma mexicanum) and the Australian lungfish (Neoceratodus forsteri): conservation and innovation across the fish-tetrapod transition.
The fish-tetrapod transition was one of the major events in vertebrate evolution and was enabled by many morphological changes. Although the transformation of paired fish fins into tetrapod limbs has been a major topic of study in recent years, both from paleontological and comparative developmental perspectives, the interest has focused almost exclusively on the distal part of the appendage and in particular the origin of digits. Relatively little attention has been paid to the transformation of the pelvic girdle from a small unipartite structure to a large tripartite weight-bearing structure, allowing tetrapods to rely mostly on their hindlimbs for locomotion. In order to understand how the ischium and the ilium evolved and how the acetabulum was reoriented during this transition, growth series of the Australian lungfish Neoceratodus forsteri and the Mexican axolotl Ambystoma mexicanum were cleared and stained for cartilage and bone and immunostained for skeletal muscles. In order to understand the myological developmental data, hypotheses about the homologies of pelvic muscles in adults of Latimeria, Neoceratodus and Necturus were formulated based on descriptions from the literature of the coelacanth (Latimeria), the Australian Lungfish (Neoceratodus) and a salamander (Necturus). In the axolotl and the lungfish, the chondrification of the pelvic girdle starts at the acetabula and progresses anteriorly in the lungfish and anteriorly and posteriorly in the salamander. The ilium develops by extending dorsally to meet and connect to the sacral rib in the axolotl. Homologous muscles develop in the same order with the hypaxial musculature developing first, followed by the deep, then the superficial pelvic musculature. Development of the pelvic endoskeleton and musculature is very similar in Neoceratodus and Ambystoma. If the acetabulum is seen as being a fixed landmark, the evolution of the ischium only required pubic pre-chondrogenic cells to migrate posteriorly. It is hypothesized that the iliac process or ridge present in most tetrapodomorph fish is the precursor to the tetrapod ilium and that its evolution mimicked its development in modern salamanders.


The biomechanical contribution of varying posterior constructs following anterior thoracolumbar corpectomy and reconstruction.
Thoracolumbar corpectomy is a procedure commonly required for the treatment of various pathologies involving the vertebral body. Although the biomechanical stability of anterior reconstruction with plating has been studied, the biomechanical contribution of posterior instrumentation to anterior constructs remains unknown. The purpose of this study was to evaluate biomechanical stability after anterior thoracolumbar corpectomy and reconstruction with varying posterior constructs by measuring bending stiffness for the axes of flexion/extension, lateral bending, and axial rotation. Seven fresh human cadaveric thoracolumbar spine specimens were tested intact and after L-1 corpectomy and strut grafting with 4 different fixation techniques: anterior plating with bilateral, ipsilateral, contralateral, or no posterior pedicle screw fixation. Bending stiffness was measured under pure moments of +/- 5 Nm in flexion/extension, lateral bending, and axial rotation, while maintaining an axial preload of 100 N with a follower load. Results for each configuration were normalized to the intact condition and were compared using ANOVA. Spinal constructs with anterior-posterior spinal reconstruction and bilateral posterior pedicle screws were significantly stiffer in flexion/extension than intact spines or spines with anterior plating alone. Anterior plating without pedicle screw fixation was no different from the intact spine in flexion/extension and lateral bending. All constructs had reduced stiffness in axial rotation compared with intact spines. The addition of bilateral posterior instrumentation provided significantly greater stability at the thoracolumbar junction after total corpectomy than anterior plating and should be considered in cases in which anterior column reconstruction alone may be insufficient. In cases precluding bilateral posterior fixation, unilateral posterior instrumentation may provide some additional stability.


Age-Dependent Translocation of Gold Nanoparticles across the Air-Blood Barrier.
Do immature lungs have air-blood barriers that are more permeable to inhaled nanoparticles than those of fully developed mature lungs? Data supporting this notion and explaining the underlying mechanisms do not exist as far as we know. Using a rat model of postnatal lung development, here the data exactly supporting this notion, that is, significantly more gold nanoparticles (NPs) cross from the air space of the lungs to the rest of the body in neonates than in adults, are presented. Moreover, in neonates the translocation of gold NPs is not size dependent, whereas in adult animals smaller NPs cross the air-blood lung barrier much more efficiently than larger NPs. This difference in air-blood permeability in neonate versus adult animals suggests that NP translocation in the immature lungs may follow different rules than in mature lungs. Supporting this notion, we propose that the paracellular transport route may play a more significant role in NP translocation in immature animals, as suggested by protein expression studies. Findings from this study are critical to design optimal ways of inhalation drug delivery using NP nanocarriers for this age group, as well as for better understanding of the potential adverse health effects of nanoparticle exposures in infants and young children.


PDE7B, NMBR and EPM2A Variants and Schizophrenia: A Case-Control and Pharmacogenetics Study.
We investigated phosphodiesterase 7B (PDE7B), neuromedin B receptor (NMBR) and epilepsy progressive myoclonus type 2A (EPM2A) genes in schizophrenia (SCZ). To the best of our knowledge, these genes have been poorly investigated in studies of SCZ. Five hundred and seventy-three SCZ inpatients of Korean ethnicity and 560 healthy controls were genotyped for 2 PDE7B, 3 NMBR and 3 EPM2A polymorphisms. Differences in the allelic and genetic frequencies among healthy subjects and patients were calculated using the x03C7;2 statistics. Repeated-measure ANOVA was used to test possible influences of single-nucleotide polymorphisms on treatment efficacy. In case of positive findings, clinical and demographic variables were added as covariates, in order to investigate possible stratixFB01;cation bias. The rs2717 and rs6926279 within the NMBR gene and rs702304 and rs2235481 within the EPM2A gene were associated with SCZ liability. rs1415744 was also associated with Positive and Negative Symptom Scale negative clinical improvement. The results remained the same after inclusion of the covariates and were partially confirmed in the allelic and haplotype analyses. Our preliminary findings suggest a possible role of NMBR and EPM2A genes in SCZ susceptibility and, for the second one, also in antipsychotic pharmacogenetics. Nonetheless, further research is needed to conxFB01;rm our findings.


[The psychiatric assessment and mental status examination from an EBM perspective].
Psychiatric assessment is a broader term than mental status examination. Psychiatric assessment requires the study of 'the comprehensive collection of data relevant for diagnosis and treatment', whereas mental status examination refers to 'the systematic registration of objective and subjective psychiatric symptoms at the time of assessment or during the current illness episode'. The evidence and the systematics of psychiatric assessment and mental status examination are based primarily on conventions established over time, on medical tradition and on the clinical experience of psychiatric experts. With regard to the mental status examination, according to Dutch tradition the symptoms are grouped on the basis of the 'classical' division of mental functions, the three groups being cognitive, affective and conative. The Dutch guidelines of 2004 is based primarily on 'expert opinion' and 'non-comparative research'. There is need for further scientific research which recognises that psychiatry is an applied clinical and idiographic science requiring an understanding and hermeneutic approach.


[The Schönlein-Henoch syndrome with severe multisystemic involvement].
A case of Henoch-Schönlein purpura (HSP) characterized by several unusual complications and exceedingly prolonged course is reported. A 6-year-old boy, hospitalized with a typical clinical picture of HSP, developed after a few days a severe gastrointestinal vasculitis leading to digestive hemorrhages and food intolerance. The treatment included continuous gastrointestinal infusion, parenteral nutrition, and corticosteroids during the exacerbations of symptoms. Intestinal ultrasonography showed diffuse submucous edema and widespread mural hematomas; hydrops of the gallbladder and edematous swelling of the pancreas were also detected. A gastro-duodenoscopy revealed diffuse and severe mucosal vasculitis with ulcers and petechial lesions. One week after admission the occurrence of weight gain, hyponatremia, and hypoprotidemia in the absence of proteinuria suggested a protein-losing enteropathy. The elevation of serum and urine amylases was consistent with pancreatic involvement. The course was characterized by recurrent exacerbations of gastrointestinal manifestations; symptoms subsided slowly to such a degree that oral feeding could be gradually restarted only seven weeks after admission. The use of high-frequency intestinal ultrasonography proved useful and sensitive in monitoring the evolution of intestinal involvement. During hospitalization the child complained of acute painful scrotal swelling. Ultrasonography showed scrotal hemorrhage and testicular swelling but no signs of testicular torsion, thus helping to avoid surgical exploration. In the recovery phase the child complained of colicky abdominal pain with vomiting. A plain abdominal roentgenogram showed bilateral staghorn pelvic urolithiasis. This finding was confirmed by an intravenous pyelography which also revealed a bilateral pyeloureteritis with edema of the ureteral wall and partial stenosis of the lumen.(ABSTRACT TRUNCATED AT 250 WORDS)


[Determination of intravascular and extravascular lung water after open heart surgery (author's transl)].
Total lung water (169 measurements) and intravascular lung volume (72 measurements) were determined postoperatively on 11 patients with aortic or mitral valve prostheses, by means of thermodilution (diffusable) and cardiogreen (non-diffusable). No loss of heat from the lungs occurred after injection into the trunk of the pulmonary artery and recordings in the left atrium. The admixture of the tracers was satisfactory. The extravascular volume was found to be higher than that measured by other authors, presumably owing to the greater efficacy of the thermodilution technique as compared to the use of tritiated water.


Ruptured valsalva sinus aneurysm to pericardium simulated aortic root dissection.
Ruptured valsalva sinus aneurysm to pericardium is a rare condition. Here, we described a case presented with tamponade. Initially, hemopericardium was partially drained and then, imaging evaluations were done. Transesophageal echocardiography showed limited dissection of aortic sinus and CT angiography of the ascending aorta showed deformed dilated right coronary sinus. Besides, surgery showed that windsock tract of the right coronary sinus had ruptured into the pericardium with avulsed right coronary aortic cusp. This case indicated a rare cause of cardiac tamponade and insufficiency of imaging modalities for making an accurate diagnosis.


Non-participation during azithromycin mass treatment for trachoma in The Gambia: heterogeneity and risk factors.
There is concern that untreated individuals in mass drug administration (MDA) programs for neglected tropical diseases can reduce the impact of elimination efforts by maintaining a source of transmission and re-infection. Treatment receipt was recorded against the community census during three MDAs with azithromycin for trachoma in The Gambia, a hypo-endemic setting. Predictors of non-participation were investigated in 1-9 year olds using random effects logistic regression of cross-sectional data for each MDA. Two types of non-participators were identified: present during MDA but not treated (PNT) and eligible for treatment but absent during MDA (EBA). PNT and EBA children were compared to treated children separately. Multivariable models were developed using baseline data and validated using year one and two data, with a priori adjustment for previous treatment status. Analyses included approximately 10000 children at baseline and 5000 children subsequently. There was strong evidence of spatial heterogeneity, and persistent non-participation within households and individuals. By year two, non-participation increased significantly to 10.4% overall from 6.2% at baseline, with more, smaller geographical clusters of non-participating households. Multivariable models suggested household level predictors of non-participation (increased time to water and household head non-participation for both PNT and EBA; increased household size for PNT status only; non-inclusion in a previous trachoma examination survey and younger age for EBA only). Enhanced coverage efforts did not decrease non-participation. Few infected children were detected at year three and only one infected child was EBA previously. Infected children were in communities close to untreated endemic areas with higher rates of EBA non-participation during MDA. In hypo-endemic settings, with good coverage and no association between non-participation and infection, efforts to improve participation during MDA may not be required. Further research could investigate spatial hotspots of infection and non-participation in other low and medium prevalence settings before allocating resources to increase participation.


Risk adjustment of nursing home quality indicators.
The purpose of this study was to develop a method for risk adjusting nursing home quality indicators (QI's). The QI's measure incidence and prevalence of resident-level care processes and outcomes which are indicative of care quality. Risk adjustment was carried out by stratifying residents into risk groups (high and low), calculating QI rates within groups, and then drawing comparisons across facilities. The method was examined through analysis of data from over 800 nursing homes in four states. Results showed that facilities differed substantially in QI rates even after risk had been taken into account. Also, results suggested differences in care quality which may not have been apparent without controlling for risk.


Gene expression profiling identifies MMP-12 and ADAMDEC1 as potential pathogenic mediators of pulmonary sarcoidosis.
Little is known about the genetic regulation of granulomatous inflammation in sarcoidosis. To determine if tissue gene array analysis would identify novel genes engaged in inflammation and lung remodeling in patients with sarcoidosis. Gene expression analysis was performed on tissues obtained from patients with sarcoidosis at the time of diagnosis (untreated) (n = 6) compared with normal lung tissue (n = 6). Expression of select genes was further confirmed in lung tissue from a second series of patients with sarcoidosis and disease-free control subjects (n = 11 per group) by semi-quantitative RT-PCR. Interactive gene networks were identified in patients with sarcoidosis using Ingenuity Pathway Analysis (Ingenuity Systems, Inc., Redwood, CA) software. The expression of proteins corresponding to selected overexpressed genes was determined using fluorokine multiplex analysis, and immunohistochemistry. Selected genes and proteins were then analyzed in bronchoalveolar lavage fluid in an independent series of patients with sarcoidosis (n = 36) and control subjects (n = 12). A gene network engaged in Th1-type responses was most significantly overexpressed in the sarcoidosis lung tissues, including genes not previously reported in the context of sarcoidosis (e.g., IL-7). MMP-12 and ADAMDEC1 transcripts were most highly expressed (> 25-fold) in sarcoidosis lung tissues, corresponding with increased protein expression by immunohistochemistry. MMP-12 and ADAMDEC1 gene and protein expression were increased in bronchoalveolar lavage samples from patients with sarcoidosis, correlating with disease severity. Tissue gene expression analyses provide novel insights into the pathogenesis of pulmonary sarcoidosis. MMP-12 and ADAMDEC1 emerge as likely mediators of lung damage and/or remodeling and may serve as markers of disease activity.


Conscious sedation versus general anaesthesia during mechanical thrombectomy for stroke: a propensity score analysis.
Debate exists as to whether patients with acute ischemic stroke who are undergoing mechanical thrombectomy should receive general anaesthesia or conscious sedation during the procedure. Using a multihospital administrative database, we compared outcomes and complications of patients receiving mechanical thrombectomy, who were receiving general anaesthesia and conscious sedation, and studied trends in usage over time. Premier database patients who underwent mechanical thrombectomy from 2006 to 2013 for acute ischemic stroke were identified. Using propensity score analysis, recipients of general anaesthesia and conscious sedation underwent 1:1 matching. Outcomes including usage trends, discharge status, mortality, length of stay, haemorrhage and pneumonia were examined. A total of 2512 patients receiving mechanical thrombectomy were identified. 1999 (80%) received general anaesthesia and 513 (20%) received conscious sedation. Following 1:1 matching by the propensity score matching, 507 general anaesthesia and 507 conscious sedation patients were matched. Patients who received general anaesthesia during their procedure had significantly higher rates of in-hospital mortality (25% vs 12%, OR=2.37 95% CI 1.68 to 3.37, p<0.0001), and pneumonia (17.0% vs 9.3%, OR=2.0, 95% CI 1.35 to 2.96, p=0.0005) compared with patients of thrombectomy who received conscious sedation. ICH/SAH rates were similar between patients receiving general anaesthesia and patients receiving conscious sedation (11% vs 12%, p=0.62). Usage rate of general anaesthesia decreased from 83.8% in 2006 and 74.0% in 2013. In our cohort, thrombectomy patients receiving conscious sedation have decreased in-hospital mortality, decreased rates of pneumonia, and lower hospital costs and lengths of stay when compared with patients who received general anaesthesia. However, most practitioners continue to use general anaesthesia in the setting of acute stroke interventions.


Regional difference in sodium chloride content in home-made and store-bought preparations of miso paste.
Miso, a fermentation product of salted soya beans and rice (or soya beans and barley), is one of the leading sources of sodium chloride intake for Japanese people. Sodium chloride contents in 973 home-made preparations collected from 39 Regions in 20 Prefectures in Japan showed wide variation from 9.1 to 18.2% on the Region average, while the levels in store-bought samples were rather low and constant at 10 to 12%. When classified by Regions or Prefectures, positive and significant correlations were observed between indices of sodium chloride intake via miso (i.e., sodium chloride in home-made miso, or frequency of miso soup intake) and death rate indices for cerebrovascular diseases.


Ventastega curonica and the origin of tetrapod morphology.
The gap in our understanding of the evolutionary transition from fish to tetrapod is beginning to close thanks to the discovery of new intermediate forms such as Tiktaalik roseae. Here we narrow it further by presenting the skull, exceptionally preserved braincase, shoulder girdle and partial pelvis of Ventastega curonica from the Late Devonian of Latvia, a transitional intermediate form between the 'elpistostegids' Panderichthys and Tiktaalik and the Devonian tetrapods (limbed vertebrates) Acanthostega and Ichthyostega. Ventastega is the most primitive Devonian tetrapod represented by extensive remains, and casts light on a part of the phylogeny otherwise only represented by fragmentary taxa: it illuminates the origin of principal tetrapod structures and the extent of morphological diversity among the transitional forms.


Suppressing of Src-Hic-5-JNK-AKT Signaling Reduced GAPDH Expression for Preventing the Progression of HuCCT1 Cholangiocarcinoma.
Cholangiocarcinoma (CCA) is a malignant neoplasm of the bile ducts, being the second most common type of cancer in the liver, and most patients are diagnosed at a late stage with poor prognosis. Targeted therapy aiming at receptors tyrosine kinases (RTKs) such as c-Met or EGFR have been developed but with unsatisfactory outcomes. In our recent report, we found several oncogenic molecules downstream of RTKs, including hydrogen peroxide clone-5 (Hic-5), Src, AKT and JNK, were elevated in tissues of a significant portion of metastatic CCAs. By inhibitor studies and a knockdown approach, these molecules were found to be within the same signal cascade responsible for the migration of HuCCT1 cells, a conventionally used CCA cell line. Herein, we also found Src inhibitor dasatinib and Hic-5 siRNA corporately suppressed HuCCT1 cell invasion. Moreover, dasatinib inhibited the progression of the HuCCT1 tumor on SCID mice skin coupled with decreasing the expression of Hic-5 and EGFR and the activities of Src, AKT and JNK. In addition, we found a glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and several cytoskeletal molecules such as tubulin and cofilin were dramatically decreased after a long-term treatment of the HuCCT1 tumor with a high dose of dasatinib. Specifically, GAPDH was shown to be a downstream effector of the Hic-5/Src/AKT cascade involved in HuCCT1 cell migration. On the other hand, TFK1, another CCA cell line without Hic-5 expression, exhibited very low motility, whereas an ectopic Hic-5 expression enhanced the activation of Src and AKT and marginally increased TFK1 migration. In the future, it is tempting to investigate whether cotargeting Src, Hic-5 and/or GAPDH is efficient for preventing CCA progression in future clinical trials.


Biomechanical effects of cranioplasty for defects using autogenous calvarial bone.
Harvesting autogenous calvarial bone grafts can potentially weaken the donor site and make it more susceptible to trauma. Conversely, restoring the integrity of the cranial vault structure can result in better dissipation of traumatic energy. This study proposes to mathematically model traumatic situations to evaluate the effect of cranioplasty on biomechanical properties of the craniofacial skeleton. Preoperative and 6-month postoperative computed tomography-generated DICOM data were used to extract a tetrahedral volumetric representation of the craniofacial skeleton. These data were then used in finite element solver-simulating traumatic events. Deformational stresses accumulate around defect edges and can serve as seed points for calvarial fractures at much lower energy levels in the preoperative models when compared to the postoperative models. Accumulation of stresses in the orbital roof/medial orbital wall areas was observed, similar to fracture patterns observed in the younger pediatric population Restoring architectural integrity of the craniofacial skeleton results in significant increased resistance to deformational stresses despite structural weakening caused by harvesting cranial bone.


Clarifying the role of sodium in the silica oligomerization reaction.
Silica oligomerization is the key reaction in zeolite synthesis. NaOH is a common additive in the zeolite synthesis that decreases the reaction rate of smaller silica oligomers and also affects the final structure of the zeolite. Here we report a study of the role of sodium in the initial stages of silica oligomerization. We performed ab initio molecular dynamics simulations using explicit aqueous solution in order to obtain the free energy profile and study the behavior of sodium during the reaction. Our study confirms that sodium decreases the reaction rates of oligomerization for smaller silica chains. Analysis of the molecular dynamics trajectories shows that sodium does not increase the reaction barriers by direct coordination to the silica. However, sodium is often present in the second solvation shell of the reactive atoms. Correlation between sodium presence in the first or the second shell of the reactive oxygen and a decrease in hydrogen bonding for that oxygen was found for the first reaction step. Therefore, the presence of sodium could contribute to an increase in reaction barriers for silica oligomerization by some rearrangement of the hydrogen bond network of water solution around the reactants.


Koala and Wombat Gammaherpesviruses Encode the First Known Viral NTPDase Homologs and Are Phylogenetically Divergent from All Known Gammaherpesviruses.
There is a large taxonomic gap in our understanding of mammalian herpesvirus genetics and evolution corresponding to those herpesviruses that infect marsupials, which diverged from eutherian mammals approximately 150 million years ago (mya). We compare the genomes of two marsupial gammaherpesviruses, Phascolarctid gammaherpesvirus 1 (PhaHV1) and Vombatid gammaherpesvirus 1 (VoHV1), which infect koalas (Phascolarctos cinereus) and wombats (Vombatus ursinus), respectively. The core viral genomes were approximately 117 kbp and 110 kbp in length, respectively, sharing 69% pairwise nucleotide sequence identity. Phylogenetic analyses showed that PhaHV1 and VoHV1 formed a separate branch, which may indicate a new gammaherpesvirus genus. The genomes contained 60 predicted open reading frames (ORFs) homologous to those in eutherian herpesviruses and 20 ORFs not yet found in any other herpesvirus. Seven of these ORFs were shared by the two viruses, indicating that they were probably acquired prespeciation, approximately 30 to 40 mya. One of these shared genes encodes a putative nucleoside triphosphate diphosphohydrolase (NTPDase). NTPDases are usually found in mammals and higher-order eukaryotes, with a very small number being found in bacteria. This is the first time that an NTPDase has been identified in any viral genome. Interrogation of public transcriptomic data sets from two koalas identified PhaHV1-specific transcripts in multiple host tissues, including transcripts for the novel NTPDase. PhaHV1 ATPase activity was also demonstrated in vitro, suggesting that the encoded NTPDase is functional during viral infection. In mammals, NTPDases are important in downregulation of the inflammatory and immune responses, but the role of the PhaHV1 NTPDase during viral infection remains to be determined.IMPORTANCE The genome sequences of the koala and wombat gammaherpesviruses show that the viruses form a distinct branch, indicative of a novel genus within the Gammaherpesvirinae Their genomes contain several new ORFs, including ORFs encoding a β-galactoside α-2,6-sialyltransferase that is phylogenetically closest to poxvirus and insect homologs and the first reported viral NTPDase. NTPDases are ubiquitously expressed in mammals and are also present in several parasitic, fungal, and bacterial pathogens. In mammals, these cell surface-localized NTPDases play essential roles in thromboregulation, inflammation, and immune suppression. In this study, we demonstrate that the virus-encoded NTPDase is enzymatically active and is transcribed during natural infection of the host. Understanding how these enzymes benefit viruses can help to inform how they may cause disease or evade host immune defenses.


The application of finite state machine in modeling and control of gene mutation process.
This paper extends our previous study on discrete events system formulations of DNA hybridization, and focuses discussions on metabolism and gene mutation in molecular biology. Finite state machine (FSM) theory is extensively applied to represent key concepts and analyzes the processes related to the biological phenomena mentioned above. The goal is to mathematically represent and interpret the process of gene mutation and the effects on structures of protein macro molecule caused by gene mutation. We hope the proposed model will provide a foothold for introducing the information science and the control theory tools in molecular biology.


Only one DQ-beta restriction fragment pattern of each DR specificity is associated with insulin-dependent diabetes.
Insulin-dependent diabetes is generally associated with the serologic HLA-DR specificities 3 and 4, in particular with DR-3,4 heterozygosity. The disease is negatively associated with DR-2. To investigate these associations further at the genomic level, DNA from 13 families with a proband having insulin-dependent diabetes, from 11 other individuals with the same disease, and from HLA-DR-matched control individuals was subjected to restriction fragment analysis. Three different enzymes (Bam HI, Eco RI, and Pvu II) and cDNA clones for three HLA-D region class II antigen alpha- and beta-chains (DR-beta, DQ-beta, and DQ-alpha) were used. In six families, a total of 11 siblings HLA-DR-identical to the proband were examined. There was no discrepancy between the hybridization patterns of the proband and those of the DR-identical siblings. Two different DQ-B fragment patterns were detected with each one of the serologic specificities DR-2 and DR-4. In both cases, only one of the patterns correlated significantly with diabetes. Thus, DQ-beta genomic hybridization may be used in conjunction with HLA-DR typing to identify individuals with higher relative risk to acquire insulin-dependent diabetes. These results may suggest that insulin-dependent diabetes is associated with the DQ rather than with the DR locus.


Metallated Isoindigo-Porphyrin Covalent Organic Framework Photocatalyst with a Narrow Band Gap for Efficient CO2 Conversion.
Photocatalytic CO2 reduction into formate (HCOO-) has been widely studied with semiconductor and molecule-based systems, but it is rarely investigated with covalent organic frameworks (COFs). Herein, we report a novel donor-acceptor COF named Co-PI-COF composed of isoindigo and metallated porphyrin subunits that exhibits high catalytic efficiency (∼50 μmol formate g-1 h-1) at low-power visible-light irradiation and in the absence of rare metal cocatalysts. Density functional theory calculations and experimental diffuse-reflectance measurements are used to explain the origin of catalytic efficiency and the particularly low band gap (0.56 eV) in this material. The mechanism of photocatalysis is also studied experimentally and is found to involve electron transfer from the sacrificial agent to the excited Co-PI-COF. The observed high-efficiency conversion could be ascribed to the enhanced CO2 adsorption on the coordinatively unsaturated cobalt centers, the narrow band gap, and the efficient transfer of the charge originating from the postsynthetic metallation. It is anticipated that this study will pave the way toward the design of new simple and efficient catalysts for photocatalytic CO2 reduction into useful products.


Diagnostic criteria for renovascular disease: where are we now?
Renovascular disease, especially atherosclerotic renal artery stenosis (ARAS) in older subjects, is commonly encountered in clinical practice. This is at least in part due to the major advances in non-invasive imaging techniques that allow greater diagnostic sensitivity and accuracy than ever before. Despite increased awareness of ARAS, renal revascularization is less commonly performed, likely as a result of several prospective, randomized, clinical trials which fail to demonstrate major benefits of renal revascularization beyond medical therapy alone. Primary care physicians are less likely to investigate renovascular disease and nephrologists likely see more patients after a period of unsuccessful medical therapy with more advanced ARAS. The goal of this review is to revisit current diagnostic and therapeutic paradigms in order to characterize more clearly which patients will likely benefit from further evaluation and intensive treatment of renal artery stenosis.


Induction of polyclonal prostate cancer-specific CTL using dendritic cells transfected with amplified tumor RNA.
Polyvalent cancer vaccines targeting the entire antigenic spectrum on tumor cells may represent a superior therapeutic strategy for cancer patients than vaccines solely directed against single Ags. In this study, we show that autologous dendritic cells (DC) transfected with RNA amplified from microdissected tumor cells are capable of stimulating CTL against a broad set of unidentified and critical prostate-specific Ags. Although the polyclonal CTL responses generated with amplified tumor RNA-transfected DC encompassed as a subcomponent a response against prostate-specific Ag (PSA) as well as against telomerase reverse transcriptase, the tumor-specific CTL were consistently more effective than PSA or telomerase reverse transcriptase CTL to lyse tumor targets, suggesting the superiority of the polyclonal response. Although tumor RNA-transfected DC stimulated CTL, which recognized not only tumor but also self-Ags expressed by benign prostate tissue, these cross-reactive CTL were exclusively specific for the PSA, indicating an immunodominant role of PSA in the prostate cancer-specific immune response. Our data suggest that tumor RNA-transfected DC may represent a broadly applicable, potentially clinically effective vaccine strategy for prostate cancer patients, which is not limited by tumor tissue availability for Ag preparation and may minimize the risk of clonal tumor escape.


Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects.
The ability to induce cortical plasticity with non-invasive brain stimulation (NBS) techniques has provided novel and exciting opportunities for examining the role of the human cortex during a variety of behaviours. Additionally, and importantly, the induction of lasting changes in cortical excitability can, under some conditions, reversibly modify behaviour and interact with normal learning. Such findings have driven a large number of recent studies examining whether by using such approaches it might be possible to induce functionally significant changes in patients with a large variety of neurological and psychiatric conditions including stroke, Parkinson's disease and depression. However, even in neurologically normal subjects the variability in the neurophysiological and behavioural response to such brain stimulation techniques is high. This variability at present limits the therapeutic usefulness of these techniques. The cause of this variability is multifactorial and to some degree still unknown. However, a number of factors that can influence the induction of plasticity have been identified. This review will summarise what is known about the causes of variability in healthy subjects and propose additional factors that are likely to be important determinants. A greater understanding of these determinants is critical for optimising the therapeutic applications of non-invasive brain stimulation techniques.


A Versatile and Highly Selective Colorimetric Sensor for the Detection of Amines.
The utility of Meldrum's activated furan (MAF) for the colorimetric detection of sub ppm levels of amines in solution, on solid supports, and as vapors is reported. MAF is synthesized in one step from inexpensive and commercially available starting materials and exhibits high selectivity for primary and secondary amines in the presence of competing nucleophiles. The reaction between activated furans and amines results in a distinct color change, discernable by the naked eye. UV/Vis absorption spectroscopy was utilized to monitor reactions in solution and determine detection limits. Additionally, solutions of MAF were useful as stains for thin layer chromatography and for monitoring solid-phase synthesis of peptides and peptidomimetics. Finally, MAF was used to detect volatile amines released from fish samples, demonstrating potential for food spoilage applications.


Gait analysis using floor markers and inertial sensors.
In this paper, a gait analysis system which estimates step length and foot angles is proposed. A measurement unit, which consists of a camera and inertial sensors, is installed on a shoe. When the foot touches the floor, markers are recognized by the camera to obtain the current position and attitude. A simple planar marker with 4,096 different codes is used. These markers printed on paper are placed on the floor. When the foot is moving off the floor, the position and attitude are estimated using an inertial navigation algorithm. For accurate estimation, a smoother is proposed, where vision information and inertial sensor data are combined. Through experiments, it is shown that the proposed system can both track foot motion and estimate step length.


Identification of nucleic acid binding sites on translin-associated factor X (TRAX) protein.
Translin and TRAX proteins play roles in very important cellular processes such as DNA recombination, spatial and temporal expression of mRNA, and in siRNA processing. Translin forms a homomeric nucleic acid binding complex and binds to ssDNA and RNA. However, a mutant translin construct that forms homomeric complex lacking nucleic acid binding activity is able to form fully active heteromeric translin-TRAX complex when co-expressed with TRAX. A substantial progress has been made in identifying translin sites that mediate its binding activity, while TRAX was thought not to bind DNA or RNA on its own. We here for the first time demonstrate nucleic acid binding to TRAX by crosslinking radiolabeled ssDNA to heteromeric translin-TRAX complex using UV-laser. The TRAX and translin, photochemically crosslinked with ssDNA, were individually detected on SDS-PAGE. We mutated two motifs in TRAX and translin, designated B2 and B3, to help define the nucleic acid binding sites in the TRAX sequence. The most pronounced effect was observed in the mutants of B3 motif that impaired nucleic acid binding activity of the heteromeric complexes. We suggest that both translin and TRAX are binding competent and contribute to the nucleic acid binding activity.