Mechanisms of HIV-associated lymphocyte apoptosis.
Infection with the human immunodeficiency virus (HIV) is associated with a progressive decrease in CD4 T-cell number and a consequent impairment in host immune defenses. Analysis of T cells from patients infected with HIV, or of T cells infected in vitro with HIV, demonstrates a significant fraction of both infected and uninfected cells dying by apoptosis. The many mechanisms that contribute to HIV-associated lymphocyte apoptosis include chronic immunologic activation; gp120/160 ligation of the CD4 receptor; enhanced production of cytotoxic ligands or viral proteins by monocytes, macrophages, B cells, and CD8 T cells from HIV-infected patients that kill uninfected CD4 T cells; and direct infection of target cells by HIV, resulting in apoptosis. Although HIV infection results in T-cell apoptosis, under some circumstances HIV infection of resting T cells or macrophages does not result in apoptosis; this may be a critical step in the development of viral reservoirs. Recent therapies for HIV effectively reduce lymphoid and peripheral T-cell apoptosis, reduce viral replication, and enhance cellular immune competence; however, they do not alter viral reservoirs. Further understanding the regulation of apoptosis in HIV disease is required to develop novel immune-based therapies aimed at modifying HIV-induced apoptosis to the benefit of patients infected with HIV.


Downregulation of AMPK accompanies leucine- and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle.
Branched-chain amino acids, such as leucine and glucose, stimulate protein synthesis and increase the phosphorylation and activity of the mammalian target of rapamycin (mTOR) and its downstream target p70S6 kinase (p70S6K). We examined in skeletal muscle whether the effects of leucine and glucose on these parameters and on insulin resistance are mediated by the fuel-sensing enzyme AMP-activated protein kinase (AMPK). Rat extensor digitorum longus (EDL) muscle was incubated with different concentrations of leucine and glucose with or without AMPK activators. Muscle obtained from glucose-infused rats was also used as a model. In the EDL, incubation with 100 or 200 μmol/l leucine versus no added leucine suppressed the activity of the α2 isoform of AMPK by 50 and 70%, respectively, and caused concentration-dependent increases in protein synthesis and mTOR and p70S6K phosphorylation. Very similar changes were observed in EDL incubated with 5.5 or 25 mmol/l versus no added glucose and in muscle of rats infused with glucose in vivo. Incubation of the EDL with the higher concentrations of both leucine and glucose also caused insulin resistance, reflected by a decrease in insulin-stimulated Akt phosphorylation. Coincubation with the AMPK activators AICAR and α-lipoic acid substantially prevented all of those changes and increased the phosphorylation of specific sites of mTOR inhibitors raptor and tuberous sclerosis complex 2 (TSC2). In contrast, decreases in AMPK activity induced by leucine and glucose were not associated with a decrease in raptor or TSC2 phosphorylation. The results indicate that both leucine and glucose modulate protein synthesis and mTOR/p70S6 and insulin signaling in skeletal muscle by a common mechanism. They also suggest that the effects of both molecules are associated with a decrease in AMPK activity and that AMPK activation prevents them.


Amorphous Carbon Generation as a Photocatalytic Reaction on DNA-Assembled Gold and Silver Nanostructures.
Background signals from in situ-formed amorphous carbon, despite not being fully understood, are known to be a common issue in few-molecule surface-enhanced Raman scattering (SERS). Here, discrete gold and silver nanoparticle aggregates assembled by DNA origami were used to study the conditions for the formation of amorphous carbon during SERS measurements. Gold and silver dimers were exposed to laser light of varied power densities and wavelengths. Amorphous carbon prevalently formed on silver aggregates and at high power densities. Time-resolved measurements enabled us to follow the formation of amorphous carbon. Silver nanolenses consisting of three differently-sized silver nanoparticles were used to follow the generation of amorphous carbon at the single-nanostructure level. This allowed observation of the many sharp peaks that constitute the broad amorphous carbon signal found in ensemble measurements. In conclusion, we highlight strategies to prevent amorphous carbon formation, especially for DNA-assembled SERS substrates.


A healthy, sustainable and safe food system: examining the perceptions and role of the Australian policy actor using a Delphi survey.
There is an urgent need to identify and develop cross-sectoral policies which promote and support a healthy, safe and sustainable food system. To help shape the political agenda, a critical first step is a shared definition of such a system among policy makers across relevant sectors. The aim of the present study was to determine how Australian policy actors define, and contribute to, a healthy, safe and sustainable food system. A Delphi survey, consisting of two rounds, was conducted. Participants were asked how they define, and contribute to, a healthy, safe and sustainable food system (Round 1) and indicate their level of agreement with summary statements (Round 2). This was an online Delphi survey conducted in Australia. Twenty-nine and fourteen multisectoral and multilevel policy makers completed Round 1 and Round 2, respectively. The definition included food processing regulation, environmentally friendly food production and access to nutritious food. All agreed that it was important for them to improve access and supply of healthy food and ensure healthy planning principles are applied. There were cross-sectoral differences in definitions and contributions; however, critical consensus was achieved. The study contributes to the definition of key elements of a cross-sectoral food and nutrition policy to meet today's environmental, health, social and economic challenges; however, further research using a more representative multisectoral sample is warranted.


Extensive characterization of Campylobacter jejuni chicken isolates to uncover genes involved in the ability to compete for gut colonization.
Campylobacter jejuni is responsible for human foodborne enteritis. This bacterium is a remarkable colonizer of the chicken gut, with some strains outcompeting others for colonization. To better understand this phenomenon, the objective of this study was to extensively characterize the phenotypic performance of C. jejuni chicken strains and associate their gut colonizing ability with specific genes. C. jejuni isolates (n = 45) previously analyzed for the presence of chicken colonization associated genes were further characterized for phenotypic properties influencing colonization: autoagglutination and chemotaxis as well as adhesion to and invasion of primary chicken caecal cells. This allowed strains to be ranked according to their in vitro performance. After their in vitro capacity to outcompete was demonstrated in vivo, strains were then typed by comparative genomic fingerprinting (CGF). In vitro phenotypical properties displayed a linear variability among the tested strains. Strains possessing higher scores for phenotypical properties were able to outcompete others during chicken colonization trials. When the gene content of strains was compared, some were associated with different phenotypical scores and thus with different outcompeting capacities. Use of CGF profiles showed an extensive genetic variability among the studied strains and suggested that the outcompeting capacity is not predictable by CGF profile. This study revealed a wide array of phenotypes present in C. jejuni strains, even though they were all recovered from chicken caecum. Each strain was classified according to its in vitro competitive potential and its capacity to compete for chicken gut colonization was associated with specific genes. This study also exposed the disparity existing between genetic typing and phenotypical behavior of C. jejuni strains.


Uveoscleral outflow--a review.
The uveoscleral outflow route was described more than 40 years ago. Part of aqueous leaves the eye through the iris root. The ciliary muscle, and there are large species differences in the fraction of aqueous outflow that leaves the eye through this route. In non-human primates 40-50% of aqueous leaves the eye by the uveoscleral route. In human eyes most data has been collected by indirect calculations, with results suggesting a similar fraction, at least in eyes from younger individuals. An age-dependent reduction in uveoscleral flow in human eyes may explain the initial difference seen between non-human primate and human eyes. Unlike trabecular outflow, intraocular pressures within the normal range have little effect on uveoscleral outflow. This may be explained by the fact that changes in intraocular pressure have little effect on the pressure gradient for flow through the ciliary muscle, which is likely to be the rate-limiting step in uveoscleral outflow. The state of the ciliary muscle is important and contraction reduces while relaxation increases uveoscleral flow. Similar effects are achieved with cholinergic agonists and antagonists. Epinephrine increases uveoscleral flow, most likely through stimulating beta(2)-adrenergic receptors. Prostaglandin F(2alpha) and prostaglandin F(2alpha)-analogues effectively reduce intraocular pressure by increasing uveoscleral flow. This is mediated by structural changes in the extracellular matrix of the ciliary muscle, and is likely to contribute to a valuable excess route for aqueous and proteins during intraocular inflammation. Whether uveoscleral flow plays a significant role in any other eye disease is not clear. Thus, 40 years later we are able to successfully increase aqueous flow through the uveoscleral route, a valuable contribution to glaucoma treatment, but we still have only a limited understanding on its physiological role.


Adrenal peripheral oscillator in generating the circadian glucocorticoid rhythm.
The mammalian circadian timing system is organized into hierarchical structures with a central clock in the suprachiasmatic nucleus (SCN) and subsidiary peripheral oscillators. After the discovery of the local clockwork in peripheral organs and tissues, which have a molecular makeup similar to the central pacemaker SCN, uncovering the roles of the peripheral clock in the rhythmic physiology has been an emerging goal in chronobiology. Glucocorticoid (GC) is a multifunctional adrenal steroid hormone that shows a robust circadian rhythm. The daily GC rhythm has long been thought to be governed by the SCN via the hypothalamus-pituitary-adrenal neuroendocrine axis. Recent findings, however, indicate that multiple regulatory mechanisms, including the adrenal intrinsic mechanism by the peripheral clock, are also involved. GC regulates diverse physiological processes and acts as a signal for resetting peripheral clocks, which suggests the importance of the GC rhythm in harmonizing overall circadian physiology and behavior. Therefore, in this review, we will discuss the important role of the adrenal peripheral clockwork in the circadian regulation of GC and its physiological relevance in the circadian timing system.


Ipsilateral whiskers suppress experience-dependent plasticity in the barrel cortex.
Each cerebral hemisphere processes sensory input from both sides of the body, but the impact of this convergence on shaping and modifying receptive field properties remains controversial. Here we investigated the effect of chronic deprivation of ipsilateral sensory whiskers on receptive field plasticity in primary somatosensory cortex. In the absence of ipsilateral whiskers, cortical receptive fields were significantly larger than control after 1 week. Removal of all but a single whisker from one side of the face [single-whisker experience (SWE)] has been shown to result in the expansion of the cortical area responding to the spared whisker. We compared the effects of SWE in the presence (SWE-unilateral) and absence (SWE-bilateral) of ipsilateral whiskers. SWE-bilateral deprivation results in a significant increase in neuronal responses to spared whisker stimulation both in its cognate barrel column and in adjacent, surrounding barrel columns compared with control and SWE-unilateral deprived animals. Surround receptive fields in deprived columns were maintained in SWE-bilateral treated animals but depressed in SWE-unilateral animals. The increase in spared whisker responses was progressive with longer deprivation periods. These data show that ipsilateral whiskers can constrain receptive field size in the barrel cortex.


Health care-associated native valve endocarditis: importance of non-nosocomial acquisition.
The clinical profile and outcome of nosocomial and non-nosocomial health care-associated native valve endocarditis are not well defined. To compare the characteristics and outcomes of community-associated and nosocomial and non-nosocomial health care-associated native valve endocarditis. Prospective cohort study. 61 hospitals in 28 countries. Patients with definite native valve endocarditis and no history of injection drug use who were enrolled in the ICE-PCS (International Collaboration on Endocarditis Prospective Cohort Study) from June 2000 to August 2005. Clinical and echocardiographic findings, microbiology, complications, and mortality. Health care-associated native valve endocarditis was present in 557 (34%) of 1622 patients (303 with nosocomial infection [54%] and 254 with non-nosocomial infection [46%]). Staphylococcus aureus was the most common cause of health care-associated infection (nosocomial, 47%; non-nosocomial, 42%; P = 0.30); a high proportion of patients had methicillin-resistant S. aureus (nosocomial, 57%; non-nosocomial, 41%; P = 0.014). Fewer patients with health care-associated native valve endocarditis had cardiac surgery (41% vs. 51% of community-associated cases; P < 0.001), but more of the former patients died (25% vs. 13%; P < 0.001). Multivariable analysis confirmed greater mortality associated with health care-associated native valve endocarditis (incidence risk ratio, 1.28 [95% CI, 1.02 to 1.59]). Patients were treated at hospitals with cardiac surgery programs. The results may not be generalizable to patients receiving care in other types of facilities or to those with prosthetic valves or past injection drug use. More than one third of cases of native valve endocarditis in non-injection drug users involve contact with health care, and non-nosocomial infection is common, especially in the United States. Clinicians should recognize that outpatients with extensive out-of-hospital health care contacts who develop endocarditis have clinical characteristics and outcomes similar to those of patients with nosocomial infection. None.


A Mechanistic Neural Field Theory of How Anesthesia Suppresses Consciousness: Synaptic Drive Dynamics, Bifurcations, Attractors, and Partial State Equipartitioning.
With the advances in biochemistry, molecular biology, and neurochemistry there has been impressive progress in understanding the molecular properties of anesthetic agents. However, there has been little focus on how the molecular properties of anesthetic agents lead to the observed macroscopic property that defines the anesthetic state, that is, lack of responsiveness to noxious stimuli. In this paper, we use dynamical system theory to develop a mechanistic mean field model for neural activity to study the abrupt transition from consciousness to unconsciousness as the concentration of the anesthetic agent increases. The proposed synaptic drive firing-rate model predicts the conscious-unconscious transition as the applied anesthetic concentration increases, where excitatory neural activity is characterized by a Poincaré-Andronov-Hopf bifurcation with the awake state transitioning to a stable limit cycle and then subsequently to an asymptotically stable unconscious equilibrium state. Furthermore, we address the more general question of synchronization and partial state equipartitioning of neural activity without mean field assumptions. This is done by focusing on a postulated subset of inhibitory neurons that are not themselves connected to other inhibitory neurons. Finally, several numerical experiments are presented to illustrate the different aspects of the proposed theory.


Neural circuit interactions between the dorsal raphe nucleus and the lateral hypothalamus: an experimental and computational study.
Orexinergic/hypocretinergic (Ox) neurotransmission plays an important role in regulating sleep, as well as in anxiety and depression, for which the serotonergic (5-HT) system is also involved in. However, little is known regarding the direct and indirect interactions between 5-HT in the dorsal raphe nucleus (DRN) and Ox neurons in the lateral hypothalamus (LHA). In this study, we report the additional presence of 5-HT1BR, 5-HT2AR, 5-HT2CR and fast ligand-gated 5-HT3AR subtypes on the Ox neurons of transgenic Ox-enhanced green fluorescent protein (Ox-EGFP) and wild type C57Bl/6 mice using single and double immunofluorescence (IF) staining, respectively, and quantify the colocalization for each 5-HT receptor subtype. We further reveal the presence of 5-HT3AR and 5-HT1AR on GABAergic neurons in LHA. We also identify NMDAR1, OX1R and OX2R on Ox neurons, but none on adjacent GABAergic neurons. This suggests a one-way relationship between LHA's GABAergic and Ox neurons, wherein GABAergic neurons exerts an inhibitory effect on Ox neurons under partial DRN's 5-HT control. We also show that Ox axonal projections receive glutamatergic (PSD-95 immunopositive) and GABAergic (Gephyrin immunopositive) inputs in the DRN. We consider these and other available findings into our computational model to explore possible effects of neural circuit connection types and timescales on the DRN-LHA system's dynamics. We find that if the connections from 5-HT to LHA's GABAergic neurons are weakly excitatory or inhibitory, the network exhibits slow oscillations; not observed when the connection is strongly excitatory. Furthermore, if Ox directly excites 5-HT neurons at a fast timescale, phasic Ox activation can lead to an increase in 5-HT activity; no significant effect with slower timescale. Overall, our experimental and computational approaches provide insights towards a more complete understanding of the complex relationship between 5-HT in the DRN and Ox in the LHA.


Fc-epsilon-RI, the high affinity IgE-receptor, is robustly expressed in the upper gastrointestinal tract and modulated by mucosal inflammation.
The role of the high affinity IgE receptor, FcεRI, in IgE-mediated immune responses of the gastrointestinal (GI) mucosa is poorly understood. Currently, a detailed characterization of FcεRI expression throughout the human gut is lacking. The aim of this study was to define the expression pattern of FcεRI in the GI tract. We compared FcεRI expression in children with gastritis/esophagitis (n = 10), celiac disease (n = 10), inflammatory bowel disease (IBD) (n = 9), and normal mucosa (n = 5). The α-subunit of FcεRI (FcεRIα), detected by immunohistochemistry, was found on cells infiltrating the mucosa of the esophagus, the stomach, and the duodenum, but was rarely detected in more distal sections of the GI tract. Accordingly, quantitative RT-PCR analysis on esophagus, stomach, duodenum, colon, and rectum biopsies revealed that FcεRIα and -β expression levels decreased towards the distal intestine. mRNA transcripts of the common Fc-receptor-γ chain were present in the entire GI mucosa. Double-immunofluorescence staining of esophageal specimens confirmed that FcεRIα was expressed on intraepithelial mast cells and Langerhans cells. The mRNA expression levels of the α, β, and γ subunits of FcεRI did not correlate with total serum IgE but were associated with mucosal inflammation. Our data define the upper GI tract as the main site for IgE-mediated immune activation via FcεRI. Tissue mRNA levels of FcεRIα are regulated by inflammatory conditions rather than serum IgE, indicating that FcεRI might also play a role in pathologies other than allergy.


Development knowledge and experience--from Bangladesh to Afghanistan and beyond.
In Afghanistan the challenges of development are daunting, mainly as a result of many years of conflict. The formation of a new government in 2001 paved the way for new initiatives from within and outside the country. BRAC (formerly Bangladesh Rural Advancement Committee), a Bangladeshi nongovernmental organization with a long history of successful work, extended its development model to Afghanistan in 2002. Provincial Afghanistan. BRAC has implemented programmes in Afghanistan in the areas of health, education, microfinance, women's empowerment, agriculture, capacity development and local government strengthening, and has taken many of these programmes to scale. With a total staff of over 3000 (94% Afghan and the rest Bangladeshis), BRAC now works in 21 of the country's 34 provinces. BRAC runs 629 non-formal primary schools with 18 155 students, mostly girls. In health, BRAC has trained 3589 community workers who work at the village level in preventive and curative care. BRAC runs the largest microfinance programme in the country with 97 130 borrowers who cumulatively borrowed over US$ 28 million with a repayment rate of 98%. Initial research indicates significant improvement in access to health care. Over three years, much has been achieved and learned. This paper summarizes these experiences and concludes that collaboration between developing countries can work, with fine-tuning to suit local contexts and traditions.


Clinical Studies of Cell Therapy in Cardiovascular Medicine: Recent Developments and Future Directions.
Given the rising prevalence of cardiovascular disease worldwide and the limited therapeutic options for severe heart failure, novel technologies that harness the regenerative capacity of the heart are sorely needed. The therapeutic use of stem cells has the potential to reverse myocardial injury and improve cardiac function, in contrast to most current medical therapies that only mitigate heart failure symptoms. Nearly 2 decades and >200 trials for cardiovascular disease have revealed that most cell types are safe; however, their efficacy remains controversial, limiting the transition of this therapy from investigation to practice. Lessons learned from these initial studies are driving the design of new clinical trials; higher fidelity of cell isolation techniques, standardization of conditions, more consistent use of state of the art measurement techniques, and assessment of multiple end points to garner insights into the efficacy of stem cells. Translation to clinical trials has almost outpaced our mechanistic understanding, and individual patient factors likely play a large role in stem cell efficacy. Therefore, careful analysis of dosing, delivery methods, and the ideal patient populations is necessary to translate cell therapy from research to practice. We are at a pivotal stage in the field in which information from many relatively small clinical trials must guide carefully executed efficacy trials. Larger efficacy trials are being launched to answer questions about older, first-generation stem cell therapeutics, while novel, second-generation products are being introduced into the clinical realm. This review critically examines the current state of clinical research on cell-based therapies for cardiovascular disease, highlighting the controversies in the field, improvements in clinical trial design, and the application of exciting new cell products.


The Distribution of Quill Mites (Betasyringophiloidus seiuri) Among Flight Feathers of the Ovenbird (Seiurus aurocapilla).
Quill mites of the family Syringophilidae (Acariformes: Prostigmata) are permanent ectoparasites that live inside the hollow quills of feathers and use their long chelicerae to pierce the quill wall to feed on living tissue of the quill follicle. Ovenbirds (Parulidae: Seiurus aurocapilla (Linnaeus)) are host to the quill mite Betasyringophiloidus seiuri (Clark), which has been previously reported to infest only 5.1% of this host's tail feathers; however, this species has also been reported to inhabit the wing feathers of ovenbirds, but without any data on prevalence or intensity. We examined all 1,008 flight feathers from 21 dead ovenbirds from Canada for quill mites and calculated infestation parameters per feather location. Nine of the 21 birds were infested with mites (prevalence of 42.9%). Feathers with the highest prevalence were Primaries 1 and 2 and Secondaries 1, 2, and 5. Only 2 of the 9 infested birds had mites in their tail feathers; in each case, only a single feather was infested. Mean intensity was 28.4 mites/feather with a range of 2-135.6, and ∼88% of the adult mites were female. To determine if quill volume and quill wall thickness correlated with mite presence and abundance, we took quill measurements from the flight feathers of 3 additional ovenbirds. There was a strong positive correlation between quill volume and mean mite intensity. Feathers that had quill walls thicker in some areas than the mites' extended chelicerae had lower prevalences than did feathers with walls consistently thinner than the length of the chelicerae. We conclude that B. seiuri is much more likely to be found in wing than in tail feathers and that it has greater reproductive success in quills with both large volumes and thin walls; however, whether foundress mites preferentially choose to colonize these feathers requires more study.


The group I strain of Streptococcus mutans, UA140, produces both the lantibiotic mutacin I and a nonlantibiotic bacteriocin, mutacin IV.
Strains of Streptococcus mutans produce at least three mutacins, I, II, and III. Mutacin II is a member of subgroup AII in the lantibiotic family of bacteriocins, and mutacins I and III belong to subgroup AI in the lantibiotic family. In this report, we characterize two mutacins produced by UA140, a group I strain of S. mutans. One is identical to the lantibiotic mutacin I produced by strain CH43 (F. Qi et al., Appl. Environ. Microbiol. 66:3221-3229, 2000); the other is a nonlantibiotic bacteriocin, which we named mutacin IV. Mutacin IV belongs to the two-peptide, nonlantibiotic family of bacteriocins produced by gram-positive bacteria. Peptide A, encoded by gene nlmA, is 44 amino acids (aa) in size and has a molecular mass of 4,169 Da; peptide B, encoded by nlmB, is 49 aa in size and has a molecular mass of 4,826 Da. Both peptides derive from prepeptides with glycines at positions -2 and -1 relative to the processing site. Production of mutacins I and IV by UA140 appears to be regulated by different mechanisms under different physiological conditions. The significance of producing two mutacins by one strain under different conditions and the implication of this property in terms of the ecology of S. mutans in the oral cavity are discussed.


Variable Cadence Walking and Ground Adaptive Standing With a Powered Ankle Prosthesis.
This paper describes a control approach that provides walking and standing functionality for a powered ankle prosthesis, and demonstrates the efficacy of the approach in experiments with a unilateral transtibial amputee subject. Both controllers incorporate a finite-state structure that emulates healthy ankle joint behavior via a series of piecewise passive impedance functions. The walking controller additionally modifies impedance parameters based on estimated cadence, while the standing controller modulates the ankle equilibrium angle in order to adapt to the ground slope and user posture, and the supervisory controller selects between the walking and standing controllers. The system is shown to reproduce several essential biomechanical features of the healthy joint during walking, particularly relative to a passive prosthesis, and is shown to adapt to various cadences. The system is also shown to adapt to slopes over a range of ±15°, providing support to the user, as validated by quasi-static stiffness measurements recorded by the prosthesis. The subject is shown to place more weight on the powered prosthesis than on his passive prosthesis when standing on sloped surfaces, particularly at angles of 10° or greater. The authors also demonstrated that the prosthesis typically began providing support within 1 s of initial ground contact. Further, the supervisory controller was shown to effectively switch between walking and standing, as well as determine ground slope just prior to the transition from the standing controller to the walking controller, where the estimated ground slope was accurate to within 1.25° for all trials.


Conditional immortalization of Gunn rat hepatocytes: an ex vivo model for evaluating methods for bilirubin-UDP-glucuronosyltransferase gene transfer.
Viral vectors and protein carriers utilizing asialoglycoprotein receptor (ASGR)-mediated endocytosis are being developed to transfer genes for the correction of bilirubin-UDP-glucuronosyltransferase (bilirubin-UGT) deficiency. Ex vivo evaluation of these gene transfer vectors would be facilitated by a cell system that lacks bilirubin-UGT, but expresses differentiated liver functions, including ASGR. We immortalized primary Gunn rat hepatocytes by transduction with a recombinant Moloney murine leukemia virus expressing a thermolabile mutant SV40 large T antigen (tsA58). At 33 degrees C, the immortalized hepatocyte clones expressed SV40 large T antigen, synthesized DNA, and doubled in number every 2 to 3 days. At this temperature, differentiated hepatocyte markers, e.g., albumin, ASGR, and androsterone-UGT, were expressed at 5% to 10% of the levels found in primary hepatocytes maintained in culture for 24 hours. Glutathione-S-transferase Yp (GST-Yp), an oncofetal protein, was expressed in these cells at 33 degrees C, but was undetectable in primary hepatocytes. In contrast, when the cells were cultured at 39 degrees C or 37 degrees C, the large T antigen was degraded, DNA synthesis and cell growth stopped, and morphologic characteristics of differentiated hepatocytes were observed. The expression of albumin, ASGR, and androsterone-UGT, and their corresponding mRNAs, increased to 25% to 40% of the level in primary hepatocytes, whereas GST-Yp expression decreased. Functionality of ASGR was demonstrated by internalization of Texas red-labeled asialoorosomucoid, and binding and degradation of 125I-asialoorosomucoid. After liposome-mediated transfer of a plasmid containing the coding region of human bilirubin-UGT1, driven by the SV40 large T promoter, active human bilirubin-UGT1 was expressed in these cells. The immortalized cells were not tumorigenic after transplantation into severe combined immunodeficiency mice. These conditionally immortalized cells will be useful for ex vivo evaluation of bilirubin-UGT gene transfer vectors.


Best practices in NCLEX-RN readiness preparation for baccalaureate student success.
Success for first-time takers of the NCLEX-RN has implications for the students, faculty, and nursing programs. As the passing standard for the NCLEX-RN has risen, some programs have experienced a corresponding decrease in their graduates' first-time pass rates. This article describes one baccalaureate program's journey from low first-time NCLEX-RN pass rates in 2001 to greater student and program success using a data-based, analytical approach. Although passing an exit exam was a program requirement for 20 years, the change to computerized testing and more in-depth test preparation has enhanced opportunities for success for students and reduced stress.among faculty. The resulting best practices for preparing students for NCLEX-RN success are described.


Visual mate preference evolution during butterfly speciation is linked to neural processing genes.
Many animal species remain separate not because their individuals fail to produce viable hybrids but because they "choose" not to mate. However, we still know very little of the genetic mechanisms underlying changes in these mate preference behaviours. Heliconius butterflies display bright warning patterns, which they also use to recognize conspecifics. Here, we couple QTL for divergence in visual preference behaviours with population genomic and gene expression analyses of neural tissue (central brain, optic lobes and ommatidia) across development in two sympatric Heliconius species. Within a region containing 200 genes, we identify five genes that are strongly associated with divergent visual preferences. Three of these have previously been implicated in key components of neural signalling (specifically an ionotropic glutamate receptor and two regucalcins), and overall our candidates suggest shifts in behaviour involve changes in visual integration or processing. This would allow preference evolution without altering perception of the wider environment.


Sensitivity to sunburn is associated with susceptibility to ultraviolet radiation-induced suppression of cutaneous cell-mediated immunity.
Skin cancer incidence is highest in white-skinned people. Within this group, skin types I/II (sun sensitive/tan poorly) are at greater risk than skin types III/IV (sun tolerant/tan well). Studies in mice demonstrate that ultraviolet radiation (UVR)-induced suppression of cell-mediated immune function plays an important role in the development of skin cancer and induces a susceptibility to infectious disease. A similar role is suspected in humans, but we lack quantitative human data to make risk assessments of ambient solar exposure on human health. This study demonstrates that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo (n = 93). There was a linear relationship between increase in erythema and suppression of CHS (P < 0.001), and a moderate sunburn (two minimal erythema doses [2 MED]) was sufficient to suppress CHS in all volunteers by 93%. However, a single suberythemal exposure of either 0.25 or 0.5 MED suppressed CHS responses by 50 and 80%, respectively, in skin types I/II, whereas 1 MED only suppressed CHS by 40% in skin types III/IV. The two- to threefold greater sensitivity of skin types I/II for a given level of sunburn may play a role in their greater sensitivity to skin cancer.


Retention in care among HIV-infected pregnant and breastfeeding women on lifelong antiretroviral therapy in Uganda: A retrospective cohort study.
In 2013, Uganda updated its prevention of maternal-to-child transmission of HIV program to Option B+, which requires that all HIV-infected pregnant and breastfeeding women be started on lifelong antiretroviral therapy (ART) regardless of CD4 count. We describe retention in care and factors associated with loss to follow-up (LTFU) among women initiated on Option B+ as part of an evaluation of the effectiveness of the national program. We conducted a retrospective cohort analysis of data abstracted from records of 2,169 women enrolled on Option B+ between January and March 2013 from a representative sample of 145 health facilities in all 24 districts of the Central region of Uganda. We defined retention as "being alive and receiving ART at the last clinic visit". We used Kaplan-Meier analysis to estimate retention in care and compared differences between women retained in care and those LTFU using the chi-squared test for dichotomized or categorical variables. The median follow-up time was 20.2 months (IQR 4.2-22.5). The proportion of women retained in HIV care at 6, 12 and 18 months post-ART initiation was 74.2%, 66.7% and 62.0%, respectively. Retention at 18 months varied significantly by level of health facility and ranged from 70.0% among those seen at hospitals to 56.6% among those seen at lower level health facilities. LTFU was higher among women aged less than 25 years, 59.3% compared to those aged 25 years and above, 40.7% (p = 0.02); among those attending care at lower level facilities, 44.0% compared to those attending care at hospitals, 34.1% (p = 0.01), and among those who were not tested for CD4 cell count at ART initiation, 69.4% compared to those who were tested, 30.9% (p = 0.002). Retention of women who were initiated on Option B+ during the early phases of roll-out was only moderate, and could undermine the effectiveness of the program. Identifying reasons why women drop out and designing targeted interventions for improved retention should be a priority.


Organ transplantation and skin cancer: basic problems and new perspectives.
Solid organ transplant and subsequent graft survival have increased worldwide, while immunosuppression has prevented rejection with increasing success. Side effects of cutaneous infection and neoplasm, however, affect the majority of solid organ transplant recipients (OTRs). Squamous cell carcinoma of the skin (SCC) is the most common neoplasm overall following organ transplant with a risk that is 60-100 times greater than for the immunocompetent population. This review focuses on questions of ongoing debate about SCC formation in OTRs such as viral carcinogenesis, systemic photoprotection, photosensitization by drugs, the impact of immunosuppressive drugs and inflammation as a driver of carcinogenesis.


An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug.
Powder blend homogeneity is a critical attribute in formulation development of low dose and potent active pharmaceutical ingredients (API) yet a complex process with multiple contributing factors. Excipient characteristics play key role in efficient blending process and final product quality. In this work the effect of excipient type and properties, blending technique and processing time on content uniformity was investigated. Powder characteristics for three commonly used excipients (starch, pregelatinised starch and microcrystalline cellulose) were initially explored using laser diffraction particle size analyser, angle of repose for flowability, followed by thorough evaluations of surface topography employing scanning electron microscopy and interferometry. Blend homogeneity was evaluated based on content uniformity analysis of the model API, ergocalciferol, using a validated analytical technique. Flowability of powders were directly related to particle size and shape, while surface topography results revealed the relationship between surface roughness and ability of excipient with high surface roughness to lodge fine API particles within surface groves resulting in superior uniformity of content. Of the two blending techniques, geometric blending confirmed the ability to produce homogeneous blends at low dilution when processed for longer durations, whereas manual ordered blending failed to achieve compendial requirement for content uniformity despite mixing for 32 minutes. Employing the novel dry powder hybrid mixer device, developed at Aston University laboratory, results revealed the superiority of the device and enabled the production of homogenous blend irrespective of excipient type and particle size. Lower dilutions of the API (1% and 0.5% w/w) were examined using non-sieved excipients and the dry powder hybrid mixing device enabled the development of successful blends within compendial requirements and low relative standard deviation.


Identification of independent biological sensors-electromyogram example.
To ensure that no biological event that may be important is missed, redundancy of sensors is provided. While this is useful, there are shortcomings when there is need to separate the signals from different sources using blind source separation techniques. An example of such a situation is over-complete surface electromyogram (sEMG) recording. Techniques such as principal component analysis (PCA) and entropy measures are used to identify the suitable channels. The shortcomings in these are the need for prior estimation of the number of channels. This paper has used the determinant of the global matrix of the mixtures to determine the number of independent sources in a mixture. The results indicate that the technique is able to distinguish between dependent and independent channels and this may be applied for determining the number of independent sources. The applications of this include data reduction by identifying redundant data, and for pre-processing of the data prior to use of any data classification techniques.


AMP-Activated Protein Kinase and Glycogen Synthase Kinase 3β Modulate the Severity of Sepsis-Induced Lung Injury.
Alterations in metabolic and bioenergetic homeostasis contribute to sepsis-mediated organ injury. However, how AMP-activated protein kinase (AMPK), a major sensor and regulator of energy expenditure and production, affects development of organ injury and loss of innate capacity during polymicrobial sepsis remains unclear. In the present experiments, we found that cross-talk between the AMPK and GSK3β signaling pathways controls chemotaxis and the ability of neutrophils and macrophages to kill bacteria ex vivo. In mice with polymicrobial abdominal sepsis or more severe sepsis induced by the combination of hemorrhage and intraabdominal infection, administration of the AMPK activator metformin or the GSK3β inhibitor SB216763 reduced the severity of acute lung injury (ALI). Improved survival in metformin-treated septic mice was correlated with preservation of mitochondrial complex V (ATP synthase) function and increased amounts of ETC complex III and IV. Although immunosuppression is a consequence of sepsis, metformin effectively increased innate immune capacity to eradicate P. aeruginosa in the lungs of septic mice. We also found that AMPK activation diminished accumulation of the immunosuppressive transcriptional factor HIF-1α as well as the development of endotoxin tolerance in LPS-treated macrophages. Furthermore, AMPK-dependent preservation of mitochondrial membrane potential also prevented LPS-mediated dysfunction of neutrophil chemotaxis. These results indicate that AMPK activation reduces the severity of polymicrobial sepsis-induced lung injury and prevents the development of sepsis-associated immunosuppression.


Gene expression profiling of genetically determined growth variation in bivalve larvae (Crassostrea gigas).
Growth rates in animals are governed by a wide range of biological factors, many of which remain poorly understood. To identify the genes that establish growth differences in bivalve larvae, we compared expression patterns in contrasting phenotypes (slow- and fast-growth) that were experimentally produced by genetic crosses of the Pacific oyster Crassostrea gigas. Based on transcriptomic profiling of 4.5 million cDNA sequence tags, we sequenced and annotated 181 cDNA clones identified by statistical analysis as candidates for differential growth. Significant matches were found in GenBank for 43% of clones (N=78), including 34 known genes. These sequences included genes involved in protein metabolism, energy metabolism and regulation of feeding activity. Ribosomal protein genes were predominant, comprising half of the 34 genes identified. Expression of ribosomal protein genes showed non-additive inheritance - i.e. expression in fast-growing hybrid larvae was different from average levels in inbred larvae from these parental families. The expression profiles of four ribosomal protein genes (RPL18, RPL31, RPL352 and RPS3) were validated by RNA blots using additional, independent crosses from the same families. Expression of RPL35 was monitored throughout early larval development, revealing that these expression patterns were established early in development (in 2-day-old larvae). Our findings (i) provide new insights into the mechanistic bases of growth and highlight genes not previously considered in growth regulation, (ii) support the general conclusion that genes involved in protein metabolism and feeding regulation are key regulators of growth, and (iii) provide a set of candidate biomarkers for predicting differential growth rates during animal development.


The assessment, serial evaluation, and subsequent sequelae of acute kidney injury (ASSESS-AKI) study: design and methods.
The incidence of acute kidney injury (AKI) has been increasing over time and is associated with a high risk of short-term death. Previous studies on hospital-acquired AKI have important methodological limitations, especially their retrospective study designs and limited ability to control for potential confounding factors. The Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study was established to examine how a hospitalized episode of AKI independently affects the risk of chronic kidney disease development and progression, cardiovascular events, death, and other important patient-centered outcomes. This prospective study will enroll a cohort of 1100 adult participants with a broad range of AKI and matched hospitalized participants without AKI at three Clinical Research Centers, as well as 100 children undergoing cardiac surgery at three Clinical Research Centers. Participants will be followed for up to four years, and will undergo serial evaluation during the index hospitalization, at three months post-hospitalization, and at annual clinic visits, with telephone interviews occurring during the intervening six-month intervals. Biospecimens will be collected at each visit, along with information on lifestyle behaviors, quality of life and functional status, cognitive function, receipt of therapies, interim renal and cardiovascular events, electrocardiography and urinalysis. ASSESS-AKI will characterize the short-term and long-term natural history of AKI, evaluate the incremental utility of novel blood and urine biomarkers to refine the diagnosis and prognosis of AKI, and identify a subset of high-risk patients who could be targeted for future clinical trials to improve outcomes after AKI.


Detrimental effects of verapamil in patients with primary pulmonary hypertension.
Calcium channel blockade provides a logical approach to the treatment of pulmonary hypertension because these drugs exert direct vasodilator effects in the highly constricted pulmonary circulation. To determine the effectiveness of verapamil in the treatment of primary pulmonary hypertension the haemodynamic effects of the drug were evaluated in seven patients with this disorder; 10 mg was given intravenously to six patients and 120 mg orally to one patient. Verapamil produced a 20% decline in pulmonary vascular resistance and a 27% decrease in mean pulmonary arterial pressure without significant changes in systemic vascular resistance. One patient who received verapamil 480 mg orally daily for three months showed sustained haemodynamic and clinical improvement. Concomitant with its beneficial effects on the pulmonary circulation, however, verapamil produced a pronounced decrease in right ventricular stroke work index (42%) and increase in right ventricular filling pressure (50%), indicating a direct depressant effect of the drug on right ventricular function. In one patient these cardiodepressant effects were sufficiently pronounced to produce severe hypotension and cardiac arrest. In conclusion, although verapamil appears to exert preferential vasodilator effects on the pulmonary circulation, its negative inotropic effects may be particularly detrimental to patients with primary pulmonary hypertension who have pre-existing right ventricular dysfunction; hence, treatment with verapamil is not recommended in such cases.


First return to work following injury: does it reflect a composite or a homogeneous outcome?
To test whether return to work as a binary (yes/no) outcome that includes all persons who returned to work regardless of mode of return reflects a composite or a homogeneous outcome in a cohort of workers who have sustained acute orthopaedic trauma resulting in hospitalisation. Prospective cohort study. One hundred and sixty-eight participants were recruited and followed for 6 months. The study achieved 89% follow-up. Baseline data were obtained at study recruitment and participants were further surveyed by phone at three timepoints during the study. Polytomous logistic regression was used to simultaneously examine the association between potential predictors and different modes of first return to work (RTW). A test of the equality of the ORs associated with the independent predictor variables was also undertaken. Of the 152 participants with full follow-up, 46 (30%) returned first to full duties, 58 (38%) returned first to modified work and 48 (32%) did not return to work during the study period. Significant determinants of the two modes of return to work were different. A test of the equality of ORs indicated that the relative ORs for the difference in the slope coefficients for five of the 10 independent factors in the two polytomous logistic regression sub-models corresponding to each mode of return to work were statistically significant. This raises the likelihood that first RTW reflects a composite rather than a homogeneous outcome. The study provides evidence that RTW may reflect a composite outcome when it includes different modes of first RTW. The identified predictive factors appear to exert different mechanisms of action depending on the mode of RTW. The findings suggest that the different modes of RTW may need to be considered independently. The results of the study have potentially important implications for research and insurance practice.


In-situ nanospectroscopic pH monitoring by plasmon resonance energy transfer (PRET).
Real-time detection of pH value in a living cell is in central importance for research about cells and diseases. In spite of the great advances in science and technology, pH measurement in a living cell is still limited in spatial resolution, in-situ detection, and intracellular monitoring. Here, we designed a nanoscale pH meter by Plasmon Resonance Energy Transfer (PRET). In order to highly sensitively measure pH with nanoscale spatial resolution, we choose 80 nm spherical gold nanoparticle (GNP) and phenol red which is commonly used in cell media for pH determination. The resonance energy of GNP is transferred to phenol red because the scattering intensity of GNP is overlapped with the second absorption intensity of phenol red at near 560 nm. Meanwhile, the absorption intensity of phenol red molecules is changing with pH value of the solution. For that reason, the intensity of PRET from GNP to phenol red molecules also changes by the acidity of phenol red solution. Then we can detect pH values with nanoscale spatial resolution through the Rayleigh scattering intensity of GNP. As we changed pH value from 6.0 to 9.0, the scattering intensity of GNP is decreased because the absorbance of phenol red at 560 nm wavelength is increased with increasing pH value. The Gaussian peak of a difference in Rayleigh scattering spectra of GNP between pH 6.0 and pH 9.0 indicates exactly the same as UV-vis spectral difference between basic and acidic phenol red solution. We expect that this pH measuring technique has a significant impact on the pH detection of living cells with nanoscale, and it can make possibility to image the cell structure by pH variation.


Nano-lens diffraction around a single heated nano particle.
The action of a nanoscopic spherically symmetric refractive index profile on a focused Gaussian beam may easily be envisaged as the action of a phase-modifying element, i.e. a lens: Rays traversing the inhomogeneous refractive index field n(r) collect an additional phase along their trajectory which advances or retards their phase with respect to the unperturbed ray. This lens-like action has long been understood as being the mechanism behind the signal of thin sample photothermal absorption measurements [Appl. Opt. 34, 41-50 (1995)], [Jpn. J. Appl. Phys. 45, 7141-7151 (2006)], where a cylindrical symmetry and a different lengthscale is present. In photothermal single (nano-)particle microscopy, however, a complicated, though prediction-wise limited, electrodynamic scattering treatment was established [Phys. Rev. B 73, 045424 (2006)] during the emergence of this new technique. Our recent study [ACS Nano, DOI: 10.1021/nn300181h] extended this approach into a full ab-initio model and showed for the first time that the mechanism behind the signal, despite its nanoscopic origin, is also the lens-like action of the induced refractive index profile only hidden in the complicated guise of the theoretical generalized Mie-like framework. The diffraction model proposed here yields succinct analytical expressions for the axial photothermal signal shape and magnitude and its angular distribution, all showing the clear lens-signature. It is further demonstrated, that the Gouy-phase of a Gaussian beam does not contribute to the relative photothermal signal in forward direction, a fact which is not easily evident from the more rigorous EM treatment. The presented model may thus be used to estimate the signal shape and magnitude in photothermal single particle microscopy.


Environmental asbestos exposure and risk of mesothelioma.
Mesothelioma is commonly considered an occupational disease occurring as a result of asbestos exposure in the workplace. Several avenues for environmental asbestos exposures have been described and may be associated with asbestos related disease, including mesothelioma. Worker take-home asbestos, or para-occupational exposure, has been well documented and is the most commonly reported pathway for asbestos exposure among mesothelioma cases that do not have history of occupational asbestos exposure. Observational studies have evaluated several communities with elevated mesothelioma incidence and environmental exposures attributed to local asbestos-related industries. Potential, but uncertain, mesothelioma risk also may be associated with general population asbestos exposure through contact with asbestos-containing commercial products, particularly housing materials that can be easily disturbed through normal activity. Finally, studies have described elevated mesothelioma incidence in several areas where populations are exposed to naturally occurring asbestos materials. These various environmental asbestos exposure pathways are poorly understood, and further studies should be pursued to evaluate their respective importance for population mesothelioma risk.


CR1 (CD35) and CR3 (CD11b/CD18) mediate infection of human monocytes and monocytic cell lines with complement-opsonized HIV independently of CD4.
Peripheral blood and tissue mononuclear phagocytes serve as major viral reservoirs in HIV-infected individuals. We investigated the role of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) in mediating productive infection with complement-opsonized HIV-1 and HIV-2 of cultured normal human peripheral blood monocytes, the promonocytic cell line THP-1, the monocytic cell line Mono Mac 6 and the glial cell line U251-MG. Cells were infected with the HTLV-IIIB strain of HIV-1 or the LAV-2 strain of HIV-2 that had been preopsonized with fresh human normal HIV seronegative serum. Productive infection was assessed by syncytia formation, the MTT cytotoxicity assay and/or release of p24 antigen in culture supernatants. Using suboptimal amounts of virus to infect the cells, we observed a higher and earlier productive infection of the cells with complement-opsonized HIV than with unopsonized virus. The enhancing effect of complement was totally suppressed by blocking CR1 or CR3 function with F(ab)'2 fragments of anti-receptor MoAbs; while blocking of the LFA-1 antigen had no effect. The infection of monocytic cells with complement-opsonized virus occurred independently of CD4 since it was not inhibited by F(ab)'2 fragments of a MoAb against the gp120 binding site of CD4 and since infection also occurred with Mono Mac 6 and U251-MG cells, which lack expression of the CD4 antigen and of CD4 mRNA. These observations suggest that complement may mediate productive infection of cells of the monocytic lineage with 'lymphocytotropic' HIV strains independently of CD4.


Evaporating droplet hologram simulation for digital in-line holography setup with divergent beam.
Generalized Lorenz-Mie theory (GLMT) for a multilayered sphere is used to simulate holograms produced by evaporating spherical droplets with refractive index gradient in the surrounding air/vapor mixture. Simulated holograms provide a physical interpretation of experimental holograms produced by evaporating Diethyl Ether droplets with diameter in the order of 50 μm and recorded in a digital in-line holography configuration with a divergent beam. Refractive index gradients in the surrounding medium lead to a modification of the center part of the droplet holograms, where the first fringe is unusually bright. GLMT simulations reproduce this modification well, assuming an exponential decay of the refractive index from the droplet surface to infinity. The diverging beam effect is also considered. In both evaporating and nonevaporating cases, an equivalence is found between Gaussian beam and plane wave illuminations, simply based on a magnification ratio to be applied to the droplets' parameters.


Emphysematous Pyelonephritis Associated With Emphysematous Gastritis and Air in the Portal Vein.
Emphysematous gastritis with portal venous air is a rare condition usually caused by gas forming organisms. This may be secondary to local spread of an infection through the mucosa or rarely hematogenous dissemination from a distant focus. We present a young diabetic woman with uncontrolled diabetes mellitus who was admitted with sepsis and severe abdominal symptoms. Investigation revealed emphysematous pyelonephritis due to E. coli infection associated with emphysematous gastritis and air in the portal tract. She improved with broad spectrum antibiotics, fluid resuscitation and electrolyte and diabetic management. To our knowledge this is the first report showing the association between emphysematous pyelonephritis and gastritis with air in the portal system.


The sense of touch: embodied simulation in a visuotactile mirroring mechanism for observed animate or inanimate touch.
Previous studies have shown a shared neural circuitry in the somatosensory cortices for the experience of one's own body being touched and the sight of intentional touch. Using functional magnetic resonance imaging (fMRI), the present study aimed to elucidate whether the activation of a visuotactile mirroring mechanism during touch observation applies to the sight of any touch, that is, whether it is independent of the intentionality of observed touching agent. During fMRI scanning, healthy participants viewed video clips depicting a touch that was intentional or accidental, and occurring between animate or inanimate objects. Analyses showed equal overlapping activation for all the touch observation conditions and the experience of one's own body being touched in the bilateral secondary somatosensory cortex (SII), left inferior parietal lobule (IPL)/supramarginal gyrus, bilateral temporal-occipital junction, and left precentral gyrus. A significant difference between the sight of an intentional touch, compared to an accidental touch, was found in the left primary somatosensory cortex (SI/Brodmann's area [BA] 2). Interestingly, activation in SI/BA 2 significantly correlated with the degree of intentionality of the observed touch stimuli as rated by participants. Our findings show that activation of a visuotactile mirroring mechanism for touch observation might underpin an abstract notion of touch, whereas activation in SI might reflect a human tendency to "resonate" more with a present or assumed intentional touching agent.


CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide.
CD11c/CD18 is a member of the leukocyte integrin family, heterodimeric adhesion molecules that interact with a diverse repertoire of ligands, including bacterial lipopolysaccharide (LPS). Their role as signal transducing receptors remains uncertain. We used a heterologous expression system to determine if CD11c/CD18 was capable of initiating signal transduction in response to LPS-binding, as assessed by the induced translocation of nuclear factor-kappa B. We have previously reported that Chinese hamster ovary (CHO)-K1 fibroblasts, normally unresponsive to LPS, acquire serum-dependent macrophage-like responses to LPS when transfected with CD14 (Golenbock, D.T., Y. Liu, F. Millham, M. Freeman, and R. Zoeller. 1993. J. Biol. Chem. 268:22055-22059), a known LPS receptor. In contrast, CHO cells acquired serum-independent responses to Gram-negative bacteria and LPS when transfected with CD11c/CD18 (CHO/CD11c). In comparison to CHO cells transfected with CD14 (CHO/CD14), responses in CHO/CD11c cells were slower, required higher endotoxin concentrations for maximal response, and were not inhibited by the presence of antibodies to CD14. CD11c/CD18 is, thus, the second phagocyte receptor, in addition to CD14, which has been shown to have the capacity to activate cells after binding to LPS. The function of this receptor in normal phagocytes may be limited to the recognition of LPS in infected tissues, where LPS-CD14 interactions are not favored because of the absence of serum proteins.


Healthcare, Sickness Absence, and Disability Pension Cost Trajectories in the First 5 Years After Diagnosis with Multiple Sclerosis: A Prospective Register-Based Cohort Study in Sweden.
The aim was to longitudinally explore the healthcare, sickness absence (SA), and disability pension (DP) cost trajectories among newly diagnosed people with multiple sclerosis (MS), and investigate whether trajectories differ by year of MS diagnosis, sociodemographics, and multi-morbidity. People with MS in Sweden, aged 25-60 years and with a new MS diagnosis in the years 2006, 2007, 2008, or 2009 (four different cohorts) were identified in nationwide registers and followed prospectively for 5 years, determining the annual, per patient, direct (inpatient and specialised outpatient healthcare, co-payments, and dispensed drugs) and indirect (SA and DP) costs. Descriptive statistics and group-based trajectories were computed. In total, 3272 people with new MS were identified. In all cohorts, direct costs increased the year after diagnosis and thereafter declined (e.g. from €8261 to €9128, and to €7953, 5 years after diagnosis, for the 2006 cohort). SA costs continuously decreased over 5 years, while DP costs increased (e.g. from €9795 to €2778 vs. from €7277 to €15,989, respectively, for the 2006 cohort). When pooling all cohorts, four trajectories of direct and indirect costs were identified. A total of 32.1% of people with MS had high direct and indirect costs, which first increased and then decreased; the contrary was seen for trajectories with low direct and indirect costs. There is heterogeneity in the development of MS costs over time after diagnosis; decreasing cost trajectories could be associated with the use of innovative MS therapies, slowing disease progression over time.


Spatial and ecological population genetic structures within two island-endemic Aeonium species of different niche width.
The Crassulacean genus Aeonium is a well-known example for plant species radiation on oceanic archipelagos. However, while allopatric speciation among islands is documented for this genus, the role of intra-island speciation due to population divergence by topographical isolation or ecological heterogeneity has not yet been addressed. The aim of this study was to investigate intraspecific genetic structures and to identify spatial and ecological drivers of genetic population differentiation on the island scale. We analyzed inter simple sequence repeat variation within two island-endemic Aeonium species of La Palma: one widespread generalist that covers a large variety of different habitat types (Ae. davidbramwellii) and one narrow ecological specialist (Ae. nobile), in order to assess evolutionary potentials on this island. Gene pool differentiation and genetic diversity patterns were associated with major landscape structures in both species, with phylogeographic implications. However, overall levels of genetic differentiation were low. For the generalist species, outlier loci detection and loci-environment correlation approaches indicated moderate signatures of divergent selection pressures linked to temperature and precipitation variables, while the specialist species missed such patterns. Our data point to incipient differentiation among populations, emphasizing that ecological heterogeneity and topographical structuring within the small scales of an island can foster evolutionary processes. Very likely, such processes have contributed to the radiation of Aeonium on the Canary Islands. There is also support for different evolutionary mechanisms between generalist and specialist species.


Information content of the near field: two-dimensional samples.
Limits on the effective resolution of many optical near-field experiments are investigated. The results are applicable to variants of total-internal-reflection microscopy (TIRM), photon-scanning-tunneling microscopy (PSTM), and near-field-scanning-optical microscopy (NSOM) in which the sample is weakly scattering and the direction of illumination may be controlled. Analytical expressions for the variance of the estimate of the complex susceptibility of an unknown two-dimensional object as a function of spatial frequency are obtained for Gaussian and Poisson noise models, and a model-independent measure is examined. The results are used to explore the transition from near-zone to far-zone detection. It is demonstrated that the information content of the measurements made at a distance of even one wavelength away from the sample is already not much different from the information content of the far field.


The risks, needs and stages of recovery of a complete forensic patient cohort in an Australian state.
Routine outcome measures are increasingly being mandated across mental health services in Australia and overseas. This requirement includes forensic mental health services, but their utility in such specialist services and the inter-relationships between the measures remain unclear. This study sought to characterise the risks, needs and stages of recovery of an entire cohort of forensic patients in one jurisdiction in Australia. Local expert groups, comprising of members of the forensic patient treating teams, were formed to gather information about the status and needs of all forensic patients in the State of New South Wales, Australia. The expert groups provided demographic information and completed three assessment tools concerning the risks, needs and stages of recovery of each forensic patient. The cohort of 327 forensic patients in NSW appears to be typical of forensic mental health service populations internationally when considering factors such as gender, diagnosis, and index offence. A number of important differences across the three structured tools for forensic patients in different levels of secure service provision are presented. The DUNDRUM Quartet demonstrated interesting findings, particularly in terms of the therapeutic security needs, the treatment completion, and the stages of recovery for the forensic patients in the community. The CANFOR highlighted the level of needs across the forensic patient population, whilst the HCR-20 data showed there was no significant difference in the mean clinical and risk management scores between male forensic patients across levels of security. To the authors' knowledge this is the first study of its kind in New South Wales, Australia. We have demonstrated the utility of using a suite of measures to evaluate the risks, needs, and stages of recovery for an entire cohort of forensic patients. The data set helps inform service planning and development, together with providing various avenues for future research.


Field dependency and the sense of object-presence in haptic virtual environments.
Virtual environment (VE) users often report having a sense of being present in the virtual place or a sense that the virtual object is present in their environment. This sense of presence depends on both the technological fidelity (e.g., in graphics, haptics) and the users' cognitive/ personality characteristics. This study examined the correlation between user's cognitive style on the field-dependency dimension and the level of object-presence they reported in a haptic VE. Results indicated that field-independent individuals reported higher presence ratings compared to field-dependent participants. We hypothesize that field-independents' advantage in reorganizing the perceptual field and constructing it according to their previously acquired internal knowledge enables them to cognitively reconstruct the VE experience more efficiently by selectively attending only to the relevant cues and by filling in the gap of missing information with their previous knowledge and creative imagination. This active and creative cognitive process may be behind the enhanced sense of presence. In addition, we raise a possible linkage between field dependency, the sense of presence, and simulator sickness phenomenon.


The 2009 H1N1 influenza outbreak in its historical context.
Of the 16 known serotypes of influenza A haemagglutinin, 6 have been isolated from humans at the molecular level (H1, H2, H3, H5, H7, H9). 3 of these have been involved in past pandemics (H1, H2, H3). Traditional pandemic surveillance has focussed on monitoring antigenic shift, meaning the re-assortment of novel haemagglutinins into seasonal human influenza A viruses during rare events of double infection with seasonal and zoonotic strains. H5, from avian H5N1 influenza, has been the major cause for concern in recent years. However, the 2009 H1N1 zoonotic event demonstrates that even serotypes already encountered in past human pandemics may constitute new pandemic threats. The protein sequence divergence of the 2009 zoonotic H1 from human seasonal influenza H1 is around 20-24%. A similar level of divergence is found between the 2009 H1 and European swine flu. By contrast, its divergence from North American swine flu strains is around 1-9%. Given that the divergence between H1 and its nearest serotype neighbour H2 is around 40-46%, the 2009 H1 may be broadly considered as halfway towards a new serotype. The current situation is one of antigenic pseudo-shift.


Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study.
As perspectives on cannabis continue to shift, understanding the physiological and behavioral effects of cannabis use is of paramount importance. Previous data suggest that cannabis use influences food intake, appetite, and metabolism, yet human research in this regard remains scant. The present study investigated the effects of cannabis administration, via different routes, on peripheral concentrations of appetitive and metabolic hormones in a sample of cannabis users. This was a randomized, crossover, double-blind, placebo-controlled study. Twenty participants underwent four experimental sessions during which oral cannabis, smoked cannabis, vaporized cannabis, or placebo was administered. Active compounds contained 6.9 ± 0.95% (~50.6 mg) ∆9-tetrahydrocannabinol (THC). Repeated blood samples were obtained, and the following endocrine markers were measured: total ghrelin, acyl-ghrelin, leptin, glucagon-like peptide-1 (GLP-1), and insulin. Results showed a significant drug main effect (p = 0.001), as well as a significant drug × time-point interaction effect (p = 0.01) on insulin. The spike in blood insulin concentrations observed under the placebo condition (probably due to the intake of brownie) was blunted by cannabis administration. A significant drug main effect (p = 0.001), as well as a trend-level drug × time-point interaction effect (p = 0.08) was also detected for GLP-1, suggesting that GLP-1 concentrations were lower under cannabis, compared to the placebo condition. Finally, a significant drug main effect (p = 0.01) was found for total ghrelin, suggesting that total ghrelin concentrations during the oral cannabis session were higher than the smoked and vaporized cannabis sessions. In conclusion, cannabis administration in this study modulated blood concentrations of some appetitive and metabolic hormones, chiefly insulin, in cannabis users. Understanding the mechanisms underpinning these effects may provide additional information on the cross-talk between cannabinoids and physiological pathways related to appetite and metabolism.


PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20.
Ubiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid segregation and anaphase. The anaphase-promoting complex/cyclosome and its coactivator CDC20 (APC/CCDC20) form the main ubiquitin E3 ligase for these two proteins. APC/CCDC20 is regulated by CDK1-cyclin B and counteracting PP1 and PP2A family phosphatases through modulation of both activating and inhibitory phosphorylation. Here, we report that PP1 promotes cyclin B destruction at the onset of anaphase by removing specific inhibitory phosphorylation in the N-terminus of CDC20. Depletion or chemical inhibition of PP1 stabilizes cyclin B and results in a pronounced delay at the metaphase-to-anaphase transition after chromosome alignment. This requirement for PP1 is lost in cells expressing CDK1 phosphorylation-defective CDC206A mutants. These CDC206A cells show a normal spindle checkpoint response and rapidly destroy cyclin B once all chromosomes have aligned and enter into anaphase in the absence of PP1 activity. PP1 therefore facilitates the metaphase-to-anaphase transition by promoting APC/CCDC20-dependent destruction of cyclin B in human cells.


Non-cyclooxygenase-derived prostanoids (F2-isoprostanes) are formed in situ on phospholipids.
We recently reported the discovery of a series of bioactive prostaglandin F2-like compounds (F2-isoprostanes) that are produced in vivo by free radical-catalyzed peroxidation of arachidonic acid independent of the cyclooxygenase enzyme. Inasmuch as phospholipids readily undergo peroxidation, we examined the possibility that F2-isoprostanes may be formed in situ on phospholipids. Initial support for this hypothesis was obtained by the finding that levels of free F2-isoprostanes measured after hydrolysis of lipids extracted from livers of rats treated with CCl4 to induce lipid peroxidation were more than 100-fold higher than levels in untreated animals. Further, increased levels of lipid-associated F2-isoprostanes in livers of CCl4-treated rats preceded the appearance of free compounds in the circulation, suggesting that the free compounds arose from hydrolysis of peroxidized lipids. This concept was supported by demonstrating that free F2-isoprostanes were released after incubation of lipid extracts with bee venom phospholipase A2 in vitro. When these lipid extracts were analyzed by HPLC, fractions that yielded large quantities of free F2-isoprostanes after hydrolysis eluted at a much more polar retention volume than nonoxidized phosphatidylcholine. Analysis of these polar lipids by fast atom bombardment mass spectrometry established that they were F2-isoprostane-containing species of phosphatidylcholine. Thus, unlike cyclooxygenase-derived prostanoids, F2-isoprostanes are initially formed in situ on phospholipids, from which they are subsequently released preformed, presumably by phospholipases. Molecular modeling of F2-isoprostane-containing phospholipids reveals them to be remarkably distorted molecules. Thus, the formation of these phospholipid species in lipid bilayers may contribute in an important way to alterations in fluidity and integrity of cellular membranes, well-known sequelae of oxidant injury.


Challenges and opportunities of airborne metagenomics.
Recent metagenomic studies of environments, such as marine and soil, have significantly enhanced our understanding of the diverse microbial communities living in these habitats and their essential roles in sustaining vast ecosystems. The increase in the number of publications related to soil and marine metagenomics is in sharp contrast to those of air, yet airborne microbes are thought to have significant impacts on many aspects of our lives from their potential roles in atmospheric events such as cloud formation, precipitation, and atmospheric chemistry to their major impact on human health. In this review, we will discuss the current progress in airborne metagenomics, with a special focus on exploring the challenges and opportunities of undertaking such studies. The main challenges of conducting metagenomic studies of airborne microbes are as follows: 1) Low density of microorganisms in the air, 2) efficient retrieval of microorganisms from the air, 3) variability in airborne microbial community composition, 4) the lack of standardized protocols and methodologies, and 5) DNA sequencing and bioinformatics-related challenges. Overcoming these challenges could provide the groundwork for comprehensive analysis of airborne microbes and their potential impact on the atmosphere, global climate, and our health. Metagenomic studies offer a unique opportunity to examine viral and bacterial diversity in the air and monitor their spread locally or across the globe, including threats from pathogenic microorganisms. Airborne metagenomic studies could also lead to discoveries of novel genes and metabolic pathways relevant to meteorological and industrial applications, environmental bioremediation, and biogeochemical cycles.


Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress and brain edema following experimental subarachnoid hemorrhage in rabbits.
Increasing experimental and clinical data indicate that early brain injury (EBI) after subarachnoid hemorrhage (SAH) largely contributes to unfavorable outcomes, and it has been proved that EBI following SAH is closely associated with oxidative stress and brain edema. The present study aimed to examine the effect of hydrogen, a mild and selective cytotoxic oxygen radical scavenger, on oxidative stress injury, brain edema and neurology outcome following experimental SAH in rabbits. The level of MDA, caspase-12/3 and brain water content increased significantly at 72 hours after experimental SAH. Correspondingly, obvious brain injury was found in the SAH group by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) and Nissl staining. Similar results were found in the SAH+saline group. In contrast, the upregulated level of MDA, caspase-12/3 and brain edema was attenuated and the brain injury was substantially alleviated in the hydrogen treated rabbits, but the improvement of neurology outcome was not obvious. The results suggest that treatment with hydrogen in experimental SAH rabbits could alleviate brain injury via decreasing the oxidative stress injury and brain edema. Hence, we conclude that hydrogen possesses the potential to be a novel therapeutic agent for EBI after SAH.


Rapid activation of ERK1/2 mitogen-activated protein kinase by corticosterone in PC12 cells.
Although the nongenomic effects of glucocorticoids have been well acknowledged, its precise intracellular signal transduction pathway remains to be elucidated. The present study using Western immunoblot and protein kinase activity assay, for the first time, showed that corticosterone (B) can induce a rapid activation of Erk1/2 mitogen-activated protein kinase (MAPK) in PC12 cells. The dose-response curve was bell shaped, with the maximal activation at 10(-9) M in 15 min. The results from immunofluorescence staining also revealed that the activated Erk1/2 MAPK was translocated from cytoplasm to nucleus of PC12 cells in 15 min. Activation of Erk1/2 MAPK by B was apparently not mediated by the classical cytosolic steroid receptors, for B-BSA can induce the phosphorylation of Erk1/2 MAPK, but the antagonist (RU38486) cannot block the phosphorylation of Erk1/2 MAPK induced by B. Phosphorylation of Erk1/2 MAPK induced by B was not affected by a tyrosine kinase inhibitor (genistein), suggesting that the pathway did not involve the tyrosine kinase activity. On the other hand, protein kinase C activator (PMA) can activate and protein kinase C inhibitor (Gö6976) can block the activation of Erk1/2 MAPK induced by B. Taken together, these data clearly demonstrated that B might act via putative membrane receptor and rapidly activate Erk1/2 MAPK through protein kinase C alpha in PC12 cells.


Factors Associated with the High Prevalence of Dementia in Older Aboriginal Australians.
Dementia prevalence in Aboriginal and Torres Strait Islander Australians is three to five times higher than the general Australian population. A better understanding of the underlying biomedical and social risk factors is needed to guide dementia prevention in Aboriginal Australians. The current study is the first to examine potential risk factors for dementia in the majority urban and regional population, with a representative sample of 336 Aboriginal Australians aged 60 years and older. Participants included 45 people with a dementia diagnosis (n = 27 probable/possible Alzheimer's disease); and 286 people without dementia. Univariate logistic regression analyses (controlling for age) identified childhood trauma, mid-life factors (history of unskilled work, past high-risk alcohol use), and medical factors (history of stroke, head injury with loss of consciousness, epilepsy) as risk factors for dementia. Multivariable analysis revealed age, childhood trauma, unskilled work, stroke, and head injury as independent predictors of all-cause dementia. A range of comorbid factors related to dementia was also identified (i.e., functional impairment, incontinence, recent hospital admission, low body mass index, living in residential care, depression, current high-risk alcohol use, social isolation, low physical activity levels). These findings extend previous outcomes in a remote Aboriginal population by highlighting that life-course social determinants of health, in addition to neurological disorders, likely play an important role in elevating dementia risk. Certain psychosocial and medical exposures are highly prevalent in Aboriginal Australians, similar to other indigenous populations, and should be considered when designing targeted and culturally appropriate prevention initiatives to reduce the burden of dementia.


Atypical and typical neuroleptic treatments induce distinct programs of transcription factor expression in the striatum.
Atypical and typical neuroleptics, when administered chronically, can bring about profound but contrasting changes in schizophrenic symptoms and motor activation and dramatically modulate brain neurochemistry. To explore the transcriptional events that might be involved in this neurochemical regulation, we used immunohistochemistry and immunoblotting to examine the expression patterns of two bZip transcription factors, c-Fos and FosB, in the striatum of rats treated acutely and chronically with neuroleptic drugs of different classes. Typical and atypical neuroleptic drugs produced contrasting regulatory effects on a FosB-like protein of ca. 36-39 kDa, the molecular weight of truncated FosB (delta FosB). Chronic treatments with two typical neuroleptics, haloperidol and metoclopramide, but not with the atypical neuroleptic clozapine, led to markedly enhanced FosB-like immunoreactivity in the caudoputamen. Further, c-Fos-like protein in the striatum, considered a marker for the induction of antipsychotic actions by neuroleptic treatments, was downregulated by chronic treatment with the two potent antipsychotic drugs tested, but not by chronic treatment with metoclopramide, which has low antipsychotic efficacy but induces extrapyramidal side effects. These results suggest that chronic treatments with neuroleptics having different effects on cognitive and motor behavior induce different long-term changes in transcription factor expression in the striatum. Nevertheless, we found that neuroleptics of both classes regulated transcription factor expression in overlapping populations of striatal neurons expressing enkephalin or DARPP-32. Contrasting patterns of transcriptional regulation in these neurons may thus contribute to the distinct neurochemical and behavioral effects that characterize neuroleptics of different classes.


Predictive values for procalcitonin in the diagnosis of neonatal sepsis.
Early diagnosis of neonatal sepsis followed by appropriate treatment decreases mortality and morbidity in infants. The aim of this study is to assess the role of procalcitonin (PCT) as a marker in the early diagnosis of neonatal sepsis. We present a cross sectional study where 35 neonates with early onset sepsis (admitted to the Neonatal Intensive Care Units at El-Minia Children University Hospital from August 2012 to August 2013) were included in the study. Another 35 healthy neonates with no clinical or biological data of infection were included as a control group. Subjects were subjected to a thorough history taking and routine laboratory investigations. Serum PCT and C-reactive protein (CRP) levels were determined by enzyme-linked immunosorbent assay (ELISA). Mean levels of PCT and CRP in neonates with sepsis were significantly higher than in the control group (p=0.0001). There was a moderate, but significant, positive correlation between PCT and C-reactive protein (p=0.001, r=0.55) and an insignificant correlation between procalcitonin and total leukocytic count among the neonates with sepsis (p=0.2, r=0.2). In addition, procalcitonin had high sensitivity, specificity, a high positive predictive value, and a high negative predictive value (80%, 85.7%, 84.8%, and 81.1% respectively). Procalcitonin showed higher sensitivity when compared to CRP. Procalcitonin is a sensitive, independent, and useful biomarker in comparison to CRP in early diagnosis of neonatal sepsis.


Evidence for the Adaptive Learning Function of Work and Work-Themed Play among Aka Forager and Ngandu Farmer Children from the Congo Basin.
Work-themed play may allow children to learn complex skills, and ethno-typical and gender-typical behaviors. Thus, play may have made important contributions to the evolution of childhood through the development of embodied capital. Using data from Aka foragers and Ngandu farmer children from the Central African Republic, we ask whether children perform ethno- and gender-typical play and work activities, and whether play prepares children for complex work. Focal follows of 50 Aka and 48 Ngandu children were conducted with the aim of recording children's participation in 12 categories of work and work-themed play. Using these data, we test a set of hypotheses regarding how age, gender, ethnicity, and task complexity influence children's activities. As hypothesized, we find performance of work-themed play is negatively correlated with age. Contrary to our hypothesis, children do not play more than they work at complex tasks, but they work more than they play at simple ones. Gender and ethnicity are associated with play and work at culturally salient activities, despite availability of other-gender and other-ethnicity social partners. Our findings show that ethnic and gender biases are apparent in the play and work behavior of Aka and Ngandu children. Moreover, our results show that play helps both forager and farmer children learn complex skills, consistent with play having an adaptive learning function.


Hybrid dopamine uptake blocker-serotonin releaser ligands: a new twist on transporter-focused therapeutics.
As part of our program to study neurotransmitter releasers, we report herein a class of hybrid dopamine reuptake inhibitors that display serotonin releasing activity. Hybrid compounds are interesting since they increase the design potential of transporter related compounds and hence represent a novel and unexplored strategy for therapeutic drug discovery. A series of N-alkylpropiophenones was synthesized and assessed for uptake inhibition and release activity using rat brain synaptosomes. Substitution on the aromatic ring yielded compounds that maintained hybrid activity, with the two disubstituted analogues (PAL-787 and PAL-820) having the most potent hybrid activity.


Emerging roles of ozone in skin diseases.
Ozone was discovered in the mid-nineteenth century and is proven to have many therapeutic effects, including its common application as a disinfectant to kill microorganisms in various conditions. Ozone therapies have been utilized for various purposes ever since it was discovered. Extensive studies over a century have verified its therapeutic effects, consistency, and safety with minimal and preventable side effects in medical care. Emerging evidence revealed that ozone also plays important roles in the management and prevention of various skin disorders including infectious skin diseases, skin related allergic diseases, erythema scaly diseases, wound healing and ulcer recovery. Herein, the author now summarizes the recent clinical applications of ozone therapy in dermatology and provide commentary on what we have learned in our practice. Our focuses are the efficacy and safety of ozone therapies as well as the application prospects of ozone on various skin disorders. In addition, the author discusses the potential mechanisms involved in ozone therapy and the efforts we should make for.


Is the argument from marginal cases obtuse?
Elizabeth Anderson claims that the argument from marginal cases is 'the central argument' behind the claim that nonhuman animals have rights. But she thinks, along with Cora Diamond, that the argument is 'obtuse'. Two different meanings could be intended here: that the argument from marginal cases is too blunt or dull to dissect the reasons why it makes sense to say that nonhuman animals have rights or that the argument from marginal cases is insensitive regarding nonrational human beings (the marginal cases of humanity). The purpose of the present article is to argue that, despite Anderson's and Diamond's nuanced and perceptive treatments of the argument from marginal cases, this argument is not obtuse in either sense of the term.


Serum YKL-40: a potential biomarker for psoriasis or endothelial dysfunction in psoriasis?
Psoriasis is a disease that can contribute to a risk of atherosclerosis. In several studies, impaired endothelial dysfunction (ED) is correlated with psoriasis. Serum YKL-40 is a new inflammatory biomarker of vascular damage, like ED and cardiovascular diseases. The aim of the study was to compare relevance of serum YKL-40 levels in psoriasis patients and healthy subjects according to ED diagnosis and identifiable cardiovascular risk factors. Sixty (31 female, 29 male) patients with plaque psoriasis, and 30 (18 female, 12 male) healthy controls were selected according to whether they had at least one or no identifiable risk factors for cardiovascular disease. All subjects were evaluated ultrasonographically for endothelial function and diagnosed as with or without ED and all groups compared for serum YKL-40 levels. YKL-40 levels of psoriatic patients with ED were higher than healthy controls with ED (P = <0.05). There were no statistical differences in between subjects without ED. YKL-40 levels of patients over age of 40 were higher than younger ones (P < 0.05). But in healthy controls, there were no differences. In comparison of cardiovascular risk-positive (RP) patients and RP healthy subjects, YKL-40 levels were higher in RP patients (P = <0.05). The elevation of plasma YKL-40 in psoriasis can be associated not only with inflammation of the disease, but also with ED. YKL-40 can be used as a marker for predicting and preventing cardiovascular diseases in RP psoriatic patients with age above 40.


Postoperative acalculous cholecystitis due to Torulopsis glabrata.
Acute acalculous cholecystitis due to Torulopis glabrata, an opportunistic yeast, developed postoperatively in a 70-year-old man who had an extremely complicated course after resection of an abdominal aortic aneurysm. The infection first appeared as an acute surgical abdomen, three days after resumption of solid food intake subsequent to a prolonged ileus and after 31 days of parenteral hyperalimentation. The condition was successfully treated by cholecystostomy; at the time of writing, six months after cholecystostomy, there are no gastrointestinal symptoms.


Peptide segments in protein-protein interfaces.
An important component of functional genomics involves the understanding of protein association. The interfaces resulting from protein-protein interactions - (i) specific, as represented by the homodimeric quaternary structures and the complexes formed by two independently occurring protein components, and (ii) non-specific, as observed in the crystal lattice of monomeric proteins - have been analysed on the basis of the length and the number of peptide segments. In 1000 A2 of the interface area, contributed by a polypeptide chain, there would be 3.4 segments in homodimers, 5.6 in complexes and 6.3 in crystal contacts. Concomitantly, the segments are the longest (with 8.7 interface residues) in homodimers. Core segments (likely to contribute more towards binding) are more in number in homodimers (1.7) than in crystal contacts (0.5), and this number can be used as one of the parameters to distinguish between the two types of interfaces. Dominant segments involved in specific interactions, along with their secondary structural features, are enumerated.


Computed tomographic evaluation of pancreatic perfusion in healthy dogs.
To evaluate the feasibility of contrast-enhanced CT for assessment of pancreatic perfusion in healthy dogs. 6 healthy purpose-bred female Treeing Walker Coonhounds. Contrast-enhanced CT of the cranial part of the abdomen was performed with 3-mm slice thickness. Postprocessing computer software designed for evaluation of human patients was used to calculate perfusion data for the pancreas and liver by use of 3-mm and reformatted 6-mm slices. Differences in perfusion variables between the pancreas and liver and differences in liver-specific data of interest were evaluated with the Friedman test. Multiple pancreatic perfusion variables were determined, including perfusion, peak enhancement index, time to peak enhancement, and blood volume. The same variables as well as arterial, portal, and total perfusion and hepatic perfusion index were determined for the liver. Values for 6-mm slices appeared similar to those for 3-mm slices. The liver had significantly greater median perfusion and peak enhancement index, compared with the pancreas. Measurement of pancreatic perfusion with contrast-enhanced CT was feasible in this group of dogs. Hepatic arterial and pancreatic perfusion values were similar to previously published findings for dogs, but hepatic portal and hepatic total perfusion measurements were not. These discrepancies might have been attributable to physiologic differences between dogs and people and related limitations of the CT software intended for evaluation of human patients. Further research is warranted to assess reliability of perfusion variables and applicability of the method for assessment of canine patients with pancreatic abnormalities.


The potential of small chemical functional groups for directing the differentiation of kidney stem cells.
In the future, stem-cell-based therapies could offer new approaches to treat kidney disease and reduce the incidence of ESRD (end-stage renal disease), but, as yet, research in this area is only being conducted in rodents and it is not clear whether or when it could be applied to human patients. Drug therapies, on the other hand, have been very effective at delaying the progression of kidney disease, but, for various reasons, current drug regimes are not suitable for all patients. A greater understanding of the molecular mechanisms that underlie disease progression in chronic kidney disease could help to identify novel drug targets. However, progress in this area is currently hindered due to the lack of appropriate in vitro culture systems for important renal cell types, such as proximal tubule cells and podocytes. This problem could be overcome if it were possible to direct the differentiation of kidney stem cells to renal cell types in vitro. In the present review, we highlight the potential of surface gradients of small chemical functional groups to direct the differentiation of kidney stem cells.


Neuromorphic behavior in percolating nanoparticle films.
We show that the complex connectivity of percolating networks of nanoparticles provides a natural solid-state system in which bottom-up assembly provides a route to realization of neuromorphic behavior. Below the percolation threshold the networks comprise groups of particles separated by tunnel gaps; an applied voltage causes atomic scale wires to form in the gaps, and we show that the avalanche of switching events that occurs is similar to potentiation in biological neural systems. We characterize the level of potentiation in the percolating system as a function of the surface coverage of nanoparticles and other experimentally relevant variables, and compare our results with those from biological systems. The complex percolating structure and the electric field driven switching mechanism provide several potential advantages in comparison to previously reported solid-state neuromorphic systems.


Cryogenian glaciation and the onset of carbon-isotope decoupling.
Global carbon cycle perturbations throughout Earth history are frequently linked to changing paleogeography, glaciation, ocean oxygenation, and biological innovation. A pronounced carbonate carbon-isotope excursion during the Ediacaran Period (635 to 542 million years ago), accompanied by invariant or decoupled organic carbon-isotope values, has been explained with a model that relies on a large oceanic reservoir of organic carbon. We present carbonate and organic matter carbon-isotope data that demonstrate no decoupling from approximately 820 to 760 million years ago and complete decoupling between the Sturtian and Marinoan glacial events of the Cryogenian Period (approximately 720 to 635 million years ago). Growth of the organic carbon pool may be related to iron-rich and sulfate-poor deep-ocean conditions facilitated by an increase in the Fe:S ratio of the riverine flux after Sturtian glacial removal of a long-lived continental regolith.