Study of three hypervariable DNA loci (D1S7; D7S22 and D12S11) in three European populations.
To investigate the population genetic characteristics and genetic affinity, DNA profiles of three highly polymorphic VNTR (variable number of tandem repeats) loci (D1S7; D7S22 and D12S11) were studied in 405 individuals from three major European populations (English, Spanish and Basques). Like other studies on VNTRs, a large significant heterozygote deficiency was observed in all three populations. This decrease was ascribed to the limitation, coalescence and non-detectibility of alleles associated with the RFLP (restriction fragment length polymorphism) technique, through which the VNTR loci are genotyped. When the non-detectable alleles were taken into consideration, analyses of fragment sizes at these loci within each sample, as well as their fixed binned analyses, reveal that the assumptions of independence of allelelic occurrences within and between loci are valid for this European data. By comparing genetic variation at three VNTR loci with 17 blood groups, proteins and HLA loci in three well defined European populations, it is shown that the pattern of differentiation at these sets of loci are in general parallel especially for the hypervariable loci HLA and VNTR. Fixed-bin allele frequencies, therefore, are the best descriptions of such a database both for population genetic and forensic calculation studies. The Basques, with regard to VNTR loci, do not show any reduced genetic variability compared to other two European populations (English and Spanish).


systematized review of telemedicine applications in treating burn patients.
Background: Telemedicine has been used in different fields of medicine in the past 20 years. The main advantages of this technology include saving costs, improving quality of care, and increasing access to specialists. This study aimed to review telemedicine applications in treating burn patients. Methods: In this systematized review study, related papers were searched using various databases, including PubMed, Scopus, and Science Direct. The time frame was between January 2000 and March 2016; finally, 32 papers were included in the study. Results: The findings revealed that telemedicine was used in burn care in three different ways: Remote patient follow-up, teleconsultation, and patient assessment. Conclusion: It seems that telemedicine can be easily applied in treating burn patients even when there is a limited financial resource. The use of this technology can help reduce possible errors in categorizing burn patients and decrease patients' transportation and treatment costs.


Knowledge, practices and seroprevalence of Taenia species in smallholder farms in Gauteng, South Africa.
Porcine cysticercosis and associated human infections are endemic in Sub-Saharan Africa, Latin America, and Asia. Poor agricultural practices, sanitary practices, and lack of knowledge increase the burden of the diseases in susceptible populations. This study investigates the seroprevalence of Taenia spp. in township pigs in Gauteng, South Africa and describes knowledge and farming practices of pig farmers regarding T. solium infections. Blood samples were collected from 126 pigs in three Gauteng township areas, and analyzed for active Taenia spp. infection using the B158/B60 Ag-ELISA. Farmer questionnaire surveys were conducted in four township areas to investigate the level of knowledge and practices associated with porcine cysticercosis and neurocysticercosis. Logistic regression models were used to assess the relationship between predictor variables and the outcome variable, knowledge of porcine cysticercosis or knowledge of neurocysticercosis. Overall, 7% of the pigs were seropositive for active Taenia spp. infection. 46% of farmers practiced a free-ranging system, while 25% practiced a semi-intensive system. Latrines were absent on all farms; however, 95% of farmers indicated that they have access to latrines at home. Most farmers had no knowledge of porcine cysticercosis (55%) or neurocysticercosis (79%), and this was not associated with any of the factors investigated. The prevalence of active Taenia spp. infection was reasonably low in this study, yet the knowledge level was also low, thus calling for further educational and training programmes to prevent Taenia spp. transmission in these communities.


The metabolic pathways of tianeptine, a new antidepressant, in healthy volunteers.
The metabolism of tianeptine, a novel antidepressant that presents original neurochemical properties, was studied after a single oral administration of radioisotopically (14C) labeled compound to six healthy male volunteers. After 7 days, approximately 66% of the dose was eliminated by renal excretion (55% during the first 24 hr). Tianeptine is extensively metabolized, and 24 hr after the administration, the unchanged molecule contributed in urine for less than 3% of the administered dose. Chromatographic and mass spectral studies showed that beta-oxidation of the amino acid side chain is the major route of biotransformation for tianeptine. Three major metabolites, accounting for 29% of the dose, were products of beta-oxidation. The metabolite profiles of tianeptine in feces and plasma were qualitatively similar to that in urine.


[Hemiplegia and cerebral palsy - multidisciplinary treatment of the spastic upper extremity].
Spastic hemiplegia and cerebral palsy often lead to typical deformities of the upper extremity. Muscle- and joint-contractures may be painful and aesthetically unappealing and may interfere with function and hygiene. Within the first weeks after the cerebral incidence the vital threat is dominating and the exact amount of neurologic impairment is not assessable. During this period, conservative treatment should counteract the development of contractures. After spontaneous neurologic recovery, surgical options should be taken into account. When choosing surgical procedures, factors as volitional motor control, sensibility and cognition must be taken into account besides the morphologic changes. This is best achieved in a multidisciplinary setting of neurologists, rehabilitation specialists, physiotherapists and surgeons.


Echocardiographic evaluation of cardiac function in female patients with thyroid disorders.
The aim of this study was to assess echocardiographic changes in female patients with untreated dysfunctional thyroid states and whether the therapy aimed to normalize the thyroid dysfunction could lead to improvement in cardiac systolic and diastolic function. The study included 90 female subjects who performed control of thyroid hormonal status at the Institute of Nuclear Medicine at the University of Sarajevo Clinics Centre and who previously were untreated for the thyroid functional disorders. The study sample was divided in three groups based on the thyroid hormones levels: a) hyperthyroid group (n= 30) b) hypothyroid group (n=30) and c) euthyroid (control). Echocardiography measurements were performed on commercially available Toshiba, SSH 140. Before the therapy no statistically significant differences in the peak early and late mitral inflow velocities (E/A) values between the study groups was observed, but the mean left ventricular ejection fraction (LVEF) in hypothyroid group was significantly lower (58.30+/-1.05) compared to control (64.96+/-0.71) and hyperthyroid group (64.69+/-1.31) (p<0.001). In hypothyroid group we found significant increase in mean LVEF (58.30+/-1.05 vs. 64.95+/-0.86, p<0.01) and E/A (1.06+/-0.07 vs. 1.17+/-0.08; p=0.01) values after the normalization of thyroid hormone status.Thyroid dysfunctional states were not associated with impaired diastolic function, probably due to the short duration of thyroid dysfunction and timely and successful conversion therapy. Systolic function however was significantly reduced in hypothyroid patients but subsequently improved after the adequate therapy. Early diagnostic approach in patients with thyroid dysfunctional states is important for avoidance of cardiac complications that accompany these disorders.


Tailoring surface plasmons of high-density gold nanostar assemblies on metal films for surface-enhanced Raman spectroscopy.
Plasmonic systems based on metal nanoparticles on a metal film have generated great interest for surface-enhanced Raman spectroscopy (SERS) chemical sensors. In this study, we describe the fabrication of ultrasensitive SERS substrates based on high-density gold nanostar assemblies on silver films with tailored surface plasmons, where multiple field enhancements from particle-film and interparticle plasmon couplings and lightening rod effects of sharp tips of nanostars contribute to the enormous Raman enhancements. We show that the interplay between interparticle and particle-film plasmon couplings of high-density gold nanostars (GNSs) on metal and dielectric films as a function of interparticle separation can be tailored to provide maximum SERS effects. We observe that the SERS enhancement factor (EF) of GNSs on a metal film as a function of interparticle separation follows a broken power law function, where the EF increases with the interparticle separation for the strong interparticle coupling range below an interparticle separation of ~0.8 times the GNS size, but decreases for the weak interparticle coupling range (for an interparticle separation of >0.8 times the GNS size). Finally, we demonstrate the use of tailored plasmonic substrates as ultrasensitive SERS chemical sensors with an attomole level of detection capability of 2,4-dinitrotoluene, a model compound of nitroaromatic explosives.


Lipopolysaccharide acts synergistically with the dengue virus to induce monocyte production of platelet activating factor and other inflammatory mediators.
Platelet Activating Factor (PAF) has been shown to be an important mediator of vascular leak in acute dengue. Antibody dependent enhancement (ADE) and microbial translocation has also shown to contribute to severe dengue. Since monocytes are one of the primary targets of the dengue virus (DENV) we sought to investigate if monocytes were a source of PAF, and the effect of ADE and microbial endotoxin (LPS) on DENV infected monocytes. PAF and cytokine levels were evaluated in serial blood samples, in patients with acute dengue infection. The effect of ADE and LPS in production of PAF and cytokines from DENV infected primary human monocytes derived macrophages (MDMθ) was assessed. Gene expression analysis was undertaken to investigate mechanisms by which LPS potentiates PAF and cytokine production by DENV infected MDMθ. Serum PAF levels significantly correlated with both TNF-α (p < 0.0001) and IL-1β (p < 0.0001) in patients with acute DENV infection. Although primary human MDMθ produced inflammatory cytokines following infection with the DENV, they did not produce PAF following in vitro DENV infection alone, or in the presence of dengue immune serum. Levels of PAF produced by DENV infected MDMθ co-cultured with LPS was significantly higher than uninfected MDMθs co-cultured with LPS. Although TLR-4 was upregulated in uninfected MDMθs co-cultured with LPS, this upregulation was not significant in DENV infected MDMθ. Only expression of RIG-I was significantly up regulated (p < 0.05) when DENV infected MDMθ were co-cultured with LPS. LPS acts synergistically with the DENV to induce production of PAF and other inflammatory cytokines, which suggests that microbial translocation that has shown to occur in acute dengue, could contribute to dengue disease severity.


Glycoproteomic Profiling Provides Candidate Myocardial Infarction Predictors of Later Progression to Heart Failure.
We hypothesized that identifying plasma glycoproteins that predict the development of heart failure following myocardial infarction (MI) could help to stratify subjects at risk. Plasma collected at visit 2 (2005-2008) from an MI subset of Jackson Heart Study participants underwent glycoproteomics and was grouped by the outcome: (1) heart failure hospitalization after visit 2 (n = 15) and (2) without hospitalization by 2012 (n = 45). Proteins were mapped for biological processes and functional pathways using Ingenuity Pathway Analysis and linked to clinical characteristics. A total of 198 glycopeptides corresponding to 88 proteins were identified (data available via ProteomeXchange with identifier PXD009870). Of these, 14 glycopeptides were significantly different between MI and MI + HF groups and corresponded to apolipoprotein (Apo) F, transthyretin, Apo C-IV, prostaglandin-D2 synthase, complement C9, and CD59 (p < 0.05 for all). All proteins were elevated in the MI + HF group, except CD59, which was lower. Four canonical pathways were upregulated in the MI + HF group (p < 0.05 for all): acute phase response, liver X receptor/retinoid X receptor, and macrophage reactive oxygen species generation. The coagulation pathway was significantly downregulated in the MI + HF group (p < 0.05). Even after adjustment for age and sex, Apo F was associated with the increased risk for heart failure (OR = 21.84; 95% CI 3.20-149.14). In conclusion, glycoproteomic profiling provided candidate early MI predictors of later progression to heart failure.


Limitations of the scientific basis for the management of air quality in urban New Zealand.
As enumerated by Ministry for the Environment, planned reductions in levels of air pollution in New Zealand sufficient to allow compliance with the National Environmental Standards for Air Quality will save, in a cost-effective manner, numerous lives per year. However, as indicated by careful study of the literature and of the methods employed to perform the relevant calculations, such claims are flawed. Instead of a precise number of deaths avoided, small changes in regional life expectancy are a more likely tangible consequence of compliance and, as such, are better suited to assisting calculation of the associated benefits and costs. Some basic data relevant to communities and regions potentially susceptible to the effects of 'poor quality' or inclement air are provided. These support the view that urban air pollution as officially measured and normally encountered in New Zealand nowadays probably has comparatively small substantive mortality consequences.


Weight cycling in adolescent Taekwondo athletes.
Weight reduction cycles are used by weight classed athletes in Taekwondo to make a weight category. Tension, dizziness, headaches, and confusion have been associated with rapid weight loss (RWL). There is a lack of research in weight cycling and its benefits among Taekwondo athletes. To investigate the rate of weight cycling in Junior Taekwondo athletes and its effect on performance. Athletes were weighed prior to competition, then again before their first match. Body mass difference in relation to winning was compared. A significant increase from weigh-in to pre-match measurements was consistently found in both genders with no significant difference between them. Winners had a mean body mass gain (1.02 kg) which was non-significantly less than the non-winners (1.09 kg). RWL practices do not define which athlete will perform better. Negative effects of weight cycling coupled with RWL has unclear performance benefits which indicates a need for further research.


Optical and x-ray technology synergies enabling diagnostic and therapeutic applications in medicine.
X-ray and optical technologies are the two central pillars for human imaging and therapy. The strengths of x-rays are deep tissue penetration, effective cytotoxicity, and the ability to image with robust projection and computed-tomography methods. The major limitations of x-ray use are the lack of molecular specificity and the carcinogenic risk. In comparison, optical interactions with tissue are strongly scatter dominated, leading to limited tissue penetration, making imaging and therapy largely restricted to superficial or endoscopically directed tissues. However, optical photon energies are comparable with molecular energy levels, thereby providing the strength of intrinsic molecular specificity. Additionally, optical technologies are highly advanced and diversified, being ubiquitously used throughout medicine as the single largest technology sector. Both have dominant spatial localization value, achieved with optical surface scanning or x-ray internal visualization, where one often is used with the other. Therapeutic delivery can also be enhanced by their synergy, where radio-optical and optical-radio interactions can inform about dose or amplify the clinical therapeutic value. An emerging trend is the integration of nanoparticles to serve as molecular intermediates or energy transducers for imaging and therapy, requiring careful design for the interaction either by scintillation or Cherenkov light, and the nanoscale design is impacted by the choices of optical interaction mechanism. The enhancement of optical molecular sensing or sensitization of tissue using x-rays as the energy source is an important emerging field combining x-ray tissue penetration in radiation oncology with the molecular specificity and packaging of optical probes or molecular localization. The ways in which x-rays can enable optical procedures, or optics can enable x-ray procedures, provide a range of new opportunities in both diagnostic and therapeutic medicine. Taken together, these two technologies form the basis for the vast majority of diagnostics and therapeutics in use in clinical medicine.


Surface modification of chromatography adsorbents by low temperature low pressure plasma.
In this study we show how low temperature glow discharge plasma can be used to prepare bi-layered chromatography adsorbents with non-adsorptive exteriors. The commercial strong anion exchange expanded bed chromatography matrix, Q HyperZ, was treated with plasmas in one of two general ways. Using a purpose-designed rotating reactor, plasmas were employed to either: (i) remove anion exchange ligands at or close to the exterior surface of Q HyperZ, and replace them with polar oxygen containing functions ('plasma etching and oxidation'); or (ii) bury the same surface exposed ligands beneath thin polymer coatings ('plasma polymerization coating') using appropriate monomers (vinyl acetate, vinyl pyrrolidone, safrole) and argon as the carrier gas. X-ray photoelectron spectroscopy analysis (first ∼10 nm depth) of Q HyperZ before and after the various plasma treatments confirmed that substantial changes to the elemental composition of Q HyperZ's exterior had been inflicted in all cases. The atomic percent changes in carbon, nitrogen, oxygen, yttrium and zirconium observed after being exposed to air plasma etching were entirely consistent with: the removal of pendant Q (trimethylammonium) functions; increased exposure of the underlying yttrium-stabilised zirconia shell; and introduction of hydroxyl and carbonyl functions. Following plasma polymerization treatments (with all three monomers tested), the increased atomic percent levels of carbon and parallel drops in nitrogen, yttrium and zirconium provided clear evidence that thin polymer coats had been created at the exteriors of Q HyperZ adsorbent particles. No changes in adsorbent size and surface morphology, nor any evidence of plasma-induced damage could be discerned from scanning electron micrographs, light micrographs and measurements of particle size distributions following 3 h exposure to air (220 V; 35.8 W L(-1)) or 'vinyl acetate/argon' (170 V; 16.5 W L(-1)) plasmas. Losses in bulk chloride exchange capacity before and after exposure to plasmas enabled effective modification depths within hydrated Q HyperZ adsorbent particles to be calculated as 0.2-1.2 μm, depending on the conditions applied. The depth of plasma induced alteration was strongly influenced by the power input and size of the treated batch, i.e. dropping the power or increasing the batch size resulted in reduced plasma penetration and therefore shallower modification. The selectivity of 'surface vs. core' modification imparted to Q HyperZ by the various plasma treatments was evaluated in static and dynamic binding studies employing appropriate probes, i.e. plasmid DNA, sonicated calf thymus DNA and bovine serum albumin. In static binding studies performed with adsorbents that had been exposed to plasmas at the 5 g scale (25 g L(-1) of plasma reactor), the highest 'surface/core' modification selectivity was observed for Q HyperZ that had been subjected to 3 h of air plasma etching at 220 V (35.8 W L(-1)). This treatment removed ∼53% of 'surface' DNA binding at the expense of a 9.3% loss in 'core' protein binding. Even more impressive results were obtained in dynamic expanded bed adsorption studies conducted with Q HyperZ adsorbents that had been treated with air (220 V, 3 h) and 'vinyl acetate/argon' (170 V, 3 h) plasmas at 10.5 g scale (52.5 g L(-1) of plasma reactor). Following both plasma treatments: the 10% breakthrough capacities of the modified Q HyperZ adsorbents towards 'surface' binding DNA probes dropped very significantly (30-85%); the DNA induced inter-particle cross-linking and contraction of expanded beds observed during application of sonicated DNA on native Q HyperZ was completely eradicated; but the 'core' protein binding performance remained unchanged cf. that of the native Q HyperZ starting material.


Ethylene is required for both the initiation and progression of softening in pear (Pyrus communis L.) fruit.
In order to investigate the physiological role of ethylene in the initiation and subsequent progression of softening, pear fruit were treated with propylene, an analogue of ethylene or 1-methylcyclopropene (1-MCP), a gaseous inhibitor of ethylene action at the preclimacteric or ripening stages. The propylene treatment at the pre-ripe stage stimulated ethylene production and flesh softening while the 1-MCP treatment at the same stage markedly retarded the initiation of the ripening-related events. Moreover, 1-MCP treatment after the initiation of ripening markedly suppressed the subsequent flesh softening and ethylene production. These results clearly indicate that ethylene is not merely a by-product, but plays a crucial role in both the initiation and maintenance of regulating the softening process during ripening. The observations also suggest that ethylene in ripening is regulated entirely in an autocatalytic manner. The mRNA accumulation of pear polygalacturonases (PG) genes, PC-PG1 and PC-PG2, was in parallel with the pattern of fruit softening in both propylene and 1-MCP treatments. However, the expression pattern of pear endo-1,4-beta-D-glucanases (EGase) genes, PC-EG1 and PC-EG2, was not affected in both treatments. The results suggest that ethylene is required for PGs expression even in the late ripening stage, but not for EGases.


In vivo Glx and Glu measurements from GABA-edited MRS at 3 T.
In vivo quantification of glutamate (Glu) and γ-aminobutyric acid (GABA) using MRS is often achieved using two separate sequences: a short-echo point resolved spectroscopy (PRESS) acquisition for Glu and a Mescher-Garwood PRESS (MEGA-PRESS) acquisition for GABA. The purpose of this study was to examine the agreement of Glu and Glx (the combined signal of glutamate + glutamine) quantified from two different GABA-edited MEGA-PRESS acquisitions (GABA plus macromolecules, GABA+, TE = 68 ms, and macromolecule suppressed, MMSup, TE = 80 ms) with Glu and Glx quantified from a short-echo PRESS (PRESS-35, TE = 35 ms) acquisition. Fifteen healthy male volunteers underwent a single scan session, in which data were acquired using the three acquisitions (GABA+, MMSup and PRESS-35) in both the sensorimotor and anterior cingulate cortices using a voxel size of 3 × 3 × 3 cm3 . Glx and Glu were quantified from the MEGA-PRESS data using both the OFF sub-spectra and the difference (DIFF) spectra. Agreement was assessed using correlation analyses, Bland-Altman plots and intraclass correlation coefficients. Glx quantified from the OFF sub-spectra from both the GABA+ and MMSup acquisitions showed poor agreement with PRESS-35 in both brain regions. In the sensorimotor cortex, Glu quantified from the OFF sub-spectra of GABA+ showed moderate agreement with PRESS-35 data, but this finding was not replicated in the anterior cingulate cortex. Glx and Glu quantified using the DIFF spectra of either MEGA-PRESS sequence were in poor agreement with the PRESS-35 data in both brain regions. In conclusion, Glx and Glu measured from MEGA-PRESS data generally showed poor agreement with Glx and Glu measured using PRESS-35.


Predator-vole interactions in Northern Europe: the role of small mustelids revised.
The cyclic population dynamics of vole and predator communities is a key phenomenon in northern ecosystems, and it appears to be influenced by climate change. Reports of collapsing rodent cycles have attributed the changes to warmer winters, which weaken the interaction between voles and their specialist subnivean predators. Using population data collected throughout Finland during 1986-2011, we analyse the spatio-temporal variation in the interactions between populations of voles and specialist, generalist and avian predators, and investigate by simulations the roles of the different predators in the vole cycle. We test the hypothesis that vole population cyclicity is dependent on predator-prey interactions during winter. Our results support the importance of the small mustelids for the vole cycle. However, weakening specialist predation during winters, or an increase in generalist predation, was not associated with the loss of cyclicity. Strengthening of delayed density dependence coincided with strengthening small mustelid influence on the summer population growth rates of voles. In conclusion, a strong impact of small mustelids during summers appears highly influential to vole population dynamics, and deteriorating winter conditions are not a viable explanation for collapsing small mammal population cycles.


Quantal release of transmitter is not associated with channel opening on the neuronal membrane.
The traditional view that quantal release of neurotransmitter results from the fusion of transmitter-containing vesicles with the neuronal membrane has been recently challenged. Although various alternative mechanisms have been proposed, a common element among them is the release of cytoplasmic transmitter, which, in one view, could occur through large conductance channels on the presynaptic membrane. Six nerve-muscle cell pairs were examined with a whole-cell patch clamp for the presence of such channels that are associated with the production of miniature end-plate potentials. Examination of the neuronal membrane current during the occurrence of 822 miniature end-plate potentials produced no evidence of large channels. Thus it is unlikely that quantal release is mediated by such channels in the neuromuscular junction.


B-cell activation by lipopolysaccharide. Distinct pathways for induction of mitosis and antibody production.
The role played by macrophages in two effects of lipopolysaccharide (LPS) on the immune system of the mouse-substitution for helper T cells and induction of B-cell mitosis-has been investigated. C3H/HeJ mice are unresponsive and do not produce (as other strains do) antibody to 2,4,6-trinitrophenol (TNP) conjugated with autologous mouse erythrocytes (MRBC-TNP) in the presence of LPS. We found that C3H/HeJ spleen cells produce antibody to MRBC-TNP when (a) LPS and macrophages from LPS-responsive C3HeB/FeJ mice or (b) tumor necrosis serum ([TNS] induced by LPS in responsive mice) are added. The mitotic response was not restored. The findings suggest that adjuvanticity and mitogenicity represent distinct pathways of B-cell activation by LPS, subject to different regulatory mechanisms.


A mouse model for South African (R59W) variegate porphyria: construction and initial characterization.
Variegate porphyria is inherited as an autosomal dominant disease with variable penetrance. It is characterized clinically by photocutaneous sensitivity and acute neurovisceral attacks, and biochemically by abnormal porphyrin excretion in the urine and feces. While the world-wide incidence of variegate porphyria is relatively low, in South Africa it is one of the most common genetic diseases in humans. Due to the large number of patients with variegate porphyria in South Africa, and the fact that variegate porphyria is representative of both the so-called "acute" and the "photocutaneous" porphyrias, it would be valuable to have an animal model in which to study the disease. In this study we have produced a mouse model of "South African" variegate porphyria with the R59W mutation in C57/BL6 mice via targeted gene replacement. Hepatic protoporphyrinogen oxidase activity was reduced by approximately 50% in mice heterozygous for the mutation. Urine and fecal samples from these mice, in the absence of exogenous inducers of hepatic haem synthesis, contain elevated concentrations of porphyrins and porphyrin precursors in a pattern similar to that found in human variegate porphyric subjects. Bypassing the rate-limiting step in haem biosynthesis by feeding 5-aminolevulinic acid to these mice, results in an accentuated porphyrin excretory pattern characteristic of the variegate porphyric phenotype and urinary porphobilinogen is increased significantly. This initial characterization of these mice suggest that they are a good model for variegate porphyria at the biochemical level.


Functional MRI in healthy subjects during acupuncture: different effects of needle rotation in real and false acupoints.
The cerebral activation pattern due to acupuncture is not completely understood. Although the effect of acupuncture on cerebral haemodynamics has been studied, no previous report has focused on different puncture and stimulation methods. We used functional MRI (fMRI) in 15 healthy subjects to investigate cortical activation during stimulation of two real acupoints (Liv3 and G40) and one sham point, needled in a random and, for the subjects, blinded order employing rotating and non-rotating methods, using a blocked paradigm on a 1.5 tesla imager. Compared to the non-rotating stimulation method, during rotating stimulation of the real acupoints, we observed an increase in activation in both secondary somatosensory cortical areas, frontal areas, the right side of the thalamus and the left side of the cerebellum; no such effects of the needling technique were seen while stimulating the sham point. The observation that rotating the needle strengthened the effects of acupuncture only at real acupoints suggests that, as claimed in Chinese traditional medicine, stimulation of these acupoints has a specific effect on cortical neuronal activity, absent with sham acupoints. These specific cerebral activation patterns might explain the therapeutic effects of acupuncture in certain subjects.


Tau Protein is Associated with Longitudinal Memory Decline in Cognitively Healthy Subjects with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels.
We investigated a sample of cognitively healthy subjects with normal Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker levels to identify the earliest variables related to longitudinal memory changes. Employing a new highly demanding learning and memory test (the Ancient Farming Equipment Test; AFE-T), we aimed to investigate whether a biomarker related to neurodegeneration (i.e., CSF tau) was associated with longitudinal memory decline. Thirty-two cognitively and biologically normal (CBN) subjects underwent MRI, neuropsychological assessment, and the AFE-T at baseline and 18 months later. To explore the relationship between cognitive performance and relevant factors, a linear model was set up. For a secondary analysis that further explore the effect of tau, the subjects were divided into CBN-Tau↓ (tau < 228.64 pg/ml; n = 16) and CBN-Tau↑ (tau > 228.64 pg/ml; n = 16). We also performed voxel-based morphometry (VBM) to identify regions of grey matter volume that would predict both baseline and longitudinal cognitive performance. Our main finding was an association between CSF tau and longitudinal memory decline measured with AFE-T (B = -0.17, p < 0.05; r = -0.414; p < 0.01), and further analyses showed different evolvement between subgroups, with an accelerated decline in individuals with higher tau (F(1,31) = 8.37; p < 0.01). VBM results suggested that AFE-T performance is related to grey matter volume in a medial temporal, middle frontal, and posterior cerebellar network at baseline, and that there are strategic brain areas driving the longitudinal cognitive changes. The present findings provide evidence for structural and biological markers linked to cognitive aging by highlighting the role of tau, a marker of neurodegeneration, which can be related with the earliest memory changes in healthy subjects.


A user-oriented web crawler for selectively acquiring online content in e-health research.
Life stories of diseased and healthy individuals are abundantly available on the Internet. Collecting and mining such online content can offer many valuable insights into patients' physical and emotional states throughout the pre-diagnosis, diagnosis, treatment and post-treatment stages of the disease compared with those of healthy subjects. However, such content is widely dispersed across the web. Using traditional query-based search engines to manually collect relevant materials is rather labor intensive and often incomplete due to resource constraints in terms of human query composition and result parsing efforts. The alternative option, blindly crawling the whole web, has proven inefficient and unaffordable for e-health researchers. We propose a user-oriented web crawler that adaptively acquires user-desired content on the Internet to meet the specific online data source acquisition needs of e-health researchers. Experimental results on two cancer-related case studies show that the new crawler can substantially accelerate the acquisition of highly relevant online content compared with the existing state-of-the-art adaptive web crawling technology. For the breast cancer case study using the full training set, the new method achieves a cumulative precision between 74.7 and 79.4% after 5 h of execution till the end of the 20-h long crawling session as compared with the cumulative precision between 32.8 and 37.0% using the peer method for the same time period. For the lung cancer case study using the full training set, the new method achieves a cumulative precision between 56.7 and 61.2% after 5 h of execution till the end of the 20-h long crawling session as compared with the cumulative precision between 29.3 and 32.4% using the peer method. Using the reduced training set in the breast cancer case study, the cumulative precision of our method is between 44.6 and 54.9%, whereas the cumulative precision of the peer method is between 24.3 and 26.3%; for the lung cancer case study using the reduced training set, the cumulative precisions of our method and the peer method are, respectively, between 35.7 and 46.7% versus between 24.1 and 29.6%. These numbers clearly show a consistently superior accuracy of our method in discovering and acquiring user-desired online content for e-health research. The implementation of our user-oriented web crawler is freely available to non-commercial users via the following Web site: http://bsec.ornl.gov/AdaptiveCrawler.shtml. The Web site provides a step-by-step guide on how to execute the web crawler implementation. In addition, the Web site provides the two study datasets including manually labeled ground truth, initial seeds and the crawling results reported in this article.


Native hip joint septic arthritis in 20 adults: delayed presentation beyond three weeks predicts need for excision arthroplasty.
Septic arthritis of native hip joints is an uncommon condition in adults in Western Europe, but continues to present a challenge to medical and surgical management. We set out to study the natural history and bacteriology of the disease in this group, with a particular focus on patients requiring excision arthroplasty (EA). We retrospectively studied 26 secondary referral cases (20 adults) managed by a specialist bone infection unit over a 12 year period. Our patient cohort was diverse, affecting all age groups in the presence and absence of co-morbid conditions. The commonest pathogen was Staphylococcus aureus. Of 20 adults studied, five (25%) required EA. Symptom duration prior to presentation was a statistical predictor of the requirement for EA (p<0.003); in particular, symptom duration of over three weeks was strongly associated with requirement for this procedure (p<0.0003). In cases that present promptly, combined surgical drainage and intravenous antibiotics should be expected to eradicate infection and to salvage the femoral head. Cases presenting following a delay are more likely to require EA and subsequent hip reconstruction.


Quinacrine and 2-(4-phenylpiperidino)cyclohexanol (AH5183) inhibit acetylcholine release and synthesis in rat brain slices.
The effects of 2-(4-phenylpiperidino)cyclohexanol (AH5183) and quinacrine, two potent inhibitors of acetylcholine transport into vesicles isolated from Torpedo electric organ, were examined on acetylcholine metabolism in rat cortical slices. K+-stimulated acetylcholine release was reduced in a concentration-dependent manner by AH5183 and quinacrine, with IC50 values of 1 microM and 50 microM, respectively. Both drugs also reduced the synthesis of acetylcholine in slices and inhibited synaptosomal high affinity choline transport. The inhibitory effect of AH5183 appears to be directed primarily on the release of acetylcholine while the major effect of quinacrine is on the synthesis of acetylcholine. Examination of the subcellular distribution of acetylcholine in brain slices incubated in high K+ showed that AH5183 increased S3 (cytoplasmic) acetylcholine levels but did not alter P3 (vesicular) acetylcholine levels. P3 acetylcholine levels were reduced by AH5183 in a low K+ media while the S3 acetylcholine levels were the same as controls. These results are consistent with the concept that there is a small, active, highly labile fraction of vesicles that are the source of the released acetylcholine and that the loading of these vesicles is blocked by AH5183.


Quality of pharmaceutical advertisements in medical journals: a systematic review.
Journal advertising is one of the main sources of medicines information to doctors. Despite the availability of regulations and controls of drug promotion worldwide, information on medicines provided in journal advertising has been criticized in several studies for being of poor quality. However, no attempt has been made to systematically summarise this body of research. We designed this systematic review to assess all studies that have examined the quality of pharmaceutical advertisements for prescription products in medical and pharmacy journals. Studies were identified via searching electronic databases, web library, search engine and reviewing citations (1950 - February 2006). Only articles published in English and examined the quality of information included in pharmaceutical advertisements for prescription products in medical or pharmacy journals were included. For each eligible article, a researcher independently extracted the data on the study methodology and outcomes. The data were then reviewed by a second researcher. Any disagreements were resolved by consensus. The data were analysed descriptively. The final analysis included 24 articles. The studies reviewed advertisements from 26 countries. The number of journals surveyed in each study ranged from four to 24 journals. Several outcome measures were examined including references and claims provided in advertisements, availability of product information, adherence to codes or guidelines and presentation of risk results. The majority of studies employed a convenience-sampling method. Brand name, generic name and indications were usually provided. Journal articles were commonly cited to support pharmaceutical claims. Less than 67% of the claims were supported by a systematic review, a meta-analysis or a randomised control trial. Studies that assessed misleading claims had at least one advertisement with a misleading claim. Two studies found that less than 28% of claims were unambiguous clinical claims. Most advertisements with quantitative information provided risk results as relative risk reduction. Studies were conducted in 26 countries only and then the generalizability of the results is limited. Evidence from this review indicates that low quality of journal advertising is a global issue. As information provided in journal advertising has the potential to change doctors' prescribing behaviour, ongoing efforts to increase education about drug promotion are crucial. The results from our review suggest the need for a global pro-active and effective regulatory system to ensure that information provided in medical journal advertising is supporting the quality use of medicines.


A Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia, and Subjective Sialorrhea: A Systematic Review Sponsored by the World Workshop on Oral Medicine VI.
Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality of life. However, no evidence-based lists of the medications that cause these disorders exist. Our objective was to compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea. Electronic databases were searched for relevant articles published until June 2013. Of 3867 screened records, 269 had an acceptable degree of relevance, quality of methodology, and strength of evidence. We found 56 chemical substances with a higher level of evidence and 50 with a moderate level of evidence of causing the above-mentioned disorders. At the first level of the Anatomical Therapeutic Chemical (ATC) classification system, 9 of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous, and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices. While xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when administered in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or was not detected in our search. We compiled a comprehensive list of medications with documented effects on salivary gland function or symptoms that may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful in helping practitioners anticipate adverse effects and consider alternative medications.


Accident and emergency attendances by children under the age of 1 year as a result of injury.
To examine all accident and emergency (A&E) department attendances by children under the age of 1 year over a period of 12 months. Also to try to identify the prevalence and severity of accident types in small children and to suggest ways to reduce such accidents. The A&E department of the Royal Aberdeen Children's Hospital (RACH) serves a population of over half a million. All children under 1 year of age attending this department in the year 2000 had their case notes reviewed by the author and the cause, type, and severity of the illness or injury noted. During the 12 month audit period 1416 new cases under the age of 1 year presented to RACH, 790 of which presented directly to A&E. Six hundred and eighteen (78%) were self referred and 116 children attended A&E on more than one occasion during the year. Four hundred and thirty four (55%) of the A&E attendances were classed as "accidents", the remainder were mainly for medical conditions such as respiratory distress. Two hundred and sixty four (61%) were caused by falls and 38% were admitted for inpatient management. Two hundred and twenty nine (29%) required radiographs, which revealed 30 fractures. Thirty seven children sustained scalds/burns and there were 33 accidental ingestions. Six cases were judged to be non-accidental. There is a surprisingly high rate of "accidental" injury in this age group, bringing into question the effectiveness of current accident prevention strategies. Perhaps specific prevention advice should be targeted at parents and carers of young children. There should always be a high index of suspicion for non-accidental injury.


Study of alleles of the second complement component (C2) on Canadian HLA haplotypes.
Typing for genetic variation in the second complement component C2 was performed on sera from HLA haplotyped Canadian families. Part of the data has been studied and analysed as a population; in addition there is a further random collection of haplotypes bearing the C2*2 allele. In the population data there were 444 separate haplotypes from unrelated parents or other founders: 4.7% of the haplotypes carried the uncommon allele C2*2; one haplotype carried the rare C2*3. Study of C2 2-1 heterozygotes in the population data revealed 59 haplotypes which carried the common C2*1 allele and one which carried a deficiency allele C2*0. The remaining haplotypes carried either C2*1 or else an undetectable C2*0 allele. In the entire data there were 281 meioses informative for C2. The only recombinant between HLA-B and C2 showed the C2 locus to be on the DR side of the B locus. Strong allelic association between C2 *2 and Bw22 and less strong association between C2 *2 and B15 suggested the possibility of two ancestral C2 mutants. Examination of other markers on these and subsequently collected haplotypes do not conflict with this idea since the B15 haplotypes mostly carry C4A *4, C4B *2 whilst the Bw22 haplotypes mostly carry C4A *4, C4B *4. The alternative idea, that there was one original mutant which crossed over from a B15 to a Bw22 haplotype or vice versa is not excluded, however. Since approximate equilibrium has been reached between Bw22 and the HLA-A locus alleles on these C2 *2 bearing haplotypes, we conclude that this mutation is at least 5000 years old. Other haplotypes carrying C2 *2 are assumed to be ancestral recombinants; if this is true, the C2 locus map position between HLA-B and HLA-DR is confirmed. Study of C2 mutation may provide a model for understanding the genetics of some disease susceptibility genes in the HLA region.


Cerebral Venous Sinus Thrombosis as a Rare Complication of Systemic Lupus Erythematosus: Subgroup Analysis of the VENOST Study.
Systemic lupus erythematosus (SLE) is an unusual risk factor for cerebral venous sinus thrombosis (CVST). As few CVST patients with SLE have been reported, little is known regarding its frequency as an underlying etiology, clinical characteristics, or long-term outcome. We evaluated a large cohort of CVST patients with SLE in a multicenter study of cerebral venous thrombosis, the VENOST study, and their clinical characteristics. Among the 1144 CVST patients in the VENOST cohort, patients diagnosed with SLE were studied. Their demographic and clinical characteristics, etiological risk factors, venous involvement status, and outcomes were recorded. In total, 15 (1.31%) of 1144 CVST patients had SLE. The mean age of these patients was 39.9 ± 12.1 years and 13 (86.7%) were female. Presenting symptoms included headache (73.3%), visual field defects (40.0%), and altered consciousness (26.7%). The main sinuses involved were the transverse (60.0%), sagittal (40.0%), and sigmoid (20.0%) sinuses. Parenchymal involvement was not seen in 73.3% of the patients. On the modified Rankin scale, 92.9% of the patients scored 0-1 at the 1-month follow-up and 90.9% scored 0-1 at the 1-year follow-up. SLE was found in 1.31% of the CVST patients, most frequently in young women. Headache was the most common symptom and the CVST onset was chronic in the majority of cases. The patient outcomes were favorable. CVST should be suspected in SLE patients, even in those with isolated chronic headache symptoms with or without other neurological findings.


Current practice in the assessment and management of acute diabetes-related foot complications.
A retrospective audit of client histories from 1 April 2004 to 31 March 2005 was conducted. Assessment, investigations on admission, management, length of stay and outcomes were assessed and compared with evidence-based guidelines. A total of 62 clients with 115 admissions were identified. The finding that HBA(1c) (glycated haemoglobin) levels were measured on admission 50% of the time suggested there is significant variability in assessment, investigation and management of acute diabetes-related foot complications. There is a need to better utilise evidence-based clinical guidelines, and for greater emphasis on linking individuals who are at risk of hospitalisation into appropriate outpatient services to improve outcomes.


Design and standards for genetic evaluation of swine seedstock populations.
The purpose of this article is to describe a program for evaluation of seedstock populations in the swine industry. Differences among seedstock populations for economically important traits must be identified in order for pork producers to efficiently use available genetic resources. National genetic evaluation programs have the potential to identify the important differences among populations and to increase the rate of genetic improvement in a population. Program results provide performance benchmarks that stimulate testing and selection procedures by seedstock suppliers that further increase the rate of genetic improvement. A Terminal Sire Line Genetic Evaluation Program was designed and conducted in the United States by the National Pork Producers Council (Des Moines, IA) to compare seedstock populations for use in crossbreeding systems. High levels of statistical accuracy for program results were established; the ability to detect differences of 0.25 SD per trait, a power of test of 75%, and a 5% significance level were selected. Pure breeds and breeding company sire lines were nominated for the program. Semen was collected from nominated boars and distributed to cooperating commercial producers during eight 1-wk breeding periods. Pigs were produced in 136 commercial herds and transported to testing facilities at 8 to 23 d of age. Nine of the 11 sire lines originally entered in the program completed the sampling requirements for statistical analysis. High levels of statistical accuracy and a large, representative sample of boars with restrictions on genetic relationships ensured that the program results included unbiased, highly accurate sire line data for growth, carcass, meat quality, and eating quality traits of economic importance. This program has shown commercial producers that they have several choices of sire lines for changing their crossbreeding programs in desired trait areas. Commercial product evaluation must be an ongoing process, and this program serves as a model for future testing and evaluation of diverse genetic seedstock populations.


Loss of Panx1 Impairs Mammary Gland Development at Lactation: Implications for Breast Tumorigenesis.
Pannexin1 (Panx1) subunits oligomerize to form large-pore channels between the intracellular and extracellular milieu that have been shown to regulate proliferation, differentiation and cell death mechanisms. These key cellular responses are ultimately necessary for normal tissue development and function but the role of Panx1 in development, differentiation and function in many tissues remains unexplored, including that of the breast. Panx1 was identified to be expressed in the mammary gland through western blot and immunofluorescent analysis and is dynamically upregulated during pregnancy and lactation. In order to evaluate the role of Panx1 in the context of mammary gland development and function, Panx1-/- mice were evaluated in comparison to wild-type mice in the mammary glands of virgin, lactating and involuting mice. Our results revealed that Panx1 ablation did not affect virgin or involuting mammary glands following histological and whole mount analysis. Panx1 was necessary for timely alveolar development during early lactation based on a decreased number of alveolar lumen following histological analysis and reduced proliferation following Ki67 immunofluorescent labelling. Importantly, the loss of Panx1 in lactating mammary glands did not overtly affect epithelial or secretory differentiation of the mammary gland suggesting that Panx1 is not critical in normal mammary gland function. In addition, PANX1 mRNA expression was correlated with negative clinical outcomes in patients with breast cancer using in silico arrays. Together, our results suggest that Panx1 is necessary for timely alveolar development following the transition from pregnancy to lactation, which may have implications extending to patients with breast cancer.


Genetic determinants of renal transplant outcome: where do we stand?
Kidney transplantation has become the preferred method of renal replacement. However, the rate of long term allograft survival has not changed over the last decade. Donor and recipient genetic interplay influences kidney transplant outcome but our knowledge of these complex interactions is limited. Until recently, investigations have been limited to small candidate gene studies, usually restricted to allograft recipients. Genome-wide association studies have been slow to emerge in transplantation but the first has recently been reported and will be reviewed here. Much larger studies involving donor and recipients pairs are ongoing. We are now entering the era of epigenetics and whole genome sequencing which will hopefully provide a more in-depth knowledge of the genetic influences on renal transplant outcome. This may lead to a more accurate assessment of post-transplant risk, potentially allowing for the development of risk predication models leading to a more personalized approach to kidney transplant care. In this article, we examine the current and emerging literature in the field and discuss the limitations of current studies and technologies.


Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells.
The embryonic stem cell-specific cell cycle-regulating (ESCC) family of microRNAs (miRNAs) enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. Here we show that the human ESCC miRNA orthologs hsa-miR-302b and hsa-miR-372 promote human somatic cell reprogramming. Furthermore, these miRNAs repress multiple target genes, with downregulation of individual targets only partially recapitulating the total miRNA effects. These targets regulate various cellular processes, including cell cycle, epithelial-mesenchymal transition (EMT), epigenetic regulation and vesicular transport. ESCC miRNAs have a known role in regulating the unique embryonic stem cell cycle. We show that they also increase the kinetics of mesenchymal-epithelial transition during reprogramming and block TGFβ-induced EMT of human epithelial cells. These results demonstrate that the ESCC miRNAs promote dedifferentiation by acting on multiple downstream pathways. We propose that individual miRNAs generally act through numerous pathways that synergize to regulate and enforce cell fate decisions.


Effects of COVID-19 related government response stringency and support policies: Evidence from European firms.
In this paper we employ survey information on more than 10,000 Southern and Eastern European firms to assess the effects of the COVID-19 related lockdown and government support policies on the business operations of enterprises. Our findings reveal considerable size- and sector-related heterogeneity, with small firms, and firms such as hotels and restaurants operating in the facilities sector reporting the largest losses in terms of sales when governments increase the strictness of confinement measures. Fixed effects regression estimates suggest that a complete lockdown results in an average year-on-year sales growth that is approximately 63 percentage points lower than it would be without any curtailment measures. The magnitude of the coefficient on year-on-year sales change for a complete lockdown is 14 percentage points higher for small compared to large enterprises. Furthermore, our results suggest that state aid in the form of deferral of payments or wage subsidies are associated with firms' firms' labor market and financial outcomes in times of crisis. For instance, deferrals of payments are linked to between 0.7 and 1.5 fewer layoffs per firm in the surveyed enterprises compared to other types of support.


Historical perspectives on plant developmental biology.
The early studies of plant growth and development focused on embryogenesis. In the past twenty five years, it became possible to successfully analyze many more developmental processes, hence plant developmental biology became the generally accepted terminology. It refers to a multidisciplinary approach using expertise and tools from genetics, molecular biology and cell biology to study processes in development also beyond the formation of the embryo. Around that time, initiatives were taken to address biological questions in just a few model systems, such as Arabidopsis thaliana, Zea mays, Antirrhinum majus and Petunia hybrida, while the <<old>> model systems, i.e. potato, tobacco, used in regeneration and grafting experiments, were increasingly abandoned. International research programs were initiated in Arabidopsis at first to create stock centers and databases to proceed faster with the scientific research and to get deeper insight into plant biology. During the last five years the maize community made tremendous progress in developing tools and resources for their system. Milestones in plant developmental biology discussed relate to the molecular-genetic approach to study embryogenesis, autoregulation of meristems, leaf and flower initiation, leaf and flower formation and cell specification in the root. Developmental biology changed the research from descriptive to causal resulting in a number of genetic models. Future developments in research will focus on the study of a specific gene activity in a genome-wide context. The building of molecular networks will allow computer modeling of biological processes and its use for predictions and further experimentation. Sequence information derived from the multiple genome projects will be exploited in comparative biology.


Dietary Diversity in Cambodian Garment Workers: The Role of Free Lunch Provision.
The objective of this paper is to compare food consumption by Cambodian garment workers with and without access to a free model lunch provision through a factory-based canteen. Data from an exploratory randomised controlled trial were analysed. In total, 223 female Cambodian garment workers were allocated to an intervention arm (six-month lunch provision) or a control arm. Dietary intake on workdays was assessed by qualitative 24-h recalls at baseline and twice at follow-ups during the period of lunch provision using the Food and Agricultural Organization (FAO) guideline on assessing women's dietary diversity. In total, 158 participants provided complete data on the dietary intake over workdays at all interviews. Lunch provision resulted in a more frequent consumption of dark green leafy vegetables (DGLV), vitamin A-rich fruits, other fruits, and oils and fats during lunch breaks. In contrast, flesh meats, legumes, nuts and seeds, as well as sweets, were eaten at a lower frequency. Except for a higher consumption rate of vitamin A-rich fruits and a lower intake frequency of sweets, lunch provision had a less clear impact on total 24-h intake from different food groups and was not associated with a higher women's dietary diversity score (WDDS). A more gap-oriented design of the lunch sets taking into account underutilised foods and the nutritional status of the workers is recommended.


Apoflavodoxin: structure, stability, and FMN binding.
Flavodoxins are one domain alpha/beta electron transfer proteins that participate in photosynthetic reactions. All flavodoxins carry a molecule of flavin mononucleotide (FMN), non-covalently bound, that confers redox properties to the protein. There are two structurally distinct flavodoxins, short ones and long flavodoxins; the latter contain an extra loop with unknown function. We have undertaken the study of the stability and folding of the apoflavodoxin from Anabaena (a long flavodoxin) and the analysis of the interaction between the apoflavodoxin and FMN. Our studies indicate that apoflavodoxin folds in a few seconds to a form that is competent in FMN binding. The stability of this apoflavodoxin is low and its urea denaturation can be described by a two-state mechanism. The role of the different parts of the apoflavodoxin in the stability and structure of the whole protein is being investigated using mutagenesis and specific cleavage to generate apoflavodoxin fragments. The X-ray structure of apoflavodoxin is very similar to that of its complex with FMN, the main difference being the conformation of the two aromatic residues that sandwich FMN in the complex. In apoflavodoxin these groups interact with each other so closing the FMN binding site. Despite this fact, apoflavodoxin binds FMN tightly and rapidly, and the resulting holoflavodoxin displays a high conformational stability. We have found that one role of the aromatic residues that interact with FMN is to help to retain bound the reduced form of the cofactor whose complex with apoflavodoxin is otherwise too weak.


Protein supplement consumption is linked to time spent exercising and high-protein content foods: A multicentric observational study.
The main aim of this study is to analyze if protein supplement consumption and food patterns vary across three geographical regions and secondly to identify possible factors that increase the likelihood of ingesting protein supplements. A total of 916 responses from gym users of 3 countries (Italy, Turkey and UK) were entered for analysis. Questions were related to supplement consumption (protein and other supplements), food intake and training habits. A descriptive analysis, analysis of variance (ANOVA), and logistic regression were performed. No differences were found across groups regarding: prevalence of protein supplement consumption, typology of other ingested supplement and food intake. No relation was found between level of education (r = .12) or geographical region (r = .16) and protein consumption. The analysis showed that the coach is the main source of suggestion for the intake of protein supplements (52.3%). The logistic regression model highlighted that gym users who exercised more (OR 1.51, p < 0.001) and consumed higher quantities of chicken (OR 1.39, p < 0.001) eggs (OR 1.18, p < 0.001) and canned tuna (OR 1.15, p < 0.05) were more likely to use protein supplements. Geographical area does not seem to influence the supplementation pattern. Time spent exercising and high protein foods are factors associated with protein supplement consumption.


Concurrent resistance and aerobic exercise stimulates both myofibrillar and mitochondrial protein synthesis in sedentary middle-aged men.
We determined myofibrillar and mitochondrial protein fractional synthesis rates (FSR), intramuscular signaling protein phosphorylation, and mRNA expression responses after isolated bouts of resistance exercise (RE), aerobic exercise (AE), or in combination [termed concurrent exercise (CE)] in sedentary middle-aged men. Eight subjects (age = 53.3 ± 1.8 yr; body mass index = 29.4 ± 1.4 kg·m(2)) randomly completed 8 × 8 leg extension repetitions at 70% of one repetition-maximum, 40 min of cycling at 55% peak aerobic power output (AE), or (consecutively) 50% of the RE and AE trials (CE). Biopsies were obtained (during a primed, constant infusion of l-[ring-(13)C(6)]phenylalanine) while fasted, and at 1 and 4 h following postexercise ingestion of 20 g of protein. All trials increased mitochondrial FSR above fasted rates (RE = 1.3-fold; AE = 1.5; CE = 1.4; P < 0.05), although only CE (2.2) and RE (1.8) increased myofibrillar FSR (P < 0.05). At 1 h postexercise, phosphorylation of Akt on Ser(473) (CE = 7.7; RE = 4.6) and Thr(308) (CE = 4.4; RE = 2.9), and PRAS40 on Thr(246) (CE = 3.8; AE = 2.5) increased (P < 0.05), with CE greater than AE for Akt Ser(473)-Thr(308) and greater than RE for PRAS40 (P < 0.05). Despite increased phosphorylation of Akt-PRAS40, phosphorylation of mammalian target of rapamycin (Ser(2448)) remained unchanged (P > 0.05), while rpS6 (Ser(235/236)) increased only in RE (10.4) (P < 0.05). CE and AE both resulted in increased peroxisome proliferator receptor-γ coactivator 1-α (PGC1α) expression at 1 h (CE = 2.9; AE = 2.8; P < 0.05) and 4 h (CE = 2.6; AE = 2.4) and PGC1β expression at 4 h (CE = 2.1; AE = 2.6; P < 0.05). These data suggest that CE-induced acute stimulation of myofibrillar and mitochondrial FSR, protein signaling, and mRNA expression are equivalent to either isolate mode (RE or AE). These results occurred without an interference effect on muscle protein subfractional synthesis rates, protein signaling, or mRNA expression.


Gastric MALT lymphoma treated with primary radiotherapy in the setting of autoimmune disease.
Autoimmune and microbial-induced immune reactions are associated with lymphomagenesis, particularly of extranodal marginal zone B-cell lymphomas. This report presents a case of Helicobacter pylori-negative gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the setting of Sjögren syndrome and Hashimoto thyroiditis treated with primary involved-field radiotherapy. This report describes etiologic data, diagnostic and treatment considerations, and sophisticated radiation therapy techniques aimed at reducing long-term toxicity in this indolent disease.


Differential resilience of Amazonian otters along the Rio Negro in the aftermath of the 20th century international fur trade.
Commercial hunting for the international trade in animal hides in the 20th century decimated many populations of aquatic wildlife in Amazonia. However, impacts varied significantly between different species and regions, depending upon hunting intensity, accessibility of habitat, and the inherent resilience of various species and their habitats. We investigated the differential responses of two Amazonian Mustelid species, the neotropical otter and giant otter, to commercial hunting pressure along the upper Rio Negro in Brazil, and examined historical factors that influenced spatial and temporal variation in commercial exploitation. We analyzed previously unanalyzed data from historical records of hide shipments to track changes in hide sales and prices for the two species in the late 20th century. We also gathered oral histories from older Baniwa people who had witnessed or participated in commercial otter hunting. These complimentary data sources reveal how intrinsic biological and social characteristics of the two otter species interacted with market forces and regional history. Whereas giant otter populations were driven to local or regional extinction during the late 20th century by commercial hunting, neotropical otters persisted. In recent decades, giant otter populations have returned to some parts of the upper Rio Negro, a development which local people welcome as part of a generalized recovery of the ecosystems in their territory as a result of the banning of animal pelt exports and indigenous land demarcation. This paper expands the scope of the field historical ecology and reflects on the role of local knowledge in biodiversity conservation.


The phosphodiesterase inhibitors pentoxifylline and rolipram prevent diabetes in NOD mice.
Interleukin (IL)-12, interferon (IFN)-gamma, and other inflammatory cytokines play an important role in the pathogenesis of autoimmune insulitis and diabetes in NOD mice, and inhibition of these cytokines is likely to be beneficial. In this study, we found that Pentoxifylline (PTX) and Rolipram (phosphodiesterase [PDE] inhibitors that induce increased intracellular cAMP) can block inflammatory cytokine production. Inhibition of IL-12 and IFN-gamma secretion was demonstrated in macrophages activated with lipopolysaccharide or T-cells stimulated through the CD3/T-cell receptor complex, respectively. Moreover, strong inhibition of IL-12 was demonstrated in vivo in superantigen-immunized mice. Rolipram was inhibitory at concentrations as low as 10(-8) to 10(-7) mol/l, and on a molar basis, it was 100-fold more effective than PTX. Tumor necrosis factor-alpha was also inhibited, but IL-4 was less sensitive to suppression. In NOD mice, both PTX and Rolipram reduced the severity of insulitis and prevented diabetes, with or without cyclophosphamide administration (which precipitates onset of disease). This protection of NOD mice was still apparent over 10 weeks after withdrawal of the drug treatment. It appears that blocking the activity of type IV PDE is sufficient to mediate the effects reported in this study, since Rolipram inhibits only this isoform, unlike PTX (a general inhibitor). PTX and Rolipram may be effective in the treatment of autoimmune diabetes or other conditions characterized by excessive production of inflammatory cytokines.


How informed is our consent? Patient awareness of radiation and radical prostatectomy complications.
To evaluate patient's recall of pretreatment counseling for radical prostatectomy and radiation therapy for the treatment of prostate cancer. A retrospective review of all patients presenting to our reconstructive urology clinic for the management of the complications of prostate cancer treatment was conducted over 24 months. Patients treated with only surgery or radiotherapy were included in the study. Patients were asked a standard series of questions to assess their recall of their pre-prostate cancer treatment counseling. We identified 206 patients that met inclusion criteria. Of those, 153 underwent radical prostatectomy and 53 patients received radiation therapy. Median age at presentation was 72 years in the surgery group and 75 in the radiation therapy group. Mean time since treatment was 8.8 years in those that recalled being counseled and 9.9 years in those who did not (p=0.21). In the surgery group, the adverse effects experienced by 119 (77.8%) patients recalled, and counselled were related to the risk of treatment. In the surgical patients that had records with documentation of pretreatment counseling, 41/48 (85.4%) endorsed recall. In the surgery group, 117 (76.5%) stated that their treating physician was aware of their complication. In the radiation group, 5 patients (9.4%) endorsed recall (p<0.0001). In the subgroup of radiation patients with documentation of pre-treatment counseling, no patients endorsed recall. In the surgery group, 117 (76.5%) patients stated that their treating physicians were aware of their complication, while in the radiation group, only 16 (30.2%) of treating physicians were aware of the complications (p<0.0001). Patient recall of potential complications of prostate cancer treatment is poor. It's unclear if this is secondary to poor recall, selective memory loss or inadequate counseling.


Hyperbaric oxygen therapy alleviates vascular dysfunction and amyloid burden in an Alzheimer's disease mouse model and in elderly patients.
Vascular dysfunction is entwined with aging and in the pathogenesis of Alzheimer's disease (AD) and contributes to reduced cerebral blood flow (CBF) and consequently, hypoxia. Hyperbaric oxygen therapy (HBOT) is in clinical use for a wide range of medical conditions. In the current study, we exposed 5XFAD mice, a well-studied AD model that presents impaired cognitive abilities, to HBOT and then investigated the therapeutical effects using two-photon live animal imaging, behavioral tasks, and biochemical and histological analysis. HBOT increased arteriolar luminal diameter and elevated CBF, thus contributing to reduced hypoxia. Furthermore, HBOT reduced amyloid burden by reducing the volume of pre-existing plaques and attenuating the formation of new ones. This was associated with changes in amyloid precursor protein processing, elevated degradation and clearance of Aß protein and improved behavior of 5XFAD mice. Hence, our findings are consistent with the effects of HBOT being mediated partially through a persistent structural change in blood vessels that reduces brain hypoxia. Motivated by these findings, we exposed elderly patients with significant memory loss at baseline to HBOT and observed an increase in CBF and improvement in cognitive performances. This study demonstrates HBOT efficacy in hypoxia-related neurological conditions, particularly in AD and aging.


The Role of Mass Spectrometry in the "Omics" Era.
Mass spectrometry (MS) is one of the key analytical technology on which the emerging ''-omics'' approaches are based. It may provide detection and quantization of thousands of proteins and biologically active metabolites from a tissue, body fluid or cell culture working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. It can be expected that the high performance of MS technology, coupled to routine data handling, will soon bring fruit in the request for a better understanding of human diseases, leading to new molecular biomarkers, hence affecting drug targets and therapies. In this review, we focus on the main advances in the MS technologies, influencing genomics, transcriptomics, proteomics, lipidomics and metabolomics fields, up to the most recent MS applications to meta-omic studies.


STUDIES WITH THE ELECTROCARDIOGRAPH ON THE ACTION OF THE VAGUS NERVE ON THE HUMAN HEART : II. THE EFFECTS OF VAGUS STIMULATION ON THE HEARTS OF CHILDREN WITH CHRONIC VALVULAR DISEASE.
The electrocardiographic records taken during vagus stimulation by pressure from children suffering with chronic heart disease have shown that the stimulation of the vagi in these cases is strikingly effectual. In some of the cases, a definite difference was demonstrated between the action of the right and left vagi. The control of the rate of the heart-beat seemed to predominate usually in the right vagus nerve, while the control of stimulus conduction from auricles to ventricles apparently predominated usually in the left vagus. This difference in the two nerves probably exists on account of the difference in their anatomical distribution, the right vagus going especially to that part of the heart which controls the rate of contraction, the sinus node above the right auricle, and the left vagus going especially to that part in which the conducting mechanism is found. Each nerve, however, has to a lesser degree the function which predominates in the other. The whole heart seems to respond, as a rule, more promptly to right than to left vagus pressure, and fairly constant differences have been seen in the effects which stimulation of each nerve has on the various waves of the electrocardiograms. The stimulation of each vagus may influence directly the contractions of the ventricles, causing great diminution in their force. Right vagus stimulation was followed at times by a complete dissociation of auricles and ventricles. The auricular rhythm was slowed sufficiently at this time to allow the ventricles, whose inherent rhythmicity is apparently unaffected by right vagus stimulation, to take up their own independent rhythm. The heightened ventricular rhythmicity in these cases allowed this to take place after only moderate slowing of the auricles. The independent ventricular rhythm was sometimes established in the region of the node of Tawara, for no disturbance of the ventricular portion of the electrocardiogram occurred. At another time, some other point in the ventricles inaugurated the stimuli of the independent ventricular contractions and an abnormal electrocardiogram resulted. The resemblance of our curves, showing dissociation, to those obtained during right vagus and left accelerator stimulation in dogs is definite. That analogy, the clinical picture, and the form of the electrocardiograms of these cases have led us to the belief that an important feature in the pathological physiology of these cases is hypertonus of the cardiac accelerator nerves. This factor, as a cause of symptoms and as a hindrance to the establishment of cardiac rest, may prove of great importance, against which a new form of cardiac therapeutics must be directed.


[Surgeon dentist's profile inserted in the Strategy of Family Health in cities in the state of Pernambuco, Brazil].
This article intends to approach the incorporation of the oral health to the Family Health Strategy which included the odontology professionals into the primary health care. As the odontology has the work based in a practice of healing with emphasis in restoring activities, the implantation from this new model of attention to the health is questioned in relation to the responsible for the execution of that politics - the human resources. The objective of this article is to characterize the profile of surgeons dentists inserted in the Family Health Strategy in the cities of Pernambuco state connecting it with the specificities of the program. It was used a database of the research Model of Attention in Oral Health and Education of the Surgeon DentisI inserted in the Family Health Strategy in the State of Pernambuco. The results showed that 70.4% of the surgeons dentists are female, with predominance of the age group from 31 to 49 years old, and 65.2% of those were admitted under the contract form. Concerning education, 67.8% have specialization in the Strategy of Family Health, in which 92.3% considered it pertinent, in addition 89.6% of the dentists told to accomplish educational activities.


Fullerene derivatives with increased dielectric constants.
The invention of new organic materials with high dielectric constants is of extreme importance for the development of organic-based devices such as organic solar cells. We report on a synthetic way to increase the dielectric constant of fullerene derivatives. It is demonstrated that introducing triethylene glycol monoethyl ether (teg) side chains into fulleropyrrolidines increases the dielectric constant by ~46 percent without devaluation of optical properties, electron mobility and the energy level of the compound.


Quantitative regulation of FLC via coordinated transcriptional initiation and elongation.
The basis of quantitative regulation of gene expression is still poorly understood. In Arabidopsis thaliana, quantitative variation in expression of FLOWERING LOCUS C (FLC) influences the timing of flowering. In ambient temperatures, FLC expression is quantitatively modulated by a chromatin silencing mechanism involving alternative polyadenylation of antisense transcripts. Investigation of this mechanism unexpectedly showed that RNA polymerase II (Pol II) occupancy changes at FLC did not reflect RNA fold changes. Mathematical modeling of these transcriptional dynamics predicted a tight coordination of transcriptional initiation and elongation. This prediction was validated by detailed measurements of total and chromatin-bound FLC intronic RNA, a methodology appropriate for analyzing elongation rate changes in a range of organisms. Transcription initiation was found to vary ∼ 25-fold with elongation rate varying ∼ 8- to 12-fold. Premature sense transcript termination contributed very little to expression differences. This quantitative variation in transcription was coincident with variation in H3K36me3 and H3K4me2 over the FLC gene body. We propose different chromatin states coordinately influence transcriptional initiation and elongation rates and that this coordination is likely to be a general feature of quantitative gene regulation in a chromatin context.


Exploring mechanisms of resistance to respiratory inhibitors in field strains of Botrytis cinerea, the causal agent of gray mold.
Respiratory inhibitors are among the fungicides most widely used for disease control on crops. Most are strobilurins and carboxamides, inhibiting the cytochrome b of mitochondrial complex III and the succinate dehydrogenase of mitochondrial complex II, respectively. A few years after the approval of these inhibitors for use on grapevines, field isolates of Botrytis cinerea, the causal agent of gray mold, resistant to one or both of these classes of fungicide were recovered in France and Germany. However, little was known about the mechanisms underlying this resistance in field populations of this fungus. Such knowledge could facilitate resistance risk assessment. The aim of this study was to investigate the mechanisms of resistance occurring in B. cinerea populations. Highly specific resistance to strobilurins was correlated with a single mutation of the cytb target gene. Changes in its intronic structure may also have occurred due to an evolutionary process controlling selection for resistance. Specific resistance to carboxamides was identified for six phenotypes, with various patterns of resistance levels and cross-resistance. Several mutations specific to B. cinerea were identified within the sdhB and sdhD genes encoding the iron-sulfur protein and an anchor protein of the succinate dehydrogenase complex. Another as-yet-uncharacterized mechanism of resistance was also recorded. In addition to target site resistance mechanisms, multidrug resistance, linked to the overexpression of membrane transporters, was identified in strains with low to moderate resistance to several respiratory inhibitors. This diversity of resistance mechanisms makes resistance management difficult and must be taken into account when developing strategies for Botrytis control.


HDM2 antagonist MI-219 (spiro-oxindole), but not Nutlin-3 (cis-imidazoline), regulates p53 through enhanced HDM2 autoubiquitination and degradation in human malignant B-cell lymphomas.
Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, thereby compromising p53 activity. Therefore, lymphoma is a suitable model for studying the therapeutic value of disrupting the HDM2-p53 interaction by small-molecule inhibitors (SMIs). HDM2 have been developed and are under various stages of preclinical and clinical investigation. Previously, we examined the anti-lymphoma activity of MI-319, the laboratory grade of a new class of HDM2 SMI, the spiro-oxindole, in follicular lymphoma. Since then, MI-219, the clinical grade has become readily available. This study further examines the preclinical effects and mechanisms of MI-219 in a panel of human lymphoma cell lines as well as a cohort of patient-derived B-lymphocytes for its potential clinical use. Preclinical assessment of MI-219 was evaluated by means of an in vitro and ex vivo approach and compared to Nutlin-3, the gold standard. Characterization of p53 activity and stability were assessed by quantitative PCR, Western blot, and immunoprecipitation. Biological outcome was measured using Trypan blue exclusion assay, Annexin V/PI, PARP and caspase-3 cleavage. Surprisingly, the overall biological effects of Nutlin-3 were more delayed (48 h) while MI-219 triggered an earlier response (12-24 h), predominantly in the form of apoptotic cell death. Using a cell free autoubiquitination assay, neither agent interfered with HDM2 E3 ligase function. MI-219 was more effective in upregulating wt-p53 stabilization compared to Nutlin-3. MI-219, but not Nutlin-3, enhanced the autoubiquitination and degradation of HDM2. Our data reveals unexpected differences between MI-219 and the well-studied Nutlin-3 in lymphoma cell lines and patient samples. We suggest a novel mechanism for MI-219 that alters the functional activity of HDM2 through enhanced autoubiquitination and degradation. Additionally, this mechanism appears to correspond to biological outcome. Our results provide evidence that different classes of HDM2 SMIs elicit molecular events that extend beyond HDM2-p53 dissociation which may be of biological and potentially therapeutic importance.


A manganese superoxide dismutase (SOD2)-mediated adaptive response.
Very low doses of ionizing radiation, 5 to 100 mGy, can induce adaptive responses characterized by elevation in cell survival and reduction in micronuclei formation. Utilizing these end points, RKO human colon carcinoma and transformed mouse embryo fibroblasts (MEF), wild-type or knockout cells missing TNF receptors 1 and 2 (TNFR1(-)R2(-)), and C57BL/6 and TNFR1(-)R2(-) knockout mice, we demonstrate that intact TNF signaling is required for induction of elevated manganese superoxide dismutase (SOD2) activity (P < 0.001) and the subsequent expression of these SOD2-mediated adaptive responses when cells are challenged at a later time with 2 Gy. In contrast, amifostine's free thiol form WR1065 can directly activate NF-κB giving rise to elevated SOD2 activity 24 h later and induce an adaptive response in both MEF wild-type and TNF signaling defective TNFR1(-)R2(-) cells. Transfection of cells with SOD2 siRNA completely abolishes both the elevation in SOD2 activity and expression of the adaptive responses. These results were confirmed in vivo using a micronucleus assay in splenocytes derived from C57BL/6 and TNFR1(-)R2(-) knockout mice that were exposed to 100 mGy or 400 mg/kg amifostine 24 h prior to exposure to a 2 Gy whole-body dose. A dose of 100 mGy also conferred enhanced protection to C57BL/6 mice exposed 24 h later to 100 mg/kg of N-Ethyl-N-nitrosourea (ENU). While very low radiation doses require an intact TNF signaling process to induce a SOD2-mediated adaptive response, amifostine can induce a similar adaptive response in both TNF receptor competent and knockout cells, respectively.


The Hispanic Paradox: Race/Ethnicity and Nativity, Immigrant Enclave Residence and Cognitive Impairment Among Older US Adults.
Hispanics, and particularly foreign-born Mexican Americans, have been shown to fare better across a range of health outcomes than might be expected given the generally higher levels of socioeconomic disadvantage in this population, a phenomena termed the "Hispanic Paradox". Previous research on social disparities in cognitive aging, however, has been unable to address both race/ethnicity and nativity (REN) in a nationally-representative sample of US adults leaving unanswered questions about potentially "paradoxical" advantages of Mexican ethnic-origins and the role of nativity, socioeconomic status (SES), and enclave residence. We employ biennial assessments of cognitive functioning to study prevalent and incident cognitive impairment (CI) within the three largest US REN groups: US-born non-Hispanic whites (US-NHW), US-born non-Hispanic blacks (US-NHB), US-born Mexican Americans (US-MA), and foreign-born Mexican Americans (FB-MA). Data come from a nationally-representative sample of community-dwelling older adults in the Health and Retirement Study linked with the 2000 Census and followed over 10 years (N = 8,433). Large disadvantages in prevalent and incident CI were observed for all REN minorities respective to US-born non-Hispanic whites. Individual and neighborhood SES accounted substantially for these disadvantages and revealed an immigrant advantage: FB-MA odds of prevalent CI were about half those of US-NHW and hazards of incident CI were about half those of US-MA. Residence in an immigrant enclave was protective of prevalent CI among FB-MA. The findings illuminate important directions for research into the sources of cognitive risk and resilience and provide guidance about CI screening within the increasingly diverse aging US population.


Human papillomavirus infection and reinfection in adult women: the role of sexual activity and natural immunity.
There is a paucity of data on whether or not women can be reinfected with human papillomavirus (HPV) types to which they were exposed to earlier in life and on the role of natural immunity. The observation of HPV infection at older ages may be explained by the reactivation of a latent infection or new exposure from sexual activity. Our objective was to analyze the association between reinfection and sexual activity. We analyzed data from 2,462 women enrolled in the Ludwig-McGill cohort and followed every 4 to 6 months for up to 10 years. We performed HPV typing and viral load measurements via PCR and determined HPV-16 seroreactivity at enrollment. Incidence of infection and reinfection were estimated for individual types. Adjusted relative risks (RR) for the association between infection/reinfection and new sexual partners were calculated using Cox regression. Rates of initial infection and reinfection postclearance were statistically comparable. RRs of initial infection or reinfection were consistently associated with new sexual partners [2.4 (95% confidence intervals; 95% CI, 2.0-3.1) for first infection, 3.7 (1.1-13.8) for reinfection with the same type, and 2.3 (1.5-3.7) for reinfection with a different type]. Reinfection in older women was also associated with new sexual partners (RR, 2.8; 95% CI, 1.4-5.3) as were new infections with HPV-16 among women with serologic evidence of prior HPV-16 exposure (RR, 3.0; 95% CI, 1.6-5.3). Viral loads at initial infection and at reinfection were comparable. HPV infection and reinfection were strongly associated with sexual activity. This study suggests that natural immunity does not play a role in controlling the extent of reinfections.


Molecular cloning and functional characterization of a type-I neurotensin receptor (NTR) and a novel NTR from the bullfrog brain.
Neurotensin (NT) is a tridecapeptide that functions as a neurotransmitter and neuromodulator in the nervous system. To date, three different types of NT receptor (NTR), NTR1, NTR2 and NTR3, have been identified only in mammalian species. In the present study we isolated the cDNAs for an NTR1 and a novel NTR in the bullfrog brain, designated bfNTR1 and bfNTR4 respectively. bfNTR1 and bfNTR4 encode 422- and 399-amino acid residue proteins respectively. bfNTR1 has a 64% amino acid identity with mammalian NTR1, and 34-37% identity with mammalian NTR2. bfNTR4 exhibits 43% and 45-47% identity with mammalian NTR1 and NTR2 respectively. Both receptors are mainly expressed in the brain and pituitary. bfNTR1 triggers both CRE-luc, a protein kinase A (PKA)-specific reporter, and c-fos-luc, a PKC-specific reporter, activities, indicating that bfNTR1 can activate PKA- and PKC-linked signaling pathways. However, bfNTR4 appears to be preferentially coupled to the PKA-linked pathway as it induces a higher CRE-luc activity than c-fos-luc activity. bfNTRs exhibit different pharmacological properties as compared with mammalian NTRs. Mammalian NTR1 but not NTR2 responds to NT, whereas both bfNTR1 and bfNTR4 show a high sensitivity to NT. SR 48692 and SR 142948A, antagonists for mammalian NTR1 but agonists for mammalian NTR2, function as antagonists for both bfNTR1 and bfNTR4. In conclusion, this report provides the first molecular, pharmacological and functional characterization of two NTRs in a non-mammalian vertebrate. These data should help to elucidate the phylogenetic history of the G protein-coupled NTRs in the vertebrate lineage as well as the structural features that determine their pharmacological properties.


Biosynthesis of 'essential' amino acids by scleractinian corals.
Animals rely on their diet for amino acids that they are incapable either of synthesizing or of synthesizing in sufficient quantities to meet metabolic needs. These are the so-called 'essential amino acids'. This set of amino acids is similar among the vertebrates and many of the invertebrates. Previously, no information was available for amino acid synthesis by the most primitive invertebrates, the Cnidaria. The purpose of this study was to examine amino acid synthesis by representative cnidarians within the Order Scleractinia. Three species of zooxanthellate reef coral, Montastraea faveolata, Acropora cervicornis and Porites divaricata, and two species of non-zooxanthellate coral, Tubastrea coccinea and Astrangia poculata, were incubated with 14C-labelled glucose or with the 14C-labelled amino acids glutamic acid, lysine or valine. Radiolabel tracer was followed into protein amino acids. A total of 17 amino acids, including hydroxyproline, were distinguishable by the techniques used. Of these, only threonine was not found radiolabelled in any of the samples. We could not detect tryptophan or cysteine, nor distinguish between the amino acid pairs glutamic acid and glutamine, or aspartic acid and asparagine. Eight amino acids normally considered essential for animals were made by the five corals tested, although some of them were made only in small quantities. These eight amino acids are valine, isoleucine, leucine, tyrosine, phenylalanine histidine, methionine and lysine. The ability of cnidarians to synthesize these amino acids could be yet another indicator of a separate evolutionary history of the cnidarians from the rest of the Metazoa.


Predicting 1-year mortality rate for patients admitted with an acute exacerbation of chronic obstructive pulmonary disease to an intensive care unit: an opportunity for palliative care.
The objective of this study was to develop a model to aid clinicians in better predicting 1-year mortality rate for patients with an acute exacerbation of chronic obstructive pulmonary disease admitted to the medical intensive care unit (ICU) with the goal of earlier initiation of palliative care and end-of-life communications in this patient population. This retrospective cohort study included patients from a medical ICU from April 1, 1995, to November 30, 2009. Data collected from the Acute Physiology and Chronic Health Evaluation III database included demographic characteristics; severity of illness scores; noninvasive and invasive mechanical ventilation time; ICU and hospital length of stay; and ICU, hospital, and 1-year mortality. Statistically significant univariate variables for 1-year mortality were entered into a multivariate model, and the independent variables were used to generate a scoring system to predict 1-year mortality rate. At 1-year follow-up, 295 of 591 patients died (50%). Age and hospital length of stay were identified as independent determinants of mortality at 1 year by using multivariate analysis, and the predictive model developed had an area under the operating curve of 0.68. Bootstrap analysis with 1000 iterations validated the model, age, and hospital length of stay, entered the model 100% of the time (area under the operating curve=0.687; 95% CI, 0.686-0.688). A simple model using age and hospital length of stay may be informative for providers willing to identify patients with chronic obstructive pulmonary disease with high 1-year mortality rate who may benefit from end-of-life communications and from palliative care.


The development of perceptual expertise for faces and objects in autism spectrum conditions.
Previous research indicates that individuals with autism spectrum conditions (ASC) do not develop face expertise to the same extent as typical individuals. Yet it remains unclear whether this atypicality is specific to faces or related to more pervasive perceptual or cognitive deficits involved in the actual process of gaining expertise. To address this question, we examined the extent to which adults with ASC were capable of developing expertise with non-face objects. To become experts, all participants completed a 2-week training program with novel objects, known as Greebles. Level of expertise was assessed throughout training by measuring the ability to identify Greebles on an individual level. The perceptual strategies acquired as a result of expertise were measured through an inversion effect task completed before and after training, in which performance with upright Greebles and faces was compared to performance with inverted Greebles and faces. After expertise training, it was found that individuals in both the ASC and the typical group successfully achieved expertise and showed an enhanced Greeble inversion effect as a result of training. The development of an inversion effect with Greebles suggests that individuals with ASC may employ the same processing strategies as the typical group. Although exploratory, these findings have implications for understanding the nature of the face processing deficit in ASC as well as offering potential insights into face processing interventions for individuals with ASC.


Cancer in pregnancy: safety and efficacy of systemic therapies.
Cancer in pregnancy has become increasingly frequent. It has become clear that for specific cancers under well defined circumstances, oncological treatment in pregnancy can be well tolerated and feasible for both mother and fetus. Continued critical assessment of the available literature and registration of cancer in pregnancy cases and outcomes for mother and child are necessary to work toward implementing optimal cancer treatment during pregnancy. Physiologic changes in pregnancy may alter distribution and efficacy of systemic therapy. Data on systemic therapy including, chemotherapy, hormonal therapy, and targeted therapy during pregnancy are available but incomplete. Outcomes of fetuses exposed to chemotherapy in utero are generally reassuring, but new targeted therapies are mostly discouraged in pregnancy. Cancer treatment during pregnancy is possible, depending on type and timing of systemic therapy and treatment modality. Available data are reassuring with a modest increase in complications such as growth restriction and preterm birth. The effect of new targeted therapies is often still unclear and therefore discouraged.