Are there multiple visual short-term memory stores?
Classic work on visual short-term memory (VSTM) suggests that people store a limited amount of items for subsequent report. However, when human observers are cued to shift attention to one item in VSTM during retention, it seems as if there is a much larger representation, which keeps additional items in a more fragile VSTM store. Thus far, it is not clear whether the capacity of this fragile VSTM store indeed exceeds the traditional capacity limits of VSTM. The current experiments address this issue and explore the capacity, stability, and duration of fragile VSTM representations. We presented cues in a change-detection task either just after off-set of the memory array (iconic-cue), 1,000 ms after off-set of the memory array (retro-cue) or after on-set of the probe array (post-cue). We observed three stages in visual information processing 1) iconic memory with unlimited capacity, 2) a four seconds lasting fragile VSTM store with a capacity that is at least a factor of two higher than 3) the robust and capacity-limited form of VSTM. Iconic memory seemed to depend on the strength of the positive after-image resulting from the memory display and was virtually absent under conditions of isoluminance or when intervening light masks were presented. This suggests that iconic memory is driven by prolonged retinal activation beyond stimulus duration. Fragile VSTM representations were not affected by light masks, but were completely overwritten by irrelevant pattern masks that spatially overlapped the memory array. We find that immediately after a stimulus has disappeared from view, subjects can still access information from iconic memory because they can see an after-image of the display. After that period, human observers can still access a substantial, but somewhat more limited amount of information from a high-capacity, but fragile VSTM that is overwritten when new items are presented to the eyes. What is left after that is the traditional VSTM store, with a limit of about four objects. We conclude that human observers store more sustained representations than is evident from standard change detection tasks and that these representations can be accessed at will.


What Has Changed in the Treatment of Psoriatic Arthritis After COVID-19?
Coronavirus disease 2019 is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2. Coronavirus disease 2019 leads to the rapid activation of innate immune cells, particularly in patients with severe disease. Psoriatic arthritis is a heterogeneous chronic inflammatory disease characterized by the association of psoriasis and arthritis. Similar to those with other viruses, patients with psoriatic arthritis are at a significant risk of infection with severe acute respiratory syndrome coronavirus 2. Patients with psoriatic arthritis are immunosuppressed owing to immune dysregulation during the active disease period or owing to immunosuppressive drugs administered during remission, and they are prone to infections. The severe acute respiratory syndrome coronavirus 2 is a threat to millions of people globally owing to the decline in immunity and because a significant number of people develop severe illness. In the period of coronavirus disease 2019 pandemic, we briefly present recommendations for the treatment of psoriatic arthritis. In this review, we briefly address the management options and treatment recommendations for patients with psoriatic arthritis during and after the coronavirus disease 2019 pandemic in light of recent scientific publications.


Differences between cytokine effects in the microcirculation of the rat.
We studied by in vivo microscopy in rat cremaster muscle the acute and delayed effects of short exposure to tumor necrosis factor (TNF), interleukin (IL)-1 beta, and IL-6 on basal tone and vascular reactivity of second- to fourth-order arterioles (A2-A4). A 20-min exposure to recombinant human (rh) TNF (0.1-10 ng/ml) induced a significant arteriolar vasodilation, but no significant changes in basal tone were found after exposure to the same doses of IL-1 beta. In contrast, the same exposure to IL-6 (0.1-10 ng/ml) induced a significant dose-dependent vasoconstriction (i.e., 8, 15, and 21% at 10 ng/ml in A2-A4 arterioles, respectively). This vasoconstriction was inhibited by the thromboxane A2 receptor antagonist SQ-29548. We did not find any significant effect of rhTNF or IL-6 on vascular reactivity to norepinephrine immediately after exposure to these two cytokines or 100 min after the end of the exposure. Contrastingly, a large dose-dependent decrease in reactivity to norepinephrine was found immediately after exposure to IL-1 beta and still persisted 100 min after the end of the exposure. Such a decrease was not found for the vasoconstriction in response to KCl. We conclude that, at the microvascular level, large differences exist between the three cytokines generally considered to mediate the harmful cardiovascular effects in sepsis. 1) TNF but not IL-1 beta is responsible for a vasodilatory effect, whereas the effect of IL-6 is a thromboxane A2-mediated vasoconstriction. 2) Short exposure to IL-1 beta but not to rhTNF or IL-6 diminishes the response of the arterioles to norepinephrine but not to KCl.


3D GABA imaging with real-time motion correction, shim update and reacquisition of adiabatic spiral MRSI.
Gamma-aminobutyric acid (GABA) and glutamate (Glu) are the major neurotransmitters in the brain. They are crucial for the functioning of healthy brain and their alteration is a major mechanism in the pathophysiology of many neuro-psychiatric disorders. Magnetic resonance spectroscopy (MRS) is the only way to measure GABA and Glu non-invasively in vivo. GABA detection is particularly challenging and requires special MRS techniques. The most popular is MEscher-GArwood (MEGA) difference editing with single-voxel Point RESolved Spectroscopy (PRESS) localization. This technique has three major limitations: a) MEGA editing is a subtraction technique, hence is very sensitive to scanner instabilities and motion artifacts. b) PRESS is prone to localization errors at high fields (≥3T) that compromise accurate quantification. c) Single-voxel spectroscopy can (similar to a biopsy) only probe steady GABA and Glu levels in a single location at a time. To mitigate these problems, we implemented a 3D MEGA-editing MRS imaging sequence with the following three features: a) Real-time motion correction, dynamic shim updates, and selective reacquisition to eliminate subtraction artifacts due to scanner instabilities and subject motion. b) Localization by Adiabatic SElective Refocusing (LASER) to improve the localization accuracy and signal-to-noise ratio. c) K-space encoding via a weighted stack of spirals provides 3D metabolic mapping with flexible scan times. Simulations, phantom and in vivo experiments prove that our MEGA-LASER sequence enables 3D mapping of GABA+ and Glx (Glutamate+Gluatmine), by providing 1.66 times larger signal for the 3.02ppm multiplet of GABA+ compared to MEGA-PRESS, leading to clinically feasible scan times for 3D brain imaging. Hence, our sequence allows accurate and robust 3D-mapping of brain GABA+ and Glx levels to be performed at clinical 3T MR scanners for use in neuroscience and clinical applications.


The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a multicentre, randomised, placebo-controlled, phase III trial.
High body temperature in the first 12-24 h after stroke onset is associated with poor functional outcome. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial aimed to assess whether early treatment with paracetamol improves functional outcome in patients with acute stroke by reducing body temperature and preventing fever. In a multicentre, randomised, double-blind, placebo-controlled trial, patients with ischaemic stroke or intracerebral haemorrhage and body temperature between 36 degrees C and 39 degrees C were randomly assigned treatment with paracetamol (6 g daily) or placebo within 12 h from symptom onset. Treatment allocation was based on a computer-generated list of random numbers with varying block size. The primary outcome was improvement beyond expectation on the modified Rankin scale at 3 months, according to the sliding dichotomy approach. This trial is registered, number ISRCTN74418480. Between March, 2003, and May, 2008, 1400 patients were randomly allocated treatment. 260 (37%) of 697 patients receiving paracetamol and 232 (33%) of 703 receiving placebo improved beyond expectation (adjusted odds ratio [OR] 1.20, 95% CI 0.96-1.50). In a post-hoc analysis of patients with baseline body temperature 37-39 degrees C, treatment with paracetamol was associated with improved outcome (1.43, 1.02-1.97). There were 55 serious adverse events in the paracetamol group (8%) and 70 in the placebo group (10%). These results do not support routine use of high-dose paracetamol in patients with acute stroke. Paracetamol might have a beneficial effect on functional outcome in patients admitted with a body temperature 37-39 degrees C, but this post-hoc finding needs further study. Netherlands Heart Foundation.


Versatility of bilayer metal oxide coatings on silver nanowire networks for enhanced stability with minimal transparency loss.
Silver nanowire (AgNW) networks have been lately much investigated thanks to their physical properties and are therefore foreseen to play a key role in many industrial devices as transparent electrodes, but their stability can be an issue. Although it has been shown that thin metal oxide coatings enhance the stability of AgNW networks, such stabilization is achieved at the expense of transparency. We demonstrate that by depositing a second oxide coating, which acts as an antireflective layer, it is possible to obtain highly stable and transparent composite electrodes. AgNW networks were deposited by the airbrush method, and zinc oxide (ZnO) and aluminum oxide (Al2O3) coatings were deposited, by Atmospheric Pressure Spatial Atomic Layer Deposition (AP-SALD), using both glass and plastic substrates; therefore, the proposed fabrication method is low-cost and compatible with high-throughput scalable fabrication. The mechanical stability of bare, ZnO and ZnO/Al2O3-coated AgNWs upon bending is also presented. The obtained nanocomposites exhibit highly homogeneous and conformal oxide coatings with average thicknesses of a few tens of nanometers. Samples with bilayer coatings of 70 nm ZnO/70 nm Al2O3 still exhibit very good stability after annealing in air up to 450 °C for 6 repetitive cycles.


A Novel MSCRAMM Subfamily in Coagulase Negative Staphylococcal Species.
Coagulase negative staphylococci (CoNS) are important opportunistic pathogens. Staphylococcus epidermidis, a coagulase negative staphylococcus, is the third leading cause of nosocomial infections in the US. Surface proteins like Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs) are major virulence factors of pathogenic gram positive bacteria. Here, we identified a new chimeric protein in S. epidermidis, that we call SesJ. SesJ represents a prototype of a new subfamily of MSCRAMMs. Structural predictions show that SesJ has structural features characteristic of a MSCRAMM along with a N-terminal repeat region and an aspartic acid containing C-terminal repeat region, features that have not been previously observed in staphylococcal MSCRAMMs but have been found in other surface proteins from gram positive bacteria. We identified and analyzed structural homologs of SesJ in three other CoNS. These homologs of SesJ have an identical structural organization but varying sequence identities within the domains. Using flow cytometry, we also show that SesJ is expressed constitutively on the surface of a representative S. epidermidis strain, from early exponential to stationary growth phase. Thus, SesJ is positioned to interact with protein targets in the environment and plays a role in S. epidermidis virulence.


Characterization of a synergistic interaction between two cucurbit-infecting begomoviruses: Squash leaf curl virus and Watermelon chlorotic stunt virus.
Squash leaf curl virus (SLCV) and Watermelon chlorotic stunt virus (WmCSV) are cucurbit-infecting bipartite begomoviruses. Both viruses are found in the eastern Mediterranean basin but the effects of dual infection of both viruses on melon (Cucumis melo L.) have not been described. 'Arava' melon plants were inoculated in the greenhouse, using whiteflies, with either SLCV, WmCSV, or both. Control plants were exposed to nonviruliferous whiteflies or not exposed at all. Following inoculation, plants were transplanted to a 50-mesh insect-proof nethouse and grown until fruit maturity. The experiment was performed in two melon-growing seasons: spring, transplant in May and harvest in July; and summer, transplant in August and harvest in October. Following inoculation, SLCV-infected melon plants showed mild symptoms that disappeared with time, and there was no effect on plant height. WmCSV-infected plants developed disease symptoms that became more obvious with time, and plants were somewhat shorter than control plants in the spring but not in the summer. SLCV had no effect on yield, regardless of season. WmCSV had no statistically significant effect on yield in the spring but, in the summer, reduced yield by 22%, on average. Dual-inoculated plants showed a synergistic interaction between the two viruses. They developed disease symptoms that were more pronounced than WmCSV alone, with plants being shorter than control plants by 20 to 25% regardless of season. Moreover, the yield of dual-inoculated plants was reduced on average by 21% in the spring and 54% in the summer, and fruit appearance was adversely affected. Dual inoculation did not affect WmCSV DNA level but SLCV DNA level was increased several-fold by the presence of WmCSV.


Homogenized boundary conditions and resonance effects in Faraday cages.
We present a mathematical study of two-dimensional electrostatic and electromagnetic shielding by a cage of conducting wires (the so-called 'Faraday cage effect'). Taking the limit as the number of wires in the cage tends to infinity, we use the asymptotic method of multiple scales to derive continuum models for the shielding, involving homogenized boundary conditions on an effective cage boundary. We show how the resulting models depend on key cage parameters such as the size and shape of the wires, and, in the electromagnetic case, on the frequency and polarization of the incident field. In the electromagnetic case, there are resonance effects, whereby at frequencies close to the natural frequencies of the equivalent solid shell, the presence of the cage actually amplifies the incident field, rather than shielding it. By appropriately modifying the continuum model, we calculate the modified resonant frequencies, and their associated peak amplitudes. We discuss applications to radiation containment in microwave ovens and acoustic scattering by perforated shells.


Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice.
Methamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5mg/kg-bw/ip/day/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis-vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43-57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5mg/kg/day/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5mg/kg/day/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg/kg/day/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5mg/kg/day/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation.


A Functional Group Approach for Prediction of APPI Response of Organic Synthetic Targets.
Atmospheric pressure photoionization (APPI) is a technique of choice for ionization of non-polar molecules in mass spectrometry (MS). Reported APPI-based studies tend to focus on a selected compound class, which may contain a variety of functional groups. These studies demonstrate that APPI response frequently differs substantially, indicating a certain dependence on the functional group present. Although this dependence could be employed for APPI response prediction, its systematic use is currently absent. Here, we apply APPI MS to a judiciously-compiled set of 63 compounds containing a number of diverse functional groups commonly utilized in synthesis, reactive functional groups, as well as those containing boron and silicon. Based on the outcome of APPI MS of these compounds, we propose and evaluate a simple guideline to estimate the APPI response for a novel compound, the key properties of which have not been characterized in the gas phase. Briefly, we first identify key functional groups in the compound and gather knowledge on the known ionization energies from the smallest analogues containing said functional groups. We then consider local inductive and resonance effects on said ionization energies for the compounds of interest to estimate the APPI response. Finally, application of APPI MS to compounds of interest considered herein demonstrated extended upper mass ionization limit of 3.5 kDa for non-polymeric compounds.


Anthropometric and hormone effects of an eight-week exercise-diet intervention in breast cancer patients: results of a pilot study.
To assess the feasibility of an exercise-diet intervention in sedentary, overweight breast cancer patients, we conducted a pilot 8-week intervention. Recruitment letters and interest surveys were sent to 99 stage 1 or 2 breast cancer patients, ages 25-75 years, who were identified through two Seattle breast surgery practices and the University of Washington Breast Clinic. Ten patients were eligible and interested and were enrolled in the intervention, which consisted of thrice-weekly monitored aerobic exercise sessions and a low-fat (20% of calories from fat) diet. Nine patients completed the program; all adhered well to the intervention and data collection protocol. The patients, ages 40-74 years, lost, on average, 2.6 pounds of body weight, 3.4 cm in waist circumference, 4.6 cm in hip circumference, 2.3% body fat, 3.3 systolic blood pressure points, 0.67 diastolic blood pressure points, and 4.0 pulse beats/min, and they gained an average of 2.3% lean mass. Slight, nonsignificant decreases were observed in serum concentration of total and free estradiol, estrone sulfate, total testosterone, androstenedione, and dehydroepiandrosterone. These pilot data indicate that breast cancer patients are highly motivated to join and adhere to an intense exercise-diet intervention and can experience significant measurable changes in anthropometric and fat mass measures.


Weaning diet induces sustained metabolic phenotype shift in the pig and influences host response to Bifidobacterium lactis NCC2818.
The process of weaning causes a major shift in intestinal microbiota and is a critical period for developing appropriate immune responses in young mammals. To use a new systems approach to provide an overview of host metabolism and the developing immune system in response to nutritional intervention around the weaning period. Piglets (n=14) were weaned onto either an egg-based or soya-based diet at 3 weeks until 7 weeks, when all piglets were switched onto a fish-based diet. Half the animals on each weaning diet received Bifidobacterium lactis NCC2818 supplementation from weaning onwards. Immunoglobulin production from immunologically relevant intestinal sites was quantified and the urinary (1)H NMR metabolic profile was obtained from each animal at post mortem (11 weeks). Different weaning diets induced divergent and sustained shifts in the metabolic phenotype, which resulted in the alteration of urinary gut microbial co-metabolites, even after 4 weeks of dietary standardisation. B lactis NCC2818 supplementation affected the systemic metabolism of the different weaning diet groups over and above the effects of diet. Additionally, production of gut mucosa-associated IgA and IgM was found to depend upon the weaning diet and on B lactis NCC2818 supplementation. The correlation of urinary (1)H NMR metabolic profile with mucosal immunoglobulin production was demonstrated, thus confirming the value of this multi-platform approach in uncovering non-invasive biomarkers of immunity. This has clear potential for translation into human healthcare with the development of urine testing as a means of assessing mucosal immune status. This might lead to early diagnosis of intestinal dysbiosis and with subsequent intervention, arrest disease development. This system enhances our overall understanding of pathologies under supra-organismal control.


Soluble epoxide hydrolase promotes astrocyte survival in retinopathy of prematurity.
Polyunsaturated fatty acids such as docosahexaenoic acid (DHA) positively affect the outcome of retinopathy of prematurity (ROP). Given that DHA metabolism by cytochrome P450 and soluble epoxide hydrolase (sEH) enzymes affects retinal angiogenesis and vascular stability, we investigated the role of sEH in a mouse model of ROP. In WT mice, hyperoxia elicited tyrosine nitration and inhibition of sEH and decreased generation of the DHA-derived diol 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP). Correspondingly, in a murine model of ROP, sEH-/- mice developed a larger central avascular zone and peripheral pathological vascular tuft formation than did their WT littermates. Astrocytes were the cells most affected by sEH deletion, and hyperoxia increased astrocyte apoptosis. In rescue experiments, 19,20-DHDP prevented astrocyte loss by targeting the mitochondrial membrane to prevent the hyperoxia-induced dissociation of presenilin-1 and presenilin-1-associated protein to attenuate poly ADP-ribose polymerase activation and mitochondrial DNA damage. Therapeutic intravitreal administration of 19,20-DHDP not only suppressed astrocyte loss, but also reduced pathological vascular tuft formation in sEH-/- mice. Our data indicate that sEH activity is required for mitochondrial integrity and retinal astrocyte survival in ROP. Moreover, 19,20-DHDP may be more effective than DHA as a nutritional supplement for preventing retinopathy in preterm infants.


Reliability and concurrent validity of a Smartphone, bubble inclinometer and motion analysis system for measurement of hip joint range of motion.
Traditional methods of assessing joint range of motion (ROM) involve specialized tools that may not be widely available to clinicians. This study assesses the reliability and validity of a custom Smartphone application for assessing hip joint range of motion. Intra-tester reliability with concurrent validity. Passive hip joint range of motion was recorded for seven different movements in 20 males on two separate occasions. Data from a Smartphone, bubble inclinometer and a three dimensional motion analysis (3DMA) system were collected simultaneously. Intraclass correlation coefficients (ICCs), coefficients of variation (CV) and standard error of measurement (SEM) were used to assess reliability. To assess validity of the Smartphone application and the bubble inclinometer against the three dimensional motion analysis system, intraclass correlation coefficients and fixed and proportional biases were used. The Smartphone demonstrated good to excellent reliability (ICCs>0.75) for four out of the seven movements, and moderate to good reliability for the remaining three movements (ICC=0.63-0.68). Additionally, the Smartphone application displayed comparable reliability to the bubble inclinometer. The Smartphone application displayed excellent validity when compared to the three dimensional motion analysis system for all movements (ICCs>0.88) except one, which displayed moderate to good validity (ICC=0.71). Smartphones are portable and widely available tools that are mostly reliable and valid for assessing passive hip range of motion, with potential for large-scale use when a bubble inclinometer is not available. However, caution must be taken in its implementation as some movement axes demonstrated only moderate reliability.


"We adjusted for race" now what: A systematic review of utilization and reporting of race in AJE and Epidemiology, 2020-2021.
Race is a social construct, commonly used in epidemiologic research to adjust for confounding. However, adjustment of race may mask racial disparities thereby perpetuating structural racism. We conducted a systematic review of articles published in Epidemiology and American Journal of Epidemiology between 2020 and 2021 to 1) understand how race, ethnicity, and similar social constructs were operationalized, utilized, and reported and 2) characterize good and poor practices of utilization and reporting of race data based on the extent to which they reveal or mask systemic racism. Original research articles were considered for full review and data extraction if race data were used in the study analysis. We extracted how race was categorized; utilized - as descriptor, confounder, or for effect measure modification (EMM); and reported - if the authors discussed racial disparities and systemic bias-related mechanisms responsible for perpetuating the disparities. Of the 561 articles, 299 had race data available and 192 (34.2%) used race data in analyses. Among the 160 United States-based studies, 81 different racial categorizations were used. Race was most often utilized as a confounder (52%), followed by effect measure modifier (33%), and descriptive variable (12%). Fewer than one in four articles (22.9%) exhibited good practices (EMM along with discussing disparities and mechanisms), 63.5% of the articles exhibited poor practices (confounding only or not discussing mechanisms), and 13.5% were considered neither poor nor good practices. We discuss implications and provide 13 recommendations for operationalization, utilization, and reporting of race in epidemiologic and public health research.


Predictors for adolescent visits to practitioners of complementary and alternative medicine in a total population (the Young-HUNT Studies).
To investigate the factors predicting adolescent visits to practitioners of complementary and alternative medicine (CAM). A longitudinal cohort study conducted in an adolescent total population in Central Norway (The Nord-Trøndelag Health Studies (HUNT)). In Young-HUNT 1, all inhabitants aged 13 to 19 years (N = 8944, 89% response rate) were invited to participate, and the youngest group (13 to 15 year olds) was surveyed again 4 years later (Young-HUNT 2, N = 2429, 82% response rate). The participants completed a comprehensive questionnaire on health and life style which included a question regarding visits to a CAM practitioner in the last 12 months. One in eleven (8.7%, 95%CI 7.6-9.8%) had visited a CAM practitioner, an increase of 26% in 4 years (1.8% points). The final multivariable analysis predicted increased odds of an adolescent becoming a CAM visitor four years later (p<0.05) if she or he had previously visited a CAM practitioner (adjOR 3.4), had musculoskeletal pain (adjOR 1.5), had migraine (adjOR 2.3), used asthma medicines (adjOR 1.8) or suffered from another disease lasting more than three months (adjOR 2.1). Being male predicted reduced odds of visiting a CAM practitioner in the future (adjOR 0.6). We can conclude from this study that future visits to a CAM practitioner are predicted by both predisposing factors (being female, having visited a CAM practitioner previously) and medical need factors (having had musculoskeletal pain, migraine, used asthma medicines or experienced another disease lasting more than three months). None of the specific variables associated with CAM visits were predictive for CAM visits four years later.


Repression of malignant tumor progression upon pharmacologic IGF1R blockade in a mouse model of insulinoma.
NVP-AEW541, a specific ATP-competitive inhibitor of the insulin-like growth factor-1 receptor (IGF1R) tyrosine kinase, has been reported to interfere with tumor growth in various tumor transplantation models. We have assessed the efficacy of NVP-AEW541 in repressing tumor growth and tumor progression in the Rip1Tag2 transgenic mouse model of pancreatic β-cell carcinogenesis. In addition, we have tested NVP-AEW541 in Rip1Tag2;RipIGF1R double-transgenic mice which show accelerated tumor growth and increased tumor malignancy compared with Rip1Tag2 single-transgenic mice. Previously, we have shown that high levels of IGF-2, a high-affinity ligand for IGF1R, are required for Rip1Tag2 tumor cell survival and tumor growth. Unexpectedly, treatment of Rip1Tag2 mice with NVP-AEW541 in prevention and intervention trials neither did affect tumor growth nor tumor cell proliferation and apoptosis. Yet, it significantly repressed progression to tumor malignancy, that is, the rate of the transition from differentiated adenoma to invasive carcinoma. Treatment of Rip1Tag2;RipIGF1R double-transgenic mice resulted in moderately reduced tumor volumes and increased rates of tumor cell apoptosis. Sustained expression of IGF-2 and of the IGF-2-binding form of insulin receptor (IR-A) in tumor cells suggests a compensatory role of IR-A upon IGF1R blockade. The results indicate that inhibition of IGF1R alone is not sufficient to efficiently block insulinoma growth and imply an overlapping role of IGF1R and insulin receptor in executing mitogenic and survival stimuli elicited by IGF-2. The reduction of tumor invasion upon IGF1R blockade on the other hand indicates a critical function of IGF1R signaling for the acquisition of a malignant phenotype.


A reliable diagnosis of human rabies based on analysis of skin biopsy specimens.
The number of human deaths due to rabies is currently underestimated to be 55,000 deaths per year. Biological diagnostic methods for confirmation of rabies remain limited, because testing on postmortem cerebral samples is the reference method, and in many countries, sampling brain tissue is rarely practiced. There is a need for a reliable method based on a simple collection of nonneural specimens. A new reverse-transcription, heminested polymerase chain reaction (RT-hnPCR) protocol was standardized at 3 participating centers in Cambodia, Madagascar, and France. Fifty-one patients from Cambodia, Madagascar, Senegal, and France were prospectively enrolled in the study; 43 (84%) were ultimately confirmed as having rabies. A total of 425 samples were collected from these patients during hospitalization. We studied the accuracy of the diagnosis by comparing the results obtained with use of biological fluid specimens (saliva and urine) and skin biopsy specimens with the results obtained with use of the standard rabies diagnostic procedure performed with a postmortem brain biopsy specimen. The data obtained indicate a high specificity (100%) of RT-hnPCR and a higher sensitivity (>/=98%) when the RT-hnPCR was performed with skin biopsy specimens than when the test was performed with fluid specimens, irrespective of the time of collection (i.e., 1 day after the onset of symptoms or just after death). Also, a sensitivity of 100% was obtained with the saliva sample when we analyzed at least 3 successive samples per patient. Skin biopsy specimens should be systematically collected in cases of encephalitis of unknown origin. These samples should be tested by RT-hnPCR immediately to confirm rabies; if the technique is not readily available locally, the samples should be tested retrospectively for epidemiological purposes.


Elevated plasma norepinephrine inhibits insulin secretion, but adrenergic blockade reveals enhanced β-cell responsiveness in an ovine model of placental insufficiency at 0.7 of gestation.
In pregnancies complicated by placental insufficiency (PI), fetal hypoglycemia and hypoxemia progressively worsen during the third trimester, which increases circulating norepinephrine (NE). Pharmacological adrenergic blockade (ADR-block) at 0.9 gestation revealed that NE inhibits insulin secretion and enhanced β-cell responsiveness in fetuses with PI-induced intrauterine growth restriction (IUGR). NE concentrations in PI fetuses at 0.7 gestation were threefold greater compared with age-matched controls, but the levels were similar to near-term controls. Therefore, our objective was to determine whether elevations in plasma NE concentrations inhibit insulin secretion and produce compensatory β-cell responsiveness in PI fetuses at 0.7 gestation. Fetal insulin was measured under basal, glucose-stimulated insulin secretion (GSIS) and glucose-potentiated arginine-stimulated insulin secretion (GPAIS) conditions in the absence and presence of an ADR-block. Placental weights were 38% lower (P < 0.05) in PI fetus than in controls, but fetal weights were not different. PI fetuses had lower (P < 0.05) basal blood oxygen content, plasma glucose, insulin-like growth factor-1 and insulin concentrations and greater plasma NE concentrations (891 ± 211 v. 292 ± 65 pg/ml; P < 0.05) than controls. GSIS was lower in PI fetuses than in controls (0.34 ± 0.03 v. 1.08 ± 0.06 ng/ml; P < 0.05). ADR-block increased GSIS in PI fetuses (1.19 ± 0.11 ng/ml; P < 0.05) but decreased GSIS in controls (0.86 ± 0.02 ng/ml; P < 0.05). Similarly, GPAIS was 44% lower (P < 0.05) in PI fetuses than in controls, and ADR-block increased (P < 0.05) GPAIS in PI fetuses but not in controls. Insulin content per islet was not different between treatments. We conclude that elevations in fetal plasma NE suppress insulin concentrations, and that compensatory β-cell stimulus-secretion responsiveness is present before IUGR.


Mammal population losses and the extinction crisis.
The disappearance of populations is a prelude to species extinction. No geographically explicit estimates have been made of current population losses of major indicator taxa. Here we compare historic and present distributions of 173 declining mammal species from six continents. These species have collectively lost over 50% of their historic range area, mostly where human activities are intensive. This implies a serious loss of ecosystem services and goods. It also signals a substantial threat to species diversity.


Features and functionality of the Iterapi platform for internet-based psychological treatment.
The purpose of this article is to describe an internet-based platform for improving symptoms and quality of life for people with psychological and behavioural health problems such as depression, anxiety, phobia, psychological trauma, hearing loss and tinnitus. The online platform, called Iterapi, was developed at the Department of Behavioural Sciences and Learning at Linköping University, Sweden and has been running for nearly two decades and used in many randomized controlled trials and outpatient treatments. The intention of this article is to share our experience with developing such a treatment solution and the process flow and elements of running internet-based psychological interventions. This will likely be of use to developers building similar services, therapists considering integrating such approaches in their practices and institutions, as well as researchers curious about the functions included on the platform and methodology used for running studies. We describe the security aspects of the platform, central concepts underlying its development, how the platform can be used in a study or treatment and the main features and functions the platform offers. We comment on practical considerations regarding blending of methods within the platform, such as self-help treatments with asynchronous communication and real-time text chat and video conversations. We also point out the advantages of using Internet-assisted treatments, the challenges that we have faced and future planned upgrades. Due to continuous development of the platform, its user-friendliness, accessibility across devices and numerous features, many research colleagues from Sweden as well as other countries such as Germany, United Kingdom, Romania and Israel have chosen to implement their own studies on the platform.


Risk of falls and motor vehicle collisions in glaucoma.
To investigate the risk of falls and motor vehicle collisions (MVCs) in patients with glaucoma. The sample comprised 48 patients with glaucoma (mean visual field mean deviation [MD] in the better eye = -3.9 dB; 5.1 dB SD) and 47 age-matched normal control subjects, who were recruited from a university-based hospital eye care clinic and are enrolled in an ongoing prospective study of risk factors for falls, risk factors for MVCs, and on-road driving performance in glaucoma. Main outcome measures at baseline were previous self-reported falls and MVCs, and police-reported MVCs. Demographic and medical data were obtained. In addition, functional independence in daily living, physical activity level and balance were assessed. Clinical vision measures included visual acuity, contrast sensitivity, standard automated perimetry, useful field of view (UFOV), and stereopsis. Analyses of falls and MVCs were adjusted to account for the possible confounding effects of demographic characteristics, medications, and visual field impairment. MVC analyses were also adjusted for kilometers driven per week. There were no significant differences between patients with glaucoma and control subjects with respect to number of systemic medical conditions, body mass index, functional independence, and physical activity level (P > 0.10). At baseline, 40 (83%) patients with glaucoma and 44 (94%) control subjects were driving. Compared with control subjects, patients with glaucoma were over three times more likely to have fallen in the previous year (odds ratio [OR](adjusted) = 3.71; 95% CI, 1.14-12.05), over six times more likely to have been involved in one or more MVCs in the previous 5 years (OR(adjusted) = 6.62; 95% CI, 1.40-31.23), and more likely to have been at fault (OR(adjusted) = 12.44; 95% CI, 1.08-143.99). The strongest risk factor for MVCs in patients with glaucoma was impaired UFOV selective attention (OR(adjusted) = 10.29; 95% CI, 1.10-96.62; for selective attention >350 ms compared with </=350 ms). There is an increased risk of falls and MVCs in patients with glaucoma.


Auditory and visual distractors disrupt multisensory temporal acuity in the crossmodal temporal order judgment task.
The ability to synthesize information across multiple senses is known as multisensory integration and is essential to our understanding of the world around us. Sensory stimuli that occur close in time are likely to be integrated, and the accuracy of this integration is dependent on our ability to precisely discriminate the relative timing of unisensory stimuli (crossmodal temporal acuity). Previous research has shown that multisensory integration is modulated by both bottom-up stimulus features, such as the temporal structure of unisensory stimuli, and top-down processes such as attention. However, it is currently uncertain how attention alters crossmodal temporal acuity. The present study investigated whether increasing attentional load would decrease crossmodal temporal acuity by utilizing a dual-task paradigm. In this study, participants were asked to judge the temporal order of a flash and beep presented at various temporal offsets (crossmodal temporal order judgment (CTOJ) task) while also directing their attention to a secondary distractor task in which they detected a target stimulus within a stream visual or auditory distractors. We found decreased performance on the CTOJ task as well as increases in both the positive and negative just noticeable difference with increasing load for both the auditory and visual distractor tasks. This strongly suggests that attention promotes greater crossmodal temporal acuity and that reducing the attentional capacity to process multisensory stimuli results in detriments to multisensory temporal processing. Our study is the first to demonstrate changes in multisensory temporal processing with decreased attentional capacity using a dual task paradigm and has strong implications for developmental disorders such as autism spectrum disorders and developmental dyslexia which are associated with alterations in both multisensory temporal processing and attention.


Non-invasive ventilation and gastrostomy may not impact overall quality of life in patients with ALS.
Non-invasive positive pressure ventilation (NIPPV) may improve health-related quality of life (HRQoL) in patients with ALS. The effect of percutaneous endoscopic gastrostomy (PEG) on HRQoL is not known. Instruments measuring QoL more broadly have not been used to assess effects of these interventions. This study was undertaken to do so via the ALS-Specific Quality of Life Instrument-revised (ALSSQOL-R). A retrospective review was carried out of ALS patients who had undergone one QoL assessment prior to NIPPV or PEG initiation and two assessments following one of these interventions. Random coefficients models were developed. Twenty-two patients met criteria for inclusion: six NIPPV, 11 PEG, and five NIPPV + PEG. The ALSSQoL-R did not change significantly following NIPPV or PEG or both. Function declined in all three groups over the same time-period. In conclusion, overall QoL in ALS does not appear to change after NIPPV or PEG. This may reflect the impact of non-health-related factors or may be due to a response shift. QoL instruments that include domains outside of health status may not be sensitive to changes from single interventions. Larger, prospective studies are needed.


Effect of blood collection and processing on radioimmunoassay results for apolipoprotein B in plasma.
We studied the effects of different blood collection and processing procedures on quantification of apolipoprotein (apo) B by radioimmunoassay. High-density lipoprotein subfractions HDL3 and HDL2 and isolated apoA-I did not cross-react in the assay. Analytical recovery of apoB at different doses of very-low- and low-density lipoproteins were complete. Inter- and intra-assay coefficients of variation (CVs) averaged 7.4% and 6.0%, respectively. Blood from 20 subjects was collected into tubes containing EDTA alone or EDTA with antiproteolytic and antioxidant agents; one half of each plasma was separated immediately, half after 3 h at 4 degrees C. Regardless of the addition of protective agents or the time difference in separating plasma from other blood elements, freezing plasma at -70 degrees C decreased apoB content a similar amount, an average of 6.8%. This loss of apoB immunoreactivity was not related to apoB content in fresh plasma. Analysis of variance showed no differential effect on apoB content by the various additions to whole blood or plasma. No additional apoB content was lost in once-frozen aliquots of three human plasma pools during storage at -70 degrees C for up to 18 months. We conclude that concentrations of apoB in human plasma can be measured reliably after long-term storage, although the absolute value may decrease slightly as a result of freezing.


Aromatase enzyme activity and sex determination in chickens.
During development, the genotype of the zygote determines the nature of the gonad, which then determines the male or female phenotype. The molecular events underlying this process are just beginning to be defined. A single treatment of chicken embryos with an aromatase inhibitor (which blocks the synthesis of estrogen from testosterone) at a stage when their gonads were bipotential caused genetic females to develop a permanent male phenotype. These sex-reversed females developed bilateral testes that were capable of complete spermatogenesis and had the physical appearance and behavior of normal males. This result identifies aromatase as a key developmental switch in the sex determination of chickens.


Tim-3 is dispensable for allergic inflammation and respiratory tolerance in experimental asthma.
T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) has been described as a transmembrane protein, expressed on the surface of various T cells as well as different cells of innate immunity. It has since been associated with Th1 mediated autoimmune diseases and transplantation tolerance studies, thereby indicating a possible role of this receptor in counter-regulation of Th2 immune responses. In the present study we therefore directly examined the role of Tim-3 in allergic inflammation and respiratory tolerance. First, Tim-3-/- mice and wild type controls were immunized and challenged with the model allergen ovalbumin (OVA) to induce an asthma-like phenotype. Analysis of cell numbers and distribution in the bronchoalveolar lavage (BAL) fluid as well as lung histology in H&E stained lung sections demonstrated a comparable degree of eosinophilic inflammation in both mouse strains. Th2 cytokine production in restimulated cell culture supernatants and serum IgE and IgG levels were equally increased in both genotypes. In addition, cell proliferation and the distribution of different T cell subsets were comparable. Moreover, analysis of both mouse strains in our respiratory tolerance model, where mucosal application of the model allergen before immunization, prevents the development of an asthma-like phenotype, revealed no differences in any of the parameters mentioned above. The current study demonstrates that Tim-3 is dispensable not only for the development of allergic inflammation but also for induction of respiratory tolerance in mice in an OVA-based model.


Building Family Caregiver Skills Using a Simulation-Based Intervention: A Randomized Pilot Trial.
To evaluate the feasibility, acceptability, safety, and fidelity of a psychoeducational intervention to improve family caregiver technical and communication skills using structured simulations. 18 family caregivers of adult patients receiving radiation therapy for head and neck cancer at University Hospitals Seidman Cancer Center in Cleveland, Ohio. A two-group, randomized pilot trial design was used. The intervention consisted of four one-on-one sessions between the caregiver and nurse interventionist during the patient's first, second, fourth, and sixth week of radiation treatment. Participants completed measures of self-efficacy for caregiving, anxiety, depression, and health-related quality of life at baseline, during the fifth week of radiation therapy, and four weeks after radiation therapy. 4 of the 9 caregiver participants completed the intervention. Improvements in scores for the intervention group were noted for self-efficacy, global mental health, anxiety, and depression. Refinement of the intervention is needed to improve feasibility. Although a caregiver intervention that incorporates simulation for skills training is acceptable and safe, flexibility in protocol is needed.


Colonisation of poplar trees by gfp expressing bacterial endophytes.
With the exception of nitrogen fixing bacteria, there is little known about the colonisation patterns or population sizes of bacterial endophytes in deciduous trees. This study describes the isolation, identification, construction and re-colonisation patterns of three green fluorescent protein(gfp):kanamycin(R) labelled bacterial endophytes when re-introduced into poplar trees, their original host plant. Two of these endophytes showed considerable colonisation in the roots and stems of inoculated plants. gfp expressing cells of all three strains were observed to colonise the xylem tissue of the root. All three strains proved to be efficient rhizosphere colonisers, supporting the theory that the rhizosphere can serve as a source of bacterial endophytes.


Effect of physiotherapy attendance on outcome after anterior cruciate ligament reconstruction: a pilot study.
In many centres patients are routinely referred for physiotherapy after anterior cruciate ligament (ACL) reconstruction. However, to date the role and amount of supervised physiotherapy required has not been clearly established. To establish whether there was any difference in outcome between a group of patients who attended physiotherapy regularly after ACL reconstruction and a group who attended only infrequently. Ten patients who had attended physiotherapy infrequently (mean 1.9 visits) during the first six months after ACL reconstructive surgery were matched for age, sex, graft type, and activity level and occupation before injury with 10 patients who had attended physiotherapy regularly (mean 26.5 visits). Outcome was assessed at 12 months using the Cincinnati knee rating system and the IKDC form. Compared with the regular physiotherapy group, patients in the minimal physiotherapy group had fewer symptoms (mean Cincinnati symptom score 46.2 v 43.4, p = 0.045). There was also a trend towards higher overall Cincinnati knee scores in the minimal physiotherapy group (mean 93.7 v 87.3, p = 0.06) but no difference in IKDC ratings. These preliminary results indicate that some patients who choose to attend physiotherapy on a very limited basis after ACL reconstruction can achieve satisfactory, if not better, outcomes than patients who attend physiotherapy regularly.


Structure and spin state of nonheme FeIVO complexes depending on temperature: predictive insights from DFT calculations and experiments.
The spin states (S = 1 and S = 2) of nonheme FeIVO intermediates are believed to play an important role in determining their chemical properties in enzymatic and biomimetic reactions. However, it is almost impossible to investigate the spin state effect of nonheme FeIVO species experimentally, since FeIVO models having the S = 1 and S = 2 spin states at the same time neither exist nor can be synthesized. However, recent synthesis of an FeIVO complex with an S = 1 spin state (triplet), [(Me3NTB)FeIVO]2+ (1), and a structurally similar FeIVO complex but with an S = 2 spin state (quintet), [(TQA)FeIVO]2+ (2), has allowed us to compare their reactivities at 233 K. In the present study, we show that structural variants control the spin-state selectivity and reactivity of nonheme FeIVO complexes. While 1 and 2 were proposed to be in an octahedral geometry based on DFT calculations and spectroscopic characterization done at 4 K, further DFT calculations show that these species may well assume a trigonal bipyramidal structure by losing one coordinated solvent ligand at 233 K. Thus, the present study demonstrates that the structure and spin state of nonheme FeIVO complexes can be different at different temperatures; therefore, the structural and/or spin state information obtained at 4 K should be carefully used at a higher temperature (e.g., 233 K). In addition to 1 and 2, [(TPA)FeIVO]2+ (3) with an S = 1 spin state, whose spin state was determined spectroscopically and theoretically at 233 K, is included in this study to compare the chemical properties of S = 1 and S = 2 FeIVO complexes. The present results add another dimension to the discussion of the reactivites of nonheme FeIVO species, in which the structural preference and spin state of nonheme FeIVO species can vary depending on temperature.


Genetics of multiple sclerosis.
Multiple sclerosis (MS) is probably aetiologically heterogeneous. Systematic genetic epidemiological and molecular genetic studies have provided important insights. Both genetic and non-genetic (environment, stochastic) factors may be involved in susceptibility as well as outcome, but we have yet to understand their relative roles. Any environmental factor is likely to be ubiquitous and act on a population-basis rather than within the family microenvironment. Taken together, the results of genome screening studies provide strong evidence for exclusion of a major locus in MS. There are, however, many genes that seem to be associated with MS. These include, but are in no way limited to, HLA classes I and II, T-cell receptor beta, CTLA4, ICAM1, and SH2D2A. The future of MS genetics, as for most common complex disorders, will be dependent on the resources available, ranging from biological samples and comprehensive databases of clinical and epidemiological information to the development of new technologies and statistical methods.


Towards quantitative viromics for both double-stranded and single-stranded DNA viruses.
Viruses strongly influence microbial population dynamics and ecosystem functions. However, our ability to quantitatively evaluate those viral impacts is limited to the few cultivated viruses and double-stranded DNA (dsDNA) viral genomes captured in quantitative viral metagenomes (viromes). This leaves the ecology of non-dsDNA viruses nearly unknown, including single-stranded DNA (ssDNA) viruses that have been frequently observed in viromes, but not quantified due to amplification biases in sequencing library preparations (Multiple Displacement Amplification, Linker Amplification or Tagmentation). Here we designed mock viral communities including both ssDNA and dsDNA viruses to evaluate the capability of a sequencing library preparation approach including an Adaptase step prior to Linker Amplification for quantitative amplification of both dsDNA and ssDNA templates. We then surveyed aquatic samples to provide first estimates of the abundance of ssDNA viruses. Mock community experiments confirmed the biased nature of existing library preparation methods for ssDNA templates (either largely enriched or selected against) and showed that the protocol using Adaptase plus Linker Amplification yielded viromes that were ±1.8-fold quantitative for ssDNA and dsDNA viruses. Application of this protocol to community virus DNA from three freshwater and three marine samples revealed that ssDNA viruses as a whole represent only a minor fraction (<5%) of DNA virus communities, though individual ssDNA genomes, both eukaryote-infecting Circular Rep-Encoding Single-Stranded DNA (CRESS-DNA) viruses and bacteriophages from the Microviridae family, can be among the most abundant viral genomes in a sample. Together these findings provide empirical data for a new virome library preparation protocol, and a first estimate of ssDNA virus abundance in aquatic systems.


Where to deliver? Analysis of choice of delivery location from a national survey in India.
In order to reduce maternal mortality, the Indian government has increased its commitment to institutional deliveries. We assess the determinants of home, private and public sector utilization for a delivery in a Western state. Cross sectional analyses of the National Family Health Survey - 2 dataset. Maharashtra state. The dataset had a sample size of 5391 ever-married females between the ages of 15 to 49 years. Data were abstracted for the most recent birth (n = 1510) and these were used in the analyses. Conceptual framework was the Andersen Behavioral Model. Multinomial logistic regression analyses was conducted to assess the association of predisposing, enabling and need factors on use of home, public or private sector for delivery. A majority delivered at home (n = 559, 37%); with private and public facility deliveries accounting for 32% (n = 493) and 31% (n = 454) respectively. For the choice set of home delivery versus public facility, women with higher birth order and those living in rural areas had greater odds of delivering at home, while increasing maternal age, greater media exposure, and more then three antenatal visits were associated with greater odds of delivery in a public facility. Maternal and paternal education, scheduled caste/tribe status, and media exposure were statistically significant predictors of the choice of public versus private facility delivery. As India's economy continues to grow, the private sector will continue to expand. Given the high household expenditures on health, the government needs to facilitate insurance schemes or provide grants to prevent impoverishment. It also needs to strengthen the public sector so that it can return to its mission of being the safety net.


Ethics of health research in communities: perspectives from the southwestern United States.
The increasing attention paid to community-based research highlights the question of whether human research protections focused on the individual are adequate to safeguard communities. We conducted a study to explore how community members perceive low-risk health research, the adequacy of human research protection processes, and the ethical conduct of community-based research. Eighteen focus groups were conducted among rural and urban Hispanic and Native American communities in New Mexico using a semistructured guide. Group transcriptions were analyzed using iterative readings and coding, with review of the analytic summary by group members. Although participants recognized the value of health research, many also identified several adverse effects of research in their communities, including social (community and individual labeling, stigmatization, and discrimination) and economic (community job losses, increased insurance rates, and loss of community income). A lack of community beneficence was emphasized by participants who spoke of researchers who fail to communicate results adequately or assist with follow-through. Many group members did not believe current human research and data privacy processes were adequate to protect or assist communities. Ethical review of community-based health research should apply the Belmont principles to communities. Researchers should adopt additional approaches to community-based research by engaging communities as active partners throughout the research process, focusing on community priorities, and taking extra precautions to assure individual and community privacy. Plans for meaningful dissemination of results to communities should be part of the research design.


Altered miRNA-profile dependent on ART outcome in early pregnancy targets Wnt-pathway.
Main goal of this study is to detect the possible alterations in microRNA (miRNA) expression and the pathway targeted in plasma at the time of embryo transfer and pregnancy testing dependent on the assisted reproductive treatment (ART) outcome after ovarian hyperstimulation for in vitro fertilization. Changes in miRNA expression in plasma of women, who became pregnant (n = 6) vs women who failed implantation (n = 6) following day 5 embryo transfer (ET), were investigated at the day of ET and pregnancy testing (PT). Protein expression to validate the finding was performed with a sample size of n = 20 (10 per group) using enzyme-linked immunosorbent assay. Enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using DIANA-miRPath, v3.0 software based on predicted targets by DIANA-microT-CDS. 4 miRNAs could be identified as possible biomarkers for implantation success. The 11 miRNAs showing the highest significant alterations were all associated with the regulation of WNT3 and WNT7a. While WNT7a presented with a significant decrease between ET and PT in case of ongoing pregnancy, women with implantation failure showed unaltered concentrations. WNT3 presented with a significant decrease in both groups. However, the loss of WNT3 between ET and PT was significantly higher in patients who became pregnant. Main limitation of this prospective study is its small sample size, defining it as a pilot analysis. To conclude, we could demonstrate a significant change in miRNA profile dependent on the ART outcome affecting Wnt pathway. Our findings indicate a possible prospective use of miRNA as biomarkers for implantation success.


Effect of intensive care unit environment on in-hospital delirium after cardiac surgery.
The etiology of postcardiac surgery delirium is complex. Our primary objective was to determine the effect of the postoperative environment on the prevalence of delirium by examining the in-hospital delirium rates in 2 postoperative intensive care units with differing physical infrastructure. We further sought to identify other risk factors associated with in-hospital delirium. The rates of postoperative delirium were retrospectively examined in consecutive cardiac surgery patients during 2 separate 6-month periods. Environment 1 was characterized by a lack of physical barriers between bed spaces and was windowless, and environment 2 consisted of private rooms with physical barriers for each patient and with wall-to-wall exterior windows. Univariate and multivariate analyses to determine the risk factors associated with in-hospital delirium, including the effect of environment, were undertaken. Of the 1010 patients studied, 148 (14.7%) experienced in-hospital delirium after cardiac surgery. The prevalence of delirium was not significantly different between environments 1 and 2 (16.1% vs 13.5%; P = .25). However, in patients younger than 65 years, the proportion of intensive care unit days on which delirium occurred was greater in environment 1 than in environment 2 (5.4% vs 1.7%; P = .006). Postoperative stroke or transient ischemic attack, mechanical ventilation longer than 24 hours, age 65 years or older, concomitant coronary artery bypass grafting and valve surgery, prehospital admission benzodiazepine use, a requirement for any postoperative blood product transfusion, and postoperative renal insufficiency were identified as risk factors. The intensive care unit environment did not have a significant effect on the overall prevalence of delirium. However, that does not preclude the possibility that the intensive care unit environment might interact with other factors, such as age, in a complex manner. Attempts to reduce delirium by adjusting the intensive care unit environment alone will likely not be sufficient, and instead will require a more comprehensive multimodal approach.


Pilot immunization of mice infected with an equine strain of Corynebacterium pseudotuberculosis.
This pilot study evaluated protection of an equine autogenous bacterin-toxoid vaccine against Corynebacterium pseudotuberculosis infection. Twenty-four BALB/c mice were inoculated with two doses of bacterin-toxoid vaccine or two injections of a placebo. Clinical, microbiologic, and pathologic outcomes were assessed after intradermal infection with one of two equine-origin C. pseudotuberculosis strains. Mice receiving bacterin-toxoid from fast-growing C. pseudotuberculosis showed significant protection from challenge infection, as evidenced by a higher survival rate, fewer gross and histopathologic lesions, and lower bacterial levels on culture. Successful protection via a vaccine against equine internal abscesses might provide supplementary management options against an important, potentially fatal disease.


On the Enigma of the Human Neurenteric Canal.
Existence and biomedical relevance of the neurenteric canal, a transient midline structure during early neurulation in the human embryo, have been controversially discussed for more than a century by embryologists and clinicians alike. In this study, the authors address the long-standing enigma by high-resolution histology and three-dimensional reconstruction using new and historic histological sections of 5 human 17- to 21-day-old embryos and of 2 marmoset monkey embryos of the species Callithrix jacchus at corresponding stages. The neurenteric canal presents itself as the classical vertical connection between the amniotic cavity and the yolk sac cavity and is lined (a) craniolaterally by a horseshoe-shaped "hinge of involuting notochordal cells" within Hensen's node and (b) caudally by the receding primitive streak epiblast dorsally and by notochordal plate epithelium ventrally, the latter of which covered the (longitudinal) notochordal canal on its ventral side at the preceding stage. Furthermore, asymmetric parachordal nodal expression in Callithrix and morphological asymmetries within the nodes of the other specimens suggest an early non-cilium-dependent left-right symmetry breaking mode previously postulated for other mammals. We conclude that structure and position of the mammalian neurenteric canal support the notion of its homology with the reptilian blastopore as a whole and with a dorsal segment of the blastopore in amphibia. These new features of the neurenteric canal may further clarify the aetiology of foetal malformations such as junctional neurulation defects, neuroendodermal cysts, and the split notochord syndrome.


Speckle-free holography with partially coherent light sources and camera-in-the-loop calibration.
Computer-generated holography (CGH) holds transformative potential for a wide range of applications, including direct-view, virtual and augmented reality, and automotive display systems. While research on holographic displays has recently made impressive progress, image quality and eye safety of holographic displays are fundamentally limited by the speckle introduced by coherent light sources. Here, we develop an approach to CGH using partially coherent sources. For this purpose, we devise a wave propagation model for partially coherent light that is demonstrated in conjunction with a camera-in-the-loop calibration strategy. We evaluate this algorithm using light-emitting diodes (LEDs) and superluminescent LEDs (SLEDs) and demonstrate improved speckle characteristics of the resulting holograms compared with coherent lasers. SLEDs in particular are demonstrated to be promising light sources for holographic display applications, because of their potential to generate sharp and high-contrast two-dimensional (2D) and 3D images that are bright, eye safe, and almost free of speckle.


Use of milrinone to treat cardiac dysfunction in infants with pulmonary hypertension secondary to congenital diaphragmatic hernia: a review of six patients.
Pulmonary hypertension and secondary cardiac dysfunction are important contributors of morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). Milrinone, a phosphodiesterase-3 inhibitor, may be useful in this setting for its combined actions as a pulmonary vasodilator and to improve systolic and diastolic function. This study aimed to assess the effects of milrinone on cardiac function and pulmonary artery pressure in infants with CDH. A retrospective review of echocardiograms performed on infants with CDH who received milrinone was performed. Tissue Doppler imaging velocities were used to assess systolic and diastolic function. Pulmonary artery pressure was assessed from the pattern and velocity of ductal shunting. Six infants with CDH and severe pulmonary hypertension were identified. Systolic and diastolic myocardial velocities were reduced in the right ventricle (RV) and interventricular septum (IVS) at baseline. In the 72 h after commencement of milrinone, there was a significant increase in early diastolic myocardial velocities in the RV, accompanied by increasing systolic velocities in the RV and IVS. Oxygenation index was significantly reduced, blood pressure unchanged, and ductal shunt velocity minimally altered over the same time period. Milrinone use was associated with an improvement in systolic and diastolic function in the RV, corresponding to an improvement in clinical status.


M(1) and M(2) muscarinic acetylcholine receptor subtypes mediate Ca(2+) channel current inhibition in rat sympathetic stellate ganglion neurons.
Muscarinic acetylcholine receptors (mAChRs) are known to mediate the acetylcholine inhibition of Ca(2+) channels in central and peripheral neurons. Stellate ganglion (SG) neurons provide the main sympathetic input to the heart and contribute to the regulation of heart rate and myocardial contractility. Little information is available regarding mAChR regulation of Ca(2+) channels in SG neurons. The purpose of this study was to identify the mAChR subtypes that modulate Ca(2+) channel currents in rat SG neurons innervating heart muscle. Accordingly, the modulation of Ca(2+) channel currents by the muscarinic cholinergic agonist, oxotremorine-methiodide (Oxo-M), and mAChR blockers was examined. Oxo-M-mediated mAChR stimulation led to inhibition of Ca(2+) currents through voltage-dependent (VD) and voltage-independent (VI) pathways. Pre-exposure of SG neurons to the M(1) receptor blocker, M(1)-toxin, resulted in VD inhibition of Ca(2+) currents after Oxo-M application. On the other hand, VI modulation of Ca(2+) currents was observed after pretreatment of cells with methoctramine (M(2) mAChR blocker). The Oxo-M-mediated inhibition was nearly eliminated in the presence of both M(1) and M(2) mAChR blockers but was unaltered when SG neurons were exposed to the M(4) mAChR toxin, M(4)-toxin. Finally, the results from single-cell RT-PCR and immunofluorescence assays indicated that M(1) and M(2) receptors are expressed and located on the surface of SG neurons. Overall, the results indicate that SG neurons that innervate cardiac muscle express M(1) and M(2) mAChR, and activation of these receptors leads to inhibition of Ca(2+) channel currents through VI and VD pathways, respectively.


A functional cutin matrix is required for plant protection against water loss.
The plant cuticle, a cutin matrix embedded with and covered by wax, seals the aerial organ's surface to protect the plant against uncontrolled water loss. The cutin matrix is essential for the cuticle to function as a barrier to water loss. Recently, we identified from wild barley a drought supersensitive mutant, eibi1, which is caused by a defective cutin matrix as the result of the loss of function of HvABCG31, an ABCG full transporter. Here, we report that eibi1 epidermal cells contain lipid-like droplets, which are supposed to consist of cutin monomers that have not been transported out of the cells. The eibi1 cuticle is fragile due to a defective cutin matrix. The rice ortholog of the EIBI1 gene has a similar pattern of expression, young shoot but not flag leaf blade, as the barley gene. The model of the function of Eibi1 is discussed. The HvABCG31 full transporter functions in the export of cutin components and contributed to land plant colonization, hence also to terrestrial life evolution.


Active DNA topoisomerase II with minimum molecular mass from regenerating rat liver.
We have purified the type II DNA topoisomerase from regenerating rat liver. The purified topoisomerase II migrated as two bands with molecular masses of 70 kDa and 55 kDa on SDS-PAGE. Immunoblotting analysis using antiserum against rat topoisomerase II gene product expressed in Escherichia coli suggested that the two bands on SDS-gel are proteolytic products of the intact 173 kDa form. However, these products retained the enzyme activities such as catenation and relaxation of supercoiled circular duplex monomer DNA and unknotting of knotted phage P4 DNA. These results suggest that DNA topoisomerase II consists of different functional domains and that the whole enzyme is not required for its activity. The activities of the purified enzyme were completely inhibited by 1 mM novobiocin, a bacterial gyrase inhibitor. However, no inhibitory effect was observed when another gyrase inhibitor, nalidixic acid was used.


Men's work: men's voices and actions against sexism and violence.
This short article details the initial findings from a 3-month conversation between 21 male activists who work to prevent violence against women. Using Participatory Action Research methodology, this research project investigates what men who do this work would like to learn from other men who do this work. To date, no research has been done that examines what it is that motivates and sustains men who work, as their primary effort, to prevent men's violence against women. This article examines some of the initial findings from this research, and examines the implications for engaging and mobilizing other men to prevent men's violence against women. This article begins with a description of the research project, followed by an overview of the findings, continues with a discussion of the implications from these initial findings for preventing men's violence against women, and ends with some lessons learned from the process of this research project and a brief overview of the next step of this conversation.


Biodiversity in agricultural landscapes: The effect of apple cultivar on epiphyte diversity.
In natural systems, extended phenotypes of trees can be important in determining the species composition and diversity of associated communities. Orchards are productive systems where trees dominate, and can be highly biodiverse, but few studies have considered the importance of tree genetic background in promoting associated biodiversity. We tested the effect of apple cultivar (plant genetic background) on the diversity and composition of the associated epiphytic bryophyte community across a total of seven cultivars in five productive East Anglian orchards where each orchard contained two cultivars. Data were collected from 617 individual trees, over 5 years. Species richness and community composition were significantly influenced by both orchard and cultivar. Differences among orchards explained 16% of the variation in bryophyte community data, while cultivar explained 4%. For 13 of the 41 bryophyte species recorded, apple cultivar was an important factor in explaining their distribution. While the effects of cultivar were small, we were able to detect them at multiple levels of analysis. We provide evidence that extended phenotypes act in productive as well as natural systems. With issues of food security ranking high on the international agenda, it is important to understand the impact of production regimes on associated biodiversity. Our results can inform mitigation of this potential conflict.


Diagnostic potential of real-time elastography (RTE) and shear wave elastography (SWE) to differentiate benign and malignant thyroid nodules: A systematic review and meta-analysis.
Real-time elastography (RTE) and shear wave elastography (SWE) are noninvasive and easily available imaging techniques that measure the tissue strain, and it has been reported that the sensitivity and the specificity of elastography were better in differentiating between benign and malignant thyroid nodules than conventional technologies. Relevant articles were searched in multiple databases; the comparison of elasticity index (EI) was conducted with the Review Manager 5.0. Forest plots of the sensitivity and specificity and SROC curve of RTE and SWE were performed with STATA 10.0 software. In addition, sensitivity analysis and bias analysis of the studies were conducted to examine the quality of articles; and to estimate possible publication bias, funnel plot was used and the Egger test was conducted. Finally 22 articles which eventually satisfied the inclusion criteria were included in this study. After eliminating the inefficient, benign and malignant nodules were 2106 and 613, respectively. The meta-analysis suggested that the difference of EI between benign and malignant nodules was statistically significant (SMD = 2.11, 95% CI [1.67, 2.55], P < .00001). The overall sensitivities of RTE and SWE were roughly comparable, whereas the difference of specificities between these 2 methods was statistically significant. In addition, statistically significant difference of AUC between RTE and SWE was observed between RTE and SWE (P < .01). The specificity of RTE was statistically higher than that of SWE; which suggests that compared with SWE, RTE may be more accurate on differentiating benign and malignant thyroid nodules.


Effects of phytoestrogen extracts isolated from pumpkin seeds on estradiol production and ER/PR expression in breast cancer and trophoblast tumor cells.
Phytoestrogens have a controversial effect on hormone-dependent tumours. Herein, we investigated the effect of the pumpkin seed extract (PSE) on estradiol production and estrogen receptor (ER)-α/ER-β/progesterone receptor (PR) status on MCF7, Jeg3, and BeWo cells. The PSE was prepared and analyzed by mass spectrometry. MCF7, Jeg3, and BeWo cells were incubated with various concentrations of PSE. Untreated cells served as controls. Supernatants were tested for estradiol production with an ELISA method. Furthermore, the effect of the PSE on ER-α/ER-β/PR expression was assessed by immunocytochemistry. The PSE was found to contain both lignans and flavones. Estradiol production was elevated in MCF7, BeWo, and Jeg3 cells in a concentration-dependent manner. In MCF7 cells, a significant ER-α downregulation and a significant PR upregulation were observed. The above results after properly designed animal studies could highlight a potential role of pumpkin seed's lignans in breast cancer prevention and/or treatment.


Near-optimal Integration of Magnitude in the Human Parietal Cortex.
Humans are often observed to make optimal sensorimotor decisions but to be poor judges of situations involving explicit estimation of magnitudes or numerical quantities. For example, when drawing conclusions from data, humans tend to neglect the size of the sample from which it was collected. Here, we asked whether this sample size neglect is a general property of human decisions and investigated its neural implementation. Participants viewed eight discrete visual arrays (samples) depicting variable numbers of blue and pink balls. They then judged whether the samples were being drawn from an urn in which blue or pink predominated. A participant who neglects the sample size will integrate the ratio of balls on each array, giving equal weight to each sample. However, we found that human behavior resembled that of an optimal observer, giving more credence to larger sample sizes. Recording scalp EEG signals while participants performed the task allowed us to assess the decision information that was computed during integration. We found that neural signals over the posterior cortex after each sample correlated first with the sample size and then with the difference in the number of balls in either category. Moreover, lateralized beta-band activity over motor cortex was predicted by the cumulative difference in number of balls in each category. Together, these findings suggest that humans achieve statistically near-optimal decisions by adding up the difference in evidence on each sample, and imply that sample size neglect may not be a general feature of human decision-making.


Controlling integrin specificity and stem cell differentiation in 2D and 3D environments through regulation of fibronectin domain stability.
The extracellular matrix (ECM) exerts powerful control over many cellular phenomena, including stem cell differentiation. As such, design and modulation of ECM analogs to ligate specific integrin is a promising approach to control cellular processes in vitro and in vivo for regenerative medicine strategies. Although fibronectin (FN), a crucial ECM protein in tissue development and repair, and its RGD peptide are widely used for cell adhesion, the promiscuity with which they engage integrins leads to difficulty in control of receptor-specific interactions. Recent simulations of force-mediated unfolding of FN domains and sequences analysis of human versus mouse FN suggest that the structural stability of the FN's central cell-binding domains (FN III9-10) affects its integrin specificity. Through production of FN III9-10 variants with variable stabilities, we obtained ligands that present different specificities for the integrin alpha(5)beta(1) and that can be covalently linked into fibrin matrices. Here, we demonstrate the capacity of alpha(5)beta(1) integrin-specific engagement to influence human mesenchymal stem cell (MSC) behavior in 2D and 3D environments. Our data indicate that alpha(5)beta(1) has an important role in the control of MSC osteogenic differentiation. FN fragments with increased specificity for alpha(5)beta(1) versus alpha(v)beta(3) results in significantly enhanced osteogenic differentiation of MSCs in 2D and in a clinically relevant 3D fibrin matrix system, although attachment/spreading and proliferation were comparable with that on full-length FN. This work shows how integrin-dependant cellular interactions with the ECM can be engineered to control stem cell fate, within a system appropriate for both 3D cell culture and tissue engineering.


Differentiation of human-induced pluripotent stem cell under flow conditions to mature hepatocytes for liver tissue engineering.
Hepatic differentiation of human-induced pluripotent stem cells (hiPSCs) under flow conditions in a 3D scaffold is expected to be a major step forward for construction of bioartificial livers. The aims of this study were to induce hepatic differentiation of hiPSCs under perfusion conditions and to perform functional comparisons with fresh human precision-cut liver slices (hPCLS), an excellent benchmark for the human liver in vivo. The majority of the mRNA expression of CYP isoenzymes and transporters and the tested CYP activities, Phase II metabolism, and albumin, urea, and bile acid synthesis in the hiPSC-derived cells reached values that overlap those of hPCLS, which indicates a higher degree of hepatic differentiation than observed until now. Differentiation under flow compared with static conditions had a strong inducing effect on Phase II metabolism and suppressed AFP expression but resulted in slightly lower activity of some of the Phase I metabolism enzymes. Gene expression data indicate that hiPSCs differentiated into both hepatic and biliary directions. In conclusion, the hiPSC differentiated under flow conditions towards hepatocytes express a wide spectrum of liver functions at levels comparable with hPCLS indicating excellent future perspectives for the development of a bioartificial liver system for toxicity testing or as liver support device for patients.


Relative Survival After Transcatheter Aortic Valve Implantation: How Do Patients Undergoing Transcatheter Aortic Valve Implantation Fare Relative to the General Population?
Transcatheter aortic valve implantation (TAVI) is indicated for patients with aortic stenosis who are intermediate-high surgical risk. Although all-cause mortality rates after TAVI are established, survival attributable to the procedure is unclear because of competing causes of mortality. The aim was to report relative survival (RS) after TAVI, which accounts for background mortality risks in a matched general population. National cohort data (n=6420) from the 2007 to 2014 UK TAVI registry were matched by age, sex, and year to mortality rates for England and Wales (population, 57.9 million). The Ederer II method related observed patient survival to that expected from the matched general population. We modelled RS using a flexible parametric approach that modelled the log cumulative hazard using restricted cubic splines. RS of the TAVI cohort was 95.4%, 90.2%, and 83.8% at 30 days, 1 year, and 3 years, respectively. By 1-year follow-up, mortality hazards in the >85 years age group were not significantly different from those of the matched general population; by 3 years, survival rates were comparable. The flexible parametric RS model indicated that increasing age was associated with significantly lower excess hazards after the procedure; for example, by 2 years, a 5-year increase in age was associated with 20% lower excess mortality over the general population. RS after TAVI was high, and survival rates in those aged >85 years approximated those of a matched general population within 3 years. High rates of RS indicate that patients selected for TAVI tolerate the risks of the procedure well.


Mutant selection in the self-incompatible plant radish (Raphanus sativus L. var. sativus) using two-step TILLING.
Radish (Raphanus sativus L. var. sativus), a widely cultivated root vegetable crop, possesses a large sink organ (the root), implying that photosynthetic activity in radish can be enhanced by altering both the source and sink capacity of the plant. However, since radish is a self-incompatible plant, improved mutation-breeding strategies are needed for this crop. TILLING (Targeting Induced Local Lesions IN Genomes) is a powerful method used for reverse genetics. In this study, we developed a new TILLING strategy involving a two-step mutant selection process for mutagenized radish plants: the first selection is performed to identify a BC1M1 line, that is, progenies of M1 plants crossed with wild-type, and the second step is performed to identify BC1M1 individuals with mutations. We focused on Rubisco as a target, since Rubisco is the most abundant plant protein and a key photosynthetic enzyme. We found that the radish genome contains six RBCS genes and one pseudogene encoding small Rubisco subunits. We screened 955 EMS-induced BC1M1 lines using our newly developed TILLING strategy and obtained six mutant lines for the six RsRBCS genes, encoding proteins with four different types of amino acid substitutions. Finally, we selected a homozygous mutant and subjected it to physiological measurements.


New oral therapies for type 2 diabetes.
Over the past few years, several oral agents for the treatment of type 2 diabetes have become available in the United States. Metformin, a biguanide that has been used for decades in other countries throughout the world, improves glycemic control without exacerbating hyperinsulinemia or promoting weight gain. This agent has recently been reintroduced in the United States. Acarbose is an alpha-glucosidase inhibitor that improves glycemic control by decreasing the intestinal absorption of glucose, thereby decreasing postprandial glucose elevations. The use of metformin and acarbose may be limited by their side effects and potential risks, especially the risk of lactic acidosis with metformin. The third newly available agent, troglitazone, has been shown to improve insulin sensitivity. Combinations of metformin, acarbose and troglitazone may facilitate improved glycemic control without the use of insulin, or they may allow sulfonylurea or insulin dosages to be reduced, in this way minimizing the adverse effects of hyperinsulinemia. Unfortunately, current oral therapies do not prevent the inevitable decline in glycemic control that occurs during the natural history of type 2 diabetes.


Confidence Can Be Used to Discriminate Between Accurate and Inaccurate Lie Decisions.
There is a long-standing belief that confidence is not useful at discriminating between accurate and inaccurate deception decisions. Historically, this position made sense because people showed little ability to discriminate lie-tellers from truth-tellers. But, it is now widely accepted that, under certain conditions, people can discriminate between lie-tellers and truth-tellers. Nevertheless, belief that confidence does not discriminate between accurate and inaccurate responses persists. This belief is somewhat paradoxical because, to the extent that people can discriminate between lie-tellers and truth-tellers, signal detection theory naturally predicts a positive relationship between confidence and accuracy. In line with our signal-detection-based predictions, we show that, among decisions about whether someone is lying, those made with high confidence are more accurate than those made with low confidence. This important relationship has gone unnoticed in past work because of a reliance on inappropriate measures. Past research examining the confidence-accuracy relationship in deception research relied on correlating average confidence with proportion of correctly identified lies. These correlations provide information on whether more confident judges tend to be more accurate but remain silent on the arguably more important question of whether higher confidence decisions are more accurate than lower confidence decisions. We show that confidence-accuracy characteristic analyses are uniquely suited to measuring the confidence-accuracy relationship in deception research.


Chart documentation quality and its relationship to the validity of administrative data discharge records.
The validity of administrative data may be vulnerable to how well physicians document medical charts. The objective of this study is to determine the relationship between chart documentation quality and the validity of administrative data. The charts for patients who underwent carotid endarterectomy were re-abstracted and rated for the quality of documentation. Poorly and well-documented charts were compared by patient, physician, and hospital variables, as well as on agreement between the administrative and re-abstracted data. Of the 2061 charts reviewed, 42.6 per cent were rated well documented. The proportion of charts well documented varied from 14.6 to 87.5 per cent across 17 hospitals, but did not vary significantly by patient characteristics. The kappa statistic was generally higher for well-documented charts than for poorly documented charts, but varied across comorbidities. In conclusion, poorly documented hospital charts tend to be translated into invalid administrative data, which reduces the communication of clinical information among healthcare providers.


A comparison of cone beam computed tomography and periapical radiography for the detection of vertical root fractures in nonendodontically treated teeth.
To compare in an ex vivo model, the diagnostic accuracy of periapical radiography and cone beam computed tomography (CBCT) for the detection of artificially induced incomplete and complete vertical root fractures (VRFs), and to determine whether the width of the VRFs had an impact on the diagnostic accuracy of the imaging systems. Incomplete VRFs were induced in 30 nonendodontically treated human mandibular premolar and molar teeth. VRF widths were measured using optical coherence tomography. Complete VRFs were induced in 15 of these teeth. 3D Accuitomo and i-CAT CBCT scans and periapical radiographs were taken prior to and after fracture induction. Receiver operating characteristic (ROC) analysis was carried for each imaging technique. In addition, values for sensitivity, specificity, positive and negative predictive values, inter- and intra-examiner agreement were calculated. In the ROC analysis, both CBCT scanners were significantly more accurate than periapical radiography for the detection of incomplete VRFs (P < 0.05). The overall area under the ROC curve (AUC) values for 3D Accuitomo, i-CAT and periapical radiography were 0.687, 0.659 and 0.540, respectively. The sensitivity of 3D Accuitomo, i-CAT and periapical radiography was 27%, 28% and 3% respectively. Interexaminer agreement for the detection of incomplete fractures with periapical radiographs, 3D Accuitomo and i-CAT was 0.020, 0.229 and 0.333, respectively. Both CBCT scanners were significantly more accurate (P < 0.01) in detecting VRFs of ≥50 μm compared with VRFs of <50 μm. 3D Accuitomo was significantly better than i-CAT in detecting VRFs of <50 μm (P < 0.05). For complete fractures, the AUC values for 3D Accuitomo (0.999) and i-CAT (0.998) were significantly higher (P < 0.05) than for periapical radiography (0.724). Under the conditions of this ex vivo study, periapical radiographs and CBCT were unreliable for the detection of simulated incomplete VRFs. The widths of the fractures appeared to have an impact on the diagnostic accuracy of CBCT as the detection of VRFs of ≥50 μm was significantly higher than those of <50 μm. The detection of complete fractures was significantly higher for all systems than that of incomplete fractures.


Unusual primary osseous Hodgkin lymphoma in rib with associated soft tissue mass: a case report and review of literature.
Hodgkin lymphoma (HL) typically presents as nodal lesion and may involve extranodal sites during the progression of the disease. Primary osseous HL without any lymph node association is extremely rare and only a few such cases have been described in the literature. We present a case of unusual primary HL in rib occurring in a middle-aged female patient. Computed tomography (CT) scan revealed an osteolytic lesion was located at the right second rib and was associated with a large soft tissue mass. There was no regional lymph node involvement. CT scan of neck and abdomen was performed and showed no pathologic findings, particularly no lymphadenopathy and organomegaly could be observed. Histologically, typical binucleated Reed-Sternberg (RS) cells and lacunar cells were scattered in the background of reactive inflammation with infiltration of lymphocytes, histiocytes and eosinophilic granulocytes. By immunohistochemistry, RS cells and lacunar cells were positive for CD15 and CD30 with typical membrane and paranuclear dot-like staining pattern. However, these cells were negative for Epstein-Barr virus detection by in situ hybridization. A diagnosis of primary osseous HL was made. The patient received systemic chemotherapy and local radiotherapy, and was on regular follow-up for 24 months. There was no sign of recurrence of tumor and lymph node or bone marrow involvement. Because there is a possibility of secondary bone involvement by systemic HL, strict histological analysis and thorough radiographic examination are suggested to be necessary for accurately diagnosing this tumor when it presents as a solitary bone lesion.


Effects of prior short multiple-sprint exercises with different intersprint recoveries on the slow component of oxygen uptake during high-intensity exercise.
This study compares the effects of two short multiple-sprint exercise (MSE) (6 × 6 s) sessions with two different recovery durations (30 s or 180 s) on the slow component of oxygen uptake ([Formula: see text]O(2)) during subsequent high-intensity exercise. Ten male subjects performed a 6-min cycling test at 50% of the difference between the gas exchange threshold and [Formula: see text]O(2peak) (Δ50). Then, the subjects performed two MSEs of 6 × 6 s separated by two intersprint recoveries of 30 s (MSE(30)) and 180 s (MSE(180)), followed 10 min later by the Δ50 (Δ50(30) and Δ50(180), respectively). Electromyography (EMG) activities of the vastus medialis and lateralis were measured throughout each exercise bout. During MSE(30), muscle activity (root mean square) increased significantly (p ≤ 0.04), with a significant leftward-shifted median frequency of the power density spectrum (MDF; p ≤ 0.01), whereas MDF was significantly rightward-shifted during MSE(180) (p = 0.02). The mean [Formula: see text]O(2) value was significantly higher in MSE(30) than in MSE(180) (p < 0.001). During Δ50(30), [Formula: see text]O(2) and the deoxygenated hemoglobin ([HHb]) slow components were significantly reduced (-27%, p = 0.02, and -34%, p = 0.003, respectively) compared with Δ50. There were no significant modifications of the [Formula: see text]O(2) slow component in Δ50(180) compared with Δ50 (p = 0.32). The neuromuscular and metabolic adaptations during MSE(30) (preferential activation of type I muscle fibers evidenced by decreased MDF and a greater aerobic metabolism contribution to the required energy demands), but not during MSE(180), may lead to reduced [Formula: see text]O(2) and [HHb] slow components, suggesting an alteration in motor units recruitment profile (i.e., change in the type of muscle fibers recruited) and (or) an improved muscle O(2) delivery during subsequent exercise.


Hereditary acrodermatitis enteropathica in an adult.
The condition of a 33-year-old woman who had a history of blisters following trauma on the hands, knees, and feet since 1 year of age previously had been diagnosed as epidermolysis bullosa. She also had psoriasiform plaques, a pustular crusted periorificial eruption, paronychia, alopecia, and photophobia. She had had minimal history of diarrhea. A markedly decreased serum zinc level was found, and treatment with zinc sulfate was instituted, resulting in clearing of all clinical manifestations. Since patients with hereditary acrodermatitis enteropathica may have minimal or no diarrhea and the correct diagnosis may be long delayed, the condition should not be considered strictly a disease of children.


DNA rearrangements proximal to the EVI1 locus associated with the 3q21q26 syndrome.
Specific rearrangements involving 3q21 and 3q26 are well documented in acute myeloid leukemia (AML). Aberrant expression of the Ecotropic virus integration-1 (EVI1) gene, located at 3q26, has been reported in individuals with AML and translocations or inversions of chromosome 3 long arm. We have studied six individuals with AML and inv(3)(q21q26) for disruptions to the EVI1 locus by in situ hybridization and long-range mapping. EVI1 transcripts have been detected in the blast cells of the two individuals available for expression studies. We derived a YAC containing the EVI1 gene and showed that it crossed the 3q26 inversion breakpoints in three of four cases examined. Pulsed field analysis detected aberrant fragments 3' of the EVI1 gene in all six patients. The orientation of the gene was established and the locations of the breakpoints were refined by in situ hybridization using phage clones from this region.