A homoserine lactone autoinducer regulates virulence of an insect-pathogenic bacterium, Xenorhabdus nematophilus (Enterobacteriaceae).
N-beta-Hydroxybutanoyl homoserine lactone (HBHL), the autoinducer of the luminescent system of Vibrio harveyi, has been identified as the first small compound to restore virulence to avirulent mutants of Xenorhabdus nematophilus. HBHL stimulated the level of lipase activity excreted by avirulent X. nematophilus and lowered the phenoloxidase activity in the hemolymph of insects infected with X. nematophilus, parameters that are both associated with insect pathogenesis. Moreover, mortality of the insects infected with avirulent X. nematophilus was restored upon injection with HBHL. Chloroform extraction of medium conditioned with wild-type but not avirulent X. nematophilus led to the isolation of a compound with the same chromatographic mobility as HBHL as well as the ability to stimulate the luminescence of a dim autoinducer-dependent mutant of V. harveyi. Transfer of the V. harveyi lux operon into avirulent and wild-type X. nematophilus generated dim and bright luminescent strains, respectively, which responded to HBHL and an agonist and antagonist in a manner analogous to their effects on the luminescence of dim autoinducer-deficient and bright wild-type strains of V. harveyi, indicating that similar HBHL-dependent regulatory systems exist in these two bacterial species.


CE institute style.
This article describes the philosophy and operation of The Pankey Institute for Advanced Dental Education as one example of the "institute" approach to professional development for dentists.


Total-body protein turnover in human premature neonates: effects of birth weight, intra-uterine nutritional status and diet.
1. The effects of birth weight, intra-uterine nutritional status and protein and energy intake on whole-body protein turnover, and skeletal muscle protein breakdown were examined in 40 premature infants. 2. Total-body nitrogen flux was 26% higher in the small-for-gestational-age compared with appropriate-for-gestation-age infants; similarly, whole-body protein synthesis and breakdown were increased by 26 and 35% respectively (P less than 0.01). 3. The lower-birth-weight neonates (less than 1500 g) had higher rates of skeletal muscle protein breakdown; 1.23 +/- 1.12 g day-1 kg-1, as compared with 0.54 +/- 0.28 g for the high-birth-weight group (P less than 0.05). 4. Protein intake was inversely correlated with the fraction of nitrogen flux coming from endogenous protein breakdown (P less than 0.05) and with skeletal muscle protein breakdown (P less than 0.05). There were no significant relationships found between energy intake and the parameters of protein metabolism. 5. On the basis of the turnover data, evidence is presented that the protein requirements for milk-protein fed premature neonates is less than 4.3 g day-1 kg-1.


The red and blue luminescence in silicon nanocrystals with an oxidized, nitrogen-containing shell.
Traditionally, two classes of silicon nanocrystals (SiNCs) are recognized with respect to their light-emission properties. These are usually referred to as the "red" and the "blue" emitting SiNCs, based on the spectral region in which the larger part of their luminescence is concentrated. The origin of the "blue" luminescence is still disputed and is very probably different in different systems. One of the important contributions to the discussion about the origin of the "blue" luminescence was the finding that the exposure of SiNCs to even trace amounts of nitrogen in the presence of oxygen induces the "blue" emission, even in originally "red"-emitting SiNCs. Here, we obtained a different result. We show that the treatment of "red" emitting, already oxidized SiNCs in a water-based environment containing air-related radicals including nitrogen-containing species as well as oxygen, diminishes, rather than induces the "blue" luminescence.


[Non detection of enterovirus in the bivalve Anadara tuberculosa (Bivalvia:Arcidae) caused by chemical contamination in the Pacific of Costa Rica].
Anadara tuberculosa is one of the most abundant mollusks of commercial importance in Costa Rica. Its habitat water is a potential source of fecal and chemical contamination to humans. We wanted to asses enterovirus, mainly poliovirus and hepatitis A virus and chemicals such as sulphates and nitrates in meat and body fluids. Thirteen samples were taken from four sites in Nicoya Gulf, three sites in the Sierpe-Térraba mangrove (Pacific of Costa Rica) and from five fish markets in San José, the capital of Costa Rica. Samples were tested for 1) fecal coliforms (Most Probable Number/100 ml), 2) isolation of enterovirus in cell culture (Hep-2, FrhK-4), 3) cell cytotoxicity in Vero cells and 4) the ability to inactivate 10 ID50% of poliovirus in cell culture. The Most Probable Number/100 ml in surrounding water was higher than the accepted standard for recreational waters, although the number of fecal coliforms in meats and body fluids was lower than in the external water. No cytopathogenic agents were isolated, but we found nitrate and sulphate concentrations that exceeded maxima for human consumption and recreation. The intrinsic cytotoxicity of the samples was at a 1/8 dilution, but some samples were cytotoxic at dilutions of 1/128. Body fluids were more cytotoxic than meats, but a positive correlation between cytotoxicity and chemical contamination was not determined: apparently other pollutants not identified in this study were responsible. Fluid and meat capacity to inactivate 10 ID50% of poliovirus in cell culture was demonstrated. Samples that were toxic for cell cultures also showed a higher percentage of poliovirus inactivation. Monitoring chemical pollution in these waters is highly recommended.


[The importance of loss in the genesis of depressive disorders].
The role of loss has been carefully examined in the investigation of depression since it constitutes a central aspect of most of the life events that lead to depression. In the present study, a review was made of the different studies on the role of loss, focusing on its different aspects and different types, the association between loss and some mental diseases, loss and prognosis, relationship between hopelessness and loss, variations of the events of loss based on different factors, also considering loss in the childhood. Loss constitutes a central role in the appearance of many depressive disorders. It can act as a provoking agent, a vulnerability factor or an agent that can modify the form, severity and course of a depressive disorder. Different factors such as the genetic one, gender or moment of life when the loss takes place, can modulate the influence of loss events.


Sulforaphane Inhibited the Nociceptive Responses, Anxiety- and Depressive-Like Behaviors Associated With Neuropathic Pain and Improved the Anti-allodynic Effects of Morphine in Mice.
Chronic neuropathic pain is associated with anxiety- and depressive-like disorders. Its treatment remains a serious clinical problem due to the lack of efficacy of the available therapeutic modalities. We investigated if the activation of the transcription factor Nrf2 could modulate the nociceptive and emotional disorders associated with persistent neuropathic pain and potentiated the analgesic activity of morphine. The possible mechanisms implicated in these effects have been also evaluated. Therefore, in C57BL/6 mice with neuropathic pain induced by the chronic constriction of the sciatic nerve (CCI), we assessed the antinociceptive, anxiolytic, and anti-depressant effects of the repeated intraperitoneal administration of a Nrf2 inducer, sulforaphane (SFN), and the effects of this treatment on the local antinociceptive actions of morphine. The protein levels of Nrf2, heme oxygenase 1 (HO-1), NAD(P)H:quinone oxidoreductase-1 (NQO1), CD11b/c (a microglial activator marker), mitogen-activated protein kinases (MAPK) and μ opioid receptors (MOR) in the spinal cord, prefrontal cortex and hippocampus from mice, at 28 days after CCI, were also evaluated. Our results showed that the repeated administration of SFN besides inhibiting nociceptive responses induced by sciatic nerve injury also diminished the anxiety- and depressive-like behaviors associated with persistent neuropathic pain. Moreover, SFN treatment normalized oxidative stress by inducing Nrf2/HO-1 signaling, reduced microglial activation and JNK, ERK1/2, p-38 phosphorylation induced by sciatic nerve injury in the spinal cord and/or hippocampus and prefrontal cortex. Interestingly, treatment with SFN also potentiated the antiallodynic effects of morphine in sciatic nerve-injured mice by regularizing the down regulation of MOR in the spinal cord and/or hippocampus. This study suggested that treatment with SFN might be an interesting approach for the management of persistent neuropathic pain and comorbidities associated as well as to improve the analgesic actions of morphine.


Funding HIV-vaccine research in developing countries-what is wrong with IAVI's recommendation?
The International AIDS Vaccine Initiative recommends targeting resources to research institutions in developing countries in order to accelerate the development of an effective HIV vaccine. In contrast, this paper shows that neither lump-sum nor in-kind transfers are an effective policy. We analyze several financing mechanisms as a means to overcome the lack of depth in HIV-vaccine research in a non-cooperative framework. At first, we point to cases in which financial support is actually counterproductive. Then we analyze whether in-kind transfers are preferable to lump-sum transfers. Even if donors prefer aid in kind because the incentives for moral hazard of recipients can be reduced, we demonstrate that it is effective only if recipients have cost advantages.


Relational Perspectives Regarding Countertransference in Group and Trauma.
A relational/constructivist view incorporates contemporary trends toward viewing countertransference and co-transference as results of mutual intersubjective influence. It moves toward a view of the socially constructed nature of human reality, toward recognizing the therapist's as well as the members' irreducible individuality and initiative taking, and toward therapy as about meaning-making rather than scientific discovery of The Truth. General clinical examples, and examples of working specifically with trauma, are given.


The metabolic transition during disease following infection of Arabidopsis thaliana by Pseudomonas syringae pv. tomato.
The outcome of bacterial infection in plants is determined by the ability of the pathogen to successfully occupy the apoplastic space and deliver a constellation of effectors that collectively suppress basal and effector-triggered immune responses. In this study, we examined the metabolic changes associated with establishment of disease using analytical techniques that interrogated a range of chemistries. We demonstrated clear differences in the metabolome of Arabidopsis thaliana leaves infected with virulent Pseudomonas syringae within 8 h of infection. In addition to confirmation of changes in phenolic and indolic compounds, we identified rapid alterations in the abundance of amino acids and other nitrogenous compounds, specific classes of glucosinolates, disaccharides, and molecules that influence the prevalence of reactive oxygen species. Our data illustrate that, superimposed on defence suppression, pathogens reconfigure host metabolism to provide the sustenance required to support exponentially growing populations of apoplastically localized bacteria. We performed a detailed baseline study reporting the metabolic dynamics associated with bacterial infection. Moreover, we have integrated these data with the results of transcriptome profiling to distinguish metabolomic pathways that are transcriptionally activated from those that are post-transcriptionally regulated.


Targeting and subsequent selection of somatic hypermutations in the human V kappa repertoire.
The number and distribution of nucleotide substitutions in human VkappaJkappa genes were examined using a PCR technique that analyzed nonproductive and productive rearrangements amplified from genomic DNA of individual B cells. The results indicate that the mutational mechanism introduces replacement (R) mutations comparably throughout the length of the VkappaJkappa rearrangement, but tends to target specific triplets. Moreover, hotspots of mutational activity were identified in complementarity determining regions (CDR). A marked increase in the frequency of R mutations in CDR was noted when productive were compared to nonproductive rearrangements, indicating that these were selected into the expressed repertoire. Of note, amino acids encoded by codons adjacent to hotspots of mutation were also positively selected implying that similar regions were targeted for hypermutation and subsequent selection. In contrast to the distribution of CDR mutations, R mutations in the framework (FR) regions tended to be eliminated from productive VkappaJkappa rearrangements, implying that the somatic hypermutational machinery frequently introduced amino acid changes that were deleterious to the structural integrity of the kappa chain protein. The difference in the ratio of R to silent mutations in CDR and FR in the expressed repertoire, therefore, reflects the summation of positive selection of R mutations in the CDR and the elimination of R mutations in the FR. The data indicate that the balance between targeted mutation of VkappaJkappa rearrangements and subsequent selection and elimination governs the pattern of mutations manifest within the expressed kappa repertoire.


Astronomy and Solar Physics: X-ray Gas Scintillation Spectrometer Experiment.
The payload complement on Spacelab 1 included a spectrometer for observations of the brighter cosmic x-ray sources. The primary scientific objective was to study the detailed spectral features of cosmic x-ray sources and their associated temporal variations over a wide energy range from about 2 to 80 kiloelectron volts. The instrument, based on the gas scintillation proportional counter, had a geometrical area of some 180 square centimeters with an energy resolution of about 9 percent at 7 kiloelectron volts. The results presented here show new results from two galactic binary x-ray sources, Cygnus X-3 and Centaurus X-3, and from the Perseus cluster of galaxies. The excellent energy resolution of the instrument permits line features to be identified in these sources with unprecedented quality.


The Ah Receptor: Adaptive Metabolism, Ligand Diversity, and the Xenokine Model.
The Ah receptor (AHR) has been studied for almost five decades. Yet, we still have many important questions about its role in normal physiology and development. Moreover, we still do not fully understand how this protein mediates the adverse effects of a variety of environmental pollutants, such as the polycyclic aromatic hydrocarbons (PAHs), the chlorinated dibenzo-p-dioxins ("dioxins"), and many polyhalogenated biphenyls. To provide a platform for future research, we provide the historical underpinnings of our current state of knowledge about AHR signal transduction, identify a few areas of needed research, and then develop concepts such as adaptive metabolism, ligand structural diversity, and the importance of proligands in receptor activation. We finish with a discussion of the cognate physiological role of the AHR, our perspective on why this receptor is so highly conserved, and how we might think about its cognate ligands in the future.


Stand aside stomata, another actor deserves centre stage: the forgotten role of the internal conductance to CO2 transfer.
Internal conductance describes the movement of CO(2) from substomatal cavities to sites of carboxylation. Internal conductance has now been measured in approximately 50 species, and in all of these species it is a large limitation of photosynthesis. It accounts for somewhat less than half of the decrease in CO(2) concentrations from the atmosphere to sites of carboxylation. There have been two major findings in the past decade. First, the limitation due to internal conductance (i.e. C(i)-C(c)) is not fixed but varies among species and functional groups. Second, internal conductance is affected by some environmental variables and can change rapidly, for example, in response to leaf temperature, drought stress or CO(2) concentration. Biochemical factors such as carbonic anhydrase or aquaporins are probably responsible for these rapid changes. The determinants of internal conductance remain elusive, but are probably a combination of leaf anatomy, morphology, and biochemical factors. In most plants, the gas phase component of internal conductance is negligible with the majority of resistance resting in the liquid phase from cell walls to sites of carboxylation. The internal conductance story is far from complete and many exciting challenges remain. Internal conductance ought to be included in models of canopy photosynthesis, but before this is feasible additional data on the variation in internal conductance among and within species are urgently required. Future research should also focus on teasing apart the different steps in the diffusion pathway (intercellular spaces, cell wall, plasmalemma, cytosol, and chloroplast envelope) since it is likely that this will provide clues as to what determines internal conductance.


Etiological factors, stages, and the role of the foreign body in foreign body tumorigenesis: a review.
Attempts were made to analyze the process of foreign body (FB) tumorigenesis and to identify etiologically significant factors by correlating information in the literature and recent experimental data from our labroatory. It appears that the process of FB tumorigenesis is dependent on sequence of specific conditions as expressed by the following criteria: (a) cellular proliferation and tissue infiltration during acute FB reaction; (b) fibrosis of the tissue capsule surrounding the FB; (c) quiescence of the tissue reaction, i. e., dormancy and phagocytic inactivity of FB-attached macrophages; and (d) availability of a FB surface for direct contact with clonal preneoplastic cells. There is no indication that the initial acquisition of neoplastic potential and the determination of specific tumor characteristics are based on direct physical or chemical reaction between cells and the FB. These etiological key events occur presumably in mesenchymal stem cells associated with the microvasculature no later than during the acute stage of FB reaction and certainly long before clonal descendants of these cells are first found in contact with the FB surface. In fact, there is no reason to assume that cells with neoplastic determination may be present in normal tissue prior to the introduction of a FB and that the FB would only create the conditions required for stepwise preneoplastic maturation.


Interrelationship between Vitamin D and Calcium in Obesity and Its Comorbid Conditions.
Obesity has been linked to vitamin D (VD) deficiency and low calcium (CAL) status. In the last decade, dietary supplementation of vitamin D and calcium (VD-CAL) have been extensively studied in animal experiments and human studies. However, the physiological mechanisms remain unknown as to whether the VD-CAL axis improves homeostasis and reduces biomarkers in regulating obesity and other metabolic diseases directly or indirectly. This review sought to investigate their connections. This topic was examined in scientific databases such as Web of Science, Scopus, and PubMed from 2011 to 2021, and 87 articles were generated for interpretation. Mechanistically, VD-CAL regulates from the organs to the blood, influencing insulin, lipids, hormone, cell, and inflammatory functions in obesity and its comorbidities, such as non-alcoholic fatty liver disease, cardiovascular disease, and type-2 diabetes mellitus. Nevertheless, previous research has not consistently shown that simultaneous VD-CAL supplementation affects weight loss or reduces fat content. This discrepancy may be influenced by population age and diversity, ethnicity, and geographical location, and also by degree of obesity and applied doses. Therefore, a larger prospective cohort and randomised trials are needed to determine the exact role of VD-CAL and their interrelationship.


Effect of botulinum toxin type A, motor imagery and motor observation on motor function of hemiparetic upper limb after stroke.
In rehabilitation settings, motor imagery, motor observation and mirror therapy serve as techniques for the recovery of paretic upper limb in patients with movement disorders after stroke, whereas botulinum toxin type A (BTX-A) offers the best treatment for focal spasticity. After haemorrhagic stroke, three patients (two men and one woman, mean age: 61.2 +/- 7.03) presented with hemiparesis of the left or right hand and arm with flexion of fingers, wrist and elbow, with no disturbance to sensitivity but with loss of use handoff the limb to write, eat or dress. After BTX-A injections, the patients underwent a daily rehabilitation programme based on motor imagery and motor observation for 1 month. Before and after the combined treatment, the motor function, spasticity and functional deficits of the patient were extensively measured. After a 3-month follow-up, upper limb spasticity measured with the Modified Ashworth Scale had worsened, yet the associated score remained lower than that at baseline. However, in these three patients a large improvement of motor function of the hemiparetic upper limb was observed. Combined treatment may be a viable rehabilitation option in post-stroke patients with disability to upper-extremity motor function, however further investigations are needed to determine its reproducibility in larger case series or clinical trials.


Mapping Slow Waves by EEG Topography and Source Localization: Effects of Sleep Deprivation.
Slow waves are a salient feature of the electroencephalogram (EEG) during non-rapid eye movement (non-REM) sleep. The aim of this study was to assess the topography of EEG power and the activation of brain structures during slow wave sleep under normal conditions and after sleep deprivation. Sleep EEG recordings during baseline and recovery sleep after 40 h of sustained wakefulness were analyzed (eight healthy young men, 27 channel EEG). Power maps were computed for the first non-REM sleep episode (where sleep pressure is highest) in baseline and recovery sleep, at frequencies between 0.5 and 2 Hz. Power maps had a frontal predominance at all frequencies between 0.5 and 2 Hz. An additional occipital focus of activity was observed below 1 Hz. Power maps ≤ 1 Hz were not affected by sleep deprivation, whereas an increase in power was observed in the maps ≥ 1.25 Hz. Based on the response to sleep deprivation, low-delta (0.5-1 Hz) and mid-delta activity (1.25-2 Hz) were dissociated. Electrical sources within the cortex of low- and mid-delta activity were estimated using eLORETA. Source localization revealed a predominantly frontal distribution of activity for low-delta and mid-delta activity. Sleep deprivation resulted in an increase in source strength only for mid-delta activity, mainly in parietal and frontal regions. Low-delta activity dominated in occipital and temporal regions and mid-delta activity in limbic and frontal regions independent of the level of sleep pressure. Both, power maps and electrical sources exhibited trait-like aspects.


Hepatic manifestations of women with polycystic ovary syndrome.
Women with polycystic ovary syndrome (PCOS) have a higher prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) than the general population. The link between NAFLD/NASH and PCOS is not just a coincidence. Indeed, both of these disorders comprise common risk factors, including central obesity, insulin resistance, chronic low-grade inflammation, and hyperandrogenemia. The characteristics of hyperandrogenemia in women with PCOS include elevated total and free testosterone levels and low sex hormone-binding globulin levels and are reported to be associated with NAFLD and elevated liver enzymes; however, not all elevated androgen levels in women with PCOS have the same adverse effects on the liver. With the exception of weight loss and encouraging exercise in obese women, few evidence-based effective treatments target NAFLD/NASH in women with PCOS. Selective antiandrogens and insulin sensitizers might be beneficial in treating NAFLD/NASH in women with PCOS, but further elucidation is needed.


Vaccines for preventing hepatitis B in health-care workers.
Hepatitis B causes acute and chronic liver disease and may be prevented by vaccination. To assess the effectiveness and safety of plasma-derived vaccines against acute and chronic hepatitis B in health-care workers in protecting them from hepatitis B infection and its consequences. MEDLINE and Excerpta Medica Database (EMBASE) search using standard Cochrane strategy, Cochrane Library, full text searching of the journal "Vaccine", bibliography of retrieved studies and correspondence with authors, researchers and manufacturers. All original prospective randomised comparisons of yeast-derived vaccines and plasma-derived vaccines against no intervention, placebo, or vaccines against other disease (control vaccines). Assessment of trial quality was made according to: 1. generation of allocation schedule 2. measure(s) taken to conceal treatment allocation 3. drop-out of allocated health-care worker participants from the analysis of trial results 4. measures taken to implement double blinding Trial reports were blinded by removal of authors and their affiliation, journal reference, introduction, results, and discussion. To assess efficacy the incidence rates of acute hepatitis B were observed in the surveillance of the vaccinated and control groups of the trials included in the review. Safety was assessed from side-effect rates, classified as systemic (malaise, nausea, fever, arthralgias, rash, headache) or local (induration and soreness at the site of the inoculation). Four trials fulfilling the criteria were identified and the data synthesised. All trials compared plasma-derived vaccines versus placebo. Differences in the settings (and level of incidence) between three of the trial settings and Dienstag's led us to stratify our comparison grouping the three trials performed in dialysis units together. After our stratification, the Desmyter, Smuzness and Crosnier group appears to be homogeneous (Chi-square = 0.11, degrees of freedom = 2). Our estimates of effectiveness and safety in the high risk group favour treatment, the OR for cases of HB being 0.34; 95% CI (0.21, 0.55). The analysis also revealed a non-significant trend towards benefit in the lower risk health-care workers (Dienstag trial, OR 0.26 (0.05, 1.30). Overall the evidence strongly favours vaccination (OR=0.33; 95% CI (0.21, 0.53)). There was no difference in the incidence and severity of side-effects between the two arms of the trials. We calculated that it was necessary to vaccinate between 145 (assuming a baseline rate of 10 cases/1000/year) and 7 (for a baseline rate of 200/1000/year) health-care workers with plasma-derived vaccines to avoid one case of hepatitis B. Completeness of trial reporting was not good with all four trials failing to report titre results on antibodies against hepatitis B surface antigen and hepatitis B core antigen in the placebo arms (correspondence with two of the four authors failed to shed light on the reasons for such an omission). All four trials achieved low scores in the four quality dimensions assessed (generation of allocation schedule, measure(s) taken to conceal treatment allocation, exclusion of allocated participants from the analysis of the trial and measures taken to implement and protect double blinding). Mean length of follow-up was 14.5 months. Plasma-derived vaccines appear to be efficacious and safe for use in high risk health-care workers, such as staff of renal dialysis and transplant units. There is some uncertainty concerning the effectiveness of the vaccine in lower risk health-care workers, although the trend is towards benefit. We found no evidence of a long-term protective effect due to the short follow-up time of the four trials included in this review. We found relatively poor standard of trial reporting, possibly related to the age of the trials.


How to improve organ donation in the MESOT countries.
There are more than 29 countries that have membership of the Middle East Society for Organ Transplantation (MESOT) with more than 600 million populations. These include all Arab countries, Iran, Turkey, Pakistan and countries of Central Asia. There are common features of organ transplantation in the Middle East Countries that include inadequate preventive medicine, uneven health infrastructure, poor awareness of the medical community and public at large of the importance of the organ donation and transplantation, high level of ethnicity and poor government support of organ transplantation. In addition, there is lack of team spirit among transplant physicians, lack of planning for organ procurement and transplant centers and lack of effective health insurance. Patients seek commercial transplantation most of the time. Patients on waiting lists for organ transplantation increase with time and there is a considerably growing gap between supply and demand of organs in the MESOT countries. Living organ donation is the most widely practiced type of donation in the Middle East and includes kidney and partial liver. Cadaver organ donation has a great potential in the Middle East. Nevertheless, this source is still not utilized properly due to the continued debate in the medical community about the concept of brain death and inadequate awareness of the public of the importance of organ donation and transplantation in many countries in this region.. There are three dominant and distinctive models for practice including the Saudi, Iranian and Pakistani models. The Saudi model includes the presence of a national organ procurement center as a governmental agency to supervise organ donation and transplantation. The Iranian model consists of renal grafts donation from the living genetically unrelated persons to the benefit of patients with end-stage renal disease. The Pakistani model is an interesting funding model for management of end-stage organ failure in the developing countries. We conclude that organ donation and transplantation are hampered with obstacles in the MESOT countries. Solutions need continuous work on many fronts. Local experiences can be implemented into new improved models that can help overcoming current obstacles.


Pharmacokinetics of dapsone gel, 5% for the treatment of acne vulgaris.
Oral dapsone has been available for over 60 years and has been used to treat severe acne vulgaris; however, the oral formulation is known to cause dose-dependent haematological reactions and is currently indicated only for diseases such as dermatitis herpetiformis and Hansen's disease. A gel formulation of dapsone was recently developed to treat acne vulgaris. As dapsone is administered topically, it was expected that systemic absorption would be considerably lower than that observed with oral dapsone therapy, thereby avoiding any adverse haematological effects. To report the pharmacokinetic profile of topically applied dapsone gel, 5% in the treatment of acne vulgaris. Three prospective, open-label studies enrolled a total of 548 subjects with acne vulgaris: two phase I pharmacokinetic studies (crossover and drug interaction) and one phase III long-term safety study. In the crossover study (n = 18), topical dapsone gel applied twice daily for a total of 14 days to 22.5% of the body surface area was compared with a single dose of oral dapsone 100mg (the typical clinical dose). In the drug-interaction study (n = 24), oral trimethoprim/sulfamethoxazole monotherapy, topical dapsone gel monotherapy and the two in combination were used twice daily for 7, 21 and 7 days, respectively. In the long-term safety study (n = 506), topical dapsone gel was applied twice daily to acne-affected areas for up to 12 months. Blood samples were drawn at various timepoints in each study to assess drug and metabolite concentrations. Systemic concentrations of dapsone, N-acetyl dapsone, dapsone hydroxylamine, trimethoprim and sulfamethoxazole were determined, according to the study design. In the crossover study, the mean area under the plasma concentration-time curve (AUC) from 0 to 24 hours for dapsone was 417.5 ng x h/mL after 2 weeks of dapsone gel therapy (n = 10), compared with an AUC from time zero to infinity of 52,641 ng x h/mL after a single dose of oral dapsone; this represents a 126-fold lower systemic exposure for dapsone gel at typical therapeutic doses. In the drug-interaction study, the AUC from 0 to 12 hours for dapsone was 221.52 ng x h/mL after 3 weeks of dapsone gel monotherapy compared with 320.3 ng x h/mL after 1 week of coadministration with trimethoprim/sulfamethoxazole. In the long-term safety study, the mean plasma dapsone concentrations ranged from 7.5 to 11 ng/mL over 12 months. Overall, total systemic exposures to dapsone and its metabolites were approximately 100-fold less for dapsone gel than for oral dapsone, even in the presence of trimethoprim/sulfamethoxazole. There were no reports of any haematological adverse events. Topical application of dapsone gel in various settings ranging from 2 weeks to 12 months resulted in systemic exposures to dapsone and its metabolites that were approximately 100-fold less than those after oral dapsone at a therapeutic dose level. The concentrations of dapsone and its metabolites reached steady state and did not increase during prolonged treatment.


Transferrin, iron, and dermatophytes. I. Serum dematophyte inhibitory component definitively identified as unsaturated transferrin.
The factor present in normal human serum which inhibits growth of dematophytic fungi is characterized and identified. Serum inhibitory factor (SIF) is nondialyzable, heat stable at 56 degrees C. for 4 hours, and fungistatic. SIF was found to be an inhibitor of the dermatophyte genera Trichophyton, Microsporium, and Epidermophyton as well as the dimorphic yeast Candida albicans. SIF activity directly correlated with a serum's unbound iron-binding capacity (UIBC) in that lower UIBC'S were less inhibitory. Addition of iron to serum neutralized the inhibitory activity and this neutrilization was shown to be specific for iron since zinc, magnesium, managnese, and copper failed to alter serum inhibitory activity. Furthermore, addition of purified iron-free transferrin to a neutralized serum restored the SIF activity in parallel with the UIBC. Removal of transferrin from serum by affinity chromatography was confirmed by polyacrylamide gel electrophoresis and iron-binding assays. Transferrin-free serum produced by this procedure was shown to lack inhibitory activity. These data indicate that SIF is unsaturated transferrin and strongly suggests that it inhibits dermatophytes by binding iron which many organisms need for growth.


Release from perceptual masking for children and adults: benefit of a carrier phrase.
The purpose of this study was to test the hypothesis that a carrier phrase can improve word recognition performance for both children and adults by providing an auditory grouping cue. It was hypothesized that the carrier phrase would benefit listeners under conditions in which they have difficulty in perceptually separating the target word from the competing background. To test this hypothesis, word recognition was examined for maskers that were believed to vary in their ability to create perceptual masking. In addition to determining the conditions under which a carrier-phrase benefit is obtained, age-related differences in both susceptibility to masking and carrier-phrase benefit were examined. Two experiments were conducted to characterize developmental effects in the ability to benefit from a carrier phrase (i.e., "say the word") before the target word. Using an open-set task, word recognition performance was measured for three listener age groups: 5- to 7-year-old children, 8- to 10-year-old children, and adults (18-30 years). For all experiments, target words were presented in each of two carrier-phrase conditions: (1) carrier-present and (2) carrier-absent. Across experiments, word recognition performance was assessed in the presence of multi-talker babble (Experiment 1), two-talker speech (Experiment 2), or speech-shaped noise (Experiment 2). Children's word recognition performance was generally poorer than that of adults for all three masker conditions. Differences between the two age groups of children were seen for both speech-shaped noise and multi-talker babble, with 5- to 7-year-olds performing more poorly than 8- to 10-year-olds. However, 5- to 7-year-olds and 8- to 10-year-olds performed similarly for the two-talker masker. Despite developmental effects in susceptibility to masking, both groups of children and adults showed a carrier-phrase benefit in multi-talker babble (Experiment 1) and in the two-talker masker (Experiment 2). The magnitude of the carrier-phrase benefit was similar for a given masker type across age groups, but the carrier-phrase benefit was greater in the presence of the two-talker masker than in multi-talker babble. Specifically, the children's average carrier-phrase benefit was 7.1% for multi-talker and 16.8% for the two-talker masker condition. No carrier-phrase benefit was observed for any age group in the presence of speech-shaped noise. Effects of auditory masking on word recognition performance were greater for children than for adults. The time course of development for susceptibility to masking seems to be more prolonged for a two-talker speech masker than for multi-talker babble or speech-shaped noise. Unique to the present study, this work suggests that a carrier phrase can provide an effective auditory grouping cue for both children and adults under conditions expected to produce substantial perceptual masking.


HGF/c-Met signaling mediated mesenchymal stem cell-induced liver recovery in intestinal ischemia reperfusion model.
Liver injury triggered by intestinal ischemia-reperfusion (IIR) usually presage multiorgan dysfunction and death in patients. Recent studies suggest mesenchymal stem cells (MSCs) possess a protective potential against organ damage. Since relative evidence is insufficient and the mechanism is not well understood, we investigated the effect of hepatocyte growth factor c-Met signaling (HGF/c-Met) on recruitment of MSCs and subsequent protection against liver injury triggered by IIR in a rat model. IIR models were built as rats were subjected to 75 min of superior mesenteric artery occlusion and subsequent 4 h reperfusion. Either of pure MSCs and MSCs pretreated with HGF or SU11274 (c-Met inhibitor) were injected into rat models. Biochemical and pathologic alterations of liver in IIR model were measured to evaluate the therapeutic effect of MSCs and drug treatment. Concurrently, the effect of HGF and SU11274 on c-Met and phosphorylated Met expression in MSCs and MSCs migration were assessed in in vitro experiment. IIR-induced liver injury was manifested by significant increase in serum ALT, AST and HGF levels as well as pathological change. MSCs with highly c-Met expression ameliorated the increase of serum transaminase levels and hepatic histopathological change, while SU11274 weaken these effects. HGF upregulated c-Met and phosphorylated Met expression in MSCs and enhanced its liver protection effect. Transwell assays demonstrated HGF promoted MSCs migration, which was blocked by SU11274. HGF/c-Met signaling pathway plays an essential role in the homing of MSCs towards injured liver triggered by intestinal ischemia-reperfusion, and then mediates MSC-induced liver repair.


Selective neuronal vulnerability to oxidative stress in the brain.
Oxidative stress (OS), caused by the imbalance between the generation and detoxification of reactive oxygen and nitrogen species (ROS/RNS), plays an important role in brain aging, neurodegenerative diseases, and other related adverse conditions, such as ischemia. While ROS/RNS serve as signaling molecules at physiological levels, an excessive amount of these molecules leads to oxidative modification and, therefore, dysfunction of proteins, nucleic acids, and lipids. The response of neurons to this pervasive stress, however, is not uniform in the brain. While many brain neurons can cope with a rise in OS, there are select populations of neurons in the brain that are vulnerable. Because of their selective vulnerability, these neurons are usually the first to exhibit functional decline and cell death during normal aging, or in age-associated neurodegenerative diseases, such as Alzheimer's disease. Understanding the molecular and cellular mechanisms of selective neuronal vulnerability (SNV) to OS is important in the development of future intervention approaches to protect such vulnerable neurons from the stresses of the aging process and the pathological states that lead to neurodegeneration. In this review, the currently known molecular and cellular factors that contribute to SNV to OS are summarized. Included among the major underlying factors are high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response in vulnerable neurons. The contribution to the selective vulnerability of neurons to OS by other intrinsic or extrinsic factors, such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity, are also discussed.


Blood lactate concentration and clearance in elite swimmers during competition.
Blood lactate concentration, [BLa], after swimming events might be influenced by demographic features and characteristics of the swim race, whereas active recovery enhances blood lactate removal. Our aims were to (1) examine how sex, age, race distance, and swim stroke influenced [BLa] after competitive swimming events and (2) develop a practical model based on recovery swim distance to optimize blood lactate removal. We retrospectively analyzed postrace [BLa] from 100 swimmers who competed in the finals at the Canadian Swim Championships. [BLa] was also assessed repeatedly during the active recovery. Generalized estimating equations were used to evaluate the relationship between postrace [BLa] with independent variables. Postrace [BLa] was highest following 100-200 m events and lowest after 50 and 1500 m races. A sex effect for postrace [BLa] was observed only for freestyle events. There was a negligible effect of age on postrace [BLa]. A model was developed to estimate an expected change in [BLa] during active recovery (male = 0; female = 1): [BLa] change after active recovery = -3.374 + (1.162 × sex) + (0.789 × postrace [BLa]) + (0.003 × active recovery distance). These findings indicate that swimmers competing at an elite standard display similar postrace [BLa] and that there is little effect of age on postrace [BLa] in competitive swimmers aged 14 to 29 y.


Measurement of generic patient reported outcome measures (PROMs) in an acute admission unit: A feasibility study.
Measuring patient-reported outcome measures (PROMs) is a challenge in Acute Admission Units (AAUs), where patients present with a variety of pathologies. Generic PROMs may be used to measure the quality of care in this population. The main objective of this study was to assess the feasibility of measuring generic PROMs in a Dutch AAU. Longitudinal cohort study Setting: An AAU of a tertiary hospital in Amsterdam, the Netherlands Participants: 123 patients admitted to the AAU during 5 weeks in May and June 2015 METHODS: Patients admitted to the AAU were asked to fill out a questionnaire relating to three time points: 7 days before, during, and within 2 weeks after admission. Additionally, patients were asked to report on their experienced level of safety on the AAU and the contribution of the AAU to their recovery. There were significant trends in generic PROMs for all three domains. Physical functioning decreased during hospital admission and almost fully returned to the previous level after discharge. Satisfaction with social role and anxiety significantly decreased over time. Measuring generic PROMs in the AAU is feasible. The analysis of the PROMs took little effort and results could be reported back to the healthcare workers on the AAU quickly. Patients appreciated being asked about their own perceived health and the quality of care. Given that this is the first study focusing on PROMs in AAU patients in the Netherlands, future studies with larger sample sizes, and from other nations are needed to further investigate PROMs in this patient group to establish International reference values.


Lymphocele after anterior lumbar interbody fusion: a review of 1322 patients.
Anterior lumbar interbody fusion (ALIF) is an effective surgical modality for many lumbar degenerative pathologies, but a rare and infrequently reported complication is postoperative lymphocele. The goals of the present study were to review a large consecutive series of patients who underwent ALIF at a high-volume institution, estimate the rate of lymphocele occurrence after ALIF, and investigate the outcomes of patients who developed lymphocele after ALIF. A retrospective review of the electronic medical record was completed, identifying all patients (≥ 18 years old) who underwent at a minimum a single-level ALIF from 2012 through 2019. Postoperative spinal and abdominal images, as well as radiologist reports, were reviewed for mention of lymphocele. Clinical data were collected and reported. A total of 1322 patients underwent a minimum 1-level ALIF. Of these patients, 937 (70.9%) had either postoperative abdominal or lumbar spine images, and the resulting lymphocele incidence was 2.1% (20/937 patients). The mean ± SD age was 67 ± 10.9 years, and the male/female ratio was 1:1. Patients with lymphocele were significantly older than those without lymphocele (66.9 vs 58.9 years, p = 0.006). In addition, patients with lymphocele had a greater number of mean levels fused (2.5 vs 1.8, p < 0.001) and were more likely to have undergone ALIF at L2-4 (95.0% vs 66.4%, p = 0.007) than patients without lymphocele. On subsequent multivariate analysis, age (OR 1.07, 95% CI 1.01-1.12, p = 0.013), BMI (OR 1.10, 95% CI 1.01-1.18, p = 0.021), and number of levels fused (OR 1.82, 95% CI 1.05-3.14, p = 0.032) were independent prognosticators of postoperative lymphocele development. Patients with symptomatic lymphocele were successfully treated with either interventional radiology (IR) drainage and/or sclerosis therapy and achieved radiographic resolution. The mean ± SD length of hospital stay was 9.1 ± 5.2 days. Ten patients (50%) were postoperatively discharged to a rehabilitation center: 8 patients (40%) were discharged to home, 1 (5%) to a skilled nursing facility, and 1 (5%) to a long-term acute care facility. After ALIF, 2.1% of patients were diagnosed with radiographically identified postoperative lymphocele and had risk factors such as increased age, BMI, and number of levels fused. Most patients presented within 1 month postoperatively, and their clinical presentations included abdominal pain, abdominal distension, and/or wound complications. Of note, 25% of identified lymphoceles were discovered incidentally. Patients with symptomatic lymphocele were successfully treated with either IR drainage and/or sclerosis therapy and achieved radiographic resolution.


Beyond the Warburg Effect: Oxidative and Glycolytic Phenotypes Coexist within the Metabolic Heterogeneity of Glioblastoma.
Glioblastoma (GBM) is the most aggressive primary brain tumor, with a median survival at diagnosis of 16-20 months. Metabolism represents a new attractive therapeutic target; however, due to high intratumoral heterogeneity, the application of metabolic drugs in GBM is challenging. We characterized the basal bioenergetic metabolism and antiproliferative potential of metformin (MF), dichloroacetate (DCA), sodium oxamate (SOD) and diazo-5-oxo-L-norleucine (DON) in three distinct glioma stem cells (GSCs) (GBM18, GBM27, GBM38), as well as U87MG. GBM27, a highly oxidative cell line, was the most resistant to all treatments, except DON. GBM18 and GBM38, Warburg-like GSCs, were sensitive to MF and DCA, respectively. Resistance to DON was not correlated with basal metabolic phenotypes. In combinatory experiments, radiomimetic bleomycin exhibited therapeutically relevant synergistic effects with MF, DCA and DON in GBM27 and DON in all other cell lines. MF and DCA shifted the metabolism of treated cells towards glycolysis or oxidation, respectively. DON consistently decreased total ATP production. Our study highlights the need for a better characterization of GBM from a metabolic perspective. Metabolic therapy should focus on both glycolytic and oxidative subpopulations of GSCs.


The role of mast cells in bronchial asthma: mechanisms and possible therapeutic implications.
The role of mast cells in human biology is important and complex. They probably play a dual role both in protecting the host and in causing disease symptoms. For example: mast-cell-mediated vasopermeability is an important manifestation of asthma, but it also provides access of antibody and other blood factors which are brought to the tissue and help in defense. Therefore, these cells, with their abundant mediators, may play an important role in both homeostasis and disease.


Child care subsidies and the school readiness of children of immigrants.
This study is the first to test whether receipt of a federal child care subsidy is associated with children of immigrants' school readiness skills. Using nationally representative data (n ≈ 2,900), this study estimates the associations between subsidy receipt at age 4 and kindergarten cognitive and social outcomes, for children of immigrant versus native-born parents. Among children of immigrants, subsidized center-based care (vs. subsidized and unsubsidized home-based care) was positively linked with reading. Among children of native-born parents, those in subsidized center care displayed poorer math skills than those in unsubsidized centers, and more externalizing problems than those in unsubsidized home-based care.


[Productive social activities in mothers of intellectually disabled children moderate the relationship between caregiver burden and self-rated health].
Recently, the length of time for which intellectually disabled children receive homecare has increased; hence, the mothers caring for these intellectually disabled children at home are being exposed to increasingly heavy caregiver burden. Previous studies have reported that negative psychological states, including caregiver burden, influence self-rated health status; however, when elderly people engaged in productive social activities, they experienced heightened positive psychological states. Therefore, the objective of this study was to investigate whether mothers' participation in productive social activities influenced the relationship between caregiver burden and self-rated health status. We performed a cross-sectional study using a questionnaire that included items on self-rated health, the modified Japanese version of the Zarit Caregiver Burden Interview, productive social activities, and various confounding variables. We sent the questionnaires to 270 mothers belonging to patient and family advocacy groups. We then compared the self-rated health and caregiver burden between a group of mothers involved in productive social activities and a group not involved in such activities. The relationships between self-rated health, caregiver burden, and productive social activities were analyzed using analysis of variance (ANOVA) and post-hoc testing. We obtained 120 valid responses. Mothers with greater burden had worse self-rated health than the other group (r=-0.305). According to the ANOVA results, the self-rated health of mothers involved in productive social activities did not significantly differ between caregiver burden groups (mild burden group: 3.4 vs. severe burden group: 3.12; F=1.3, P=.253), whereas the self-rated health of mothers without productive social activities showed a significant difference between caregiver burden groups (mild burden group: 3.4 vs. severe burden group: 2.7; F=5.6, P=.017). Mothers with greater burden had worse self-rated health. However, in mothers who were engaged in productive social activities, self-rated health did not differ between the mild burden and severe burden groups. Therefore, productive social activities can favorably moderate the relationship between caregiver burden and self-rated health.


Association between smoking and health outcomes in an economically deprived population: the Liverpool Lung Project.
The association between smoking and several health outcomes among those from the most deprived communities in the UK has not previously been detailed. The aim of this study is to examine the impact of smoking on health outcomes specifically among a particularly deprived population in a developed country (Liverpool; one of the most deprived local authorities in England). The Liverpool Lung Project recruited a prospective cohort of 8753 participants from across Liverpool, aged 45-79 years between 1998 and 2008. Participants were followed annually through the Hospital Episode Statistics until 31 January 2013. Logistic regression models were used to identify health outcomes of smoking. From our study population, 5195 were smokers and 3558 were non-smokers. Smoking was associated with male gender (OR 1.62, 95% CI 1.48 to 1.77), pneumonia (1.28, 95% CI 1.10 to 1.49), chronic obstructive pulmonary disease (1.30, 95% CI 1.14 to 1.48), emphysema (5.46, 95% CI 3.48 to 8.55), bronchitis (1.85, 95% CI 1.65 to 2.07), other cancers (1.69, 95% CI 1.44 to 1.99), lung cancer (6.0, 95% CI 3.72 to 9.69), diabetes (1.21, 95% CI 1.02 to 1.43) and cardiovascular disease (1.45, 95% CI 1.25 to 1.67). Smokers from deprived backgrounds in Liverpool showed increased risk of developing pneumonia, emphysema, chronic obstructive pulmonary disease, bronchitis, lung cancer, other types of cancer, cardiovascular disease and diabetes. These findings are in line with the literature and may help to inform public health policies and ultimately work towards addressing smoking-related health inequalities.


Activin A suppresses osteoblast mineralization capacity by altering extracellular matrix (ECM) composition and impairing matrix vesicle (MV) production.
During bone formation, osteoblasts deposit an extracellular matrix (ECM) that is mineralized via a process involving production and secretion of highly specialized matrix vesicles (MVs). Activin A, a transforming growth factor-β (TGF-β) superfamily member, was previously shown to have inhibitory effects in human bone formation models through unclear mechanisms. We investigated these mechanisms elicited by activin A during in vitro osteogenic differentiation of human mesenchymal stem cells (hMSC). Activin A inhibition of ECM mineralization coincided with a strong decline in alkaline phosphatase (ALP(1)) activity in extracellular compartments, ECM and matrix vesicles. SILAC-based quantitative proteomics disclosed intricate protein composition alterations in the activin A ECM, including changed expression of collagen XII, osteonectin and several cytoskeleton-binding proteins. Moreover, in activin A osteoblasts matrix vesicle production was deficient containing very low expression of annexin proteins. ECM enhanced human mesenchymal stem cell osteogenic development and mineralization. This osteogenic enhancement was significantly decreased when human mesenchymal stem cells were cultured on ECM produced under activin A treatment. These findings demonstrate that activin A targets the ECM maturation phase of osteoblast differentiation resulting ultimately in the inhibition of mineralization. ECM proteins modulated by activin A are not only determinant for bone mineralization but also possess osteoinductive properties that are relevant for bone tissue regeneration.


Computer-assisted quantification of CD3+ T cells in follicular lymphoma.
The advance of high resolution digital scans of pathology slides allowed development of computer based image analysis algorithms that may help pathologists in IHC stains quantification. While very promising, these methods require further refinement before they are implemented in routine clinical setting. Particularly critical is to evaluate algorithm performance in a setting similar to current clinical practice. In this article, we present a pilot study that evaluates the use of a computerized cell quantification method in the clinical estimation of CD3 positive (CD3+) T cells in follicular lymphoma (FL). Our goal is to demonstrate the degree to which computerized quantification is comparable to the practice of estimation by a panel of expert pathologists. The computerized quantification method uses entropy based histogram thresholding to separate brown (CD3+) and blue (CD3-) regions after a color space transformation. A panel of four board-certified hematopathologists evaluated a database of 20 FL images using two different reading methods: visual estimation and manual marking of each CD3+ cell in the images. These image data and the readings provided a reference standard and the range of variability among readers. Sensitivity and specificity measures of the computer's segmentation of CD3+ and CD- T cell are recorded. For all four pathologists, mean sensitivity and specificity measures are 90.97 and 88.38%, respectively. The computerized quantification method agrees more with the manual cell marking as compared to the visual estimations. Statistical comparison between the computerized quantification method and the pathologist readings demonstrated good agreement with correlation coefficient values of 0.81 and 0.96 in terms of Lin's concordance correlation and Spearman's correlation coefficient, respectively. These values are higher than most of those calculated among the pathologists. In the future, the computerized quantification method may be used to investigate the relationship between the overall architectural pattern (i.e., interfollicular vs. follicular) and outcome measures (e.g., overall survival, and time to treatment). © 2017 International Society for Advancement of Cytometry.


[Hemangio-endothelioma of the liver (case report) (author's transl)].
The infantile hemangio-endothelioma (IHE) of the liver, a rare neoplasm, may lead the clinician and the surgeon to suspect the presence of a malignant tumor, whereas histologic examination often reveals a benign condition; our case report illustrates this discrepancy in a 3 1/2-month-old girl suffering from multiple nodules in the liver. Conservative steroid treatment resulted in a marked reduction in tumor size; the girl is in good health more than two years after diagnosis. More than 80% of hepatic IHE are diagnosed during the first six months of life. Hepatomegaly, congestive heart failure and hemangiomas of the skin combine to the classic symptomatic triad. Since the mortality is high in untreated cases, early diagnosis is of importance. IHE may regress spontaneously. Therefore, conservative therapy, such as steroid medication and treatment of the secondary, tumor-induced complications appear indicated. Alternatively, embolization and/or resection of the tumor may be considered. Signs of cardiac or hepatic insufficiency at diagnosis and a low degree of histologic differentiation are of unfavorable prognostic significance.


The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth.
Sarcopenia is a common complication affecting liver disease patients, yet the underlying mechanisms remain unclear. We aimed to elucidate the cellular mechanisms that drive sarcopenia progression using an in vitro model of liver disease. C2C12 myotubes were serum and amino acid starved for 1-h and subsequently conditioned with fasted ex vivo serum from four non-cirrhotic non-alcoholic fatty liver disease patients (NAFLD), four decompensated end-stage liver disease patients (ESLD) and four age-matched healthy controls (CON) for 4- or 24-h. After 4-h C2C12 myotubes were treated with an anabolic stimulus (5 mM leucine) for 30-min. Myotube diameter was reduced following treatment with serum from ESLD compared with CON (−45%) and NAFLD (−35%; p < 0.001 for both). A reduction in maximal mitochondrial respiration (24% and 29%, respectively), coupling efficiency (~12%) and mitophagy (~13%) was identified in myotubes conditioned with NAFLD and ESLD serum compared with CON (p < 0.05 for both). Myostatin (43%, p = 0.04) and MuRF-1 (41%, p = 0.03) protein content was elevated in myotubes treated with ESLD serum compared with CON. Here we highlight a novel, experimental platform to further probe changes in circulating markers associated with liver disease that may drive sarcopenia and develop targeted therapeutic interventions.


High-intensity exercise of short duration alters bovine bone density and shape.
The ability of short-duration high-intensity exercise to stimulate bone formation in confinement was investigated using immature Holstein bull calves as a model. Eighteen bull calves, 8 wk of age, were assigned to one of three treatment groups: 1) group-housed (GR, which served as a control), 2) confined with no exercise (CF), or 3) confined with exercise (EX). The exercise protocol consisted of running 50 m on a concrete surface once daily, 5 d/wk. Confined calves remained stalled for the 42-d duration of the trial. Blood samples were taken to analyze concentrations of osteocalcin and deoxypyridinoline, markers of bone formation and resorption. At the completion of the trial, calves were humanely killed, and both forelegs were collected. The fused third and fourth metacarpal bone was scanned using computed tomography for determination of cross-sectional geometry and bone mineral density. Three-point bending tests to failure were performed on metacarpal bones. The exercise protocol resulted in the formation of a rounder bone in EX as well as in increased dorsal cortex thickness compared with those in the GR and CF. The exercised calves had a significantly smaller medullary cavity than CF and GR (P < 0.01) and a larger percentage of cortical bone area than CF (P < 0.01). Dorsal, palmar, and total bone mineral density was greater in EX than in CF (P < 0.05), and palmar and total bone mineral densities were greater (P < 0.05) in EX than in GR. There was a trend for the bones of EX to have a higher fracture force than CF (P < 0.10). Osteocalcin concentrations normalized from d 0 were higher in EX than CF (P < 0.05). Therefore, the exercise protocol altered bone shape and seemed to increase bone formation comparison with the stalled and group-housed calves.


Role of the alkyl hydroperoxide reductase (ahpCF) gene in oxidative stress defense of the obligate Anaerobe bacteroides fragilis.
In this study we report the identification and role of the alkyl hydroperoxide reductase (ahp) gene in Bacteroides fragilis. The two components of ahp, ahpC, and ahpF, are organized in an operon, and the deduced amino acid sequences revealed that B. fragilis AhpCF shares approximately 60% identity to orthologues in other gram-positive and gram-negative bacteria. Northern blot hybridization analysis of total RNA showed that the ahpCF genes were transcribed as a polycistronic 2.4-kb mRNA and that ahpC also was present as a 0.6-kb monocistronic mRNA. ahpC and ahpCF mRNAs were induced approximately 60-fold following H(2)O(2) treatment or oxygen exposure of the parent strain but were constitutive in a peroxide-resistant strain. Further investigation using an ahpCF'::beta-xylosidase gene transcriptional fusion confirmed that ahpCF had lost normal regulation in the peroxide-resistant strain compared to the parent. The ahpCF mutant was more sensitive to growth inhibition and mutagenesis by organic peroxides than the parent strain, as determined by disk inhibition assays and the frequency of mutation to fusidic acid resistance. This finding suggests that the ahp genes play an important role in peroxide resistance in B. fragilis. Under anaerobic conditions, we observed increases in the number of spontaneous fusidic acid-resistant mutants of five- and sevenfold in ahpCF and ahpF strain backgrounds, respectively, and eightfold in the ahpCF katB double mutant strain compared to the parent and katB strains. In addition, ahpCF, ahpF, and ahpCF katB mutants were slightly more sensitive to oxygen exposure than the parent strain. Moreover, the isolation of a strain with enhanced aerotolerance and high-level resistance to alkyl hydroperoxides from an ahpCF katB parent suggests that the physiological responses to peroxide toxicity and to the toxic effects of molecular oxygen are overlapping and complex in this obligate anaerobe.


"Whose second life is this?" How avatar-based racial cues shape ethno-racial minorities' perception of virtual worlds.
Research on social identity contingencies suggests that situational cues, such as a numerical representation of social identities in a given social environment, can trigger identity-associated threat for individuals whose social identity is marginalized. Given that popular virtual worlds (e.g., Second Life [SL]) are often criticized for White-avatar dominance or White bias, we examined the psychological effects of the alleged White dominance in avatar-based virtual worlds by conducting two experiments in which participants read fictitious profiles of SL resident avatars. White and non-White participants were randomly assigned to view either a set of White-dominant avatar profiles or a set of racially diverse ones. After reading the profiles, participants had an opportunity to customize avatars using the SL interface. The findings of Experiment 1 (n=59) revealed that non-White participants exposed to the White-dominant avatar profiles, when compared with those exposed to the racially diverse profiles, reported significantly lower levels of sense of belonging and intention to participate in SL. Experiment 2 (n=64) demonstrated that non-White participants exposed to the White-dominant avatar profiles gave significantly higher estimation of the White user population within SL; the data also showed that exposure to the White-dominant avatar profiles resulted in a greater sense of limitation on skin customization among non-White participants than among White participants. The present research suggests that ethno-racial minorities, when exposed to avatar-based cues that signal White dominance, may perceive the virtual world as identity threatening, thereby feeling psychologically disconnected and detached from it. Implications regarding racial/ethnic diversity in virtual worlds are discussed.


Covert attention increases spatial resolution with or without masks: support for signal enhancement.
Visual attention can increase spatial resolution even when it leads to a decrease in performance. Whether this effect is mediated by reduction of external noise or by signal enhancement is an unsettled question. Although we previously demonstrated that attention can improve speed and accuracy in an acuity task, those experiments made use of a local postmask, which could be considered a source of external noise. In this work, a peripheral cue improved observers' abilities to indicate which side of a Landolt-square target had a gap whether or not a local postmask was used and with both central- and spread-neutral cues. In addition, we documented the presence of visual field inhomogeneities in a resolution task. Given that these experiments presented the target alone with no external noise added (i.e., without distracters or masks), our results indicate that transient attention enhanced the quality of the stimulus representation. Furthermore, because performance in the Landolt-square task indexes resolution, this attentional benefit indicates that transient attention can produce signal enhancement through finer spatial resolution.


Designing metallic glass matrix composites with high toughness and tensile ductility.
The selection and design of modern high-performance structural engineering materials is driven by optimizing combinations of mechanical properties such as strength, ductility, toughness, elasticity and requirements for predictable and graceful (non-catastrophic) failure in service. Highly processable bulk metallic glasses (BMGs) are a new class of engineering materials and have attracted significant technological interest. Although many BMGs exhibit high strength and show substantial fracture toughness, they lack ductility and fail in an apparently brittle manner in unconstrained loading geometries. For instance, some BMGs exhibit significant plastic deformation in compression or bending tests, but all exhibit negligible plasticity (<0.5% strain) in uniaxial tension. To overcome brittle failure in tension, BMG-matrix composites have been introduced. The inhomogeneous microstructure with isolated dendrites in a BMG matrix stabilizes the glass against the catastrophic failure associated with unlimited extension of a shear band and results in enhanced global plasticity and more graceful failure. Tensile strengths of approximately 1 GPa, tensile ductility of approximately 2-3 per cent, and an enhanced mode I fracture toughness of K(1C) approximately 40 MPa m(1/2) were reported. Building on this approach, we have developed 'designed composites' by matching fundamental mechanical and microstructural length scales. Here, we report titanium-zirconium-based BMG composites with room-temperature tensile ductility exceeding 10 per cent, yield strengths of 1.2-1.5 GPa, K(1C) up to approximately 170 MPa m(1/2), and fracture energies for crack propagation as high as G(1C) approximately 340 kJ m(-2). The K(1C) and G(1C) values equal or surpass those achievable in the toughest titanium or steel alloys, placing BMG composites among the toughest known materials.


A Novel Reverse Periauricular Flap Reconstruction Method That Uses Additional Anastomosis to Avoid Venous Congestion for Periorbital Defects.
The aim of this study was to introduce and evaluate a method to prevent venous congestion in periauricular flap pedicled on the frontal branch of the superficial temporal artery (STA). Flaps based on the STA are therefore extremely versatile in reconstruction of the face and scalp. The literature on reconstructive possibilities provided by temporal flaps describes venous congestion, but there are currently no methods for preventing this problem. In this brief report, we describe a method to anastomose the parietal branch of superficial temporal vein and the middle temporal vein to ensure venous flow when a concomitant vein of the frontal branch of the STA is unavailable. The flap survived without venous congestion and donor sites healed with satisfactory outcomes. Color and texture match of the flap were excellent and morbidity at the donor site was usually minimal. IV.


Renal manifestations in 2007 Korean patients with Behçet's disease.
Behçet's disease (BD) theoretically affects all sizes and types of blood vessels and results in multi-organ involvement. However, renal BD has not been fully characterized, though the kidneys are histologically rich in blood vessels. A total of 2007 patients who fulfilled the diagnostic criteria for BD were enrolled in this study. We reviewed the medical records and test results of the BD patients and used univariate and multivariate logistic regression analyses to determine the clinical significance of renal involvement in BD. Among the 2007 BD patients, we noted hematuria in 412 (20.5%) and proteinuria in 29 (1.4%). Univariate analysis showed that the BD patients with hematuria were predominantly female and older, had higher erythrocyte sedimentation rates (ESRs), and more frequently presented with genital ulcerations. BD patients with proteinuria had higher ESR levels compared to BD patients without proteinuria. In the multivariate analysis, age, sex, and ESR were found to be significantly associated with hematuria in BD patients, whereas only ESR was associated with proteinuria in BD patients. We also found that IgA nephropathy was the most common pathologic diagnosis in 12 renal BD patients who underwent renal biopsies. We suggest that routine urinalysis and serum renal function tests be performed for the early detection of renal BD, especially in older female BD patients with recurrent hematuria, high ESR levels, and frequent genital ulcers, as well as in BD patients with proteinuria and high ESR levels.


Predicting diabetes mellitus using SMOTE and ensemble machine learning approach: The Henry Ford ExercIse Testing (FIT) project.
Machine learning is becoming a popular and important approach in the field of medical research. In this study, we investigate the relative performance of various machine learning methods such as Decision Tree, Naïve Bayes, Logistic Regression, Logistic Model Tree and Random Forests for predicting incident diabetes using medical records of cardiorespiratory fitness. In addition, we apply different techniques to uncover potential predictors of diabetes. This FIT project study used data of 32,555 patients who are free of any known coronary artery disease or heart failure who underwent clinician-referred exercise treadmill stress testing at Henry Ford Health Systems between 1991 and 2009 and had a complete 5-year follow-up. At the completion of the fifth year, 5,099 of those patients have developed diabetes. The dataset contained 62 attributes classified into four categories: demographic characteristics, disease history, medication use history, and stress test vital signs. We developed an Ensembling-based predictive model using 13 attributes that were selected based on their clinical importance, Multiple Linear Regression, and Information Gain Ranking methods. The negative effect of the imbalance class of the constructed model was handled by Synthetic Minority Oversampling Technique (SMOTE). The overall performance of the predictive model classifier was improved by the Ensemble machine learning approach using the Vote method with three Decision Trees (Naïve Bayes Tree, Random Forest, and Logistic Model Tree) and achieved high accuracy of prediction (AUC = 0.92). The study shows the potential of ensembling and SMOTE approaches for predicting incident diabetes using cardiorespiratory fitness data.


Acceptance or rejection of prophylactic medicine in patients with migraine: a cross-sectional study.
Most patients with two or more migraine attacks per month do not use prophylactic medication. The aim of this study is to investigate how many patients use prophylaxis or would like to use them, and which aspects of migraine contribute to the choice to use prophylactic treatment. In a cross-sectional survey in three general practices, patients were selected who were diagnosed with migraine or had prescriptions for migraine medication. A questionnaire was sent to 283 patients and completed by 166 patients, of whom 15 were excluded. A total of 129 females and 22 males were included (median age 41 years). Most patients had two or more attacks per month (66.2%). Fifty-five per cent of patients with two or more attacks per month wanted to use prophylaxis; only 8% actually used this treatment. To get more insight into the ideas for or against prophylactic use, qualitative research is indicated.


Axillary and inguinal striae induced by systemic absorption of a topical corticosteroid.
A 21-year-old woman developed huge atrophic striae in the axillary and inguinal areas from the topical application, with occlusion, of potent corticosteroid preparation applied to the axillary or inguinal areas. It is postulated that the mechanism is systemic absorption of enough medication to produce a state of hyperadrenalism with subsequent striae formation as a sequela.


COVID-19 Pandemic Impact on Care for Stroke in Australia: Emerging Evidence From the Australian Stroke Clinical Registry.
We present information on acute stroke care for the first wave of the COVID-19 pandemic in Australia using data from the Australian Stroke Clinical Registry (AuSCR). The first case of COVID-19 in Australia was recorded in late January 2020 and national restrictions to control the virus commenced in March. To account for seasonal effects of stroke admissions, patient-level data from the registry from January to June 2020 were compared to the same period in 2019 (historical-control) from 61 public hospitals. We compared periods using descriptive statistics and performed interrupted time series analyses. Perceptions of stroke clinicians were obtained from 53/72 (74%) hospitals participating in the AuSCR (80% nurses) via a voluntary, electronic feedback survey. Survey data were summarized to provide contextual information for the registry-based analysis. Data from the registry covered locations that had 91% of Australian COVID-19 cases to the end of June 2020. For the historical-control period, 9,308 episodes of care were compared with the pandemic period (8,992 episodes). Patient characteristics were similar for each cohort (median age: 75 years; 56% male; ischemic stroke 69%). Treatment in stroke units decreased progressively during the pandemic period (control: 76% pandemic: 70%, p < 0.001). Clinical staff reported fewer resources available for stroke including 10% reporting reduced stroke unit beds. Several time-based metrics were unchanged whereas door-to-needle times were longer during the peak pandemic period (March-April, 2020; 82 min, control: 74 min, p = 0.012). Our data emphasize the need to maintain appropriate acute stroke care during times of national emergency such as pandemic management.


Arthroscopic Hip Revision Surgery for Residual Femoroacetabular Impingement (FAI): Surgical Outcomes Compared With a Matched Cohort After Primary Arthroscopic FAI Correction.
There are limited data reporting outcomes after revision arthroscopic surgery for residual femoroacetabular impingement (FAI). (1) Revision arthroscopic FAI correction results in improved outcomes, but they are inferior to those of primary arthroscopic FAI correction. (2) Improved postrevision radiographic parameters are predictive of better outcomes. Cohort study; Level of evidence, 3. Patients who underwent arthroscopic hip revision for residual FAI were reviewed. Pathomorphological findings, intraoperative findings, and preoperative and postoperative modified Harris Hip Score (MHHS), Short Form-12 (SF-12), and pain on a visual analog scale (VAS) values were evaluated. Outcomes after revision arthroscopic FAI correction were compared with outcomes of a matched cohort who underwent primary arthroscopic FAI correction. A total of 79 patients (85 hips) with a mean age of 29.5 years underwent arthroscopic revision FAI correction (mean follow-up, 26 months). The labrum was debrided (27 hips), repaired (49 hips), or reconstructed (7 hips). Two labrums were stable and required no treatment. The results of revision arthroscopic FAI correction were compared with those of 220 age- and sex-matched patients (237 hips) who underwent primary arthroscopic FAI correction (mean follow-up, 23 months). The mean improvement in outcome scores after revision FAI correction was 17.8 (MHHS), 12.5 (SF-12), and 1.4 (VAS) points compared with 23.4 (MHHS), 19.7 (SF-12), and 4.6 (VAS) points after primary arthroscopic FAI correction. The mean improvement was significantly better in the primary cohort compared with the revision cohort (P < .01 for MHHS, SF-12, and VAS values). Good/excellent results were achieved in 81.7% of the primary cohort and 62.7% of the revision cohort (P < .01). Greater postoperative head-neck offset (P = .024), subspine/anterior inferior iliac spine (AIIS) decompression (P = .014), labral repair/reconstruction (P = .009), and capsular plication (P = .032) were significant predictors for better outcomes after revision surgery. Arthroscopic hip revision surgery for residual FAI yielded significantly improved outcome measures, but these were inferior to those after primary arthroscopic FAI corrective surgery. Improved femoral head-neck offset after cam decompression, identification and treatment of subspine/AIIS impingement, labral preservation/reconstruction, and capsular preservation/plication may be paramount to achieve satisfactory outcomes.


Helicobacter pylori-associated gastroduodenal disease in childhood.
Helicobacter pylori is responsible for one of the most frequently encountered infectious diseases worldwide. Infection due to H pylori can lead to the development of gastritis and peptic ulcer disease. The presence of H pylori in the human stomach also represents an increased risk for gastric cancer and gastric lymphoma. Recent epidemiologic data obtained in adults suggest that the actual colonization with H pylori is in fact determined by childhood factors. Therefore, the pediatric age group represents the ideal target population for studies concerning the pathogenesis and epidemiology of H pylori infection. This review addresses the spectrum of H pylori-associated gastroduodenal disease in childhood.


Influence of weekend lifestyle patterns on body weight.
To determine whether alterations in diet and/or activity patterns during weekends contribute to weight gain or hinder weight loss. Randomized, controlled trial comparing 1 year of caloric restriction (CR) with 1 year of daily exercise (EX). Subjects included 48 healthy adults (30F, 18M) aged 50-60 years with BMI 23.5-29.9 kg/m(2). Body weight was measured on 7 consecutive mornings for a total of 165 weeks at baseline and 437 weeks during the 1-year interventions. Daily weight changes were calculated for weekends (Friday to Monday) and weekdays (Monday to Friday). Daily energy intake was estimated using food diaries; daily physical activity was measured using accelerometers. Both measures were validated against doubly labeled water (DLW). At baseline, participants consistently gained weight on weekend days (+0.06 +/- 0.03 kg/day, (mean +/- s.e.), P = 0.02), but not on weekdays (-0.02 +/- 0.02 kg/day, P = 0.18). This was attributable to higher dietary intake on Saturdays and lower physical activity on Sundays relative to weekdays (both P < 0.05). During the interventions, both CR and EX participants were in negative energy balance on weekdays (P < 0.005). On weekends, however, CR participants stopped losing weight, and EX participants gained weight (+0.08 +/- 0.03 kg/day, P < 0.0001) due to higher dietary intakes on weekends. This helps to explain the slower-than-expected rate of weight loss during the interventions. Alterations in lifestyle behaviors on weekends contribute to weight gain or cessation of weight loss on weekends. These results provide one explanation for the relatively slow rates of weight loss observed in many studies, and the difficulty with maintaining significant weight loss.


The current state of pancreas transplantation.
For many patients with type 1 diabetes mellitus and selected patients with type 2 diabetes mellitus, a successful pancreas transplant is the only definitive long-term treatment that both restores euglycaemia without the risk of severe hypoglycaemia and prevents, halts or reverses secondary complications. These benefits come at the cost of major surgery and lifelong immunosuppression. Nevertheless, pancreas transplants are safe and effective, with patient survival rates currently >95% at 1 year and >88% at 5 years; graft survival rates are almost 85% at 1 year and >60% at 5 years. The estimated half-life of a pancreas graft is now 7-14 years. The improvements in graft survival are attributable to considerable reductions in technical failures and in immunologic graft losses. Pancreas recipients have reduced mortality compared with waiting candidates or patients with diabetes mellitus who undergo a kidney transplant alone. Pancreas transplants should be more frequently offered to nonuraemic patients with brittle diabetes mellitus to prevent the development of secondary diabetic complications and to avoid the need for a kidney transplant. Although the results of islet transplantation have also improved, islet recipients rarely maintain long-term insulin independence despite the use of multiple organ donor pancreases. Pancreas transplants and islet transplants should be considered complementary, not mutually exclusive, procedures that are chosen on the basis of the individual patient's surgical risk.


Virtual rapid response: the next evolution of tele-ICU.
The first of its kind in the Veterans Affairs (VA) system, the Denver VA Medical Center's tele-intensive care unit (ICU) program is unique because it is entirely nurse driven. A nontraditional tele-ICU model, the program was tailored to meet the needs of rural veterans by using critical care nursing expertise in Denver, Colorado. An experienced CCRN-certified nurse manages the system 24 hours a day, 7 days a week, from Eastern Colorado Health Care System. The virtual ICU provides rapid response interventions through virtual technology. This tele-ICU technology allows for a "virtual handshake" by nursing staff at the start of the shift and a report on potential patient issues. Clinical relationships have been strengthened between all 5 VA facilities in the Rocky Mountain Region, increasing the likelihood of early consultation at the onset of clinical decline of a patient. In addition, the tele-ICU nurse is available for immediate nursing consultation and support, coordinates point-to-point virtual consultation between physicians at the rural sites and specialists in Denver, and assists in expediting critical care transfers. The primary objectives for the tele-ICU program include improving quality and access of care to critical care services in rural sites, reducing community fee basis costs and frequency of transfers, and increasing collaboration and collegiality among nursing and medical staff in all Region 19's medical centers.


Comprehensive effects of climate, land use/cover and management practices on runoff and nutrient variations in a rapidly urbanizing watershed.
As non-point source pollution has emerged as a significant global and regional concern, climate change (CC), land use/cover transformation (LUCT), and management practices (MP) play vital roles in addressing nutrient pollution. However, current studies lack comprehensive quantification and consistent conclusions on the response to these factors, especially for management practices. To quantify and elucidate the impact of representative environmental factors on rapidly urbanizing regions, this study focused on the Shenzhen River, which serves as the most typical urbanizing watershed. Using a process-based distributed hydrological model with a factor-controlled simulation method, we identified significant differences in nutrient concentrations and the impacts of climate variability, land use/cover changes, and anthropogenic interventions from 2003 to 2020. Moreover, effective measures greatly improved water quality in the Shenzhen River during study period, as evident from trend and cluster analysis. However, ecological water supplements implemented since 2016 have led to a slight reduction in simulated runoff performance, and CC may amplify the synergistic effects of precipitation and temperature on the river system. While the implemented practices have been effective in reducing total nitrogen (TN) and total phosphorus (TP) loads, strong TN pollution control is still needed in rapidly urbanizing areas due to the results of land use/cover type changes. Our findings emphasize the intricate interplay among CC, LUCT, and MP in shaping water quality and hydrological processes in rapidly urbanizing watersheds, and clarify the independent effects of these factors on nutrients. This study contributes to a better understanding of the complex interactions between multiple factors in watersheds and provides guidance for sustainable watershed management.


Development of Trust in an Online Breast Cancer Forum: A Qualitative Study.
Online health forums provide peer support for a range of medical conditions including life-threatening and terminal illnesses. Trust is an important component of peer-to-peer support, although relatively little is known about how trust forms within online health forums. The aim of this paper is to examine how trust develops and influences sharing among users of an online breast cancer forum. An interpretive qualitative approach was adopted. Data were collected from forum posts from 135 threads on 9 boards on the UK charity, Breast Cancer Care (BCC). Semistructured interviews were conducted with 14 BCC forum users. Both datasets were analyzed thematically using Braun and Clarke's approach and combined to triangulate analysis. Trust operates in 3 dimensions, structural, relational, and temporal, and these intersect with each other and do not operate in isolation. The structural dimension relates to how the affordances and formal rules of the site affected trust. The relational dimension refers to how trust was necessarily experienced in interactions with other forum users: it emerged within relationships and was a social phenomenon. The temporal dimension relates to how trust changed over time and was influenced by the length of time users spent on the forum. Trust is a process that changes over time and which is influenced by structural features of the forum, as well as informal but collectively understood relational interactions among forum users. The study provides a better understanding of how the intersecting structural, relational, and temporal aspects that support the development of trust facilitate sharing in online environments. These findings will help organizations developing online health forums.


Potassium accumulation in muscle: a test of the binding hypothesis.
Living frog skeletal muscle can accumulate potassium in vitro to concentrations up to 580 millimolar. Both the amount of potassium accumulated and the relationship between intracellular and extracellular potassium concentrations indicate that potassium is "free" under all conditions, rather than bound to cellular macromolecules. The data also indicate that at most 20 percent of the cell water is "bound" in the sense that it excludes electrolytes.


General populations' preferences for colorectal cancer screening: rationale and protocol for the discrete choice experiment in the SIGMO study.
In Germany, the organised colorectal cancer (CRC) screening programme includes the immunologic faecal occult blood test and colonoscopy. The sigmoidoscopy is recommended for individuals rejecting colonoscopy but is not included into the screening programme. To examine whether the evidence based sigmoidoscopy should be additionally offered, the first objective of this study is to evaluate the demand for sigmoidoscopy by analysing the German general populations' preferences for CRC screening. Preference data will be collected using a discrete choice experiment (DCE). Identification and selection of the attributes and their levels will be supported by evidence resulting from a systematic literature search and focus groups. An efficient, fractional factorial choice design will be generated. In a cross-sectional study, the DCE will be administered as a written questionnaire to a random sample of 4000 members of the statutory health insurance company in Lower Saxony (AOK Lower Saxony). Insured persons 50-60 years of age without CRC or a chronic inflammatory bowel disease will be eligible. The collected choice data will be analysed by conducting a conditional logit regression model and latent class models. Ethical approval for this study was obtained from the Ethics Committee of Hannover Medical School (reference number 8671_BO_K_2019). The study results will be disseminated via conference presentations, publications in peer-reviewed journals and, to participants, the membership magazine of the AOK Lower Saxony. DRKS00019010.


What You See Is What You Hear: Sounds Alter the Contents of Visual Perception.
Visual object recognition is not performed in isolation but depends on prior knowledge and context. Here, we found that auditory context plays a critical role in visual object perception. Using a psychophysical task in which naturalistic sounds were paired with noisy visual inputs, we demonstrated across two experiments (young adults; ns = 18-40 in Experiments 1 and 2, respectively) that the representations of ambiguous visual objects were shifted toward the visual features of an object that were related to the incidental sound. In a series of control experiments, we found that these effects were not driven by decision or response biases (ns = 40-85) nor were they due to top-down expectations (n = 40). Instead, these effects were driven by the continuous integration of audiovisual inputs during perception itself. Together, our results demonstrate that the perceptual experience of visual objects is directly shaped by naturalistic auditory context, which provides independent and diagnostic information about the visual world.


Highly Diastereoselective Synthesis and Application of Functionalized 2,3-Dihydrofuran Derivatives from Enynones and Bis(diazo) Compounds.
A highly efficient Ag(I)-catalyzed cascade Michael addition/cyclization of enynones with 1,3-(bis)diazo compounds has been established, providing functionalized 2,3-dihydrofuran derivatives containing a diazo group and an acetylenic bond with excellent diastereoselectivity. Transformation of the diazo group and hydration of the carbon-carbon triple bond have been performed successfully in different reaction systems.


Exhaled ethane concentration in patients with cancer of the upper gastrointestinal tract - a proof of concept study.
There has been growing interest in the measurement of breath ethane as an optimal non-invasive marker of oxidative stress. High concentrations of various breath alkanes including ethane have been reported in a number of malignancies. Our aim was to investigate the use of novel laser spectroscopy for rapid reporting of exhaled ethane and to determine whether breath ethane concentration is related to a diagnosis of upper gastrointestinal malignancy. Two groups of patients were recruited. Group A (n = 20) had a histo-pathological diagnosis of either esophageal or gastric malignancy. Group B (n = 10) was made up of healthy controls. Breath samples were collected from these subjects and the ethane concentration in these samples was subsequently measured to an accuracy of 0.2 parts per billion, ppb. Group A patients had a corrected exhaled breath ethane concentration of 2.3 +/- 0.8 (mean +/- SEM) ppb. Group B patients registered a mean of 3.1 +/- 0.5 ppb. There was no statistically significant difference between the two groups (p = 0.39). In conclusion, concentrations of ethane in collected breath samples were not significantly elevated in upper gastrointestinal malignancy. The laser spectroscopy system provided a reliable and rapid turnaround for breath sample analysis.


Managing Cutaneous Side Effects From Targeted Molecular Inhibitors for Melanoma and Nonmelanoma Skin Cancer.
Targeted anticancer therapies can cause cutaneous adverse events different from classical chemotherapeutic toxicities. To review the literature on dermatologic adverse events (DAEs) of targeted molecular inhibitors for melanoma and nonmelanoma skin cancers with a focus on management options. A comprehensive literature search related to the side effects and management of these side effects from vemurafenib, dabrafenib, trametinib (BRAF inhibitors), pembrolizumab (antiprogrammed-death-receptor-1 antibody), imatinib (tyrosine kinase inhibitor), ipilimumab (anticytotoxic T-lymphocyte antigen-4 antibody), cetuximab (epidermal growth factor receptor inhibitor), sorafenib (multikinase inhibitor), and vismodegib (smoothened receptor inhibitor). No large controlled studies specifically examining the management of DAEs of targeted molecular inhibitors exist, although there are case report-based recommendations and algorithms developed by expert panels to manage these adverse events. Many options for managing the cutaneous side effects of targeted molecular inhibitors are similar to those used in general dermatology practice. When used effectively, drug dosing and patient quality of life may be optimized.


Media reports on disability: a binational comparison of types and causes of disability as reported in major newspapers.
The study aimed to examine the way in which newspapers in two countries relate to problems of disability and people with disabilities. In particular, we looked at the way the extent, type and focus of newspaper articles in both countries varied with the type and cause of the disability under discussion. A content analysis of over 400 newspaper articles collected over a 3 month period in Canada and Israel was carried out. The findings show that physical disabilities received the most media attention and positive treatment in both countries, followed by psychiatric disabilities and then developmental disabilities. Likewise, disabilities stemming from congenital problems were treated more positively. The Canadian press was somewhat more progressive than the Israeli press at naming individuals with disability, using appropriate labelling and focusing on somewhat more progressive issues. On the other hand, people with developmental disabilities received more favourable treatment in the Israeli press. The press has an important role in reflecting and shaping public attitudes. In many ways media coverage reinforces negative attitudes towards people with disabilities, particularly those with psychiatric and developmental disabilities. While there were some differences between the two countries, overall the results suggest that these tendencies, which have been observed in other countries as well, are not limited by national boundaries.