Acoustical and neural aspects of hearing in the Australian gleaning bats, Macroderma gigas and Nyctophilus gouldi.
1. The maximum acoustic gain of the external ear in Macroderma gigas was found to be 25-30 dB between 5-8 kHz and in Nyctophilus gouldi it reached 15-23 dB between 7-22 kHz. Pinna gain reached a peak of 16 dB near 4.5-6 kHz in M. gigas and 12-17 dB between 7-12 kHz in N. gouldi, with average gain of 6-10 dB up to 100 kHz. Pinna gain curves resemble that of a finite conical horn, including resonance. 2. The directional properties of the external ear in both species result from sound diffraction at the pinna face, as it approximates a circular aperture. The frequency dependent movement of the acoustic axis in azimuth and elevation is attributed to the asymmetrical structure of the pinnae. 3. Evoked potentials and neuronal responses were studied in the inferior colliculus. In M. gigas, the neural audiogram has sensitivity peaks at 10-20 kHz and 35-43 kHz, with extremely low thresholds (-18 dB SPL) in the low frequency region. In N. gouldi, the neural audiogram has sensitivity peaks at 8-14 kHz (lowest threshold 5 dB SPL) and 22-45 kHz. Removal of the contralateral pinna causes a frequency dependent loss in neural threshold sensitivity of up to 10-15 dB in both species. 4. The high frequency peak in the audiogram coincides with the sonar energy band in both species, whereas the low frequency region is used for social communication. Highly sensitive low frequency hearing is discussed in relation to hunting in bats by passive listening.


Attachment as a Core Feature of Resilience: A Systematic Review and Meta-Analysis.
Research has pointed to secure attachment as a possible key factor of resilience in adulthood. We aimed to investigate the role of secure attachment as a potential core feature in the properties of resilience. We conducted a systematic review in accordance with PRISMA guidelines followed by a meta-analysis. Thirty-three studies were included in the review, and 10 of these, including 2305 subjects, were used for meta-analysis. The raw correlation coefficients ranged from .20 to .57, which indicated weak to moderate correlations between resilience and attachment. The synthesized correlation coefficients indicated that the correlations were significant and highly unlikely to be due to random variation. All studies are also reported on qualitatively. In both of our meta-analyses and in the narratively reported studies, we found that secure attachment is associated with the presence of resilience.


Multiple-artery renal transplantation: emphasis on extracorporeal methods of donor arterial reconstruction.
The operative techniques to transplant kidneys with multiple renal arteries and our recent experience with them are reviewed. The preferred methods are anastomosis with a Carrel aortic patch and extracorporeal arterial repair before transplantation. These are simple and effective methods that avoid subjecting the kidney to prolonged ischemia. Revascularization of all renal arteries is important to obviate ischemic allograft complications.


Prolactin receptors in the hypoprolactinemic male rat (IPL nude rat): measurement in testis and induction in liver.
In order to evaluate the importance of PRL in the regulation of its own receptors, characteristics of specific binding for PRL were studied in membrane preparations from liver and testis of a new hypoprolactinemic male rat, the IPL nude male rat, and this was compared to those found for normal male rats. Under basal conditions, hepatic specific binding of PRL in IPL nude rats, as in normal rats was not detectable. Following castration, it became detectable in both groups, and was 6.99 +/- 0.78% and 6.34 +/- 0.87% for IPL nude and normal rats respectively. Under such conditions, the apparent affinity constant (Ka) and the binding capacity (Nmax) obtained were also similar for both groups (Ka) = 1.36 +/- 0.14.10(9) M-1, Nmax = 102 +/- 14 fmol/mg protein in IPL and Ka = 1.34 +/- 0.28.10(9) M-1, Nmax = 97 +/- 11 fmol/mg protein in normal rats) although a decrease in serum levels of PRL was observed in both groups. This decrease was greater for IPL nude rats. As already reported, estradiol injection following castration was able to further increase the percentage of PRL hepatic specific binding (4 times). Furthermore, our results demonstrated that the affinity constant was significantly increased by estradiol injection in both groups. On the other hand, for testicular PRL binding characteristics, a statistically significant difference was found between IPL nude and normal rats. The PRL specific binding percentage was 7.01 +/- 0.85% for the IPL nude rat and 10.07 +/- 0.64% for the normal rat. By Scatchard analysis, the Ka of testicular membranes for labelled oPRL was similar in both groups, while the capacity differed (Nmax = 9.82 +/- 1.25 fmol/mg protein for IPL nude rat and Nmax = 26.06 +/- 4.39 fmol/mg protein for normal rats). These data established the fact that IPL nude male rats presented characteristics of hepatic PRL receptors similar to those of normal rats, while their testicular oPRL binding significantly differed. These findings therefore suggest that in genetic hypoprolactinemic rats (IPL nude rats), PRL might be more involved in the regulation of testicular PRL receptors than in that of hepatic receptors.


Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers.
The health benefits of pomegranate (POM) consumption are attributed to ellagitannins and their metabolites, formed and absorbed in the intestine by the microbiota. In this study twenty healthy participants consumed 1000 mg of POM extract daily for four weeks. Based on urinary and fecal content of the POM metabolite urolithin A (UA), we observed three distinct groups: (1) individuals with no baseline UA presence but induction of UA formation by POM extract consumption (n = 9); (2) baseline UA formation which was enhanced by POM extract consumption (N = 5) and (3) no baseline UA production, which was not inducible (N = 6). Compared to baseline the phylum Actinobacteria was increased and Firmicutes decreased significantly in individuals forming UA (producers). Verrucomicrobia (Akkermansia muciniphila) was 33 and 47-fold higher in stool samples of UA producers compared to non-producers at baseline and after 4 weeks, respectively. In UA producers, the genera Butyrivibrio, Enterobacter, Escherichia, Lactobacillus, Prevotella, Serratia and Veillonella were increased and Collinsella decreased significantly at week 4 compared to baseline. The consumption of pomegranate resulted in the formation of its metabolites in some but not all participants. POM extract consumption may induce health benefits secondary to changes in the microbiota.


A computational model of hemorrhage and dehydration suggests a pathophysiological mechanism: Starling-mediated protein trapping.
We sought to understand the degree to which a single computational cardiovascular model could replicate the typical responses of healthy subjects through a breadth of blood loss patterns and whether such a model could illuminate the cause-effect relationships that underlie the observed responses. The model consisted of compartments for the upper body, lower body, viscera, and kidneys as well as a four-chambered heart and a pulmonary compartment. Transcapillary fluid flux was governed by Starling forces, whereas lymphatic flow was driven by hydrostatic tissue pressure and scaled by a lymphatic activation term. We adjusted parameters based on results from one protocol involving moderate continual blood loss in a canine model. Next, we simulated six additional protocols spanning euvolemic and dehydrated subjects and compared in silico behavior with in vivo hemodynamic responses and fluid shifts. The model was able to replicate group-averaged behavior (i.e., within 1 or 2 SEs) of the rate and quantity of vascular refill and the associated cardiac output during slow, moderate, and rapid ongoing blood losses, the restitution after the cessation of blood loss, and the absence of restitution in dehydrated subjects. The model suggested that the earlier phase of restitution, i.e., transcapillary fluid shifts, was antagonistic to the later phase of restitution, i.e., protein return via lymphatics. This phenomenon was termed "interstitial protein trapping." In conclusion, the model appears valid for a range of blood loss patterns and prehydration states. Further investigation into the in vivo relevance of interstitial protein trapping is justified.


PPARalpha agonists inhibit tissue factor expression in human monocytes and macrophages.
Monocytic tissue factor (TF) expression may contribute to thrombogenicity associated with plaque rupture and may propagate thrombus formation at the site of vascular lesions. Induction of monocytic TF expression by endotoxin is mediated by the activation of transcription factors such as AP-1 and NF-kappaB. Both these signaling pathways are modulated by peroxisome proliferator-activated receptor-alpha (PPARalpha). Therefore, we have studied the effects of fibrates and other PPARalpha agonists on the expression of TF. We show that PPARalpha protein, like primary human monocytes, is also expressed in the human monocytic THP-1 cell line. Fenofibric acid, WY14643, and GW2331 inhibited TF mRNA upregulation after stimulation of THP-1 cells with lipopolysaccharide or interleukin-1ss. In primary human monocytes and macrophages, the lipopolysaccharide- or interleukin-1ss-mediated induction of TF activity was also inhibited by fenofibric acid, WY14643, or GW2331. These data indicate that activation of PPARalpha results in the downregulation of the TF gene. Our results suggest a novel role for PPARalpha in the control of atherosclerotic plaque thrombogenicity through its effects on TF expression in monocytes and macrophages.


Roentgenographic in vitro investigation of frequency and location of curvatures in human maxillary premolars.
The aim of this study was to determine the location of the root canal curvature and measure the distance from the CEJ to the first curvature using in vitro methods. Extracted maxillary premolars (n = 358) were fixed and digitally radiographed using the parallel technique. Excluded from further analysis were teeth with root caries, artificial crowns, extensive fillings, or endodontic treatments. The results were descriptively analyzed and the cumulative frequencies were calculated. The median values of the distance between CEJ and first curvature were for the first right premolars 8.4 mm (buccal) and 8.5 mm (palatal), for the first left premolars 9.1 mm (buccal) and 8.9 mm (palatal). The median distances in the second premolars were 10.7 mm (right side) and 10.2 mm (left side). The results showed that a high number of maxillary premolars had a curvature with a median value of 8 mm apically from the CEJ. Our findings suggest that such measurements may be useful to consider during endodontic treatment and post insertion.


The role of alcohol in unplanned pregnancy.
About 25% of all pregnancies are unplanned. While age, marital status, social class and contraceptive practice have all been considered, little attention has been paid to alcohol as a possible aetiological factor. The present study based on a questionnaire was devised to ascertain the role of alcohol in conception. One hundred and sixteen pregnant women participated and these were attending the ante-natal clinic for the first time. In only 2 cases was alcohol thought to be a likely factor in conception although only a few had never consumed alcohol. A further study on 100 clients attending the regional day care abortion unit revealed that less than one tenth felt that alcohol was a factor in the conception. Unplanned pregnancies may result from alcohol consumption in less than 10% of cases, lack of motivation to use some form of contraception would appear to play a more prominent part.


The evolution of aposematism is accompanied by increased diversification.
Although the use of distinct colors to indicate unprofitability to predators (i.e. aposematism) is commonly thought of as an adaptation, our knowledge of its macroevolutionary effects is limited. Because aposematism is expected to decrease attacks by predators, we hypothesized that aposematic lineages should be larger on average than their non-aposematic sister groups because of the decreased probability of extinction and/or increased probability of speciation (i.e. increased diversification). The results of our sister-group analysis are consistent with the hypothesis that the evolution of aposematism is accompanied by increased diversification of lineages, with the aposematic focal group having more species in 11 of 14 pairs of sister groups. Despite the apparent advantages of reduced predation risk on diversification rates, the evolution of aposematism is relatively rare and reversions to a cryptic state are not uncommon. In addition to the difficulties in evolving a trait that initially decreases the survivorship of prey among naive predators, we discuss other factors that may limit the apparent prevalence and success of aposematism. It is hoped that the results of our analysis will encourage further analyses of the phylogenetic relationships among aposematic groups and their relatives, and of the evolutionary time scales over which the benefits of aposematism are the greatest to lineages with this condition.


The impact of uncertainties in the CT conversion algorithm when predicting proton beam ranges in patients from dose and PET-activity distributions.
The advantages of a finite range of proton beams can only be partly exploited in radiation therapy unless the range can be predicted in patient anatomy with <2 mm accuracy (for non-moving targets). Monte Carlo dose calculation aims at 1-2 mm accuracy in dose prediction, and proton-induced PET imaging aims at ∼2 mm accuracy in range verification. The latter is done using Monte Carlo predicted PET images. Monte Carlo methods are based on CT images to describe patient anatomy. The dose calculation algorithm and the CT resolution/artifacts might affect dose calculation accuracy. Additionally, when using Monte Carlo for PET range verification, the biological decay model and the cross sections for positron emitter production affect predicted PET images. The goal of this work is to study the effect of uncertainties in the CT conversion on the proton beam range predicted by Monte Carlo dose calculations and proton-induced PET signals. Conversion schemes to assign density and elemental composition based on a CT image of the patient define a unique Hounsfield unit (HU) to tissue parameters relationship. Uncertainties are introduced because there is no unique relationship between HU and tissue parameters. In this work, different conversion schemes based on a stoichiometric calibration method as well as different numbers of tissue bins were considered in three head and neck patients. For Monte Carlo dose calculation, the results show close to zero (<0.5 mm) differences in range using different conversion schemes. Further, a reduction of the number of bins used to define individual tissues down to 13 did not affect the accuracy. In the case of simulated PET images we found a more pronounced sensitivity on the CT conversion scheme with a mean fall-off position variation of about 1 mm. We conclude that proton dose distributions based on Monte Carlo calculation are only slightly affected by the uncertainty on density and elemental composition introduced by unique assignment to each HU if a stoichiometric calibration is used. Calculated PET images used for range verification are more sensitive to conversion uncertainties causing an intrinsic limitation due to CT conversion alone of at least 1 mm.


Genetic variation of the Y chromosome in Chibcha-speaking Amerindians of Costa Rica and Panama.
Genetic variation of the Y chromosome in five Chibchan tribes (Bribri, Cabecar, Guaymi, Huetar, and Teribe) of Costa Rica and Panama was analyzed using six microsatellite loci (DYS19, DYS389A, DYS389B, DYS390, DYS391, and DYS393), the Y-chromosome-specific alphoid system (alphah), the Y-chromosome Alu polymorphism (YAP), and a specific pre-Columbian transition (C-->T) (M3 marker) in the DYS 199 locus that defines the Q-M3 haplogroup. Thirty-nine haplotypes were found, resulting in a haplotype diversity of 0.937. The Huetar were the most diverse tribe, probably because of their high levels of interethnic admixture. A candidate founder Y-chromosome haplotype was identified (15.1% of Chibchan chromosomes), with the following constitution: YAP-, DYS199*T, alphah-II, DYS19*13, DYS389A*17, DYS389B*10, DYS390*24, DYS391*10, and DYS393*13. This haplotype is the same as the one described previously as one of the most frequent founder paternal lineages in native American populations. Analysis of molecular variance indicated that the between-population variation was smaller than the within-population variation, and the comparison with mtDNA restriction data showed no evidence of differential structuring between maternally and paternally inherited genes in the Chibchan populations. The mismatch-distribution approach indicated estimated coalescence times of the Y chromosomes of the Q-M3 haplogroup of 3,113 and 13,243 years before present; for the mtDNA-restriction haplotypes the estimated coalescence time was between 7,452 and 9,834 years before present. These results are compatible with the suggested time for the origin of the Chibchan group based on archeological, linguistic, and genetic evidence.


[Biology and pathogenicity of fungi].
Men live with a multitude of fungal species and few species can become parasites. Some species are obligatory pathogenic (dermatophytes, dimorphic fungi...) and the majority is opportunistic pathogen. Host-parasite complex is indissociable. For example, Candida albicans is a commensal of the gastrointestinal tract and can dramatically proliferate when host defences are alterated. Passage from the commensal status to pathogenicity is accompanied by modifications of the fungus, which then act as virulence factors (development of filamentous forms, changes in surface hydrophobicity...). Biologic, genetic and antigenic modifications are also observed. Colonisation and adhesion, penetration, multiplication and survival are necessary for infectiosity in a host. Host defence mechanisms are described with non-specific mechanisms by humoral and cellular factors and more specific immune mechanisms involving antibodies, T lymphocytes and the role of cytokines.


Pachyonychia congenita: a case report of a successful treatment with rosuvastatin in a patient with a KRT6A mutation.
Pachyonychia congenita (PC) is a rare autosomal dominant disorder characterized by nail dystrophy and palmoplantar keratoderma with severe plantar pain affecting quality of life. There is no effective treatment. Heterozygous mutations in the keratin genes KRT6A, KRT6B, KRT6C, KRT16 and KRT17 have been reported as a cause of PC. Herein we present a female patient with an amino acid substitution mutation in KRT6A (c.1381G>A, p.Glu461Lys in exon 7) and classic features of PC associated with oral leucokeratosis and follicular hyperkeratosis. We also demonstrate successful treatment of the patient with rosuvastatin. A 3.6-mm reduction in plantar callosity thickness was demonstrated by sonography. Our patient also experienced significant pain relief that allowed her to increase physical activity (Children's Dermatology Life Quality Index score dropped nine points following treatment). Collectively, these improvements suggest that rosuvastatin may offer a promising treatment for PC. What's already known about this topic? Pachyonychia congenita (PC) is an autosomal dominant disease characterized by nail dystrophy and painful plantar keratoderma. Keratolytics, emollients, retinoids and steroids have been used for treatment but with limited benefits. What does this study add? A patient with PC who had a KRT6A mutation was treated with rosuvastatin with significant improvement in plantar hyperkeratosis and pain. Statins could be a promising treatment for PC with long-term safety, but further studies are needed.


Effect of concentration, pH, and preservative on in vitro transcorneal permeation of ibuprofen and flurbiprofen from non-buffered aqueous drops.
Influence of drug concentration, pH of aqueous drops and some commonly used preservatives on in vitro transcorneal permeation of ibuprofen and flurbiprofen were investigated using goat cornea. Increase in drug concentration in the drops made in normal saline resulted in increase in quantity permeated but decrease in cumulative percent permeation of both drugs. Permeation of each drug from 0.5% drops was maximum at acidic pH (6.4) and decreased with increase in pH of the drops. Normal saline, as a vehicle, favoured permeation of each drug, hence retained in the formulation. Benzalkonium chloride and chlorobutanol enhanced cumulative percent permeation of ibuprofen while benzalkonium chloride and phenyl mercuric nitrate increased permeation of flurbiprofen. Benzalkonium chloride being incompatible with 0.5% drops (pH 6.4) of either drug, chlorobutanol appears suitable for ibuprofen drops and phenyl mercuric nitrate for flurbiprofen drops.


Using cardinality to compare quantities: the role of social-cognitive conflict in early numeracy.
A key question in early number development is how 4- and 5-year-olds learn the roles that counting and cardinal numbers play when comparing quantities. Children who wrongly used length to identify numerosity were assigned to five experimental groups and trained to judge whether a puppet--who sometimes miscounted--created equivalent sets. Over three training sessions, children who were asked to compare sets after they were counted learned to base their judgments on cardinal numbers when the puppet counted accurately by being given feedback. However, only the groups who were also asked to explain either their own or the experimenter's reasoning made progress in identifying the puppet's miscounts. This ability to recognize the importance of counting accuracy for quantitative comparisons predicted whether children would spontaneously count to compare sets on a post-test. The importance of asking children to identify miscounts is discussed alongside the social factors that influence children's recognition of the relationship between procedural counting, cardinality and relative number.


Increased 8-hydroxydeoxyguanosine in high-grade gliomas is associated with activation of autophagy.
To understand the interaction between oxidative stress and autophagy in gliomas of different grades. In the present study, we analyzed levels of oxidative stress in 45 human glioma tumors, using the DNA oxidation marker 8-hydroxydeoxyguanosine (8-OHdG). In addition, we determined activation of autophagy in gliomas samples by assessing expression of microtubule-associated protein 1 light chain-3B (LC3B). To confirm our in vivo findings, in vitro studies using U87 cells were conducted. It was determined that the grade of gliomas, that is, different malignant degrees according to WHO classification, significantly affected level of 8-OHdG. High levels of 8-OHdG were present in high-grade gliomas. This trend was significant in male patients and in young adult patients (<50 years old). Further study showed increased expression of LC3B in high-grade gliomas. In addition, levels of 8-OHdG and expression of LC3B were positively correlated. Reducing autophagic activity by 3-methyladenine resulted in significantly increased intracellular reactive oxygen species (ROS) in U87 cells. Our study provides evidence that high levels of oxidative stress in high-grade gliomas are associated with autophagy activation that may play a protective role promoting the survival of high-grade gliomas under severe oxidative stress.


Growth of perovskite nanocrystals in poly-tetra fluoroethylene based microsystem: on-line and off-line measurements.
Cesium lead halide perovskite nanocrystals are photoelectric nanomaterials that have potential applications in a variety of areas due to their excellent photoelectric and tunable photo luminescent properties. In this work, we investigate the synergetic effects of reaction temperature, reaction-capillary length and flow rate on the growth kinetics of perovskite nanocrystals in a PTFE-based microsystem and the photoluminescence characteristics of the perovskite nanocrystals both on-line and off-line. The on-line measurement finds that increasing the reaction temperature leads to the increase of the wavelength of the PL emission peak of the synthesized nanocrystals and reduces the average size of the perovskite nanocrystals synthesized in long reaction-capillaries. The intensity of the PL emission peak of the nanocrystals synthesized at different reaction temperatures decreases with the increase of the flow rate. The off-line measurement reveals that increasing the flow rate generally leads to the blueshift of the PL emission peaks and the decrease of the average size of the perovskite nanocrystals synthesized at the reaction temperature of 160 °C in the capillary length of 60 cm. Increasing temperature leads to the increase of the emission wavelength of the perovskite nanocrystals from 560 to 608 nm. The temperature dependence of the average size of the synthesized nanocrystals with the same synthesis conditions at different temperatures can be described by the Arrhenius relationship with an activation energy of 8.54 kJ mol-1. Five different cross-sections of the synthesized perovskite nanocrystals are observed, including rhombus, hexagon, rectangle, square and quadrangle with three of them being observed for the first time.


Common Pathogenic Mechanisms Between Idiopathic Pulmonary Fibrosis and Lung Cancer.
Abundant epidemiologic evidence supports an association between idiopathic pulmonary fibrosis (IPF) and lung cancer. Lung tumors in patients with IPF develop preferentially in the periphery immediately adjacent to fibrotic areas, with different histologic distribution and immunohistochemical features compared with non-IPF-associated lung tumors. In this context, evidence indicates that IPF and lung cancer share many pathogenic similarities including genetic and epigenetic markers. It has been suggested that specific germline mutations predispose toward both IPF and lung cancer, leading to imbalance between oncogenes and tumor suppressor genes and ultimately carcinogenesis within fibrotic lungs. Aberrant epigenetic regulation due to methylation, histone modifications, and mainly deregulation of common noncoding RNAs represents a possible pathogenic link between the two disease paradigms. Genetic and epigenetic alterations lead to abnormal activation of common transduction pathways, including Wnt/β-catenin and phosphoinositide 3-kinase/protein kinase B, mediating metaplasia and hyperproliferation in alveolar type II epithelial cells. Cellular transformations in the mesenchymal phenotype represent a common link between lung fibrosis and carcinogenesis. In this review we summarize current data on common cellular and molecular pathogenic mechanisms between IPF and lung cancer and highlight promising therapeutic targets for this disease combination.


The iron content of serum ferritin: physiological importance and diagnostic value.
In this paper we present a method for determining the iron saturation of ferritin as a possible independent predictor of iron stores. Serum ferritin was purified by immunochemical precipitation, and could be completely recovered from serum without any contamination from transferrin. The iron content of the precipitated ferritin was determined by flameless atomic absorption spectrophotometry (FAAS) and the ferritin-iron saturation was calculated using the original serum ferritin concentration. The intra- and inter-assay variation coefficients were 4.2% and 13.4% respectively. The first results with this assay indicate that serum ferritin contains a considerable amount of iron. Furthermore the results show that the iron saturation of ferritin in patients with acute phase response is significantly lower than the saturation found in healthy volunteers (19.3% and 24.3% respectively). These results suggest a possible role for the ferritin-iron saturation in the assessment of iron stores in patients suffering from acute phase response. In addition, the considerable amount of iron in ferritin suggests the need to revise the physiological role of this substance in relation to the serum iron homeostasis.


[Autologous hematopoietic cell transplantation in the Czech Republic].
Transplantations of the autologous hematopoietic cell have been performed in the Czech Republic since 1993. Their total number has increased during the past ten years from 43 to more than three hundred procedures annually. Presented article describes, how the indications for autologous transplants have gradually changed according to the accumulating scientific evidence and it also gives examples of Czech researchers contributing to the advances in this field. Currently, autologous transplants belong to the standard treatment of a number of hemato-oncological diseases and further studies, both national and international, are being performed in Czech Republic. Their aim is to improve this role of the treatment modality in the global care for patients with these diagnoses.


[The role and future task of the occupational health nurse].
The Industrial Safety and Health Act was enacted focusing on occupational disease prevention in 1972. It has been revised over the years to include consideration of work associated diseases, and the participation and cooperation of employer and employees. From now, positive participation of employer-and-employees in occupational health activity becomes important in order to achieve the expanded purpose of the law. It is necessary to empower all workers to be able to perform occupational health activity independently. Florence Nightingale defined nursing in the 1850's. "Nursing is to put the patient in the best condition by improvement of environment, including a population approach. The goal of nursing is to enable the patient to use his faculty fully." The Public Health Nurse is, "assistance to the process of solving one's health, identifying health issues based on a community, using systematic measures which lead to prevention, and aiming at public responsibility." The daily activity of Nurses including Occupational Health Nurses (OHNs) is based on the theory and technology of "empowerment". In promoting the employer-and-employees independent Occupational Safety and Health Activity, the OHN's professional specialty of "empowerment" can play an important role.


Selective depletion of clear synaptic vesicles and enhanced quantal transmitter release at frog motor nerve endings produced by trachynilysin, a protein toxin isolated from stonefish (Synanceia trachynis) venom.
Our previous observation that low concentrations of stonefish (Synanceia trachynis) venom elicit spontaneous quantal acetylcholine release from vertebrate motor nerve terminals prompted our present study to purify the quantal transmitter-releasing toxin present in the venom and to characterize the toxin's ability to alter the ultrastructure and immunoreactivity of frog motor nerve terminals. Fractionation of S. trachynis venom by sequential anion exchange fast protein-liquid chromatography (FPLC) and size-exclusion FPLC yielded a highly purified preparation of a membrane-perturbing (haemolytic) protein toxin, named trachynilysin. Trachynilysin (2-20 micrograms/ml) significantly increased spontaneous quantal acetylcholine release from motor endings, as detected by recording miniature endplate potentials from isolated frog cutaneous pectoris neuromuscular preparations. Ultrastructural analysis of nerve terminals in which quantal acetylcholine release was stimulated to exhaustion by 3 h exposure to trachynilysin revealed swelling of nerve terminals and marked depletion of small clear synaptic vesicles. However, trachynilysin did not induce a parallel depletion of large dense-core vesicles. Large dense core vesicles contained calcitonin gene-related peptide (CGRP), as revealed by colloidal gold immunostaining, and trachynilysin-treated nerve endings exhibited CGRP-like immunofluorescence similar to that of untreated terminals. Our results indicate that the ability of stonefish venom to elicit spontaneous quantal acetylcholine release from vertebrate motor nerve terminals is a function of trachynilysin, which selectively stimulates the release of small clear synaptic vesicles and impairs the recycling of small clear synaptic vesicles but does not affect the release of large dense-core vesicles. Trachynilysin may be a valuable tool for use in other secretory terminals to discriminate between neurotransmitter and neuropeptide release.


Trichinella spp. imported with live animals and meat.
Nematodes of the genus Trichinella are widely distributed throughout the world in omnivorous and carnivorous animals (mammals, birds, and reptiles) and in incidental hosts. To prevent the transmission of these zoonotic parasites to humans, meat samples from Trichinella spp. susceptible animals are tested at the slaughterhouse or in game processing plants. The aim of the present review was to collect documented cases on Trichinella infected animals, meat, or meat derived products which reached the international trade or were illegally introduced from one to another country in personal baggage. In the course of the last 60 years in the international literature, there have been 43 reports of importation of Trichinella spp. infected animals or meat, most of which (60%, 26/43) related to live horses or their meat. Meat or meat derived products from pigs, wild boar and bears, account only for 18.6% (8/43), 4.7% (3/43), and 14.3% (6/43), respectively. However, only live horses or their meat intended for human consumption, meat from a single wild boar, and live polar bears caught in the wild for zoos, were imported through the international market; whereas, meat from pigs, wild boars and bears were illegally introduced in a country in personal baggage. Trichinella infected animals or meat which were officially or illegally introduced in a country were the source of 3443 Trichinella infections in humans in a 40-year period (1975-2014). Most of these infections (96.8%) have been linked to horsemeat consumption, whereas meat from pigs, wild boars and bears accounted only for 2.2%, 0.7% and 0.3% of cases, respectively. This review shows the Trichinella spp. risk in the international animal and meat trade has been linked mainly to horses and only one time to wild boar, if they carcasses are not adequately tested, whereas pigs and other wild animals or their derived products infected with Trichinella spp. are unlikely to reach the international market by the official animal and meat trade.


Posttranscriptional regulation of protein expression in human epithelial carcinoma cells by adenine-uridine-rich elements in the 3'-untranslated region of tumor necrosis factor-alpha messenger RNA.
Eukaryotic mRNAs contain 3'-untranslated regions (UTR) that are involved in posttranscriptional control of gene expression. AU-rich octanucleotide repeats, UUAUUUAU, present in the 3'-UTR of mature lymphokine and other cytokine transcripts, have been implicated in the regulation of mRNA stability and translational efficiency. For example, previous evidence suggests that the AU-rich element (ARE) present in the 3'-UTR of murine tumor necrosis factor-alpha (TNF-alpha) can affect the posttranscriptional regulation of murine TNF-alpha gene expression in hematopoietic cells. Although cytokines are produced in epithelial cells, little is known about the regulation of TNF-alpha and other cytokine gene expression by 3'-UTR elements in human malignant epithelial cells. To better understand the function of the 3'-UTR of the human TNF-alpha gene in the regulation of TNF-alpha protein production in human epithelial cancer cells, a series of luciferase reporter constructs with portions of the 3'-UTR of human TNF-alpha was transfected into human breast carcinoma cell lines ZR-75-1 and ZR-75-1R (which overexpresses TNF-alpha). The 3'-UTR of TNF-alpha markedly suppressed luciferase activity in both cell lines, and the suppression of activity was reversed by deletion of the AU-rich sequences. This suppression was quantitative, with six repeats causing more inhibition than two repeats. Increased levels of luciferase activity were observed 3 h after TNF-alpha stimulation in ZR-75-1 cells transfected by constructs containing AU-rich repeats. In addition, cytoplasmic extracts from both cell lines were assayed for factors that bind to the 3'-UTR of human TNF-alpha mRNA. RNA-protein binding activities were found in both cell lines. Competition studies showed that these proteins specifically bound to AU-rich repeats present in the 3'-UTR of TNF-alpha. No binding activity was observed when the AU-rich repeats were deleted. TNF-alpha exposure markedly increased activity of several RNA-binding proteins, especially a novel Mr 50,000-55,000 RNA-binding protein. The binding activity in untreated ZR-75-1R was higher than that in untreated ZR-75-1 cells, suggesting that the level of RNA-protein binding correlates with the expression level of TNF-alpha in human epithelial cancer cells and that the RNA-binding proteins may control expression of TNF-alpha in ZR-75-1 cells. We conclude that the AU-rich repeats in the 3'-UTR of human TNF-alpha mRNA may regulate gene expression in human epithelial cancer cells by binding to AU sequence-specific proteins, including a previously undescribed Mr 50,000-55,000 protein not observed in hematopoietic cells.


Ain't misbehavin': the effects of age and intentionality on judgments about misconduct.
In 2 person perception experiments, young and older perceivers read a scenario about a young or old female target who leaves a store without paying for a hat. In Experiment 1, the target claims she forgot she was wearing the hat when questioned by the manager. Perceivers thought the manager would have greater sympathy, less anger, and would recommend less punishment when the target was old. In Experiment 2, the target clearly forgot to pay for the hat, clearly stole it, or had ambiguous intentions. In the ambiguous condition, perceivers attributed the young target's behavior more to stealing and the old target's behavior more to forgetting. In the forget condition, young perceivers had equal sympathy for the young and old targets and held them similarly responsible, but older perceivers had greater sympathy for the forgetful old target and held her less responsible than they did the forgetful young target.


Spirometry for the primary care physician.
The clinician wishing to employ a spirometer in the office must be aware of the equipment available and the current standards for validating and maintaining such equipment. Indications for spirometry are fairly frequent in general medical practice for both diagnosis, response to therapy, and for risk assessment prior to surgery. The criteria for characterizing a spirogram as normal, obstructive or restrictive, are well defined. The information obtained may be very helpful to point to additional specific diagnostic studies or to outline a specific treatment plan.


Intraobserver and interobserver repeatability of ocular components measurement in cataract eyes using a new optical low coherence reflectometer.
The purpose of the study was to assess intraobserver and interobserver repeatability of eight ocular components measurement in cataract eyes using the optical low-coherence reflectometer Lenstar LS 900®. Five consecutive measurements of ocular components were taken by two examiners using the Lenstar. Components analyzed were: central corneal thickness, lens thickness, anterior chamber depth, axial length, retinal thickness, keratometry, white-to-white distance, and pupillometry. Within-subject standard deviation and the coefficient of variation were calculated for evaluation of intraobserver repeatability. Bland-Altman analysis was used for assessment of interobserver repeatability. Thirty-two eyes of 22 patients were included. For both observers, the smallest intraobserver coefficient of variation was obtained for axial length, while the largest was found for corneal steepest meridian position. Interobserver repeatability demonstrated less repeatable results for white-to-white distance and corneal steepest meridian position. Considering axial length and anterior chamber depth values, predicted refractive error was 0 ± 0.05 D and 0.02 ± 0.19 D respectively in 95% of observations. The Lenstar LS 900® evidenced excellent repeatability and observers´ independent results of all components analyzed except white-to-white distance and corneal steepest meridian position measurements. To the best of our knowledge, this is the first study on interobserver repeatability of optical low-coherence reflectometry in cataract eyes.


AEG-1/MTDH/LYRIC: A Promiscuous Protein Partner Critical in Cancer, Obesity, and CNS Diseases.
Since its original discovery in 2002, AEG-1/MTDH/LYRIC has emerged as a primary regulator of several diseases including cancer, inflammatory diseases, and neurodegenerative diseases. AEG-1/MTDH/LYRIC has emerged as a key contributory molecule in almost every aspect of cancer progression, including uncontrolled cell growth, evasion of apoptosis, increased cell migration and invasion, angiogenesis, chemoresistance, and metastasis. Additionally, recent studies highlight a seminal role of AEG-1/MTDH/LYRIC in neurodegenerative diseases and obesity. By interacting with multiple protein partners, AEG-1/MTDH/LYRIC plays multifaceted roles in the pathogenesis of a wide variety of diseases. This review discusses the current state of understanding of AEG-1/MTDH/LYRIC regulation and function in cancer and other diseases with a focus on its association/interaction with several pivotal protein partners.


Radical pathway in catecholase activity with zinc-based model complexes of compartmental ligands.
Four dinuclear and three mononuclear Zn(II) complexes of phenol-based compartmental ligands (HL(1)-HL(7)) have been synthesized with the aim to investigate the viability of a radical pathway in catecholase activity. The complexes have been characterized by routine physicochemical studies as well as X-ray single-crystal structure analysis: [Zn(2)(H(2)L(1))(OH)(H(2)O)(NO(3))](NO(3))(3) (1), [Zn(2)L(2)Cl(3)] (2), [Zn(2)L(3)Cl(3)] (3), [Zn(2)(L(4))(2)(CH(3)COO)(2)] (4), [Zn(HL(5))Cl(2)] (5), [Zn(HL(6))Cl(2)] (6), and [Zn(HL(7))Cl(2)] (7) [L(1)-L(3) and L(5)-L(7) = 2,6-bis(R-iminomethyl)-4-methylphenolato, where R= N-ethylpiperazine for L(1), R = 2-(N-ethyl)pyridine for L(2), R = N-ethylpyrrolidine for L(3), R = N-methylbenzene for L(5), R = 2-(N-methyl)thiophene for L(6), R = 2-(N-ethyl)thiophene for L(7), and L(4) = 2-formyl-4-methyl-6-N-methylbenzene-iminomethyl-phenolato]. Catecholase-like activity of the complexes has been investigated in methanol medium by UV-vis spectrophotometric study using 3,5-di-tert-butylcatechol as model substrate. All complexes are highly active in catalyzing the aerobic oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-di-tert-butylbenzoquinone (3,5-DTBQ). Conversion of 3,5-DTBC to 3,5-DTBQ catalyzed by mononuclear complexes (5-7) is observed to proceed via formation of two enzyme-substrate adducts, ES1 and ES2, detected spectroscopically, a finding reported for the first time in any Zn(II) complex catalyzed oxidation of catechol. On the other hand, no such enzyme-substrate adduct has been identified, and 3,5-DTBC to 3,5-DTBQ conversion is observed to be catalyzed by the dinuclear complexes (1-4) very smoothly. EPR experiment suggests generation of radicals in the presence of 3,5-DTBC, and that finding has been strengthened by cyclic voltammetric study. Thus, it may be proposed that the radical pathway is probably responsible for conversion of 3,5-DTBC to 3,5-DTBQ promoted by complexes of redox-innocent Zn(II) ion. The ligand-centered radical generation has further been verified by density functional theory calculation.


Influence of pregnancy after bioprosthetic valve replacement in young women: a prospective five-year study.
Prosthetic heart valve placement in young women does not normally prevent successful pregnancy, though either thrombosis in mechanical prostheses or degeneration in biological prostheses may cause risks for both mother and fetus. Although pericardial prostheses avoid the risks of anticoagulation therapy, it has been suggested that pregnancy accelerates structural degeneration in bioprostheses. The study aim was to assess the influence of pregnancy on five-year outcome after pericardial bioprosthesis replacement. A total of 85 women was studied prospectively over five years from prosthesis implantation, using annual clinical and echocardiographic investigations. Women were allocated to two groups based on pregnancy occurring during follow up: 48 patients (56%; group A) became pregnant, and 37 (44%; group B) did not. At five-year follow up, the clinical events occurred in 29 patients (34.1%): 11 (22.9%) women in group A (mean (+/-SE) linearized rate 3.6+/-0.24%/patient-year (pt-yr)), and 18 (45.6%) in group B (linearized rate 8.6+/-0.30%/pt-yr). Probability of freedom from clinical events was higher (p = 0.0096) in group A (77.9+/-6.1 versus 51.3+/-8.2%). Structural bioprosthesis degeneration, thrombosis or infective endocarditis occurred in 13 patients (27.1%) in group A (linearized rate 2.75+/-0.20%/pt-yr) and 11 (29.7%) in group B (linearized rate 2.5+/-0.18%/pt-yr). Probability of structural bioprosthesis degeneration (e.g. stenosis, calcification or rupture) did not differ (p = 0.6440) between groups (85.4+/-5.1 versus 89.5+/-5.1%), even after age-adjusted analysis (p = 0.3112). Structural changes found at five years after bioprosthesis placement may be attributed to the natural course of the bioprosthesis, and independent of any occurrence of pregnancy.


N-heterocyclic carbene catalyzed addition of aldehydes to diazo compounds: stereoselective synthesis of N-acylhydrazones.
An innovative stereoselective synthesis of N-acylhydrazones via an unprecedented N-heterocyclic carbene catalyzed addition of aldehydes to diazo compounds is presented. Enals exclusively afforded N-acylhydrazones, in yields up to 91%. The observed regioselectivity was traced back to the reaction of the vinylogous Breslow intermediate via the acyl anion pathway over competing homoenolate, enol, and acyl azolium pathways. This unusual reaction profile was studied based on DFT calculations, which revealed that the reaction is under orbital control, rather than being ruled by charge.


Cocreating a communicative space to develop a mindfulness meditation manual for women in recovery from substance abuse disorders.
Mindfulness-Based Stress Reduction (MBSR) programs are becoming more integrated into the treatment of persons with substance use disorders (SUDs). A focus of MBSR is to increase awareness of sensations in the body and accept them in the moment without judgment. Little is known about the readiness of women, with posttraumatic stress disorder (PTSD), and their level of comfort to participate in MBSR programs. Habermas' ideal speech situation guided a cooperative inquiry with 45 women at 3 treatment centers. Women engaged in activities of MBSR and shared opinions on how to develop a manual that would address the readiness of women with SUDs-PTSD to participate in MBSR.


Prepectoral Versus Subpectoral Direct to Implant Immediate Breast Reconstruction.
Implant-based reconstruction is currently the most common postmastectomy breast reconstruction modality with over 86,000 procedures performed in 2017. Although various methods for reconstruction techniques have been described, partial subpectoral implant placement with or without acellular dermal matrix coverage remains the most popular approach. Recently, prepectoral implant placement has gained increased recognition as a method that avoids some of the potential morbidities of submuscular implant placement. Currently, few studies have examined the outcomes of performing this approach. The purpose of this study was to evaluate and compare the outcomes of prepectoral and subpectoral direct to implant (DTI) immediate breast reconstruction. Data from a prospective cohort of consecutive patients undergoing prepectoral DTI immediate breast reconstructions at our institution from February 2016 to November 2017 were collected. The incidence of complications such as mastectomy skin flap necrosis, seroma, hematoma, infection, implant loss, and unexpected reoperation were recorded and compared with a cohort of consecutive patients who underwent subpectoral DTI immediate breast reconstruction from May 2014 to July 2015. One hundred twelve prepectoral DTI immediate breast reconstructions were performed on 62 patients. Four breasts (4.4%) were diagnosed with infection. There were 8 breasts (7.1%) that suffered from mastectomy skin flap necrosis (5 partial thickness necrosis, 3 full thickness necrosis). There was 1 implant loss related to full thickness necrosis that required salvage with autologous tissue reconstruction. Prepectoral breast reconstruction had less esthetic revisions and comparable complications when compared with the historical subpectoral cohort. When compared with the subpectoral DTI approach, prepectoral DTI breast reconstruction grants favorable complication rates and improved esthetic outcomes. Prepectoral DTI breast reconstruction is a safe modality that should be considered in any patient who is a candidate for immediate breast reconstruction.


Toehold-mediated DNA logic gates based on host-guest DNA-GNPs.
A simple, toehold-mediated two-way input DNA machine has been developed. Utilizing symmetric and asymmetric protector sequences, INH, XOR logic gates and a half-subtractor are designed based on this two-way structure.


Fabrication of Highly Sensitive Nonenzymatic Electrochemical H₂O₂ Sensor Based on Pt Nanoparticles Anchored Reduced Graphene Oxide.
A highly sensitive nonenzymatic hydrogen peroxide (H2O2) sensor was fabricated using platinum nanoparticles decorated reduced graphene oxide (Pt/rGO) nanocomposite. The Pt/rGO nanocomposite was prepared by single-step chemical reduction method. Nanocomposite was characterized by various analytical techniques including Raman spectroscopy, X-ray diffraction, field emission scanning electron microscope and high-resolution transmission electron microscopy. Screen printed electrodes (SPEs) were fabricated and the nanocomposite was cast on the working area of the SPE. Cyclic voltammetry and amperometry demonstrated that the Pt/rGO/SPE displayed much higher electrocatalytic activity towards the reduction of H2O2 than the other modified electrodes. The sensor exhibited wide linear detection range (from 10 μM to 8 mM), very high sensitivity of 1848 μA mM-1 cm-2 and a lower limit of detection of 0.06 μM. The excellent performance of Pt/rGO/SPE sensor were attributed to the reduced graphene oxide being used as an effective matrix to load a number of Pt nanoparticles and the synergistic amplification effect of the two kinds of nanomaterials. Moreover, the sensor showed remarkable features such as good reproducibility, repeatability, long-term stability, and selectivity.


Correction to: Four novel interaction partners demonstrate diverse modulatory effects on voltage-gated CaV2.2 Ca2+ channels.
The article was originally published with one author missing. The name of the co-author Roman Moravcik was inadvertently omitted. His name and affiliation have now been added to the author list. The original article has been corrected.


Evidence for the presence of topoisomerase like activity in mitochondria of Saccharomyces cerevisiae.
During studies on the enzymology of DNA replication in mitochondria of Saccharomyces cerevisiae, a topoisomerase like activity was detected for the first time. Crude extracts of mitoplast were found to show enzyme activities which could both catenate and relax supercoiled plasmid DNA. Chromatography of the mitoplast lysate on a phosphocellulose column, using Tris-HCl (pH 7.5) buffer containing 0.6 M NaCl as eluent, was found to yield a topoisomerase like activity capable of relaxing supercoiled plasmid DNA (Fraction 1). This fraction was not dependent on ATP for its activity. The other fraction eluting at 1M NaCl showed predominantly catenating activity, which was found to be ATP dependent.


Magnitudes of muscle activation of spine stabilizers, gluteals, and hamstrings during supine bridge to neutral position.
The aim of this study was to compare the magnitude of selective core muscle activation during supine bridging to neutral exercises (three on a stable and three on an unstable surface). Surface EMG analysis was performed on the lumbar multifidus, gluteus medius, gluteus maximus, and hamstrings from 13 male and 13 female subjects. Lumbar multifidus recruitment was not influenced by exercise or condition and ranged between 29.2 and 35.9% of maximum voluntary isometric contraction (MVIC). Peak gluteus medius activation (42.0% MVIC) occurred in unstable single-leg bridge. Maximum recruitment of gluteus maximus (32.6% MVIC) appeared during stable single-leg bridge. Peak hamstring activation (59.6% MVIC) occurred during stable double-leg hamstring curl. Regardless of condition, hamstrings demonstrated high (51.9-59.6% MVIC) muscle recruitment during double-leg hamstring curls compared with the single-leg bridge or double-leg bridge. Various supine bridging to neutral exercises activated the hamstrings at levels conducive to strengthening, whereas recruitment of lumbar multifidus, gluteus medius, and gluteus maximus promoted endurance training. Clinically, we were unable to conclude the unstable support surface was preferable to the stable surface for boosting muscle recruitment of spine stabilizers, gluteals, and hamstring muscles during supine bridge to neutral position.


Determination of the Substrate Specificity of Protein Kinases with Peptide Micro- and Macroarrays.
Elucidation of the key determinants for the phosphorylation site specificities of protein kinases facilitates identification of their physiological substrates, and serves to better define their critical roles in the signaling networks that underlie a multitude of cellular activities. Albeit with some apparent limitations, such as the lack of contextual information for secondary substrate-binding sites, the synthetic peptide-based approach has been adopted widely for the kinase specificity profiling studies, especially when they are used in an array format, which permits the screening of large numbers of potential peptide substrates in parallel. In this chapter, we present detailed protocols for determining protein kinase substrate specificity using an approach that involves both peptide microarrays and macroarrays. In particular, SPOT synthesis on macroarrays can be used to follow up on in silico predictions of protein kinase substrate specificity with predictive algorithms.


Intertrial coherence and causal interaction among independent EEG components.
Over the past few years there has been an increased interest in studying the underlying neural mechanism of attention and cognitive brain activity. This paper aims towards identifying and analyzing distinct responses in an auditory working memory paradigm, as independent components with variable latency, frequency and phase characteristics. The event-related nature of components (either phase or non-phase-locked) over multiple trials is thoroughly examined through intertrial coherence measures. Furthermore, the functional coupling of independent components is investigated through the concept of partial directed coherence depicted as a directed graph. Using these tools, the paper compares issues of activation, connectivity and directionality in the synchronization maps of two populations, of control and Alzheimer's subjects. The results on real data from an oddball experiment verify and further enhance the findings of previous studies and illustrate the potential of the proposed analysis framework.


An invasive and a noninvasive approach for the automatic differentiation of obstructive and central hypopneas.
The automatic differentiation of obstructive and central respiratory events is a major challenge in the diagnosis of sleep-disordered breathing. Esophageal pressure (Pes) measurement is the gold-standard method to identify these events. This study presents a new classifier that automatically differentiates obstructive and central hypopneas with the Pes signal and a new approach for an automatic noninvasive classifier with nasal airflow. An overall of 28 patients underwent night polysomnography with Pes recording, and a total of 769 hypopneas were manually scored by human experts to create a gold-standard annotation set. Features were automatically extracted from the Pes signal to train and test the classifiers (discriminant analysis, support vector machines, and adaboost). After a significantly (p < 0.01) higher incidence of inspiratory flow limitation episodes in obstructive hypopneas was objectively, invasively assessed compared to central hypopneas, the feasibility of an automatic noninvasive classifier with features extracted from the airflow signal was demonstrated. The automatic invasive classifier achieved a mean sensitivity, specificity, and accuracy of 0.90 after a 100-fold cross validation. The automatic noninvasive feasibility study obtained similar hypopnea differentiation results as a manual noninvasive classification algorithm. Hence, both systems seem promising for the automatic differentiation of obstructive and central hypopneas.


Blockade of glycine transporter 1 by SSR-504734 promotes cognitive flexibility in glycine/NMDA receptor-dependent manner.
Accumulating evidence suggests that cognitive processes may be regulated by glycine concentration in the local environment of glutamate N-methyl-d-aspartate receptor (NMDAR). The concentration of glycine is controlled, among other factors, by the glycine transporter 1 (GlyT1). While GlyT1 inhibitors are developed for a number of indications including cognitive improvement, little is known about their effects in tasks depending on prefrontal cortical function. We examined the effect of GlyT1 inhibitor SSR-504734 on cognitive flexibility assessed in the attentional set-shifting task in rats (ASST). The second goal was to elucidate whether SSR-504734 effect has been due to the compound's action at glycine/NMDAR site. Rats treated with SSR-504734 (3 and 10 mg/kg, IP) required significantly less trials to criteria during extra-dimensional shift (EDs) phase of the ASST. The effect of SSR-504734 (3 mg/kg) was completely prevented by the glycine/NMDAR site antagonist, L-687,414 (30 mg/kg, IP) that by itself exerted no effect on cognitive flexibility. Present study demonstrates that the elevation of glycine concentration through the blockade of its reuptake facilitates cognitive flexibility. As this effect was fully blocked by glycine/NMDAR antagonist, SSR-504734-induced cognitive improvement is likely mediated through glycine action at NMDAR. It is suggested that GlyT1 inhibitors like SSR-504734 may represent a useful pharmacological approach for cognitive enhancement, especially in domains critically affected in schizophrenia.


Evaluation of metal allergies in patients with coronary stents.
In-stent restenosis is a complication which impairs the success of coronary stenting. Recently, it was supposed that a delayed hypersensitivity reaction to nickel and molybdenum might be one of the triggering factors in in-stent restenosis. We have analyzed the data collected in our centre with respect to this hypothesis. Altogether, 34 patients were investigated (24 male, 10 female). Patch tests were performed with the standard series of the German Contact Dermatitis Research Group and a metal series containing the metal components of 316 L stainless steel. A positive patch test reaction to nickel was observed in 4 (11.8%) patients. None of the patients showed sensitization to the other metals. Retrospective analysis was performed in 20 patients: 2 of these patients had a positive patch test reaction to nickel, one of whom had an in-stent restenosis, and the other not. Restenoses were predominantly observed in patients with negative patch test reactions to nickel (6/18 patients). Out of the patients who were investigated prospectively only one showed sensitization to nickel. Restenosis was observed in 2 patients: neither patient had nickel allergy. Although it still cannot be excluded that metal allergy may play a role in the restenosis process in coronary stenting, there is at present little evidence for it.


Dynamic glucose-enhanced (DGE) MRI in the human brain at 7 T with reduced motion-induced artifacts based on quantitative R1ρ mapping.
Dynamic glucose-enhanced (DGE)-MRI based on chemical exchange-sensitive MRI, that is, glucoCEST and gluco-chemical exchange-sensitive spin-lock (glucoCESL), is intrinsically prone to motion-induced artifacts because the final DGE contrast relies on the difference of images, which were acquired with a time gap of several mins. In this study, identification of different types of motion-induced artifacts led to the development of a 3D acquisition protocol for DGE examinations in the human brain at 7 T with improved robustness in the presence of subject motion. DGE-MRI was realized by the chemical exchange-sensitive spin-lock approach based either on relaxation rate in the rotating frame (R1ρ )-weighted or quantitative R1ρ imaging. A 3D image readout was implemented at 7 T, enabling retrospective volumetric coregistration of the image series and quantification of subject motion. An examination of a healthy volunteer without administration of glucose allowed for the identification of isolated motion-induced artifacts. Even after coregistration, significant motion-induced artifacts remained in the DGE contrast based on R1ρ -weighted images. This is due to the spatially varying sensitivity of the coil and was found to be compensated by a quantitative R1ρ approach. The coregistered quantitative approach allowed the observation of a clear increase of the DGE contrast in a patient with glioblastoma, which did not correlate with subject motion. The presented 3D acquisition protocol enables DGE-MRI examinations in the human brain with improved robustness against motion-induced artifacts. Correction of motion-induced artifacts is of high importance for DGE-MRI in clinical studies where an unambiguous assignment of contrast changes due to an actual change in local glucose concentration is a prerequisite.


Synthesis of 6-acetamido-5-amino- and -5-guanidino-3, 4-dehydro-N-(2-ethylbutyryl)- 3-piperidinecarboxylic acids related to zanamivir and oseltamivir, inhibitors of influenza virus neuraminidases.
[reaction: see text] 6-Acetamido-5-amino- and -5-guanidino-3, 4-dehydro-N-(2-ethylbutyryl)-3-piperidinecarboxylic acids (8 and 9) have been synthesized starting from natural siastatin B, a bacterial neuraminidase inhibitor isolated from Streptomyces culture in a stereospecific fashion. These compounds are related to zanamivir and oseltamivir, inhibitors of influenza virus neuraminidases.


No alterations in the performance of two interval timing operant tasks after alpha-difluoromethylornithine (DFMO)-induced cerebellar stunting.
The cerebellum is critically involved in temporal processes in the millisecond range and may be involved in longer time estimations (i.e. in the seconds range). Estimates in the millisecond range are impaired after developmentally induced cerebellar alterations, however, little is known about the effects of similar alterations on longer timing performance. Appropriately timed DFMO treatment reliably causes cerebellar stunting in rats, however, its effects on temporal estimation performance are unknown. Here, male and female Sprague-Dawley rats were treated with subcutaneous injections of 500 mg/kg DFMO on postnatal days 5-12, causing a 10% cerebellar weight reduction at adulthood. As adults, subjects were tested under one of two paradigms - a differential reinforcement of low response rate (DRL) task requiring that subjects withhold a lever press response for 10-14 s or a temporal response differentiation (TRD) task requiring that subjects maintain a lever press response for 10-14 s. Training and steady-state performance of the DRL and TRD tasks were not significantly altered by DFMO treatment. Performance after acute challenges with two dopaminergic agonists (2.00-7.50 mg/kg methylphenidate and 0.10-1.00 mg/kg d-amphetamine) was measured after which all subjects underwent behavioral extinction. Generally, performance after methylphenidate and d-amphetamine was similar in control and DFMO-treated rats and DFMO treatment had no differential effects on performance during extinction. These results support findings from an earlier study [Ferguson SA, Paule MG, Holson RR. Neonatal dexamethasoneon day 7 in rats causes behavioral alterations reflective of hippocampal, but not cerebellar, deficits. Neurotoxicol Teratol, 2001; 23:57-69] indicating that developmental cerebellar stunting has few effects on time estimation within the range of seconds.


Does preeclampsia have any adverse effect on fetal heart?
To determine whether preeclampsia causes fetal cardiac cell damage by assessing umbilical artery NT-proBNP, cardiac troponin I and homocysteine. A cross-sectional study with 73 fetuses between 26 and 40 weeks of gestation was performed. Thirty-three healthy mothers' fetuses were control group (Group I). While 12 mildly pre-eclamptic mothers' fetuses constituted Group II, 28 fetuses of severe pre-eclamptic mothers were Group III. Umbilical cord mean NT-proBNP levels of Group I, II and III are 520.8 ± 404.5 pg/ml; 664.2 ± 215.9 pg/ml; and 1932.8 ± 2979.5 pg/ml, respectively (p = 0.0001). The number of neonates with NT-proBNP > 500 pg/mL that indicates severe cardiac damage is higher in Group III (p = 0.001). The mean homocysteine levels are also statistically significantly higher in Group III. Cardiac troponin I levels are not different between the groups (p = 0.46). Increased NT-proBNP and homocysteine might not only indicate some degree of in-utero cardiac cell damage but also feto-placental endothelial injury in the fetuses of severe pre-eclamptic mothers. Our finding that shows no evidence of correlation between cardiac troponin I levels with cell damage and endothelial injury requires further research.


[Chronic postoperative endophthalmitis caused by Propionibacterium acnes].
There is a report of three cases of chronic postoperative endophthalmitis following cataract operations. In two patients there was proven Propionibacterium acnes. There is presented a technique to obtain specimens for microbiological examination and an overview of clinical experience in treatment of the mentioned less common types of endophthalmitis. Early surgical treatment as well as intraocular injection of vancomycin can help to restore a good visual acuity despite of longlasting inflammation.


Information exchange.
•We have established an enrolled nurse support group, aimed at identifying local ENs' needs and obtaining information on further training opportunities.


Antagonism of kynurenine-induced seizures by picolinic, kynurenic and xanthurenic acids.
Picolinic, kynurenic, xanthurenic and anthranilic acids are metabolites of L-kynurenine which, when administered intraperitoneally (i.p.) antagonized (in descending order of potency) the seizures induced by intracerebroventricular (i.c.v.) injections of l-kynurenine sulfate in SHR and C57BL/6 mice. Picolinic and anthranilic acids were also effective after oral administration. Picolinic acid completely prevented seizures. Kynurenic acid, when injected i.c.v. prior to l-kynurenine sulfate, appeared to be more effective than after i.p. administration while picolinic and anthranilic acids were less effective. This suggest that the antikynurenine effect of metabolites of kynurenine (kynurenines) is related to different brain structures, i.e. kynurenic acid predominantly affects structures adjacent to ventricles (e.g. hippocampus, caudate nucleus) while picolinic and anthranilic acids act on other brain structures or the periphery. Xanthurenic, kynurenic and picolinic acids merely prolonged the latency of seizures induced by i.c.v. quinolinic acid (another metabolite of kynurenine) or by subcutaneous strychnine sulfate and i.p. pentylenetetrazole, and did not modify seizures induced by i.p. caffeine and thiosemicarbazide. This selective antagonism of the tested kynurenines against kynurenine might be an important anticonvulsant factor in kynurenine-dependent seizures. It is suggested that increased excretion of xanthurenic, kynurenic and picolinic acids in patients with convulsive states may be manifestations of compensatory processes.


Evaluation of cumulative effects of MR imaging on pacemaker systems at 1.5 Tesla.
The purpose of this study was to evaluate possible cumulative effects of repeated magnetic resonance imaging (MRI) examinations on pacemaker systems in patients with cardiac pacemakers. The records of pacemaker patients who underwent repetitive MRI examinations in our institution were reviewed to identify patients who underwent two or more MRI examinations at 1.5T of any anatomical region. Using these criteria, a total of 47 patients who underwent a total 171 MRI examinations were identified and included in this study. Institutional Review Board approval for all pacemaker investigations was obtained. Written informed consent was obtained from all patients. Pacemakers were interrogated immediately before and after MR imaging, and after 3 months, including measurement of pacing capture threshold (PCT), lead impedance (LI), and battery voltage (BV). PCT, LI, and BV were analyzed for changes dependant on the number of MRI exams performed. Mean changes over time and changes between first and last pacemaker interrogation of PCT, LI, and BV were calculated. A statistically significant (P < 0.05), but clinically irrelevant trend for decrease in PCT and BV was found. No significant or clinically relevant changes in LI were observed. In this first study, no clinically relevant, cumulative changes in PCT, LI, or BV could be detected in PM patients who underwent two or more MRI examinations. However, a careful benefit/risk evaluation, among other MRI- and pacemaker-related safety precautions, remains mandatory, as clinically relevant alterations to the PM system cannot be excluded by all means.


Ketanserin in mild to moderate hypertension in the elderly: a double-blind study versus methyldopa.
In a double-blind study of 30 elderly patients with mild to moderate essential hypertension, the antihypertensive effects of ketanserin and methyldopa were compared. The patients were randomly assigned to receive 20 mg of ketanserin or 250 mg of methyldopa twice daily for two weeks; the dose was then doubled for the rest of the three-month period. Two of the ketanserin group dropped out of treatment, one because of psychic depression, the other because of epigastric pain. After three months of therapy with ketanserin, systolic blood pressure decreased in a dose-dependent manner from 190 +/- 20 to 175 +/- 20 mmHg (P less than 0.05) and diastolic blood pressure from 106 +/- 8 to 91 +/- 9 mmHg (P less than 0.001). Blood pressure was reduced to 160/90 mmHg or less in eight of the 13 ketanserin patients and in five of the 15 methyldopa patients. In both groups heart rate and body weight remained constant. No orthostatic hypotension or hypertensive rebound after ketanserin withdrawal was recorded. It is concluded that 40 mg of ketanserin twice daily can control hypertension in the elderly.


Echocardiographic diagnosis of right ventricular hypertrophy: correlation with ECG and necropsy findings in 248 patients.
Measurements of right ventricular wall thickness (RVWT) by echocardiography and at necropsy correlated well (r = 0.83) in 36 patients. Echocardiography had a sensitivity of 93% and a specificity of 95% in diagnosing right ventricular hypertrophy (RVH) at necropsy; electrocardiography (ECG) had a sensitivity of 31% and a specificity of 85% in diagnosing RVH. An additional 212 patients were studied by echocardiography and ECG. Based on echocardiographic criteria of RVH (RVWT Greater Than or Equal To 5 mm), 134 of 212 patients had RVH, and 78 were without RVH: the ECG had a sensitivity of 27% and a specificity of 88% for diagnosing RVH when correlated with the echocardiographic criteria. The mean diastolic RVWT was 6.0 +/- 1.4 mm in 134 RVH patients and 3.4 +/- 0.8 mm in 78 no-RVH patients (P Less Than 0.05). Diagnosis of RVH was difficult by ECG in 73 patients due to conduction defects or old myocardial infarction; the RVWT measurements were useful in evaluating RVH in these patients. We conclude that echocardiographic measurements of RVWT are useful in the diagnosis of RVH and are more sensitive than the ECG criteria in adults.


Effects of cognitive psychotherapy on the biological rhythm of patients with depression.
Stability between internal and external biological regulators are essential to stable mood states. However, the literature needs studies investigating the effect of brief psychotherapies in the biological rhythm regularization. To verify the capacity regulation of biological rhythms in two models of brief psychotherapy for the remission of depressive symptoms. We conducted a randomized clinical trial with young adults aged 18-29 years old who met diagnostic criteria for depression according to the Structured Clinical Interview for DSM (SCID). In order to evaluate the biological rhythm the Biological Rhythm of assessment in Neuropsychiatry (BRIAN) interview was used; whereas the severity of depression was assessed by the Hamilton Depression Rating Scale (HDRS). The psychotherapy models consisted of two cognitive psychotherapies: Cognitive Narrative Therapy (CNT) and Cognitive-Behavioral Therapy (CBT). The sample consisted of 97 randomized into two models of brief psychotherapy. The patients regulated the biological rhythm from baseline to post-intervention (p=.001) and follow up (p=.003). We also found a positive moderate correlation between biological rhythm regularization and remission of the depressive symptoms (r=.594; p<.001). The two models of brief psychotherapies were effective in the remission of depressive symptoms as well as the regulation of biological rhythms in the follow-up of 6 months. We did not assess genetic, hormonal and neurochemical factors. Also, we did not include patients in pharmaceutical treatment, and with severe symptomatology.


Molecular characteristics of liver metastases from uveal melanoma.
The liver is the most common site of systemic metastases from uveal melanoma (UM). Such metastases usually continue to develop despite the application of current treatment modalities. This study was conducted to obtain insight into the molecular pathways that underlie the development of UM metastasis and thus to identify potential novel therapeutic pathways for this disease. Microarray analysis of seven primary UMs and seven liver metastases from UMs was performed by using oligonucleotide microarrays containing 35,035 features. Bioinformatics was applied to identify expression patterns associated with metastases. Results were validated with real-time quantitative RT-PCR (QPCR) and immunohistochemistry (IHC). Metastasis-associated expression was detected for 193 genes at the false discovery rate (FDR) level of 0%. QPCR confirmed microarray results for all 11 genes that were evaluated (r(2) = 0.9, P = 0.0001), and IHC validated microarray data for the two proteins (NFKB2 and CDK4) that were assessed. The gene expression pattern of UM liver metastases demonstrated a resemblance to normal liver tissue. Bioinformatics facilitate identification of transcription factors, among them NFKB, which potentially regulate expression of several metastasis-associated genes. Liver metastases from UMs have a distinct gene expression pattern compared with the primary tumor while sharing similarities with gene expression patterns of normal liver. Several candidate genes for involvement in UM metastasis have been identified -- among them several in the NFKB pathway.


Comparative effects of cytokines and cytokine combinations on complement component C3 secretion by HepG2 cells.
The mechanisms that control complement protein synthesis are incompletely understood. Recent evidence suggests that cytokines are involved in the regulation of hepatic synthesis of circulating complement components. Therefore, we compared the effects of human recombinant IL-1alpha, IL-1beta, IL-6, IFN-gamma, and TNF-alpha individually or in combination, on HepG2 secretion of complement component C3, the major opsonic protein of the complement system. HepG2 cells were incubated with each cytokine alone and with various combinations of the cytokines. At 24, 48, 72, and 96 h of incubation, the C3 and albumin secreted by the HepG2 cells were quantified by a sandwich ELISA. IL-1alpha and IFN-gamma significantly enhanced C3 secretion by the cells (P<0.02 vs. control cells). IL-1beta when combined with either IL-6 or IFN-gamma also increased C3 secretion (P<0.03 vs. control cells). The stimulatory effect on HepG2 cells by the IL-1beta/IL-6 combination was synergistic. With the exception of IL-1alpha, which increased albumin secretion, HepG2 secretion of albumin was not affected by incubation with individual cytokines or the cytokine combinations. Therefore, IL-1alpha, IFN-gamma, and the combination of IL-1beta with IL-6 or IFN-gamma specifically enhanced C3 secretion by HepG2 cells. The greatest magnitude of C3 secretion was induced by the combination of IL-1beta and IL-6.


Posterior parietooccipital hypometabolism may differentiate mild cognitive impairment from dementia in Parkinson's disease.
Patients with Parkinson's disease (PD) may have normal cognition, mild cognitive impairment (MCI) or dementia. We investigated differences in cerebral metabolism associated with these three cognitive states and the relationship between metabolism and cognitive dysfunction. FDG PET and a battery of neuropsychological tests were used to study PD patients with dementia (n = 19), MCI (n = 28) and normal cognition (n = 21), and control subjects (n = 20). Regional glucose metabolism in patients and controls was analysed using statistical parametric mapping (SPM8) corrected for age, motor severity and depression. Correlations between the mini-mental state examination score and Z-score values of the different cognitive domains with respect to cerebral FDG uptake were assessed using SPM8. PD patients with MCI (PD-MCI patients) exhibited decreased FDG uptake in the frontal lobe, and to a lesser extent in parietal areas compared with cognitively normal patients. Patients with dementia showed reduced metabolism in the parietal, occipital and temporal areas and a less extensive reduction in the frontal lobe compared with PD-MCI patients, while widespread hypometabolism was seen in comparison with patients with normal cognition. PD-MCI patients exhibited reduced FDG uptake in the parietal and occipital lobes and in localized areas of the frontal and temporal lobes compared with controls, whereas patients with dementia showed a widespread reduction of cortical metabolism. Mini-mental state examination score correlated positively with metabolism in several lobes, executive function with metabolism in the parietooccipitotemporal junction and frontal lobe, memory with temporoparietal metabolism, visuospatial function with occipitoparietal and temporal metabolism, and language with frontal metabolism. PD patients with MCI exhibited hypometabolism in several cortical regions compared with controls, and in the frontal and parietal regions compared with cognitively normal patients. Hypometabolism was higher in patients with dementia than in those with MCI, mainly in the posterior cortical areas where it was correlated with visuospatial, memory and executive functions.


[A rare cause of posterior mediastinal tumors: extramedullary hematopoiesis].
We report a case of a patient with intrathoracic extramedullary hematopoiesis presenting as a posterior mediastinal tumor, without associated myelofibrosis. Pathophysiology and the options for diagnosis and treatment in this condition are discussed.


Giant vesical calculus formed around arterial graft incorporated into bladder.
A case is described of a giant vesical calculus formed around an arterial graft incorporated into the bladder. Awareness that a variety of foreign bodies may serve as a nidus for a calculus is necessary to prevent catastrophic consequences.


Subclavian Steal Flow-Related Aneurysm Formation.
Subclavian steal phenomenon can cause retrograde flow through the ipsilateral vertebral artery as a result of atherosclerosis of the subclavian artery. Clinically this can present as intermittent vertebrobasilar ischemia or claudication of the affected extremity, but rarely it poses a serious risk of neurologic morbidity or mortality. Aneurysm formation at the vertebrobasilar junction is rare but may occur as a sequela of increased flow through 1 vertebral artery, as occurs in subclavian steal syndrome. Here, we present a rare case of subarachnoid hemorrhage from a vertebrobasilar junction aneurysm related to subclavian steal syndrome.


Reduced nurse working time and surgical productivity and economics.
Working time reduction is an issue in many sectors of the economy of several countries. In the health care sector, this reduction is mostly felt in regions with a shortage of personnel. In The Netherlands, this is the operating theater suite. We designed this study to evaluate the effects of a policy reduction in working time from 38 to 36 h/wk on the performance of the operating theater suite. The study describes the policy process and its context. For retrospective before-and-after analyses of various performance variables, multivariate linear regression techniques were used. A 4% decrease to a 36-h work week was implemented in our hospital during a period of shortage of personnel in the labor market. This resulted in a 2% decrease in the number of surgical operations performed. The expected increased demand for nursing personnel is reflected in larger wages and the introduction of additional benefits. Additionally, the introduction of a 36-h work week and the 4-day working schedule was accompanied by an increase in absenteeism. Taken together, this resulted in an increase in nursing costs per average operation of 20%. This means that a small reduction in working time during a period of labor shortage can cause an important decrease in surgical productivity. In our hospital, this was accompanied by an increase in sick leave, resulting in a substantial increase of nursing costs per operation. Our retrospective study describes an increase of 20% in nursing costs after a 4% decrease in nurse working time. During the period of implementation of the new working schedule, an increase in sick leave was observed. The interaction between shortage of nursing personnel, working time, and wages is discussed.


Stm1p, a ribosome-associated protein, is important for protein synthesis in Saccharomyces cerevisiae under nutritional stress conditions.
Stm1p is a Saccharomyces cerevisiae protein that has been implicated in several biological processes, ranging from apoptosis to telomere biosynthesis. Likewise, Stm1p has been identified as a protein associated with supramolecular structures, including ribosomes and nuclear telomere cap complexes. Using a variety of biochemical methods, we found that the vast majority of cellular Stm1p is associated with free cytosolic 80S ribosomes and polysomes. In its association with ribosomes, Stm1p interacts in an equimolar complex with both ribosomal subunits and is not associated with mRNA. Functionally, targeted disruption of the STM1 gene results in rapamycin hypersensitivity and a defect in recovery following nitrogen starvation and replenishment. These effects coincide with severe polysome depletion and reduced total protein synthesis. Taken together, our data indicate that Stm1p plays a critical role in facilitating translation under nutrient stress conditions and suggest that Stm1p acts in concert with the target of rapamycin (TOR) signaling pathway.


Isolation and amplification of human IgE Fd encoding mRNA from human peripheral blood lymphocytes.
In order to establish the feasibility of applying recombinatorial library technologies to investigate human in vivo IgE responses, and as a pre-requisite of recombinatorial library construction, we have attempted to determine workable peripheral blood sample volumes required for isolation of mRNA for polymerase chain reaction (PCR) amplification of human IgE Fd encoding sequences. Cells secreting chimeric human IgE monoclonal antibody specific for the hapten NIP were used to establish the conditions for specific amplification of C epsilon 1 domain and Fd encoding sequences, as determined by Southern hybridisation. Amplification of C epsilon 1 domain sequences could be achieved using as few as ten cultured cells as the source of RNA. Specific IgE+ B cell enrichment using immuno-magnetic particles prior to RNA extraction was, however, required to obtain amplification of IgE C epsilon 1 and Fd fragments from lymphocytes prepared from 40 ml human peripheral blood. IgG1+ B cell enrichment from similar samples was not required for detectable amplification of human C gamma 1 cDNA sequences. However, this procedure improved amplification efficiency. Optimisation of methods to separate specific B cell populations, or specific RNA/cDNA sequences, will facilitate in vitro generation of human IgE Fab fragments from peripheral blood.


Curious parallels and curious connections--phylogenetic thinking in biology and historical linguistics.
In The Descent of Man (1871), Darwin observed "curious parallels" between the processes of biological and linguistic evolution. These parallels mean that evolutionary biologists and historical linguists seek answers to similar questions and face similar problems. As a result, the theory and methodology of the two disciplines have evolved in remarkably similar ways. In addition to Darwin's curious parallels of process, there are a number of equally curious parallels and connections between the development of methods in biology and historical linguistics. Here we briefly review the parallels between biological and linguistic evolution and contrast the historical development of phylogenetic methods in the two disciplines. We then look at a number of recent studies that have applied phylogenetic methods to language data and outline some current problems shared by the two fields.


Influence of exercise on insulin sensitivity.
An important determinant of insulin sensitivity in humans, the insulin-induced glucose uptake in skeletal muscle (directed into glycogen synthesis), has been found to be markedly enhanced in endurance-trained individuals compared with sedentary controls. This enhanced insulin action is accompanied by a decreased insulin response during an oral glucose load. Available evidence indicates that the enhanced insulin action is not a genuine training effect, but merely a lasting effect of the previous exercise session(s). In the young, insulin sensitivity increases with a single exercise session, but the increase may appear only after several training sessions in middle-aged or older individuals. The effect disappears after 3-6 days. The exercise-induced reduction in muscle glycogen is an important factor underlying the increased insulin sensitivity in the period after exercise. There are reports that endurance and strength training enhances whole-body insulin sensitivity to a similar extent, and available evidence suggests that, provided total energy expenditure is held constant, low-intensity and high-intensity exercise are equally effective in promoting insulin sensitivity. Differences in sex steroids may explain the observation of a markedly higher insulin sensitivity in women than in men. Adaptations, which might underlie the increased insulin sensitivity in trained individuals, include increases in levels of the glucose transporter protein GLUT-4 and in muscle glycogen synthase activity, a decrease in the serum triglyceride concentration and, possibly, an increase in the muscle capillary network.


A new link between steroid resistance, glucocorticoid receptor and nuclear factor kappa B p65 in idiopathic nephrotic syndrome.
The aim of our study was to investigate levels of glucocorticoid receptor (GRalpha), nuclear factor kappa B (NFkappaB) p65/p50 and inhibitor of NFkappaB alpha (IkappaBalpha) in the peripheral mononuclear blood cells (PMBC) of children with idiopathic nephrotic syndrome (INS). The expression of GRalpha, NFkappaBp65/p50 and IkappaBalpha was determined in 59 patients (age 10.2+/-5.1) and 25 healthy controls (CO) (age 13.1+/-3.4) using Western blot analysis. Patients were labeled according to their clinical sensitivity to glucocorticoids (GCs) as responders (RE), partial responders (PR), and non-responders (NR). Significantly higher expressions of GRalpha were observed in RE than in PR, NR (p<0.01) and even CO (p<0.05). Similarly, expression of NFkappaBp65 was higher in RE in comparison to PR, NR and CO (p<0.05). These differences were more emphasized in the relapse: levels of GRalpha were significantly lower in PR than in RE and CO (p<0.01). Significant differences were also observed in expression of NFkappaB: RE showed significantly higher expression of NFkappaBp65 in comparison to PR, NR and even CO (p<0.01). Lower levels of both GRalpha and NFkappaBp65 are associated with poor or no response to GCs and the difference is more pronounced in patients experiencing relapse of INS.


Method for local temperature measurement in a nanoreactor for in situ high-resolution electron microscopy.
In situ high-resolution transmission electron microscopy (TEM) of solids under reactive gas conditions can be facilitated by microelectromechanical system devices called nanoreactors. These nanoreactors are windowed cells containing nanoliter volumes of gas at ambient pressures and elevated temperatures. However, due to the high spatial confinement of the reaction environment, traditional methods for measuring process parameters, such as the local temperature, are difficult to apply. To address this issue, we devise an electron energy loss spectroscopy (EELS) method that probes the local temperature of the reaction volume under inspection by the electron beam. The local gas density, as measured using quantitative EELS, is combined with the inherent relation between gas density and temperature, as described by the ideal gas law, to obtain the local temperature. Using this method we determined the temperature gradient in a nanoreactor in situ, while the average, global temperature was monitored by a traditional measurement of the electrical resistivity of the heater. The local gas temperatures had a maximum of 56 °C deviation from the global heater values under the applied conditions. The local temperatures, obtained with the proposed method, are in good agreement with predictions from an analytical model.


Surface alterations of zirconia and titanium substrates after Er,Cr:YSGG irradiation.
This study investigated changes in the roughness parameters (Sa in μm(2) and Ra in μm) of yttrium-stabilized tetragonal zirconia polycrystal (Y-TZP) and large-grit sandblasted acid-etched (SLA) titanium (TI) materials after decontamination by erbium chromium-doped:yttrium, scandium, gallium, and garnet (Er,Cr:YSGG) laser irradiation. Twenty disks were analyzed in this study: 10 disks of Y-TZP (5 mm in diameter and 3 mm in height), standardized with CAD-CAM procedures, and 10 disks of SLA TI (5 mm in diameter and 4 mm in thickness). Disks were randomized into four groups (n = 5), according to whether laser irradiation was performed: Y-TZP_G1 and TI_G1 were not treated by laser (control groups), whereas Y-TZP_G2 and TI_G2 were irradiated with Er,Cr:YSGG laser (1.5 W/20 Hz, air-water cooling proportion of 80%/25%). The surface topography of the disks was analyzed by confocal light microscopy. The mean Sa and Ra values were calculated from five profiles from each group. The results were statistically analyzed by t-test at the 95% confidence level (α = 0.05). For Y-TZP, the Sa results (in mean ± SD) for Y-TZP_G1 and Y-TZP_G2 were 2.60 ± 1.1 and 0.80 ± 0.17 μm(2), respectively, and the Ra results were 2.01 ± 0.71 and 0.18 ± 0.15 μm, respectively (both p < .05). For SLA TI, the Sa results for TI_G1 and TI_G2 were 1.99 ± 0.5 and 3.37 ± 0.75 μm(2), respectively, and the Ra results were 1.78 ± 0.53 and 3.84 ± 0.63 μm, respectively (both p < .05). Er,Cr:YSGG laser irradiation alters the surface roughness of zirconia and SLA TI.


Biological activity of transcripts synthesized in vitro from full-length and mutated DNA copies of tobacco rattle virus RNA 2.
Full-length cDNA clones of RNA 2 of tobacco rattle virus (TRV) strain PLB have been cloned into the transcription vector pPM1. Products of in vitro transcription by Escherichia coli RNA polymerase, either capped or uncapped, were as infectious as native RNA 2 when coinoculated with RNA 1 of TRV strain TCM. At least 70% of the internal sequence of the cDNA could be deleted without reduction of the replication efficiency of the transcripts. Sequences of 340 nucleotides at the 5' end and 405 nucleotides at the 3' end of PLB RNA 2 were found to be sufficient for replication. The encapsidation of deletion mutants of PLB RNA 2 was investigated after addition of native PLB RNA 1 and RNA 2. Accumulation of these mutants was distinguished from that of wild-type RNA 2 by insertion of nonviral sequences in the deleted parts. Three mutant forms of RNA 2 with extensive deletions in the coat protein (CP) gene were replicated but failed to encapsidate, while mutants with nonviral sequences inserted downstream from the CP gene showed a large reduction in replication efficiency.


Evaluation of the activated whole blood clotting time (ACT) in vitro.
The activated whole blood clotting time (ACT) was analyzed in vitro using blood samples from normal individuals and from patients with heart disease, scheduled for open heart surgery. The ACT was found to be normally distributed in a group of normal individuals with a mean of 135 sec. In patients with heart diseases, the average ACT was slightly shorter than in normal individuals. A linear relationship between ACT and heparin concentrations was established. Haemodilution and depletion of platelets did not significantly influence the ACT. When a clean venipuncture with disposable needles is used, ACT is a reliable, uncomplicated bedside technique by which heparinisation can be monitored.


Effects of withdrawal of phasic lung inflation during normocapnia and hypercapnia on the swallowing reflex in humans.
This study was done to test the hypothesis that hypercapnia has a direct, inhibitory effect on swallowing. We investigated changes in the frequency and timing of repeated swallows induced by continuous infusion of water into the pharynx before, during, and after transient airway occlusion at normocapnia and hypercapnia in 12 healthy volunteers. Hypercapnia was induced by adding a dead space. Ventilation was monitored using a pneumotachograph, and swallowing was identified by submental electromyogram. We found that hypercapnia decreased the frequency of swallows (8.2 +/- 3.7 vs 11.4 +/- 5.3 swallows.min-1 [mean +/- SD]: hypercapnia vs normocapnia; P < 0.05), together with a loss of the preponderant coupling of swallows with expiratory phase observed at normocapnia. We also found that the withdrawal of phasic lung inflation produced by airway occlusion at end-expiration suddenly increased the swallowing frequency, both at normocapnia (from 11.4 +/- 5.3 to 16.7 +/- 3.7 swallows.min-1; P < 0.01) and at hypercapnia (from 8.2 +/- 3.7 to 22.0 +/- 6.7 swallows.min-1; P < 0.01). Although the degree of increased swallowing frequency during airway occlusion was more prominent at hypercapnia than at normocapnia ( P < 0.05), the distribution of the timing of swallows in relation to the phase of the respiratory cycle during airway occlusion at hypercapnia was similar to that during airway occlusion at normocapnia. The results of our study strongly suggest that the attenuation of the swallowing reflex during hypercapnia is not due to the direct, inhibitory effect of CO2 on the swallowing center, but, rather, is due to the increased inhibitory influence of a lung-volume-related reflex.


Ocular surface effects of repeated application of povidone iodine in patients receiving frequent intravitreal injections.
The aim of this study was to investigate the patient reported symptoms and objective signs of tear film and ocular surface abnormalities experienced by patients undergoing repeated exposure to povidone iodine as a consequence of requiring frequent intravitreal injections for wet macular degeneration. This was a prospective study of consecutive patients who had received recent povidone 5% solution for sterile preparation of intravitreal injection less than 3 months prior to inclusion with a total of at least 3 intravitreal injections for macular degeneration. Each patient had one study eye which was undergoing regular intravitreal injection and a fellow eye which was not undergoing any injections. Each patient underwent evaluations of various tear film parameters on a single occasion for both eyes. The primary outcome was severity of dry eye symptoms as measured by the Schein dry eye questionnaire. The secondary outcomes were tear film osmolarity and corneal punctate staining using the Oxford Grading Scale. A total of 90 patients were included in the study. 43.3% n = 39, were using ocular lubricating medication on a regular basis. A significantly greater proportion of study eyes had a Schein dry eye questionnaire score of 7 or higher; 12.2%, n = 11 amongst study eyes vs 4.4%, n = 4 amongst control, fellow eyes (p < 0.05). In terms of secondary outcomes, the study eyes had a slightly higher mean tear film osmolality compared to control, fellow eyes: 305.5 ± 1.7 in study eyes vs 302 ± 1.6 in control eyes although this difference was not statistically significant (p = 0.087). The study eyes had statistically significantly worse corneal staining as determined by the Oxford grading scale; 0.69 in study eyes vs 0.58 in control, fellow eyes (p = 0.02). Our results confirm the detrimental impact of repeated application of povidone iodine for intravitreal injection procedures on symptoms of dry eyes as experienced and reported by patients.