Surgical management of moderate ischemic mitral valve regurgitation: Where do we stand?
Ischemic mitral regurgitation (IMR) represents a common complication after myocardial infarction. The valve is anatomically normal and the incompetence is the result of papillary muscles displacement and annular dilatation, causing leaflets tethering. Functionally the leaflets present a restricted systolic motion due to tethering forces that displaces the coaptation surface toward the left ventricle apex. The patients present poor left ventricular function at the time of surgery and the severity of the mitral regurgitation increases the risk of mortality. Currently there is general agreement to treat surgically severe IMR nevertheless strong evidences for patient with moderate insufficiency remains poor and proper treatment debated. The most effective surgical approach for the treatment of IMR remains debated. Some authors demonstrated that coronary artery bypass graft (CABG) alone is beneficial in patients with IMR. Conversely, in most patients, moderate IMR will persist or worsen after CABG alone which translate in higher long-term mortality as a function of residual mitral regurgitation severity. A probable reason for this unclear surgical management of functional MR is due to the contemporary suboptimal results of reparative techniques. The standard surgical treatment of chronic IMR is CABG associated with undersized annuloplasty using complete ring. Though, the recurrence of mitral regurgitation remains high (> 30%) because of continous left ventricle remodeling. To get better long term results, in the last decade, several subvalvular procedures in adjunct to mitral anuloplasty have been developed. Among them, surgical papillary muscle relocation represents the most appreciated option capable to restore normal left ventricle geometry. In the next future new preoperative predictors of increased mitral regurgitation recurrence are certainly needed to find an individual time period of treatment in each patient with moderate IMR.


Inhibition of autophagy exerts anti-colon cancer effects via apoptosis induced by p53 activation and ER stress.
Although some molecularly targeted drugs for colorectal cancer are used clinically and contribute to a better prognosis, the current median survival of advanced colorectal cancer patients is not sufficient. Autophagy, a basic cell survival mechanism mediated by recycling of cellular amino acids, plays an important role in cancer. Recently, autophagy has been highlighted as a promising new molecular target. The unfolded protein response (UPR) reportedly act in complementary fashion with autophagy in intestinal homeostasis. However, the roles of UPR in colon cancer under autophagic inhibition remain to be elucidated. We aim to clarify the inhibitory effect of autophagy on colon cancer. We crossed K19 (CreERT) and Atg5 (flox/flox) mice to generate Atg5 (flox/flox)/K19 (CreERT) mice. Atg5 (flox/flox)/K19 (CreERT) mice were first treated with azoxymethane/dextran sodium sulfate and then injected with tamoxifen to inhibit autophagy in CK19-positive epithelial cells. To examine the anti-cancer mechanisms of autophagic inhibition, we used colon cancer cell lines harboring different p53 gene statuses, as well as small interfering RNAs (siRNAs) targeting Atg5 and immunoglobulin heavy-chain binding protein (BiP), a chaperone to aid folding of unfolded proteins. Colon tumors in Atg5 (flox/flox)/K19 (CreERT) mice showed loss of autophagic activity and decreased tumor size (the total tumor diameter was 28.1 mm in the control and 20.7 mm in Atg5 (flox/flox)/K19 (CreERT) mice, p = 0.036). We found that p53 and UPR/endoplasmic reticulum (ER) stress-related proteins, such as cleaved caspase 3, and CAAT/enhancer-binding protein homologous protein, are up-regulated in colon tumors of Atg5 (flox/flox)/K19 (CreERT) mice. Although Atg5 and BiP silencing, respectively, increased apoptosis in p53 wild type cells, Atg5 silencing alone did not show the same effect on apoptosis in p53 mutant cells. However, co-transfection of Atg5 and BiP siRNAs led to increased apoptosis in p53 mutant cells. Blocking autophagy has potential in the treatment of colon cancer by inducing apoptosis via p53 and ER stress, and suppressing the UPR pathway is a valid strategy to overcome resistance to autophagic inhibition.


TIGER2 with solvent energy averaging (TIGER2A): An accelerated sampling method for large molecular systems with explicit representation of solvent.
The recently developed "temperature intervals with global exchange of replicas" (TIGER2) accelerated sampling method is found to have inaccuracies when applied to systems with explicit solvation. This inaccuracy is due to the energy fluctuations of the solvent, which cause the sampling method to be less sensitive to the energy fluctuations of the solute. In the present work, the problem of the TIGER2 method is addressed in detail and a modification to the sampling method is introduced to correct this problem. The modified method is called "TIGER2 with solvent energy averaging," or TIGER2A. This new method overcomes the sampling problem with the TIGER2 algorithm and is able to closely approximate Boltzmann-weighted sampling of molecular systems with explicit solvation. The difference in performance between the TIGER2 and TIGER2A methods is demonstrated by comparing them against analytical results for simple one-dimensional models, against replica exchange molecular dynamics (REMD) simulations for sampling the conformation of alanine dipeptide and the folding behavior of (AAQAA)3 peptide in aqueous solution, and by comparing their performance in sampling the behavior of hen egg-white lysozyme in aqueous solution. The new TIGER2A method solves the problem caused by solvent energy fluctuations in TIGER2 while maintaining the two important characteristics of TIGER2, i.e., (1) using multiple replicas sampled at different temperature levels to help systems efficiently escape from local potential energy minima and (2) enabling the number of replicas used for a simulation to be independent of the size of the molecular system, thus providing an accelerated sampling method that can be used to efficiently sample systems considered too large for the application of conventional temperature REMD.


Bull'S eye maculopathy in a patient taking sertraline.
To report a very rare case of bilateral Bull's eye maculopathy caused by sertraline. Clinical case report and literature review. A 14-year-old girl. A 14-year-old girl with no significant medical history developed bilateral Bull's eye maculopathy after taking sertraline for 1 year. Diagnostic work-up, which consisted of electrooculography, electroretinography, and genetic testing, yielded no abnormal results. Three-year follow-up examination after discontinuation of sertraline showed no improvement in visual acuity (20/200 bilaterally) or retinal pigment epithelium. This is the second published case, and according to the National Registry of Drug-Induced Ocular Side Effects, this is only the fifth reported case of presumed sertraline maculopathy. Although Bull's eye maculopathy related to sertraline is rare, physicians and patients need to be aware of the possible toxicity.


The use of advanced imaging and representation of workers compensation in vertebral augmentation: a single-center comparison with the INVEST Trial.
Vertebral augmentation (VA) techniques have changed the paradigm of treatment during the past decade and involve injection of polymethylmethacrylate (PMMA) cement directly into a compressed vertebral body. During the summer of 2009, the INVEST trial was one of 2 randomized controlled studies that reported equivalence between vertebroplasty and a control procedure. In this analysis, we sought to compare the subset of patients studied in the INVEST trial to a tertiary academic institution with respect to 2 variables: Workers compensation status and presence of advanced imaging prior to the procedure. Retrospective review of 634 procedures. We performed a retrospective review of 634 vertebral augmentation procedures at our institution between June 2004 and August 2008, overlapping with the dataset of the INVEST trial. The primary comparison was whether patients received Workers compensation and/or advanced imaging prior to the procedure. The study was IRB approved, and in accordance with HIPAA guidelines. There were 409 patients who underwent 634 procedures between June 2004 and August 2008. Among 634 procedures, only 3 included Workers compensation. Therefore, the majority of patients (> 99%) did not receive Workers compensation compared to the INVEST trial (11 - 13%). Similarly, in 629 out of 634 procedures (99.2%), patients underwent advanced imaging comprised of magnetic resonance imaging (MRI), computed tomography (CT) or bone scan. We simply looked at 2 elements of the patient demographic in a time-matched fashion and compared it to the U.S. based INVEST trial. It is possible that despite our diligent efforts to review the data set, we have inadvertently excluded some patients, the incorporation of whom might have changed the statistics. We reviewed our time-matched database in terms of 2 variables we thought curious in the INVEST trial. In comparison to our practice, where advanced imaging is essentially required and Workers compensation largely not seen, these aspects of the INVEST trial's population stood out.


Women Representation as First and Corresponding Authors in Neuroanesthesiology and Neurocritical Care Journals: A Retrospective Analysis.
There is limited literature on the representation of women in leading roles in neuroanesthesiology and neurocritical care academia. We aimed to determine the representation of women as first and corresponding authors in articles published in 3 dedicated journals of neuroanesthesiology and neurocritical care during last 5 years. Articles published in the Journal of Neurosurgical Anesthesiology, Neurocritical Care, and Journal of Neuroanaesthesiology and Critical Care between July 1, 2015 and June 30, 2020 were included in this study. The primary outcome was the proportion of women first authors, and secondary outcomes were the percentage of women corresponding authors, and representation of women as first and corresponding author by article type and country of affiliation. Of the 1164 articles included in the study, 403 (34.6%) had a woman first author. Women first authorship was highest for Special Articles (5/11; 45.5%), Clinical Reports (44/113; 38.9%) and Narrative Review Articles (58/151; 38.4%) and lowest for Original Research Articles (198/597; 33.2%). Women accounted for 29.6% (344/1164) of corresponding authors across all article types. Overall, the United States and India had the highest representation of women first authors (159/403; 39.0% and 107/344; 31.0%, respectively), and India also had highest proportion of women corresponding authors (107/272; 39.3%). Women were underrepresented compared with men as first author of articles published in 3 dedicated neuroanesthesiology and neurocritical care journals over the last 5 years. Women had the lowest representation as authors of Original Research Articles.


Whole-genome sequencing of Brassica oleracea var. capitata reveals new diversity of the mitogenome.
Plant mitochondrial genomes (mtDNAs) vary in sequence structure. We assembled the Brassica oleracea var. capitata mtDNA using a mean coverage depth of 25X whole genome sequencing (WGS) and confirmed the presence of eight contigs/fragments by BLASTZ using the previously reported KJ820683 and AP012988 mtDNA as reference. Assembly of the mtDNA sequence reads resulted in a circular structure of 219,975 bp. Our assembled mtDNA, NCBI acc. no. KU831325, contained 34 protein-coding genes, 3 rRNA genes, and 19 tRNA genes with similarity to the KJ820683 and AP012988 reference mtDNA. No large repeats were found in the KU831325 assembly. However, KU831325 showed differences in the arrangement of bases at different regions compared to the previously reported mtDNAs. In the reference mtDNAs KJ820683 and AP012988, contig/fragment number 4 is partitioned into two contigs/fragments, 4a and 4b. However, contig/fragment number 4 was a single contig/fragment with 29,661 bp in KU831325. PCR and qRT-PCR using flanking markers from separate parts of contig/fragment number 4 confirmed it to be a single contig/fragment. In addition, genome re-alignment of the plastid genome and mtDNAs supported the presence of heteroplasmy and reverse arrangement of the heteroplasmic blocks within the other mtDNAs compared to KU831325 that might be one of the causal factors for its diversity. Our results thus confirm the existence of different mtDNAs in diverse B. oleracea subspecies.


Social regulation of neurogenesis in teleosts.
Salmonid fishes such as the rainbow trout (Oncorhynchus mykiss) are frequently used to study behavioral and neuroendocrine effects of socially induced stress. A predictable aggressive response to territorial intrusion, a well described neuroanatomy, and many essential similarities in the stress response in fishes and other vertebrates are among the advantages of this comparative model. One conspicuous difference when compared to mammals, however, is that in teleost fish and other non-mammalian vertebrates, neurogenesis persists into adulthood to a much higher degree. Very little is known about the functional significance of individual differences in the rate of brain cell proliferation in fish, or whether structural changes in the fish brain are influenced by the social environment. In this paper we discuss the observation that brain cell proliferation is reduced in subordinate fish, focusing in particular on whether such individual variation reflects a difference in coping style or is indeed a response to social interactions.


Understanding Signal and Background in a Thermally Resolved, Single-Branched DNA Assay Using Square Wave Voltammetry.
Electrochemical bioanalytical sensors with oligonucleotide transducer molecules have been recently extended for quantifying a wide range of biomolecules, from small drugs to large proteins. Short DNA or RNA strands have gained attention recently due to the existence of circulating oligonucleotides in human blood, yet challenges remain for adequately sensing these targets at electrode surfaces. In this work, we have developed a quantitative electrochemical method which uses target-induced proximity of a single-branched DNA structure to drive hybridization at an electrode surface, with readout by square-wave voltammetry (SWV). Using custom instrumentation, we first show that precise control of temperature can provide both electrochemical signal amplification and background signal depreciation in SWV readout of small oligonucleotides. Next, we thoroughly compared 25 different combinations of binding energies by their signal-to-background ratios and differences. These data served as a guide to select the optimal parameters of binding energy, SWV frequency, and assay temperature. Finally, the influence of experimental workflow on the sensitivity and limit of detection (LOD) of the sensor is demonstrated. This study highlights the importance of precisely controlling temperature and SWV frequency in DNA-driven assays on electrode surfaces while also presenting a novel instrumental design for fine-tuning of such systems.


Neonatal hypertonia - a diagnostic challenge.
In comparison to hypotonia, hypertonia is less commonly expressed in the neonatal period. The scientific literature on the causes of neonatal hypertonia is scant, with no suggested diagnostic algorithm easily available to clinicians. Aetiologies include conditions affecting the central nervous system and spine, and rare peripheral neuromuscular disorders leading to hypertonia. Aetiology onset may be antepartum, peripartum with either transient hypertonia or persistent hypertonia which may appear later, or from a postnatal event/disease. This review discusses neonatal hypertonia and a diagnostic approach to neonatal hypertonia is suggested.


Plasticity and reprogramming of differentiated ocular tissue of tadpoles of the frog, Euphlyctis cyanophlyctis under the influence of vitamin A.
Present study has shown that differentiated cell types may loose their definitive characteristics and acquire features of another specialized cell type. Young (3 toe stage) and mature (5 toe stage) tadpoles of the frog, Euphylictis cyanophlyctis were employed as experimental animals. Experiments were completed in two phases: in the first part of experiment, lenses were extracted from right eye balls of tadpoles and treated with vitamin A; in the second part of the experiment, meshed lentectomized eye ball tissues were implanted into the pit made on mid lateral position of the tail of young and mature tadpoles and were treated with vitamin A. The results obtained gave clear evidence of plasticity and reprogramming of terminally differentiated ocular tissue into lens, retina and even complete eye. Vitamin A was found to be good model for accelerating the reprogramming of differentiated ocular tissue in anuran frog tadpoles.


Expression of connective tissue stromal elements in human cholangiocarcinomas. An immunohistochemical and ultrastructural study.
The results of the study of ten cholangiocarcinomas from intrahepatic or extrahepatic origins are reported. Using both light microscopic immunohistochemistry and transmission electron microscopy the scirrhous stroma of the tumour showed clear evidence for the production of its collagenous, elastic and possibly other fibrillar elements by the neoplastic cells. Our findings refute the view that the occasional spindle cells (i.e. fibroblasts, myofibroblasts or even smooth muscle cells) could play a major role in the production of such a voluminous amount of the various connective tissue elements. Therefore, it seems reasonable to suggest that the scirrhous stroma of cholangiocarcinomas is produced by the malignant cells similar to those of the breast, oesophagus, stomach and ureter.


Pathophysiology and management of recurrent hypoglycaemia and hypoglycaemia unawareness in diabetes.
Iatrogenic hypoglycaemia is a well-known complication of insulin therapy in patients with diabetes mellitus and a limiting factor for glycaemic control. In a setting of endogenous insulin deficiency (type 1 and advanced type 2 diabetes), one episode of hypoglycaemia reduces both counterregulatory hormone responses to and subjective awareness of subsequent hypoglycaemia, thus impairing physiological defences against hypoglycaemia. This phenomenon may lead to a vicious cycle of recurrent hypoglycaemia and glucose counterregulatory failure, of which hypoglycaemia unawareness (i.e. the inability to perceive symptoms of hypoglycaemia) is the clinical representative. The underlying mechanism of hypoglycaemia-induced counterregulatory failure has not yet been disclosed. Patients with clinical hypoglycaemia unawareness are at high risk of severe hypoglycaemia that requires third-party assistance. Management options include avoidance of hypoglycaemic events and optimisation of insulin therapy to limit deterioration of glycaemic control associated with hypoglycaemia avoidance. Several counterregulatory-stimulating agents have been found to improve hypoglycaemic awareness in small clinical trials, but none have been tested in sufficiently large randomised studies to justify their use in daily practice. More research is required to elucidate the pathogenesis of counterregulatory failure and to develop adequate treatment strategies.


The prevalence of asthma in schoolchildren in Montevideo (Uruguay).
A study of the prevalence of asthma in schoolchildren in Montevideo was undertaken with the use of an appropriate questionnaire. Data consisted of cumulative prevalence, point-prevalence, variations referred to sexes, the age of onset of symptoms and their variation of frequency, the duration of symptoms, personal and family history of atopy and the limitation attributed to asthma in schooling, sporting and physical activities. In the study entered 4,296 children, with a mean age of 12.3 years. Cumulative prevalence was 12.4% for the group with no difference between boys and girls. A tendency for a significant difference in cumulative prevalence was noted comparing industrial and suburban zones. Point-prevalence was 7.5% with no difference between sexes. The mean age of onset of asthma was 3.7 years for boys and 3.5 years for girls. Mean duration of symptoms was 7.6 years for boys and 7.4 years for the girls. Fourteen percent had a personal history and 11% a family history of eczema. Fifty-six percent had a personal history, while 55% a family history of rhinitis and 58% had a family history of asthma. These figures differ significantly from the non-asthmatic population sampled. Limitation in physical and sporting activities attributed to asthma was found in 35% of the boys and 41% of the girls.


How meta-analytic evidence impacts clinical decision making in oral implantology: a Delphi opinion poll.
To investigate the impact of meta-analytic evidence in scientific literature on clinical decision making in the field of oral implantology. A Delphi opinion poll was performed at the meeting of the "Next Generation" Committees of the Austrian, German and Swiss Societies for Implantology (ÖGI, DGI and SGI). First, the experts gave their opinion on 20 questions regarding routine implant treatment (uninformed decisions), then they were confronted with up-to-date Level I evidence from scientific literature on these topics and again asked to give their opinion (informed decisions) as well as to rate the available evidence as satisfactory or insufficient. Topics involved surgical issues, such as immediate implant placement, flapless surgery, tilted and short implants and bone substitute materials, as well as opinions on prosthodontic paradigms, such as immediate loading, abutment materials and platform switching. Compared to their uninformed decisions prior to confrontation with recent scientific literature, on average, 37% of experts (range: 15-50%) changed their opinion on the topic. When originally favoring one treatment alternative, less than half were still convinced after review of meta-analytic evidence. Discrepancy between uninformed and informed decisions was significantly associated with insufficient evidence (P = 0.014, 49% change of opinion vs. 26% on topics rated as sufficiently backed with evidence). Agreement regarding strength of evidence could be reached for eight topics (40%), in three issues toward sufficiency and in five issues toward lack of evidence. Confrontation with literature results significantly changes clinical decisions of implantologists, particularly in cases of ambiguous or lacking meta-analytic evidence.


Influence of Hospital Characteristics on Hospital Transfer Destinations for Patients With Stroke.
Patients with stroke are frequently transferred between hospitals. This may have implications on the quality of care received by patients; however, it is not well understood how the characteristics of sending and receiving hospitals affect the likelihood of a transfer event. Our objective was to identify hospital characteristics associated with sending and receiving patients with stroke. Using a comprehensive statewide administrative dataset, including all 78 Massachusetts hospitals, we identified all transfers of patients with ischemic stroke between October 2007 and September 2015 for this observational study. Hospital variables included reputation (US News and World Report ranking), capability (stroke center status, annual stroke volume, and trauma center designation), and institutional affiliation. We included network variables to control for the structure of hospital-to-hospital transfers. We used relational event modeling to account for complex temporal and relational dependencies associated with transfers. This method decomposes a series of patient transfers into a sequence of decisions characterized by transfer initiations and destinations, modeling them using a discrete-choice framework. Among 73 114 ischemic stroke admissions there were 7189 (9.8%) transfers during the study period. After accounting for travel time between hospitals and structural network characteristics, factors associated with increased likelihood of being a receiving hospital (in descending order of relative effect size) included shared hospital affiliation (5.8× higher), teaching hospital status (4.2× higher), stroke center status (4.3× and 3.8× higher when of the same or higher status), and hospitals of the same or higher reputational ranking (1.5× higher). After accounting for distance and structural network characteristics, in descending order of importance, shared hospital affiliation, hospital capabilities, and hospital reputation were important factor in determining transfer destination of patients with stroke. This study provides a starting point for future research exploring how relational coordination between hospitals may ensure optimized allocation of patients with stroke for maximal patient benefit.


Paracoccus hibiscisoli sp. nov., isolated from the rhizosphere of Mugunghwa (Hibiscus syriacus).
A Gram-reaction-negative, aerobic, non-motile, short-rod-shaped bacterium (THG-T2.31T) was isolated from the rhizosphere of Mugunghwa (Hibiscus syriacus). Growth occurred at 10-35 °C (optimum 28 °C), at pH 5.0-8.0 (optimum pH 7.0) and with 0-4.0 % NaCl (optimum 1.0 %). Based on 16S rRNA gene sequence analysis, the nearest phylogenetic neighbours of strain THG-T2.31T were identified as Paracoccus marcusii DSM 11574T (98.4 %), Paracoccus haeundaensis BC74171T (98.3 %), Paracoccus carotinifaciens E-396T (98.3 %), Paracoccus aestuarii B7T (97.3 %) and Paracoccus seriniphilus MBT-A4T (97.0 %); levels of similarity with the type strains of other species of the genus Paracoccus were lower than 97.0 %. The polar lipids were diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, one unidentified aminolipid and two unidentified phospholipids. The major fatty acids were C16 : 0, C18 : 0, C10 : 0 3-OH, and C18 : 1ω7c. The quinone was ubiquinone-10 (Q-10). The DNA G+C content of strain THG-T2.31T was 69.1 mol%. DNA-DNA hybridization values between strain THG-T2.31T and P. marcusii DSM 11574T, P. haeundaensis BC74171T, P. carotinifaciens E-396T, P. aestuarii B7T and P. seriniphilus MBT-A4T were 38.9 % (34.9 %, reciprocal analysis), 29.1 % (23.5 %), 28.0 % (19.7 %), 18.9 % (9.3) and 13.1 % (6.2 %). On the basis of the phylogenetic analysis, chemotaxonomic data, physiological characteristics and DNA-DNA hybridization data, strain THG-T2.31T represents a novel species of the genus Paracoccus, for which the name Paracoccus hibiscisoli sp. nov. is proposed. The type strain is THG-T2.31T (=KACC 18933T=CCTCC AB 2016182T).


Transmission and fluorescence X-ray absorption spectroscopy cell/flow reactor for powder samples under vacuum or in reactive atmospheres.
X-ray absorption spectroscopy is an element-specific technique for probing the local atomic-scale environment around an absorber atom. It is widely used to investigate the structures of liquids and solids, being especially valuable for characterization of solid-supported catalysts. Reported cell designs are limited in capabilities-to fluorescence or transmission and to static or flowing atmospheres, or to vacuum. Our goal was to design a robust and widely applicable cell for catalyst characterizations under all these conditions-to allow tracking of changes during genesis and during operation, both under vacuum and in reactive atmospheres. Herein, we report the design of such a cell and a demonstration of its operation both with a sample under dynamic vacuum and in the presence of gases flowing at temperatures up to 300 °C, showing data obtained with both fluorescence and transmission detection. The cell allows more flexibility in catalyst characterization than any reported.


Proof of concept in utilizing in-trans surface display system of Lactobacillus plantarum as mucosal tuberculosis vaccine via oral administration in mice.
Tuberculosis is one of the most common and deadliest infectious diseases worldwide affecting almost a third of the world's population. Although this disease is being prevented and controlled by the Bacille Calmette Guérin (BCG) vaccine, the protective efficacy is highly variable and substandard (0-80%) in adults. Therefore, novel and effective tuberculosis vaccine that can overcome the limitations from BCG vaccine need to be developed. A novel approach of utilizing an in-trans protein surface display system of Lactobacillus plantarum carrying and displaying combination of Mycobacterium tuberculosis subunit epitope antigens (Ag85B, CFP-10, ESAT-6, Rv0475 and Rv2031c) fused with LysM anchor motif designated as ACERL was constructed, cloned and expressed in Esherichia coli Rossetta expression host. Subsequently the binding capability of ACERL to the cell wall of L. plantarum was examined via the immunofluorescence microscopy and whole cell ELISA where successful attachment and consistent stability of cell wall binding up to 4 days was determined. The immunization of the developed vaccine of L. plantarum surface displaying ACERL (Lp ACERL) via the oral route was studied in mice for its immunogenicity effects. Lp ACERL immunization was able to invoke significant immune responses that favor the Th1 type cytokine response of IFN-γ, IL-12 and IL-2 as indicated by the outcome from the cytokine profiling of spleen, lung, gastrointestinal tract (GIT), and the re-stimulation of the splenocytes from the immunized mice. Co-administration of an adjuvant consisting of Lactococcus lactis secreting mouse IL-12 (LcIL-12) with Lp ACERL was also investigated. It was shown that the addition of LcIL-12 was able to further generate significant Th1 type cytokines immune responses, similar or better than that of Lp ACERL alone which can be observed from the cytokine profiling of the immunized mice's spleen, lung and GIT. This study represents a proof of concept in the development of L. plantarum as a carrier for a non-genetically modified organism (GMO) tuberculosis vaccine, which may be the strategy in the future for tuberculosis vaccine development.


Luminal volume reconstruction from angioscopic video images of casts from human coronary arteries.
Intravascular angioscopy has been hampered by its limitation in quantifying obtained images. To circumvent this problem, a lightwire was used, which projects a ring of light onto the endoluminal wall in front of the angioscope. This investigation was designed to quantify luminal dimensions of casts from stenotic human coronary arteries and to investigate the feasibility of performing volume reconstruction. Angioscopic video recordings were made during simultaneous motorized pullback (2 mm/s) of an angioscopic catheter and light-emitting fiber through 4 epoxy casts from human coronary arteries. Quantification of the images was performed using a computerized cross-sectional area measurement system. The coronary casts were divided into cross-sectional segments of 4 to 10 mm in thickness, with the true volume of each segment determined by means of a microdispenser. Because of vessel curvature and luminal narrowing, complete visualization of the ring of light at all 1-mm-distant locations was only possible in 19 of 40 segments. For these 19 segments, linear regression analysis showed a good correlation between measured and true segmental volume (r = 0.97, y = 0.88x + 6.58 mm3, standard error of estimate = 3.48 mm3). The relative error in the measured segmental volumes was 3.9 +/- 7.1% (mean +/- SD). These initial results of endoluminal volume reconstruction demonstrate the feasibility of this technique in vitro with high accuracy and low variability, but further technical improvements are necessary to increase the success rate, especially in the quantitative assessment of vessels with complex morphology.


Gradually increasing predominance of self-mutilation in upper extremity arterial injuries: less morbidity but with high threat to society.
Although vascular trauma of the upper extremity is increasingly more common, mortality and morbidity rates remain low, at between 0-8%. Self-mutilation has become evident in recent years. We planned this study to compare the results of self-mutilation with other penetrating trauma in upper extremity vascular injuries and also to emphasize the dangers of self-mutilation for society. Data of 249 patients with penetrating vascular injury of the upper extremity were retrospectively analyzed. There were 214 male (86%) and 35 female (14%) patients, with a mean age of 24.76 ± 11.28 years (range: 2-69 years). Of these, 129 (52%) were self-mutilators. The ulnar artery was the most frequently affected (n=140, 56%). There was no mortality or limb loss. However, eight (3.21%) patients, who had penetrating trauma, had restriction in finger motions. Male predominance, substance abuse and associated nerve injury were significantly more common among self-mutilators (p values <0.001, <0.001 and 0.005, respectively), whereas brachial artery injury, vein graft interposition and fasciotomy rates were higher among the penetrating trauma group (p<0.001 for all). The form of and reason for injuries and presence of substance abuse in case of self-mutilation must be investigated cautiously, and the immediate commencement of psychiatric treatment must be provided to the self-mutilators.


[Possible vertebrate use of a mechanism of chromatin reduction to fuse the V and C genes of immunoglobulins].
Diminution of a chromatin fragment separating V- and C-immunoglobulin genes is suggested as possible mechanism of fusion of V- and C-genes into one functionally active cisrtron. During the early stage of immunodifferentiation of lymphocytes, the chromatin fibrills unfold, and V- and C-genes bring together by DNA-DNA and DNA-protein interaction. The endonucleases excise the chromatin fragment interlocated between V- and C-genes, then the repair enzymes restore the intactness of chromating structure by fusion of V- and C-genes. A number of human pathologic syndromes, the elimination of nucleus during erythrocyte differentiation in mammals indicate the possibility of manifestation on diminution mechanism in vertebrates. Fusion of V- and C-genes by chromatin diminution fits the number of immunologic phenomena, and it may display for different paths of V-gene coding and may be experimentally verified.


Extra-articular manifestations in a community-based sample of patients with rheumatoid arthritis: incidence and relationship to treatment with TNF inhibitors.
To determine the incidence of severe extra-articular rheumatoid arthritis (ExRA) in a community-based cohort of RA patients, and to evaluate whether treatment with tumour necrosis factor (TNF) inhibitors has any effect on the risk of ExRA. In a review of clinical records from 1 July 1997 to 31 December 2004, severe ExRA manifestations were classified according to predefined criteria. Patients were censored at the development of ExRA, death, emigration, or 31 December 2004. Exposure to anti-TNF treatment has continuously and independently been recorded as part of a regional follow-up system. During treatment with TNF inhibitors, there were two patients with new onset of ExRA in 408 person-years at risk (pyr) [0.49/100 pyr, 95% confidence interval (CI) 0.06-1.77]. Among those without anti-TNF treatment there were 63 patients with ExRA in 5425 pyr (1.16/100 pyr, 95% CI 0.89-1.49). The relative risk comparing those treated to those not treated with TNF inhibitors was 0.42 (95% CI 0.10-1.73). Our data show a lower incidence of ExRA in patients treated with TNF inhibitors but further studies with a larger sample size are needed for a more accurate estimate of the size of the effect.


Patients' Satisfaction with Breakthrough Cancer Pain Therapy: A Secondary Analysis of IOPS-MS Study.
Cancer pain is one of the most important symptoms for patients. Pharmacological control is central for clinical management and to ensure well-being. In cancer patients, the management of breakthrough cancer pain (BTcP) is also crucial. This study aims to identify factors that can predict patients' satisfaction with pain relief for BTcP. This was a secondary analysis of the IOPS-MS study, a large, observational, multicenter, national study where thirty-two Italian centers were involved to explore BTcP management. Clinical and pathologic features were recorded, as well as the patients' degree of satisfaction with BTcP medications classified as dissatisfied (not or indifferent satisfied) versus satisfied (or very satisfied). Frequency distributions and the chi-squared test of independence were performed. A multivariate model was carried out by selecting significant variables upon univariate analysis using logistic regression. From the original 4016 patients enrolled, 3840 were available for the study purpose. Seventy-one per cent of patients declared satisfaction with BTcP medications. Young age [odds ratio (OR) 1.29 (95% confidence interval, CI: 1.12-1.50)], non-metastatic cancer stage [OR 1.53 (95% CI: 1.22-1.91)], high Karnofsky performance status [OR 1.63 (95% CI:1.33-1.99)], the absence of anticancer treatment [OR 1.42 (95% CI: 1.19-1.69)], the NSAIDs/paracetamol use for background pain [OR 1.56 (95% CI: 1.34-1.82)] and a high BTcP interference in activities of daily living [OR 2.34 (95% CI: 1.81-3.01)] resulted positively correlated with dissatisfaction in the multivariate analyses. Also, the setting of care was related to difference in BTcP therapy satisfaction. This study proposes several key points to be considered in the pharmacological management of BTcP, useful to ensure patients' satisfaction and optimal quality of life.


Giving acoustics a fairer hearing.
Ken Marriott, an independent acoustics consultant with Industrial Commercial & Technical Consultants (ICTC), outlines some of the key acoustics considerations for those planning new hospital build or refurbishment schemes, cautioning that, all too often, this important area is not properly considered at a sufficiently early project stage.


Simvastatin Combined with Resistance Training Improves Outcomes in Patients with Chronic Heart Failure by Modulating Mitochondrial Membrane Potential and the Janus Kinase/Signal Transducer and Activator of Transcription 3 Signaling Pathways.
Chronic heart failure (CHF) is the end stage of cardiac disease with a 5-year mortality rate reaching 50%. Simvastatin is an antioxidant with lipid-lowering effects, which is commonly used to treat CHF. Resistance training is a nondrug treatment for CHF and exerts a positive effect on both the myocardial structure and function. This study is aimed at exploring the effects and outcomes of simvastatin combined with resistance training on the mitochondrial membrane potential (MMP) of peripheral blood lymphocytes and the Janus kinase/signal transducer and activator of the transcription 3 (JAK/STAT3) signaling pathway in patients with CHF. One hundred and eleven patients with CHF were allocated to the control group (CNG) (n = 55) and intervention group (IG) (n = 56) using the random number table method. The CNG received simvastatin treatment only, whereas the IG received simvastatin treatment plus resistance training. Treatment efficacy, diastolic interventricular septal thickness (IVST), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDD), MMP fluorescence intensity, JAK mRNA and STAT3 mRNA relative expression levels, serum C-reactive protein (CRP), galectin-3, interleukin-6 (IL-6), N-terminal-probrain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and heart-type fatty acid-binding protein (H-FABP) levels were compared in both groups. After 6 months of treatment, diastolic IVST, LVDD, and serum levels of CRP, galectin-3, IL-6, NT-proBNP, hs-cTnT, and H-FABP decreased in both groups and were lower in the IG than in the CNG (P < 0.05), whereas LVEF, JAK and STAT3 mRNA relative expression levels, and MMP fluorescence intensity of peripheral blood lymphocytes were higher in the IG than in the CNG (P < 0.05). Simvastatin combined with resistance training improves heart function and reduces myocardial damage as well as the occurrence of adverse cardiac events compared with simvastatin alone. The mechanism may be related to the increase of expression of MMP, JAK, and STAT3, the regulation of MMP and JAK/STAT3 signaling pathways in peripheral lymphocytes, the alleviation of mitochondrial damage, and the inhibition of inflammatory response.


Distribution of tight DNA-protein complexes along the barley chromosome 1H, as revealed by microsatellite marker analysis.
The distribution of DNA complexes with proteins resistant to routine deproteinisation procedures (tightly bound proteins, TBP) was studied on the barley chromosome 1H by means of microsatellite analysis. The polypeptide spectrum of the barley shoot TBP was similar to that formerly described for other organisms. In order to reveal developmental changes in the distribution of the TBP, DNA was extracted from dry grains, coleoptiles, root tips, and young and old leaves. In the seeds, all the studied DNA sites were evenly distributed between free DNA and DNA containing the tight DNA-protein complexes. Germination made the interaction between TBP and chromosomal loci specific. In coleoptile DNA, sites containing microsatellites located in the distal part of the long arm of the chromosome were not bound to the TBP anymore, however, the centromeric markers were found exclusively in the tight DNA-protein complexes. A similar but not identical distribution of markers was observed in the root tips and young leaves. Leaf senescence was accompanied by a loss in interaction specificity between chromosomal loci and tightly bound proteins. These results are considered to reflect changes in chromatin domain interaction with the nuclear matrix during plant development.


Three-dimensional reconstruction of dust particle trajectories in the NSTX.
Highly mobile incandescent dust particles are routinely observed on NSTX using two fast cameras operating in the visible region. An analysis method to reconstruct dust particle trajectories in space using two fast cameras is presented in this paper. Position accuracies of a few millimeters depending on the particle's location have been achieved and particle velocities between 10 and 200 ms have been observed.


Genetic Coding Variant in GPR65 Alters Lysosomal pH and Links Lysosomal Dysfunction with Colitis Risk.
Although numerous polymorphisms have been associated with inflammatory bowel disease (IBD), identifying the function of these genetic factors has proved challenging. Here we identified a role for nine genes in IBD susceptibility loci in antibacterial autophagy and characterized a role for one of these genes, GPR65, in maintaining lysosome function. Mice lacking Gpr65, a proton-sensing G protein-coupled receptor, showed increased susceptibly to bacteria-induced colitis. Epithelial cells and macrophages lacking GPR65 exhibited impaired clearance of intracellular bacteria and accumulation of aberrant lysosomes. Similarly, IBD patient cells and epithelial cells expressing an IBD-associated missense variant, GPR65 I231L, displayed aberrant lysosomal pH resulting in lysosomal dysfunction, impaired bacterial restriction, and altered lipid droplet formation. The GPR65 I231L polymorphism was sufficient to confer decreased GPR65 signaling. Collectively, these data establish a role for GPR65 in IBD susceptibility and identify lysosomal dysfunction as a potentially causative element in IBD pathogenesis with effects on cellular homeostasis and defense.


Gamma Knife surgery for glossopharyngeal neuralgia.
Gamma Knife surgery (GKS) is widely recognized as an effective, minimally invasive treatment for intractable trigeminal neuralgia, but the role of GKS in glossopharyngeal neuralgia (GPN) remains unclear. This study involved 2 patients with medically intractable GPN who were treated using GKS. One patient required 2 treatments because of a recurrence of symptoms (at maximum doses of 60 and 70 Gy), and the other patient had a single intervention (at a maximum dose of 75 Gy). The GKS target was the distal part of the glossopharyngeal nerve. Patients were investigated prospectively, treated, and then assessed periodically with respect to pain relief and neurological function. Complete pain relief was achieved initially after all 3 interventions. The first patient was pain free without medication for 2 months after the first treatment (60 Gy) and for 4 months after the second treatment (70 Gy). The second patient (treated with 75 Gy) was still pain free without medication at the last follow-up (12 months). Neither patient had any neurological complications. The initial response of GPN to low-dose GKS was favorable, but symptoms may recur. No adverse neurological effects were observed in any of the lower cranial nerves. It will be necessary to investigate the optimal radiation dose and target of GKS for achieving long-term pain relief in GPN.


A hydatid cyst of the thyroid gland.
Echinococcosis, although eradicated in many countries, is still widespread in communities in which agriculture is dominant, and cystic hydatidosis is a significant public health problem in regions where echinococcosis is endemic. Hydatid cysts may be found in almost any part of the body, but most often in the liver and lungs. Other organs affected occasionally include the brain, muscle, kidney, bone, heart and pancreas. This report documents a rare case with a cystic nodule in the thyroid detected by ultrasonography. The patient was a 40-year-old woman with an euthyroid multinodular goitre. Ultrasonography revealed a cystic nodule, and the ultrasonic appearance of the cyst liquid showed multiple echoes, suggesting that the nodule could be a hydatid cyst. Bilateral subtotal thyroidectomy was performed. Postoperative examination of the nodule showed it to be a solitary primary thyroid hydatid cyst.


A Kirkwood-Buff derived force field for the simulation of aqueous guanidinium chloride solutions.
A force field for the simulation of aqueous guanidinium chloride solutions is presented. The force field was parametrized to reproduce the experimental density and Kirkwood-Buff integrals as a function of composition. Consequently, a reasonable description of the salt activity is obtained. The model also performs well for other properties such as the relative permittivity and enthalpy of mixing.


The Impact of Stage and Molecular Subtypes on Survival Outcomes in Young Women with Breast Cancer.
Young women form a unique cohort in breast cancer, with evidence suggesting a later stage at presentation with more aggressive cancers. We aimed at evaluating the prognostic significance of young age and the impact of stage and molecular subtypes on survival. We conducted an audit of a prospectively maintained database at our institute between 2010 and 2014. All women with available receptor status and documented follow-up were included. The young breast cancer (YBC) cohort comprised 103 women and 230 women constituted the comparator arm (45-55 years). The median follow-up was 4 years. The YBC had a higher incidence of hormone negative tumors (61.1% vs. 46.3%, p = 0.012, significant [S]); however, both groups were similar in their stage at presentation. On classification into luminal subtypes, triple negative breast cancer was more common in the YBC cohort (50.5% vs. 29.6%, p = 0.001, S). The 5-year disease-free survival (DFS) was significantly worse in the YBC cohort (70.3% vs. 78%, p = 0.03, S). This detriment appeared to be significantly more in women presenting with operable breast cancer (77.2% vs. 82.6%, p = 0.012, S). Among the Luminal subtypes, there was no significant difference in the DFS between the two groups. Young age is a negative prognostic factor among women presenting with breast cancer. Further studies are required to evaluate whether any specific stage or molecular sub-type is particularly vulnerable to a poor outcome despite treatment.


[Safety of food contact articles in RASFF system].
Materials and articles intended for contact with food must comply with the requirements set in the Regulation EC No 1935/2007. According to article 3 of this Regulation in normal conditions of use they could not transfer their components into food in the amounts which could endanger human health, cause unacceptable changes in the composition of food or cause a deterioration in the organoleptic characteristics. The Regulation EC No 178/2002 related to the food law provides the legal basis for the Rapid Alert System for Food and Feed (RASFF). RASFF, besides food and feed, deals with materials and articles intended to contact with food. The structure of RASFF system in the EU is functioning as a network of the official contact points in the Member States. In Poland the General Sanitary Inspectorate as a national contact point coordinates the activity of RASFF system. The products, which do not comply with the specific regulation and on the base of the risk assessment can pose the hazard to human health, are notified to this system. The notifications are classified as: alert notification, information notification and news. The notifications are published as weekly and annual reports. The majority of notifications in 2002-2006 concerned non-compliance of food contact articles with the allowed limits of overall and specific migration of the following substances: primary aromatic amines (PAA), formaldehyde, plasticizers, semicarbazide, isoprophylthioxanthone and metals. The number of notifications systematically grows up from 5 notifications in 2002 to 189 notifications in 2006. Majority of notified articles were made in China. Including of food contact materials into RASFF system allows for rapid withdrawal of non-complying products from the market.


Tissue and cell specificity of immobilin biosynthesis.
The mechanisms for the initiation of sperm motility have been poorly understood until recently. Immobilin is a novel mucin glycoprotein of high molecular weight found in the cauda epididymis of the rat that, at concentrations equivalent to those found in native cauda epididymal fluid, reversibly inhibits sperm motility. In this study, immobilin was purified from rat cauda epididymal fluid to apparent homogeneity and used to generate polyclonal antibody in rabbits. The antibody was characterized by immunoblotting, and immunofluorescence was used to localize immobilin in paraffin sections of components of the reproductive system of adult male rats. Immobilin was not detectable in the efferent duct and was first detectable in the apical portion of some epithelial cells of the initial segment of the caput epididymis. Immobilin was detectable intracellularly only in cells of the caput epididymis. In the corpus and cauda epididymis immobilin was detectable only in the lumen of the tubules. Immunoprecipitation of immobilin radiolabeled in vitro confirmed that immobilin biosynthesis in the adult rat is restricted to the caput epididymis. Principal cells in the caput epididymis synthesize immobilin and secrete it into the lumen of the tubules to travel with the sperm into the cauda.


Complex histories of genes encoding 3-hydroxy-3-methylglutaryl-CoenzymeA reductase.
The mevalonate pathway for the synthesis of isoprenoids can be found in organisms from all domains of life. It has been previously demonstrated that the first gene specific to that pathway, which encodes the enzyme 3-hydroxy-3-methylglutaryl-CoenzymeA reductase (HMGR), has been transferred between domains by lateral gene transfer on several occasions. Here we look within the domain Bacteria at lateral acquisition of HMGR, whether as a single gene or as part of a mevalonate pathway cluster. We observe a complex history of multiple transfer events probably reflecting the fact that HMGR could be beneficial in a variety of physiological and genetic contexts. We demonstrate that even in Vibrio species, where HMGR is not clustered with other genes to form an operon or a metabolic cluster, it is under strong purifying selection.


The association between dietary vitamin K intake and serum undercarboxylated osteocalcin is modulated by vitamin K epoxide reductase genotype.
Vitamin K acts as a cofactor during the gamma-carboxylation of vitamin K-dependent proteins. Undercarboxylated osteocalcin (ucOC) is a suggested biomarker of vitamin K status. The +2255 polymorphism of the vitamin K epoxide reductase gene (VKORC1) was shown to be associated with the recycling rate of the active form of vitamin K. We investigated the association between dietary vitamin K intake and serum ucOC and hypothesized that this association might vary by VKORC1 genotype. ucOC and total intact osteocalcin (iOC) concentrations were quantified using specific ELISA tests in serum samples of 548 male and female participants (aged 18-81 years) of the Bavarian Food Consumption Survey II. ucOC was expressed relative to iOC (ucOC/iOC ratio). Dietary intake of vitamin K (phylloquinone and menaquinones) was estimated from three 24 h dietary recalls using previously published food composition data. The association between dietary vitamin K intake and ucOC/iOC ratio was analysed using linear and non-linear regression models. Median intakes of phylloquinone/menaquinones were 83.4/37.6 microg/d in men and 79.6/29.8 microg/d in women, respectively. As expected, vitamin K intake was significantly inversely associated with the ucOC/iOC ratio. The ucOC/iOC ratio differed significantly across variants of the +2255 polymorphism in the VKORC1 gene. Stratification by VKORC1+2255 genotype revealed that only in carriers of the GG genotype (39 % of all participants) did the ucOC/iOC ratio significantly decrease with increasing intake of vitamin K. Thus, the results show that the inverse association between dietary vitamin K intake and serum ucOC depends on a functionally relevant allelic variant of the VKORC1 gene.


Vitamin D and systemic lupus erythematosus: continued evolution.
Vitamin D is a steroid hormone that has well-established roles in calcium and bone metabolism. Vitamin D has more recently become recognized for its role in the immune response and its potential immunomodulatory effects in autoimmune diseases, including systemic lupus erythematosus (SLE). This review provides a summary of the recent literature regarding vitamin D and SLE, as well as current recommendations for vitamin D supplementation in patients with SLE.


A novel technique to reach the contralateral iliac artery in Leriche syndrome.
The endovascular approach is the first choice of treatment in high-risk patients suffering from Leriche syndrome. Although many techniques and devices have been developed, there are still difficulties in accessing the true lumen. Herein, we reported a novel technique to increase the support and ease of crossing the lesion. We presented a case report of a 45-year-old male patient with Leriche syndrome. The patient refused surgery; therefore, he was scheduled for endovascular treatment. We attempted to cross the right and left common iliac occlusions by intraluminal crossing. The left common iliac artery couldn't be cannulated despite the stiff wires and percutaneous intentional extraluminal revascularization (PIER). Afterward, a cross-over approach was performed from the right side to reach the ostium of the left common iliac artery. To increase the support, a non-absorbable suture was stitched up to the tip of the guiding catheter and kept slightly taut like a lasso. Finally, successful penetration was achieved with the novel assistive technique. Endovascular treatment for Leriche syndrome is a precious alternative to open surgery. Intraluminal crossing, PIER, and re-entry devices are the most preferred techniques. Increasing the technical success of intraluminal crossing and PIER leads to an apparent reduction in cost.


[Effects of Lewis Y oligosaccharide on secretion and gene expression of EGF and EGF-R in mouse embryos].
Implantation is a complicated developmental process. Some hormones and cytokines are involved in the regulation of the implantation by regulating functions of the endometrium and the embryo. Oligosaccharide antigen Lewis Y is specifically expressed on embryo surface and plays an important role in implantation. In this study, effects of Lewis Y on secretion and gene expression of EGF and EGF receptor of the embryo were investigated. Embryos were pre-incubated with Le(Y) specific antibody AH6 for 3 h, then antibody was removed, immuno-dot blots and RT-PCR were used to analyze the secretion of EGF and EGF receptor and their gene expression in the embryo at different times after pre-incubation. The results showed that, when blocked by AH6 antibody for 1.5 h, the secretion and expression of EGF in the embryo were significantly declined, and the alteration was continued to over 6 h; and those of EGF-R were slightly decreased after blocking. The results suggest that Lewis Y oligosaccharide on the surface of embryo may be involved in the regulation of embryo development and implantation, by affecting the expression and secretion of EGF in embryo.


Effect of glaucoma on eye movement patterns and laboratory-based hazard detection ability.
The mechanisms underlying the elevated crash rates of older drivers with glaucoma are poorly understood. A key driving skill is timely detection of hazards; however, the hazard detection ability of drivers with glaucoma has been largely unexplored. This study assessed the eye movement patterns and visual predictors of performance on a laboratory-based hazard detection task in older drivers with glaucoma. Participants included 30 older drivers with glaucoma (71±7 years; average better-eye mean deviation (MD) = -3.1±3.2 dB; average worse-eye MD = -11.9±6.2 dB) and 25 age-matched controls (72±7 years). Visual acuity, contrast sensitivity, visual fields, useful field of view (UFoV; processing speeds), and motion sensitivity were assessed. Participants completed a computerised Hazard Perception Test (HPT) while their eye movements were recorded using a desk-mounted Tobii TX300 eye-tracking system. The HPT comprises a series of real-world traffic videos recorded from the driver's perspective; participants responded to road hazards appearing in the videos, and hazard response times were determined. Participants with glaucoma exhibited an average of 0.42 seconds delay in hazard response time (p = 0.001), smaller saccades (p = 0.010), and delayed first fixation on hazards (p<0.001) compared to controls. Importantly, larger saccades were associated with faster hazard responses in the glaucoma group (p = 0.004), but not in the control group (p = 0.19). Across both groups, significant visual predictors of hazard response times included motion sensitivity, UFoV, and worse-eye MD (p<0.05). Older drivers with glaucoma had delayed hazard response times compared to controls, with associated changes in eye movement patterns. The association between larger saccades and faster hazard response time in the glaucoma group may represent a compensatory behaviour to facilitate improved performance.


On the number of EINECS compounds that can be covered by (Q)SAR models for acute toxicity.
The new EU legislation for managing chemicals called REACH aims to fill in gaps in toxicity information that exist for the chemicals listed on the European Inventory of Existing Chemical Substances (EINECS). REACH advocates the use of alternatives to animal experimentation including, amongst others, (quantitative) structure-activity relationship models [(Q)SARs] to help fill in the toxicity data gaps. The aim of the present study was to provide a science-based estimate of the number of EINECS compounds that can be covered by (Q)SAR models for acute toxicity. Using the ECOSAR software, 54% of the 100196 EINECS chemicals were classified into 49 classes that can be potentially covered by (Q)SAR models. The largest proportion of the classified compounds (40% of the EINECS list) falls into the classes of non-polar and polar narcotics. Compounds that were not classified include, for example, fish oils, botanical and animal extracts, and crude oil distillates. With rapid improvements in analytical tools, the number of EINECS compounds for which toxicity evaluations may be based on (Q)SAR approaches may be extended by further developing the method recently developed for the safety assessment of natural flavor complexes used as ingredients in food. This method is based on identification of the individual components in a mixture, and judgment of the safety of these identified individual compounds using toxicity information on structurally similar congeners in the respective classes. Such (Q)SAR approaches may be applied to an additional 2938 EINECS compounds, representing botanical and animal extracts, leading to a total estimate of 57% of the EINECS compounds for which (Q)SAR-based approaches may assist in their safety assessment. It is concluded that, despite the fact that individual (Q)SARs may often each cover only a limited number, i.e. less than 1%, of the EINECS compounds, the potential for applying (Q)SAR approaches for safety assessment of EINECS compounds may prove to be significant.


Band modulation and in-plane propagation of surface plasmons in composite nanostructures.
In this work, we have experimentally and theoretically studied band modulation and in-plane propagation of surface plasmons (SPs) in composite nanostructures with aperture arrays and metallic gratings. It is shown that the plasmonic band structure of the composite system can be significantly modulated because of coupling between the aperture and grating. By changing the relative positions between these optical components, the resonant modes would shift or split. And the resonant SP modes launched on the structure surface can be effectively modified by the geometric parameters. Further, we provide an experimental observation to directly show the SP in-plane propagation by using far-field measurements, which agree with the simulated results. Our study offers a convenient way for observing the SP propagation in far field, and provides unique composite nanostructures for possible applications in subwavelength optodevices, such as optical sensors and detectors.


Probing the catalytic mechanism of Escherichia coli amine oxidase using mutational variants and a reversible inhibitor as a substrate analogue.
Copper amine oxidases are homodimeric enzymes containing one Cu(2+) ion and one 2,4,5-trihydroxyphenylalanine quinone (TPQ) per monomer. Previous studies with the copper amine oxidase from Escherichia coli (ECAO) have elucidated the structure of the active site and established the importance in catalysis of an active-site base, Asp-383. To explore the early interactions of substrate with enzyme, we have used tranylcypromine (TCP), a fully reversible competitive inhibitor, with wild-type ECAO and with the active-site base variants D383E and D383N. The formation of an adduct, analogous to the substrate Schiff base, between TCP and the TPQ cofactor in the active site of wild-type ECAO and in the D383E and D383N variants has been investigated over the pH range 5.5-9.4. For the wild-type enzyme, the plot of the binding constant for adduct formation (K(b)) against pH is bell-shaped, indicating two pK(a)s of 5.8 and approximately 8, consistent with the preferred reaction partners being the unprotonated active-site base and the protonated TCP. For the D383N variant, the reaction pathway involving unprotonated base and protonated TCP cannot occur, and binding must follow a less favoured pathway with unprotonated TCP as reactant. Surprisingly, for the D383E variant, the K(b) versus pH behaviour is qualitatively similar to that of D383N, supporting a reaction pathway involving unprotonated TCP. The TCP binding data are consistent with substrate binding data for the wild type and the D383E variant using steady-state kinetics. The results provide strong support for a protonated amine being the preferred substrate for the wild-type enzyme, and emphasize the importance of the active-site base, Asp-383, in the primary binding event.


Prenatal and perinatal factors in childhood cancer.
The material consists of malignant tumours in childhood notified to the Finnish Cancer Registry in 1959-1968. The maternity health centre cards for these children were collected through the National Board of Health. The immediately preceding parturient of the same maternity health centre was selected as the control. The number of complete pairs obtained for the final analysis was 972. All data concerning the parents, the pregnancy, parturition and the child were extracted from the cards. Information on the cancer patient and the paired control was compared. The results are presented as a comparison of the total tumour series and the controls, but also in smaller sub-groups: leukaemias (373 cases), brain tumours (245 cases) and other tumours (354 cases). Other tumours are further divided into: kidney tumours (96), eye tumours (37) and bone tumours (56). No significant correlations were found between potential aetiologic factors and the cases of cancer. The risk ratio for leukaemia in the group with pelvic radiography was 1.9, and in the group given vaccination against polio 1.8. However, because of the rare occurrence of the exposure mentioned these groups were small and the increase in the risk ratio statistically insignificant. BCG vaccination of children was common (90%) and no differences were established between the tumour and the control groups in this respect.


Uncommon frame-shift exon 19 EGFR mutations are sensitive to EGFR tyrosine kinase inhibitors in non-small cell lung carcinoma.
Exons 19-21 EGFR activating mutations are predictive biomarkers of response to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). However, uncommon exon 19 EGFR mutations, due to their low frequency, have an uncertain biological and clinical significance and very little is known about their TKI sensitivity. This study was designed to describe the TKI sensitivity of a small cohort of lung adenocarcinomas bearing uncommon exon 19 mutations and to evaluate in silico the correlation between frame-shift exon 19 mutations and EGFR sequence/structure modification. Among 1168 NSCLCs screened for EGFR mutational status in our Institutions between 2011 and 2016, seven uncommon exon 19 EGFR mutations were further evaluated: five complex mutations, characterized by a deletion followed by a single-nucleotide insertion, a macrodeletion of 25 bp, and a 19 bp duplication. Interestingly, three patients harboring frame-shift mutations (i.e., one complex mutation, the macrodeletion, and the duplication) showed disease stability and considerably long PFS and OS upon TKI therapy. By contrast, three patients with in-frame complex deletions, independently of the mutation starting point, showed poor/lack of response to TKI therapy. In silico structural analysis showed that sensitivity to TKIs correlates with structural changes in the length and conformation of EGFR C-helix in frame-shift mutations. These data suggest that not all uncommon exon 19 EGFR mutations have the same TKI sensitivity and that frame-shift mutations are responsive to TKIs therapy.


Efficacy of Intravenous Acetaminophen in Periimplantation Pain of Cardiac Electronic Devices: A Randomized Double-Blinded Study.
Although intravenous acetaminophen has been administered to reduce postoperative pain, it has not been used during cardiac implantable electronic devices (CIEDs) implantation. This was a randomized double-blinded interventional study. Thirty-two patients who were referred for new CIED implantation during July 2012 until April 2013 randomly received placebo or 1 g of intravenous acetaminophen. All patients were treated with local anesthesia. Pain score during incision, pocket creation, and in the recovery room, and the patients' need for analgesics during the 6 hours after the procedure were recorded in both groups. Seventeen and 15 patients received acetaminophen and placebo, respectively. Pain scores in patients treated with acetaminophen were significantly lower (4.4 vs 2.9, P = .004), and they received less analgesics (17% vs 60%, P = .014). Intravenous administration of acetaminophen is effective for pain relief in patients undergoing CIED implantation and decreases the need for postoperative analgesics.


High carbohydrate and high monounsaturated fatty acid diets similarly affect LDL electrophoretic characteristics in men who are losing weight.
We compared the effects of ad libitum consumption of a defined high complex carbohydrate (CHO) diet (% of energy: CHO, 58.3; fat, 25.8) vs. a defined high monounsaturated fatty acid (MUFA) diet (% of energy: CHO, 44.7; fat, 40.1; MUFA, 22.5) on LDL electrophoretic characteristics. Healthy men [n = 65; age, 37.5 +/- 11.2 (mean +/- SD) y; BMI, 29.2 +/- 4.9 kg/m2] were randomly assigned to one of the two diets that they consumed for 6-7 wk. The high CHO diet significantly reduced body weight (-2%). The diet-induced reduction in plasma LDL cholesterol (C) levels in the high-CHO diet group was due mainly to concurrent reductions in the cholesterol content of small (<25.5 nm, P < 0.01) and medium-sized LDL (25.5-26.0 nm, P = 0.01). The high MUFA diet also reduced body weight, and LDL-C and LDL-apolipoprotein (apo)B levels, which were comparable to those in the high CHO group. The cholesterol levels of small LDL particles tended to be reduced (P = 0.24) in the high MUFA group (-12%), similar to changes in the high CHO group. These results suggest that, when associated with weight loss, ad libitum consumption of high CHO and high MUFA diets may be considered to be equally beneficial for the management of LDL-related atherogenic dyslipidemia. However, the high MUFA diet more favorably affected triglyceride levels, suggesting that it may be preferable to a high CHO diet in cardiovascular disease prevention.


A knockout approach indicates a minor vasoconstrictor role for vascular alpha1B-adrenoceptors in mouse.
Pharmacological analysis alone has failed to clarify the role of the three alpha(1)-adrenoceptor subtypes in modulating vascular tone, due to a lack of sufficiently selective antagonists, particularly for the alpha (1B)-adrenoceptor, and the complexity when three receptor subtypes are potentially activated by the same agonist. We adopted a combined genetics/ pharmacology strategy based on the alpha(1B)-adrenoceptor knockout (KO) mouse. The potency of three alpha(1)-adrenoceptor antagonists vs. phenylephrine was tested in aorta, carotid, mesenteric, and caudal isolated arteries from KO and wild-type (WT) mice. In the KO mouse the pharmacology became straightforward, showing alpha(1D) in two major conducting arteries (aorta and carotid) and alpha(1A) in two distributing arteries (mesenteric and caudal). By combining antagonist pharmacology and genetics, we provide a simplified analysis of alpha(1)-mediated vasoconstriction, demonstrating that alpha(1D) and alpha(1A) are the major subtypes involved in vasoconstriction, with a minor but definite contribution from alpha(1B) in every vessel.


Anatomy and physiology of chronic scrotal pain.
This article reviews the anatomy and physiology of the scrotum and its contents as it pertains to chronic scrotal pain. Physiology of chronic pain is reviewed, as well as the pathophysiology involved in the development of chronic pain.


Radiolucent halos beneath composite restorations do not justify restoration replacement.
To determine the correlation between the presence of radiolucent areas (RA) beneath composite restorations and gaps and remaining demineralized tissue (RDT). 50 extracted teeth (sound and carious) were studied. After caries removal, cavities were filled. Artificial cavities were created and filled in the sound teeth. Samples were sectioned and analyzed with stereomicroscopy. Gap/RDT was observed in 38.9% [95% confidence interval (CI) =28.2-50.5] and 68.9% (95% CI = 57-78.6) of sound and carious teeth, respectively, (P = 0.001). Gap/RDT was associated with RA (P < 0.001). Sensitivity, specificity, predictive positive values (PPV), predictive negative value, and accuracy for carious teeth were 77.1% (95% CI = 63.7-87.3), 54.5% (95% CI = 33.8-74.1), 78.7% (95% CI = 65.3- 88.7), 52.2% (95% CI = 32.1-71.7), and 70% (95% CI = 58.5-79.8), and for sound teeth were 73.7% (95% CI = 62.9-82.6), 59.1% (95% CI = 47.0-70.4), 67.5% (95% CI = 56.9-76.9), 66.1% (95% CI = 53.4-77.3), and 66.9% (95% CI = 58.9-74.3). Only the PPV differed between the sound and carious teeth (P = 0.024).There was a correlation between radiolucency and gap/RDT, but a high number of false positives were found.


Chronic cutaneous mycobacterial ulcers due to Mycobacterium ulcerans (Buruli ulcer): the first indigenous case report from Jordan and a literature review.
Buruli ulcer is the third most common mycobacterial infection worldwide. It is endemic in tropical, subtropical, and temperate climates. It causes devastating disease with morbidity and mortality. The treatment duration is long and the regimens considered are limited. Chronic cutaneous ulcers of mycobacterial etiology have been reported previously in Amman, but these were not associated with Mycobacterium ulcerans infection. The case patient's initial diagnosis was based on chronological and morphological features, combined with appropriate diagnostic tests. The skin features were assessed histopathologically. Skin testing was positive for acid-fast bacilli (AFB), and M. ulcerans was identified by DNA strip test (GenoType Mycobacterium CM/AS, Hain Lifescience), which is based on a PCR technique targeting a 23S rRNA gene region, followed by reverse hybridization and a line probe technology. The skin mycobacterial infection was evaluated and verified as having a Mycobacterium marinum-M. ulcerans pattern in the GenoType CM assay. It was then counted as a pattern representing individual species and was resolved with the GenoType AS assay as having an M. ulcerans pattern. M. ulcerans DNA was isolated and amplified by PCR, and then detected against reverse hybridization probes in the strip assay. An indigenous case of M. ulcerans (Buruli ulcer) is reported for the first time from Jordan and the surrounding region.


Control of T-2 toxin in Fusarium langsethiae and Geotrichum candidum co-culture.
Due to contamination of barley grains by Fusarium langsethiae, T-2 toxin can be present in the brewing process. It has been observed that the presence of the yeast Geotrichum candidum during malting can reduce the final concentration of this mycotoxin in beer. In this work, a co-culture method was carried out for both microorganisms in order to evaluate the effect on T-2 mycotoxin concentration in comparison with the pure culture of F. langsethiae in the same conditions. The microbial growth of both microorganisms was assessed using three different methods: dry weight, DOPE-FISH, and DNA quantification. In coculture, both microorganisms globally developed less than in pure cultures but G. candidum showed a better growth than F. langsethiae. The concentration of T-2 was reduced by 93 % compared to the pure culture. Hence, the interaction between G. candidum and F. langsethiae led to a drastic mycotoxin reduction despite the only partial inhibition of fungal growth.


Tricuspid edge-to-edge repair for tricuspid valve prolapse and flail leaflet. Feasibility in comparison to patients with secondary tricuspid regurgitation.
Transcatheter tricuspid edge-to-edge repair (T-TEER) has gained widespread use for the treatment of tricuspid regurgitation in symptomatic patients with high operative risk. Although secondary TR is the most common pathology, some patients exhibit primary or predominantly primary TR. Characterization of patients with these pathologies in the T-TEER context has not been systematically performed. Patients assigned to T-TEER by the interdisciplinary Heart Team were consecutively recruited in two European centers over 4 years. Echocardiographic images were evaluated to distinguish between primary and secondary causes of TR. Both groups were compared concerning procedural results. 339 patients were recruited, 13% with primary TR and 87% with secondary TR. Patients with primary TR had a smaller right ventricle (basal diameter 45 vs. 49 mm, p = 0.004), a better right ventricular function (fractional area change 45 vs. 41%, p = 0.001), a smaller right (28 vs. 34cm², p = 0.021) and left (52 vs. 67 ml/m², p = 0.038) atrium, and a better left ventricular ejection fraction (60 vs. 52%, p = 0.005). The severity of TR was similar in primary and secondary TR at baseline (TR vena contracta width pre-interventional 13 ± 4 vs. 14 ± 5 mm, p = 0.19), and T-TEER significantly reduced TR in both groups (TR vena contracta width post-interventional 4 ± 3 vs. 5 ± 5 mm, p = 0.10). These findings remained stable after propensity score matching. Complications were similar between both groups. T-TEER confers equally safe and effective reduction of TR in patients with primary and secondary TR.


Capacitance-voltage characteristics of sub-nanometric Al2O3 / TiO2 laminates: dielectric and interface charge densities.
Advanced amorphous sub-nanometric laminates based on TiO2 and Al2O3 were deposited by atomic layer deposition at low temperature. Low densities of 'slow' and 'fast' interface states are achieved with values of 3.96 · 1010 cm-2 and 4.85 · 10-9 eV-1 cm-2, respectively, by using a 40 nm laminate constituted of 0.7 nm TiO2 and 0.8 nm Al2O3. The sub-nanometric laminate shows a low hysteresis width of 20 mV due to the low oxide charge density of about 3.72 · 1011 cm-2. Interestingly, such properties are required for stable and reliable performance of MOS capacitors and transistor operation. Thus, decreasing the individual layer thickness to the sub-nanometric range and combining two dielectric materials with oppositely charged defects may play a major role in the electrical response, highly promising for the application in future micro and nano-electronics applications.


Hyperbilirubinemia in otherwise healthy infants.
Treatment of hyperbilirubinemia in otherwise healthy infants is controversial, since hyperbilirubinemia in the absence of hemolytic disease, hepatobiliary disease or prematurity is not clearly associated with kernicterus or other long-term morbidity. Phototherapy, exchange transfusion and the withholding of breast milk are the only treatments that have proved effective. Home phototherapy may be useful in treating infants for whom hospitalization is otherwise unnecessary.


Peptide aptamers with binding specificity for the intracellular domain of the ErbB2 receptor interfere with AKT signaling and sensitize breast cancer cells to Taxol.
The ErbB2 receptor tyrosine kinase is overexpressed in approximately 30% of breast tumor cases and its overexpression correlates with an unfavorable prognosis. A major contributor for this course of the disease is the insensitivity of these tumors toward chemotherapy. Monoclonal antibodies, inhibiting the ligand-induced activation of the receptor and tyrosine kinase inhibitors acting on the intrinsic enzymatic activity of the intracellular domain, have been developed as targeted drugs. Both have been shown to be beneficial for breast cancer patients. We targeted a third aspect of receptor function: its association with intracellular signaling components. For this purpose, we selected peptide aptamers, which specifically interact with defined domains of the intracellular part of the receptor. The peptide aptamers were selected from a random peptide library using a yeast two-hybrid system with the intracellular tyrosine kinase domain of ErbB2 as a bait construct. The peptide aptamer AII-7 interacts with high specificity with the ErbB2 receptor in vitro and in vivo. The aptamers colocalized with the intracellular domain of ErbB2 within cells. We investigated the functional consequences of the aptamer interaction with the ErbB2 receptor within tumor cells. The aptamer sequences were either expressed intracellularly or introduced into the cells as recombinant aptamer proteins. The phosphorylation of p42/44 mitogen-activated protein kinase was nearly unaffected and the activation of signal transducers and activators of transcription-3 was only modestly reduced. In contrast, they strongly inhibited the induction of AKT kinase in MCF7 breast cancer cells treated with heregulin, whereas AKT activation downstream of insulin-like growth factor I or epidermal growth factor receptor was not or only slightly affected. High AKT activity is responsible for the enhanced resistance of ErbB2-overexpressing cancer cells toward chemotherapeutic agents. Peptide aptamer interference with AKT activation resulted in the restoration of regular sensitivity of breast cancer cells toward Taxol.


Study of four new kindreds with inherited thyroxine-binding globulin abnormalities. Possible mutations of a single gene locus.
Five families with inherited thyroxine-binding globulin (TBG) abnormalities were studied. On the basis of serum thyroxine (T(4))- binding capacity of TBG in affected males, three family types were identified: TBG deficiency, low TBG, and high TBG capacity. In all families evidence for X-linked inheritance was obtained and in one family all criteria establishing this mode of inheritance were met. Only females were heterozygous, exhibiting values intermediate between affected males and normals. Overlap in heterozygotes was most commonly encountered in families with low TBG. QUANTITATIVE VARIATION IN THE SERUM CONCENTRATION OF FUNCTIONALLY NORMAL TBG WAS DEMONSTRATED BY: (a) failure of serum from TBG-deficient subjects to react with anti-TBG antibodies; (b) normal kinetics of T(4) and triiodothyronine-binding to TBG in sera from subjects with low TBG and high TBG capacity; (c) concordance of estimates of TBG concentration by T(4) saturation and by immunological methods; and (d) normal rate of heat inactivation of TBG. No abnormalities in serum transport of cortisol, testosterone, aldosterone, or thyroxine bound to prealbumin could be detected. These observations suggest that all the TBG abnormalities thus far observed reflect mutations at a single X-linked locus involved in the control of TBG synthesis.


Postradiation Matrix Metalloproteinase-20 Expression and Its Impact on Dental Micromorphology and Radiation-Related Caries.
Recent evidence suggests that head-and-neck radiotherapy (HNRT) increases active forms of matrix metalloproteinase-20 (MMP-20) in human tooth crowns, degrading the dentin-enamel junction (DEJ) and leading to enamel delamination, which is a pivotal step in the formation of radiation-related caries (RRC). Additional participation of enzymatic degradation of organic matrix components in caries progression was attributed to MMP-20 in dentin. Therefore, the current study tested the hypothesis that MMP-20 is overexpressed in the DEJ, dentin-pulp complex components, and carious dentin of post-HNRT patients, leading to detectable micromorphological changes to the enamel and dentin. Thirty-six teeth were studied, including 19 post-HNRT specimens and 17 nonirradiated controls. Optical light microscopy was used to investigate the micromorphological components of the DEJ, dentin-pulp complex components, and carious dentin. The samples were divided into 2 subgroups: nondemineralized ground sections (n = 20) and demineralized histological sections (n = 16). In addition, immunohistochemical analysis using the immunoperoxidase technique was conducted to semiquantitatively assess MMP-20 expression in the DEJ, dentin-pulp complex components, and carious dentin. No apparent damage to the DEJ microstructure or other dentin-pulp complex components was observed and no statistically significant differences were detected in MMP-20 expression (p > 0.05) between the irradiated and control groups. This study rejected the hypothesis that MMP-20 is overexpressed in the DEJ, dentin-pulp complex components, and carious dentin of post-HNRT patients, leading to detectable micromorphological changes. Hence, direct effects of radiation may not be regarded as an independent factor to explain aggressive clinical patterns of RRC.


Managing rapid metabolizers of antidepressants.
Depressed patients who rapidly metabolize antidepressants may be common, and may not respond to even high doses of antidepressants if subtherapeutic plasma levels are produced. Rapid metabolizers (RMs) are identifiable if patients are on tricyclic antidepressants (TCAs), and TCA plasma levels (commonly available) are monitored. Strategies to achieve therapeutic levels in RMs include: (1) megaprescribing, or (2) inhibiting the metabolism of the parent drug. Megaprescribing TCAs runs the risk of markedly elevating levels of potentially toxic hydroxy metabolites. In this study twelve depressed, non-responding RMs were identified while taking the TCA, desipramine. Fluoxetine or paroxetine, selective serotonin re-uptake inhibitors (SSRIs) known to potently inhibit cytochrome P450 2D6 (the isoenzyme responsible for desipramine metabolism), was then added to continuing desipramine. Therapeutic range desipramine levels were achieved in ten patients, and seven of the ten achieved excellent or good sustained responses. The combination SSRI and TCA therapy was well tolerated. Whether response primarily reflected the TCA at therapeutic range levels, or a synergistic serotonin-noradrenaline interaction between the respective antidepressants, requires further clarification. The results of this open study suggest the need for controlled trials of antidepressant metabolism inhibition in RMs.


Cross-cultural adaptation, reliability, and validity of the work role functioning questionnaire to Brazilian Portuguese.
The study objectives were to translate and adapt the Work Role Functioning Questionnaire (WRFQ) into the Brazilian Portuguese language and evaluate its reliability in patients experiencing musculoskeletal disorders. The cross-cultural adaptation was performed according to the internationally recommended methodology, using the following guidelines: translation, back-translation, revision by a committee, and pretest. At first, the questionnaire was independently translated by two bilingual translators, who had Portuguese as their mother language. Subsequently, two other translators whose mother language was English did the back-translation. A committee composed of five specialists revised and compared the translations obtained, developing the final version for pretest application. The pretest was carried out with 30 patients experiencing musculoskeletal disorders. Psychometric properties were evaluated by administering the questionnaire to 105 subjects with musculoskeletal disorders and receiving physical therapy treatment. The reliability was estimated through stability and homogeneity assessment. The construct validity was tested comparing subjects experiencing musculoskeletal disorders to healthy workers. The results indicated good content validity and internal consistency (Cronbach alpha = 0.95). Cronbach alpha for each scale was >0.85, except for the social demand scale. The Intraclass Correlation Coefficient for the test-retest reliability was satisfactory for mental demands (ICC = 0.68) and excellent for the others (0.82-0.91). In relation to the construct validity, the mean score obtained for each scale was lower for physical, work scheduling, and output demands in the subjects with musculoskeletal disorders. There was a significant difference (p < 0.001) between the groups in comparison to work scheduling, physical, and output demands. The data showed that the cross-cultural adaptation process was successful and the adapted instrument demonstrated psychometric properties making it reliable to use in Brazilian culture.


Computer-based medical decision support system in diagnosis and treatment of musculoskeletal disorders and injuries.
The use of information technologies in health care systems around the world dates back to the 1970s. But it was only the dynamic development of information technology in the 1990s that enabled significant development of IT systems supporting broadly defined medical activity. The ongoing process of transformation of the Polish healthcare system has been forcing health care providers to expend financial, material and human resources increasing efficiency. At the same time, the very dynamic development of medical sciences and information technologies has brought about a significant increase in the number of papers of importance for the effectiveness and quality of medical care. As a result, medical specialists are not able to keep up with the constantly updated medical knowledge. These factors are making standardization of health care processes a growing necessity. This paper is an introductory work presenting, on the basis of the available literature and the authors' research experience, a historical outline, stages of development and state of the art of information technology in medicine, as well as theoretical objectives of the project, which are specified in the title of this paper.


[The course of diffuse hyperthyroidism in Basedow disease].
An investigation of a large group of patients with Graves' disease demonstrates that this autoimmune disorder of the thyroid is a chronic process with an often protracted course and therefore requires virtually life-long management. Drug therapy (with thionamides) is associated with a high rate of relapse of 60-70%-reliable criteria for the cessation of the autoimmune process are not available. Surgical therapy may also fail to provide lasting control of hyperthyroidism.


The impact of Hispanic and white group cues on attitudes towards the violation of generic norms.
While much work in political science has examined the impact of racial cues on individual perceptions, we know little about how individuals evaluate members of minority outgroups on issues that are not linked to stereotypes. We measure the impacts of Hispanic and White cues on individual assessments related to a stereotype-independent norm violation: alcoholism. We test three competing theories--cognition, intergroup emotions, and social identity--using a population-based vignette experiment included in the General Social Survey. Our results contradict much of the literature, but keep with social identity theory's predictions. Hispanic alcoholics, when Hispanics constitute the outgroup, are assessed less negatively than White alcoholics in the ingroup, the latter experiencing what is called the black sheep effect. The black sheep effect occurs when ingroup members are more punitive towards members of the ingroup than the outgroup. However, the black sheep effect does not extend to measures that are more consistent with outgroup stereotypes, such as violence or money mismanagement; Hispanic alcoholics are evaluated more negatively than Whites on these measures. The implication is that the effect of racial cues depends strongly on issue linkages to group stereotypes.


[Preliminary study on microRNA regulated osteogenic and chondrogenic differentiation of mouse stem cells].
To investigate the specific microRNA (miRNA) in osteogenic and chondrogenic differentiations of C3H10Tl/2 cells. C3H10Tl/2 cells were induced to differentiate into osteoblasts and chondrocytes. Specific miRNA more than 2 fold change and 2 average normalized probe signal between C3H10Tl/2 and C3H10Tl/2-derived osteoblast, and' between C3Hl0Tl/2 and C3H10Tl/2-derived chondrocytes were screened out by miRNA microarray, and verified by real-time fluorescence quantitative PCR (RT-qPCR). Alkaline phosphatase expression of osteogenic induced group was significantly higher than that of control group at 7 days after induced (P < 0.05). RT-qPCR results showed the expressions of Runx2, serine protease (Sp7), collagen type I, and osteopontin (OPN) genes were significantly increased at 7, 14, and 21 days after induced when compared with before induced (P < 0.05). Western blot results showed the expressions of Runx2, Sp7, collagen type I, and OPN proteins of osteogenic induced group were significantly higher than those of control group at 21 days after induced (P < 0.05). The expressions of SOX9, collagen type II, Aggrecan, and Has2 were significantly increased at 5, 10, and 15 days after induced when compared with before induced (P < 0.05). The expressions of SOX9, collagen type 2, Aggrecan, and Has2 proteins of chondrogenic induced group were significantly higher than those of control group at 15 days after induced (P < 0.05). Totally, 10 osteogenic and 3 chondrogenic miRNA more than 2 fold change and 2 average normalized probe signal were screened out by miRNA microarray. RT-qPCR results of these specific miRNAs were similar to microarray results except miR-455-3p. Specific miRNAs are screened out by microarray and it is a good foundation for the future study on miRNA functional verification and target gene prediction.


Anatomy of corpus callosum in prenatally malnourished rats.
The effect of prenatal malnutrition on the anatomy of the corpus callosum was assessed in adult rats (45-52 days old). In the prenatally malnourished animals we observed a significant reduction of the corpus callosum total area, partial areas, and perimeter, as compared with normal animals. In addition, the splenium of corpus callosum (posterior fifth) showed a significant decrease of fiber diameters in the myelinated fibers without changing density. There was also a significant decrease in diameter and a significant increase in density of unmyelinated fibers. Measurements of perimeter's fractal dimensions from sagittal sections of the brain and corpus callosum did not show significant differences between malnourished and control animals. These findings indicate that cortico-cortical connections are vulnerable to the prenatal malnutrition, and suggest this may affect interhemispheric conduction velocity, particularly in visual connections (splenium).


A Novel Framework Based on the Improved Job Demands-Resources (JD-R) Model to Understand the Impact of Job Characteristics on Job Burnout from the View of Emotion Regulation Theory.
It has been suggested that individual job characteristics have a significant impact on job burnout, and the process is subject to the regulation of demographic variables. However, the influence path of job characteristics on job burnout is still a "black box". On the basis of a systematic literature review by employing Pub Med, Science Direct, Web of Science, Google Scholar, CNKI and Scopus for required information with the several keywords "Job burnout", "Emotion regulation", "Personality traits", and "Psychological stress", in this study, an improved mine rescue workers-oriented job demands-resources (JD-R) model was put forward. Then, a novel analysis framework, to explore the impact of job characteristics on job burnout from the view of emotion regulation theory, was proposed combining the personality trait theory. This study argues that job burnout is influenced by job demands through expressive suppression and by job resources through cognitive reappraisal respectively. Further more, job demands and job resources have the opposite effects on job burnout through the "loss-path" caused by job pressure and the "gain-path" arised from job motivation, respectively. Extrovert personality traits can affect the way the individual processes the information of work environment and then how individual further adopts emotion regulation strategies, finally resulting in indirectly affecting the influence path of mine rescue workers' job characteristics on job burnout. This present study can help managers to realize the importance of employees' psychological stress and job burnout problems. The obtained conclusions provide significant decision-making references for managers in intervening job burnout, managing emotional stress and mental health of employees.


Transanal Versus Transabdominal Minimally Invasive (Completion) Proctectomy With Ileal Pouch-anal Anastomosis in Ulcerative Colitis: A Comparative Study.
This study aims to compare surgical outcome of transanal ileal pouch-anal anastomosis (ta-IPAA) with transabdominal minimal invasive approach in ulcerative colitis (UC), using the comprehensive complication index (CCI). Recent evolutions in rectal cancer surgery led to transanal dissection of the rectum resulting in a better exposure of the distal rectum and presumed better outcome. The same approach was introduced for patients with UC, resulting in decreased invasiveness. All patients, undergoing minimally invasive restorative proctocolectomy in 1, 2, or 3 stages between January 2011 and September 2016 in 3 referral centers were included. Only patients who underwent either multiport, single port, single port with 1 additional port, hand-assisted, or robotic (R) laparoscopy were included in the analysis. CCI, registered during 90 days after pouch construction, was compared between the transanal and the transabdominal approach. Ninety-seven patients (male: 52%) with ta-IPAA were compared to 119 (male: 53%) with transabdominal IPAA. Ninety-nine (46%) patients had a defunctioning ileostomy at time of pouch construction. A 2-step model showed that the odds for postoperative morbidity were 0.52 times lower in the ta-IPAA group (95% confidence interval [0.29; 0.92] P = 0.026). In patients with morbidity, mean CCI of the transanal approach was 2.23 points lower than the transabdominal approach (95% confidence interval: [-6.64-3.36] P = 0.13), which was not significant. Ta-IPAA for UC is a safe procedure, resulting in fewer patients with morbidity, but comparable CCI when morbidity is present. Overall, ta-IPAA led to lower CCI scores.


Induction of parental behavior in Japanese quail (Coturnix coturnix japonica).
The Japanese quail is a precocial species, and because of its relatively rapid development, sexual maturation in about 40 days after hatching, and prolific breeding capacity, it promises to become an organism well suited for avian research. One stumbling block has been the inability to induce, with any consistency, parental behavior in laboratory stocks. The study reported herein demonstrates a method for establishing a self-perpetuating population under seminaturalistic conditions. In addition, given the limitions of finite space, chick mortality appears to have been mostly density dependent, thus indicating that the increase in the size of the population is circumscribed in part by population density.