Educational inequalities in cause-specific mortality in middle-aged and older men and women in eight western European populations.
Studies of socioeconomic disparities in patterns of cause of death have been limited to single countries, middle-aged people, men, or broad cause of death groups. We assessed contribution of specific causes of death to disparities in mortality between groups with different levels of education, in men and women, middle-aged and old, in eight western European populations. We analysed data from longitudinal mortality studies by cause of death, between Jan 1, 1990, and Dec 31, 1997. Data were included for more than 1 million deaths in 51 million person years of observation. Absolute educational inequalities in total mortality peaked at 2127 deaths per 100000 person years in men, and at 1588 deaths per 100000 person years in women aged 75 years and older. In this age-group, rate ratios were greater than 1.00 for total mortality and all specific causes of death, apart form prostate cancer in men and lung cancer in women, showing increased mortality in low versus high educational groups. In men, cardiovascular diseases accounted for 39% of the difference between low and high educational groups in total mortality, cancer for 24%, other diseases for 32%, and external causes for 5%. Among women, contributions were 60%, 11%, 30%, and 0%, respectively. The contributions of cerebrovascular disease, other cardiovascular diseases, pneumonia, and COPD strongly increased by age, whereas those of cancer and external causes declined. Although relative inequalities in total mortality were closely similar in all populations, we noted striking differences in the contribution of specific causes to these inequalities. Research needs to be broadened to include older populations, other diseases, and populations from different parts of Europe. Effective interventions should be developed and implemented to reduce exposure to cardiovascular risk factors in low-educational groups.


[Nonspecific resistance in germ-free and E. coli monocontaminated miniature piglets].
Phagocytic activity of leukocytes, as well as the complement, properdin, and lysozyme levels in the blood serum of miniature piglets, germfree and monocontaminated with E. coli 055 and E. coli 083, were studied. E. coli 055 phagocytosis was decreased in the presence of autologous serum and complement and increased under the effect of specific opsonins (antibodies to E. coli 055). Complement, properdin, and lysozyme levels were decreased in the germfree, in comparison with conventional animals. In the E. coli contaminated piglets properdin and complement production was stimulated most, and lysozyme formation--less. No antibodies to E. coli 055 were revealed in monocontaminated piglets. The highest lysozyme levels were found in the ex-germfree animals, this indicating the participation of factors other than E. coli contamination in lysozyme stimulation. It is concluded that microbial contamination played an important role in the development of cellular and humoral factors of the organism resistance.


Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method.
We applied a novel method to detect single or multiple exon deletions and amplifications in the BRCA1 gene. The test, called multiplex ligation-dependent probe amplification (MLPA), uses probes designed to hybridize adjacently to the target sequence. After ligation, the joined probes are amplified and quantified. Our two diagnostic laboratories have tested in the recent years 805 families by conventional PCR-based techniques, and found 116 BRCA1 and 28 BRCA2 mutation-positive families. Using MLPA, we have tested the remaining 661 noninformative breast cancer families and identified five distinct BRCA1 germ-line mutations in five families: a deletion of exon 8, a deletion of exons 20-22, a duplication of exon 13 and exons 21-23, respectively, and a triplication, encompassing exons 17-19. Genomic deletions of BRCA1 constitute a substantial fraction of mutations in Dutch breast cancer families. If MLPA had been included in our initial BRCA1 testing, 33 families with a deletion or duplication would have been identified, representing 27% of the total 121 BRCA1 mutation-positive families. The MLPA test for BRCA1 ensures a sensitive and comprehensive high-throughput screening test for genomic rearrangement and can easily be implemented in the molecular analysis of BRCA1.


Microbial community changes in hydraulic fracturing fluids and produced water from shale gas extraction.
Microbial communities associated with produced water from hydraulic fracturing are not well understood, and their deleterious activity can lead to significant increases in production costs and adverse environmental impacts. In this study, we compared the microbial ecology in prefracturing fluids (fracturing source water and fracturing fluid) and produced water at multiple time points from a natural gas well in southwestern Pennsylvania using 16S rRNA gene-based clone libraries, pyrosequencing, and quantitative PCR. The majority of the bacterial community in prefracturing fluids constituted aerobic species affiliated with the class Alphaproteobacteria. However, their relative abundance decreased in produced water with an increase in halotolerant, anaerobic/facultative anaerobic species affiliated with the classes Clostridia, Bacilli, Gammaproteobacteria, Epsilonproteobacteria, Bacteroidia, and Fusobacteria. Produced water collected at the last time point (day 187) consisted almost entirely of sequences similar to Clostridia and showed a decrease in bacterial abundance by 3 orders of magnitude compared to the prefracturing fluids and produced water samplesfrom earlier time points. Geochemical analysis showed that produced water contained higher concentrations of salts and total radioactivity compared to prefracturing fluids. This study provides evidence of long-term subsurface selection of the microbial community introduced through hydraulic fracturing, which may include significant implications for disinfection as well as reuse of produced water in future fracturing operations.


Quality of life in patients with colorectal cancer 1 year after diagnosis compared with the general population: a population-based study.
Quality of life (QOL) has become an important outcome measure for patients with cancer, but long-term results from population-based studies are rare. The objective of our study was to identify specific limitations of QOL in survivors of colorectal cancer in comparison with men and women from the general population 1 year after diagnosis when acute treatment effects are expected to have declined. QOL was assessed 1 year after diagnosis in a population-based cohort of 439 patients with colorectal cancer from Saarland (Germany) using the EORTC-QLC30 questionnaire. Specific functional and symptom QOL scores were compared with published reference data from the general population. Of 439 patients, 378 of them survived the first year after tumor diagnosis (86.1%). Of these, 309 returned the questionnaire (response rate, 81.7%). Compared with the general population, colorectal cancer patients scored their physical, role, cognitive, and global health functioning only slightly worse. More severe limitations were observed for the emotional and social functioning scales and for the symptom subscales of fatigue, dyspnea, insomnia, constipation, diarrhea, and financial difficulties. The differences regarding functional and symptom scores were predominantly found in younger age groups whereas older cancer patients and controls rated their health and QOL similarly. Deficits in emotional and social functioning and specific limitations like fatigue, dyspnea, insomnia, constipation, diarrhea, and financial difficulties are main factors hampering the QOL among colorectal cancer patients and seem to affect predominantly younger patients.


Sticking out versus fitting in: A social context perspective of ingratiation and its effect on social exchange quality with supervisors and teammates.
Research indicates that whereas ingratiation directed toward one's supervisor enhances employee-supervisor social exchange quality, it diminishes social exchange quality with those who observe this behavior, such as team members. However, because researchers have largely overlooked the role of social context in shaping supervisors' and teammates' reactions to ingratiatory employees, current understanding of how ingratiation plays out in complex organizational settings may be incomplete, and perhaps misleading. In this study, we augment a social context perspective with social exchange theory to propose that comparative levels of ingratiation, determined by the focal employee's ingratiation in the context of other team members' ingratiation, shape social exchange quality with supervisors and teammates. The results from a multi-wave multi-source field study of 222 employees and their supervisors from 64 teams show that higher levels of ingratiation relative to other team members increases the employee's social exchange quality with the supervisor, whereas congruence between the employee's and other team members' ingratiation enhances social exchange quality with team members. We also find that relative ingratiation and ingratiation congruence increase citizenship received from supervisors and team members, respectively, via social exchange quality with the corresponding actor(s). Overall, our research contributes to a more complete understanding of ingratiation, especially in regard to how reactions to this behavior are largely a function of the social context in which it occurs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


The climate commons dilemma: how can humanity solve the commons dilemma for the global climate commons?
In the era when human activities can fundamentally alter the planetary climate system, a stable climate is a global commons. However, the need to develop the economy to sustain the growing human population poses the Climate Commons Dilemma. Although citizens may need to support policies that forgo their country's economic growth, they may instead be motivated to grow their economy while freeriding on others' efforts to mitigate the ongoing climate change. To examine how to resolve the climate commons dilemma, we constructed a Climate Commons Game (CCG), an experimental analogue of the climate commons dilemma that embeds a simple model of the effects of economic activities on global temperature rise and its eventual adverse effects on the economy. The game includes multiple economic units, and each participant is tasked to manage one economic unit while keeping global temperature rise to a sustainable level. In two experiments, we show that people can manage the climate system and their economies better when they regarded the goal of environmentally sustainable economic growth as a singular global goal that all economic units collectively pursue rather than a goal to be achieved by each unit individually. In addition, beliefs that everyone shares the knowledge about the climate system help the group coordinate their economic activities better to mitigate global warming in the CCG. However, we also found that the resolution of the climate commons dilemma came at the cost of exacerbating inequality among the economic units in the current constrains of the CCG. The online version contains supplementary material available at 10.1007/s10584-021-02989-2.


New bioinformatic tool for quick identification of functionally relevant endogenous retroviral inserts in human genome.
Endogenous retroviruses (ERVs) and LTR retrotransposons (LRs) occupy ∼8% of human genome. Deep sequencing technologies provide clues to understanding of functional relevance of individual ERVs/LRs by enabling direct identification of transcription factor binding sites (TFBS) and other landmarks of functional genomic elements. Here, we performed the genome-wide identification of human ERVs/LRs containing TFBS according to the ENCODE project. We created the first interactive ERV/LRs database that groups the individual inserts according to their familial nomenclature, number of mapped TFBS and divergence from their consensus sequence. Information on any particular element can be easily extracted by the user. We also created a genome browser tool, which enables quick mapping of any ERV/LR insert according to genomic coordinates, known human genes and TFBS. These tools can be used to easily explore functionally relevant individual ERV/LRs, and for studying their impact on the regulation of human genes. Overall, we identified ∼110,000 ERV/LR genomic elements having TFBS. We propose a hypothesis of "domestication" of ERV/LR TFBS by the genome milieu including subsequent stages of initial epigenetic repression, partial functional release, and further mutation-driven reshaping of TFBS in tight coevolution with the enclosing genomic loci.


Physalaemin: an amphibian tachykinin in human lung small-cell carcinoma.
Immunoreactivity to the amphibian peptide physalaemin was characterized from extracts of a human lung small-cell carcinoma by immunological, chemical, and pharmacological means. Tumor-related peptide cross-reacted with three antiserums to physalaemin to yield 1.1 to 1.6 nanomoles per gram of tissue. Physalaemin and tumor peptide had similar retention times on high-performance liquid chromatography after chemical and enzymic modifications that included pH changes, oxone oxidation, use of a hydrophilic ion-pairing reagent, and digestion with trypsin and pyroglutamate aminopeptidase. Both physalaemin and the tumor peptide produced a contractile response of isolated guinea pig ileum at threshold concentrations of approximately 100 to 150 picograms per milliliter. These data suggest that small-cell carcinoma of the lung contains a physalaemin-like peptide that has structural and biological homology to its amphibian counterpart.


Characterization of a photoaffinity analog of UTP, 5-azido-UTP for analysis of the substrate binding site on E. coli RNA polymerase.
The substrate binding site on E. coli RNA polymerase was investigated by photoaffinity labeling with a photoaffinity analog of UTP, 5-azido-UTP. We have established that 5-azido-UTP is a substrate for RNA polymerase by specific transcription on 229 bp DNA containing the gene II promoter of M13 phage. Analysis of the initial rate of RNA synthesis gives Km(5-azido-UTP) approximately 80 microM. Photolabeling with varying concentrations of 5-azido-UTP follows a saturation curve with the midpoint occurring at a 5-azido-UTP concentration of 65 microM near to the Km obtained by kinetic analysis. 5-Azido-UTP photolabels the beta', beta, and sigma subunits to about the same extent, both in the presence (33, 31, and 36%) and absence (35, 30 and 35%) of DNA. This labeling pattern is somewhat different from that obtained with 8-azido-ATP (beta' greater than sigma much greater than beta greater than alpha).


MR imaging and CT of the biliary tract.
Magnetic resonance (MR) imaging and computed tomography (CT) can be useful in the diagnosis of biliary disease, with both modalities allowing detailed evaluation of the biliary tract. Careful interrogation of the images is critical, regardless of modality. The identification of dilated bile ducts necessitates evaluation for strictures or filling defects, which is best performed with thin-section imaging. Smooth, concentric short-segment strictures favor a benign cause, whereas abrupt, eccentric long-segment strictures favor a malignancy. At MR imaging, extrabiliary entities such as crossing vessels or metallic clip artifact may mimic strictures and should not be mistaken for disease. A stone is the most common biliary filling defect and may occur in the absence of dilated ducts. Stones commonly have a lamellated, geometric shape and are found in a dependent portion of the duct. Identification of bile duct wall thickening raises concern for cholangitis or malignancy. Improved diagnosis of biliary disease can be achieved with a knowledge of the benefits and limitations of modern MR and CT cholangiographic techniques, including the use of biliary-excreted contrast material and of various postprocessing techniques. Familiarity with the radiologic appearances of the duct lumen, wall, and surrounding structures is also important for accurate image interpretation. The rapidly evolving technology for both MR imaging and CT of the biliary tract will continue to present radiologists with opportunities as well as challenges.


[Imaging of breast tumors using MR elastography].
Imaging of breast tumors using MR-Elastography. Low-frequency mechanical waves are transmitted into breast-tissue by means of an oscillator. The local characteristics of the mechanical wave are determined by the elastic properties of the tissue. By means of a motion-sensitive spin-echo-sequence these waves can be displayed within the phase of the MR image. Subsequently, these images can be used to reconstruct the local distribution of elasticity. In-vivo measurements were performed in 3 female patients with malignant tumors of the breast. All patients tolerated the measurement set-up without any untoward sensation in the contact area of skin and oszillator. The waves completely penetrated the breast, encompassing the axilla and regions close to the chest wall. All tumors were localized by MRE as structures of markedly stiffer tissue when compared to the surrounding tissue. Furthermore, in one patient, a metastasis in an axillary lymph node was detected. In all patients, local regions of increased elasticity were found in the remaining parenchyma of the breast, which, however, did not reach the high levels of elasticity found in the tumors. MRE is an imaging modality enabling adjunct tissue differentiation of mammary tumors.


The andropause: fact or fiction?
The so-called andropause is an ill-defined collection of symptoms in a group of men who may have low but may also have normal androgen levels. Unlike the proven benefits of hormone replacement therapy in women, the effects of testosterone supplementation in men are equivocal. It may increase sexual interest, but rarely to a level thought adequate by the patient. It has no proven beneficial effect on erectile dysfunction and other possible beneficial effects on haemopoesis, bone metabolism, lipids and fibrinolysis have yet to be demonstrated. With the availability of the testosterone patch, sustained increases in the serum testosterone levels will be readily achieved and could theoretically significantly affect the behaviour of subclinical prostate cancer. At the present time, testosterone replacement therapy in hypogonadal men is of proven clinical benefit; this is not the case, however, for eugonadal men with symptoms attributed to the andropause. The symptoms of the andropause fatigue can readily be explained by stress and there is no scientifically valid, placebo-controlled study that shows any benefit for testosterone supplements in this not uncommon group of patients.


Predicting Resting Oral Commissure Tone Outcomes Following Masseter Nerve Transfer in Facial Reanimation.
Objective: To quantify the degree of oral commissure resting tone improvement in patients undergoing masseter to facial nerve transfer. Methods: A retrospective cohort study was completed in a tertiary academic medical practice. Consecutive cases of masseter nerve transfer patients within a patient database were evaluated from 6/2012 to 9/2017. Inclusion criteria were patients >18 years of age, with complete unilateral paralysis, receiving a masseter to facial nerve transfer, with at least 12 months of recovery, and possessing complete pre- and postoperative data. Patients were excluded if a simultaneous adjunctive procedure was performed so that tone could not be attributed to masseter transfer alone. The main outcome measure was the facial asymmetry index (FAI): the measured difference in distance between the medial canthus and oral commissure of the healthy and paralyzed sides. Results: Twenty-nine patients met inclusion and exclusion criteria and were further analyzed for this study. The oral commissure symmetry improved from 4.7 ± 2.8 mm preoperatively to 2.2 ± 2.3 mm postoperatively. In multivariate analysis, the preoperative FAI was the only significant predictive factor for improvement in commissure symmetry at rest (r = 0.589). This suggests that for each 1.0 mm of worse preoperatively oral commissure asymmetry, the improvement postoperatively was 0.6 mm. Age, gender, body mass index, side of paralysis, duration of paralysis, and recipient branch of facial nerve were not significant predictors in a multivariate analysis. Conclusion: Masseter to facial nerve transfer yields an estimated 60% correction in the oral commissure asymmetry. This estimation may be helpful in determining if adjunctive procedures should be utilized.


Cross-pharmacology analysis of G protein-coupled receptors.
The degree of applicability of chemogenomic approaches to protein families depends on the accuracy and completeness of pharmacological data and the corresponding level of pharmacological similarity observed among their protein members. The recent public domain availability of pharmacological data for thousands of small molecules on 204 G protein-coupled receptors (GPCRs) provides a firm basis for an in-depth cross-pharmacology analysis of this superfamily. The number of protein targets included in the cross-pharmacology profile of the different GPCRs changes significantly upon varying the ligand similarity and binding affinity criteria. However, with the exception of muscarinic receptors, aminergic GPCRs distinguish themselves from the rest of the members in the family by their remarkably high levels of pharmacological similarity among them. Clusters of non-GPCR targets related by cross-pharmacology with particular GPCRs are identified and the implications for unwanted side-effects, as well as for repurposing opportunities, discussed.


Acceleration of hippocampal atrophy in a non-demented elderly population: the SNAC-K study.
Brain atrophy in Alzheimer's disease (AD) includes not only AD-specific brain atrophy but also the atrophy induced by normal aging. Atrophy of the hippocampus has been one diagnostic marker of AD, but it was also found to emerge in healthy adults, along with increasing age. It was reported that the important age when age-related shrinkage of the hippocampus starts was around the mid-40s. The aim is to study the aging atrophy speed and acceleration of brain atrophy in a cross-sectional database, to identify the age at which acceleration of hippocampal atrophy starts in non-demented elderly persons. 544 subjects (aged 60-97 years; 318 female and 226 male) were recruited into the MRI study by using a subsample of an epidemiological sample of 3363 healthy non-demented elderly people (over 60 years of age). Hippocampus and ventricle sizes were measured. The normalized volumes (by intracranial volume, ICV) of the hippocampus in males were smaller than those in females. The right hippocampus was larger than the left. The expansion of the lateral ventricles (2.80% per year in males, 2.95% in females) and third ventricle (1.58% and 2.28%, respectively) was more marked than the hippocampal shrinkage (0.68% and 0.79%, respectively). The suggested age at which acceleration of hippocampal atrophy starts is 72 years. Males present smaller hippocampus volumes (normalized by ICV) than females; however, females are more vulnerable to hippocampal atrophy in a non-demented elderly population. An acceleration of hippocampal atrophy may emerge and start around 72 years of age in a non-demented elderly population.


Dynamically Programmable Magnetic Fields for Controlled Movement of Cells Loaded with Iron Oxide Nanoparticles.
Cell-based therapies are becoming increasingly prominent in numerous medical contexts, particularly in regenerative medicine and the treatment of cancer. However, since the efficacy of the therapy is largely dependent on the concentration of therapeutic cells at the treatment area, a major challenge associated with cell-based therapies is the ability to move and localize therapeutic cells within the body. In this article, a technique based on dynamically programmable magnetic fields is successfully demonstrated to noninvasively aggregate therapeutic cells at a desired location. Various types of therapeutically relevant cells (neural stem cells, monocytes/macrophages, and chimeric antigen receptor T cells) are loaded with iron oxide nanoparticles and then focused at a particular site using externally controlled electromagnets. These experimental results serve as a readily scalable prototype for designing an apparatus that patients can wear to focus therapeutic cells at the anatomical sites needed for treatment.


[Full thickness chest wall resection for recurrent breast cancer with reference to prognostic factors].
Full thickness chest wall resection surgery has been carried out in 16 patients with local recurrence after previous mastectomy. Seven of 16 patients had isolated chest wall recurrence, but 9 had mediastinal invasion and/or distant metastasis of carcinoma. Recurrent breast carcinoma involving the bony chest wall was resected, and the chest wall defects were reconstructed with myocutaneous flaps using rectus abdominis or latissimus dorsi, or breast flap. Marlex mesh was utilized under the flap in 10 patients. The 3 year survival probability was 79% and the 5 year one was 57% with mean follow-up period of 43 month. Local recurrence was classified into 3 types according to cancer infiltration; i.e., demarcated, scattered and diffuse types. The patients with demarcated type showed better prognosis than those with diffuse type. Patients who received curative surgery showed better prognosis than those receiving palliative surgery. A disease free interval (DFI) after mastectomy longer than 5 years correlated well with a long survival rate after chest wall resection. Thus, local recurrence presenting demarcated tumor with possible curative surgery as well as a longer DFI after mastectomy is a favorable prognostic factor for full thickness chest wall resection.


Weighted-persistent-homology-based machine learning for RNA flexibility analysis.
With the great significance of biomolecular flexibility in biomolecular dynamics and functional analysis, various experimental and theoretical models are developed. Experimentally, Debye-Waller factor, also known as B-factor, measures atomic mean-square displacement and is usually considered as an important measurement for flexibility. Theoretically, elastic network models, Gaussian network model, flexibility-rigidity model, and other computational models have been proposed for flexibility analysis by shedding light on the biomolecular inner topological structures. Recently, a topology-based machine learning model has been proposed. By using the features from persistent homology, this model achieves a remarkable high Pearson correlation coefficient (PCC) in protein B-factor prediction. Motivated by its success, we propose weighted-persistent-homology (WPH)-based machine learning (WPHML) models for RNA flexibility analysis. Our WPH is a newly-proposed model, which incorporate physical, chemical and biological information into topological measurements using a weight function. In particular, we use local persistent homology (LPH) to focus on the topological information of local regions. Our WPHML model is validated on a well-established RNA dataset, and numerical experiments show that our model can achieve a PCC of up to 0.5822. The comparison with the previous sequence-information-based learning models shows that a consistent improvement in performance by at least 10% is achieved in our current model.


[Optical parameters of Tm3+ in oxyfluoride glass ceramic].
Optical-absorption spectrum of Tm3+ ions in oxyfluoride glass ceramic was measured, from which the measured oscillator strengths were obtained. The Judd-Ofelt intensity parameters omega t (t = 2, 4, 6) were determined by a best fit of the calculated and measured oscillator strengths, the rms deviation was 3.9 x 10(-7). Some predicted spectroscopic parameters of the excited states, like the spontaneous radiative transition rate, radiative lifetime, branching ratio and integrated emission cross section were given using the intensity parameters. The spectroscopic parameters were comparable with some laser materials, and some of them were better.


Subthalamic somatosensory evoked potentials in Parkinson's disease.
Deep brain stimulation (DBS) of subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease. It also provides an opportunity to record neural activity from the human basal ganglia. In this study, to investigate the involvement of the human STN in sensory functions, we recorded somatosensory evoked potentials (SEPs) elicited by contralateral median-nerve stimulation, from STN electrodes implanted for DBS in patients with Parkinson's disease. We suggest that the STN N18 component of SEPs in Parkinson's disease is a mainly local field potential elicited by muscle afferent input to the nucleus.


Promoting ectopic pancreatic fates: pancreas development and future diabetes therapies.
Diabetes is a disease that could be treated more effectively with a better understanding of pancreas development. This review examines the role of master regulator genes driving crucial steps in pancreas development, from foregut specification to differentiation of the five endocrine cell types. The roles of Pdx1, Ptf1a, and Ngn3 are particularly examined as they are both necessary and sufficient for promoting pancreatic cell fates (Pdx1, Ptf1a) and endocrine cell development (Ngn3). The roles of Arx and Pax4 are studied as they compose part of the regulatory mechanism balancing development of different types of endocrine cells within the iselts and promote the development of alpha/PP and beta/delta cell progenitors, respectively. The roles of the aforementioned genes, and the consequences of misexpression of them for functionality of the pancreas, are examined through recent studies in model organisms, particularly Xenopus and zebrafish. Recent developments in cell replacement therapy research are also covered, concentrating on stem cell research (coaxing both adult and embryonic stem cells toward a beta cell fate) and transdifferentiation (generating beta cells from other differentiated cell types).


Synthesis, SAR and biological evaluation of natural and non-natural hydroxylated and prenylated xanthones as antitumor agents.
In order to explore the detailed structure-activity relationship (SAR) around xanthone scaffold bearing hydroxyl and prenyl moieties, twenty-nine natural and non-natural hydroxylated and prenylated xanthones have been synthesized and evaluated for their in vitro anti-proliferative activities against five human cancer cell lines, including HepG2 (hepatocelluar carcinoma), HCT-116 (colon carcinoma), A549 (lung carcinoma), BGC823 (gastric carcinoma) and MDAMB- 231 (breast carcinoma). The SAR analysis revealed that the anti-proliferative activity of the xanthones is substantially influenced by the position and number of attached hydroxyl and prenyl groups, and the presence of hydroxyl group ortho to the carbonyl function of xanthone scaffold contributes significantly to their cytotoxicity. The new prenylated xanthone 20 with a relatively simple structure, namely 1,3,8-trihydroxy-2-prenylxanthone, was found to exhibit potent antitumor activities comparable to α-mangostin against all the five cancer cell lines. Further mechanistic studies suggested that compound 20 induces apoptosis and causes cell cycle arrest at S phase in HepG2 cells. These results have highlighted compound 20 as a new potential lead candidate for future development of novel potent broad-spectrum antitumor agents.


Binding of all-trans-retinoic acid to MLTC-1 proteins.
The covalent incorporation of [(3)H]all-trans-retinoic acid into proteins has been studied in tumoural Leydig (MLTC-1) cells. The maximum retinoylation activity of MLTC-1 cell proteins was 710+/-29 mean+/-SD) fmoles/8 x 10(4) cells at 37 degrees C. About 90% of [(3)H]retinoic acid was trichloroacetic acid-soluble after proteinase-K digestion and about 65--75% after hydrolysis with hydroxylamine. Thus, retinoic acid is most probably linked to proteins as a thiol ester. The retinoylation reaction was inhibited by 13-cis-retinoic acid and 9-cis-retinoic acid with IC(50) values of 0.9 microM and 0.65 microM, respectively. Retinoylation was not inhibited by high concentrations of palmitic or myristic acids (250 microM); but there was an increase of the binding activity of about 25% and 130%, respectively. On the other hand, the retinoylation reaction was inhibited (about 40%) by 250 microM lauric acid. After pre-incubation of the cells with different concentrations of unlabeled RA, the retinoylation reaction with 100 nM [(3)H]RA involved first an increase at 100 nM RA and then a decrease of retinoylation activity between 200 and 600 nM RA. After cycloheximide treatment of the tumoural Leydig cells the binding activity of [(3)H]RA was about the same as that in the control, suggesting that the bond occurred on proteins in pre-existing cells.


[Species composition of agents of the horsetail common (Equisetum arvense L.) bacteriosises].
Bacterial diseases of weeds horsetail common (Equisetum arvense L.) were revealed in the crops of wheat and soya in the fields of Kyiv and Vinnitsia Regions of Ukraine. The distinctive symptoms of bacterial affections on the root neck, on stalks of vegetative and spore shoots, on twigs were brown, dark brown or almost black necrotic spots of oblong form. The necroses increased in size, embraced the stalks. The stalks broke, the plants dried up. Patterns of affected plants, isolated and identified phytopathogenic bacteria Pseudomonas syringae, Pectobacterium carotovorum subsp. carotovorum, Pantoea agglomerans and Curtobacterium sp. were analyzed These bacteria caused pathological process on the horsetail common, wheat and soy under the conditions of artificial inoculation. The composition of bacteria species was different in different years depending on temperature conditions of vegetative period.


A novel isoform of acetylcholinesterase exacerbates photoreceptors death after photic stress.
To study the involvement of stress-induced acetylcholinesterase (AChE) expression in light-induced retinal damage in albino rats. Adult albino rats were exposed for 24 hours to bright, damaging light. AChE expression was monitored by in situ hybridization, by histochemistry for AChE activity, and by immunocytochemistry. An orphan antisense agent (Monarsen; Ester Neurosciences, Ltd., Herzlia Pituach, Israel) was administered intraperitoneally to minimize light-induced AChE expression. The electroretinogram (ERG) was recorded to assess retinal function. Twenty-four-hour exposure to bright light caused severe reduction in the ERG responses and augmented expression of mRNA for the "read-through" variant of AChE (AChE-R) in photoreceptor inner segments (IS), bipolar cells, and ganglion cells. AChE activity increased in IS. The expressed AChE protein was a novel variant, characterized by an extended N terminus (N-AChE). Systemic administration of the orphan antisense agent, Monarsen, reduced the photic induction of mRNA for AChE-R, and of the N-AChE protein. Rats exposed to bright, damaging light and treated daily with Monarsen exhibited larger ERG responses, relatively thicker outer nuclear layer (ONL), and more ONL nuclei than did rats exposed to the same damaging light but treated daily with saline. The findings indicate that the photic-induced novel variant of AChE (N-AChE-R) may be causally involved with retinal light damage and suggest the use of RNA targeting for limiting such damage.


JUDOCA: junction detection operator based on circumferential anchors.
In this paper, we propose an edge-based junction detector. In addition to detecting the locations of junctions, this operator specifies their orientations as well. In this respect, a junction is defined as a meeting point of two or more ridges in the gradient domain into which an image can be transformed through Gaussian derivative filters. To accelerate the detection process, two binary edge maps are produced; a thick-edge map is obtained by imposing a threshold on the gradient magnitude image, and another thin-edge map is obtained by calculating the local maxima. Circular masks are centered at putative junctions in the thick-edge map, and the so-called circumferential anchors or CA points are detected in the thin map. Radial lines are scanned to determine the presence of junctions. Comparisons are made with other well-known detectors. This paper proposes a new formula for measuring the detection accuracy. In addition, the so-called junction coordinate systems are introduced. Our operator has been successfully used to solve many problems such as wide-baseline matching, 3-D reconstruction, camera parameter enhancing, and indoor and obstacle localization.


Long term stability of rh-Cu/Zn-superoxide dismutase (SOD)-liposomes prepared by the cross-flow injection technique following International Conference on Harmonisation (ICH)-guidelines.
The current market position of liposomes as drug carriers is still being discussed with regard to large scale production, product characterisation and the stability of the dispersions. In this study, long term stability of liposomal suspensions with encapsulated rh-Cu/Zn-superoxide dismutase was tested according to the International Conference on Harmonisation (ICH) recommendations. The guidelines of the ICH provide general requirements for stability testing for registration and export in particular. The Institute of Applied Microbiology has examined a process to produce large amounts of pharmaceutical-grade liposomes for the treatment of inflammatory diseases by topical application. For the evaluation of its long-term storage stability, liposomal stability and protein stability were tested under appropriate conditions. Therefore, size alterations of the vesicles, protein release and protein activity were evaluated. During the observation period, neither significant alterations of the liposomes nor any protein degradation could be detected. In the light of these findings our liposomal formulations seem to provide chemical, physical and biological stability according to the definitions of the ICH. Appropriate lipid compounds and environmental factors, in combination with an optimised process and adequate storage conditions, facilitate the production of liposome dispersions suitable as drug carriers on the market.


Lidocaine concentration in mandibular bone after subperiosteal infiltration anesthesia decreases with elevation of periosteal flap and irrigation with saline.
It has been reported that the action of infiltration anesthesia on the jawbone is attenuated significantly by elevation of the periosteal flap with saline irrigation in clinical studies; however, the reason is unclear. Therefore, the lidocaine concentration in mandibular bone after subperiosteal infiltration anesthesia was measured under several surgical conditions. The subjects were 48 rabbits. Infiltration anesthesia by 0.5 mL of 2% lidocaine with 1 : 80,000 epinephrine (adrenaline) was injected into the right mandibular angle and left mandibular body, respectively. Under several surgical conditions (presence or absence of periosteal flap, and presence or absence of saline irrigation), both mandibular bone samples were removed at a fixed time after subperiosteal infiltration anesthesia. The lidocaine concentration in each mandibular bone sample was measured by high-performance liquid chromatography. As a result, elevation of the periosteal flap with saline irrigation significantly decreased the lidocaine concentration in the mandibular bone. It is suggested that the anesthetic in the bone was washed out by saline irrigation. Therefore, supplemental conduction and/or general anesthesia should be utilized for long operations that include elevation of the periosteal flap with saline irrigation.


Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.
In cirrhosis, activated hepatic stellate cells (HSC) play a major role in increasing intrahepatic vascular resistance and developing portal hypertension. We have shown that cirrhotic livers have increased reactive oxygen species (ROS), and that antioxidant therapy decreases portal pressure. Considering that mitochondria produce many of these ROS, our aim was to assess the effects of the oral mitochondria-targeted antioxidant mitoquinone on hepatic oxidative stress, HSC phenotype, liver fibrosis and portal hypertension. Ex vivo: Hepatic stellate cells phenotype was analysed in human precision-cut liver slices in response to mitoquinone or vehicle. In vitro: Mitochondrial oxidative stress was analysed in different cell type of livers from control and cirrhotic rats. HSC phenotype, proliferation and viability were assessed in LX2, and in primary human and rat HSC treated with mitoquinone or vehicle. In vivo: CCl4 - and thioacetamide-cirrhotic rats were treated with mitoquinone (5 mg/kg/day) or the vehicle compound, DecylTPP, for 2 weeks, followed by measurement of oxidative stress, systemic and hepatic haemodynamic, liver fibrosis, HSC phenotype and liver inflammation. Mitoquinone deactivated human and rat HSC, decreased their proliferation but with no effects on viability. In CCl4 -cirrhotic rats, mitoquinone decreased hepatic oxidative stress, improved HSC phenotype, reduced intrahepatic vascular resistance and diminished liver fibrosis. These effects were associated with a significant reduction in portal pressure without changes in arterial pressure. These results were further confirmed in the thioacetamide-cirrhotic model. We propose mitochondria-targeted antioxidants as a novel treatment approach against portal hypertension and cirrhosis.


Human mucin genes assigned to 11p15.5: identification and organization of a cluster of genes.
Four distinct genes that encode mucins have previously been mapped to chromosome 11p15.5. Three of these genes (MUC2, MUC5AC, and MUC6) show a high level of genetically determined polymorphism and were analyzed in the CEPH families. Linkage analysis placed all three genes on the genetic map in a cluster between HRAS and INS, and more detailed analysis of recombinant breakpoints revealed that MUC6 is telomeric to MUC2. Using these recombinants D11S150 was mapped close to MUC2. Ten of the 11 recombinant chromosomes studied in detail were paternal, and the recombinant events were distributed throughout the 11p15 region, suggesting that the high level of recombination observed in 11p15.5 is not due to a particular recombinational hot spot. Pulsed-field gel electrophoresis was used to make a detailed physical map of the MUC cluster and to integrate the physical and genetical maps. The gene order was determined to be HRAS-MUC6-MUC2-MUC5AC-MUC5B-IGF2. The MUC genes span a region of some 400 kb and the map extends 770 kb and contains 15 putative CpG islands. The order of the MUC genes on the map corresponds to the relative order of their expression along the anterior-posterior axis of the body, suggesting a possible functional significance to the gene order.


Anther Morphological Development and Stage Determination in Triticum aestivum.
Anther development progresses through 15 distinct developmental stages in wheat, and accurate determination of anther developmental stages is essential in anther and pollen studies. A detailed outline of the development of the wheat anther through its entire developmental program, including the 15 distinct morphological stages, is presented. In bread wheat (Triticum aestivum), anther developmental stages were correlated with five measurements, namely auricle distance, spike length, spikelet length, anther length and anther width. Spike length and auricle distance were shown to be suitable for rapid anther staging within cultivars. Anther length is an accurate measurement in determining anther stages and may be applicable for use between cultivars. Tapetal Programmed Cell Death (PCD) in wheat begins between late tetrad stage (stage 8) and the early young microspore stage (stage 9) of anther development. Tapetal PCD continues until the vacuolate pollen stage (stage 11), at which point the tapetum fully degrades. The timing of tapetal PCD initiation is slightly delayed compared to that in rice, but is two stages earlier than in the model dicot Arabidopsis. The MYB80 gene, which encodes a transcription factor regulating the timing of tapetal PCD, reaches its peak expression at the onset of tapetal PCD in wheat.


Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP System.
There are 4 registries of hematopoietic cell transplantation in Japan; the Japan Society for Hematopoietic Cell Transplantation (JSHCT), Japanese Society of Pediatric Hematology, Japan Marrow Donor Program, and Japan Cord Blood Bank Network; each play an important role in society by reporting the number and outcomes of transplantations and contributing new findings obtained from studies on individual topics. However, there have been a number of issues with the difficulty of analyzing data in overlapping registries and multiple databases at centers affiliated with each of the 4 registry organizations. JSHCT was pivotal in orchestrating the computerization and unification of hematopoietic stem cell transplantation registries for the purpose of resolving these issues and providing a more accurate awareness of hematopoietic stem cell transplantations being performed in Japan. JSHCT played a central role in developing the "Transplant Registry Unified Management Program (TRUMP)" to enable transplantation institutes to manage patient information with emphases on convenience to institutes, safety of patient information, and quality of data management. While enhancing domestic registries, the program seeks to coordinate with other hematopoietic cell transplantation registries around the world to contribute to the development of registries throughout Asia.


"Apical thinning": Relations between myocardial wall thickness and apical left ventricular tracer uptake as assessed with positron emission tomography myocardial perfusion imaging.
A reduction in left ventricular apical tracer uptake (apical thinning) is frequently observed in myocardial perfusion imaging (MPI), yet its cause remains a matter of debate, particularly in perfusion emission tomography (PET). This analysis sought to determine whether apical thinning in PET-MPI is attributable to true anatomical thinning of the left ventricular apical myocardium. We retrospectively analyzed 57 patients without any history or signs of apical myocardial infarction who underwent rest PET-MPI with 13N-ammonia and contrast-enhanced cardiac computed tomography (CT). Semi-quantitative normalized percent apical 13N-ammonia uptake at rest, myocardial blood flow (MBF), and k2 wash-out rate constants were compared to apical myocardial wall thickness measurements derived from CT and base-to-apex gradients were calculated. Apical thinning was found in 93% of patients and in 74% when analysis of normalized apical tracer uptake was confined to end-systole. No significant correlation was found between apical myocardial thickness and apical tracer uptake (r = - 0.080, P = .553), MBF (r = - 0.211, P = .115), or k2 wash-out rate (r = - 0.023, P = .872), nor between apical myocardial thickness and any gradients. A statistically significant but small difference in apical myocardial thickness was observed in patients with moderately to severely reduced apical tracer uptake vs patients with normal to mildly reduced uptake (4.3 ± 0.7 mm vs 4.7 ± 0.7 mm; P = .043). Apical thinning is a highly prevalent finding during 13N-ammonia PET-MPI that is not solely attributable to true anatomical apical wall thickness or the partial volume effect. Other factors that yet need to be identified seem to have a more prominent impact.


Gating-ML: XML-based gating descriptions in flow cytometry.
The lack of software interoperability with respect to gating due to lack of a standardized mechanism for data exchange has traditionally been a bottleneck, preventing reproducibility of flow cytometry (FCM) data analysis and the usage of multiple analytical tools. To facilitate interoperability among FCM data analysis tools, members of the International Society for the Advancement of Cytometry (ISAC) Data Standards Task Force (DSTF) have developed an XML-based mechanism to formally describe gates (Gating-ML). Gating-ML, an open specification for encoding gating, data transformations and compensation, has been adopted by the ISAC DSTF as a Candidate Recommendation. Gating-ML can facilitate exchange of gating descriptions the same way that FCS facilitated for exchange of raw FCM data. Its adoption will open new collaborative opportunities as well as possibilities for advanced analyses and methods development. The ISAC DSTF is satisfied that the standard addresses the requirements for a gating exchange standard.


CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity.
Clustered regularly interspaced short palindromic repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing and can be repurposed for numerous DNA targeting applications including transcriptional control.


Reduced glenohumeral rotation, external rotation weakness and scapular dyskinesis are risk factors for shoulder injuries among elite male handball players: a prospective cohort study.
To determine whether rotator cuff strength, glenohumeral joint range of motion and scapular control are associated with shoulder injuries among elite male handball players. A total of 206 players in the Norwegian elite handball league for men were tested prior to the 2011-2012 season. Measures included: (1) glenohumeral internal and external rotation range of motion, (2) isometric internal rotation, external rotation and abduction strength and (3) assessment of scapular dyskinesis. Players were followed prospectively for the entire regular season (30 weeks), with shoulder problems registered bi-weekly using the Oslo Sports Trauma Research Center Overuse Injury Questionnaire. A cumulative severity score was calculated for each player based on their questionnaire responses. This was used as the outcome measure in risk factor analyses. The average prevalence of shoulder problems throughout the season was 28% (95% CI 25% to 31%). The prevalence of substantial shoulder problems, defined as those leading to moderate or severe reductions in handball participation or performance, or to time loss, was 12% (95% CI 11% to 13%). Significant associations were found between obvious scapular dyskinesis (OR 8.41, 95% CI 1.47 to 48.1, p<0.05), total rotational motion (OR 0.77 per 5° change, 95% CI 0.56 to 0.995, p<0.05) and external rotation strength (OR 0.71 per 10 Nm change, 95% CI 0.44 to 0.99, p<0.05) and shoulder injury. Injury prevention programmes should incorporate interventions aimed at improving glenohumeral rotational range of motion, external rotation strength and scapular control.


C-Reactive Protein as Predictor for Infectious Complications after Robotic and Open Esophagectomies.
The value of C-reactive protein (CRP) as a predictor of anastomotic leakage (AL) after esophagectomy has been addressed by numerous studies. Despite its increasing application, robotic esophagectomy (RAMIE) has not been considered separately yet in this context. We, therefore, aimed to evaluate the predictive value of CRP in RAMIE. Patients undergoing RAMIE or completely open esophagectomy (OE) at our University Center were included. Clinical data, CRP- and Procalcitonin (PCT)-values were retrieved from a prospectively maintained database and evaluated for their predictive value for subsequent postoperative infectious complications (PIC) (AL, gastric conduit leakage or necrosis, pneumonia, empyema). Three hundred and five patients (RAMIE: 160, OE: 145) were analyzed. PIC were noted in 91 patients on postoperative day (POD) 10 and 123 patients on POD 30, respectively. Median POD of diagnosis of PIC was POD 8. Post-operative CRP-values in the robotic-group peaked one and two days later, respectively, and converged from POD 5 onward compared to the open-group. In the group with PIC, CRP-levels in the robotic-group were initially lower and started to differ significantly from POD 3 onward. In the open-group, increases were already noticed from POD 3 on. Procalcitonin levels did not differ. Best Receiver operating curve (ROC)-results were on POD 4, highest negative predictive values at POD 5 (RAMIE) and POD 4 (OE) with cut-off values of 70 mg/L and 88.3 mg/L, respectively. Post-operative CRP is a good negative predictor for PIC, after both RAMIE and OE. After RAMIE, CRP peaks later with a lower cut-off value.


Marked decline in atmospheric carbon dioxide concentrations during the Paleogene.
The relation between the partial pressure of atmospheric carbon dioxide (pCO2) and Paleogene climate is poorly resolved. We used stable carbon isotopic values of di-unsaturated alkenones extracted from deep sea cores to reconstruct pCO2 from the middle Eocene to the late Oligocene (approximately 45 to 25 million years ago). Our results demonstrate that pCO2 ranged between 1000 to 1500 parts per million by volume in the middle to late Eocene, then decreased in several steps during the Oligocene, and reached modern levels by the latest Oligocene. The fall in pCO2 likely allowed for a critical expansion of ice sheets on Antarctica and promoted conditions that forced the onset of terrestrial C4 photosynthesis.


The effects of stimulus location on the gating of touch by heat- and cold-induced pain.
The influence of heat- and cold-induced pain on tactile sensitivity, a "touch gate", was measured under conditions in which the location of the noxious stimuli was varied with respect to the tactile stimulus applied to the thenar eminence of humans. Vibrotactile thresholds were measured in the absence of pain and during administration of a painful stimulus, with the stimulus frequencies selected to activate independently the four psychophysical channels hypothesized to exist in human glabrous skin. Heat-induced pain produced by spatially co-localizing the noxious stimuli with the tactile stimuli was found, on average, to elevate threshold amplitude by 2.2 times (6.7 dB). Co-localized, cold-induced pain raised the average thresholds by about 1.5 times (3.6 dB). Heat-induced pain presented contralaterally produced no change in vibrotactile sensitivity indicating that the effect is probably not due to attentional mechanisms. Ipsilateral heat-induced pain caused an elevation in tactile thresholds even when the noxious and non-noxious stimuli were not co-localized, and the effect may seem to require that the painful stimulus be within the somatosensory region defined possibly in terms of dermatomal organization. Thus the effect is probably related to somatotopic organization and is not peripherally mediated. A brief discussion as to the possible locus of the touch gate within the nervous system is also given.


Characterizing DNA preservation in degraded specimens of Amara alpina (Carabidae: Coleoptera).
DNA preserved in degraded beetle (Coleoptera) specimens, including those derived from dry-stored museum and ancient permafrost-preserved environments, could provide a valuable resource for researchers interested in species and population histories over timescales from decades to millenia. However, the potential of these samples as genetic resources is currently unassessed. Here, using Sanger and Illumina shotgun sequence data, we explored DNA preservation in specimens of the ground beetle Amara alpina, from both museum and ancient environments. Nearly all museum specimens had amplifiable DNA, with the maximum amplifiable fragment length decreasing with age. Amplification of DNA was only possible in 45% of ancient specimens. Preserved mitochondrial DNA fragments were significantly longer than those of nuclear DNA in both museum and ancient specimens. Metagenomic characterization of extracted DNA demonstrated that parasite-derived sequences, including Wolbachia and Spiroplasma, are recoverable from museum beetle specimens. Ancient DNA extracts contained beetle DNA in amounts comparable to museum specimens. Overall, our data demonstrate that there is great potential for both museum and ancient specimens of beetles in future genetic studies, and we see no reason why this would not be the case for other orders of insect.


A prospective examination of the impact of a supported employment program and employment on health-related quality of life, handicap, and disability among Veterans with SCI.
To investigate impact of participation in a supported employment program and impact of employment itself on health-related quality of life (HRQOL), disability, and handicap among Veterans with spinal cord injury (SCI). We used a prospective, randomized, controlled, multi-site trial of supported employment (SE) versus treatment as usual (TAU) for vocational issues. Subjects were 157 Veterans with SCI who received either SE or TAU for vocational issues. Outcomes were examined in terms of type of vocational treatment received and whether competitive employment was obtained. Outcomes investigated were HRQOL as measured by the Veterans RAND 36-item health survey (VR-36), handicap as measured by the Craig Handicap Assessment and Reporting Technique (CHART), and disability as measured by the functional independence measure (FIM). Subjects were assessed at baseline and at 3, 6, 9, and 12 months. There were no significant differences between Veterans who participated in SE compared to those who received TAU in study measures. Participants obtaining competitive employment demonstrated significantly higher scores on the Social Integration, Mobility, and Occupation dimensions of the CHART. There were no observed differences in VR-36 scores or FIM scores for those obtaining competitive employment. This study suggests that employment has a positive effect on an individual's ability to participate in social relationships, move about their home and community, and spend time in productive and usual roles. Inability to detect differences across other domains of handicap or any changes in HRQOL may have been due to several factors including level and intensity of employment, insufficient follow-up period, or measurement limitations.


Repetitive transarterial chemoembolization (TACE) of liver metastases from renal cell carcinoma: local control and survival results.
The purpose was to evaluate the effectiveness of transarterial chemoembolization (TACE) in local tumor control and survival in patients with hepatic metastases from renal cell carcinoma (RCC). Prospective evaluation of TACE treatment outcome in 22 patients recruited from 1999 and 2005 was performed. The chemotherapeutic agent used was mitomycin only in 45% of the patients and mitomycin together with gemcitabine in the other 55%. The embolizing materials used in all of the patients were iodized oil (lipiodol) and degradable starch microspheres. Local response was evaluated by MRI and judged according to Response Evaluation Criteria in Solid Tumors (RECIST). Mean and median survival and survival probability after diagnosis and treatment were both calculated by Kaplan-Meier method. Partial response was achieved in 13.7%, stable disease in 59% and progressive disease in 27.3% of patients. Survival time from the diagnosis of metastases ranged from 18 to 307 months and from 2.2 to 35 months from the start of TACE treatment. The median and mean survival times from the date of diagnosis were 68.6 and 102.9 months, respectively. The median and mean survival times from the start of TACE were 8.2 and 11.7 months, respectively. Survival probability from the start of treatment was 31% after 1 year and 6% after 2 years. TACE can result in a favorable local tumor response in patients with hepatic metastases from RCC, but survival results are still limited.


Prevalence, determinants and health care-seeking behavior of childhood acute respiratory tract infections in Bangladesh.
Acute respiratory infections (ARIs) are one of the leading causes of child mortality worldwide and contribute significant health burden for developing nations such as Bangladesh. Seeking care and prompt management is crucial to reduce disease severity and to prevent associated morbidity and mortality. This study investigated the prevalence and care-seeking behaviors among under-five children in Bangladesh and identified factors associated with ARI prevalence and subsequent care-seeking behaviors. The present study analyzed cross-sectional data from the 2014 Bangladesh Demographic Health Survey. Bivariate analysis was performed to estimate the prevalence of ARIs and associated care-seeking. Logistic regression analysis was used to determine the influencing socio-economic and demographic predictors. A p-value of <0.05 was considered as the level of significance. Among 6,566 under-five children, 5.42% had experienced ARI symptoms, care being sought for 90% of affected children. Prevalence was significantly higher among children < 2 years old, and among males. Children from poorer and the poorest quintiles of households were 2.40 (95% CI = 1.12, 5.15) and 2.36 (95% CI = 1.06, 5.24) times more likely to suffer from ARIs compared to the wealthiest group. Seeking care was significantly higher among female children (AOR = 2.19, 95% CI = 0.94, 5.12). The likelihood of seeking care was less for children belonging to the poorest quintile compared to the richest (AOR = 0.03, 95% CI = 0.01, 0.55). Seeking care from untrained providers was 3.74 more likely among rural residents compared to urban (RRR = 3.74, 95% CI = 1.10, 12.77). ARIs continue to contribute high disease burden among under-five children in Bangladesh lacking of appropriate care-seeking behavior. Various factors, such as age and sex of the children, wealth index, the education of the mother, and household lifestyle factors were significantly associated with ARI prevalence and care-seeking behaviors. In addition to public-private actions to increase service accessibility for poorer households, equitable and efficient service distribution and interventions targeting households with low socio-economic status and lower education level, are recommended.


Affective enhancement of working memory is maintained in depression.
We currently know little about how performance on assessments of working memory capacity (WMC) that are designed to mirror the concurrent task demands of daily life are impacted by the presence of affective information, nor how those effects may be modulated by depression-a syndrome where sufferers report global difficulties with executive processing. Across 3 experiments, we investigated WMC for sets of neutral words in the context of processing either neutral or affective (depressogenic) sentences, which had to be judged on semantic accuracy (Experiments 1 and 2) or self-reference (Experiment 3). Overall, WMC was significantly better in the context of depressogenic compared with neutral sentences. However, there was no support for this effect being modulated by symptoms of depression (Experiment 1) or the presence of recurrent major depressive disorder (MDD; Experiments 2 and 3). Implications of these findings for cognitive theories of the role of WM in depression are discussed in the context of a growing body of research showing no support for a differential impact of depressogenic compared with neutral information on WM accuracy. (PsycINFO Database Record


[Indications, techniques and anatomic results of the tympanoplasty using palisade cartilage].
One of the major unsolved problems of the middle ear is Eustachian tube disfunction and abnormalities in gas exchange through the middle ear mucosa, which produces negative pressure and may cause retraction pockets, adhesions, or atelectasis. Postoperatively, ear surgeons face a similar problem when conventional autologous material was used to reconstruct the tympanum. Sooner or later, the new tympanic membrane experience retraction, re-perforation and/or extrusion or displacement of the reconstructed ossicular chain. This paper proposes using cartilage as an alternative method of tympanic membrane reconstruction in a personal modification of Heermann's technique. The indications for the "palisade" reconstruction technique with cartilage, technical aspects, and anatomic results after an average of 20 months after surgery are discussed.


The Family Environment as a Source for Creating the Dietary Attitudes of Primary School Students-A Focus Group Interview: The Junior-Edu-Żywienie (JEŻ) Project.
The family environment plays a crucial role in creating the health behaviours of children and youth. This study aimed to explore the attitudes of parents with children aged 7-12 who represent an influential environment for creating the eating behaviours of children. A qualitative study was conducted using focus-group interviews (FGI) involving 101 parents from various socioeconomic backgrounds. Three categories of parents were identified based on their level of involvement and awareness of nutrition: 'aware', 'determined', and 'relaxed'. Among parents of 10-12-year-old students, an additional category, 'distanced' parents, was identified. The study revealed that parents require support in terms of providing compelling arguments and practical recommendations related to meals and reducing or eliminating their children's consumption of sweets, snacks, fast food, and, in the case of older students, energy drinks. Parents reported that their children had a moderate understanding of the principles of proper nutrition. The majority of respondents viewed this knowledge as primarily theoretical and expressed a need for practical guidance and activities, which they believe should be offered by schools. To achieve positive outcomes in educational activities related to food and nutrition, it is essential to involve children, parents, guardians, teachers, and other school staff in these efforts.


NMR-based metabolomic profiling identifies inflammation and muscle-related metabolites as predictors of incident type 2 diabetes mellitus beyond glucose: The firstname.lastname@example.com study.
The aim of this study was to combine nuclear magnetic resonance-based metabolomics and machine learning to find a glucose-independent molecular signature associated with future type 2 diabetes mellitus development in a subgroup of individuals from the email@example.com study. The study group included 145 individuals developing type 2 diabetes mellitus during the 8-year follow-up, 145 individuals matched by age, sex and BMI who did not develop diabetes during the follow-up but had equal glucose concentrations to those who did and 145 controls matched by age and sex. A metabolomic analysis of serum was performed to obtain the lipoprotein and glycoprotein profiles and 15 low molecular weight metabolites. Several machine learning-based models were trained. Logistic regression performed the best classification between individuals developing type 2 diabetes during the follow-up and glucose-matched individuals. The area under the curve was 0.628, and its 95% confidence interval was 0.510-0.746. Glycoprotein-related variables, creatinine, creatine, small HDL particles and the Johnson-Neyman intervals of the interaction of Glyc A and Glyc B were statistically significant. The model highlighted a relevant contribution of inflammation (glycosylation pattern and HDL) and muscle (creatinine and creatine) in the development of type 2 diabetes as independent factors of hyperglycemia.


Detection of von Willebrand disorder and identification of qualitative von Willebrand factor defects. Direct comparison of commercial ELISA-based von Willebrand factor activity options.
Two von Willebrand factor (vWF):collagen binding (activity) assay (CBA) kit methods are commercially available. A monoclonal antibody (MAB)-based enzyme-linked immunosorbent assay (ELISA) system reported to correlate with a standard vWF:ristocetin cofactor (RCof) assay is also commercially available. It is marketed as a vWF:Activity assay and is available in 2 assay version formats. In the present study, these 4 vWF-activity options were compared directly with in-house vWF:CBA ELISAs for their ability to detect von Willebrand disease (vWD) and identify qualitative vWF defects. The 2 MAB-based systems detected vWD but could not specifically identify qualitative vWF defects, although the recently modified Mark II kit was more effective for the latter compared with the original Mark I kit. All vWF:CBA methods, including in-house and commercial, also effectively detected vWD but differed in their ability to identify qualitative vWF defects. Effectiveness was highest using the in-house reference vWF:CBA (using a type I/III collagen mix product from equine tendon), the Gradipore vWF:CBA (also uses equine tendon-derived collagen), or the in-house vWF:CBA methods using type III human collagen at a relatively low concentration (1 or 3 micrograms/mL, without covalent linkage). The IMMUNO vWF:CBA seemed to be the least effective among the vWF:CBA methods for detection of qualitative vWF defects.


Imaging with a rectangular phase grating applied to displacement metrology.
We achieved displacement metrology with a high-amplitude signal by using a rectangular phase grating as the pupil in a grating imaging system. The imaging phenomenon with a pupil transmission grating that has a bilevel profile with a 50% duty ratio is discussed on the basis of the optical transfer function. By optimizing the imaging condition, we obtained high-contrast images with high light power under a magnified or demagnified imaging system. The amplitude of the signal in the displacement measurement was four times higher than that of the conventional grating imaging system with amplitude gratings.


The nature of human altruism.
Some of the most fundamental questions concerning our evolutionary origins, our social relations, and the organization of society are centred around issues of altruism and selfishness. Experimental evidence indicates that human altruism is a powerful force and is unique in the animal world. However, there is much individual heterogeneity and the interaction between altruists and selfish individuals is vital to human cooperation. Depending on the environment, a minority of altruists can force a majority of selfish individuals to cooperate or, conversely, a few egoists can induce a large number of altruists to defect. Current gene-based evolutionary theories cannot explain important patterns of human altruism, pointing towards the importance of both theories of cultural evolution as well as gene-culture co-evolution.


Chloride dysregulation and inhibitory receptor blockade yield equivalent disinhibition of spinal neurons yet are differentially reversed by carbonic anhydrase blockade.
Synaptic inhibition plays a key role in processing somatosensory information. Blocking inhibition at the spinal level is sufficient to produce mechanical allodynia, and many neuropathic pain conditions are associated with reduced inhibition. Disinhibition of spinal neurons can arise through decreased GABAA/glycine receptor activation or through dysregulation of intracellular chloride. We hypothesized that these distinct disinhibitory mechanisms, despite all causing allodynia, are differentially susceptible to therapeutic intervention. Specifically, we predicted that reducing bicarbonate efflux by blocking carbonic anhydrase with acetazolamide (ACTZ) would counteract disinhibition caused by chloride dysregulation without affecting normal inhibition or disinhibition caused by GABAA/glycine receptor blockade. To test this, responses to innocuous tactile stimulation were recorded in vivo from rat superficial dorsal horn neurons before and after different forms of pharmacological disinhibition and again after application of ACTZ. Blocking GABAA or glycine receptors caused hyperresponsiveness equivalent to that caused by blocking the potassium chloride cotransporter KCC2, but, consistent with our predictions, only disinhibition caused by KCC2 blockade was counteracted by ACTZ. ACTZ did not alter responses of neurons with intact inhibition. As pathological downregulation of KCC2 is triggered by brain-derived neurotrophic factor, we also confirmed that ACTZ was effective against brain-derived neurotrophic factor-induced hyperresponsiveness. Our results argue that intrathecal ACTZ has antiallodynic effects only if allodynia arises through chloride dysregulation; therefore, behavioral evidence that ACTZ is antiallodynic in nerve-injured animals affirms the contribution of chloride dysregulation as a key pathological mechanism. Although different disinhibitory mechanisms are not mutually exclusive, these results demonstrate that their relative contribution dictates which specific therapies will be effective.


Cytologic features of islet-cell tumors.
Although a number of reports have demonstrated the accuracy of fine needle aspiration (FNA) in the diagnosis of nonendocrine pancreatic carcinomas, the cytomorphology of islet-cell tumors (pancreatic endocrine tumors) is not well defined. This paper describes the cytologic features of three histologically confirmed cases of islet-cell tumors. The three tumors occurred in one man and two women, who were 63, 64 and 70 years of age, respectively. Each patient underwent FNA of pancreatic mass with computed body tomography guidance. The aspirates contained large numbers of tumor cells in two cases and a smaller number in one case. The cells, distributed singly and in small groups, were small and round or polygonal, with scant to more often abundant, dense or granular cytoplasm. The nuclei were often located eccentrically and were round to oval, with smooth nuclear borders and finely stippled chromatin. Many nuclei contained a single nucleolus. Multinucleated cells were present and generally contained two or three nuclei. Although the diagnosis of islet-cell tumors in fine needle aspirates is difficult, the cytomorphologic features of these tumors are sufficiently distinctive to suggest the diagnosis, especially when a relatively monomorphic population composed predominantly of single cells is present.


The hsp70 protein is involved in the acquisition of gamete self-sterility in the ascidian Ciona intestinalis.
In the hermaphrodite ascidian Ciona intestinalis, gamete self-incompatibility is a mechanism that prevents self-fertilization and is based on the ability of the oocyte vitelline coat to distinguish and accept only heterologous spermatozoa. The onset of self-sterility occurs during oogenesis and involves or is controlled by the follicle cells. Gamete self-nonself discrimination, a process that can be likened to an immune recognition event, represents a useful model with which to study the evolution of self-nonself recognition. Hsp70 genes, which belong to the major histocompatibility complex (MHC) class III, are supposedly ancestors of the MHC class I and II genes, and chaperonins are known to be involved in antigen processing and presentation. We have isolated and characterized an hsp70 gene (Cihsp70) that is constitutively expressed during oogenesis in the follicle cells of previtellogenic and vitellogenic oocytes. Using a polyclonal antibody against Cihsp70 protein, we demonstrate that the expression of Cihsp70 is required for the switch from self-fertility to self-sterility. The functional involvement of Cihsp70 in gamete self-nonself recognition provides evidence for an ancestral MHC-like system in protochordates.


Optimization of a new adaptive intervention using the SMART Design to increase COVID-19 testing among people at high risk in an urban community.
COVID-19 has impacted the health and social fabric of individuals and families living across the USA, and it has disproportionately affected people living in urban communities with co-morbidities, those working in high-risk settings, refusing or unable to adhere to CDC guidelines, and more. Social determinants of health (SDH), such as stigmatization, incarceration, and poverty, have been associated with increased exposure to COVID-19 and increased deaths. While vaccines and booster shots are available, it will take time to reach herd immunity, and it is unclear how long newly developed vaccines provide protection and how effective they are against emerging variants. Therefore, prevention methods recommended by the Centers for Disease and Control (CDC)-i.e., testing, hand-washing, social distancing, contact tracing, vaccination and booster shots, and quarantine-are essential to reduce the rates of COVID-19 in marginalized communities. This project will adapt and test evidence-based HIV interventions along the prevention and treatment cascade to help address COVID-19 prevention needs. The study aims to (1) optimize an adaptive intervention that will increase rates of testing and adherence to New Jersey State COVID-19 recommendations (testing, social distancing, quarantine, hospitalization, contact tracing, and acceptance of COVID-19 vaccination and booster shots) among high-risk populations and (2) identify predictors of testing completion and adherence to New Jersey recommendations. This study follows Community Based Participatory Research (CBPR) principles to conduct a Sequential, Multiple Assignment Randomized Trial (SMART) with 670 COVID-19 medically/socially vulnerable people. Participants will be recruited using a variety of strategies including advertisements on social media, posting fliers in public places, street outreach, facility-based, and snowball sampling. Participants complete a baseline survey and are randomized to receive navigation services or an electronic brochure. They then complete a follow-up 7 days after baseline and are randomized again to either continue with their original assignment or switch to the other intervention or critical dialog or brief counseling. Participants then complete a 5-week post-baseline follow-up. Guided by the COVID-19 Continuum of Prevention, Care, and Treatment, the analysis will explore the factors associated with COVID-19 testing within 7 days of the intervention. This paper describes the protocol of the first study to use SMART following CBPR to adapt evidence-based HIV prevention interventions to COVID-19. The findings will inform the development of an effective and scalable adaptive intervention to increase COVID-19 testing and adherence to public health recommendations, including vaccination and booster shots, among a marginalized and difficult-to-engage population. ClinicalTrials.gov NCT04757298 . Registered on February 17, 2021.


Facile mass preparation and characterization of Al/copper ferrites metastable intermolecular energetic nanocomposites.
In the present work, a novel Al/copper ferrites metastable intermolecular energetic nanocomposite was prepared by a simple and mild sol-gel method followed by low temperature calcination, and characterized by various analytical techniques. The X-ray diffraction (XRD) analysis suggests that the products contain crystal forms of aluminum and spinel-type ferrite crystal forms which are CuFe2O4 with many crystal defects. The scanning electron microscopy (SEM) and nitrogen adsorption-desorption analyses reveal that the prepared Al/copper ferrites are mesoporous structures with large specific surface areas of up to 184.47 m2 g-1 and further reveal the pore construction of this material. Its crystal defects and large specific surface area provide the possibility for its excellent catalytic performance. Al/copper ferrites have 45% better exothermic properties with higher energy output efficiency, faster burning rate, and higher reactivity than traditional Al/Fe2O3 prepared by the same method. Due to the synergistic catalytic effect of Cu-Fe oxides, Al/copper ferrites have a better catalytic effect on AP thermal decomposition and can reduce the HTD peak temperature of AP 33% more than Al/Fe2O3. The catalytic mechanism of Al/copper ferrites for the thermal decomposition of AP is obtained based on the electron transfer theories, synergistic catalytic mechanism, and the porous structure of Al/copper ferrites. Due to the mild reaction conditions and low calcination temperature, dozens of grams of product can be safely obtained at one time with low cost and easily available raw materials to meet the requirements of propellant up to several kilograms or other industrial applications.


Multiple gamma oscillations in the brain: a new strategy to differentiate functional correlates and P300 dynamics.
Brain oscillations in the gamma frequency band, - i.e. oscillations greater than 25 Hz - have attracted increasing attention over the last few decades in the research of sensory-cognitive processes. In the neuroscience research literature, a great number of reports aim to describe the functional correlates of oscillatory responses in the gamma frequency window. However, analysis using a broadband frequency window often leads to divergent functional interpretations and controversies. In order to provide a more exact approach, we have used a strategy by defining multiple frequency and multiple time windows according to the combined analysis of conventional power spectral windows, frequency adaptive multiple filters, and inter-trial coherence. The analysis in frequency windows of 25-30 Hz, 30-35 Hz, and 40-48 Hz enables the investigator to provide a distinction of cognitive and/or sensory responses. Moreover, according to topological differentiation and the consideration of neuroanatomic pathways, more reliable interpretations of gamma responses are reached.


Developing a Model for Pharmaceutical Palliative Care in Rural Areas-Experience from Scotland.
Palliative care is increasingly delivered in the community but access to medicines, particularly 'out of hours' remains problematic. This paper describes the experience of developing a model to deliver pharmaceutical palliative care in rural Scotland via the MacMillan Rural Palliative Care Pharmacist Practitioner (MRPP) project. The focus of the service was better integration of the MRPP into different care settings and professional teams, and to develop educational resources for the wider MDT including Care Home and Social Care staff on medicine related issues in palliative care. A variety of integration activities are reported in the paper with advice on how to achieve this. Similarly, many resources were developed, including bespoke training on pharmaceutical matters for Care Home staff. The experience allowed for a three step service and sustainability model for community pharmacy palliative care services to be developed. Moving through the steps, the key roles and responsibilities of the MRPP gradually shift towards the local Community Pharmacist(s), with the MRPP starting from a locality-based hands-on role to a wider supportive facilitating role for local champions. It is acknowledged that successful delivery of the model is dependent on alignment of resources, infrastructure and local community support.


[Acute and chronic progressive abdominal pain: what is the role of radiogical imaging?].
There are many causes for acute or chronic progressive abdominal pain. Although only about one percent of these patients suffer from acute mesenteric ischemia (MI), an efficient diagnostic work-up is mandatory to reduce the high mortality. An overview about the possibilities of conventional and modern imaging modalities is given. Plain films and ultrasonography are still important in the basic work-up, however, its sensitivity is limited. Angiography has a high sensitivity and specitivity. However, angiography is not always available. Modern spiral-CT is widely available and its sensitivity is already similar to angiography. An other advantage of CT is the possibility to detect the most other frequent causes of abdominal pain. Therefore CT should be performed as fast as possible.


Quality of Handoffs in Community Pharmacies.
The aims of the study were to characterize handoffs in community pharmacies and to examine factors that contribute to perceived handoff quality. A cross-sectional study of community pharmacists in a Midwest State of the United States. Self-administered questionnaires were used to collect information on participant and practice setting characteristics. Data were analyzed using descriptive statistics and multivariate logistic regression. A total of 445 completed surveys were returned (response rate, 82%). In almost half of the time, handoffs that occur in a community pharmacy setting were inaccurate or incomplete. Nearly half of the time handoffs occur in environments full of interruptions and distractions. More than 90% of the respondents indicated that they have undergone no formal training on proper ways of handing off information. Nearly 40% of respondents reported that their pharmacy dispensing technology does not have adequate functionality to support handing off information and that at least 50% of the time, poor handoffs result in additional work to the pharmacist because of the need for complete information before providing patient care. Multivariate analysis showed that being very familiar with patients, lower daily prescription volume, not having a 24-hour operation, and larger percentage of handoffs occurring in a synchronous fashion are all associated with better handoff quality. Handoffs occur frequently and are problematic in community pharmacies. Current pharmacy environments offer limited support to conduct good handoffs, and as a result, pharmacists report loss of information. This could present as a significant patient safety hazard. Future interventions should target facilitating better communication during shift changes.


The nucleotide sequence of the coat protein gene and 3' untranslated region of azuki bean mosaic potyvirus, a member of the bean common mosaic virus subgroup.
The relationship of azuki bean mosaic potyvirus (AzMV) to members of the bean common mosaic virus (BCMV) subgroup has been unclear. Degenerate oligonucleotide primers and the polymerase chain reaction were used to amplify and clone the coat protein (CP) gene and 3' untranslated region (UTR) of AzMV. The deduced amino acid sequence of the CP is 94% identical to that of dendrobium mosaic virus, establishing the two as strains of the same virus. While the CP amino acid identities between AzMV and potyviruses of the BCMV species are at or below 90%, the 91 to 94% identity between their UTRs suggests that AzMV could be considered a strain of BCMV. Interestingly, the grouping of potyviruses within the greater BCMV subgroup on a coat protein amino acid tree correlates with a grouping based on the response elicited on bean containing the I gene for resistance to BCMV.


Contribution of a response regulator to the virulence of Streptococcus pneumoniae is strain dependent.
Bacterial two-component signal transduction systems (TCS) enable bacteria to respond to environmental changes and regulate a range of genes accordingly. They have a crucial role in regulating many cellular responses and have excellent potential as antibacterial-drug targets. We have constructed mutations in a TCS response regulator gene for two different strains of the human pathogen Streptococcus pneumoniae. These mutants have been analyzed in our murine model of infection. Data suggest that in a D39 background the response regulator gene is essential for virulence; an isogenic mutant is avirulent via intraperitoneal, intranasal, and intravenous routes of infection. This mutant, which does not show impaired growth in vitro, is unable to grow in the lung tissue or in blood. Mutation of the response regulator in a 0100993 background results in a strain that is fully virulent intraperitoneally and intravenously but shows decreased levels of bacteremia and increased murine survival following intranasal infection. The ability to grow in the lung tissue is not impaired in this mutant, suggesting that it has an impaired ability to disseminate from the lungs to the systemic circulation. Our data highlight the importance of assessing the contribution of putative virulence factors to the infection process at different sites of infection and provide evidence that virulence determinants can behave very differently based on the genetic background of the bacterial strain. These important findings may be relevant to other bacterial pathogens.


Seeds of discontent: expert opinion, mass media messages, and the public image of agricultural biotechnology.
Survey data are presented on opinions about agricultural biotechnology and its applications held by agricultural science faculty at highly ranked programs in the United States with and without personal involvement in biotechnology-oriented research. Respondents believed biotech holds much promise, but policy positions vary. These results underscore the relationship between opinion and stakeholder interests in this research, even among scientific experts. Media accounts are often seen as causes, rather than artifacts, of the existence of public controversy; European and now U.S. opposition to food biotechnology is often explained away in terms of such a relationship. The authors argue that where even experts are divided, public opposition cannot reasonably be attributed to poor public understanding or sensationalistic media accounts. Ethical implications for communicating science are explored.


Long term effects of cyclophosphamide treatment on lung function and survival in scleroderma patients with interstitial lung disease.
Scleroderma (SSc) patients with active interstitial lung disease (ILD) experience a decline in lung function and increased mortality; cyclophosphamide (CYC) therapy may stabilize lung function at one and two years follow-up. Long-term lung function and survival outcomes of SSc patients with ILD following CYC treatment remain largely unknown. We reviewed records of SSc patients with active ILD who had received at least six months of CYC treatment and had pulmonary function tests (PFTs) performed at least two years from the onset of treatment. Thirty eight patients meeting eligibility criteria had a mean follow-up period from start of CYC to the last follow-up PFT of 5.1 years (range 2.3 -10.8 years). At a median of 4.1 years (range 9 months - 8.4 years), 12/38 (32%) patients had a significant decline in % predicted Forced Vital Capacity from their baseline PFT. At a median of 3.9 years (range 7 months - 8.4 years); 12/36 (33%) patients experienced a significant decline in their % predicted carbon monoxide diffusing capacity. Three patients died at a follow-up between 4.5-6 years and two received bilateral lung transplants because of severe restrictive lung disease. While the majority of SSc patients treated with CYC for active ILD experience long-term lung function stability and survive, greater than 1/3 of patients will experience either lung function decline, death, or require a lung transplant. This suggests that despite aggressive immune suppressing therapy, a subset of patients will have continued lung function decline, highlighting the need for ongoing monitoring and better therapeutic options.


Bioinformatic analyses and an expression study of a novel gene associated with metabolic syndrome.
The investigation of novel genes involved in the derangement of glucose and lipid metabolism is of particular importance in understanding the development of metabolic syndrome (MS). In the present study, bioinformatic analyses were carried out to explore the structures and roles of the proteins encoded by the four cDNA sequences identified in our previous studies as associated with MS. Homology analyses demonstrated that the proteins encoded by Sequence 1, Sequence 2, Sequence 3, and Sequence 4 were homologous with fibrinogen gamma polypeptide, liver fibrinogen-like 1, chromosome 10 open reading frame 104, and an unnamed protein product, respectively. Because the structures were well-known for fibrinogen gamma polypeptide and liver fibrinogen-like 1, further analyses were performed only for Sequence 3 and Sequence 4. Analyses of functional domains showed that the predicted proteins encoded by Sequence 3 and Sequence 4 had multiple phosphorylation and myristoylation sites. These results indicated that the two predicted proteins might be intermediate proteins in some signaling pathways. In order to explore the possible association of Sequence 3 with MS, HepG2 cells, a human hepatoma cell line, were treated with different concentrations of glucose (mannitol as osmotic control) for 48 h. Glucose at concentrations of 22 and 33.3 mM significantly increased the mRNA expression of Sequence 3 compared to glucose at 5.6 mM while mannitol had no significant effect on the mRNA expression of Sequence 3. These results indicated that the mRNA expression of Sequence 3 was positively associated with glucose higher than physiological concentrations.


A marker set for construction of a genetic map of the silver fox (Vulpes vulpes).
The silver fox, a variant of the red fox (Vulpes vulpes), is a close relative of the dog (Canis familiaris). Cytogenetic differences and similarities between these species are well understood, but their genomic organizations have not been compared at higher resolution. Differences in their behavior also remain unexplained. Two silver fox strains demonstrating markedly different behavior have been generated at the Institute of Cytology and Genetics of the Russian Academy of Sciences. Foxes selected for tameness are friendly, like domestic dogs, while foxes selected for aggression resist human contact. To refine our understanding of the comparative genomic organization of dogs and foxes, and enable a study of the genetic basis of behavior in these fox strains, we need a meiotic linkage map of the fox. Towards this goal we generated a primary set of fox microsatellite markers. Four hundred canine microsatellites, evenly distributed throughout the canine genome, have been identified that amplify robustly from fox DNA. Polymorphism information content (PIC) values were calculated for a representative subset of these markers and population inbreeding coefficients were determined for tame and aggressive foxes. To begin to identify fox-specific single nucleotide polymorphisms (SNPs) in genes involved in the neurobiology of behavior, fox and dog orthologs of serotonin 5-HT1A and 5-HT1B receptor genes have been cloned. Sequence comparison of these genes from tame and aggressive foxes reveal several SNPs. The close relationship of the fox and dog enables canine genomic tools to be utilized in developing a fox meiotic map and mapping behavioral traits in the fox.


Biology of the lymphatic marker LYVE-1 and applications in research into lymphatic trafficking and lymphangiogenesis.
The pace of research into the lymphatic system continues to accelerate with the availability of new molecular markers. One such marker, LYVE-1, the lymphatic receptor for the extracellular matrix mucopolysaccharide hyaluronan, has been a key component of many important studies on embryonic and tumour-induced lymphangiogenesis, and continues to be used for the detection and isolation of lymphatic endothelial cells. However, LYVE-1 is interesting in its own right. Being a member of the Link protein family whose only other major hyaluronan receptor is directly involved in leukocyte migration and tumour metastasis, LYVE-1 is already implicated in the trafficking of cells within lymphatic vessels and lymph nodes. The current challenge is to determine the precise roles played by LYVE-1 and other scavenger type receptors in the immune functions of the lymphatics as well as to use LYVE-1 and other markers to investigate the way in which tumours exploit lymphatic vessels for metastasis.


[Chronic conjunctivitis caused by oral anaerobic germs].
A patient with chronic, unilateral conjunctivitis is presented. The predominant bacterial flora consisted mainly of Prevotella intermedia (formerly Bacteroides intermedius) and Peptostreptococcus micros. Restriction endonuclease fingerprinting of genomic DNA demonstrated that P. intermedia most probably originated from the oral cavity. In the oral cavity this species was recovered from the dorsum of the tongue, the tonsillar area and the periodontal pockets. Topical treatment with various antibiotics had failed to cure the infection in the past. The condition was cured after systemic therapy with metronidazole and amoxicillin.