Asymmetric Total Syntheses and Biological Studies of Tuberostemoamide and Sessilifoliamide A.
The first asymmetric total syntheses of tuberostemoamide, sessilifoliamide A, and their epimers have been accomplished via the common intermediate ethylstemoamide. The stereochemistry control relationship at C8/C9/C10 of ethylstemoamide is clearly revealed for the first time, and a subtle difference of substituent at the C10 position between stemoamide and ethylstemoamide (Me vs Et) drastically changes the stereoselectivity, which is significantly valuable for syntheses of ethylstemoamide structurally related Stemona alkaloids. Biological studies reveal that the activities of each epimer show a significant difference. 11,13-Bis- epi-sessilifoliamide A is expected to be a selective and reversible BChE inhibitor for the treatment of neurodegenerative diseases, and sessilifoliamide A may be a part of the anti-inflammatory substances in Stemonaceae plants.


Imprinting on chromosome 20: tissue-specific imprinting and imprinting mutations in the GNAS locus.
The GNAS locus on chromosome 20q13.11 is the archetypal complex imprinted locus. It comprises a bewildering array of alternative transcripts determined by differentially imprinted promoters which encode distinct proteins. It also provides the classic example of tissue-specific imprinted gene expression, in which the canonical GNAS transcript coding for Gsalpha is expressed predominantly from the maternal allele in a set of seemingly unrelated tissues. Functionally, this rather obscure imprinting is nevertheless of considerable clinical significance, as it dictates the nature of the disease caused by inactivating mutations in Gsalpha, with end organ hormone resistance specifically on maternal transmission (pseudohypoparathyroidism type 1a, PHP1a). In addition, there is a bona fide imprinting disorder, PHP1b, which is caused specifically by DNA methylation defects in the differentially methylated regions (DMRs) that determine tissue-specific monoallelic expression of GNAS. Although the genetic defect in PHP1a and the disrupted imprinting in PHP1b both essentially result in profound reduction of Gsalpha activity in tissues with monoallelic GNAS expression, and despite a growing awareness of the overlap in these two conditions, there are important pathophysiological differences between the two whose basis is not fully understood. PHP1b is one of the only imprinted gene syndromes in which cis-acting mutations have been discovered that disrupt methylation of germline-derived imprint marks; such imprinting mutations in GNAS are helping to provide important new insights into the mechanisms of imprinting establishment generally.


Modeling colonization rates over time: Generating null models and testing model adequacy in phylogenetic analyses of species assemblages.
A central theme connecting macroevolutionary processes to macroecological patterns is the shaping of regional biodiversity over time through speciation, extinction, migration, and range shifts. The use of phylogenies to explore the dynamics of diversification due to variation in speciation and extinction rates has been well-developed and there are established methods for inferring speciation times from phylogenies and generating its null distributions (as represented by node heights on molecular phylogenies). But inferring colonization events from phylogenies is more challenging. Unlike speciation events, represented by nodes, colonization events could occur at any point along a branch connecting species in the assemblage to the regional pool. We account for uncertainty in identification of colonization lineages and timing of colonization events by using an efficient analytical solution to inferring the distribution of colonization times from an assemblage phylogeny. Using the same solution, we efficiently derive the null distribution of colonization times, which provides us with a general approach to testing the adequacy of a model to describe colonization events into the assemblage. We illustrate this approach by demonstrating how the movement of squamate lineages into Madagascar has been uneven over time, peaking in the early Cenozoic when ocean conditions favored colonization.


Pharmacological Treatment of Secondary Lymphedema.
Lymphedema is a chronic disease that results in swelling and decreased function due to abnormal lymphatic fluid clearance and chronic inflammation. In Western countries, lymphedema most commonly develops following an iatrogenic injury to the lymphatic system during cancer treatment. It is estimated that as many as 10 million patients suffer from lymphedema in the United States alone. Current treatments for lymphedema are palliative in nature, relying on compression garments and physical therapy to decrease interstitial fluid accumulation in the affected extremity. However, recent discoveries have increased the hopes of therapeutic interventions that may promote lymphatic regeneration and function. The purpose of this review is to summarize current experimental pharmacological strategies in the treatment of lymphedema.


Transcriptomic analysis unveils correlations between regulative apoptotic caspases and genes of cholesterol homeostasis in human brain.
Regulative circuits controlling expression of genes involved in the same biological processes are frequently interconnected. These circuits operate to coordinate the expression of multiple genes and also to compensate dysfunctions in specific elements of the network. Caspases are cysteine-proteases with key roles in the execution phase of apoptosis. Silencing of caspase-2 expression in cultured glioblastoma cells allows the up-regulation of a limited number of genes, among which some are related to cholesterol homeostasis. Lysosomal Acid Lipase A (LIPA) was up-regulated in two different cell lines in response to caspase-2 down-regulation and cells silenced for caspase-2 exhibit reduced cholesterol staining in the lipid droplets. We expanded this observation by large-scale analysis of mRNA expression. All caspases were analyzed in terms of co-expression in comparison with 166 genes involved in cholesterol homeostasis. In the brain, hierarchical clustering has revealed that the expression of regulative apoptotic caspases (CASP2, CASP8 CASP9, CASP10) and of the inflammatory CASP1 is linked to several genes involved in cholesterol homeostasis. These correlations resulted in altered GBM (Glioblastoma Multiforme), in particular for CASP1. We have also demonstrated that these correlations are tissue specific being reduced (CASP9 and CASP10) or different (CASP2) in the liver. For some caspases (CASP1, CASP6 and CASP7) these correlations could be related to brain aging.


Chlorthalidone-modulated vascular responses to vasodilator stimuli in DOCA-salt hypertensive rats.
This study was carried out to test the effect of chlorthalidone (Chlor) treatment on the vascular responsiveness to acetylcholine (Ach) and adenosine disphosphate (ADP) under different extracellular calcium concentrations (Cae2+) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Half of the DOCA-salt hypertensive rats were simultaneously given Chlor (8 mg day-1, p.o.), after the twentieth day of DOCA, until the fortieth day. Mean arterial pressure (MAP) was reduced (P < 0.01) in DOCA-salt-Chlor (121 +/- 3 mmHg) compared to DOCA-salt (175 +/- 3 mmHg) rats. Chlor reduced the high plasma sodium of DOCA-salt to levels of the normotensive groups. The basal perfusion pressure of the isolated mesenteric vascular bed (MVB) was not modified by Cae2+ changing or previous addition of ouabain. At normal and low Cae2+ the vasodilator effect of Ach in the MVB was reduced (P < 0.01) in DOCA-salt and less (P < 0.05) in the salt-control rats. Chlor shifted the curve of DOCA-salt backward to control group curves. In high Cae2+ the vasodilator responses to Ach were reduced (P < 0.01) both in normal-control and DOCA-salt+Chlor but not in salt-control but not in salt-control and DOCA-salt group. The vasodilator effect of ADP to different Cae2+ was similar in presence of normal and low Cae2+ in normal-control rats and it was reduced (P < 0.01) in presence of high Cae2+ in the DOCA-salt group. Chlor restored the responses to ADP to normal-control level. Under ouabain-treatment, the vasodilation duration was reduced (P < 0.05) in all groups. It was shorter (P < 0.01) in DOCA-salt than in the other ones. Chlor completely abolished this difference. The MAP reduction in DOCA-salt rats by chlor could also be associated with a restored normal responsiveness of endothelial cells to endogenous vasodilator, for example Ach and ADP, since sodium nitroprusside did not exhibit differences among the various treatments. This diuretic agent seems to elicit its effect through a reduction in plasma sodium content of DOCA-salt hypertensive rats.


Learning multisensory integration and coordinate transformation via density estimation.
Sensory processing in the brain includes three key operations: multisensory integration-the task of combining cues into a single estimate of a common underlying stimulus; coordinate transformations-the change of reference frame for a stimulus (e.g., retinotopic to body-centered) effected through knowledge about an intervening variable (e.g., gaze position); and the incorporation of prior information. Statistically optimal sensory processing requires that each of these operations maintains the correct posterior distribution over the stimulus. Elements of this optimality have been demonstrated in many behavioral contexts in humans and other animals, suggesting that the neural computations are indeed optimal. That the relationships between sensory modalities are complex and plastic further suggests that these computations are learned-but how? We provide a principled answer, by treating the acquisition of these mappings as a case of density estimation, a well-studied problem in machine learning and statistics, in which the distribution of observed data is modeled in terms of a set of fixed parameters and a set of latent variables. In our case, the observed data are unisensory-population activities, the fixed parameters are synaptic connections, and the latent variables are multisensory-population activities. In particular, we train a restricted Boltzmann machine with the biologically plausible contrastive-divergence rule to learn a range of neural computations not previously demonstrated under a single approach: optimal integration; encoding of priors; hierarchical integration of cues; learning when not to integrate; and coordinate transformation. The model makes testable predictions about the nature of multisensory representations.


Meta-Analytic Evidence for a Reversal Learning Effect on the Iowa Gambling Task in Older Adults.
Iowa Gambling Task (IGT) is one of the most widely used tools to assess economic decision-making. However, the research tradition on aging and the Iowa Gambling Task (IGT) has been mainly focused on the overall performance of older adults in relation to younger or clinical groups, remaining unclear whether older adults are capable of learning along the task. We conducted a meta-analysis to examine older adults' decision-making on the IGT, to test the effects of aging on reversal learning (45 studies) and to provide normative data on total and block net scores (55 studies). From the accumulated empirical evidence, we found an average total net score of 7.55 (±25.9). We also observed a significant reversal learning effect along the blocks of the IGT, indicating that older adults inhibit the prepotent response toward immediately attractive options associated with high losses, in favor of initially less attractive options associated with long-run profit. During block 1, decisions of older adults led to a negative gambling net score, reflecting the expected initial pattern of risk-taking. However, the shift toward more safe options occurred between block 2 (small-to-medium effect size) and blocks 3, 4, 5 (medium-to-large effect size). These main findings highlight that older adults are able to move from the initial uncertainty, when the possible outcomes are unknown, to decisions based on risk, when the outcomes are learned and may be used to guide future adaptive decision-making.


[Behçet's disease--clinical presentation, diagnostic and therapeutic approach].
Behçet's disease is a complex, multisystem disease first described in 1937 by the Turkish dermatologist, Hulusi Behçet. In his original description, Behçet referred to a symptom complex of recurrent oral aphthous ulcers, genital aphthae, and iritis that could lead to blindness. Today we know that Behçet's disease is much more than a "triad syndrome" and it may also involve the gastrointestinal, central nervous system and large vessels. As yet, there are no existing diagnostic laboratory tests or curative treatments for Behçet's disease. Howver, genetic studies have identified those who are at risk and newer molecular biologic investigations further elucidate the pathogenesis of the disease. The treatment of Behçet's disease depends on clinical manifestations and the severity of the disease. Although various therapeutic modalities have been employed for Behçet's disease, treatment is still unsatisfactory. Treatment modalities include local, systemic, or surgical approaches. Only limited success has been achieved with classic agents such as: colchicine, indomethacin, chlorambucil, and systemic corticosteroids. New therapeutic approaches have been introduced for Behçet's disease using cyclosporine, thalidomide, interferon, high-dose corticosteroids or cyclophosphamide therapy. In this article we summarized the clinical and diagnostic approach for Behçet's disease and the current therapy indicated for different clinical presentations of the disease.


Bacteriophage T4 self-assembly: localization of gp3 and its role in determining tail length.
Gene 3 of bacteriophage T4 participates at a late stage in the T4 tail assembly pathway, but the hypothetical protein product, gp3, has never been identified in extracts of infected cells or in any tail assembly intermediate. In order to overcome this difficulty, we expressed gp3 in a high-efficiency plasmid expression vector and subsequently purified it for further analysis. The N-terminal sequence of the purified protein showed that the initial methionine had been removed. Variant C-terminal amino acid sequences were resolved by determining the cysteine content of the protein. The molecular mass of 20.6 kDa for the pure protein was confirmed by Western blotting, using a specific anti-gp3 serum for which the purified protein was the immunogen. We also demonstrated, for the first time, the physical presence of gp3 in the mature T4 phage particle and localized it to the tail tube. By finding a nonleaky, nonpermissive host for a gene 3 mutant, we could clearly demonstrate a new phenotype: the slow, aberrant elongation of the tail tube in the absence of gp3.


A SHATTERPROOF-like gene controls ripening in non-climacteric strawberries, and auxin and abscisic acid antagonistically affect its expression.
Strawberries (Fragaria×ananassa) are false fruits the ripening of which follows the non-climacteric pathway. The role played by a C-type MADS-box gene [SHATTERPROOF-like (FaSHP)] in the ripening of strawberries has been studied by transiently modifying gene expression through either over-expression or RNA-interference-mediated down-regulation. The altered expression of the FaSHP gene caused a change in the time taken by the over-expressing and the down- regulated fruits to attain the pink stage, which was slightly shorter and much longer, respectively, compared to controls. In parallel with the modified ripening times, the metabolome components and the expression of ripening-related genes also appeared different in the transiently modified fruits. Differences in the response time of the analysed genes suggest that FaSHP can control the expression of ripening genes either directly or indirectly through other transcription factor-encoding genes. Because fleshy strawberries are false fruits these results indicate that C-type MADS-box genes like SHATTERPROOF may act as modulators of ripening in fleshy fruit-like structures independently of their anatomical origin. Treatment of strawberries with either auxin or abscisic acid had antagonistic impacts on both the expression of FaSHP and the expression of ripening-related genes and metabolome components.


RNArchitecture: a database and a classification system of RNA families, with a focus on structural information.
RNArchitecture is a database that provides a comprehensive description of relationships between known families of structured non-coding RNAs, with a focus on structural similarities. The classification is hierarchical and similar to the system used in the SCOP and CATH databases of protein structures. Its central level is Family, which builds on the Rfam catalog and gathers closely related RNAs. Consensus structures of Families are described with a reduced secondary structure representation. Evolutionarily related Families are grouped into Superfamilies. Similar structures are further grouped into Architectures. The highest level, Class, organizes families into very broad structural categories, such as simple or complex structured RNAs. Some groups at different levels of the hierarchy are currently labeled as 'unclassified'. The classification is expected to evolve as new data become available. For each Family with an experimentally determined three-diemsional (3D) structure(s), a representative one is provided. RNArchitecture also presents theoretical models of RNA 3D structure and is open for submission of structural models by users. Compared to other databases, RNArchitecture is unique in its focus on structure-based RNA classification, and in providing a platform for storing RNA 3D structure predictions. RNArchitecture can be accessed at http://iimcb.genesilico.pl/RNArchitecture/.


Red-winged blackbirds (Agelaius phoeniceus) with higher baseline glucocorticoids also invest less in incubation and clutch mass.
Glucocorticoid hormones facilitate responses to environmental challenges by mediating diverse physiological and behavioral changes, including resource mobilization and altered reproductive effort. Elevated glucocorticoids might indicate that an individual is facing high levels of environmental challenges and thus, elevated concentrations might be associated with reduced fitness (CORT-fitness hypothesis). Alternatively, the energetic demands of reproduction might be a challenge that requires elevated glucocorticoids to mobilize resources to support reproductive effort, ultimately increasing reproductive investment and fitness (CORT-adaptation hypothesis). Investigations of glucocorticoid-fitness relationships have yielded mixed results. Variation in the direction of this relationship could be caused in part by differences in the contexts in which the relationship was assessed. Incorporating context, such as life history stage, could be key to understanding the role of glucocorticoids in influencing fitness outcomes. We investigated the relationship between corticosterone and reproductive effort and success within a single life history stage: incubation of eggs. In an observational study, we measured baseline corticosterone in incubating female red-winged blackbirds (Agelaius phoeniceus), monitored incubation behavior, and determined hatching success for each nest. Incubating birds with higher baseline corticosterone concentrations had more frequent, shorter incubation bouts and spent less time overall incubating their clutches of eggs than birds with lower corticosterone concentrations. Elevated corticosterone was also associated with lower clutch mass, but neither corticosterone nor incubation effort were correlated with hatching success. Although experimental tests are needed to establish causation, these results suggest that during the incubation period, corticosterone might shift resource investment towards self-maintenance, and away from current reproductive effort.


Leaf epidermal characteristics of Cissampelos L. (Menispermaceae) species from Northeastern Brazil.
The morphological similarities among the species of Cissampelos are remarkable and the difficult to distinguish them as well. This article presents a comparative anatomical study of the leaves of common Northeastern Brazilian species of Cissampelos, carried out using light and scanning electron microscopy. The leaf epidermal was studied to obtain data on epidermal characteristics and to evaluate their taxonomic significance. As results, some micromorphological characters on the leaf epidermal like the cuticular waxes, the presence of papillae in epidermis and nonglandular trichomes, the anticlinal walls epidermal cells, the distribution, density and type of trichomes, and also the type and distribution of epicuticular wax proved to be the most useful characteristics to distinguish the species in taxonomic studies.


Involvement of microtubules in lipoprotein degradation and utilization for steroidogenesis in cultured rat luteal cells.
Cells isolated from superovulated rat ovaries metabolize low density lipoprotein (LDL) and high density lipoprotein (HDL) of human or rat origin and use the lipoprotein-derived cholesterol as a precursor for progesterone production. Under in vitro conditions, both lipoproteins are internalized and degraded in the lysosomes, although degradation of HDL is of lower magnitude than that of LDL. In this report we have examined the role of cellular microtubules in the internalization and degradation of human LDL and HDL in cultured rat luteal cells. The microtubule depolymerizing agents colchicine, podophyllotoxin, vinblastine, and nocodazole as well as taxol, deuterium oxide, and dimethyl sulfoxide, which are known to rapidly polymerize cellular tubulin into microtubules, were used to block the function of microtubules. When these antimicrotubule agents were included in the incubations, degradation of the apolipoproteins of [125I]iodo-LDL and [125I]iodo-HDL by the luteal cells was inhibited by 50-85% compared to untreated control values. Maximum inhibitory effects were observed when the cells were preincubated with the inhibitor for at least 4 h at 37 C before treatment with the labeled lipoprotein. Lipoprotein-stimulated progesterone production by luteal cells was also inhibited by 50% or more in the presence of antimicrotubule agents. However, basal and hCG-stimulated progesterone production were unaffected by these inhibitors. The binding of [125I]iodo-LDL and [125I]iodo-HDL to luteal cell plasma membrane receptors was not affected by the microtubule inhibitors. Although binding was unaffected and degradation was impaired in the presence of the inhibitors, there was no detectable accumulation of undegraded lipoprotein within the cells during the 24 h of study. From this study we conclude that the uptake and utilization of LDL and HDL by cultured rat luteal cells are mediated by cellular microtubules.


Quantitative disease resistance and quantitative resistance Loci in breeding.
Quantitative disease resistance (QDR) has been observed within many crop plants but is not as well understood as qualitative (monogenic) disease resistance and has not been used as extensively in breeding. Mapping quantitative trait loci (QTLs) is a powerful tool for genetic dissection of QDR. DNA markers tightly linked to quantitative resistance loci (QRLs) controlling QDR can be used for marker-assisted selection (MAS) to incorporate these valuable traits. QDR confers a reduction, rather than lack, of disease and has diverse biological and molecular bases as revealed by cloning of QRLs and identification of the candidate gene(s) underlying QRLs. Increasing our biological knowledge of QDR and QRLs will enhance understanding of how QDR differs from qualitative resistance and provide the necessary information to better deploy these resources in breeding. Application of MAS for QRLs in breeding for QDR to diverse pathogens is illustrated by examples from wheat, barley, common bean, tomato, and pepper. Strategies for optimum deployment of QRLs require research to understand effects of QDR on pathogen populations over time.


[Analysis of breakdown in family care for patients with dementia].
Although it has been stressed that patients with dementia should be cared for at home, family care seems to break down sooner or later. On the other hand, the number of demented patients is now increasing at a far greater rate than can be handled by institutions for the elderly. For these reasons, the appropriate use of social resources is now being emphasized. As early as 1960, Macmillan pointed out that the emotional relationship between an elderly patient and the relative responsible for him determines whether family care will breakdown, and stressed the importance of troublesome behavior in this relationship. Since then, researchers have studied the problem of troublesome behavior in demented patients and the burden that this creates for relatives nursing them. Such studies have stressed that the support of caring relatives is indispensable for the community care of demented patients. In the present study an attempt was made to analyze in detail the breakdown of family care for demented patients. To facilitate systematic study, we complied a pair of check lists containing criteria of troublesome behavior and care burden, adapted from the Disability and Handicap criteria of the WHO. For the purpose of the study, we regarded troublesome behavior as Disability, and care burden as Handicap. The subjects were 40 demented patients and their respective main carers, who had requested institutional care. Before the breakdown, the author had been in charge of all of the patients. The mean period of patient observation was 12 months. At the point when the decision of institutionalization was made by family members, visits were made to each patient-carer pair, and the check lists were used to assess troublesome behavior and care burden. In order to clarify the features of the subject group, the author also visited and examined another 30 patient-carer pairs, who still lived in their home communities, between June and September, 1990. The mean period of observation for these patients was 18 months. There were no significant differences in sex, diagnosis, duration of illness, cognitive function, or number of physical complications between the two groups. No significant difference was found in the total score for the behavior check list between the two groups. In contrast, however, there was a significantly higher score for the burden check list representing those caring for the patients in the study group. Furthermore, it was revealed that social activity, individual free time and familial interaction, as well as many emotional and physical aspects, were more severely affected in the subject carers. This result appeared to confirm that the care burden itself, rather than troublesome behavior is responsible for breakdown. In all of the 70 pairs analyzed, a significant correlation was found between the total score for the behavior check list and that for the burden check list. The result of this study highlighted several new emerging problems. One serious problem is that of patients driving by themselves. In addition, many of carers reported recurrent falls by the patients. As to the problems faced by carers themselves, an appreciable number had been forced to give up their jobs to devote themselves to patient care. In general, female carers with husbands younger than 65 years reported economic distress. Additionally, unlike the situation in most western reports, as many as 43% of the main carers in this study were daughters in law. These problems faced by carers seem to be common in Japan, and are perhaps characteristic of Japanese society.(ABSTRACT TRUNCATED AT 400 WORDS)


Which region of the median palate is a suitable location of temporary orthodontic anchorage devices? A histomorphometric study on human cadavers aged 15-20 years.
Endosseus implants can provide a reliable anchorage during orthodontic treatment. The midpalatal structures around the sutura palatina mediana (SPM) are of special interest due to increasing placement of orthodontic implants in this area. Knowledge about the osseous conditions at this site is necessary to predict the expected degree of implant osseointegration. The upper jaws of 10 human cadavers, aged 15-20 years, were decalcified, and cross-sectional specimens were obtained from four anterior-to-posterior palatal regions for histomorphometric analysis. The analyses focused on the amount of bone and the width of the SPM to determine the anatomical requirements for reliable insertion of palatal implants. Bone density [bone-volume (BV)/ tissue-volume (TV)] in all measured areas was 40-60%. The maximum density was measured at the level of the first premolars (54.9+/-5.9%) and the least values (44.2+/-9.6%) were measured at the level of the interconnecting line of the canines. The mean width of the SPM varies from 1.2 to 0.3 mm in different sections of the palate. In the median sagittal plane, the mean values of bone height to nasal cavity reached >5 mm as far as the level distal of the second premolars. Bone height 2 mm paramedian to the SPM decreased consistently from anterior (4.3+/-0.9 mm) to posterior (2.5+/-0.8 mm). Our results indicate that the amount and quality of bone along the anterior palatal midline in 15-to-20-year olds is sufficient for orthodontic implantation. Even implantation posterior to the recommended first premolar level, at which orthodontic implants are most often placed, may be suitable. There are some limitations, however, due to small number of samples and variations of anatomical structures.


The wide and growing range of lamin B-related diseases: from laminopathies to cancer.
B-type lamins are fundamental components of the nuclear lamina, a complex structure that acts as a scaffold for organization and function of the nucleus. Lamin B1 and B2, the most represented isoforms, are encoded by LMNB1 and LMNB2 gene, respectively. All B-type lamins are synthesized as precursors and undergo sequential post-translational modifications to generate the mature protein. B-type lamins are involved in a wide range of nuclear functions, including DNA replication and repair, regulation of chromatin and nuclear stiffness. Moreover, lamins B1 and B2 regulate several cellular processes, such as tissue development, cell cycle, cellular proliferation, senescence, and DNA damage response. During embryogenesis, B-type lamins are essential for organogenesis, in particular for brain development. As expected from the numerous and pivotal functions of B-type lamins, mutations in their genes or fluctuations in their expression levels are critical for the onset of several diseases. Indeed, a growing range of human disorders have been linked to lamin B1 or B2, increasing the complexity of the group of diseases collectively known as laminopathies. This review highlights the recent findings on the biological role of B-type lamins under physiological or pathological conditions, with a particular emphasis on brain disorders and cancer.


Malignant Transformation of Pediatric Low-grade Gliomas: Report of Two Cases and Review of a Rare Pathological Phenomenon.
Low-grade gliomas (LGGs) are the commonest benign central nervous system (CNS) tumors seen in children. Unlike LGGs in adults, pediatric LGGs rarely undergo malignant transformation. The incidence of malignant transformation of LGGs in the pediatric population has been reported to be up to 10%. Of these, a few patients have demonstrated this phenomenon even without adjuvant radiation therapy. We report two such unusual cases. A 7-year-old girl presented with a left temporal lesion that was operated upon and was reported as pilocytic astrocytoma (WHO grade I). She presented with a malignant transformation of the tumour 8 years later. The second case was a 10-year-old boy, who had a left frontoparietal ganglioglioma (WHO grade I) that demonstrated malignant transformation to an anaplastic ganglioglioma (WHO grade III) 10 months after the initial surgery. Multiple studies have thrown light on the molecular genetics behind malignant transformation of LGGs in children. These genetic changes can perhaps serve as targets for potential future therapeutic interventions. It is important that patients with LGGs at risk of malignant transformation must be identified early so that a more aggressive treatment strategy can be adopted.


Causes of dysregulation of lipid metabolism in chronic renal failure.
End-stage renal disease (ESRD) is associated with accelerated atherosclerosis and premature death from cardiovascular disease. These events are driven by oxidative stress inflammation and lipid disorders. ESRD-induced lipid abnormalities primarily stem from dysregulation of high-density lipoprotein (HDL), triglyceride-rich lipoprotein metabolism, and oxidative modification of lipoproteins. In this context, production and plasma concentration of Apo-I and Apo-II are reduced, HDL maturation is impaired, HDL composition is altered, HDL antioxidant and anti-inflammatory functions are depressed, clearance of triglyceride-rich lipoproteins and their atherogenic remnants is impaired, their composition is altered, and their plasma concentration is elevated in ESRD. The associated defect in HDL maturation is largely caused by acquired lecithin-cholesterol acyltransferase deficiency while its triglyceride enrichment is due to hepatic lipase deficiency. Hypertriglyceridemia, abnormal composition, and impaired clearance of triglyceride-rich lipoproteins and their remnants are mediated by down-regulation of lipoprotein lipase, hepatic lipase, very low-density lipoprotein (VLDL) receptor, and LDL receptor-related protein, relative reduction in ApoC-II/ApoC-III ratio, up-regulation of acyl-CoA cholesterol acyltransferase, and elevated plasma level of cholesterol ester-poor prebeta HDL. Impaired clearance and accumulation of oxidation-prone VLDL and chylomicron remnants and abnormal LDL composition in the face of oxidative stress and inflammation favors their uptake by macrophages and resident cells in the artery wall. The effect of heightened influx of lipids is compounded by impaired HDL-mediated reverse cholesterol transport leading to foam cell formation which is the central event in atherosclerosis plaque formation and subsequent plaque rupture, thrombosis, and tissue damage.


Ectopic production of VapCs from Enterobacteria inhibits translation and trans-activates YoeB mRNA interferase.
Toxin-antitoxin loci have been identified in almost all free-living prokaryotes, often in high copy numbers. The biological function and molecular targets of the abundant vapBC loci are not yet known. Here we analyse the vapBC loci of Salmonella LT2 and Shigella plasmid pMYSH6000. Both loci encode putative PIN (PilT N-terminal) domain toxins, and antitoxins that may regulate vapBC transcription. We show that vapBC(LT2) and vapBC(pMYSH) are bona fide TA loci: (i) both VapCs inhibited cell growth very efficiently and were counteracted by the cognate VapBs; (ii) both VapCs inhibited translation; (iii) transcription of the vapBC loci was induced by amino acid starvation and chloramphenicol, consistent with the proposal that VapB is an unstable inhibitor of vapBC transcription; (iv) ectopic expression of both VapCs induced a bacteriostatic condition that could be reversed by the cognate antitoxins. Unexpectedly, induction of vapC in Escherichia coli resulted in mRNA cleavage at stop-codons. Surprisingly, these cleavages depended on the yefM yoeB locus, indicating cross-activation between different toxins, that is, VapC activated YoeB mRNA interferase. Activation of YoeB depended on Lon, indicating that Lon degrades YefM antitoxin. Based on these results we present a model that explains activation of YoeB.


Regional metastasis in head and neck squamous cell carcinoma: revised value of US with US-guided FNAB.
To verify the acclaimed accuracy of ultrasound (US) combined with US-guided fine-needle aspiration biopsy (FNAB) in the detection of lymph node metastasis in the neck and to evaluate the interobserver variability. In a prospective, multicenter study of 185 patients with head and neck squamous cell carcinoma, US (n=238 neck sides) with US-guided FNAB (n=178 neck sides) was used for evaluation of the lymph node status of the neck. Findings were correlated with those of histopathologic examination in 238 neck sides. US with US-guided FNAB had a sensitivity of 77% and a specificity of 100%. Nineteen of 178 aspirations were nondiagnostic. There were no significant differences between the four participating hospitals or the individual sonologists (P>.05). Sensitivity of US with US-guided FNAB was slightly lower compared with previous reports. Specificity was similar to previous reports. Interobserver variability appeared to be low. The validity of US with US-guided FNAB is high and warrants widespread use of the procedure for evaluation of the neck.


Combination of In Silico Methods in the Search for Potential CD4(+) and CD8(+) T Cell Epitopes in the Proteome of Leishmania braziliensis.
The leishmaniases are neglected tropical diseases widespread throughout the globe, which are caused by protozoans from the genus Leishmania and are transmitted by infected phlebotomine flies. The development of a safe and effective vaccine against these diseases has been seen as the best alternative to control and reduce the number of cases. To support vaccine development, this work has applied an in silico approach to search for high potential peptide epitopes able to bind to different major histocompatibility complex Class I and Class II (MHC I and MHC II) molecules from different human populations. First, the predicted proteome of Leishmania braziliensis was compared and analyzed by modern linear programs to find epitopes with the capacity to trigger an immune response. This approach resulted in thousands of epitopes derived from 8,000 proteins conserved among different Leishmania species. Epitopes from proteins similar to those found in host species were excluded, and epitopes from proteins conserved between different Leishmania species and belonging to surface proteins were preferentially selected. The resulting epitopes were then clustered, to avoid redundancies, resulting in a total of 230 individual epitopes for MHC I and 2,319 for MHC II. These were used for molecular modeling and docking with MHC structures retrieved from the Protein Data Bank. Molecular docking then ranked epitopes based on their predicted binding affinity to both MHC I and II. Peptides corresponding to the top 10 ranked epitopes were synthesized and evaluated in vitro for their capacity to stimulate peripheral blood mononuclear cells (PBMC) from post-treated cutaneous leishmaniasis patients, with PBMC from healthy donors used as control. From the 10 peptides tested, 50% showed to be immunogenic and capable to stimulate the proliferation of lymphocytes from recovered individuals.


Use of Na-Nuclear Magnetic Resonance To Follow Sodium Uptake and Efflux in NaCl-Adapted and Nonadapted Millet (Panicum miliaceum) Suspensions.
Cellular Na(+) transport was followed in vivo by (23)Na nuclear magnetic resonance (NMR) using anionic dysprosium-based shift reagents to resolve internal and external (23)Na(+) resonances. Proso millet (Panicum miliaceum) cell suspensions adapted for rapid growth on 130 mm NaCl had biphasic (23)Na efflux kinetics when shifted to low Na(+) medium, while nonadapted cells had little measurable Na(+) efflux after preloading with (23)NaCl. Uptake of (23)Na was also observed using (23)Na NMR. The resonance frequency of the external Na(+)-dysprosium (III) triphosphate, relative to that of the (23)Na in the cells, was sensitive to pH, permitting the pH of the external medium to be followed during the course of in vivo experiments.


[Prosthesis endocarditis: incidence, diagnosis, therapeutic decisions and prognosis].
In 2711 patients with heart valve replacement performed between 1965 and 1986 the cumulative incidence of prosthetic valve endocarditis (PVE) was 1.19 +/- 0.24% (n = 61). In patients operated on before 1976 (group A; n = 583) early PVE was observed in 3.43%, and in patients operated on between 1976 and 1986 (group B; n = 2128) in only 0.42%. PVE after the 60th postoperative day occurred with a linear incidence of 0.21 events per 100 patient-years (A: 0.11%; B: 0.27%). In 54% of PVE cases the aortic, and in 34% the mitral was involved; in 12% both left-sided prostheses were involved after double valve replacement. In the four weeks before the manifestation of initial symptoms of PVE, bacterial infections and diagnostic or therapeutic interventions had occurred in 74.2%. All interventions had been performed without endocarditis prophylaxis. Diagnosis of PVE was established in 57% by history and clinical examination, in 20% by microbiologic examinations and in 12% by echocardiography. Due to improved diagnostic methods and earlier surgical intervention, mortality declined during the follow-up period from 81% (1965-1970) to 18% (1981-1986). The prognosis was worse in patients who developed therapy-resistant heart failure due to hemodynamically significant prosthetic valve malfunction, or who had sepsis that persisted for more than 72 hours despite antibiotic therapy, major septic embolism or acute renal failure. The retrospective prognosis was more favourable for patients with early valve re-replacement than for patients who had been treated medically alone.


Altered expression of alpha-smooth muscle isoactin in Hirschsprung's disease.
To analyze the expression of smooth muscle actin (SMA) contractile proteins in the intestinal muscle of patients with Hirschsprung's disease. A total of 56 colonic whole-wall specimens were tested with immunohistochemistry and monoclonal antibodies directed against, respectively, alpha and pan (alpha and gamma) SMA. The study included both aganglionic and dilated normoganglionic colonic samples from 29 children who had undergone definitive surgery for Hirschsprung's disease. Morphologically normal (n = 6) and dilated colons (n = 5) from 11 patients suffering from conditions unrelated to Hirschsprung's disease served as controls. The alphaSMA immunostaining showed a pattern identical to normal controls in all the aganglionic areas and in 70% of the normoganglionic segments. In contrast, a lack of alphaSMA expression confined to the circular muscle cells was observed in 30% of the normoganglionic specimens and in the five dilated control specimens. The same areas showed a faintly reduced immunoreactivity with the antibody to pan SMA, consistent with the absence of alpha-isoactin, but implying the presence of gamma-isoactin. In the Hirschsprung's disease cases, the absence of alphaSMA expression at the time of surgery was associated with the occurrence of long-term postoperative motility problems (p<.01). These data suggest that alphaSMA expression defect in Hirschsprung's disease may be acquired and related to chronic colonic obstruction and subsequent dilatation. The observed changes correlate with disturbances of peristalsis and could be used to assess the risk of intestinal dysmotility frequently reported after surgical removal of the aganglionic bowel.


Mercury and selenium interaction in vivo: effects on thioredoxin reductase and glutathione peroxidase.
Mercury compounds exert toxic effects via interaction with many vital enzymes involved in antioxidant regulation, such as selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx). Selenium supplementation can reactivate the mercury-inhibited TrxR and recover the cell viability in vitro. To gain an insight on how selenium supplementation affects mercury toxicity in vertebrates, we investigated the effects of selenium on the mercury accumulation and TrxR and GPx activities in a fish model. Juvenile zebra-seabreams were exposed either to methylmercury (MeHg) or inorganic mercury (Hg(2+)) in the presence or absence of sodium selenite (Se) for 28 days followed by 14 days of depuration. Mercury accumulation was found to be 10-fold higher under MeHg exposure than under Hg(2+) exposure. Selenium supplementation caused a half decrease of the accumulation of MeHg but did not influence Hg(2+) accumulation. Exposure to both mercurials led to a decrease of the activity of TrxR (<50% of control) in all organs. Se supplementation coincident with Hg(2+) exposure protected the thioredoxin system in fish liver. However, supplementation of Se during the depuration phase had no effects. The activity of GPx was only affected in the brain of fishes upon the exposure to MeHg and coexposure to MeHg and Se. Selenium supplementation has a limited capacity to prevent mercury effects in brain and kidney. These results demonstrate that Se supplementation plays a protective role in a tissue-specific manner and also highlight the importance of TrxR as a main target for mercurials in vivo.


Mid-life African-American women with type 2 diabetes: influence on work and the multicaregiver role.
Few studies have examined the multicaregiver role, including the work role, of African-American women and the influence of that role on diabetes self-management and the ability to cope with type 2 diabetes. Therefore, the purpose of this study was to explore the perceptions of work and the multicaregiver role of a group of such women to more clearly identify the influence of these factors on diabetic self-management and personal coping. Focus group methodology was used to collect data from 12 mid-life African-American women. After data inspection, the research team extracted themes related to work and the multicaregiver role. Identification of relationships among and between themes helped delineate explanations of data and refine questions for future research. Focus group analysis of participant responses elicited 4 themes. Family as core represented the participant's role as leader of her household. Work as survival defined the stresses of work and the physical and psychosocial responses to not working due to the social and economic costs of diabetes. Participants also identified pressures of balancing work and family responsibilities due to diabetes, a theme of impaired role function. The final theme, inner-strengthening, defined participants' methods of self-preservation through introspection and spiritual behaviors. Despite their identification of physical and psychosocial struggles with diabetes, participants did not think of diabetes as a life-long illness because it affected their ability to remain at "the head of the table," to continue engaging in paid work outside the home, and to provide for their families. Historical, social, political, and economic factors supported the themes of the study and provide a foundation for further research and healthcare delivery system changes focused on improving the lives of these women and their families, who are facing the challenges of chronic illness.


Prevalence of dog erythrocyte antigens 1, 4, and 7 in galgos (Spanish Greyhounds).
Galgos (Spanish Greyhounds), in common with other sighthounds, have higher hematocrits, hemoglobin concentrations, and red blood cell counts than other breeds. In addition to these hematological characteristics, the physical characteristics of these dogs (medium to large dogs with an easily accessible jugular vein and a good temperament) make galgos ideal blood donors. However, to date, there are only published reports concerning dog erythrocyte antigen (DEA) 1 in this breed. Information on DEAs 4 and 7 would be useful when recruiting blood donors to donation programs, as DEA 1 and 7-negative and DEA 4-positive dogs can be considered universal donors. Ethylenediamine tetra-acetic acid-anticoagulated jugular blood samples were collected from 205 galgos. Dogs were aged between 1 and 10 years, 102 were female (49.8%) and 103 male (50.2%), and all were living in South Madrid, Spain. All 205 blood samples were tested for DEA 1 by card agglutination, and 150 of these samples were tested for DEA 4 and DEA 7 by gel column agglutination using polyclonal anti-DEA antibodies. Of the 205 galgos blood samples typed, 112 out of 205 (54.6%) were positive for DEA 1. Of the 150 blood samples tested, all (150/150, 100%) were positive for DEA 4, and 12 out of 150 (8%) samples tested positive for DEA 7. Of these samples, 70 out of 150 (46.7%) were positive only for DEA 4. There was no relationship between blood types and sex. In addition to the hematological characteristics previously reported and the physical characteristics of these dogs, the relative prevalence of blood types DEA 1, 4, and 7 make galgos good candidates for blood donation in blood donor programs.


Some observations on the collection of medical event data.
A review of the philosophy, strategies, and methods for the collection of medical event (ME) information in clinical trials sponsored by the Research and Development Division of THe Upjohn Company is presented. Goals for collection of ME information for Phase I, II, and III trials are reviewed. Case report form and terminology issues are discussed, with particular emphasis placed on procedures that avoid premature decisions on ME causality and incomplete reporting of events. Procedures for separating the seriousness from the intensity of the MEs are reviewed. Analysis issues are considered insofar as they impact on data collection procedures and goals. Recommendations are made with respect to protocol content, data collection forms, and related analysis issues.


In vitro effects of meloxicam on the number, Foxp3 expression, production of selected cytokines, and apoptosis of bovine CD25+CD4+ and CD25-CD4+ cells.
The purpose of this study was to evaluate the effect of meloxicam (MEL) on selected immune parameters of bovine CD25(high)CD4+, CD25(low)CD4+, and CD25-CD4+ cells. Peripheral blood mononuclear cells (PBMCs) collected from 12-month-old heifers were treated with MEL at a concentration corresponding to the serum level of this medication following administration at the recommended dose (MEL 5 × 10(⁻6) M) and at a concentration 10 times lower (MEL 5 × 10(⁻7) M). After 12 and 24 h of incubation with the drug, the percentage of CD25(high)CD4+ cells decreased; however, this disturbance was quickly reversed. Furthermore, the absolute number of CD25(high)CD4+ cells in the PBMC populations treated with MEL 5 × 10(⁻6) M for 48 and 168 h was increased. Prolonged (168 h) exposure to the drug increased the percentage of Foxp3+ cells in the CD25(high)CD4+ cell subpopulation. The higher dose of MEL was found to significantly increase the percentage of IFN-γ+ cells among the CD25-CD4+ cells. These results indicated that MEL does not exert an immunosuppressive effect by depleting CD4+ cells and suppression of IFN-γ+ production by these cells. Furthermore, IL-10 and TGF-β production was not changed following exposure to MEL.


Characteristics of patients with hepatitis C virus infection and antiviral treatment initiation in Taiwan: The MOSAIC study.
Hepatitis C virus (HCV) infection is the leading cause of chronic liver diseases worldwide. Monitoring its epidemiology, diagnosis, and treatment patterns are important for the management of patients with chronic HCV infection from both individual and public health perspectives. The MOSAIC study was an observational study conducted in 20 countries, including Taiwan; its primary objective was to describe epidemiology and treatment initiation patterns in patients seeking HCV care. Of the 111 chronic HCV patients enrolled from Taiwan, 58 (52.3%) had not previously received treatment. HCV genotype 1 was reported in 58 (52.3%) patients, of whom the majority (n = 47; 81.0%) were identified as having subtype 1b. Sixty-two (55.9%) patients had HCV RNA level > 800 000 IU/mL. Liver cirrhosis was found in 35 (29.3%) patients and was more prevalent in patients who previously received treatment (71.0%). Interferon (IFN)-based treatment was started within 12 weeks from study inclusion in 12 (10.8%) patients, of whom 11 (91.7%) who had not previously received treatment. Anti-HCV treatment was not recommended by physicians in 70 (71.4%) and was refused by 23 (23.5%) patients. The MOSAIC study provides data on the epidemiology of HCV infection and IFN-based treatment decision patterns in Taiwan. Further studies are needed to observe the impact of IFN-free treatment on the treatment selection pattern.


RNA polymerase II transcription inhibits DNA repair by photolyase in the transcribed strand of active yeast genes.
Yeast uses nucleotide excision repair (NER) and photolyase (photoreactivation) to repair cyclobutane pyrimidine dimers (CPDs) generated by ultraviolet light. In active genes, NER preferentially repairs the transcribed strand (TS). In contrast, we recently showed that photolyase preferentially repairs the non-transcribed strands (NTS) of the URA3 and HIS3 genes in minichromosomes. To test whether photoreactivation depends on transcription, repair of CPDs was investigated in the transcriptionally regulated GAL10 gene in a yeast strain deficient in NER [AMY3 (rad1Delta)]. In the active gene (cells grown in galactose), photoreactivation was fast in the NTS and slow in the TS demonstrating preferential repair of the NTS. In the inactive gene (cells grown in glucose), both strands were repaired at similar rates. This suggests that RNA polymerases II blocked at CPDs inhibit accessibility of CPDs to photolyase. In a strain in which both pathways are operational [W303-1a (RAD1)], no strand bias was observed either in the active or inactive gene, demonstrating that photoreactivation of the NTS compensates preferential repair of the TS by NER. Moreover, repair of the NTS was more quickly in the active gene than in the repressed gene indicating that transcription dependent disruption of chromatin facilitates repair of an active gene.


Spatial heterogeneity of inhibitory surrounds in the middle temporal visual area.
A recurrent theme in the organization of vertebrate visual cortex is that of receptive fields with an associated "silent" opponency component. In the middle temporal area (area MT), a cortical visual area involved in the analysis of retinal motion in primates, this opponency appears in the form of a region outside the classical receptive field (CRF) that in itself gives no response but suppresses responses to motion evoked within the CRF. This antagonistic motion surround has been described as very large and symmetrically arrayed around the CRF. On the basis of this view, the primary function of the surround has long been thought to consist of simple figure-ground segregation based on movement. We have made use of small stimulus patches to map the form and extent of the surround and find evidence that the surround inhibition of many MT cells is in fact confined to restricted regions on one side or on opposite sides of the CRF. Such regions endow MT cells with the ability to make local-to-local motion comparisons, capable of extracting more complex features from the visual environment, and as such, may be better viewed as intrinsic parts of the receptive field, rather than as separate entities responsible for local-to-global comparisons.


Epidemiologic and clinical characteristics of 42 deaths caused by SARS-CoV-2 infection in Wuhan, China: A retrospective study.
This study described the epidemiologic and clinical characteristics of patients who died from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and pointed out the potential risk factors associated with fatal outcomes. Retrospective data from 42 death cases due to SARS-CoV-2 infection at Tongji Hospital Affiliated to Huazhong University of Science and Technology, Wuhan, China was analyzed. Demographics, clinical detection, laboratory findings, and treatments of the deceased were collected and analyzed. The average time between onset of symptoms and admission to the hospitals was 11 ± 5 days of hospitalization. Among the deceased, 60% were with co-morbidities. All of them were having fever and bilateral pneumonia on computed tomography, abnormal infection-related biomarkers, and renal impairment. Abnormal blood coagulation parameters that appeared in more than half of them, were consistent with disseminated intravascular coagulation. All of the patients were treated in the ICU. Based on the fact that SARS-CoV-2 infection carries a risk of mortality, we may infer a few older male patients with underlying comorbidities are likely to have the increased risk. Impaired consciousness level, markers of renal impairment and coagulation abnormalities may be poor prognostic factors.


How does care coordination provided by registered nurses "fit" within the organisational processes and professional relationships in the general practice context?
The aim of this study was to develop understanding about how a registered nurse-provided care coordination model can "fit" within organisational processes and professional relationships in general practice. In this project, registered nurses were involved in implementation of registered nurse-provided care coordination, which aimed to improve quality of care and support patients with chronic conditions to maintain their care and manage their lifestyle. Focus group interviews were conducted with nurses using a semi-structured interview protocol. Interpretive analysis of interview data was conducted using Normalization Process Theory to structure data analysis and interpretation. Three core themes emerged: (1) pre-requisites for care coordination, (2) the intervention in context, and (3) achieving outcomes. Pre-requisites were adequate funding mechanisms, engaging organisational power-brokers, leadership roles, and utilising and valuing registered nurses' broad skill base. To ensure registered nurse-provided care coordination processes were sustainable and embedded, mentoring and support as well as allocated time were required. Finally, when registered nurse-provided care coordination was supported, positive client outcomes were achievable, and transformation of professional practice and development of advanced nursing roles was possible. Registered nurse-provided care coordination could "fit" within the context of general practice if it was adequately resourced. However, the heterogeneity of general practice can create an impasse that could be addressed through close attention to shared and agreed understandings. Successful development and implementation of registered nurse roles in care coordination requires attention to educational preparation, support of the individual nurse, and attention to organisational structures, financial implications and team member relationships.


Evaluation of pulp cavity/chamber changes after tooth-borne and bone-borne rapid maxillary expansions: a CBCT study using surface-based superimposition and deviation analysis.
To compare volume and shape changes of pulp chamber of maxillary posterior teeth between tooth-borne and bone-borne maxillary expansions in adolescents. This study included 36 adolescents with bilateral maxillary crossbite who received tooth-borne rapid maxillary expansion (TB group, average age 14.4 years) or bone-borne rapid maxillary expansion (BB group, average age 14.7 years). Cone beam computed tomography (CBCT) was taken before treatment (T1) and after a 6-month retention period (T2). Volumetric and shape changes of pulp chamber of maxillary first molars and premolars were detected by referring to a specific 3D digital technology involving deviation analysis of T1/T2 CBCT-derived models of pulp chamber. Student's t tests were used to (1) compare T1 and T2 volumes of pulp chambers in TB and BB groups and (2) assess differences between the two groups in the post-treatment volumetric changes and in the percentage of matching of 3D pulp models. All investigated teeth showed a reduction of pulp volume, being this difference significant in both TB (p < 0.0001) and BB (p < 0.0001) groups. The volumetric reduction was greater in the TB group; also, subjects in the TB group showed a lower percentage of matching between T1 and T2 pulp models (p < 0.0001). The area most affected by shape change was that of pulp horns. TB expander could induce a higher volumetric reduction of pulp chamber of posterior teeth compared with BB expander, in the short term. The present findings add new information concerning the effects of RME protocols on pulp tissue.


A Complete Multimode Equivalent-Circuit Theory for Electrical Design.
This work presents a complete equivalent-circuit theory for lossy multimode transmission lines. Its voltages and currents are based on general linear combinations of standard normalized modal voltages and currents. The theory includes new expressions for transmission line impedance matrices, symmetry and lossless conditions, source representations, and the thermal noise of passive multiports.


Brain metabolism during fasting.
Catheterization of cerebral vessels in three obese patients undergoing 5-6 wk of starvation demonstrated that beta-hydroxybutyrate and acetoacetate replaced glucose as the predominant fuel for brain metabolism. A strikingly low respiratory quotient was also observed, suggesting a carboxylation mechanism as a means of disposing of some of the carbon of the consumed substrates.


E. coli K5 fermentation and the preparation of heparosan, a bioengineered heparin precursor.
Heparosan is an acidic polysaccharide natural product, which serves as the critical precursor in heparin biosynthesis and in the chemoenzymatic synthesis of bioengineered heparin. Heparosan is also the capsular polysaccharide of Escherichia coli K5 strain. The current study was focused on the examination of the fermentation of E. coli K5 with the goal of producing heparosan in high yield and volumetric productivity. The structure and molecular weight properties of this bacterial heparosan were determined using polyacrylamide gel electrophoresis (PAGE) and Fourier transform mass spectrometry. Fermentation of E. coli K5 in a defined medium using exponential fed-batch glucose addition with oxygen enrichment afforded heparosan at 15 g/L having a number average molecular weight of 58,000 Da and a weight average molecular weight of 84,000 Da.


The dystrophic murine skeletal muscle cell plasma membrane is structurally intact but "leaky" to creatine phosphokinase. A freeze-fracture analysis.
Skeletal muscle cells of genetically dystrophic mice (dy/dy) of the REJ-129 Bar Harbor strain exhibit reduced cytoplasmic levels of the enzyme creatine phosphokinase (CPK) when compared with normal (+/+) mice following SDS-gel electrophoresis of sarcoplasmic proteins. This observation has been thought to reflect "leakage" of CPK from dystrophic muscle cells through lesions in the sarcolemma. The present study has employed the freeze-fracture method to examine vast expanses of sarcolemma fracture face for determination of whether lesions do exist in the membrane or an alternate route is present for extravasation of CPK from dystrophic muscle cells. Most of the dystrophic cells examined in this study appeared intact and were therefore presumed viable. The intramembrane lipoprotein particles characteristic of PF-fracture face membrane were reduced in dystrophic as compared with normal murine skeletal muscle, and the plasmalemma possessed a greatly amplified population of caveolae as compared with nondiseased sarcolemma. No abnormal structural feature of these dystrophic muscle plasma membranes could be interpreted as a perforating focal "delta" lesion, such as the structures seen in thin plastic sections by other investigators. However, a second group of cells, generally few in number, that exhibited features indicative of necrosis (and loss of viability), were seen in both thin sections and platinum replicas. These moribund cells were usually embedded in dense sheaves of connective tissue along with other dystrophic cells that lacked signs of necrosis. The cytoplasm of the necrotic muscle cells was disorganized, as was the contractile machinery. The sarcolemma showed numerous perforations, through which CPK could escape into the tissue extracellular compartment. We conclude on the basis of our observations that the "focal lesions" reported by other investigators are not a structural feature of viable dystrophic muscle cell plasma membranes and are found only in necrotic or dying cells, and that the elevated serum levels of CPK associated with muscular dystrophy may result either from escape of the enzyme through lesions present in necrotic or dying cells or by extravasation along avenues provided by the hyperplastic mass of membrane caveolae present in dystrophic sarcolemma.


The novel fluorescent CDP-analogue (Pbeta)MABA-CDP is a specific probe for the NMP binding site of UMP/CMP kinase.
Direct thermodynamic and kinetic investigations of the binding of nucleotides to the nucleoside monophosphate (NMP) site of NMP kinases have not been possible so far because a spectroscopic probe was not available. By coupling a fluorescent N-methylanthraniloyl- (mant) group to the beta-phosphate of CDP via a butyl linker, a CDP analogue [(Pbeta)MABA-CDP] was obtained that still binds specifically to the NMP site of UmpKdicty, because the base and the ribose moieties, which are involved in specific interactions, are not modified. This allows the direct determination of binding constants for its substrates in competition experiments.


Early Changes in the Sequential Organ Failure Assessment Score Among Patients With Sepsis-Induced Disseminated Intravascular Coagulation.
It is unclear whether initial infection control or anticoagulant therapy exerts a greater effect on early changes in the Sequential Organ Failure Assessment (SOFA) score among patients with sepsis-induced disseminated intravascular coagulation (DIC). This retrospective propensity score cohort study aimed to evaluate whether adequacy of infection control or anticoagulation therapy had a greater effect on early changes in the SOFA scores among 52 patients with sepsis-induced DIC. Inadequate initial infection control was associated with a lower 28-day survival rate among patients with sepsis-induced DIC (odds ratio [OR]: 0.116, 95% confidence interval [CI]: 0.022-0.601; P = .010); however, the adequacy was not associated with an early improvement in the SOFA score. However, despite adjusting for inadequate initial infection control, administration of recombinant human soluble thrombomodulin was associated with an early improvement in the SOFA score (OR: 5.058, 95% CI: 1.047-24.450; P = .044). Therefore, early changes in the SOFA score within 48 hours after the DIC diagnosis were more strongly affected by the administration of recombinant human soluble thrombomodulin than the adequacy of initial infection control.


Forecasting COVID-19 Testing Load Using Google Trends: Experience from a Lower Middle-Income Country with over 10 Million Diagnostic Tests.
The ability to forecast changing trends of COVID-19 can help drive efforts to sustain the increasing burden on the healthcare system, specifically the clinical laboratories. We aimed to assess whether the trends of SARS-CoV-2 testing in Pakistan can be predicted using COVID-19 symptoms as search terms and analyzing the data from Google Trends. The number of weekly SARS-CoV-2 tests performed were retrieved from online COVID-19 data resource. Google Trends data for the search terms with most common COVID-19 symptoms was analyzed for cross-correlation with the number of tests performed nationally. A total of 10,066,255 SARS-CoV-2 diagnostic tests were analyzed. Search terms of fever, headache, and shortness of breath displayed a statistically significant correlation with total number of tests performed with a 1-week time lag. Google Trends data can be used to forecast the changing trends in COVID-19 testing. This information can be used for careful planning and arrangements to meet increased diagnostic and healthcare demands in difficult times.


Characterization of proanthocyanidins in grape seeds using electrospray mass spectrometry.
Two proanthocyanidin (PA) fractions, one (Sdp3) with the mean degree of polymerization (mDP) of 3 and the other (Sdp9) with mDP of 9, were obtained from a Vitis vinifera cv. Shiraz grape seed extract. The PA fractions were directly analyzed by electrospray ionization mass spectrometry (ES-MS) and negative ion mass spectra were recorded. The mass spectrum of Sdp3 exhibited only singly charged ions corresponding to the molecular mass of PA with a degree of polymerization (DP) up to 9 (nonamers). In contrast, Sdp9 yielded rather complex mass spectra featuring ions with single [M - H](-), double [M - 2H](2-) and triple [M - 3H](3-) charge representing the molecular masses of PAs up to a DP of 28. In addition, the degree of galloylation per procyanidin (DG) was observed to be up to 5 (pentagallates) in Sdp3 and 8 (octagallates) in the Sdp9. This is the first evidence obtained by mass spectrometry for the distribution of grape seed PAs with such a high degree of polymerization and a broad diversity of galloylation. ES-MS data together with the complementary information provided by acid hydrolysis provides a detailed picture of the composition of grape seed PAs.


Importance of starting age for myelotoxicity study in dietary restricted rats.
The aim of this study was to prove our hypothesis that adult rats with lowering of body weight gain, rats at 12 weeks of age as an example, are suitable for evaluation of myelotoxicity. Age-related differences between young rats (6-week-old study) and adult rats (12-week-old study) were analyzed in hematological examination values. The data of the young rats were reprinted from our previous report (Miyata et al., 2009) since our hypothesis was verified by comparison with that previous report. Several experimental groups were defined for the 12-week-old study as well as for the 6-week-old study; these included 5-fluorouracil (5-FU) treated groups receiving 12, 15 and 18 mg/kg/day (FU12, FU15 and FU18), pair-feeding groups (R12, R15 and R18 receiving the same amount of food as in the FU12, FU15 and FU18 groups, respectively) and a nontreated control group. Numerous hematologic and bone marrow parameters in the 5-FU treated groups were comparable to those in the corresponding pair-feeding groups in both age studies. Generally, the influences of undernutrition were more apparent in the young rats than in the adult rats. Histopathological examinations showed a decrease in hematopoiesis in the bone marrow in the 5-FU treated and pair-feeding groups. No apparent differences were observed in the decreased hematopoiesis between the 5-FU treated and pair-feeding groups in the 6-week-old study, but a difference between these groups was noted in the 12-week-old study; decreased hematopoiesis was more frequently noted in the 5-FU treated groups. These facts suggest that adult rats are more suitable than young rats for evaluation of 5-FU-induced myelotoxicity.


Primate species richness is determined by plant productivity: implications for conservation.
The explanation of patterns in species richness ranks among the most important tasks of ecology. Current theories emphasize the interaction between historical and geographical factors affecting the size of the regional species pool and of locally acting processes such as competitive exclusion, disturbance, productivity, and seasonality. Local species richness, or alpha diversity, of plants and primary consumers has been claimed to peak in habitats of low and intermediate productivity, which, if true, has major implications for conservation. Here, by contrast, we show that local richness of Neotropical primates (platyrrhines) is influenced by both historical biogeography and productivity but not by tree species richness or seasonality. This pattern indicates that habitats with the highest plant productivity are also the richest for many important primary consumers. We show further that fragmentation of Amazonian rain forests in the Pleistocene, if it occurred, appears to have had a negligible influence on primate alpha species richness.


Adult onset acquired myasthenia gravis in three Great Dane littermates.
Acquired canine myasthenia gravis is an autoimmune disease in which autoantibodies are directed against muscle postsynaptic nicotinic acetylcholine receptors. Three adult great dane littermates were evaluated over a four month time period for an acute onset of generalised neuromuscular signs. All three dogs had elevated serum acetylcholine receptor antibody titres, which were considered diagnostic for acquired myasthenia gravis. Identification of three littermates with acquired myasthenia gravis in a breed with a low relative risk of developing the disease suggests a familial and possibly a genetic predisposition to myasthenia gravis in this family of dogs.


"What" and "where" in the intraparietal sulcus: an FMRI study of object identity and location in visual short-term memory.
The intraparietal sulcus (IPS) has been closely linked to limitations of visual short-term memory capacity (VSTM; Todd and Marois 2004; Xu and Chun 2006). It is not clearly known, however, to what extent IPS activation reflects VSTM for object identity (What) versus spatial location (Where) information. The present study was designed to manipulate selectively the amount of What and Where information retained in VSTM in order to determine, using functional magnetic resonance imaging, the effect of VSTM for each of these 2 dimensions on IPS activation. The results showed an increase in IPS activation only in response to increasing Where memory load, with no effect of What load suggesting that capacity-related activation in the IPS primarily reflects the amount of spatial information retained in VSTM.


Evaluation of the use of script concordance test in a multicampus psychiatric pharmacy elective course.
Evaluating a student's ability to accept complexity, uncertainty, and ambiguity as part of clinical practice is difficult in a classroom setting using written tests. This study was conducted to explore the feasibility and validation of using a script concordance test (SCT) to evaluate pharmacy student knowledge and clinical competence in a psychiatry elective course. This study involved prospective validation of psychiatry-focused SCT questions using a panel of practicing psychiatric pharmacists and retrospective review of student performance on the same SCT questions. The reliability of the SCT was also evaluated using Cronbach alpha coefficient. A total of 13 practicing psychiatric pharmacists participated in the validation phase of the study of 75 questions. Pharmacy student scores (n = 17) averaged 39.79 (±5.02) points, and psychiatric pharmacist scores averaged 50.11 (±4.51) points, representing mean percentages of 61.2% and 77.1%, respectively, on the adjusted exam. The Cronbach alpha was 0.94. The development of a valid and reliable SCT to test student psychiatric pharmacy knowledge and clinical competence after taking a psychiatry elective course was feasible.


Distribution and localization of a novel cholecystokinin-releasing factor in the rat gastrointestinal tract.
The purpose of this study was to examine the distribution and localization of an intestinal cholecystokinin (CCK)-releasing factor, called luminal CCK-releasing factor (LCRF), in the gastrointestinal tract and pancreas of the rat. RIA analysis indicates that LCRF immunoreactivity is found throughout the gut including the pancreas, stomach, duodenum, jejunum, ileum, and colon with the highest levels in the small intestine. Immunohistochemistry analysis shows LCRF immunoreactivity staining in intestinal villi, Brunner's glands of the duodenum, the duodenal myenteric plexus, gastric pits, pancreatic ductules, and pancreatic islets. These results indicate potential sources for secretagogue-stimulated release of luminal LCRF and support the hypothesis that LCRF is secreted into the intestinal lumen to stimulate CCK release from mucosal CCK cells.


Inpatient Rehabilitation Facility Change in Self-Care and Change in Mobility Quality Measures: Development and Reliability and Validity Testing.
To describe the development, implementation and reliability and validity testing of the inpatient rehabilitation facility (IRF) Change in Self-Care and Change in Mobility quality measures. We describe the activities involved in developing and implementing the 2 facility-level quality measures, including public comment opportunities. We examined facility-level reliability using split-half testing and Pearson product-moment correlations, Spearman rank correlations, and intraclass correlation coefficients (ICC2,1). We examined validity by comparing facility-level quality measure scores and facility disease-specific certification status. All 1117 IRFs in the United States with at least 20 Medicare stays that ended in 2017. Facility-level quality measure scores (N=1117) were derived from data from 427,517 (self-care) and 427,956 (mobility) Medicare fee-for-service and Medicare Advantage IRF patient stays in 2017. Not applicable. Facility-level Change in Self-Care and Change in Mobility quality measure scores and facility Disease-Specific Certification for Stroke Rehabilitation from The Joint Commission were used in validity analysis. The split-half quality measure scores showed strong, positive correlations for the facility-level self-care (Pearson=0.903, Spearman=0.884, ICC=0.903, P<.0001) and mobility (Pearson=0.903, Spearman=0.884, ICC= 0.903, P<.0001) quality measure scores, providing evidence of reliability. ICCs remained strong when stratifying by provider volume. IRFs with stroke certification had slightly higher mean and median quality measure scores than IRFs without certification, and IRFs with the higher quality measure scores tended to have a higher percentage of certified IRFs. Our analyses support the reliability and validity of the Change in Self-Care and Change in Mobility quality measure scores in IRFs.


Pharmacokinetic drug interactions with cyclosporin (Part I).
This article reviews the reported pharmacokinetic interactions between cyclosporin and other drugs. Both rifampicin and the majority of anticonvulsants can decrease cyclosporin concentrations to levels that are at or below the limit of detection for most assays. There have been no reports of any interaction between valproic acid and cyclosporin. Other drugs that have been reported to decrease cyclosporin concentration include sulfadimidine and trimethoprim, nafcillin and octreotide. Erythromycin, ketoconazole and some calcium channel blockers have been clearly shown to increase the concentration of cyclosporin. Other less well documented interactions have been reported with other macrolide antibiotics, other azole antifungal drugs, high dose methylprednisolone, metoclopramide, fluoroquinolones, imipenem/cilastatin, oral contraceptives/danazol, sulindac, methyltestosterone, colchicine, acetazolamide, alcohol and cimetidine. Although the most commonly reported mechanism is inhibition of cyclosporin metabolism, there is increasing evidence that erythromycin, metoclopramide and probably other drugs increase the bioavailability of oral cyclosporin. Two calcium channel blockers which have not been reported to interact with cyclosporin are nifedipine and nitrendipine. With increasing use of cyclosporin, the number of drugs reported to interact will rise. Prudent clinicians should monitor the concentration of this agent more frequently when another drug is added or discontinued and cyclosporin dosage should be adjusted when appropriate. Sustained changes in cyclosporin concentration can result in graft rejection (or graft-versus-host disease) or renal toxicity. Further studies are needed to determine the mechanism of most of these interactions.


[Endoscopic surgery of stress urinary incontinence, using the Stamey needle].
To describe the utility of endoscopic management of stress urinary incontinence with Stamey's needle. 50 multiparas (2-8 deliveries; mean 4) aged 26-72 years (mean 42) consulted for stress urinary incontinence. All patients were evaluated by the Valsalva maneuver, cough and perineal ultrasound and were classified as mild (8 cases), moderate (26 cases) and severe (16 cases). Thirty-eight patients had cystocele. Bladder neck suspension with Stamey's needle was performed in all patients. A cystostomy and not a urethrovesical catheter, was left indwelling in all patients. Multiparity and management at childbirth were the most common factors associated with stress urinary incontinence. Perineal ultrasound was found to be useful in the evaluation of the incontinent patient and the surgical procedure. The endoscopic procedure permits physiologic correction of stress urinary incontinence and cystocele. Endoscopic surgery with Stamey's needle reduces the operating time, length of hospital stay, recovery time and surgery-related pain. Patient management is facilitated by cystostomy.


Potential retinal hazards of visible-light photopolymerization units.
We evaluated the potential for retinal damage, both thermal and photochemical, from commercially available visible-light photopolymerization units. The spectral radiance profiles of 11 visible-light photopolymerization units were measured by means of a spectroradiometer and the results weighted according to the American Conference of Governmental Industrial Hygienists (ACGIH) Blue Light Hazard Function and Thermal Hazard Function. The values were then integrated by means of the proposed ACGIH hazard formulae, so that we could determine the maximum permissible exposure (tMAX) duration for each light. This calculation assumed a worst-case condition of direct vision of the light source from a distance of 25 cm. The results indicate that there is no thermal hazard to the retina. The tMAX duration values for the photochemical (blue light) hazard to the retina ranged from 2.4 minutes per day (for the most hazardous unit) to 16.0 minutes per day (for the least hazardous). None of these hazard times is short enough to be of concern unless the individual operator elects to focus on the light source or the reflected output from these visible-light photopolymerization units for an extended period of time.


Impact of stromal tumor-infiltrating lymphocytes (sTILs) on response to neoadjuvant chemotherapy in triple-negative early breast cancer in the WSG-ADAPT TN trial.
Higher density of stromal tumor-infiltrating lymphocytes (sTILs) at baseline has been associated with increased rates of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). While evidence supports favorable association of pCR with survival in TNBC, an independent impact of sTILs (after adjustment for pCR) on survival is not yet established. Moreover, the impact of sTIL dynamics during NACT on pCR and survival in TNBC is unknown. The randomized WSG-ADAPT TN phase II trial compared efficacy of 12-week nab-paclitaxel with gemcitabine versus carboplatin. This preplanned translational analysis assessed impacts of sTIL measurements at baseline (sTIL-0) and after 3 weeks of chemotherapy (sTIL-3) on pCR and invasive disease-free survival (iDFS). Predictive performance of sTIL-0 and sTIL-3 for pCR was quantified by ROC analysis and logistic regression; Kaplan-Meier estimation and Cox regression (with mediation analysis) were used to determine their impact on iDFS. For prediction of pCR, the AUC statistics for sTIL-0 and sTIL-3 were 0.60 and 0.63, respectively, in all patients; AUC for sTIL-3 was higher in NP/G. The positive predictive value (PPV) of "lymphocyte-predominant" status (sTIL-0 ≥ 60%) at baseline was 59.3%, though only 13.0% of patients had this status. To predict non-pCR, the cut point sTIL-0 ≤ 10% yielded PPV = 69.5% while addressing 33.8% of patients. Higher sTIL levels (particularly at 3 weeks) were independently and favorably associated with better iDFS, even after adjusting for pCR. For example, the adjusted hazard ratio for 3-week sTILs ≥ 60% (vs. < 60%) was 0.48 [0.23-0.99]. Low cellularity in 3-week biopsies was the strongest individual predictor for pCR (in both therapy arms), but not for iDFS. The independent impact of sTILs on iDFS suggests that favorable immune response can influence key tumor biological processes for long-term survival. The results suggest that the reliability of pCR following neoadjuvant therapy as a surrogate for survival could vary among subgroups in TNBC defined by immune response or other factors. Dynamic measurements of sTILs under NACT could support immune response-guided patient selection for individualized therapy approaches for both very low levels (more effective therapies) and very high levels (de-escalation concepts). Clinical trials No: NCT01815242, retrospectively registered January 25, 2013.


Personality Traits Modulate the Impact of Emotional Stimuli During a Working Memory Task: A Near-Infrared Spectroscopy Study.
The purpose of the present study was to examine the influence of personality traits on the impact of emotional stimuli focusing on n-back task performance and brain activity changes. Previous neuroimaging studies have reported that individual differences in emotional processing can be attributed to personality traits, which is linked to the hemisphere-specific activity of the dorsolateral prefrontal cortex (DLPFC) in response to emotional stimuli. Thirty right-handed healthy young male participants were recruited in this study and classified into two groups, the behavioral inhibition system (BIS) group and behavioral activation system (BAS) group, based on their scores on the BIS/BAS scale. Participants saw six emotional images (two each with negative, neutral, and positive valence), which were selected from the International Affective Picture System and validated in a preliminary experiment. Then, a dual 2-back task that simultaneously employed auditory-verbal and visuospatial stimuli was conducted. Additionally, the concentration of oxygenated hemoglobin (Oxy-Hb) changes in the DLPFC was measured during the image presentation and dual 2-back task by near-infrared spectroscopy (NIRS). The task performance showed a significantly increased reaction time (RT) in the negative valence independent of personality traits. The results of Oxy-Hb changes showed a significant interaction between personality traits and emotional valence. Further, the hemisphere-subgroup analysis revealed that the right DLPFC activity was significantly higher in the negative valence than in the neutral valence in the BIS group; the right DLPFC activity was also significantly higher in the BIS group than in the BAS group in the positive valence. There was no main effect or interaction in the left DLPFC activity. These findings suggest the importance of considering personality traits when examining the impact of emotional stimuli. Further studies with large sample sizes warranted to examine the influence emotional stimuli exert on working memory performance, considering the personality traits to better understand individual differences in emotional processing.


A major mRNA of the human epididymal principal cells, HE5, encodes the leucocyte differentiation CDw52 antigen peptide backbone.
HE5, a very abundant human epididymal gene product, was cloned by a differential screening procedure which employed testis as the primary negative control tissue. Sequencing of the HE5 cDNA showed it to be identical to that encoding the peptide backbone of the human leucocyte differentiation antigen CDw52. Since human genomic DNA contained only one cross-hybridizing fragment, this implies that both products were transcribed from the same gene. Northern blot analysis and in situ transcript hybridization revealed a highly tissue- and cell-type-specific expression pattern for HE5, showing the gene product to originate from epithelial cells of the epididymal and deferent duct. The possible identity of the HE5 product with the CDw52 antigen suggests a link between the immune and reproductive systems.


Humin: No longer inactive natural organic matter.
The discovery of the function of humin (HM), an insoluble fraction of humic substances (HSs), as an extracellular electron mediator (EEM) in 2012 has provided insight into the role of HM in nature and its potential for in situ bioremediation of pollutants. The EEM function is thought to enable the energy network of various microorganisms using HM. Recently, a number of studies on the application of HM as EEM in anaerobic microbial cultures have been conducted. Even so, there is a need for developing a holistic view of HM EEM function. In this paper, we summarize all the available information on the properties of HM EEM function, its applications, possible redox-active structures, and the interaction between HM and microbial cells. We also suggest scopes for future HM research.


Behavioral self-management strategies for practice and exercise should be included in neurologic rehabilitation trials and care.
Rehabilitation trials and postacute care to lessen impairments and disability after stroke, spinal cord injury, and traumatic brain injury almost never include training to promote long-term self-management of skills practice, strengthening and fitness. Without behavioral training to develop self-efficacy, clinical trials, and home-based therapy may fail to show robust results. Behavioral theories about self-management and self-efficacy for physical activity have been successfully incorporated into interventions for chronic diseases, but rarely for neurologic rehabilitation. The elements of behavioral training include education about the effects of practice and exercise that are relevant to the person, goal setting, identification of possible barriers, problem solving, feedback about performance, tailored instruction, decision making, and ongoing personal or social support. Mobile health and telerehabilitation technologies offer new ways to remotely enable such training by monitoring activity from wearable wireless sensors and instrumented exercise devices to allow real-world feedback, goal setting, and instruction. Motivation, sense of responsibility, and confidence to practice and exercise in the home can be trained to increase adherence to skills practice and exercise both during and after formal rehabilitation. To optimize motor learning and improve long-term outcomes, self-management training should be an explicit component of rehabilitation care and clinical trials.


Simultaneous measurement of refractive index and temperature based on a reflection-mode long-period grating and an intrinsic Fabry-Perot interferometer sensor.
We have demonstrated a single fiber probe for simultaneous measurement of external refractive index and temperature based on two interferometers: a reflection-mode long-period grating (LPG) for refractometry and an intrinsic Fabry-Perot interferometer (IFPI) for temperature measurement. Since the output signal of the combined structure is a superposition of signals produced by both sensors, which have different spatial frequencies, the original signals needed for the index and temperature measurements can be separated and recovered through digital filters.


Spectrum of 18F-FDG Uptake in Bilateral Lung Parenchymal Diseases on PET/CT.
Bilateral lung parenchymal involvement is seen in infective as well as noninfective conditions, appearing as focal or diffuse lung disease. PET/CT with FDG helps in characterization (increased glucose utilization is seen by both inflammatory and neoplastic cells). In this article, we describe the spectrum of patterns of FDG uptake and associated CT changes involving bilateral lung parenchyma. Benign conditions described are aspiration pneumonia; pulmonary toxicity by bleomycin; infections, namely, sarcoidosis, miliary pulmonary tuberculosis, and pulmonary nocardiosis; and inflammatory conditions such as pulmonary Langerhans cell histiocytosis and pulmonary alveolar proteinosis. Neoplastic conditions described are bilateral pulmonary metastases and lymphangitic carcinomatosis.


[« Golden hour » and the Sellick manoeuvre in emergency care: we must not throw out the baby with the bathwater].
This article evaluates 3 controversial subjects of pre-hospital emergency care : 1) The concept of the « Golden hour » predicates an increased morbidity and mortality for injured patients, if pre-hospital care exceeds 1 hour. In the subgroup of patients presenting with severe hemorrhagic injuries or penetrating trauma to the torso, a transport of 60 minutes or less decreases mortality ; 2) The Sellick manoeuvre is used to decrease the risk of bronchoaspiration in patients undergoing an emergency intubation. In view of the low incidence of bronchoaspiration and the inherent risks of cricoid pressure, it should be used only in selected patients ; 3) Improvised cricothyroidotomy using non-medical devices may be feasible if a knife to perform an incision in the cricothyroid membrane and an endotracheal tube of sufficient diameter are available.


Viral kinetics in the treatment of chronic hepatitis C.
Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatic fibrosis, and chronic infection can frequently progress to cirrhosis, end-stage liver disease and hepatocellular carcinoma. Treatment with pegylated interferons (INFs) plus ribavirin has been shown to be more effective than pegylated INFs alone or standard INFs with or without ribavirin. The early response of HCV to treatment with peg-INF has been used to predict treatment outcomes in infected patients, emphasizing the importance of viral kinetics and genotyping in their treatment. Mathematic modelling of viral dynamics has shown the importance of optimal doses of drug, with early virologic response at week 12 predictive of sustained virologic response. Maintaining INF concentration above a therapeutically effective level is necessary to prevent viral rebound and subsequent treatment failure. Once-weekly dosing with peg-INF-alpha2a, which has a longer half-life than other forms of INF, plus daily dosing with ribavirin, has been shown to be effective in reducing viral load.


Integrating Prior Knowledge in Mixed-Initiative Social Network Clustering.
We propose a new approach-called PK-clustering-to help social scientists create meaningful clusters in social networks. Many clustering algorithms exist but most social scientists find them difficult to understand, and tools do not provide any guidance to choose algorithms, or to evaluate results taking into account the prior knowledge of the scientists. Our work introduces a new clustering approach and a visual analytics user interface that address this issue. It is based on a process that 1) captures the prior knowledge of the scientists as a set of incomplete clusters, 2) runs multiple clustering algorithms (similarly to clustering ensemble methods), 3) visualizes the results of all the algorithms ranked and summarized by how well each algorithm matches the prior knowledge, 4) evaluates the consensus between user-selected algorithms and 5) allows users to review details and iteratively update the acquired knowledge. We describe our approach using an initial functional prototype, then provide two examples of use and early feedback from social scientists. We believe our clustering approach offers a novel constructive method to iteratively build knowledge while avoiding being overly influenced by the results of often randomly selected black-box clustering algorithms.


Effects of two-phase reactions on composition and potential response of zirconium(IV)-tetraphenylporphyrin complexes as carrier for citrate-selective electrode.
The reactions between zirconium(IV)-tetraphenylporphyrin(tpp)-hydroxide complexes ([ZrIV2(OH)4(tpp)2] and [ZrIV(OH)2(tpp)]) in chlorobenzene and various acids (HX: HClO4, HCl, HNO3, CH3COOH) in water were studied. Three species [ZrIV2(OH)3(tpp)2],X, [ZrIV(OH)X(tpp)], and [ZrIVX2(tpp)] were identified, and their stability constants were determined. The extent of formation of each species depends on the coordination ability and lipophilicity of X-. The performance of these complexes was evaluated as a carrier of an anion-selective electrode. The cationic complex [ZrIV2(OH)3(tpp)2],X exhibited selectivity following the Hofmeister series to weakly coordinating anions, while showing a super-Nernstian response to strongly coordinating citrates. The latter suggests the cleavage of the dimeric structure. The dichloro complex [ZrIVCl2(tpp)] was prone to hydrolyze in contact with an aqueous solution and gave drifting potentials. The monochloro complex [ZrIV(OH)Cl(tpp)] was more stable and strongly responded to acetates, which may be ascribed to substitution of a weakly bound chloride. A slow hydrolysis giving [ZrIV(OH)2(tpp)], however, caused gradual deterioration of this strong response to acetates. Conditioning of the membrane in 1 M HCl regenerated the once-deteriorated carrier [ZrIV(OH)Cl(tpp)], while continuous conditioning extended its operating life. This carrier was effectively used to continuously monitor the acetate in a flow system. The dihydroxo complex [ZrIV(OH)2(tpp)] showed lower responses to common anions due to strong Zr-OH bonding and was thus successfully used for selective potentiometry of citrates.