Yellow nail syndrome: analysis of 41 consecutive patients.
Yellow nail syndrome (YNS) is a rare condition defined by the presence of yellow nails associated with lymphedema and/or chronic respiratory manifestations. Several aspects of this disorder remain poorly defined. We sought to clarify the clinical features and course associated with YNS by analyzing 41 consecutive cases evaluated at a tertiary referral medical center. There were 20 men and 21 women; median age at diagnosis was 61 years (range, 18 to 82 years). None had a family history of YNS. All but one patient had chronic respiratory manifestations that included pleural effusions (46%), bronchiectasis (44%), chronic sinusitis (41%), and recurrent pneumonias (22%); 26 patients (63%) had lymphedema. Treatment included rotating antibiotic therapy for bronchiectasis, thoracenteses, oral vitamin E, and corticosteroid therapy. Eight patients underwent surgical management of recurrent pleural effusions including pleurodesis and decortication; two additional patients underwent pleurodesis via tube thoracostomy. The yellow nails improved or resolved in 14 of 25 patients (56%) for whom relevant data were available. Median survival of this cohort using the Kaplan-Meier method was 132 months, significantly lower than (p = 0.01) the control population. Among those still alive (20 patients), the disease appeared stable. In most cases, YNS is an acquired disorder and associated respiratory manifestations are generally manageable with a regimen of medical and surgical treatments. Yellow nails improve in about one half of patients, often without specific therapy.


Detailed formation processes of stable dislocations in graphene.
We use time-dependent HRTEM to reveal that stable dislocation pairs in graphene are formed from an initial complex multi-vacancy cluster that undergoes multiple bond rotations and adatom incorporation. In the process, it is found that the transformation from the formed complex multi-vacancy cluster can proceed without the increase of vacancy because many atoms and dimers are not only evaporated but also actively adsorbed. In tight-binding molecular dynamics simulations, it is confirmed that adatoms play an important role in the reconstruction of non-hexagonal rings into hexagonal rings. From density functional theory calculations, it is also found from simulations that there is a favorable distance between two dislocations pointing away from each other (i.e. formed from atom loss). For dislocation pairs pointing away from each other, the hillock-basin structure is more stable than the hillock-hillock structure for dislocation pairs pointing away from each other (i.e. formed from atom loss).


Glycoforest 1.0.
Tandem mass spectrometry, when combined with liquid chromatography and applied to complex mixtures, produces large amounts of raw data, which needs to be analyzed to identify molecular structures. This technique is widely used, particularly in glycomics. Due to a lack of high throughput glycan sequencing software, glycan spectra are predominantly sequenced manually. A challenge for writing glycan-sequencing software is that there is no direct template that can be used to infer structures detectable in an organism. To help alleviate this bottleneck, we present Glycoforest 1.0, a partial de novo algorithm for sequencing glycan structures based on MS/MS spectra. Glycoforest was tested on two data sets (human gastric and salmon mucosa O-linked glycomes) for which MS/MS spectra were annotated manually. Glycoforest generated the human validated structure for 92% of test cases. The correct structure was found as the best scoring match for 70% and among the top 3 matches for 83% of test cases. In addition, the Glycoforest algorithm detected glycan structures from MS/MS spectra missing a manual annotation. In total 1532 MS/MS previously unannotated spectra were annotated by Glycoforest. A portion containing 521 spectra was manually checked confirming that Glycoforest annotated an additional 50 MS/MS spectra overlooked during manual annotation.


Nuclear mutations that block group II RNA splicing in maize chloroplasts reveal several intron classes with distinct requirements for splicing factors.
To elucidate mechanisms that regulate chloroplast RNA splicing in multicellular plants, we sought nuclear mutations in maize that result in chloroplast splicing defects. Evidence is presented for two nuclear genes whose function is required for the splicing of group II introns in maize chloroplasts. A mutation in the crs1 (for chloroplast RNA splicing 1) gene blocks the splicing of only the atpF intron, whereas a mutation in the crs2 gene blocks the splicing of many chloroplast introns. In addition, a correlation was observed between the absence of plastid ribosomes and the failure to splice several chloroplast introns. Our results suggest that a chloroplast-encoded factor and a nuclear-encoded factor whose activity requires crs2 function facilitate the splicing of distinct sets of group II introns. These two genetically defined intron sets also differ with regard to intron structure: one set consists of only subgroup IIA introns and the other of only subgroup IIB introns. Therefore, it is likely that distinct splicing factors recognize subgroup-specific features of intron structure or facilitate subgroup-specific aspects of the splicing reaction. Of the 12 pre-mRNA introns in the maize chloroplast genome, only one is normally spliced in both crs2 mutants and in mutants lacking plastid ribosomes, indicating that few, if any, of the group II introns in the chloroplast genome undergo autocatalytic splicing in vivo.


The Evaluation of Undergraduate Nursing Students' Knowledge of Post-op Pain Management after Participation in Simulation.
The purpose of this paper was to assess undergraduate nursing students' pain knowledge after participation in a simulation scenario. The Knowledge and Attitudes of Survey Regarding Pain (KASRP) was used to assess pain knowledge. In addition, reflective questions related to the simulation were examined. Student preferences for education method and reactions to the simulation (SIM) were described. Undergraduate nursing students' knowledge of pain management is reported as inadequate. An emerging pedagogy used to educate undergraduate nurses in a safe, controlled environment is simulation. Literature reports of simulation to educate students' about pain management are limited. As part of the undergraduate nursing student clinical coursework, a post-operative pain management simulation, the SIM was developed. Students were required to assess pain levels and then manage the pain for a late adolescent male whose mother's fear of addiction was a barrier to pain management. The students completed an anonymous written survey that included selected questions from the KASRP and an evaluation of the SIM experience. The students' mean KASRP percent correct was 70.4% ± 8.6%. Students scored the best on items specific to pain assessment and worst on items specific to opiate equivalents and decisions on PRN orders. The students' overall KASRP score post simulation was slightly better than previous studies of nursing students. These results suggest that educators should consider simulations to educate about pain assessment and patient/family education. Future pain simulations should include more opportunities for students to choose appropriate pain medications when provided PRN orders.


Telomeres and telomerase: implications for cancer and aging.
Maintenance of telomere stability is required for cells to escape from replicative senescence and proliferate indefinitely. Telomere length is maintained by a balance between processes that lengthen telomeres (telomerase) and processes that shorten telomeres (the end-replication problem). Telomerase is a cellular ribonucleoprotein reverse transcriptase which stabilizes telomere length by adding hexameric (TTAGGG) repeats to the telomeric ends of the chromosomes, thus compensating for the continued erosion of telomeres. Introduction of the telomerase catalytic protein component into normal telomerase-negative human cells results in restoration of telomerase activity and extension of cellular life span. Human cells with introduced telomerase maintain a normal chromosome complement and continue to grow in a normal manner. Telomerase-induced manipulations of telomere length may thus be important not only for cell and tissue engineering but also for dissecting the molecular mechanisms underlying inherited genetic diseases, as well as defining the genetic pathways leading to cancer. Because almost all human tumors express telomerase activity, inhibition of telomerase may result in gradual erosion of telomeres and eventual cessation of cell proliferation or induction of apoptosis. Thus telomerase may also be a promising target for cancer therapy.


Different sequence requirements for expression in erythroid and megakaryocytic cells within a regulatory element upstream of the GATA-1 gene.
The lineage-restricted transcription factor GATA-1 is required for differentiation of erythroid and megakaryocytic cells. We have localized a 317 base pair cis-acting regulatory element, HS I, associated with a hematopoietic-specific DNase I hypersensitive site, which lies approx. 3.7 kilobases upstream of the murine hematopoietic-specific GATA-1 IE promoter. HS I directs high-level expression of reporter GATA-1/lacZ genes to primitive and definitive erythroid cells and megakaryocytes in transgenic mice. Comparative sequence analysis of HS I between human and mouse shows approx. 63% nucleotide identity with a more conserved core of 169 base pairs (86% identity). This core contains a GATA site separated by 10 base pairs from an E-box motif. The composite motif binds a multi-protein hematopoietic-specific transcription factor complex which includes GATA-1, SCL/tal-1, E2A, Lmo2 and Ldb-1. Point mutations of the GATA site abolishes HS I function, whereas mutation of the E-box motif still allows reporter gene expression in both lineages. Strict dependence of HS I activity on a GATA site implies that assembly of a protein complex containing a GATA-factor, presumably GATA-1 or GATA-2, is critical to activating or maintaining its function. Further dissection of the 317 base pair region demonstrates that, whereas all 317 base pairs are required for expression in megakaryocytes, only the 5' 62 base pairs are needed for erythroid-specific reporter expression. These findings demonstrate differential lineage requirements for expression within the HS I element.


Three-dimensional confinement of polaritons in ZnO microcylinder.
High quality ZnO microcylinders (MCDs), which naturally form three-dimensional (3D) optical microcavities, were synthesized by a simple vapor transportation deposition method. The exciton-polariton effects in these 3D microcavities were investigated through the angle-resolved micro-photoluminescence (µ-PL) mappings. By using the coupled oscillator model, the 3D confinement effect of polaritons, i.e., two-dimensional (2D) whispering gallery (WG) type confinement in the cross section of the ZnO MCD, overlapping with the one-dimensional (1D) Fabry-Pérot (F-P) type confinement along the c-axis, was well interpreted.


Push and pushback: Control behavior as a precipitant of verbal and violent disputes.
We examine to what extent control behavior precipitates disputes involving adversaries in different social relationships. We hypothesize that disputes between intimate partners and illegal business partners are more likely than other disputes to involve control because they involve a higher level of interdependence between the participants. A sample of male inmates (n = 479) and nonoffenders (n = 206) were asked whether control behaviors (e.g., verbal commands) precipitated their most recent disputes (n = 1184). Bivariate probit regression models allowed us to examine mutual control as well as unilateral control. Disputes between intimate partners were more likely than disputes between adversaries in other relationships to be precipitated by mutual control, but not unilateral or one-sided control by men. Disputes between illegal business partners also predicted mutual control, but not unilateral control. Discussions of the motives for violence would benefit from consideration of the classic social psychological literature on power and influence.


Automated eloquent cortex localization in brain tumor patients using multi-task graph neural networks.
Localizing the eloquent cortex is a crucial part of presurgical planning. While invasive mapping is the gold standard, there is increasing interest in using noninvasive fMRI to shorten and improve the process. However, many surgical patients cannot adequately perform task-based fMRI protocols. Resting-state fMRI has emerged as an alternative modality, but automated eloquent cortex localization remains an open challenge. In this paper, we develop a novel deep learning architecture to simultaneously identify language and primary motor cortex from rs-fMRI connectivity. Our approach uses the representational power of convolutional neural networks alongside the generalization power of multi-task learning to find a shared representation between the eloquent subnetworks. We validate our method on data from the publicly available Human Connectome Project and on a brain tumor dataset acquired at the Johns Hopkins Hospital. We compare our method against feature-based machine learning approaches and a fully-connected deep learning model that does not account for the shared network organization of the data. Our model achieves significantly better performance than competing baselines. We also assess the generalizability and robustness of our method. Our results clearly demonstrate the advantages of our graph convolution architecture combined with multi-task learning and highlight the promise of using rs-fMRI as a presurgical mapping tool.


Evolutionary Evidence of Algal Polysaccharide Degradation Acquisition by Pseudoalteromonas carrageenovora 9T to Adapt to Macroalgal Niches.
About half of seaweed biomass is composed of polysaccharides. Most of these complex polymers have a marked polyanionic character. For instance, the red algal cell wall is mainly composed of sulfated galactans, agars and carrageenans, while brown algae contain alginate and fucose-containing sulfated polysaccharides (FCSP) as cell wall polysaccharides. Some marine heterotrophic bacteria have developed abilities to grow on such macroalgal polysaccharides. This is the case of Pseudoalteromonas carrageenovora 9T (ATCC 43555T), a marine gammaproteobacterium isolated in 1955 and which was an early model organism for studying carrageenan catabolism. We present here the genomic analysis of P. carrageenovora. Its genome is composed of two chromosomes and of a large plasmid encompassing 109 protein-coding genes. P. carrageenovora possesses a diverse repertoire of carbohydrate-active enzymes (CAZymes), notably specific for the degradation of macroalgal polysaccharides (laminarin, alginate, FCSP, carrageenans). We confirm these predicted capacities by screening the growth of P. carrageenovora with a large collection of carbohydrates. Most of these CAZyme genes constitute clusters located either in the large chromosome or in the small one. Unexpectedly, all the carrageenan catabolism-related genes are found in the plasmid, suggesting that P. carrageenovora acquired its hallmark capacity for carrageenan degradation by horizontal gene transfer (HGT). Whereas P. carrageenovora is able to use lambda-carrageenan as a sole carbon source, genomic and physiological analyses demonstrate that its catabolic pathway for kappa- and iota-carrageenan is incomplete. This is due to the absence of the recently discovered 3,6-anhydro-D-galactosidase genes (GH127 and GH129 families). A genomic comparison with 52 Pseudoalteromonas strains confirms that carrageenan catabolism has been recently acquired only in a few species. Even though the loci for cellulose biosynthesis and alginate utilization are located on the chromosomes, they were also horizontally acquired. However, these HGTs occurred earlier in the evolution of the Pseudoalteromonas genus, the cellulose- and alginate-related loci being essentially present in one large, late-diverging clade (LDC). Altogether, the capacities to degrade cell wall polysaccharides from macroalgae are not ancestral in the Pseudoalteromonas genus. Such catabolism in P. carrageenovora resulted from a succession of HGTs, likely allowing an adaptation to the life on the macroalgal surface.


Decreased IP-10 and elevated TGFbeta1 levels are associated with viral clearance following therapy in patients with hepatitis C virus.
The role of pro-fibrogenic cytokines in the outcome of infections with hepatitis C virus (HCV) and the response to treatment with pegylated interferon-alpha (pegIFNalpha) and ribavirin remains unclear. To address this issue, we assessed hepatic fibrosis and plasma markers pertinent to T-cell mediated fibrogenesis and inflammation at the start of treatment. Levels of soluble (s)CD30, interleukin-13 receptor alpha 2 (IL-13Ralpha2), total and active transforming growth factor-beta 1 (TGFbeta1), interleukin-18 (IL-18) and interferon-gamma inducible protein-10 (IP-10, CXCL10) were correlated with the severity of fibrosis and with treatment outcome using multiple logistic regression modelling. The Hepascore algorithm was confirmed as a marker of fibrosis, but was a poor predictor of treatment outcome. Inclusion of all immunological markers improved prediction based on Hepascore alone (p=0.045), but optimal prediction was achieved with an algorithm ("TIPscore") based on TGFbeta1 (total), IP-10, age, sex and HCV genotype (p=0.003 relative to Hepascore). Whilst this was only marginally more effective than predictions based on HCV genotype age and sex (p=0.07), it associates high TGFbeta1 and low IP-10 levels with a failure of therapy.


Effect of anisotropic diffusion on spinodal decomposition.
We study the phase transition dynamics of a fluid system in which the particles diffuse anisotropically in space. The motivation to study such a situation is provided by systems of interacting magnetic colloidal particles subject to the Lorentz force. The Smoluchowski equation for the many-particle probability distribution then acquires an anisotropic diffusion tensor. We show that in comparison to the isotropic case, anisotropic diffusion results in qualitatively different dynamics of spinodal decomposition. Using the method of dynamical density functional theory, we predict that the intermediate-stage decomposition dynamics are slowed down significantly by anisotropy; the coupling between different Fourier modes is strongly reduced. Numerical calculations are performed for a model (Yukawa) fluid that exhibits gas-liquid phase separation.


Caries experience in schoolchildren in Bucharest, Romania: the PAROGIM study.
This cross-sectional study aimed to investigate the prevalence and experience of dental caries among children from public middle schools in Bucharest in relation to socioeconomic status and access to school-based dental care. Clinical data were collected from 1,595 schoolchildren aged 10-17 years, randomly allocated by clusters into a stratified sample population. The dental caries were scored according to the World Health Organization (WHO) clinical criteria and expressed based on tooth and surface levels [Decayed-Missing-Filled Teeth/Surfaces indices (DMFT/DMFS)]. A questionnaire was administered to the children to determine the education level of their parents and their living standard. The caries prevalence was 75 percent, and 64 percent had untreated caries. The mean DMFT value for the entire sample was 2.8, and its highest component was decayed teeth (mean DT 2). Parental education level had the strongest influence on the caries scores; 70 percent of children whose parents had not completed a university degree had untreated caries (%DT) compared to only 49 percent of children whose parents had a higher level of education (P < 0.05). Children with access to school-based dental care had significantly better dental health (P < 0.05). Compared to previous national surveys, the caries rates among schoolchildren in Bucharest are slowly declining. However, there was still a high proportion of untreated caries with a clear socioeconomic gradient, and a change in the school-based oral preventive strategy is needed to meet the needs of the children.


Crystalline silicon core fibres from aluminium core preforms.
Traditional fibre-optic drawing involves a thermally mediated geometric scaling where both the fibre materials and their relative positions are identical to those found in the fibre preform. To date, all thermally drawn fibres are limited to the preform composition and geometry. Here, we fabricate a metre-long crystalline silicon-core, silica-cladded fibre from a preform that does not contain any elemental silicon. An aluminium rod is inserted into a macroscopic silica tube and then thermally drawn. The aluminium atoms initially in the core reduce the silica, to produce silicon atoms and aluminium oxide molecules. The silicon atoms diffuse into the core, forming a large phase-separated molten silicon domain that is drawn into the crystalline silicon core fibre. The ability to produce crystalline silicon core fibre out of inexpensive aluminium and silica could pave the way for a simple and scalable method of incorporating silicon-based electronics and photonics into fibres.


Nesting ecology and cuticular microbial loads in dampwood (Zootermopsis angusticollis) and drywood termites (Incisitermes minor, I. schwarzi, Cryptotermes cavifrons).
Termites form one-piece nests in wood that can vary in their moisture content and degree of decomposition, and thus microbial richness. To estimate the microbial load of nests and the potential risk they pose for colony members, we quantified the number of microbes in the nest and on the cuticle of the dampwood termite, Zootermopsis angusticollis, and three drywood termites, Incisitermes minor, I. schwarzi, and Cryptotermes cavifrons. The number of colony forming units (CFUs) cultured from nest material samples and washes of the cuticle of larvae and nymphs were determined. CFUs recorded from nest material was low (fewer than 60 CFUs/g) in the drywood termites and comparatively high in the dampwood species, as more than 800 bacterial and fungal CFUs/g were cultured from the nest material of Z. angusticollis. Similarly, cuticular microbial loads were negligible in the drywood termites sampled, ranging from 0.5 to fewer than 16 CFUs/cm2, whereas approximately 200 CFUs/cm2 were cultured from Z. angusticollis. The nesting and feeding habits of these basal species likely influence colony microbial load and the degree of pathogen exposure, which in turn could favor adaptations to resist disease that vary with termite nesting biology.


Cannabis Use Disorder and Epilepsy: A Cross-National Analysis of 657 072 Hospitalized Patients.
Recent evidence has suggested that cannabis use precipitates cerebrovascular events. We investigated the relationship between cannabis use disorder (CUD) and hospitalization for epilepsy. Nationwide inpatient sample (NIS) was analyzed from 2010 to 2014 for patients (age 15-54) with a primary diagnosis of epilepsy (N = 657 072) and comparison was made between patients with ICD-9 classification of CUD and without CUD. We utilized logistic regression to study the association (odds ratio [OR]) between CUD and epilepsy. The incidence of CUD in epilepsy patients was 5.77%, and patients with CUD had a threefold higher likelihood of emergency admissions. Patients with CUD were younger (25-34 years), male and African American. In regression analysis, adjusted for confounders, cannabis (OR, 1.56), tobacco (OR, 1.20), and alcohol (OR, 1.63) use disorders were found to be associated with higher odds of epilepsy hospitalization, but lower odds with cocaine (OR, 0.953), amphetamine (OR, 0.893), and opioid (OR, 0.828) use disorders. With the increasing prevalence of medical marijuana legalization, there is increased use of medicinal marijuana. Studies of cannabidiol and marijuana for epilepsy have been highly publicized, leading to its off-label use for treatment. There is limited evidence to suggest that the cannabinoids may also induce a seizure. This study found that CUD is independently associated with a 56% increased likelihood of epilepsy hospitalization and this association persists even after adjusting for other substance use disorders and confounders. (Am J Addict 2019;28:353-360).


Molecular characterization of the resolvase gene, res, carried by a multicopy plasmid from Clostridium perfringens: common evolutionary origin for prokaryotic site-specific recombinases.
Clostridium perfringens strain CPN50 harbours a 10.2 kb plasmid known as pIP404 which, in addition to a set of UV-inducible genes involved in bacteriocin production, carries res, a gene probably encoding a site-specific recombinase. The RES protein is highly homologous to the resolvases of transposons from both Gram-negative and Gram-positive bacteria as well as enzymes involved in site-specific DNA inversion. A likely role for the RES protein would be to stabilize pIP404 by reducing the number of plasmid multimers resulting from homologous recombination. A putative resolution site for RES action was found overlapping the res promoter. Phylogenetic analysis of the primary structures of ten site-specific recombinases suggested a common descent and showed the RES protein to be closest to the resolvase encoded by Tn917 from Streptococcus faecalis.


SnugDock: paratope structural optimization during antibody-antigen docking compensates for errors in antibody homology models.
High resolution structures of antibody-antigen complexes are useful for analyzing the binding interface and to make rational choices for antibody engineering. When a crystallographic structure of a complex is unavailable, the structure must be predicted using computational tools. In this work, we illustrate a novel approach, named SnugDock, to predict high-resolution antibody-antigen complex structures by simultaneously structurally optimizing the antibody-antigen rigid-body positions, the relative orientation of the antibody light and heavy chains, and the conformations of the six complementarity determining region loops. This approach is especially useful when the crystal structure of the antibody is not available, requiring allowances for inaccuracies in an antibody homology model which would otherwise frustrate rigid-backbone docking predictions. Local docking using SnugDock with the lowest-energy RosettaAntibody homology model produced more accurate predictions than standard rigid-body docking. SnugDock can be combined with ensemble docking to mimic conformer selection and induced fit resulting in increased sampling of diverse antibody conformations. The combined algorithm produced four medium (Critical Assessment of PRediction of Interactions-CAPRI rating) and seven acceptable lowest-interface-energy predictions in a test set of fifteen complexes. Structural analysis shows that diverse paratope conformations are sampled, but docked paratope backbones are not necessarily closer to the crystal structure conformations than the starting homology models. The accuracy of SnugDock predictions suggests a new genre of general docking algorithms with flexible binding interfaces targeted towards making homology models useful for further high-resolution predictions.


It's all in the eyes: subcortical and cortical activation during grotesqueness perception in autism.
Atypical face processing plays a key role in social interaction difficulties encountered by individuals with autism. In the current fMRI study, the Thatcher illusion was used to investigate several aspects of face processing in 20 young adults with high-functioning autism spectrum disorder (ASD) and 20 matched neurotypical controls. "Thatcherized" stimuli were modified at either the eyes or the mouth and participants discriminated between pairs of faces while cued to attend to either of these features in upright and inverted orientation. Behavioral data confirmed sensitivity to the illusion and intact configural processing in ASD. Directing attention towards the eyes vs. the mouth in upright faces in ASD led to (1) improved discrimination accuracy; (2) increased activation in areas involved in social and emotional processing; (3) increased activation in subcortical face-processing areas. Our findings show that when explicitly cued to attend to the eyes, activation of cortical areas involved in face processing, including its social and emotional aspects, can be enhanced in autism. This suggests that impairments in face processing in autism may be caused by a deficit in social attention, and that giving specific cues to attend to the eye-region when performing behavioral therapies aimed at improving social skills may result in a better outcome.


Activation of nuclear factor kappa B in brains from children with HIV-1 encephalitis.
Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system is associated with decreased neuronal density in discrete areas of the brain. Neuronal loss may occur via apoptosis, initiated by soluble neurotoxic factors secreted from HIV-1 infected macrophages and microglia. To examine further the molecular events involved in HIV-1 neuropathogenesis, we assessed the activity of NF kappa B, an inducible transcription factor involved in the activation of multiple proinflammatory, and potentially neurotoxic, genes. NF kappa B was analysed by immunocytochemistry using specific antisera to the NF kappa B p. 50 and p. 65 subunits. Brains from children with HIV-1 encephalitis and progressive encephalopathy were found to contain increased numbers of NF kappa B immunoreactive cells, relative to control brains (HIV-1 negative, or HIV-1 positive without encephalitis). Double-labelling studies using antibodies to CD68, or RCA-1 lectin, markers for cells of monocyte/macrophage lineage, revealed an increase in the number of microglia and macrophages with nuclear immunoreactivity for NF kappa B in association with HIV-1 encephalitis. NF kappa B positive multinucleated giant cells were also detected, as were cells which contained both NF kappa B and HIV-1 antigen. In contrast, the number of neurons and GFAP-positive astrocytes that were immunoreactive for NF kappa B was approximately the same in all groups of subjects. These data are consistent with the hypothesis that persistent, high-level activation of NF kappa B may promote the sustained production of neurotoxins by microglia and macrophages during HIV-1 encephalitis.


Quality of Life Changes in Acute Coronary Syndromes Patients: A Systematic Review and Meta-Analysis.
There is little up-to-date evidence about changes in quality of life following treatment for acute coronary syndrome (ACS) patients. The main aim of this review was to assess the changes in QoL in ACS patients after treatment. We undertook a systematic review and meta-analysis of quantitative studies. The search included studies that described the change of QoL of ACS patients after receiving treatment options such as percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical therapy (MT). We synthesized findings using content analysis and pooled the estimates using meta-analysis. We used the PRISMA guidelines to select and appraise the studies and report the findings. Twenty-nine (29) articles were included in the review. We found a significant improvement of QoL in ACS patients after receiving treatment. Particularly, the meta-analytic association found that the mean QoL of patients diagnosed with ACS was higher after receiving treatment compared to baseline (overall pooled mean difference = 31.88; 95% CI = 31.64-52.11, I2 = 98) with patients on PCI having slightly lower QoL gains (pooled mean difference = 30.22; 95% CI = 29.9-30.53, I2 = 0%) compared to those on CABG (pooled mean difference = 34.01; 95% CI = 33.66-34.37, I2 = 0%). The review confirmed that QoL of ACS patients improved after receiving treatment therapies although varied by the treatment options and patients' preferences. This suggests the need to perform further study on the QoL, patient preferences and physicians' decision to prescription of treatment options.


Paenibacillus seodonensis sp. nov., isolated from a plant of the genus Campanula.
Strain DCT-19T, representing a Gram-stain-positive, rodshaped, aerobic bacterium, was isolated from a native plant belonging to the genus Campanula on Dokdo, the Republic of Korea. Comparative analysis of the 16S rRNA gene sequence showed that this strain was closely related to Paenibacillus amylolyticus NRRL NRS-290T (98.6%, 16S rRNA gene sequence similarity), Paenibacillus tundrae A10bT (98.1%), and Paenibacillus xylanexedens NRRL B-51090T (97.6%). DNADNA hybridization indicated that this strain had relatively low levels of DNA-DNA relatedness with P. amylolyticus NRRL NRS-290T (30.0%), P. xylanexedens NRRL B-51090T (29.0%), and P. tundrae A10bT (24.5%). Additionally, the genomic DNA G + C content of DCT-19T was 44.8%. The isolated strain grew at pH 6.0-8.0 (optimum, pH 7.0), 0-4% (w/v) NaCl (optimum, 0%), and a temperature of 15-45°C (optimum 25-30°C). The sole respiratory quinone in the strain was menaquinone-7, and the predominant fatty acids were C15:0 anteiso, C16:0 iso, and C16:0. In addition, the major polar lipids were diphosphatidylglycerol and phosphatidylethanolamine. Based on its phenotypic properties, genotypic distinctiveness, and chemotaxonomic features, strain DCT-19T is proposed as a novel species in the genus Paenibacillus, for which the name Paenibacillus seodonensis sp. nov. is proposed (=KCTC 43009T =LMG 30888T). The type strain of Paenibacillus seodonensis is DCT-19T.


Development of a 'toolkit' to identify medical students at risk of failure to thrive on the course: an exploratory retrospective case study.
An earlier study at Nottingham suggested that 10-15% of the medical student intake was likely to fail completely or have substantial problems on the course. This is a problem for the students, the Faculty, and society as a whole. If struggling students could be identified early in the course and additional pastoral resources offered, some of this wastage might be avoided. An exploratory case study was conducted to determine whether there were common indicators in the early years, over and above academic failure, that might aid the identification of students potentially at risk. The study group was drawn from five successive cohorts. Students who had experienced difficulties were identified in any of four ways: from Minutes of the Academic Progress Committee; by scanning examination lists at key stages (end of the first two years, and finals at the end of the clinical course); from lists of students flagged to the Postgraduate Deanery as in need of extra monitoring or support; and from progress files of those who had left the course prematurely. Relevant data were extracted from each student's course progress file into a customised database. 1188 students were admitted over the five years. 162 (14%) were identified for the study, 75 of whom had failed to complete the course by October 2010. In the 87 who did graduate, a combination of markers in Years 1 and 2 identified over half of those who would subsequently have the most severe problems throughout the course. This 'toolkit' comprised failure of 3 or more examinations per year, an overall average of <50%, health or social difficulties, failure to complete Hepatitis B vaccination on time, and remarks noted about poor attitude or behaviour. A simple toolkit of academic and non-academic markers could be used routinely to help identify potential strugglers at an early stage, enabling additional support and guidance to be given to these students.


Cell-based and in vivo spectral analysis of fluorescent proteins for multiphoton microscopy.
Multiphoton microscopy of cells and subcellular structures labeled with fluorescent proteins is the state-of-the-art technology for longitudinal imaging studies in tissues and living animals. Successful analysis of separate cell populations or signaling events by intravital microscopy requires optimal pairing of multiphoton excitation wavelengths with spectrally distinct fluorescent proteins. While prior studies have analyzed two photon absorption properties of isolated fluorescent proteins, there is limited information about two photon excitation and fluorescence emission profiles of fluorescent proteins expressed in living cells and intact tissues. Multiphoton microscopy was used to analyze fluorescence outputs of multiple blue, green, and red fluorescent proteins in cultured cells and orthotopic tumor xenografts of human breast cancer cells. It is shown that commonly used orange and red fluorescent proteins are excited efficiently by 750 to 760 nm laser light in living cells, enabling dual color imaging studies with blue or cyan proteins without changing excitation wavelength. It is also shown that small incremental changes in excitation wavelength significantly affect emission intensities from fluorescent proteins, which can be used to optimize multi-color imaging using a single laser wavelength. These data will direct optimal selection of fluorescent proteins for multispectral two photon microscopy.


Characteristics of highly successful orthopedic surgeons: a survey of orthopedic chairs and editors.
Highly successful orthopedic surgeons are a small group of individuals who exert a large influence on the orthopedic field. However, the characteristics of these leaders have not been well-described or studied. Orthopedic surgeons who are departmental chairs, journal editors, editorial board members of the Journal of Bone and Joint Surgery (British edition), or current or past presidents of major orthopedic associations were invited to complete a survey designed to provide insight into their motivations, academic backgrounds and accomplishments, emotional and physical health, and job satisfaction. In all, 152 surgeons completed the questionnaire. We identified several characteristics of highly successful surgeons. Many have contributed prolific numbers of publications and book chapters and obtained considerable funding for research. They were often motivated by a "desire for personal development (interesting challenge, new opportunities)," whereas "relocating to a new institution, financial gain, or lack of alternative candidates" played little to no role in their decisions to take positions of leadership. Most respondents were happy with their specialty choice despite long hours and high levels of stress. Despite challenges to their time, successful orthopedic surgeons made a strong effort to maintain their health; compared with other physicians, they exercise more, are more likely to have a primary care physician and feel better physically. Departmental chairs, journal editors and presidents of orthopedic associations cope with considerable demands of clinical, administrative, educational and research duties while maintaining a high level of health, happiness and job satisfaction.


Structural plasticity in Ig superfamily domain 4 of ICAM-1 mediates cell surface dimerization.
The Ig superfamily (IgSF) intercellular adhesion molecule-1 (ICAM-1) equilibrates between monomeric and dimeric forms on the cell surface, and dimerization enhances cell adhesion. A crystal structure of ICAM-1 IgSF domains (D) 3-5 revealed a unique dimerization interface in which D4s of two protomers fuse through edge beta-strands to form a single super beta-sandwich domain. Here, we describe a crystal structure at 2.7-A resolution of monomeric ICAM-1 D3-D5, stabilized by the monomer-specific Fab CA7. CA7 binds to D5 in a region that is buried in the dimeric interface and is distal from the dimerization site in D4. In monomeric ICAM-1 D3-D5, a 16-residue loop in D4 that is disordered in the dimeric structure could clearly be traced as a BC loop, a short C strand, and a CE meander with a cis-Pro followed by a solvent-exposed, flexible four-residue region. Deletions of 6 or 10 residues showed that the C-strand is essential for monomer stability, whereas a distinct six-residue deletion showed little contribution of the CE meander. Mutation of two inward-pointing Leu residues in edge beta-strand E to Lys increased monomer stability, confirming the hypothesis that inward-pointing charged side chains on edge beta-strands are an important design feature to prevent beta-supersheet formation. Overall, the studies reveal that monomer-dimer transition is associated with a surprisingly large, physiologically relevant, IgSF domain rearrangement.


Alternative treatment in Hepatitis B by using polyherbal formulation.
The hepatitis B is most prevalent diseases (along with morbidities) in Asian countries. This research study has been conducted to provide an alternative treatment which is safe, effective and cost-effective to comprehend relations of disease, symptoms, patients response and the clinical response via better management of hepatitis B. The goal of this research is to evaluate efficacy and safety of herbal medicine as compared to allopathic medicine in patients suffering from hepatitis B. This was a single blind, randomized controlled clinical trial conducted at Shifa-ul-Mulk Memorial Hospital Hamdard University, Karachi and Dar ul Shifa Unani Dawakhana Karachi, Pakistan. The patients of both genders ranging from 25 to 50 years with symptoms and diagnosed for hepatitis B that fulfilled the criteria for membership, and consented for participation were registered. Ethical committee clearance and permission was obtained from the concerned committee at Faculty of Eastern Medicine, Hamdard University, Karachi, Pakistan. No significant difference was identified after treatment and it was found that the efficacy of Alpha (Control drug) is same as Safoof akseer e jigar (Test drug). The data offered support to the null hypothesis and therefore research hypothesis was rejected. According to the statistical analysis by chi square, hepatitis B was recorded as negative in 26 patients (57.77%) out of 45 patients by the use of Interferon Alpha (control therapy) and in 27 patients (64.28%) out of 42 patients by the use of Safoof akseer e jigar (test drug). Comparison of the data recorded of the patients was determined as both drugs showed significant improvement and p value>0.05. The efficacy response is equal in both drugs while test drug showed more safety response. It is concluded that Safoof akseer e jigar possesses as effective a therapeutic value in treating hepatitis B as allopathic medicine.


Nd-YAG laser hyaloidotomy for malignant glaucoma following one-piece 7 mm intraocular lens implantation.
Three cases of malignant glaucoma following extracapsular cataract extraction with 7 mm one-piece posterior chamber intraocular lens implantation are presented. Nd-YAG laser hyaloidotomy was successfully performed in all eyes, but was difficult and required several sessions in two eyes. In the third eye, which had a sector iridectomy, laser hyaloidotomy applied over the edge of the lens optic through the iridectomy resulted in brisk deepening of the anterior chamber and reduction of intraocular pressure. We propose that the one-piece 7 mm optic posterior chamber intraocular lens may constitute an obstacle to successful hyaloidotomy, mainly owing to its large size, as it may block aqueous percolation from the vitreous into the anterior chamber. Eyes prone to develop malignant glaucoma after surgery should have a sector or large peripheral iridectomy to facilitate postoperative Nd-YAG laser hyaloidotomy if required.


Determination of physical emulsion stabilization mechanisms of wood hemicelluloses via rheological and interfacial characterization.
Materials manufacturing industries seek efficient, economic, and sustainable compounds for stabilizing dispersed systems such as emulsions. In this study, novel, abundant biobased hydrocolloids spruce galactoglucomannans (GGM) and birch glucuronoxylans (GX) were obtained from a forestry biorefining process and characterized as versatile stabilizers of rapeseed oil-in-water emulsions. For the first time, GGM and GX isolated by pressurized hot water extraction (PHWE) of spruce and birch saw meal, respectively, were studied in emulsions. The PHWE wood hemicelluloses-polysaccharides with relatively low molar mass-facilitated the formation of emulsions with small average droplet size and efficiently prevented droplet coalescence. GGM and GX lowered the surface tension of emulsions' oil-water interface and increased the viscosity of the continuous phase. However, viscosity of the wood hemicellulose-based systems was low compared to that of commercial polymeric stabilizers. GGM-stabilized emulsions with varying oil volume fractions were characterized in terms of their rheological properties, including large amplitude oscillation shear (LAOS) measurements, and compared to emulsions prepared with a classical small-molecular surfactant, Tween20. The physical emulsion stabilization mechanisms of GGM and GX are suggested as steric repulsion assisted by Pickering-type stabilization. Wood hemicelluloses have potential as highly promising future bioproducts for versatile industrial applications involving colloidal systems and soft materials.


[Epitopes of the envelope of the hepatitis B virus: a structural approach].
Hepatitis B is a major public health problem. More than 300 million people are chronically infected by the virus. During infection very large quantities of complete virions and empty envelopes, consisting of spherical or filamentous lipoprotein particles, are present in the blood. DNA genome coding for envelopes is divided into three domains, preS1, preS2 and S. All available data suggest that the preS1 and preS2 products are exposed at the surface of the virions. These proteins are more immunogenic than S in terms of in vivo antibody response and the number of epitopes identified. The three dimensional mapping of antigenic sites of the HBV will provide important strategic information for vaccine development and identification of targets for immunorecognition or immunoregulation of the disease.


Systematic review of the effectiveness and cost-effectiveness, and economic evaluation, of myocardial perfusion scintigraphy for the diagnosis and management of angina and myocardial infarction.
To assess the effectiveness and cost-effectiveness of single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy for the diagnosis and management of angina and myocardial infarction (MI). Major electronic databases. Two reviewers independently extracted data and assessed study quality. A decision tree model was used to model the diagnosis decision and a Markov model was developed for the management of patients with suspected coronary artery disease. Costs for the treatments and interventions within strategies were derived from the literature and expressed in 2001-02 pounds sterling. Quality-adjusted life-year (QALY) weights for the different Markov model states were also obtained from the literature. Twenty-one diagnostic and 46 prognostic studies were included, plus two studies comparing SPECT with electrocardiography (ECG)-gated SPECT and one study comparing SPECT with attenuation-corrected SPECT. The diagnostic values of SPECT were generally higher than those of stress ECG, indicating that SPECT provided a better diagnostic performance. SPECT also provided higher positive and lower negative likelihood ratios than stress ECG but heterogeneity was evident among studies. The subgroup of studies including patients with previous MI tended to report a better diagnostic performance for SPECT than stress ECG, but there were too few studies to assess this reliably. The extent and size of the perfusion defect, and whether reversible or fixed, were important factors in predicting future cardiac events such as cardiac death or non-fatal MI. SPECT may be able to identify lower risk patients for whom coronary angiography (CA) might be avoided. Normal SPECT scans were associated with a benign prognosis and the option of medical rather than invasive management. Four studies of patients post-MI reported SPECT to be valuable in stratifying patients into at-risk groups for further cardiac events. The two studies comparing SPECT with ECG-gated SPECT, one diagnostic and the other prognostic, found in favour of gated SPECT. The study comparing SPECT with attenuation-corrected SPECT reported the latter to be more accurate. The systematic review of economic evaluations indicated that strategies involving SPECT were likely either to be dominant or to produce more QALYs at an acceptable cost. There was less agreement about which of the strategies involving SPECT was optimal. The model suggested that, for low prevalence, the incremental cost per unit of output (true positives diagnosed, accurate diagnosis, QALY) for the move from stress ECG-SPECT-CA and from stress ECG-CA to SPECT-CA might be considered worthwhile. Even after allowing for different values for sensitivity or specificity, the least costly and least effective strategy was stress ECG-SPECT-CA. The sensitivity analysis suggested that the cost-effectiveness of SPECT-CA improved if it was assumed that SPECT results allowed for the adoption of a management strategy without recourse to CA. As the time horizon reduced, the incremental cost per QALY increased (as the cost of initial diagnosis and treatment were not offset by survival and quality of life gains). There was a considerable variability in terms of measurement of outcomes, management, setting and patient characteristics, however the direction of evidence tended to favour SPECT in terms of test sensitivity, although these conclusions are based on a relatively small number of diagnostic studies. SPECT, in a variety of settings and patient populations, provided valuable independent and incremental prognostic information to that provided by stress ECG and/or CA that helped to risk-stratify patients and influence the way in which their condition was managed. However, all of the prognostic studies were observational studies and may be biased by unknown confounding factors. Although the ECG-gated and attenuation-corrected SPECT findings seem promising, it is difficult to draw conclusions from so few studies. Further research is needed on the effectiveness and cost-effectiveness, diagnostically and prognostically, of (a) gated and attenuation-corrected SPECT compared with standard SPECT, (b) standard SPECT compared with stress echocardiography and (c) the uncertainty surrounding the results presented in the cost-effectiveness analysis.


Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group.
This phase III randomized trial was designed to determine if granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicity and morbidity induced by chemoradiotherapy in limited-stage small-cell lung cancer (SCLC). This multicenter prospective trial randomized 230 patients to receive chemotherapy and radiotherapy (RT) with or without GM-CSF given on days 4 to 18 of each of six cycles. The primary end point was hematologic toxicity. Secondary end points included the following: nonhematologic toxicities; days of (1) fever, (2) antibiotics, (3) hospitalization, and (4) infection; number of transfusions; drug doses delivered; and response rates and survival. There was a statistically significant increase in the frequency and duration of life-threatening thrombocytopenia (P < .001) in patients randomized to GM-CSF. GM-CSF patients had significantly more toxic deaths (P < .01), more nonhematologic toxicities, more days in hospital, a higher incidence of intravenous (IV) antibiotic usage, and more transfusions. Patients randomized to GM-CSF had higher WBC and neutrophil nadirs (P < .01), but no significant difference in the frequency of grade 4 leukopenia or neutropenia. Patients randomized to GM-CSF had a lower complete response rate (36% v 44%), but the differences were not significant (P = .29). There were no significant differences in survival (median, 14 months on GM-CSF and 17 months on no GM-CSF; P = .15). GM-CSF, as delivered in this study, should not be included with concurrent chemoradiotherapy treatment programs for limited-stage SCLC. The simultaneous use of hematopoietic colony-stimulating factors (CSFs) and chemoradiotherapy should be performed only in experimental settings. Chemoradiotherapy programs with cisplatin and etoposide ([VP-16] PE) and simultaneous chest RT produce grade 4 neutropenia and thrombocytopenia in a small-enough proportion of patients that prophylactic hematopoietic growth factors are clinically unnecessary.


Factors Influencing Fixation Stability Area: A Comparison of Two Methods of Recording.
The authors analyze factors influencing bivariate contour ellipse area (BCEA) in healthy and pathologic eyes and how such factors may affect isolated (static BCEA) or microperimetric fixation (dynamic BCEA). They conclude that aging increases both dynamic BCEA and examination time, whereas static BCEA offers less variance and the maximum distinction with pathologic eyes. The aim of this study was to assess factors influencing BCEA and the recording method that offer less variability and thus maximum distinction between healthy and pathologic eyes. A total of 136 eyes were retrospectively reviewed, 85 eyes without ophthalmic disorders (logMAR acuity ≦0.0) and 51 eyes with late age-related macular degeneration (AMD) were enrolled. All patients underwent two consecutive examinations, a 30-second isolated fixation (static BCEA) and a microperimetric test with continuous fixation recording (dynamic BCEA). All the examinations were carried out using MP1 microperimeter (NAVIS software version 1.7.6; Nidek Technologies, Padova, Italy). Dynamic BCEA was significantly correlated with age (r = 0.38, P < .001), total (r = 0.32, P = .03), and tracking time (r = 0.33, P = .02) in controls, whereas no significant relationships were found in the AMD group. The greatest difference between static and dynamic BCEA was observed in 70- to 79-year decade in healthy subjects (P < .01). Logistic regression analysis showed that late AMD status was significantly predicted by ±2 SD and ±3 SD static BCEA (both P = .03). Dynamic BCEA is influenced by a certain degree of variability in advanced-age healthy subjects. In such cases, the use of ±2 SD and ±3 SD static BCEAs seems to offer a more accurate detection of fixation stability changes in the AMD group with respect to normal subjects.


The Effect of Marshallagia marshalli on Serum Gastrin Concentrations in Experimentally Infected Lambs.
: Because there appeared to be no data available on serum gastrin concentrations in animals infected with Marshallagia marshalli, and considering the high prevalence of this parasite in livestock throughout many countries, we decided to perform research in the field using experimental infection. After surgical implantation of abomasal cannula into 10 male Baluchi sheep, each animal was orally infected with 5,000 M. marshalli larvae. Serum gastrin concentrations and abomasal pH were measured with a human ELISA kit and a PHM LE438 standard pH electrode, respectively. According to the results obtained from the study, serum gastrin increased after 14 and 21 days post-infection (dpi), while abomasal pH increased after 7 dpi and reached a maximal value 16 dpi. The increase in serum gastrin concentration was revealed 6 days after elevation in abomasal pH, which could be the result of reduced acid secretion. Generally, the present study pointed out that a limited number of M. marshalli could increase serum gastrin concentrations.


PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation.
During activation, T cells undergo metabolic reprogramming, which imprints distinct functional fates. We determined that on PD-1 ligation, activated T cells are unable to engage in glycolysis or amino acid metabolism but have an increased rate of fatty acid β-oxidation (FAO). PD-1 promotes FAO of endogenous lipids by increasing expression of CPT1A, and inducing lipolysis as indicated by elevation of the lipase ATGL, the lipolysis marker glycerol and release of fatty acids. Conversely, CTLA-4 inhibits glycolysis without augmenting FAO, suggesting that CTLA-4 sustains the metabolic profile of non-activated cells. Because T cells utilize glycolysis during differentiation to effectors, our findings reveal a metabolic mechanism responsible for PD-1-mediated blockade of T-effector cell differentiation. The enhancement of FAO provides a mechanistic explanation for the longevity of T cells receiving PD-1 signals in patients with chronic infections and cancer, and for their capacity to be reinvigorated by PD-1 blockade.


Peripheral vascular disease. Rheologic variables during controlled ischemia.
The quantitative and qualitative behavior of hemorheologic factors both at rest and after treadmill exercise in 30 male patients with stage II peripheral vascular disease compared with 20 sex- and age-matched healthy controls have been studied. The aim of our study was to identify functional rheologic markers for peripheral vascular disease. At rest, whole blood viscosity (corrected for hematocrit at both high and low shear rates), fibrinogen levels (4.23 +/- 1.39 vs. 3.23 +/- 1.5), and white blood cell count (7.05 +/- 1.25 vs. 6.03 +/- 1.28) were significantly different between patients and controls. After treadmill exercise, white blood cell counts increased in both patients and controls, whereas only the filterability of mononuclear leukocytes showed a significant variation in the patient group (5.47 +/- 1.54 vs. 7.26 +/- 2.00, p less than 0.002). In this group, mononuclear filterability improved during the recovery period. The results suggest a relation between exercise-induced ischemia of the lower limb and mononuclear filterability in patients with peripheral vascular disease. Mononuclear filterability could be a functional rheologic marker for peripheral vascular disease.


The C. elegans peroxidasin PXN-2 is essential for embryonic morphogenesis and inhibits adult axon regeneration.
Peroxidasins form a highly conserved family of extracellular peroxidases of unknown cellular function. We identified the C. elegans peroxidasin PXN-2 in screens for mutants defective in embryonic morphogenesis. We find that PXN-2 is essential for specific stages of embryonic morphogenesis and muscle-epidermal attachment, and is also required postembryonically for basement membrane integrity. The peroxidase catalytic activity of PXN-2 is necessary for these developmental roles. pxn-2 mutants display aberrant ultrastructure of the extracellular matrix, suggesting a role in basement membrane consolidation. PXN-2 affects specific axon guidance choice points in the developing nervous system but is dispensable for maintenance of process positions. In adults, loss of pxn-2 function promotes regrowth of axons after injury, providing the first evidence that C. elegans extracellular matrix can play an inhibitory role in axon regeneration. Loss of function in the closely related C. elegans peroxidasin pxn-1 does not cause overt developmental defects. Unexpectedly, pxn-2 mutant phenotypes are suppressed by loss of function in pxn-1 and exacerbated by overexpression of wild-type pxn-1, indicating that PXN-1 and PXN-2 have antagonistic functions. These results demonstrate that peroxidasins play crucial roles in development and reveal a new role for peroxidasins as extracellular inhibitors of axonal regeneration.


Cryptic diversity and ecosystem functioning: a complex tale of differential effects on decomposition.
Marine ecosystems are experiencing accelerating population and species loss. Some ecosystem functions are decreasing and there is growing interest in the link between biodiversity and ecosystem functioning. The role of cryptic (morphologically identical but genetically distinct) species in this biodiversity-ecosystem functioning link is unclear and has not yet been formally tested. We tested if there is a differential effect of four cryptic species of the bacterivorous nematode Litoditis marina on the decomposition process of macroalgae. Bacterivorous nematodes can stimulate or slow down bacterial activity and modify the bacterial assemblage composition. Moreover, we tested if interspecific interactions among the four cryptic species influence the decomposition process. A laboratory experiment with both mono- and multispecific nematode cultures was conducted, and loss of organic matter and the activity of two key extracellular enzymes for the degradation of phytodetritus were assessed. L. marina mainly influenced qualitative aspects of the decomposition process rather than its overall rate: an effect of the nematodes on the enzymatic activities became manifest, although no clear nematode effect on bulk organic matter weight loss was found. We also demonstrated that species-specific effects on the decomposition process existed. Combining the four cryptic species resulted in high competition, with one dominant species, but without complete exclusion of other species. These interspecific interactions translated into different effects on the decomposition process. The species-specific differences indicated that each cryptic species may play an important and distinct role in ecosystem functioning. Functional differences may result in coexistence among very similar species.


Discrete hierarchical organization of social group sizes.
The 'social brain hypothesis' for the evolution of large brains in primates has led to evidence for the coevolution of neocortical size and social group sizes, suggesting that there is a cognitive constraint on group size that depends, in some way, on the volume of neural material available for processing and synthesizing information on social relationships. More recently, work on both human and non-human primates has suggested that social groups are often hierarchically structured. We combine data on human grouping patterns in a comprehensive and systematic study. Using fractal analysis, we identify, with high statistical confidence, a discrete hierarchy of group sizes with a preferred scaling ratio close to three: rather than a single or a continuous spectrum of group sizes, humans spontaneously form groups of preferred sizes organized in a geometrical series approximating 3-5, 9-15, 30-45, etc. Such discrete scale invariance could be related to that identified in signatures of herding behaviour in financial markets and might reflect a hierarchical processing of social nearness by human brains.


Women Benefit More Than Men in Response to College-based Meditation Training.
Objectives: While recent literature has shown that mindfulness training has positive effects on treating anxiety and depression, there has been virtually no research investigating whether effects differ across genders-despite the fact that men and women differ in clinically significant ways. The current study investigated whether college-based meditation training had different effects on negative affect for men and women. Methods: Seventy-seven university students (36 women, age = 20.7 ± 3.0 years) participated in 12-week courses with meditation training components. They completed self-report questionnaires of affect, mindfulness, and self-compassion before and after the course. Results: Compared to men, women showed greater decreases in negative affect and greater increases on scales measuring mindfulness and self-compassion. Women's improvements in negative affect were correlated to improvements in measures of both mindfulness skills and self-compassion. In contrast, men showed non-significant increases in negative affect, and changes in affect were only correlated with ability to describe emotions, not any measures of experiential or self-acceptance. Conclusion: These findings suggest that women may have more favorable responses than men to school-based mindfulness training, and that the effectiveness of mindfulness-based interventions may be maximized by gender-specific modifications.


Neutrophils from human immunodeficiency virus (HIV)-seronegative donors induce HIV replication from HIV-infected patients' mononuclear cells and cell lines: an in vitro model of HIV transmission facilitated by Chlamydia trachomatis.
Infection with a sexually transmitted disease (STD) increases the risk for human immunodeficiency virus (HIV) infection. Polymorphonuclear leukocytes (PMNs) are recruited into the genital tract by STD pathogens, such as Chlamydia trachomatis. Semen of HIV-infected men contains HIV associated with mononuclear cells. This study investigated the interaction among PMNs from HIV-uninfected persons, C. trachomatis, and HIV-infected cells and examined the mechanisms for enhanced HIV replication. We demonstrated that PMNs from HIV-seronegative donors induced HIV replication in mononuclear cells from 17 HIV-infected patients in medium without exogenous IL-2. HIV in the cell-free supernatants from cocultures of PMNs and patients' peripheral blood mononuclear cells (PBMCs) was replication competent, as indicated by their capacity to propagate HIV in a second round of culture using PBMCs from HIV-seronegative individuals and by the fact that proviral DNA was found in these cells. PMNs from HIV-seronegative donors increased HIV replication over 100-fold in chronically HIV-infected cell lines of the monocytic, T, and B cell lineages. Moreover, PMNs increased U1 cells' production of p24 antigen by as much as ninefold when compared with U1 cells cocultured with PBMCs. The addition of C. trachomatis to PMN and U1 coculture increased HIV replication by an additional ninefold at 24 h, whereas C. trachomatis alone had no effect on p24 antigen production by U1 cells. Thus, C. trachomatis serves not only to recruit PMNs, but also to interact with PMNs to increase HIV replication. HIV replication is triggered by contact of HIV-infected cells with PMNs, by the generation of reactive oxygen intermediates (ROIs), and by soluble factors such as TNF-alpha and IL-6. This is based on the findings that production of p24 antigen, IL-6, and TNF-alpha induced by PMNs is abrogated by disrupting or partitioning PMNs from HIV-infected cells; is inhibited by superoxide dismutase and catalase, enzymes that destroy ROIs; is enhanced by differentiated HL60 cells capable of producing ROIs; and is induced by PMNs tested negative for CMV. Furthermore, the production of ROIs is independent of HIV infection of mononuclear cells, since PMNs cocultured with HIV-uninfected parental monocytic and T cell lines generated ROIs. Therefore, the increased risk for acquiring HIV infection associated with chlamydia cervicitis may be related to the local recruitment of PMNs by C. trachomatis and the induction of infectious virus from mononuclear cells present in semen. These observations provide a rationale for strategies to reduce HIV transmission by control of STD.


Women and the Affordable Care Act of 2010.
This issue brief analyzes how, over the next decade, the Affordable Care Act (ACA) is likely to stabilize and reverse women's growing exposure to health care costs. Up to 15 million women who now are uninsured could gain subsidized coverage under the law. In addition, 14.5 million insured women will benefit from provisions that improve coverage or reduce premiums. Women who have coverage through the individual insurance market and are charged higher premiums than men, who have been unable to secure coverage for the cost of pregnancy, or who have a preexisting health condition excluded from their benefits will ultimately find themselves on a level playing field with men, enjoying a full range of comprehensive benefits.


Failure of gelsolin overexpression to regulate lymphocyte apoptosis.
The actin regulatory protein gelsolin cleaves actin filaments in a calcium- and polyphosphoinositide-dependent manner. Gelsolin has recently been described as a novel substrate of the cysteinyl protease caspase-3, an effector protease activated during apoptosis. Cleavage by caspase-3 generates an amino-terminal fragment of gelsolin that can sever actin filaments independently of calcium regulation. The disruption of the actin cytoskeleton by cleaved gelsolin is hypothesized to mediate many of the downstream morphological changes associated with apoptosis. In contrast, overexpression of full-length gelsolin has also been reported to inhibit apoptotic cell death upstream of the activation of caspase-3, suggesting that gelsolin may also act prior to commitment to cell death. The authors previously observed that actin stabilization by the cell permeant agent jasplakinolide enhanced cell death upon interleukin (IL)-2 or IL-3 withdrawal from growth-factor-dependent lymphocyte cell lines, and hypothesized that actin polymerization could alter the activity of gelsolin, thus enhancing apoptosis. Here the authors show that constitutive overexpression of gelsolin did not, however, inhibit or dramatically enhance apoptotic cell death upon growth-factor withdrawal, nor did it modify sensitivity to jasplakinolide. In contrast to previous reports, overexpression of gelsolin in Jurkat T cells did not prevent or delay apoptosis induced by Fas ligation or ceramide treatment. Overexpressed gelsolin protein was cleaved during apoptosis, as seen previously in this and other cell types. In these model systems, therefore, the level of gelsolin expression was not a rate-limiting determinant in commitment to or time to the morphological changes of apoptosis.


Cytokine reversal of morphine-induced suppression of the antibody response.
Female C3HeB/FeJ mice implanted with a morphine pellet exhibit a decreased primary antibody response in vitro as measured by the plaque-forming cell (PFC) assay. Suppression was detected at 24 hr following pellet implantation, was maximal at 48 hr and returned to normal by 120 hr. Splenocytes from control mice cocultured with splenocytes from morphine-treated mice (3:1 ratio) did not show a significant suppression, suggesting that morphine is not inducing the production of suppressor cells and/or factors. However, cells from morphine-treated mice cocultured with control cells (3:1) had a restored response. Further coculture experiments demonstrated that addition of adherent cells, but not nonadherent cells, restored the antibody response, suggesting that the macrophages from morphine-treated mice were deficient or defective. In vitro addition of interleukin (IL)-6, IL-1 beta or interferon-gamma (0.5-50 U/ml) attenuated the suppression of the PFC response in cells from morphine-treated mice, whereas higher doses (100 U/ml) restored completely the PFC response to control levels. Addition of IL-2, IL-4 or IL-5 to cultures from morphine-treated mice had little effect. Thus, morphine appears to cause immune suppression by reducing macrophage numbers or by interfering with the production or release of specific cytokines which are needed for a normal antibody response. Collectively, these data suggest that the macrophage is a key cellular target for the suppressive effects of morphine on the antibody response.


Sexual behavior among unmarried business process outsourcing employees in Chennai: gender differences and correlates associated with it.
Premarital sex is often associated with high risk sexual behavior such as early age of initiation, multiple partners and inconsistent condom use. Evidence shows that such sexual behavior pre-disposes to sexually transmitted diseases including HIV. This paper tried to investigate the correlates of premarital sexual behavior among male and female business process outsourcing (BPO) employees to highlight the gender differences that exist in relation to it. Data were collected from 526 unmarried BPO employees during behavioral surveillance survey in Chennai, in the year 2009. The results showed that about one-third of respondents (males - 39.6%, females - 26.1%) had experienced premarital sex. Men reported having had their first sexual intercourse at 12 years and women at 16 years of age. While the prevalence of premarital sex was found to be high, the percentage using a condom during last sex was also high, especially, among the female employees (82.4%). Logistic regression showed that monthly individual income, work in shifts, migration, peer influence and friends with previous sexual experience were significant predictors of premarital sex among the male BPO employees. Visit to night clubs was significantly associated with a higher prevalence of premarital sex among the female employees. The study concludes that there is a significant gender dimension in the premarital sexual behavior among the BPO employees and that even as the sexual behavior of the young people is transitioning; their ability to negotiate safe sex behavior is also increasing. It is recommended to enhance efforts to advocate safe sex behavior among young adults employed in the BPO industry.


The mouse gave life to the mountain: Gramsci and health promotion.
Health promotion and salutogenesis are embodied in people's everyday lives and in their stories. The assumptions of these scientific theories are similar to Gramsci's theory for better wellbeing in a community, where praxis and capacity building for reflective practice is the way forward for an equal global change. By explaining the road for transformation through narratives, particularly fables, Gramsci manages to reach people from all walks of life, from academics to children. One of these fables, the mouse and the mountain, is here presented as a trigger to health promotion action and as a metaphor for salutogenic thinking. The narrative paradigm for health promotion is the context within which the analogies among 'the mouse's plan', health promotion theory, the salutogenic model, empowerment as well as the practitioners' opinions and experience are discussed and presented. In so doing, a 'storytelling bridge' is created between academics, practitioners and other stakeholders from the health, social and pedagogical arenas in knowledge construction environments. Hence, the article confers the possible contribution of Gramsci's educational perspective within health promotion by presenting a practical example of the use of narratives for capacity building. This is described through the interpretation of the same story in a hypothetical speech told by different storytellers, communicating their personal vision of the mouse's plan and so create a narrative-centered health promotion communication for meaning-making and for embracing theories among scholars and practitioners.


Comorbidity effects on cocaine dependence treatment and examination of reciprocal relationships between abstinence and depression.
We examined comorbid disorders' prevalence, their impact on abstinence, and the impact of depressive symptoms on abstinence and of abstinence on depressive symptoms. A randomized controlled trial's data on outcomes from treating cocaine dependence were used. It compared abstinence-contingent housing and work to contingency management plus behavioral day treatment. Regardless of original trial arm assignment, groups of participants with no additional Axis I disorders (n = 87) and 1 or more additional Axis I disorders (n = 113) were compared for abstinence. Changes in depression symptoms, measured by the Beck Depression Inventory, were analyzed as a function of 4 cohorts of increased consecutive weeks abstinent. An autoregressive cross-lagged path model examined reciprocal relationships between depression and abstinence. Most prevalent additional disorders were depressive disorders, followed by anxiety disorders. Additional disorders did not significantly affect abstinence. Cohorts with more abstinence were linearly related to lower depression symptoms. The cross-lagged model showed that longer abstinence predicted decreases in depressive symptoms at 6 months. However, depressive symptoms did not predict changes in abstinence. Our study adds to others that have found an effective treatment targeted at specific problems such as substance abuse, social anxiety disorder, and posttraumatic stress disorder that may have the side benefit of reducing depression. Additionally, we find that depression does not interfere with effective substance abuse treatment for cocaine dependency. This may be the 1st formal analysis comparing the ability of cocaine abstinence to predict future depressive symptoms versus depressive symptoms to predict future cocaine abstinence.


Spontaneous neonatal pneumomediastinum: radiological or clinical diagnosis?
Spontaneous neonatal pneumomediastinum (PNM) is associated with the aspiration of blood or meconium and birth-related trauma and it seems to be more frequent in post-term newborns. It is generally asymptomatic, but it is occasionally accompanied by mild tachypnoea. Only rarely, it requires oxygen therapy or develops into pneumothorax. To evaluate the relationship between the radiological and clinical diagnosis in this uncommon problem, from January 2005 to August 2009, 35 newborns with spontaneous PNM were enrolled in the study. Treatment protocol provides for execution of a chest X-ray, clinical check, SatO(2) and heart rate monitoring. Clinical diagnosis was accomplished particularly early, within the first 24 h of life. Paraphonic and distant tones discovered by cardio-auscultatory exam disappeared within the following 72 h. A total of 28 newborns were asymptomatic (80%); seven were symptomatic (20%); five had transient tachypnoea of the newborn; two developed an RDS, with Silverman score ≥ 3 and required O(2) therapy. It is necessary to affirm the importance of early diagnosis of this condition, carrying out careful monitoring of newborns at risk, to begin timely therapeutic treatments, as oxygen-therapy and to heighten alertness for complications, such as pneumothorax.


A mandatory single blastocyst transfer policy with educational campaign in a United States IVF program reduces multiple gestation rates without sacrificing pregnancy rates.
To reduce the twin rate in our IVF program. A prospective educational study of infertile couples; a retrospective review of IVF outcomes before vs. after mandatory single embryo transfer (mSBT) policy change. University-based infertility center. One hundred ten of 120 consecutive new infertile couples completed the educational study. Outcomes of all embryo transfers (n = 693) performed 17 months before and 17 months after mSBT were evaluated. A 1-page educational summary of comparative risks of twins vs. singletons to maternal and child health. Knowledge of twin risks and desired number of embryos transferred before and after education. Pregnancy rates, number of embryos transferred, and multiple-gestation rates before and after mSBT policy. After education, knowledge of twin risks improved and a significant number of subjects changed their desired outcome to a lower gestational number. There was no change in ongoing pregnancy rates with blastocyst transfer before and after mSBT (63% vs. 58%; NS). Program-wide number of embryos transferred (2.1 +/- 0.6 vs. 1.9 +/- 0.7) and multiple-gestation rates (35% vs. 19%) decreased significantly while pregnancy rates were maintained. Simple educational materials can improve knowledge of twin pregnancy risks and affect decision making. In high-risk patients, mSBT results in pregnancy rates similar to two-blastocyst transfer, with decreased twin rates.


Investigation of the role of Ca2+ and calmodulin in the regulation of platelet guanylate cyclase activity.
Both soluble and particulate forms of human platelet guanylate cyclase were found to be sensitive to sub-micromolar concentrations of free Ca2+; soluble enzyme activity increased as Ca2+ was increased from 10 nM to 1 microM; particulate enzyme activity showed a biphasic response to Ca2+, with maximal enzyme activity between 1 and 10 nM free Ca2+ and inhibition occurring at higher Ca2+ concentrations. Neither Ca2+-sensitivity appeared to be calmodulin-dependent.


Environmental heat stress on maternal physiology and fetal blood flow in pregnant subsistence farmers in The Gambia, west Africa: an observational cohort study.
Anthropogenic climate change has caused extreme temperatures worldwide, with data showing that sub-Saharan Africa is especially vulnerable to these changes. In sub-Saharan Africa, women comprise 50% of the agricultural workforce, often working throughout pregnancy despite heat exposure increasing the risk of adverse birth outcomes. In this study, we aimed to improve understanding of the pathophysiological mechanisms responsible for the adverse health outcomes resulting from environmental heat stress in pregnant subsistence farmers. We also aimed to provide data to establish whether environmental heat stress also has physiological effects on the fetus. We conducted an observational cohort study in West Kiang, The Gambia, at the field station for the Medical Research Council Unit The Gambia at London School of Hygiene & Tropical Medicine (named the MRC Keneba field station). Pregnant women who were aged 16 years or older and who were at <36 weeks' gestation of any gravida or parity were invited to participate in the study. Participants were eligible if they were involved in agricultural or related manual daily tasks of living. Participants were ineligible if they refused to provide consent, had multiple pregnancies (eg, if they had twins), were acutely unwell, or were diagnosed with pre-eclampsia or eclampsia. Heat stress was measured by wet bulb globe temperature (WBGT) and by using the universal thermal climate index (UTCI), and maternal heat strain was directly measured by modified physiological strain index calculated from heart rate and skin temperature. Outcome measures of fetal heart rate (FHR) and fetal strain (defined as a FHR >160 beats per min [bpm] or <115 bpm, or increase in umbilical artery resistance index) were measured at rest and during the working period. Multivariable repeated measure models (linear regression for FHR, and logistic regression for fetal strain) were used to evaluate the association of heat stress and heat strain with acute fetal strain. Between Aug 26, 2019, and March 27, 2020, 92 eligible participants were recruited to the study. Extreme heat exposure was frequent, with average exposures of WBGT of 27·2°C (SD 3·6°C) and UTCI equivalent temperature of 34·0°C (SD 3·7°C). The total effect of UTCI on fetal strain resulted in an odds ratio (OR) of 1·17 (95% CI 1·09-1·29; p<0·0001), with an adjusted direct effect of OR of 1·12 (1·03-1·21; p=0·010) with each 1°C increase in UTCI. The adjusted OR of maternal heat strain on fetal strain was 1·20 (1·01-1·43; p=0·038), using the UTCI model, with each unit increase. Data from our study show that decreasing maternal exposure to heat stress and heat strain is likely to reduce fetal strain, with the potential to reduce adverse birth outcomes. Further work that explores the association between heat stress and pregnancy outcomes in a variety of settings and populations is urgently needed to develop effective interventions. The Wellcome Trust.


Iron-catalyzed transfer hydrogenation of imines assisted by an iron-based Lewis acid.
An iron-catalyzed transfer hydrogenation of N-aryl and N-alkyl imines using isopropanol as the hydrogen donor is reported for the first time. A combination of two iron complexes serving different roles is the key for the success of this catalytic system. As a result, an environmentally friendly and precious metal-free transfer hydrogenation of imines has been developed. The use of a suitable co-catalyst as an activator not only led to efficient transfer hydrogenation, but also showed potential in enantioselective transformation.


N-glycosylation site occupancy in serum glycoproteins using multiple reaction monitoring liquid chromatography-mass spectrometry.
Congenital disorders of glycosylation (CDGs) are a family of N-linked glycosylation defects associated with severe clinical manifestations. In CDG type-I, deficiency of lipid-linked oligosaccharide assembly leads to the underoccupancy of N-glycosylation sites on glycoproteins. Although the level of residual glycosylation activity is known to correlate with the clinical phenotype linked to individual CDG mutations, it is not known whether the degree of N-glycosylation site occupancy by itself correlates with the severity of the disease. To quantify the extent of underglycosylation in healthy control and in CDG samples, we developed a quantitative method of N-glycosylation site occupancy based on multiple reaction monitoring LC-MS/MS. Using isotopically labeled standard peptides, we directly quantified the level of N-glycosylation site occupancy on selected serum proteins. In healthy control samples, we determined 98-100% occupancy for all N-glycosylation sites of transferrin and alpha(1)-antitrypsin. In CDG type-I samples, we observed a reduction in N-glycosylation site occupancy that correlated with the severity of the disease. In addition, we noticed a selective underglycosylation of N-glycosylation sites, indicating preferential glycosylation of acceptor sequons of a given glycoprotein. In transferrin, a preferred occupancy for the first N-glycosylation site was observed, and a decreasing preference for the first, third, and second N-glycosylation sites was observed in alpha(1)-antitrypsin. This multiple reaction monitoring LC-MS/MS method can be extended to multiple glycoproteins, thereby enabling a glycoproteomics survey of N-glycosylation site occupancies in biological samples.


Seeding plants for long-term multiple ecosystem service goals.
The historical management of agroecological systems, such as California's rangelands, have received criticism for a singular focus on agricultural production goals, while society has shifting expectations to the supply of multiple ecosystem services from these working landscapes. The sustainability and the multiple benefits derived from these complex social-ecological systems is increasingly threatened by weed invasion, extreme disturbance, urban development, and the impacts of a rapidly changing and increasingly variable climate. California's grasslands, oak savannas, and oak woodlands are among the most invaded ecosystems in the world. Weed eradication efforts are rarely combined with seeding on these landscapes despite support for the inclusion of the practice in a weed management program. Depending on seed mix choice, cost and long-term uncertainty, especially for native seed, is an impediment to adoption by land managers. We investigated four seeding mixes (forage annual, native perennial, exotic perennial, and exotic-native perennial) to evaluate how these treatments resist reinvasion and support the delivery of simultaneous multiple ecosystem services (invasion resistance, native richness, nitrogen fixing plants, pollinator food sources, plant community diversity, forage quality, and productivity). We found the increase of exotic and native perennial cover will drive resistance to an invading weedy summer flowering forb Centaurea solstitialis but provides a mixed response to resisting invasive annual grasses. The resistance to invasion is coupled with little tradeoff in forage productivity and quality and gains in plant diversity and native cover.


The relationship between wasting and stunting in young children: A systematic review.
In 2014, the Emergency Nutrition Network published a report on the relationship between wasting and stunting. We aim to review evidence generated since that review to better understand the implications for improving child nutrition, health and survival. We conducted a systematic review following PRISMA guidelines, registered with PROSPERO. We identified search terms that describe wasting and stunting and the relationship between the two. We included studies related to children under five from low- and middle-income countries that assessed both ponderal growth/wasting and linear growth/stunting and the association between the two. We included 45 studies. The review found the peak incidence of both wasting and stunting is between birth and 3 months. There is a strong association between the two conditions whereby episodes of wasting contribute to stunting and, to a lesser extent, stunting leads to wasting. Children with multiple anthropometric deficits, including concurrent stunting and wasting, have the highest risk of near-term mortality when compared with children with any one deficit alone. Furthermore, evidence suggests that the use of mid-upper-arm circumference combined with weight-for-age Z score might effectively identify children at most risk of near-term mortality. Wasting and stunting, driven by common factors, frequently occur in the same child, either simultaneously or at different moments through their life course. Evidence of a process of accumulation of nutritional deficits and increased risk of mortality over a child's life demonstrates the pressing need for integrated policy, financing and programmatic approaches to the prevention and treatment of child malnutrition.


Improved outcome in early induction deaths in patients with acute promyelocytic leukemia after therapeutic and supportive interventions: a follow up study of seven-years' experience at a tertiary care center.
Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia with characteristic morphology and clinical features. Early mortality rate of 30% has been reported in developed countries despite prompt initiation of treatment. We have previously reported an early induction mortality of approximately 62% in our cohort. Based on this mortality rate, we made changes in our treatment protocol. The objective of this follow-up study was to report the early induction mortality and overall survival of patients with APL after incorporating changes in chemotherapy and supportive care regimen. This was a prospective descriptive study conducted at Aga Khan University Karachi, Pakistan from October 2012 till October 2019. Data of patients included clinical features, morphological findings, cytogenetic and PCR studies, cytotoxic protocols, overall outcome and causes of early induction mortality. The changes in treatment protocol included prophylactic infusion of fresh frozen plasma, dexamethasone therapy and other changes in supportive care regimen. Results were recorded as frequencies and percentages. Statistical Package for the Social Sciences version 19.0 (SPSS Inc., Chicago, IL, USA) was used to analyze patient's data. Survival curves were calculated using the Kaplan-Meier method. During the study period, total of 447 patients presented with acute myeloid leukemia at our institution out of which 40 patients were diagnosed with acute promyelocytic leukemia (9%). Out of these 40 patients 24 were males and 16 were females. The median age was 37 years. Twenty-five patients were in low risk group whereas 15 were high-risk. Differentiation syndrome was seen in 14 patients. As a part of induction chemotherapy, 13 patients received only ATRA because they were not eligible for chemotherapy and 17 patients received a combination of ATRA and anthracycline. Among the remaining patients, four received ATRA, arsenic and anthracycline while two received ATRA and arsenic only. Four patients did not receive any treatment because of rapid deterioration of clinical condition and death. The overall survival was 65% and early induction mortality was 30%. The early induction mortality decreased to 30% from 62% in this study and the overall survival was 65%. With the introduction of prophylactic infusion of fresh frozen plasma, dexamethasone and appropriate supportive treatment during the induction chemotherapy, we were able to improve the induction mortality and overall survival of patients.


A phylogenetic hypothesis for species of the genus Taenia (Eucestoda : Taeniidae).
Cladistic analysis of a numerical data matrix describing 27 characters for species of Taenia resulted in 4 most parsimonious phylogenetic trees (174 steps; consistency index = 0.28; homoplasy index = 0.72; retention index = 0.48). Monophyly for Taenia is diagnosed by the metacestode that is either a cysticercus or a form derived from a bladder-like larva; no other unequivocal synapomorphies are evident. Tree structure provides no support for recognition of a diversity of tribes or genera within the Taeniinae: Fimbriotaeniini and Taeniini have no phylogenetic basis. Hydatigera, Fimbriotaenia, Fossor, Monordotaenia, Multiceps, Taeniarhynchus, Tetratirotaenia must be subsumed within Taenia as synonyms. Taenia saginata and Taenia asiatica are sister species and distantly related to Taenia solium. Cospeciation with respect to carnivorous definitive hosts and Taenia appears to be limited. Although felids are putative ancestral hosts, contemporary associations appear to have resulted from extensive host-switching among felids, canids, hyaenids, and others. In contrast, relationships with herbivorous intermediate hosts are indicative of more pervasive coevolution; rodents as intermediate hosts are postulated as ancestral for the Taeniidae, Taenia + Echinococcus. Patterns appear consistent with rapid shifts between phylogenetically unrelated carnivores but among those that historically exploited a common prey resource within communities in specific biogeographic regions.


Intrahepatic expression of programmed death-1 and its ligands in patients with HBV-related acute-on-chronic liver failure.
Hepatitis B virus (HBV) infection is a major public health problem, and HBV-related acute-on-chronic liver failure (HBV-ACLF) has an extremely poor prognosis due to a lack of understanding of pathogenesis as well as a lack of effective treatments. Signals from the inhibitory receptor programmed death-1 (PD-1) have been demonstrated to be involved in regulating the pathogenesis of infectious diseases. However, the expression of PD-1 and its ligands in HBV-ACLF patients has yet to be evaluated. In this study, the expression of PD-1 and its ligands, PD-L1 and PD-L2, in liver biopsies from HBV-ACLF as well as chronic hepatitis B (CHB) patients were analyzed by immunohistochemistry. The results showed that all three molecules were observed in the HBV-ACLF samples and their levels were significantly higher than they were in CHB. Immunofluorescence double-staining showed that PD-1 was found on CD3(+), CD8(+) T cells, CD56(+) NK cells, CD68(+) macrophages, CK-18(+) epithelial cells, and CD16(+) monocytes. The PD-L1 expression was observed on all cell types detected and the PD-L2 was chiefly on CK-18(+) epithelial cells and CD31(+) endothelial cells. Interestingly, high levels of virus-induced procoagulant molecule fibrinogen-like protein 2 (FGL2) were observed in liver sections from HBV-ACLF, and PD-L1 and PD-L2 expression was also observed on FGL2(+) cells in these patients. Our combined results suggest that the expression of PD-L1 and PD-L2 may be biomarkers to identify and diagnose ACLF, and a clear understanding of their functional roles should further elucidate the pathogenesis of this disease.


Ferric uptake regulator (Fur) mutants of Pseudomonas aeruginosa demonstrate defective siderophore-mediated iron uptake, altered aerobic growth, and decreased superoxide dismutase and catalase activities.
Pseudomonas aeruginosa is considered a strict aerobe that possesses several enzymes important in the disposal of toxic oxygen reduction products including iron- and manganese-cofactored superoxide dismutase and catalase. At present, the nature of the regulation of these enzymes in P. aeruginosa Is not understood. To address these issues, we used two mutants called A4 and C6 which express altered Fur (named for ferric uptake regulation) proteins and constitutively produce the siderophores pyochelin and pyoverdin. Both mutants required a significant lag phase prior to log-phase aerobic growth, but this lag was not as apparent when the organisms were grown under microaerobic conditions. The addition of iron salts to mutant A4 and, to a greater extent, C6 cultures allowed for an increased growth rate under both conditions relative to that of bacteria without added iron. Increased manganese superoxide dismutase (Mn-SOD) and decreased catalase activities were also apparent in the mutants, although the second catalase, KatB, was detected in cell extracts of each fur mutant. Iron deprivation by the addition of the iron chelator 2,2'-dipyridyl to wild-type bacteria produced an increase in Mn-SOD activity and a decrease in total catalase activity, similar to the fur mutant phenotype. Purified wild-type Fur bound more avidly than mutant Fur to a PCR product containing two palindromic 19-bp "iron box" regions controlling expression of an operon containing the sodA gene that encodes Mn-SOD. All mutants were defective in both ferripyochelin- and ferripyoverdin-mediated iron uptake. Two mutants of strain PAO1, defective in pyoverdin but not pyochelin biosynthesis, produced increased Mn-SOD activity. Sensitivity to both the redox-cycling agent paraquat and hydrogen peroxide was greater in each mutant than in the wild-type strain. In summary, the results indicate that mutations in the P. aeruginosa fur locus affect aerobic growth and SOD and catalase activities in P. aeruginosa. We postulate that reduced siderophore-mediated iron uptake, especially that by pyoverdin, may be one possible mechanism contributing to such effect.