A novel role for glucocorticoid-induced leucine zipper protein in epithelial sodium channel-mediated sodium transport.
The steroid hormone aldosterone stimulates sodium (Na+) transport in tight epithelia by altering the expression of target genes that regulate the activity and trafficking of the epithelial sodium channel (ENaC). We performed microarray analysis to identify aldosterone-regulated transcripts in mammalian kidney epithelial cells (mpkC-CD(c14)). One target, glucocorticoid-induced leucine zipper protein (GILZ), was previously identified by serial analysis of gene expression (SAGE); however, its function in epithelial ion transport was unknown. Here we show that GILZ expression is rapidly stimulated by aldosterone in mpkCCD(c14) and that GILZ, in turn, strongly stimulates ENaC-mediated Na+ transport by inhibiting extracellular signal-regulated kinase (ERK) signaling. In Xenopus oocytes with activated ERK, heterologous GILZ expression consistently inhibited phospho-ERK expression and markedly stimulated ENaC-mediated Na+ current, in a manner similar to that of U0126 (a pharmacologic inhibitor of ERK signaling). In mpkCCD(c14) cells, GILZ transfection similarly consistently inhibited phospho-ERK expression and stimulated transepithelial Na+ transport. Furthermore, aldosterone treatment of mpkCCD(c14) cells suppressed phospho-ERK levels with a time course that paralleled their increase of Na+ transport. Finally, GILZ expression markedly increased cell surface ENaC expression in epidermal growth factor-treated mammalian kidney epithelial cells, HEK 293. These observations suggest a novel link between GILZ and regulation of epithelial sodium transport through modulation of ERK signaling and could represent an important pathway for mediating aldosterone actions in health and disease.


Nuclear magnetic resonance spectroscopic and principal components analysis investigations into biochemical effects of three model hepatotoxins.
1H NMR spectroscopy of urine combined with pattern recognition (PR) methods of data analysis has been used to investigate the time-related biochemical changes induced in Sprague-Dawley rats by three model hepatotoxins: alpha-naphthyl isothiocyanate (ANIT), d-(+)-galactosamine (GalN), and butylated hydroxytoluene (BHT). The development of hepatic lesions was monitored by conventional plasma analysis and liver histopathology. Urine was collected continuously postdosing up to 144 h and analyzed by 600-MHz 1H NMR spectroscopy. NMR spectra of the urine samples showed a number of time-dependent perturbations of endogenous metabolite levels that were characteristic for each hepatotoxin. Biochemical changes common to all three hepatotoxins included a reduction in the urinary excretion of citrate and 2-oxoglutarate and an increased excretion of taurine and creatine. Increased urinary excretion of betaine, urocanic acid, tyrosine, threonine, and glutamate was characteristic of GalN toxicity. Both GalN and ANIT caused increased urinary excretion of bile acids, while glycosuria was evident in BHT- and ANIT-treated rats. Data reduction of the NMR spectra into 256 integrated regions was used to further analyze the data. Mean values of each integrated region were analyzed by principal components analysis (PCA). Each toxin gave a unique time-related metabolic trajectory that could be visualized in two-dimensional PCA maps and in which the maximum distance from the control point corresponded to the time of greatest cellular injury (confirmed by conventional toxicological tests). Thereafter, the metabolic trajectories changed direction and moved back toward the control region of the PR map during the postdose recovery phase. The combination of urinary metabolites which were significantly altered at various time points allowed for differentiation between biliary and parenchymal injury. This NMR-PR approach to the noninvasive detection of liver lesions will be of value in furthering the understanding of hepatotoxic mechanisms and assisting in the discovery of novel biomarkers of hepatotoxicity.


Cryolipolysis for Noninvasive Contouring of the Periumbilical Abdomen With a Nonvacuum Conformable-Surface Applicator.
Although most cryolipolysis treatments are performed with vacuum applicators, some patients may have areas of fibrous, nonpinchable fat or find vacuum suction to be uncomfortable. This study evaluates a nonvacuum conformable-surface applicator for cryolipolysis of the periumbilical abdomen. Twenty subjects with periumbilical subcutaneous fat were treated with a nonvacuum cryolipolysis applicator in this prospective, single-center, open-label clinical trial. Each subject underwent a single treatment cycle with an optional second treatment 10 weeks later. Efficacy was evaluated by blinded review of digital photographs. Subject satisfaction was assessed at 10-week follow-up. Twenty subjects completed one treatment, of which 6 underwent the optional retreatment. Independent review demonstrated 77% correct identification of baseline photographs after one treatment, which improved to 100% after a second treatment. Patient questionnaires after one treatment revealed 50% satisfaction, with 60% willing to recommend the procedure and 60% reporting visible fat reduction. After second treatment, however, 100% were satisfied, 83% were willing to recommend, and 100% reported visible fat reduction. Cryolipolysis with a nonvacuum conformable-surface applicator is safe, effective, and well tolerated for noninvasive reduction of fibrous periumbilical abdominal fat. Efficacy and subject satisfaction is significantly greater with 2 treatments than with a single session.


Substance P-, FMRFamide-, and gastrin/cholecystokinin-like immunoreactive neurons in the thoraco-abdominal ganglia of the flies Drosophila and Calliphora.
Immunocytochemical analysis of the thoraco-abdominal ganglia of the flies Drosophila melanogaster and Calliphora vomitoria revealed neurons displaying substance P- (SPLI), FMRFamide-(FLI), and cholecystokinin-like (CCKLI) immunoreactivity. It could be demonstrated that a number of neurons contain peptides reacting with antisera against all the three types of substances, others were either FLI or CCKLI alone. No neurons displayed only SPLI. Instead, the total number (about 30) of SPLI neurons constitute a subpopulation of the FLI/CCKLI neurons. Many of the identifiable immunoreactive neurons seem to be homologous in the two fly species. One set of six large neurons, termed ventral thoracic neurosecretory neurons (VTNCs), are among those that are SPLI, FLI, and CCKLI in both Drosophila and Calliphora. With the present immunocytochemical technique, the detailed morphology of the VTNCs could be resolved. These neurosecretory neurons supply the entire dorsal neural sheath of the thoraco-abdominal ganglia with terminals, thus forming an extensive neurohaemal area. The VTNCs also have processes connecting the thoracic neuromeres to the cephalic suboesophageal ganglion, as well as extensive arborizations in the thoracic ganglia, suggesting an important role in integrating and/or regulating large portions of the central nervous system, in addition to their neurosecretory function. Most of the other SPLI, FLI, and CCKLI neurons in the thoraco-abdominal ganglia seem to be interneurons. However, there are four FLI neurons that appear to be efferents innervating the hindgut and a few abdominal FLI and CCKLI neurons may be additional neurosecretory cells. From the present study it appears as if neuropeptides related to substance P, FMRFamide and CCK have roles as neurotransmitters/neuromodulators and circulating neurohormones in Drosophila and Calliphora.


Relationship between the number of glaucoma medications, ocular surface disorder, and treatment adherence.
To determine the relationship of ocular surface disease, the number of glaucoma medications prescribed and its influence on treatment adherence. In this cross-sectional study, demographic data of patients with glaucoma were collected, and patients completed the ocular surface disease index questionnaire and the glaucoma treatment compliance assessment tool. Ocular surface parameters were assessed by "Keratograph 5M." Patients were stratified into two groups according to the amount of prescribed ocular hypotensive eye drops (Group 1, one or two classes of medications; Group 2, three or four classes). In total, 27 eyes of 27 patients with glaucoma were included: 17 using 1 or 2 topical medications (Group 1) and 10 eyes using 3 or 4 classes (Group 2). For the Keratograph assessment, patients using ≥3 medications had significantly smaller tear meniscus height (0.27 ± 0.10 vs. 0.43 ± 0.22; p=0.037). The analysis of Ocular Surface Disease Index questionnaire showed higher scores among the groups using more hypotensive eye drops (18.67 ± 13.53 vs. 38.82 ± 19.72; p=0.004). Regarding the glaucoma treatment compliance assessment tool, Group 2 had worse scores in components of forgetfulness (p=0.027) and barriers due to lack of drops (p=0.031). Patients with glaucoma using more hypotensive eye drops had worse tear meniscus height and ocular surface disease index scores than those using fewer topical medications. Patients using three or four drug classes had worse predictors of glaucoma adherence. Despite worse ocular surface disease results, no significant difference in self-reported side effects was found.


Bacteroides fragilis Enterotoxin Induces Formation of Autophagosomes in Endothelial Cells but Interferes with Fusion with Lysosomes for Complete Autophagic Flux through a Mitogen-Activated Protein Kinase-, AP-1-, and C/EBP Homologous Protein-Dependent Pathway.
Bacteroides fragilis enterotoxin (BFT), a virulence factor of enterotoxigenic B. fragilis (ETBF), plays an essential role in mucosal inflammation. Although autophagy contributes to the pathogenesis of diverse infectious diseases, little is known about autophagy in ETBF infection. This study was conducted to investigate the role of BFT in the autophagic process in endothelial cells (ECs). Stimulation of human umbilical vein ECs (HUVECs) with BFT increased light chain 3 protein II (LC3-II) conversion from LC3-I and protein expression of p62, Atg5, and Atg12. In addition, BFT-exposed ECs showed increased indices of autophagosomal fusion with lysosomes such as LC3-lysosome-associated protein 2 (LAMP2) colocalization and the percentage of red vesicles monitored by the expression of dual-tagged LC3B. BFT also upregulated expression of C/EBP homologous protein (CHOP), and inhibition of CHOP significantly increased indices of autophagosomal fusion with lysosomes. BFT activated an AP-1 transcription factor, in which suppression of AP-1 activity significantly downregulated CHOP and augmented autophagosomal fusion with lysosomes. Furthermore, suppression of Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase (MAPK) significantly inhibited the AP-1 and CHOP signals, leading to an increase in autophagosomal fusion with lysosomes in BFT-stimulated ECs. These results suggest that BFT induced accumulation of autophagosomes in ECs, but activation of a signaling pathway involving JNK, AP-1, and CHOP may interfere with complete autophagy.


Intraoperative use of dextran is associated with cardiac complications after carotid endarterectomy.
Although dextran has been theorized to diminish the risk of stroke associated with carotid endarterectomy (CEA), variation exists in its use. We evaluated outcomes of dextran use in patients undergoing CEA to clarify its utility. We studied all primary CEAs performed by 89 surgeons within the Vascular Study Group of New England database (2003-2010). Patients were stratified by intraoperative dextran use. Outcomes included perioperative death, stroke, myocardial infarction (MI), and congestive heart failure (CHF). Group and propensity score matching was performed for risk-adjusted comparisons, and multivariable logistic and gamma regressions were used to examine associations between dextran use and outcomes. There were 6641 CEAs performed, with dextran used in 334 procedures (5%). Dextran-treated and untreated patients were similar in age (70 years) and symptomatic status (25%). Clinical differences between the cohorts were eliminated by statistical adjustment. In crude, group-matched, and propensity-matched analyses, the stroke/death rate was similar for the two cohorts (1.2%). Dextran-treated patients were more likely to suffer postoperative MI (crude: 2.4% vs 1.0%; P = .03; group-matched: 2.4% vs 0.6%; P = .01; propensity-matched: 2.4% vs 0.5%; P = .003) and CHF (2.1% vs 0.6%; P = .01; 2.1% vs 0.5%; P = .01; 2.1% vs 0.2%; P < .001). In multivariable analysis of the crude sample, dextran was associated with a higher risk of postoperative MI (odds ratio, 3.52; 95% confidence interval, 1.62-7.64) and CHF (odds ratio, 5.71; 95% confidence interval, 2.35-13.89). Dextran use was not associated with lower perioperative stroke but was associated with higher rates of MI and CHF. Taken together, our findings suggest limited clinical utility for routine use of intraoperative dextran during CEA.


Towards a systems approach for chronic diseases, based on health state modeling.
Rising pressure from chronic diseases means that we need to learn how to deal with challenges at a different level, including the use of systems approaches that better connect across fragments, such as disciplines, stakeholders, institutions, and technologies. By learning from progress in leading areas of health innovation (including oncology and AIDS), as well as complementary indications (Alzheimer's disease), I try to extract the most enabling innovation paradigms, and discuss their extension to additional areas of application within a systems approach. To facilitate such work, a Precision, P4 or Systems Medicine platform is proposed, which is centered on the representation of health states that enable the definition of time in the vision to provide the right intervention for the right patient at the right time and dose. Modeling of such health states should allow iterative optimization, as longitudinal human data accumulate. This platform is designed to facilitate the discovery of links between opportunities related to a) the modernization of diagnosis, including the increased use of omics profiling, b) patient-centric approaches enabled by technology convergence, including digital health and connected devices, c) increasing understanding of the pathobiological, clinical and health economic aspects of disease progression stages, d) design of new interventions, including therapies as well as preventive measures, including sequential intervention approaches. Probabilistic Markov models of health states, e.g. those used for health economic analysis, are discussed as a simple starting point for the platform. A path towards extension into other indications, data types and uses is discussed, with a focus on regenerative medicine and relevant pathobiology.


The Fungus among Us: Cryptococcus neoformans and Cryptococcus gattii Ecological Modeling for Colombia.
The environmental isolation of Cryptococcus spp. is typically a difficult undertaking. Collecting samples in the field is costly in terms of travel, personnel time and materials. Furthermore, the recovery rate of Cryptococcus spp. may be very low, thereby requiring a large number of samples to be taken without any guarantee of success. Ecological niche modeling is a tool that has traditionally been used to forecast the distribution of plant and animal of species for biodiversity and conservation purposes. Here, we use it in a public health application to produce risk area maps for cryptococcal disease in Colombia. The Genetic Algorithm for Ruleset Production (GARP) was used to create models for Cryptococcus neoformans (C. neoformans) and Cryptococcus gattii (C. gattii), based on environmental sampling and clinical records data recorded since 1987. These maps could be used to focus public health messaging related to cryptococcal disease, and it enables us to characterize the ecological niche for Cryptococcus in Colombia. We found that the OPEN ACCESS J. Fungi 2015, 1 333 ecological niche for C. gattii in Colombia is quite diverse, establishing itself in sub-tropical and temperate ecoregions within the country. This suggests that C. gattii is highly adaptive to different ecological conditions in Colombia and different regions of the world.


HPLC-ESI-MS analysis of oral human fluids reveals that gingival crevicular fluid is the main source of oral thymosins beta(4) and beta(10).
Thymosin beta(4) (Tbeta(4)), its sulfoxide, and thymosin beta(10 )(Tbeta(10)) were detected in human saliva and identified by different strategies based on RP HPLC coupled to electrospray multidimensional IT MS. Tbeta(4 )was almost always detected in whole saliva, its sulfoxide sporadically, Tbeta(10) rarely. Tbeta(4) was undetectable in parotid saliva and less concentrated in submandibular/sublingual saliva than in whole saliva. Analysis of gingival crevicular fluid revealed high relative amounts of Tbeta(4), Tbeta(4) sulfoxide, and Tbeta(10) in all the samples. Tbeta(4) mean concentration was 200 times higher in crevicular fluid (20 micromol/L, N = 9) than in whole saliva (0.1 micromol/L, N = 9). Crevicular fluid concentration of Tbeta(4 )(ca. 5% represented by its sulfoxide) and beta(10 )significantly correlated (r = 0.856; N = 9), and their ratio was about 5. A significant correlation was also observed between Tbeta(4 )concentrations in whole saliva and gingival crevicular fluid (r = 0.738; N = 9). Immunohistochemical analysis of the major salivary glands showed that immunoreactivity for Tbeta(4) is restricted to ductal cells, with minor degree of focal positivity in some acinar cells. On the whole, results indicate that gingival sulcus is a main, although not the sole, source for oral Tbeta(4 )and Tbeta(10).


Structural classification of protein kinases using 3D molecular interaction field analysis of their ligand binding sites: target family landscapes.
Protein kinases are critical components of signaling pathways and trigger various biological events. Several members of this superfamily are interesting targets for novel therapeutic approaches. All known eukaryotic protein kinases exhibit a conserved catalytic core domain with an adenosine 5'-triphosphate (ATP) binding site, which often is targeted in drug discovery programs. However, as ATP is common to kinases and other proteins, specific protein-ligand interactions are crucial prerequisites for valuable ATP site-directed ligands. In the present study, a set of 26 X-ray structures of eukaryotic protein kinases were classified into subfamilies with similar protein-ligand interactions in the ATP binding site using a chemometrical approach based on principal component analysis (PCA) and consensus PCA. This classification does not rely on protein sequence similarities, as descriptors are derived from three-dimensional (3D) binding site information only computed using GRID molecular interaction fields. The resulting classification, which we refer to as "target family landscape", lead to the identification of common binding pattern and specific interaction sites for particular kinase subfamilies. Moreover, those findings are in good agreement with experimental selectivity profiles for a series of 2,6,9-substituted purines as CDK inhibitors. Their interpretation in structural terms unveiled favorable substitutions toward selective CDK inhibitors and thus allowed for a rational design of specific ligands with minimized side effects. Additional 3D-quantitative structure-activity relationship (QSAR) analyses of a larger set of CDK-directed purines lead to the identification of essential structural requirements for affinity in this CDK ATP binding site. The combined interpretation of 3D-QSAR and the kinase target family landscape provides a consistent view to protein-ligand interactions, which are both favorable for affinity and selectivity in this important subfamily.


Human acute myeloid leukaemia cells express adhesion proteins and bind to bone marrow fibroblast monolayers and extracellular matrix proteins.
Adhesion protein expression by acute myeloid leukaemia (AML) cells may affect bone marrow stromal localization and determine exposure of leukaemic cells to stromal derived myeloid growth factors. We have analysed the surface expression by myeloid leukaemic cells of proteins with known adhesive function and the ability of AML cells to adhere to bone marrow fibroblasts and the extracellular matrix proteins fibronectin and laminin. Cells from all six patients tested adhered to bone marrow fibroblast monolayers (mean binding 28.8 +/- 12.8%) and to purified fibronectin in five cases studied (mean binding 33.8 +/- 15.3%). Cells from four patients with AML also adhered to laminin (mean binding 20.9 +/- 4.0%). AML cells from the majority of patients with leukaemia at diagnosis or relapse expressed the ligand pair LFA-1 and ICAM-1, the CD2 ligand LFA-3, alpha and beta chains of the integrins VLA-4, VLA-5 and VLA-6, and the hyaluronate receptor CD44. Antibodies to CD11a, CD18, VLA-4 alpha, and VLA-5 alpha failed to inhibit binding of AML cells to bone marrow fibroblasts but anti-VLA-5 alpha antibodies inhibited AML cell binding to fibronectin by approximately 50%. The ability of AML cells to adhere to bone marrow fibroblasts and extracellular matrix proteins such as fibronectin and laminin may to help explain the capacity of AML cells to persist in the marrow during periods of apparent complete remission and to subsequently proliferate under the influence of locally secreted myeloid growth factors.


Partial trisomy 18 with minimal anomalies: lack of correspondence between phenotypic manifestations and triplicated loci along chromosome 18.
A 2-year-old boy with microcephaly, developmental delay, and minimal anomalies was found to have an extra submetacentric chromosome equivalent to 18pter----q12. Review of the phenotypes produced by various triplicated 18 regions supports the hypothesis that no one chromosome 18 region is sufficient to produce the phenotype of trisomy 18. The mild phenotype of trisomy 18p, the variable phenotype of trisomy 18pter----q12, and the discontinuous phenotype of triplication for band 18q12 alone emphasizes that the contribution of triplicated loci to the phenotype is neither additive nor invariant.


Laser-induced plasmonic colours on metals.
Plasmonic resonances in metallic nanoparticles have been used since antiquity to colour glasses. The use of metal nanostructures for surface colourization has attracted considerable interest following recent developments in plasmonics. However, current top-down colourization methods are not ideally suited to large-scale industrial applications. Here we use a bottom-up approach where picosecond laser pulses can produce a full palette of non-iridescent colours on silver, gold, copper and aluminium. We demonstrate the process on silver coins weighing up to 5 kg and bearing large topographic variations (∼1.5 cm). We find that colours are related to a single parameter, the total accumulated fluence, making the process suitable for high-throughput industrial applications. Statistical image analyses of laser-irradiated surfaces reveal various nanoparticle size distributions. Large-scale finite-difference time-domain computations based on these nanoparticle distributions reproduce trends seen in reflectance measurements, and demonstrate the key role of plasmonic resonances in colour formation.


Development of SCAR Markers for the Identification of Phytophthora katsurae Causing Chestnut Ink Disease in Korea.
Sequence characterized amplified region (SCAR) markers are one of the most effective and accurate tools for microbial identification. In this study, we applied SCAR markers for the rapid and accurate detection of Phytophthora katsurae, the casual agent of chestnut ink disease in Korea. In this study, we developed seven SCAR markers specific to P. katsurae using random amplified polymorphic DNA (RAPD), and assessed the potential of the SCAR markers to serve as tools for identifying P. katsurae. Seven primer pairs (SOPC 1F/SOPC 1R, SOPC 1-1F/SOPC 1-1R, SOPC 3F/SOPC 3R, SOPC 4F/SOPC 4R, SOPC 4F/SOPC 4-1R, SOPD 9F/SOPD 9R, and SOPD 10F/SOPD 10R) from a sequence derived from RAPD fragments were designed for the analysis of the SCAR markers. To evaluate the specificity and sensitivity of the SCAR markers, the genomic DNA of P. katsurae was serially diluted 10-fold to final concentrations from 1 mg/mL to 1 pg/mL. The limit of detection using the SCAR markers ranged from 100 µg/mL to 100 ng/mL. To identify the limit for detecting P. katsurae zoospores, each suspension of zoospores was serially diluted 10-fold to final concentrations from 10 × 10(5) to 10 × 10(1) zoospores/mL, and then extracted. The limit of detection by SCAR markers was approximately 10 × 10(1) zoospores/mL. PCR detection with SCAR markers was specific for P. katsurae, and did not produce any P. katsurae-specific PCR amplicons from 16 other Phytophthora species used as controls. This study shows that SCAR markers are a useful tool for the rapid and effective detection of P. katsurae.


Biological indicators for radiation damage.
Methods for estimating radiation dose using biological indicators have made rapid progress during recent years. Chromosome analysis in lymphocytes still plays a central role, but it is no longer the only quantitative system in biological dosimetry. The best approach seems to be to combine several of the assays exploiting their specific advantages: the high sensitivity in the case of dicentrics in lymphocytes (starting at about 0.05 Gy low-LET radiation), the broad dose range covered by the electron spin resonance technique (0.5-100 Gy), the possibility of identifying the localization of partial-body exposure when determining hair diameter, and the individual prognostic information obtained from changes in the frequency of blood cells after exposures exceeding about 1 Gy. In specific situations other methods may replace or supplement these indicators for radiation damage.


Management of hypertension in renal disease.
The treatment of systemic hypertension in chronic renal disease is now mostly based on the administration of drugs which are able to reduce proteinuria and to slow down the progressive functional deterioration. Angiotensin-converting-enzyme inhibitors (ACEI), which lower both proteinuria and blood pressure, have emerged as drugs of choice in proteinuric patients with either normal renal function or mild to moderate chronic renal failure. In non proteinuric nephropathies no controlled studies exist demonstrating the superiority of ACEI over other drugs. In these conditions calcium antagonists might also be used. The approach to patients with hypertension and renal disease should always take into consideration the quality of the results that are to be achieved. If the aim is to control blood pressure and to protect other organs at risk, then a variety of drugs can be used. If the aim is to reduce proteinuria and slow down progression, then ACEI, possibly associated with calcium antagonists, are the drugs of choice.


Value of lymph node ratio as a prognostic factor of recurrence in medullary thyroid cancer.
The purpose of this study is to evaluate the relationship between lymph node status (the number of resected lymph nodes; the number of metastatic lymph nodes, LNM, and lymph node ratio, LNR) and biochemical recurrence, disease-free survival (DFS), as well as overall survival (OS) in medullary thyroid carcinoma (MTC). This study enrolled MTC patients at Tianjin Medical University Cancer Institute and Hospital between 2011 and 2019. We used Logistic regression analysis, Cox regression models and Kaplan-Meier test to identify risk factors influencing biochemical recurrence, DFS, and OS. We identified 160 patients who satisfied the inclusion criteria from 2011 to 2019. We used ROC analysis to define the cut-off value of LNR with 0.24. Multifocality, preoperative calcitonin levels, pathologic N stage, resected lymph nodes, LNM, LNR, and the American Joint Committee on Cancer (AJCC) clinical stage were significant (P < 0.05) prognostic factors influencing biochemical cure. In univariable analyses, gross extrathyroidal extension, preoperative calcitonin levels, pathologic T classification, pathologic N stage, resected lymph nodes, LNM, LNR, AJCC clinical stage, and biochemical cure were significant (P < 0.05) factors of DFS. When the multivariable analysis was performed, LNR was identified as predictor of DFS (HR = 4.818, 95% CI [1.270-18.276]). Univariable Cox regression models reflected that tumor size, pathologic N stage, and LNR were predictor of OS. Furthermore, multivariable analysis manifested that LNR was predictor of OS (HR = 10.061, 95% CI [1.222-82.841]). This study illustrated that LNR was independent prognostic factor of DFS and OS in MTC. In addition, LNR influenced biochemical cure. Further investigations are needed to determine the optimal cut-off value for predicting prognosis.


Fermentation characteristics of bedded pack barn dairy cattle manure on methane yield, carbon, and nitrogen content in solid-state anaerobic digestion.
This study aimed to estimate the fermentation characteristics of bedded pack barn dairy cattle manure (BDCM) in terms of methane yield, fibrous material, and nitrogen content in batch solid-state anaerobic digestion (SSAD). SSAD was performed in triplicate using a 1,400 ml polypropylene bottle at a constant temperature of 39 °C until less than 1% methane was produced. The cumulative methane content of BDCM was 142.5 N mL/g volatile solids (VSs). The methane content rapidly increased for 18 days, reaching 63.4 ± 4.6% until the end of the experiment. The ultimate biodegradability and total VS removal of BDCM were 23.1 and 19.0%, respectively. The slopes of the non-fibrous and hemicellulose carbon fractions, and acid detergent insoluble carbon by digestion time were -0.174 (p < 0.001), -0.141 (p = 0.003), and -0.051 (p < 0.001), respectively. The non-fibrous and hemicellulose nitrogen fraction contents quadratically decreased during SSAD (p = 0.001 and p = 0.008). No significant decrease was observed in the acid detergent insoluble nitrogen content (p = 0.840). The results of the present study provide basic data on the digestion characteristics of BDCM and could help determine fermentation conditions in the anaerobic digestion of BDCM.


Role of CD8+ lymphocytes in chronic rejection of transplanted hearts.
The contribution of CD8(+) lymphocytes to the pathogenesis of cardiac allograft vasculopathy, or chronic rejection in heart transplants, remains undefined. We used both major histocompatibility complex class I mismatched and major histocompatibility complex class II mismatched models of cardiac allograft vasculopathy to characterize the role of CD8(+) lymphocytes in the development of cardiac allograft vasculopathy. Donor hearts from B10.A mice were transplanted into B10.BR recipients (major histocompatibility complex class I mismatched). Donor hearts were harvested at 1, 7, 14, and 30 days after transplantation and (1) quantitated morphometrically for lesion development, (2) stained immunohistochemically, or (3) digested for isolation of graft-infiltrating cells. The cytotoxic phenotype of graft-infiltrating CD8(+) lymphocytes was determined with flow cytometry. Intracellular cytokine staining of CD8(+) and CD4(+) lymphocytes for interleukin 2, interferon g, interleukin 4, and interleukin 10 was performed with 2-color flow cytometry. Finally, B6.C-H2(bm12) donor hearts were transplanted into either C57BL/6 wild-type (major histocompatibility complex class II mismatched) or CD8 -/- knockout recipients and examined for the development of cardiac allograft vasculopathy. In the major histocompatibility complex class I mismatched model, CD8(+) lymphocytes were the predominant T-lymphocyte subset that infiltrated the allografts and demonstrated markers of activation. The intracellular cytokine-staining assay demonstrated that CD8(+) lymphocytes were the primary sources of allograft interleukin 2 and interferon gamma. Intimal lesions developed in the allografts by day 14 (12.0% +/- 4.0%) and further increased by day 30 (44.0% +/- 5.0%). In the major histocompatibility complex class II mismatched model, the donor hearts in the CD8 -/- knockout recipients had substantially less severe intimal lesions when compared with the donor hearts in wild-type recipients (19.0% +/- 6.0% vs 50.0% +/- 7.0%, respectively; P <.05). In both major histocompatibility complex class I and II mismatched models, CD8(+) lymphocytes contribute significantly to chronic rejection. The findings of this study suggest that control of chronic rejection requires interventions directed at CD8(+) lymphocytes.


Role of sepsis modulated circulating microRNAs.
Sepsis is a life-threating condition with dysregulated systemic host response to microbial pathogens leading to disproportionate inflammatory response and multi-organ failure. Various biomarkers are available for the diagnosis and prognosis of sepsis; however, these laboratory parameters may show limitations in these severe clinical conditions. MicroRNAs (miRNA) are single-stranded non-coding RNAs with the function of post-transcriptional gene silencing. They normally control numerous intracellular events, such as signaling cascade downstream of Toll-like receptors (TLRs) to avoid excessive inflammation after infection. In contrast, abnormal miRNA expression contributes to the development of sepsis correlating with its clinical features and outcomes. Based on recent clinical studies altered levels of circulating miRNAs can act as potential diagnostic and prognostic biomarkers in sepsis. In this review, we summarized the available data about TLR-mediated inflammatory signaling with its intracellular response in immune cells and platelets upon sepsis, which are, at least in part, under the regulation of miRNAs. Furthermore, the role of circulating miRNAs is also described as potential laboratory biomarkers in sepsis.


Determination of alpha-emitting Pu isotopes in environmental samples.
This paper presents an improved radiochemical procedure for the determination of alpha-emitting Pu isotopes in environmental samples (soils, sediments, vegetation) by alpha-particle spectrometry. Quantitative Pu recovery yields were obtained (average 60%), 0.1 mBq being the average minimum detectable activity by the complete technique. Special efforts were made to ensure the removal of traces of different natural alpha-emitting radionuclides, which can interfere with the correct determination of 239+240Pu and 238Pu concentrations. The radiochemical procedure was validated by application to reference material and by participation in intercomparison exercises. This radiochemical procedure was applied to the different layers of a high-resolution sediment core taken from a lake in Sweden. The 239+240Pu and 238Pu/239+240Pu profiles obtained in the high-resolution sediment core correctly reproduced the expected evolution of these quantities as observed historically in the atmosphere, validating the procedure for this purpose and showing the power of these radionuclides for dating purposes.


Porous TiO2/Co9S8 core-branch nanosheet arrays with high electrocatalytic activity for a hydrogen evolution reaction.
Exploring new non-noble metallic catalysts with highly efficient and stable catalytic performance toward a hydrogen evolution reaction (HER) is a major requirement in the field of electrochemical water splitting. In this study, we report a facile strategy to synthesize a three-dimensional (3D) porous TiO2/Co9S8 core-branch nanosheet arrays on Ni foam with superior HER catalytic activity. The hierarchically 3D porous architecture not only provides rich active sites, but also enables fast electron transport and easy electrolyte permeation. Consequently, the TiO2/Co9S8 core-branch nanosheet arrays achieve a remarkably low overpotential of 150 mV at 10 mA cm-2, small Tafel slope of 71 mV Dec-1 and outstanding long-term stability for the HER reaction. The elaborate design should provide a new strategy to controllably synthesize porous and rational nanostructured materials as a prominent electrocatalyst for water splitting applications.


The treatment of depressive disorders in children and adolescents.
Depressive disorders are among the more common mental illnesses around the world. About 3% of prepubertal children and 6% of postpubertal children and adolescents are affected. Many physicians are unsure about which treatment approaches are effective and how the treatment should be planned. A systematic literature search was carried out in electronic databases and study registries and as a manual search. More than 450 studies (mostly randomized controlled trials [RCTs]) were identified and summarized in five evidence tables. The ensuing recommendations were agreed upon in a consensus conference in which 23 organizations were represented. The recommended treatment of first choice for children from age 8 onward and for adolescents is either cognitive behavioral therapy (CBT) (Cohen's d [effect strength]: 0.5-2) or interpersonal psychotherapy (Cohen's d: 0.5-0.6). Fluoxetine is recommended for drug treatment (Cohen's d: 0.3-5.6), either alone or in combination with CBT. The analysis revealed a lower level of evidence for psychodynamic or systemic psychotherapy or for drug treatment with escitalopram, citalopram, or sertraline. For mild or moderate depression, psychotherapy is recommended; for severe depression, combination therapy. Particularly for children, there is a lack of adequately informative comparative studies on these treatment approaches as well as on other, complementary interventions (e.g., art therapy, sleep deprivation, youth welfare services). There is adequate evidence to support some recommendations for the treatment of depressive disorders in adolescents, but evidence for children is lacking. There is a pressing need for intervention research in this area for both children and adolescents.


Cavography and lymphangiography in hodgkin's disease.
In a material of 89 patients with Hodgkin's disease, 98 combined examinations, including lymphangiography, cavography and urography, were performed. Lymphangiography disclosed signs of expansive lesion 33 times, cavography 21 times and urography 17 times. The diagnostic accuracy of lymphangiography was high. Routine cavography in Hodgkin's disease is not advocated; it may be restricted to cases with equivocal lymphographic findings.


Impact of Different Independent Dose Verification Software Programs for Secondary Check.
A multi-institutional study was performed to identify the impact of different independent dose verification programs on independent dose verification software program. Data for 1,543 treatment fields were collected in three institutions. RADCALC and Simple MU Analysis (Simple MU) using the Clarkson-based algorithm were used. RADCALC needs the input of radiological path length (RPL) from radiotherapy treatment planning systems (RTPSs) (Eclipse or Pinnacle3). The Simple MU computes the RPL using CT images independently from the RTPSs. Ion-chamber measurements were performed for commissioning the two programs and the RTPSs. Next, the results of the two programs were compared to the RTPSs obtained in the clinically-approved plans in all three institutions. The commissioning results showed ±1.5% variation in the ion-chamber measurements and there was slight difference between the institutions. The RADCALC (0.9±2.2%) and the Simple MU (1.7±2.1%) results showed a slight systematic difference. Pinnacle3 computed longer RPLs because it used CT-physical density tables. Thus, there was an impact on the accuracy in the treatment plans involving bone and other high-density materials. Dose calculation algorithms in different dose verification programs provided similar results. However, care must be taken because different RPL calculation methods in the RTPSs may affect dose difference between different independent dose verification programs by 1%.


Acute lithium toxicity--chorea, hypercalcemia and hyperamylasemia.
Lithium is widely used in the management of patients with manic depressive illnesses. It is a valuable drug with a good safety record but occasionally causes severe disorders. A 71-year-old woman is described who previously had a good response to lithium carbonate treatment of a manic depressive illness. Because the patient appeared depressed and withdrawn, lithium carbonate dosage was increased. The development of confusion and choreiform movements precipitated hospital admission. The symptoms were relieved when lithium was stopped but recurred with the reinstitution of lithium. Spontaneous choreiform movements were again relieved on lithium withdrawal. Associated with the abnormal movements were alterations in the serum calcium concentrations, a rise in the parathyroid hormone concentration and a rise in the serum amylase concentration without features of acute pancreatitis.


Indications and Future Perspectives of a Minimally Invasive Ultrasound-guided Double-needle Joint Lavage.
Arthroscopic joint lavage was proposed as a treatment option for different joint conditions such as septic or inflammatory arthritis. Ultrasound (US) is today considered a fundamental tool in musculoskeletal diseases as for diagnostic and guide for interventional procedures such as synovial fluid sampling and drug injections. To enable faster recovery and to have an alternative to surgery, to reduce risks and costs, we performed an US-guided double-needle lavage of the shoulder joint. Here, we present two different clinical cases, the first with septic arthritis and the second with recalcitrant gouty arthritis, successfully treated with this technique.


Predicting direct and indirect breeding values for survival time in laying hens using repeated measures.
Minimizing bird losses is important in the commercial layer industry. Selection against mortality is challenging because heritability is low, censoring is high, and individual survival depends on social interactions among cage members. With cannibalism, mortality depends not only on an individual's own genes (direct genetic effects; DGE) but also on genes of its cage mates (indirect genetic effects; IGE). To date, studies using DGE-IGE models have focussed on survival time but their shortcomings are that censored records were considered as exact lengths of life and models assumed that IGE were continuously expressed by all cage members even after death. However, since dead animals no longer express IGE, IGE should ideally be time-dependent in the model. Neglecting censoring and timing of IGE expression may reduce accuracy of estimated breeding values (EBV). Thus, our aim was to improve prediction of breeding values for survival time in layers that present cannibalism. We considered four DGE-IGE models to predict survival time in layers. One model was an analysis of survival time and the three others treated survival in consecutive months as a repeated binomial trait (repeated measures models). We also tested whether EBV were improved by including timing of IGE expression in the analyses. Approximate EBV accuracies were calculated by cross-validation. The models were fitted to survival data on two purebred White Leghorn layer lines W1 and WB, each having monthly survival records over 13 months. Including the timing of IGE expression in the DGE-IGE model reduced EBV accuracy compared to analysing survival time. EBV accuracy was higher when repeated measures models were used. However, there was no universal best model. Using repeated measures instead of analysing survival time increased EBV accuracy by 10 to 21 and 2 to 12 % for W1 and WB, respectively. We showed how EBV and variance components estimated with repeated measures models can be translated into survival time. Our results suggest that prediction of breeding values for survival time in laying hens can be improved using repeated measures models. This is an important result since more accurate EBV contribute to higher rates of genetic gain.


Optimizing spectral compositions of multichannel LED light sources by IES color fidelity index and luminous efficacy of radiation.
The trade-off between the color fidelity index (Rf) released recently by the Illuminating Engineering Society of North America (IES) and luminous efficacy of radiation (LER) was investigated by adjusting the peak wavelengths, spectral widths, and intensities of four-channel LEDs utilizing a multiobjective optimization algorithm based on differential evolution in the correlated color temperature (CCT) ranging from 2800 to 6500 K for general lighting. The results indicate that Rf at a specific LER value decreases with the increasing CCT, and vice versa, and that Rf has significant improvements over the Commission Internationale de l'Eclairage (CIE) color rendering index (CRI) in avoiding spectral gaming and evaluating the light sources even with negative CIE general CRI (Ra). Further, the optimal peak wavelengths with regard to Rf were identified as 629 nm, 568 nm, 504 nm, and 447 nm, yielding high color rendering in terms of Rf(93∼94) and Ra(95∼97) and relatively excellent LER (299 lm/W∼339 lm/W) over a wide range of CCTs from 2800 to 6500 K. This suggests that Rf can be compatible with Ra, making it possible to obtain a common set of optimal peak wavelengths for Rf and Ra. Besides, the IES method could assess saturated red and skin tones more fairly than the CIE CRI. With a practical 17-channel LED array covering the resulted four optimal peak wavelengths, the improvements of the IES method over the CIE CRI were validated further.


Exploratory laparotomy and splenectomy in the diagnosis of Hodgkin's disease in children.
Thirty-three children with histologically proved Hodgkin's disease underwent exploratory laparotomy with splenectomy and biopsy of lumbar lymph nodes, liver, and bone marrow. In 13 patients (39%) the lesion of spleen and/or splenic hilar lymph nodes was diagnosed. The involvement of spleen was mostly found in patients with mixed cellularity type, in the presence of systemic symptoms ("B"), and in the biological stage "b." Involvement of the liver was found in 1 patient, of the hepatic hilar lymph nodes in 3 patients, and of the bone marrow in 4 patients. The lymphographic and histologic data as regards lumbar lymph nodes coincided in 65% of cases. After operation the stage of the disease was changed in 48% patients. The early and late complications were not numerous.


A study of package inserts in southern India.
Package insert is an officially approved document that accompanies a drug. It is intended to provide information for the safe and effective use of a drug and contains information based on regulatory guidelines. Sometimes, information provided in the package inserts is suboptimal which can led to medication errors. This study was undertaken to assess the presentation and completeness of clinical information provided in the currently available package inserts for anti-diabetic, anti-hypertensive and hypolipedemic drugs in India. Around 130 package inserts were collected from pharmacies located at different areas of Bangalore. They were analyzed based on criteria mentioned in Schedule D of Drug and Cosmetic act 1945. Out of 134 package inserts, 64 were anti-diabetics, 40 anti-hypertensives, and 30 hypolipedemics. Out of them, 31 (23.14%) belonged to Grade 'A' (including all injectable preparations) and remaining 76.86% to Grade 'B'. None of the PIs belonged to Grade 'C'. The inserts were inadequate in many aspects; for example, they had unclear instructions about generic name of other ingredients used, about handling, undesirable effects, pediatric and geriatric use, and guidelines for use of the drugs. This study indicated that information relevant to the safe and effective use of medication was not mentioned in the analyzed package inserts. It is, therefore, recommended to update the existing package inserts based on criteria mentioned in the Schedule D of Drug and Cosmetic Act, 1945.


Electrophoretic properties of ovomucoid.
1. The nature of the electrophoretic heterogeneity of ovomucoid was investigated. Optimum resolution of the fractions on starch-gel electrophoresis occurred over a narrow range of pH and ionic strength. The pattern was not altered in the presence of 8m-urea but the bands were sharper. Ovomucoid-trypsin complex is stable at pH4.6 but dissociated in 6m-urea. 2. The two major fractions of ovomucoid were eluted from the gels. One of these was virtually free of sialic acid and the other, which contained 0.4mole of sialic acid/mole of protein, split into two components on electrophoresis after neuraminidase treatment. It was concluded that these two components, and likewise the two major fractions of ovomucoid, differ by a unit charge/mol. Differences in sialic acid content account for only part of the electrophoretic heterogeneity of ovomucoid.


Paper-based synthetic gene networks.
Synthetic gene networks have wide-ranging uses in reprogramming and rewiring organisms. To date, there has not been a way to harness the vast potential of these networks beyond the constraints of a laboratory or in vivo environment. Here, we present an in vitro paper-based platform that provides an alternate, versatile venue for synthetic biologists to operate and a much-needed medium for the safe deployment of engineered gene circuits beyond the lab. Commercially available cell-free systems are freeze dried onto paper, enabling the inexpensive, sterile, and abiotic distribution of synthetic-biology-based technologies for the clinic, global health, industry, research, and education. For field use, we create circuits with colorimetric outputs for detection by eye and fabricate a low-cost, electronic optical interface. We demonstrate this technology with small-molecule and RNA actuation of genetic switches, rapid prototyping of complex gene circuits, and programmable in vitro diagnostics, including glucose sensors and strain-specific Ebola virus sensors.


Spatial acuity after digit amputation.
Digit amputation in human and non-human primates results in reorganization of somatosensory cortex in which the representations of adjacent, intact digits expand to fill the cortical region previously devoted to the amputated digits. Whether this expanded representation results in improved sensory performance has not been determined. Consequently, we measured the ability to recognize small objects (raised letters) with a digit adjacent to the amputation and the same digit on the normal, contralateral hand in 15 amputees. The same digits were also tested in 15 age-matched, amputation-free subjects. There was no significant difference in recognition scores between digits in the amputees or between amputees and control subjects. More detailed analyses of specific confusion patterns and of the improvement with practice showed no significant differences. As far as we could determine, the cortical expansion that is presumed to accompany digit amputation had no effect on tactile pattern recognition performance.


Overall Accuracy of Radiological Digital Planning for Total Hip Arthroplasty in a Specialized Orthopaedics Hospital.
Preoperative radiological planning is a key factor in the prediction of implant size and positioning that influences surgical time, the risk of complications, and functional outcomes. We have tested the accuracy of the digital templating performed in our hospital for a sample of 215 patients that underwent total hip arthroplasty. We assessed the accuracy of correctly predicting implant size for the femoral and acetabular components, as well as the stem neck length. We found that our method of templating proved accurate (within one size) in 95.8% of cases for the stem and 94.9% for the cup when using the anteroposterior view only, while the lateral view was accurate in 95.8% of cases for the stem and 97.2% for the cup. Exact prediction of the stem size was obtained in 77.7% of cases using the anteroposterior view and 67.0% of cases on the lateral view, and 73.0% and 74.4% of cases for the cup on the AP and LL views, respectively. Stem neck size was predicted exactly in 75.35% of cases and within one size in 93.49% of cases. We concluded that our method of digital templating using dedicated software is highly effective in accurately predicting implant size.


The Low-Expression Variant of FABP4 Is Associated With Cardiovascular Disease in Type 1 Diabetes.
Fatty acid binding protein 4 (FABP4) is implicated in the pathogenesis of cardiometabolic disorders. Pharmacological inhibition or genetic deletion of FABP4 improves cardiometabolic health and protects against atherosclerosis in preclinical models. As cardiovascular disease (CVD) is common in type 1 diabetes, we examined the role of FABP4 in the development of complications in type 1 diabetes, focusing on a functional, low-expression variant (rs77878271) in the promoter of the FABP4 gene. For this, we assessed the risk of CVD, stroke, coronary artery disease (CAD), end-stage kidney disease, and mortality using Cox proportional hazards models for the FABP4 rs77878271 in 5,077 Finnish individuals with type 1 diabetes. The low-expression G allele of rs77878271 increased the risk of CVD, independent of confounders. Findings were tested for replication in 852 Danish and 3,678 Finnish individuals with type 1 diabetes. In the meta-analysis, each G allele increased the risk of stroke by 26% (P = 0.04), CAD by 26% (P = 0.006), and CVD by 17% (P = 0.003). In Mendelian randomization, a 1-SD unit decrease in FABP4 increased risk of CAD 2.4-fold. Hence, in contrast with the general population, among patients with type 1 diabetes the low-expression G allele of rs77878271 increased CVD risk, suggesting that genetically low FABP4 levels may be detrimental in the context of type 1 diabetes.


Effect of sampling and short isolation methodologies on the recovery of human pathogenic Yersinia enterocolitica from pig tonsils.
The objective of this study was to determine the effect of sampling (swab samples compared to destructive samples) on isolation rates of human pathogenic Yersinia enterocolitica from pig tonsils. Moreover, the relative efficiency of different rapid, routinely applicable isolation methods was evaluated. Therefore, swab and destructive samples from tonsils of 120 pigs at slaughter were analyzed in parallel using direct plating and different enrichment methods. Salmonella-Shigella-desoxycholate-calcium chloride (SSDC) agar, cefsulodin-irgasan-novobiocin (CIN) agar, and Yersinia enterocolitica chromogenic medium (YeCM) were used as selective agar media. For enrichment, irgasan-ticarcillin-potassium chlorate (ITC) broth and peptone-sorbitol-bile (PSB) broth were incubated at 25°C for 48 h. Overall, 55 tonsils (45.8%) were positive for Y. enterocolitica bioserotype 4/O:3. Recovery was significantly higher using the destructive method compared to the swabbing method. Direct plating resulted in 47 and 28 Y. enterocolitica-positive destructive and swab samples, respectively. Alkali treatment of PSB and ITC enrichment broths significantly increased recovery of pathogenic Y. enterocolitica from destructive tonsil samples. The performance of YeCM for qualitative and quantitative isolation of pathogenic Y. enterocolitica from pig tonsils was equal to SSDC and CIN. In conclusion, direct plating and ISO 10273: 2003 with minor modifications are suitable and rapid methods for isolation of pathogenic Y. enterocolitica from destructive tonsil samples.


Molecular recognition through the exact placement of functional groups on non-covalent molecularly imprinted polymers.
To investigate the extent of the placement of functional groups in the non-covalent molecularly imprinted polymers contributing to selectivity, three kinds of molecularly imprinted methacrylic acid-ethylene glycol dimethacrylate copolymers were prepared at higher polymerization temperature (60 degrees C) using 2-L-phenylalanylamino-pyridine, 3-L-phenylalanylamino-pyridine, or 4-L-phenylalanylamino-pyridine as a template molecule, respectively. The enantiomeric recognition performance of these molecularly imprinted polymers (MIPs) in the high-performance liquid chromatography (HPLC) mode was investigated. The polymers exhibited efficient enantiomeric resolution of the racemic mixture of their printing molecules and could hardly resolve the enantiomers of other substrates that were structurally analogous to the imprinting molecules, but different from spatial interaction sites on the polymer with the methacrylic acid residues. Our results showed that the shape and spatial orientation of functionality of imprinted binding sites were critical for recognition and the recognition properties of MIPs were greatly influenced by the minor difference of N position on the pyridine ring and caused by the distance accuracy of functional groups in the binding sites. The implication of these findings with respect of the mechanism of recognition was discussed.


Rheumatologic Skin Disease.
In common rheumatologic diseases skin findings are an important diagnostic clue for astute clinicians. Skin manifestations can help identify systemic disease or may require therapy uniquely targeted at the cutaneous problem. This article discusses 3 common rheumatologic conditions seen in adults by dermatologists: cutaneous lupus, dermatomyositis, and morphea. The focus is on the cutaneous findings and clinical presentation. Some approaches to treatment are explored. Clues to help identify systemic disease are also highlighted.


Conformation-Dependent Photostability among and within Single Conjugated Polymers.
The relationship between photostability and conformation of 2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene (MEH-PPV) conjugated polymers was studied via excitation polarization modulation depth (M) measurements. Upon partial photobleaching, M distributions of collapsed, highly ordered MEH-PPV molecules shifted toward lower values. Conversely, M distributions of MEH-PPV molecules with random coil conformations moved toward higher values after partial photobleaching. Monte Carlo simulations of randomly distributed dipole moments along polymer chains subjected to partial photobleaching revealed that a statistical effect leads to an increase in peak M value. Decreases in M values seen experimentally in the population of MEH-PPV molecules with high M values, however, are due to conformation-dependent photostability within single MEH-PPV polymers. We show that, while folded MEH-PPV molecules are relatively more photostable than extended MEH-PPV molecules in an ensemble, extended portions of particular molecules are more photostable than folded domains within single MEH-PPV molecules.


Body Composition Assessment in Axial CT Images Using FEM-Based Automatic Segmentation of Skeletal Muscle.
The proportions of muscle and fat tissues in the human body, referred to as body composition is a vital measurement for cancer patients. Body composition has been recently linked to patient survival and the onset/recurrence of several types of cancers in numerous cancer research studies. This paper introduces a fully automatic framework for the segmentation of muscle and fat tissues from CT images to estimate body composition. We developed a novel finite element method (FEM) deformable model that incorporates a priori shape information via a statistical deformation model (SDM) within the template-based segmentation framework. The proposed method was validated on 1000 abdominal and 530 thoracic CT images and we obtained very good segmentation results with Jaccard scores in excess of 90% for both the muscle and fat regions.


Immune-related gene polymorphisms in pulmonary diseases.
Between the DNA sequences of two randomly-selected human genomes, which consist of over 3 billion base pairs and twenty five thousand genes, there exists only 0.1% variation and 99.9% sequence identity. During the last couple of decades, extensive genome-wide studies have investigated the association between single-nucleotide polymorphisms (SNPs), the most common DNA variations, and susceptibility to various diseases. Because the immune system's primary function is to defend against myriad infectious agents and diseases, the large number of people who escape serious infectious diseases underscores the tremendous success of this system at this task. In fact, out of the third of the global human population infected with Mycobacterium tuberculosis during their lifetime, only a few people develop active disease, and a heavy chain smoker may inexplicably escape all symptoms of chronic obstructive pulmonary disease (COPD), lung cancer, and other smoke-associated lung diseases. This may be attributable to the genetic makeup of the individual(s), including their SNPs, which provide some resistance to the disease. Pattern recognition receptors (PRRs), transcription factors, cytokines and chemokines all play critical roles in orchestrating immune responses and their expression/activation is directly linked to human disease tolerance. Moreover, genetic variations present in the immune-response genes of various ethnicities may explain the huge differences in individual outcomes to various diseases and following exposure to infectious agents. The current review focuses on recent advances in our understanding of pulmonary diseases and the relationship of genetic variations in immune response genes to these conditions.


Reflectance spectroscopy for noninvasive evaluation of hair follicle stage.
Hair follicle offers an excellent model for systems biology and regenerative medicine. So far, the stages of hair follicle growth have been evaluated by histological examination. In this work, a noninvasive spectroscopy was proposed by measuring the diffuse reflectance of mouse skin and analyzing the melanin value. Results show that the skin diffuse reflectance was relatively high when hair follicles were at the telogen stage and at the beginning of the anagen stage, and decreased with the progression of the anagen stage. When the hair follicle entered into the catagen stage, the diffuse reflectance gradually increased. The changes in the melanin content of skin had contrary dynamics. Substages of the hair follicle cycle could be distinguished by comparing the changes in melanin value with the histological examination. This study provided a new method for noninvasive evaluation of the hair follicle stage, and should be valuable for basic and therapeutic investigations on hair regeneration.


In vitro and in vivo cytokine-induced facilitation of immunohematopoietic reconstitution in mice undergoing bone marrow transplantation.
The aim of this study was to test whether colony stimulating factors (CSF) and other cytokines facilitate the recovery of a variety of immunohematopoietic functions in lethally irradiated mice undergoing bone marrow transplantation (BMT). Two experimental systems were employed: (a) lethally irradiated mice transplanted with syngeneic or T cell-depleted semi-allogeneic bone marrow (BM) cells (0.1-10 x 10(6)), subsequently treated by multiple doses of cytokines; and (b) lethally irradiated mice transplanted with BM cells that had previously been cultivated with cytokines. The cytokines used were: pure natural mouse interleukin-3 (IL-3); recombinant mouse granulocyte-macrophage CSF (rGM-CSF); recombinant human interleukin-2 (rIL-2); and crude cytokine preparations obtained from the culture supernatants of murine leukemia WEHI-3b cells (containing mainly IL-3), and of phorbol myristate acetate (PMA)-stimulated EL4 leukemia cells and concanavalin A-stimulated rat splenocytes (each containing a multitude of cytokines). For BM cultures (1-9 days), the cytokines were used at a dosage of 1-100 U/ml; for in vivo treatment, 2 x 10(2)-5 x 10(4) units were administered intraperitoneally and subcutaneously at different schedules for varying periods (1-3 weeks). The following parameters were tested 1-10 weeks post-BMT: white blood cell count, colony formation in agar and in the spleen of lethally irradiated mice, proliferative responses to mitogens and alloantigens, allocytotoxicity and antibody production (serum agglutinins and plaque-forming cells) against sheep red blood cells. Under appropriate conditions, cytokine treatment either in vitro or in vivo significantly enhanced (2- to 50-fold compared with controls) most functions tested at 2-8 weeks post-BMT, and shortened the time interval required for full immunohematopoietic recovery by 2-5 weeks. In recipients of semi-allogeneic, T lymphocyte-depleted BM no evidence of graft-versus-host disease was found. It is suggested that judicious application in vitro and/or in vivo of certain pure cytokines (e.g. GM-CSF, IL-3) or cytokine 'cocktails' might be beneficial in enhancing hematopoiesis and in the treatment of immunodeficiency associated with BMT.


[Food intolerance--etiology of functional disorders and therapeutic possibilities].
Patients often complain about food intolerances and accuse them of causing diarrhea, constipation, meteorism, flatulence and abdominal pain. With alarm symptoms, patients usually suffer from structural diseases, which have to be clarified immediately by extensive diagnostic steps. With no alarm symptoms present, patients usually suffer from functional disorders. Their workup should be done stepwise. Therapy is dependent on the underlying disorder and often symptom-adapted. General measures of prevention for food-preparation and nutrition are important.


Definition of an inhibitory juxtamembrane WW-like domain in the platelet-derived growth factor beta receptor.
A variety of tumors contain activating mutations in the cytoplasmic juxtamembrane domain of the type III family of receptor-tyrosine kinases, and some constructed mutations in this domain induce ligand-independent receptor activation. To explore the role of this domain in regulation of receptor activity, we subjected the juxtamembrane domain of the murine platelet-derived growth factor (PDGF) beta receptor to alanine-scanning mutagenesis. The mutant receptors were expressed in Ba/F3 cells and tested for constitutive tyrosine phosphorylation, association with phosphatidylinositol 3'-kinase, and their ability to induce cell survival and proliferation in the absence of interleukin-3. The mutant receptors accumulated to similar levels and appeared to undergo a normal PDGF-induced increase in tyrosine phosphorylation. Alanine substitutions at numerous positions located throughout the juxtamembrane domain caused constitutive receptor activation, as did an alanine insertion in the membrane-proximal segment of the juxtamembrane domain and a six-amino acid deletion in the center of the domain. It is possible to model the PDGF receptor juxtamembrane domain as a short alpha-helix followed by a three-stranded beta-sheet very similar to the known structures of WW domains. Strikingly, the activating mutations clustered in the central portions of the first and second beta strands and along one face of the beta-sheet, whereas the loops connecting the strands were largely devoid of mutationally sensitive positions. These findings provide strong support for the model that the activating mutations in the juxtamembrane region stimulate receptor activity by disrupting an inhibitory WW-like domain.


Current concepts in the rehabilitation of the athletic shoulder.
The rehabilitative process of the overhead athlete represents a significant challenge to the clinician. Overhead athletes (thrower, tennis player, swimmer) repetitively subject their shoulder joints to high microtraumatic stresses that, due to the accumulative effects, may lead to a variety of shoulder injuries. This type of athletic patient exhibits uniquely specific physical characteristics, such as hypermobility of the anterior shoulder capsule, excessive external rotation, hypomobility of the posterior capsule, limited internal rotation, and generalized ligamentous laxity of the glenohumeral joint. However, the overhead athlete must exhibit functional stability for pain-free sports participation. Functional stability is accomplished through the proficient balance of static (passive) and dynamic (active) stabilizers. During the rehabilitation process, various concepts, such as neuromuscular control, proprioception, force couple efficiency, plyometrics, eccentrics, and scapular stability, can enhance dynamic functional stability for the overhead athlete. The evaluation and treatment of the shoulder patient is in perpetual change, and the purpose of this paper is to discuss several current concepts in the rehabilitative treatment of the athletic shoulder patient.


Genetic analysis, ultrasound phenotype, and pregnancy outcomes of fetuses with Xp22.33 or Yp11.32 microdeletions.
The phenotypes of Xp22.33 or Yp11.32 microdeletions comprising the short-stature homeobox (SHOX) gene have been extensively described in adults and children. Herein, the prenatal ultrasound phenotype and pregnancy outcomes of fetuses with Xp22.33/Yp11.32 microdeletions were analyzed to improve our understanding, diagnosis, and monitoring of this genetic condition in the fetal stage. A total of 9,100 pregnant women referred to tertiary units for prenatal diagnosis were evaluated by chromosomal microarray analysis(CMA). Seven (0.08 %) fetuses had Xp22.33/Yp11.32 microdeletions, ranging from 243 kb to 1.1 Mb, that comprised SHOX. The ultrasonic phenotypes differed among these fetuses, with three fetuses presenting abnormal bone development, one had labial-palatal deformity and strawberry head, two had an abnormal ultrasonic soft marker, and one had no abnormalities. After genetic counseling, only one couple underwent pedigree assessment, which confirmed the paternal origin of the microdeletion. This infant presented delayed speech development, whereas other three infants showed a typical postnatal development. In three cases, the parents chose to terminate the pregnancy. The ultrasonic phenotype of fetuses with Xp22.33/Yp11.32 microdeletions resulting in SHOX heterozygosity loss is variable. Prenatal CMA can quickly and effectively diagnose Xp22.33/Yp11.32 microdeletions and SHOX loss, which may help prenatal counseling.


Measurement of bone density by gas displacement.
Small bone volumes, porous and irregular structured objects with volumes 0.05-2 cm3, were measured by differential pressure of displaced air. The differential air pressure was measured by a piezoelectric resistor pressure gauge. The gas-displacement system was used to measure the volumes of 234 bone specimens for calculation of bone density. The operation of the system, calibration, sensitivity, and errors of measurement are described.


Variant proteins of Plasmodium vivax are not clonally expressed in natural infections.
Plasmodium vivax is the most widely distributed human malaria parasite and responsible for 70-80 million clinical cases each year and a large socio-economical burden. The sequence of a chromosome end from P. vivax revealed the existence of a multigene superfamily, termed vir (P. vivax variant antigens), that can be subdivided into different subfamilies based on sequence similarity analysis and which represents close to 10-20% of the coding sequences of the parasite. Here we show that there is a vast repertoire of vir genes abundantly expressed in isolates obtained from human patients, that different vir gene subfamilies are transcribed in mature asexual blood stages by individual parasites, that VIR proteins are not clonally expressed and that there is no significant difference in the recognition of VIR-tags by immune sera of first-infected patients compared with sera of multiple-infected patients. These data provide to our knowledge the first comprehensive study of vir genes and their encoding variant proteins in natural infections and thus constitute a baseline for future studies of this multigene superfamily. Moreover, whereas our data are consistent with a major role of vir genes in natural infections, they are inconsistent with a predominant role in the strict sense of antigenic variation.


Nodes of Ranvier in skin biopsies of patients with diabetes mellitus.
Paranodal demyelination has been discussed as a potential mechanism of nerve fiber damage in diabetic neuropathy (DNP). Studies on human tissue are limited, as nerve biopsies are invasive and only rarely performed in patients with confirmed DNP. Skin biopsy has recently been suggested as a tool to analyze paranodal and nodal changes of myelinated fibers. We analyzed the myelinated fibers of skin biopsies of 35 patients with DNP, 17 patients with diabetes mellitus (DM) without neuropathy, and 30 normal controls. Immunofluorescence of skin sections with antibodies against Caspr, neurofascin, sodium channels, and myelin basic protein was performed to assess paranodal/nodal architecture, segmental demyelination, and myelinated nerve fibers. Staining with antibodies against protein gene product 9.5 was used to quantify unmyelinated nerve fibers. There was an increase of elongated Ranvier nodes and a dispersion of neurofascin at the distal leg in patients with DM with and without neuropathy and at the finger in patients with DNP. An increased dispersion of Caspr was only found in biopsies of the finger in patients with DNP. Skin biopsy may be an appropriate tool to analyze nodes of Ranvier in patients with DM. Structural nodal changes are detectable in DNP and even in diabetic patients without neuropathy.


Ultrafast, 2 min synthesis of monolayer-protected gold nanoclusters (d < 2 nm).
An ultrafast synthesis method is presented for hexanethiolate-coated gold nanoclusters (d < 2 nm, <250 atoms per nanocluster), which takes only 2 min and can be easily reproduced. With two immiscible solvents, gold nanoclusters are separated from the reaction byproducts fast and easily without any need for post-synthesis cleaning.


Endometriosis-associated changes in serum levels of interferons and chemokines.
The aim of the study was to evaluate the serum concentration of main chemokines and interferons in patients with diagnosed endometriosis. A total of 160 women were divided in two study groups (group 1 - endometriosis; group 2 - healthy women). Serum levels of IFN-α, IFN-γ, MCP-1, MIP-1α, MIP-1β, RANTES, eotaxin, IL-8, MIG, IP-10, and IL-17A were measured with Human Multiplex Cytokine Panels. Results. Serum levels of IFN-γ, MCP-1, and IL-8 were significantly higher (mean 14.03, 57.24, and 534.24, respectively, compared to 0.58, 20.51, and 259.82, respectively), and serum levels of IP-10 and eotaxin were significantly lower in women with endometriosis compared to the controls (mean 1.15 and 1.01, respectively, compared to 3.90 and 3.22, respectively). Conclusions. According to our results women with endometriosis have elevated levels IFN-γ, MCP-1, and IL-8, and lower serum levels of IP-10 and eotaxin, indicating unbalanced immune activity in endometriosis.


A Method for Inferring an Individual's Genetic Ancestry and Degree of Admixture Associated with Six Major Continental Populations.
The determination of the ancestry and genetic backgrounds of the subjects in genetic and general epidemiology studies is a crucial component in the analysis of relevant outcomes or associations. Although there are many methods for differentiating ancestral subgroups among individuals based on genetic markers only a few of these methods provide actual estimates of the fraction of an individual's genome that is likely to be associated with different ancestral populations. We propose a method for assigning ancestry that works in stages to refine estimates of ancestral population contributions to individual genomes. The method leverages genotype data in the public domain obtained from individuals with known ancestries. Although we showcase the method in the assessment of ancestral genome proportions leveraging largely continental populations, the strategy can be used for assessing within-continent or more subtle ancestral origins with the appropriate data.


Synthesis and characterization of PEG dimethacrylates and their hydrogels.
Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and poly(ethylene glycol) urethane-dimethacrylates (PEGUDM) are described. Poly(ethylene glycol)s of various molecular masses (M(n) = 1000 to 8000 g/mol) were reacted with methacrylic anhydride or with 2-isocyanatoethyl methacrylate to form PEGDMs and PEGUDMs, respectively. PEGDMs were also prepared by a microwave-assisted route to achieve fast reaction conversions under solvent free conditions. Combined analyses of (1)H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). Aqueous solutions of the PEGDMs and PEGUDMs (10% and 20% by mass fraction) were photopolymerized to yield hydrogels. Bovine chondrocytes, seeded in the hydrogels, were used to assess the biocompatibility. Preliminary rheology and uniaxial compression measurements showed varied mechanical response, and biocompatibility studies showed that cells are completely viable in both types of hydrogels after two weeks.


Changes in cannabinoid CB(1) receptor functionality in the female rat prefrontal cortex following a high fat diet.
A high fat diet (HFD) has been found to affect neurotransmission in the prefrontal cortex, but the effects of this dietary regime upon the endocannabinoid system has not been studied in this brain region. In consequence, in the present study, we have investigated the effect of HFD for up to 20 weeks upon the endocannabinoid system in the prefrontal cortex of female rats. CB1 receptor functionality was measured using CP55,940-stimulated [(35)S]GTPγS autoradiography. Fatty acid amide hydrolase and monoacylglycerol lipase activities were analysed in brain regions by assessing rates of [(3)H]anandamide and JZL184-sensitive [(3)H]2-oleoylglycerol hydrolysis, respectively. In the prefrontal cortex, a significantly greater stimulation of [(35)S]GTPγS binding by CP55,940 was seen following 4-12, but not 16-20 weeks of HFD. No significant changes were seen for the caudate-putamen, CA1-CA3 region of the hippocampus or the dentate gyrus. The increased response for the 12 week animals was not accompanied by a significant change in the receptor density, measured with [(3)H]CP55,940 autoradiography. No significant changes in the activity of the endocannabinoid hydrolytic enzymes fatty acid amide or monoacylglycerol lipase were seen in the prefrontal cortex, hippocampus, amygdala or hypothalamus following either 12 or 20 weeks of HFD. It is concluded that HFD produces an increased CB1 receptor functionality in the prefrontal cortex of female rats. Given that the endocannabinoid system regulates neurotransmission in the prefrontal cortex, the present data would implicate this system in the disturbed prefrontal cortical activity in this region following a high fat diet.


Lip and oral venous varices treated by photocoagulation with high-intensity diode laser.
Lip and oral venous varices are acquired benign vascular lesions characterized by a darkblue to violaceous papule or nodule, commonly found on the ventral tongue and lower lip. Although these lesions are usually asymptomatic, they can bleed if injured. This study assessed the effectiveness of photocoagulation with high-intensity diode laser in the treatment of these lesions. Thirty-two patients (14 men and 18 women; mean age, 56 years) with lip and oral venous varices were examined and treated with a noncontact diode laser. With one exception, all cases were successfully treated with a single irradiation exposure session. Healing was complete in about 2 to 3 weeks; none of the patients experienced complications or recurrence. Photocoagulation with high-intensity diode laser was proven to be safe and effective for the treatment of lip and oral venous varices, with consistent results.


A polypyrrole-coated eightfold-helical Wells-Dawson POM-based Cu-FKZ framework for enhanced colorimetric sensing.
To explore a novel colorimetric biosensor with high sensibility and selectivity, a new Wells-Dawson-type polyoxometalate (POM)-based metal-organic framework (MOF) with an eightfold helix, [Cu9(FKZ)12(H2O)8][H3P2W18O62]2·4H2O (CuFKZP2W18) (HFKZ = 1-(2,4-difluorophenyl)-1,1-bis[(1H-1,2,4-triazol-1-yl)methyl] ethanol), was successfully synthesized; then, polypyrrole (PPy) was introduced to fabricate CuFKZP2W18/PPy(n) nanocomposites (n = 7%, 15%, 30%) via a facile in situ oxidation polymerization process. All the results indicate that CuFKZP2W18/PPy(15%) as a colorimetric biosensor exhibits lower limits of detection (0.07 μM towards H2O2 and 0.627 μM towards ascorbic acid), smaller Km values (0.106 mM for H2O2 and 0.042 mM for o-phenylenediamine) and higher sensitivity (0.0227 1 μM-1 towards H2O2 and 0.0025 1 μM-1 to ascorbic acid) than most reported enzyme mimetics to the best of our knowledge.


Dynamically oriented psychotherapy with borderline patients.
This article outlines a basic framework and strategy for a dynamically oriented psychotherapy with borderline patients. Focus includes arrangements and guidelines for psychotherapy, neutrality, the stability of the therapeutic environment, the therapeutic alliance, transference, the countertransference, activity of the therapist, types of interventions, style of interventions, interventions regarding core difficulties, the conceptual framework of anxiety and defense, trends in the psychotherapy, and termination. A differentiation between analytically oriented psychotherapy and dynamically oriented psychotherapy is provided. For one group of borderline patients, a modified analytically oriented approach is utilized throughout the entire treatment. For a second group, there is a switch from analytically oriented psychotherapy to a dynamically oriented psychotherapy, after the therapeutic alliance has become reasonably stable. Two clinical vignettes are provided.


Lower extinction risk in sleep-or-hide mammals.
An ever larger proportion of Earth's biota is affected by the current accelerating environmental change. The mismatches between organisms and their environments are now increasing in both magnitude and frequency, resulting in lowered fitness and hence the decline of populations. Under this scenario, species with behavioral and/or physiological traits that provide them shelter from the environment are predicted to be less vulnerable to population declines than species that are always exposed to the elements. Here, we coded 4,536 living mammal species for sleep-or-hide (SLOH) behavior, including hibernation, torpor, and the use of burrows, among other related traits. We demonstrate that species that exhibit SLOH behavior are underrepresented in high-risk International Union for Conservation of Nature Red List categories. We found that SLOH behavior contributes to lowering extinction risk even after we accounted for other factors that directly or indirectly buffer species against extinction, such as larger geographic ranges and smaller body sizes. This result is robust to analyses using phylogenetically independent contrasts. Sleep-or-hide behavior, made possible by a related suite of physiological adaptations, allows mammals to function at lower metabolic rates and/or buffer them from changing physical elements. Mammals with SLOH behavior have a greater propensity to survive in the current extinction crisis and probably also in past crises because of reduced exposure to environmental stress.


Overall Impact of Coronavirus Disease 2019 Outbreak in Children With Functional Abdominal Pain Disorders: Results From the First Pandemic Phase.
We aimed to assess how the first phase of coronavirus disease 2019 (COVID-19) pandemic influenced symptoms in children with functional abdominal pain disorders (FAPDs) and to characterize their quality of life (QoL), anxiety and global health. This was a multicenter, observational, international study conducted between April and July 2020 at six different referral centers. Children diagnosed with FAPDs between October 2019 and February 2020 were enrolled and prospectively interviewed at 4 months of follow-up during the first pandemic phase (Quarantine group). Patients were asked to complete PedsQL 4.0 Generic Core Scale and PROMIS Anxiety and Global Health questionnaires. A cohort of children diagnosed with FAPDs between October 2018 and February 2019 was used as a Control group. Three-hundred-fifty-six children were enrolled of whom 180 (mean age at diagnosis: 14 ± 2.8 years) in the Quarantine group and 176 (mean age at diagnosis: 13 ± 2.8 years) in the Control group. At 4 months of follow-up, we observed a significant reduction of children reporting >5 episodes of abdominal pain per month when compared to baseline, in both groups (Quarantine group: 63.9% vs 42.2%, P < 0.001; Control group: 83.5% vs 50%, P < 0.001). The Quarantine group had median QoL values of 84.8 with 16.6% of children showing high anxiety values and 55% having decreased global health score. We demonstrated symptoms' improvement at 4 months of follow-up in both cohorts. During the first months of the COVID-19 quarantine children with FAPDs showed satisfactory QoL and anxiety scores, suggesting positive effects of school closure and increased parental attention.


Living with bronchial asthma: A qualitative study among patients in a hill village in Nepal.
Bronchial asthma continues to be a problem in the Himalayan country of Nepal. This study explored the impact of bronchial asthma on patients' lives in a hill village in Syangja district, Nepal, and obtained information about the perceived impact of the illness, knowledge of the disease, self-care behaviors and treatment among patients. The study site is the village of Jyamire (located at an elevation between 900 to 1200 m) Syangja district. Individuals suffering from asthma residing in the village aged 18 years or above were included. Semi-structured interviews were conducted face-to-face with the respondents at their homes using an interview guide. The interviews were audio recorded, transcribed in the Nepali language, and then translated into English for further analysis. Most participants were female, between 18 to 60 years of age, and housewives. Most houses were built of mud and poorly ventilated. Gas was used for cooking though firewood was also used. Most used to get an average of three serious attacks a year both during winter and summer. The themes that emerged were the number and seasonal variation in attacks, the perceived effect of asthma on their lives and social interactions, the knowledge of the interviewee about the disease, the impact of asthma on their socioeconomic status, and treatment and self-care behaviors. Residing in a hill village required them to walk up and down several times a day and the disease seriously impacted their lives. The smoke produced during different ceremonies and during cooking also worsened their asthma. Findings suggest, the existence of multiple factors, a few unique to Nepal contributing to poor asthma control. Though the recent socioeconomic improvement has led to improved prevention and treatment options, asthma seriously affected the patients.


Measures of extents of laterality for high-frequency "transposed" stimuli under conditions of binaural interference.
Our purpose in this study was to determine whether across-frequency binaural interference would occur if ITD-based extents of laterality were measured using high-frequency transposed stimuli as targets. The results of an earlier study [L. R. Bernstein and C. Trahiotis, J. Acoust. Soc. Am. 116, 3062-3069 (2004)], which focused on threshold-ITDs, rather than extents of laterality, suggested that high-frequency transposed stimuli might be "immune" to binaural interference effects resulting from the addition of a spectrally remote, low-frequency interferer. In contrast to the earlier findings, the data from this study indicate that high-frequency transposed targets are susceptible to binaural interference. Nevertheless, high-frequency transposed targets, even when presented along with an interferer, yielded greater extents of ITD-based laterality than did high-frequency Gaussian noise targets presented in isolation. That is, the "enhanced potency" of ITDs conveyed by transposed stimuli persisted, even in the presence of a low-frequency interferer. Predictions made using an extension of the model of Heller and Trahiotis [L. M. Heller and C. Trahiotis, J. Acoust. Soc. Am. 99, 3632-3637 (1996)] accounted well for across-frequency binaural interference obtained with conventional Gaussian noise targets but, in all but one case, overpredicted the amounts of interference found with the transposed targets.


Evaluation of Diagnostic Values of Clinical Assessment in Determining the Maturation of Arteriovenous Fistulas for Satisfactory Hemodialysis.
Fistulas are the preferred permanent hemodialysis vascular access, but a significant obstacle to increasing their prevalence is the fistula's high "failure to mature" (FTM) rate. This study aimed to identify postoperative clinical characteristics that are predictive of fistula FTM. This descriptive cross-sectional study was performed on 80 end-stage renal disease patients who referred to Al Zahra Hospital, Isfahan, for brachiocephalic fistula placement. After 4 weeks, the clinical criteria (trill, firmness, vein length, and venous engorgement) examined and the fistulas situation divided to favorable or unfavorable by each criterion, and the results comprised with dialysis possibility. Data were analyzed with SPSS version 21. Diagnostic index for CLINICAL examination was calculated. Among the 80 cases, 25 (31.2%) female and 55 (68.8%) male were studied with the mean age of 51.9 (standard deviation = 17) year ranged between 18 and 86 years old. Sixty-two (77.5%) cases had successful hemodialysis. All four clinical assessments were significantly more acceptable in patients with successful dialysis (P < 0.001). According to the results of our study, the accuracy of all physical assessments was above 70% and except vein length other criteria had a sensitivity and negative predictive value of 100%. In this study, firmness of vein has highest specificity and positive predictive value (83.9% and 64.3%, respectively). Results of our study showed that high sensitivity and relatively low specificity of the clinical criterion. It means that unfavorable results of each clinical criterion predict unfavorable dialysis. Clinical evaluation of a newly created fistula 4-6 weeks after surgery should be considered mandatory.


Stomatal and non-stomatal factors regulated the photosynthesis of soybean seedlings in the present of exogenous bisphenol A.
Bisphenol A (BPA) is an emerging environmental endocrine disruptor that has toxic effects on plants growth. Photosynthesis supplies the substances and energy required for plant growth, and regulated by stomatal and non-stomatal factors. Therefore, in this study, to reveal how BPA affects photosynthesis in soybean seedlings (Glycine max L.) from the perspective of stomatal and non-stomatal factors, the stomatal factors (stomatal conductance and behaviours) and non-stomatal factors (Hill reaction, apparent quantum efficiency, Rubisco activity, carboxylation efficiency, the maximum Rubisco carboxylation velocity, ribulose-1,5-bisphospate regeneration capacities mediated by maximum electron transport rates, and triose phosphate utilization rate) were investigated using a portable photosynthesis system. Moreover, the pollution of BPA in the environment was simulated. The results indicate that low-dose BPA enhanced net photosynthetic rate (Pn) primarily by promoting stomatal factors, resulting in increased relative growth rates and accelerated soybean seedling growth. High-dose BPA decreases the Pn by simultaneously inhibiting stomatal and non-stomatal factors, and this inhibition decreases the relative growth rates further reducing soybean seedling growth. Following the withdrawal of BPA, all of the indices were restored to varying degrees. In conclusion, low-dose BPA increased the Pn by promoting stomatal factors while high-dose BPA decreased the Pn by simultaneously inhibiting stomatal and non-stomatal factors. These findings provide a model (or, hypothesis) for the effects of BPA on plant photosynthesis.


3-[2-(1H-1,3-Benzodiazol-2-yl)eth-yl]-1,3-oxazolidin-2-one.
In the title compound, C(12)H(13)N(3)O(2), the dihedral angle between the oxazolone ring and the benzimidazole unit is 45.0 (5)°, exhibiting a staggered conformation at the Cα-Cβ bond. In the crystal, a strong N-H⋯N hydrogen bond links the mol-ecules into a C(4) chain along the c axis while a C-H⋯O hydrogen-bonding inter-action generates a C(5) chain along the a axis, i.e. perpendicular to the other chain.


[The attendance of the first screening round (2002-2003) of the Hungarian organized breast cancer screening program and its effect on the number of diagnostic and screening mammography].
Organised, nationwide screening for breast cancer with mammography in the age group 45-65 years with 2 years screening interval started in Hungary in January 2002. The aim of this study is to analyze the attendance rate of breast screening programme, including the analysis of the ratio of screening and diagnostic mammography examinations. The data derive from the financial database of the National Health Insurance Fund Administration (NHIFA) covering the period 2000-2003. The ratio of women was calculated in the age group 45-65 years having either a screening mammography or a diagnostic mammography. The analysis was carried out for the years 2000-2001 (mainly opportunistic screening) before and 2002-2003 after the implementation of nationwide organized programme. In the years 2000-2001 7,26% of the women aged 45-65 had an opportunistic screening mammography while in 2002-2003 33,95% of the target population had screening mammography within the organized programme. During the same periods 19,67% (2000-2001) and 22,05% (2002-2003) of women aged 45-65 had a diagnostic mammography. Thus the total (screening and diagnostic) coverage of mammography increased from 25,85% (2000-2001) to 53,46% (2002-2003). The attendance of the Hungarian organized breast cancer screening programme - compared to the previous period before the implementation of the organized screening programme - is promising, although to achieve the expected results in mortality decrease a further improvement of the uptake is necessary.


Phenotype and genetic analysis of data collected within the first year of NeuroDev.
Genetic association studies have made significant contributions to our understanding of the etiology of neurodevelopmental disorders (NDDs). However, these studies rarely focused on the African continent. The NeuroDev Project aims to address this diversity gap through detailed phenotypic and genetic characterization of children with NDDs from Kenya and South Africa. We present results from NeuroDev's first year of data collection, including phenotype data from 206 cases and clinical genetic analyses of 99 parent-child trios. Most cases met criteria for global developmental delay/intellectual disability (GDD/ID, 80.3%). Approximately half of the children with GDD/ID also met criteria for autism. Analysis of exome-sequencing data identified a pathogenic or likely pathogenic variant in 13 (17%) of the 75 cases from South Africa and 9 (38%) of the 24 cases from Kenya. Data from the trio pilot are publicly available, and the NeuroDev Project will continue to develop resources for the global genetics community.


Macular retinoschisis in highly myopic eyes.
To describe the characteristics and evolution of macular retinoschisis in high myopia observed by optical coherence tomography (OCT). A consecutive, retrospective, observational case series. Twenty-one highly myopic eyes (mean refractive error, -15.2, range -6 to -25) of 17 patients presenting with the unusual feature of macular thickening without a macular hole and associated with a posterior staphyloma were examined by biomicroscopy and OCT. Ten patients (13 eyes) were followed up for 12 months or more. On biomicroscopy, the macula of all 21 eyes had a microcystic appearance without macular hole. In all eyes, OCT showed that retinal thickening was mainly due to an extensive hyporeflective space splitting the neuroretina into a thick inner layer and a thin outer layer. We called this condition outer retinoschisis. In six cases, inner splitting, termed inner retinoschisis, was also present. The macular profile exhibited a foveal cyst in 10 eyes, a lamellar hole in six, and a foveal detachment in six. In four of the 21 eyes, a hyperreflective preretinal structure resembling the posterior hyaloid was stretched over the retinoschisis, causing foveal traction. Two of these four eyes subsequently evolved into a full-thickness macular hole. Macular retinoschisis is not uncommon in highly myopic eyes with staphyloma and is better characterized by OCT than by biomicroscopy. Intraretinal splitting occurs in both the outer and inner layers of the retina, leading to the formation of cystoid spaces. In most cases, the condition is fairly stable in terms of visual acuity and retinal thickness and change occurs slowly over time. However, a macular hole may occur when the retinoschisis is associated with tangential traction of the posterior hyaloid.


HpaC controls substrate specificity of the Xanthomonas type III secretion system.
The Gram-negative bacterial plant pathogen Xanthomonas campestris pv. vesicatoria employs a type III secretion (T3S) system to inject bacterial effector proteins into the host cell cytoplasm. One essential pathogenicity factor is HrpB2, which is secreted by the T3S system. We show that secretion of HrpB2 is suppressed by HpaC, which was previously identified as a T3S control protein. Since HpaC promotes secretion of translocon and effector proteins but inhibits secretion of HrpB2, HpaC presumably acts as a T3S substrate specificity switch protein. Protein-protein interaction studies revealed that HpaC interacts with HrpB2 and the C-terminal domain of HrcU, a conserved inner membrane component of the T3S system. However, no interaction was observed between HpaC and the full-length HrcU protein. Analysis of HpaC deletion derivatives revealed that the binding site for the C-terminal domain of HrcU is essential for HpaC function. This suggests that HpaC binding to the HrcU C terminus is key for the control of T3S. The C terminus of HrcU also provides a binding site for HrpB2; however, no interaction was observed with other T3S substrates including pilus, translocon and effector proteins. This is in contrast to HrcU homologs from animal pathogenic bacteria suggesting evolution of distinct mechanisms in plant and animal pathogenic bacteria for T3S substrate recognition.