Targeting B-cell receptor signaling in leukemia and lymphoma: how and why?
B-lymphocytes are dependent on B-cell receptor (BCR) signaling for the constant maintenance of their physiological function, and in many B-cell malignancies this signaling pathway is prone to aberrant activation. This understanding has led to an ever-increasing interest in the signaling networks activated following ligation of the BCR in both normal and malignant cells, and has been critical in establishing an array of small molecule inhibitors targeting BCR-induced signaling. By dissecting how different malignancies signal through BCR, researchers are contributing to the design of more customized therapeutics which have greater efficacy and lower toxicity than previous therapies. This allows clinicians access to an array of approaches to best treat patients whose malignancies have BCR signaling as a driver of pathogenesis.


Ankyrin repeat: a unique motif mediating protein-protein interactions.
Ankyrin repeat, one of the most widely existing protein motifs in nature, consists of 30-34 amino acid residues and exclusively functions to mediate protein-protein interactions, some of which are directly involved in the development of human cancer and other diseases. Each ankyrin repeat exhibits a helix-turn-helix conformation, and strings of such tandem repeats are packed in a nearly linear array to form helix-turn-helix bundles with relatively flexible loops. The global structure of an ankyrin repeat protein is mainly stabilized by intra- and inter-repeat hydrophobic and hydrogen bonding interactions. The repetitive and elongated nature of ankyrin repeat proteins provides the molecular bases of the unique characteristics of ankyrin repeat proteins in protein stability, folding and unfolding, and binding specificity. Recent studies have demonstrated that ankyrin repeat proteins do not recognize specific sequences, and interacting residues are discontinuously dispersed into the whole molecules of both the ankyrin repeat protein and its partner. In addition, the availability of thousands of ankyrin repeat sequences has made it feasible to use rational design to modify the specificity and stability of physiologically important ankyrin repeat proteins and even to generate ankyrin repeat proteins with novel functions through combinatorial chemistry approaches.


Histidine 6.55 is a major determinant of ligand-biased signaling in dopamine D2L receptor.
In our previous studies, we demonstrated that the mutation of His393(6.55) to alanine results in an increased affinity of 1,4-disubstituted phenylpiperazines to the dopamine D(2L) receptor. This change most likely accounts for the reduced steric hindrance in this part of the binding pocket. In this work, we investigated the role of the steric hindrance imposed by the residue His393(6.55) for the receptor activation modulated by 1,4-disubstituted aromatic piperidines/piperazines. Site-directed mutagenesis and ligand modifications were used to probe the structural basis of ligand efficacy. The operational model of agonism was used to quantify the ligand bias between the ability of compounds to inhibit cAMP accumulation and stimulate extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Whereas substantial ligand-biased signaling was observed for the D(2L) wild-type receptor, an overall increase in agonism was observed for the D(2L) H393(6.55)A mutant without noteworthy functional selectivity. Targeted chemical modification of the phenylpiperazine moiety at the site of its interaction with the residue His393(6.55) led to the functionally selective ligand {3-[4-(2,3-dihydro-benzofuran-7-yl)-piperazin-1-yl]-propyl}-pyrazol[1,5-a]pyridine-3-carboxamide (FAUC350) that has distinct signaling profiles toward adenylyl cyclase and ERK1/2. FAUC350 behaves as an antagonist in the inhibition of cAMP accumulation and as a partial agonist in the stimulation of ERK1/2 phosphorylation (efficacy = 55%). Overall, the residue His393(6.55) and proximate molecular substructures of receptor ligands were identified to be crucial for multidimensional ligand efficacy.


Non-random associations between fears, beliefs and behaviors among panic patients.
Self-report questionnaires have been used to compare panic patients' fears, anxious thoughts and behaviors with those of a group of controls. Individual items revealed significant differences between groups in all three areas: factor analysis revealed group differences in the pattern of intraquestionnaire associations between items. Correlational analysis of factor scores revealed significant group differences in the pattern of interquestionnaire associations. These findings only partly support a formulation of panic based upon "catastrophic interpretations." On the other hand, they do provide evidence of cognitive rigidity among panic patients which can be interpreted as evidence of impaired effortful processing when anxious.


[Adult laryngeal cavernous hemangioma: a case report].
We describe a case of laryngeal venous malformation, discovered by dysphonia. This malformation has a different histology and evolution compared to infant laryngeal hemangioma. The histological exam shows large and multiple vessels lined by regular endothelium. There is no spontaneous regression; this malformation can be stable or increase and induce a laryngeal obstruction. Although inconstant, a bluish colour, seen at endoscopy, suggests the presence of venous malformation. The diagnostic is confirmed by MRI, which shows local extension. We propose regular clinical and radiological supervision for asymptomatic venous malformations. Treatment is recommended only for symptomatic patients usually by laryngeal microsurgery or cervicotomy. Per cutaneous sclerosis is an interesting alternative therapy alone or prior to surgery. Regular follow-up is essential in order to detect frequent recurrences.


Whither managerialism in the Italian National Health Service?
In the last decade, the Italian National Health Service has been characterized by the introduction of managerial concepts and techniques, according to the New Public Management paradigm. Recently, these reforms have been increasingly criticized. This article examines the implementation of managerialism in an attempt to evaluate its overall achievements and shortcomings. Overall, managerialism seems to have made good progress: managerial skills are improving; several management tools have been adapted to health-care and public-sector peculiarities; health-care organizations have adopted a wide range of technical solutions to fit their specific needs. At the same time, managerial innovations have often focused on structures as opposed to processes, on the way the organization looks as opposed to the way it works, on the tools it has as opposed to those it actually needs and uses. We thus suggest that research, training and policy-making should stop focusing on the technical features and theoretical virtues of specific tools and should redirect their emphasis on change management.


A comparison of the training value of two types of anesthesia simulators: computer screen-based and mannequin-based simulators.
In this study, we compared two different training simulators (the computer screen-based simulator versus the full-scale simulator) with respect to training effectiveness in anesthesia residents. Participants were evaluated in the management of a simulated preprogrammed scenario of anaphylactic shock using two variables: treatment score and diagnosis time. Our results showed that simulators can contribute significantly to the improvement of performance but that learning in treating simulated crisis situations such as anaphylactic shock did not significantly vary between full-scale and computer screen-based simulators. Consequently, the initial decision on whether to use a full-scale or computer screen-based training simulator should be made on the basis of cost and learning objectives rather than on the basis of technical or fidelity criteria. Our results support the contention that screen-based simulators are good devices to acquire technical skills of crisis management. Mannequin-based simulators would probably provide better training for behavioral aspects of crisis management, such as communication, leadership, and interpersonal conflicts, but this was not tested in the current study. We compared two different training simulators (computer screen-based versus full-scale) for training anesthesia residents to better document the effectiveness of such devices as training tools. This is an important issue, given the extensive use and the high cost of mannequin-based simulators in anesthesiology.


On the Winstein rearrangement: equilibrium and mechanism.
Allylic azides are underutilized in organic synthesis when compared to other organic azides or other allylic functionality. This is likely because allylic azides rearrange at room temperature, resulting in a potentially complex mixture of azides. This rearrangement has been termed the Winstein rearrangement. Understanding the mechanism and basic principles governing the allylic azide equilibrium may aid in developing applications for these molecules based on either alkene or azide functionalization. Presented herein is a compilation of the key observations regarding the nature of the allylic azide rearrangement. Mechanistic considerations are explicitly addressed with key examples from the literature.


Chemistry, Bioactivity, and Prediction of the Quality Marker (Q-Marker) of Ferula Plants in China: A Review.
The genus of Ferula belongs to the family Apiaceae, and many Ferula plants are used as traditional Chinese medicines. Ferula plants were initially identified as early as the "Newly Revised Materia Medica" written in the Tang Dynasty (AD 659), and several of them are also recognized as the traditional medicines of the Uygur, Kazakh, and Mongolian. Ferula plants are distributed in China, Russia, India, Africa, Central Asia, and other places. Currently, the chemical components derived from Ferula plants are mainly coumarins, sesquiterpenes, and volatile oils. Ferula plants can exhibit diverse pharmacological activities such as anti-allergy, analgesia, relieving cough, anticoagulation, and anti-tumor. Therefore, this article summarized the domestic research conducted on the genus Ferula, appropriately combines the research status of the foreign genus Ferula, and describes the chemical composition, biological activity, toxicity issues, and Q-marker prediction. In addition, all the related studies about the genus Ferula are summarized by analyzing the various databases such as CNKI, Wanfang data, PubChem and SciFinder.


[Meta-analysis of the Effects of Metal Mining on Soil Heavy Metal Concentrations in Southwest China].
Metal mining is one of the main contributors of soil heavy metals. Previous studies examining the impact of metal mining on surrounding soil have mainly focused on one or a few metal mining areas. However, such studies cannot effectively inform the management of heavy metal pollution in soil at an inter-provincial scale. As part of this study, literature was collected on soil heavy metals (i.e., As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) affected by metal mining in regions of Southwest China (i.e., Yunnan Province, Sichuan Province, Guizhou Province, Chongqing Municipality, and Tibet Autonomous Region); Next, the impact of metal mining on the soil concentrations of these metals was quantified through meta-analysis, and the relationships between the selected factors (i.e., different sub-regions, metal minerals, and land-use types) and soil heavy metal concentrations were explored. Finally, the literature data was tested for publication bias. The results showed that metal mining in Southwest China has significantly increased the concentrations of heavy metals in topsoil. The different metals were ranked according to their weight effect sizes (ES+) in the following order Cd > Pb > Hg > Zn > As > Cu > Ni > Cr. Metal mining in both Sichuan and Yunnan led to higher effect sizes of soil Cd (ES+Sichuan=4.16, ES+Yunnan=3.20) and Pb (ES+Sichuan=3.47, ES+Yunnan=2.54) than those of the other heavy metals, while metal mining in Guizhou led to a higher effect size of soil Hg (ES+=2.80). The effect size of metal mining on soil heavy metals was higher in cultivated soil (ES+=1.42) than in forested soil (ES+=0.50). The mining of lead-zinc and tin significantly increased the concentrations of soil Cd, Pb, and Zn, and the mining of copper significantly increased the concentrations of soil Cu, Cd, and Pb. Of the investigated soil heavy metals in Southwest China, Pb and Zn showed slight potential publication biases (P<0.05). The above results can provide more effective information for the environmental protection of soil in metal mining areas of Southwest China.


Controlling the Rigidity of Kinesin-Propelled Microtubules in an In Vitro Gliding Assay Using the Deep-Sea Osmolyte Trimethylamine N-Oxide.
The biomolecular motor protein kinesin and its associated filamentous protein microtubule have been finding important nanotechnological applications in the recent years. Rigidity of the microtubules, which are propelled by kinesin motors in an in vitro gliding assay, is an important metric that determines the success of utilization of microtubules and kinesins in various applications, such as transportation, sensing, sorting, molecular robotics, etc. Therefore, regulating the rigidity of kinesin-propelled microtubules has been critical. In this work, we report a simple strategy to regulate the rigidity of kinesin-propelled microtubules in an in vitro gliding assay. We demonstrate that rigidity of the microtubules, propelled by kinesins in an in vitro gliding assay, can be modulated simply by using the natural osmolyte trimethylamine N-oxide (TMAO). By varying the concentration of TMAO in the gliding assay, the rigidity of microtubules can be modulated over a wide range. Based on this strategy, we are able to reduce the persistence length of microtubules, a measure of microtubule rigidity, ∼8 fold by using TMAO at the concentration of 1.5 M. Furthermore, we found that the decreased rigidity of the kinesin-propelled microtubules can be restored upon elimination of TMAO from the in vitro gliding assay. Alteration in the rigidity of microtubules is accounted for by the non-uniformity of the force applied by kinesins along the microtubules in the presence of TMAO. This work offers a facile strategy to reversibly regulate the rigidity of kinesin-propelled microtubules in situ, which would widen the applications of the biomolecular motor kinesin and its associated protein microtubule in various fields.


Cerebrospinal fluid extracellular vesicles undergo age dependent declines and contain known and novel non-coding RNAs.
Brain development requires precise orchestration of cellular events through the coordinate exchange of information between distally located cells. One mechanism by which intercellular communication is achieved is through the transfer of extracellular vesicles (EVs). Exosomes are EVs that carry lipids, nucleic acids, and proteins and are detectable in most biological fluids including cerebrospinal fluid (CSF). Here we report that CSF EV concentrations undergo age dependent fluctuations. We characterized EV RNA content by next generation small RNA sequencing and miRNA microarray analysis and identified a temporal shift in CSF EV content. CSF EVs encapsulated miRNAs that contain a conserved hnRNPA2/B1 recognition sequence. We found that hnRNPA2/B1-containing EVs were produced by choroid plexus epithelial cells and that hnRNPA2/B1 containing EVs decreased with age. These results provide insight into EV exchange of miRNAs within the central nervous system and a framework to understand how changes in EVs may have an important impact on brain development.


Plasma levels of lysine, tyrosine, and valine during pregnancy are independent risk factors of insulin resistance and gestational diabetes.
This study compared plasma concentrations of amino acids in pregnant women with and without gestational diabetes mellitus (GDM) and identified the association between plasma amino acid levels and GDM, insulin resistance, and insulin secretion at 24-28 weeks of pregnancy. Circulating amino acid levels were evaluated using high-performance liquid chromatography at 24-28 weeks of pregnancy in 25 non-GDM and 64 GDM women after adjusting for covariates such as maternal age, body mass index (BMI) before pregnancy, BMI and gestational age at screening GDM, and daily caloric intake. Backward stepwise logistic regression analysis was used to identify the predictors of developing GDM, and homeostatic model assessments for insulin resistance (HOMA-IR) and β-cell function (HOMA-B). Circulating levels of amino acids except threonine and tyrosine were significantly higher in GDM women than non-GDM women. Along with the intakes of energy, protein, and fat from animal sources, the intakes of each amino acid were significantly higher in the GDM group without a direct correlation to plasma amino acid levels. The variation in GDM development was explained by maternal age, diastolic blood pressure, and plasma lysine levels (R(2)=0.691). Height, BMI before pregnancy, systolic blood pressure, and plasma tyrosine and valine levels accounted for the variation in HOMA-IR (R(2)=0.589). The 53.3% variation of HOMA-B was explained by maternal age, BMI at GDM screening, plasma insulin level at 1 h during the oral glucose tolerance test (OGTT), and plasma valine level. Circulating concentrations of lysine, tyrosine, and valine were independently and positively associated with GDM through modifying insulin resistance and secretion.


Efficacy of flow- vs impedance-guided autoadjustable continuous positive airway pressure: a randomized cross-over trial.
Autoadjustable continuous positive airway pressure (CPAP) devices are increasingly used in the treatment of obstructive sleep apnea (OSA). Since different measurements of upper airway obstruction are applied, it is uncertain whether these devices are equally effective in controlling sleep-disordered breathing. Hypothesizing that differences in therapeutic efficacy were to come out, we compared the performance of the AutoSet device (ResMed; Sydney, Australia), which features autoadjustable positive airway pressure (APAP) guided by detection of flow limitation (APAPfl), with the SOMNOsmart device (Weinmann; Hamburg, Germany), which features APAP guided by the forced oscillation technique (APAPfot). A double-blind, randomized, cross-over trial. The sleep disorders center and sleep laboratory of a university hospital. An overnight CPAP autotitration procedure was performed in 30 patients with OSA. A split-night protocol allowed that each patient used both devices. Using polysomnography, sleep, indexes of sleep-disordered breathing, snoring, and CPAP levels were recorded. No significant differences were found in conventional sleep variables. While the apnea-hypopnea index (AHI) was lower with APAPfl (3.5 +/- 5.6/h) as compared to APAPfot (9.9 +/- 31.0/h), the difference was not statistically significant (mean +/- SD). The snoring index, however, was significantly lower with APAPfl (35.3 +/- 53.7/h vs 111.6 +/- 175.4/h, respectively; p = 0.01). The median and 95th percentile pressure levels rose from wakefulness to sleep in APAPfl, but decreased in APAPfot. Higher pressure variability was present in the latter method. These findings suggest that the APAPfl is superior to APAPfot in the control of snoring. While a lower AHI was achieved with APAPfl, at the expense of a higher median pressure but less pressure variability, the difference with APAPfot was not statistically significant.


Caries risk in children: determined by levels of mutans streptococci and Lactobaccilus.
Lactobacullus sp. and S. mutans are microorganisms with cariogenic capacity, however, their presence do not determine the presence of dental caries. We evaluated the relationship between the presence of Lactobacillus sp. and S. mutans and dental caries in a schoolchildren population. The relation PI-DMFT have a value of significance p = 0.001489. In dental caries risk evaluation, the S. mutans and Lactobacillus sp. detection in saliva is a good predictor and contributing to the caries development.


Effects of metabolic traits, lifestyle factors, and pharmacological interventions on liver fat: mendelian randomisation study.
To investigate the effects of metabolic traits, lifestyle factors, and drug interventions on liver fat using the mendelian randomisation paradigm. Mendelian randomisation study. Publicly available summary level data from genome-wide association studies. Genome-wide association studies of 32 974 to 1 407 282 individuals who were predominantly of European descent. Genetic variants predicting nine metabolic traits, six lifestyle factors, four lipid lowering drug targets, three antihypertensive drug targets, and genetic association estimates formagnetic resonance imaging measured liver fat. Mendelian randomisation analysis was used to investigate the effects of these exposures on liver fat, incorporating sensitivity analyses that relaxed the requisite modelling assumptions. Genetically predicted liability to obesity, type 2 diabetes, elevated blood pressure, elevated triglyceride levels, cigarette smoking, and sedentary time watching television were associated with higher levels of liver fat. Genetically predicted lipid lowering drug effects were not associated with liver fat; however, β blocker and calcium channel blocker antihypertensive drug effects were associated with lower levels of liver fat. These analyses provide evidence of a causal effect of various metabolic traits, lifestyle factors, and drug targets on liver fat. The findings complement existing epidemiological associations, further provide mechanistic insight, and potentially supports a role for drug interventions in reducing the burden of hepatic steatosis and related disease. Further clinical study is now warranted to investigate the relevance of these genetic analyses for patient care.


Anomalous temperature dependence of nuclear quadrupole interactions in strongly hydrogen-bonded systems from first principles.
We present an analysis of the effect of finite temperatures on the deuteron nuclear quadrupole coupling constants in a strongly hydrogen-bonded molecular crystal by means of first-principles Car-Parrinello molecular-dynamics simulations. Our findings agree well with experiments and provide a microscopic explanation of the anomalous increase of the quadrupole coupling in this class of systems. We show that a simple model based on the anharmonicity of the hydrogen bond potential fails to describe the temperature dependence of the couplings even qualitatively. Instead, the inclusion of fluctuations and disorder in terms of atomic motion of the surrounding molecules turns out to be important to obtain the correct magnitude of the temperature effect.


Of mice and men: a novel dietary supplement for the treatment of ulcerative colitis.
Curcumin, green tea polyphenols and selenium possess anti-inflammatory and anti-oxidant properties. Individually they have demonstrated some efficacy in animal models and human subjects with inflammatory bowel disease (IBD). To evaluate the efficacy and safety of Coltect [Curcumin (500 mg), green tea (250 mg) and selenium (100 µg)] in vivo and in patients with ulcerative colitis (UC). Each component was compared to placebo in a DSS mice colitis model. The efficacy was validated in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) rat colitis model. Twenty patients with mild-to-moderate UC received two Coltect tablets twice daily for 8 weeks. Enrollees underwent sigmoidoscopy at study entrance and closure, and physical and laboratory evaluation at baseline, 4 and 8 weeks. Coltect showed a synergistic therapeutic effect in the DSS and TNBS models. Disease activity was significantly higher in the placebo versus the treated group (p < 0.05). Selenium was the more active component. The contribution of green tea was minor. In the TNBS model, the Wallace scores for macroscopic lesions were 4.8 ± 1.5 (treatment) and 8.2 ± 0.5 (placebo) (p = 0.01). In humans, Coltect was well tolerated and effective. Fourteen subjects (70%) improved: nine (45%) went into complete remission, four (20%) experienced marked improvement and one (5%) experienced moderate improvement at the end of the trial. Clinical activity index decreased significantly at 4 and 8 weeks (p < 0.001). Two patients had no change in their symptoms, and one withdrew after 4 weeks. Flare-up in four subjects caused three to withdraw from the study after less than 4 weeks. Endoscopic improvement was observed in 11 (69%) patients, and four patients (25%) achieved complete remission. Coltect may serve as a first-line or add-on therapy in patients with mild-to-moderate UC.


[Community structure of soil meso- and micro-fauna in different habitats of urbanized region].
Investigations were made in May, June, and November 2007 and January 2008 to study the structural characteristics and their seasonal variations of soil meso- and micro-fauna communities in six habitats of three land use types (forest land, constructed grassland and farmland) in Tianhe District of Guangzhou City. The horizontal spatial distribution of soil fauna differed with habitat. During the investigation periods, the Botanical Garden of South China Agricultural University had the highest individual number (1286) of soil mesa- and micro-fauna, while the farmland, especially in the Fenghuang Street area, had the lowest number of individuals and groups. The seasonal variation of the individual number was in order of autumn (1815) > spring (1623) > winter (1365) > summer (1276). Hierarchical clustering and detrended correspondence analysis also showed that the community composition of soil meso- and micro-fauna in different habitats exhibited distinct seasonal variation. In the same seasons, the community structure and composition of soil meso- and micro-fauna in different habitats were correlated to the degrees of human interferences and the properties of soil environment.


Prediction of time-integrated activity coefficients in PRRT using simulated dynamic PET and a pharmacokinetic model.
To investigate the accuracy of predicted time-integrated activity coefficients (TIACs) in peptide-receptor radionuclide therapy (PRRT) using simulated dynamic PET data and a physiologically based pharmacokinetic (PBPK) model. PBPK parameters were estimated using biokinetic data of 15 patients after injection of (152±15)MBq of 111In-DTPAOC (total peptide amount (5.78±0.25)nmol). True mathematical phantoms of patients (MPPs) were the PBPK model with the estimated parameters. Dynamic PET measurements were simulated as being done after bolus injection of 150MBq 68Ga-DOTATATE using the true MPPs. Dynamic PET scans around 35min p.i. (P1), 4h p.i. (P2) and the combination of P1 and P2 (P3) were simulated. Each measurement was simulated with four frames of 5min each and 2 bed positions. PBPK parameters were fitted to the PET data to derive the PET-predicted MPPs. Therapy was simulated assuming an infusion of 5.1GBq of 90Y-DOTATATE over 30min in both true and PET-predicted MPPs. TIACs of simulated therapy were calculated, true MPPs (true TIACs) and predicted MPPs (predicted TIACs) followed by the calculation of variabilities v. For P1 and P2 the population variabilities of kidneys, liver and spleen were acceptable (v<10%). For the tumours and the remainders, the values were large (up to 25%). For P3, population variabilities for all organs including the remainder further improved, except that of the tumour (v>10%). Treatment planning of PRRT based on dynamic PET data seems possible for the kidneys, liver and spleen using a PBPK model and patient specific information.


Non-diagnostic based approaches to helping children who could be labelled ADHD and their families.
Mental health services are not always good for you. There are some troubling facts to confront such as the increase in the use of diagnostic based approaches and psychotropic medications for children and young people being associated with poorer rather than better outcomes. In this article I will outline some of the evidence around outcome as a result of treatment for young people diagnosed with attention deficit hyperactivity disorder (ADHD) and for those who are prescribed long-term stimulants. I will then discuss clinical approaches that move beyond a focus on symptom management that diagnostic paradigms encourage. This includes clinical models that take account of the diversity of contextual and relational issues that young patients present with and the possibility afforded of engaging in more positive and hopeful therapeutic approaches such as the Relational Awareness Programme (RAP).


Revisiting the conformational state of albumin conjugated to gold nanoclusters: A self-assembly pathway to giant superstructures unraveled.
Bovine serum albumin (BSA) is often employed as a proteinaceous component for synthesis of luminescent protein-stabilized gold nanoclusters (AuNC): intriguing systems with many potential applications. Typically, the formation of BSA-AuNC conjugate occurs under strongly alkaline conditions. Due to the sheer complexity of intertwined chemical and structural transitions taking place upon BSA-AuNC formation, the state of albumin enveloping AuNCs remains poorly characterized. Here, we study the conformational properties of BSA bound to AuNCs using an array of biophysical tools including vibrational spectroscopy, circular dichroism, fluorescence spectroscopy and trypsin digestion. The alkaline conditions of BSA-AuNC self-assembly appear to be primary responsible for the profound irreversible disruption of tertiary contacts, partial unfolding of native α-helices, hydrolysis of disulfide bonds and the protein becoming vulnerable to trypsin digestion. Further unfolding of BSA-AuNC by guanidinium hydrochloride (GdnHCl) is fully reversible equally in terms of albumin's secondary structure and conjugate's luminescent properties. This suggests that binding to AuNCs traps the albumin molecule in a state that is both partly disordered and refractory to irreversible misfolding. Indeed, when BSA-AuNC is subjected to conditions favoring self-association of BSA into amyloid-like fibrils, the buildup of non-native β-sheet conformation is less pronounced than in a control experiment with unmodified BSA. Unexpectedly, BSA-AuNC reveals a tendency to self-assemble into giant twisted superstructures of micrometer lengths detectable with transmission electron microscopy (TEM), a property absent in unmodified BSA. The process is accompanied by ordering of bound AuNCs into elongated streaks and simultaneous decrease in fluorescence intensity. The newly discovered self-association pathway appears to be specifically accessible to protein molecules with a certain restriction on structural dynamics which in the case of BSA-AuNC arises from binding to metal nanoclusters. Our results have been discussed in the context of mechanisms of protein misfolding and applications of BSA-AuNC.


Situational optimization function analysis: An ideal performance analysis inspired on Lewin's equation.
This study presents the situational optimization function analysis (SOFA) and has three aims. First, to develop a Bayesian implementation of SOFA. Second, to compare this implementation with three other maximum likelihood-based models in their accuracy to estimate true scores. The third aim is to show how joint modeling can be used for validity research. A simulation study was used to examine the second aim, while an empirical example was used to illustrate the third aim. The simulation study used three data generating processes, with varying degrees of deviation from linear models and with different sample sizes. Results of the simulation study showed that the Bayesian implementation supersedes the other models. In the empirical example, data collected from 66 participants using an iterated prisoner dilemma and a scale measuring cooperation-competition attitudes were used. Results showed that joint modeling is the best fitting model, also increasing the correlation between the true scores of both measures (deviations from the iterated prisoner dilemma and the scale). Finally, implications, limitations and future studies are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Diseases of the generative nail apparatus. Part I: Nail matrix.
Disorders of the generative structures of the nail produce a characteristic set of outcomes. The matrix is the seat of nail development and diseases or insults of this germinative epithelium will tell a story in the signs that unfold in the ensuing nail growth. This story will be influenced by the intensity, duration and extent of this pathology. A method of categorizing changes associated with the generative matrix of the nail will be presented.


Outcomes of large colorectal polyp endoscopic resections during small audience live endoscopy events with endoscopist at their home endoscopy unit.
Background and study aims Live endoscopy courses are popular. The safety of performing live endoscopy has been questioned. In this study, we compared outcomes of large colorectal polyp resections during live endoscopy events (LEEs) (with a small audience of 2 to 5 physicians) to those removed during standard procedure days (SPDs) (without an audience). All procedures were performed at the endoscopist's home unit. Methods Retrospective assessment of the adverse event (AE) and recurrence rates for large ( ≥ 20 mm) non-pedunculated colorectal lesions removed during LEEs. Logistic regression was used to assess whether presence of an audience predicted worse outcomes. Results From January 2017 to May 2021, 317 lesions were removed with a live audience and 866 were removed on SPDs. Polyp pathology and procedure length were similar in both groups. There were 16 (5.0 %) total adverse events in the LEE group and 30 (3.4 %) in the SPD group ( P = 0.224). The majority in both groups were delayed hemorrhage. There were 2 (0.6 %) perforations in the LEE and 3 (0.3 %) in the SPD group. Increasing polyp size was associated with more AEs and higher recurrence. Increasing patient age predicted higher recurrence, and thermal injury of the resection margin predicted lower recurrence. There were no other predictors of AEs or recurrence, including presence of a live audience. Conclusions Removing large colorectal polyps with a small live audience did not increase adverse outcomes.


Excitonic absorption spectra in graphene nanoflakes: Tuning of exciton binding energy by dielectric environments.
By solving the Bethe-Salpeter equation within the Hartree-Fock formalism, we study the excitonic absorption spectra of graphene nanoflakes embedded in various dielectric environments. With the excitonic effects fully taken into account, the exciton binding energy as a function of the dielectric constant is found to be well described by a single scaling rule in which the scaling factor is found to vary slowly with the size of the nanoflakes. Furthermore, it is revealed that the exciton binding energy scales almost linearly with the on-site interaction energy and exhibits more sensitive dependence in smaller nanoflakes. Our results are found to agree well with the recent experiment.


Interactions between splanchnic and vagus nerves in the control of mean intragastric pressure in the ferret.
To determine whether splanchnic nerves relax the stomach by direct or indirect mechanisms, ramp inflations of the stomach, section and electrical stimulation of the vagus and greater splanchnic nerves, and step inflations of the duodenum were used. A high threshold, sustained inhibition of the gastric pressure response to ramp inflation was mediated by the vagus. Prior splanchnectomy increased vagal inhibition. The greater splanchnic nerves had no effect on gastric responses to inflation, although after vagotomy they were shown to be mediators of a low threshold, powerful but transient inhibition of the stomach. This was not dependent on intrinsic neurones with nicotinic receptors. Electrical stimulation of the greater splanchnic nerves produced a relaxation of the stomach, the magnitude of which was determined by resting pressure. Splanchnically mediated relaxation was not abolished by atropine, nor was it reduced by concurrent vagal stimulation. At submaximal levels of vagal stimulation the two nerves had a partially additive effective on relaxation. Duodenal inflation had an effect on intracorpus pressure similar to that of electrical stimulation of the greater splanchnic nerves on intragastric pressure. Reflex relaxation of the corpus evoked by duodenal distension was decreased by atropine but greatly increased by atropine coupled with vagotomy. These changes were caused by variations in resting pressure. It was concluded that the principal effect of splanchnic nerves on mean gastric pressure is direct and does not depend on inhibition of cholinergic neurones either centrally or peripherally. Evidence is presented for central interactions between the vagus and the greater splanchnic nerves in the anaesthetized ferret.


Chemical matrixectomy for ingrown toenails: Is there an evidence basis to guide therapy?
Chemical matrixectomy for ingrown toenails is one of the most common surgical procedures performed on the foot. The procedure was first described in 1945 by Otto Boll, who discussed the use of phenol to correct ingrown toenails. In the years that followed, many variations of technique and method have been described. This article reviews the pertinent literature detailing chemical matrixectomies and advocates the use of an evidence basis for care.


Erectile dysfunction post-radical prostatectomy - a challenge for both patient and physician.
Post-radical prostatectomy erectile dysfunction (post RP ED) is a major postoperative complication with a great impact on the quality of life of the patients. Until present, no proper algorithm or guideline based on the clinical trials has been established for the management of post RP ED. According to literature, it is better to initiate a penile rehabilitation program as soon as possible after surgery than doing nothing, in order to prevent and limit the postoperative local hypoxygenation and fibrosis. The results of numerous clinical trials regarding the effectiveness of the phosphodiesterase 5 inhibitors therapy on post RP ED have made them the gold standard treatment. Encouraging results have been achieved in studies with vacuum erectile devices, intraurethral suppositories with alprostadil and intracavernosal injections, but due to their side effects, especially in the cases of intracavernosal injections and intraurethral suppositories, their clinical use was limited therefore making them a second line option for the post RP ED treatment. What should not be forgotten is that penile implant prosthesis has proven very effective, numerous studies confirming high rates of satisfaction for both patients and partners.


Clinical use of sensory gardens and outdoor environments in norwegian nursing homes: a cross-sectional e-mail survey.
Gardens and outdoor environments offer multiple therapeutic possibilities for the residents in nursing homes. Web-based questionnaires were sent to 488 nursing home leaders and 121 leaders responded. The clinical impressions of the leaders and staff regarding the benefits of sensory gardens (SGs) to the residents were consistent with previous research. SGs facilitated taking residents outdoors, offered convenient topics for communication and facilitated social privacy for relatives. For improved clinical use of SGs and outdoor environments, systematic assessment of residents' interests, performance and experiences when outdoors, implementation of seasonal clinical programmes and educational programmes for leaders and staff are recommended.


[Effects of topically applied bunazosin hydrochloride on choroidal capillary blood flow and intraocular pressure of rabbit eye].
The effects of topically applied bunazosin hydrochloride, a selective alpha 1 blocker under development as a drug to treat glaucoma, were studied in regard to the choroidal capillary blood flow, intraocular pressure (IOP), and blood pressure in albino rabbit eyes in comparison with propranolol hydrochloride, a non-selective beta blocker. The capillary blood flow was measured using a thermal diffusion flowmeter. Single instillations (50 ul) of 0.005% bunazosin hydrochloride, lowered the IOP to almost the same degree as did 1.0% propranolol hydrochloride. The maximum decreases from initial IOP were 3.3 +/- 1.2, 3.6 +/- 1.7 mmHg for bunazosin hydrochloride and propranolol hydrochloride, respectively. No significant effect on mean blood pressure was observed with these instillations. The choroidal capillary blood flow was reduced by propranolol hydrochloride for 3 hours after instillation (maximum rate of decrease was 10.0 +/- 4.6%), while it was increased by bunazosin hydrochloride for 150 min. (maximum rate of increase was 8.3 +/- 3.8%). When phenylephrine hydrochloride (0.5%), an alpha 1 agonist, was instilled with bunazosin hydrochloride (0.005%), the choroidal capillary blood flow showed no significant change. This was felt to imply an action mechanism involving the alpha 1 receptor.


Enzymatic conversion of atmospheric aldehydes into alcohol in a phospholipid polymer film.
We developed a unique method for converting atmospheric aldehyde into alcohol using formaldehyde dehydrogenase from Pseudomonas putida (PFDH) doped in a polymer film. A film of poly(2-methacryloyloxyethylphosphorylcholine-co-n-butyl methacrylate) (PMB), which has a chemical structure similar to that of a biological membrane, was employed for its biocompatibility. A water-incorporated polymer film entrapping PFDH and its cofactor NAD(+) was obtained by drying a buffered solution of PMB, PFDH, and NAD(+). The aldehydes in the air were absorbed into the polymer film and then enzymatically oxidized by PFDH doped in the PMB film. Interestingly, alcohol and carboxylic acid were produced by the enzymatic reaction, indicating that PFDH catalyzes dismutation of aldehyde in the PMB film. Importantly, a PFDH-PMB film catalyzes aldehyde degradation without consuming the nucleotide cofactor, thereby allowing repeated use of the film. The activity of PFDH in the PMB film was higher than that in other common water-soluble polymers, suggesting that the hydrational state in a phospholipid polymer matrix is suitable for enzymatic activity.


Nanosystems based on siRNA silencing HuR expression counteract diabetic retinopathy in rat.
We evaluated whether specifically and directly targeting human antigen R (HuR), a member of embryonic lethal abnormal vision (ELAV) proteins family, may represent a new potential therapeutic strategy to manage diabetic retinopathy. Nanosystems loaded with siRNA silencing HuR expression (lipoplexes), consisting of solid lipid nanoparticles (SLN) and liposomes (SUV) were prepared. Photon correlation spectroscopy analysis, Zeta potential measurement and atomic force microscopy (AFM) studies were carried out to characterize the complexation of siRNA with the lipid nanocarriers. Nanosystems were evaluated by using AFM and scanning electron microscopy. The lipoplexes were injected into the eye of streptozotocin (STZ)-induced diabetic rats. Retinal HuR and VEGF levels were detected by Western blot and ELISA, respectively. Retinal histology was also carried out. The results demonstrated that retinal HuR and VEGF are significantly increased in STZ-rats and are blunted by HuR siRNA treatment. Lipoplexes with a weak positive surface charge and with a 4:1 N/P (cationic lipid nitrogen to siRNA phosphate) ratio exert a better transfection efficiency, significantly dumping retinal HuR and VEGF levels. In conclusion, we demonstrated that siRNA can be efficiently delivered into the rat retina using lipid-based nanocarriers, and some of the lipoplexes loaded with siRNA silencing HuR expression are potential candidates to manage retinal diseases.


Response to crizotinib in a lung adenocarcinoma patient harboring EML4-ALK translocation with adnexal metastasis: A Case Report.
Lung cancer with ovarian metastasis or adnexal metastasis harboring anaplastic lymphoma kinase (ALK) gene translocation is rare. Crizotinib, a novel ALK tyrosine kinase inhibitor, has already shown an impressive single-agent activity in ALK positive lung cancer. To summarize the case of clinical data and treatment of a 33-year-old woman with pelvic adnexal metastasis NSCLC. Histological examination of the tumors showed lung adenocarcinoma. The right lung biopsy tissue and left adnexal mass biopsy tissue both revealed the presence of an ALK rearrangement by Ventana (D5F3) ALK immunohistochemistry assay (Ventana Medical Systems, Roche, Inc., Tuscon, AZ). The patient experienced a remarkable tumor response to crizotinib treatment. Although the adnexal location is an uncommon metastasis site from lung cancer, oncologists should be aware of the possibility of such metastasis for female patients with ALK rearrangement NSCLC. Considering this remarkable response, we conclude that the presence of adnexal metastasis in NSCLC patients with ALK rearrangement should be attentive.


Automated ribotyping, a rapid typing method for analysis of Erysipelothrix spp. strains.
Automated ribotyping classified 70 Erysipelothrix species strains, previously classified into 14 RAPD patterns and into 63 PFGE patterns, into 27 ribogroups. Twenty-three strains of the 70 analyzed and classified into 13 ribogroups were previously classified into six ribotypes by the traditional ribotyping method. Moreover, automated ribotyping differentiated seven strains that were not differentiated by PFGE. Therefore, automated ribotyping was more sensitive than RAPD and traditional ribotyping, and it might be a useful method for a rapid screening in epidemiological study of strains of this genus, and more accurate results can be obtained when this method is used together with PFGE.


Theory of lethal mutagenesis for viruses.
Mutation is the basis of adaptation. Yet, most mutations are detrimental, and elevating mutation rates will impair a population's fitness in the short term. The latter realization has led to the concept of lethal mutagenesis for curing viral infections, and work with drugs such as ribavirin has supported this perspective. As yet, there is no formal theory of lethal mutagenesis, although reference is commonly made to Eigen's error catastrophe theory. Here, we propose a theory of lethal mutagenesis. With an obvious parallel to the epidemiological threshold for eradication of a disease, a sufficient condition for lethal mutagenesis is that each viral genotype produces, on average, less than one progeny virus that goes on to infect a new cell. The extinction threshold involves an evolutionary component based on the mutation rate, but it also includes an ecological component, so the threshold cannot be calculated from the mutation rate alone. The genetic evolution of a large population undergoing mutagenesis is independent of whether the population is declining or stable, so there is no runaway accumulation of mutations or genetic signature for lethal mutagenesis that distinguishes it from a level of mutagenesis under which the population is maintained. To detect lethal mutagenesis, accurate measurements of the genome-wide mutation rate and the number of progeny per infected cell that go on to infect new cells are needed. We discuss three methods for estimating the former. Estimating the latter is more challenging, but broad limits to this estimate may be feasible.


RAPD analysis and sequencing of ITS1/5.8S rRNA/ITS2 and Fe-hydrogenase as tools for genetic classification of potentially pathogenic isolates of Trichomonas gallinae.
Trichomonas gallinae is a worldwide parasite that causes oropharyngeal avian trichomonosis. During eight years, 60 axenic isolates were obtained from different bird species and characterized by three molecular methods: RAPD analysis and PCR-sequencing of ITS1/5.8S rRNA/ITS2 fragment and Fe-hydrogenase gene. We have found two genotypes of ITS1/5.8S rRNA/ITS2 widely distributed among bird populations, a new variant and also two sequences with mixed pattern. Genotype ITS-OBT-Tg-1 was associated with the presence of gross lesions in birds. We have found eight genotypes of the Fe-hydrogenase (A1, A2, C2, C2.1, C4, C5, C6 and C7), three of them are new reports (C5, C6 and C7), and also three sequences with mixed pattern. Subtype A1 of the Fe-hydrogenase was also related with the presence of lesions. RAPD analyses included most of the strains isolated from animals with lesions in one of the sub-clusters. Potentially pathogenic isolates of T. gallinae obtained in this study fulfill the following criteria with one exception: isolated from lesions+ITS-OBT-Tg-1 genotype+FeHyd A1+RAPD sub-cluster I2.


Silylcyclopropanes by Selective [1,4]-Wittig Rearrangement of 4-Silyl-5,6-dihydropyrans.
4-Silyl-5,6-dihydropyrans undergo remarkably selective [1,4]-Wittig rearrangements to give silylcyclopropanes in good yields. The selectivity is independent of the silyl group, but it is influenced by the electronic character of the migrating center. Electron-rich and electron-neutral (hetero)aryl groups and aliphatic substituents at the migrating center lead to exclusive [1,4]-migration, whereas electron-deficient aryl groups predominantly afford [1,2]-Wittig products.


IgA nephropathy: common nephritis leading to end-stage renal failure.
IgA nephropathy (IgAN) characterized by mesangial proliferative glomerulonephritis with predominant mesangial IgA deposition is the commonest glomerulonephritis worldwide. In contrast to the initial report indicated a favorable prognosis, subsequent reports have shown a highly variable outcome leading to end-stage renal failure (ESRF) in a significant proportion of patients. Many centers report a high incidence (ranging from 10-22%) of patients with idiopathic IgAN amongst the total population of patients on maintenance dialysis. Most of these patients develop ESRF at their middle-age and hence, will pose a significant and important workload in the dialysis and transplantation programme. Because IgAN is a disease with a variable rate of progression leading to chronic renal failure amongst younger patients and with neither effective nor specific treatment, identification of the clinical and pathologic prognostic indicators for these patients is of paramount importance in planning the long-term renal replacement program.


Lack of association between gene polymorphism of transporters associated with antigen processing and allergic rhinitis in a Japanese population.
Gene products of TAP1 and TAP2 (transporters associated with antigen processing) are involved in antigen presentation. It has been reported that polymorphisms in the TAP1 gene are associated with atopy in Tunisians. We designed a case-control study to investigate the potential association of polymorphisms of the TAP1 gene with allergic rhinitis in a Japanese population. We used the amplification refractory mutation system polymerase chain reaction to characterize TAP1 gene polymorphisms in 60 unrelated Japanese patients with allergic rhinitis and 62 healthy control subjects. There was no significant difference in the distribution of TAP1 alleles between the patient group and the control group. These findings suggest that the TAP1 gene is not primarily involved in susceptibility to allergic rhinitis in the Japanese population.


Does the evidence about health risks associated with nitrate ingestion warrant an increase of the nitrate standard for drinking water?
Several authors have suggested that it is safe to raise the health standard for nitrate in drinking water, and save money on measures associated with nitrate pollution of drinking water resources. The major argument has been that the epidemiologic evidence for acute and chronic health effects related to drinking water nitrate at concentrations near the health standard is inconclusive. With respect to the chronic effects, the argument was motivated by the absence of evidence for adverse health effects related to ingestion of nitrate from dietary sources. An interdisciplinary discussion of these arguments led to three important observations. First, there have been only a few well-designed epidemiologic studies that evaluated ingestion of nitrate in drinking water and risk of specific cancers or adverse reproductive outcomes among potentially susceptible subgroups likely to have elevated endogenous nitrosation. Positive associations have been observed for some but not all health outcomes evaluated. Second, the epidemiologic studies of cancer do not support an association between ingestion of dietary nitrate (vegetables) and an increased risk of cancer, because intake of dietary nitrate is associated with intake of antioxidants and other beneficial phytochemicals. Third, 2-3 % of the population in Western Europe and the US could be exposed to nitrate levels in drinking water exceeding the WHO standard of 50 mg/l nitrate, particularly those living in rural areas. The health losses due to this exposure cannot be estimated. Therefore, we conclude that it is not possible to weigh the costs and benefits from changing the nitrate standard for drinking water and groundwater resources by considering the potential consequences for human health and by considering the potential savings due to reduced costs for nitrate removal and prevention of nitrate pollution.


Pivoting a Community-Based Participatory Research Project for Mental Health and Immigrant Youth in Philadelphia During COVID-19.
Research has documented the need for mental health services among refugee and immigrant youth. A joint collaboration on a community-based participatory research (CBPR) research project between a university, a local art and health collective, and an immigrant and refugee organization sought to identify and understand the mental health needs and strategies for immigrant youth in Philadelphia through youth discussion and engagement in a variety of art workshops. As a result of the COVID-19 pandemic, this CBPR research project was forced to make several programmatic changes, such as shifting to a virtual setting, that impacted project implementation and intended outcomes. These changes highlight valuable lessons and practical implications in pivoting a program during COVID-19 to continue working with marginalized communities with limited resources, including barriers to technology access, at a time when effectively addressing mental health for immigrant youth has become both more challenging and pressing.


Aortic root reoperation: a technical challenge.
It is well known that aortic root re-replacement presents a formidable technical challenge. Thus, the study aim was to describe the authors' experience with this high-risk cohort. Between August 1996 and January 2009, a total of 26 patients (mean age 51 years; range: 16-72 years) underwent aortic root re-replacement surgery at the authors' institution. Previous aortic root operations included mechanical valved conduit (n = 9), tissue valved conduit (n = 5), Ross procedure (n = 4), homograft (n = 4), David procedure (n = 2) and Yacoub procedure (n = 2). The indications for surgery included endocarditis (n = 16), Ross procedure failure (n = 4), valve degeneration (n = 3), anastomotic aneurysm (n = 2), and severe valve insufficiency (n = 1). The reoperations performed were classified as follows: aortic homograft (n = 11), mechanical conduit (n = 9), tissue valved conduit (n = 4) and David procedure (n = 2). The mean cardiopulmonary bypass time was 219 min (range: 101-398 min), and the mean cross-clamp time 142 min (range: 89-253 min). The mean ICU stay was 8 days (range: 1-45 days), and the mean hospital stay 20 days (range: 3-64 days). Four rethoracotomies were performed for postoperative bleeding or tamponade (14%). Two patients (8%) died within 30 days of surgery, and three (12%) required pacemaker implantation due to atrioventricular block (grade III). Aortic root reoperation, even in the setting of endocarditis, can be carried out with excellent results. The major goals of this concept include a clinical examination and preoperative diagnosis, in addition to computed tomography to identify possible pitfalls during re-sternotomy. Care must also be taken to provide adequate myocardial and organ protection, by utilizing blood cardioplegia and individual selective perfusion techniques.


[Mortality study of residents of the municipality of Piazzola sul Brenta (Veneto Region, Northern Italy), 2003-2018].
Currently, there are more and more requests for a characterization of the health profile by populations living in areas affected by several types of environmental contaminations, notably for the presence of previously unknown and accidentally discovered landfills. The aim of the present paper is to describe the mortality profile of the residents of Piazzola sul Brenta (Veneto Region, Northern Italy). In this area, it was discovered an environmental contamination of the soil in the nearby of a large school building, where was formerly located a phosphate fertiliser plant. Using cause of death data provided by the Italian National Institute of Health, 10th International Classification 2013-2018, standardised mortality ratios (SMRs) and 90% confidence intervals (CIs) were calculated by gender and specific causes of death. Compared to the provincial reference population, no excess was found, for both genders, for all-causes mortality and for circulatory diseases. However, an excess for malignant tumours was found, 523 observed deaths over 498 expected deaths, an SMR of 105 (IC90% 98-113), and 85% probability of excess cancer mortality; lung cancer (SMR 117; IC90% 100-135) and lympho-hematopoietic tumours (in men only, SMR 134; IC90% 101-178).In light of these results and of the potential human exposure to carcinogenic substances, present results support further epidemiological investigations and environmental remediation.


Excellent Repigmentation of Generalized Vitiligo with Oral Baricitinib Combined with NB-UVB Phototherapy.
Vitiligo is an acquired autoimmune skin disorder, clinically characterized by distinct white macules and patches resulting from progressive melanocyte destruction. JAK-STAT pathway plays an important role in the loss of epidermal melanocytes. Baricitinib can block the JAK-STAT pathway and the downstream chemokines as a new JAK1/2 inhibitor. In this report, we describe the successful treatment of 2 patients with oral baricitinib combined with NB-UVB phototherapy, which provides a good alternative and supplementary to treat refractory vitiligo.


P2Y2 Receptors Mediate Masseter Muscle Mechanical Hypersensitivity in Rats.
P2Y2 receptors (P2Y2Rs) are among the various receptors that play an important role in nociception. The goal of this research was to investigate possible P2Y2R expression changes in the trigeminal ganglion (TRG) in bilateral masseter muscle (MM) hypersensitivity following unilateral MM inflammation. The impact of unilateral intramasseteric administration of P2Y2R antagonist on bilateral MM hypersensitivity was also explored. Bilateral MM hypersensitivity was provoked by unilateral intramasseteric injection of complete Freund's adjuvant (CFA). The head withdrawal threshold (HWT) was assessed bilaterally 4 days later. Bilateral TRG and MM isolation were followed, and quantitative real-time polymerase chain reaction (qRT-PCR) and histopathological analysis were carried out on these tissues, respectively. The involvement of P2Y2Rs in nocifensive behavior was evaluated by administering two doses of P2Y2R antagonist AR-C118925 (0.2 or 1 mg/100 μL) in inflamed MM 4 days post-CFA administration. Bilateral HWT was assessed at different time points following antagonist injection. qRT-PCR analysis demonstrated P2Y2R up-regulation in TRG ipsilateral to the site of CFA administration. Compared to the controls, both doses of AR-C118925 injected ipsilateral to the TRG increased the bilateral HWT at 30, 60, 90, and 120 minutes after antagonist administration. The findings suggest that P2Y2Rs may affect MM inflammatory hypersensitivity owing to its up-regulation in the TRG in MM inflammatory pain states.


Tox21Enricher-Shiny: an R Shiny application for toxicity functional annotation analysis.
Inference of toxicological and mechanistic properties of untested chemicals through structural or biological similarity is a commonly employed approach for initial chemical characterization and hypothesis generation. We previously developed a web-based application, Tox21Enricher-Grails, on the Grails framework that identifies enriched biological/toxicological properties of chemical sets for the purpose of inferring properties of untested chemicals within the set. It was able to detect significantly overrepresented biological (e.g., receptor binding), toxicological (e.g., carcinogenicity), and chemical (e.g., toxicologically relevant chemical substructures) annotations within sets of chemicals screened in the Tox21 platform. Here, we present an R Shiny application version of Tox21Enricher-Grails, Tox21Enricher-Shiny, with more robust features and updated annotations. Tox21Enricher-Shiny allows users to interact with the web application component (available at http://hurlab.med.und.edu/Tox21Enricher/) through a user-friendly graphical user interface or to directly access the application's functions through an application programming interface. This version now supports InChI strings as input in addition to CASRN and SMILES identifiers. Input chemicals that contain certain reactive functional groups (nitrile, aldehyde, epoxide, and isocyanate groups) may react with proteins in cell-based Tox21 assays: this could cause Tox21Enricher-Shiny to produce spurious enrichment analysis results. Therefore, this version of the application can now automatically detect and ignore such problematic chemicals in a user's input. The application also offers new data visualizations, and the architecture has been greatly simplified to allow for simple deployment, version control, and porting. The application may be deployed onto a Posit Connect or Shiny server, and it uses Postgres for database management. As other Tox21-related tools are being migrated to the R Shiny platform, the development of Tox21Enricher-Shiny is a logical transition to use R's strong data analysis and visualization capacities and to provide aesthetic and developmental consistency with other Tox21 applications developed by the Division of Translational Toxicology (DTT) at the National Institute of Environmental Health Sciences (NIEHS).


Phyllanthus Niruri Standardized Extract Alleviates the Progression of Non-Alcoholic Fatty Liver Disease and Decreases Atherosclerotic Risk in Sprague-Dawley Rats.
Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague-Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC-HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis.


Needle aspiration biopsy of localized pulmonary lesions.
Needle aspiration biopsy of localized pulmonary lesions is a direct, safe, relatively inexpensive method of diagnosis which is applicable for both in-patients and out-patients. It should be performed under direct visualization with image amplifier guidance. Proper application of this method can greatly increase diagnostic yield, diminish the diagnostic interval and expense and minimize the risks involved.


Intermolecular (4+3) cycloadditions of aziridinyl enolsilanes.
Upon activation by strong Brønsted acids, aziridinyl enolsilanes undergo (4+3) cycloadditions with dienes to afford aminoalkylated cycloheptenones as products. The use of a highly polar medium such as nitroalkane facilitates high cycloaddition yields of up to 99%. Optically pure aziridinyl enolsilanes react to yield (4+3) cycloadducts with up to 99% ee.


Clinical features and management of BRCA1 and BRCA2-associated prostate cancer.
It is thought that over forty percent of an individual's risk of developing prostate cancer (PCa) is related to familial and genetic factors. Although multiple genes have been implicated in the development of PCa, few confer as high a risk as mutations in the genes associated with early-onset breast cancer (BRCA1 and BRCA2). Not only do mutations in BRCA genes increase the risk of PCa, but they have also been related to adverse disease characteristics and outcomes. Therefore, a better understanding of the association between BRCA gene mutations and PCa may provide the backdrop for individualized management of patients with PCa who are carriers of a gene mutation. Such management may include an individualized approach to screening and treatment including chemotherapeutic regimens targeted to the underlying genetic mechanism of disease. In this paper, we review the evidence relating BRCA gene mutations to the risk of PCa, as well as outcomes and response to therapy, and suggest an approach to the management of such patients.


Invasive pulmonary aspergillosis. MRI, CT, and plain radiographic findings and their contribution for early diagnosis.
A prospective study was conducted in 38 patients with nodular lesions on plain chest radiographs and the clinical suspicion of invasive pulmonary aspergillosis (IPA) to assess the diagnostic accuracy of magnetic resonance imaging (MRI) and computed tomography (CT). For early diagnosis of IPA (clinical signs and symptoms < 10 days), CT scans with demonstration of the halo sign had a high sensitivity (16/22) and specificity (8/8). Magnetic resonance imaging performed at the same time revealed a relatively higher sensitivity (22/22), but a very poor specificity (0/8). Gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA) enhanced images did not improve specificity. In the later course of infection (clinical signs and symptoms > 10 days), MRIs showed typical nodular target-like lesions with Gd-DTPA enhancement of the rim area that was not seen in the early course of the disease or in patients with Pseudomonas or staphylococcal infection. In conclusion, MRI findings are not as characteristic as the CT halo sign in diagnosing IPA in the early course of the disease, but the MRI target sign with Gd-DTPA enhancement of the rim area and the "reverse target" on T2-weighted images are strongly suggestive of IPA at a later stage of the disease.


Comparative Effectiveness Research in Musculoskeletal Imaging.
The primary goal of comparative effectiveness research (CER) is to define the optimal choice among alternative diagnostic and interventional strategies for a given clinical scenario among major stakeholders in the health care system. In an era where health care decision makers are demanding greater evidence of improved patient outcomes from the use of medical technologies, musculoskeletal (MSK) imagers must be more engaged in generating quality CER. We provide an overview of CER and its expanding role in U.S. health care, the current funding environment for CER and MSK imaging, potential areas for CER in MSK radiology, and a discussion of foreseeable challenges for CER in MSK imaging.


[Tri-phalā (Three Myrobalans) as Described in the Second Part of the Bower Manuscript, the Nāvanītaka].
In India, since ancient times Tri-phalā (meaning "three fruits" in Sanskrit) has been considered to be a combination of the following fruits: -Harītakī (Terminalia chebula, Retz.), Āmalaka (Embelica officinalis Gaertn), and Vibhītaka (Terminalia belerica Roxb.). These plants are also listed in the Ayurvedic Pharmacopoeia of India. Harītakī and Āmalaka have also been used for medicinal purposes since ancient times in Japan under the Japanese names of (see text) (Kariroku) and (see text) (Annmaroku), respectively. Both have been carefully preserved as treasured drugs in the nationally important Shosoin treasure storehouse. This study attempts to clarify the description of Tri-phalā in the Nāvanītaka, which is the second part of the Bower Manuscript (Bower Ms.), and examines the reasons why these plants were combined. This paper begins with a summary description of Tri-phalā in the context of traditional Asian medicine, followed by the delineation of drug selection principles in Ayurveda. Tri-phalā formulas in the Nāvanītaka are then examined. The Carakasamhitā (CS) treats Tri-phalā as a purifier and tonic (rasāyana), describing it as a formula for rejuvenation and longevity. On the other hand, the Susrutasamhitd (SS) regards Tri-phalā as having the efficacy of balancing kapha (phlegm) and pitta (bile), and also as being a medicine to promote excretion and enhance digestive functions for better nutritional intake. It is described to have an effect of curing diseases by keeping the tridhāu (theree element) valance. Tri-phalā is thus used as an ingredient of laxatives for diseases that result from kapha imbalance and tonic. The Aşţāngahŗdayasamhitā (AHS) considers Tri-phalā to have a particular superiority among cure-all medicines with the power to dispel illness. It controls kapha and overcomes blood diseases. Tri-phalā formulas found in the Nāvanītaka were prescribed for the treatment of abdominal tumors induced by vāyu (wind) disorder as well as for coughs caused by pitta and kapha disorder. Tri-phalā was also administered to facilitate nutrient absorption, regulate bowel function, and promote excretion. Tri-phalā thus restores the balance of tridhāu by facilitating water distribution in the body. For these reasons, the optimal combination of Tri-phalā was then established to adjust kapha for most efficient purification effects.


[Antibacterial mechanism of sulforaphane on Escherichia coli].
To investigate the antibacterial mechanism of sulforaphaneon (SFN) on Escherichia coli. To determine membrane penetrability, changes of SDS-PAGE protein spectra, soluble protein and alkaline phosphatase and reducing sugar were determined. Cellular nucleic acid synthesis was detected by 4, 6- diamidino-2-phenylindole (DAPI) staining assay. SFN affected the membrane permeability of Escherichia coli. Ions and small molecules could leak out of the cells. But it did not destroy the membrane integrity directly. After 16 hours of treatment with SFN, the total contents of intracellular and extracellular proteins decreased by 42.5% and 17.6%, respectively, while the quantity of DNA and RNA reduced by 34.8% and 48.5% respectively. SFN can affect cell membrane permeability, material and energy metabolism and inhibit the synthesis of nucleic acid and protein.


ORF3 as a sensitive and specific diagnostic index for hepatitis E.
We explored the significance of the expression of hepatitis E virus (HEV) open reading frame 3 (ORF3) in hepatitis E rat models. We also investigated its diagnostic value. Forty Sprague-Dawley (SD) rats were infected with HEV and 10 uninfected rats were selected for the control group. Rats were sacrificed at 14, 21, 35 and 70 days after infection. They were divided into 4 groups: Model group 1, model group 2, model group 3 and model group 4. ORF3 protein expression level in liver tissue, level of adipokines [fatty acid synthase (FAS), tissue inhibitor of metalloproteinase-2 (TIMP-2) and angiotensin-converting enzyme inhibitor 2 (ACE-2)], Th1/Th2 cells balance [interferon (IFN), interleukin-4 (IL-4) and Th1/Th2] and the level of immune outcome (levels of CD4+, CD8+ T lymphocytes and CD4+/CD8+) were measured and compared among groups. Our results showed that HEV IgG and HEV RNA levels in the model group 3 were higher than those in the other 3 groups. Compared with the control group, expression level of ORF3 protein in the liver tissue as well as Fas and TIMP levels were significantly higher in the model group 3. ACE-2 level was significantly lower than that of the control group (P<0.05). In the model group 3, IFN-γ, IL-4 and Th1/Th2 levels were meaningfully higher than those of the control group. CD4+ T lymphocytes and CD4+/CD8+ ratio were obviously lower than those in the control group (P<0.05). The expression level of ORF3 was positively correlated with levels of Fas, TIMP-2 and Th1/Th2. It was negatively correlated with ACE-2 and CD4+/CD8+ levels (P<0.05). We concluded that ORF3 expression level was directly related to severity and prognosis, and that ORF3 protein can be considered as a sensitive and specific diagnostic index.


A nonhypoglycemic chlorpropamide analog that inhibits aldehyde dehydrogenase.
Chlorpropamide (CP), a sulfonylurea-type oral hypoglycemic agent, is known to provoke a flushing reaction reminiscent of the disulfiram-ethanol reaction in certain individuals. This is manifested in rodents by an increase in blood acetaldehyde levels after ethanol administration. When the sulfonamide N1-nitrogen of CP was substituted with an ethyl group, the product, N1-ethylchlorpropamide, was found to be three times as active as CP in raising ethanol-derived blood acetaldehyde. However, whereas CP lowered fasting blood glucose in rats measured over 6 h, N1-ethylchlorpropamide was devoid of hypoglycemic activity, suggesting that the latter might be potentially useful as an alcohol deterrent agent.


Impact of probiotic Lactobacillus plantarum TENSIA in different dairy products on anthropometric and blood biochemical indices of healthy adults.
The blood pressure-lowering effect of dairy products holds the potential to decrease the risk of cardiovascular disease (CVD). An open question is if the successful expression of functional properties of the probiotic strain depends on host biomarkers and/or food matrix properties. The probiotic Lactobacillus plantarum strain TENSIA® (DSM 21380) is a novel microorganism with antimicrobial and antihypertensive functional properties. The aim of this study was to characterise the functional properties of the probiotic L. plantarum TENSIA and compare its effects on host anthropometric, clinical, and blood biomarkers when consumed with cheese or yoghurt. This study involved two double-blinded randomised placebo-controlled exploratory trials (ISRCTN15061552 and ISRCTN79645828) of healthy adults over a three-week period. The three-week consumption of probiotic L. plantarum TENSIA in a daily dose of 1×1010 cfu in probiotic cheese or a daily dose of 6×109 cfu in yoghurt with different content of carbohydrates, proteins, and lipids did not significantly change the body mass index (BMI), plasma glucose and lipid levels, or inflammatory markers in the blood. Reduced lowered systolic and diastolic blood pressure values were detected, regardless of food matrix or baseline values for blood pressure and BMI. In conclusion, our study showed that three-week consumption of the probiotic L. plantarum TENSIA either in cheese or yoghurt lowered diastolic and systolic blood pressure regardless of food matrix and baseline values of blood pressure and BMI, confirming the impact of the functional properties of the probiotic strain in decreasing CVD risk.


Dysautonomia associated with immune checkpoint inhibitors.
The purpose of this study is to report the clinical characteristics of dysautonomia associated with immune checkpoint inhibitors (ICIs). We reported two patients with autoimmune autonomic ganglionopathy (AAG) occurring as immune-related adverse events (irAEs). We also performed a review of previous case reports presenting dysautonomia during ICI therapy. Moreover, we conducted pharmacovigilance analyses using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to investigate dysautonomia associated with ICI. Two patients in our care developed both AAG and autoimmune encephalitis following ICI therapy for lung cancers. We comprehensively reviewed 13 published cases (M:F = 11:2, mean onset age of 53 years) with ICI-associated dysautonomia including AAG (n = 3) and autonomic neuropathy (n = 10). Of these, ICI monotherapy was performed in seven and combination ICI use in six. In 6 of 13 patients, dysautonomia appeared within one month after the start of ICIs. Orthostatic hypotension was observed in 7 and urinary incontinence or retention in five. All patients except three showed gastrointestinal symptoms. Anti-ganglionic acetylcholine receptor antibodies were undetectable. All but two patients received immune-modulating therapy. Immuno-modulating therapy was effective in three patients with AAG and two patients with autonomic neuropathy, but ineffective in the others. Five patients died, of either the neurological irAE (n = 3) or cancer (n = 2). The pharmacovigilance analyses using FAERS showed that ipilimumab monotherapy and the combination of nivolumab and ipilimumab constituted significant risks for developing dysautonomia, consistent with the review of literature. ICIs can cause dysautonomia including AAG, and autonomic neuropathy is a neurological irAE.


Natural selection drives population divergence for local adaptation in a wheat pathogen.
Evolution favors the emergence of locally-adapted optimum phenotypes that are likely to differ across a wide array of environmental conditions. The emergence of favorable adaptive characteristics is accelerated in agricultural pathogens due to the unique properties of agro-ecosystems. We performed a QST - FST comparison using 164 strains of Parastagonospora nodorum sampled from eight global field populations to disentangle the predominant evolutionary forces driving population divergence in a wheat pathogen. We used digital image analysis to obtain quantitative measurements of growth rate and melanization at different temperatures and under different fungicide concentrations in a common garden experiment. FST measures were based on complete genome sequences obtained for all 164 isolates. Our analyses indicated that all measured traits were under selection. Growth rates at 18 °C and 24 °C were under stabilizing selection (QST < FST), while diversifying selection (QST > FST) was the predominant evolutionary force affecting growth under fungicide and high temperature stress. Stabilizing selection (QST < FST) was the predominant force affecting melanization across the different environments. Melanin production increased at 30 °C but was negatively correlated with higher growth rates, consistent with a trade-off under heat stress. Our results demonstrate that global populations of P. nodorum possess significant evolutionary potential to adapt to changing local conditions, including warmer temperatures and applications of fungicides.


Functional reconstructions using only ulnar nerve and ulnar nerve-innervated muscles for traumatic musculocutaneous, median and radial nerve palsies.
A 20-year-old right-handed fisherman experienced a severe injury in a high-energy traffic accident. These injuries included a shaft fracture of the right humerus, open comminuted fracture of the right forearm and multiple peripheral nerve palsies involving the musculocutaneous, median and radial nerves. Six months after the initial treatment, the patient was referred to our hand surgeons for further treatment. Several operations for functional reconstruction using only the ulnar nerve and ulnar nerve-innervated muscles were performed: the main procedures included a partial ulnar nerve transfer for elbow flexion, flexor carpi ulnaris transfer for reconstruction of wrist and finger extension and opponensplasty using the abductor digiti minimi. Three years after the initial injury, the patient had relatively good function including elbow flexion and stable side pinch and grasp. Functional reconstruction using a combination of the ulnar nerve and ulnar nerve-innervated muscles may be useful in specific cases involving multiple peripheral nerve injuries.


Evaluating Predictive Factor of Systemic Inflammatory Response Syndrome and Postoperative Pain in Patients Without Ureteral Stent Placement After Ureteral Access Sheath Use in Flexible Ureteroscopy for Stone Management.
Background and Objective: This retrospective cohort study aimed to evaluate the safety of stentless flexible ureteroscopy (fURS) using a ureteral access sheath (UAS) for stone management. Patients and Methods: A total of 270 ureteral stentless postoperative patients were analyzed. Stentless indication was characterized by having no ureteral wall or mucosa injury with only slight erosion, <1 hour operative time, and no endoscopic stone fragments with or without stone dust. Postoperative complications and pain were analyzed for safety measurements. In addition, preoperative and intraoperative risk factors associated with the incidence of systemic inflammatory response syndrome (SIRS) and postoperative pain were evaluated. Results: The most common UAS sizes were 10/12F (69.6%) and 9.5/11.5F (28.1%). The rate of patients who were stone free was 95.9%. The median operation time was 34 minutes. Only three grade 1 ureteral injuries occurred intraoperatively. Postoperative SIRS occurred in 8.8% of patients, and postoperative use of analgesics was 35.9%. Only four patients were required to undergo eventual ureteral stenting. Less than 10/12F UAS was the only factor positively associated with preventing postoperative SIRS (odds ratio [OR], 4.733; 95% confidence interval [CI], 1.085-20.644). Older age and preoperative ureteral stenting were positively associated with preventing postoperative pain (OR, 0.970; 95% CI, 0.951-0.990 and OR, 0.427; 95% CI, 0.232-0.786; respectively). Conclusion: Stentless fURS with UAS in stone management was feasible for selected patients. UAS size of <10/12F, older age, and preoperative stenting are possible keystones to achieving stentless fURS with UAS postoperatively. IRB approval number; 20216101.


Differing HIV risks and prevention needs among men and women injection drug users (IDU) in the District of Columbia.
Washington, DC has among the highest HIV/AIDS rates in the US. Gender differences among injection drug users (IDUs) may be associated with adoption of prevention opportunities including needle exchange programs, HIV testing, psychosocial support, and prevention programming. National HIV Behavioral Surveillance data on current IDUs aged ≥18 were collected from 8/09 to 11/09 via respondent-driven sampling in Washington, DC. HIV status was assessed using oral OraQuick with Western Blot confirmation. Weighted estimates were derived using RDSAT. Stata was used to characterize the sample and differences between male and female IDU, using uni-, bi-, and multivariable methods. Factors associated with HIV risk differed between men and women. Men were more likely than women to have had a history of incarceration (86.6 % vs. 66.8 %, p < 0.01). Women were more likely than men to have depressive symptoms (73.9 % vs. 47.4 %, p < 0.01), to have been physically or emotionally abused (66.1 % vs. 16.1 %, p < 0.0001), to report childhood sexual abuse (42.7 % vs. 4.7 %, p < 0.0001), and pressured or forced to have sex (62.8 % vs. 4.0 %, p < 0.0001); each of these differences was significant in the multivariable analysis. Despite a decreasing HIV/AIDS epidemic among IDU, there remain significant gender differences with women experiencing multiple threats to psychosocial health, which may in turn affect HIV testing, access, care, and drug use. Diverging needs by gender are critical to consider when implementing HIV prevention strategies.


Associations between physical activity patterns and dietary patterns in a representative sample of Polish girls aged 13-21 years: a cross-sectional study (GEBaHealth Project).
Similar to other countries, trends of decreasing levels of physical activity (PA) and an increasing prevalence of unhealthy dietary patterns are observed among girls in Poland. Better understanding of potentially inter-related behaviours within this population can help to design tailored interventions. The purpose of this study was to determine associations between PA patterns and dietary patterns in a representative sample of Polish girls. Girls aged 13-21 years (n = 1107) were randomly selected for the study. PA was assessed using International Physical Activity Questionnaire - Long (IPAQ-L). Dietary data were collected with food frequency questionnaires. PA patterns and dietary patterns were drawn separately by Principal Component Analysis (PCA). Logistic regression was used to find the associations between PA patterns and dietary patterns. Four major PA patterns ('School/work activity', 'Active recreation', 'Yard activity' and 'Walking and domestic activity') and four dietary patterns ('Traditional Polish', 'Fruit & vegetables', 'Fast food & sweets' and 'Dairy & fats') were identified. Level of PA was the highest in the upper tertile of 'School/work activity' pattern (mean 1372.2 MET-minutes/week, 95 % Confidence Intervals [CI]: 1285.9-1458.5). Girls in upper tertiles of 'Yard activity', 'Active recreation' and 'School/work activity' patterns had significantly higher chances of being in the upper tertile of the 'Fruit and vegetables' dietary pattern (odds ratio [OR] 2.17, 95 % CI: 1.50-3.14, p < 0.0001; OR 2.02, 95 % CI: 1.41-2.91; p < 0.001 and OR 1.76, 95 % CI: 1.24-2.51, p < 0.01 respectively; all adjusted for confounders) in comparison to bottom tertiles. Weak, but significant inverse associations were found between upper tertiles of 'Active recreation' and 'Yard activity' patterns and unhealthy dietary patterns. We found associations between PA patterns and dietary patterns in the population of Polish girls. Girls with the highest adherence to the 'School/work activity' pattern had the highest levels of PA and presented pro-healthy dietary behaviours. School should be recognised as potentially efficient and important setting to maximise girls' PA potential. The after-school time is the area that should also be targeted to increase daily PA or to at least sustain the level of PA after completing education.


Problems of Domain Factors with Small Factor Loadings in Bi-Factor Models.
Many measurement designs produce domain factors with small variances and factor loadings. The current study investigates the cause, prevalence, and problematic consequences of such domain factors. We collected a meta-analytic sample of empirical applications, conducted a simulation study on statistical power and estimation precision, and provide a reanalysis of an empirical example. The meta-analysis shows that about a quarter of all standardized domain factor loadings is in the range of -.2<λ<.2 and about a third of all domains is measured by five or fewer indicators, resulting in small factor variances. The simulation study examines the associated difficulties concerning statistical power, trait recovery, irregular estimates, and estimation precision for a range of such realistic cases. The empirical example illustrates the challenge to develop measures that produce clearly interpretable domain factors. Study planning and interpretation need to take the (expected) sum of squared factor loadings per domain factor into account. This is relevant even if influences of domain factors are desired to be small, and equally applies to different model variants. We propose several strategies for how researchers may better unlock the bifactor model's full potential and clarify its interpretation.


Optimized operation of silicon nanowire field effect transistor sensors.
Ion-sensitive field effect transistors have been advanced in recent years by utilizing silicon nanowires (Si-NWs), but establishing their optimized operation regime is an area of ongoing research. We propose a modified configuration of SiNWs in the form of a honeycomb structure to obtain high signal to noise ratio and high current stability. The low-frequency noise characteristics and the electrical stress are systematically considered for the optimization and compared against conventional SiNW devices. The operation voltage of the device severely affects the sensing stability; as the gate voltage is increased, the signal-to-noise ratio is enhanced, however, the stress effect becomes severe, and vice versa. The honeycomb nanowire structure shows enhanced noise characteristics in low voltage operation, proving to be an optimum solution for achieving highly stable sensor operation.


Growth of nanostructured polycrystalline cerium oxide through a solvothermal precipitation using near-supercritical fluids.
Well-crystallized cerium dioxide with cubic phase were formed and self-assembly grown to nanofibers or nanosheets via a solvothermal precipitation from near-supercritical fluids without any help of metal catalysts or capping agents. The self-assembly attachment process without any preferred or selective orientation dominated the growth of the polycrystalline nanofibers or nanosheets consisting of grains of approximately 3 nm to which are formed by the coalescence of the single crystalline cerium oxide seeds. The growth is attributed to be driven by phase separation due to partial compatibility between ethyl alcohol and supercritical carbon dioxide fluid during the precipitation reaction, not by different surface energies or defects. With increasing temperature, the nanofibers with a weblike network structure were formed and then fused to large spherical particles. As a result, the polycrystalline fibers or sheets consisting of pure cerium dioxide phase were produced by the solvothermal reaction with an aid of the supercritical carbon dioxide from the alcoholic metal salt solution.


Prognostic factors for non-cleaved follicular center-cell lymphomas and immunoblastic sarcoma. A Bayesian approach.
The Bayesian multivariate statistical method was applied to determine the relative strength and optimal combination of 17 variables in predicting survival of 151 patients with non-Hodgkin's lymphomas assigned as non-cleaved follicular center-cell and immunoblastic sarcoma types according to the classification of Lukes & Collins. Considering all the factors simultaneously, the analysis showed that the combination of stage, Hb level and location of the lymphoma was included in the best predictive model at each survival time studied. Additional factors were erythrocyte sedimentation rate, thrombocyte count and leucocyte count. Of the histological variables, only growth pattern and mitotic ratio in the biopsy specimen remained significant. At manually controlled computer simulation with these best indicators, this model would have given a correct classification for 69-78% of the patients at the 4 survival times studied. One can thus expect about 70% correct prognoses using this model.


Conjugated Microporous Polymer as Heterogeneous Ligand for Highly Selective Oxidative Heck Reaction.
A series of pyridine-type ligands containing C≡C bonds were designed and synthesized for selective oxidative Heck reaction. These ligands were utilized as functional units and integrated into the skeleton of conjugated microporous polymers. 6,6'-diiodo-2,2'-bipyridine and 1,3,5-triethynylbenzene were polycondensed via Sonogashira cross-coupling strategy to afford CMP-1 material. The resultant CMP-1 was used as a heterogeneous catalytic ligand for the PdII-catalyzed oxidative Heck reaction with high linear selectivity. The linear selectivity of CMP-1 is about 30 times higher than that of bipyridine-based monomer ligand. This work opens a new front of using CMP as an intriguing platform for developing highly efficient catalysts in controlling the regioselectivity in organic reactions.


Spectroscopic studies of the biosorption of gold(III) by dealginated seaweed waste.
Gold biosorption by dealginated seaweed waste has been studied to elucidate the mechanisms of metal uptake from solution. Dealginated seaweed was able to retain up to 1 mmol g(-1) of Au from solution at pH 3. FT-IR showed the presence of carboxylate groups on the surface of the biosorbent; however, the changes observed for the Au-bound samples suggested very little sorption to the carboxyl moieties. Colloidal Au formed on the surface of dealginated seaweed by reduction of Au(III) to Au(0) was observed using ESEM and four different types of particles were clearly identified. The Au distribution matched closely that obtained for S atoms indicating a possible link between these elements. EXAFS measurements showed that colloidal Au is present on the surface of the biosorbent. Evidence of gold reduction from Au(III) to Au(I) and Au(0) was also confirmed by the measured bond distances characteristic of the metal. The coordination number obtained by EXAFS indicated that approximately 75% of the Au on the sample was present in the colloidal form and the remaining Au was bound to S as nearest neighbor. The proposed mechanisms for Au removal from solution are reduction of Au species by components on the surface of the biosorbent to form colloidal metal followed by retention of the ionic Au(I) species at the sulfur containing sites. The results show that dealginated seaweed can be used for the cleanup of gold-containing effluents.


BTN2A2, a new biomarker and therapeutic target for glioma.
Protein casein 2A2 (BTN2A2) is a costimulatory molecule first identified in antigen-presenting cells. Studies have shown the involvement of BTN2A2 in immunity. However, the exact role and the mechanism of BTN2A2 in tumors are still unclear. First, we performed real-time PCR to measure BTN2A2 expression in glioma cell lines. Next, we performed Genes Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to understand the mechanism of BTN2A2 in glioma. Next, we used the "ESTIMATE", "ssGSEA" and "CIBERSORT" algorithms to analyze the correlation between BTN2A2 and immune cell infiltration (ICI). Finally, we performed immunohistochemistry, growth curve, transwell, and colony formation assays to determine the functions of BTN2A2 in glioma. Our results showed an increase in BTN2A2 expression levels in glioma tissues and cells. Next, we determined that BTN2A2 was correlated with the prognosis of patients with glioma. Then, using the ESTIMATE, ssGSEA, and CIBERSORT algorithms, we discovered that BTN2A2 was significantly associated with immune cell infiltration (ICI) in glioma. We observed an increase in BTN2A2 expression levels with an increase in the patient's tumor grade. Furthermore, BTN2A2 significantly enhanced the proliferative and migratory abilities of glioma cells. Our results showed a significant increase in BTN2A2 expression levels in glioma cells and tissues. Furthermore, the prognosis of patients expressing high BTN2A2 levels was poor. Moreover, BTN2A2 was correlated with progression and ICI in patients with glioma. Together, this indicates that BTN2A2 could be a therapeutic target for patients with glioma.


A pilot study examining if satisfaction of basic needs can ameliorate negative effects of shift work.
The objective of the present study was to investigate if satisfaction of the basic needs of autonomy, competence, and relatedness is related to shift work tolerance, specifically physical and mental fatigue, insomnia, and digestive troubles in a sample of shift workers. This is a cross-sectional pilot questionnaire study, including 252 shift workers employed in a municipality in Norway. Autonomy was negatively related to physical fatigue and digestive troubles, while competence was negatively related to mental fatigue. Relatedness showed significant correlations with insomnia and mental fatigue, but did not reach significance in the regression model controlling for the two other basic needs as well as work scheduling, night work exposure, and sleep medication. Sleep medication was significant in the final regression model for insomnia, but unrelated to fatigue and digestive troubles. The demographic variables, work hours per week, work schedule, and night work exposure were unrelated to all four measures of shift work tolerance. Autonomy and competence may be more important for fatigue and digestive troubles among shift workers than work arrangement variables, night work exposure, and sleep medication use.


Catalytic asymmetric addition of carbon dioxide to propylene oxide with unprecedented enantioselectivity.
New chiral catalyst systems were developed for the reaction of carbon dioxide with propylene oxide (PO) at atmospheric pressure to generate enantiomerically enriched propylene carbonate (PC). The best selectivity was achieved with a Co(III)(salen)-trifluoroacetyl complex and bis(triphenylphosphoranylidene)ammonium fluoride (PPN+F-) as catalysts, affording PC in 40% yield and 83% ee (selectivity factor = 19). In addition, PC was prepared for the first time by kinetic resolution of PO with tetrabutylammonium methyl carbonate (TBAMC, nBu4N+ (-)OOCOMe). With TBAMC as "activated CO2", up to 71% ee was obtained.