A comparative study on the development of Chinese and English abilities of Chinese primary school students through two bilingual reading modes: human-AI robot interaction and paper books.
To address the challenges encountered by Chinese primary school students, particularly left-behind and migrant children, who exhibit a preference for animations, video games, and short videos over reading books and struggle with Chinese-English bilingual skills, this study introduces an educational robot AI-assisted method for simultaneous bilingual reading. To assess the effectiveness of this method, a 6-month Chinese-English bilingual extracurricular reading comparative experiment was conducted involving 85 grade 5 students from two classes in a primary school in Hangzhou, China. The AI-assisted class freely read 100 bilingual/English electronic picture books and 200 Chinese electronic classic serial picture books by employing the AI-assisted human-computer interactive electronic reading mode of the "Educational Robot+Audio Electronic Picture Book+Character-play Based Reading." In contrast, the paper book group read the same content presented in the traditional paper book format, following the "regular independent reading" mode. Post-experimental analyses were conducted employing t-tests and MANCOVA and the results revealed that: the primary factors influencing reading effectiveness are the choice of reading materials, reading tools, and reading mode, while reading time does not emerge as the principal influencing factor. Furthermore, students in the AI class demonstrated significant enhancements in bilingual reading motivation, reading amount, reading comprehension, independent learning ability, pronunciation proficiency, and test scores compared to their peers in the paper book class. The AI-assisted reading mode utilizing educational robots garnered positive feedback from teachers, parents, and students. It offers the potential to effectively substitute parental involvement in parent-child reading and English tutoring, while also enabling the simultaneous acquisition of bilingual proficiency in both Chinese and English. This approach proves to be highly effective, cost-efficient, and convenient, particularly for enhancing children's foreign language abilities. Moreover, it fosters positive reading habits and independent learning skills among primary school students, contributes to the establishment of lofty aspirations, and enhances bilingual performance. Overall, this innovative mode offers an effective means of facilitating children's acquisition of bilingualism and foreign language skills, as well as promoting reading education.


Unusual stability of protein molecules in the presence of multivalent counterions.
Proteins are known to undergo denaturation and form different phases with varying physicochemical parameters. We report unusual stability of bovine serum albumin protein against commonly used denaturants (temperature and surfactant) in the charged reversal reentrant phase, caused by the multivalent counterions. Unlike monovalent counterions, which promote the denaturants' induced protein unfolding, the unfolding is restricted in the presence of multivalent ions. The observations are beyond the scope of general understanding of protein unfolding and are believed to be governed by ion-ion correlations driven strong condensation of the multivalent ions.


The basal ganglia and pain.
The basal ganglia are associated with motor functions of the brain, although it is becoming clear that they may subserve many nonmotor functions as well. A review of the literature reveals an association between the basal ganglia and pain, and raises the question of a new function for the basal ganglia in selective attention.


FoxO1 mediates an autofeedback loop regulating SIRT1 expression.
Forkhead transcription factor FoxO1 and the NAD(+)-dependent histone deacetylase SIRT1 are evolutionarily conserved regulators of the development of aging, oxidative stress resistance, insulin resistance, and metabolism in species ranging from invertebrates to mammals. SIRT1 deacetylates FoxO1 and enables activation of FoxO1 transcription in multiple systems. The functional consequences of the interactions between FoxO1 and SIRT1 remain incompletely understood. Here, we demonstrate that the 1.5-kb rat sirt1 promoter region contains a cluster of five putative FoxO1 core binding repeat motifs (5×IRS-1) and a forkhead-like consensus binding site (FKHD-L). Luciferase promoter assays demonstrate that FoxO1 directly activates SIRT1 promoter activity and that both the IRS-1 and FKHD-L enable FoxO1-dependent SIRT1 transcription. Electrophoretic mobility shift and chromatin immunoprecipitation assays show that FoxO1 binds to the IRS-1 and FKHD-L sites of the SIRT1 promoter. Consistently, FoxO1 overexpression increases SIRT1 expression, and FoxO1 depletion by siRNA reduces SIRT1 expression at both the messenger RNA and protein levels in vascular smooth muscle cells and HEK293 cells. Thus, endogenous FoxO1 is a positive transcriptional regulator of SIRT1. Conversely, SIRT1 promotes FoxO1-driven SIRT1 autotranscription through interacting with and deacetylating FoxO1. Moreover, resveratrol, a plant polyphenol activator of SIRT1, increases FoxO1-dependent SIRT1 transcription activity and thus induces its expression. These findings suggest that positive feedback mechanisms regulate FoxO1-dependent SIRT1 transcription and indicate a previously unappreciated function for FoxO1. This signaling network may coordinate multiple pathways acting upon immune, inflammatory, regenerative, and metabolic processes.


Role of the hexapeptide disulfide loop in the gamma-carboxyglutamic acid domain of protein C in Ca2+-mediated structural and functional properties.
The anticoagulant and immunomodulatory effects of protein C (PC) rely on the presence of the N-terminal gamma-carboxyglutamic acid (Gla) domain. This domain is strongly conserved among vitamin K-dependent blood proteins and, in addition to a high relative content of Gla, contains a hexapeptide disulfide loop between Cys residues 17 and 22. In the present study, the contribution of the hexapeptide loop toward Gla domain structure and function was evaluated using wild-type and Cys17/Cys22-alkylated synthetic peptide analogues of the 47-residue Gla domain/helical stack of PC. Circular dichroism and intrinsic fluorescence measurements revealed significant differences in the metal ion-dependent conformations of the two peptides. Disruption of the disulfide loop slightly altered the capacity of the peptide to interact with acidic phospholipid (PL) vesicles. The affinity of the alkylated peptide for soluble endothelial protein C receptor (EPCR), as demonstrated by surface plasmon resonance studies, was increased compared with the wild-type species, although total binding was compromised. These results suggest that the disulfide loop of PC contributes to the overall Ca(2+)-dependent conformation but is not strictly required for PL membrane binding or EPCR recognition.


Impact of the 2018 revised Pregnancy Prevention Programme by the European Medicines Agency on the use of oral retinoids in females of childbearing age in Denmark, Italy, Netherlands, and Spain: an interrupted time series analysis.
Background: In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. Objective: To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. Methods: An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs. Results: From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively. Conclusion: This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use.


JViz.Rna--a Java tool for RNA secondary structure visualization.
Many tools have been developed for visualization of RNA secondary structures using a variety of techniques and output formats. However, each tool is typically limited to one or two of the visualization models discussed in this paper, supports only a single file format, and is tied to a specific platform. In order for structure prediction researchers to better understand the results of their algorithms and to enable life science researchers to interpret RNA structure easily, it is helpful to provide them with a flexible and powerful tool.jViz.Rna is a multiplatform visualization tool capable of displaying RNA secondary structures encoded in a variety of file formats. The same structure can be viewed using any of the models supported, including linked graph, circle graph, dot plot, and classical structure. Also, the output is dynamic and can easily be further manipulated by the user. In addition, any of the drawings produced can be saved in either the EPS or PNG file formats enabling easy usage in publications and presentations.


Breast Implant Mycobacterial Infections: An Epidemiologic Review and Outcome Analysis.
Epidemiologic evidence of periprosthetic mycobacterial infections is limited. The recent boom in cosmetic surgery tourism has been associated with a rise of surgical-site infections in returning patients. This review aims to explore available data, examine trends of documented periprosthetic mycobacterial infections, and analyze outcomes of management techniques. A search in the Biosis, Embase, LILACS, MEDLINE, and Web of Science databases from inception until December of 2017 for "Breast Implants" and "Mycobacterial Infections" and equivalents was performed. Data were pooled after two screening rounds following full-text retrieval and cross-referencing. Forty-one reports describing 171 female patients who had breast prosthesis-related mycobacterial infections were identified. Bibliometric case-based analysis revealed a rise of periprosthetic mycobacterial infections in developing countries since the start of the millennium. The mean patient's age was 37.9 years and the majority of patients had undergone bilateral breast augmentation. Most patients presented with breast pain or tenderness, after an average incubation period of 9 months. Mycobacterium fortuitum was isolated from 90 cases (52.6 percent). Immediate explantation with or without delayed reimplantation was the most commonly used surgical strategy, complemented by combination antimicrobial therapy for an average of 4.6 months. The mean follow-up time was 39.7 months, during which recurrence was observed in 21 of 171 patients (12.3 percent). The emergence of periprosthetic mycobacterial infections in relation to cosmetic medical tourism alerts clinicians to the importance of educating the public about the associated risks. In addition, this study identifies risk factors associated with recurrence of periprosthetic mycobacterial infections.


No association between symptom severity and MMN impairment in schizophrenia: A meta-analytic approach.
The mismatch negativity (MMN) is an event-related potential that is consistently attenuated in people with schizophrenia. Within the predictive coding model of psychosis, MMN impairment is thought to reflect the same prediction failures that are also thought to underlie the development and crystallization of delusions and hallucinations. However, the true relationship between symptom severity and MMN impairment across studies has not yet been established. The present meta-analysis used meta-regressions to examine the relationship between MMN impairment (quantified as Hedges' g) and PANSS positive and negative symptom totals across 62 and 68 samples, respectively. Furthermore, we examined the relationship between MMN impairment and group differences in educational achievement (n = 47 samples), cognitive ability (n = 36 samples), and age (n = 86 samples). Overall, we found no significant associations between MMN impairment and symptom severity (p's > 0.50); however, we did observe a trend-level association between MMN impairment and lower education (p = 0.07) and a significant association with older age (p < 0.01) in the schizophrenia patient group. Taken together, these results challenge a simple predictive coding model of psychosis, and suggest that MMN impairment may be more closely associated with premorbid functioning than with the expression of psychotic symptoms.


Photoconductive cadmium sulfide hemicylindrical shell nanowire ensembles.
We report the synthesis and characterization of hemicylindrical shell nanowires (HSNWs) composed of nanocrystalline cadmium sulfide (CdS). CdS HSNWs were synthesized by first electrodepositing microcrystalline cadmium (Cd) nanowires by electrochemical step-edge decoration on graphite electrode surfaces and then converting these Cd nanowires into CdS by exposure to H2S at elevated temperature. These nanowires had a hemicylindrical shell morphology that was produced by the Kirkendall effect, involving disparate rates for diffusion of Cd and S atoms within the nascent CdS layer during the conversion from Cd to CdS. The outer diameter of the CdS HSNWs was 1.6-2.4 times that of Cd precursor nanowires and was adjustable over the range from 116 to 550 nm. CdS HSNWs showed strong, band-edge photoluminescence at 2.45 eV and a fast, reversible, and stable photoconductivity response in air characterized by "on" and "off" times of less than 15 ms.


Isolation of plasma membranes from ram spermatozoa by a two-phase polymer system.
The plasma membranes of ram spermatozoa were disrupted in a hypotonic EDTA medium and isolated by using a two-phase polymer system of dextran--polyethyleneglycol. The plasma membranes obtained were of a relatively high degree of purity (approximately 70%) as judged by electron microscopy observations and measurements of the marker enzymes alkaline phosphatase, ATPase and AMPase. The activity of succinate cytochrome C reductase, a marker of mitochondrial membranes, was very low.


Surface analysis by X-ray photoelectron spectroscopy of sol-gel silica modified with covalently bound peptides.
Chemical surface characterization of biologically modified sol-gel derived silica is critical but somewhat limited. This work demonstrates the ability of x-ray photoelectron spectroscopy (XPS) to characterize the surface chemistry of peptide modified sol-gel thin films based on the example of four different free peptide-silanes, denoted RGD, NID, KDI ,and YIG. The N 1s and C 1s peaks were found to be good fingerprints of the peptides, whereas O 1s overlapped with the signal of substrate oxygen and, therefore, the O 1s peak was not informative in the case of the thin films. The C 1s peak was fitted and the contribution of the residual hydrocarbons was sorted out. The curve-fitting procedure of the C 1s peak accounted for the different chemical states of carbon atoms in the peptide structure. The curve-fitting procedure was validated by analyzing free peptides in the powder form and was then applied to the characterization of the peptide-modified thin films. The XPS measured ratio between nitrogen and carbon for the peptide thin film was similar to the corresponding value calculated from the peptide structures. Angle resolved XPS confirmed the surface nature of peptides in modified thin films. The coverage and thickness of the peptides on the thin film surface depended on the peptide sequence. The coverage was in the range of 10% of a monolayer, and the layer thickness varied from 10 to 30 A. We believe that the different thicknesses and surface coverage are due to the local structure of the peptides, with the RGD and NID peptides taking a globule conformation and the YIG and KDI peptides adopting a more linear structure.


A rational mechanism for combination treatment of Huntington's disease using lithium and rapamycin.
Huntington's disease (HD) is caused by a polyglutamine expansion mutation in the huntingtin protein that confers a toxic gain-of-function and causes the protein to become aggregate-prone. Aggregate-prone proteins are cleared by macroautophagy, and upregulating this process by rapamycin, which inhibits the mammalian target of rapamycin (mTOR), attenuates their toxicity in various HD models. Recently, we demonstrated that lithium induces mTOR-independent autophagy by inhibiting inositol monophosphatase (IMPase) and reducing inositol and IP3 levels. Here we show that glycogen synthase kinase-3beta (GSK-3beta), another enzyme inhibited by lithium, has opposite effects. In contrast to IMPase inhibition that enhances autophagy, GSK3beta inhibition attenuates autophagy and mutant huntingtin clearance by activating mTOR. In order to counteract the autophagy inhibitory effects of mTOR activation resulting from lithium treatment, we have used the mTOR inhibitor rapamycin in combination with lithium. This combination enhances macroautophagy by mTOR-independent (IMPase inhibition by lithium) and mTOR-dependent (mTOR inhibition by rapamycin) pathways. We provide proof-of-principle for this rational combination treatment approach in vivo by showing greater protection against neurodegeneration in an HD fly model with TOR inhibition and lithium, or in HD flies treated with rapamycin and lithium, compared with either pathway alone.


The Role of Exosomes in Diseases Related to Infertility.
Exosomes, small extracellular vesicles with diameters of 40-100nm, are generated through the fusion of multivessel with plasma membrane and secreted by a variety of living cells. Exosomes contain lipid bilayer membrane and releasable functionally active proteins, mRNA and microRNAs (miRNAs). This article reviews the latest progress of researches on exosomes in diseases that lead to infertility.


Dimensions of elongated mineral particles: a study of more than 570 fibers from more than 90 cases with implications for pathogenicity and classification as asbestiform vs. cleavage fragments.
Asbestos is well-recognized as the cause of a variety of disorders of the respiratory tract, including neoplastic as well as non-neoplastic conditions. Fiber dimensions and biopersistence are important determinants of the pathologic response, and analytical electron microscopy is a powerful technique for determining the fiber content of lung tissue samples. For decades our laboratory has examined lung tissue samples counting fibers measuring 5 µm or greater in length. More recent observations have indicated that fibers 10 µm or greater in length are pathogenic, and that a length of 10 µm and diameter less than 1.0 µm are useful features for distinguishing asbestiform fibers from cleavage fragments. We examined more than 570 fibers from more than 90 cases to determine the dimensions of fibers that might be classified as asbestos. The vast majority of fibers classified as amosite or crocidolite met the criteria for length greater than 10 µm and diameter less than 1.0 µm. However, a significant proportion of fibers classified as tremolite, actinolite, or anthophyllite did not meet these criteria. These findings have important implications for the identification and classification of elongated mineral particles, both in terms of pathogenicity as well as classification as asbestiform vs. cleavage fragments.


A cost-effectiveness analysis of maternal CYP2D6 genetic testing to guide treatment for postpartum pain and avert infant adverse events.
Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine. Pharmacogenetic testing may be a valuable tool to identify such mothers, but testing can be costly. The objective of the study was to determine the incremental costs of genotyping to avert neonatal adverse events during maternal pharmacotherapy. A cost-effectiveness analysis, using a decision model, was performed with a hypothetical cohort of prenatal subjects. Parameter estimates, costs and ranges for sensitivity analyses were ascertained from the literature and expert opinion. Sensitivity analyses were conducted to assess the robustness of the results. Probabilistic sensitivity analysis revealed an incremental cost-effectiveness (ICER) of $10 433 (Canadian dollars) for genotyping compared to no genotyping per adverse event averted. Results were sensitive to hospital admission costs. The ICER was lower when evaluating only subjects having caesarean deliveries or those from ethnic populations known to have a high prevalence of ultra-rapid metabolizers. Although genotyping to guide pharmacotherapy was not cost saving, the cost to avert an infant adverse event may represent good value for money in specific populations. With a growing demand for personalized medicine, these findings are relevant for decision makers, clinicians and patients.


A fatal presentation of dermatomyositis.
Dermatomyositis (DM) is an autoimmune disease that mainly affects the skin, muscle, and lung. The pathogenesis of skin inflammation in DM is not well understood. We present a 40-year-old male who presented with four months history of generalized skin lesion, pain and weakness. He had elevated transaminases with detectable muscle weakness. This case highlights the need to consider dermatomyositis with skin lesion and weakness; and the use of aggressive immunosuppressive therapies due to its associated vasculopathies.


Results of arthroscopic fixation of osteochondritis dissecans lesion of the knee with cylindrical autogenous osteochondral plugs.
In situ fixation of unstable lesions of osteochondral dissecans of the knees with cylindrical osteochondral autograft transplantation has been reported to provide excellent results with healing of the osteochondral dissecans fragment. To evaluate the clinical results and magnetic resonance imaging findings of the osteochondral dissecans of knees treated with in situ fixation of the osteochondral fragments with osteochondral autograft transplantation. Case series; Level of evidence, 4. Twelve knees (12 patients; mean age, 16.0 years) with osteochondral dissecans lesions were treated with in situ fixation with autogenous osteochondral plugs. The mean lesion size was 2.4 cm(2) (range, 1.0-4.9 cm(2)). The osteochondral dissecans lesions were located on the medial femoral condyle in 10 patients and on the lateral femoral condyle in 2 patients. Seven lesions were located in the weightbearing area. The International Cartilage Repair Society classification in arthroscopic findings was grade II in 1 patient, grade III in 8 patients, and grade IV in 3 patients. All patients were evaluated with the Hughston Rating Scale form with the mean follow-up at 4.5 years (range, 2.8-5.9 years). The interface between the osteochondral fragment and subchondral bone and changes in donor site of the osteochondral graft were evaluated with T2-weighted magnetic resonance image up to 12 months postoperatively. The Hughston Rating Scale scored 8 knees as excellent, 3 as good, and 1 as fair. The interface between the osteochondral fragment and subchondral bone had disappeared on magnetic resonance image by 3 months postoperatively in all cases. No complications arising from the donor site area were observed. Signal intensity of donor site changed from high signal preoperatively to homogeneous surrounding cancellous bone by 1 year postoperatively. Biological fixation of the osteochondral dissecans lesion with cylindrical osteochondral autograft provided healing of the osteochondral fragments.


The interaction between steep waves and a surface-piercing column.
Experimental observations are presented of a single surface-piercing column subject to a wide range of surface gravity waves. With the column diameter, D, chosen such that the flow lies within the drag-inertia regime, two types of high-frequency wave scattering are identified. The first is driven by the run-up and wash-down on the surface of the column in the vicinity of the upstream and downstream stagnation points. The second concerns the circulation of fluid around the column, leading to the scattering of a pair of non-concentric wavefronts. The phasing of the wave cycle at which this second mode evolves is dependent upon the time taken for fluid to move around the column. This introduces an additional time-scale, explaining why existing diffraction solutions, based upon a harmonic analysis of the incident waves, cannot describe this scattered component. The interaction between the scattered waves and the next (steep) incident wave can produce a large amplification of the scattered waves, particularly the second type. Evidence is provided to show that these interactions can produce highly localized free-surface effects, including vertical jetting, with important implications for the setting of deck elevations, the occurrence of wave slamming and the development of large run-up velocities.


Connections Underlying Translation and mRNA Stability.
Gene expression and regulation in organisms minimally depends on transcription by RNA polymerase and on the stability of the RNA product (for both coding and non-coding RNAs). For coding RNAs, gene expression is further influenced by the amount of translation by the ribosome and by the stability of the protein product. The stabilities of these two classes of RNA, non-coding and coding, vary considerably: tRNAs and rRNAs tend to be long lived while mRNAs tend to be more short lived. Even among mRNAs, however, there is a considerable range in stability (ranging from seconds to hours in bacteria and up to days in metazoans), suggesting a significant role for stability in the regulation of gene expression. Here, we review recent experiments from bacteria, yeast and metazoans indicating that the stability of most mRNAs is broadly impacted by the actions of ribosomes that translate them. Ribosomal recognition of defective mRNAs triggers "mRNA surveillance" pathways that target the mRNA for degradation [Shoemaker and Green (2012) ]. More generally, even the stability of perfectly functional mRNAs appears to be dictated by overall rates of translation by the ribosome [Herrick et al. (1990), Presnyak et al. (2015) ]. Given that mRNAs are synthesized for the purpose of being translated into proteins, it is reassuring that such intimate connections between mRNA and the ribosome can drive biological regulation. In closing, we consider the likelihood that these connections between protein synthesis and mRNA stability are widespread or whether other modes of regulation dominate the mRNA stability landscape in higher organisms.


Intramedullary Fixation for Displaced Clavicle Fractures in the Adolescent Athlete.
The role of intramedullary (IM) fixation of displaced mid-shaft clavicle fractures in adolescents has not been described. This study analyzes characteristics and outcomes of IM fixation in adolescent clavicle fractures. Patients < 18 years with acute, mid-shaft clavicle fractures treated with IM clavicle pins between March 2007 and August 2013 were reviewed. Outcomes of interest were activity level, fracture pattern, time to union, return to sports and complications. Twenty-nine patients (14.8 years (range 11.4-17.9)) underwent IM pin fixation for a displaced, mid-shaft clavicle fracture, including 7 (24.1%) that were multi-fragmentary (length unstable). Complete displacement (> 100%) occurred in 27/29 (93.1%), with average preoperative shortening length of 18 mm. Union occurred in 100% of patients, at a mean duration of 8 weeks. Among student-athletes (25/29, 86.2%), average return to sport was at 18 weeks post-injury. IM pinning offers stable fixation of clavicle fractures in the active adolescent population.(Journal of Surgical Orthopaedic Advances 29(2):81-87, 2020).


Pathogenesis of paraquat-induced pulmonary hemorrhage in hamsters with special reference to arterial constriction.
Three dimensional reconstructions of pulmonary arteries and the bronchial tree were made to evaluate the cause of hemorrhage in the lungs of hamsters treated with a single intraperitoneal injection of paraquat at a dose of 15 mg/kg b.w. The hemorrhage corresponding to the respiratory bronchiolar segment formed the minimum hemorrhagic unit; larger hemorrhages were composed of conglomerations of such units. The respiratory bronchiolar segment was fed by a single respiratory bronchiolar arteriole which had a distinct muscular medial coat. No evidence of breakage of the arterial wall passing through the hemorrhagic lesion could be detected even by careful observation with serial histological sections. Accordingly, the cause of the lung hemorrhage was sought in the combined effects of paraquat toxicity to the capillary endothelium and vasoconstriction of the respiratory bronchiolar arterioles.


circRNA hsa_circ_0005909 Predicts Poor Prognosis and Promotes the Growth, Metastasis, and Drug Resistance of Non-Small-Cell Lung Cancer via the miRNA-338-3p/SOX4 Pathway.
Circular RNAs (circRNAs) are powerful factors in regulating various cancer behaviors. It has been manifested in previous researches that circular RNA hsa_circ_0005909 (circ_0005909) exhibits a regulatory function in osteosarcoma. However, there are no other studies on whether circ_0005909 displays potential functions on the progression of non-small-cell lung cancer (NSCLC). RT-PCR was applied to examine the expression of circ_0005909 in NSCLC. To study the specific behaviors of NSCLC cells after circ_0005909 knockdown, cell counting kit-8 (CCK-8) assays, colony formation assays, Transwell assays, and xenograft tumor model assays were conducted. Bioinformatics and luciferase reporter assays were employed to study the association among circ_0005909, miRNA-338-3p, and SOX4. In this research, our group firstly showed that circ_0005909 expressions were distinctly increased in NSCLC specimens and cell lines. Clinical studies revealed that high circ_0005909 expressions were associated with poor prognosis of NSCLC patients. Functionally, knockdown of circ_0005909 was observed to suppress the proliferation, metastasis, and drug resistance of NSCLC cells. In the terms of mechanism, circ_0005909 could act as a sponge of miRNA-338-3p, and miRNA-338-3p could target SOX4. In addition, miRNA-338-3p inhibitors reversed the suppressor ability of circ_0005909 silence on NSCLC behaviors. circ_0005909 promoted the progression of NSCLC via the modulation of the miRNA-338-3p/SOX4 axis, which may be a therapeutic target for NSCLC.


Impact of a stand-alone course in gerontological nursing on undergraduate nursing students' perceptions of working with older adults: A Quasi-experimental study.
With an aging population, it is critical that nurses are educated and prepared to offer quality healthcare to this client group. Incorporating gerontology content into nursing curricula and addressing students' perceptions and career choices in relation to working with older adults are important faculty concerns. To examine the impact of a stand-alone course in gerontological nursing on undergraduate nursing students' perceptions of working with older adults and career intentions. Quasi-experimental, pre- and post-test design. Medium-sized state university in the Mid Western United States PARTICIPANTS: Data were collected from three student cohorts during the spring semesters of 2012 (n=98), 2013 (n=80) and 2014 (n=88) for a total of N=266 with an average response rate of 85%. A survey instrument was administered via Qualtrics and completed by students prior to, and following completion of the course. There was an overall significant increase (p=0.000) in positive perceptions of working with older adults among nursing students following completion of the course. The majority of participants (83.5%) reported having previous experience with older adults. Those with previous experience had higher perception scores at pre-test than those without (p=0.000). Post-test scores showed no significant difference between these two groups, with both groups having increased perception scores (p=0.120). Student preferences for working with different age groups suggested an overall increase in preference for working with older adults following the course. A course in gerontological nursing, incorporating learning partnerships with community dwelling older adults, promotes positive perceptions of working with older adults, independently of the quality of prior experience. There was some evidence that students changed their preferences of working with different age groups in favor of working with older adults. Further research should be conducted to determine the mechanisms through which this takes place.


Antibody levels in Ethiopian children five years after vaccination with two different doses of hepatitis B vaccine: is there a need for booster vaccine?
It was hypothesized that, following effective initial vaccination, a booster dose of hepatitis B vaccine will not be necessary in areas of hyperendemicity for hepatitis B virus (HBV) infection. A total of 314 Ethiopian children, ranging from two to 14 years old, were alternatively vaccinated with 10 and 20 micrograms hepatitis B vaccine doses, using the initial, one- and six-month schedule. Five years later, 210 of the vaccinees were retested for anti-HBV surface antibody titres. Both 10 and 20 micrograms doses of hepatitis B rDNA yeast vaccine were equally immunogenic and protective against HBV infection for at least five years despite marked reduction of mean antibody levels and geometric mean titres, with 11% of the vaccinees showing antibodies below the protective level. For firm further recommendations a longer follow-up period of vaccinees is suggested.


The journey is just as important as the destination-Digital neuropsychological assessment provides performance stability measures in patients with acquired brain injury.
Cognitive performances on neuropsychological paper-and-pencil tests are generally evaluated quantitatively by examining a final score (e.g., total duration). Digital tests allow for a quantitative evaluation of "how" a patient attained a final score, which opens the possibility to assess more subtle cognitive impairment even when final scores are evaluated as normal. We assessed performance stability (i.e., the number of fluctuations in test performance) to investigate (1) differences in performance stability between patients with acquired brain injury (ABI) and healthy controls; (2) the added value of performance stability measures in patients with ABI; and (3) the relation between performance stability and cognitive complaints in daily life in patients with ABI. We administered three digital neuropsychological tests (Rey Auditory Verbal Learning Test, Trail Making Test, Stroop Colour and Word Test) and the Cognitive Complaints-Participation (CoCo-P) inventory in patients with ABI (n = 161) and healthy controls (n = 91). Patients with ABI fluctuated more in their performance on all tests, when compared to healthy controls. Furthermore, 4-15% of patients who performed inside normal range on the conventional final scores were outside normal range on the performance stability measures. The performance stability measures, nor the conventional final scores, were associated with cognitive complaints in daily life. Stability in test performance of patients was clearly dissociable from healthy controls, and may assess additional cognitive weaknesses which might not be observed or objectified with paper-and-pencil tests. More research is needed for developing measures better associated with cognitive complaints.


Mothers' groups enrich diet and culture through promoting traditional Quichua foods.
Indigenous Peoples in Latin America bear a disproportionate burden of undernutrition, yet traditional foods, including wild leafy greens, can contribute nutritional value to diets. As part of a community nutrition intervention using local foods in highland Tungurahua, Ecuador, mothers' groups promoted the consumption of wild leafy greens through community cooking clubs and recipe competitions at local fairs. The objective was to assess the social, cultural, and nutritional potential of a mothers' club intervention that promoted 2 indigenous greens (stinging nettle/Urtica dioica L. and round-leaved dock/Rumex obtusifolius L.) into children's diets. Key informant interviews and focus groups were conducted with 54 mothers and 16 elders to identify perceptions of the intervention and traditional foods. Social and cultural dimensions were identified through content analysis. The nutritional contribution of the leafy greens was estimated through semiquantitative food frequency questionnaires conducted with 160 participant mothers and 98 mothers living in comparison communities who had not been exposed to the intervention. The use of local foods generated pride for mothers and elders. Nonfood uses of the nettle proved an initial barrier to acceptance; however, peer support within mothers' groups enabled increased consumption. The greens were estimated to contribute an additional 8% vitamin A, 7% iron, 12% vitamin C, and 27% folate to children's recommended dietary intakes. By promoting wild leafy greens, mothers' groups improved food security and the cultural and nutritional value of their diets. Additionally, mothers' cooking clubs increased self-efficacy and cultural identity for Quichua women, offering a highly acceptable nutrition intervention model.


3D-Printed Porous Scaffolds of Hydrogels Modified with TGF-β1 Binding Peptides to Promote In Vivo Cartilage Regeneration and Animal Gait Restoration.
The treatment of cartilage injury and osteoarthritis has been a classic problem for many years. The idea of in situ tissue regeneration paves a way for osteochondral repair in vivo. Herein, a hydrogel scaffold linked with bioactive peptides that can selectively adsorb transforming growth factor β1 (TGF-β1) was hypothesized to not only afford cell ingrowth space but also induce the endogenous TGF-β1 recruitment for chondrogenesis promotion. In this study, bilayered porous scaffolds with gelatin methacryloyl (GelMA) hydrogels as a matrix were constructed via three-dimensional (3D) printing, of which the upper layer was covalently bound with bioactive peptides that can adsorb TGF-β1 for cartilage repair and the lower layer was blended with hydroxyapatite for subchondral regeneration. The scaffolds showed promising therapeutic efficacy proved by cartilage and osteogenic induction in vitro and osteochondral repair of rats in vivo. In particular, the animal gait behavior was recovered after the in situ tissue regeneration, and the corresponding gait analysis demonstrated the promotion of tissue regeneration induced by the porous hydrogels with the binding peptides.


Social relations and loneliness among older patients consulting their general practitioner.
Social relations are important for people and affect their quality of life, morbidity and mortality. This holds true especially for older persons. General practitioners (GPs) are in a unique position to address social relations and loneliness; however, no GP population-based studies have assessed older patients' social relations and loneliness. The aim of this study was to analyse the social relations and loneliness of patients aged 65 years and above consulting their GP. This survey counted the participation of 12 general practices in the Capital Region of Denmark. During a three-week period, the practices invited their patients to fill out a questionnaire on health, social relations and loneliness. Of 767 eligible patients, 474 were included and 461 answered one or more items about social participation or loneliness. A total of 36.2% had a high, 45.5% had a medium and 18.3% had a low social participation; and 17.9% often or occasionally felt lonely. Higher social participation was associated with a lower degree of loneliness. However, several patients answered in a manner not fitting the expected association. Anxiety and depressive symptoms, living alone and low social participation were the most important predictive variables for loneliness. Only 15.2% of the lonely patients had talked to their GP about their loneliness. A total of 17.9% of older patients stated that they were lonely either often or occasionally. The most important predictors were: anxiety and depressive symptoms, living alone and low social participation. The lonely patients rarely shared these issues with their GP. The study also reveals a need to discuss the assessment of social participation and loneliness in both research and practice. Danish Agency for Culture and Palaces. The EGV Foundation. The Committee of Multipractice Studies in General Practice. not relevant.


Does the declining prevalence of Helicobacter pylori unmask patients with idiopathic peptic ulcer disease? Trends over an 8 year period.
Recent studies have suggested that the prevalence of Helicobacter pylori infection in patients with ulcer disease who were not using non-steroidal anti-inflammatory drugs (NSAIDs) has been overestimated. The decreasing prevalence of H. pylori could lead to a relative increase in the number of patients with this idiopathic peptic ulcer disease (IPUD). This study aimed to investigate the prevalence of IPUD and any possible trends. The reports of all upper gastro-intestinal endoscopies performed in a Dutch regional hospital over the period 1991 to 1998 were reviewed. If a gastric and/or duodenal ulcer had been diagnosed, data concerning possible H. pylori infection (culture, histology, rapid in-house urease test) were retrieved. If H. pylori tests were negative, hospital files were examined for possible use of NSAIDs or other rare causes of ulcer disease. When these were not found, stored biopsy specimens were tested for H. heilmanii by using the polymerase chain reaction technique. Ulcer disease was diagnosed in 405 patients who had undergone endoscopy (159 with gastric ulcer, 235 with duodenal ulcer, and 11 with both gastric and duodenal ulcer). H. pylori infection was found in 349 of these patients (86.2%). Thirty-three of the 56 H. pylori negative patients used NSAIDs and three patients had Crohn's disease, leaving 20 patients with IPUD (4.9%, 12 gastric ulcer and eight duodenal ulcer). Time trends over the study period showed a decrease of H. pylori associated peptic ulcer disease (P <0.002) and an increase of NSAID associated peptic ulcer disease (P <0.0005). The prevalence of IPUD remained stable (P=0.978). The prevalence of patients with H. pylori negative ulcer disease significantly decreased in our study population due to an increase in the number of patients with NSAID associated peptic ulcer disease. IPUD was rare and its prevalence did not increase over a period of 8 years.


A 1 kHz A-scan rate pump-probe laser-ultrasound system for robust inspection of composites.
We recently built a fiber-optic laser-ultrasound (LU) scanner for nondestructive evaluation (NDE) of aircraft composites and demonstrated its greatly improved sensitivity and stability compared with current noncontact systems. It is also very attractive in terms of cost, stability to environmental noise and surface roughness, simplicity in adjustment, footprint, and flexibility. A new type of a balanced fiber-optic Sagnac interferometer is a key component of this all-optical LU pump-probe system. Very high A-scan rates can be achieved because no reference arm or stabilization feedback are needed. Here, we demonstrate LU system performance at 1000 A-scans/s combined with a fast 2-D translator operating at a scanning speed of 100 mm/s with a peak acceleration of 10 m/s(2) in both lateral directions to produce parallel B-scans at high rates. The fast scanning strategy is described in detail. The sensitivity of this system, in terms of noise equivalent pressure, was further improved to be only 8.3 dB above the Nyquist thermal noise limit. To our knowledge, this is the best reported sensitivity for a noncontact ultrasonic detector of this dimension used to inspect aircraft composites.


Combined deficiencies of Msx1 and Msx2 cause impaired patterning and survival of the cranial neural crest.
The neural crest is a multipotent, migratory cell population that contributes to a variety of tissues and organs during vertebrate embryogenesis. Here, we focus on the function of Msx1 and Msx2, homeobox genes implicated in several disorders affecting craniofacial development in humans. We show that Msx1/2 mutants exhibit profound deficiencies in the development of structures derived from the cranial and cardiac neural crest. These include hypoplastic and mispatterned cranial ganglia, dysmorphogenesis of pharyngeal arch derivatives and abnormal organization of conotruncal structures in the developing heart. The expression of the neural crest markers Ap-2alpha, Sox10 and cadherin 6 (cdh6) in Msx1/2 mutants revealed an apparent retardation in the migration of subpopulations of preotic and postotic neural crest cells, and a disorganization of neural crest cells paralleling patterning defects in cranial nerves. In addition, normally distinct subpopulations of migrating crest underwent mixing. The expression of the hindbrain markers Krox20 and Epha4 was altered in Msx1/2 mutants, suggesting that defects in neural crest populations may result, in part, from defects in rhombomere identity. Msx1/2 mutants also exhibited increased Bmp4 expression in migratory cranial neural crest and pharyngeal arches. Finally, proliferation of neural crest-derived mesenchyme was unchanged, but the number of apoptotic cells was increased substantially in neural crest-derived cells that contribute to the cranial ganglia and the first pharyngeal arch. This increase in apoptosis may contribute to the mispatterning of the cranial ganglia and the hypoplasia of the first arch.


Nonlinear information fusion algorithms for data-efficient multi-fidelity modelling.
Multi-fidelity modelling enables accurate inference of quantities of interest by synergistically combining realizations of low-cost/low-fidelity models with a small set of high-fidelity observations. This is particularly effective when the low- and high-fidelity models exhibit strong correlations, and can lead to significant computational gains over approaches that solely rely on high-fidelity models. However, in many cases of practical interest, low-fidelity models can only be well correlated to their high-fidelity counterparts for a specific range of input parameters, and potentially return wrong trends and erroneous predictions if probed outside of their validity regime. Here we put forth a probabilistic framework based on Gaussian process regression and nonlinear autoregressive schemes that is capable of learning complex nonlinear and space-dependent cross-correlations between models of variable fidelity, and can effectively safeguard against low-fidelity models that provide wrong trends. This introduces a new class of multi-fidelity information fusion algorithms that provide a fundamental extension to the existing linear autoregressive methodologies, while still maintaining the same algorithmic complexity and overall computational cost. The performance of the proposed methods is tested in several benchmark problems involving both synthetic and real multi-fidelity datasets from computational fluid dynamics simulations.


Lattice-gas model based on field mediators for immiscible fluids.
A Boolean lattice-gas model based on field mediators is proposed for simulating the flow of immiscible fluids. The field mediators introduced here simulate long-range action, enabling the use of local rules in separation step and, by avoiding the optimization step, reduce computer processing time with respect to previous models. In addition, field strength and interaction distance is modeled by introducing distinct emission P(e) and extinction P(a) probabilities, for field mediators, enabling us to control interfacial tension and transition thickness. The model's microdynamics is fully described and macroscopic parameters are related to model's parameters after a Chapman-Enskog asymptotic expansion for the ensemble-average distributions. Simulation results are presented for several sample case studies, including the verification of Laplace's law, coalescence phenomenon, interaction of a pair of wetting and nonwetting fluids with solid surfaces, and droplet formation under the action of gravity. These results are compared with available data.


Nutritional management of the patient with chronic obstructive pulmonary disease.
The prevalence and prognostic importance of malnutrition in chronic obstructive pulmonary disease (COPD), the factors that contribute to development of nutritional depletion, and the available evidence regarding effects of nutrition support in these patients are the subjects of this review. Nutritional depletion, as indicated by weight loss and loss of lean body mass, is a common complication of advanced COPD (particularly, but not limited to, the emphysematous type). Low body weight or recent weight loss and in particular depleted lean body mass in patients with COPD have been shown to be independent predictors of mortality, outcomes after acute exacerbations, hospital admission rates, and need for mechanical ventilation. The factors thought to contribute to nutritional depletion in these patients include elevated resting and activity-related energy expenditure, reduced dietary intake relative to resting energy expenditure, accelerated negative nitrogen balance, particularly during acute exacerbations of COPD, medication effects, and perhaps most importantly an elevated systemic inflammatory response. Studies to date suggest that, although it can help limit weight loss and negative energy balance in these patients, the effect of nutritional supplementation alone on clinically significant outcomes such as pulmonary function and exercise capacity is minimal. However, nutritional supplementation may have a role in the management of COPD when provided as part of an integrated rehabilitation program incorporating a structured exercise component as an anabolic stimulus.


Analysis of genetic diversity and structure in Ethiopian populations of Phytolacca dodecandra using RAPD.
The genetic diversity and structure in 17 wild populations (249 individuals) of Phytolacca dodecandra (endod) sampled along altitudinal gradients of 1600-3000 meters above sea level (m.a.s.l.) in Ethiopia was studied using random amplified polymorphic DNA (RAPD). A total of 70 polymorphic loci (P) scored from 12 RAPD primers were used to calculate different diversity indices within and between populations, habitats, geographical regions, climatic zones and altitude groups. The number of polymorphic loci and overall Shannon information measure (H) in the populations varied from 30 to 55 and from 0.228 to 0.418, respectively. In general, differences in population variability were found significantly correlated to effective population size. Both P and H were significantly higher in an undisturbed than in a disturbed habitat, and in the lowland and central-highland than in the highland altitude group. However, for both parameters the differences were not statistically significant between regions and climatic zones. Genetic distance between populations varied from 0.301 to 0.628. Cluster analysis performed using the genetic distance matrix revealed a clear separation of the highland populations (2501-3000 m.a.s.l.) from those of the lowland/central-highlands (1600-2500 m.a.s.l.) irrespective of their geographical regions and climatic zones. Analysis of molecular variance (AMOVA) indicated that differences in habitat, geographical regions and climatic zones explained 4.6%, 2.5% and 4.6%, respectively. But none of these differences were significant. Altitude explained 17.2% of the total variance and was highly significant. The data, therefore, clearly indicated the association of genetic structure in endod with altitude. The proportion of RAPD variation found among populations (21.2-35.0%) was somewhat intermediate between values reported for selfing and outcrossing species. The fixation index (FST) values (0.350 to 0.384) indicated very high genetic differentiation among populations.


Quantification of selected elements in ovarian tumours and their potentials as a tissue classifier.
Neoplastic and healthy ovarian tissues were analysed to identify the changes in the spatial distribution and concentration of elements using synchrotron induced micro X-ray fluorescence spectroscopy. High-resolution distribution maps of minor and trace elements were drawn. Significant amounts of elements such as P, S, Cl, K, Ca, Fe, Cu, Zn, Br and Rb were present in all neoplastic tissues analysed. The study showed significant diversifications in elemental distributions depending on the structure of tissue. The efficacy of micro X-ray fluorescence spectroscopy to distinguish between various types of ovarian tumours based on the concentrations of studied elements was confirmed by multivariate discriminant analysis. Our analysis showed that the most important elements for tissue classification are S, Cl, K, Fe, Zn, Br and Rb.


PDGFRA amplification is common in pediatric and adult high-grade astrocytomas and identifies a poor prognostic group in IDH1 mutant glioblastoma.
High-grade astrocytomas (HGAs), corresponding to World Health Organization grades III (anaplastic astrocytoma) and IV (glioblastoma; GBM), are biologically aggressive, and their molecular classification is increasingly relevant to clinical management. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs. A range of PDGFRA FISH patterns were identified and cases were scored as non-amplified (normal and polysomy) or amplified (low-level and high-level). PDGFRA amplification was frequent in pediatric (29.3%) and adult (20.9%) tumors. Amplification was not prognostic in pediatric HGAs. In adult tumors diagnosed initially as GBM, the presence of combined PDGFRA amplification and isocitrate dehydrogenase 1 (IDH1)(R132H) mutation was a significant independent prognostic factor (P = 0.01). In HGAs, PDGFRA amplification is common and can manifest as high-level and focal or low-level amplifications. Our data indicate that the latter is more prevalent than previously reported with copy number averaging techniques. To our knowledge, this is the largest survey of PDGFRA status in adult and pediatric HGAs and suggests PDGFRA amplification increases with grade and is associated with a less favorable prognosis in IDH1 mutant de novo GBMs.


Heavy metal resistance in halophilic Bacteria and Archaea.
Heavy metals are dense chemicals with dual biological role as micronutrients and intoxicants. A few hypersaline environmental systems are naturally enriched with heavy metals, while most metal-contaminated sites are a consequence of human activities. Numerous halotolerant and moderately halophilic Bacteria possess metal tolerance, whereas a few archaeal counterparts share similar features. The main mechanisms underlying heavy metal resistance in halophilic Bacteria and Archaea include extracellular metal sequestration by biopolymers, metal efflux mediated by specific transporters and enzymatic detoxification. Biotransformation of metals by halophiles has implications both for trace metal turnover in natural saline ecosystems and for development of novel bioremediation strategies.


Expression of beta1-integrins and N-cadherin in bladder cancer and melanoma cell lines.
Changes in the expression of integrins and cadherins might contribute to the progression, invasion and metastasis of transitional cell cancer of the bladder and of melanomas. The expression of alpha5 (P < 0.001), alpha2 and beta1 (P < 0.05 - P < 0.001) integrin subunits in melanoma cells from noncutaneous metastatic sites (WM9, A375) were significantly increased as compared to cutaneous primary tumor (WM35) and metastatic (WM239) cell lines. These differences might be ascribed to the invasive character of melanoma cells and their metastasis to the noncutaneous locations. The significantly heterogeneous expression of beta1 integrin subunit in two malignant bladder cancer cell lines (T24 and Hu456) and nonsignificant differences in the expression of alpha2, alpha3, and alpha5 subunits between malignant and non-malignant human bladder cell lines do not allow an unanimous conclusion on the role of these intergrin subunits in the progression of transitional cancer of bladder. The adhesion molecule, expressed in all studied melanoma and bladder cell lines, that reacted with anti-Pan cadherin monoclonal antibodies was identified as N-cadherin except in the HCV29 non-malignant ureter cell line. However, neither this nor any other bladder or melanoma cell line expressed E-cadherin. The obtained results imply that the replacement of E-cadherin by N-cadherin accompanied by a simultaneous increase in expression of alpha2, alpha3 and alpha5 integrin subunits clearly indicates an increase of invasiveness of melanoma and, to a lesser extent, of transitional cell cancer of bladder. High expression of N-cadherin and alpha5 integrin subunit seems to be associated with the most invasive melanoma phenotype.


Descending colon cancer in a patient with situs inversus totalis: a case report and literature review.
Situs inversus totalis (SIT) is a congenital disorder of anatomical position, and the operation of patients with total visceral inversion often brings great challenges to surgeons. Although there have been previously documented on patients with SIT and colonic cancer, this is the first case report of descending colon cancer in patient with SIT. The current report presents a case of a 67-year-old female patient with descending colon cancer and SIT. After preoperative preparation and discussion, open left hemicolectomy was performed for the patient. The postoperative recovery of the patient was smooth; however, there was a mild lymphatic leakage in the patient, which was cured by conservative treatment for 5 days. The patient was discharged on postoperative Day 10. There was no tumor recurrence or other discomfort in 1 year follow-up period.


[The application of multi-slice CT and MRI on maxillofacial region soft tissue measurement].
To evaluate the value of multi-slice CT and MRI on maxillofacial region soft tissue measurement. A total of 12 cases of dentofacial orthodontic underwent X-ray photograph, multi-slice CT and MRI scanning. The angle and distance of maxillofacial region soft tissue were measured respectively. All data were analyzed statistically for ANOVA with SPSS11.0 software package. There was no significant difference among the three measurement methods: X-ray photograph, multi-slice CT and MRI(P>0.05). MRI had advantages on depicting hierarchical structure of maxillofacial region, especially soft tissues, while multi-slice CT had advantages on depicting structure of maxillofacial region, both hard and soft tissues. Multi-slice CT and MRI are useful on maxillofacial region soft tissues measurement. MRI is superior to multi-slice CT and X-ray photograph on maxillofacial region soft tissue measurement.


Millard-Gubler Syndrome due to Parenchymal Neuro-Behcet's Syndrome Lesion: a Rare Case Report.
Behcet's disease; it is a vascular-inflammatory chronic recurrent disease that can affect many systems in the body. Millard Gubler syndrome is one of the brainstem syndromes that occurs due to lesions involving the ventral part of the caudal pons. We wanted to present a case of Millard Gubler syndrome, which developed due to Behçet's syndrome lesion in the pons ventral region in a patient who presented with limitation of outward gaze on the left, inability to close the left eye completely, inability to completely wrinkle the left side of the forehead, and loss of contralateral muscle strength. Keywords: Behcet's syndrome, parenchymal, abducens, facial, lesion.


A new orally bioavailable synthetic androstene inhibits collagen-induced arthritis in the mouse: androstene hormones as regulators of regulatory T cells.
Dehydroepiandrosterone (DHEA) has attracted much interest because of its many antiaging, metabolic and immune-modulating effects in rodents. Synthetic derivatives, such as 5-androstene-16alpha-fluoro-17-one (HE2500) and certain natural metabolites also provide benefit in various animal models of autoimmune and metabolic diseases. But, like DHEA, low potency and low oral bioavailability suggested limited usefulness of these compounds in humans. We hypothesized that HE3286, a novel 17-ethynyl derivative would be orally bioavailable, more potent, and chemically more useful in man than its parent compound. We found that on a dose/mass basis, HE3286 demonstrated up to 25% oral bioavailability in mice. In the DBA mouse model of collagen-induced arthritis (CIA), animals receiving oral treatment with HE3286 (50 mg/kg), beginning at onset of disease, significantly decreased CIA peak scores and daily severity of arthritis scores. Benefit was associated with decreases in: (1) production of TNF-alpha, IL-6, and IL-17; and (2) decreases in joint inflammation, erosion, and synovial proliferation as judged by histological analysis. HE3286 was not found to be immune suppressive in any of the classical models tested, including mitogen-induced proliferation, delayed-type hypersensitivity, or mixed lymphocyte reaction. Instead, benefit was associated with increases in numbers and function of CD4+CD25+FOXp3+CD127- regulatory T cells (T reg). To our knowledge, this is probably the first study to report that an orally bioavailable synthetic analogue of DHEA can ameliorate ongoing disease in a CIA mouse model with relevance to rheumatoid arthritis (RA) and to correlate that finding with decreases in proinflammatory cytokines and increases in T reg cells. Hormones targeting T reg cells hold the intriguing potential to treat autoimmune, infectious, and neoplastic diseases.


Fibrinogen-erythrocyte binding and hemorheology measurements in the assessment of essential arterial hypertension patients.
Some studies have reported a positive association between plasma fibrinogen levels, erythrocyte aggregation and essential arterial hypertension (EAH). The aim of this study was to understand how the interaction between fibrinogen and its erythrocyte membrane receptor is altered in EAH. EAH patients (n = 31) and healthy blood donors (n = 65) were enrolled in the study. EAH patients were therapeutically controlled for the disease, presenting a systolic blood pressure between 108 and 180 mmHg and a diastolic blood pressure between 66 and 123 mmHg. Clinical evaluation included blood pressure monitoring, electrocardiography, echocardiography and blood cell count. The hemorheological parameters were also analyzed. Fibrinogen-erythrocyte binding force and frequency were evaluated quantitatively, at the single-molecule level, using atomic force microscopy (AFM). Changes in erythrocyte elasticity were also evaluated. Force spectroscopy data showed that the average fibrinogen-erythrocyte binding forces increase from 40.4 ± 3.0 pN in healthy donors to 73.8 ± 8.1 pN in patients with EAH, despite a lower binding frequency for patients compared to the control group (7.9 ± 1.6% vs. 27.6 ± 4.2%, respectively). Elasticity studies revealed an increase of erythrocyte stiffness in the patients. The stronger fibrinogen binding to erythrocytes from EAH patients and alteration in cell elasticity may lead to changes in the whole blood flow. The patients' altered hemorheological parameters may also contribute to these blood flow perturbations. The transient bridging of two erythrocytes, by the simultaneous binding of fibrinogen to both of them, promoting erythrocyte aggregation, could represent an important cardiovascular risk factor.


Fluoroscopically guided percutaneous suprapubic cystostomy for long-term bladder drainage: an alternative to surgical cystostomy.
Percutaneous large-bore suprapubic cystostomy catheters were placed under fluoroscopic guidance in 60 patients as an alternative to surgical cystostomy. Foley catheters (16-20 F) were placed in 57 of the patients in a one-stage procedure. Ten-French catheters were initially placed in three patients because of difficulty in dilating percutaneous tracks because of obesity (one patient) or dense scar tissue (two patients). Three weeks later, 18-F Foley catheters were placed in these three patients when mature tracks had developed, making dilation easier. Minor complications occurred in three patients, including superficial track bleeding in two and urosepsis in one. Fifteen patients were lost to follow-up. Suprapubic catheters provided excellent long-term drainage (range, 0.5-36 months; mean, 16 months; median, 18 months) in the remaining 45 patients. The authors conclude that percutaneous suprapubic catheter placement is a safe and effective procedure that provides excellent long-term bladder drainage.


Nicastrin haploinsufficiency alters expression of type I interferon-stimulated genes: the relationship to familial hidradenitis suppurativa.
Hidradenitis suppurativa (HS), also called acne inversa, is a chronic skin disease. The symptoms can be severe, and include intensely painful nodules and abscesses in apocrine-gland rich inverse skin, such as the buttocks, under the arms and in the groin. Autosomal dominant forms of HS exist, but are rare. Some of these kindred have heterozygous loss-of-function rare variants in the γ-secretase complex component nicastrin (NCSTN). To investigate the effect of NCSTN haploinsufficiency on human keratinocytes and assess potential mechanisms for lesion development. NCSTN was knocked down using a small hairpin RNA construct in both a keratinocyte cell line (HEK001) and an embryonic kidney cell line (HEK293), and differential gene expression was assessed using RNA microarray. Using the HEK293 line, a heterozygous deletion of NCSTN was created with CRISPR/Cas9 genome editing, and nuclear factor kappa B activity was assessed using a luciferase reporter. Compared with controls, the keratinocyte NCSTN knockdown cell line showed a significantly increased expression of genes related to the type I interferon response pathway. Both HEK001 and HEK293 knockdowns demonstrated evidence of altered growth. There was a small but significant increase in nuclear factor kappa B signalling in response to tumour necrosis factor treatment in HEK293 cells genome-edited for reduced NCSTN. Our data suggest a role for increased keratinocyte inflammatory responsiveness in familial HS. Confirming this phenotype and characterizing additional effects in different cell types will require study beyond cell lines, such as in primary cells and tissues.


A unique case of massive gastrointestinal bleeding.
Lipomas are the second most common benign tumors of the small bowel, and most lipomas are asymptomatic. However, lipomas with diameters of >20 mm tend to be symptomatic, for example, to cause bleeding, obstructive jaundice, abdominal pain, intestinal obstruction, intussusception, and/or perforation. We report a case of massive gastrointestinal bleeding from a jejunal lipoma combined with intussusception. A preoperative diagnosis of gastrointestinal bleeding derived from a jejunal lipoma combined with intussusception was made based on double-balloon enteroscopy and contrast-enhanced computed tomography, and partial resection of the small intestine was performed. After surgery, there was no additional gastrointestinal bleeding. There have only been a few reports about cases of jejunal lipoma involving simultaneous bleeding and intussusception. Double-balloon enteroscopy is useful for preoperatively diagnosing bleeding from a lipoma. Our case highlights that jejunal lipoma can cause massive unexplained gastrointestinal bleeding.


Fowlpox-based survivin vaccination for malignant mesothelioma therapy.
Survivin protein is an attractive candidate for cancer immunotherapy since it is abundantly expressed in most common human cancers and mostly absent in normal adult tissues. Malignant mesothelioma (MM) is a deadly cancer associated with asbestos or erionite exposure for which no successful therapies are currently available. In this study, we evaluated the therapeutic efficacy of a novel survivin-based vaccine by subcutaneous or intraperitoneum injection of BALB/c mice with murine fiber-induced MM tumor cells followed by vaccination with recombinant Fowlpox virus replicons encoding survivin. Vaccination generated significant immune responses in both models, leading to delayed tumor growth and improved animal survival. Flow cytometry and immunofluorescence analyses of tumors from vaccinated mice showed CD8(+) T-cell infiltration, and real-time PCR demonstrated increased mRNA and protein levels of immunostimulatory cytokines. Analyses of survivin peptide-pulsed spleen and lymph node cells from vaccinated mice using ELISPOT and intracellular cytokine staining confirmed antigen-specific, interferon-γ-producing CD8(+) T-cell responses. In addition pentamer-based flow cytometry showed that vaccination generated survivin-specific CD8(+) T cells. Importantly, vaccination did not affect fertility or induce autoimmune abnormalities in mice. Our results demonstrate that vaccination with recombinant Fowlpox expressing survivin improves T-cell responses against aggressive MM tumors and may form the basis for promising clinical applications.


Heat shock protein 90 in plants: molecular mechanisms and roles in stress responses.
The heat shock protein 90 (Hsp90) family mediates stress signal transduction, and plays important roles in the control of normal growth of human cells and in promoting development of tumor cells. Hsp90s have become a currently important subject in cellular immunity, signal transduction, and anti-cancer research. Studies on the physiological functions of Hsp90s began much later in plants than in animals and fungi. Significant progress has been made in understanding complex mechanisms of HSP90s in plants, including ATPase-coupled conformational changes and interactions with cochaperone proteins. A wide range of signaling proteins interact with HSP90s. Recent studies revealed that plant Hsp90s are important in plant development, environmental stress response, and disease and pest resistance. In this study, the plant HSP90 family was classified into three clusters on the basis of phylogenetic relationships, gene structure, and biological functions. We discuss the molecular functions of Hsp90s, and systematically review recent progress of Hsp90 research in plants.


Fat-Soluble Vitamin Deficiency in Pediatric Patients with Biliary Atresia.
To analyze the levels of fat-soluble vitamins (FSVs) in pediatric patients with biliary atresia (BA) before and after the Kasai procedure. Pediatric patients with obstructive jaundice were enrolled in this study. The FSV levels and liver function before, 2 weeks after, and 1, 3, and 6 months after the Kasai procedure were measured. FSV deficiency was more obvious in patients with BA than in patients with other cholestatic liver diseases, especially vitamin D deficiency. 25-Hydroxy vitamin D (25-(OH)D) deficiency was more pronounced in younger patients before surgery. The 25-(OH)D level was significantly higher in patients with than without resolution of jaundice 3 months after surgery. At 6 months after surgery, the 25-(OH)D level was abnormally high at 8.76 ng/ml in patients with unresolved jaundice. Preoperative FSV deficiency, particularly vitamin D deficiency, is common in patients with BA. 25-(OH)D deficiency is more pronounced in younger children before surgery. Postoperative FSV deficiency was still prevalent as shown by the lower 25-(OH)D levels in patients with BA and unresolved jaundice. This required long-term vitamin AD supplementation for pediatric patients with BA and unresolved jaundice after surgery.


Number needed to treat: A primer for neurointerventionalists.
The number needed to treat is a commonly used statistical term in modern neurointerventional practice. It represents the number of patients that need to be treated for one patient to benefit from an intervention. Given its growing popularity in reflecting study results, understanding the basics behind this statistic is of practical value to the neurointerventionalist. Here, we review the basic theory and calculation of the number needed to treat, its application to stroke interventions, and its limitations. In addition, we demonstrate several simple methods of calculating the number needed to treat utilizing recent thrombectomy trial results. By presenting the number needed to treat as a universal metric, we provide a comprehensive comparative of the number needed to treat for key stroke therapies, including mechanical thrombectomy, tissue plasminogen activator, carotid endarterectomy, and prevention with antiplatelet and statin drugs. In comparison with available stroke therapies, mechanical thrombectomy stands out as the most effective acute intervention in patients with emergent large-vessel occlusions. Understanding how the number needed to treat is derived and its implications helps provide perspective to clinical trial data, identify health-care resource priorities, and improve communication with patients, health-care providers, and additional key stakeholders.


Hand-assisted laparoscopic colorectal surgery.
The use of laparoscopic techniques in the treatment of colorectal diseases was first described in the early 1990s. Even though its clinical benefits have been well documented, laparoscopic colorectal surgery has been slow to gain adoption in the surgical community, given its technical demands. To help overcome these challenges while preserving the clinical benefits derived from a minimally invasive approach, hand-assisted laparoscopic surgery (HALS) was proposed. HALS can decrease the learning curve by restoring tactile sensation and improving proprioception, and it may be more accessible for surgeons already in practice. A meta-analysis of the 3 published RCTs comparing hand-assisted laparoscopic to conventional laparoscopic colorectal resection showed a significantly lower rate of conversion in the hand-assist patients, while morbidity rates were equivalent. The meta-analysis further indicated that short-term postoperative benefits of conventional laparoscopic colectomies were preserved and costs were likely to be offset by reduced operative time and specific need of laparoscopic equipment. HALS represents a valuable option for performing colorectal resections.


The importance of fiberbronchoscopy in respiratory burns.
Respiratory burns worsen considerably the prognosis of the patients. Fiberoptic endoscopy facilitated the examination of respiratory burns and determined the degree and extent of mucosal damage. At the same time, aspiration and lavage of the affected bronchi can be advantageously used in therapy. 22 patients with respiratory burns were hospitalized at the Burn Centre, Works Institute of Health Care, East Slovak Iron Works, Kosice (Czechoslovakia); 13 of them died, i.e. 59.1%. The paper analyzes fiberbronchoscopy applied to respiratory burns, anaesthetic technique and intubation, and the results are compared with post mortem findings. Some clinical findings are demonstrated, too.


Rights of people with mental disorders: Realities in healthcare facilities in Tunisia.
Mental disorders have been associated worldwide with human rights' violations. Controversially, many occur in mental health facilities. This work aimed to assess the rights of people with mental disorders in healthcare facilities in Tunisia. A cross-sectional study, using the World Health Organization (WHO) quality-rights toolkit, assessed the human rights levels of achievement in Elrazi Hospital, the only psychiatric hospital in Tunisia, in comparison with the National Institute of Nutrition (NIN). The framework was the Convention on the Rights of Persons with Disabilities (CRPD). The assessment was carried through observation, documentation review, and interviews with service users, staff, and family members. The sample was composed of 113 interviewees. In Elrazi Hospital, three out of the five evaluated rights were assessed as only initiated: the right to an adequate standard of living, to exercise legal capacity and to be free from inhuman treatment. By comparison, these rights were partially achieved in the NIN. The right to enjoyment of the highest attainable standard of health was partially achieved and the right to live independently and to be included in the community was not even initiated. These last two rights were at the same level of achievement in the NIN. Significant improvements are needed to adapt the practice in Elrazi Hospital to comply with human rights, especially since the achievement level of these rights is lower than in a non-psychiatric hospital. Our study emphasizes the importance of spreading the CRPD as a standardized framework.


Cryo-electron microscopy structure of the glucagon receptor with a dual-agonist peptide.
Unimolecular dual agonists of the glucagon (GCG) receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) are a new class of drugs that are potentially superior to GLP-1R-specific agonists for the management of metabolic disease. The dual-agonist, peptide 15 (P15), is a glutamic acid 16 analog of GCG with GLP-1 peptide substitutions between amino acids 17 and 24 that has potency equivalent to those of the cognate peptide agonists at the GCGR and GLP-1R. Here, we have used cryo-EM to solve the structure of an active P15-GCGR-Gs complex and compared this structure to our recently published structure of the GCGR-Gs complex bound to GCG. This comparison revealed that P15 has a reduced interaction with the first extracellular loop (ECL1) and the top of transmembrane segment 1 (TM1) such that there is increased mobility of the GCGR extracellular domain and at the C terminus of the peptide compared with the GCG-bound receptor. We also observed a distinct conformation of ECL3 and could infer increased mobility of the far N-terminal His-1 residue in the P15-bound structure. These regions of conformational variance in the two peptide-bound GCGR structures were also regions that were distinct between GCGR structures and previously published peptide-bound structures of the GLP-1R, suggesting that greater conformational dynamics may contribute to the increased efficacy of P15 in activation of the GLP-1R compared with GCG. The variable domains in this receptor have previously been implicated in biased agonism at the GLP-1R and could result in altered signaling of P15 at the GCGR compared with GCG.


Virtual fluorescence emission difference microscopy based on photon reassignment.
A method for high-resolution imaging that we call virtual fluorescence emission difference microscopy (vFED) is presented. In vFED the analyzed samples are scanned only by a doughnut-shaped pattern and imaged by a detector array, which is very different from the previous FED system. By using photon reassignment, we can obtain imaging results with matched solid and hollow point spread functions, and the difference between them is used to estimate the spatial distribution of the analyzed sample. This method results in greatly simplified equipment in the configuration and enhanced imaging speed. Results show that the resolution can be enhanced by at least 27% compared with that in confocal microscopy with a point detector, or is 1.8-2-fold higher than that in wide-field microscopy. Plus, negative intensities can be avoided by using vFED during the subtraction process, leading to the elimination of the deformation in reconstructed images.


[Changes in the spirography of paraplegics related to different postures in the air and water].
Respiratory insufficiencies in subjects with spinal cord injury were studied in five situations: in the air (sitting, dorsal supine position, declivous--15 degrees), and immersed in water up to the neck (sitting, dorsal supine position). Results were compared to those for a group of normal subjects. Total lung capacity (TLC), residual volume (RV), functional residual capacity (FRC), vital capacity (VC), forced expiratory volume per second (FEV1) and peak expiratory flow (PEF) were measured and their ratios with theoretical values of each subject were calculated. In handicapped subjects, FEV1 is less significantly diminished than VC and PEF. TLC does not vary, FRC is higher only sitting in the air, RV is more increased. Between situations, FEV1 never varies. In normal subjects, RV does not vary but, sitting in the air, TLC, VC, FRC and PEF increase. In handicapped subjects sitting in the air, VC decreases, RV and FRC increase, TLC and PEF do not vary. In normal and handicapped subjects, the other situations are comparable all together.


Enantioselective Norrish-Yang cyclization reactions of N-(omega-oxo-omega-phenylalkyl)-substituted imidazolidinones in solution and in the solid state.
The four N-(omega-oxo-omega-phenyl-alkyl)-substituted imidazolidinones 5-8 were prepared from N-acetylimidazolidinone (4). Upon irradiation, these substrates underwent Norrish-Yang cyclization to the racemic products rac-9-rac-12 (51-75%). The reactions of the N-2-oxoethylimidazolidinones 5 and 6 were conducted in tBuOH, and yielded 1:1 mixtures of exo/endo diastereoisomers rac-9a/rac-9b and rac-10a/rac-10b, accompanied by Norrish type II cleavage products. The reactions of the N-3-oxopropylimidazolidinones 7 and 8 were performed in toluene. The exo diastereoisomers rac-11a and rac-12a were the major diastereoisomers (d.r. approximately equal to 4:1). In the presence of the chiral compounds 1-3, the photocyclization of substrate 8 proceeded with significant enantiomeric excess (5-60% ee). The more sophisticated complexing agents 3 and ent-3 provided better enantiofacial differentiation (up to 60% ee) than the lactams 1 and 2 (up to 26% ee). Low temperatures and an excess of the complexing agent helped to increase the enantioselectivity. The absolute configuration of the major exo product 12a obtained from compound 8 in the presence of complexing agent 3 was unambiguously established by single-crystal X-ray crystallography of its chiral N-methoxyphenylacetyl derivative 15a. In a similar fashion, the absolute configurations of the endo products 12b and ent-12b were established. The N-2-oxoethylimidazolidinone 5, which crystallized in a chiral space group, was irradiated in the solid state. At low levels of conversion, the product 9a/ent-9a was formed with high enantiomeric excess (78% ee). The enantioselectivity deteriorated at higher levels of conversion.


Sirolimus- versus paclitaxel-eluting stent implantation for unprotected left main coronary artery stenosis.
We performed this study in order to compare the immediate and mid-term outcomes of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in lesions of the unprotected left main coronary artery (LMCA). We assessed 54 patients from 5 centers who had undergone unprotected LMCA stenting (35 SES and 19 PES). The procedural success rates were 100 and 95%, respectively, in the SES and PES patients (p = 0.19). At the 6-month clinical follow-up, the event-free probability was 100% in the SES group, and 88% in the PES group (p = 0.07). At the 6-month angiographic follow-up (n = 24), the SES group exhibited a slightly lower late loss than did the PES group (0.24 +/- 0.44 vs. 0.65 +/- 0.60 mm, p = 0.09), and the restenosis rates were 8 and 9% (p = 0.94) in the SES and PES patients, respectively. In conclusion, both groups exhibited excellent in-hospital and 6-month outcomes with no significant differences between them.


Higher-accuracy method for measuring minichromosome stability in Saccharomyces cerevisiae.
The minichromosome maintenance assay isfrequently used to characterize mutations genetically that affect the initiation of DNA replication or to decipherfunctional components in autonomously replicating sequences. The assay determines minichromosome loss by measuring the percentage of plasmid-containing cells in cultures after a period of growth in nonselective medium. Here we analyze data acquisition errors that contribute to the low accuracy of the routine versions of the assay. We propose modifications that eliminate errors in the acquisition of two variables and significantly improve the accuracy of the assay.


Multiple roles of glutathione binding-site residues of glutathione s-transferase.
This study was designed to characterize residues in the glutathione binding site of AdGSTD4-4 from the mosquito malaria vector Anopheles dirus. The data revealed that Leu33, His38 and His50 each play a role in enzyme catalysis and glutathione binding. The mutants of these three residues also displayed differences in hydrophobic substrate specificity, suggesting that changes in the active site conformation occurred. Differences in conformations was also suggested by protein stability changes. These results indicate that residues in the glutathione binding site are not only important in the catalytic function but also play a role in the structural integrity of the enzyme.


Quality control in diagnostic immunohistochemistry: integrated on-slide positive controls.
Standardization in immunohistochemistry is a priority in modern pathology and requires strict quality control. Cost containment has also become fundamental and auditing of all procedures must take into account both these principles. Positive controls must be routinely performed so that their positivity guarantees the appropriateness of the immunohistochemical procedure. The aim of this study is to develop a low cost (utilizing a punch biopsy-PB-tool) procedure to construct positive controls which can be integrated in the patient's tissue slide. Sixteen frequently used control blocks were selected and multiple cylindrical samples were obtained using a 5-mm diameter punch biopsy tool, separately re-embedding them in single blocks. For each diagnostic immunoreaction requiring a positive control, an integrated PB-control section (cut from the appropriate PB-control block) was added to the top right corner of the diagnostic slide before immunostaining. This integrated control technique permitted a saving of 4.75% in total direct lab costs and proved to be technically feasible and reliable. Our proposal is easy to perform and within the reach of all pathology labs, requires easily available tools, its application costs is less than using external paired controls and ensures that a specific control for each slide is always available.


Free fatty acids and heart failure in the Multi-Ethnic Study of Atherosclerosis (MESA).
Free fatty acids (FFAs) may be associated with heart failure (HF) risk, but prospective research is lacking. This study investigated associations between fasting FFAs and HF incidence overall and by ejection fraction (EF) subtypes [HF with preserved EF (HFpEF) and HF with reduced EF (HFrEF)] to evaluate FFAs as a potential biomarker for HF risk prediction. This study was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA) prospective cohort among 6,667 participants with complete baseline (2000-2002) FFAs and HF follow-up (through 2015). Associations between FFAs and HF incidence were evaluated with Cox proportional hazards regression. Cross-sectional associations between FFAs and HF risk markers were also evaluated using linear regression [N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular (LV) mass index] and logistic regression [LV hypertrophy (LVH)]. Stratification and cross-product terms were utilized to evaluate differences by age, sex, race/ethnicity and diabetes. FFAs were not associated with HF overall or with HFrEF. FFAs were not associated with HFpEF in the overall population or among males, but were borderline positively associated with risk among females (fully-adjusted tertile 3 vs. 1 HR=2.17, 95% CI: 1.06, 4.42) (sex P-interaction=0.05). FFAs were not associated with NT-proBNP, but were inversely associated with LV mass index and LVH with stronger associations among females (P-interaction≥0.10). Associations did not differ by age, race/ethnicity or diabetes status. FFAs generally do not appear to be an independent predictor for HF risk. Additional research is needed to confirm findings particularly studies evaluating associations by sex and EF subtypes.


Optimizing Trap Design and Trapping Protocols for Drosophila suzukii (Diptera: Drosophilidae).
Drosophila suzukii Matsumura (Diptera: Drosophilidae) is a recent invasive pest of fruit crops in North America and Europe. Carpophagous larvae render fruit unmarketable and may promote secondary rot-causing organisms. To monitor spread and develop programs to time application of controls, further work is needed to optimize trap design and trapping protocols for adult D. suzukii. We compared commercial traps and developed a new, easy-to-use plastic jar trap that performed well compared with other designs. For some trap types, increasing the entry area led to increased D. suzukii captures and improved selectivity for D. suzukii when populations were low. However, progressive entry area enlargement had diminishing returns, particularly for commercial traps. Unlike previous studies, we found putting holes in trap lids under a close-fitting cover improved captures compared with holes on sides of traps. Also, red and black traps outperformed yellow and clear traps when traps of all colors were positioned 10-15 cm apart above crop foliage. In smaller traps, attractant surface area and entry area, but not other trap features (e.g., headspace volume), appeared to affect D. suzukii captures. In the new, plastic jar trap, tripling attractant volume (360 vs 120 ml) and weekly attractant replacement resulted in the highest D. suzukii captures, but in the larger commercial trap these measures only increased by-catch of large-bodied Diptera. Overall, the plastic jar trap with large entry area is affordable, durable, and can hold high attractant volumes to maximize D. suzukii capture and selectivity.


Three-dimensional dental arch changes of patients submitted to orthodontic-surgical treatment for correction of Class II malocclusion.
This study assessed the three-dimensional changes in the dental arch of patients submitted to orthodontic-surgical treatment for correction of Class II malocclusions at three different periods. Landmarks previously identified on upper and lower dental casts were digitized on a three-dimensional digitizer MicroScribe-3DX and stored in Excel worksheets in order to assess the width, length and depth of patient's dental arches. During orthodontic preparation, the maxillary and mandibular transverse dimensions measured at the premolar regions were increased and maintained throughout the follow-up period. Intercanine width was increased only in the upper arch during orthodontic preparation. Maxillary arch length was reduced during orthodontic finalization, only. Upper and lower arch depths were stable in the study periods. Differences between changes in centroid and gingival points suggested that upper and lower premolars buccaly proclined during the pre-surgical period. Maxillary and mandibular dental arches presented transverse expansion at premolar regions during preoperative orthodontic preparation, with a tendency towards buccal tipping. The transverse dimensions were not altered after surgery. No sagittal or vertical changes were observed during the follow-up periods.


Effectiveness of Health Promotion Interventions in Primary Schools-A Mixed Methods Literature Review.
School-based health promotion interventions (HPIs) are commonly used in schools, but scientific evidence about the structures of effective interventions is lacking. Therefore, we conducted a mixed methods systematic literature review to recognize the HPI structures related to their effectiveness. Based on the inclusion criteria, 49 articles were selected for the literature review. The articles, published in 2011-2022, described 46 different school-based interventions conducted in 20 different countries. The average duration of the interventions was 12 months, and they were implemented mostly with an RCT study design (61.2%) and by targeting children (69.4%). Three main groups of interventions were identified and explained: (1) extensive and long-term interventions; (2) school policy-changing interventions; and (3) highly effective interventions. Effective school-based HPIs included multiple target groups, multiple providers with external experts, and an efficient duration and timing of follow-ups. The implications for educational research and school practice are presented. Evidence on the effectiveness of health-related interventions is still lacking and needs to be addressed in further studies.


Research and Evaluation on Wear in Power-Shift Steering Transmission Through Oil Spectral Analysis with RKPCA Method.
The most common methodology used in element concentration measurement and analyzing of wear particles is Atomic emission (AE) spectroscopy. The present paper presents an evaluation method on wear in power-shift steering transmission (PSST). By removing the problematic components which were highly correlated with oil additives, the robust kernel principal component analysis (RKPCA) method and the principal component analysis (PCA) method were accessed to extract the principal components of spectral data for oil samples collected from the life-cycle test of PSST in different stage and to calculate the amount of each principal component and its contribution rate respectively. A comparison between the above mentioned two methods was made to show that RKPCA method has fewer amounts of principal components and higher cumulative contribution rate indicating that RKPCA method acts more effectively in variable dimension reduction due to the outliers and nonlinearity of spectral data. Therefore, the effectiveness of RKPCA method in classification and identification of the wear in friction pairs was demonstrated subsequently. through the correlation analysis between the variable coefficients of RKPCA and metal elements of friction pairs. The demonstration showed that RKPCA functioned precisely in the classification and identification of the wear in friction pairs, and in the evaluation on the wear in PSST. Thereafter, to detect the threshold point where the wear took place, the fuzzy C-means clustering algorithm was introduced to classify the RKPCA eigenvalues, and the results were compared with that of the spectral clustering algorithm. The fuzzy C-means clustering algorithm showed higher sensitivity in detecting the threshold point indicting a more precise evaluation on the wear in PSST. It is clear that the introduction of RKPCA method in wear evaluation, which takes the eigenvalues of spectral data as a critical variable to classify and identify the wear in different friction pairs as well as in the integral PSST configuration, shows better accuracy in wear prediction and will contribute to the reliable determination of life between overhauls and the accurate positioning of worn-out parts. As might be expected, the proposed method can be extended to other cases of wear detection and evaluation in complex mechanical system.


Cost-effectiveness Analysis of Rivaroxaban versus Acenocoumarol in the Prevention of Stroke in Patients with Non-valvular Atrial Fibrillation in Spain.
Objective: The aim of this study was to evaluate, from the Spanish National Health System perspective, the cost-effectiveness of rivaroxaban (20 mg/day) versus use of acenocoumarol (5 mg/day) for the treatment of patients with non-valvular atrial fibrillation (NVAF) at moderate to high risk for stroke. Methods: A Markov model was designed and populated with local cost estimates, efficacy and safety of rivaroxaban in stroke prevention in NVAF compared with adjusted-dose warfarin clinical results from the pivotal phase III ROCKET AF trial and utility values obtained from the literature. Warfarin and acenocoumarol were assumed to have therapeutic equivalence. Results: Rivaroxaban treatment was associated with fewer ischemic strokes and systemic embolisms (0.289 vs. 0.300 events), intracranial bleeds (0.051 vs. 0.067), and myocardial infarctions (0.088 vs. 0.102) per patient compared with acenocoumarol. Over a lifetime time horizon, rivaroxaban led to a reduction of 0.041 life-threatening events per patient, and increases of 0.103 life-years and 0.155 quality-adjusted lifeyears (QALYs) versus acenocoumarol treatment. This resulted in an incremental cost-effectiveness ratio of €7045 per QALY and €10 602 per life-year gained. Sensitivity analysis indicated that these results were robust and that rivaroxaban is cost-effective compared with acenocoumarol in 89.4% of cases should a willingness-to-pay threshold of €30 000/QALY gained be considered. Conclusions: The present analysis suggests that rivaroxaban is a cost-effective alternative to acenocoumarol therapy for the prevention of stroke and systemic embolisms in patients with NVAF in the Spanish healthcare setting.