Characterization of outer membrane proteins from Actinobacillus actinomycetemcomitans.
Outer membranes were prepared from whole cells of various strains of Actinobacillus actinomycetemcomitans and analysed by SDS-polyacrylamide gel (12.5%) electrophoresis (SDS-PAGE). In all strains four common major outer membrane proteins (OMPs) with molecular masses of 30, 34, 36 and 39 kDa could be distinguished. Heating the OMP preparation of strain Y4 at 60, 70, 90 and 100 degrees C produced a band of 30 kDa, which gradually lost its intensity from 70 degrees C onwards concomitantly with the development of two new protein bands of 34 and 36 kDa. Furthermore, the 36 kDa OMP appeared susceptible to proteolysis by trypsin; degraded products apparently produced a new electrophoretic band of 27 kDa. Y4-derived OMP fractions were solubilized with a Triton-SDS mixture to investigate the presence of peptidoglycan-associated proteins. The 39 kDa OMP was found to be peptidoglycan-associated.


Unusual Renal Mass in a Pediatric Patient.
Renal cell carcinoma (RCC) is rare in the pediatric population, comprising about 5% of renal neoplasms in children.1 Out of all childhood cases of RCC, translocation RCCs (tRCC) is the most common.2 It is well described in the literature that exposure to alkylating agents such as cyclophosphamide and/or topoisomerase II inhibitors such as doxorubicin and etoposide, is a risk factor for the development of Xp11 (or TFE3) tRCC.3 Herein is a case of tRCC development in a patient with history of exposure to topoisomerase II inhibitors and alkylating agents to treat a common childhood malignancy.


Effect of murine retroviral infection on hair and serum levels of cocaine and morphine.
LP-BM5 retrovirally infected female C57BL/6J mice were administered cocaine, morphine or both by daily intraperitoneal injection for 9 weeks. Drug concentrations were measured by radioimmunoassay in serum and in hair extracts. Hair samples obtained from all drug-treated mice were positive for the drug injected, while none of the saline-treated mice had detectable drug levels in hair or serum. The average morphine concentration obtained from non-infected mice was 11 ng/mg hair whereas the amount found in the LP-BM5-infected mice was significantly higher (20 ng/mg hair). Mice injected with both morphine and cocaine were given 50% of the regular dose of each drug and drug levels in the hair of these animals were approximately half that of mice injected with the full dose of the single drug. Non-infected mice treated with both drugs had a mean value of 7 ng morphine/mg hair and 374 ng cocaine/mg hair while retrovirus-infected mice had significantly higher concentrations, 10 ng morphine/mg hair and 1160 ng cocaine/mg hair (P less than 0.001). Serum concentrations of cocaine and morphine were significantly higher (P less than 0.01) in the retrovirus-infected animals from 40 min to 1.5 h. The increased concentrations of cocaine and morphine in serum during retrovirus infection are accompanied by a significant increase in the amount of drug incorporated into the hair matrix. This change indicates that retroviral infection may influence the disposition of these drugs in the systemic circulation.


Bringing "play" to life: the use of experiential marketing in the VERB campaign.
Given the abundance of advertising and media that children and adolescents are exposed to today, it is increasingly important to incorporate nontraditional channels and venues in strategies designed to reach them. One such channel that the CDC's VERB campaign employed was experiential marketing, which is defined here as a live event or experience that gives the target audience the opportunity to see a product and experience it for themselves. Experiential marketing and the tactics that the VERB campaign used to reach children aged 9-13 years (tweens) with health messages about physical activity are described, including a discussion about how other public health campaigns might use experiential marketing and other commercial marketing techniques to reach the public with public health messages.


[Approach to severe functional deficiencies: evaluating the efficacy of a special multidisciplinary consultation].
A global approach is required to evaluate severe functional deficits. We have developed a multidisciplinary consultation and assessed its usefulness after one year. A total of 62 patients were evaluated (mean age 35 years), usually for neurological functional deficit (50%). Among the 62 patients, surgery was proposed in 72.6% (operations performed in 66%). Others were managed with non-surgical procedures or abstention. The functional outcome as assessed by patients and physicians was poor (or no result) for 6%, fair for 15%, good or very good for 79%. These results suggest that such a multidisciplinary approach is worth being pursued. Some adjustments for psychological dysfunction may further improve outcomes.


Accumulation of toxicants in tadpoles of the common frog (Rana temporaria) in high mountains.
We analyzed the accumulation of inorganic and organic toxicants in tadpoles from nine populations of the common frog (Rana temporaria) at different altitudes of the Hohe Tauern National Park in Austria). Lead and cadmium concentrations in tadpoles increased with the acidity and metal-to-HCO3(-) ratio in the water exceeding those found in tadpoles from agricultural areas. Organochlorines (DDTs, polychlorinated biphenyls, lindane) and polyaromatic hydrocarbons were present in all of the populations, but only DDTs accumulated significantly compared with the concentrations in their diet.


Dientamoeba fragilis in Denmark: epidemiological experience derived from four years of routine real-time PCR.
The intestinal protozoon Dientamoeba fragilis remains a clinical entity of dubious significance. While several previous studies address questions of epidemiology, only a handful have systematically employed and reported on the results from real-time polymerase chain reaction (qPCR), the best currently available diagnostic modality, and the comparison of results from different studies is, therefore, difficult. Since 2007, Statens Serum Institut (Denmark) has utilised qPCR for D. fragilis as routine diagnostic work-up for intestinal parasitosis, testing more than 22,000 samples from 2008 through 2011, and the aim of this study was to report on the results and experiences gained in the process. We demonstrate a staggeringly high proportion (43%) of investigated patients positive for D. fragilis, ranging from 12 to 71% depending on age group, showing a bimodal age distribution peaking in children and adults of parental age, as well as a clear association between exposure to children and risk of D. fragilis infection. We discuss these findings in light of the pinworm egg vector hypothesis and substantiate further our knowledge of risk factors pertaining to D. fragilis carriage.


Pharmacokinetics of Glepaglutide, A Long-Acting Glucagon-Like Peptide-2 Analogue: A Study in Healthy Subjects.
Glepaglutide is a novel, long-acting, glucagon-like peptide-2 analogue in a stable aqueous formulation for subcutaneous dosing to treat patients with short bowel syndrome. This study was conducted primarily to characterise the pharmacokinetics of glepaglutide in healthy subjects. In this open-label, partially randomised, parallel-group study, healthy subjects were evenly randomised to glepaglutide 5 or 10 mg dosed subcutaneously once weekly for 6 weeks or to a single intravenous infusion of glepaglutide 1 mg. Each group comprised 15 subjects. Blood samples were drawn to determine plasma concentrations of the parent drug and its two main metabolites. Concentrations of glepaglutide were calculated as the sum of these three analytes. Citrulline was included as a pharmacodynamic biomarker. Safety was assessed throughout the study. From a comparison of pharmacokinetic parameters following subcutaneous versus intravenous dosing, it is concluded that the pharmacokinetics of glepaglutide following subcutaneous dosing are primarily determined by slow release of the two main glepaglutide metabolites from a subcutaneous depot. For subcutaneous dosing once weekly, the two main metabolites accounted for >98% of the overall glepaglutide exposure at steady state, with the parent drug contributing to less than 1% of exposure. The estimated mean (95% confidence interval) effective half-life for glepaglutide 5 and 10 mg was 124 (73-185) h and 88 (31-146) h, respectively. There was an increase in the citrulline concentration for both glepaglutide subcutaneous dose levels. No safety issues were identified. Slow release of active metabolites following subcutaneous dosing leads to a significantly protracted pharmacokinetic profile for glepaglutide. These results support that once- or twice-weekly subcutaneous dosing of glepaglutide could be an efficacious therapy for intestinal rehabilitation. NCT03279302.


Molecular-shape selectivity by naphthalimido-modified silica stationary phases: Insight into the substituents effect of naphthalene on shape recognition and π-π interactions via electrostatic potential.
This report describes the molecular-shape selectivity of four naphthalimido-modified silica (NIM) stationary phases. To investigate the selectivity, several alkylbenzenes and polycyclic aromatic hydrocarbons (PAHs) were tested using capillary electrochromatography (CEC) with each NIM stationary phase. Results revealed that nitro group-substituted NIM phases had outstanding molecular-shape recognition ability toward PAHs; a strong negative correlation existed between the k' value and L/B ratio that is opposite those observed for C18 phases, in addition, one possessed 10-fold greater molecular-shape recognition ability compared to existing stationary phases. In addition, the position of the nitro group on the naphthalimide moiety modulated the π-stacking interaction due to steric hindrance. Furthermore, structure optimization and electrostatic potential (ESP) surfaces were used to clarify the mechanism of recognition. Based on this high recognition ability, separations of several positional isomers were examined. Results indicated that structure optimization and ESP maps could reveal the effect of functional groups on π-π interactions, which will aid in the design of new NIM stationary phases with shape selectivity, while taking advantage of electrostatic interactions.


Ultrasound-assisted synthesis of highly functionalized benzo[1,3]thiazine via Cu-catalyzed intramolecular CH activation reaction from isocyanides, aniline-benzoyl(acetyl) isothiocyanate adduct.
A facile sonochemical route for the synthesis of benzo[1,3]thiazine derivatives via a one pot, multicomponent, intramolecular CH activation reaction from isocyanides, aniline and benzoyl (acetyl) isothiocyanate adduct catalyzed by copper (I) iodide in acetone at 30 °C have been reported. The advantages of the described method include using simple and readily available starting materials and performing under mild copper-catalytic reaction conditions and also obtaining pure product with high yield without applying column chromatography. Furthermore, using the sonochemical methodology as an efficient method led to reduce the reaction times.


High-dose folinic acid and 5-fluorouracil bolus and continuous infusion in advanced colorectal cancer: poor response rate in unselected patients.
We have conducted a retrospective study of high-dose folinic acid and 5-fluorouracil in 96 patients with advanced colorectal cancer. Patients received 200 mg m-2 (maximum 300-350 mg) folinic acid by infusion over 2 h followed by an i.v. bolus of 5-fluorouracil 400 mg m-2 then an infusion of 5-fluorouracil 600 mg m-2 over 22 h. This was repeated over the next 24 h. The schedule was given every 2 weeks for four cycles; thereafter patients with objective response continued to a maximum of eight cycles. The overall response rate was 10.6% in 85 evaluable patients. The median duration of response was 11 months. The median survival was 6 months. Toxicity was low, only one patient experiencing toxicity greater than WHO grade II (grade IV platelet toxicity). Diarrhoea, nausea, vomiting and mucositis also occurred but were mild and infrequent. Our low response rate may be related to factors such as patient characteristics or duration of treatment.


Liquid boundary movements in cylindrical and convex hydrophobic matrix tablets: Effects on tablet cracking and drug release.
The aim of this study was to investigate liquid penetration into both cylindrical and convex hydrophobic matrix tablets and to relate the changes in tablet structure to drug release. Starch acetate with degree of substitution of 2.7 was used as a hydrophobic matrix former and anhydrous caffeine as a freely soluble model drug. Phenolred was used as a colouring agent to enhance the visual detection of the liquid boundary movements, which were examined in axial and radial directions for both types of tablets. The tablets started to expand during the dissolution, resulting in cracking as the liquid boundary penetrated into tablet. The cracking influences drug release by shortening the diffusion path and decreasing the tortuosity. The liquid boundaries proceed differently in cylindrical and convex tablets, this being attributable to differences in pore structure and density distribution. Cylindrical tablets are quite homogeneous in terms of density, but convex tablets have more porous areas at the domes of the tablet.


Effects of long-term administration of chlorpromazine on the pineal gland of rats.
Long-term (6 months) administration of 25 mg/kg body weight/day chlorpromazine (CPZ) to rats resulted in remarkable inhibition of normal increase with age of osmiophilic lipid droplets (OLD) in the pineal gland, and atrophy of pinealocytes. The breeding conditions such as illumination, humidity, and room temperature were strictly controlled. Hence, these changes were ascribed solely to the effects of the drug. OLD are considered as an indicator of physiological activity of the gland. In view of the possible functional relations of this organ to endocrine or autonomic nervous activity, our finding may give a clue to the clarification of the possible cause of some side-effects of the drug.


A sustainable avenue for the synthesis of propargylamines and benzofurans using a Cu-functionalized MIL-101(Cr) as a reusable heterogeneous catalyst.
A heterogeneous copper-catalyzed A3 coupling reaction of aldehydes, amines, and alkynes for the synthesis of propargylamines and benzofurans has been developed. Here, the modified metal-organic framework MIL-101(Cr)-SB-Cu complex was chosen as the heterogeneous copper catalyst and prepared via post-synthetic modification of amino-functionalized MIL-101(Cr). The structure, morphology, thermal stability, and copper content of the catalyst were determined by FT-IR, PXRD, SEM, TEM, EDX, TGA, XPS, and ICP-OES. The catalyst shows high catalytic activity for the aforementioned reactions under solvent-free reaction conditions. High yields, low catalyst loading, easy catalyst recovery and reusability with not much shrink in catalytic activity, and a good yield of 82% in gram-scale synthesis are some of the benefits of this protocol that drove it towards sustainability.


Mycobacterium abscessus infection complicating hand rejuvenation with structural fat grafting.
We report a case of Mycobacterium abscessus infection of the hands in a 55 year old lady following hand rejuvenation with structural fat grafting. A review of the literature on M. abscessus infection to discuss common presentations, diagnosis and treatment is presented. Awareness and high suspicion of such as atypical mycobacterial infections complicating hand surgery and other plastic surgery procedures is imperative to successful management.


Beta amyloid peptide (25-35) leading to inflammation through Toll-like receptors and the anti-inflammatory effect of genistein in BV-2 cells.
Genistein, the main soy isoflavone component, has received much attention for its potential multifunction. Here, we reported that in BV-2 cells, genistein significantly inhibited beta amyloid peptides 25-35 (Aβ25-35)-induced inflammatory response. The results indicated that Aβ25-35-stimulated BV-2 cells upregulated Toll-like receptors 2 and 4, Myd88, and IKK gene expression with the increasing expression of IL-6 and decreasing expression of TGF-β and IL-10. Further, inhibiting TLR4 expression with small interfering RNA prevented the inflammatory response induced by Aβ25-35, indicating the key role of TLRs in Aβ-mediated inflammation. Genistein pre-treated BV-2 cells showed less inflammatory response when exposed to Aβ25-35. These results suggested that Aβ induced BV-2 cells inflammation though TLRs and genistein has an anti-inflammatory effect in vitro.


Fasciola hepatica: perturbation of secretory activity in the vitelline cells by the sodium ionophore monensin.
The effect of the sodium ionophore monensin on the vitelline cells of Fasciola hepatica has been determined both in vitro and in vivo by means of transmission electron microscopy. In intact flukes in vitro, vacuolation of the Golgi complex of the intermediate, shell protein secreting vitelline cells is evident after 1.5 hr incubation in monensin (1 X 10(-6) M). The vacuolation becomes progressively greater with time, eventually spreading to the late stem cells and mature cells. In addition, there is a block in the normal migration of the shell protein globules to the periphery, the shell globule clusters becoming very loosely packed and empty, and distended single globules accumulate in the perinuclear region of the cell. Disruption of the nurse cell cytoplasm is apparent from 6 hr onwards, giving the follicle a less compact appearance. Morphological changes induced by higher concentrations of monensin (up to 1 X 10(-4) M) followed a similar time course and pattern to that described for 1 X 10(-6) M) followed a similar time course and pattern to that described for 1 X 10(-6) M. In tissue-slice material (1 X 10(-6) M) these effects of monensin are evident more rapidly, and to a far greater extent: the condition of the vitelline cells in slices after only 1.5 hr resembles that reached in intact flukes after more than a 12-hr incubation. Incubation in ouabain, an inhibitor of Na+/K+-ATPase activity, has little effect on vitelline morphology over a 6-hr period (1 X 10(-3) M), although brief (0.5 hr) exposure to ouabain followed by monensin treatment (1 X 10(-4) M, 3 hr) does lead to gross vacuolation of the intermediate cells, the condition resembling that in tissue-slice material. In contrast, in vivo treatment of infected laboratory rats (1 X 5 mg/kg) only leads to a transient effect on the ultrastructure of the intermediate vitelline and nurse cells. The specific perturbation of the Golgi complex and secretory traffic in the vitelline cells of F. hepatica by monensin follows the classic pattern observed in other cell types.


Global transcriptome analysis of pig induced pluripotent stem cells derived from six and four reprogramming factors.
Pigs are important, both for agriculture and as animal models for human diseases. However, due to the lack of embryonic stem cells, the possibility of genetic modification is quite limited. To overcome this limitation, induced pluripotent stem (iPS) cells have been derived from pigs. Despite the public availability of a large number of expression datasets from mice, rats, and primates-derived iPS cells, the expression profile of pig-derived iPS cells is quite limited. Furthermore, there is no dataset focused on the profiling of pig-derived iPS cell with six reprogramming factors (Oct3/4, Sox2, Klf4, c-Myc, Lin28, and Nanog). Here, we used Illumina RNA sequencing platform to characterize the mRNA expression of four-factor derived and six-factor derived pig iPS cells. We observed that the expression levels of whole genes in our established six factors derived iPS cells and parent fibroblast, and compared with that of iPS cells with four factors in public database. These data are valuable in understanding species difference in the reprogramming process of stem cells, and could help identify the key regulating genes involved in the process.


Structural Brain Alterations and Their Associations With Function in Children, Adolescents, and Young Adults With Congenital Heart Disease.
Most neonates who receive surgery for complex congenital heart disease (CHD) will survive well into adulthood, however, many of them will face functional challenges at one point during their life as a consequence of their atypical neurodevelopment. Recent advances in neuroscience and the increasing accessibility of magnetic resonance imaging have allowed numerous studies to identify the nature and extent of the brain alterations that are particular to survivors with CHD. Nevertheless, and considering that the range of outcomes is broad in this population, the functional consequences of these brain differences is not always evident. In this review, we summarize the present state of knowledge regarding the structure-function relationships evaluated in children, adolescents, and young adults with CHD using structural magnetic resonance imaging. Overall smaller total and regional brain volume, as well as lower fractional anisotropy in numerous brain regions, were frequently associated with lower cognitive outcomes including executive functioning and memory in adolescents and young adults with CHD. However, we identify several gaps in knowledge including the limited number of prospective investigations involving neonatal imaging and follow-up during childhood or adolescence, as well as the need for studies that evaluate a broader range of functional outcomes and not only the cognitive abilities. Future interdisciplinary investigations using multimodal imaging techniques could help address these gaps.


Targeting the microenvironment in acute myeloid leukemia.
The bone marrow microenvironment plays a critical role in the development, progression, and relapse of acute myeloid leukemia (AML). Similar to normal hematopoietic stem cells, AML blasts express receptors on their surface, allowing them to interact with specific components of the marrow microenvironment. These interactions contribute to both chemotherapy resistance and disease relapse. Preclinical studies and early phase clinical trials have demonstrated the potential for targeting the tumor-microenvironment interactions in AML. Agents currently under investigation include hypoxia-inducible agents and inhibitors of CXCR4 and adhesion molecules such as VLA-4 and E-selectin.


Gold(III)-mediated aldol condensations provide efficient access to nitrogen heterocycles.
Quinolines, dihydroquinolines, and aza-xanthones can be synthesized efficiently and under mild reaction conditions by means of a reaction sequence employing Au(III)-catalyzed aldol reactions as the key step.


Community-acquired pneumonia by Legionella pneumophila. Do we need to include new recommendations for inflammatory bowel disease patients under immunomodulators?
We present the case of a community-acquired pneumonia by Legionella Pneumophila in a 31-year-old patient with Crohn's disease under anti-TNF agents. Following this and other similar cases reported in literature, we propose to include recommendations to prevent this infection in patients starting treatment with immunosuppressant drugs through simple measures regarding the control of water in the patients' home.


Long-term results after primary intraocular lens implantation in children with juvenile idiopathic arthritis-associated uveitis.
To evaluate the long-term outcome after cataract surgery with primary intraocular lens implantation in children with juvenile idiopathic arthritis-associated uveitis. The medical records of all 24 children (34 eyes) with chronic juvenile idiopathic arthritis-associated uveitis who underwent cataract surgery between 1990 and 2013 were reviewed retrospectively. Primary intraocular lens implantation was performed in all patients. Median age at diagnosis of uveitis in the first eye was 5.3 years (range: 2.7-9.4 years) and median age at the time of cataract surgery in the first eye was 9.7 years (range: 4.1-16.9 years). Postoperative follow-up time ranged from 1 to 23.1 years, with a median of 10.9 years. Best corrected visual acuity at the last follow-up was good (⩾20/40) in 65% of the eyes. Postoperatively, glaucoma developed in 8 eyes (24%), posterior capsular opacification and secondary membrane formation requiring surgery in 15 eyes (44%), macular oedema in 5 eyes (15%) and phthisis in 2 eyes (6%). This study shows a favourable visual outcome in most of the cases. Primary intraocular lens implantation may be considered in juvenile idiopathic arthritis-associated uveitis complicated by cataract in patients with well-controlled inflammation.


Behaviors and Interactions of Insects in Mid-Mesozoic Ecosystems of Northeastern China.
During the past 20 years, more than 1,600 species of well-preserved fossil insects, including members of over 270 families within 24 orders, have been described from the Middle Jurassic Yanliao Entomofauna and Early Cretaceous Jehol Entomofauna in Northeastern China. Diversified fossil insects not only document the origin, systematics, and early evolution of many lineages, but also reveal these lineages' behaviors and interactions with coexisting plants, vertebrates, and other insects in their ecosystems. Fossil evidence has been documented, for example, regarding insects' feeding and pollination mutualism with gymnosperms; ectoparasitic feeding on blood of vertebrates; camouflage, mimicry of gymnosperm plants, and eyespot warning; sound stridulation for attracting potential mates; and sexual display, mating, egg-laying, and parental care. In this article, we review the diverse taxonomy of mid-Mesozoic insects of Northeastern China and elucidate their behaviors and interactions within their ecosystems, which have impacted their early evolution and development into extant insects.


Environmental impacts of solar photovoltaic systems: A critical review of recent progress and future outlook.
Photovoltaic (PV) systems are regarded as clean and sustainable sources of energy. Although the operation of PV systems exhibits minimal pollution during their lifetime, the probable environmental impacts of such systems from manufacturing until disposal cannot be ignored. The production of hazardous contaminates, water resources pollution, and emissions of air pollutants during the manufacturing process as well as the impact of PV installations on land use are important environmental factors to consider. The present study aims at developing a comprehensive analysis of all possible environmental challenges as well as presenting novel design proposals to mitigate and solve the aforementioned environmental problems. The emissions of greenhouse gas (GHG) from various PV systems were also explored and compared with fossil fuel energy resources. The results revealed that the negative environmental impacts of PV systems could be substantially mitigated using optimized design, development of novel materials, minimize the use of hazardous materials, recycling whenever possible, and careful site selection. Such mitigation actions will reduce the emissions of GHG to the environment, decrease the accumulation of solid wastes, and preserve valuable water resources. The carbon footprint emission from PV systems was found to be in the range of 14-73 g CO2-eq/kWh, which is 10 to 53 orders of magnitude lower than emission reported from the burning of oil (742 g CO2-eq/kWh from oil). It was concluded that the carbon footprint of the PV system could be decreased further by one order of magnitude using novel manufacturing materials. Recycling solar cell materials can also contribute up to a 42% reduction in GHG emissions. The present study offers a valuable management strategy that can be used to improve the sustainability of PV manufacturing processes, improve its economic value, and mitigate its negative impacts on the environment.


A G-rich sequence element common to Dictyostelium genes which differ radically in their patterns of expression.
Removal of a G-rich element from the DIF-inducible, prestalk-, and stalk-specific ecmB gene reduces expression but cell-type specificity is retained. The ecmB element will functionally substitute for a homologous sequence upstream of CP2, a cAMP-inducible gene and is bound by GBF, the factor which interacts with the CP2 G box. These results suggest that the G box may play a similar stimulatory role in these two independently regulated genes where it presumably interacts with different ancillary promoter elements.


Interpretability, credibility, and usability of hospital-specific template matching versus regression-based hospital performance assessments; a multiple methods study.
Hospital-specific template matching (HS-TM) is a newer method of hospital performance assessment. To assess the interpretability, credibility, and usability of HS-TM-based vs. regression-based performance assessments. We surveyed hospital leaders (January-May 2021) and completed follow-up semi-structured interviews. Surveys included four hypothetical performance assessment vignettes, with method (HS-TM, regression) and hospital mortality randomized. Nationwide Veterans Affairs Chiefs of Staff, Medicine, and Hospital Medicine. Correct interpretation; self-rated confidence in interpretation; and self-rated trust in assessment (via survey). Concerns about credibility and main uses (via thematic analysis of interview transcripts). In total, 84 participants completed 295 survey vignettes. Respondents correctly interpreted 81.8% HS-TM vs. 56.5% regression assessments, p < 0.001. Respondents "trusted the results" for 70.9% HS-TM vs. 58.2% regression assessments, p = 0.03. Nine concerns about credibility were identified: inadequate capture of case-mix and/or illness severity; inability to account for specialized programs (e.g., transplant center); comparison to geographically disparate hospitals; equating mortality with quality; lack of criterion standards; low power; comparison to dissimilar hospitals; generation of rankings; and lack of transparency. Five concerns were equally relevant to both methods, one more pertinent to HS-TM, and three more pertinent to regression. Assessments were mainly used to trigger further quality evaluation (a "check oil light") and motivate behavior change. HS-TM-based performance assessments were more interpretable and more credible to VA hospital leaders than regression-based assessments. However, leaders had a similar set of concerns related to credibility for both methods and felt both were best used as a screen for further evaluation.


Continued maturation of thymic emigrants in the periphery.
Developing thymocytes are selected for recognition of molecules encoded by the major histocompatibility complex, purged of self-reactive cells and committed to either the CD4 or CD8 lineage. The 1% of thymocytes that complete these tasks emigrate and join the population of peripheral lymphocytes. Whether T cell maturation is complete at the time of thymic exit has been a subject of debate. Using mice transgenic for green fluorescent protein driven by the recombination activating gene 2 promoter to identify recent thymic emigrants, we now show that T cell differentiation continues post-thymically, with progressive maturation of both surface phenotype and immune function. In addition, the relative contribution of CD4 and CD8 recent thymic emigrants was modulated as they entered the peripheral T cell pool. Thus, T cell maturation and subset contribution are both finalized in the lymphoid periphery.


Preparation and antibacterial effects of Ag/AgCl-doped quaternary ammonium-modified silicate hybrid antibacterial material.
Organic-inorganic hybrid antibacterial materials based on Ag/AgCl and quaternary ammonium-modified silicate (Ormosil(NR4+Cl-)) were prepared by sol-gel processes and an in situ reduction method. The physical properties of Ormosil(NR4+Cl-) and the Ormosil(NR4+Cl-)/Ag hybrids were examined using FTIR, UV-Vis, SEM, XRD and NMR spectroscopy. The results indicated that Ag/AgCl was incorporated into the Ormosil(NR4+Cl-) matrix after impregnation. Morphological analysis by SEM showed uniformly-distributed Ag and AgCl particles in the Ormosil(NR4+Cl-) matrix, of spherical nature and a size around 5-20 and <200 nm. The antibacterial effects of Ormosil(NR4+Cl-) and the Ormosil(NR4+Cl-)/Ag hybrids against Gram-negative P. aeruginosa and E. coli, and Gram-positive S. aureus and B. subtilis, were assessed in terms of the zone of inhibition, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and plate-counting method, and an excellent antibacterial performance was discovered. Moreover, the antibacterial performance of the Ormosil(NR4+Cl-)/Ag hybrid was better than that of Ormosil(NR4+Cl-) and the Ormosil/Ag hybrids.


Human papillomavirus 16-specific cell-mediated immunity in children born to mothers with incident cervical intraepithelial neoplasia (CIN) and to those constantly HPV negative.
HPV infections are detected in sexually naive children. This has raised the question about the role of early HPV infections in either protecting or predisposing to further HPV infections. HPV16-specific cell-mediated immunity (CMI) was studied in 10 case-children born to mothers with an incident cervical intraepithelial neoplasia (CIN) diagnosed during their 14-year follow-up (FU), and in 21 children born to mothers, who remained constantly HPV-negative (controls). The mean age of children was 12.3 years. Peripheral blood mononuclear cells were isolated from blood and stimulated with peptide pools covering HPV16 E2, E6 and E7. Proliferation of lymphocytes, their secretion of cytokines, and the frequency of regulatory T-cells were determined. The results were correlated with the HPV status and analyzed in a nested case-control setting. All children, except two controls, displayed CMI against HPV16 E2, E6 and/or E7 peptides associated with type 1 and 2 cytokine secretion. Only two statistically significant differences were found in the nested case-control setting; (1) case-children had a higher TNF-α response to HPV16 E2 (p = 0.004) than controls and (2) controls had no response to HPV16 E7.2 peptide pool while 3/10 case-children had (p = 0.013). Totally, 50 and 57 % of the cases and controls, respectively, had HPV positive oral samples at some FU-visit. In addition, the children without any HPV antibodies before the age of 6 months showed proliferative responses of PBMC after HPV16 exposure more frequently than other children (p = 0.045). HPV16-specific CMI is common in young, sexually inexperienced children. This suggests that oral HPV infections occur frequently in children. Our results might also explain the previous findings that half of healthy adults demonstrate HPV-specific CMI irrespective of their partner/sexual status.


Virus transmission by ultrasonic scaler and its prevention by antiviral agent: An in vitro study.
It is well recognized that dental procedures represent a potential way of infection transmission. With the COVID-19 pandemic, the focus of dental procedure associated transmission has rapidly changed from bacteria to viruses. The aim was to develop an experimental setup for testing the spread of viruses by ultrasonic scaler (USS) generated dental spray and evaluate its mitigation by antiviral coolants. In a virus transmission tunnel, the dental spray was generated by USS with saline coolant and suspension of Equine Arteritis Virus (EAV) delivered to the USS tip. Virus transmission by settled droplets was evaluated with adherent RK13 cell lines culture monolayer. The suspended droplets were collected by a cyclone aero-sampler. Antiviral activity of 0.25% NaOCl and electrolyzed oxidizing water (EOW) was tested using a suspension test. Antiviral agents' transmission prevention ability was evaluated by using them as a coolant. In the suspension test with 0.25% NaOCl or EOW, the TCID50/mL was below the detection limit after 5 seconds. With saline coolant, the EAV-induced cytopathic effect on RK13 cells was found up to the distance of 45 cm, with the number of infected cells decreasing with distance. By aero-sampler, viral particles were detected in concentration ≤4.2 TCID50/mL. With both antiviral agents used as coolants, no EAV-associated RK-13 cell infection was found. We managed to predictably demonstrate EAV spread by droplets because of USS action. More importantly, we managed to mitigate the spread by a simple substitution of the USS coolant with NaOCl or EOW.


Rectal perforation during barium enema. Report of a case.
Perforation of the colon or rectum during the course of barium-enema examination is estimated to occur in approximately 500 patients annually in the United States. It has been over 30 years since the last collective review on this subject reported a prohibitively high mortality and morbidity. Since that time, much has been learned about the treatment of patients with peritonitis and bowel perforation, many new and more effective antibiotics have become available, and the management of shock has become infinitely more sophisticated. A review of recently reported cases suggests that the mortality rate and possibly the early morbidity have fallen markedly. Late complications such as adhesive small-bowel obstruction and retroperitoneal fibrosis with ureteral stenosis are well described, but data on the incidence of these long-term sequelae are still not available.


IMPROVED PHYSICAL FUNCTION WITH COMPLEMENTARY USE OF A DIETARY SUPPLEMENT FOR MILD KNEE OSTEOARTHRITIS: A SUBGROUP ANALYSIS.
The aim: In this study, we present a sub-analysis of physical functionality in sufferers of mild knee osteoarthritis (OA) following a clinical assessment of a novel nutraceutical supplement Tregocel® complementary to standard treatment. Materials and methods: We evaluated the results of a multicenter, open-label, single-arm efficacy and safety evaluation of a polyherbal nutraceutical, performed in subjects with symptomatic, mild knee OA (n = 107, 59.7 ± 10.8 yrs, 68.2% female) over 36 weeks. Physical function was assessed using a standardized walking challenge (6-min walk test), combined with WOMAC indices and leg flexion measurements. Sub-analysis was performed using a linear mixed model that tracked changes in the walking challenge outcomes over time, adjusted for age, gender, and OA duration. Results: Walking distance was significantly improved with the duration of nutraceutical use, increasing by 0.72 m (95% CI: 0.56, 0.88) per week of product administration. Similarly, there were significant decreases in WOMAC indices per week for stiffness (-1.6, 95% CI: -1.8, 1.4), daily functioning (-13.5, 95% CI: 14.9, 11.9) and global outcome (-19.2, 95% CI -21.3 - -17.1). Furthermore, supine heel-to-high flexion distance was improved relative to the duration of nutraceutical use. Conclusions: The use of a polyherbal nutraceutical resulted in clinical improvements in several indices of physical functioning in mild knee OA suffers. Trial registration: NCT03636035.


Inhibition of nitric oxide synthases prevents and reverses alpha,beta-meATP-induced neck muscle nociception in mice.
Tension-type headache (TTH) is associated with noxious input from neck muscles. Intravenous administration of the unspecific nitric oxide synthase inhibitor L-NMMA in chronic TTH patients caused analgesia and reduction of neck muscle tenderness. The unspecific nitric oxide synthase inhibitor L-NMMA was applied in an experimental model for neck muscle nociception in anesthetized mice (N = 25). Local injection of α,β-meATP into semispinal neck muscles induced sustained facilitation of brainstem nociception as monitored by the jaw-opening reflex. Preceding intraperitoneal administration of L-NMMA (0.05, 0.1, 1 mg/kg) prevented reflex facilitation evoked by α,β-meATP in a dose-dependent manner. Intraperitoneal injection of L-NMMA subsequent to intramuscular α,β-meATP application reversed established brainstem reflex facilitation back to baseline values. Both experiments with preceding and subsequent L-NMMA indicate the involvement of nitric oxide synthases in the induction and maintenance of facilitation. However, future experiments will have to address the involvement of various isoenzymes in order to provide for new therapeutic concepts in TTH.


Are adolescents' physical activity and body-related factors associated with medically attended injuries?
Injuries are the major cause of disability and death during adolescence, representing a significant public health burden among youth. Body-related factors such as body composition and cardiovascular fitness (CVF) may affect adolescents' vulnerability to injuries. As evidence is lacking, we aimed to explore the associations of medically attended injuries with adolescents' physical activity (PA) and body-related factors, and whether these associations are modified by age, gender and family affluence. We used data on 888 11- to 15-year-old adolescents (mean age = 13.5, 56% boys) from the Health Behaviour in School-aged Children study conducted in 2018 in Slovakia. We used binary logistic regression analysis to assess the association of medically attended injuries with adolescents' PA and body-related factors (body composition, CVF), considering age, gender and family affluence. Adolescents were more likely to report medically attended injuries if they were physically very active (odds ratio/confidence interval OR/CI:2.76/1.83-4.15) or active (OR/CI:1.91/1.27-2.87) rather than inactive. Body-related factors were not associated with medically attended injuries among adolescents. Moreover, age, gender and family affluence did not modify the association of medically attended injuries with adolescents' PA and body-related factors. The only exception was the modifying effect of gender: the association of medically attended injuries with being very active was stronger in boys (OR/CI: 3.04/1.32-6.99). Very physically active adolescent boys are the most vulnerable group of adolescents in terms of injuries. PA promotion programmes should further consider gender-specific strategies aimed at preventing injuries.


Production of serotonin syndrome by 8-OH DPAT in Cryptotis parva.
We have previously shown that the 5-HT2A/C agonist, DOI, potently and in a dose-dependent manner produces the head-twitch response in the least shrew (Cryptotis parva) via the activation of serotonergic 5-HT2A receptors. The purpose of the present study was to determine whether activation of 5-HT1A receptors by its selective agonist, 8-OH DPAT, can induce the serotonin syndrome (SS) in this species. In the rat, the symptoms of SS include: forepaw splaying, hindleg abduction, forepaw treading, flat body posture, tremor, and straub tail. Intraperitoneal (i.p.) administration of 8-OH DPAT produced four classic symptoms (forepaw splaying, hindleg abduction, forepaw treading, and straub tail) of SS in the least shrew in a dose-dependent manner in the 30-min observation period. The mean total cumulative score for all components of SS also significantly increased in intensity in a dose-dependent fashion. Administration of selective 5-HT1A antagonists [S(-)UH 301 or NAN-190] potently blocked the 8-OH DPAT-induced mean total SS score in a dose-dependent manner. Moreover, these antagonists had similar potencies as indicated by their identical ID50 values (0.5 and 0.52 mg/kg respectively). However, unexpectedly and unlike the published findings in the rat, the nonselective 5-HT1A antagonist with b-blocking activity, propranolol, failed to attenuate the induced response in this species. As was expected, the selective 5-HT2A/C antagonist, SR 46349B, did not affect the intensity 8-OH DPAT-induced symptoms. Overall, these data suggest that the SS produced by 8-OH DPAT in the least shrew is mediated via the activation of serotonergic 5-HT1A receptors. In addition, propranolol is not a useful 5-HT1A antagonist in this species.


Echocardiographic assessment of canine degenerative mitral valve disease.
Degenerative mitral valve disease (MVD), the most common acquired heart disease in small-sized dogs, is characterized by valvular degeneration resulting in systolic mitral valve regurgitation (MR). Worsening of MR leads to several combined complications including cardiac remodeling, increased left ventricular filling pressure, pulmonary arterial hypertension, and myocardial dysfunction. Conventional two-dimensional, M-mode, and Doppler examination plays a critical role in the initial and longitudinal assessment of dogs affected by MVD, providing information on mitral valve anatomy, MR severity, left ventricular (LV) size and function, as well as cardiac and vascular pressures. Several standard echocardiographic variables have been shown to be related to clinical outcome. Some of these markers (e.g., left atrium to aorta ratio, regurgitation fraction, pulmonary arterial pressure) may also help in identifying asymptomatic MVD dogs at higher risk of early decompensation, which remains a major issue in practice. However, both afterload and preload are altered during the disease course. This represents a limitation of conventional techniques to accurately assess myocardial function, as most corresponding variables are load-dependent. Recent ultrasound techniques including tissue Doppler imaging, strain and strain rate imaging, and speckle tracking echocardiography, provide new parameters to assess regional and global myocardial performance (e.g., myocardial velocities and gradients, deformation and rate of deformation, and mechanical synchrony). As illustration, the authors present new data obtained from a population of 91 dogs (74 MVD dogs, 17 age-matched controls) using strain imaging, and showing a significant longitudinal systolic alteration at the latest MVD heart failure stage.


Clinicopathological characteristics and prognosis of patients with IgA nephropathy and renal vasculitic lesions.
We studied patients with IgA nephropathy (IgAN) and compared those with and without renal vasculitic lesions (RVLs). From January 2006 to December 2011, patients with biopsy-proven primary IgAN at our institution were retrospectively examined and assigned to an RVL group or a no-RVL group. RVLs were defined as thromboses in arteries and/or arterioles, necrosis of capillary loops, crescent formation, and fibrinoid necrosis of small blood vessels. The association of RVLs with clinical outcomes was analyzed using multivariate models. The primary composite endpoint was end-stage renal disease or doubling of serum creatinine. There were 1570 patients, 50.2% (788) with RVLs and 49.8% (782) without RVLs. The RVL group was younger; had shorter disease course, more severe proteinuria and hematuria, worse renal function; and were prescribed more steroids and/or immunosuppressants. The RVL group had a greater prevalence of global glomerular sclerosis, more crescents, and a higher Oxford classification grade. A total of 501 patients in the RVL group (50.7%) and 487 in the no-RVL group (49.3%) completed follow-up. The RVL group was more likely to reach the composite endpoint after 1, 3, and 5 years (all P < 0.001). Proteinuria, anemia, low eGFR, and global and segmental sclerosis were independent predictors of progression to the composite endpoint in patients with RVLs. Almost half of our IgAN patients had RVLs, and these patients were younger and had worse renal function, with more severe proteinuria, hematuria, and severe pathologic lesions. IgAN patients with RVLs had worse renal outcomes than those without RVLs.


Detection of a new piperideine alkaloid in the pygidial glands of some Stenus beetles.
Rove beetles of the genus Stenus produce and store bioactive alkaloids like stenusine (3), 3-(2-methylbut-1-enyl)pyridine (4), and cicindeloine (5) in their pygidial glands to protect themselves from predation and microorganismic infestation. The biosynthesis of stenusine (3), 3-(2-methylbut-1-enyl)pyridine (4), and cicindeloine (5) was previously investigated in Stenus bimaculatus, Stenus similis, and Stenus solutus, respectively. The piperideine alkaloid cicindeloine (5) occurs also as a major compound in the pygidial gland secretion of Stenus cicindeloides. The three metabolites follow the same biosynthetic pathway, where the N-heterocyclic ring is derived from L-lysine and the side chain from L-isoleucine. The different alkaloids are finally obtained by few modifications of shared precursor molecules, such as 2,3,4,5-tetrahydro-5-(2-methylbutylidene)pyridine (1). This piperideine alkaloid was synthesized and detected by GC/MS and GC at a chiral phase in the pygidial glands of Stenus similis, Stenus tarsalis, and Stenus cicindeloides.


Oncological Outcomes Following Transoral CO2 Laser Microsurgery for T1 Glottic Cancer.
The objective of this study is to analyze oncological outcomes for treatment of Tis and T1 glottic squamous cell carcinoma after transoral laser microsurgery. This study is retrospective analysis of previously untreated, suspected lesion of glottis, staged cT1a and cT1b squamous cell carcinoma in a tertiary care hospital and 53 patients were included in the study. End points for analysis were local control, overall and disease specific survival rates. The local control, ultimate local control with laser alone, 3-year overall survival, 3-year disease specific survival and organ preservation rates were 86.7, 90.5, 92.4, 98.1 and 98.1% respectively. The involvement of anterior commissure did not show any significant impact on local control or survival. TLM is safe and effective treatment of early glottis cancer, associated with less morbidity and a high percentage of local control, survival and organ preservation rates.


Response to: "The robust concept of mineral-associated organic matter saturation: A letter to Begill et al. (2023)".
In this response to a letter to the editor, we provide evidence that the findings regarding a non-detectable limit of mineral-associated organic carbon as published in Begill et al. (2023) are robust. This is mainly done by showing that no methodological bias was present and that the main correlation was not driven by a few exceptional soils.


Molecular mechanisms of the synergistic induction of ornithine decarboxylase by asparagine and glucagon in primary cultured hepatocytes.
In primary cultures of adult rat hepatocytes maintained in a salts/glucose medium, a more than 100-fold increase in ornithine decarboxylase (EC 188.8.131.52) activity was caused by asparagine and glucagon in a synergistic manner. The synthesis rate of ornithine decarboxylase was determined by [35S]methionine incorporation into the enzyme protein, and the amount of ornithine decarboxylase-mRNA was measured by hybridization with a cloned rat liver ornithine decarboxylase-cDNA. The synthesis rate of ornithine decarboxylase was stimulated more than 20-fold by asparagine and glucagon together, but the amount of ornithine decarboxylase-mRNA was increased only 3-4-fold, indicating that translational stimulation was involved in the induction process. Asparagine alone stimulated the synthesis of ornithine decarboxylase without substantial effect on the amount of ornithine decarboxylase-mRNA, whereas glucagon alone increased the amount of ornithine decarboxylase-mRNA about 3-fold without a detectable change in either enzyme activity or enzyme synthesis. Asparagine, at least in part, also suppressed degradation of ornithine decarboxylase.


Isolation and characterization of Drosophila melanogaster U2 small nuclear RNA genes.
We describe here the organization of DNA sequences complementary to Drosophila melanogaster U2 small nuclear (sn) RNA. From a genomic library we isolated two recombinants containing two genes each. Genomic reconstruction experiments and Southern analysis revealed that D. melanogaster possesses only four to five U2 snRNA genes or very closely related sequences. The nucleotide sequence of one of the clones analysed shows 77% homology with rat U2 snRNA. A stretch of 12 nucleotides that has been implicated in heterogeneous nuclear RNA splicing is conserved between rat and Drosophila. The genomic organization of these genes is very similar in different melanogaster strains but diverges highly in different Drosophila species.


An experimental workflow to assess the applicability of microemulsions for conformance improvement in oil-bearing reservoir.
A comprehensive workflow approach is necessary to link multiple experimental tasks and identify microemulsion (ME) formulations with 'optimal' stability, displacement behavior and technical feasibility in the petroleum industry. In this paper, a systematic approach is described with the aid of a case study which involves the formulation of an anionic sodium dodecyl sulfate-based microemulsion. The design of such ME systems requires a proper methodology, substantial laboratory work, and functional assessment from research/industrial viewpoints. The surfactant has been screened in terms of its micellization potential, followed by phase behavior analysis and Winsor classification of prepared microemulsions. The desired composition(s) are characterized via several tools to determine droplet size, morphology, oil/water solubilization potentials and salinity scan results. The suitability of the microemulsion system for conformance improvement technology (CIT) is proposed to be assessed via physicochemical evaluation studies encompassing two attributes: rheology and stability. For a favorable 'conforming' drive, the microemulsion must exhibit phase stability, sufficient injectivity, and moderate-to-high viscosity under shear. Technical assessment by the industry and research team must also include factors related to cost, availability of chemicals, environmental degradation, and reservoir considerations. The article demonstrates a comprehensive all-inclusive workflow methodology to design and formulate surfactant-stabilized microemulsions via case study analysis for application in CIT. This represents a sound approach to identifying efficient, cost-effective injection fluid systems and provides a framework to identify useful parameters for ME formulation design and employ the proposed (effective) strategy for conformance control.


Calcite saturation in the River Dee, NE Scotland.
The spatial and temporal variations in calcite (calcium carbonate) solubility within the Dee basin of NE Scotland were assessed using water chemistry data gathered from a network of 59 sites monitored for water quality from June 1996 to May 1997. Calcite solubility, expressed in terms of a saturation index (SIcalcite), was determined from measured streamwater pH, Gran alkalinity and calcium concentrations and water temperature. In general, the waters of the Dee system are undersaturated with respect to calcite, though the saturation index is higher during the summer months indicating a dependency on flow conditions and biological activity. Under low-flow conditions, the streamwaters are dominated by water derived from the lower soil horizons and deeper groundwater stores and therefore, ions such as Gran alkalinity and calcium are at their highest concentrations as they are derived mainly from bedrock weathering. The influence of biological activity on the carbonate system is also evident as the observed pH and estimated EpCO2 values indicate strong seasonal patterns, with the highest pH and lowest EpCO2 values occurring during the summer low-flow periods. Only at three sites in the lowland region of the catchment, during the summer low-flow period, are the waters oversaturated. As such, the Dee system represents an extreme 'end-member' case when compared to many UK rivers that span both under- and oversaturated conditions during the year. Regression analysis highlights a systematic change in the SIcalcite-pH relationship in a broad east-west direction across the Dee system. At sites draining the relatively impermeable upland areas, the regression of SIcalcite against pH gives a straight line with a gradient in the range 1.6-2.4. Correspondingly, under the most extreme alkaline conditions found at sites draining lowland agricultural areas, a straight-line relationship exists but with a gradient of unity. It is concluded that these changes in the SIcalcite-pH relationship are due to variations in the bicarbonate system induced by the flow conditions and biological activity. Given the waters are undersaturated, then calcite precipitation and hence phosphorus co-precipitation cannot occur within the water column.


Treatment of Drug-Susceptible Tuberculosis.
Mycobacterium tuberculosis is a major public health concern and requires prompt treatment. Goals of treatment include curing the individual patient and protecting the community from ongoing tuberculosis transmission. To achieve durable cure, regimens must include multiple agents given concurrently and in a manner to ensure completion of therapy. This article focuses on preferred regimens of drug-susceptible tuberculosis under current guidelines by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America and World Health Organization. In addition, topics including patient centered care, poor treatment outcomes, and adverse effects are also discussed.


Application of a new hybrid organic-inorganic monolithic column for efficient deoxyribonucleic acid purification.
A new hybrid organic-inorganic monolithic column for efficient deoxyribonucleic acid (DNA) extraction was prepared in situ by polymerization of N-(beta-aminoethyl)-gamma-aminopropyltriethoxysilane (AEAPTES) and tetraethoxysilane (TEOS). The main extraction mechanism was based on the Coulombic force between DNA and the amino silica hybrid monolithic column. DNA extraction conditions, such as pH, ion concentration and type, and loading capacity, were optimized online by capillary electrophoresis with laser-induced fluorescence detection. Under optimal condition, a 6.0-cm monolithic column provided a capacity of 48 ng DNA with an extraction efficiency of 74+/-6.3% (X+/-RSD). The DNA extraction process on this monolithic column was carried out in a totally aqueous system for the successful purification of DNA and removal of proteins. The PBE2 plasmid could be extracted from Bacillus subtilis (B. subtilis) crude lysate within 25 min, and the purified DNA was suitable for the amplification of a target fragment by polymerase chain reaction. This study demonstrates a new attractive solid-phase support for DNA extraction to meet the increasingly miniaturized and automated trends of genetic analyses.


Beta-trace protein, cystatin C, beta(2)-microglobulin, and creatinine compared for detecting impaired glomerular filtration rates in children.
Because of the limitations of serum creatinine as a marker of glomerular filtration rate (GFR) in children, we assessed the diagnostic accuracy of the novel marker beta-trace protein (BTP) in comparison with cystatin C (Cys-C), beta(2)-microglobulin (beta(2)-MG), and creatinine as conventional indicators of reduced GFR. We obtained serum samples from 225 children (age range, 0.2-18 years) with various renal pathologies who were referred for nuclear medicine clearance investigations (technetium-diethylenetriamine pentaacetic acid or chromium-EDTA). We measured Cys-C, BTP (nephelometric tests; Dade Behring), beta(2)-MG (Tinaquant; Roche), and creatinine (enzymatic assay; Creatinine-PAP; Roche). Seventy-five children had reduced GFR (<90 mL x min(-1) x 1.73 m(-2)). One hundred fifty children (independent of gender and age) with values >90 mL x min(-1) x 1.73 m(-2) comprised the control group with gaussian distributions of BTP and Cys-C concentrations. The upper reference limits (97.5 percentile) were 1.01 mg/L for BTP and 1.20 mg/L for Cys-C. The correlations of nuclear medicine clearance with the reciprocals of BTP, Cys-C, and the Schwartz GFR estimate were significantly higher (r = 0.653, 0.765, and 0.706, respectively; P <0.05) than with the reciprocal of creatinine or beta(2)-MG (r = 0.500 and 0.557, respectively). ROC analysis showed a significantly higher diagnostic accuracy of BTP, Cys-C, and the GFR estimate for the detection of impaired GFR than serum creatinine (P <0.05). Compared to creatinine, BTP increased the diagnostic sensitivity by approximately 30%, but it was not more sensitive than Cys-C or the Schwartz GFR estimate. BTP is superior to serum creatinine and an alternative for Cys-C to detect mildly reduced GFR in children, but it is not better than the Schwartz GFR estimate.


Genetic parameters for behavioral and growth traits of Nellore cattle.
The growing concern of consumers with the welfare of production animals searches welfare in a production system extremely important; thus, the study of animal temperament is necessary to select less excitable temperament animals resulting in healthy development and fewer accidents. The objective of this study was to estimate genetic parameters for traits related to animal temperament and growth traits of Nellore cattle. In addition to exploring the genetic pattern of these traits through cluster and principal component analysis (PCA), to reveal possible groups of individuals that express less excitable temperament and greater growth. A total of 2,332 measurements from 1,245 male and female Nellore cattle born between 2008 and 2016 were utilized in the study. The (co)variance components were estimated by Bayesian inference using a two-trait animal model. The heritability for temperament score (TS), flight speed (FS), body condition score (BCS), live weight (LW), and hip height (HH) were 0.08, 0.12, 0.06, 0.13, and 0.48, respectively. The genetic correlation between the temperament indicator traits was strong and positive (0.78 ± 0.24). The TS and FS showed a favorable or null genetic correlation with LW, BCS, and HH. The third cluster included animals with low EBV for TS and FS and with high EBV for BCS, LW, and HH. In the PCA, the PC1 was what best evidenced the aim of this study; thus, our findings suggest that we could explore select animals based on cluster 3 and PC1 in breeding programs to select Nellore cattle with less excitable temperament and greater growth.


Efficient removal of Sb(III) from water using β-FeOOH-modified biochar:Synthesis, performance and mechanism.
Since the toxicity of Sb(III) is 10 times as high as that of Sb(V) in the environment, it is urgent to find a way to cut down Sb(III). β-FeOOH-modified biochar (β-FeOOH/BC) was prepared and used to remove Sb(III). The characterization results suggested that oxygen-containing functional groups formed on β-FeOOH/BC, which increased the Sb(III) removal efficiency. Even under complex water matrix conditions, the outstanding adsorption performance of β-FeOOH/BC for Sb(III) was obtained. The adsorption reaction rapidly reached a high removal efficiency within 5 min and approached adsorption equilibrium in about 6 h. The adsorption process was fitted to pseudo-second-order kinetics. Amount of maximum adsorption was 202.53 mg g-1 at 308 K according to Langmuir model. β-FeOOH/BC removed Sb(III) mainly through pore-filling complexation, cation-π and coordination exchange. The CO sites and persistent free radicals (PFRs) acted as electron acceptors, facilitating the electron transfer. In brief, β-FeOOH/BC adsorbent material could adsorb and oxidize Sb(III), which showed excellent prospects for reducing the risk of Sb(III).


Comparative proteome and metabolome analyses of latex-exuding and non-exuding Taraxacum koksaghyz roots provide insights into laticifer biology.
Taraxacum koksaghyz has been identified as one of the most promising alternative rubber crops. Its high-quality rubber is produced in the latex of laticifers, a specialized cell type that is organized in a network of elongated tubules throughout the entire plant body. In order to gain insights into the physiological role(s) of latex and hence laticifer biology, we examine the effects of barnase-induced latex RNA degradation on the metabolite and protein compositions in the roots. We established high-quality datasets that enabled precise discrimination between cellular and physiological processes in laticifers and non-laticifer cell types of roots at different vegetative stages. We identified numerous latex-specific proteins, including a perilipin-like protein that has not been studied in plants yet. The barnase-expressing plants revealed a phenotype that did not exude latex, which may provide a valuable genetic basis for future studies of plant-environment interactions concerning latex and also help to clarify the evolution and arbitrary distribution of latex throughout the plant kingdom. The overview of temporal changes in composition and protein abundance provided by our data opens the way for a deeper understanding of the molecular interactions, reactions, and network relationships that underlie the different metabolic pathways in the roots of this potential rubber crop.


Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids.
Racemic 1-(β-hydroxypropyl)azoles were prepared by solvent-free direct regioselective ring opening of 1,2-propylene oxide with imidazole or 1,2,4-triazole. Lipase-catalyzed transesterification of alcohols with vinyl acetate resulted in kinetic enantiomers resolution. Separated (S)-enantiomers of (+)-1-(1H-imidazol-1-yl)propan-2-ol and (+)-1-(1H-1,2,4-triazol-1-yl)propan-2-ol were quaternized with alkyl bromides or iodides, yielding novel optically active ionic liquids. Racemic salts were tested against a wide range of microorganisms.


Acute exercise exacerbates ischemia-induced diastolic rigor in hypertensive myocardium.
Previous studies have shown that acute exercise preconditions the myocardium from ischemic injury. The purpose of this study was to test whether acute exercise protects the hypertensive myocardium from ischemia-induced diastolic rigor, and to compare the response between normotensive and uncompensated hypertensive hearts. Hearts harvested from female Wistar-Kyoto (WKY; n = 24) and spontaneously hypertensive rats (SHR; n = 27) (age:10-12 weeks) were exposed to ischemia (Langendorff isovolumic preparation; 22 minutes of no flow ischemia and studied following prior conditions of: 1) no exercise (WKY-CON, n=8; SHR-CON, n=8); 2) ischemia initiated one hour post-acute exercise (WKY-1HR, n = 8; SHR-1HR, n = 11); and 3) ischemia initiated 24 hours post-acute exercise (WKY-24HR; n = 8; SHR-24HR, n = 8). Acute exercise consisted of one bout of treadmill running at 25 m/min for 60 minutes. Heart weight was similar between WKY and SHR despite elevated in vivo resting systolic blood pressure and rate pressure product in SHR (P<0.05). During normoxic perfusion, left ventricular (LV) Langendorff performance was similar between WKY and SHR over the post-exercise time course. However, during ischemia, LV diastolic rigor was less in WKY vs. SHR (P<0.05). Acute exercise augmented ischemia-induced LV dysfunction one hour post-exercise in SHR (P<0.05), with gradual recovery by 24 hours post-exercise. These data suggest that acute exercise promotes ischemic diastolic rigor in SHR, even prior to the development of cardiac hypertrophy.


Isolation and identification of thiocyanate utilizing chemolithotrophs from gold mine soils.
A mixed bacterial culture capable of growing in potassium-thiocyanate containing medium (200 mg KSCN) has been isolated from bacterial suspensions of soil samples collected near gold mines in Kumjung (Korea). The isolates were initially characterized by metabolic profile analysis and were identified as Bacillus thermoglucosidasius, Bacillus cereus, Bacillus licheniformis, Bacillus mycoides, Brevibacterium epidermidis, Brevibacterium otitidis, and Corynebacterium nitrilophilus. One of the seven isolates was initially characterized as Brevibacterium epidermidis, which is not known to degrade thiocyanate. However, using 16S rDNA sequencing, this strain was identified as a member of Klebsiella. The strain shows high similarity values (95.8 to 96.4%) with Klebsiella species, and the closest known relative was found to be K. ornithinolytica ATCC 31898. The result indicates that species of the genus Klebsiella were the closest phylogenetic relatives of the investigated strain. This is the first known report of a member of Klebsiella that is capable of utilizing thiocyanate as sole source of carbon and nitrogen.


Two-year outcomes of intravitreal aflibercept in a Swiss routine treat and extend regimen for patients with neovascular age-related macular degeneration.
The aim of this observational study was to assess the use and outcome of intravitreal aflibercept in a treat and extend regimen in treatment-naïve neovascular AMD patients in routine practice. This both retrospective and prospective study was conducted in four larger Swiss retina clinics (ASTERIA study). The primary endpoint was the mean change in best-corrected visual acuity (BCVA) in ETDRS letters from baseline to 12 months. Between December 2017 and August 2018, 160 patients were included. For patients with available data, the mean change in BCVA was + 8.4 (± 14.4) letters at month 12 (n = 139) and + 5.0 (± 11.4) letters at month 24 (n = 95). A mean number of 8.3 (± 2.4) injections were administered within the first year and 5.4 (± 2.9) injections during the second year. On average, the observed treatment interval at month 12 was 63.3 (± 22.0) days and increased to 69.1 (± 28.6) days at month 24. For 37% of the patients, a treatment interval ≥ 12 weeks was attained at month 24. In conclusion, intravitreal aflibercept in a Swiss real-life treat and extend regimen resulted in comparable anatomic and functional outcomes as were observed in the prospective registration trials of aflibercept for nAMD treatment.


Broadening learning communities during COVID-19: developing a curricular framework for telemedicine education in neurology.
In response to the cancellation of clinical clerkships due to COVID-19, the Johns Hopkins (JH) Neurology Education Team developed a virtual elective to enhance medical students' clinical telemedicine skills and foster community between academic institutions. This two-week clinical elective, entitled "Virtual Patient Rounds in Neurology," was administered once in April 2020 and once in May 2020. The curriculum included attending/fellow-led Virtual Rounds, Student Presentations, and Asynchronous Educational Activities. We also developed a new lecture series entitled JHNeuroChats, which consisted of live synchronous lectures presented by JH faculty and Virtual Visiting Professors. Trainees and faculty from outside institutions were invited to participate in the JHNeuroChats. Students and faculty completed pre- and post-elective surveys to assess the educational impact of the elective. Student's t-tests were used to compare scores between pre- and post-elective surveys. Seven JH medical students enrolled in each iteration of the elective, and an additional 337 trainees and faculty, representing 14 different countries, registered for the JHNeuroChats. We hosted 48 unique JHNeuroChats, 32 (66.7%) of which were led by invited Virtual Visiting Professors. At the end of the elective, students reported increased confidence in virtually obtaining a history (P < 0.0001) and performing a telehealth neurological physical exam (P < 0.0001), compared to the start of the course. In addition, faculty members reported increased confidence in teaching clinical medicine virtually, although these findings were not statistically significant (P = 0.15). Despite the constraints imposed by COVID-19, this virtual Neurology elective increased medical students' confidence in certain telemedicine skills and successfully broadened our learning community to encompass learners from around the world. As virtual medical education becomes more prevalent, it is important that we are intentional in creating opportunities for shared learning across institutions. We believe that this elective can serve as a model for these future educational collaborations.


Analysis of methane monooxygenase genes in mono lake suggests that increased methane oxidation activity may correlate with a change in methanotroph community structure.
Mono Lake is an alkaline hypersaline lake that supports high methane oxidation rates. Retrieved pmoA sequences showed a broad diversity of aerobic methane oxidizers including the type I methanotrophs Methylobacter (the dominant genus), Methylomicrobium, and Methylothermus, and the type II methanotroph Methylocystis. Stratification of Mono Lake resulted in variation of aerobic methane oxidation rates with depth. Methanotroph diversity as determined by analysis of pmoA using new denaturing gradient gel electrophoresis primers suggested that variations in methane oxidation activity may correlate with changes in methanotroph community composition.


Evolving a model for integrated treatment in a residential setting for people with psychiatric and substance use disorders.
This paper discusses the implementation of a residential, integrated treatment program serving dually diagnosed people with histories of homelessness. Attention is focused on the program structure and how the program developed over time. Program modifications tended to relax program rules and embrace a motivational, stage-wise model using harm-reduction principles. Despite initial skepticism regarding these modifications, outcomes such as program retention, abstinence from substances, employment, and hospitalization improved.


Health-related knowledge and preferences in low socio-economic kindergarteners.
The aim of the present study was to determine physical activity (PA) and nutrition knowledge and preferences in low socio-economic status kindergarten children. Following height and weight measurement, 795 low socio-economic status kindergarten children (age 3.8-6.8 y.o) completed a photo-pair knowledge and preferences food and exercise questionnaire. No difference was found between nutrition and PA knowledge scores (52.3 ± 0.9 versus 52.6 ± 0.8%, respectively). There was no difference between the nutrition knowledge and preference score (52.3 ± 0.9 versus 50.9 ± 0.9%, respectively). PA preference was significantly higher than knowledge (56.9 ± 1.5 versus 52.6 ± 0.8%, respectively; p < 0.0001). Significant correlations were found between nutrition knowledge and preferences (r = 0.55, p < 0.0001), physical activity knowledge and preferences (r = 0.46, p < 0.0001), and nutrition and PA preferences (r = 0.46, p < 0.001). Nutrition preference scores were significantly lower in overweight compared to normal weight kindergartners 48.1 ± 1.7 versus 52.0 ± 1.0%; p < 0.05). PA knowledge and preference scores were significantly higher among male compared to the female kindergartners (p < 0.001 for both). Our data demonstrate diversities in physical activity and nutrition knowledge and preferences among low socio-economic status kindergarten children. These findings may be important for the development of health promotion programs in low socioeconomic kindergarten children.


Understanding Health Behaviors, Weight Perceptions, and Body Appreciation of Young Adult Women Engaged in the Body Positivity Movement.
The body positivity movement on social media is thought to foster body appreciation, but pervasive societal concern persists about the body positivity movement and the body image, health behaviors, and "normalization of obesity" of young adult women. This study explored the relationship between engagement in the body positivity movement on social media and weight status, body appreciation, body dissatisfaction, and the health behaviors of intuitive eating and physical activity in young adult women (18-35 years). Participants (N = 521; ∼64% engaged in body positivity content on social media) were recruited using Qualtrics online panels for this cross-sectional survey during February 2021. Outcomes included weight status, weight consideration, weight perception, body appreciation, body dissatisfaction, physical activity, and intuitive eating. Logistic and linear regression models adjusted for age, race, ethnicity, education level, and household income were used to assess the association between engagement in the body positivity movement and specified outcomes. Engagement with body positivity content was associated with greater body dissatisfaction (β = 2.33, t(519) = 2.90 p = .017), body appreciation (β = 0.26, t(519) = 2.90 p = .004), and greater likelihood of reporting high amounts of physical activity (odds ratio = 2.28; p < .05) relative to nonengaged peers; these associations remained significant after further adjustment for weight status. Body positivity engagement was not associated with weight status, weight perception, or intuitive eating. Engagement in the body positivity movement is associated with higher body dissatisfaction and body appreciation in young adult women, which suggests they may be drawn to and engage in the body positivity movement as a protective or coping mechanism for body dissatisfaction.


An experimental anatomical study on the optic nerve fibers in the rat: courses of the accessory optic tract.
By means of silver impregnation and an HRP method, courses of the accessory optic tract were examined in albino and pigmented rats. The accessory optic tract is composed of 3 fasciculi: anterior, lateral and dorsal. The anterior fasciculus gives off fibers to the subthalamic nucleus and terminates in the medial terminal nucleus. The lateral fasciculus branches from the main optic tract at the level of the ventral nucleus of the lateral geniculate body and descends the lateral surface of the crus cerebri to enter the medial terminal nucleus after contributing a few fibers to the lateral terminal nucleus. The dorsal fasciculus originates from the brachium colliculi superioris and descends the posterior surface of the medial geniculate body and the posterolateral surface of the crus cerebri as an independent fasciculus to enter the medial terminal nucleus. This fasciculus supplies many fibers to the dorsal terminal nucleus.


Friendship Conflict, Drinking to Cope, and Alcohol-Related Problems: A Longitudinal Actor-Partner Interdependence Model.
Drinking to cope with negative affect is a strong predictor of alcohol-related problems. We hypothesized that the association between friendship conflict and alcohol-related problems would be mediated by coping-with-depression motives in emerging adults' close friendships. We used a 4-wave, 4-month longitudinal self-report survey design measuring friendship conflict, coping motives, and alcohol-related problems from 174 same-sex friendship dyads. Participants were recruited from Nova Scotia, Canada between September 2016 and February 2019. Participants had a mean age of 18.66 (SD = 1.17) and were 66.1% female. Data were analyzed using multilevel structural equation modeling. Coping-with-depression motives mediated the link between conflict and alcohol-related problems at the between- and within-subject levels. Unexpectedly, coping-with-anxiety motives was an additional mediator at the within-subjects level. Interventions for emerging adults' problem drinking should consider the influence of friendship conflict and its impact on emerging adults' tendencies to drink to cope with both depression and anxiety. Materials/Syntax: https://osf.io/krs3v/.


Mucin mutations and aberrant expression are associated with the pathogenesis of immune thrombocytopenia.
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease of unknown aetiology. In this study, we aimed to identify the mutations and aberrant expression of mucins associated with ITP pathogenesis. First, we investigated the DNA mutation profile of bone marrow samples from patients with ITP (n = 20) by using next-generation sequencing (NGS). In addition, MUC3A, MUC5B and MUC6 were mutated in all patients with ITP. ELISA (enzyme-linked immunoassay) was used to measure MUC3A, MUC5B and MUC6 levels in the plasma of bone marrow fluid mononuclear cells (BMMCs) and peripheral blood mononuclear cells (PBMCs). Real-time quantitative PCR was used to study the mRNA expression levels of MUC3A, MUC5B and MUC6 in BMMCs and PBMCs. The results indicated that there were 3998 missense mutations involving 2269 genes in more than 10 individuals. MUC3A levels were not significantly different among the three groups, whereas MUC5B and MUC6 expression were significantly down-regulated in patients with ITP compared with healthy controls. In addition, serum MUC5B and MUC6 levels were significantly higher in patients with ITP in clinical remission than in patients with active ITP. Taken together, these results suggest that genetic alterations and the aberrant serum expression of mucins might be involved in the pathogenesis of ITP.


Highly sensitive and rapid determination of theophylline, theobromine and caffeine in human plasma and urine by gradient capillary high-performance liquid chromatography-frit-fast atom bombardment mass spectrometry.
A sensitive and reliable analytical procedure has been established for the detection of theophylline (TH), theobromine (TB) and caffeine (CA) in human plasma and urine by gradient capillary high-performance liquid chromatography (HPLC)-frit-fast atom bombardment mass spectrometry (FAB-MS) (LC-frit-FAB-MS). Two capillary columns and a column-switching valve were used in this LC system to allow all of the sample injected to be introduced into the MS system. 7-Ethyltheophylline was used as the internal standard (I.S.). The xanthines in the specimen were extracted with an Extrelut column. The lowest detected amount was ca. 5 ng/ml using this method.


A multicentre trial of the aldose-reductase inhibitor, tolrestat, in patients with symptomatic diabetic neuropathy.
The effects of the aldose-reductase inhibitor, tolrestat, on chronic symptomatic diabetic sensorimotor neuropathy were studied during a placebo-controlled, randomised, 52-week multicentre trial. Of the four tolrestat doses investigated, only the highest dose group, 200 mg once daily, showed subjective and objective benefit over baseline and placebo, and further analyses are confined to this group (n = 112) and placebo (n = 107). Painful and paraesthetic symptoms were analysed separately: improvement in paraesthetic symptoms were seen at one year (p = 0.04), though painful symptoms improved on both placebo and active therapies. Significant improvement in both tibial and peroneal motor nerve conduction velocities were seen at 52 weeks. Tolrestat 200 mg once daily was significantly better than placebo in producing concordant improvements in both motor nerve conduction velocities and paraesthetic symptom scores at 24 weeks (p = 0.01), 42 weeks (p = 0.01) and 52 weeks (p = 0.02). Long-term benefit [concordant improvement at 24 weeks maintained until 52 weeks] was seen in 28% of treated patients compared to 5% on placebo (p = 0.001). It is concluded that some sustained improvement in symptomatic diabetic neuropathy may be obtained following aldose-reductase inhibition with tolrestat 200 mg once daily.


A flow cytometric assay to monitor antimicrobial activity of defensins and cationic tissue extracts.
To determine the antibacterial activity of defensins and other antimicrobial peptides in biopsy extracts, we evaluated a flow cytometric method with the membrane potential sensitive dye bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC4(3)]. This assay enables us to discriminate intact non-fluorescent and depolarized fluorescent bacteria after exposure to antimicrobial peptides by measurement at the direct target, the cytoplasmic membrane and the membrane potential. The feasibility of the flow cytometric assay was evaluated with recombinant human beta-defensin 3 (HBD-3) against 25 bacterial strains representing 12 species. HBD-3 showed a broad-spectrum dose dependent activity and the minimal dose to cause depolarization ranged from 1.25 to >15 microg/ml HBD-3, depending on the species tested. The antibacterial effect was diminished with sodium chloride or dithiothreitol and could be abrogated with a HBD-3 antibody. Additionally, isolated cationic extracts from human intestinal biopsies showed a strong bactericidal effect against Escherichia coli K12, E. coli ATCC 25922 and Staphylococcus aureus ATCC 25923, which was diminished towards E. coli at 150 mM NaCl, whereas the activity towards S. aureus ATCC 25923 remained unaffected at physiological salt concentrations. DTT blocked the bactericidal effect of biopsy extracts completely.


The long 3'-untranslated regions of the PDGF-A and -B mRNAs are only distantly related.
A cDNA clone of about 2300 base pairs was prepared from the human osteosarcoma cell line U-2 OS by hybridization with a 22-mer oligonucleotide complementary to the NH2-terminus of PDGF-A. Restriction and sequence analysis showed that this clone contains the entire coding region for PDGF-A and a long 3'-untranslated region which is only distantly related to that in the mRNA of PDGF-B.


Fetal choroid plexus cysts in association with cri du chat (5p-) syndrome.
The significance of fetal choroid plexus cysts is controversial. We report a case of antenatally detected cri du chat syndrome (5p-) in one fetus of a twin pregnancy in association with bilateral fetal choroid plexus cysts and unassociated with other structural malformations. Choroid plexus cysts may be nonspecific markers for chromosomal anomalies.


Mild and efficient synthesis of new tetraketones as lipoxygenase inhibitors and antioxidants.
A mild and efficient route to tetraketones (2-22) has been developed by way of tetraethyl ammonium bromide (Et(4)N(+)Br(- )) mediated condensation of dimedone (5,5-dimethylcyclohexane-1,3-dione, 1) with a variety of aldehydes. All these compounds showed significant lipoxygenase inhibitory activity and moderate to strong antioxidant potential. Compounds 19 (IC(50) = 7.8 microM), 22 (IC(50) = 12.5 microM), 3 (IC(50) = 16.3 microM), 11 (IC(50) = 17.5 microM) and 8 (IC(50) = 21.3 microM) showed significant inhibitory potential against lipoxygenase (baicalein, IC(50) = 22.4 microM). On the other hand compound 19 (IC(50) = 33.6 microM) also showed strong antioxidant activity compared to the standard (IC(50) = 44.7 microM). This study is likely to lead to the discovery of therapeutically efficient agents against very important disorders including inflammation, asthma, cancer and autoimmune diseases.


Immunoreactivity for LN2 and LN3 distinguishes small cell carcinomas from non-small cell carcinomas in the lung.
Immunoreactivity to LN2 and LN3, monoclonal antibodies that recognize components of the class II major histocompatibility complex, was assessed in 72 cases of non-small cell lung carcinoma (NSCLC) (32 biopsy specimens, 40 resection specimens) and 64 cases of small cell carcinoma (56 biopsy specimens, 8 resections) of the lung. All cases were reviewed independently by three pathologists for histological classification. Only 1 of the 64 small cell carcinomas showed immunoreactivity for LN2, and none of the 64 cases showed reactivity for LN3. Among the non-small cell carcinomas, 25 of 48 cases were positive for LN2 and 43 of 71 were positive for LN3; the sensitivity was greater for adenocarcinoma (78.5%) than for squamous cell carcinoma (37%). A combined sensitivity of 64.7% was observed when the results of LN2 and LN3 were combined, and this sensitivity was not significantly diminished in the biopsy subset of cases (59.4%). Differentiation within histological subtypes of NSCLC (ie, well, moderate, or poorly differentiated) did not alter test sensitivity. In conclusion, LN2 and LN3, used alone or in combination, appear highly specific for non-small cell carcinoma and moderately sensitive in both biopsy and resection specimens; therefore, these antibodies may be diagnostically useful in distinguishing small cell from non-small cell carcinoma of the lung.


Evaluating the invariance of the Multigroup Ethnic Identity Measure across foreign-born, second-generation and later-generation college students in the United States.
Past research has established that the Multigroup Ethnic Identity Measure (MEIM) exhibits measurement invariance across diverse ethnic groups. However, relatively little research has evaluated whether this measure is invariant across generational status. Thus, the present study evaluates the invariance of the MEIM across foreign-born, second-generation, and later-generation respondents. A large, ethnically diverse sample of college students completed the MEIM as part of an online survey (N = 9,107; 72.8% women; mean age = 20.31 years; SD = 3.38). There is evidence of configural and metric invariance, but there is little evidence of scalar invariance across generational status groups. This study suggests that the MEIM has an equivalent factor structure across generation groups, indicating it is appropriate to compare the magnitude of associations between the MEIM and other variables across foreign-born, second-generation, and later-generation individuals. However, the lack of scalar invariance suggests that mean-level differences across generational status should be interpreted with caution. (PsycINFO Database Record


Leiomyosarcoma of the pancreas: report of a case.
Leiomyosarcoma of the pancreas is a rare neoplasm, with only 34 reported cases in the literature. We encountered a rare case of leiomyosarcoma of the pancreas, treated successfully by surgery. A 41-year-old woman was referred to our hospital for further examinations of a pancreatic tumor. Imaging studies demonstrated a solid and lobular mass, about 4 cm in diameter, in the body of pancreas. This mass had a nonuniform content and was encapsulated. We performed distal pancreatectomy and splenectomy for an assumed diagnosis of invasive ductal carcinoma. Macroscopically, a sagittal section of the operative specimen showed a well-circumscribed yellowish-white mass without any cystic changes. Immunohistological examination revealed that α-smooth muscle actin, desmin, and vimentin were positive, and the labeling index of MIB-1 was 50% or more. Based on these findings, we confirmed a diagnosis of leiomyosarcoma originating from the pancreas. During 14 months of follow-up to date, there has not been any evidence of local recurrence or distant metastasis.


Thymectomy modifies androgenizing effects of a testis transplant during critical period for neuroprogramming.
Thymectomy simultaneous with transplantation of a syngeneic testis from a littermate to Fischer 344 rats ameliorated the androgenizing effects of the testis transplant on ovarian morphology at 90 days of age.


SIMREP: a program simulating differential DNA replication.
During endoreplication, different organisms in different taxa carry out DNA syntheses without nuclear division. The result of such endocycles is either a polyploid nucleus or a polytene architecture of the chromosomes. Since not all sequences of the genome may be reduplicated simultaneously and to the same extent, endocycles provide an opportunity for primary cell differentiation at the DNA level as a result of DNA amplification or underreplication. We have designed a numerical model which simulates differential endoreplications. The program SIMREP is written in TURBO PASCAL 4.0 and can be executed on a PC/XT/AT with MS-DOS greater than or equal to 2.0. It uses diploid DNA contents derived from meiotic or mitotic nuclei together with data on amounts of DNA present after a given number of endocycles. SIMREP can be applied to genomes containing arbitrary numbers of chromosomes (maximum N = 24) to model details of their replication behaviour. It is also useful in analysing differential replication of single genes. The application of SIMREP is illustrated with two examples. (1) Female and male specific types of underreplication were found in the chironomid midge Prodiamesa olivacea. The heterosomes which appear homomorphic in metaphases were identified by their differential polytenization. (2) The Y chromosome of Drosophila nasutoides was assessed to ascertain whether its replication is regulated in parallel with, or independently from the large chromosome pair 4.


Evidence of a right-shift factor affecting infant hand-use preferences from 7 to 11 months of age as revealed by latent class analysis.
Infant hand-use preferences for apprehending objects were assessed three times at 7, 9, and 11 months of age for 154 infants (79 males) using a reliable and valid procedure. Two classification procedures (differing in Type I classification error rates) were used to identify an infant's preference (right, left, no preference) at each age, and these data were examined using two- and three-group latent class analysis models. These analyses revealed the importance of using a handedness classification procedure with low Type I error rates and evidence of a right-shift factor similar to that expressed in child and adult handedness. Thus, infant hand-use preferences for apprehending objects are likely a developmental precursor of adult handedness. The relation of the right-shift factor to increased susceptibility to social influences during development and the evolution of human abilities also is discussed.


Overlapping subdeletions within a 348-bp in the 5' exon of the LAT region that facilitates epinephrine-induced reactivation of HSV-1 in the rabbit ocular model do not further define a functional element.
A previous study identified a 348-bp region at the 5' end of the 8.5-kb latency-associated transcript (LAT) of HSV-1 strain 17Syn+ that is necessary for maximum adrenergically induced reactivation following transcorneal iontophoresis of epinephrine (D.C. Bloom et al., 1996, J. Virol. 70, 2449-2459). In that study, the construct with complete deletion of the 348-bp region, 17delta348, failed to achieve the high reactivation frequency demonstrated by the parent (17Syn+) and rescued (17delta348R) viruses. To further characterize the function of the 348-bp region, we analyzed two genetic constructs with partial deletions in the same 348-bp region, 17delta201 and 17delta207, in the rabbit model. Both constructs exhibited the same high reactivation frequencies demonstrated by the parent 17Syn+ and the rescued 17delta348R viruses. These results suggest that the control of reactivation is distributed over a large portion of the 348-bp region, rather than being confined within a smaller, more discrete region. To assess whether the low reactivation phenotype of the 17delta348 construct was caused by a requirement for proper spacing of elements outside the 348-bp region, we constructed a virus (17delta348St) that contained a 360-bp stuffer fragment of heterologous DNA (lacZ) to maintain the proper spacing. The 17delta348St construct also displayed a low reactivation phenotype, similar to that of 17delta348, suggesting that the effect of deleting this segment of the 5' exon of LAT is obtained through a mechanism other than the disruption of spacing.


Effect of primidone concentration on glass transition temperature and dissolution of solid dispersion systems containing primidone and citric acid.
The glass transition temperatures of glasses containing various concentrations of primidone in citric acid were measured and found to increase as the primidone concentration increased. Dissolution studies of these systems and particle-size measurements of primidone precipitated during dissolution of devitrified glasses suggest that the increase in the dissolution rate of the devitrified systems is due to both the small size of the precipitated crystals and the excellent wettability of these systems.


Structures, Functions, and Interactions of ClpT1 and ClpT2 in the Clp Protease System of Arabidopsis Chloroplasts.
Plastid ClpT1 and ClpT2 are plant-specific proteins that associate with the ClpPR protease. However, their physiological significance and structures are not understood. Arabidopsis thaliana loss-of-function single clpt1 and clpt2 mutants showed no visible phenotypes, whereas clpt1 clpt2 double mutants showed delayed development, reduced plant growth, and virescent, serrated leaves but were viable and produced seed. The clpt1 and clpt1 clpt2 mutants showed partial destabilization of the ClpPR complex, whereas clpt2 null mutants showed only marginal destabilization. Comparative proteomics of clpt1 clpt2 plants showed a proteostasis phenotype similar to viable mutants in ClpPR core subunits, indicating reduced Clp protease capacity. In vivo and in vitro assays showed that ClpT1 and ClpT2 can independently interact with the single ClpP ring and ClpPR core, but not with the single ClpR ring. We determined ClpT1 and ClpT2 structures (2.4- and 2.0-Å resolution) and detailed the similarities to the N-domains of bacterial ClpA/C chaperones. The ClpT structures suggested a conserved MYFF motif for interaction with the ClpPR core near the interface between the P- and R-rings. In vivo complementation showed that ClpT function and ClpPR core stabilization require the MYFF motif. Several models are presented that may explain how ClpT1,2 contribute to ClpPR protease activity.


Molecular cloning and mRNA expression of cytochrome P4501A1 and 1A2 in the liver of common minke whales (Balaenoptera acutorostrata).
This study presents full-length cDNA sequences of CYP1A1 and 1A2, in common minke whale (Balaenoptera acutorostrata) from the North Pacific. Both CYP1A1 and CYP1A2 cDNAs had an open reading frame of 516 amino acid residues, and predicted molecular masses were 58.3 kDa and 58.1 kDa, respectively. The deduced full-length amino acid sequence of CYP1A1 revealed higher identities with those of sheep (86%) and pig (87%), and that of CYP1A2 was most closely related to human (82%) and monkey CYP1A2 (82%) among species from which CYP1A2 has been isolated so far. Differences in certain conserved and functional amino acid residues of CYP1A1 and 1A2 between common minke whale and other mammalian species indicate the possibility of their specific metabolic function. Concentrations of organochlorine compounds (OCs) including PCBs and DDTs analyzed in common minke whale liver showed no significant correlation with hepatic mRNA expression levels of CYP1A1 and CYP1A2, indicating no induction of these enzymes by such OCs.