Characterization and comparison of raft-like membranes isolated by two different methods from rat submandibular gland cells.
Lipid rafts are defined as cholesterol and sphingolipid enriched domains in biological membranes. Their role in signalling and other cellular processes is widely accepted but the methodology used for their biochemical isolation and characterization remains controversial. Raft-like membranes from rat submandibular glands were isolated by two different protocols commonly described in the literature; one protocol was based on selective solubilization by Triton X-100 at low temperature and the other protocol consisted in extensive sonication. In both cases a low density vesicular fraction was obtained after ultracentrifugation in a sucrose density gradient. These fractions contained about 20% of total cholesterol but less than 8% of total proteins, and were more rigid than bulk membranes. Fatty acid analyses revealed a similar composition of raft-like membranes isolated by the two different methods, which was characterized by an enrichment in saturated fatty acids in detriment of polyunsaturated acids when compared with the whole cell membranes. Protein profile of detergent resistant membranes or raft-like membranes prepared by sonication was assessed by silver staining after SDS-PAGE and by MALDI-TOF. Both analyses provided evidence of a different protein composition of the Triton X-100 and sonication preparations. Immunoblot experiments revealed that raft-like membranes prepared by detergent extraction or sonication were free of Golgi apparatus or endoplasmic reticulum protein markers (beta-COP and calnexin, respectively) and that they were not substantially contaminated by transferrin receptor (a non-raft protein). While caveolin-1 was highly enriched in raft-like membranes prepared by the two methods, the P2X(7) receptor was enriched in raft-like membrane fractions prepared by sonication, but almost undetectable in the detergent resistant membranes. It can be concluded that both methods can be used to obtain raft-like membranes, but that detergent may affect protein interactions responsible for their association with different membrane domains.


Integration of community health teaching in the undergraduate medicine curriculum at the University of Toronto.
In 1999, Determinants of Community Health was introduced at the Faculty of Medicine, University of Toronto. The course spanned all 4 years of the undergraduate curriculum and focused on addressing individual patient and community needs, prevention and population health, and diverse learning contexts. To demonstrate the value of an integrated, longitudinal approach to the efficiency of delivering a public health curriculum. Time-series comparing the curricular change over two periods of time. Undergraduate medical students from 1993 to 2009. Using a spiral curriculum, the educational materials are integrated across all 4 years, based on the concept of medical decision making in a community context. This study compares measures of student satisfaction and national rankings of the University of Toronto with the other 16 Canadian medical schools for the "Population Health, Ethical, Legal, and Organizational aspects of the practice of medicine" component of the Medical Council of Canada Qualifying Examination Part 1. The University of Toronto has been ranked either first or second place nationally, in comparison to lower rankings in previous years (p<0.02 on the Kruskal-Wallis test). Student ratings indicated the course was comparable to others in the curriculum. For the same amount of curricular time, an integrated spiral curriculum for teaching public health appears to be more effective than traditional approaches.


Relation among, trait anxiety, intolerance to uncertainty and early maltreatment experiences on fear discrimination learning and avoidance generalization online task.
Early aversive experiences, which have been associated with elevated anxiety and intolerance of uncertainty (IUS), may contribute negatively to fear conditioning learning. The aim of the present study was to analyze the relation among individual differences in childhood maltreatment experiences, trait anxiety, and IUS in adulthood; and to determine how these variables could affect fear learning discrimination and avoidance generalization. We adapted an avoidance procedure in an online fear learning task. Two pictures of different lamp colors (CS+) were first associated with two aversive images (US), while a third color was not (CS-). Next, clicking a button during one CS + could effectively avoid the US (CS + av), but not during the other (CS + unav). Finally, avoidance generalization was tested to lamp colors that were between CS- and CS + av (safety dimension) and CS + av and CS + unav (avoidability dimension). With a sample of 67 participants, we measured ratings of relief, expectancy, and anxiety, as well as button presses and individual differences (STAI, IUS and MAES). Aversive early experiences were positively related to trait anxiety and intolerance of uncertainty. The results of the task further suggested that maltreatment experience contributes to be more attentive to aversive signals, which could be implicated in leading to difficulties in discrimination learning. Online experiments implies some loss of control over subjects and environment that can threaten internal validity. Likewise, the commitment of participants may be low. Results suggest that early aversive experience and anxiety could contribute to the development of IUS, which likely contributes to the development of avoidance behavior.


Transcutaneous oxygen monitoring and retinopathy of prematurity.
This study was performed to determine whether the use of continuous tcPO2 monitoring could reduce the incidence of ROP in preterm infants receiving oxygen therapy. Two hundred and ninety-six infants with birth weights less than or equal to 1300 grams were randomly assigned to a continuous monitoring (CM) or a standard care (SC) group. CM infants had tcPO2 monitored continuously as long as they required supplemental oxygen while SC infants had tcPO2 monitored only during the more acute state of their illness. Management of both groups was otherwise identical. One hundred and one of 148 infants in the CM and 113 of 148 patients in the SC groups survived. Mean birth weights and gestational age were similar in both groups. Duration of mechanical ventilation and oxygen therapy was also similar. The overall incidence of ROP was 51% in the CM and 59% in the SC group. As birth weight for infants greater than or equal to 1000 grams increased a higher risk for developing ROP was noted in the SC group. Four infants in the CM and 5 in the SC group developed cicatricial ROP. These results suggest that continuous tcPO2 monitoring may reduce the incidence of ROP in infants with birth weights greater than 1000 grams, but not in the smaller infants in whom this complication occurs more frequently and is more severe.


Age-associated decline in neural, endocrine, and immune responses in men and women: Involvement of intracellular signaling pathways.
The aim of this study was to investigate the alterations in the neuroendocrine-immune functions by using human peripheral blood mononuclear cells (hPBMCs) from three age groups (young, middle-aged, and old) of men and women for the analyses of lymphocyte proliferation and cytokine production, expression of cell signaling molecules, nitric oxide (NO) production, and expression of p-tyrosine hydroxylase (TH). Serum was examined for levels of testosterone in men, 17-β-estradiol in women, and cortisol in both sexes. Lymphoproliferation, expression of p-ERK, p-CREB, p-Akt, and p-TH, and levels of serum sex steroid hormones declined with age in men and women. However, TNF-α production and serum cortisol level increased with age in men and women. mTOR expression was higher in older men while it was lower in older women. IFN-γ and IL-6 production and expression of p-TH and p-mTOR were differentially regulated in men and women. These results suggest that intracellular signaling mediators may be involved in the age-related alterations in the neuroendocrine-immune interactions in men and women.


Matrix metalloproteinase-1 gene polymorphisms and periodontitis susceptibility: a meta-analysis based on 11 case-control studies.
Matrix metalloproteinase-1 has been implicated in periodontal disease, but the association between the most-studied Matrix metalloproteinase-1 1G-to-2G polymorphism and the risk of periodontal disease were reported with inconclusive results. Therefore, the aim of this study was to investigate the association between the Matrix metalloproteinase-1 1G-to-2G polymorphism and periodontal disease. Electronic databases search yielded 11 studies with 1447 patients and 1710 control subjects evaluated the association of the polymorphisms of Matrix metalloproteinase-1 1G-to-2G and periodontitis risk were brought into this study. The association was evaluated by odds ratio (OR) and its 95% confidence interval (CI). The overall results showed that the variant genotypes were associated with a significantly increased risk of periodontitis (OR=1.45, 95% CI=1.02-1.26 for 2G/2G vs 1G/1G, and OR=2.27, 95% CI=1.22-4.23 for 2G/2G vs 1G/2G+1G/1G). In the stratified analyses, there was a significantly increased risk for the studies of periodontitis (OR=1.59, 95% CI=1.15-2.21 for 2G/2G vs 1G/1G; OR=3.48, 95% CI=1.39-8.71 for 2G/2G vs 1G/2G+1G/1G), which remained for the studies of Asian populations. And there was a significantly increased risk of severe periodontitis (OR=2.15, 95% CI=1.35-3.43 for 2G/2G vs 1G/1G; OR=2.86, 95% CI=1.31-2.64 for 2G/2G vs 1G/2G+1G/1G; OR=1.6, 95% CI=1.12-2.39 for 1G/2G+2G/2G vs 1G/1G; OR=1.61, 95% CI=1.28-2.03 for 2G allele vs 1G allele). The current study demonstrated that the Matrix metalloproteinase-1-1607 1G-to-2G polymorphism was associated with susceptibility to periodontitis, apparently, severe periodontitis.


Non-symmetric subcutaneous lipomatosis associated with familial combined hyperlipidaemia.
A family with familial combined hyperlipidaemia in which affected members had nonsymmetric subcutaneous lipomatosis (NSSCL) is described. Affected members had high serum levels of total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol. By contrast, family members without NSSCL had normal lipid levels. There was also a correlation between the degree of hyperlipidaemia and the amount of subcutaneous lipomas. The occurrence of hyperlipidaemia in family members with NSSCL suggests the existence of a genetic linkage between these two characteristics, but did not show any association with HLA haplotyping. To our knowledge this association between lipid abnormalities and NSSCL has not been previously reported.


Pvr regulates cyst stem cell division in the Drosophila testis niche, and has functions distinct from Egfr.
Regulation of the rate of stem cell division is one of the key determinants of the abundance of differentiating progeny in stem cell-supported tissues, and mis-regulation can lead to tumorigenesis. The well-studied Drosophila testis niche is an excellent model system to study the regulation of stem cell division in vivo. This niche supports two stem cell populations-the germline stem cells (GSCs) and cyst stem cells (CySCs), which cluster around a group of cells called the hub. The differentiating cells of these two stem cell populations cooperate together to produce sperm. Signal transduction initiated by the epidermal growth factor receptor (Egfr) is a key regulatory pathway in the cyst lineage, and much of the study of this stem cell population has centered around understanding the complexities of the requirements for Egfr signaling. We examined another receptor tyrosine kinase, Pvr, the sole Drosophila PDGF/VEGF homolog, and found that it accumulates in the cyst lineage cells of the testis, while its ligand Pvf1 accumulates in the hub. Pvr inhibition caused a reduction in both CySC numbers and the proportion of CySCs in S phase, similar to Egfr inhibition. However, testes with Pvr inhibition exhibited a low-penetrance non-autonomous germ cell differentiation defect distinct from that observed with Egfr inhibition. Cyst cells with constitutively activated Pvr failed to support germ cell differentiation, as observed with constitutively activated Egfr. However, constitutively activated Pvr promoted tumorous accumulation of cyst cells outside of the niche, a phenotype not observed with constitutively activated Egfr. Thus, Egfr and Pvr have some receptor-specific functions and some shared functions in the cyst lineage cells of the testis.


Organization, alternative splicing, polymorphism, and phylogenetic position of lamprey CD45 gene.
CD45 of jawed vertebrates is a receptor-type protein tyrosine phosphatase regulating lymphocyte development and activation. To shed light on the evolution of the CD45 gene, the organization of its orthologue in the lamprey, a jawless vertebrate, was determined. Compared to its mammalian and fugu counterparts, the lamprey gene was found to be lacking several exons in the segment encoding the extracellular part of the protein. In consequence, this part contains only one instead of the two or three fibronectin type III domains typical of the mammalian molecules. The lamprey transcripts of the CD45 gene occur in several variants originating by alternative splicing, including some not observed previously in other vertebrates. Most remarkable of these are splice variants generated by the use of intra-exonic splicing signals and thus lacking one half, one third, or two thirds of an exon and yet apparently translated in the correct reading frame. The lamprey gene contains polymorphic sites not only in the segment encoding the extracellular portion but also in the segment specifying the cytoplasmic part of the molecule. Polymorphism is generated by both mutations and recombination. Some of the alleles may have persisted long enough to represent transspecies polymorphism presumably maintained by positive selection. Phylogenetic analysis suggests that ancestors of the CD45 gene may have existed before the divergence of coelomate from pseudocoelomate metazoans.


Metabolomics-driven of relationships among kidney, bone marrow and bone of rats with postmenopausal osteoporosis.
As a global public health problem, postmenopausal osteoporosis (PMOP) poses a great threat to old women's health. Bone is the target organ of PMOP, and the dynamic changes of bone marrow could affect the bone status. Kidney is the main organ regulating calcium and phosphorus homeostasis. Kidney, bone marrow and bone play crucial roles in PMOP, but the relationships of the three tissues in the disease have not been completely described. Here, metabolomics was employed to investigate the disease mechanism of PMOP from the perspectives of kidney, bone marrow and bone, and the relationships among the three tissues were also discussed. Six-month-old female Sprague-Dawley (SD) rats were randomly divided into ovariectomized (OVX) group (with bilateral ovariectomy) and sham group (with sham surgery). 13 weeks after surgery, gas chromatography-mass spectrometry (GC-MS) was performed to analyze the metabolic profiling of two groups. Multivariate statistical analysis revealed that the number of differential metabolites in kidney, bone marrow and bone between the two groups were 37, 16 and 17, respectively. The common differential metabolites of the three tissues were N-methyl-L-alanine. Kidney and bone marrow had common differential metabolites, including N-methyl-L-alanine, 2-hydroxybutyric acid, (R)-3-hydroxybutyric acid (β-hydroxybutyric acid, βHBA), urea and dodecanoic acid. There were three common differential metabolites between kidney and bone, including N-methyl-L-alanine, α-tocopherol and isofucostanol. The common differential metabolite of bone marrow and bone was N-methyl-L-alanine. Some common metabolic pathways were disturbed in multiple tissues of OVX rats, such as glycine, serine and threonine metabolism, purine metabolism, tryptophan metabolism, ubiquinone and other terpenoid-quinone biosynthesis and fatty acid biosynthesis. In conclusion, our study demonstrated that profound metabolic changes have taken place in the kidney, bone marrow and bone, involving common differential metabolites and metabolic pathways. The evaluation of differential metabolites strengthened the understanding of the kidney-bone axis and the metabolic relationships among the three tissues of OVX rats.


Eriocitrin: A review of pharmacological effects.
The present study aimed to recognize the recent literature to highlight the pharmacological impacts and highlight the therapeutic potential of the active molecule eriocitrin. Citrus limon are a good resource of the flavanone eriocitrin (eriodictyol 7-O-β-D-rutinoside). Eriocitrin has potent biological actions due to its strong antioxidant, antitumor, anti-allergic, antidiabetic and anti-inflammatory activities. Eriocitrin is more potent in suppressing oxidative stress in diabetes mellitus (DM) and other chronic diseases incurred by excessive oxidative stress. During metabolism, eriocitrin is metabolized by gut microbiota, and a chain of molecules such as eriodictyol, methy-eriodictyol, 3,4-dihydroxyhydrocinnamic acid (DHCA), and much more conjugated molecules. More in-depth studies are recommended to explore this drug for clinical trials.


Treatment of gastric eosinophilia by epicutaneous immunotherapy in piglets sensitized to peanuts.
Eosinophilic gastrointestinal disorders (EGIDs) are hypersensitivity disorders frequently triggered by food allergy and manifested by mucosal eosinophilic infiltration at any level of the gastrointestinal tract. This study established a model of gastric eosinophilia in peanut-sensitized piglets to evaluate the efficacy of epicutaneous immunotherapy (EPIT) for its treatment. Experiments were carried out in piglets first sensitized by three intra-peritoneal injections of peanut protein extract (PPE) with adjuvant, and then given PPE orally for 10 days, a sequence leading to gastric eosinophilia assessed by endoscopy. For 3 months, eight piglets received active EPIT, using Viaskin® loaded with PPE, applied daily on the ear, while eight received placebo EPIT (Placebo). Piglets were exposed to a second 10-day period of PPE orally. Lesions were scored by endoscopy on the last day of PPE exposure. After killing, all parts of the digestive tract were analysed by a pathologist unaware of the piglets' status. IgE response was measured, and mechanistic parameters were analysed in the spleen. After sensitization, a significant increase of total IgE was observed in sensitized compared to naive animals (61.1 ± 13.3 vs 27.8 ± 6 ng/mL, P < .01). Following oral intake of PPE, sensitized piglets developed moderate gastritis compared to naive piglets (1.5 vs 1.0, median score). After 3 months of immunotherapy, median IgE was significantly reduced in EPIT vs placebo piglets (61.4 ± 16.3 vs 105.9 ± 25.6 ng/mL, P < .01). Active EPIT significantly reduced gastric mucosal lesions induced by PPE oral intake (macroscopic score 0 [0-2] vs 2 [1-3], P < .01, respectively, active vs placebo) and gastric mucosa eosinophils counts (239 eosinophils/mm2 [59-645] vs 2554 eosinophils/mm2 [462-8057], P < .01, respectively active vs placebo). GATA-3, IL-5 and eotaxin mRNA expression decreased significantly after EPIT (P < .05). This study describes a large animal model of gastric eosinophil in peanut-sensitized piglets. Utilizing this model, we demonstrated the efficacy of EPIT in treating peanut-induced EGIDs.


Do perceived high performance work systems influence the relationship between emotional labour, burnout and intention to leave? A study of Australian nurses.
The purpose of this article was to explore the relationships between perceived high performance work systems, emotional labour, burnout and intention to leave among nurses in Australia. Previous studies show that emotional labour and burnout are associated with an increase in intention to leave of nurses. There is evidence that high performance work systems are in association with a decrease in turnover. There are no previous studies that examine the relationship between high performance work systems and emotional labour. A cross-sectional, correlational survey. The study was conducted in Australia in 2008 with 183 nurses. Three hypotheses were tested with validated measures of emotional labour, burnout, intention to leave, and perceived high performance work systems. Principal component analysis was used to examine the structure of the measures. The mediation hypothesis was tested using Baron and Kenny's procedure and the moderation hypothesis was tested using hierarchical regression and the product-term. Emotional labour is positively associated with both burnout and intention to leave. Burnout mediates the relationship between emotional labour and intention to leave. Perceived high performance work systems negatively moderates the relationship between emotional labour and burnout. Perceived high performance work systems not only reduces the strength of the negative effect of emotional labour on burnout but also has a unique negative effect on intention to leave. Ensuring effective human resource management practice through the implementation of high performance work systems may reduce the burnout associated with emotional labour. This may assist healthcare organizations to reduce nurse turnover.


Principal component analysis and quantitative image analysis to predict effects of toxics in anaerobic granular sludge.
Principal component analysis (PCA) was applied to datasets gathering morphological, physiological and reactor performance information, from three toxic shock loads (SL1 - 1.6 mg(detergent)/L; SL2 - 3.1mg(detergent)/L; SL3 - 40 mg(solvent)/L) applied in an expanded granular sludge bed (EGSB) reactor. The PCA allowed the visualization of the main effects caused by the toxics, by clustering the samples according to its operational phase, exposure or recovery. The aim was to investigate the variables or group of variables that mostly contribute for the early detection of operational problems. The morphological parameters showed to be sensitive enough to detect the operational problems even before the COD removal efficiency decreased. As observed by the high loadings in the plane defined by the first and second principal components. PCA defined a new latent variable t[1], gathering the most relevant variability in dataset, that showed an immediate variation after the toxics were fed to the reactors. t[1] varied 262%, 254% and 80%, respectively, in SL1, SL2 and SL3. The high loadings/weights of the morphological parameters associated with this new variable express its influence in shock load monitoring and control, and consequently in operational problems recognition.


An overview of cytogenetics of the tribe Meliponini (Hymenoptera: Apidae).
The present study provides a comprehensive review of cytogenetic data on Meliponini and their chromosomal evolution. The compiled data show that only 104 species of stingless bees, representing 32 of the 54 living genera have been studied cytogenetically and that among these species, it is possible to recognize three main groups with n = 9, 15 and 17, respectively. The first group comprises the species of the genus Melipona, whereas karyotypes with n = 15 and n = 17 have been detected in species from different genera. Karyotypes with n = 17 are the most common among the Meliponini studied to date. Cytogenetic information on Meliponini also shows that although chromosome number, in general, is conserved among species of a certain genus, other aspects, such as chromosome morphology, quantity, distribution and composition of heterochromatin, may vary between them. This reinforces the fact that the variations observed in the karyotypes of different Meliponini groups cannot be explained by a single theory or a single type of structural change. In addition, we present a discussion about how these karyotype variations are related to the phylogenetic relationships among the different genera of this tribe.


[The effect of an extract of Baikal skullcap (Scutelleria baicalensis) on succinic acid oxidation by the brain mitochondria in rats with hypoxia].
Oxidative phosphorylation in the mitochondria of rat brain in normobaric hypercapnic hypoxia and preventive administration of Scutellaria baicalensis extract was studied by polarography. Hypoxia causes diminution of energy of the rat brain mitochondria with separation of oxidative phosphorylation and inhibition of the reactions of rapid metabolic cluster of Krebs' cycle. Scutellaria baicalensis extract prevents diminution of energy of the brain mitochondria in hypoxia, inhibits restriction of succinate dependent energy production, and preserves intactness of the mitochondrial membranes.


[Pressure wave shape comparison between two non-invasive tonometric devices].
Pulse wave analysis is a pivotal instrument to estimate central hemodynamic parameters. Applanation tonometry on radial and/or carotid arteries is usually used to detect pressure waveforms. Available commercial devices have been validated against invasive catheterism, showing a good agreement of harmonics pattern. In a previous investigation, we observed differences on radial second systolic peak (rSPB2) between two commonly used devices: SphygmoCor (AtCor, Australia) and PulsePen (Diatecne, Italy). The aim of our study was to further quantify differences on radial and carotid signals from the two devices. We measured radial and carotid pressure waveforms in 38 patients where systolic, diastolic blood pressure and heart rate presented minimal changes between measurements. Waveforms were digitally extracted for off-line analysis. Radial rSBP2, mean arterial pressure, form factor and augmentation index were different with SphygmoCor providing lower values. Carotid augmentation index and form factor were similar. However, carotid systolic pressure (cSBP) from PulsePen was higher that cSBP from SphygmoCor (2.7 ± 4.4 mmHg, P<0.001). PulsePen and SphygmoCor sensors are not equivalent and provide different wave shapes. These differences on wave shape have important consequences on parameters computed from these waveforms with more discrepancy on radial derived parameters such as rSBP2 and mean arterial pressure than on carotid derived parameters. Further studies are required to compare invasive pressure parameters to indices derived from these two devices.


The HVL in soft tissue and the AAPM and IEC exposure indices.
Manual exposure settings for radiographic projections were once based on a points system which assumed that the HVL in soft tissue is 3.0 cm and that each change of 1.0 cm of soft tissue corresponded to a change of 25% in image receptor dose. A set of mAs steps and equivalent kVp steps was estimated that would give appropriate technique factors for changes in patient thickness. With the advent of rare-earth screen-film systems and AEC systems the points system fell into disuse. Screen-film imaging systems have almost entirely been replaced by CR or DR systems and recently, standardised exposure indices have been recommended by the AAPM and IEC to provide exposure guidance for these systems. If the fundamental assumptions on which the points system was based are still valid for modern high-frequency generators and digital imaging systems, then there would be an elegant correspondence between the predictions of the points system and the requirements for correction of exposure errors indicated by the AAPM and IEC indices. This study estimated the HVL and attenuation per cm in soft tissue using computer simulation, finding that practically, the HVL is between 2.0 and 5.0 cm and attenuation per cm ranges from 15 to 25%. The study concluded that agreement between the points system predictions and the true effects of technique factors changes on dose to the image receptor was moderately good, that use of the points system and technique charts based on this system should be encouraged and that use of the IEC or AAPM digital exposure indices should be standardised.


Effect of inhalation anesthetics on antipyrine pharmacokinetics of mice.
The effects of the volatile anesthetics, enflurane, isoflurane and halothane, on the pharmacokinetics of antipyrine were examined in mice. The administration of 0.75% isoflurane or 1.0% enflurane in air resulted in a 173 and a 206% increase, respectively, in antipyrine plasma half-life and a 29.1 and a 41.2% decrease in antipyrine total body clearance. There was also an almost 2-fold increase in the volume of distribution of antipyrine. Halothane, at 0.5% in air, had no significant effect upon antipyrine plasma half-life or its volume of distribution. There was no significant change in antipyrine total body clearance and volume of distribution 4 hr after exposure to the volatile agents, but there was a small increase in half-life. The exposures to the volatile anesthetics were also carried out in an atmosphere of 8% oxygen. Antipyrine plasma half-life was increased significantly by 48% in mice breathing 8% oxygen, compared to mice breathing air. Isoflurane in 8% oxygen increased the plasma half-life of antipyrine by 296% compared to mice breathing 8% oxygen. This increase was greater than the effect of isoflurane seen in mice breathing air. Mice breathing halothane in 8% oxygen exhibited a 21% increase in antipyrine plasma half-life and mice breathing enflurane in 8% oxygen, a 117% increase in antipyrine plasma half-life, although the changes were not markedly different from those seen in mice breathing air. Enflurane and isoflurane produced a significant increase in the volume of distribution for antipyrine in the mice breathing 8% oxygen. Total body clearance of antipyrine was decreased markedly in mice breathing isoflurane and enflurane but showed a lesser decrease in mice breathing halothane in 8% oxygen. In vitro in mouse microsomes, halothane, enflurane and isoflurane were all inhibitors of aminopyrine metabolism. Possible mechanisms for these results are discussed.


AF Ablation: Do You Need a Mapping System for Ablation?
Radiofrequency ablation has become a mainstay in the therapy for atrial fibrillation (AF). Although there are many different techniques for achieving adequate results, the cornerstone of AF remains pulmonary vein isolation. Three-dimensional (3D) electroanatomical mapping systems play an important role in the reduction of fluoroscopy and the identification of electrical and anatomic landmarks and are used commonly in AF ablation procedures. In this article, the authors discuss the advantages and limitations of 3D mapping systems and try to answer the question: Are they needed for successful AF ablation?


In-loop flow [11 C]CO2 fixation and radiosynthesis of N,N'-[11 C]dibenzylurea.
Cyclotron-produced carbon-11 is a highly valuable radionuclide for the production of positron emission tomography (PET) radiotracers. It is typically produced as relatively unreactive carbon-11 carbon dioxide ([11 C]CO2 ), which is most commonly converted into a more reactive precursor for synthesis of PET radiotracers. The development of [11 C]CO2 fixation methods has more recently enabled the direct radiolabelling of a diverse array of structures directly from [11 C]CO2 , and the advantages afforded by the use of a loop-based system used in 11 C-methylation and 11 C-carboxylation reactions inspired us to apply the [11 C]CO2 fixation "in-loop." In this work, we developed and investigated a new ethylene tetrafluoroethylene (ETFE) loop-based [11 C]CO2 fixation method, enabling the fast and efficient, direct-from-cyclotron, in-loop trapping of [11 C]CO2 using mixed DBU/amine solutions. An optimised protocol was integrated into a proof-of-concept in-loop flow radiosynthesis of N,N'-[11 C]dibenzylurea. This reaction exhibited an average 78% trapping efficiency and a crude radiochemical purity of 83% (determined by radio-HPLC), giving an overall nonisolated radiochemical yield of 72% (decay-corrected) within just 3 minutes from end of bombardment. This proof-of-concept reaction has demonstrated that efficient [11 C]CO2 fixation can be achieved in a low-volume (150 μL) ETFE loop and that this can be easily integrated into a rapid in-loop flow radiosynthesis of carbon-11-labelled products. This new in-loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for good manufacturing practice production) thereby contributing to the widespread usage of [11 C]CO2 trapping/fixation reactions for the production of PET radiotracers.


Psychometric characteristics and response times for one-best-answer questions in relation to number and source of options.
The research reported here investigated the impact of number and source of response options on the psychometric characteristics and response times for one-best-answer MCQs. Ninety sets of MCQs were used in two studies; numbers of options in base versions of items ranged from 11 to 25. For each set, a United States Medical Licensing Examination Step 2 item-writing committee selected the five options viewed as most appropriate. For 40 used sets, two NBME staff constructed five- and eight-option versions to maximize item discrimination. All versions of items were embedded unscored on 2003-04 Step 2 test forms. Versions of items with more options were harder and required more testing time; no differences in item discrimination were observed in either study, but previous versions of the items in extended matching format were more discriminating than those used in the study. Use of smaller numbers of options (and more items) results in more efficient use of testing time.


Filtering impacts of larval and sessile zebra mussels (Dreissena polymorpha) in western Lake Erie.
We assessed the feeding biology of veliger larvae of the introduced zebra mussel (Dreissena polymorpha Pallas) in laboratory experiments using inert microspheres as food analogues. Mean clearance rate on 2.87-μm beads ranged between 247 and 420 μL veliger-1 day-1. Clearance rate was unrelated to bead concentration up to 100 beads μL-1, but was positively correlated with veliger shell length. Clearance rates of Dreissena veligers are within the range of those reported for marine bivalve veligers of similar size and for herbivorous Great Lakes microzooplankton, but are orders of magnitude lower than those of settled, conspecific adults. The impact of settled zebra mussel grazing activities on phytoplankton stocks may be up to 1162 times greater than that exerted by veliger populations in western Lake Erie. Based on 1990 size-frequency distributions and associated literature-derived clearance rates, reef-associated Dreissena populations in western Lake Erie (mean depth ∼7 m) possess a tremendous potential to filter the water column (up to 132 m3 m-2 day-1) and redirect energy from pelagic to benthic foodwebs. Preliminary analyses indicate that chlorophyll a concentration is strongly depleted (<1 μg L-1) above Dreissena beds in western Lake Erie.


Three-dimensional ultrasonography for volume measurement of thyroid nodules in children.
The aim of this study was to compare the accuracy of thyroid nodule volume measurements performed by 2- and 3-dimensional ultrasonography and to evaluate the dependence of volume measurement results on nodule size and echographic characteristics. Results of multiple 2- and 3-dimensional ultrasonographic volume measurements of thyroid nodules in 102 children with different variants of thyroid nodular disease were reviewed retrospectively. The standardized difference, within-observer variability, and repeatability were estimated for both 2- and 3-dimensional ultrasonography. The mean age of the patients +/- SD in the examined group was 14.9 +/- 2.8 years; the mean volume of thyroid nodules was 0.78 +/- 0.13 mL. The SD of the normalized difference for 3-dimensional ultrasonography (2.8%) showed the clear superiority of its accuracy over 2-dimensional ultrasonography (15.9%; F test, P < .01). Intraobserver variability and repeatability for both examined methods had significant dependence on the nodule outline. For 2-dimensional ultrasonography, the intraobserver variability increased from 14.0% in nodules with a regular outline to 24.5% in those with an irregular outline (P < .001), and for 3-dimensional ultrasonography, it increased from 5.1% to 9.3% (P < .001). Intraobserver repeatability dropped from 85.4% in regular nodules to 74.6% in irregular nodules (P < .001) for 2-dimensional ultrasonography and from 94.7% to 90.4% (P < .001) for 3-dimensional ultrasonography. Volume measurements by 3-dimensional ultrasonography are more accurate, showing lower intraobserver variability and higher repeatability, than those made by 2-dimensional ultrasonography with less dependence on nodule size and echographic characteristics.


Muscarinic binding sites in a catecholaminergic human neuroblastoma cell line.
Tyrosine hydroxylase (TH) a characteristic enzyme activity for the catecholaminergic clonal cell line LA-N-1 and choline acetyltransferase (ChAT) a characteristic enzyme activity for the cholinergic clonal cell line LA-N-2 were previously shown to be increased in these cells exposed to 10(-5) M retinoic acid (RA) as differentiating agent. An investigation of the receptor characteristics suggests a complementarity between the two cell lines. The binding of QNB, a muscarinic ligand, was undetectable with the LA-N-2 cells but was present in the LA-N-1 cells and possessed a kD of 1.8 nM and 2.2 nM and a Bmax of 0.56 and 0.68 for control and RA grown cells respectively. There was a gradual increase in QNB binding to LA-N-1 cells from 2 days in vitro (DIV) until 6 DIV in both control and RA grown cells. An IC50 of 2.5 x 10(-8) M and 0.9 x 10(-8) M for atropine inhibition was obtained for the control and RA grown cells respectively. The corresponding values for carbachol inhibition were 7 x 10(-2) M and 3 x 10(-2) M respectively. The inhibition by the agonist oxotremorine is comparable to that of carbachol and 1 mM pilocarpine inhibited the binding by 21%. QNB binding showed a low affinity for pirenzepine and for AF-DX-116 but was inhibited with a rather high affinity by 4-DAMP (IC50:110 microM) thus suggesting the presence of an M3 receptor. Acetylcholine (100 microM) plus eserine (50 microM) and BW284c55 (1 microM), an acetylcholinesterase inhibitor, reduced the binding of QNB by approximately 25%.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of a 345 nm Femtosecond Laser for Corneal Surgery with Respect to Intraocular Radiation Hazard.
We report our findings from a preclinical safety study designed to assess potential side effects of corneal ultraviolet femtosecond laser treatment on lens and retina. Refractive lenticules (-5 dpt) with a diameter of 6 mm were created in the right cornea of eight Dutch Belted rabbits. Radiant exposure was 0.5 J/cm² in two animals and 18 J/cm² in six animals. The presence of lens opacities was assessed prior to and up to six months following laser application using Scheimpflug images (Pentacam, Oculus) and backscatter analysis (Opacity Lensmeter 702, Interzeag). Ganzfeld flash and flicker electroretinogram (ERG) recordings were obtained from both eyes prior to and up to six weeks following laser application. At the study endpoint, retinas were examined by light microscopy. Independent of energy dose applied, no cataract formation could be observed clinically or with either of the two objective methods used. No changes in ERG recordings over time and no difference between treated and untreated eye were detected. Histologically, retinal morphology was preserved and retinal pigment epithelium as well as photoreceptor inner and outer segments appeared undamaged. Quantitative digital image analysis did not reveal cell loss in inner or outer nuclear layers. Our analysis confirms theoretical considerations suggesting that ultraviolet femtosecond laser treatment of the cornea is safe for intraocular tissues. Transmitted light including stray light induces no photochemical effects in lens or retina at energy levels much higher than required for the clinical purpose. These conclusions cannot be applied to eyes with pre-existing retinal damage, as these may be more vulnerable to light.


Comparison between 1.5-T and 3.0-T MRI for the diagnosis of placenta accreta spectrum disorders.
Accurate antenatal diagnosis of placenta accreta spectrum (PAS) is important for optimal management. The purpose of this study was to compare the respective capabilities of 1.5-T and 3.0-T MRI in the diagnosis of PAS. Between March 2016-March 2021, 190 pregnant women at high risk for PAS underwent dedicated prenatal MRI with either 1.5-T or 3.0-T units at a tertiary imaging center. Cesarian section and MRI were performed less than 6 weeks from each other. Prospectively collected data were evaluated by two experienced genitourinary radiologists for presence and extent of PAS. A comparative study was designed to investigate differences in predictive ability between 1.5-T and 3.0-T MRI groups. Sensitivity, specificity, accuracy, negative and positive prognostic values relative to intraoperative/histological findings, were computed for both groups and were compared with chi-square (χ 2) test. Interobserver agreement was estimated using Kappa test. One hundred-eighty-two gravid women were included in the study; of these, 91/182 (50%) women were evaluated with 1.5-T (mean age, 35 ± 5.1 [SD] years; mean gestational age: 32.5 weeks) and 91/182 (50%) with 3.0-T MRI (mean age, 34.9 ± 4.9 [SD] years; mean gestational age, 32.1 weeks). 1.5-T MRI yielded 95.7% sensitivity (95% CI: 87.8-99.1) and 81.8% specificity (95% CI: 59.8) and 3.0-T MRI 93.8% sensitivity (95% CI: 86.0-97.9) and 83.3% specificity (95% CI: 48.2-97.7) for PAS identification, with no differences between the two groups (P = 0.725 and P >0.999, respectively). MRI showed excellent predictive ability for detecting extrauterine placental spread with 100% sensitivity (95% CI: 89.4-100.0), 96.7% specificity (95% CI: 88.1-99.6) for 1.5-T and 97% sensitivity (95% CI: 84.2-99.9), 96.7% specificity (95% CI: 88.1-99.6) for 3.0-T without differences between the two groups (P > 0.999). Interobserver agreement was excellent for both groups. The most frequently detected MRI signs of PAS for both 1.5-T and 3.0-T groups were placental heterogeneity (n = 85, 93.5% vs. n = 90, 98.9%; P = 0.413), and intraplacental fetal vessels (n = 64, 70.3% vs. n = 65, 71.4%; P = 0.870). This study suggests that 3.0-T MRI and 1.5-T MRI are equivalent for the diagnosis of PAS.


Circulating FGF18 is decreased in pleural mesothelioma but not correlated with disease prognosis.
Pleural mesothelioma (PM) is a relatively rare malignancy with limited treatment options and dismal prognosis. We have previously found elevated FGF18 expression in PM tissue specimens compared with normal mesothelium. The objective of the current study was to further explore the role of FGF18 in PM and evaluate its suitability as a circulating biomarker. FGF18 mRNA expression was analyzed by real-time PCR in cell lines and in silico in datasets from the Cancer Genome Atlas (TCGA). Cell lines overexpressing FGF18 were generated by retroviral transduction and cell behavior was investigated by clonogenic growth and transwell assays. Plasma was collected from 40 PM patients, six patients with pleural fibrosis, and 40 healthy controls. Circulating FGF18 was measured by ELISA and correlated to clinicopathological parameters. FGF18 showed high mRNA expression in PM and PM-derived cell lines. PM patients with high FGF18 mRNA expression showed a trend toward longer overall survival (OS) in the TCGA dataset. In PM cells with low endogenous FGF18 expression, forced overexpression of FGF18 resulted in reduced growth but increased migration. Surprisingly, despite the high FGF18 mRNA levels observed in PM, circulating FGF18 protein was significantly lower in PM patients and patients with pleural fibrosis than in healthy controls. No significant association of circulating FGF18 with OS or other disease parameters of PM patients was observed. FGF18 is not a prognostic biomarker in PM. Its role in PM tumor biology and the clinical significance of decreased plasma FGF18 in PM patients warrant further investigation.


A rare case of angiodysplasia: penetration of inguinal lymph nodes by large superficial leg veins. Report of five cases.
Five cases of veno-lymphatic angiodysplasia with penetration of one or several inguinal lymph nodes by the long saphenous vein, or one of its major branches, are reported. This malformation is usually detected during surgery for varicose veins with ligation of the long saphenous vein in the fossa ovalis. The significance of the anomaly is not clear, but in some cases it might be the reason for development of varicose veins.


Large-scale generation of autologous dendritic cells for immunotherapy in patients with acute myeloid leukemia.
Mononuclear cells (MNCs) of severely impaired acute myeloid leukemia (AML) patients may be collected by leukapheresis for large-scale generation of dendritic cells (AML-DCs) under good manufacturing practice (GMP) conditions for adoptive immunotherapy. In five end-stage AML patients, a leukapheresis procedure was performed with a cell separator (either COBE Spectra [Gambro BCT] or Amicus [Baxter]). For large-scale AML-DC generation, the MNCs of a single leukapheresis concentrate were isolated by density gradient and plated into a cell factory under GMP conditions. The AML-DCs were harvested on Day 8 of culture, and their viability, the mature morphology, and the phenotype were evaluated. The AML-DCs were injected subcutaneously into five AML patients up to four times at a biweekly interval. All AML patients entered the leukapheresis procedure with a highly pathologic blood count. In a mean separation time of 198 +/- 33 minutes, a mean of 1.3 +/- 0.2-fold the total blood volume was processed with a white blood cell (WBC) yield of 9 x 10(9) to 70 x 10(9) per collection dependent on the precollection WBC count. After density gradient a mean of 2.2 x 10(9) +/- 0.3 x 10(9) MNCs were plated into a cell factory. This resulted in a mean viable and mature DC yield of 0.01 x 10(9) of MNCs. The leukapheresis procedure is a feasible and safe procedure even in patients with hematologic malignancies and highly pathologic blood counts. Sufficient amounts of MNCs can be collected in leukopenic patients and the large-scale generation of AML-DCs in cell factories under GMP conditions yields in an adequate quantity of viable and mature AML-DCs.


Issues in physician contracting.
Dermatologists will enter into a number of different contracts during their professional careers. It is important that in each agreement they enter, dermatologists reap the benefits that they aspire for and understand the consequences of each provision. This article addresses just a few of the different issues that arise in physician contracting, such as choosing the appropriate form of business entity; the importance of a writing; term and termination of the contract; compensation models; benefits, vacation and other time off included in the contract; malpractice insurance; and restrictive covenants. Each provision should be carefully analyzed to ensure that it will protect the best interests of the dermatologist in that situation.


Nephropathy in asymptomatic patients with active Schistosoma mansoni infection.
In this study 240 patients with active Schistosoma mansoni infection with no symptoms suggestive of glomerular disease were subjected to investigation. All were evaluated clinically and their urine was examined for proteinuria. Out of the 240 patients 48 (20%) had proteinuria as detected by the dipstick test. All these patients were found to be free of any secondary cause other than schistosomiasis which could explain their proteinuria. Out of these 48 patients, 15 agreed to be subjected to kidney biopsy. When examined by light microscopy and immunofluorescent microscopy, kidney biopsies showed positive findings in 8 cases. These were mainly focal mesangial proliferation and immunofluorescent deposits which were mainly IgM and C3. We have concluded that early kidney lesions could be detected in 20% of this particular group of patients.


Hydrothermal conversion of urban food waste to chars for removal of textile dyes from contaminated waters.
Hydrothermal carbonization of urban food waste was carried out to prepare hydrochars for removal of Acridine Orange and Rhodamine 6G dyes from contaminated water. The chemical composition and microstructure properties of the synthesized hydrochars were investigated in details. Batch adsorption experiments revealed that hydrochars with lower degree of carbonization were more efficient in adsorption of dyes. Operational parameters such as pH and temperature had a strong influence on the dye uptake process. The adsorption equilibrium data showed excellent fit to the Langmuir isotherm. The pseudo-second-order kinetic model provided a better correlation for the experimental kinetic data in comparison to the pseudo-first-order kinetic model. Thermodynamic investigations suggested that dye adsorption onto hydrochars was spontaneous and endothermic. The mechanism of dye removal appears to be associated with physisorption. An artificial neural network (ANN)-based modelling was further carried out to predict the dye adsorption capacity of the hydrochars.


Training Primary Care Physicians to Employ Self-Efficacy-Enhancing Interviewing Techniques: Randomized Controlled Trial of a Standardized Patient Intervention.
Primary care providers (PCPs) have few tools for enhancing patient self-efficacy, a key mediator of myriad health-influencing behaviors. To examine whether brief standardized patient instructor (SPI)-delivered training increases PCPs' use of self-efficacy-enhancing interviewing techniques (SEE IT). Randomized controlled trial. Fifty-two family physicians and general internists from 12 primary care offices drawn from two health systems in Northern California. Experimental arm PCPs received training in the use of SEE IT training during three outpatient SPI visits scheduled over a 1-month period. Control arm PCPs received a single SPI visit, during which they viewed a diabetes treatment video. All intervention visits (experimental and control) were timed to last 20 min. SPIs portrayed patients struggling with self-care of depression and diabetes in the first 7 min, then delivered the appropriate intervention content during the remaining 13 min. The primary outcome was provider use of SEE IT (a count of ten behaviors), coded from three audio-recorded standardized patient visits at 1-3 months, again involving depression and diabetes self-care. Two five-point scales measured physician responses to training: Value (7 items: quality, helpfulness, understandability, relevance, feasibility, planned use, care impact), and Hassle (2 items: personal hassle, flow disruption). Pre-intervention, study PCPs used a mean of 0.7 behaviors/visit, with no significant between-arm difference (P = 0.23). Post-intervention, experimental arm PCPs used more of the behaviors than controls (mean 2.7 vs. 1.0 per visit; adjusted difference 1.7, 95 % CI 1.1-2.2; P < 0.001). Experimental arm PCPs had higher training Value scores than controls (mean difference 1.05, 95 % CI 0.68-1.42; P < 0.001), and similarly low Hassle scores. Primary care physicians receiving brief SPI-delivered training increased their use of SEE IT and found the training to be of value. Whether patients visiting SEE IT-trained physicians experience improved health behaviors and outcomes warrants study. CLINICALTRIALS. NCT01618552.


Acute relaxant effects of 17-beta-estradiol through non-genomic mechanisms in rabbit carotid artery.
Estrogens could play a cardiovascular protective role not only by means of systemic effects but also by means of direct effects on vascular structure and function. We have studied the acute effects and mechanisms of action of 17-beta-estradiol on vascular tone of rabbit isolated carotid artery. 17-Beta-estradiol (10, 30, and 100 microM) elicited concentration-dependent relaxation of 50 mM KCl-induced active tone in male and female rabbit carotid artery. The stereoisomer 17-alpha-estradiol showed lesser relaxant effects in male rabbits. Endothelium removal did not modify relaxation induced by 17-beta-estradiol. The NO synthase inhibitor L-NAME (100 microM) only reduced significantly relaxation produced by 30 microM 17-beta-estradiol. Relaxation was not modified by the estrogen receptor antagonist ICI 182,780 (1 microM), the protein synthesis inhibitor cycloheximide (1 microM), and the selective K(+) channel blockers charybdotoxin (0.1 microM) and glibenclamide (1 microM). CaCl(2) (30 microM -10 mM) induced concentration-dependent contraction in rabbit carotid artery depolarized by 50 mM KCl in Ca(2+) free medium. Preincubation with 17-beta-estradiol (3, 10, 30, or 100 microM) or the L-type Ca(2+) channel blocker nicardipine (0.01, 0.1, 1, or 10 nM) produced concentration-dependent inhibition of CaCl(2)-induced contraction. In conclusion, 17-beta-estradiol induces endothelium-independent relaxation of rabbit carotid artery, which is not mediated by classic estrogen receptor and protein synthesis activation. The relaxant effect is due to inhibition of extracellular Ca(2+) influx to vascular smooth muscle, but activation of K(+) efflux is not involved. Relatively high pharmacological concentrations of estrogen causing relaxation preclude acute vasoactive effects of plasma levels in the carotid circulation.


Vitamin C intake potentially lowers total cholesterol to improve endothelial function in diabetic patients at increased risk of cardiovascular disease: A systematic review of randomized controlled trials.
Vitamin C is one of the most consumed dietary compounds and contains abundant antioxidant properties that could be essential in improving metabolic function. Thus, the current systematic review analyzed evidence on the beneficial effects of vitamin C intake on cardiovascular disease (CVD)-related outcomes in patients with diabetes or metabolic syndrome. To identify relevant randomized control trials (RCTs), a systematic search was run using prominent search engines like PubMed and Google Scholar, from beginning up to March 2022. The modified Black and Downs checklist was used to assess the quality of evidence. Findings summarized in the current review favor the beneficial effects of vitamin C intake on improving basic metabolic parameters and lowering total cholesterol levels to reduce CVD-risk in subjects with type 2 diabetes or related metabolic diseases. Moreover, vitamin C intake could also reduce the predominant markers of inflammation and oxidative stress like C-reactive protein, interleukin-6, and malondialdehyde. Importantly, these positive outcomes were consistent with improved endothelial function or increased blood flow in these subjects. Predominantly effective doses were 1,000 mg/daily for 4 weeks up to 12 months. The included RCTs presented with the high quality of evidence. Clinical evidence on the beneficial effects of vitamin C intake or its impact on improving prominent markers of inflammation and oxidative stress in patients with diabetes is still limited. Thus, more RCTs are required to solidify these findings, which is essential to better manage diabetic patients at increased risk of developing CVD.


Correction with blood T1 is essential when measuring post-contrast myocardial T1 value in patients with acute myocardial infarction.
Post-contrast T1 mapping by modified Look-Locker inversion recovery (MOLLI) sequence has been introduced as a promising means to assess an expansion of the extra-cellular space. However, T1 value in the myocardium can be affected by scanning time after bolus contrast injection. In this study, we investigated the changes of the T1 values according to multiple slicing over scanning time at 15 minutes after contrast injection and usefulness of blood T1 correction. Eighteen reperfused acute myocardial infarction (AMI) patients, 13 cardiomyopathy patients and 8 healthy volunteers underwent cardiovascular magnetic resonance with 15 minute-post contrast MOLLI to generate T1 maps. In 10 cardiomyopathy cases, pre- and post-contrast MOLLI techniques were performed to generate extracellular volume fraction (Ve). Six slices of T1 maps according to the left ventricular (LV) short axis, from apex to base, were consecutively obtained. Each T1 value was measured in the whole myocardium, infarcted myocardium, non-infarcted myocardium and LV blood cavity. The mean T1 value of infarcted myocardium was significantly lower than that of non-infarcted myocardium (425.4 ± 68.1 ms vs. 540.5 ± 88.0 ms, respectively, p < 0.001). T1 values of non-infarcted myocardium increased significantly from apex to base (from 523.1 ± 99.5 ms to 561.1 ± 81.1 ms, p = 0.001), and were accompanied by a similar increase in blood T1 value in LV cavity (from 442.1 ± 120.7 ms to 456.8 ± 97.5 ms, p < 0.001) over time. This phenomenon was applied to both left anterior descending (LAD) territory (from 545.1 ± 74.5 ms to 575.7 ± 84.0 ms, p < 0.001) and non-LAD territory AMI cases (from 501.2 ± 124.5 ms to 549.5 ± 81.3 ms, p < 0.001). It was similarly applied to cardiomyopathy patients and healthy volunteers. After the myocardial T1 values, however, were adjusted by the blood T1 values, they were consistent throughout the slices from apex to base (from 1.17 ± 0.18 to 1.25 ± 0.13, p > 0.05). The Ve did not show significant differences from apical to basal slices. Post-contrast myocardial T1 corrected by blood T1 or Ve, provide more stable measurement of degree of fibrosis in non-infarcted myocardium in short- axis multiple slicing.


Schematic modelling of peripheral astigmatism in real eyes.
A method is described whereby any schematic eye possessing a two-surfaced, monoindicial lens can be manipulated to yield the same amounts of peripheral astigmatism as found in real eyes. Its optical performance is discussed and it is demonstrated that schematic eyes of this type cannot simultaneously yield the amounts of peripheral astigmatism and spherical aberration that are observed in real eyes.


Identification of tubulin drug binding sites and prediction of relative differences in binding affinities to tubulin isotypes using digital signal processing.
Microtubules are involved in numerous cellular processes including chromosome segregation during mitosis and, as a result, their constituent protein, tubulin, has become a successful target of several chemotherapeutic drugs. In general, these drugs bind indiscriminately to tubulin within both cancerous and healthy cells, resulting in unwanted side effects. However, differences between beta-tubulin isotypes expressed in a wide range of cell types may aid in the development of anti-tubulin drugs having increased specificity for only certain types of cells. Here, we describe a digital signal processing (DSP) method that is capable of predicting hot spots for the tubulin family of proteins as well as determining relative differences in binding affinities to these hot spots based only on the primary sequence of 10 human tubulin isotypes. Due to the fact that several drug binding sites have already been characterized within beta-tubulin, we are able to correlate hot spots with the binding sites for known chemotherapy drugs. We have also verified the accuracy of this method using the correlation between the binding affinities of characterized drugs and the tubulin isotypes. Additionally, the DSP method enables the rapid estimation of relative differences in binding affinities within the binding sites of tubulin isotypes that are yet to be experimentally determined.


Evaluation of glycemic control of type II diabetes mellitus treated only with diet.
Assays of HbA1c, after few years or months from the registration of new diagnosed type II diabetes mellitus, provide interesting information about the balance of glycaemic control. In a very high percentage, the value of HbAlc needs to be treated. It is imperative to introduce a new program in treating more aggressively the diabetes from the beginning, to reach the target and maintain the glycaemic control at this level for as long time as possible.


Impact of intracellular beta-amyloid in transgenic animals and cell models.
The present commentary based on cell and animal models of intracellular beta-amyloid (iAbeta) expression indicates that low levels of microscopically undetectable iAbeta could have a physiological role in the modulation of the cyclic AMP response element (CRE)-dependent gene expression and, as a consequence, a positive influence on synaptic plasticity (the 'good' Abeta?). On the other hand, high levels of iAbeta resembling the pathological and microscopically visible accumulation of this amyloid peptide, akin to that observed in Down syndrome and Alzheimer's disease, disrupt CRE-regulated gene expression, therefore compromising the protein synthesis-dependent component of long-term potentiation (the 'bad' Abeta?). Moreover, intracellular pathology would be independent and additive to the toxic effects of the extracellular Abeta burden.


MicroRNA-144 relieves chronic constriction injury-induced neuropathic pain via targeting RASA1.
MicroRNAs (miRNAs) have been shown to participate in development of neuropathic pain. However, the role of microRNA-144 (miR-144) in neuropathic pain remains unclear. In the present study, we established a neuropathic pain mouse model via chronic constriction injury (CCI)-induction. The successful establishment of this model was confirmed via evaluation of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). By using this model, we found that miR-144 was significantly downregulated in CCI-induced neuropathic pain mice. In addition, intrathecal injection of miR-144 agomiR alleviated mechanical and thermal hyperalgesia in neuropathic pain mice as shown by the increased of PWT and PWL. Moreover, miR-144 negatively regulated neuroinflammation by decreasing the expression of proinflammatory mediators, including TNF-α (tumor necrosis factor-α), IL (interleukin)-1β, and IL-6, thus facilitating the inhibition of neuropathic pain development. Mechanistically, RASA1 (RAS P21 Protein Activator 1) was downregulated following the injection of agomiR-144, and was verified to be a target of miR-144. Furthermore, overexpression of RASA1 reversed the inhibitory effect of miR-144 on neuropathic pain. Therefore, the present study suggested that miR-144 has the potential to be explored as therapeutic target for treatment of neuropathic pain.


A rapid method of screening for N-acetyltransferase (NAT2) phenotype by use of the WAVE DNA fragment analysis system.
N-Acetyltransferase 2 (NAT2) is involved in Phase II biotransformation of a variety of toxicants. Polymorphisms in the NAT2 gene result in a slow acetylator phenotype, which has been associated with various cancers and neurodegenerative diseases. To date most studies investigating NAT2 genotype/phenotype have adopted an RFLP approach, which is both expensive and time-consuming. Using the Wave DNA fragment analysis system, we have developed a fast and robust method of identifying two polymorphisms (C282T and T341C) of the NAT2 gene which allows identification of the most common slow acetylator alleles found in Caucasian populations: NAT2*5, NAT2*6, NAT2*7, and NAT2*14. This was done by comparing phenotype status in 126 samples genotyped by RFLP analysis and also by Wave analysis for the polymorphisms C282Tand T341C. All 126 samples analyzed by both RFLP and Wave analysis gave consistent phenotype results and 100% correlation was achieved between the two methods.


Expression of autophagy and UPR genes in the developing brain during ethanol-sensitive and resistant periods.
Fetal alcohol spectrum disorders (FASD) results from ethanol exposure to the developing fetus and is the leading cause of mental retardation. FASD is associated with a broad range of neurobehavioral deficits which may be mediated by ethanol-induced neurodegeneration in the developing brain. An immature brain is more susceptible to ethanol neurotoxicity. We hypothesize that the enhanced sensitivity of the immature brain to ethanol is due to a limited capacity to alleviate cellular stress. Using a third trimester equivalent mouse model of ethanol exposure, we demonstrated that subcutaneous injection of ethanol induced a wide-spread neuroapoptosis in postnatal day 4 (PD4) C57BL/6 mice, but had little effect on the brain of PD12 mice. We analyzed the expression profile of genes regulating apoptosis, and the pathways of ER stress response (also known as unfolded protein response, UPR) and autophagy during these ethanol-sensitive and resistant periods (PD4 versus PD12) using PCR microarray. The expression of pro-apoptotic genes, such as caspase-3, was much higher on PD4 than PD12; in contrast, the expression of genes that regulate UPR and autophagy, such as atf6, atg4, atg9, atg10, beclin1, bnip3, cebpb, ctsb, ctsd, ctss, grp78, ire1α, lamp, lc3 perk, pik3c3, and sqstm1 was significantly higher on PD12 than PD4. These results suggest that the vulnerability of the immature brain to ethanol could result from high expression of pro-apoptotic proteins and a deficiency in the stress responsive system, such as UPR and autophagy.


Suspected extracolonic neoplasms detected on CT colonography: literature review and possible outcomes.
This study summarizes the literature on the detection of cancer among indeterminate extracolonic findings on computed tomographic (CT) colonography in five targeted organs. We searched PubMed for English-language literature published between January 1, 1994, and December 31, 2010. We describe extracolonic findings in the kidney, lung, liver, pancreas, and ovary suspect for malignancy as they are associated with high mortality. For each organ, we calculated the median prevalence, positive predictive value (PPV), and false positive rate of malignancy and a pooled false-positive rate across studies. Of 91 publications initially identified, 24 were eligible for review. Indeterminate renal masses on CT colonography had 20.5% median PPV and low pooled false positive rate of 1.3% (95% confidence interval 0.6-2.0). In contrast, indeterminate masses of the lung, liver, pancreas, and ovary had low PPV (median values ranged from 0% to 3.8%). Indeterminate masses of the ovary resulted in the highest pooled false-positive rate of 2.2%. Results were similar in studies of both screening and nonscreening populations. We estimated the probability of false positive results through the detection of significant extracolonic findings as 46 per 1000 for men and 68 per 1000 for women. Indeterminate renal masses newly detected on CT colonography have an estimated one in five chance of malignancy and therefore warrant further follow-up to provide a definitive diagnosis. Conversely, indeterminate masses of the lung, liver, pancreas, and ovary are associated with high false positive rates and merit more conservative clinical follow-up.


Invited review: Total solids concentration in milk or milk replacer for dairy calves.
Restricting milk or milk replacer (MR) fed to dairy calves to 10% of body weight at 12.5% total solids (TS) concentration is a common feeding strategy that promotes early weaning and lowers total feed costs for raising young calves. However, this strategy has been associated with inferior performance and compromised welfare. Because a restricted liquid nutrition plan limits calf growth due to limited supply of nutrients, research on increased supply of nutrients from liquid has shown improved growth, health, and welfare of calves. Nutrient supply may be increased by feeding larger amounts of milk or MR averaging 12.5% TS, or by increasing TS above the usual 12.5% TS by increasing MR TS concentration alone (TS+), or by increasing TS concentration and volume simultaneously (TSV+). The objective of this review is to discuss liquid nutrition plans with greater TS concentration in MR or in milk diets, considering the effects of such strategies on performance and digestive tract development before weaning and the future performance of dairy calves. This review will focus on liquid nutrition plans that are based on increased TS concentration (i.e., TS+ or TSV+); therefore, enhanced liquid nutrition plans based only on increased volumes will not be the discussed. Improved growth rates have been observed in calves fed TSV+ programs. However, reduced starter intake preweaning can also have negative effects on dry matter intake, average daily gain, and digestibility postweaning. Feeding a TS+ program may reduce impairment of starter intake and therefore have positive effects on performance, nutrient digestibility, and health. When considering an accelerated nutrition plan with TS+ or TSV+, it is important to consider osmolality of the liquid diet. Further studies are necessary to confirm this hypothesis and the cost-benefit of alternative liquid nutrition plans, as well as the optimal TS concentration of milk or MR fed to dairy calves.


Differential expression of the 5-HT(3A) and 5-HT(3B) receptor in differentiated NG108-15 cells.
Previous work from this laboratory has shown that the serotonin (5-HT) induced response is significantly augmented in differentiated NG108-15 (NG) cells treated with dibutyryl cAMP (Bt(2)cAMP) due to qualitative and quantitative changes in the expression of the 5-HT(3) receptor as demonstrated by specific [(3)H] LY-278584 (a selective 5HT(3) receptor antagonist) binding. In this study, we investigated whether there is any change in the relative expression of the 5-HT(3A) and 5-HT(3B) subunits in NG cells differentiated following Bt(2)cAMP treatment cells. The major findings of this study were that the relative amount of 5-HT(3B) subunit mRNA in Bt(2)cAMP-treated NG cells 5 days following Bt(2)cAMP-treatment was greater than that in the untreated cells. In contrast, the relative expression of the 5-HT(3B) subunit protein in the Bt(2)cAMP-treated NG cells was much less than in the untreated cells, but the relative expression of the 5-HT(3A) subunit in the Bt(2)cAMP-treated NG cells was similar to the untreated cells. Therefore, no relationship between mRNA and protein expression for 5-HT(3A) and 5-HT(3B) subunits in Bt(2)cAMP treated and untreated NG cells were observed. It was also found that fluorescent intensity for the 5-HT(3B) subunit in the cell body of the Bt(2)cAMP treated and untreated NG cells gradually decreased from the day 1-5 after Bt(2)cAMP treatment. However, in specific areas such as the varicosity and nerve endings of the Bt(2)cAMP treated cells, staining intensity for the 5-HT(3B) subunits was stronger than in the untreated cells at the all time points, peaking at day 5 post-treatment. These results suggest that the augmented response induced by 5-HT acting via 5-HT(3) receptors in differentiated NG cells may be due to changes in the relative amount of the 5-HT(3B) subunit, particularly the ratio and distribution of the 5-HT(3A) to (3B) subunits.


Stimulation with phytohaemagglutinin induces the synthesis of catecholamines in human peripheral blood mononuclear cells: role of protein kinase C and contribution of intracellular calcium.
Although it is now established that immunocompetent cells produce catecholamines (CA), which in turn may act as autocrine/paracrine mediators, little is known about the mechanisms regulating CA production in these cells. In the present study, evidence is provided that stimulation of human cultured peripheral blood mononuclear cells (PBMCs) with phytohaemagglutinin (PHA) induces the expression of tyrosine hydroxylase (TH) mRNA and subsequently increases intracellular CA levels through protein kinase C (PKC) activation and the contribution of intracellular Ca(++)-dependent mechanisms. Increased production of CA in PHA-stimulated PBMCs suggests a preferential involvement of catecholaminergic pathways in the functional modulation of activated cells. These findings may help to better define the role of immunocompetent cell-derived CA in the neuroimmune network.


Research Progress and Perspective on Lithium/Sodium Metal Anodes for Next-Generation Rechargeable Batteries.
With the development of consumer electronic devices and electric vehicles, lithium-ion batteries (LIBs) are vital components for high energy storage with great impact on our modern life. However, LIBs still cannot meet all the essential demands of rapidly growing new industries. In pursuance of higher energy requirement, metal batteries (MBs) are the next-generation high-energy-density devices. Li/Na metals are considered as an ideal anode for high-energy batteries due to extremely high theoretical specific capacity (3860 and 1165 mAh g-1 for Li and Na, respectively) and low electrochemical potential (-3.04 V for Li and -2.71 V for Na vs. standard hydrogen electrode). Unfortunately, uncontrolled dendrite growth, high reactivity, and infinite volume change induce severe safety concerns and poor cycle efficiency during their application. Consequently, MBs are far from commercialization stage. This Review represents a comprehensive overview of failure mechanism of lithium/sodium metal anode and its progress for rechargeable batteries through (i) electrolyte optimization, (ii) artificial solid-electrolyte interphase (SEI) layer formation, and (iii) nanoengineering at materials level in current collector, anode, and host. The challenges in current MBs research and potential applications of lithium/sodium metal anodes are also outlined and summarized.


Coagulation disorders in patients with cirrhosis and severe sepsis.
In patients with cirrhosis, severe sepsis may stimulate the extrinsic coagulation pathway resulting in thrombin generation and fibrin formation. To compare 23 patients with severe sepsis to 13 infected patients without severe sepsis and 18 patients without infection. Zymogen forms of clotting factors involved in the extrinsic pathway (i.e., factors VII + X, V, prothrombin), and the presence of soluble fibrin were assessed. Zymogen forms of clotting factors were significantly lower, while Child-Pugh score and the proportion of patients with soluble fibrin were higher in the severe-sepsis group than in the other groups. Decreased zymogen levels were independently correlated with an elevated Child-Pugh score and the presence of severe sepsis. In the severe-sepsis group, after adjustment for the severity of cirrhosis, decreased zymogen levels were associated with significant increases in the relative risk ratios of in-hospital death. Cirrhotic patients with severe sepsis have decreased blood levels of zymogen forms of factors VII+X, V, and prothrombin, which may be due not only to the severity of cirrhosis but also, at least in part, to the consumption of these zymogens by the extrinsic coagulation pathway.


Radionuclide renography to evaluate urodynamically expected upper tract obstruction in patients with meningomyelocele.
Radionuclide renography showed an obstructed pattern in 6 patients with meningomyelocele without dilatation of the upper urinary tract or reflux when the bladder was filled to the volume that during previous urodynamic testing had resulted in an intravesical pressure of 40 cm. water but not when these patients were studied with an empty bladder. Therefore, this study indicates that treatment should be directed at avoiding long-standing intravesical pressure exceeding 40 cm. water in patients with meningomyelocele.


Parasites and pregnancy: the problems of malaria and toxoplasmosis.
Infections caused by parasites are common and not limited to the developing world. The spectrum of interactions between pregnancy and parasite infection ranges from minor discomfort to fetal death and are well illustrated by the problems of toxoplasmosis and malaria.


Sleep-Disordered Breathing and Free Fatty Acid Metabolism.
Sleep-disordered breathing (SDB) is independently associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. However, data on whether SDB alters the metabolism of free fatty acids (FFAs) are lacking. The primary objective of the current study was to characterize alterations in FFA metabolism across the spectrum of SDB severity. The study sample included 118 participants with and without SDB who underwent full-montage polysomnography, the frequently sampled IV glucose tolerance test (FSIGTT), and body composition measurements including determination of percent body fat. Parameters of lipolysis suppression, time to FFA nadir, and FFA rebound after an IV glucose challenge were derived using a mathematical model. Multivariable regression analyses were used to characterize the independent associations between SDB severity and parameters of FFA metabolism. SDB severity, as assessed by the apnea-hypopnea index, was associated with adipocyte insulin resistance, a decrease in the glucose- and insulin-mediated suppression of lipolysis, a longer duration to reach a nadir in FFA levels during the FSIGTT, and a sluggish rebound in FFA levels after suppression. Severity of SDB-related hypoxemia was independently associated with adipocyte insulin resistance and the time to reach the FFA nadir during the FSIGTT. Finally, a higher percentage of stage N3 sleep was positively associated with greater suppression of lipolysis and a faster rebound in the FFA levels during the FSIGTT. Independent of adiposity, SDB is associated with impairments in FFA metabolism, which may contribute to the development of glucose intolerance and type 2 diabetes in SDB.


The impact of touch-tone data entry on reports of HIV and STD risk behaviors in telephone interviews.
Respondents concerns about privacy can decrease reporting of HIV and STD risk behaviors in general population telephone surveys. The purpose of this paper is to describe the results of an experimental study evaluating whether one method for increasing privacy, touch-tone data entry (TTDE), is effective in increasing estimates of sexual behaviors from a population-based survey. We conducted a random-digit-dial telephone survey of adults in New Jersey (n = 405), with half the respondents using TTDE for answering sexual behavior questions. TTDE led to increased reports of same-sex sexual behavior, certain HIV and STD risk factors, and concern about one s risk for HIV and STD transmission. TTDE also narrowed the difference between men s and women s reports of the number of different sexual partners over the past 10 years. The feasibility and limitations of TTDE are discussed, as well as possible alternative interpretations that consider the impact of TTDE on the dynamics of the interaction between the respondent and the interviewer.


The more the merrier: how homo-oligomerization alters the interactome and function of ribonucleotide reductase.
Stereotyped as a nexus of dNTP synthesis, the dual-subunit enzyme - ribonucleotide reductase (RNR) - is coming into view as a paradigm of oligomerization and moonlighting behavior. In the present issue of 'omics', we discuss what makes the larger subunit of this enzyme (RNR-α) so interesting, highlighting its emerging cellular interactome based on its unique oligomeric dynamism that dictates its compartment-specific occupations. Linking the history of the field with the multivariable nature of this exceedingly sophisticated enzyme, we further discuss implications of new data pertaining to DNA-damage response, S-phase checkpoints, and ultimately tumor suppression. We hereby hope to provide ideas for those interested in these fields and exemplify conceptual frameworks and tools that are useful to study RNR's broader roles in biology.


Report on 4 cases with decreased recovery due to neutralizing antibodies specific for PEGylated recombinant factor VIII.
The immunogenicity, safety, and efficacy of recombinant factor VIII (rFVIII) have gained increasing interest after the introduction of extended half-life products with various modifications of the rFVIII molecule, such as covalent attachment of polyethylene glycol (PEG). Anti-PEG antibodies may be associated with a temporary reduction of FVIII recovery, but according to previous studies, they usually disappear after continuous dosing. Anti-PEG antibodies with an inhibitory capacity have never been demonstrated in patients treated with PEGylated rFVIII products. To routinely switch from standard half-life to PEGylated extended half-life rFVIII products in patients with hemophilia A. From December 2022 until May 2023, 83 adults with hemophilia A attending Oslo Haemophilia Comprehensive Care Centre received a test dose with a PEGylated rFVIII product to switch treatment. Four patients presented with decreased recovery without the presence of an FVIII inhibitor. Accordingly, we performed a variant inhibitor test utilizing different rFVIII concentrates as a source of FVIII and enzyme-linked immunosorbent assay to search for anti-PEG antibodies. We found inhibitory anti-PEG/anti-PEGylated rFVIII antibodies in 4 patients (5%), both persistent and transient, explaining the impaired recovery. The patients had neutralizing anti-PEG antibodies prior to the first dosing of PEGylated rFVIII. We demonstrated neutralizing antibodies (mainly immunoglobuline G) specific for PEG and all 3 commercially available PEGylated rFVIII products. The number of patients with inhibitory anti-PEG antibodies was significant, and the presence of inhibitors against PEGylated rFVIII emphasizes the importance of individual monitoring when switching FVIII concentrates to ensure safety and efficacy of the treatment.


Post-inflammatory Polyp Burden as a Prognostic Marker of Disease-outcome in Patients with Inflammatory Bowel Disease.
Post-inflammatory polyps [PIPs] are considered as indicators of previous episodes of severe inflammation and mucosal ulceration. Inflammatory bowel disease [IBD], namely Crohn's disease [CD] and ulcerative colitis [UC], exhibit a perpetuating, relapsing and remitting pattern, and PIPs are a frequent sequela of chronicity. The aim of this study was to determine whether a high PIP burden is associated with a more severe disease course in patients with IBD. This was a multinational, multicentre, retrospective study. IBD patients previously diagnosed with PIPs were retrieved from the endoscopic database of each centre. PIP burden was evaluated and associated with demographic and clinical data as well as factors indicating a more unfavourable disease course. A total of 504 IBD patients with PIPs were recruited [male: 61.9%]. The mean age at IBD diagnosis was 36.9 [±16.8] years. Most patients [74.8%] were diagnosed with UC. A high PIP burden was present in 53.4% of patients. On multivariable Cox regression analysis, a high PIP burden was independently associated with treatment escalation (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.04-1.75; p = 0.024), hospitalization [HR 1.90; 95% CI 1.24-2.90; p = 0.003], need for surgery [HR 2.28; 95% CI 1.17-4.44, p = 0.02] and younger age at diagnosis [HR 0.99, 95% CI 0.98-0.99; p = 0.003]. PIP burden was associated with a more severe outcome. Future prospective studies should focus on the characterization of PIP burden as to further risk stratify this patient cohort.


Accuracy and reproducibility of biometry using partial coherence interferometry.
To determine whether partial coherence interferometry is comparable to standard contact ultrasonic biometry in accuracy, reproducibility, and ease of use. Academic university practice. In this prospective study, simultaneous biometry was performed in 91 consecutive patients (111 eyes) using partial coherence interferometry (IOLMaster, Zeiss Humphrey Systems) and ultrasonic biometry (I(3), Innovative Imaging, Inc.). The differences between the predicted spherical equivalent in diopters (D) and the actual results with both techniques were compared. The IOLMaster was significantly better in the mean absolute error (0.533 D +/- 0.589 [SD] versus 0.757 +/- 0.723 D; P = .012) and the percentage of eyes within +/-0.5 D (61.2% versus 42.3%; P = .003) and +/-1.0 D (87.4% versus 77.5%; P =.05) of the predicted refraction. The IOLMaster was more accurate and reproducible than the contact ultrasonographic technique.


Spontaneous Spinal Epidural Hematoma: A Surgical Case Series of Ten Patients.
Spontaneous spinal epidural hematoma (SS-EDH) is a rare neurosurgical emergency. Little is known about predictive factors of outcome in patients with SS-EDH. Here, we present a case series of patients operated on for an SS-EDH. We reviewed all cases of patients operated on for an SS-EDH between January 2009 and February 2016 in a large academic neurosurgical center. We recorded preadmission functional status, bleeding characteristics, and postsurgery outcome. Good outcome was defined, according to the Nurick score, as at least being able to walk in a way that did not prevent employment. Mean follow-up time was 19 months (standard deviation, 25 months). Ten patients, with a mean age of 70 years (standard deviation, 10), with SS-EDH were included. The location of SS-EDH was binomially distributed, with the highest frequencies in the upper thoracic region (Th3-5) and middle to low cervical region (C4-6). Five patients had a poor outcome. Of these, 3 remained chair bound or bedridden. No statistically significant association could be found between preoperative characteristics and outcome, but patients with poor preoperative motor function, thoracic hematoma, and more than 4 involved segments had a high rate of poor neurologic outcome. We could not establish any association between time delay from symptom onset to surgery and outcome. In our series, half of the patients with SS-EDH recovered well after surgery. Although no statistically significant association could be established, hematoma location, size, and preoperative motor function seem to be some of the most important predictive factors of postoperative recovery.


Pregnancy after kidney transplantation: graft, mother, and newborn complications.
An important benefit associated with kidney transplantation (KT) in women of childbearing age is increased fertility. We retrospectively evaluated the complications associated with 24 pregnancies among our KT over 28 years. In particular, we examined the evolution of serum creatinine as well as maternal and fetal complications. To assess the impact on graft survival, our control group included women without pregnancy who were matched for age at KT, year of KT, and follow-up time. Most women (79.2%) were primiparous. All were prescribed a calcineurin inhibitor, which in 75% of the cases was cyclosporine. Overall, 45.8% had prior hypertension, only one of whom remained on the previous antihypertensive regimen. The drugs most often used were nifedipine and methyldopa. The median age at time of KT was 24.16 (interquartile range [IQR] 21.33 to 29.72) years and at delivery, 28.39 (IQR 25.59 to 33.88) years. The average interval between KT and delivery was 4.5 ± 2.7 years (range, 1 to 10 years). Maternal complications were anemia (n = 16), graft pyelonephritis (n = 6), preeclampsia (n = 6), de novo proteinuria > 1 g/d (n = 3), or gestational diabetes mellitus (n = 2). There was no acute rejection episode or opportunistic infection. The fetal complications included delayed intrauterine growth (n = 8), preterm deliveries (n = 13), or congenital enzymatic deficit (n = 1). One case was a twin pregnancy. The average gestational age was 35.2 ± 3 weeks, and the mean birth weight 2318.2 ± 597.1 grams. In 16 pregnancies, deliveries were performed by caesarean section. The median serum creatinine at 1 month before conception was 1.20 (IQR 0.97 to 1.37) mg/dL and at 1 year after delivery it had tended to increase to 1 to 20 (IQR 1.03 to 1.50) mg/dL. Death-censored graft survival did not differ from the control group. In conclusion, pregnancy after KT may be associated with serious maternal and fetal complications. We did not observe an increased risk of graft loss.


Examining the effect of cue exposure and introspective responses to cues on impulsivity in restrained and unrestrained eaters.
The current study extends cue-reactivity research by evaluating impulsive valuation as an outcome of exposure to food cues. This study also separates introspection after viewing cues (e.g., responding to questions about craving and affect) from mere cue exposure, to examine if introspection changes self-regulation behaviors in response to food cues. Finally, we compared restrained and unrestrained eaters to ascertain the influence of motivation toward food on how cue-reactivity influences impulsive behavior. In the current study, restrained and unrestrained eaters were randomly assigned to view food or neutral cues and were randomized to respond to cues with either craving and affect questions (e.g., introspection) or filler questions. Following cue exposure, participants completed a purchase task as a measure of impulsive lack of self-control. Results revealed that unrestrained eaters who introspected on craving and affect showed decreased impulsive behavior, whereas restrained eaters who introspected on craving and affect showed increased impulsive behavior. Although there was no effect of food cues on impulsive behavior, the interaction of introspective response and restraint status suggests that attending to craving and affect has differential effects on subsequent self-control behavior for restrained and unrestrained eaters. Implications for further cue-reactivity work and treatment of chronic dieters (i.e., restrained eaters) will be discussed.


The impact of severe depression on the survival of older patients with end-stage kidney disease.
Incidence of depression increases in patients with end-stage kidney disease (ESKD). We evaluated the association between depression and mortality among older patients with ESKD, which has not been studied previously. This nationwide prospective cohort study included 487 patients with ESKD aged >65 years, who were categorized into minimal, mild-to-moderate, and severe depression groups based on their Beck Depression Inventory-II (BDI-II) scores. Predisposing factors for high BDI-II scores and the association between the scores and survival were analyzed. The severe depression group showed a higher modified Charlson comorbidity index value and lower serum albumin, phosphate, and uric acid levels than the other depression groups. The Kaplan-Meier curve revealed a significantly lower survival in the severe depression group than in the minimal and mild-to-moderate depression groups (p = 0.011). Multivariate Cox regression analysis confirmed that severe depression was an independent risk factor for mortality in the study cohort (hazard ratio, 1.39; 95% confidence interval, 1.01-1.91; p = 0.041). Additionally, BDI-II scores were associated with modified Charlson comorbidity index (p = 0.009) and serum albumin level (p = 0.004) in multivariate linear regression. Among the three depressive symptoms, higher somatic symptom scores were associated with increased mortality. Severe depression among older patients with ESKD increases mortality compared with minimal or mild-to-moderate depression, and patients with concomitant somatic symptoms require careful management of their comorbidities and nutritional status.


[Acute pancreatitis during "diabetic lipemia": unusual disclosure of insulin-dependent diabetes (author's transl)].
A case of diabetic lipemia is reported in a 27 year-old man admitted for acute pancreatitis. Initial investigations revealed gross hyperlipoproteinemia and ketoacidosis. Hyperlipoproteinemia was progressively corrected up to normalization in four weeks under insulin-therapy; the metabolic control of diabetes was obtained in parellel. This feature is caracteristic of "diabetic lipemia". The following sequence could be suggested: onset of diabetes, occurence of diabetic lipemia and then acute pancreatitis.


Strength-fracture toughness synergy strategy in ostrich tibia's compact bone: Hierarchical and gradient.
Ostriches are the fastest bipeds in the world, but their tibias are very thin. How the thin tibia can withstand the huge momentum impacts of the heavy body during running? The present work revealed that the combination of hierarchical and gradient design strategies was the main reason for their high strength and fracture toughness. The microstructure of ostrich's tibias compact bone was self-assembled into the 6-level hierarchical structure from the hydroxyapatite (HAP) crystals, collagen fiber (sub-nano), mineralized collagen fiber (nano-), mineralized collagen fiber bundle (sub-micro), lamellae (micro-) and osteon (macro-scales). The most distinctive design in the ostrich compact bone was that the HAP crystals were embedded in collagen fibers as well as wrapped in the outer layer of mineral collagen fibers (MCFs) in the form of HAP nanocrystals, thus achieving a high degree of soft and hard combination from the nanoscale. The bending strength was gradient-structure dependent and up to 787.2 ± 40.5 MPa, 4 times that of a human's compact bone. The fracture toughness (KJc) is 5.8 ± 0.1 MPa m1/2. Several toughening mechanisms, such as crack deflection/twist, bridging, HAP fibers pulling-out, and fracture of the MCF bundles were found in the compact bone.


Identifying the Mental Health Profiles of Black Adolescents Who Experience School Policing and School Discipline: A Person-Centered Approach.
Educational environments that are structured by race perpetuate poor mental health for Black adolescents. This empirical relationship is pronounced when it is examined through Racial Battle Fatigue theory, which provides a framework that links educational environments and poor psychological health of Black students. School police have a major effect on Black adolescents' educational and health experiences and trajectories. The purpose of this person-centered study was to assess the risk of Black students' depressive symptoms who were stopped by school police, saw other students stopped by school police, or experienced school discipline. Data on Black student youths from the Fragile Families Study Year 15 wave (N = 1,601) were used to conduct a latent class analysis to identify subgroups of school policing (ie, being stopped by school police, seeing other students stopped by school police) and school discipline on the distal outcome of depressive symptoms. Covariates included demographic and school attachment. We identified 4 distinct Black student subgroups: (1) unscathed [no school policing or discipline reported]; (2) school disciplined; (3) combined school policing; and (4) school policed [arrested by police]. Each subgroup had an incremental increase in mean depressive symptom scores. Compared to the unscathed subgroup, each subgroup also had lower school attachment. This study disrupts the notion that education environments are a social determinant of health and a great equalizer. This study critically exposes how educational institutions complicit with school policing are associated with racism-related mental health conditions of Black youths.


Effects of Bisphosphonates on Bone of Osteoporotic Men With Different Androgen Levels: A Case-Control Study.
Osteoporosis in men has been neglected despite its association with disability and mortality. We evaluated the effect of bisphosphonates (BPs) on bone mineral density (BMD) and bone turnover biomarkers of osteoporotic men with different androgen levels. This case-control study included 136 osteoporotic men who were divided into normal group (n = 75) and hypogonadism group (n = 61) (patients treated with testosterone were excluded) according to their serum testosterone levels (cutoff value, 350 ng/dL). BMD, serum testosterone, total alkaline phosphatase, and cross-linked C-telopeptide of type I collagen were detected. The relationship between testosterone levels and BMD at baseline was evaluated. All patients were treated with BPs for 2 years. We compared the effects of BPs on BMD and bone turnover biomarkers between the 2 groups. At baseline, there were no significant differences in BMD and bone turnover biomarkers between the 2 groups. Testosterone levels were positively correlated with BMD in the hypogonadism group. After treatment, the lumbar BMD increased by 7.65% ± 1.54% and 7.47% ± 1.88% in normal and hypogonadism groups, respectively (both P < .01 vs baseline) and hip BMD increased without significant differences between the 2 groups. Serum cross-linked C-telopeptide of type I collagen and alkaline phosphatase levels decreased without significant differences between the 2 groups (all P < .01 vs baseline). Testosterone level is positively correlated with BMD in men with hypogonadism. In osteoporotic men, BPs significantly increase spine and hip BMD and decrease bone resorption. The efficacy of BPs is similar in men with or without hypogonadism.


Poly-L-lactic acid - hydroxyapatite (PLLA-HA) bioabsorbable interference screws for tibial graft fixation in anterior cruciate ligament (ACL) reconstruction surgery: MR evaluation of osteointegration and degradation features.
We evaluated with magnetic resonance imaging (MRI) the degradation and osteointegration features of a new type of bioabsorbable interference (BioRCI) screw composed of poly-L-lactic acid and hydroxyapatite (PLLA-HA) used for tibial graft fixation in anterior cruciate ligament (ACL) reconstruction. Thirty-one patients underwent arthroscopic surgery for ACL reconstruction using doubled gracilis and semitendinosus tendons fixed to the tibial tunnel with PLLA-HA (BioRCI-HA) screws. Two groups of patients were evaluated, one group 10-13 months after surgery and the other after 30-40 months. The standard knee ligament evaluation form of the International Knee Documentation Committee (IKDC) was used for clinical assessment and MRI for the radiological assessment. MRI after 10-13 months revealed findings referable to healing and integration of the bone-graft-screw system, findings that disappeared at later follow-up examinations. The BioRCI-HA screw remained constantly visible in all patients, although with changes in signal intensity over time. BioRCI-HA screws allow adequate primary stability and superior osteoconduction and biocompatibility in comparison with plain PLLA screws. The absence of ferromagnetic artefacts allows accurate MRI follow-up and adequate evaluation of ligament synovialisation, screw degradation and graft osteointegration.