Photo-Cross-Linkable, Injectable, and Highly Adhesive GelMA-Glycol Chitosan Hydrogels for Cartilage Repair.
Hydrogels provide a promising platform for cartilage repair and regeneration. Although hydrogels have shown some efficacy, they still have shortcomings including poor mechanical properties and suboptimal integration with surrounding cartilage. Herein, hydrogels that are injectable, cytocompatible, mechanically robust, and highly adhesive to cartilage are developed. This approach uses GelMA-glycol chitosan (GelMA-GC) that is crosslinkable with visible light and photoinitiators (lithium acylphosphinate and tris (2,2'-bipyridyl) dichlororuthenium (II) hexahydrate ([RuII(bpy)3 ]2+ and sodium persulfate (Ru/SPS)). Ru/SPS-cross-linked hydrogels have higher compressive and tensile modulus, and most prominently higher adhesive strength with cartilage, which also depends on inclusion of GC. Tensile and push-out tests of the Ru/SPS-cross-linked GelMA-GC hydrogels demonstrate adhesive strength of ≈100 and 46 kPa, respectively. Hydrogel precursor solutions behave in a Newtonian manner and are injectable. After injection in focal bovine cartilage defects and in situ cross-linking, this hydrogel system remains intact and integrated with cartilage following joint manipulation ex vivo. Cells remain viable (>85%) in the hydrogel system and further show tissue regeneration potential after three weeks of in vitro culture. These preliminary results provide further motivation for future research on bioadhesive hydrogels for cartilage repair and regeneration.


The effects of pre- and postoperative fibrinogen levels on blood loss after cardiac surgery: a systematic review and meta-analysis.
Fibrinogen concentrate is increasingly used in cardiac surgery when bleeding is anticipated or ongoing. Since randomized clinical studies to support this are lacking, it is relevant to know whether lower fibrinogen levels are associated with excessive bleeding. We performed a systematic review and meta-analysis to define the association between fibrinogen levels and blood loss after cardiac surgery. A database search (January 2013) was performed on publications assessing the association between pre- and postoperative fibrinogen levels and postoperative blood loss in adult patients undergoing cardiac surgery. Cohort studies and case-control studies were eligible for inclusion. The main outcome was the pooled correlation coefficient, calculated via Fisher's Z transformation scale, in a random-effects meta-analysis model stratified for the time point at which fibrinogen was measured. A total of 20 studies were included. The pooled correlation coefficient of studies (n = 9) concerning preoperative fibrinogen levels and postoperative blood loss was -0.40 (95% confidence interval: -0.58, -0.18), pointing towards more blood loss in patients with lower preoperative fibrinogen levels. Among papers (n = 16) reporting on postoperative fibrinogen levels and postoperative blood loss, the pooled correlation coefficient was -0.23 (95% confidence interval: -0.29, -0.16). Our meta-analysis indicated a significant but weak-to-moderate correlation between pre- and postoperative fibrinogen levels and postoperative blood loss in cardiac surgery. This moderate association calls for appropriate clinical studies on whether fibrinogen supplementation will decrease postoperative blood loss.


Narcotic use in southeast Asia and afterward. An interview study of 898 Vietnam returnees.
From all US Army enlistees leaving Vietnam in September 1971, a random sample of 943 men was selected. Of these, 470 represented a "general" sample of all enlistees returning at that time, and 495 represented a "drug positive" sample whose urine samples had been positive for opiates at the time of departure. We attempted to locate and personally interview all of the men in the samples. Results indicate that before arrival, hard drug use was largely casual, and less than 1% had ever been addicted to narcotics. In Vietnam, almost half of the general sample tried narcotics and 20% reported opiate addiction. After return, usage and addiction essentially decreased to pre-Vietnam levels. We discuss the use of nonnarcotic drugs, predictors and correlates of drug use in the samples, and the relationship of drugs to post-Vietnam social adjustment.


Effect of lens status in the surgical success of 23-gauge primary vitrectomy for the management of rhegmatogenous retinal detachment: the Pan American Collaborative Retina Study (PACORES) group results.
To determine the effects of lens status on the success rate of primary pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment using either perfluoropropane gas (C3F8) or silicone oil (SO) tamponade. A retrospective chart analysis was made of 97 eyes from 92 patients with rhegmatogenous retinal detachment with no proliferative vitreoretinopathy that were treated with primary 23-gauge PPV. Eyes included in this were phakic (n = 28), pseudophakic (n = 41), or phakic eyes subject to simultaneous phacoemulsification, intraocular lens implantation, and PPV during primary rhegmatogenous retinal detachment repair (n = 28). Tamponade at the end of PPV was with either C3F8 (n = 65) or SO (n = 32). Success was defined as retinal reattachment at 1 year follow-up after a single procedure in eyes submitted to C3F8 injection; in eyes treated with SO injection, the success rate was defined as retina reattached 1 year after oil removal. Statistical comparisons were made between groups using chi-square, Fisher's exact test, Kruskal-Wallis, Mann-Whitney, and multivariate analysis. All eyes were operated by 2 experienced retina surgeons and had a minimum follow-up of 12 months. The vitreoretinal redetachment rate in eyes subjected to C3F8 tamponade was significantly higher (28.6%) for phakic eyes (P = 0.011) compared with pseudophakic or phakic eyes that underwent to phacoemulsification and intraocular lens implantation (4.5%). Eyes in which SO was used at the end of the surgical procedure demonstrated a similar trend of higher reoperation rates in phakic eyes (28.6%) compared with pseudophakic or phakic eyes (8%) subjected to phacoemulsification and intraocular lens implantation; however, no statistically significant difference was observed (P = 0.201). No statistically significant differences were found between groups in relation to the number of tears (P = 0.863) and their location (inferior: P = 0.189, superior: P = 0.708, nasal: P = 0.756, and temporal: P = 0.08). The success rates of primary 23-gauge PPV with either C3F8 or SO tamponade in pseudophakic eyes with rhegmatogenous retinal detachment was higher than the same procedure performed in phakic eyes. Still, the retrospective and limited data presented is too preliminary to suggest or recommend that practitioners perform simultaneous combined cataract surgery with retinal detachment and requires further studies in a larger and prospective design to confirm these present findings.


Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-) produced by targeted disruption of the gene defective in Morquio A disease.
Mucopolysaccharidosis IVA is an autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), a lysosomal enzyme required for the stepwise degradation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S). To generate a model for studies of the pathophysiology and of potential therapies, we disrupted exon 2 of Galns, the homologous murine gene. Homozygous Galns-/- mice have no detectable GALNS enzyme activity and show increased urinary glycosaminoglycan (GAGs) levels. These mice accumulate GAGs in multiple tissues including liver, kidney, spleen, heart, brain and bone marrow. At 2 months old, lysosomal storage is present primarily within reticuloendothelial cells such as Kupffer cells and cells of the sinusoidal lining of the spleen. Additionally, by 12 months old, vacuolar change is observed in the visceral epithelial cells of glomeruli and cells at the base of heart valves but it is not present in parenchymal cells such as hepatocytes and renal tubular epithelial cells. In the brain, hippocampal and neocortical neurons and meningeal cells had lysosomal storage. KS and C6S were more abundant in the cytoplasm of corneal epithelial cells of Galns-/- mice compared with wild-type mice by immunohistochemistry. Radiographs revealed no change in the skeletal bones of mice up to 12 months old. Thus, targeted disruption of the murine Galns gene has produced a murine model, which shows visceral storage of GAGs but lacks the skeletal features. The complete absence of GALNS in mutant mice makes them useful for studies of pharmacokinetics and tissue targeting of recombinant GALNS designed for enzyme replacement.


[Pulmonary histiocytosis X. Report of a case and review of the literature].
Histiocytosis X or Langerhans cell histiocytosis is an infrequent disease, which consists on proliferation of Langerhans cells. The etiology is unknown. Diagnosis is reached by electron microscope study of the biopsy, in which the Birbeck intracytoplasmatic granules of the Langerhans cells are found and/or by immunohistochemistry procedures able to detect S-100 antigen and CD1 cells. Diagnosis can also be reached with a bronchoalveolar lavage in which CD1 cells will appear in a score higher than 5%. We present the case of a 16 year-old girl that first appeared with a pulmonary lesion with a honey comb X-ray pattern and unsyntomatic mandibular bone affectation. Diagnosis was reached by biopsy study using S-100 antigen detection procedures. We consider this case an important one due to the infrequency of this particular disease.


Compliance, mass, and shape of the canine left ventricle after global ischemia analyzed with two-dimensional echocardiography.
End-diastolic pressure (EDP)-volume (EDV) curves were constructed for the left ventricle (LV) in 10 dogs on cardiopulmonary bypass before and after 45 min of normothermic ischemic arrest. LVEDV and mass were calculated from three perpendicular two-dimensional echocardiographic sections using a Simpson's rule algorithm. The echocardiographic method employed was specially developed in earlier work for physiologic studies in dogs. Postmortem pressure-volume curves were measured for comparison by direct saline infusion into sealed ventricles. LVEDV was plotted against LVEDP (0-20 mm Hg) and data were analyzed by two-way analysis of variance and also by exponential curve fitting to the relation EDP = alpha e beta EDV, where beta is the derived exponential constant reflecting slope and thereby ventricular stiffness. Postischemic EDP-EDV curves shifted to the left and the beta constant increased (beta = 0.02 +/- 0.005 (SE) vs 0.05 +/- 0.01, P less than 0.05). LV eccentricity, the ratio between long- and short-axis measurements, was unchanged (1.43 +/- 0.05 vs 1.46 +/- 0.06 postischemia, NS), but LV mass increased (105 +/- 7 vs 128 +/- 9 g postischemia, P less than 0.001). Postischemic LV mass by echo was not significantly different from measured postmortem LV mass (r = 0.87). The nonparallel alteration in the EDP-EDV curves, lack of change in LV shape (eccentricity), and increase in LV mass in the postischemic ventricle suggest that increased ventricular stiffness rather than direct encroachment by the edematous endocardium on chamber volume is responsible for postischemic changes in LV diastolic properties.


The genetic control of leaf and petal allometric variations in Arabidopsis thaliana.
Organ shape and size covariation (allometry) factors are essential concepts for the study of evolution and development. Although ample research has been conducted on organ shape and size, little research has considered the correlated variation of these two traits and quantitatively measured the variation in a common framework. The genetic basis of allometry variation in a single organ or among different organs is also relatively unknown. A principal component analysis (PCA) of organ landmarks and outlines was conducted and used to quantitatively capture shape and size variation in leaves and petals of multiparent advanced generation intercross (MAGIC) populations of Arabidopsis thaliana. The PCA indicated that size variation was a major component of allometry variation and revealed negatively correlated changes in leaf and petal size. After quantitative trait loci (QTL) mapping, five QTLs for the fourth leaf, 11 QTLs for the seventh leaf, and 12 QTLs for petal size and shape were identified. These QTLs were not identical to those previously identified, with the exception of the ER locus. The allometry model was also used to measure the leaf and petal allometry covariation to investigate the evolution and genetic coordination between homologous organs. In total, 12 QTLs were identified in association with the fourth leaf and petal allometry covariation, and eight QTLs were identified to be associated with the seventh leaf and petal allometry covariation. In these QTL confidence regions, there were important genes associated with cell proliferation and expansion with alleles unique to the maximal effects accession. In addition, the QTLs associated with life-history traits, such as days to bolting, stem length, and rosette leaf number, which were highly coordinated with climate change and local adaption, were QTL mapped and showed an overlap with leaf and petal allometry, which explained the genetic basis for their correlation. This study explored the genetic basis for leaf and petal allometry and their interaction, which may provide important information for investigating the correlated variation and evolution of organ shape and size in Arabidopsis.


Initial SEM observations of Herpes simplex virus infected chicken chorioallantoic membranes.
Chorioallantoic membranes (CAMs) of 10 day old embryonated chicken eggs were experimentally infected with types 1 and 2 Herpes simplex virus (HSV) and observed by scanning electron microscopy. This preliminary report examined CAMs at time periods ranging from 30 minutes to 24 hours post-infection. Samples also were taken for transmission electron microscopy to correlate topographic alterations with ultrastructural changes. Uninfected control CAMs, throughout the study, consisted of a homogeneous population of flattened chorionic ectodermal cells whose surface were covered with uniformly distributed microvilli of varying lengths and fairly constant diameter. At thirty minutes post infection, irrespective of infecting herpes type, microvilli were markedly decreased in numbers with those remaining showing noted blunting. Later stages of infection with type 1 HSV strains showed a cytopathic process consisting of a generalized rounding of individual cells and the presence of cells apparently containing multilobulated nuclei. CAMs infected with type 2 strains demonstrated a more focal spread of infection and the presence of intranuclear filamentous structures by transmission electron microscopy.


Shc contains two Grb2 binding sites needed for efficient formation of complexes with SOS in B lymphocytes.
Cross-linking of the B-cell antigen receptor (BCR) induces tyrosine phosphorylation of Shc, which is believed to lead to the activation of Ras. Previous work has shown that tyrosine-phosphorylated Shc forms complexes with another adapter protein, Grb2, and the Ras guanine nucleotide exchange factor SOS. Here, we demonstrate that phosphorylation of Shc by the hematopoietic cell-specific tyrosine kinase Syk induces binding of Grb2 to Shc, suggesting that Syk phosphorylates Shc in stimulated B cells. Surprisingly, Syk-phosphorylated Shc possesses two Grb2 binding sites rather than the one site that has been previously reported. Both of these sites are required for efficient formation of Shc-Grb2-SOS complexes in vitro and in vivo. We suggest that two Grb2 proteins anchored by a single Shc protein bind simultaneously to one SOS molecule, resulting in a complex that is more stable than a complex containing only a single Grb2 protein bound to one SOS molecule. This model is consistent with our observation that BCR stimulation greatly increases the amount of SOS associated with Grb2.


Enhanced Biofilm Formation by Ferrous and Ferric Iron Through Oxidative Stress in Campylobacter jejuni.
Campylobacter is a leading foodborne pathogen worldwide. Biofilm formation is an important survival mechanism that sustains the viability of Campylobacter under harsh stress conditions. Iron affects biofilm formation in some other bacteria; however, the effect of iron on biofilm formation has not been investigated in Campylobacter. In this study, we discovered that ferrous (Fe2+) and ferric (Fe3+) iron stimulated biofilm formation in Campylobacter jejuni. The sequestration of iron with an iron chelator prevented the iron-mediated biofilm stimulation. The level of total reactive oxygen species (ROS) in biofilms was increased by iron. However, the supplementation with an antioxidant prevented the total ROS level from being increased in biofilms by iron and also inhibited iron-mediated biofilm stimulation in C. jejuni. This suggests that iron promotes biofilm formation through oxidative stress. Based on the results of fluorescence microscopic analysis, Fe2+ and Fe3+ enhanced both microcolony formation and biofilm maturation. The levels of extracellular DNA and polysaccharides in biofilms were increased by iron supplementation. The effect of iron on biofilm formation was also investigated with 70 C. jejuni isolates from raw chicken. Regardless of the inherent levels of biofilm formation, iron stimulated biofilm formation in all tested strains; however, there were strain variations in iron concentrations affecting biofilm formation. The biofilm formation of 92.9% (65 of 70) strains was enhanced by either 40 μM Fe2+ or 20 μM Fe3+ or both (the iron concentrations that enhanced biofilm formation in C. jejuni NCTC 11168), whereas different iron concentrations were required to promote biofilms in the rest of the strains. The findings in this study showed that Fe2+ and Fe3+ contributed to the stimulation of biofilm formation in C. jejuni through oxidative stress.


Nitric oxide does not significantly contribute to changes in pulse pressure amplification during light aerobic exercise.
NO modulates resting blood pressure and wave reflection. The effect of NO on exercise central hemodynamics is unknown but has important implications relating to cardiovascular risk. The aim of this study was to determine the contribution of NO to pulse pressure (PP) amplification and wave reflection during exercise. Twelve healthy men aged 29+/-1 years (mean+/-SEM) undertook cycle exercise at 60% of their maximal heart rate. Noninvasive measures of central blood pressure, estimated aortic pulse wave velocity, and wave reflection (augmentation index) were obtained by pulse wave analysis during intravenous infusion of saline (control), N(G)-monomethyl-l-arginine (a NO-synthase inhibitor), or noradrenaline (control vasoconstrictor). PP amplification was defined as the ratio of peripheral to central PP. Cardiac output and stroke volume were determined by electric bioimpedance. Both N(G)-monomethyl-l-arginine and noradrenaline caused a significant increase in mean arterial pressure (P<0.01) and augmentation index (P<0.01), as well as reduced ratio of peripheral to central PP (P<0.05) at baseline. Exercise caused a significant increase in the ratio of peripheral to central PP (P<0.001), whereas augmentation index and estimated aortic pulse wave velocity declined (for both P<0.05) during all 3 of the infusion protocols. However, no significant differences were observed in augmentation index, ratio of peripheral to central PP, or estimated aortic pulse wave velocity between infusion procedures (P>0.50) during exercise. Also, heart rate, peripheral vascular resistance, and cardiac output did not differ during exercise between saline, N(G)-monomethyl-l-arginine, or noradrenaline. Although we cannot rule out other vasodilator mechanisms having adjusted for NO blockade, our results indicate that NO does not solely contribute to systemic arterial stiffness or altered blood pressure amplification during light exercise.


Rosacea: symptoms and support.
Rosacea is a common skin condition, especially for middle-aged and some older adults. However, it is often wrongly perceived as cosmetic facial redness caused by alcohol. This can be very distressing for rosacea patients, as it is a facial vascular condition with subtypes, varying in severity. Rosacea should be effectively treated, as physical symptoms such as burning, stinging and soreness, as well as facial disfigurement are very distressing and can have a major impact on quality of life. This articles seeks to explain what rosacea is, including a description of sub-types and possible causes and trigger factors. Treatments for different severities of rosacea and the nurse's role in supporting patients will also be discussed.


Spectrum of transient focal neurological episodes in cerebral amyloid angiopathy: multicentre magnetic resonance imaging cohort study and meta-analysis.
Transient focal neurological episodes (TFNE) are recognized in cerebral amyloid angiopathy (CAA) and may herald a high risk of intracerebral hemorrhage (ICH). We aimed to determine their prevalence, clinical neuroimaging spectrum, and future ICH risk. This was a multicenter retrospective cohort study of 172 CAA patients. Clinical, imaging, and follow-up data were collected. We classified TFNE into: predominantly positive symptoms ("aura-like" spreading paraesthesias/positive visual phenomena or limb jerking) and predominantly negative symptoms ("transient ischemic attack-like" sudden-onset limb weakness, dysphasia, or visual loss). We pooled our results with all published cases identified in a systematic review. In our multicenter cohort, 25 patients (14.5%; 95% confidence interval, 9.6%-20.7%) had TFNE. Positive and negative symptoms were equally common (52% vs 48%, respectively). The commonest neuroimaging features were leukoaraiosis (84%), lobar ICH (76%), multiple lobar cerebral microbleeds (58%), and superficial cortical siderosis/convexity subarachnoid hemorrhage (54%). The CAA patients with TFNE more often had superficial cortical siderosis/convexity subarachnoid hemorrhage (but not other magnetic resonance imaging features) compared with those without TFNE (50% vs 19%; P=0.001). Over a median period of 14 months, 50% of TFNE patients had symptomatic lobar ICH. The meta-analysis showed a risk of symptomatic ICH after TFNE of 24.5% (95% confidence interval, 15.8%-36.9%) at 8 weeks, related neither to clinical features nor to previous symptomatic ICH. TFNE are common in CAA, include both positive and negative neurological symptoms, and may be caused by superficial cortical siderosis/convexity subarachnoid hemorrhage. TFNE predict a high early risk of symptomatic ICH (which may be amenable to prevention). Blood-sensitive magnetic resonance imaging sequences are important in the investigation of such episodes.


Childhood Polyvictimization and the Life Course: Associations With Depression and Crime.
Exposure to multiple forms of victimization has been shown to have increasingly negative outcomes, but their unique trajectory-setting effects have been largely unexplored. Using a life course approach, this article examines the life trajectories of child polyvictims. I use a nationwide sample including 3,652 respondents after cleaning and preparation. Seemingly unrelated regressions were used to predict depression and criminal behavior in childhood and adulthood. Results suggest that children who experience multiple forms of parental abuse tend to have life trajectories which grow increasingly worse through the life course. However, life trajectories of children experiencing violence outside the home have less persistent negative outcomes. Researchers and interventions should take differing life trajectories into account when attempting to aid different types of polyvictims.


Thyroidkeeper: a healthcare management system for patients with thyroid diseases.
Thyroid diseases, especially thyroid tumors, have a huge population in China. The postoperative patients, under China's incomplete tertiary diagnosis and treatment system, will frequently go to tertiary hospitals for follow-up and medication adjustment, resulting in heavy burdens on both specialists and patients. To help postoperative patients recover better against the above adverse conditions, a novel mobile application ThyroidKeeper is proposed as a collaborative AI-based platform that benefits both patients and doctors. In addition to routine health records and management functions, ThyroidKeeper has achieved several innovative points. First, it can automatically adjust medication dosage for patients during their rehabilitation based on their medical history, laboratory indicators, physical health status, and current medication. Second, it can comprehensively predict the possible complications based on the patient's health status and the health status of similar groups utilizing graph neural networks. Finally, the employing of graph neural network models can improve the efficiency of online communication between doctors and patients, help doctors obtain medical information for patients more quickly and precisely, and make more accurate diagnoses. The preliminary evaluation in both laboratory and real-world environments shows the advantages of the proposed ThyroidKeeper system.


[Application of the system for rheolytic thrombectomy in patients with acute myocardial infarction].
The authors present first experience of application of the system for rheolytic therapy AngioJet in a group of patients with acute myocardial infarction. They describe principle of the work of rheolytic systems, possible procedure related complications. They also discuss results of clinical studies analyzing efficacy of antithrombotic therapy, efficacy and safety of rheolytic therapy in patients with acute coronary syndrome and complicated atherosclerotic plaques in coronary arteries.


Avoiding Medicare fraud. Part 1.
In 1997, Congress authorized payments to nurse practitioners (NPs) for Medicare-provided services. NP services are now reimbursed at 85% of the physician fee schedule. As this source of reimbursement was realized, so was a new area of liability for NPs. Failure to follow billing rules can result in payment denial, repayment of fees already paid, mandated educational activities, fines, fraud prosecution, loss of Medicare-billing ability, and loss of employment. Appropriate billing entails adhering to guidelines for selecting procedure codes and proper medical documentation. This article identifies high-risk areas for NPs who bill Medicare and provides resources for accessing additional information.


[Differential reaction of human cardiac macro- and microvascular endothelial cells with respect to leucocyte adhesion and exposition to atherogenic lipoproteins].
While the cellular mechanisms of atherosclerosis have been intensively studied, the mechanisms leading to preferential localization of atherosclerotic lesions are less well understood. To further define these mechanisms, endothelial cells from coronary arteries, i.e., vessels with frequent atherosclerotic lesions, were isolated and grown in vitro. In order to compare the reactions of both cell types, endothelial cells derived from microvessels of human hearts were isolated and cultured under identical conditions. Incubation of endothelial cells with oxidized LDL (75 microg/ml protein) induced a significant increase in PAI-1 activity (182%, p < 0.05) in coronary macrovascular endothelial cells. This stimulatory effect of ox-LDL was less significant in microvascular endothelial cells (144%, p < 0.05). n-LDL did not influence secreted PAI-1 activity. Stimulation with angiotensin II induced expression of E-selectin more effectively in coronary macrovascular than in microvascular endothelial cells. In addition, angiotensin II-induced E-selectin expression led to increased E-selectin-dependent adhesion of HL60 cells to coronary macrovascular endothelial cells under flow conditions, while only little effect was observed with cardiac microvascular endothelial cells. In contrast, L-selectin-dependent adhesion, which has been shown to play an important role in inflammatory reactions, was preferentially observed in cardiac microvascular endothelial cells and could only be stimulated with TNFalpha, not by angiotensin II. Therefore, these cellular differences may in part explain specific properties of cardiac endothelial cells: Such that atherosclerotic lesions are localized in macrovascular vessel segments, whereas inflammatory responses are predominantly found in the microvasculature.


Two cases of cardiac arteriovenous malformation complicated by a local angioproliferative process.
Vascular malformations of the heart are extremely rare with only a few cases of the arteriovenous type of vascular malformation (AVM) reported. We investigated the pathology of two additional cases, which were complicated by the occurrence of a local vasoproliferative response of immature but benign vessels. We suppose that the mass forming effect of this vasoproliferative response, which has also been reported recently as a complication of congenital AVM elsewhere in the body, has significantly contributed to the onset of symptoms and ultimate death of both patients.


Evidence of heterogeneity by race/ethnicity in genetic determinants of QT interval.
QT interval (QT) prolongation is an established risk factor for ventricular tachyarrhythmia and sudden cardiac death. Previous genome-wide association studies in populations of the European descent have identified multiple genetic loci that influence QT, but few have examined these loci in ethnically diverse populations. Here, we examine the direction, magnitude, and precision of effect sizes for 21 previously reported SNPs from 12 QT loci, in populations of European (n = 16,398), African (n = 5,437), American Indian (n = 5,032), Hispanic (n = 1,143), and Asian (n = 932) descent as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. Estimates obtained from linear regression models stratified by race/ethnicity were combined using inverse-variance weighted meta-analysis. Heterogeneity was evaluated using Cochran's Q test. Of 21 SNPs, 7 showed consistent direction of effect across all 5 populations, and an additional 9 had estimated effects that were consistent across 4 populations. Despite consistent direction of effect, 9 of 16 SNPs had evidence (P < 0.05) of heterogeneity by race/ethnicity. For these 9 SNPs, linkage disequilibrium plots often indicated substantial variation in linkage disequilibrium patterns among the various racial/ethnic groups, as well as possible allelic heterogeneity. These results emphasize the importance of analyzing racial/ethnic groups separately in genetic studies. Furthermore, they underscore the possible utility of trans-ethnic studies to pinpoint underlying casual variants influencing heritable traits such as QT.


Martensitic transformation between competing phases in Ti-Ta alloys: a solid-state nudged elastic band study.
A combined density functional theory and solid-state nudged elastic band study is presented to investigate the martensitic transformation between β → (α″, ω) phases in the Ti-Ta system. The minimum energy paths along the transformation are calculated and the transformation mechanisms as well as relative stabilities of the different phases are discussed for various compositions. The analysis of the transformation paths is complemented by calculations of phonon spectra to determine the dynamical stability of the β, α″, and ω phase. Our theoretical results confirm the experimental findings that with increasing Ta concentration there is a competition between the destabilisation of the α″ and ω phase and the stabilisation of the high-temperature β phase.


Structural Priors Guided Network for the Corneal Endothelial Cell Segmentation.
The segmentation of blurred cell boundaries in cornea endothelium microscope images is challenging, which affects the clinical parameter estimation accuracy. Existing deep learning methods only consider pixel-wise classification accuracy and lack of utilization of cell structure knowledge. Therefore, the segmentation of the blurred cell boundary is discontinuous. This paper proposes a structural prior guided network (SPG-Net) for corneal endothelium cell segmentation. We first employ a hybrid transformer convolution backbone to capture more global context. Then, we use Feature Enhancement (FE) module to improve the representation ability of features and Local Affinity-based Feature Fusion (LAFF) module to propagate structural information among hierarchical features. Finally, we introduce the joint loss based on cross entropy and structure similarity index measure (SSIM) to supervise the training process under pixel and structure levels. We compare the SPG-Net with various state-of-the-art methods on four corneal endothelial datasets. The experiment results suggest that the SPG-Net can alleviate the problem of discontinuous cell boundary segmentation and balance the pixel-wise accuracy and structure preservation. We also evaluate the agreement of parameter estimation between ground truth and the prediction of SPG-Net. The statistical analysis results show a good agreement and correlation.


Long-term results of maintenance of lacrimal silicone stent in patients with functional epiphora after external dacryocystorhinostomy.
To evaluate long-term outcomes of maintenance of lacrimal silicone stent for the management of functional epiphora after anatomically patent external dacryocystorhinostomy (DCR). We retrospectively reviewed the medical records of 101 eyes of 75 patients who were diagnosed to have functional epiphora after external DCR from 2005 to 2014. Functional epiphora was defined as epiphora that persisted or recurred even after patent DCR confirmed by a lacrimal irrigation test. Secondary silicone intubation was indicated when the patients wanted a further intervention. The stent was intended to be kept in situ unless there was a stent-related complication or the patient wanted removal. In total, 34 of 75 patients (45.3%, 52 eyes) who agreed to the intervention underwent secondary silicone intubation. The success rates at 1, 3, and 5 years after surgery were 96.2%, 75.5%, and 70.2%, respectively. At the final follow-up (mean 72.7 ± 26.4 months), 32 (61.5%) eyes chose to retain the silicone tube: silicone stent was well maintained without epiphora and complications once inserted in 18 eyes (34.6%), whereas tube replacement was needed in 14 eyes (26.9%) because of nasal crust or whitish plaque formation on the tube surface. In 13 cases (25.0%), silicone stent was removed because of tube-related complications, and the most common complication was canaliculitis (n = 8, 15.4%). Secondary intubation and maintenance of the stent is an effective and simple procedure for functional epiphora. The main obstacle to long-term maintenance is tube-associated canaliculitis.


COX-2 inhibition, apoptosis, and chemoprevention by nonsteroidal anti-inflammatory drugs.
Non-steroidal anti-inflammatory drugs (NSAIDs) have as their common mechanism the inhibition of cyclooxygenase (COX) enzymes, of which two isoforms (COX-1 and COX-2) exist. The effect of NSAIDs on chemoprevention and tumor regression has been shown in animal models, epidemiologic studies, and in treatment of patients. The exact biochemical and cellular mechanisms underlying each of these phenomena is only partially understood. Processes that have been recently implicated as being important include the inhibition of tumor cell growth, prevention of angiogenesis, and induction of apoptosis in neoplastic cells.


Cystathionine γ-lyase deficiency protects mice from galactosamine/lipopolysaccharide-induced acute liver failure.
Acute liver failure (ALF) is a fatal syndrome attributed to massive hepatocyte death. Hydrogen sulfide (H2S) has been reported to exert cytoprotective or cytotoxic effects. Here, we examined the role of cystathionine γ-lyase (CSE, an enzyme produces H2S) in ALF induced by D-Galactosamine (GalN) and lipopolysaccharide (LPS). Wild-type (WT) mice exhibited high mortality rate, prominent liver injury, and increased plasma alanine aminotransferase levels after GalN/LPS challenge. Congenital deficiency or chemical inhibition of CSE by DL-propargylglycine attenuated GalN/LPS-induced liver injury. CSE deficiency markedly improved survival rate and attenuated GalN/LPS-induced upregulation of inflammatory cytokines and activation of caspase 3 and poly (ADP-ribose) polymerase (PARP) in the liver. CSE deficiency protected primary hepatocytes from GalN/tumor necrosis factor-α (TNF-α)-induced cell death without affecting LPS-induced TNF-α production from primary peritoneal macrophages. Beneficial effects of CSE deficiency were associated with markedly elevated homocysteine and thiosulfate levels, upregulation of NF-E2 p45-related factor 2 (Nrf2) and antioxidant proteins, activation of Akt-dependent anti-apoptotic signaling, and inhibition of GalN/LPS-induced JNK phosphorylation in the liver. Finally, administration of sodium thiosulfate (STS) attenuated GalN/LPS-induced liver injury via activation of Akt- and Nrf2-dependent signaling and inhibition of GalN/LPS-induced JNK phosphorylation in WT mice. These results suggest that inhibition of CSE or administration of STS prevents acute inflammatory liver failure by augmenting thiosulfate levels and upregulating antioxidant and anti-apoptotic defense in the liver. Congenital deficiency or chemical inhibition of CSE increases thiosulfate levels in the liver and prevents ALF at least in part by augmentation of antioxidant and anti-apoptotic mechanisms.


Self-Assembled Nanocube-Based Plasmene Nanosheets as Soft Surface-Enhanced Raman Scattering Substrates toward Direct Quantitative Drug Identification on Surfaces.
We report on self-assembled nanocube-based plasmene nanosheets as new surface-enhanced Raman scattering (SERS) substrates toward direct identification of a trace amount of drugs sitting on topologically complex real-world surfaces. The uniform nanocube arrays (superlattices) led to low spatial SERS signal variances (∼2%). Unlike conventional SERS substrates which are based on rigid nanostructured metals, our plasmene nanosheets are mechanically soft and optically semitransparent, enabling conformal attachment to real-world solid surfaces such as banknotes for direct SERS identification of drugs. Our plasmene nanosheets were able to detect benzocaine overdose down to a parts-per-billion (ppb) level with an excellent linear relationship (R(2) > 0.99) between characteristic peak intensity and concentration. On banknote surfaces, a detection limit of ∼0.9 × 10(-6) g/cm(2) benzocaine could be achieved. Furthermore, a few other drugs could also be identified, even in their binary mixtures with our plasmene nanosheets. Our experimental results clearly show that our plasmene sheets represent a new class of unique SERS substrates, potentially serving as a versatile platform for real-world forensic drug identification.


Maximal activity of phosphate-dependent glutaminase and glutamine metabolism in septic rats.
The activity of phosphate-dependent glutaminase and glutamine metabolism by tissues known markedly to utilize or synthesize glutamine (or both) were studied in rats made septic by cecal ligation and puncture technique and compared with the same measures in rats that underwent sham operation (laparotomy). Blood glucose level was not markedly different in septic rats, but lactate, pyruvate, alanine, and glutamine levels were markedly increased. Conversely, blood ketone body concentrations were significantly decreased in septic rats. Both plasma insulin and glucagon levels were markedly elevated in response to sepsis. The maximal activity of phosphate-dependent glutaminase was decreased in the small intestine, increased in the kidney and mesenteric lymph nodes, and unchanged in the liver of septic rats. Arteriovenous concentration difference measurements across the gut showed a decrease in the net glutamine removed from the circulation in septic rats. Arteriovenous concentration difference measurements for glutamine showed that both renal uptake and skeletal muscle release of the amino acid were increased in response to sepsis, whereas measurements across the hepatic bed showed a net uptake of glutamine in septic rats. Enterocytes isolated from septic rats exhibited a decreased rate of utilization of glutamine and production of glutamate, alanine, and ammonia, whereas lymphocytes isolated from septic rats showed an enhanced rate of utilization of glutamine and production of glutamate, aspartate, and ammonia. It is concluded that, during sepsis, glutamine uptake and metabolism are enhanced in renal and lymphoid tissue but decreased in that of the small intestine, with increased rates of release by skeletal muscle; however, the liver appears to utilize glutamine in septic rats.


Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies.
Two phase 3 studies evaluated the efficacy and safety of rosiglitazone (RSG), a type 2 diabetes treatment, in an extended release (RSG XR) form as adjunctive therapy to ongoing acetylcholine esterase inhibitor (AChEI) treatment in AD (REFLECT-2, adjunctive to donepezil; REFLECT-3, to any AChEI). An open-label extension study (REFLECT-4) assessed RSG XR long-term safety. In these two double-blind, placebo-controlled studies, subjects with mild-to-moderate probable AD were randomized within 2 apolipoprotein E (APOE) allelic strata (APOE ε4-positive, APOE ε4-negative) to once daily placebo, 2 mg RSG XR, or 8 mg RSG XR for 48 weeks (REFLECT-2, N=1,496; REFLECT-3, N=1,485). Co-primary efficacy endpoints were change from baseline in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Clinical Dementia Rating scale - Sum of Boxes (CDR-SB) scores at week 48. Three populations were analyzed: APOE4-negative, all subjects except APOE ε4 homozygotes, and the full intent-to-treat population. No statistically or clinically relevant differences between treatment groups were observed on the a priori primary endpoints in REFLECT-2 or REFLECT-3. Edema was the most frequent adverse event with RSG in each study (14% and 19%, respectively, at 8 mg RSG XR). No evidence of statistically or clinically significant efficacy in cognition or global function was detected for 2 mg or 8 mg RSG XR as adjunctive therapy to ongoing AChEIs. There was no evidence of an interaction between treatment and APOE status. Safety and tolerability of RSG XR was consistent with the known profile of rosiglitazone.


The use of circulating tumor cells in guiding treatment decisions for patients with metastatic castration-resistant prostate cancer.
The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has drastically changed over the past decade with the advent of several new anti-tumor agents. Oncologists increasingly face dilemmas concerning the best treatment sequence for individual patients since most of the novel compounds have been investigated and subsequently positioned either pre- or post-docetaxel. A currently unmet need exists for biomarkers able to guide treatment decisions and to capture treatment resistance at an early stage thereby allowing for an early change to an alternative strategy. Circulating tumor cells (CTCs) have in this context intensively been investigated over the last years. The CTC count, as determined by the CellSearch System (Janssen Diagnostics LLC, Raritan, NJ), is a strong, independent prognostic factor for overall survival in patients with mCRPC at various time points during treatment and, as an early response marker, outperforms traditional response evaluations using serum prostate specific antigen (PSA) levels, scintigraphy as well as radiography. The focus of research is now shifting toward the predictive value of CTCs and the use of the characterization of CTCs to guide the selection of treatments with the highest chance of success for individual patients. Recently, the presence of the androgen receptor splice variant 7 (AR-V7) has been shown to be a promising predictive factor. In this review, we have explored the clinical value of the enumeration and characterization of CTCs for the treatment of mCRPC and have put the results obtained from recent studies investigating the prognostic and predictive value of CTCs into clinical perspective.


Mutations in the anti-sigma H factor RshA confer resistance to econazole and clotrimazole in Mycobacterium smegmatis.
Azole drugs such as econazole, are active on Mycobacterium tuberculosis and Mycobacterium smegmatis ; however, the identification of their target(s) is still pending. It has been reported that mutations in the non-essential system mmpL5-mmpS5 conferred resistance to econazole in M. tuberculosis . We herein report that an azole-resistant mutant screen in M. smegmatis rendered mutations in rshA, encoding a non-essential anti-sigma H protein.


Safety of therapeutic monoclonal antibodies.
Therapeutic monoclonal antibodies (mAbs) including antibody fusion proteins and antibody conjugates present an innovative class of (bio-)pharmaceuticals with increasing clinical importance. MAbs were initially perceived as comparatively safe drugs. As more mAbs appear on the market, characteristics of their safety profiles become apparent, including immunogenicity, i.e. the potential induced formation of human anti-drug antibodies (HADAs) in patients. European Public Assessment Reports were reviewed to provide an overview about main safety concerns and the immunogenicity of mAbs in chronic inflammatory diseases and oncology/haematology, including strategies for their prevention and clinical management. In total, both mechanism-related and non-specific adverse drug reactions (ADRs) have been reported, with infectious complications and administration-related reactions observed across the majority of mAbs. Most ADRs were predictable and manageable, although some have emerged unexpectedly. Immunogenicity occurred with almost all mAbs, with widely differing extent. Adverse consequences of HADAs were only identified for few mAbs. In conclusion, mAbs are generally safe but as they may be associated with significant ADRs, the individual risks need to be weighed against the expected therapeutic benefit. As several of the recently introduced mAbs are directed against new targets, and considering the limited understanding of immunogenicity, special caution and patient monitoring is highly recommended.


Green tea (Camellia sinensis) extract and its possible role in the prevention of cancer.
The American Cancer Society estimates that in the 1980s more than 4. 5 million Americans died of cancer. In addition, there were nearly nine million new cases and about 12 million people were under medical care for cancer. With cancer being the second most common cause of death in the United States population, the possibility that readily-available natural substances may be beneficial in the prevention of cancer warrants closer examination. A growing body of research has demonstrated green tea polyphenols to be powerful antioxidants with anticarcinogenic properties. These polyphenolic compounds, specifically the catechins epigallocatechin-3-gallate (EGCG), epigallocatechin (EGC), and epicatechin-3-gallate (ECG), which account for 30-40 percent of the extractable solids of green tea leaves, are believed to mediate many of the cancer chemopreventive effects. Mechanisms of action may include antioxidant and free-radical scavenging activity, and stimulation of detoxification systems through selective induction or modification of phase I and phase II metabolic enzymes. In addition, green tea may inhibit biochemical markers of tumor initiation and promotion, including the rate of cell replication and thus inhibition of the growth and development of neoplasms. Current studies are hopeful, as they show an inverse association between green tea consumption and cancer risk, supporting a possible chemopreventive effect of green tea. Based on the knowledge that green tea is inexpensive, non-toxic, and is a popular beverage consumed worldwide, clinical trials should be conducted to evaluate the in-vivo effectiveness of green tea polyphenols on the inhibition and chemopreventive treatment of cancer.


Dosing of Health and Wellness Coaching for Obesity and Type 2 Diabetes: Research Synthesis to Derive Recommendations.
Health and wellness coaching (HWC) is an effective intervention for lifestyle disease such as obesity and type 2 diabetes. The evolving HWC profession needs recommendations to guide clinical practice, particularly the appropriate dose of coaching. The purpose of this paper was to systematically review and synthesize HWC literature to derive HWC programming recommendations. Of 102 papers retrieved, 88 were retained with data extracted determining HWC session number, frequency, duration, program length, and total coaching load. Differential analysis yielded no statistical difference in programming variables for randomized control trials and other designs, nor for studies with significant findings v. those not finding statistical significance, allowing these data to be pooled. The HWC intervention for obesity was slightly more intense (15 sessions over 7-8 mo) than the diabetes programming (12 sessions over 9-10 mo). On average, HWC programming applied in the peer-reviewed literature was 12-15 sessions of 35-40 min duration over 7-9 months. These recommendations for HWC programming variables are put forth as initial practice guidelines and should be examined with comparative effectiveness study for optimization. HWC best practice guidelines for other patient groups (e.g., heart disease, cancer, and chronic pain) should also be studied once an adequate literature data base is available.


Effects of morphine and cocaine on breathing control in neonatal animals: a minireview.
From observational studies in humans and experimental studies in animal models, there is a strong indication that prenatal exposure to morphine or cocaine causes at least transient abnormalities of breathing control in the neonate. If these abnormalities persist, sudden death may occur in the infant. Mechanisms responsible for alterations in breathing control by drugs of abuse and the relationship of these alterations to SIDS are not proven at this time. The complex nature of breathing control and neurodevelopment, as well as the confounding variables in human drug abuse, have so far prevented a definitive understanding of the link between drug abuse during pregnancy and SIDS. Further investigations are required to explore the biology of this important public health problem.


Development and characterization of conditionally immortalized osteoblast precursor cell lines from human bone marrow stroma.
Although the differentiation of mature osteoblasts has been well studied, there is still a need for a convenient way to study preosteoblast differentiation. Our laboratory has recently described a method for isolating small numbers of authentic osteoblast precursor cells from human bone marrow (Rickard et al., J Bone Miner Res 11:312-324, 1996). Here we describe the conditional immortalization of these cells by retroviral transfection with the amphotrophic vector, pZipSV40tsa58, which encodes for a temperature-sensitive mutant form of the simian virus large T-antigen. At the permissive temperature of 34 degrees C, the cell lines proliferated, but differentiation was arrested, whereas at the restrictive temperature of 39.5 degrees C, proliferation was decreased and differentiation was induced. As assessed by semiquantitative reverse transcriptase PCR after 4 days of culture at 39.5 degrees C, the six cell lines expressed similar mRNA levels both constitutively and in response to dexamethasone (Dex) and 1alpha,25-dihydroxyvitamin D3 (1,25(OH2)D3) for osteoblast (alkaline phosphatase [ALP], type I collagen [Col I], osteocalcin [OC], and parathyroid hormone receptor [PTH-R] and adipocyte (lipoprotein lipase [LPL]) genes. In the presence of 10(-8) M Dex, gene expression for ALP, PTH-R, and LPL increased, but that for OC decreased. Stimulation with 10(-8) M 1,25(OH2)D3 increased gene expression for ALP, OC, and Col I. Changes in protein production for ALP, OC, and type I procollagen in response to Dex and 1,25(OH2)D3 were similar to changes in mRNA levels. When cultured at 39.5 degrees C with ascorbate and beta1-glycerolphosphate for 21 days, mineralization of matrix occurred, whereas culture with Dex plus 1,25(OH2)D3, or rabbit serum led to enhanced formation of cytoplasmic lipid droplets within 6 days. Thus, these cell lines are capable of bipotential differentiation and should serve as an excellent tool to study the molecular mechanisms that regulate and select for osteoblast and adipocyte differentiation in humans.


Formulation and evaluation of once daily minocycline hydrochloride extended release matrix tablets.
The present study was aimed to develop once daily extended release matrix tablets of minocycline hydrochloride, using hydroxypropylmethylcellulose either alone or in combination with ethyl cellulose as the matrix material in different proportions. The formulated tablets were also compared with a marketed product. The results of the dissolution study indicate that formulations FC-IV, FC-V and FC-VI showed maximum drug release upto 24 h, whereas the marketed product was found to extend the release only up to 14 h. Incase of formulations containing combination of hydroxypropylmethylcellulose and ethyl cellulose (FC-I to FC-IX), the release of the drug was found to be dependent on the relative proportions of hydroxypropylmethylcellulose and ethyl cellulose used in the tablet matrix. Mathematical treatment of the in vitro drug release data suggests that, all the formulations best fitted into first order release kinetics. Drug release from the matrix occurred by combination of two mechanisms, diffusion of drug from tablet matrix and erosion of tablet surface, which was reflected from Higuchi's model and Erosion plot.


Recent advances in oxidative phenol coupling for the total synthesis of natural products.
Covering: 2008 to 2023This review will describe oxidative phenol coupling as applied in the total synthesis of natural products. This review covers catalytic and electrochemical methods with a brief comparison to stoichiometric and enzymatic systems assessing their practicality, atom economy, and other measures. Natural products forged by C-C and C-O oxidative phenol couplings as well as from alkenyl phenol couplings will be addressed. Additionally, exploration into catalytic oxidative coupling of phenols and other related species (carbazoles, indoles, aryl ethers, etc.) will be surveyed. Future directions of this particular area of research will also be assessed.


Alternaria measures in inner-city, low-income housing by immunoassay and culture-based analysis.
Sensitivity to Alternaria allergens has been associated with severe asthma and life-threatening exacerbations, and a high prevalence of Alternaria sensitivity has been reported among inner-city populations. Traditionally, epidemiologic studies have measured indoor Alternaria concentrations by cultural analyses; however, the number of viable spores may not be a good proxy for allergen levels. Furthermore, other genera share epitopes with Alternaria that may contribute to the allergenic effect. To compare measures of Alternaria antigen by enzyme-linked immunosorbent assay with measures of Alternaria and cross-reactive genera (Ulocladium, Curvularia, Epicoccum, and Stemphylium) by cultural analysis. Antigen assays and cultural analyses were performed on vacuum-collected bed dust samples collected between June 18, 2002, and February 9, 2004, from 3 inner-city, low-income public housing developments. Alternaria antigen was found in all bed dust samples regardless of season. However, culturable Alternaria, Ulocladium, Curvularia, Epicoccum, and Stemphylium were only found in 50%, 35%, 6%, 11%, and 0% of bed samples, respectively. No correlations were found between Alternaria antigen and culturable concentrations of Alternaria or of its cross-reactive genera except for marginal correlation with Ulocladium culturable concentrations. The results confirm that exposure to Alternaria antigens and allergens can occur even in the absence of culturable Alternaria or its cross-reactive genera, so further refinement and use of assays are essential for characterizing the distribution and determinants of indoor fungal allergen levels forsensitive populations.


Advances in nanotechnology and the benefits of using cellulose nanofibers in animal nutrition.
The production of cellulose nanofibers promotes the utilization of plant residues that are generated in agro-industries during food processing. The utilization of these plant by-products reduces environmental contamination. Cellulose nanofibers are used in several sectors, including the drug, food, and animal nutrition industries. Many sources of nanofibers used in animal diets can be used as potential fiber substitutes after being processed to improve efficiency. For instance, including nanometric particles of plant fibers (<100 nm) in animal feed may provide excellent physical properties such as high reactivity, a large surface area, and improved nutrient absorption from the diet. Nanotechnology improves the characteristics of fibers that are important for gastrointestinal transit and their utilization as energy sources and substrates for microbial fermentation in the digestive tract of animals. Nanofibers can improve the synthesis of volatile fatty acids and the blood lipid profile, with positive effects on the intestinal health of animals. Moreover, in vitro and in vivo studies have demonstrated promising effects in reducing blood glucose levels without toxic effects on the body. Supplying nanofibers in the diet improve animal performance, increase productivity, and work toward a more sustainable economic development of agribusinesses. The quality of animal products such as meat, milk, and eggs is also reported to be improved with the inclusion of nanominerals in the feed. Overall, the application of nanotechnology to harness the by-products of agro-industries can increase economic viability and sustainability in animal production systems. Therefore, this review presents a current survey on the main research and advances in the utilization of nanotechnology, focusing on cellulose nanofibers in animal feed to improve animal performance.


Management of aphthous ulcers.
Aphthous ulcers are a common and painful problem. Benign aphthae tend to be small (less than 1 cm in diameter) and shallow. Aphthous ulcers that occur in conjunction with symptoms of uveitis, genital ulcerations, conjunctivitis, arthritis, fever or adenopathy should prompt a search for a serious etiology. The lack of clarity regarding the etiology of aphthous ulcers has resulted in treatments that are largely empiric. These treatments include antibiotics, anti-inflammatories, immune modulators, anesthetics and alternative (herbal) remedies.


Cytotoxic Effect of Portulaca Oleracea Extract on the Regulation of CDK1 and P53 Gene Expression in Pancreatic Cancer Cell Line.
The growth of pancreatic cancer has a high predominance in the world. Different therapeutic methods were unsuccessful due to tumor invasion and rapid metastasis. Plants have natural products that were used as therapeutic agents. Accordingly, the purpose of this research was to assess the cytotoxic effect of Portulaca Oleracea against PANC-1 cancer cell line. MTT technique and flow cytometry were done to evaluate the cytotoxicity of P.Oleracea extracts against PANC-1 cancer cell line. For finding the change of CDK and P53 expression levels, qPCR carries out. The findings of the MTT assay exhibited that P.Oleracea extracts had toxicity potential on PANC- one cancer cell line. Also, the results of gene expression showed the high expression of P53 and reduction of CDK gene expression following treatment of cancer cells with plant extracts in. The flow cytometry assay showed apoptosis induced after P.Oleracea extract treatment in PANC- one cancer cell line. Also, microscopic observation is in agreement with flow cytometry and MTT assay. Results of the current study indicated that P.Oleracea extracts significantly induce apoptosis by regulating P53 and CDK expression, consequently. Therefore, P.Oleracea may be considered as a novel finding for pancreatic cancer treatment consequently of its cytotoxic and apoptotic activity.


Associations of maternal and cord blood adipokines with offspring adiposity in Project Viva: is there an interaction with child age?
Higher leptin and lower adiponectin correlate with adult and childhood adiposity, but it is unclear how exposure to these adipokines during gestation relates to offspring growth. We aimed to investigate the relationships of maternal and cord adipokines with offspring adiposity across childhood to early adolescence, as well as interactions with child age. In mother-child pairs in the Project Viva cohort, we measured adipokines in mothers at second trimester (n=1106) and in cord blood at birth (n=657). We measured offspring adiposity indices at early childhood (mean 3.3±s.d. 0.3 years), mid-childhood (7.9±0.8 years) and early adolescence (13.2±0.9 years). We analyzed associations of maternal and cord adipokines with offspring longitudinal adiposity using a linear mixed model adjusting for pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and other confounders. Mothers with higher BMI and GWG had higher leptin. Offspring born to mothers with the highest vs lowest quartile of leptin had lower BMI z-score (-0.49 units, 95% confidence interval (CI):-0.72,-0.26), waist circumference (-2.6 cm, 95% CI: -3.7,-1.5) and sum of subscapular and triceps skinfolds (-2.8 mm, 95% CI: -4.1,-1.4) in early life. An interaction term between maternal leptin and child age was positive, suggesting that the associations between maternal leptin and child adiposity were not constant over time. Offspring born to mothers with lowest vs highest quartile of maternal adiponectin had lower early life adiposity (BMI z-score -0.27 units, 95% CI: -0.48,-0.05). Results were similar for cord leptin but not cord adiponectin. Our findings showed higher maternal and cord leptin, and lower maternal adiponectin are associated with lower offspring adiposity from childhood to early adolescence, independent of maternal BMI and GWG. However, the strength of these associations was not constant over time.


Musculoskeletal manifestations of Lyme arthritis.
Lyme disease is a treatable and curable infectious disease that can be diagnosed with relative confidence with attention to the details of the syndrome and proper use of serologic testing to confirm the clinical diagnosis. Lyme disease should not be a "diagnosis of exclusion," made on the basis of isolated serologic reactivity or because of the presence of symptoms compatible with Lyme disease. The pathogenesis of chronic complaints following infection with B. burgdorferi is often unclear, but such persistent complaints should not automatically be ascribed to ongoing infection. There is no proven role for long-term antibiotics or combination regimens.


Agreement in Metastatic Spinal Cord Compression.
Metastatic epidural spinal cord compression (ESCC) is a devastating medical emergency. The purpose of this study was to determine the reliability of the 6-point ESCC scoring system and the identification of the spinal level presenting ESCC. Clinical data and imaging from 90 patients with biopsy-proven spinal metastases were provided to 83 specialists from 44 hospitals. The spinal levels presenting metastases and the ESCC scores for each case were calculated twice by each clinician, with a minimum of 6 weeks' interval. Clinicians were blinded to assessments made by other specialists and their own previous assessment. Fleiss kappa (κ) statistic was used to assess intraobserver and interobserver agreement. Subgroup analyses were performed according to clinicians' specialty (medical oncology, neurosurgery, radiology, orthopedic surgery, and radiation oncology), years of experience, and type of hospital. Intraobserver and interobserver agreement on the location of ESCC was substantial (κ>0.61). Intraobserver agreement on the ESCC score was "excellent" (κ=0.82), whereas interobserver agreement was substantial (κ=0.64). Overall agreement with the tumor board classification was substantial (κ=0.71). Results were similar across specialties, years of experience and hospital category. The ESCC score can help improve communication among clinicians involved in oncology care.


Fetal sex determination of macaque monkeys by a nested PCR using maternal plasma.
Non-invasive fetal sex determination is required for biomedical studies, in which some sexual difference would be expected in fetal events, in order to make a choice of male or female fetus. To detect male fetal DNA of the sex-determining region Y gene (SRY) in maternal macaque plasma, nested real-time PCR using the SYBR Green system was developed. In all cases of pregnant macaques with male fetuses, a nested PCR product of SRY was amplified from the mother's plasma, while no amplicon was detected in any case of pregnancy with a female fetus. Interestingly, fetal SRY DNA appeared to be cleared rapidly from the maternal blood after parturition. The current method is sensitive and can be performed with a regular PCR machine.


Mercury-induced autoimmune glomerulonephritis in inbred rats. I. Kinetics and species specificity of autoimmune responses.
The nephropathy observed in rats after administration of mercuric chloride can be used to clarify the mechanisms underlying renal autoimmunity induced by chemicals. As a necessary preliminary step in the study of this animal model, we have investigated the kinetics and species-specificity of autoimmune responses to renal antigens. By a recently developed enzyme-linked immunosorbent assay (ELISA), circulating autoantibodies to the glomerular basement membrane of the kidney (anti-GBM) have been detected within 8 days after the initiation of mercuric chloride treatment. Anti-GBM antibodies reach a peak by 15 days and then decrease rapidly in the following 2 weeks. Extensive cross-reactions between rat and human GBM antigens have been detected by ELISA, indicating a high degree of conservation of some renal autoantigens and suggesting certain similarities between the autoimmune response induced in rats by mercuric chloride and that observed in human glomerulonephritis caused by anti-GBM. Dose-response studies have been performed to ascertain whether anti-GBM responses are correlated with massive kidney damage and release of renal antigens. We have noted that a wide range of levels of mercuric chloride are capable of stimulating the production of anti-GBM and that animals receiving this chemical in as low a concentration as 0.02 mg/100 g body weight (i.e. a dose ten times lower than those causing massive nephrotoxic effects) still have anti-GBM specifically bound to their kidneys. Thus, it is possible that the administration of mercury compounds to BN rats results in kidney autoimmunity not only because of the release of renal autoantigens, but also through the activation of specific lymphocytes and/or disruption of regulatory networks. Finally, we have observed that both BN and MAXX rats produce anti-GBM after mercuric chloride treatment, while M520 rats do not. Since the MAXX strain was initially obtained from a cross of BN and Lewis rats and shares antigens of the major histocompatibility complex with the BN strain, our findings stress the importance of genetic factors in chemical-induced autoimmunity and suggest that a similar situation may occur in human subjects exposed to environmental chemicals.


[Intraoperative digital radiography for diagnosis of nonpalpable breast lesions].
A procedure for performing intraoperative digital radiography of diagnostic breast specimens directly in the operating suite with teleradiologic assessment by a radiologist is presented. The efficiency of this procedure is compared with that of conventional magnification mammography performed in the radiology department. Thirty-six specimen radiographs obtained by conventional magnification mammography were compared with 38 intraoperative digital magnification radiographs (DIMA Soft P42 prototype, Feinfocus Inc., Garbsen). The radiographs were assessed for lesion conspicuity and time savings for the surgeon, anesthesiologist, and radiologist. The new procedure identified all 38 labeled pathological lesions, and the conventional technique likewise had a detection rate of 100% (36/36). The new technique resulted in considerable time savings for the surgeon and the radiologist. The duration of surgery was shorter and the time interval from removal of the specimen to reporting of the results was reduced from about 23 min to about 13 min. A single radiograph was sufficient for complete visualization of the specimen in all cases. Digital intraoperative specimen radiography considerably reduces the time of surgery depending on the local conditions and is highly accurate in locating a suspicious area within the tissue.


Autonomy, evidence and intuition: nurses and decision-making.
This paper is a report of a study conducted to examine how nurses represent professional clinical decision-making processes, and to determine what light Jamous and Peloille's 'Indeterminacy/Technicality ratio' concept can shed on these representations. Classic definitions of professional work feature autonomy of decision-making and control over the field of work. Sociologists Jamous and Peloille have described professional work as being high in 'indeterminacy' (the use of tacit judgements) relative to technicality (activity able to be codified). The rise of the evidence-based practice movement has been seen as increasing the realm of technical decision-making in healthcare, and it is relevant to analyse nurses' professional discourse and study how they respond to this increase. Three focus groups with qualified nurses attending post-qualifying courses at a London university were held in 2008. Participants were asked to talk about influences on their decision-making. The discussions were tape-recorded, transcribed and subjected to discourse analysis. Participants described their decision-making as influenced by both indeterminate and technical features. They acknowledged useful influences from both domains, but pointed to their personal 'experience' as the final arbiter of decision-making. Their accounts of decision-making created a sense of professional autonomy while at the same time protecting it against external critique. Pre- and post-registration nurse education could encourage robust discussion of the definition and roles of 'irrational' aspects of decision-making and how these might be understood as components of credible professional practice.


Identifying and defining the dimensions of community capacity to provide a basis for measurement.
Although community capacity is a central concern of community development experts, the concept requires clarification. Because of the potential importance of community capacity to health promotion, the Division of Chronic Disease Control and Community Intervention, Centers for Disease Control and Prevention (CDC), convened a symposium in December 1995 with the hope that a consensus might emerge regarding the dimensions that are integral to community capacity. This article describes the dimensions that the symposium participants suggested as central to the construct, including participation and leadership, skills, resources, social and interorganizational networks, sense of community, understanding of community history, community power, community values, and critical reflection. The dimensions are not exhaustive but may serve as a point of departure to extend and refine the construct and to operationalize ways to assess capacity in communities.


Reliability of Pro-adrenomedullin and Interleukin 1β in Predicting Severity of Community-Acquired Pneumonia in Pediatric Patients.
Community-acquired pneumonia (CAP) in children is one of the most important causes of mortality and morbidity in developing countries. Therefore, it is very important for clinicians to detect the presence and severity of pneumonia. Proadrenomedullin (Pro-ADM) and Interleukin-1β (IL-1β) are thought to have potential for CAP evaluation in children. We sought to investigate the value of Pro-ADM and IL-1β levels for severity assessment and outcome prediction in children with CAP. A total of 66 hospitalized CAP patients were included in a prospective observational study. Complete blood count, serum C-reactive protein (CRP), Pro-ADM and IL-1β levels were studied in blood samples obtained from the patients upon admission. Respiratory Clinical Score (RCS) was performed to determine the respiratory distress and severity. The comparison of data with laboratory-severity groups: serum CRP, Pro-ADM and IL-1β levels increased in parallel with the disease severity. Pro-ADM was the best biomarker for severity stratification. Logistic regression analysis revealed that RCS >6 points and Pro-ADM values >1.75 nmol/L combination had the most significant results (OR: 15.38, 95% CI 1.35-166.66, p=0.027). Moreover, a relationship was found between the high serum levels of IL-1β and requirement of intervention procedures in patients with pleural effusion. Serum Pro-ADM and IL-1β levels may offer additional risk/severity stratification in children with CAP. In addition, they may be helpful in predicting the development of complications, requirements for ntensive care unit admission, and intervention procedures.


A Layered Polydiacetylene Containing Hydrogen-Bonding 4,4'-Bipyridyl Guests: Reversible Color Changes with a Wide-Range Temperature Response.
Layered organic polymers have intercalation capabilities and dynamic properties. In classical intercalation chemistry, the interlayer guests are intercalated in the host layers via electrostatic interaction. The present work shows the organic layered materials with the host-guest interlayer interaction via hydrogen bond. Polydiacetylene (PDA) exhibits color changes from blue to red with the application of external stimuli, such as thermal and mechanical stresses. Here we report on a layered PDA containing 4,4'-bipyridyl in the interlayer space as a hydrogen-bonding guest. Whereas the layered PDA without interlayer guest shows the color transition at 65 °C, gradual color changes with two-stage reversibility are observed in the temperature range of -20-240 °C by the introduction of the hydrogen-bonding guest. The weaker interlayer interaction via the hydrogen bond promotes the dynamic motion directing the thermoresponsive color changes in a wide temperature range.


[Novel concepts in biology of diffuse endocrine system: results and future investigations].
Diffuse endocrine system is a largest part of endocrine system of vertebrates. Recend findings showed that DES-cells are not neuroectodermal but have ectodermal, mesodermal, and entodermal ontogeny. The article reviews novel concept of diffuse endocrine system anatomy and physiology, functional role of DES hormones and poorly investigated aspects like DES-cell morphology, hormones secretion in normal and pathologic conditions. Further research of diffuse endocrine system has a great significance for biochemistry, morphology, and clinical medicine.


Best practices for controlled ovarian stimulation in in vitro fertilization.
As applications for IVF have expanded over the years, so too have approaches to controlled ovarian stimulation (COS) for IVF. With this expansion and improved knowledge of basic reproductive biology, there is increasing interest in how COS practice influences IVF outcomes, and whether or not specific treatment scenarios call for personalized approaches to COS. For the majority of women undergoing COS and their treating physicians, the goal is to achieve a healthy live birth through IVF in a fresh cycle. Opinions on how COS strategy best leads to this common goal varies among centers as many clinicians base COS strategy not on evidence obtained through prospective randomized trials, but rather through observational studies and experience. Overall, when it comes to COS most clinicians recognize the approach should not be "one size fits all," but rather a patient-centered approach that takes the existing evidence into consideration. We outline the existing evidence for best practices in COS for IVF, highlighting how these practices may be incorporated into a patient-centered approach.


Identification and functional characterization of Arabidopsis AP180, a binding partner of plant alphaC-adaptin.
Clathrin-mediated endocytosis is a well-studied uptake mechanism for nutrients and signalling receptors in mammalian cells that depends on the coordinated interaction of coat proteins and endocytic network proteins to perform the internalization. In this process AP180 promotes the assembly of clathrin triskelia into coated membrane patches at the plasma membrane, while alpha-adaptin interacts with various network proteins that are in turn required for the budding of the coated pits. The process of clathrin-mediated endocytosis in plants has not been dissected at the molecular level, nor have the members of an analogous uptake machinery been functionally described. In this respect, we have investigated the AP180 and alpha-adaptin orthologs from Arabidopsis thaliana: At-AP180 and At-alphaC-Ad. Both plant proteins display the same structural features as their mammalian counterparts and fulfill the same basic functions. To identify their interacting partners, the ear region of At-alphaC-Ad and the C-terminal region of At-AP180 were used as fusion proteins in pull-down experiments and plasmon-resonance measurements. At-alphaC-Ad binds several mammalian endocytic proteins, and its interaction with At-AP180 requires the DPF motif. At-AP180 functions as a clathrin assembly protein that promotes the formation of cages with an almost uniform size distribution. Deletion of the single DLL motif abolished the assembly activity of At-AP180 almost completely, but did not affect its binding to triskelia, suggesting the existence of additional binding determinants.


A Highly Active Form of XCL1/Lymphotactin Functions as an Effective Adjuvant to Recruit Cross-Presenting Dendritic Cells for Induction of Effector and Memory CD8+ T Cells.
The chemokine receptor XCR1 is known to be selectively expressed by cross-presenting dendritic cells (DCs), while its ligand XCL1/lymphotactin is mainly produced by activated CD8+ T cells and natural killer cells. Recent studies have shown that XCL1-antigen fusion proteins efficiently induce CD8+ T cell responses by preferentially delivering antigens to XCR1+ DCs. However, XCL1 per se was found to be a poor adjuvant for induction of CD8+ T cell responses. XCL1 is unique because of its lack of one of the two disulfide bonds commonly conserved in all other chemokines and thus has an unstable structure with a relatively weak chemokine activity. In the present study, we generated a variant form of murine XCL1 termed mXCL1-V21C/A59C that contained a second disulfide bond to stabilize its chemokine structure. We confirmed that mXCL1-V21C/A59C had much more potent chemotactic and calcium mobilization activities than the wild type XCL1 (mXCL1-WT). Intradermal injection of mXCL1-V21C/A59C, but not that of mXCL1-WT, significantly increased the accumulation of XCR1+CD103+ DCs in the injection site, and most of the accumulated XCR1+CD103+ DCs were found to take up co-injected ovalbumin (OVA). Furthermore, recruited XCR1+CD103+ DCs efficiently migrated to the draining lymph nodes and stayed for a prolonged period of time. Consequently, mXCL1-V21C/A59C strongly induced OVA-specific CD8+ T cells. The combination of OVA and mXCL1-V21C/A59C well protected mice from E.G7-OVA tumor growth in both prophylactic and therapeutic protocols. Finally, memory CTL responses were efficiently induced in mice immunized with OVA and mXCL1-V21C/A59C. Although intradermal injection of OVA and polyinosinic-polycytidylic acid (poly(I:C)) as an adjuvant also induced CD8+ T cell responses to OVA, poly (I:C) poorly recruited XCR1+CD103+ DCs in the injection site and failed to induce significant memory CTL responses to OVA. Collectively, our findings demonstrate that a highly active form of XCL1 is a promising vaccine adjuvant for cross-presenting DCs to induce antigen-specific effector and memory CD8+ T cells.


Adjuvant therapy of pancreatic cancer.
There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This year at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposium, the randomized phase III study presented by Uesaka et al. from Japan (Abstract #145) represents a newer paradigm of oral adjuvant S-1 chemotherapy in place of the traditional standard of care intravenous gemcitabine in terms of prolonging patients' survival. Another study by Fan et al. (Abstract #269) examined the value of targeted therapy using erlotinib with adjuvant chemoradiation and chemotherapy. We present the summary of these two studies and discuss the potential impact on our clinical practice on this highly lethal cancer.


Physician characteristics correlate with hospital readmission rates.
Hospital readmission rates are used as a metric to measure quality patient care. While several tools predict readmissions based on patient-specific characteristics, this study assesses if physician characteristics correlate with hospital readmission rates.In a 5-year retrospective electronic record review at a single institution, 31 internal medicine attending physicians' discharges were tracked for a total of 70 physician years, and 15,933 hospital discharges. Each physician's yearly 7-day, 8 to 30-day, and 30-day readmission rates were compared. Each rate was also correlated with years of post-graduate clinical experience, discharge volume, physician sex, and fiscal year.Individual physicians had significantly different 7-day, 8 to 30-day, and 30-day readmission rates from each other. The rates were not related to sex, years after post-graduate training, or fiscal year. However, physician patient volume correlated with 7-day readmission rates. Physicians who discharged ≤100 patients per year had a higher 7-day readmission rate than physicians who discharged >100 patients per year. This correlation with patient volume did not hold for the 8 to 30-day and 30-day readmission rates.Individual physicians differ in their patient readmission rates in 7-day, 8 to 30-day, and 30-day categories. A critical level of a physician's hospital activity, as reflected by the number of patient discharges per year (>100), results in lower 7-day readmission rates. Sex, post-graduate years of clinical experience, and fiscal year did not play a role. The lack of correlation between each physicians' 7-day and 8 to 30-day readmission rates suggests that different physician factors are involved in these 2 rates.


beta-Adrenergic receptor activation induces internalization of cardiac Cav1.2 channel complexes through a beta-arrestin 1-mediated pathway.
Voltage-dependent calcium channels (VDCCs) play a pivotal role in normal excitation-contraction coupling in cardiac myocytes. These channels can be modulated through activation of beta-adrenergic receptors (beta-ARs), which leads to an increase in calcium current (I(Ca-L)) density through cardiac Ca(v)1 channels as a result of phosphorylation by cAMP-dependent protein kinase A. Changes in I(Ca-L) density and kinetics in heart failure often occur in the absence of changes in Ca(v)1 channel expression, arguing for the importance of post-translational modification of these channels in heart disease. The precise molecular mechanisms that govern the regulation of VDCCs and their cell surface localization remain unknown. Our data show that sustained beta-AR activation induces internalization of a cardiac macromolecular complex involving VDCC and beta-arrestin 1 (beta-Arr1) into clathrin-coated vesicles. Pretreatment of myocytes with pertussis toxin prevents the internalization of VDCCs, suggesting that G(i/o) mediates this response. A peptide that selectively disrupts the interaction between Ca(V)1.2 and beta-Arr1 and tyrosine kinase inhibitors readily prevent agonist-induced VDCC internalization. These observations suggest that VDCC trafficking is mediated by G protein switching to G(i) of the beta-AR, which plays a prominent role in various cardiac pathologies associated with a hyperadrenergic state, such as hypertrophy and heart failure.


[Methodology to forecast risk of toxic effects caused by contemporary household chemicals].
The article contains to forecast risk of toxic effects caused by contemporary household chemicals. The article contains data on evaluating potential risk of health disorders among individuals contacting synthetic detergents and cleansers. The authors summarized experience of Public Health Research center on toxicologic hygienic research of various household chemicals, conducted for safety certification of the end products household application.


OnabotulinumtoxinA for treatment of focal cancer pain after surgery and/or radiation.
To report the relief from refractory focal post-radiation and/or postsurgical cancer pain after local treatment with onabotulinumtoxinA. We studied the effect of onabotulinumtoxinA in seven cancer patients who suffered from severe focal pain (visual analog scale >5) at the site of local surgery or radiotherapy or both. OnabotulinumtoxinA (20-100 units) was injected into the focal pain areas (skin or muscle or both). Five of seven patients were followed beyond 1 year (1.5-5 years) with repeat treatment. All seven patients reported a significant improvement in pain (mean drop in visual analog scale score of 5.1). They described their response on the patient global assessment as satisfactory (two patients) or very satisfactory (five patients). Six of seven patients found the pain relief associated with significant improvement in quality of life. One patient developed weakness of jaw muscles after bilateral masseter injection that was not observed during second injection (reduced dose). Improvements with treatment persisted with repeat injections during long-term follow-up (five patients). Local treatment with onabotulinumtoxinA can significantly reduce pain and improve quality of life in cancer patients suffering from pain in the area of surgery and radiation and was well tolerated in cancer patients.


The effect of scenario-based training on the Core competencies of nursing students: a semi-experimental study.
Competency is defined as the variety of skills and knowledge required to perform a specific task. Due to the specificity of pediatric nursing, students face some challenges in acquiring core competencies. Therefore, the use of new training methods in pediatric nursing is necessary. One of the modern learning methods is learning based on clinical scenarios. Thus, this study aimed to investigate the effect of scenario-based education on the core competencies of nursing students. This quasi-experimental study employed a pre-test and post-test design. All participants (n = 72) were selected via the census method and randomly divided into intervention (N = 33) and control groups (N = 40). The data were collected using a demographic information questionnaire and the Nursing Students' Clinical Competencies Questionnaire. Before the intervention, both groups completed the pre-tests. After one month, the students in both groups completed post-tests. The average score of core competencies for the students in the intervention group after the training (247.05, SD = 36.48) increased compared to before the intervention (229.05, SD = 36.58) (P > 0.05). The average score of the core competencies for the students in the control group after the training was 240.76 (SD = 35.36) compared to 235.56 (SD = 27.94) before the intervention, with no significant difference (P < 0.05). The independent t-test did not show a significant difference between the control and intervention groups before and after the intervention (P > 0.05). The results indicated the effectiveness of scenario-based training on the core competencies of students in the intervention group. Accordingly, nursing administrators and professors are recommended to incorporate new scenario-based teaching and learning methods in educational programs of universities. It is also necessary to conduct more research into the effectiveness of this method in combination with other training methods like team-based and problem-based training.


Cocaine Use and Levamisole-Induced Vasculitis: A Multiple Case Study.
Levamisole is an immunomodulatory medication previously used to treat rheumatoid arthritis and some types of cancers; it was banned for use in humans in 2000 owing to its harmful side effects. Use of levamisole-laced cocaine is associated with a life-threatening syndrome characterized by a necrotizing purpuric rash leading to tissue destruction and necrotic wounds. This Clinical Challenges article summarizes our experience with the care of 2 adult women diagnosed with levamisole-related vasculitis. Case 1 is a 46-year-old woman who presented with joint pain in her hands and legs, along with bilateral ear pain, swelling, and bleeding. She was initially diagnosed with vasculitis and possible systemic lupus erythematosus. She experienced multiple recurrences and exacerbation of her condition over a period of months. She was ultimately diagnosed with levamisole-related vasculitis from recurrent cocaine use resulting in bilateral above the knee amputations. The second case is a 50-year-old woman who presented to our emergency department with redness and swelling of her bilateral lower extremities. She developed blisters and pustules that rapidly evolved into abscesses and red lesions over the course of several months. Her wounds also deteriorated despite topical therapy that occurred in a context of recurring use of cocaine. Our experience with these cases suggests that WOC nurses should consider levamisole-induced vasculitis in all patients presenting with unexplained vasculitis-type lesions, and particularly when these lesions occur in the context of known or suspected use of illicit substances such as cocaine. Given the absence of clinical guidelines for this increasingly prevalent condition, we recommend wound care based on principles of moist wound healing, combined with judicious use of therapies with antimicrobial activity and nonadherent dressings to reduce pain. Finally, we strongly recommend that care of these patients occurs as one part of a multidisciplinary care approach that focuses on cessation of the use of cocaine and all other illicit substances.


Prevalence of sleep disturbance in chronic pain.
Sleep is a vital function for human beings, which can be affected by several factors. Chronic pain is one of these factors where it is the most frequent cause for seeking medical care in combination with insomnia. The aim of this study is to examine the prevalence and relationship between sleep disturbance and chronic pain. After approval, a total of 85 Family Medicine Units from over 170 in Tokat were randomly selected using a 50% sampling. A sample of 2635 subjects, over the age of 19 years, who were registered with the selected Family Medicine Units, were assessed due to gender, age group, and the urban/rural population size of Tokat using the stratified sampling method. The sample size distribution was calculated as 1515 urban subjects, 1120 rural subjects; 1345 female subjects, 1290 male subjects; 1123 subjects between 20-39 years of age, 1103 subjects between the ages of 40-64, and 409 subjects over 64 years of age. After sampling, subjects were invited to participate in the study via an invitation letter, and agreeing individuals were taken to the Family Medicine Unit for face-to-face meetings. Written, informed consent was obtained, along with demographic data. The presence of chronic pain was recorded. According to the presence of chronic pain, all subjects were separated into two groups as Group Chronic Pain and Group Non-Chronic Pain. The visual analog scale for pain intensity, and Pittsburgh Sleep Quality Index for sleep quality, were performed with all subjects. A multiple linear regression model was used to assess the predictors of sleep quality. Analyses were conducted using the Statistical Package for Social Sciences program (SPSS Inc., Chicago, IL, USA), version 20.0. The statistical significance for all analyses was set at p < 0.05. The mean global Pittsburgh Sleep Quality Index score of Group Chronic Pain (5.30 ± 4.29) was significantly higher than in Group Non-Chronic Pain (3.22 ± 3.30; p < 0.01). The mean Pittsburgh Sleep Quality Index scores of females (5.69 ± 4.40) were significantly higher than males (4.54 ± 3.96) in Group Chronic Pain (p = 0.000045). A total of 40.7% of patients in Group Chronic Pain, and 21.9% in Group Non-Chronic Pain demonstrated poorer sleep quality according to the Pittsburgh Sleep Quality Index scores, with a cut-off level > 5. A moderate positive correlation was found between the global Pittsburgh Sleep Quality Index and Visual Analog Scale scores (r = 0.310, p < 0.01). A multiple linear regression analysis showed that age, gender, income, Visual Analog Scale, and presence of depression were the significant predictors for Pittsburgh Sleep Quality Index score. The current study revealed that chronic pain and pain intensity are important predictors of sleep quality.


[Clinical aspects of acute circulatory disorders in open-heart operations].
An analysis of 705 open-heart operations under extracorporeal circulation for acquired and congenital valvular defects is presented. Acute circulatory disorders (ACD) were diagnosed on the basis of combined hemodynamic, metabolic and clinical findings. The mechanisms of ACD developing at open-heart operations are always multifarious. The hemodynamic pattern is conditioned by narcosis, extracorporeal circulation, cardiac manipulations and myocardial injury, blood loss, the interference with the patient's internal environment, etc. Reduced myocardial contractility and the cardiac index diminished below 2.2 l/m2/minute are stable features associated with ACD. Characteristically, systemic peripheral resistance shows no compensatory increase in some ACD cases or is reduced significantly due to narcotic vasoplegia or allergic vascular response. Reduced venous return to the heart due to reduced vascular volume and increased vascular bed capacity is sometimes masked by reduced myocardial contractility, as manifested in an increase of diastolic heart-filling parameters (right atrial pressure, occlusion pressure), which is, however, unevenly distributed between the right and left departments of the heart, a fact not to be ignored in the diagnosis. In 70% of the cases, ACD correspond to various rhythm disorders which can be of primary importance. Dynamic patterns of various parameters (atrial blood pressure, right atrial pressure, occlusion pressure, heart rate, ECG, venous HbO2, etc.) are more important in the assessment of circulation compared to absolute values. The treatment of ACD should be combined to include the best anesthetic method, the control of myocardial contractility and volume, heart rate, vascular tone and various internal environmental parameters (pulmonary gaseous exchange, acid-base balance, electrolytic balance etc.), and also antiallergic therapy. Catecholamines are effective in particularly severe cases.


Effects of group therapy on parents of children with cancer.
Group therapy for parents of children with cancer has been suggested as a means of relieving stress. This quasi-experimental study sought to determine the effect of participation in a support group for parents of children aged 10 to 14 years with cancer. Parents completed the Wallston Health Locus of Control (HLOC) Scale and the Social Adjustment Scale-Self Report (SAS-SR) both before and following seven group sessions. Descriptive data were collected from the cotherapists' process log and the participants' evaluation. A significant t test score (P = .017) was obtained for the HLOC Scale questionnaire. The group process log showed recurrent themes of helplessness and powerlessness. The Parent Support Group Evaluation (PSGE) developed by the researchers, demonstrated satisfaction and revealed that school and community activities were considered the most helpful. Tentative conclusions support the value of such a group in providing a forum for the parents to discuss concerns and decrease their sense of isolation. However, more study is needed with a larger sample before definitive conclusions can be reached.


High-yield production of functionally active human serum transferrin using a baculovirus expression system, and its structural characterization.
Recently, there has been much interest in expressing recombinant human serum transferrin (HST) and mutants thereof for structural and functional studies. We have developed a baculovirus expression system for the rapid and efficient production of large quantities of HST (> 20 mg/l). Like native HST, the recombinant protein can bind two ferric ions in the presence of bicarbonate, and is actively taken up by receptor-mediated endocytosis. Secondary structure calculations from CD measurements indicate a content of 42% alpha-helix and 28% beta-sheet. This is the first reported use of a non-mammalian expression system to produce functional HST, and will provide a practical tool to allow expression of a wide range of HST variants for mutagenesis studies.