ESWL for difficult bile duct stones: a 15-year single centre experience.
To evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) for the management of refractory bile duct cholelithiasis in a third level referral centre. The clinical records of all patients treated with a second generation electromagnetic lithotripter (Lithostar Plus, SIEMENS) from October 1990 to April 2005 were evaluated. All patients were monitored during the procedure and antibiotics were administered in case of cholangitis. The chi(2) test and logistic regression analysis were performed as appropriate. Two hundred and fourteen patients (102 males, 112 females; mean age 74.8 +/- 0.84 years--single stone 97, multiple stones 117) underwent ESWL. The mean number of sessions and shock waves were 3.5 +/- 0.13 and 3477.06 +/- 66.17, respectively. The maximum stone size was 5 cm. Complete stone clearance was achieved in 192 (89.7%) patients. Of the remaining patients 15 required surgery, 2 a palliative stent and in 5 patients stone fragmentation led to effective bile drainage with clinical resolution despite incomplete clearance. Age, sex and stone characteristics were not related to treatment outcome. Major complications occurred in two patients (haemobilia and rectal bleeding) and minor complications in 25 (3 vomiting, 22 arrhythmias). No procedure-related deaths occurred. ESWL is a safe and effective technique for clearance of refractory bile duct stones.


[Changes of prevalence of hypertension and blood pressure levels in 1061 adults in Chengdu from 1992 to 2007].
To investigate the changes of blood pressure (BP) levels of a general population in Chengdu, China from 1992 to 2007. A baseline survey on CVD risk factors was carried out in a general population of Chengdu in 1992. A total of 1365 adults aged 35-64 years were recruited randomly. In 2007, 1061 of the participants completed a follow up survey. 1) The systolic blood pressure (SBP) levels increased with age in both men and women, and larger increase was found in older people. The diastolic blood pressure (DBP) levels also increased with age, however, the smallest increase was found in the age group of 45 to 54 years. 2) People of 50-64 years old in 2007 had higher SBP than those of the same age in 1992. Similar changes were also found for DBP in men, but not in women. 3) From 1992 to 2007, the prevalence of hypertension increased in all of the age groups. The greater increase occurred in the younger population. 4) During the 15 years, the prevalence of hypertension increased from 13.2% to 51.2% in men, and from 14.0% to 45.1% in women. People of 50-64 years old had higher prevalence of hypertension in 2007 than those of the same age in 1992. SBP and DBP increase with age, and younger people have larger increase than older people. The prevalence of hypertension increases with age, and the greater increase also occurred in younger people. In people with the same age of 50-64 years, the prevalence of hypertension and SBP and DBP levels are higher in 2007 than in 1992, except for DBP in women.


A rapid and reliable flow cytometric routine method for counting leucocytes in leucocyte-depleted platelet concentrates.
To ensure a proper quality control it is important to use a reliable method to count low numbers of leucocytes in leucocyte-reduced platelet concentrates (PCs). A modified flow cytometric method for counting low numbers of leucocytes, based on a reference population contained in tubes with an exact number of fluorescent beads and staining with propidium iodide was used. To increase the number of events, the original sample volume was increased. There was a good correlation in the number of leucocytes (r = 0.99) between the modified flow cytometric method and microscopy of samples from unfiltered and expected numbers from serially diluted PCs. Samples from leucocyte-reduced PCs obtained by apheresis or filtered buffy coats showed no correlation between results from the modified flow cytometric method and microscopy (Nageotte). Counting by microscopy gave a lower number of leucocytes than the modified flow cytometric method when counting a low number of cells. However, analysis of the serially diluted PCs proved that the modified flow cytometric method was reliable and rapid, making it suitable for clinical routine use.


Therapeutic Yoga for the Management of Chronic Nonspecific Neck Pain: Current Evidence and Mechanisms.
Chronic nonspecific neck pain (CNNP), which is neck pain in the absence of attributable structural and neurological findings, is often challenging for medical and rehabilitation professionals to treat. Conventional treatments such as medications and physical therapy often fail to provide lasting relief, which leads patients to pursue complementary therapies such as yoga. This review discusses the evidence from nine studies, including four randomized controlled trials, which suggests that a supervised yoga program may decrease pain intensity, disability, and mood symptoms in adults with CNNP. Cervical range of motion and quality of life (both physical and mental) may also improve with yoga intervention, although this is less consistent across studies. Evidence of yoga's superiority to other exercise-based practices such as pilates was conflicting. Adverse effects of yoga, such as exacerbation of neck pain, were relatively uncommon, minor, and often transient. This article also comprehensively reviews the pathophysiology of CNNP, therapeutic mechanisms of yoga, and limitations in the evidence (including risk-of-bias assessment). Future studies should attempt to: (1) compare the effectiveness of different lineages of yoga for individuals with CNNP, (2) determine the optimal length and duration of these yoga interventions, (3) better characterize the physical and psychological mechanisms of yoga, (4) compare yoga to other exercise- and mindfulness-based practices, (5) evaluate the effect of yoga on sleep in the CNNP population, and (6) explore the applicability/efficacy of virtual yoga instruction.


Sulfonated glycosaminoglycan bioinspired carbon dots for effective cellular labelling and promotion of the differentiation of mesenchymal stem cells.
Although carbon dots (CDs) have been synthesized and applied in a variety of biological fields, such as disease diagnosis and gene/drug delivery, the exploration of facile bioinspired synthesis and applications of CDs is still of great significance. Particularly, recent increasing research has clearly confirmed that nanomaterials can affect a series of physiological behaviors and functions of mesenchymal stem cells (MSCs) (e.g., differentiation and pluripotency). Therefore, it is very important to develop multifunctional nanomaterials to simultaneously realize the cellular labelling and regulation of MSC behaviors in practical applications. Herein, sulfonated glycosaminoglycan-bioinspired CDs as bi-functional nanomaterials were ingeniously designed for cellular imaging and promoting the differentiation of rat bone MSCs (rBMSCs) in different culture media, which simultaneously met the two fundamental requirements in the field of MSC-based treatments (e.g., precisely directing the differentiation of MSCs and effective cellular labeling). These bifunctional CDs were successfully prepared via one-pot hydrothermal synthesis by using d-glucosamine hydrochloride (GA·HCl) and sodium p-styrenesulfonate (NaSS) as the reactants. The synthesized CDs with a uniform particle size (around 4 nm) dispersed well in aqueous solutions and exhibited remarkable fluorescence stability under different conditions. Additionally, cell viability and proliferation results demonstrated that the CDs possessed good biocompatibility, having negligible effects on the self-renewal potential of rBMSCs. The as-prepared CDs presented a cytoplasmatic distribution after being ingested by rBMSCs; thus, they are particularly suitable for cellular imaging. More importantly, the addition of CDs to osteogenic and chondrogenic induction media (OIM and CIM), respectively, was capable of effectively promoting the osteogenic and chondrogenic differentiation of rBMSCs due to the generation of reactive oxygen species (ROS) while having no influence on their pluripotency. In brief, this study not only implements a cellular labeling method based on CDs that were synthesized by a biomimicking strategy, but also paves a new way to regulate the differentiation of MSCs by designing multifunctional nanomaterials; this will enable the extensive development of facile synthesis methods and new applications of CDs and will also provide some research foundations for MSC-based fields.


Risk of meningioma and common variation in genes related to innate immunity.
The etiology of meningioma, the second most common type of adult brain tumor in the United States, is largely unknown. Prior studies indicate that history of immune-related conditions may affect the risk of meningioma. To identify genetic markers for meningioma in genes involved with innate immunity, we conducted an exploratory association study of 101 meningioma cases and 330 frequency-matched controls of European ancestry using subjects from a hospital-based study conducted by the National Cancer Institute. We genotyped 1,407 "tag" single nucleotide polymorphisms (SNP) in 148 genetic regions chosen on the basis of an r2>0.8 and minor allele frequency of >5% in Caucasians in HapMap1. Risk of meningioma was estimated by odds ratios and 95% confidence intervals. Seventeen SNPs distributed across 12 genetic regions (NFKB1 (3), FCER1G (3), CCR6 (2), VCAM1, CD14, TNFRSF18, RAC2, XDH, C1D, TLR1/TLR10/TLR6, NOS1, and DEFA5) were associated with the risk of meningioma with P<0.01. Although individual SNP tests were not significant after controlling for multiple comparisons, gene region-based tests were statistically significant (P<0.05) for TNFRSF18, NFKB1, FCER1G, CD14, C1D, CCR6, and VCAM1. Our results indicate that common genetic polymorphisms in innate immunity genes may be associated with risk of meningioma. Given the small sample size, replication of these results in a larger study of meningioma is needed.


Antagonism of norepinephrine by clonidine in the isolated rat mesenteric vascular bed.
Experiments were done in isolated, perfused mesenteric vascular beds from Sprague-Dawley rats. Bolus injections of norepinephrine (3-100 nmol) induced dose-dependent increases in perfusion pressure with a maximum increase greater than 100 mm Hg. In the same dose range, clonidine had no effect on perfusion pressure. In the presence of an elevated pressure caused by constant infusions of norepinephrine (6-20 microM), bolus injections of clonidine (0.1-10 nmol) or acetylcholine (0.007-7 nmol) caused dose-related decreases in perfusion pressure. Procedures which damage endothelium (brief exposure to methylene blue or reactive oxygen radicals) abolished the depressor action of acetylcholine but only moderately reduced the depressor action of clonidine. The depressor action of clonidine was not antagonized by the alpha-2 adrenoceptor antagonist, idazoxan. Acetylcholine produced depressor responses in the presence of 5-hydroxy-tryptamine or vasopressin, but clonidine did not. Dose-response curves to bolus doses of norepinephrine were shifted markedly to the right by an alpha-1 selective concentration of prazosin (1 nM) and were shifted to the right with depression of maximum by infusions of clonidine (0.3 and 1.0 microM). It is concluded that, in the mesenteric vasculature of the rat: 1) the role of alpha-2 adrenoceptors, in responses to clonidine, is minimal; 2) endothelial factors play little role, if any, in the depressor effects of clonidine and 3) clonidine has a potent ability to interfere with the alpha-1 adrenoceptor-mediated vasoconstriction induced by norepinephrine. This antagonistic action may be at the level of the receptor but could involve postreceptor steps.


Real-time monitoring unsafe behaviors of portable multi-position ladder worker using deep learning based on vision data.
Fatal fall from height accidents, especially on construction sites, persist, underscoring the importance of monitoring and managing worker behaviors to enhance safety. Deep learning showed the possibility of substituting the manual work of safety managers. However, applying detection results to determine compliance with safety regulations has limitations. This study estimated the actual working height depending on the height of the object detection bounding box by specifying the consistent hinge part as a target marker based on ladder manufacturing regulations. Furthermore, an attempt was made to improve the separation between workers, coworkers, and persons unconnected to ladder activities by applying an optimized loss function alongside an attention mechanism. The experimental results showed that an average precision increased from 87.60% to 90.44%. The performance of the monitoring unsafe behavior of ladder worker following the Korea Occupational Safety and Health Agency (KOSHA) guide was evaluated by 91.40 F1-Score, which accumulated sorted according to the working height. Experimental results show the feasibility of the real-time automate safety monitoring in ladder work. By linking the estimated working height and deep learning multi-detection results to established safety regulations, the proposed method shows the potential to automatically monitoring unsafe behaviors in construction site.


Protein-templated gold nanoclusters as specific bio-imaging probes for the detection of Hg(ii) ions in in vivo and in vitro systems: discriminating between MDA-MB-231 and MCF10A cells.
Gold nanoclusters (AuNCs) synthesized within a protein (Human Serum Albumin, HSA) template exhibited intense red luminescence accompanied by a quantum yield >10% and remarkable photo and cluster-core stability for a prolonged period (more than a year). These photoluminescent nanoclusters (NCs) were resistant to chemical and thermal perturbations but break down selectively and highly sensitively in the presence of mercury, Hg(ii), ions. The AuNCs were efficient in quantifying Hg(ii) ions in solution as well as bound to the hormone insulin. By exploiting the auto-fluorescence of these AuNCs, we demonstrated that our AuNCs were able to sense Hg(ii) ions at single-molecule sensitivity using Fluorescence Correlation Spectroscopy (FCS), highlighting a detection limit in the sub-nanomolar regime. The translational diffusion time of the AuNCs decreased significantly upon the interaction with Hg(ii) ions and resulted in the formation of smaller sized clusters. A cell viability study reveals the non-toxic nature of these nano-probes, which thus can be used for cell imaging. Interestingly, a cell line-based study reveals that the fluorescence intensity of AuNCs could be detected in cancerous MDA-MB-231 cells but not in non-cancerous breast-derived MCF10A cells. Further, time lapse fixed cell imaging by confocal microscopy revealed that the fluorescence of AuNCs could be quenched by Hg(ii) ions inside the MDA-MB-231 cells. Thus the objective of our study is to appraise the sensitive in vivo as well as in vitro detection of Hg(ii) ions using AuNCs as a probe.


Antibacterial activity of Thymoquinone, an active principle of Nigella sativa and its potency to prevent bacterial biofilm formation.
Thymoquinone is an active principle of Nigella sativa seed known as "Habbah Al-Sauda" in Arabic countries and "Sinouj" in Tunisia. Bacterial biofilms tend to exhibit significant tolerance to antimicrobials drugs during infections. The antibacterial activity of Thymoquinone (TQ) and its biofilm inhibition potencies were investigated on 11 human pathogenic bacteria. The growth and development of the biofilm were assessed using the crystal violet (CV) and the 2, 3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. TQ exhibited a significant bactericidal activity against the majority of the tested bacteria (MICs values ranged from 8 to 32 μg/ml) especially Gram positive cocci (Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis CIP 106510). Crystal violet assay demonstrated that the minimum biofilm inhibition concentration (BIC50) was reached with 22 and 60 μg/ml for Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis CIP 106510 respectively. In addition our data revealed that cells oxidative activity was influenced by TQ supplementation. In the same way, TQ prevented cell adhesion to glass slides surface. The ability of TQ to prevent biofilm formation warrants further investigation to explore its use as bioactive substances with antibiofilm potential.


Sleep disorderd breathing and recurrence of cerebrovascular events, case-fatality, and functional outcome in patients with ischemic stroke or transient ischemic attack.
Ninety one patients with stroke or transient ischemic attack (TIA) were screened for sleep-disordered breathing (SDB). Case fatality, rate of recurrence of cerebrovascular events, and functional outcome were analyzed during a 2-year follow-up. The patients were stratified into groups: without (AH < or =5) and with SDB (AHI >5). SDB was present in 61 (67.7%) patients with stroke or TIA. The rate of recurrence of TIA or stroke in patients with SDB was significantly higher (12 patients, OR=1.52, P<0.05) as compared with patients without SDB (3 patients) within two years of observation. Case-fatality rates were not significantly different (4 patients with SDB and 2 patients without SDB). Our data show that SDB significantly increases the incidence of recurrent cerebrovascular events in patients with TIA or stroke in a two-year follow-up. SDB in patient with stroke or TIA did not influence functional outcome of stroke during the long-term observation.


Association of spectrin-like proteins with the actin-organized aggregate of endoplasmic reticulum in the Spitzenkörper of gravitropically tip-growing plant cells.
Spectrin-like epitopes were immunochemically detected and immunofluorescently localized in gravitropically tip-growing rhizoids and protonemata of characean algae. Antiserum against spectrin from chicken erythrocytes showed cross-reactivity with rhizoid proteins at molecular masses of about 170 and 195 kD. Confocal microscopy revealed a distinct spherical labeling of spectrin-like proteins in the apices of both cell types tightly associated with an apical actin array and a specific subdomain of endoplasmic reticulum (ER), the ER aggregate. The presence of spectrin-like epitopes, the ER aggregate, and the actin cytoskeleton are strictly correlated with active tip growth. Application of cytochalasin D and A23187 has shown that interfering with actin or with the calcium gradient, which cause the disintegration of the ER aggregate and abolish tip growth, inhibits labeling of spectrin-like proteins. At the beginning of the graviresponse in rhizoids the labeling of spectrin-like proteins remained in its symmetrical position at the cell tip, but was clearly displaced to the upper flank in gravistimulated protonemata. These findings support the hypothesis that a displacement of the Spitzenkörper is required for the negative gravitropic response in protonemata, but not for the positive gravitropic response in rhizoids. It is evident that the actin/spectrin system plays a role in maintaining the organization of the ER aggregate and represents an essential part in the mechanism of gravitropic tip growth.


Fe3 O4 nanozyme coating enhances light-driven biohydrogen production in self-photosensitized Shewanella oneidensis-CdS hybrid systems.
Solar-driven biohybrid systems that produce chemical energy are a valuable objective in ongoing research. However, reactive oxygen species (ROS) that accompany nanoparticle production under light radiation severely affect the efficiency of biohybrid systems. In this study, we successfully constructed a two-hybrid system, Shewanella oneidensis-CdS and S. oneidensis-CdS@Fe3 O4 , in a simple, economical, and gentle manner. With the Fe3 O4 coating, ROS were considerably eliminated; the hydroxyl radical, superoxide radical, and hydrogen peroxide contents were reduced by 66.7%, 65.4%, and 72%, respectively, during light-driven S. oneidensis-CdS hydrogen production. S. oneidensis-CdS@Fe3 O4 showed a 2.6-fold higher hydrogen production (70 h) than S. oneidensis-CdS. Moreover, the S. oneidensis-CdS system produced an additional 367.8 μmol g-dcw-1 (70 h) of hydrogen compared with S. oneidensis during irradiation. The apparent quantum efficiencies of S. oneidensis-CdS and S. oneidensis-CdS@Fe3 O4 were 6.2% and 11.5%, respectively, exceeding values previously reported. In conclusion, a stable nanozyme coating effectively inhibited the cytotoxicity of CdS nanoparticles, providing an excellent production environment for bacteria. This study provides a rational strategy for protecting biohybrid systems from ROS toxicity and contributes to more efficient solar energy conversion in the future.


Hypertension, perceived clinician empathy, and patient self-disclosure.
The purpose of this study was to compare groups of outpatient hypertensive and diabetic patients to a control group (no known chronic illnesses) on their perceptions of clinician empathy and the importance and difficulty of disclosing information about themselves to health care providers. It was hypothesized that hypertensives would differ from the other groups in perceiving less clinician empathy and in attributing less importance, but greater difficulty, to self-disclosing. The sample was 54 hypertensives, 47 diabetics, and 115 nonchronically ill patients. Each subject completed the Empathy scale of the Barrett-Lennard Relationship Inventory and a patient self-disclosure questionnaire. The empathy hypothesis was supported but the self-disclosure hypotheses were not. Hypertensive patients differed from other patients in perceiving the least clinician empathy and in attributing the greatest importance to discussing their responses to health care.


Chromosomal evolution and patterns of introgression in helianthus.
Knowledge of the nature and extent of karyotypic differences between species provides insight into the evolutionary history of the genomes in question and, in the case of closely related species, the potential for genetic exchange between taxa. We constructed high-density genetic maps of the silverleaf sunflower (Helianthus argophyllus) and Algodones Dune sunflower (H. niveus ssp. tephrodes) genomes and compared them to a consensus map of cultivated sunflower (H. annuus) to identify chromosomal rearrangements between species. The genetic maps of H. argophyllus and H. niveus ssp. tephrodes included 17 linkage groups each and spanned 1337 and 1478 cM, respectively. Comparative analyses revealed greater divergence between H. annuus and H. niveus ssp. tephrodes (13 inverted segments, 18 translocated segments) than between H. annuus and H. argophyllus (10 inverted segments, 8 translocated segments), consistent with their known phylogenetic relationships. Marker order was conserved across much of the genome, with 83 and 64% of the H. argophyllus and H. niveus ssp. tephrodes genomes, respectively, being syntenic with H. annuus. Population genomic analyses between H. annuus and H. argophyllus, which are sympatric across a portion of the natural range of H. annuus, revealed significantly elevated genetic structure in rearranged portions of the genome, indicating that such rearrangements are associated with restricted gene flow between these two species.


Category Learning Stretches Neural Representations in Visual Cortex.
We review recent work that shows how learning to categorize objects changes how those objects are represented in the mind and the brain. After category learning, visual perception of objects is enhanced along perceptual dimensions that were relevant to the learned categories, an effect we call dimensional modulation (DM). DM stretches object representations along category-relevant dimensions and shrinks them along category-irrelevant dimensions. The perceptual advantage for category-relevant dimensions extends beyond categorization and can be observed during visual discrimination and other tasks that do not depend on the learned categories. fMRI shows that category learning causes ventral stream neural populations in visual cortex representing objects along a category-relevant dimension to become more distinct. These results are consistent with a view that specific aspects of cognitive tasks associated with objects can account for how our visual system responds to objects.


Hepatitis C virus NS5A binds to the mRNA cap-binding eukaryotic translation initiation 4F (eIF4F) complex and up-regulates host translation initiation machinery through eIF4E-binding protein 1 inactivation.
Initiation, a major rate-limiting step of host protein translation, is a critical target in many viral infections. Chronic hepatitis C virus (HCV) infection results in hepatocellular carcinoma. Translation initiation, up-regulated in many cancers, plays a critical role in tumorigenesis. mTOR is a major regulator of host protein translation. Even though activation of PI3K-AKT-mTOR by HCV non-structural protein 5A (NS5A) is known, not much is understood about the regulation of host translation initiation by this virus. Here for the first time we show that HCV up-regulates host cap-dependent translation machinery in Huh7.5 cells through simultaneous activation of mTORC1 and eukaryotic translation initiation factor 4E (eIF4E) by NS5A. NS5A, interestingly, overexpressed and subsequently hyperphosphorylated 4EBP1. NS5A phosphorylated eIF4E through the p38 MAPK-MNK pathway. Both HCV infection and NS5A expression augmented eIF4F complex assembly, an indicator of cap-dependent translation efficiency. Global translation, however, was not altered by HCV NS5A. 4EBP1 phosphorylation, but not that of S6K1, was uniquely resistant to rapamycin in NS5A-Huh7.5 cells, indicative of an alternate phosphorylation mechanism of 4EBP1. Resistance of Ser-473, but not Thr-308, phosphorylation of AKT to PI3K inhibitors suggested an activation of mTORC2 by NS5A. NS5A associated with eIF4F complex and polysomes, suggesting its active involvement in host translation. This is the first report that implicates an HCV protein in the up-regulation of host translation initiation apparatus through concomitant regulation of multiple pathways. Because both mTORC1 activation and eIF4E phosphorylation are involved in tumorigenesis, we propose that their simultaneous activation by NS5A might contribute significantly to the development of hepatocellular carcinoma.


Casein kinase II-mediated phosphorylation of general repressor Maf1 triggers RNA polymerase III activation.
Maf1 protein is a global negative regulator of RNA polymerase (Pol) III transcription conserved from yeast to man. We report that phosphorylation of Maf1 by casein kinase II (CK2), a highly evolutionarily conserved eukaryotic kinase, is required for efficient Pol III transcription. Both recombinant human and yeast CK2 were able to phosphorylate purified human or yeast Maf1, indicating that Maf1 can be a direct substrate of CK2. Upon transfer of Saccharomyces cerevisiae from repressive to favorable growth conditions, CK2 activity is required for the release of Maf1 from Pol III bound to a tRNA gene and for subsequent activation of tRNA transcription. In a yeast strain lacking Maf1, CK2 inhibition showed no effect on tRNA synthesis, confirming that CK2 activates Pol III via Maf1. Additionally, CK2 was found to associate with tRNA genes, and this association is enhanced in absence of Maf1, especially under repressive conditions. These results corroborate the previously reported TFIIIB-CK2 interaction and indicate an important role of CK2-mediated Maf1 phosphorylation in triggering Pol III activation.


Early chimerism threshold predicts sustained engraftment and NK-cell tolerance in prenatal allogeneic chimeras.
The failure of engraftment in human cases of in utero hematopoietic cell transplantation (IUHCT) in which no immunodeficiency exists suggests the presence of an unrecognized fetal immune barrier. A similar barrier in murine IUHCT appears to be dependent on the chimerism level and is poorly explained by a lack of T-cell tolerance induction. Therefore, we studied the effect of the chimerism level on engraftment and host natural killer (NK)-cell education in a murine model of IUHCT. The dose of transplanted cells was found to exhibit a strong correlation with both the engraftment rate and chimerism level. More specifically, a threshold level of initial chimerism (> 1.8%) was identified that predicted durable engraftment for allogeneic IUHCT, whereas low initial chimerism (< 1.8%) predicted a loss of engraftment. NK cells taken from chimeras above the "chimerism threshold" displayed durable calibration of alloresponsive Ly49A receptors and tolerance to donor antigens. Depletion of recipient NK cells stabilized engraftment in low-level chimeras (< 1.8%). These studies illustrate the importance of the early chimerism threshold in predicting long-term engraftment and host NK-cell tolerance after in utero transplantation.


Change in Carotid Plaque Components: A 4-Year Follow-Up Study With Serial MR Imaging.
The goal of this study was to determine how carotid plaque components (e.g., intraplaque hemorrhage [IPH], calcification, lipid core) change over time and which cardiovascular risk factors are associated with the development of each component. Carotid atherosclerotic plaque components are important markers of plaque vulnerability. How these components change and which factors lead to the development and changes in the components remain unclear. A total of 198 participants (mean age 67.5 ± 10.6 years) from the population-based Rotterdam Study, all with carotid wall thickening on ultrasound, underwent 2 magnetic resonance imaging scans for carotid plaque characterization (mean interscan interval 4.1 ± 0.2 years). Presence of IPH, calcification, and lipid-rich necrotic core was assessed on both sides on the baseline and follow-up scans. The association between cardiovascular risk factors and incident carotid plaque components was assessed. In the 396 arteries, all plaque components significantly changed over time. Incidence of IPH, calcification, and lipid core was, respectively, 18.5%, 59.2%, and 39.6%. The factor most strongly associated with the incidence of IPH was use of antihypertensive drugs (multivariate adjusted odds ratio [OR]: 3.87; 95% confidence interval [CI]: 1.90 to 7.90) and severe hypertension (multivariate adjusted OR: 4.70; 95% CI: 1.50 to 14.80). The incidence of calcification was associated with hypertension (OR: 2.20; 95% CI: 1.07 to 4.40). Higher cholesterol levels were associated with incidence of lipid cores (multivariate adjusted OR per unit increase in cholesterol: 1.40; 95% CI: 1.10 to 1.70). In these community-dwelling subjects, characteristics of plaque composition changed dramatically within a few years, and cardiovascular risk factors played a major role in these changes. Hypertension and its treatment and serum cholesterol levels were the main risk factors for the development of atherosclerotic plaque components over time.


Dietary Protein Intake and Transition between Frailty States in Octogenarians Living in New Zealand.
Adequate nutritional status may influence progression to frailty. The purpose of this study is to determine the prevalence of frailty and examine the relationship between dietary protein intake and the transition between frailty states and mortality in advanced age. We used data from a longitudinal cohort study of Māori (80-90 years) and non-Māori (85 years). Dietary assessments (24-h multiple pass dietary recalls) were completed at the second year of follow-up (wave 2 and forms the baseline in this study). Frailty was defined using the Fried Frailty criteria. Multi-state modelling examined the association of protein intake and transitions between frailty states and death over four years. Over three quarters of participants were pre-frail or frail at baseline (62% and 16%, respectively). Those who were frail had a higher co-morbidity (p < 0.05), where frailty state changed, 44% showed a worsening of frailty status (robust → pre-frail or pre-frail → frail). Those with higher protein intake (g/kg body weight/day) were less likely to transition from robust to pre-frail [Hazard Ratio (95% Confidence Interval): 0.28 (0.08-0.91)] but also from pre-frail to robust [0.24 (0.06-0.93)]. Increased protein intake was associated with lower risk of transitioning from pre-frailty to death [0.19 (0.04-0.80)], and this association was moderated by energy intake [0.22 (0.03-1.71)]. Higher protein intake in this sample of octogenarians was associated with both better and worse outcomes.


Factorization of the polarization transformation matrix in integrated photoelasticity.
In integrated photoelasticity, assessment of stresses in a three-dimensional specimen is based on the measurement of the change of polarization on many light rays that pass the specimen. Since the medium is optically anisotropic and inhomogeneous, the optical phenomena are nonlinear and solution of the inverse problem is complicated. Several methods of solving the inverse problem demand an efficient algorithm for solving the direct problem, i.e., for the calculation of the polarization transformation matrix on the basis of the stress field in the medium. We propose for this use factorization of the transformation matrix. We show that if the transformation of polarization is described by characteristic parameters, the three characteristic parameters can be determined by solving a single third-order differential equation. Since characteristic parameters can be measured experimentally, this approach can be used in practical three-dimensional stress analysis with integrated photoelasticity.


A history of treatments for myasthenia gravis.
Much of the improvement in the treatment of myasthenia gravis (MG) over the past 125 years can be attributed to the effectiveness of general medical measures such as advances in respiratory care and the discovery of antibiotics. Although MG became the model of an antibody-mediated autoimmune disease in the 1970s (the most documented antigen being the muscle acetylcholine receptor at the neuromuscular junction), the pathogenesis of MG has not been the rationale for most treatments found to be useful for this disease. The serendipitous benefit of anticholinesterases for MG in the 1930s subsequently focused attention on the neuromuscular junction. The beginnings of the controversy over thymectomy for MG in the 1940s and 1950s preceded the discovery in 1960 of the function of the thymus. Before the autoimmune pathogenesis of MG was known, adrenocorticotropic hormone (ACTH) and steroids for MG were tried for reasons that turned out to be incorrect. Further immunosuppressive treatments for MG were largely empirical, following their use in organ transplantation and other autoimmune diseases. More specific treatments, based on our knowledge of pathogenesis, are still experimental but hopefully will be the history of the future.


Chronic ethanol consumption modulates growth factor release, mucosal cytokine production, and microRNA expression in nonhuman primates.
Chronic alcohol consumption has been associated with enhanced susceptibility to both systemic and mucosal infections. However, the exact mechanisms underlying this enhanced susceptibility remain incompletely understood. Using a nonhuman primate model of ethanol (EtOH) self-administration, we examined the impact of chronic alcohol exposure on immune homeostasis, cytokine, and growth factor production in peripheral blood, lung, and intestinal mucosa following 12 months of chronic EtOH exposure. EtOH exposure inhibited activation-induced production of growth factors hepatocyte growth factor (HGF), granulocyte colony-stimulating factor (G-CSF), and vascular-endothelial growth factor (VEGF) by peripheral blood mononuclear cells (PBMC). Moreover, EtOH significantly reduced the frequency of colonic Th1 and Th17 cells in a dose-dependent manner. In contrast, we did not observe differences in lymphocyte frequency or soluble factor production in the lung of EtOH-consuming animals. To uncover mechanisms underlying reduced growth factor and Th1/Th17 cytokine production, we compared expression levels of microRNAs in PBMC and intestinal mucosa. Our analysis revealed EtOH-dependent up-regulation of distinct microRNAs in affected tissues (miR-181a and miR-221 in PBMC; miR-155 in colon). Moreover, we were able to detect reduced expression of the transcription factors STAT3 and ARNT, which regulate expression of VEGF, G-CSF, and HGF and contain targets for these microRNAs. To confirm and extend these observations, PBMC were transfected with either mimics or antagomirs of miR-181 and miR-221, and protein levels of the transcription factors and growth factors were determined. Transfection of microRNA mimics led to a reduction in both STAT3/ARNT as well as VEGF/HGF/G-CSF levels. The opposite outcome was observed when microRNA antagomirs were transfected. Chronic EtOH consumption significantly disrupts both peripheral and mucosal immune homeostasis, and this dysregulation may be mediated by changes in microRNA expression.


Pancreaticoduodenal Artery Aneurysm Complicated by Median Arcuate Ligament Syndrome.
To highlight median arcuate ligament syndrome as a potential cause for celiac artery stenosis and pancreaticoduodenal artery aneurysm, and describe treatment options in this setting. A 63-year-old male presented with a pancreaticoduodenal artery aneurysm and concomitant celiac artery stenosis that was treated with celiac artery stenting and aneurysm coiling. He subsequently developed stent fracture and celiac artery occlusion secondary to previously unrecognized median arcuate ligament syndrome causing reperfusion of the aneurysm. This was treated with open median arcuate ligament release and aorta to common hepatic artery bypass with good clinical result and stable 20-month surveillance imaging. It is critical to recognize median arcuate ligament syndrome as a cause of celiac artery stenosis in the setting of pancreaticoduodenal artery aneurysm given the high risk of failure of endovascular stenting. Open aorto-hepatic artery bypass and endovascular aneurysm coiling should be the preferred approach in these patients.


Tumor antigen on benign adenomas and on murine lung carcinomas quantitated by a two-site monoclonal antibody assay.
TSP-180 is a Mr 180,000 cell surface protein found on several murine lung carcinomas but not on fibroblast or sarcoma cell lines. Monoclonal antibody 135-13C binds to TSP-180 with high affinity but could not be used to quantitate the protein in tumors and normal tissue (Cancer Res., 41: 3465-3470, 1981). TSP-180 was purified from a transplantable BALB/c carcinoma (line 1 cells) by immunoaffinity chromatography and used as an immunogen to produce another monoclonal antibody (346-11A) to a different epitope on the molecule. A two-site solid-phase radioimmunoassay for TSP-180 was developed to quantitate TSP-180 in tissue extracts. The assay can detect as little as 3 ng of TSP-180 in samples up to 10 mg of protein. Analyses of several lung carcinoma cell lines confirmed that TSP-180 is present in all (five of five) cell lines ranging from 40 to 800 ng per mg of cell protein extract. Mouse tissues from normal and tumor-bearing mice were analyzed for TSP-180. Values for line 1 tumors growing i.m. were about 70 ng of TSP-180 per mg of protein. Normal tissue from normal and tumor-bearing mice contained low levels of TSP-180 from less than 0.3 ng/mg of protein for liver to a high of about 11 ng/mg of protein for leg muscle. Finally, small benign urethane-induced adenomas (1 to 2 mm) from BALB/c mice had moderate amounts of TSP-180 (11 ng/mg of protein), while two primary lung adenocarcinomas in the same animals had 20 and 47 ng/mg of protein, respectively, suggesting that TSP-180 expression may increase with increasing cancer of these tumors. Analyses of individual urethane-induced lung tumors from A/J mice showed that 11 of 13 carcinomas had high levels of TSP-180, while only 1 of 6 adenomas had a detectable amount of TSP-180, and that was at a moderate level. Specific quantitation of tumor markers in normal, benign, and malignant lung tissue may be helpful in identifying different levels of gene expression as tumors progress to more malignant states.


Withania somnifera Extracts Promote Resilience against Age-Related and Stress-Induced Behavioral Phenotypes in Drosophila melanogaster; a Possible Role of Other Compounds besides Withanolides.
Withania somnifera (WS) extracts have been used in traditional medicine for millennia to promote healthy aging and wellbeing. WS is now also widely used in Western countries as a nutritional supplement to extend healthspan and increase resilience against age-related changes, including sleep deficits and depression. Although human trials have supported beneficial effects of WS, the study designs have varied widely. Plant material is intrinsically complex, and extracts vary widely with the origin of the plant material and the extraction method. Commercial supplements can contain various other ingredients, and the characteristics of the study population can also be varied. To perform maximally controlled experiments, we used plant extracts analyzed for their composition and stability. We then tested these extracts in an inbred Drosophila line to minimize effects of the genetic background in a controlled environment. We found that a water extract of WS (WSAq) was most potent in improving physical fitness, while an ethanol extract (WSE) improved sleep in aged flies. Both extracts provided resilience against stress-induced behavioral changes. WSE contained higher levels of withanolides, which have been proposed to be active ingredients, than WSAq. Therefore, withanolides may mediate the sleep improvement, whereas so-far-unknown ingredients enriched in WSAq likely mediate the effects on fitness and stress-related behavior.


99mTechnetium-labeled methylene diphosphonate uptake in maxillary bone during and after rapid maxillary expansion.
The purpose of this study was to evaluate bone activity at the midpalatal suture that had been biomechanically stimulated by rapid maxillary expansion (RME). A rigid acrylic-bonded expansion device with a maxiskeleton screw was used for RME in three patients who were in three different growth periods. The screw was activated twice a day by 1/4 turns. After sufficient expansion, the screw was fixed with acrylic resin, and the same appliance was used as a removable retention plate for three months. Single photone emission computed tomography (SPECT) bone scintigraphy records were obtained before (T1) and at the end of RME (T2) and three months after the retention period (T3). According to the scintigraphic records, the increase in bone activity was highest in the anterior and medial sections on both the left and right sides of the maxilla in all cases. After three months of retention, the bone activity returned to its original level. Therefore, it may be stated that the retention period of three months was sufficient for bone reorganization.


Integrating enhanced hepatitis C testing and counselling in research.
The hepatitis C virus (HCV) affects over 170 million people worldwide. In Australia, over 225,000 people have been diagnosed with HCV infection with 13,000 infections reported annually; 90% are attributed to injecting drug use. Burnet Institute (BI) researchers have been studying the HCV epidemic since the virus was identified in 1989 including community based cohort studies (1990-1995), numerous studies involving Vietnamese-Australian people who inject drugs (PWID) (1996-2004) and social network studies (2000-2002, 2005-2007). Through this work the BI has developed a model of research practice for HCV and PWID, developed in recognition that much research relating to BBV infections - and HCV in particular - could be improved in terms of provision of test results to study participants. Our model endeavours to provide all participants with the highest quality HCV test results, delivered in accordance with best practice for pre- and post-test counselling by engaging participants in environments in which they are comfortable, building trust and rapport and being available throughout and beyond the research study. This paper will discuss the benefits and lessons learned over numerous studies in providing pre- and post-test counselling to PWID in an outreach capacity.


Predicting dose-volume histograms for organs-at-risk in IMRT planning.
The objective of this work was to develop a quality control (QC) tool to reduce intensity modulated radiotherapy (IMRT) planning variability and improve treatment plan quality using mathematical models that predict achievable organ-at-risk (OAR) dose-volume histograms (DVHs) based on individual patient anatomy. A mathematical framework to predict achievable OAR DVHs was derived based on the correlation of expected dose to the minimum distance from a voxel to the PTV surface. OAR voxels sharing a range of minimum distances were computed as subvolumes. A three-parameter, skew-normal probability distribution was used to fit subvolume dose distributions, and DVH prediction models were developed by fitting the evolution of the skew-normal parameters as a function of distance with polynomials. Cohorts of 20 prostate and 24 head-and-neck IMRT plans with identical clinical objectives were used to train organ-specific average models for rectum, bladder, and parotids. A sum of residuals analysis quantifying the integrated difference between the clinically approved DVH and predicted DVH evaluated similarity between DVHs. The ability of the average models to prospectively predict DVHs was evaluated on an independent validation cohort of 20 prostate plans. Statistical comparison of the sums of residuals between training and validation cohorts quantified the accuracy of the average model. Restricted sums of residuals (RSR) were used to identify potential outliers, where large values of RSR indicate a clinical DVH that exceeds the predicted DVH by a considerable amount. A refined model was obtained for each organ by excluding outliers with large RSR values from the training cohort. The refined model was applied to the original training cohort and restricted sums of residuals were utilized to estimate potential DVH improvements. All cases were replanned and evaluated by the physician that approved the original plan. The ability of the refined models to correctly identify outliers was assessed using the residual sum between the original and replanned DVHs to quantify dosimetric gains realized under replanning. Statistical analysis of average sum of residuals for rectum (SR(rectum)=0.003±0.037), bladder (SR(bladder)=-0.008±0.037), and parotid (SR(parotid)=-0.003±0.060) training cohorts yielded mean values near zero and small with respect to the standard deviations, indicating that the average models are capturing the essential behavior of the training cohorts. The predictive abilities of the average rectum and bladder models were statistically indistinguishable between the training and validation sets, with SR(rectum)=0.002±0.044 and SR(bladder)=-0.018±0.058 for the validation set. The refined models' ability to detect outliers and predict achievable OAR DVHs was demonstrated by a strong correlation between predicted gains (RSR) and realized gains after replanning with sample correlation coefficients of r = 0.92 for the rectum, r = 0.88 for the bladder, and r = 0.84 for the parotid glands. The results demonstrate that our mathematical framework and modest training cohorts successfully predict achievable OAR DVHs based on individual patient anatomy. The models correctly identified suboptimal plans that demonstrated further OAR sparing after replanning. This modeling technique requires no manual intervention except for appropriate selection of a training set with identical evaluation criteria. Clinical implementation is in progress to evaluate impact on real-time IMRT QC.


Diversity in form and function: Vertical distribution of soil fauna mediates multidimensional trait variation.
It has been widely recognized that species show extensive variation in form and function. Based on species' attributes, they can be positioned along major axes of variation, which are often defined by life-history traits, such as number of offspring, age at maturity or generation time. Less emphasis has been given in this respect to tolerance traits, especially to resistance to abiotic stress conditions, which often determine community (dis)assembly and distribution. Soil fauna species distribution is governed to a large extent by environmental conditions that filter communities according to functional traits, such as abiotic stress tolerance, morphology and body size. Trait-based approaches have been successfully used to predict soil biota responses to abiotic stress. It remains unclear, though, how these traits relate to life-history traits that determine individual performance, that is, reproduction and survival. Here, we analyse patterns in multidimensional trait distribution of dominant groups of soil fauna, that is, Isopoda, Gastropoda and Collembola, known to be important to the functioning of ecosystems. We compiled trait information from existing literature, trait databases and supplementary measurements. We looked for common patterns in major axes of trait variation and tested if vertical distribution of species in the soil explained trait variation based on three components of trait diversity (trait richness, evenness and divergence). Our results showed that two to three axes of variation structured the trait space of life-history and tolerance traits in each of the taxonomic groups and that vertical distribution in soil explained the main axis of trait variation. We also found evidence of environmental filtering on soil fauna along the vertical soil distribution, with lower trait richness and trait divergence in soil-dwelling than in surface-living species. Our study was partially limited by the lack of detailed trait measurements for the selected taxonomic groups. In this regard, there is an urgent need for standardized trait databases across invertebrate groups to improve trait-based diversity analysis and fill gaps in the mechanistic understanding behind trait distribution, trait filtering and the link with species fitness and performance.


Acetylcholinesterase reactivators modify the functional properties of the nicotinic acetylcholine receptor ion channel.
Interactions of the oximes pyridine-2-aldoxime (2-PAM) and 1-(2-hydroxyiminomethyl-1-pyridino)-3-(4-carbamoyl-1-pyridino++ +)-2-oxapropane dichloride (HI-6), reactivators of phosphorylated acetylcholinesterase enzyme, with the nicotinic acetylcholine receptor-ion channel complex were studied using electrophysiological techniques. Single channel studies revealed that both oximes increased the opening probability of channels that were activated by acetylcholine. The oximes reduced mean channel open time and burst time in a concentration- and voltage-dependent manner. End-plate current amplitude was increased by 2-PAM (10-100 microM) and HI-6 (1 microM) but depressed at higher concentrations of these agents. The oximes decreased the time constant of end-plate current decay, particularly at hyperpolarized membrane potentials. HI-6 depressed indirect twitch response of the sartorius muscle, whereas 2-PAM caused a facilitation followed by depression. Both agents directly hydrolyzed acetylthiocholine, in addition to weakly inhibiting acetylcholinesterase. Our study demonstrates a direct molecular interaction of the oximes HI-6 and 2-PAM with the natural agonist molecule and with the acetylcholine receptor-ion channel complex. These effects can explain the excitatory and inhibitory actions of both agents, and may form the basis for their antidotal effectiveness against organophosphorus poisoning. The quantitative differences between the effects of 2-PAM and HI-6 on the above parameters are important in view of their differential antidotal efficacies.


The Newly Sequenced Genome of Pisum sativum Is Replete with Potential G-Quadruplex-Forming Sequences-Implications for Evolution and Biological Regulation.
G-quadruplexes (G4s) have been long considered rare and physiologically unimportant in vitro curiosities, but recent methodological advances have proved their presence and functions in vivo. Moreover, in addition to their functional relevance in bacteria and animals, including humans, their importance has been recently demonstrated in evolutionarily distinct plant species. In this study, we analyzed the genome of Pisum sativum (garden pea, or the so-called green pea), a unique member of the Fabaceae family. Our results showed that this genome contained putative G4 sequences (PQSs). Interestingly, these PQSs were located nonrandomly in the nuclear genome. We also found PQSs in mitochondrial (mt) and chloroplast (cp) DNA, and we experimentally confirmed G4 formation for sequences found in these two organelles. The frequency of PQSs for nuclear DNA was 0.42 PQSs per thousand base pairs (kbp), in the same range as for cpDNA (0.53/kbp), but significantly lower than what was found for mitochondrial DNA (1.58/kbp). In the nuclear genome, PQSs were mainly associated with regulatory regions, including 5'UTRs, and upstream of the rRNA region. In contrast to genomic DNA, PQSs were located around RNA genes in cpDNA and mtDNA. Interestingly, PQSs were also associated with specific transposable elements such as TIR and LTR and around them, pointing to their role in their spreading in nuclear DNA. The nonrandom localization of PQSs uncovered their evolutionary and functional significance in the Pisum sativum genome.


Algorithm-based design of novel synthetic media for Metarhizium anisopliae simulating its nutritional conditions in the environment.
The objective of this study was to develop a novel synthetic growth medium for increased conidium production of the entompathogenic fungus Metarhizium anisopliae. The medium should simulate natural nutritional conditions. Macro- and micronutrients were selected in concentrations found in insects or from sources which are believed to be advantageous for virulence. Medium development was guided by a problem-oriented genetic algorithm (GA) implemented with 'mutation' and 'recombination' operators specific for this optimization problem. Following five optimization steps and a total of 181 medium variations, 19 synthetic media led to increased conidium production as compared with the standard Sabouraud dextrose agar medium: increases in conidia yields of up to 120% and a 17-fold higher conidium production per square centimetre of mycelium were achieved. Rapid germination of conidia, conidial C : N ratio, as well as spore-bound Pr1 protease production were monitored as proposed quality control markers for a virulent inoculum. It was demonstrated that our problem-oriented GA is a powerful tool for the design of chemically defined cultivation media with special/enhanced properties for anamorphic fungi. This is the first study, which demonstrates the advantage of the use of a GA for the rapid design of solid synthetic media for maximum production of virulent conidia.


Effects of Temperature and Concentration on the Rate of Photobleaching of Erythrosine in Water.
Erythrosine, a popular food dye, undergoes fast O2-sensitive bleaching in water when subjected to visible light illumination. In dilute solution, erythrosine undergoes photobleaching via first-order kinetics, where the rate of bleaching depends critically on the rate of photon absorption and on the concentration of dissolved oxygen. Kinetic studies indicate that this inherent bleaching is augmented by self-catalysis at higher concentrations of erythrosine and on long exposure times. Under the conditions used, bleaching occurs by way of geminate attack of singlet molecular oxygen on the chromophore. Despite the complexity of the overall photobleaching process, the rate constants associated with both inherent and self-catalytic bleaching reactions follow Arrhenius-type behavior, allowing the activation parameters to be resolved. Bleaching remains reasonably efficient in the solid state, especially if the sample is damp, and provides a convenient means by which to construct a simple chemical actinometer.


Preparing new doctors for clinical practice: an evaluation of pre-internship training.
A consistent finding in the literature is that newly graduated medical students often do not prossess the basic skills required to perform their jobs. Training designed to prepare newly graduated medical students for intermship was developed and delivered to 106 newly graduated medical students. Feedback on the course was obtained using anonymous pre-and post-course questionaires. A total of 32 students (52.5% of the recourse respondents) felt that they were prepared prior to the training, compared wit 51students (79.7% of the post-course respondents) who felt prepared for intership after the training. The largest effect size of the training was for the administration of medication (Cohen's d = 0.93). Futher development to the training programme is required. Nevertheless, it is suggested that this course serve as a model to address the unsatisfactory levels of preparedness for the work of a junior reported by medical students from many countries.


Index Modulation Embedded in Type I Waveguide Written by Femtosecond Laser in Fused Silica.
Slit-shaped laser beams focused in bulk optical materials can realize embedded waveguides with circular cross sections consisting of positive index change type I traces. In these kinds of waveguide traces, a peculiar periodical refractive index modulation was observed in type I waveguides with two different femtosecond lasers. The direction of refractive index modulation can be controlled with the slit configuration, and its period can be controlled by mechanical perturbation of the stages and the scanning speed. We argue that platform perturbation and dynamical thermal transport processes during the scan are generating factors in the appearance of this modulation. The embedded microstructures in waveguides can provide spectrum modulation, which may have potential applications in optical sensing, filtering, and phase control.


Associations Between Immigration-Related User Factors and eHealth Activities for Self-Care: Case of First-Generation Immigrants From Pakistan in the Oslo Area, Norway.
Immigrant populations are often disproportionally affected by chronic diseases, such as type 2 diabetes mellitus (T2DM). Use of information and communication technology (ICT) is one promising approach for better self-care of T2DM to mitigate the social health inequalities, if designed for a wider population. However, knowledge is scarce about immigrant populations' diverse electronic health (eHealth) activities for self-care, especially in European countries. With a target group of first-generation immigrants from Pakistan in the Oslo area, Norway, we aimed to understand their diverse eHealth activities for T2DM self-care in relation to immigration-related user factors specific to this target group: proficiency in relevant languages (Urdu, Norwegian, English), length of residence in Norway, and diagnosis of T2DM compared with general user factors (age, gender, education and digital skills, and self-rated health status). Data were from a survey among the target population (N=176) conducted in 2015-2016. Using logistic regression, we analyzed associations between user factors and experiences of each of the following eHealth activities for T2DM self-care in the last 12 months: first, information seeking by (1) search engines and (2) Web portals or email subscriptions; second, communication and consultation (1) by closed conversation with a few acquaintances using ICT and (2) on social network services; and third, active decision making by using apps for (1) tracking health information and (2) self-assessment of health status. Using Poisson regression, we also assessed the relationship between user factors and variety of eHealth activities experienced. The Bonferroni correction was used to address the multiple testing problem. Regression analyses yielded the following significantly positive associations: between Urdu literacy and (1) information seeking by Web portals or email subscriptions (odds ratio [OR] 2.155, 95% CI 1.388-3.344), (2) communication and consultation on social network services (OR 5.697, 95% CI 2.487-13.053), and (3) variety (estimate=0.350, 95% CI 0.148-0.552); between length of residence in Norway and (1) communication and consultation by closed conversation with a few acquaintances using ICT (OR 1.728, 95% CI 1.193-2.503), (2) communication and consultation on social network services (OR 2.098, 95% CI 1.265-3.480), and (3) variety (estimate=0.270, 95% CI 0.117-0.424); between Norwegian language proficiency and active decision making by using apps for self-assessment of health status (OR 2.285, 95% CI 1.294-4.036); between education and digital skills and active decision making by using apps for tracking health information (OR 3.930, 95% CI 1.627-9.492); and between being a female and communication and consultation by closed conversation with a few acquaintances using ICT (OR 2.883, 95% CI 1.335-6.227). This study implies immigration-related factors may confound associations between general user factors and eHealth activities. Further studies are needed to explore the influence of immigration-related user factors for eHealth activities in other immigrant groups and countries. RR2-DOI 10.2196/resprot.5468.


CD4+ and CD8+ T cell survival is regulated differentially by protein kinase Ctheta, c-Rel, and protein kinase B.
An effective immune response requires the expansion and survival of a large number of activated T cells. This study compared the role of protein kinase C (PKC)theta and associated signaling molecules in the survival of activated primary CD4+ vs CD8+ murine T cells. We demonstrate that the absence of PKCtheta resulted in a moderate survival defect in CD4+ T cells and a striking survival defect of CD8+ T lymphocytes. CD8+ T cells lacking the c-Rel, but not the NF-kappaB1/p50, member of the NF-kappaB family of transcription factors displayed a similar impairment in cell survival as PKCtheta(-/-) CD8(+) T lymphocytes. This implicates c-Rel as a key target of PKCtheta-mediated survival signals in CD8+ T cells. In addition, both c-Rel(-/-) and PKCtheta(-/-) T cells also displayed impaired expression of the antiapoptotic Bcl-x(L) protein upon activation. Changes in Bcl-x(L) expression, however, did not correlate with the survival of CD4+ or CD8+ lymphocytes. The addition of protein kinase B-mediated survival signals could restore partially CD4+ T cell viability, but did not dramatically influence CD8+ survival. Active protein kinase B was also unable to restore proliferative responses in CD8+ PKCtheta(-/-) T cells. The survival of CD4+ and CD8+ T cells deficient in either PKCtheta or c-Rel, however, was promoted by the addition of IL-2. Collectively, these data demonstrate that CD4+ and CD8+ T cell survival signals are differentially programmed.


Aluminum chloride in the treatment of symptomatic athelete's foot.
Various aluminum salts were evaluated for in vitro and in vivo antimicrobial activity and ability to bind with serum proteins (astrigency) with the object of finding a colorless substance to substitute for carbol-fuchsin solution (Castellani paint) in the treatment of symptomatic interdigital athlete's foot. Aluminum chlorohydrate was more powerful in killing bacteria and fungi than aluminum acetate and aluminum chloride. However, aluminum chloride showed pronounced astringency and was the only compound to bring about rapid resolution of the signs and symptoms of athlete's foot in open-ended clinical trials. This salt promptly controls odor, pruritus, and maceration. The beneficial effect depends largely on drying the surface, not killing organisms. A solution of 30% aluminum chloride was found to be equlvalent to carbol-fuchsin solution in effectively treating symptomatic athlete's foot.


A model for Joule heating-induced dispersion in microchip electrophoresis.
This paper presents an analytical and parameterized model for analyzing the effects of Joule heating on analyte dispersion in electrophoretic separation microchannels. We first obtain non-uniform temperature distributions in the channel resulting from Joule heating, and then determine variations in electrophoretic velocity, based on the fact that the analyte's electrophoretic mobility depends on the buffer viscosity and hence temperature. The convection-diffusion equation is then formulated and solved in terms of spatial moments of the analyte concentration. The resulting model is validated by both numerical simulations and experimental data, and holds for all mass transfer regimes, including unsteady dispersion processes that commonly occur in microchip electrophoresis. This model, which is given in terms of analytical expressions and fully parameterized with channel dimensions and material properties, applies to dispersion of analyte bands of general initial shape in straight and constant-radius-turn channels. As such, the model can be used to represent analyte dispersion in microchannels of more general shape, such as serpentine- or spiral-shaped channels.


Do Admitted COVID-19-Positive Patients on Anticoagulation Therapy Have a Reduced Hospital Stay and Disease Severity?
Background As of December 2021, the coronavirus disease 2019 (COVID-19) pandemic has resulted in the deaths of over 5 million people. It is known that infection with this virus causes a state of hypercoagulability. Because of this, there has been considerable debate on whether or not patients should be placed on anticoagulation prophylaxis/therapy. The goal of our project was to shed light on this topic by examining the effects of preexisting anticoagulation therapy in COVID-19 patients on disease severity (measured by blood clot readmissions, transfusion counts, and length of hospital stay). In this retrospective cohort study, we conducted an analysis based on data from 30,076 COVID-19-positive patients' electronic medical records. Materials and methods This is a retrospective cohort study. Patients included in this study were identified from the HCA Healthcare corporate database. Registry data was sourced from HCA East Florida hospitals. All patients included in this study were COVID-19 positive via polymerase chain reaction (PCR) or rapid antigen testing on admission and over age 18. A total of 30,076 patients were included in this study with hospital admission dates from March 1, 2020 to June 30, 2021. The analysis examined the relationship between age, sex, blood clot history, and most importantly current anticoagulation status on COVID-19 disease severity (through blood clot readmissions, length of stay, and transfusion count). Blood clot readmissions were analyzed with a logistic regression model while the length of hospital stay and transfusion count were analyzed with a linear regression model. Results Our analysis revealed that the odds of experiencing a blood clot readmission is 2.017 times more likely in patients already on anticoagulation therapy compared to those who were not (p = 0.0024). We also found that patients on anticoagulation therapy had a hospital stay of 6.90 days longer on average than patients not on anticoagulation therapy (p < 0.0001). Finally, patients on anticoagulation therapy had, on average, 0.20 more blood transfusions than patients not on anticoagulation therapy (p < 0.001). Conclusion While these findings may be affected by the underlying conditions of those on preexisting anticoagulation therapy, they provide valuable insight into the debate on whether COVID-19-positive patients should be anticoagulated on admission to a hospital.


Fluorescent periodic mesoporous organosilica nanoparticles dual-functionalized via click chemistry for two-photon photodynamic therapy in cells.
The synthesis of ethenylene-based periodic mesoporous organosilica nanoparticles for two-photon imaging and photodynamic therapy of breast cancer cells is described. A dedicated two-photon absorbing fluorophore possessing four triethoxysilyl groups and having large two-photon absorption in the near IR region, and azidopropyltriethoxysilane were incorporated into the structure. The mesoporous nanoparticles of 100 nm diameter were further functionalized by means of click chemistry with a propargylated fluorescent bromo-quinoline photosensitizer able to generate singlet oxygen. The photophysical properties and two-photon absorption properties of the nanoparticles were investigated evidencing complementary contribution of the two dyes. Both dyes contribute to the two-photon absorption response of the mesoporous nanoparticles while efficient FRET from the two-photon fluorophore to the quinoline sensitizer is observed. The dual-functionalized nanoparticles were incubated with MCF-7 breast cancer cells. Two-photon confocal imaging demonstrated the endocytosis of the nanoparticles within cancer cells. Moreover, brief two-photon irradiation (3 scans of 1.57 s) at 760 nm at high laser power (3 W) was shown to induce 40% of cancer cell death demonstrating the potential of the dual-functionalized mesoporous organosilica nanoparticles for two-photon photodynamic therapy.


Determination of Nerve Agent Metabolites by Ultraviolet Femtosecond Laser Ionization Mass Spectrometry.
Nerve agent metabolites, i.e., isopropyl methylphosphonic acid (IMPA) and pinacolyl methylphosphonic acid (PMPA), were derivatized by reacting them with 2,3,4,5,6-pentafluorobenzyl bromide (PFBBr) and were determined by mass spectrometry using an ultraviolet femtosecond laser emitting at 267 and 200 nm as the ionization source. The analytes of the derivatized compounds, i.e., IMPA-PFB and PMPA-PFB, contain a large side-chain, and molecular ions are very weak or absent in electron ionization mass spectrometry. The use of ultraviolet femtosecond laser ionization mass spectrometry, however, resulted in the formation of a molecular ion, even for compounds such as these that contain a highly bulky functional group. The signal intensity was larger at 200 nm due to resonance-enhanced two-photon ionization. In contrast, fragmentation was suppressed at 267 nm (nonresonant two-photon ionization) especially for PMPA-PFB, thus resulting in a lower background signal. This favorable result can be explained by the small excess energy in ionization at 267 nm and by the low-frequency vibrational mode of a bulky trimethylpropyl group in PMPA.


Nonmotor and extracerebellar features in Machado-Joseph disease: a review.
Spinocerebellar ataxia type 3 or Machado-Joseph disease is the most common spinocerebellar ataxia worldwide, and the high frequency of nonmotor manifestations in Machado-Joseph disease demonstrates how variable is the clinical expression of this single genetic entity. Anatomical, physiological, clinical, and functional neuroimaging data reinforce the idea of a degenerative process involving extracerebellar regions of the nervous system in Machado-Joseph disease. Brain imaging and neuropathologic studies have revealed atrophy of the pons, basal ganglia, midbrain, medulla oblongata, multiple cranial nerve nuclei, and thalamus and of the frontal, parietal, temporal, occipital, and limbic lobes. This review provides relevant information about nonmotor manifestations and extracerebellar symptoms in Machado-Joseph disease. The main nonmotor manifestations of Machado-Joseph disease described in previous data and discussed in this article are: sleep disorders, cognitive and affective disturbances, psychiatric symptoms, olfactory dysfunction, peripheral neuropathy, pain, cramps, fatigue, nutritional problems, and dysautonomia. In addition, we conducted a brief discussion of noncerebellar motor manifestations, highlighting movement disorders. © 2013 Movement Disorder Society.


[Mechanism of miR-186-5p Regulating PRKAA2 to Promote Ferroptosis in Lung Adenocarcinoma Cells].
Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer, and any change of miRNAs expression will affect the degree of target regulation, thus affecting intracellular homeostasis. This study verified that miR-186-5p could inhibit the proliferation, migration and invasion of LUAD cells by regulating PRKAA2. Previous investigations found that the expression of miR-186-5p was markedly suppressed in LUAD. Bioinformatics method is used to predict the target protein related to ferroptosis downstream and inquire about its expression level in LUAD and its influence on the survival of patients. Double luciferase verified the binding site of PRKAA2 and miR-186-5p. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of PRKAA2. The effects of miR-186-5p of LUAD cells as well as the mechanism by which miR-186-5p inhibits Fer-1's sensitivity to ferroptosis were confirmed by EdU, Transwell, and scratch assays. The effect of miR-186-5p on the amount of reactive oxygen species (ROS) in LUAD cells was discovered using ROS experiment. Malondialdehyde (MDA) and glutathione (GSH) experiments were used to detect the effects of miR-186-5p and PRKAA2 on ferroptosis index of LUAD cells. The concentration of lipid ROS (L-ROS) in LUAD cells were measured using the L-ROS tests to determine the effects of miR-186-5p and PRKAA2. The expression of PRKAA2 is up-regulated, and a high level of PRKAA2 expression was associated with a poor prognosis for patients with LUAD. Overexpression of miR-186-5p decreased the gene and protein expression of PRKAA2. By promoting ferroptosis, miR-186-5p overexpression prevented lung cancer cells from proliferating, invading, and migrating. ROS could be produced in higher amounts in LUAD cells due to miR-186-5p. Overexpression of miR-186-5p and knockdown PRKAA2 up-regulated MDA content and reduced GSH content in LUAD cells, respectively. miR-186-5p could increase the content of L-ROS and promote the ferroptosis sensitivity of LUAD cells by targeting PRKAA2. miR-186-5p promotes ferroptosis of LUAD cells through targeted regulation of PRKAA2, thus inhibiting the proliferation, invasion and migration of LUAD. .


Cross-sectional study on dysphagia evaluation in community-dwelling older adults using the Eating Assessment Tool (EAT) -10, EAT-2, and Water Swallow Test.
Dysphagia is a health concern that causes severe complications and affects the life quality of the older population. This study aimed to determine the diagnostic performance of the Eating Assessment Tool (EAT)-2 compared with the EAT-10 and the Water Swallow Test (WST) in screening for dysphagia. A cross-sectional study was conducted among 5,090 community-dwelling older adults. Dysphagia was evaluated using both a subjective measure, the 10-item EAT (EAT-10) and an objective measure, the WST. The kappa index in pairs were analyzed. The validity and reliability of EAT-2 were also assessed. The sensitivity and specificity of the EAT-2 were 96.3 % and 94.8 %, respectively. The kappa index between the EAT-2 and EAT-10 was 0.64, whereas it was 0.11 between the EAT-10 and WST. The EAT-2 was a simpler screening tool for dysphagia. Combining the subjective questionnaire (EAT-10 or EAT-2) and the objective test (WST) is recommended.


Automatic segmentation of pulmonary segments from volumetric chest CT scans.
Automated extraction of pulmonary anatomy provides a foundation for computerized analysis of computed tomography (CT) scans of the chest. A completely automatic method is presented to segment the lungs, lobes and pulmonary segments from volumetric CT chest scans. The method starts with lung segmentation based on region growing and standard image processing techniques. Next, the pulmonary fissures are extracted by a supervised filter. Subsequently the lung lobes are obtained by voxel classification where the position of voxels in the lung and relative to the fissures are used as features. Finally, each lobe is subdivided in its pulmonary segments by applying another voxel classification that employs features based on the detected fissures and the relative position of voxels in the lobe. The method was evaluated on 100 low-dose CT scans obtained from a lung cancer screening trial and compared to estimates of both interobserver and intraobserver agreement. The method was able to segment the pulmonary segments with high accuracy (77%), comparable to both interobserver and intraobserver accuracy (74% and 80%, respectively).


Thyroid hormone receptor and ERRα coordinately regulate mitochondrial fission, mitophagy, biogenesis, and function.
Thyroid hormone receptor β1 (THRB1) and estrogen-related receptor α (ESRRA; also known as ERRα) both play important roles in mitochondrial activity. To understand their potential interactions, we performed transcriptome and ChIP-seq analyses and found that many genes that were co-regulated by both THRB1 and ESRRA were involved in mitochondrial metabolic pathways. These included oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and β-oxidation of fatty acids. TH increased ESRRA expression and activity in a THRB1-dependent manner through the induction of the transcriptional coactivator PPARGC1A (also known as PGC1α). Moreover, TH induced mitochondrial biogenesis, fission, and mitophagy in an ESRRA-dependent manner. TH also induced the expression of the autophagy-regulating kinase ULK1 through ESRRA, which then promoted DRP1-mediated mitochondrial fission. In addition, ULK1 activated the docking receptor protein FUNDC1 and its interaction with the autophagosomal protein MAP1LC3B-II to induce mitophagy. siRNA knockdown of ESRRA, ULK1, DRP1, or FUNDC1 inhibited TH-induced autophagic clearance of mitochondria through mitophagy and decreased OXPHOS. These findings show that many of the mitochondrial actions of TH are mediated through stimulation of ESRRA expression and activity, and co-regulation of mitochondrial turnover through the PPARGC1A-ESRRA-ULK1 pathway is mediated by their regulation of mitochondrial fission and mitophagy. Hormonal or pharmacologic induction of ESRRA expression or activity could improve mitochondrial quality in metabolic disorders.


Optimizing single irrigation scheme to improve water use efficiency by manipulating winter wheat sink-source relationships in Northern China Plain.
Improving winter wheat grain yield and water use efficiency (WUE) with minimum irrigation is very important for ensuring agricultural and ecological sustainability in the Northern China Plain (NCP). A three-year field experiment was conducted to determine how single irrigation can improve grain yield and WUE by manipulating the "sink-source" relationships. To achieve this, no-irrigation after sowing (W0) as a control, and five single irrigation treatments after sowing (75 mm of each irrigation) were established. They included irrigation at upstanding (WU), irrigation at jointing (WJ), irrigation at booting (WB), irrigation at anthesis (WA) and irrigation at medium milk (WM). Results showed that compared with no-irrigation after sowing (W0), WU, WJ, WB, WA and WM significantly improved mean grain yield by 14.1%, 19.9%, 17.9%, 11.6%, and 7.5%, respectively. WJ achieved the highest grain yield (8653.1 kg ha-1) and WUE (20.3 kg ha-1 mm-1), and WB observed the same level of grain yield and WUE as WJ. In comparison to WU, WJ and WB coordinated pre- and post-anthesis water use while reducing pre-anthesis and total evapotranspiration (ET). They also retained higher soil water content above 180 cm soil layers at anthesis, increased post-anthesis water use, and ultimately increased WUE. WJ and WB optimized population quantity and individual leaf size, delayed leaf senescence, extended grain-filling duration, improved post-anthesis biomass and biomass remobilization (source supply capacity) as well as post-anthesis biomass per unit anthesis leaf area (PostBA-leaf ratio). WJ also optimized the allocation of assimilation, increased the spike partitioning index (SPI, spike biomass/biomass at anthesis) and grain production efficiency (GPE, the ratio of grain number to biomass at anthesis), thus improved mean sink capacity by 28.1%, 5.7%, 21.9%, and 26.7% in comparison to W0, WU, WA and WM, respectively. Compared with WA and WM, WJ and WB also increased sink capacity, post-anthesis biomass and biomass remobilization. These results demonstrated that single irrigation at jointing or booting could improve grain yield and WUE via coordinating the "source-sink" relationships with the high sink capacity and source supply capacity. Therefore, we propose that under adequate soil moisture conditions before sowing, single irrigation scheme from jointing to booting with 75 mm irrigation amount is the optimal minimum irrigation practice for wheat production in this region.


Use of health care services after stroke.
To describe the use of care before and after stroke and to evaluate equity in access to health care services after stroke. Cross sectional study. The Netherlands. 382 patients living in the community who had been admitted to hospital with a stroke six months before. Sociodemographic status and functional health status according to The Barthel index, Rankin scale, and sickness impact profile, assessed during interview, and general practitioner (GP) characteristics obtained by postal questionnaire. Univariate and multivariate analyses of the relation between patient and GP related factors and use of care. Compared with the period before stroke the use of care six months after stroke increased significantly, especially use of physical therapy, home help, and aids. Multivariate analyses showed that impaired functional health increased the use of care (range in odds ratios 1.6 to 6.7). Compared with younger patients, elderly patients were more likely to have home help (odds ratio 2.9) and aids (2.4) but less likely to receive therapy (0.4), psychosocial support (0.5), and an appreciable amount of care (0.5). Being female (1.7), living alone (4.0), and whether the GP was informed about patients' discharge (2.2) increased the use of home help. Higher financial income (2.8) and having a male GP (3.2) contributed to use of therapy. Emotional distress (1.6), living protected (3.2), and living alone (1.7) accounted for psychosocial support. Although older age, lower income, and poor discharge information to the GP decreased the use of some types of care, there is equity in access to care after stroke, primarily determined by needs in terms of functional health status and predisposing factors such as living arrangement and social circumstances. Patient oriented studies focusing on care processes and care outcomes in terms of subjective needs, perceived care deficits, and satisfaction with care are still required.


Underuse of beta-blockers by patients with COPD and co-morbid acute coronary syndrome: A nationwide follow-up study in New Zealand.
Clinical guidelines recommend the use of beta-blockers and other cardiovascular prevention drugs in patients with acute coronary syndrome (ACS). Studies in several countries have found that beta-blockers are underused in patients with chronic obstructive pulmonary disease (COPD) and co-morbid heart disease, although most have only examined use in subgroups of patients. We undertook a nationwide follow-up study in New Zealand to describe the use of beta-blockers and other cardiovascular prevention drugs in patients with COPD and ACS. National health and pharmaceutical dispensing data were used to derive the study cohort, identify patients who were admitted to hospital with ACS and/or heart failure before cohort entry and during follow-up, and ascertain drug use. The study cohort included 83 435 patients aged ≥45 years, with 290 400 person-years of follow-up. Among 2637 patients with ≥1 ACS admission during follow-up, only 56.6% received a beta-blocker in the 6 months following the first admission, while 87.7% and 81%, respectively, received aspirin and a statin. Patients with higher COPD severity were less likely to receive a beta-blocker than those with lower severity, as were those with no history of previous ACS and/or heart failure. Use of beta-blockers following an ACS admission was much lower than expected based on the findings of general audits of ACS management in New Zealand. Along with the higher proportions using aspirin and statins, and the differences in beta-blocker dispensing by COPD severity, this suggests a particular reluctance to prescribe beta-blockers to patients with COPD.


Crystallographic proof for an extended hydrogen-bonding network in small prolyl isomerases.
Parvulins compose a family of small peptidyl-prolyl isomerases (PPIases) involved in protein folding and protein quality control. A number of amino acids in the catalytic cavity are highly conserved, but their precise role within the catalytic mechanism is unknown. The 0.8 Å crystal structure of the prolyl isomerase domain of parvulin Par14 shows the electron density of hydrogen atoms between the D74, H42, H123, and T118 side chains. This threonine residue has previously not been associated with catalysis, but a corresponding T152A mutant of Pin1 shows a dramatic reduction of catalytic activity without compromising protein stability. The observed catalytic tetrad is strikingly conserved in Pin1- and parvulin-type proteins and hence constitutes a common feature of small peptidyl prolyl isomerases.


Immediate effects of rhythmic auditory stimulation with tempo changes on gait in stroke patients.
[Purpose] The aim of this study was to investigate the effects of tempo changes in rhythmic auditory stimulation (RAS) on gait in stroke patients. [Subjects] Forty-one chronic stroke patients who had had a stroke with more than 6 months previously were recruited for this study. [Methods] All participants were asked to walk under 5 different conditions in random order: (1) no RAS (baseline); (2) baseline-matched RAS (0%); and (3) -10%, (4) +10%, and (5) +20% of the baseline. A GAITRite system was used to evaluate the spatial and temporal parameters of gait. [Results] Compared with under the RAS 0% conditions, the gait velocity, cadence, and stride length on the affected side were significantly decreased under the RAS -10% conditions. Gait velocity and cadence were significantly improved, but gait symmetry was significantly decreased under the RAS +10% and +20% conditions compared with under the RAS 0% conditions. [Conclusion] A faster RAS tempo significantly improved gait velocity and cadence, and applying RAS significantly improved the gait symmetry of stroke patients.


Alpha-interferon administration in cytomegalovirus retinitis.
Four patients, including three with the acquired immunodeficiency syndrome (AIDS), were treated with high-dose, buffy coat-derived alpha-interferon for progressive cytomegalovirus retinitis. Two of these patients had decreased viruria during therapy and the other two had increased viruria. There was evidence of progression of disease despite therapy in all patients, although the retinitis eventually became quiescent in the patient without AIDS. The severe immunosuppression encountered in AIDS patients complicates the management of cytomegalovirus and other opportunistic infections.


Four bromo-substituted pyrazoline and isoxazolinone spiro derivatives.
Conformational analyses and a structural comparison of the four spiro compounds 3-bromo-1,9-diphenyl-4-p-tolyl-7-oxa-1,2,8-triazaspiro[4.4]nona-2,8-dien-6-one, (I), C(24)H(18)BrN(3)O(2), 3-bromo-4-(4-methoxyphenyl)-1,9-diphenyl-7-oxa-1,2,8-triazaspiro[4.4]nona-2,8-dien-6-one, (II), C(24)H(18)BrN(3)O(3), 3-bromo-4-(4-chlorophenyl)-1,7,9-triphenyl-1,2,7,8-tetraazaspiro[4.4]nona-2,8-dien-6-one, (III), C(29)H(20)BrClN(4)O, and 3-bromo-1,7,9-triphenyl-4-p-tolyl-1,2,7,8-tetraazaspiro[4.4]nona-2,8-dien-6-one, (IV), C(30)H(22.89)Br(1.11)N(4)O, are presented. The molecular structures are rather similar, which is as expected since the compounds are all products of concerted 1,3-dipolar attack on (Z)-4-arylidene oxazolone and pyrazolone derivatives. The observed conformations tend to favour extended pi conjugation of the benzene rings and other pi systems, as shown by a comparison of selected geometric parameters of the four structures.


Opportunities for shared decision making in kidney transplantation.
Health researchers and policy-makers increasingly urge both patient and clinician engagement in shared decision making (SDM) to promote patient-centered care. Although SDM has been examined in numerous clinical settings, it has received little attention in solid organ transplantation. This paper describes the application of SDM to the kidney transplantation context. Several distinctive features of kidney transplantation present challenges to SDM including fragmented patient-provider relationships, the time-sensitive and unpredictable nature of deceased organ offers, decision-making processes by transplant providers serving as both organ guardians (given the organ scarcity) versus advocates for specific patients seeking transplantation, variable clinical practices and policies among transplant centers, and patients' potentially compromised cognitive status and literacy levels. We describe potential barriers to and opportunities for SDM, and posit that SDM is feasible, warranting encouragement in kidney transplantation. We propose strategies to promote and overcome obstacles to SDM in kidney transplantation. We contend that engagement in SDM can be facilitated by re-organization of clinical care, communication and education of providers and patients.


Prolonged optokinetic stimulation generates podokinetic after rotation.
Previous studies showed that after prolonged stepping in place on the center of a rotating platform blindfolded subjects could no longer step in place on a firm floor. Instead, they invariably rotated themselves relative to space without perceiving their rotation, a phenomenon termed podokinetic after-rotation (PKAR). We speculated that prolonged optokinetic stimulation (OK) alone may generate similar PKAR. The purpose of this study was to evaluate the effects of prolonged OK on podokinetic (PK) responses. Ten healthy subjects participated in the study. After a control stepping test, they were seated in a circular closed cage and randomly (right or left) exposed to an OK (45 degrees /s) covering the whole visual field for 30 min. After this procedure, blindfolded subjects attempted to step in place on the stationary floor for 30 min. When trying to do so, all subjects turned relative to space without any perception of rotation. The direction of this optokinetically after-rotation (oPKAR) was opposite of that of the direction of OK. Mean peak velocity of oPKAR was 7.8 +/- 4.1 degrees /s, and it was reached after approximately 6 min of stepping. After that, there was a progressive velocity decay, which exhibited a discharging time constant on the order of 42 min toward a final positive asymptote of 3.1 degrees /s. We conclude that OK alone causes oPKAR. Long-term OK probably charges a storage element for podomotor activity with a relatively prolonged time constant. This novel form of neural interaction and adaptive plasticity may have significant implications for the treatment of vestibular and parietal lobe disorders.


Saturated fatty acid composition of human milk in Israel: a comparison between Jewish and Bedouin women.
Breast milk is well established as the ideal source of nutrition for infants. Mature human breast milk generally contains 3.5-4.5% lipids comprising mostly triacylglycerols. In general, the fat composition of maternal human milk in developing countries shows higher levels of saturated fats, reflecting diets rich in carbohydrates. To determine the profile of unsaturated fatty acids in the breast milk of two populations in southern Israel--urban Jewish and rural tent-dwelling Bedouin women. This study involved 48 lactating Israeli mothers, 29 Jewish and 19 Bedouin (16-20 weeks postpartum), whose full-term infants were fed exclusively with breast milk. Total milk lipid extracts were transmethylated and analyzed by using an improved gas chromatographic method. The breast milk of the Bedouin women contained significantly higher levels of total major saturated fatty acids, lauric acid and palmitic acid (45.2 +/- 4.7% vs. 41.0 +/- 5.6%, P = 0.005; 5.2 +/- 2.1 vs. 6.8 +/- 2.0%, P = 0.03; and 22.7 +/- 2.4 vs. 20.6 +/- 3.8%, P = 0.02) respectively. No difference was found in the myristic acid level between the groups. The level of stearic acid was significantly higher in the Jewish group compared to the Bedouin group (5.7 +/- 1.1 vs. 5.1 +/- 1.1%, P = 0.04). There was a linear correlation between the levels of C14:0 and C12:0 in the Bedouin and lewish groups respectively (R = 0.87, R = 0.82, P < 0.001). Higher levels of saturated fatty acids were measured in the breast milk of Bedouin women, an economically weaker population. The results emphasize the importance of diet among lactating women and its influence on milk quality.


Predictive Shared Control of Robotic Arms Using Simulated Brain-Computer Interface Inputs.
Low decoding accuracy makes brain-computer interface (BCI) control of a robotic arm difficult. Shared control (SC) can overcome limitations of a BCI by leveraging external sensor data and generating commands to assist the user. Our study explored whether reaching targets with a robot end-effector was easier using SC rather than direct control (DC). We simulated a motor imagery BCI using a joystick with noise introduced to explicitly control interface accuracy to be 65% or 79%. Compared to DC, our prediction-based implementation of SC led to a significant reduction in the trajectory length of successful reaches for 4 (3) out of 5 targets using the 65% (79%) accurate interface, with failure rates being equivalent to DC for 2 (1) out of 5 targets. Therefore, this implementation of SC is likely to improve reaching efficiency but at the cost of more failures. Additionally, the NASA Task Load Index results suggest SC reduced user workload.Clinical relevance-Shared control can minimise the impact of BCI decoder errors on robot motion, making robotic arm control using noninvasive BCIs more viable.


How to organise and run Schwartz rounds.
Schwartz rounds are a group-based model of reflective practice originally designed to assist medical staff to develop more compassion in their care. The aim of Schwartz rounds is to help healthcare professionals such as nurses 'reconnect' with why they first entered the caring profession. • Schwartz rounds are designed to assist multidisciplinary healthcare professionals with the emotional, social and ethical aspects of caregiving. • Schwartz rounds can also be used to support resilience training and boost workforce morale. • The use of Schwartz rounds can assist nurses to understand the moral challenges they may encounter while caring for patients. REFLECTIVE ACTIVITY: 'How to' articles can help to update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: • How this article might help you organise Schwartz rounds in your clinical area. • How you could use this information to educate your colleagues about Schwartz rounds.


An optimal decisional space for the classification of Alzheimer's disease and mild cognitive impairment.
This paper proposes to combine MRI data with a neuropsychological test, mini-mental state examination (MMSE), as input to a multi-dimensional space for the classification of Alzheimer's disease (AD) and it's prodromal stages-mild cognitive impairment (MCI) including amnestic MCI (aMCI) and nonamnestic MCI (naMCI). The decisional space is constructed using those features deemed statistically significant through an elaborate feature selection and ranking mechanism. FreeSurfer was used to calculate 55 volumetric variables, which were then adjusted for intracranial volume, age and education. The classification results obtained using support vector machines are based on twofold cross validation of 50 independent and randomized runs. The study included 59 AD, 67 aMCI, 56 naMCI, and 127 cognitively normal (CN) subjects. The study shows that MMSE scores contain the most discriminative power of AD, aMCI, and naMCI. For AD versus CN, the two most discriminative volumetric variables (right hippocampus and left inferior lateral ventricle), when combined with MMSE scores, provided an average accuracy of 92.4% (sensitivity: 84.0%; specificity: 96.1%). MMSE scores are found to improve all classifications with accuracy increments of 8.2% and 12% for aMCI versus CN and naMCI versus CN, respectively. Results also show that brain atrophy is almost evenly seen on both sides of the brain for AD subjects, which is different from right-side dominance for aMCI and left-side dominance for naMCI. Furthermore, hippocampal atrophy is seen to be the most significant for aMCI, while Accumbens area and ventricle are most significant for naMCI.