Generalization of achievement orientations for experiences of success and failure in youth sport.
Studies of achievement orientations in sport have focused on subjective success. This study explored the extent to which these orientations generalize to subjective failure. 796 youth sport participants ages 9 to 16 years (338 boys, 458 girls) recalled personal experiences of success and failure. These were then categorized as mastery, comparison or social recognition orientations. In 60% of cases, participants used the same orientation to interpret success and failure. In the middle and oldest groups, such generalization was most frequent for mastery orientations in girls but for comparative orientations in boys. In the youngest groups, mastery orientations generalized most frequently for each sex. Hence achievement orientations generalized across type of experience, but with differences by age and sex.


[Primary lymphedema of the lower limbs in childhood (author's transl)].
Report on 3 cases of primary lymphedema in childhood. Lymphangiography, introduced by Kinmonth into radiodiagnosis, is essential. Aplasia, hypoplasia and hyperplasia of the lymphatic system can thus be differentiated. Conservative treatment is discussed.


Circadian variation of the myocardial ischemic threshold in patients with ischemic heart disease.
Circadian variation of the heart rate (HR) at the myocardial ischemic threshold was compared with that of the HR at the sympathetic tone threshold in 16 cases of effort angina pectoris. The high (0.15-0.40 Hz, Hf) and low (0.03-0.15 Hz, Lf) frequency spectral components were extracted every twenty seconds, using frequency domain analysis of the RR interval recorded by a 24-hour Holter ECG with an accelerometer. HR-Hf data collected every five minutes were plotted as the X-Y coordinates, and a two-compartment analysis was performed. The HR at the autonomic tone threshold was then determined at the intersection point of the lines. A loop of the HR-ST segment was drawn during walking to determine the ischemic threshold at which heart rate ischemic ST segment depression began and circadian variation was observed. The circadian rhythm at the sympathetic tone threshold and the HR at the ischemic threshold were high during the day and low at night. The HR at the ischemic threshold was 15-20% higher than that at the sympathetic tone threshold at night but only 9-13% higher during the day. Also, there was a period during which there was no significant difference between the HR at the two thresholds. In comparing circadian variation between HR at the sympathetic tone threshold and HR at the ischemic threshold, there was a period during which there was no significant difference between the HRs. This might suggest a period in which a high incidence of cardiac ischemic attack is likely. This information could provide a feasible indicator for appropriate exercise training for patients with ischemic heart disease.


Thermal Changes of One-Piece Versus Two-Piece Implants During Setting of an Autopolymerized Acrylic Resin.
Purpose: To evaluate differences in the temperature rise at the cervical area of one-piece vs two-piece implants during the setting of relined provisional crowns. Materials and Methods: A K-type thermocouple was fixed to the coronal thread of 15 one-piece implants and 15 two-piece implants that were mounted on a plexiglass apparatus. Baseline temperature (Bl Temp) was recorded before starting the curing process. The maximum temperature (Max Temp) reached during the process in both implant groups was also recorded. Total heat flux (THF) was calculated as well as the thermal amplitude (Temp-Amp) at the implant surface. Finally, the differences between the implant types were compared using unpaired t test. Results: The increase in temperature from baseline was statistically significantly greater in the one-piece implants than in the two-piece implants (P < .01). Similarly, the THF and Temp-Amp were significantly greater in the one-piece implants compared to two-piece implants (P < .01). Conclusions: The polymerization of PMMA-based resin temporary crowns produces a significant temperature rise in both one-piece and two-piece implants. It is advisable to use two-piece implants to restore immediately loaded implants to reduce the risk to implant surroundings that may occur due to the temperature rise at the implant neck.


THE VISUAL CELLS AND VISUAL PIGMENT OF THE MUDPUPPY, NECTURUS.
Electron microscopy of the visual cells of the mudpuppy Necturus have revealed several new or hitherto neglected features of organization: (a) A system of deeply staining micelles in virtually crystalline array, probably located in the lamellae of the rod outer segments. These particles may contain the visual pigment, porphyropsin. Counts of the micelles, and microspectrophotometric measurements of porphyropsin in the retina and single rods yield the estimate that each lamellar micelle may contain about 50 molecules of porphyropsin. (b) Systems of about 30 cytoplasmic filaments (here called dendrites), continuous with the cytoplasm of the inner segment, and standing like a palisade about the outer segments of the rods and cones. In the rods, one such filament stands in the mouth of each of the approximately 30 deep fissures that carve the outer segment into a radial array of lobules. (c) A system of deeply staining particles in the membranes of the dendrites, and another in the membranes of the pigment epithelial processes. It is suggested that these may have a part in interchanges of material with the outer segments. The ciliary process is found to penetrate more deeply than is commonly supposed into the outer segments of the rods and cones. The edge of each double-membrane disc in rods forms a differentiated rim structure, both around the disc circumference and bordering the fissures. These anatomical arrangements are summarized in Figs. 13 and 14, and the relevant measurements in Table I. The dilution of visual pigment in Necturus rods and cones and a general consideration of their microstructures make it seem unlikely that such typically solid state processes as exciton migration or photoconduction can transport the effects of light far from the site of absorption. Excitation must, therefore, be conveyed to the receptor as a whole by some axial structure. Among axial structures, the plasma membrane is most likely to be the site of nervous excitation. The ciliary process probably plays its main role in the embryogenesis and regeneration of outer segments; and the dendrites and pigment epithelial processes in exchanges of material with the outer segments and perhaps with one another.


Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation.
The 3-thia fatty acids, tetradecylthioacetic acid and 3,10-dithiadicarboxylic acid are mitochondrion and peroxisome proliferators. Administration of these promotes an increased transport of endogenous fatty acids to these organelles and a higher capacity of beta-oxidation. Administration of 3-thia fatty acids to rats resulted in a significant decrease of the hepatic level of docosahexaenoic acid (DHA) (17-24%) and especially eicosapentaenoic acid (EPA) (40-80%) accompanied by increased gene expression of mitochondrial 2,4-dienoyl-CoA reductase and enoyl-CoA isomerase. The mitochondrial oxidation of EPA was increased more than 4-fold after administration of 3-thia fatty acids. EPA-CoA was a good substrate for mitochondrial carnitine acyltransferase-I and treatment with 3-thia fatty acids increased the activity 1.7-fold. DHA was a poor substrate for both mitochondrial and peroxisomal beta-oxidation. DHA-CoA was a very poor substrate for mitochondrial carnitine acyltransferase-I and -II, and the activity did not increase after treatment. However, the peroxisomal DHA-CoA oxidase increased 10-fold after 3-thia fatty acid treatment, whereas the peroxisomal EPA-CoA oxidase increased only 5-fold. In isolated hepatocytes, 16% of total metabolized EPA was oxidized and 76% was incorporated into glycerolipids, whereas DHA was oxidized very little. We conclude that under conditions of increased mitochondrial and peroxisomal proliferation by 3-thia fatty acids, a relatively higher oxidation rate of polyunsaturated n-3 fatty acids might result in a decreased hepatic level of EPA and DHA. Under these conditions DHA seems to be oxidized by the peroxisomes, whereas EPA, which can be oxidized in both organelles, is mainly oxidized by mitochondria.


Use of RAPD fingerprinting for delineating populations of hilsa shad Tenualosa ilisha (Hamilton, 1822).
RAPD was used to delineate the hilsa populations sampled from the Ganga, Yamuna, Hooghly, and Narmada Rivers at six different locations. Six degenerate primers were used to generate the fragment patterns from the samples collected. All primers were highly polymorphic and generated high numbers of amplification products. Nei's genetic distances were calculated between locations. The overall average genetic distance among all the six locations was 0.295. The Fst value within the Ganga was 0.469 and within the Hooghly it was 0.546. The overall Fst value for the six populations analyzed was 0.590. The UPGMA dendrogram clustered the hilsa into two distinct clusters: Ganga and Yamuna populations and the Hooghly and Narmada populations.


Critical appraisal. Immediate loading of implants in the esthetic zone.
The predictability of dental implants using the traditional branemark protocol has been well documented. Since its inception, this protocol has been progressively challenged to decrease treatment time, minimize the number of surgical procedures, and maximize esthetic outcomes. Today, in specific clinical situations, implants may be placed and immediately loaded with provisional restorations. Immediate loading in the edentulous mandible has been well documented. There are also good data to show that immediate loading of the edentulous maxilla is also feasible if bone quality is suitable. The focus now has shifted toward immediate loading of implants placed in the esthetic zone. Clinicians have recognized that the challenge of providing anterior tooth replacements is in preserving the hard and soft tissue components that exist around natural teeth. The advantages of immediate restoration are obvious; however, the application of immediate or early load may pose an increased risk of implant failure in single-tooth situations. The prerequisites for achieving and maintaining acceptable results are not fully known. This review examines some of the literature concerning the reliability of early or immediate loading of implants placed in the esthetic zone.


Minocycline modulates NFκB phosphorylation and enhances antimicrobial activity against Staphylococcus aureus in mesenchymal stromal/stem cells.
Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties due to their anti-inflammatory, angiogenic, and even antibacterial properties. We have shown previously that minocycline enhances the wound healing phenotype of MSCs, and MSCs encapsulated in poly(ethylene glycol) and gelatin-based hydrogels with minocycline have antibacterial properties against Staphylococcus aureus (SA). Here, we investigated the signaling pathway that minocycline modulates in MSCs which results in their enhanced wound healing phenotype and determined whether preconditioning MSCs with minocycline has an effect on antimicrobial activity. We further investigated the in-vivo antimicrobial efficacy of MSC and antibiotic-loaded hydrogels in inoculated full-thickness cutaneous wounds. Modulation of cell signaling pathways in MSCs with minocycline was analyzed via western blot, immunofluorescence, and ELISA. Antimicrobial efficacy of MSCs pretreated with minocycline was determined by direct and transwell coculture with SA. MSC viability after SA coculture was determined via a LIVE/DEAD® stain. Internalization of SA by MSCs pretreated with minocycline was determined via confocal imaging. All protein and cytokine analysis was done via ELISA. The in-vivo antimicrobial efficacy of MSC and antibiotic-loaded hydrogels was determined in Sprague-Dawley rats inoculated with SA. Two-way ANOVA for multiple comparisons was used with Bonferroni test assessment and an unpaired two-tailed Student's t test was used to determine p values for all assays with multiple or two conditions, respectively. Minocycline leads to the phosphorylation of transcriptional nuclear factor-κB (NFκB), but not c-Jun NH2-terminal kinase (JNK) or mitogen-activated protein kinase (ERK). Inhibition of NFκB activation prevented the minocycline-induced increase in VEGF secretion. Preconditioning of MSCs with minocycline led to a reduced production of the antimicrobial peptide LL-37, but enhanced antimicrobial activity against SA via an increased production of IL-6 and SA internalization. MSC and antibiotic-loaded hydrogels reduced SA bioburden in inoculated wounds over 3 days and accelerated reepithelialization. Minocycline modulates the NFκB pathway in MSCs that leads to an enhanced production of IL-6 and internalization of SA. This mechanism may have contributed to the in-vivo antibacterial efficacy of MSC and antibiotic-loaded hydrogels.


Sea lamprey enlightens the origin of the coupling of retinoic acid signaling to vertebrate hindbrain segmentation.
Retinoic acid (RA) is involved in antero-posterior patterning of the chordate body axis and, in jawed vertebrates, has been shown to play a major role at multiple levels of the gene regulatory network (GRN) regulating hindbrain segmentation. Knowing when and how RA became coupled to the core hindbrain GRN is important for understanding how ancient signaling pathways and patterning genes can evolve and generate diversity. Hence, we investigated the link between RA signaling and hindbrain segmentation in the sea lamprey Petromyzon marinus, an important jawless vertebrate model providing clues to decipher ancestral vertebrate features. Combining genomics, gene expression, and functional analyses of major components involved in RA synthesis (Aldh1as) and degradation (Cyp26s), we demonstrate that RA signaling is coupled to hindbrain segmentation in lamprey. Thus, the link between RA signaling and hindbrain segmentation is a pan vertebrate feature of the hindbrain and likely evolved at the base of vertebrates.


The economic consequences of malnutrition in Cambodia, more than 400 million US dollar lost annually.
Cambodia is among the 28 worst countries globally with the highest rates of childhood malnutrition. The aim of the assessment was to apply published evidence associating malnutrition and a variety of functional consequences to project economic implications of this high rate of childhood malnutrition. Such information is vital to advocate for appropriate programs and action plan to reduce malnutrition (from severe stunting to micronutrient deficiencies). This exercise used a "consequence model" to apply these "coefficients of loss" established in the global scientific literature to Cambodia health, demographic and economic data to develop a national estimation of the economic losses link to malnutrition. The impact of the indicators of malnutrition analysed represent a burden to the national economy of Cambodia estimated at more than $400 million annually -2.5% of GDP. Micronutrient deficiencies suggest deficits in the quality of the diet - representing a national burden of more than $200 million annually while breastfeeding behaviours account for 6% of the burden. 57% of the losses emerge from indicators measured in children, while 43% of losses are from indicators independent of childhood measurements - indicators of maternal behaviour along with maternal and adult nutrition. Given the low cost of interventions and the high baseline losses, investment in nutrition programs in Cambodia is likely to offer high returns and attractive benefit cost ratios. Since nearly half the losses are determined prior to the birth of the child, this has implications for targeting and timing of programs.


Pressure-flow analysis of portal vein and hepatic artery interactions in porcine liver.
Interactions between the hepatic arterial and portal venous circulations were investigated in nine intact and eight isolated perfused porcine livers. Pressure-flow (P-Q) relationships were obtained in either the portal vein or hepatic artery with constant baseline or low flow in the other bed and a stable hepatic venous pressure (Phv). The slope was obtained by linear regression analysis of the P-Q relationship, and effective back pressure (Pback) was obtained from the pressure intercept for the portal vein and the measured zero-flow pressure for the hepatic artery. The Pback in the hepatic artery (13.4 +/- 1.5 mmHg) and the portal vein (4.6 +/- 0.3 mmHg) were higher than Phv (P < 0.05). Reducing portal vein flow (Qpv) produced an increase in hepatic artery flow (Qha) (P < 0.05) due only to a decrease in slope (P < 0.05). Decreasing Qha caused an identical change in Pback of the portal vein (P < 0.05) in the intact and isolated liver preparations. A change in Qpv alters the hepatic arterial resistance upstream from the site of a constant arterial Pback. Changes in total flow through the common sinusoidal compartment appear to alter the Pback of the portal vein via hydraulic mechanisms.


Long-term outcomes of patients with mitral regurgitation undergoing percutaneous coronary intervention.
The most appropriate treatment for patients with ischemic mitral regurgitation (MR) remains controversial. MR has prognostic importance in patients after myocardial infarction and those undergoing coronary artery bypass surgery, but the long-term outcomes after percutaneous coronary intervention (PCI) are less well defined. We evaluated patients who underwent PCI and had assessment of MR by left ventriculography and/or echocardiography in the year 2000. We determined effects of MR on 30-day and 5-year survival. The cohort included 711 patients (67% men) with an average age of 64.5 +/- 12.4 years. MR severity was divided into 3 strata: none (n = 420, 59%), mild (n = 209, 29%), and moderate to severe (n = 82, 12%). Patients with more severe MR differed from patients with mild or no MR in that they were older (p <0.001), more frequently women (p <0.001), and more likely to have a coronary artery bypass graft (p <0.001), myocardial infarction (p <0.001), and lower ejection fraction (p <0.001). Decreased survival rates were associated with increasing MR severity (none vs mild vs moderate to severe) at 30 days (100%, 98.7%, and 96.6%, respectively; p <0.0025) and 5 years (97%, 83.3%, and 57.5%; p <0.0001). MR was an important independent predictor of survival (hazard ratio 1.57, p <0.0009). In conclusion, patients with ischemic MR undergoing PCI have significantly decreased survival rates at 5 years, and severity of MR is an independent predictor of survival.


Communication: Diffusion constant in supercooled water as the Widom line is crossed in no man's land.
According to the liquid-liquid critical point (LLCP) hypothesis, there are two distinct phases of supercooled liquid water, namely, high-density liquid and low-density liquid, separated by a coexistence line that terminates in an LLCP. If the LLCP is real, it is located within No Man's Land (NML), the region of the metastable phase diagram that is difficult to access using conventional experimental techniques due to rapid homogeneous nucleation to the crystal. However, a recent ingenious experiment has enabled measurement of the diffusion constant deep inside NML. In the current communication, these recent measurements are compared, with good agreement, to the diffusion constant of E3B3 water, a classical water model that explicitly includes three-body interactions. The behavior of the diffusion constant as the system crosses the Widom line (the extension of the liquid-liquid coexistence line into the one-phase region) is analyzed to derive information about the presence and location of the LLCP. Calculations over a wide range of temperatures and pressures show that the new experimental measurements are consistent with an LLCP having a critical pressure of over 0.6 kbar.


Knowledge of Parkinson's Disease in a Multiethnic Urban Asian Setting.
Public knowledge regarding Parkinson's disease (PD) is important to facilitate good health-seeking behavior, but the literature on this topic is scarce. We aimed to explore the level of public knowledge regarding PD in a large multiethnic urban Asian cohort, and (as a secondary aim) in a smaller cohort of PD patients and caregivers. A Knowledge of PD Questionnaire (KPDQ) was developed and administered to members of the Malaysian general public, and to PD patients and caregivers. The KPDQ tests recognition of PD symptoms and general knowledge regarding PD. 1,258 members of the general public completed the KPDQ. Tremor was the most widely recognized symptom (recognized by 79.0% of respondents); however, 83.7% incorrectly believed that all PD patients experience tremor. Memory problem was the most widely recognized NMS. Overall, motor symptoms were better recognized than NMS. Common misperceptions were that there is a cure for PD (49.8%) and that PD is usually familial (41.4%). Female gender, Chinese ethnicity, tertiary education, healthcare-related work, and knowing someone with PD were independently associated with higher KPDQ scores. PD patients (n = 116) and caregivers (n = 135) demonstrated superior knowledge compared with the general public group, but one-third of them believed that PD is currently curable. This is the only study on public knowledge regarding PD in Asia. Important gaps in knowledge were evident, which could present a barrier to early diagnosis and appropriate treatment of PD. This highlights the need for targeted education campaigns and further research in this area.


Rational Design Principles of Attenuated Cationic Lytic Peptides for Intracellular Delivery of Biomacromolecules.
Intracellular delivery of bioactive macromolecules via endocytic pathways has utility in biotechnological and medicinal applications. Various endosomolytic peptides bearing glutamic acid (Glu) residues have been developed with the aim to achieve selective lysis of endosomal membranes without damaging cell membranes (plasma membranes) to release endosome-entrapped macromolecules and obtain their bioactivity. Glu residues on peptides are negatively charged in the extracellular medium, and substitution of this residue onto membrane-lytic peptides prevents its peptide-membrane interaction and its lytic activity. On the other hand, within endosomes, which have a reduced pH of ∼5, Glu is protonated, resulting in the reduction of the hydrophilicity of the peptide, unmasking its lytic activity. Despite this, a limited number of studies have elucidated the optimum positions for Glu substitution. This report investigated the positioning of Glu and the endosomolytic activities of cationic lytic peptides, ponericin-W3, and melittin. By cell-based assays, biophysical analyses, and molecular dynamics simulations, we found that analogues with Glu positioned on the borders between the hydrophobic and hydrophilic faces of the helical structures showed better performance than placing Glu within said faces.


Universal pulse shape scaling function and exponents: critical test for avalanche models applied to Barkhausen noise.
In order to test if the universal aspects of Barkhausen noise in magnetic materials can be predicted from recent variants of the nonequilibrium zero-temperature Random Field Ising Model, we perform a quantitative study of the universal scaling function derived from the Barkhausen pulse shape in simulations and experiment. Through data collapses and scaling relations we determine the critical exponents tau and 1/sigma nu z in both simulation and experiment. Although we find agreement in the critical exponents, we find differences between theoretical and experimental pulse shape scaling functions as well as between different experiments.


The treatment of six men with a learning disability convicted of sex offences with children.
This paper describes a cognitive therapy for men with a learning disability convicted of sex offences against children. Methods are described which focus the session, emphasize confidentiality, ensure that the patient accepts responsibility for the offence, and deal with issues of intent, harm done to the victim and sequences of offending behaviour. Methods for producing cognitive change are described. Patients were assessed regularly and data are presented in detail. While all six men showed improvement, there were several variables which interfered with the course of treatment. The study attempts to address two major problems in work with sex offenders: the difficulty of employing a controlled treatment design and the importance of a long follow-up period.


The mechanism of calcitonin gene-related peptide-containing nerve innervation.
Calcitonin gene-related peptide (CGRP) is a major neurotransmitter and CGRP-containing primary sensory neurons play an important role in nociception and potent vasodilation. CGRP-containing nerves in mesenteric arteries are decreased in pathological animal models (hypertension, diabetes, and atherosclerosis). In apolipoprotein E–knockout mice, which have atherosclerosis and peripheral sensory nerve defects, nerve growth factor (NGF)-mediated CGRP nerve facilitation was down-regulated, which may have been caused by the impairment of the Akt–NO–cGMP pathway. In addition, NGF-mediated CGRP neurite outgrowth was decreased in fructose-induced insulin-resistant rats. We recently discovered that renin–angiotensin inhibitors improved CGRP innervation in spontaneously hypertensive rats, indicating that rescuing CGRP nerve innervation might improve pathophysiological conditions. To find a novel reagent that facilitates CGRP nerves, a new model, phenol-injured perivascular nerve model rats, was established. Adrenomedullin, hepatocyte growth factor, and angiotensin II type 2 receptor activation induced CGRP nerve distribution in phenol-injured rats. Furthermore, in insulin-resistant model rats, the down-regulation of CGRP nerves was likely due to the depression of phosphoinositide 3-kinase (PI3K)-dependent Akt activation. Administration of candesartan improves CGRPergic function via the PI3K–Akt pathway in insulin-resistant rats. Thus, clarification of the mechanisms of CGRP nerve defects may constitute future therapeutic targets.


Gadolinium contrast agents: their role in vascular and nonvascular diagnostic angiography and interventions.
Gadolinium-based contrast agents can be used for diagnostic and interventional angiographic procedures to reduce contrast-related nephrotoxicity or in patients with a history of severe allergic reaction to iodine-containing contrast material. These agents are best used in conjunction with CO(2) to complete nondiagnostic CO(2) angiograms and to monitor the progress of a percutaneous intervention. However, the total volume of gadolinium that can be administered, the reduced quality of gadolinium digital subtraction angiography images, and the increased cost of the gadolinium-based agents can limit their use.


The porcine M blood group system: evidence to suggest assignment of its M1 factor to a new system (P).
A new allele Maejm and a more precise genetic analysis of the Ml factor previously assigned to the M system are described after screening three generation families (Wild Boar x Pietrain, Meishan x Pietrain) for the M blood group system using a complete set of 13 M reagents. From informative families with proven parental M genotypes it was shown that the Ml antigen is controlled by an allele from another system. We propose to designate this new system P and to change the factor designation from Ml to Pa.


Substance P and arthritis: analysis of plasma and synovial fluid levels.
The uncadecapeptide substance P (SP), which is localized in peripheral and central terminals of afferent nerve fibers with polymodal nociceptors, has recently been implicated as having a neurogenic, inflammatory role in experimental arthritis. We used a radioimmunoassay to measure SP levels in plasma and synovial fluid samples from patients with rheumatoid arthritis (RA), osteoarthritis (OA), Reiter's syndrome (RS), and posttraumatic arthritis, as well as in plasma samples from 13 normal subjects. Plasma SP levels in RS patients exceeded levels in RA and OA patients, which in turn exceeded levels in posttrauma patients and in normal subjects. Synovial fluid SP levels exceeded respective plasma levels for all groups, except in RS patients, in whom the plasma level was not significantly different from that in synovial fluid. SP levels in synovial fluid of RA, OA, and RS patients did not differ significantly from each other, but the level in posttrauma patients was higher than in all other groups (P less than 0.005). These studies demonstrate localized intraarticular SP release, and significant plasma/synovial fluid SP concentration gradients in several forms of arthritis.


Laser therapy for the restoration of vaginal function.
Laser therapy has a therapeutic role in various medical conditions and most recently has gained interest as a non-hormonal treatment for genitourinary syndrome of menopause (GSM) and as a non-invasive option for stress urinary incontinence (SUI). Several therapies are available to alleviate GSM symptoms, including hormonal and non-hormonal products. Both microablative fractional CO2 laser and the non-ablative vaginal Er:YAG laser (VEL) induce morphological changes in the vaginal tissues, and data from non-randomized clinical trials suggest that laser therapy can alleviate vaginal dryness and dyspareunia. VEL has been reported to improve SUI as well as vaginal prolapse. Although large randomized trials have not been reported, the evidence suggests that VEL can be offered as a safe and efficacious alternative to hormone replacement therapy (HRT) for GSM, as well as a first-line treatment for mild to moderate SUI, before surgical procedures are resorted to. Randomized studies are needed to compare laser treatments with other therapies, as well as to assess the duration of the therapeutic effects and the safety of repeated applications. Research is presently evaluating both an automated robotic probe for VEL treatments and an intraurethral probe for the treatment of severe and type III SUI.


Gentamicin pharmacokinetics in adults with bacterial endocarditis.
The pharmacokinetics of gentamicin in adult patients with endocarditis were studied. The records were reviewed for 64 patients treated for bacterial endocarditis and for whom serum gentamicin concentrations had been requested between May 1990 and May 1993. The patients were divided into those with serum creatinine concentration (SCr) <1.2 mg/dL and those with SCr > or = 1.2 mg/dL. The measured serum gentamicin concentrations, patient demographic information, dosage interval, and SCr were entered into a pharmacokinetics program for analysis. The pharmacokinetic values evaluated were steady-state distribution volume (V), clearance (CL), elimination rate constant (k), and half-life (t1/2). The mean +/- S.D. t1/2 and V of gentamicin were 4.7 +/- 2.4 hr and 0.29 +/- 0.11 L/kg. Half-life was correlated with SCr and V. These two variables may explain 66% of the variation in t1/2. No difference in V was observed between patients with normal versus abnormal SCr. Men had a lower k than women. V and CL were lower in patients under age 60 than in older patients. Adult patients with endocarditis may have expanded gentamicin V. V and CL accounted for most of the variation in gentamicin t1/2.


Adaptation of the duodenum and ileum of the rat to mid-gut resection: enzyme activity and trace metal status.
Activities of the enzymes lactase, sucrase, maltase, alkaline phosphatase, and superoxide dismutase (SOD) were measured in mucosa of duodenum and ileum of the rat after 70% resection of mid-small intestine or sham operation (transection). We also measured the concentrations of zinc, copper, and manganese in several tissues to assess trace metal homeostasis postresection. Resection resulted in decreased specific activities of disaccharidases and alkaline phosphatase in duodenum, while specific activities remained unchanged in ileum. Specific activity of total SOD (the sum of Cu-Zn and Mn SOD) and Mn SOD was the same in duodenum after resection but was markedly increased in ileum. Tissue trace metal concentrations changed minimally. Because of postresection mucosal growth, total segmental activity of disaccharidases and alkaline phosphatase was the same in duodenum and increased in ileum of resected compared to transected rats. Segmental activity of total SOD and Mn SOD doubled in duodenum and trebled in ileum of resected as compared to transected rats. Thus, total segmental enzyme activity is maintained or increased postresection by increased enterocyte proliferation rate and mucosal growth.


Blue nevus of the prostate: incidental finding in radical prostatectomy specimen with a pre-operative echographic image of peripheral hypoechogenic nodule.
Blue nevus is a stromal melanin deposition, which is microscopically characterized by deeply pigmented melanin-filled spindle cells within the fibromuscular stroma. Cases with prominent melanosis such as those with grossly visible pigment are uncommon. Melanocytic lesions of the prostate are incidental findings with no evidence of malignant transformation. There have only been very few reports of a malignant melanoma of primary prostatic origin. We report an incidental finding of a blue nevus of the prostate, in a radical prostatectomy specimen, in a 64-years-old man with a pre-operative ecographic image of peripheral hypoechogenic nodule. The are very few reports of blue nevi associated to prostatic adenocarcinoma, but none has been evidentiated before surgery as a distinct ultrasound lesion interpreted as adenocarcinoma, therefore inducing the clinician to perform biopsies and consequently a radical prostatectomy.


False-positive results obtained for immunoglobulin M antibody tests of cerebrospinal fluid for herpes simplex virus in a patient with varicella zoster virus encephalitis.
A 66-year-old man presented with a disturbed consciousness and seizure-like movements, followed by the initial symptoms of herpes zoster. Immunoglobulin (Ig) M antibodies to varicella zoster virus (VZV) as well as herpes simplex virus (HSV) were positive in the cerebrospinal fluid (CSF), whereas polymerase chain reaction of the CSF was positive for VZV-DNA but negative for HSV-DNA. The serum/CSF IgM ratio for VZV and HSV increased in association with a clinical improvement. This is a case report of a rare case of VZV encephalitis demonstrating false-positive results for IgM to HSV in the CSF. The increase in the serum/CSF IgM ratio possibly reflects a recovery from blood-brain barrier breakdown.


Prevalence of fatigue and associated factors in chronic low back pain patients.
to determine the prevalence and key factors associated with fatigue in chronic low back pain patients. cross-sectional study of 215 chronic low back pain patients from three health care centers and two industrial corporations. The crude prevalence of fatigue and its 95% confidence interval (CI) were calculated. Associations between fatigue and the independent variables were measured. the prevalence of fatigue among the participants was 26.0% [95% CI: 20.3-32.5]. Fatigue was independently associated with depression and self-efficacy. An increase of one unit in the score of depression increased the risk of fatigue by 9%; an increase of one unit in the score of self-efficacy reduced the risk of fatigue by 2%. fatigue was prevalent in chronic low back pain patients and associated with depression and self-efficacy. Knowing these factors can direct strategies for prevention and control of fatigue in chronic low back pain patients.


Effect of pH conditioners on tooth bleaching.
The purpose of this study was to evaluate the effect of pH conditioners on tooth bleaching using hematoporphirin-stained paper and artificially discolored bovine tooth model. Experimental bleaching gels containing 23% hydrogen peroxide, adjusting pH 7.0 by different pH conditioners (NaOH, NaHCO3, Na2CO3, KOH, KHCO3, and K2CO3), were prepared. Each bleaching gel was applied on a hematoporphirin-stained paper, and the light was exposed for 5 min. Before and after bleaching, color was measured and color difference was calculated. Artificially discolored bovine tooth samples were prepared and bleached by four experimental bleaching gels containing NaOH, NaHCO3, Na2CO3, or KHCO3. The bleaching time was 10 min with light exposure, and bleaching was repeated 10 times. The color of bleached surface was measured at each bleaching period, and color difference was calculated. In the experiment using hematoporphirin-stained paper, degrees of color difference were KHCO3 > NaHCO3 > KOH > NaOH > Na2CO3 ≥ K2CO3. In the experiment using bovine teeth, degrees of color difference were KHCO3 > NaHCO3 > NaOH > Na2CO3. It was concluded that the bleaching materials with same pH and different pH conditioners showed different bleaching effects and that both cation and anion in the pH conditioners affected bleaching effect.


[Apoptosis: physiological cell death and its role in pathogenesis of diseases].
Apoptosis is a physiological process of cell death by which a single cell may be eliminated from the living tissue. Since the process is mediated by specific proteins encoded in the host's genome, it is also a programmed cell death. Apoptosis is responsible for tissue remodelling during the development and turnover of normal tissue (e.g. haematopoietic cells) throughout the life span of multicellular organisms. In contrast to cells undergoing a pathological cell death (necrosis), the morphological changes that accompany apoptosis are characterised by condensation of chromatin and cytoplasm and subsequent fragmentation of the cell into small membrane-bound segments called apoptotic bodies. The maintenance of membrane integrity in apoptosis prevents the release of deleterious cytoplasmic substances and the activation of inflammatory responses. Apoptosis can be initiated by a variety of events arising either within the cell (p53) or externally (death receptor ligands engaging specific cell surface receptors of the target cell). Following recognition of the stimuli and clustering of membrane proteins into a death domain, certain cytoplasmic proenzymes are converted to their active form (caspases). After the death effector machinery is activated, the cell enters the irreversible common degradation phase of cytoskeletal disorganisation. Survival proteins (bcl-2 family) control the caspase-driven engine of destruction. Disordered apoptotic process participates in the pathogenesis of various diseases, such as neoplasms, chronic inflammatory or systemic autoimmune diseases, and other conditions.


Endourologic Management of a 15-Year-Old Neglected, Fragmented, and Encrusted Ureteral Stent.
Background: Ureteral stents (Double-J stents) have been widely used in urology to prevent or relieve ureteral obstruction and have become an integral part of urologic practice. However, if ureteral stents are kept for a prolonged period or neglected, they can cause significant morbidity because of complications such as stent migration, encrustation, occlusion, stone formation, and fragmentation. Therefore, it is crucial to remove stents as soon as possible after they have served their purpose, to prevent complications and morbidity. Case Presentation: In this study, we present a case of a 28-year-old man who presented with broken extensively encrusted Double-J stent, with bulky stones at both ends of the stents that had been inserted 15 years ago, after an open right pyelolithotomy, and that was lost to follow-up. Cystolithotripsy, ureteroscopic laser lithotripsy, and two consecutive mini-percutaneous nephrolithotomies were necessary to extract the stent and the patient became stone free. Conclusion: Forgotten Double-J stents for long times with extensive encrustation and stone formation can be managed safely with a combined endourologic approach with minimal morbidity.


Relation of Obstructive Sleep Apnea and a Common Variant at Chromosome 4q25 to Atrial Fibrillation.
Obstructive sleep apnea (OSA) and single nucleotide polymorphisms (SNPs) at the 4q25 locus are associated with increased risk of atrial fibrillation (AF). Whether these associations are independent of traditional risk factors for AF remains unknown. Using billing code queries and manual chart review, we assembled a cohort of adults that underwent overnight polysomnography and at least 1 12-lead electrocardiogram. Case status was defined by electrocardiographic data in support of AF or documentation of AF by a staff cardiologist. Controls were defined by a lack of primary evidence of AF and absence of a diagnosis of AF in the medical record. OSA severity was categorized based on Apnea-Hypopnea Index. Genotyping for a key 4q25 SNP (rs2200733) was performed using the Sequenom platform. Logistic regression was used to test for associations of AF with OSA category and 4q25 SNP genotype while adjusting for age, gender, body mass index, ancestry, hypertension status, and heart failure status. The cohort consisted of 674 subjects (62 ± 13 years; 44% women), including 132 patients with AF. After adjustment for established risk factors, the association between AF and OSA severity was borderline significant (odds ratio 1.2, 95% CI 1.0 to 1.5). The association between AF and 4q25 SNP status remained significant in a fully adjusted model that included OSA severity (odds ratio 1.5, 95% CI 1.3 to 5.7). In conclusion, OSA severity and the chromosome 4q25 SNP genotype were associated with AF status independent of clinical risk factors. Knowledge of AF-related SNPs may enhance AF risk stratification for those undergoing polysomnography.


Differential effects of sympatholytic agents on the power spectrum of rats during the cooling-induced hemodynamic perturbations.
Cold stress-elicited hemodynamic perturbations (CEHP) its underlying mechanisms still not clear. We examined the difference of two effector arms of sympathetic outflows, the sympathoadrenal system, and postganglionic sympathetic neurons, their role in CEHP genesis by using two sympatholytic agents, fusaric acid (FA, dopamine-β-hydroxylase inhibitor) and guanethidine (GUA, norepinephrine-depleting drug). Adult male Sprague-Dawley rats were divided into three groups (n = 6, each), an intraperitoneal injection of control vehicle saline or FA or GUA and then all rats were subjected to a 10-min CS trial. Systolic blood pressure (SBP), heart rate (HR), dicrotic notch (Dn), power spectrum of blood pressure variability and HR variability (BPV, HRV), and coherence spectrum at very-low, low, and high frequency regions (VLF: 0.02-0.2 Hz, LF: 0.2-0.6 Hz, and HF: 0.6-3.0 Hz) were monitored using telemetry throughout the experiment course. We observed both FA and GUA attenuated SBP and HR and the spectral powers of BPV at VLF, LF, and HF in both baseline (PreCS) and cold stimuli (CS) conditions, but apparently, FA exerted stronger effects than GUA did. Both FA and GUA generally attenuated the responses of CS-induced pressor and tachycardia and the CS-increased VLFBPV, LFBPV, and HFBPV, but different effects between FA and GUA, when compared with control vehicle under CS. FA reduced the CS-reduced VLFHRV and the CS-increased LFBPV and HFBPV more than GUA did. We further observed in both PreCS and CS, GUA but not FA increased HFHRV; FA reduced but apparently, GUA increased the occurrence of Dn. Finally, we observed FA weakened, but GUA strengthened the coherence between BPV and HRV at both LF and HF regions. Taken together, the different effects between FA and GUA on CEHP indicate a role of the sympathoadrenal mechanism in response to CS.


Maze Procedures for Atrial Fibrillation, From History to Practice.
Atrial fibrillation may result in significant symptoms, (systemic) thrombo-embolism, as well as tachycardia-induced cardiomyopathy with cardiac failure, and consequently be associated with significant morbidity and mortality. Nowadays symptomatic atrial fibrillation can be treated with catheter-based ablation, surgical ablation or hybrid approaches. In this setting a fairly large number of surgical approaches and procedures are described and being practised. It should be clear that the Cox-maze procedure resulted from building up evidence and experience in different steps, while some of the present surgical approaches and techniques are being based only on technical feasibility with limited experience, rather than on a process of consequent methodology. Some of the issues still under debate are whether or not the maze procedure can be limited to the left atrium or even to isolation of the pulmonary veins or that bi-atrial procedures are indicated, whether or not cardiopulmonary bypass is to be applied and which route of exposure facilitates an optimal result. In addition, maze procedures are not procedures guide by electrophysiological mapping. At least in theory not in all patients all lesions of the maze procedures are necessary. A history and aspects of current practise in surgical treatment of atrial fibrillation is presented.


Prolonged length of stay associated with air leak following pulmonary resection has a negative impact on hospital margin.
Protracted hospitalizations due to air leaks following lung resections are a significant source of morbidity and prolonged hospital length of stay (LOS), with potentially significant impact on hospital margins. This study aimed to evaluate the relationship between air leaks, LOS, and financial outcomes among discharges following lung resections. The Medicare Provider Analysis and Review file for fiscal year 2012 was utilized to identify inpatient hospital discharges that recorded International Classification of Diseases (ICD-9) procedure codes for lobectomy, segmentectomy, and lung volume reduction surgery (n=21,717). Discharges coded with postoperative air leaks (ICD-9-CM codes 512.2 and 512.84) were defined as the air leak diagnosis group (n=2,947), then subcategorized by LOS: 1) <7 days; 2) 7-10 days; and 3) ≥11 days. Median hospital charges, costs, payments, and payment-to-cost ratios were compared between non-air leak and air leak groups, and across LOS subcategories. For identified patients, hospital charges, costs, and payments were significantly greater among patients with air leak diagnoses compared to patients without (P<0.001). Hospital charges and costs increased substantially with prolonged LOS, but were not matched by a proportionate increase in hospital payments. Patients with LOS <7, 7-10, and ≥11 days had median hospital charges of US $57,129, $73,572, and $115,623, and costs of $17,594, $21,711, and $33,786, respectively. Hospital payment increases were substantially lower at $16,494, $16,307, and $19,337, respectively. The payment-to-cost ratio significantly lowered with each LOS increase (P<0.001). Higher inpatient hospital mortality was observed among the LOS ≥11 days subgroup compared with the LOS <11 days subgroup (P<0.001). Patients who develop prolonged air leaks after lobectomy, segmentectomy, or lung volume reduction surgery have the best clinical and financial outcomes. Hospitals experience markedly lower payment-to-cost ratios as LOS increases. Interventions minimizing air leak or allowing outpatient management will improve financial performance and hospital margins for lung surgery.


Comparison of Two Shiga Toxin-producing Escherichia coli (STEC) Isolation Protocols in Raw Cow's Milk Cheese Enrichment Broths: Direct STEC Isolation Versus Techniques Based on Immuno-concentration.
The presence of Shiga toxin-producing Escherichia coli (STEC) in dairy products made with raw milk is a major concern for food safety authorities and industries. Two approaches have been proposed to isolate STEC from food. In the IC-Protocol (immuno-concentration protocol), specific serogroups are identified in the enrichment broth after the detection of the stx and eae genes. An immuno-concentration of the targeted serogroups is performed before isolating them on specific media. In the DI-Protocol (direct isolation protocol), a direct isolation of all STEC present in the enrichment broth is carried out after the detection of stx genes. We compared the ability of these two methods to isolate STEC O26:H11, O103:H2, O111:H8, O145:H28, and O157:H7 after artificial inoculation in four different raw milk cheeses. Across all serogroups and cheese types, STEC were isolated in 83.3% of samples when using the IC-Protocol but only 53.3% of samples with the DI-Protocol. For two cheese types, the DI-Protocol failed to isolate STEC O157:H7 strains altogether. Our results suggest that IC-Protocol is a robust methodology to effectively isolate STEC across a range of cheese types.


1-Acyl-, 3-acyl- and 1,3-diacyl-3-furfuryl-1-phenylthioureas with platelet antiaggregating and other activities.
The synthesis in excellent yields of 1-acyl-3-furfuryl-1-phenylthioureas 2 by reacting at t less than or equal to 10 degrees C 3-furfuryl-1-phenylthiourea 1, prepared in situ from furfurylamine and phenyl isothiocyanate, with aromatic or heterocyclic acyl chlorides in pyridine solution is described. 1-Acylthioureas 2 rearranged in high yields to 3-acylthioureas 3 by treatment with sodium hydroxide in heterogeneous phase. 1,3-Diacyl-3-furfuryl-1-phenylthioureas 4 were obtained in satisfactory yields by treatment of 1 with two moles of acyl chloride as in the case of 1-monoacylation. The thiourea 1 prepared in situ reacted with iodomethane in dimethylformamide solution and in the presence of sodium hydride to give in high yield the S-methyl derivative, namely the methyl ester of N-phenyl-1-furfurylaminethiocarboximidic acid. Some acylthioureas 2 and 4 showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid. The 1,3-diacylthiourea 4 c exhibited an appreciable anticonvulsant activity in mice and some compounds 2 and 4 moderate competitive antiacetylcholine and H1-antihistamine effects in vitro.


Malignant transformation in 1458 patients with potentially malignant oral mucosal disorders: a follow-up study based in a Taiwanese hospital.
It is generally accepted that the development of cancer in the oral mucosa is preceded by an identifiable non-invasive precursor lesion. The aim of this follow-up study was to estimate the rate and the time to transformation in a group of patients from southern Taiwan with potentially malignant oral epithelial lesions. The follow-up time is defined as the duration between the onset of the initial diagnosis and the occurrence of confirmed oral cancer. A total of 1458 patients with histological diagnoses of various pre-malignant oral lesions were followed up between 1991 and 2001. The average age at initial diagnosis was 47.5 years. The histological diagnoses were divided into six categories: epithelial dysplasia with hyperkeratosis/epithelial hyperplasia (8.85%); epithelial dysplasia with submucous fibrosis (2.54%); submucous fibrosis (27.57%); hyperkeratosis/epithelial hyperplasia (29.01%); lichen planus (9.80%) and verrucous hyperplasia (22.22%). Within the cohort of 1458 patients, 44 patients progressed to oral cancer in the same site as the initial lesions with an overall transformation rate of 3.02% and a mean follow-up time of 42.64 months. Eight of the 166 patients with dysplastic lesions and 15 of 423 patients with hyperkeratosis/epithelial hyperplasia progressed to malignancy. The other patients with malignant transformation originated from various pre-cancerous oral lesions and conditions (submucous fibrosis, eight of 402; lichen planus, three of 143; verrucous hyperplasia, 10 of 324). These results indicate that patients with pre-malignant oral lesions need long-term follow up.


The Development and Evaluation of an Electronic Health Record Efficiency Workshop for Providers.
The electronic health record (EHR) has historically been known to be a source of stress and dissatisfaction, leading to reduced efficiency and productivity for providers. This issue is complicated by constant changes in EHRs that are necessary to keep systems current with evolving functionality. Knowing the existence of this problem, an evidenced-based solution, known as an efficiency workshop, was developed by our information technology training and optimization team for providers as a means of ongoing professional development. The objectives of this project were to identify EHR optimization needs for providers in various clinical departments and improve their EHR satisfaction. The development of a program focused on provider efficiency tools and personalization was key and, once piloted, how to measure program success. Efficiency workshops comprised members of the IT training team who set up on site training sessions during reserved time with providers during departmental meetings. Sessions focused on reviewing EHR efficiency tools using demonstration of existing system functionality. Participating providers were given continuing medical education (CME) credits upon completion of evaluations used as a quality improvement tool for the program. Descriptive results showed that providers were satisfied with this method of EHR instruction. Subjective feedback yielded positive themes such as informative, well done, organized, and helpful. This initiative began as a pilot program and successfully expanded across clinical departments at our academic medical center. Future plans are to sustain and further invest in this program by using EHR reporting features to further customize these sessions and evaluate impact on system use.


CD44 expression in human astrocytes and oligodendrocytes in culture.
CD44 is a glycoprotein present on the surface of some lymphocyte cell populations and other non-lymphoid cells, and is involved in many functions related to cell-cell and cell-matrix interactions. In this study, expression of CD44 antigen in primary neural cell cultures derived from fetal and adult human brains was investigated. In cultures processed for double immunofluorescence staining, approximately 80% of fetal astrocytes and more than 95% of adult astrocytes expressed the CD44 antigen on the cell bodies and processes; CD44 was also detected in 50-60% of adult oligodendrocytes. Neurons in fetal brain cell cultures did not express CD44 at all. Western blot analysis performed in astrocyte- and in neuron-enriched cultures confirmed the results from immunostaining and showed that the antibody against CD44 reacted with a polypeptide, of approximately 80 kD, that is present exclusively in the astrocyte-enriched cultures, but absent in neuron-enriched cultures. Our results indicate that CD44 glycoprotein is constitutively expressed in the human cells of glial cell lineage and its role is likely to be associated with normal neuroglia-mediated adhesion/recognition processes.


Constitutive and inducible Rel/NF-kappa B activities in mouse thymus and spleen.
We have studied the expression of members of the rel family of transcription factors and ikba in mouse thymus and spleen by in situ hybridization. Our results show that the rel genes have different temporal and spatial patterns of expression suggesting distinct roles in these lymphoid tissues. The Rel/NF-kappa B proteins and I kappa B alpha in thymus and spleen were also analysed by Western blotting and electrophoretic mobility shift assays. Although RelB protein is present at significantly lower levels in thymus and spleen extracts when compared to RelA, in both tissues the predominant kappa B-binding activity consists of p50/RelB and p52/RelB heterodimers and only very little binding of RelA-containing complexes to kappa B sites was detected. Significant binding of c-Rel complexes was only found in spleen extracts. Treatment of thymus and spleen extracts with deoxycholate (DOC), however, results in a strong increase in binding to kappa B sites of both RelA and c-Rel complexes. In contrast, binding of RelB complexes is not induced after DOC treatment. Our results suggest a differential role of Rel/NF-kappa B complexes in mouse thymus and spleen with RelB heterodimers representing the constitutive kappa B-binding activity, whereas RelA and c-Rel complexes most likely are involved in inducible kappa B-binding and gene activation.


[Heart rate control in chronic heart failure patients received cardiovascular implantable electronic device therapy: effects of optimized medication].
Objective: To investigate the heart rate control situation of chronic heart failure (CHF) patients who received cardiovascular implantable electronic device (CIED) therapy, and to assess the heart rate control efficacy by optimized medication adjustment. Methods: We performed a perspective study in heart failure with reduced left ventricular ejection fraction (HFrEF) patients who received CIED according to guideline recommendations, patients were enrolled from January 2012 to January 2017. Resting heart rate (RHR) recorded by electrocardiogram after 10 minutes' rest and medication usage within 1 month were recorded at baseline. RHR less than 70 beats per minute (bpm) was regarded as well controlled. β-receptor blockers and (or) ivabradine would be added in patients whose RHR were over 70 bpm. RHR after optimized medication adjustment was recorded during follow-up period. Results: One hundred and fifty patients were included in this study with average RHR (80.6±11.9) bpm. RHR was<70 bpm in 27.3% (41/150) patients at baseline and β-receptor blockers was underused in 80.7% patients (88/109) whose RHR was>70 bpm. The overall RHR decreased to (73.1±10.4) bpm and percent of patients with RHR<70 bpm increased to 70.0% (105/150) after up-titration of β-receptor blockers compared to baseline (χ2=52.958, P<0.001). Ivabradine was added in the rest 45 patients and RHR was<70 bpm in 43 out of 45 patients after ivabradine use. The overall RHR decreased to (67.1±2.7) bpm and percent of RHR<70 bpm significantly increased to 98.7% (148/150) (χ2=44.504, P<0.001 vs. up-titration of β-receptor blockers only). Conclusion: RHR in CHF patients who received CIED therapy is not ideally controlled in this patient cohort, individual up-titration ofβ-receptor blockers and ivabradine use may help to optimize RHR in these patients.


Cardiovascular therapy and pharmacogenetics in 2007.
John Carlquist received a PhD from the Department of Cellular Viral and Molecular Biology at the University of Utah School of Medicine (UT, USA) with research emphasis in molecular immunology. After completion of his training, he received a faculty appointment in the Department of Internal Medicine, University of Utah, where he became interested in immune mechanisms in cardiovascular disease. He developed an interest in genetics through studies of human leukocyte antigen (HLA) associations with idiopathic dilated cardiomyopathy and rheumatic heart disease. He began the Molecular Diagnostics Laboratory for Intermountain Healthcare and continues to serve as Technical Director; he also directs the Intermountain Heart Study Molecular and Genetic Research Laboratory. Current research interests include the genetics of lipid metabolism as related to coronary heart disease and the genetic factors influencing drug treatment outcomes.


The effect of cyproheptadine (periactin) on rejection of rat kidney allografts.
The effect of cyproheptadine, a potent platelet deaggregator, was investigated in rats bearing renal allografts. Thirty-three bilaterally nephrectomized LEW rats received orthotopic transplants of a (LEW X BN)F-1 kidney. Fourteen rats were treated with cyproheptadine, 1.5 mg/kg i.m. daily, for 60 days after transplantation; the remaining animals served as controls. The median allograft survival time in the cyproheptadine group was prolonged to 64 days compared to 12 days in the untreated group (P less than 0.005). In the cyproheptadine group the blood urea nitrogen rose to over 150 mg/100 ml 1 week after transplantation, fell to 80-120 mg/100 ml, and then rose steadily from the day after transplantation until the death of the animals. Despite prolonged survival, cyproheptadine-treated animals usually showed the histological findings of acute and chronic renal rejection. Cyproheptadine may be a useful adjunct to immunosuppression in the management of human renal allotransplantation.


Detection of the Progression of Anthesis in Field-Grown Maize Tassels: A Case Study.
The tassel of the maize plant is responsible for the production and dispersal of pollen for subsequent capture by the silk (stigma) and fertilization of the ovules. Both the amount and timing of pollen shed are physiological traits that impact the production of a hybrid seed. This study describes an automated end-to-end pipeline that combines deep learning and image processing approaches to extract tassel flowering patterns from time-lapse camera images of plants grown under field conditions. Inbred lines from the SAM and NAM diversity panels were grown at the Curtiss farm at Iowa State University, Ames, IA, during the summer of 2016. Using a set of around 500 pole-mounted cameras installed in the field, images of plants were captured every 10 minutes of daylight hours over a three-week period. Extracting data from imaging performed under field conditions is challenging due to variabilities in weather, illumination, and the morphological diversity of tassels. To address these issues, deep learning algorithms were used for tassel detection, classification, and segmentation. Image processing approaches were then used to crop the main spike of the tassel to track reproductive development. The results demonstrated that deep learning with well-labeled data is a powerful tool for detecting, classifying, and segmenting tassels. Our sequential workflow exhibited the following metrics: mAP for tassel detection was 0.91, F1 score obtained for tassel classification was 0.93, and accuracy of semantic segmentation in creating a binary image from the RGB tassel images was 0.95. This workflow was used to determine spatiotemporal variations in the thickness of the main spike-which serves as a proxy for anthesis progression.


Effects of Lanthanum on the Photosystem II Energy Fluxes and Antioxidant System of Chlorella Vulgaris and Phaeodactylum Tricornutum.
The rare earth elements are widely used in agricultural and light industry development. They promote the growth of crop seedlings, enhance root development and change the metal properties. Due to the large amount of rare earth minerals mined in China, rare earth elements have been detected in both coastal and estuary areas. They cause pollution and threaten the health of aquatic organisms and human beings. This study investigates the effects of lanthanum on two marine bait algae, and analyzes the changes in the photosynthetic and antioxidant systems of the two algae. The results show that rare earth elements have significant inhibitory effects upon the two algae. The OJIP kinetic curve value decreases with an increasing concentration of La(NO3)3 ·6H2O. The parameters of the fluorescence value were analyzed. The ABS/RC increases and the DI0/RC decreases during the first 24 h after exposure. The effects on the photosynthetic and antioxidant systems at low concentrations (both EC10 and EC20) show that the TR0/ABS increases, and the ET0/RC, ABS/RC, and DI0/RC has a decreasing trend after 30 min. However, after 24 h, normal levels were restored. In addition, the study finds that the TR0/ABS increases after 24 h, leading to an increase in reactive oxygen species. The antioxidant system analysis also confirms the increase in the activities of antioxidant enzymes, such as SOD and GSH. The experiment is expected to support the marine pollution of rare earths and the theoretical data of the impact on marine primary producers.


Higher perceived stress and exacerbated motor symptoms in Parkinson's disease during the COVID-19 lockdown in New Zealand.
Stress plays a key role in Parkinson's disease (PD) by acting on the dopaminergic system and worsening patients' motor function. The impact of New Zealand's strict lockdown measures to contain COVID-19 on perceived stress and PD motor symptoms remains unknown. Here we examined the relationship between perceived levels of stress, changes in physical activity levels and PD motor symptoms during lockdown. During lockdown, 134 participants with PD and 49 controls completed a survey assessing perceived stress, self-reported changes in PD motor symptoms and physical activity duration and intensity prior to and during lockdown. Perceived stress was higher in PD than controls, and in those reporting a worsening of tremor, balance/gait, dyskinesia and bradykinesia compared to those indicating no change during the COVID-19 lockdown. These effects were not modulated by physical activity. Reducing stressors may be an important adjunct treatment strategy to improve motor function in PD.


Future fertility for individuals with differences of sex development: Parent attitudes and perspectives about decision-making.
Children, adolescents, and young adults (children/youth) with differences/disorders of sex development (DSD) face challenges related to future fertility; this may be due to variations in gonadal development, and, for some, gonadectomy performed to reduce the risk of malignancy. Childhood may be the only time for preservation of biological fertility potential for children/youth who undergo gonadectomy or have early gonadal failure. Fertility-related decision-making for these patients is particularly complicated, due to the need for parental proxy decision-making, potential discordance between gender identity and gonadal type, and uncertain future assisted reproductive technologies. This study aimed to assess: (1) attitudes regarding future fertility, and (2) healthcare needs for fertility-related decision-making among parents of children/youth with DSD. Semi-structured qualitative interviews about future fertility were conducted with parents of children/youth with DSD. Parents who had never discussed fertility with a healthcare provider were excluded. Grounded theory methodology was used to identify emergent themes and patterns. Demographics and clinical characteristics were assessed via survey and medical chart review. Nineteen parents were interviewed (participation rate: 60%, 14 mothers/5 fathers, median patient age at diagnosis 6 months (range 0-192), eight DSD diagnoses). The most common emergent themes are summarized in the Summary Table. Most parents identified fertility as a key concern, both at time of diagnosis and throughout development. Parents expressed difficulty with timing of disclosure about potential infertility to their children. Multiple preferences related to medical decision-making about future fertility and fertility preservation were expressed, including: a desire for step-by-step decision-making, and use of medically vetted information and research to guide decisions. This qualitative study provided new information about the perspectives of parents of children/youth with DSD regarding future fertility. Previous studies have suggested that the possibility of biological parenthood is important to many individuals with DSD. This study provided an in-depth parental perspective. This is important because many decisions that affect future fertility are made in childhood, and require parents to make decisions on behalf of their children. The study sample was limited in its geographic diversity. Strengths of the study included diversity in age of the child/youth, ethnic backgrounds, and the DSD diagnoses that were represented. Future fertility was a concern for many parents of children/youth with DSD. Parents expressed multiple priorities and preferences related to making difficult fertility-related medical decisions for their children. Many of the study findings could be incorporated into future best practices for discussions about fertility with families of children/youth with DSD.


Electrical perturbations of ultrathin bilayers: role of ionic conductive layer.
The effect of electrostatic force on the dynamics, morphological evolution, and drainage time of ultrathin liquid bilayers (<100 nm) are investigated for perfect dielectric-perfect dielectric (PD-PD) and ionic liquid-perfect dielectric (IL-PD) bilayers. The weakly nonlinear "thin film" equation is solved numerically to obtain spatiotemporal evolution of the liquid-liquid interface responses to transverse electric field. In order to predict the electrostatic component of conjoining/disjoining pressure acting on the interface for IL-PD bilayers, an analytical model is developed using the nonlinear Poisson-Boltzmann equation. It is found that IL-PD bilayers with electric permittivity ratio of layers (lower to top), εr, greater than one remain stable under an applied electric field. An extensive numerical study is carried out to generate a map based on εr and the initial mean thickness of the lower layer. This map is used to predict the formation of various structures on PD-PD bilayer interface and provides a baseline for unstable IL-PD bilayers. The use of an ionic liquid (IL) layer is found to reduce the size of the structures, but results in polydispersed and disordered pillars spread over the domain. The numerical predictions follow similar trend of experimental observation of Lau and Russel. (Lau, C. Y.; Russel, W. B. Fundamental Limitations on Ordered Electrohydrodynamic Patterning; Macromolecules 2011, 44, 7746-7751).


The ischemia-selective KATP channel antagonist, 5-hydroxydecanoate, blocks ischemic preconditioning in the rat heart.
Although the KATP channel has been demonstrated to be involved in ischemic preconditioning (IPC) in most species, controversy still exists as to the role of this channel as a mediator of PC in the rat heart. Previously, the authors' laboratories have shown that glibenclamide blocks IPC in the intact rat heart, in a time-dependent manner; however, since glibenclamide has been shown to have non-selective effects unrelated to KATP channel blockade, a structurally dissimilar and ischemia-selective KATP channel blocker, 5-hydroxydecanoate (5-HD), was used to further elucidate the role of KATP channels in mediating IPC in the rat heart. Anesthetized, open-chested Sprague-Dawley rats were subjected to one of four protocols. In Group I, control (C), rats were subjected to 30 min of left coronary artery occlusion and 90 min of reperfusion. In Group II, IPC was elicited by 1 x 5 min occlusion followed by 10 min of reperfusion, prior to the 30 min occlusion and 90 min reperfusion periods, 5-HD (5 mg/kg, i.v.) was given 15 min prior to the 30 min occlusion period in non-preconditioned animals, or given 15 min prior to IPC (5-HD+IPC) (Groups III and IV, respectively). Infarct size (IS), as a percentage of the area at risk (AAR), was determined by triphenyltetrazolium staining. Ischemic preconditioning produced a marked reduction in infarct size (47.5 +/- 3.8% to 7.9 +/- 1.9%, *P < 0.01), which was completely abolished by 5-HD (50.5 +/- 2.6%). These data further suggest that the opening of KATP channels is an important component of IPC in the intact rat heart, similar to that observed in other species.


Sustained attention in intellectually gifted children assessed using a continuous performance test.
This study aimed to investigate two aspects of sustained attention in intellectually gifted children: first, the differences to intellectually average children; second, the differences between receiving standard education and enrichment education. Study 1 compared sustained attention between 24 intellectually gifted and 26 intellectually average children. The results showed that intellectually gifted children had better performance than their average peers, not only for the whole task but also on all indices. Study 2 compared sustained attention between 24 intellectually gifted children who received standard education and 24 intellectually gifted children who received enrichment education. The results showed that intellectually gifted children who received enrichment education performed better than those who received standard education. These findings are consistent with previous work and provide support for the implementation of enrichment education for intellectually gifted children.


Proprotein convertase subtilisin/kexin type 9 levels and aortic valve calcification: A prospective, cross sectional study.
To investigate the possible association between plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and the incidence and severity of calcific aortic valve disease (CAVD). This prospective, cross sectional study involved patients with and without (controls) aortic valve calcification diagnosed by transthoracic echocardiography and dual source computed tomography (DSCT) scan. Aortic valves calcification scores were calculated from DSCT scans and patients were graded: grade 1, no calcification; grade 2, mildly calcified; grade 3, moderately calcified; grade 4, heavily calcified. Plasma PCSK9 levels were measured using an enzyme-linked immunosorbent assay. Forty patients were grade 1 (controls), 32 were grade 2, 48 were grade 3 and 32 were grade 4. Plasma levels of PCSK9 were significantly different between the four groups and the highest value was observed in the patients with grade 2 calcification. Only low-density lipoprotein cholesterol and lipoprotein (Lp)(a) were associated with the severity of CAVD. Regression analysis showed that age, Lp(a) and PCSK9 were independent predictors of CAVD. Data from this cross sectional study in a small sample of patients showed that plasma PCSK9 was correlated with the presence of CAVD but not its severity.


Antagonism by antipyretics of the hyperthermic effect of a prostaglandin precursor, sodium arachidonate, in the cat.
1. Injection of sodium arachidonate (100-400 mug) into lateral cerebral ventricles of unanaesthetized cats caused shivering and rapid development of dose-related hyperthermic responses. Unless arachidonate is hyperthermogenic per se, this indicates that in vivo formation of prostaglandins, or perhaps an endoperoxide intermediate, can cause hyperthermia. 2. Tolerance gradually developed when arachidonate was administered repeatedly at intervals of 1-7 days. Examination of the brains of several tolerant animals revealed in each case marked enlargement of the lateral ventricles which apparently accounted for the diminished response to arachidonate. 3. Sodium salicylate (40, 160 mg/kg, i.v.) antagonized arachidonate but only after a 3-4 hr latent period. 4. Paracetamol (10, 40 mg/kg, i.v.) reduced the hyperthermic effect of arachidonate but a dose of 40 mg/kg antagonized centrally administered bacterial endotoxin more effectively than it did arachidonate. 5. Indomethacin (40 mug/kg, i.v.) significantly reduced arachidonate-induced hyperthermia in only one of two studies. This reduction was comparable to the hypothermic effect of indomethacin in afebrile animals and was attributed to a non-specific action on thermoregulatory function rather than to inhibition of prostaglandin synthesis. Indomethacin antagonized endotoxin and leucocytic pyrogen to a greater degree than it did arachidonate. 6. Comparison of the relative effectiveness of the antipyretics in blocking hyperthermic responses to pyrogens and to sodium arachidonate indicates that, if prostaglandins do mediate pyrogen-induced fever, these antipyretics exert their primary at a step before prostaglandin synthesis.


Two new indole alkaloids from Nauclea officinalis and their evaluation for cytotoxic activities.
Two new indole alkaloids, naucleamide H (1) and (±)-19-O-butylangustoline (8), along with seven known alkaloids, 3,14-dihydroangustine (2), (-)-naucleofficine D (3a), (+)-naucleofficine D (3b), nauclefine (4), angustidine (5),19-O-ethylangustoline (6) and angustine (7) were isolated from the water extract of Nauclea officinalis. The structures of these compounds were established by spectroscopic analysis. Among them, the cytotoxicity of 1, 2, 6 and 8 were evaluated against six human cancer cell lines (HepG-2, SKOV3, HeLa, SGC 7901, MCF-7 and KB) in vitro for the first time with 5-fluorouracil as a positive control drug. The new compound 1 had a strong inhibitory effect on the proliferation of HepG-2 with an IC50 value of 19.59 μg/mL. The new compound 8 had a strong inhibitory effect on HepG-2, SKOV3, HeLa, MCF-7 and KB, IC50 value was 5.530, 23.11, 31.30, 32.42 and 37.26 μg/mL, respectively.


Absolute frequency references at 1529 and 1560 nm using modulation transfer spectroscopy.
We demonstrate a double optical frequency reference (1529 and 1560 nm) for the telecom C-band using 87Rb modulation transfer spectroscopy. The two reference frequencies are defined by the 5S(1/2)F=2→5P(3/2)F'=3 two-level and 5S(1/2)F=2→5P(3/2)F'=3→4D(5/2)F''=4 ladder transitions. We examine the sensitivity of the frequency stabilization to probe power and magnetic field fluctuations, calculate its frequency shift due to residual amplitude modulation, and estimate its shift due to gas collisions. The short-term Allan deviation was estimated from the error signal slope for the two transitions. Our scheme provides a simple and high performing system for references at these important wavelengths. We estimate that an absolute accuracy of ∼1 kHz is realistic.


Involvement of IKAP in peripheral target innervation and in specific JNK and NGF signaling in developing PNS neurons.
A splicing mutation in the ikbkap gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we attempted to elucidate the role of IKAP in PNS development in the chick embryo and found that IKAP is required for proper axonal outgrowth, branching, and peripheral target innervation. Moreover, we demonstrate that IKAP colocalizes with activated JNK (pJNK), dynein, and β-tubulin at the axon terminals of dorsal root ganglia (DRG) neurons, and may be involved in transport of specific target derived signals required for transcription of JNK and NGF responsive genes in the nucleus. These results suggest the novel role of IKAP in neuronal transport and specific signaling mediated transcription, and provide, for the first time, the basis for a molecular mechanism behind the FD phenotype.


Gaseous Mediators in Gastrointestinal Mucosal Defense and Injury.
Of the numerous gaseous substances that can act as signaling molecules, the best characterized are nitric oxide, carbon monoxide and hydrogen sulfide. Contributions of each of these low molecular weight substances, alone or in combination, to maintenance of gastrointestinal mucosal integrity have been established. There is considerable overlap in the actions of these gases in modulating mucosal defense and responses to injury, and in some instances they act in a cooperative manner. Each also play important roles in regulating inflammatory and repair processes throughout the gastrointestinal tract. In recent years, significant progress has been made in the development of novel anti-inflammatory and cytoprotective drugs that exploit the beneficial activities of one or more of these gaseous mediators.


Cutis laxa in Kabuki make-up syndrome.
Kabuki make-up syndrome (KMS; OMIM#147920) is a multiple congenital anomalies/mental retardation syndrome of unknown cause, first described independently by Niikawa and Kuroki. It is characterized by a peculiar facial appearance, mild to moderate mental retardation, skeletal abnormality, joint laxity, short stature, and unusual dermatoglyphic patterns. Several additional malformations (eg, cleft palate), cardiovascular defects, genitourinary and gastrointestinal tract anomalies, otologic and ophthalmologic abnormalities, and recurrent infections are also frequently present. It is mostly sporadic, although some familial cases have been reported. Inheritance is thought to be autosomal dominant or X-linked recessive; several chromosomal abnormalities have been found, but none of them seems to be specific to KMS. The fact that the majority of patients are sporadic and show a wide spectrum of clinical features rules out the hypothesis that KMS is a condition with a microdeletion involving several contiguous genes. We recently observed an Italian boy with typical KMS associated with cutis laxa, which, to our knowledge, is an uncommon finding in KMS, never reported in more than 350 KMS cases previously described in the literature.


Sqstm1 knock-down causes a locomotor phenotype ameliorated by rapamycin in a zebrafish model of ALS/FTLD.
Mutations in SQSTM1, encoding for the protein SQSTM1/p62, have been recently reported in 1-3.5% of patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration (ALS/FTLD). Inclusions positive for SQSTM1/p62 have been detected in patients with neurodegenerative disorders, including ALS/FTLD. In order to investigate the pathogenic mechanisms induced by SQSTM1 mutations in ALS/FTLD, we developed a zebrafish model. Knock-down of the sqstm1 zebrafish ortholog, as well as impairment of its splicing, led to a specific phenotype, consisting of behavioral and axonal anomalies. Here, we report swimming deficits associated with shorter motor neuronal axons that could be rescued by the overexpression of wild-type human SQSTM1. Interestingly, no rescue of the loss-of-function phenotype was observed when overexpressing human SQSTM1 constructs carrying ALS/FTLD-related mutations. Consistent with its role in autophagy regulation, we found increased mTOR levels upon knock-down of sqstm1. Furthermore, treatment of zebrafish embryos with rapamycin, a known inhibitor of the mTOR pathway, yielded an amelioration of the locomotor phenotype in the sqstm1 knock-down model. Our results suggest that loss-of-function of SQSTM1 causes phenotypic features characterized by locomotor deficits and motor neuron axonal defects that are associated with a misregulation of autophagic processes.


Mucosal immunization in perspective.
Pandemic and seasonal influenza viruses are a constant public health threat with substantial morbidity and mortality worldwide. Prophylaxis is hard to realize, but immunization provides an efficient tool to control the disease. Despite most infections occurring at or through mucosal surfaces, vaccines are predominantly administered parenterally. Recently it has been suggested that vaccines applied via mucosal surfaces may be a viable novel approach. A number of clinical studies have proven live attenuated influenza vaccine given intranasally to have equivalent or superior immunogenicity and efficacy at the upper and lower respiratory tract compared with systemic intramuscular vaccination. Intranasal application provides easy administration facilitating mass immunization campaigns which requires no strictly sterile injection and is painless to recipients.


Opioid peptides. Biological study of [D-MetO2] dermorphin analogues in relation to the plurality of opioid receptors. XI.
The opioid activity pattern of 8 dermorphin tetrapeptides, W-Tyr-D-MetO-Phe-Xaa-Y (W = H, H2N-C = (NH); Xaa = Gly, 2-aminoethanol, sarcosine; Y = NH2, NH-alkyl), was determined in guinea-pig ileum (GPI) preparations and in brain binding assays and compared with their antinociceptive potency in mice. Almost all modifications increased potency on the GPI test as well as the antinociceptive action of the parent H-Tyr-D-Ala-Phe-Gly-NH2. Dermorphin, H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2, and related tetrapeptide analogues show negligible K-binding activity and, like morphine, possess a higher affinity to mu- than delta-receptors. Nevertheless the correlation of analgesia with the effects on GPI and binding data separate the peptides from morphine. For example, in comparison with the opiate alkaloid H-Tyr-D-MetO-Phe-Gly-ol and H-Tyr-D-MetO-Phe-Gly-NH2 displayed a lower affinity for mu sites, a moderately higher potency on GPI but an exceptionally stronger analgesia, being respectively 350 and 1500 times as potent an analgesic as morphine. This may involve different subpopulations of opioid mu-receptors.


[DIAN/DIAN-J/DIAN-TU].
The Dominantly Inherited Alzheimer's Network (DIAN) observational study compared pathophysiological markers between mutation carriers and non-carriers in autosomal dominant Alzheimer's disease. This study revealed that changes in the biomarkers in the mutation carrier's brain start as early as 20 or even 25 years prior to the onset of symptoms. Doctors of the DIAN-Japan team have successfully implemented the DIAN study in Japan (DIAN-J) with effort and enthusiasm. The DIAN-J study is completely compatible with the DIAN study. All members of the DIAN-J team were certified by the NIH and Washington University. The DIAN researchers started a prevention trial (DIAN-TU) testing two monoclonal antibodies in 2013. Together with the DIAN global members including the Japanese team, they will start the new DIAN-TU NexGen Trial testing a BACE inhibitor in 2017. The API study is another clinical trial of anti-amyloid monoclonal antibody therapy for family members of patients with early-onset familial AD who carry the PSEN1 E280A mutation. This study has shown the same biomarker changes that were reported in the DIAN study.


Late treatment with anti-LFA-1 (CD11a) antibody prevents cerebral malaria in a mouse model.
CBA/Ca mice injected with Plasmodium berghei develop cerebral malaria (CM) characterized by ataxia and progressive paralysis leading to death 7-9 days after experimental infection. The development of cerebral symptoms is a function of the immune response in susceptible strains, and depends on cell-cell interactions involving T helper cells and mononuclear phagocytes. Here we ask whether antibodies to cell adhesion receptors of the immune system can influence the development of CM in this mouse model. When administrated on day 6 after infection, antibody to the leukocyte integrin leukocyte function-antigen-1 (LFA-1) but not antibodies to MAC-1, LECAM-1 (the MEL-14 antigen), alpha 4 integrin or ICAM-1 dramatically reduced the incidence of CM, leading to survival of most mice until the later onset of anemia. Anti-LFA-1 treatment did not result in a substantial decrease in the monocyte accumulation observed in cerebral vessels of susceptible mice. Its efficacy may be related to the broader roles of LFA-1 in cell-cell interactions important in the later pathogenic stages of the immune response to the parasite. Perturbation of immune cell function through interference with cell adhesion mechanisms may offer an important therapeutic tool in acute, life-threatening immune-mediated disorders.


Sublingual immunotherapy in allergic rhinitis: indications, efficacy and safety.
Sublingual immunotherapy (SLIT) is now an established treatment for allergic rhinitis. Whilst several systematic reviews have now confirmed clinical efficacy and safety, recent analysis also confirms that therapeutic benefit persists for several years after the com- pletion of SLIT. Such findings, along with the obvious ease of administration of sublingual preparations, have clearly promoted SLIT as an attractive option for treatment of allergic rhinitis resistant to medical treatment. This article reviews the development, efficacy and safety of SLIT in allergic rhinitis and the current indications for its use.


Interrelationship between the general characteristics of Korean stroke patients and the variables of the sexual functions: random forest and boosting algorithm.
[Purpose] The purpose of this study is to examine patient preferences for counseling related to sexuality post-stroke in Korea. [Subjects and Methods] A survey was conducted on 200 stroke patients. Among the 200 submitted questionnaires, 156 responded but 147 cases are available. The questionnaire is composed of 27 questions such as 8 independent variables related to the general characteristics of the patients, 7 dependent variables in conjunction with sexual intercourse and changed muscle tone, 6 questions regarding to changed sexual function, and 6 questions about a changed motor and a sensory function after stroke. To analyze the factors related to a sexual function after a stroke, we used the random forest, boosting algorithm and MANOVA. [Results] The most important variable in variable group 1 is VAR1, and then VAR22, VAR23, VAR26, VAR27, VAR25, VAR21 and VAR 24 respectively. The most important variable in variable group 2 is VAR22, and then VAR26, VAR23, VAR25, VAR1, VAR27, VAR21 and VAR 24. Finally, for variable group 3, VAR1 has the most important percentage, and we have the order as VAR26, VAR23, VAR27, VAR22, VAR25, VAR21 and VAR 24 among the rest of variables. The result of variable importance in boosting algorithm is somehow the same as that of random forest. [Conclusion] As a result of our analysis, we figured out that duration of illness, age, and education level are important factors of sexual functions for Korean Stroke patients.


Surgery for traumatic optic neuropathy.
Traumatic optic neuropathy (TON) is an important cause of severe visual loss following blunt or penetrating head trauma. Following the initial insult optic nerve swelling within the optic nerve canal or compression by bone fragments are thought to result in secondary retinal ganglion cell loss. Optic nerve decompression with steroids or surgical interventions or both have therefore been advocated to improve visual prognosis in TON. The aim of this review was to examine the effects and safety of surgical interventions in the management of TON. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 3, 2005), MEDLINE (1966 to August 2005), EMBASE (1980 to 2005 wk 31), NRR 2005 Issue 3, LILACS (September 2004) and the reference lists of other reviews and book chapters on TON. We also contacted researchers in the field. There were no date or language restrictions in the electronic searches for trials. We planned to include only randomised controlled trials of TON in which any form of surgical intervention either on its own or in combination with steroids was compared to steroids alone or no treatment. Two authors independently assessed the titles and abstracts identified from the search strategy. No studies were found that met our inclusion criteria and therefore none were included for analysis. No studies were found that met our inclusion criteria. The current body of evidence consists mostly of small, retrospective case series. Given the wide range of surgical interventions used in TON it is very difficult to compare these studies, even qualitatively. However, there is a relatively high rate of spontaneous visual recovery and no evidence that surgical decompression of the optic nerve provides any additional benefit. On the other hand surgery carries a definite risk of complications such as postoperative cerebrospinal fluid leak and meningitis. The decision to proceed with surgery in TON therefore remains controversial and each case needs to be assessed on its own merits. Although there is an urgent need for an adequately powered, randomised controlled trial of surgical intervention in TON, this will prove a difficult endeavour.


The structure of gramicidin A in dimethylsulfoxide/acetone.
It has been demonstrated by two-dimensional NMR cross-relaxation spectroscopy that gramicidin A exists in dimethylsulfoxide/acetone solution in random coil form. This contradicts earlier conclusions by Hawkes et al. [Hawkes, G. E., Lian, L. Y., Randall, E. W., Sales, K. D. & Curzon, E. H. (1987) Eur. J. Biochem. 166, 437-445] that were based on the interpretation of vicinal proton coupling constants.


Role of the lipid emulsion on an injectable formulation of lipophilic KW-3902, a newly synthesized adenosine A1-receptor antagonist.
KW-3902 (a newly synthesized adenosine A1-receptor antagonist) has potent diuretic and renal protective activities. We investigated the influence of the emulsion formulation on the pharmacokinetics of KW-3902 and its metabolite (M1) in rats using three different formulations, i.e., a lipid emulsion about 130 nm in diameter composed of egg yolk lecithin: soybean oil: oleic acid=1:1:0.048, a liposome about 100 nm in diameter composed of egg yolk lecithin, and a saline solution containing 1% (v/v) each of dimethyl sulfoxide and 1 N NaOH. There was no significant difference in the pharmacokinetic parameters of KW-3902 (elimination half-life (T1/2), area under the plasma concentration-time curves (AUC0-infinity), total body clearance (CL), mean residence time (MRT) and volume of distribution at steady-state (Vdss) and M1 (Cmax, T1/2, AUC0-infinity and MRT) after injection of these three dosage forms. Moreover, we investigated in vitro the binding of KW-3902 to blood components using these three formulations. KW-3902 was completely partitioned into the blood components regardless of its dosage form. These findings suggested that KW-3902 dissociated rapidly from the lipid emulsion or liposome in blood after injection and showed intrinsic pharmacokinetics of KW-3902 at doses of 0.1 and 1 mg/kg. Thus, the lipid emulsion formulation of KW-3902 was defined as a solvent, which was a vehicle for dissolving the drugs to prepare the injection, at its expected effective doses.


LNRRIL6, a novel long noncoding RNA, protects colorectal cancer cells by activating the IL-6-STAT3 pathway.
Long noncoding RNAs (lncRNAs) are emerging as critical regulators of cancer. There is a comparable number of lncRNAs to protein-coding genes, but the expression patterns, functions, and molecular mechanisms of most lncRNAs in colorectal cancer (CRC) remain unclear. In this study, we report the identification of a novel lncRNA, named long noncoding RNA regulating IL-6 transcription (LNRRIL6), which is upregulated in CRC tissues and cell lines. Increased LNRRIL6 expression is associated with aggressive clinicopathological characteristics and poor prognosis of CRC patients. Functional experiments showed that enhanced expression of LNRRIL6 promotes CRC cell proliferation and survival in vitro and CRC tumor growth in vivo. Conversely, depletion of LNRRIL6 inhibits CRC cell proliferation and survival in vitro and CRC tumor growth in vivo. Mechanistically, we revealed that LNRRIL6 physically binds to the IL-6 promoter, thereby increasing IL-6 transcription, inducing IL-6 autocrine signaling, and activating the IL-6/STAT3 pathway. The expression of IL-6 is positively associated with that of LNRRIL6 in CRC tissues. Blocking the IL-6/STAT3 pathway using the FDA-approved IL-6-receptor antagonist antibody, tocilizumab, abolished the oncogenic role of LNRRIL6 in CRC. Taken together, these findings identify a novel lncRNA, LNRRIL6, that promotes CRC cell survival through activation of the IL-6/STAT3 pathway and suggest that LNRRIL6 may be a potential prognostic biomarker and therapeutic target for CRC.


Hybrid Polymeric-Magnetic Nanoparticles in Cancer Treatments.
Over the last years, magnetic nanoparticles have received a great attention in cancer therapy and diagnosis. Magnetic drug targeting, is a particularly promising application in this area as the nanoparticles can be directed to the tumor by external magnetic field and concentrated the drug in this tumor tissue. In addition to this magnetic targeting, their inherent magnetic properties provide sensitive contrast enhancement in magnetic resonance imaging (MRI) and can, therefore, be visualized and used for theranostic purposes. Another important pillar of cancer therapy in which magnetic nanoparticles can be successfully employed is the hyperthermia induced either magnetically or by infrared irradiation. In addition, recent works have suggested that magnetic nanoparticles can be used for mechanical stimulation of cells affecting their viability. Most of these applications require modification of the physiochemical and surface properties of the magnetic nanoparticles to control their biodistribution, toxicity and pharmacokinetics. In relation to this, polymer coatings are probably the preference alternative to cover the magnetic nanoparticles for cancer treatment applications. In this review, we attempt to provide an overview of the recent advances in the development and applications of polymeric magnetic nanoparticles in cancer treatment and diagnosis including MRI, drug delivery, magnetic hyperthermia, photothermia and magnetolysis.


EBV viral load in tumor tissue is an important prognostic indicator for nasal NK/T-cell lymphoma.
We retrospectively studied 19 cases of nasal NK/T-cell lymphoma for various potential prognostic factors and performed real-time quantitative polymerase chain reaction for Epstein-Barr virus (EBV) viral load in tumor tissue. Patients with a low EBV viral load (<1 copy per cell) more frequently survived for more than 2 years compared with patients with a high EBV viral load (>/=1 copies/cell) (7/7 vs 3/9; P = .014; Fisher exact test). Furthermore, the patients with low EBV viral loads had a better overall survival than patients with high viral loads (50% accumulative survival: not reached vs 4-5 months; Kaplan-Meier survival analysis; P = .049). In contrast, the overall survival of the patients did not correlate with the extent of lesion, age, stage, necrosis, histologic subtypes, CD56 expression, or angiocentric or angiodestructive growth pattern. Our findings suggest that the EBV viral load in tumor tissues is a useful indicator for predicting outcome of nasal NK/T-cell lymphoma.


Northeast Asian Allorhynchium van der Vecht (Hymenoptera: Vespidae), with a key to Oriental species.
The Oriental species of Allorhynchium van der Vecht, 1963 (Hymenoptera: Vespidae: Eumeninae) are keyed for the first time and their distribution is summarised, with special reference to China and Vietnam. Archancistrocerus Giordani Soika, 1986, is synonymized with Allorhynchium van der Vecht (syn. nov.). Allorhynchium diffinis (Giordani Soika, 1986) is a new combination and A. quadrimaculatum Gusenleitner, 1997, is recorded from Vietnam for the first time.