Cognitive Behavioural Therapy for Insomnia Monotherapy in Patients with Medical or Psychiatric Comorbidities: a Meta-Analysis of Randomized Controlled Trials.
This is a meta-analysis of randomized controlled trials (RCTs) comparing cognitive behaviour therapy for insomnia (CBT-I) monotherapy with active control treatment for insomnia in patients with medical or psychiatric comorbidities. Both international (PubMed, EMBASE, PsycINFO, Cochrane Library) and Chinese (WanFang, and CNKI) databases were systematically searched. The random effects model was used. Thirteen RCTs comparing CBT-I (n = 441) and active controls (n = 412) groups were included. CBT-I group showed significant advantage over active controls at post-treatment assessment in terms of Insomnia Severity Index (ISI; SMD = -0.74), sleep onset latency (SMD = -0.36), wake after sleep onset (SMD = -0.21), sleep quality (SMD = 0.56), Pittsburgh sleep quality index total scores (PSQI; SMD = -0.76) and the total score of dysfunctional beliefs and attitudes about sleep scale (DBAS; SMD = -1.09). Subgroup analyses revealed significant improvement in sleep onset latency in patients with psychiatric disorders (SMD = -0.45), while significant reduction of number of wakeup after sleep onset was found in patients with medical conditions (SMD = -0.31). This meta-analysis found that CBT-I monotherapy had greater efficacy than other active control treatment for insomnia in patients with medical or psychiatric comorbidities.


Pedobacter koreensis sp. nov., isolated from fresh water.
A motile, rod-shaped bacterium, designated strain WPCB189(T), was isolated from fresh water collected from the Woopo wetland (Republic of Korea). The cells were found to be Gram-negative, aerobic and catalase- and oxidase-positive. A phylogenetic analysis based on 16S rRNA gene sequences showed that this isolate forms a lineage within the genus Pedobacter, showing sequence similarities of 89.7-96.4 % with respect to recognized species of the genus, and represents a novel member of this genus. The major fatty acids were iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c (summed feature 3, 29.7 %), iso-C(15 : 0) (26.4 %) and iso-C(17 : 1) 3-OH (10.1 %). The DNA G+C content was 38.0 mol%. On the basis of data obtained from this polyphasic taxonomic study, strain WPCB189(T) represents a novel species of the genus Pedobacter, for which the name Pedobacter koreensis sp. nov. is proposed. The type strain is WPCB189(T) (=KCTC 12536(T)=NBRC 101153(T)).


Beyond carbon and nitrogen: guidelines for estimating three-dimensional isotopic niche space.
Isotopic niche has typically been characterized through carbon and nitrogen ratios and most modeling approaches are limited to two dimensions. Yet, other stable isotopes can provide additional power to resolve questions associated with foraging, migration, dispersal and variations in resource use. The ellipse niche model was recently generalized to n-dimensions. We present an analogous methodology which incorporates variation across three stable dimensions to estimate the significant features of a population's isotopic niche space including: 1) niche volume (referred to as standard ellipsoid volume, SEV), 2) relative centroid location (CL), 3) shape and 4) area of overlap between multiple ellipsoids and 5) distance between two CLs. We conducted a simulation study showing the accuracy and precision of three dimensional niche models across a range of values. Importantly, the model correctly identifies differences in SEV and CL among populations, even with small sample sizes and in cases where the absolute values cannot precisely be recovered. We use these results to provide guidelines for sample size in conducting multivariate isotopic niche modeling. We demonstrate the utility of our approach with a case study of three bottlenose dolphin populations which appear to possess largely overlapping niches when analyzed with only carbon and nitrogen isotopes. Upon inclusion of sulfur, we see that the three dolphin ecotypes are in fact segregated on the basis of salinity and find the stable isotope niche of inshore bottlenose dolphins significantly larger than coastal and offshore populations.


Time- and stimulus-dependent secretion of NAP-1/IL-8 by human fibroblasts and endothelial cells.
The neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8) has in the past been extensively characterized biochemically as well as functionally. Effects of NAP-1/IL-8 on inflammatory cells like neutrophilic granulocytes and lymphocytes, as well as its production by several different cell types, point towards an important role in different inflammatory processes. Recently, monoclonal antibodies have helped to establish immunoassays for detecting the peptide. Using such antibodies, we have performed in vitro studies on the time- and stimulus-dependent production of IL-8 by endothelial cells as well as fibroblasts. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) efficiently induced both focal intracellular expression as well as secretion of the peptide when tested by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA). After stimulation with phorbol myristate acetate (PMA) and lipopolysaccharide (LPS), such effects were seen only in endothelial cells, whereas interferon (IFN)-gamma did not induce any pronounced effect on either of the cells tested. These studies demonstrated in vitro release of IL-8 by different cells upon specific stimulation, thus underlining the significance of the in vivo secretion of this peptide, as noted in recent studies.


Experimental cutaneous leishmaniasis. I. Nonspecific immunodepression in BALB/c mice infected with Leishmania tropica.
Leishmania tropica in BALB/c mice causes a fatal infection accompanied by the development of multiple metastatic lesions. Spleen cells from these mice were shown to have depressed proliferative responses to concanavalin A (Con A), phytohemagglutinin (PHA), and lipopolysaccharide (LPS). Coinciding with this immunodepression was the development of a cell population capable of suppressing normal spleen cell responses to Con A. This suppressor cell activity was first observed at 6 wk and was present throughout the remainder of the infection. At 12 wk the suppressor cells could be removed by Sephadex G-10 passage or carbonyl iron treatment; however, Sephadex G-10 passage could not reverse the suppression at 18 wk. Indomethacin, a prostaglandin synthetase inhibitor, was found to abrogate the activity of the adherent suppressor cell, suggesting that prostaglandin production may be involved in the immunosuppression seen in these mice. In addition, Sephadex G-10 passage and indomethacin were found to markedly augment spleen cell responses to leishmanial antigen, indicating that the adherent suppressor cell is capable of regulating specific immunologic responses.


Long-Term Objective Physical Activity Measurements using a Wireless Accelerometer Following Minimally Invasive Transforaminal Interbody Fusion Surgery.
We report on a case of a patient who underwent minimally invasive transforaminal lumbar interbody fusion (mi-TLIF) with objective physical activity measurements performed preoperatively and postoperatively at up to 12-months using wireless accelerometer technology. In the first postoperative month following surgery, the patient had reduced mobility, taking 2,397 steps over a distance of 1.8 km per day. However, the number of steps taken and distance travelled per day had returned to baseline levels by the second postoperative month. At one-year follow-up, the patient averaged 5,095 steps per day in the month over a distance of 3.8 km; this was a 60% improvement in both steps taken and distance travelled compared to the preoperative status. The use of wireless accelerometers is feasible in obtaining objective physical activity measurements before and after lumbar interbody fusion and may be applicable to other related spinal surgeries as well.


Transgender individuals' workplace experiences: the applicability of sexual minority measures and models.
The present study explored whether 3 existing measures of workplace constructs germane to the experiences of sexual minority people could be modified to improve their applicability with transgender individuals. To this end, the Workplace Heterosexist Experiences Questionnaire (WHEQ; C. R. Waldo, 1999); the Lesbian, Gay, Bisexual, and Transgendered Climate Inventory (LGBTCI; B. J. Liddle, D. A. Luzzo, A. L. Hauenstein, & K. Schuck, 2004); and the Workplace Sexual Identity Management Measure (WSIMM; M. Z. Anderson, J. M. Croteau, Y. B. Chung, & T. M. DiStefano, 2001) were modified to explicitly address the experiences of transgender individuals. Data from a sample of 263 transgender individuals were used to evaluate the psychometric properties of the modified measures. Analyses of the structures of the modified measures (Transgender Forms [TF]) suggested an alternative 2-factor structure for the WHEQ-TF, but provided support for the previously observed unidimensional structure for the LGBTCI-TF, and a slightly modified 3-factor structure for the WSIMM-TF. Cronbach's alpha reliability coefficients for scale or subscale items across the 3 measures were acceptable. Criterion-related validity was evident in theoretically consistent patterns of correlations between scores on the 3 modified measures and scores on indicators of job satisfaction and outness. These data provide preliminary support for transgender-specific versions of measures of 3 key constructs in the sexual minority vocational behavior research.


Editorial board interlocking across the social sciences: Modelling the geographic, gender, and institutional representation within and between six academic fields.
Editorial boards play a key role in the production, dissemination, and promotion of scientific knowledge. The cross-presence of scholars in different journals, known as editorial board interlocking, maps the connections between such bodies of governance. Former research on this topic is typically restricted to individual disciplines and has failed to consider the relevance of potential interlocking between related, but different academic fields. Further, although existing studies note a significant lack of diversity in editorial board representation, they mainly focus on a single dimension, such as gender or geography. This study addressed these knowledge gaps by offering a complex cross-disciplinary approach to the geographical, gender, and institutional compositions of editorial boards, with a specific emphasis on within- and between-fields editorial board interlocking. We used graph and social network analysis to examine editorial board connections between 281 top journals (13,084 members and 17,092 connections) of six disciplines: communication, psychology, political science, sociology, economics, and management. We found substantial differences in terms of field connections, ranging from sociology with 42% interlocking with other fields, to management with only 11%. Psychology is significantly less connected to the other five disciplines. The results also show a clear overrepresentation of American institutions and native English-speaking countries in all fields, with Harvard, Columbia, Cornell, Stanford, UC Berkeley, and New York University forming a well-connected central cluster. Although female scholars are underrepresented, there are no significant differences in terms of positioning in the network. Female scholars are even employed in more central positions than male scholars in psychology, sociology, and management. Our findings extend the literature on editorial board diversity by evidencing a significant imbalance in their gender, geographical, institutional representation, and interlocking editorship both within and between fields.


A chemically stratified lake in alaska.
A meromictic (chemically stratified) lake occupies a thawed depression in a pingo in interior Alaska, near Circle City. Increased salt concentration and anaerobic conditions characterize the zone extending from a maximum depth of 3 to 8.8 meters. The concentration of strontium and lithium is unusually high for lake water.


Ultrasound velocity measured at the proximal phalanges: precision and age-related changes in normal females.
To determine the precision of a new ultrasound device and to establish a reference curve for normal French females, amplitude-dependent speed of sound (AD-SoS, m/sec) was measured using a DBM Sonic 1200 device (IGEA, Carpi) at four proximal phalanges of the nondominant hand in healthy women. In vitro precision from 21 measurements of a plexiglass phantom was 0.3%. In vivo short-term precision was 0.84% +/- 0.48% in 15 younger adults (age 31 +/- 10 years) and 0.81% +/- 0.038% in 15 older adults (age 62 +/- 16 years). Interobserver coefficient of variation was 0.77%. One hundred twenty-eight healthy female hospital staff members or friends of hospital staff members were studied (age 51.2 +/- 17.4 years). AD-SoS decreased by 9.6% between 30 and 80 years of age. Separate analyses of pre and postmenopausal women and of ten-year age groups demonstrated that AD-SoS remained unchanged before menopause but decreased by 7.6% after menopause (age 64.14 +/- 7.5 years; range 41-80). These data from normal females were compared with those reported by others in females and males. Age at menarche apparently influenced AD-SoS in later life. Reproducibility of the device used for this study was acceptable. Our cross-sectional data suggest that AD-SoS measurement is effective for detecting postmenopausal bone loss. Further investigations in osteoporosis are warranted.


Post-transfusional iron overload in the haemoglobinopathies.
In this report, we review the recent advances in evaluation and treatment of transfusional iron overload (IO). Results of the French thalassaemia registry are described. According to the disease, thalassaemia major or sickle cell anaemia, mechanisms and toxicity of iron overload, knowledge about IO long-term outcome and chelation treatment results, respective value of IO markers, differ. The recent tools evaluating organ specific IO and the diversification of iron chelator agents make possible to individualize chelation therapy in clinical practice. The severity of IO and the level of transfusional iron intake, the preferential localization of IO (heart/liver) as well as the tolerance and adherence profiles of the patient can now be taken into account. Introduction of cardiac magnetic resonance imaging for the quantification of myocardial iron and use of oral chelators have already been reported as decreasing the cardiac mortality rate related to IO in thalassaemia major patients. Long-term observation of patients under oral chelators will show if morbidity is also improving via a more continuous control of toxic iron and/or a better accessibility to cellular iron pools.


Peer review organizations. Practical steps in dealing with them.
Peer review organizations exist to maintain high standards of medical care, not to intimidate physicians or hamper their style of practice. The author traces the history of these organizations and stresses their decentralized nature. Physicians are instructed on the optimal response to a peer review notice. In most cases, an adequate answer resolves the query. For physicians who are required to meet with the organization for further inquiry, practical advice is given regarding measures that they can take in their own defense. These include furnishing x-ray film and other evidence documenting their choice of care; bringing in additional health care personnel responsible for recording notes; and the right to legal counsel or a representative of their choice throughout the proceedings.


[Comparison of biotic index used in monitoring of 2 lotic systems in north-western Argentina].
Two lotic bodies located in a subtropical semi-arid region in north-western Argentina were studied: the Arias-Arenales and the Rosario rivers. Both rivers are located in Salta Province, and belong to the high basin of river Juramento, connected to the river Río de la Plata and the Atlantic Ocean. The study was conducted between March 1997 and March 1998. The region is known by its sustained economic development and one of the highest population growth rates in the country (4% per year). The objective of this work was the assessment of organic pollution spatial gradients in both rivers, as a function of the hydrological regime (a long period of drought from May to October and floodings the rest of the year). Three groups of biotic indices were applied to characterize the level of organic pollution and were based on planktonic microalgae to evaluate water quality. The relative performance of these indices was then compared for use to biomonitoring programs. The diversity indices: Shannon-Weaver and Whilm-Dorris were not highly sensible to detect moderate pollution. The saprobity indices (Pantle and Buck and Diatom Assemblage Index of Watanabe et al.), were useful to detect intermediate levels of organic load, but their sensitivity dropped at high pollution levels. The second index precisely discriminated the most deteriorated part of river Rosario, with values between 0.3-0.7 (extreme poli-saprobity). Raw sewage discharges along the most polluted sector of river Arias-Arenales were assigned a value between 10 and 11 in both periods of the hydrological regime. Both saprobity indices consider the same indicator pollution value of species. The first one is based on the relative abundance of the species while the second one is calculated with the species relative frequency. The second index is better than the first one in considering non-dominant species that were constant in each particular environmental condition. The principal component analysis allowed a representation of time and space pollution patterns and showed the specific microalgae assemblage for all the sampling stations and for both periods in the hydrological cycle. Only the latter proved to be fully useful and correct for the biological characterization of water quality system.


Coupling of M2 muscarinic receptors to membrane ion channels via phosphoinositide 3-kinase gamma and atypical protein kinase C.
We report a novel signaling pathway linking M2 muscarinic receptors to metabotropic ion channels. Stimulation of heterologously expressed M2 receptors, but not other Gi/Go-associated receptors (M4 or alpha2c), activates a calcium- and voltage-independent chloride current in Xenopus oocytes. We show that the stimulatory pathway linking M2 receptors to these chloride channels consists of Gbeta gamma stimulation of phosphoinositide 3-kinase gamma (PI-3Kgamma), formation of phosphatidylinositol 3,4,5-trisphosphate (PIP3), and activation of atypical protein kinase C (PKC). The chloride current is activated in the absence of M2 receptor stimulation by the injection of PIP3, and PIP3 current activation is blocked by a pseudosubstrate inhibitory peptide of atypical PKC but not other PKCs. Moreover, the current is activated by injection of recombinant PKCzeta at concentrations as low as 1 nM. M2 receptor-current coupling was disrupted by inhibiton of PI-3K and by injection of beta gamma binding peptides, but it was not affected by expression of dominant negative p85 cRNA. We also show that this pathway mediates M2 receptor coupling to metabotropic nonselective cation channels in mammalian smooth muscle cells, thus demonstrating the broad relevance of this signaling cascade in neurotransmitter signaling.


Phycocyanin Fusion Constructs for Heterologous Protein Expression Accumulate as Functional Heterohexameric Complexes in Cyanobacteria.
Overexpression of heterologous proteins from plants, bacteria, and human as fusion constructs in cyanobacteria has been documented in the literature. Typically, the heterologous protein "P" of interest is expressed as a fusion with the abundant CpcB β-subunit of phycocyanin (PC), which was placed in the leader sequence position. The working hypothesis for such overexpressions is that CpcB*P fusion proteins somehow accumulate in a soluble and stable form in the cytosol of the cyanobacteria, retaining the activity of the trailing heterologous "P" protein of interest. The present work revealed a substantially different and previously unobvious picture, comprising the following properties of the above-mentioned CpcB*P fusion constructs: (i) the CpcB*P proteins assemble as functional (α,β*P)3CpcG heterohexameric discs, where α is the CpcA α-subunit of PC, β*P is the CpcB*P fusion protein, the asterisk denotes fusion, and CpcG is the 28.9 kDa PC disc linker polypeptide CpcG1. (ii) The (α,β*P)3CpcG1 complexes covalently bind one open tetrapyrrole bilin co-factor per α-subunit and two bilins per β-subunit. (iii) The (α,β*P)3CpcG1 heterohexameric discs are functionally attached to the Synechocystis allophycocyanin (AP) core cylinders and efficiently transfer excitation energy from the assembled (α,β*P)3CpcG1 heterohexamer to the PSII reaction center, enhancing the rate of photochemical charge separation and electron transfer activity in this photosystem. (iv) In addition to the human interferon α-2 and tetanus toxin fragment C tested in this work, we have shown that enzymes such as the plant-origin isoprene synthase, β-phellandrene synthase, geranyl diphosphate synthase, and geranyl linalool synthase are also overexpressed, while retaining their catalytic activity in the respective fusion construct configuration. (v) Folding models for the (α,β*P)3CpcG1 heterohexameric discs showed the recombinant proteins P to be radially oriented with respect to the (α,β)3 compact disc. Elucidation of the fusion construct configuration and function will pave the way for the rational design of fusion constructs harboring and overexpressing multiple proteins of scientific and commercial interest.


Comparison of Fire Behaviors of Thermally Thin and Thick Rubber Latex Foam under Bottom Ventilation.
Fire behaviors of rubber latex foam under different thickness conditions (d = 1, 2, and 5 cm) were explored by using a self-built small-scale experimental platform. It can be shown that the flame spread menchanism of thermally thin and thermally thick rubber latex foam is different. Rubber latex foam with a thickness of 2 cm shows higher fire risk, whose value of flame spread rate, maximum flame height, maximum mass loss rate, and maximum temperature are 2.93 × 10-3 m/s, 851.88 mm, and 1.83 g/s, 948.00 °C, respectively. On the one hand, this may due to the different mechanisms of flame spread, resulting in different preheating zones on the surface. On the other hand, this may because the thickness of residue formed by thermally thick materials is larger than the thin ones, obstructing the contact of the rubber latex foam with fresh air. In addition, a special phenomenon is noticed during the stage II, where the bottom unburned zone is located in the four edges (thermally thin material) and middle player (thermally thick material).


[mFOLFOX6 and FOLFIRI/bevacizumab treatment in a patient on hemodialysis with metastatic colon cancer].
A 58-year-old woman, who was undergoing peritoneal dialysis( PD) for chronic kidney disease (CKD) and had been operated by sigmoidectomy for early colonic cancer, was diagnosed as peritoneal recurrence of the colonic cancer. Her treatment for CKD was switched from PD to hemodialysis. She was administered mFOLFOX6 therapy(reducing the dose to 70%). Hemodialysis was performed 1 hour after administration of oxaliplatin on day 1 and repeated two days later after the completion of drug administration. No serious adverse events were observed. After 10 courses of mFOLFOX6, an ovarian metastasis was appeared. We then changed the regimen to FOLFIRI (70% dose)/bevacizumab (BV). Neutropenia (grade 4) was observed after the second treatment. After some rest, 21 courses of FOLFIRI/BV therapy were performed safely by reducing the dose to 60%. We thought that a reduced dose of FOLFIRI/BV therapy appeared to be safe for a patient with chronic kidney disease who is on hemodialysis.


[Emergencies at a hospital center and university in a tropical area. An anesthesiologist's point of view].
The purpose of this retrospective study was to determine the profile of medical emergencies and their management in a university hospital center in a tropical area. Between July 1 and December 31, 2001, all patients examined in a medical and surgical emergency room were included. Obstetrical emergencies, pediatric emergencies, emergencies admitted directly to the cardiology, ORL emergencies and urologic emergencies were not included. A total of 6740 patients were examined for medical/surgical emergencies during the 6-month study period. Mean patient age was 23 +/- 7 years. Most patients were male with a sex ratio of 3.4. Patients were from the city of Dakar in 50% of cases, suburbs of Dakar in 35% and other regions in 15%. The mean delay between the onset of emergency and admission was 17 +/- 9 hours. Patients were transferred to the hospital in 78% of cases by private transportation. Gastrointestinal events accounted for 20.23% of cases, cardiovascular events for 9.12%, respiratory events of 8.56%, metabolic events for 1.78%, trauma for 48.20% and infectious disease for 12.09%. Surgical mortality was 2.41%. Most problems facing the intensivist treating medical emergencies in a tropical setting involved resuscitation.


Laparoscopic cholecystectomy for biliary tract emergencies: state of the art.
Although laparoscopic cholecystectomy is unusually safe and well tolerated in patients with routine symptomatic cholelithiasis, it can become a formidable procedure when used to manage biliary tract emergencies. Optimally, a reasoned and cautious approach and a low threshold for conversion can avoid major complications. One such emergency, acute cholecystitis, may be particularly hazardous because of the relatively common finding of severe inflammation with dense adhesions to adjacent viscera and gallbladder necrosis. Special modifications of technique may be required. Overall, urgent operation (within 72 hours) results in an acceptably low mortality (0.3%) but a somewhat higher conversion rate (16%) and longer hospital stay (3 days). Unnecessary delays may result in more adhesions and an increased level of operative difficulty. In patients who are at an especially high risk because of co-morbid disease, percutaneous cholecystostomy is an appropriate alternative strategy. Biliary pancreatitis may be associated with high mortality (9%) and has an unpredictable course. Accordingly, a multidisciplinary approach that may include both gastroenterologists and radiologists is generally advisable. Because common bile duct (CBD) stones are present in more than 20% of patients who present with biliary pancreatitis, endoscopic retrograde cholangiopancreatography (ERCP) can be used effectively on a selective basis during the preoperative or postoperative period; the preferred timing continues to be somewhat controversial. As an alternative approach, laparoscopic CBD exploration is gradually gaining wider acceptance. In eight reported series using a variety of techniques for stone extraction, major complications were infrequent (10%), and the conversion rate was low (5%). Acute suppurative cholangitis is a more fulminant problem that is best managed by expeditious ERCP with removal of all intraductal stones. Resuscitation should be continued until complete; laparoscopic cholecystectomy can follow at an appropriate interval.


The studies on radiological limits of color-glazed tiles used in home decoration.
This study was carried out to lay down the radiological limits of color-glazed tiles used in home decoration. The activity concentrations of various end products and raw materials as well as processed materials were measured using gamma spectroscopy. 222Rn exhalation rates from the surface of color-glazed tiles were measured using charcoal canister method. Levels of exposure to alpha ray and beta ray from the surface of glazed tiles were measured by surface alpha and beta contaminant instrument. The results show a great difference between the radioactive levels of the surface glaze and the matrix of color-glazed tiles. The 222Rn exhalation rates from the surface of color-glazed tiles are in the range of 10(-3) - 10(-4) Bq m(-2) s(-1). The concentrations of some natural radionuclides in glaze exceed the exempt limits of International Basic Safety Standards for Protection against Ionizing Radiation Sources (IAEA 1997). The limits for color-glazed tiles were deduced according to these data and the theory of UNSCEAR (1993). The activity concentration of 226Ra (Bq kg(-1)) in the glaze of color-glazed tiles should be in the range of A(226Ra) < or = 1,000 (Bq kg(-1)), and, at the same time, the specific activity of the natural radionuclides (Bq kg(-1)) should be in the range of A(232Th)/230 + A(226Ra)/310 + A(40K)/3,500 < or = 1.


Impact properties of thiol-ene networks.
In this study, a series of thiol-ene networks having glass transition temperatures ranging from -30 to 60 °C were synthesized utilizing several multifunctional thiols and two trifunctional alkenes. Thermomechanical properties were determined using dynamic mechanical analysis, and impact properties were determined using pendulum impact and drop impact testing protocols. The impact behavior was found to directly correlate to the glass transition temperature, except when the temperature at which the impact event occurs overlaps with the range of temperatures corresponding to the viscoelastic dissipation regime of the polymer. Additionally, we discuss insight into the spatial limitations of energy dissipation for thiol-ene network polymers and establish a platform for predictability in similar systems.


FBN1 exon 2 splicing error in a patient with Marfan syndrome.
Mutations in FBN1 cause the autosomal dominant condition, Marfan syndrome. A single-base mutation that results in a skipping of exon 2 of FBN1 was found in a Marfan patient. By sequencing this proband's entire FBN1 gene and comparing the mutated DNA sequence with proband's unaffected family numbers, we confirmed this alteration was the causative mutation. The skipping of exon 2 creates a frameshift and premature termination codon, and forms a truncated fibrillin-1 composed only of 55 amino acids of N-terminus plus 45 nonsense amino acids. The mRNA transcription levels of the mutated FBN1 allele and the deposition of fibrillin-1 into extracellular matrix in fibroblast cells culture were assessed.


Cyclooxygenase inhibitors induce the expression of the tumor suppressor gene EGR-1, which results in the up-regulation of NAG-1, an antitumorigenic protein.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to have chemopreventive activity, but the mechanisms involved are not clearly understood. Although NSAIDs inhibit cyclooxygenase activity, they also increase the expression of a divergent member of the transforming growth factor-beta superfamily, termed NSAID-activated gene 1 (NAG-1), a protein with an antitumorigenic and proapoptotic activity that could in part be linked to the chemoprevention activity of NSAIDs. NAG-1 is induced by some NSAIDs, but the mechanisms responsible are not clear. In this report, we have identified a cis-acting element responsive to NSAIDs located within the -73 to -51 region of the NAG-1 promoter. This region contains overlapping EGR-1 and Sp1 binding sites, and mutations in this region suggest that the transcription factors have an important role in NSAID-induced NAG-1 expression. EGR-1 was found to play a critical role in the induction of NAG-1 by sulindac sulfide and other NSAIDs. NSAIDs increase EGR-1 protein expression that occurs before the induction of NAG-1 expression, supporting the hypothesis that EGR-1 is necessary for NSAID-induced NAG-1 expression. Thus, NSAIDs induce the expression of EGR-1, a tumor suppressor gene, providing a novel mechanism to explain, in part, the antitumorigenic properties of some NSAIDs. NAG-1 seems to be an important downstream target protein of this transcription factor, EGR-1, and may mediate the chemopreventive activity of some NSAIDs.


A randomized phase II chemoprevention trial of 13-CIS retinoic acid with or without alpha tocopherol or observation in subjects at high risk for lung cancer.
No chemoprevention strategies have been proven effective for lung cancer. We evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without alpha tocopherol, as a lung cancer chemoprevention agent in a phase II randomized controlled clinical trial of adult subjects at high risk for lung cancer as defined by the presence of sputum atypia, history of smoking, and airflow obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free, >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA plus alpha tocopherol (13-cis RA/alpha toco) or observation for 12 months. Outcome measures are derived from histologic evaluation of bronchial biopsy specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome measure is treatment "failure" defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy. Seventy-five subjects were randomized (27/22/26 to observations/13-cis RA/13-cis RA/alpha toco); 59 completed the trial; 55 had both baseline and follow-up bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of 48) in the observation and combined (13 cis RA plus 13 cis RA/alpha toco) treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97; 95% confidence interval, 0.36-2.66; P = 0.95). Among subjects with complete histology data, maximum histology score in the observation arm increased by 0.37 units and by 0.03 units in the treated arms (difference adjusted for baseline, -0.18; 95% confidence interval, -1.16 to 0.81; P = 0.72). Similar (nonsignificant) results were observed for treatment effects on endobronchial proliferation as assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced nonsignificant changes in bronchial histology, consistent with results in other trials. Agents advancing to phase III randomized trials should produce greater histologic changes. The addition of alpha tocopherol did not affect toxicity.


Factors that influence midwifery students in Ghana when deciding where to practice: a discrete choice experiment.
Mal-distribution of the health workforce with a strong bias for urban living is a major constraint to expanding midwifery services in Ghana. According to the UN Millennium Development Goals (MDG) report, the high risk of dying in pregnancy or childbirth continues in Africa. Maternal death is currently estimated at 350 per 100,000, partially a reflection of the low rates of professional support during birth. Many women in rural areas of Ghana give birth alone or with a non-skilled attendant. Midwives are key healthcare providers in achieving the MDGs, specifically in reducing maternal mortality by three-quarters and reducing by two-thirds the under 5 child mortality rate by 2015. This quantitative research study used a computerized structured survey containing a discrete choice experiment (DCE) to quantify the importance of different incentives and policies to encourage service to deprived, rural and remote areas by upper-year midwifery students following graduation. Using a hierarchical Bayes procedure we estimated individual and mean utility parameters for two hundred and ninety eight third year midwifery students from two of the largest midwifery training schools in Ghana. Midwifery students in our sample identified: 1) study leave after two years of rural service; 2) an advanced work environment with reliable electricity, appropriate technology and a constant drug supply; and 3) superior housing (2 bedroom, 1 bathroom, kitchen, living room, not shared) as the top three motivating factors to accept a rural posting. Addressing the motivating factors for rural postings among midwifery students who are about to graduate and enter the workforce could significantly contribute to the current mal-distribution of the health workforce.


Efficacy of fluticasone nasal spray for pediatric obstructive sleep apnea.
We tested the hypothesis that a 6-week course of a nasal glucocorticoid spray would decrease the severity of obstructive sleep apnea in children with adenotonsillar hypertrophy. We conducted a randomized, triple-blind, placebocontrolled, parallel-group trial of nasal fluticasone propionate versus placebo in 25 children aged 1 to 10 years with obstructive sleep apnea proven on polysomnography. The primary outcome was the change from baseline in the frequency of mixed and obstructive apneas and hypopneas. Thirteen children received fluticasone, and 12 received placebo. The mixed/obstructive apnea/hypopnea index decreased from 10.7 +/- 2.6 (SE) to 5.8 +/- 2.2 in the fluticasone group but increased from 10.9 +/- 2.3 to 13.1 +/- 3.6 in the placebo group, P =.04. The mixed/obstructive apnea/hypopnea index decreased in 12 of 13 subjects treated with fluticasone versus 6 of 12 treated with placebo, P =.03. The frequencies of hemoglobin desaturation and respiratory movement/arousals also decreased more in the fluticasone group. Changes from baseline in tonsillar size, adenoidal size, and symptom score were not significantly different between groups. Nasal fluticasone decreased the frequency of mixed and obstructive apneas and hypopneas, suggesting that topical corticosteroids may be helpful in ameliorating pediatric obstructive sleep apnea.


The effectiveness of a hope intervention in coping with cold pressor pain.
Hope has been correlated with greater pain tolerance and thresholds and less reported pain severity. The present study investigated the effectiveness of a brief hope-based intervention involving guided imagery and skills instruction aimed at enhancing pain coping skills among university students performing the cold pressor task. The intervention resulted in increased hope among females and increased pain tolerance in all participants. The intervention did not affect pain threshold and resulted in marginally increased pain severity. Thus, this intervention facilitates better pain tolerance without necessarily changing the experience of the pain. Implications for practice and future research are discussed.


Use of clozapine alongside chemotherapy in a treatment-resistant bipolar disorder patient with ovarian carcinoma: A case report and brief review.
Regular monitoring of blood counts ensures the safety of clozapine use; however, certain clinical situations may pose a dilemma for management such as use of clozapine in the presence of myelosuppressive chemotherapy. Further, there is very limited literature to guide such decisions. We report a case of a clozapine-stabilized, treatment-resistant bipolar disorder patient with ovarian carcinoma requiring chemotherapy. The clinical challenges are discussed in light of a brief review of the available reports.


Understanding informed consent in bioinformatics research: cross-cultural issues.
Cultural factors, such as language, gender roles, and emphasis on individuality should be attended to in bioinformatics research studies for reasons related to ethics and generalizability. These factors must be addressed during the informed consent process when patients make decisions about study participation. Observations of Institutional Review Board meetings and interviews with principal investigators of bioinformatics studies revealed that only particular cultural factors, such as language, are considered during the informed consent process.


Two and three-dimensional computed tomography for the classification and management of distal humeral fractures. Evaluation of reliability and diagnostic accuracy.
Complex fractures of the distal part of the humerus can be difficult to characterize on plain radiographs and two-dimensional computed tomography scans. We tested the hypothesis that three-dimensional reconstructions of computed tomography scans improve the reliability and accuracy of fracture characterization, classification, and treatment decisions. Five independent observers evaluated thirty consecutive intra-articular fractures of the distal part of the humerus for the presence of five fracture characteristics: a fracture line in the coronal plane; articular comminution; metaphyseal comminution; the presence of separate, entirely articular fragments; and impaction of the articular surface. Fractures were also classified according to the AO/ASIF Comprehensive Classification of Fractures and the classification system of Mehne and Matta. Two rounds of evaluation were performed and then compared. Initially, a combination of plain radiographs and two-dimensional computed tomography scans (2D) were evaluated, and then, two weeks later, a combination of radiographs, two-dimensional computed tomography scans, and three-dimensional reconstructions of computed tomography scans (3D) were assessed. Three-dimensional computed tomography improved both the intraobserver and the interobserver reliability of the AO classification system and the Mehne and Matta classification system. Three-dimensional computed tomography reconstructions also improved the intraobserver agreement for all fracture characteristics, from moderate (average kappa [kappa2D] = 0.554) to substantial agreement (kappa3D = 0.793). The addition of three-dimensional images had limited influence on the interobserver reliability and diagnostic characteristics (sensitivity, specificity, and accuracy) for the recognition of specific fracture characteristics. Three-dimensional computed tomography images improved intraobserver agreement (kappa2D = 0.62 compared with kappa3D = 0.75) but not interobserver agreement (kappa2D = 0.24 compared with kappa3D = 0.28) for treatment decisions. Three-dimensional reconstructions improve the reliability, but not the accuracy, of fracture classification and characterization. The influence of three-dimensional computed tomography was much more notable for intraobserver comparisons than for interobserver comparisons, suggesting that different observers see different things in the scans-most likely a reflection of the training, knowledge, and experience of the observer with regard to these relatively uncommon and complex injuries.


Novel CHK1 inhibitor MU380 exhibits significant single-agent activity in TP53-mutated chronic lymphocytic leukemia cells.
Introduction of small-molecule inhibitors of B-cell receptor signaling and BCL2 protein significantly improves therapeutic options in chronic lymphocytic leukemia. However, some patients suffer from adverse effects mandating treatment discontinuation, and cases with TP53 defects more frequently experience early progression of the disease. Development of alternative therapeutic approaches is, therefore, of critical importance. Here we report details of the anti-chronic lymphocytic leukemia single-agent activity of MU380, our recently identified potent, selective, and metabolically robust inhibitor of checkpoint kinase 1. We also describe a newly developed enantioselective synthesis of MU380, which allows preparation of gram quantities of the substance. Checkpoint kinase 1 is a master regulator of replication operating primarily in intra-S and G2/M cell cycle checkpoints. Initially tested in leukemia and lymphoma cell lines, MU380 significantly potentiated efficacy of gemcitabine, a clinically used inducer of replication stress. Moreover, MU380 manifested substantial single-agent activity in both TP53-wild type and TP53-mutated leukemia and lymphoma cell lines. In chronic lymphocytic leukemia-derived cell lines MEC-1, MEC-2 (both TP53-mut), and OSU-CLL (TP53-wt) the inhibitor impaired cell cycle progression and induced apoptosis. In primary clinical samples, MU380 used as a single-agent noticeably reduced the viability of unstimulated chronic lymphocytic leukemia cells as well as those induced to proliferate by anti-CD40/IL-4 stimuli. In both cases, effects were comparable in samples harboring p53 pathway dysfunction (TP53 mutations or ATM mutations) and TP53-wt/ATM-wt cells. Lastly, MU380 also exhibited significant in vivo activity in a xenotransplant mouse model (immunodeficient strain NOD-scid IL2Rγnull ) where it efficiently suppressed growth of subcutaneous tumors generated from MEC-1 cells.


Clinical follow-up study of ceramic veneered titanium restorations--three-year results.
Eighty-four titanium restorations having 125 ceramic veneers were placed for 32 patients. One hundred sixteen (93%) of the veneers could be reexamined after 21 to 41 months. Two of the restorations required removal because of a partial veneer loss. A Kaplan-Meier survival analysis was performed, giving a survival probability of .85 for single crowns and .59 for fixed partial dentures after a time interval of 30 months, regarding the veneer cracking or chipping. There was a significantly higher survival probability for single crowns than for fixed partial dentures (P=.001, logrank test). It was concluded that ceramic veneered titanium restorations should be limited to single crowns.


Regression of iris neovascularization after subconjunctival injection of bevacizumab.
To describe three cases of neovascular glaucoma (NVG) where iris or angle neovascularization regressed remarkably after subconjunctival bevacizumab injections used as the initial treatment before pan retinal photocoagulation (PRP) and/or filtering surgery. Three consecutive NVG patients whose intraocular pressure (IOP) was not controlled with maximal medication were offered an off-label subconjunctival injection of bevacizumab (2.5-3.75 mg/0.1-0.15 mL, Avastin). Bevacizumab was injected into the subconjunctival space close to the corneal limbus in two or three quadrants using a 26-gauge needle. Serial anterior segment photographs were taken before and after the injection. Following subconjunctival injection of bevacizumab, iris or angle neovascularization regressed rapidly within several days. Such regression was accompanied by lowering of IOP in all three cases. The patients underwent subsequent PRP and/or filtering surgery, and the IOP was further stabilized. Our cases demonstrate that subconjunctival bevacizumab injection can be potentially useful as an initial treatment in NVG patients before laser or surgical treatment.


Lipoprotein (a) in patients on hemodialysis.
Lipoprotein (a) [Lp(a)] may produce thrombogenic effects by modulating the fibrinolytic system. Elevated levels of Lp(a) have also been associated with an increased risk for atherosclerosis. Because atherosclerosis is more prevalent among patients with end-stage renal disease, the role of Lp(a) among patients on hemodialysis is analyzed. Twenty patients were studied. Lp(a) was measured before and after a hemodialysis session and before the following session. Between the first and second measures there was no statistical difference but when first and third measures were compared, a statistical difference (increase) was found. In conclusion, changes in Lp(a) levels were found and perhaps these changes are related to the episodic inflammation affecting patients on hemodialysis. The significance of these changes and the role in accelerating atherosclerosis in patients with end-stage renal disease are unknown.


Rethinking perinatal policy: history and evaluation of minimum volume and level-of-care standards.
Two standards have played a dominant role in policies to organize U.S. perinatal care. Minimum volume (or size) and service levels according to technical capacity have been major components of perinatal regionalization and other reorganization efforts. These standards are consistent with structural definitions of quality of care, but not necessarily with quality definitions according to outcome. Empirical research has not demonstrated a general association between the standards and improved perinatal outcomes, although it has demonstrated improved outcomes for very low birthweight babies. The standards have contributed to the growth and financial stability of tertiary-level services, but economy in terms of lower unit costs has also not been demonstrated. These discrepancies between research findings and the paradigm of a system of large, complex centers have led to conceptual errors in explaining findings, but they have also led to a recognition of uncertainty concerning perinatal service organization.


The effect of caffeine, adenosine, and buffer ionic composition on the induction of cell-surface cAMP binding during starvation of Dictyostelium discoideum.
We have analyzed the effects of the cAMP relay inhibitor, caffeine, and the receptor antagonist, adenosine, on the regulation of the cell-surface cAMP receptor in suspension-starved Dictyostelium discoideum cells by measuring ammonium sulfate-stabilized binding of [3-H]cAMP to intact cells. When cells were starved in fast (230 r.p.m.) shaken suspension in 10 mM Na+/5 mM K+ phosphate buffer, pH 6.5, plus 1 mM CaCl2 and 2.5 mM MgCl2, and assayed for specific cAMP binding, receptor accumulation peaked at approximately 6 hours, reaching a maximum of 1.5 pmol cAMP bound/10(7) cells (saturation binding). Neither caffeine nor adenosine inhibited the accumulation of cAMP receptors. Similar results were obtained in caffeine-treated, slow shaken (90 r.p.m.) suspension cultures. These results suggest that starvation alone is sufficient stimulus to induce the cAMP receptor. We have also tested the effects of different buffer ionic compositions on the accumulation of cAMP receptors. Elevation of the monovalent ion concentration to 30-40 mM was found to significantly inhibit the induction of cAMP receptors.


Effects of different LED light spectra on rainbow trout (Oncorhynchus mykiss): in vivo evaluation of the antioxidant status.
Rainbow trout (Oncorhynchus mykiss) farming is one of the major aquacultures in Turkey. Some conditions in fish farming can induce oxidative stress leading to the deterioration in properties such as appearance/color, texture, and flavor in fish meat. This situation may cause the consumer not to prefer edible fish. Although there are some studies on the impacts of light intensity on fish welfare, the changes in the antioxidant enzyme activities have not been elucidated. In the current study, it was intended to examine in rainbow trout how cultivating under different wavelengths affects the antioxidant enzymes and acetylcholine esterase (AChE) activity, because its activity is associated with oxidative stress, and also the determination of which light is suitable for fish welfare was aimed. Rainbow trout larvae were grown under four lights with different wavelengths: natural sunlight and incandescent long-wave (red light), medium-wave (green light), and short-wave (blue light) LED light. The experiment lasted for 64 days. Biochemical assays were carried on in the brain, gill, and liver of rainbow trout. Antioxidant enzymes and AChE activity, which play an important role in the central nervous system, were assayed. In gill tissues, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glucose 6 phosphate dehydrogenase (G6PD), glutathione reductase (GR), glutathione S-transferase (GST), and AChE activities increased under all three light wavelengths. In the liver, while activities of antioxidant enzymes and AChE decreased in red light, all of them increased in blue and green light. In the brain, GPx, GST, G6PD, and SOD activities were reduced but AChE activity did not alter under all three light sources. In conclusion, light sources with different spectral structures caused important changes in the activities of antioxidant enzymes in rainbow trout. On this basis, it may be thought that this may be a response to the changing redox status of a cell. Based on our results, blue light sources may be suggested for fish welfare in rainbow trout culture, and providing fish welfare by changing light sources can be easy and cheap in fish farming.


Tracheal administration of atropine in children--effect on heart rate.
Forty-one ASA I patients, aged 2-6 years, anaesthetized for elective ear, nose and throat surgery, were studied in a double blind and randomized fashion in order to examine the effect of tracheally administered atropine 0.02 mg.kg-1 or saline 0.9% on heart rate. In patients receiving atropine heart rate increased 8.8 beats.min-1 (8.7%) and 16.2 beats.min-1 (16.0%) after 3 and 5 min respectively. No increase in heart rate was seen in the saline group. Because of the late onset of action and only moderate increase in heart rate it is concluded that tracheal administration of atropine 0.02 mg.kg-1 to children is insufficient in emergency situations.


Distribution and steroid hormone regulation of aromatase mRNA expression in the forebrain of adult male and female rats: a cellular-level analysis using in situ hybridization.
Many of the effects of gonadal steroid hormones in the male brain are due to the actions of the testosterone metabolite estradiol, which is synthesized by the actions of the P450 enzyme aromatase. Aromatase activity is present in regions of the preoptic area, hypothalamus, and limbic system. Levels of aromatase activity in the brain are highly dependent on gonadal steroid hormones in many brain regions, but not all. We examined the distribution of aromatase mRNA in adult male and female rat brains as well as the regulation of the levels of aromatase mRNA in the brains of males by gonadal steroid hormones using in situ hybridization. This method was performed using a 35S-labelled cRNA probe, transcribed in vitro from the rat ovarian aromatase cDNA. In the adult male, many heavily labelled cells were found in the encapsulated bed nucleus of the stria terminalis (BNST), the medial preoptic nucleus (MPN), the ventromedial nucleus (VMN), the medial amygdala (mAMY), and the cortical amygdala (CoAMY). The regional distribution of aromatase mRNA was similar in females, but females tended to have a lower number of aromatase mRNA expressing cells in each region compared to males. Aromatase mRNA levels in the BNST, MPN, VMN, and mAMY tended to be lower in castrated males than in intact males, whereas aromatase mRNA levels were unaltered by castration in the CoAMY. The degree of reduction in mean levels of aromatase mRNA following castration does not simply account for the large changes measured in activity following castration. Examination of the entire population of individual cells expressing aromatase mRNA in castrated males suggests that aromatase mRNA may be regulated by steroid hormones differentially in specific populations of neurons within regions where activity is known to decrease following castration.


Vaccines Europe 2009.
The Informa Life Sciences vaccines conference is an annual meeting of a relatively small number of academics and industrialists. It is split into three concurrent sessions covering vaccine discovery, quality and manufacturing. Although there were many presentations of merit, only a few will be discussed here, including the plenary speeches on adjuvants and influenza.


Yunnan Baiyao reduces hospital-acquired pressure ulcers via suppressing virulence gene expression and biofilm formation of Staphylococcus aureus.
Yunnan Baiyao (YB) as a kind of famous Chinese herbal medicine, possessed hemostatic, invigorating the circulation of blood, and anti-inflammatory effects. Identifying strategies to protect patients at risk for hospital-acquired pressure ulcers (HAPU) is essential. Herein, our results showed that YB treatment can effectively reduce the acne wound area and improve efficacy in a comparative study of 60 cases HAPU patients with S. aureus positive of acne wound pathogens. Furthermore, YB inhibited HIa expression and suppressed accessory gene regulator (agr) system controlled by regulatory RNA II and RNA III molecule using pALC1740, pALC1742 and pALC1743 S. aureus strain linked to gfpuvr reporter gene. Moreover, YB downregulated cao mRNA expression and inhibited coagulase activity by RT-PCR, slide and tube coagulase test. Additionally, YB downregulated seb, sec, sed, and tsst-1 mRNA expression to suppress enterotoxin and tsst-1 secretion and adhesion function related genes sarA, icaA, and cidA mRNA expression. Taken together, the data suggest that YB may reduce HAPU via suppressing virulence gene expression and biofilm formation of S. aureus.


Hydraulic architecture and tracheid allometry in mature Pinus palustris and Pinus elliottii trees.
Pinus palustris Mill. (longleaf pine, LL) and Pinus elliottii Engelm. var. elliottii (slash pine, SL) frequently co-occur in lower coastal plain flatwoods of the USA, with LL typically inhabiting slightly higher and better-drained microsites than SL. The hydraulic architecture and tracheid dimensions of roots, trunk and branches of mature LL and SL trees were compared to understand their role in species microsite occupation. Root xylem had higher sapwood-specific hydraulic conductivity (k(s)) and was less resistant to cavitation compared with branches and trunk sapwood. Root k(s) of LL was significantly higher than SL, whereas branch and trunk k(s) did not differ between species. No differences in vulnerability to cavitation were observed in any of the organs between species. Across all organs, there was a significant but weak trade-off between water conduction efficiency and safety. Tracheid hydraulic diameter (D(h)) was strongly correlated with k(s) across all organs, explaining >73% of the variation in k(s). In contrast, tracheid length (L(t)) explained only 2.4% of the variability. Nevertheless, for trunk xylem, k(s) was 39.5% higher at 20 m compared with 1.8 m; this increase in k(s) was uncorrelated with D(h) and cell-wall thickness but was strongly correlated with the difference in L(t). Tracheid allometry markedly changed between sapwood of roots, trunks and branches, possibly reflecting different mechanical constraints. Even though vulnerability to cavitation was not different for sapwood of roots, branches or the trunks of LL and SL, higher sapwood to leaf area ratio and higher maximum sapwood-specific hydraulic conductivity in roots of LL are functional traits that may provide LL with a competitive advantage on drier soil microsites.


Pharmacokinetics of mycophenolate mofetil (RS61443): a short review.
Overall, the PK of MMF is reasonably straightforward and relatively unaffected by the complex pathophysiological changes involved in the management of renal transplant recipients. The ability to relate plasma MPA concentrations to efficacy through the PK/PD correlation implies that, unlike for many other drugs, plasma PK has direct relevance to the clinical outcome. These features should not only greatly help the exploration of immunosuppressive regiments using MMF but also the development of clinical use of MMF in situations other than renal transplantation.


A comparison of postcesarean epidural morphine analgesia by single injection and by continuous infusion.
To assess the relative efficacy and incidence of side effects of a single injection versus a continuous infusion of epidural morphine sulfate (MS) in the postcesarean population, the authors report a prospective, randomized, double-blind study. Thirty-one patients received either a 5-mg MS bolus and subsequent saline infusion (n = 13) or a 2.6-mg MS bolus and subsequent MS infusion at 0.1 mg/hour (n = 18), such that after 24 hours both groups had received a total MS dose of 5 mg. No statistically significant differences were found between the two groups in overall satisfaction with analgesia, verbal pain scores, level of activity, need for supplemental opioids, or incidence of sedation during the 24-hour study period. The authors conclude that in this population, continuous epidural morphine infusion offers no obvious advantage over single morphine bolus therapy. However, the theoretical merits of continuous opioid infusion therapy are discussed.


Comparison of Chinese and US orthodontists' averaged evaluations of "facial attractiveness" from end-of-treatment facial photographs.
This study continues our assessment of agreement and disagreement among 25 Chinese and 20 US orthodontists in the ranking for facial attractiveness of end-of-treatment photographs of randomly sampled growing Chinese and white orthodontic patients. The main aims of this article were to (1) measure the overall pattern of agreement between the mean rankings of US and Chinese orthodontists, and (2) measure the strength of agreement between the rankings of the US and Chinese orthodontists for each patient. Each judge independently ranked standard clinical sets of profile, frontal, and frontal-smiling photographs of 43 US patients and 48 Chinese patients. For each patient, a separate mean rank was computed from the responses of each group of judges. Pearson correlations between the mean ranks of the 2 groups of judges were used to measure their overall agreement. Paired and unpaired t tests were used to measure the agreement between the judges of the 2 groups for each patient. The overall agreement between the mean rankings of the US and Chinese judges was very high. For the US patients, the correlation between the Chinese and US judges means was r = 0.92, P <0.0001. For the Chinese patients, the analogous value was r = 0.86, P <0.0001. Agreement between the 2 groups of judges concerning each patient was also generally strong. For two thirds of the patients, the mean ranks of the US and Chinese judges differed by less than 1 unit in a scale of 12. However, for 6 patients considered individually (5 Chinese and 1 US), the assessment of the 2 groups of judges was statistically significantly different at P values ranging from 0.02 to less than 0.0001, even after the Bonferroni correction. These findings demonstrate that orthodontic clinicians can reliably identify and rank subtle differences between patients, and that differences between judges and between patients can be distinguished at a high level of statistical significance, given appropriate study designs. However, the reasons clinicians give for the differences in their judgments are more difficult to investigate and will require further study.


Naegleria fowleri: enolase is expressed during cyst differentiation.
Cysts of Naegleria fowleri present an external single-layered cyst wall. To date, little information exists on the biochemical components of this cyst wall. Knowledge of the cyst wall composition is important to understand its resistance capacity under adverse environmental conditions. We have used of a monoclonal antibody (B4F2 mAb) that specifically recognizes enolase in the cyst wall of Entamoeba invadens. By Western blot assays this antibody recognized in soluble extracts of N. fowleri cysts a 48-kDa protein with similar molecular weight to the enolase reported in E. invadens cysts. Immunofluorescence with the B4F2 mAb revealed positive cytoplasmic vesicles in encysting amebas, as well as a positive reaction at the cell wall of mature cysts. Immunoelectron microscopy using the same monoclonal antibody confirmed the presence of enolase in the cell wall of N. fowleri cysts and in cytoplasmic vesicular structures. In addition, the B4F2 mAb had a clear inhibitory effect on encystation of N. fowleri.


Endoscopic and ultrasound image of an ileocolic intussusception. An unusual finding in adult patients.
We present the case of a 63-year-old woman in whom the clinical and ultrasound imaging initially suspected the existence of colon neoplasia, which finally turned out to be an ileocolic invagination, with the prognostic change that this entails. The contribution of this article is to bring readers closer to clinical cases that, although infrequent, should be taken into account. In this way, it allows the reader to suspect it in clinical practice in patients who meet the clinical characteristics mentioned.


Optical fiber sensor for membrane submicrometer vibration measurement.
This paper presents an optical fiber sensor for membrane submicrometer vibration measurement. The sensor is designed ultimately for low-cost medical audiometric applications such as determining the mobility of the tympanic membrane stimulated by the tone. The sensing method is minimally invasive, and the sensing head does not contact the surface of the membrane. Measurements were performed on tympanic membrane phantoms. Deflections of a few nanometers were measured, and vibration maps of phantoms were taken.


Feature-specific prediction errors for visual mismatch.
Predictive coding (PC) theory posits that our brain employs a predictive model of the environment to infer the causes of its sensory inputs. A fundamental but untested prediction of this theory is that the same stimulus should elicit distinct precision weighted prediction errors (pwPEs) when different (feature-specific) predictions are violated, even in the absence of attention. Here, we tested this hypothesis using functional magnetic resonance imaging (fMRI) and a multi-feature roving visual mismatch paradigm where rare changes in either color (red, green), or emotional expression (happy, fearful) of faces elicited pwPE responses in human participants. Using a computational model of learning and inference, we simulated pwPE and prediction trajectories of a Bayes-optimal observer and used these to analyze changes in blood oxygen level dependent (BOLD) responses to changes in color and emotional expression of faces while participants engaged in a distractor task. Controlling for visual attention by eye-tracking, we found pwPE responses to unexpected color changes in the fusiform gyrus. Conversely, unexpected changes of facial emotions elicited pwPE responses in cortico-thalamo-cerebellar structures associated with emotion and theory of mind processing. Predictions pertaining to emotions activated fusiform, occipital and temporal areas. Our results are consistent with a general role of PC across perception, from low-level to complex and socially relevant object features, and suggest that monitoring of the social environment occurs continuously and automatically, even in the absence of attention.


[Clinicopathologic features of small-sized peripheral lung cancer; is intentional limited resection appropriate for selected patients?].
We sought to determine the eligibility of patients with early peripheral lung cancer for intentional limited resection. The clinicopathologic features of 103 patients who underwent lobectomy and mediastinal nodal dissection for early stage peripheral lung cancer measuring 2 cm or less in maximum dimension between 1992 and 2002 were examined retrospectively. The lymph node metastasis and residual cancer after thoracoscopic partial resection were analyzed by the following categories. Three groups were divided by maximum dimension of the primary lesion in the resected specimen; 10 mm or less (n = 11), 15 mm or less (n = 33), and 20 mm or less (n = 59). Two groups were divided by lesion histology; bronchioloalveolar adenocarcinoma (BAC) [n = 42] and invasive lung cancer (n = 61). Residual cancer was found in the residual lobe after thoracoscopic partial resection in 3 of 43 patients who had no diagnosis preoperatively. Their maximum dimensions were 15 mm or less. No lymph node metastasis was detected in the patients with tumor measuring 10 mm or less, and BAC. Intentional limited resection without mediastinal nodal dissection is appropriate for patients with tumor measuring 10 mm or less and BAC. Further investigation associated with partial resection is necessary.


Transverse testicular ectopia associated with persistent Mullerian duct syndrome in infertile male: two case reports and literature review.
Transverse testicular ectopia (TTE) associated with persistent Mullerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism usually unexpectedly found at surgery for cryptorchidism or inguinal hernia in children. Its etiology and prevalence are unclear, although defects in the gene that encodes anti-Mullerian hormone (AMH) or AMH receptor has been generally considered as the major cause. Adult cases of TTE associated with PMDS are even more peculiar, as the adult patients usually present more complex medical history, require more comprehensive medical examination and management. Two adult men with normal karyotype were referred to the urology outpatient clinic for infertility and cryptorchidism. Semen analysis showed both patients were azoospermic. Ultrasound and computed tomography (CT) found both testes were located at the same side of abdominal cavity or pelvic cavity, which was confirmed during the laparoscopic exploration. A tubular structure adhering to the spermatic cord was also found in both cases. Laparoscopic-assisted transabdominal orchiopexy was performed and the tubular mass was removed. Pathological examination confirmed the existence of Mullerian duct, which showed positive immunostaining of the uterus marker genes. The principles of treatment include the restoration of testes, the preservation of fertility, and the prevention of malignancy. Much attention should be payed to avoid damage of fertile testes and vas deferens in the surgery. Long-term postoperative follow-up is necessary for assessment of malignant transformation and infertility.


Porosomes in uterine epithelial cells: Ultrastructural identification and characterization during early pregnancy.
Porosomes are plasma membrane structures in secretory cells that allow transient docking and/or partial fusion of vesicles during which they release their content then disengage. This is referred to as "kiss and run" exocytosis. During early pregnancy, at the time of receptivity, there is a high level of vesicle activity in uterine epithelial cells (UECs). One of the secretory pathways for these vesicles could be via porosomes, which have yet to be identified in UECs. This study identified porosomes in the apical plasma membrane of UECs for the first time. These structures were present on days 1, 5.5, and 6 of early pregnancy, where they likely facilitate partial secretion via "kiss and run" exocytosis. The porosomes were measured and quantified on days 1, 5.5, and 6, which showed there are significantly more porosomes on day 5.5 (receptive) compared to day 1 (nonreceptive) of pregnancy. This increase in porosome numbers may reflect major morphological and molecular changes in the apical plasma membrane at this time such as increased cholesterol and soluble NSF attachment protein receptor proteins, as these are structural and functional components of the porosome complex assembly. Porosomes were observed in both resting (inactive) and dilated (active) states on days 1, 5.5, and 6 of early pregnancy. Porosomes on day 5.5 are significantly more active than on day 1 as demonstrated by the dilation of their base diameter. Further two-way ANOVA analysis of base diameter in resting and dilated states found a significant increase in porosome activity in day 5.5 compared to day 1. This study therefore indicates an increase in the number and activity of porosomes at the time of uterine receptivity in the rat, revealing a mechanism by which the UECs modify the uterine luminal environment at this time.


Spatial Analysis of COVID-19 Vaccination: A Scoping Review.
Spatial analysis of COVID-19 vaccination research is increasing in recent literature due to the availability of COVID-19 vaccination data that usually contain location components. However, to our knowledge, no previous study has provided a comprehensive review of this research area. Therefore, in this scoping review, we examined the breadth of spatial and spatiotemporal vaccination studies to summarize previous findings, highlight research gaps, and provide guidelines for future research. We performed this review according to the five-stage methodological framework developed by Arksey and O'Malley. We screened all articles published in PubMed/MEDLINE, Scopus, and Web of Science databases, as of 21 September 2021, that had employed at least one form of spatial analysis of COVID-19 vaccination. In total, 36 articles met the inclusion criteria and were organized into four main themes: disease surveillance (n = 35); risk analysis (n = 14); health access (n = 16); and community health profiling (n = 2). Our findings suggested that most studies utilized preliminary spatial analysis techniques, such as disease mapping, which might not lead to robust inferences. Moreover, few studies addressed data quality, modifiable areal unit problems, and spatial dependence, highlighting the need for more sophisticated spatial and spatiotemporal analysis techniques.


Shape-tunable polymeric Janus nanoparticles with hollow cavities derived from polymerization induced self-assembly based crosslinked vesicles.
The fabrication of shape-tunable polymeric Janus nanoparticles with hollow cavities derived from polymerization induced self-assembly based crosslinked vesicles is reported for the first time in this work. These novel polymeric JNPs can be applied to an extensive range of applications, wherein nanoparticles with controllable hollow morphologies are needed.


Efficacy and mechanism-of-action of a novel superagonist interleukin-15: interleukin-15 receptor αSu/Fc fusion complex in syngeneic murine models of multiple myeloma.
ALT-803, a complex of an interleukin (IL)-15 superagonist mutant and a dimeric IL-15 receptor αSu/Fc fusion protein, was found to exhibit significantly stronger in vivo biologic activity on NK and T cells than IL-15. In this study, we show that a single dose of ALT-803, but not IL-15 alone, eliminated well-established 5T33P and MOPC-315P myeloma cells in the bone marrow of tumor-bearing mice. ALT-803 treatment also significantly prolonged survival of myeloma-bearing mice and provided resistance to rechallenge with the same tumor cells through a CD8(+) T-cell-dependent mechanism. ALT-803 treatment stimulated CD8(+) T cells to secrete large amounts of IFN-γ and promoted rapid expansion of CD8(+)CD44(high) memory T cells in vivo. These memory CD8(+) T cells exhibited ALT-803-mediated upregulation of NKG2D (KLRK1) but not PD-1 (PDCD1) or CD25 (IL2RA) on their cell surfaces. ALT-803-activated CD8(+) memory T cells also exhibited nonspecific cytotoxicity against myeloma and other tumor cells in vitro, whereas IFN-γ had no direct effect on myeloma cell growth. ALT-803 lost its antimyeloma activity in tumor-bearing IFN-γ knockout mice but retained the ability to promote CD8(+)CD44(high) memory T-cell proliferation, indicating that ALT-803-mediated stimulation of CD8(+)CD44(high) memory T cells is IFN-γ-independent. Thus, besides well-known IL-15 biologic functions in host immunity, this study shows that IL-15-based ALT-803 could activate CD8(+)CD44(high) memory T cells to acquire a unique innate-like phenotype and secrete IFN-γ for nonspecific tumor cell killing. This unique immunomodulatory property of ALT-803 strongly supports its clinical development as a novel immunotherapeutic agent against cancer and viral infections.


[Motor impairment in amyloid-associated muscle pseudohypertrophy].
Muscle involvement, usually associated with pseudohypertrophy, has been described very rarely in patients with AL-(primary or myeloma-associated) amyloidosis. Although precise mechanisms for the motor impairment in amyloid-associated muscle pseudohypertrophy are unknown, amyloid accumulation in the muscle has been thought to be a main cause of muscle weakness. We here describe a patient of amyloid-associated muscle pseudohypertrophy with IgA lambda plasma cell dyscrasia, and discuss possible mechanisms for the physical disability. The patient, a 65-year-old man, was admitted because of progressive stiffness of limb and bulbar muscles for approximately three years. On physical examination he appeared muscular and athletic. The muscles were firm with wooden or rock-like hardness. Superficial veins were engorged in all extremities. Macroglossia was marked. Resistance to passive movement was noted in all extremities with decreased range of motion; proximal joints were more severely affected. The patient walking for a short distance, his legs became heavy, tired and firm, which forced him to stop. Immunoelectrophoresis revealed the monoclonal secretion of IgA lambda in the serum and free lambda light chain in the urine. Bone marrow examination disclosed 30% plasma cells with a large prevalence of IgA lambda-containing cells. A bone scan showed an increased uptake of 99mTc-methylene diphosphate in the shoulder and pelvic joints. Tissue pressures of the quadriceps femoris at the supine and standing positions, and after walking were as high as 47, 89, and 112 mmHg, respectively. Venography of the left leg showed narrowing of the femoral vein and visualization of saphena magna vein.(ABSTRACT TRUNCATED AT 250 WORDS)


Wavefront-guided photorefractive keratectomy to correct ametropia following aspheric ReSTOR implantation.
To describe the clinical course of three eyes of two patients who underwent wavefront-guided photorefractive keratectomy to correct ametropia following cataract extraction and aspheric ReSTOR lens (SN6AD3; +4.00-diopter model) implantation. Pre-and postoperative uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA), manifest refraction, and WaveScans based on the Hartmann-Shack analyzer were evaluated. The VISX STAR S4 excimer with eye tracking and iris registration was used in all cases. Good quality WaveScans were obtained; UCVA improved in all cases and BSCVA improved or remained unchanged. These cases demonstrate that it is possible to obtain good quality wavefront data in patients with the ReSTOR lens and to use such data to design wavefront-guided treatment to maximize uncorrected distance and near visual acuities after ReSTOR implantation.


Periprostatic local anesthesia before ultrasound guided prostate biopsy.
We assessed the morbidity and benefit of periprostatic local anesthesia administered before ultrasound guided prostate biopsy. After placing the transrectal ultrasound probe and visualizing the prostate 50 consecutive patients received local anesthesia before prostate biopsies. There was no morbidity associated with the infiltration of local anesthesia into the periprostatic neurovascular plexus. Only 1 patient had discomfort during prostate biopsies, and 10 patients who previously underwent biopsies without anesthesia commented favorably on the dramatic difference. Many patients have pain during transrectal ultrasound guided biopsies of the prostate and few clinicians provide a periprostatic nerve block before this procedure. A periprostatic nerve block administered before the biopsies dramatically decreases discomfort. We urge all urologists to attempt this procedure, and we are confident that they will adopt it as part of their practice.


Reversible interconversion between luminescent isomeric metal-organic frameworks of [Cu(4)I(4)(DABCO)(2)] (DABCO=1,4-diazabicyclo[2.2.2]octane).
The metal-organic frameworks (MOF) of cluster [Cu(4)I(4)(DABCO)(2)] (DABCO=1,4-diazabicyclo[2.2.2]octane) have been prepared and characterized as two different crystalline forms, I and II. Form I is obtained by reaction of DABCO and CuI in aqueous solution or by solvothermal reaction, while form II is obtained by reacting DABCO and CuI in acetonitrile. Their luminescence properties in the solid state have been analyzed at room temperature and at 77 K. MOF II has bright emission with a maximum at 556 nm that shifts bathochromically at low temperature in conjunction with a marked change in the colour of the emission. The emission of MOF I has a maximum at 580 nm and a less pronounced temperature dependence. The peculiar luminescence properties of the two isomers have been interpreted by utilising current knowledge on the excited states properties of Cu(I) cubane clusters. The two isomers exhibit a high degree of porosity and can release the disordered solvent molecules trapped in the channels, whilst preserving the crystal structure. Isomer I can be converted into II on exposure to acetonitrile or methanol vapour, whereas II reverts to I when heated in a closed pan at 250 degrees C.


The topology of electronic band structures.
The study of topology as it relates to physical systems has rapidly accelerated during the past decade. Critical to the realization of new topological phases is an understanding of the materials that exhibit them and precise control of the materials chemistry. The convergence of new theoretical methods using symmetry indicators to identify topological material candidates and the synthesis of high-quality single crystals plays a key role, warranting discussion and context at an accessible level. This Perspective provides a broad introduction to topological phases, their known properties, and material realizations. We focus on recent work in topological Weyl and Dirac semimetals, with a particular emphasis on magnetic Weyl semimetals and emergent fermions in chiral crystals and their extreme responses to excitations, and we highlight areas where the field can continue to make remarkable discoveries. We further examine open questions and directions for the topological materials science community to pursue, including exploration of non-equilibrium properties of Weyl semimetals and cavity-dressed topological materials.


Applications of artificial neural networks in medical science.
Computer technology has been advanced tremendously and the interest has been increased for the potential use of 'Artificial Intelligence (AI)' in medicine and biological research. One of the most interesting and extensively studied branches of AI is the 'Artificial Neural Networks (ANNs)'. Basically, ANNs are the mathematical algorithms, generated by computers. ANNs learn from standard data and capture the knowledge contained in the data. Trained ANNs approach the functionality of small biological neural cluster in a very fundamental manner. They are the digitized model of biological brain and can detect complex nonlinear relationships between dependent as well as independent variables in a data where human brain may fail to detect. Nowadays, ANNs are widely used for medical applications in various disciplines of medicine especially in cardiology. ANNs have been extensively applied in diagnosis, electronic signal analysis, medical image analysis and radiology. ANNs have been used by many authors for modeling in medicine and clinical research. Applications of ANNs are increasing in pharmacoepidemiology and medical data mining. In this paper, authors have summarized various applications of ANNs in medical science.


Highly Oriented J-Aggregates of Nitroazo Dye and Its Surface-Induced Chromism.
Highly oriented J-aggregates of a nitroazo dye were obtained in solid thin films on aligned poly(tetrafluoroethylene) surfaces. During film deposition on a friction-transferred poly(tetrafluoroethylene) layer, a sharp peak grew in the polarized absorption spectra around 613 nm, which was red-shifted 117 nm from the peak in dilute dichloromethane solution. The peak showed remarkable optical anisotropy: dichroic ratios D of up to 22 were observed, and the intrinsic D value should substantially exceed this value. These results indicate that the peak is attributable to highly oriented J-aggregates. On glass, however, H-like aggregates grew, exhibiting an absorption peak at 410 nm. Hence, the substrate surface induced the remarkable chromism observed as a 203 nm red shift.


Pan-Cancer Analysis of Postdiagnosis Exercise and Mortality.
The impact of postdiagnosis exercise on cause-specific mortality in cancer survivors and whether this differs on the basis of cancer site is unclear. We performed an analysis of 11,480 patients with cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. Patients with a confirmed diagnosis of cancer completing a standardized survey quantifying exercise after diagnosis were included. The primary outcome was all-cause mortality (ACM); secondary end points were cancer mortality and mortality from other causes. Cox models were used to estimate the cause-specific hazard ratios (HRs) for ACM, cancer, and noncancer mortality as a function of meeting exercise guidelines versus not meeting guidelines with adjustment for important clinical covariates. After a median follow-up of 16 years from diagnosis, 4,665 deaths were documented (1,940 due to cancer and 2,725 due to other causes). In multivariable analyses, exercise consistent with guidelines was associated with a 25% reduced risk of ACM compared with nonexercise (HR, 0.75; 95% CI, 0.70 to 0.80). Compared with nonexercise, exercise consistent with guidelines was associated with a significant reduction in cancer mortality (HR, 0.79; 95% CI, 0.72 to 0.88) and mortality from other causes (HR, 0.72; 95% CI, 0.66 to 0.78). The inverse relationship between exercise and cause-specific mortality varied by exercise dose. Exercise consistent with guidelines was associated with a reduced hazard of ACM for multiple cancer sites. Reduction in cancer mortality for exercisers was only observed in head and neck and renal cancer. In this pan-cancer sample of long-term cancer survivors, exercise consistent with guidelines was associated with substantial ACM benefit driven by both reductions in cancer and noncancer mortality. The cause-specific impact of exercise differed as a function of cancer site.


Corpus Callosum Swelling after Resection of Intraventricular Central Neurocytoma.
Corpus callosum swelling has been reported to occur after ventriculoperitoneal shunting for long-standing hydrocephalus. This report presents a case of corpus callosum swelling after intraventricular tumor resection. A 34-year-old woman presented with a headache that worsened over 1 month. Magnetic resonance (MR) images revealed a mass lesion in the left lateral ventricle and obstructive hydrocephalus. She underwent subtotal resection with a transcallosal approach. After tumor resection, she had long-lasting status epilepticus followed by consciousness disturbance. T2-weighted MR images obtained 8 hr after the operation showed a hyperintense area in the corpus callosum. The patient then presented with bilateral dilated pupils 14 hr after the operation due to acute hydrocephalus and tension pneumocephalus. An emergent re-craniotomy was performed and a ventricular drain was placed. The patient recovered consciousness 3 days after the operation. However, she experienced progressive corpus callosum swelling 25 days after the operation, which improved since then. Approximately 4 months after the operation, she returned to her usual workplace with no neurocognitive functional decline. Two years later, she was doing well with no radiological abnormal findings except corpus callosum thinning. Thus, corpus callosum swelling can develop not only after shunting for chronic hydrocephalus but also after intraventricular tumor resection. It occurred relatively acutely and there was no decline in intelligence after long-term follow-up. This case suggests that corpus callosum swelling after intraventricular tumor resection is a rare but noteworthy complication that can improve without intervention.


Significant reduction of hypertrophic scarring by lateral vertical incision in skin-sparing and nipple-sparing mastectomy.
Some kinds of incisions have been reported in skin- or nipple-sparing mastectomy, but few reports have described the advantages and disadvantages of each incision. This study was conducted to compare the lateral horizontal incision with the lateral vertical incision in both mastectomies, in terms of hypertrophic scarring, breast envelope necrosis, nipple-areola necrosis. We performed a retrospective analysis of patients who underwent skin- or nipple-sparing mastectomy using lateral horizontal or lateral vertical incisions with immediate breast reconstruction. All data were obtained retrospectively from databases, operation records and postoperative pictures. We compared the frequency of hypertrophic scarring and breast envelope necrosis between lateral horizontal and lateral vertical incision groups by using Pearson's chi-square test. For nipple-sparing mastectomy, we also investigated nipple-areola necrosis. One hundred fifty cases were analyzed and identified as 89 lateral horizontal incision cases and 61 lateral vertical incision cases. Mastectomy comprised SSM in 49 cases and NSM in 101 cases. Hypertrophic scarring was significantly less frequent with lateral vertical incisions (1.6%) than with lateral horizontal incisions (14.6%) (P =0.007). No significant differences were seen in terms of breast envelope necrosis, nipple-areolar necrosis.


Clinical study of effectiveness and safety of CELcomplex® containing Cucurbita Pepo Seed extract and Flax and Casuarina on stress urinary incontinence in women.
The safety and effectiveness of a preparation containing a mix of Cucurbita Pepo Seed extract, Equisetum arvense and Linum usitatissimum - Flax A (CELcomplex®) on stress urinary incontinence (SUI) was evaluated in female patients recruited from 20 urological and gynaecological outpatient clinics in Slovakia. A total of 86 women aged from 32 to 88 with SUI (grade 1 = 44, grade 2 = 42) were enrolled in the study and followed-up for six weeks (point 1) and twelve weeks (point 2). The primary outcome of the study was evaluated by changes in day-time and nocturnal urinary frequency (bathroom visits) and urinary incontinence episodes (leaks). Also, adverse events were quantified as well as the self-perceived effectiveness of the treatment. Research Ethics Board approval was obtained for this study. After 12 weeks of treatment there was a 30% (grade 1 SUI, p < 0.01), and 35% (grade 2 SUI, p < 0.01) improvement in urinary incontinence episodes, a 40% (grade 1 SUI, p < 0.01) and 26% (grade 2 SUI, p < 0.01) improvement in day-time urination frequency and 64% (grade 1 SUI, p < 0.01) and 54% (grade 2 SUI, p < 0.01) improvement in nocturnal urinary frequency. Reported side effects were: headache (3.5%), flatulence (4.1%) and gastrointestinal discomfort (3%). A total of 89.4 % of women in the study reported no side effects from this therapy and 97% acknowledged improvement of symptoms. This clinical study demonstrated that a 12 week treatment with a mix of Cucurbita Pepo Seed extract, Equisetum arvense and Linum usitatissimum - Flax A (CELcomplex®) is highly effective on stress urinary incontinence (SUI) with minimum adverse events. Further studies may be needed in order to determine the effectiveness and efficacy of this phytotherapy in other populations.


Naïve conceptions about multimedia learning: a study on primary school textbooks.
HIGHLIGHTSThis interview study explores beliefs about the instructional role of illustrationsWe compared illustrators', teachers', students' and common people's ideasParticipants' responses were internally coherent and close to multimedia learning theoryWe propose and discuss an integrated multimedia learning model An interview study, based on specific pictures taken from textbooks used in primary schools, was carried out to investigate illustrators', teachers', students', and common people's beliefs about the role that illustrations play in facilitating learning. Participants' responses were internally coherent, indicating a systematic nature of the underlying naïve conceptions. Findings disprove Mayer's pessimistic claim that laypersons' conceptions of multimedia learning fail to match experimentally supported principles and theories. On the contrary, interviewees spontaneously came very close to the multimedia learning theory, which states that students learn better from pictures, which fit specific cognitive principles. Implications for school instruction are highlighted.


Accuracy mass screening and identification of phenolic compounds from the five parts of Abutilon theophrasti Medic. by reverse-phase high-performance liquid chromatography-electrospray ionization-quadrupoles-time of flight-mass spectrometry.
A rapid and resolutive reverse-phase high-performance liquid chromatography-electrospray ionization-quadrupoles-time of flight-mass spectrometry method was established for the screening and identification of the phenolic compounds in the 70% ethanolic extracts from the five parts (roots, stems, leaves, seeds, and exocarps) of Abutilon theophrasti Medic.. Separation and detection conditions were optimized by using a 22 mixing standard, which included phenolic acids, flavonoids and a naphthalene compound. Optimum LC separation was achieved on a C(18) analytical column (250 mm x 4.6 mm id, 5 μm) by gradient elution with water containing 0.1% v/v formic acid (pH 2.4) and acetonitrile as mobile phases, at a flow rate of 1.0 mL/min. The developed method was applied to the study on the constituents of A. theophrasti Medic., and 16 compounds were unequivocally identified with standards. Meanwhile, 37 constituents were tentatively identified by comparing with references. In addition, accurate molecular formulae were conjectured for unknown compounds. To our knowledge, little is known about how these compounds are distributed in A. theophrasti Medic.. Hence, it is clear that the comprehensive analysis of the phenolic compounds of A. theophrasti Medic. is helpful for the quality control and understanding the usage and function of the herb and its products.


Relationships between throwing mechanics and shoulder distraction in professional baseball pitchers.
The extreme forces and torques and the high speeds and excessive ranges of motion of baseball pitching place tremendous stress on the soft tissues of the throwing shoulder. Little is known about the relationship between pitching mechanics and shoulder joint stress, especially in professional athletes. The purpose of this study was to quantify joint loads and kinematic parameters of pitching mechanics at the major league level and to study their relationships. Three-dimensional, high-speed video data were collected on 40 professional pitchers during the 1998 Cactus League spring training. A clinically significant distraction force was calculated at the shoulder joint, which reached an average peak value of 947 +/- 162 N (108% +/- 16% body weight). Descriptive statistics and a multiple linear regression analysis were used to relate shoulder distraction to kinematic and kinetic parameters of pitching mechanics. This study was undertaken not only to investigate the peak forces and torques on the shoulder, but also to identify potential areas of intervention that might prevent throwing injuries. Knowledge of joint ranges of motion, angular velocities, and joint-reaction forces can provide a scientific basis for improved preventive and rehabilitative protocols for baseball pitchers.


Animal secretory endolysosome channel discovery.
Secretory pore-forming proteins (PFPs) have been identified in organisms from all kingdoms of life. Our studies with the toad species Bombina maxima found an interaction network among aerolysin family PFPs (af-PFPs) and trefoil factors (TFFs). As a toad af-PFP, BmALP1 can be reversibly regulated between active and inactive forms, with its paralog BmALP3 acting as a negative regulator. BmALP1 interacts with BmTFF3 to form a cellular active complex called βγ-CAT. This PFP complex is characterized by acting on endocytic pathways and forming pores on endolysosomes, including stimulating cell macropinocytosis. In addition, cell exocytosis can be induced and/or modulated in the presence of βγ-CAT. Depending on cell contexts and surroundings, these effects can facilitate the toad in material uptake and vesicular transport, while maintaining mucosal barrier function as well as immune defense. Based on experimental evidence, we hereby propose a secretory endolysosome channel (SELC) pathway conducted by a secreted PFP in cell endocytic and exocytic systems, with βγ-CAT being the first example of a SELC protein. With essential roles in cell interactions and environmental adaptations, the proposed SELC protein pathway should be conserved in other living organisms.


Where the Action Is-Leukocyte Recruitment in Atherosclerosis.
Atherosclerosis is the leading cause of death worldwide and leukocyte recruitment is a key element of this phenomenon, thus allowing immune cells to enter the arterial wall. There, in concert with accumulating lipids, the invading leukocytes trigger a plethora of inflammatory responses which promote the influx of additional leukocytes and lead to the continued growth of atherosclerotic plaques. The recruitment process follows a precise scheme of tethering, rolling, firm arrest, crawling and transmigration and involves multiple cellular and subcellular players. This review aims to provide a comprehensive up-to-date insight into the process of leukocyte recruitment relevant to atherosclerosis, each from the perspective of endothelial cells, monocytes and macrophages, neutrophils, T lymphocytes and platelets. In addition, therapeutic options targeting leukocyte recruitment into atherosclerotic lesions-or potentially arising from the growing body of insights into its precise mechanisms-are highlighted.


Oral Health Status in Older People with Dementia: A Case-Control Study.
Dementia is characterized by a range of cognitive defects with impaired activities of daily living that have implications for patient oral health. Objectives. A case-control study was made of the impact of dementia upon oral health. A total of 152 patients were included: 69 with dementia and 83 controls from the region of Murcia (Spain). The Global Deterioration Scale (GDS) was used to classify the patients and an oral exploration was carried out. Odds ratios (ORs) and confidence intervals (CIs) were estimated using regression models. The patients with more severe disease were significantly more likely to have fewer natural teeth (OR 11.00, 95%CI 1.28-23.22; p = 0.001), a higher plaque index (p = 0.001), and a greater bleeding index (p = 0.001) than the control group. These findings suggest that older adults with dementia have deficient oral health. A higher bleeding index increases the risk of deterioration of cognitive function. The oral hygiene and health of older people with dementia need to be improved.