Effects of orthodontic appliances on the diagnostic quality of magnetic resonance images of the head.
The influence of 4 commonly used fixed orthodontic appliances on artifact formation and diagnostic quality of magnetic resonance (MR) images of the head produced by a 3-T MR scanner was studied. Stainless steel brackets, ceramic brackets, combination of ceramic brackets and steel molar tubes, and multistranded steel mandibular lingual retainers were embedded into custom-made trays for each of 10 adult subjects. Head MR scans of 9 regions were acquired for each subject wearing these trays. Sagittal T1-weighted, axial T2-weighted, axial gradient-recalled, axial diffusion-weighted, noncontrast axial MR angiography, and axial fluid-attenuated inversion recovery MR sequences were included. Two neuroradiologists evaluated image distortions and diagnostic qualities of the 1314 acquired images (13860 image slices). The images were affected by appliance, head region, and MR sequence. Stainless steel brackets and molar tubes affected the images the most, and ceramic brackets caused minimal image distortion. Head MR images are differentially affected by orthodontic appliances. The appliance, region imaged, and MR sequence should be considered before imaging patients wearing fixed orthodontic appliances.


Isolation and bioactivities of the flavonoids morin and morin-3-O-β-D-glucopyranoside from Acridocarpus orientalis-A wild Arabian medicinal plant.
Acridocarpus orientalis is an important medicinal plant for some of the locals of Arabian region. Very little is known about its phytochemical constituents. In the present study, we aimed to isolate bioactive chemicals from the crude methanolic extract of the aerial parts of A. orientalis. The extraction and isolation resulted in the purification of two flavonoids: morin (1) and morin-3-O-β-D-glucopyranoside (2). The structure elucidation was carried out by extensive analysis of spectroscopic data and comparison with the reported data for the known constituents. The pure isolates were subjected to various biological assays for their bioactivities. The compounds 1 and 2 were significantly active against the growth of various pathogenic fungi and phytotoxic against lettuce seed at higher concentrations. Furthermore, the free radical scavenging activities, anti-lipid peroxidation, and cytotoxic effects against HepG2, HT29, and HCT116 cancer cell lines were also assayed and the results are presented in this paper.


Modulation of biological processes by mineral fiber adsorption of macromolecules in vitro.
Three classes of macromolecules (i.e., DNA, RNA, and protein) were shown to be adsorbed to asbestiform minerals. The cytotoxicity exerted by the fibers on a normal human fibroblast cell line, which may be an indicator of the carcinogenic potential of mineral fibers, correlated positively with the degree of macromolecular adsorption of the fiber, namely: chrysotile greater than amosite greater than glass fiber. Asbestiform fibers also induce an alteration in in vitro DNA hydrolysis by bovine pancreatic deoxyribonuclease. This phenomenon suggests that adsorption by asbestiform minerals may modulate biological processes by inducing a conformational change in biological macromolecules as a result of coulombic interaction between the surface charge of the fiber and the hydrophilic groups on the macromolecule.


Direct and indirect effects of the 13-valent pneumococcal conjugate vaccine administered to infants and young children.
This paper analyzes the most recent reports regarding the direct and indirect effects of the 13-valent pneumococcal conjugate vaccine (PCV13) when administered to infants and young children. PCV13 extends the protective effects reported for the 7-valent pneumococcal conjugate vaccine (PCV7). A further reduction in the incidence of invasive pneumococcal disease, community-acquired pneumonia, acute otitis media, rhinosinusitis and carriage of PCV13 serotypes in vaccinated and unvaccinated subjects was found with PCV13 compared with PCV7. However, further studies are required to establish the effectiveness of PCV13 against serotypes 1, 5 and 3, the role of cross-protective antibodies evoked by serotype 6A on serotype 6C and the importance of the serotype replacement phenomenon following the extension of PCV13 use.


Early life stress explains reduced positive memory biases in remitted depression.
There is contradictory evidence regarding negative memory biases in major depressive disorder (MDD) and whether these persist into remission, which would suggest their role as vulnerability traits rather than correlates of mood state. Early life stress (ELS), common in patients with psychiatric disorders, has independently been associated with memory biases, and confounds MDD versus control group comparisons. Furthermore, in most studies negative biases could have resulted from executive impairments rather than memory difficulties per se. To investigate whether memory biases are relevant to MDD vulnerability and how they are influenced by ELS, we developed an associative recognition memory task for temporo-spatial contexts of social actions with low executive demands, which were matched across conditions (self-blame, other-blame, self-praise, other-praise). We included fifty-three medication-free remitted MDD (25 with ELS, 28 without) and 24 healthy control (HC) participants without ELS. Only MDD patients with ELS showed a reduced bias (accuracy/speed ratio) towards memory for positive vs. negative materials when compared with MDD without ELS and with HC participants; attenuated positive biases correlated with number of past major depressive episodes, but not current symptoms. There were no biases towards self-blaming or self-praising memories. This demonstrates that reduced positive biases in associative memory were specific to MDD patients with ELS rather than a general feature of MDD, and were associated with lifetime recurrence risk which may reflect a scarring effect. If replicated, our results would call for stratifying MDD patients by history of ELS when assessing and treating emotional memories.


Police Response to Latina Immigrant Intimate Partner Violence Victims: A Qualitative Analysis.
While an increasing body of literature has assessed police response to intimate partner violence (IPV), a dearth of this research has examined police decision-making with formal reports of IPV among Latina immigrants. Using a LatCrit theoretical framework, the current study addressed this substantive gap through the systematic methods of the grounded theory approach to assess a sample of 36 police case files drawn from an agency located in one of the fifth most populous and diverse US cities. Results from the current study identified five themes related to shortcomings in police response to Latina immigrant IPV victims. The themes included cultural coercive control, language barriers, victim participation, case clearance efforts, and service provision. Policy implications and avenues for future research are discussed.


Beyond GnRH, LH and FSH: The role of kisspeptin on hypothalalmic-pituitary gonadal (HPG) axis pathology and diagnostic consideration.
Kisspeptin as a neuropeptide was established initially as regulator for gonadotropin-releasing hormone for pulse frequency and intensity. In the current review, initial search on PubMed was done with key word "Kisspeptin" with further filters to include reviews and trials from the last 10 years. Of the 313 articles shortlisted, 160(51%) dealt with kisspeptin pathology and diagnostic evaluation in various physiological conditions like puberty, while 57(18.2%) dealt with pathological conditions like hypogonadism, 53(17%) infertility, and 43(13.7%) with polycystic ovarian syndrome. This review explored existing data regarding understanding of the negative and positive influences on the kisspeptin hormone-release kinetics. It highlighted the recently identified ligands and pathways which could affect the gonadal steroids, including various metabolic alterations and environmental triggers. Also, the review highlighted the kisspepetin/G-protein coupled receptor-54 interaction which were influenced by neighbouring endocannabinoid system, Gamma aminobutyric acid (GABA)-ergic neuronal outputs and other chemical agents. It was also highlighted that the release of kisspepetin was identified as a group of neurons termed kisspeptin, neurokinin B, and dynorphin, or KNDy, in the arcuate nuclei. The data indicated the use of kisspepetin as a diagnostic marker for precocious puberty, puberty confirmation, hypogonadism, infertility and polycystic ovarian syndrome.


Learning experiences of oral hygiene students in the clinical environment.
To determine how students used daily and term-based clinical assessment tools, students' experience of clinical teaching and clinical assessment. This was a descriptive, cross-sectional study. The study population included final-year Degree in Oral Health (BOH) students (n = 34). Data were collected by means of a self-administered questionnaire using open- and closed-ended questions. The response rate was 85% (n = 29). Respondents reported that term-based assessment tools were more useful than daily assessment tools in preparing for clinical sessions, in guiding their patient management and as a reflection of their competence. Factors influencing student experiences include authentic learning opportunities such as performing a variety of procedures, patient appreciation and positive reinforcement from supervisors; consistent and appropriate feedback on their performance, feedback in the presence of a patient; supervisor qualities of being patient, respectful, non-threatening and being positive role models; and organizational aspects such as punctuality and availability of supervisors. Inconsistencies were found in student experiences in terms of the quality of feedback received. Assessment experiences include inconsistency between supervisors and not being informed of assessment scores. Regular verbal feedback or being appraised of their assessment scores was reported more frequently for term-based assessment (77%) than for daily assessment (27%). The results of this study suggest that a blueprint defining assessment as a means to drive student learning is inadequate. A more comprehensive approach encompassing all the parameters that impact the learning process may be more useful.


Apoptotic splenocytes drive the autoimmune response to poly(ADP-ribose) polymerase 1 in a murine model of lupus.
Although defects in apoptosis have been linked to both human and murine lupus, the exact mechanisms remain unknown. Moreover, it is not clear whether such defects are primary or secondary events in disease pathogenesis. To address these issues, we used an induced model of murine lupus, the parent-into-F(1) model of chronic graft-versus-host disease (cGVHD) in which a lupus-like phenotype highly similar to human systemic lupus erythematosus is reliably induced in normal F(1) mice. We addressed the role of nuclear Ags modified by caspases during apoptosis as potential targets of the autoantibody response and our results identify poly(ADP-ribose) polymerase 1 (PARP-1) as a frequently targeted autoantigen. Additional proteins cleaved during apoptosis were also targeted by the immune response. Importantly, female mice exhibited significantly greater numbers of apoptotic cells in germinal centers and higher serum anti-PARP-1 Ab levels compared with male cGVHD mice. Serum anti-PARP-1 levels in male cGVHD mice could be elevated to levels comparable to those of female cGVHD mice by the injection of apoptotic syngeneic F(1) splenocytes early in the disease course. These results provide a mechanism by which lupus autoantibodies target apoptotic molecules. Specifically, T cell-driven polyclonal B cell activation characteristic of systemic lupus erythematosus is sufficient to saturate otherwise normal apoptotic clearance mechanisms, permitting apoptotic material to accumulate, serve as autoantigens, and drive autoantibody production.


Neuroendocrine effects of cytokines in the rat.
The necessity ot maintain and/or restore homeostasis is an essential feature of mammals. This requires complex interactions between body cells, such as those from the immune and neuroendocrine systems, and in particular implies that the occurrence of immune activation be conveyed to the brain. It is now widely recognized that following infection, injury or inflammation, some immune cells (particularly macrophages) produce polypeptides called cytokines, interleukins or lymphokines /48/. These proteins provide the basis for intercellular communication between leukocytes (hence the name "interleukins") and mediate the immunoinflammatory responses (in particular T and B lymphocyte proliferation) /4,177/. In addition, interleukins (IL) can enter the general circulation and reach cells of the neuroendocrine axes, a phenomenon which represents one arm of the bidirectional communication links between the immune and the endocrine systems /25/. The early events which take place after presentation of an antigen (the so-called "acute-phase response" /89/) include metabolic and endocrine changes, such as changes in the circulating levels of insulin, TSH, GH, LH and ACTH, as well as adrenal and gonadal steroids /7,14/. This article reviews our present state of knowledge with regard to the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes of the rodent in response to interleukins.


ERADicate ER stress or die trying.
Stress within the endoplasmic reticulum (ER) induces a sophisticated network of pathways termed the unfolded protein response (UPR), which is mediated through the ER transmembrane sensors PERK, ATF6, and IRE1. The UPR coordinates the temporary downregulation of protein translation, the upregulation of ER chaperones and folding machinery, and the enhanced expression of components necessary for ER-associated degradation (ERAD) essential for decreasing ER stress by clearing terminally misfolded proteins from the ER. Repetitive but futile folding attempts not only prolong ER stress but can also result in reactive oxygen species (ROS) generation, both of which may result in cell death. Additional mechanisms for decreasing stress and the protein load in the ER have been recently revealed. They include a newly identified function of IRE1 in degradation of select secretory protein mRNAs, a "preemptive" quality control responsible for averting translocation of select secretory proteins into the ER, upregulation of forward trafficking to allow misfolded proteins with intact exit signals to exit the ER, and upregulation of autophagy. The saturation or failure of some or all of these mechanisms can result in cell death and disease, including diabetes and a number of late-onset neurologic diseases.


Patellar reconstruction following previous patellectomy: a review of the literature and a case series using distal femoral autograft during total knee arthroplasty.
During total knee arthroplasty, the reconstruction of the patella following a previous patellectomy is challenging, and is undertaken to improve functional outcomes and patient satisfaction. In this case series, we have reconstructed the patella using a femoral condyle resected during total knee arthroplasty. The resected femoral condyle with best available bone stock is selected and secured to the extensor mechanism. We reviewed the preoperative indications and postoperative outcomes of two patients who underwent the above procedure at our Institute, and compared this to the literature. The cases include a 68-year old male (6 months follow-up) who sustained a multi-fragmentary fracture of his right patella and underwent a patellectomy 30 years previously, and a 45-year old female (4 years follow-up) who underwent a left-sided patellectomy 15 years previously following polytrauma. As a result of progressive osteoarthritis they required total knee arthroplasty, and simultaneous patella reconstruction with a femoral condyle autograft. Compared to their preoperative range of motion, both patients demonstrated an improvement post-operatively with successful pain-free knee function, with no radiological signs of graft resorption. In this limited, small series we have reported two patients who are clinically and functionally satisfied by the outcome of surgery, with comparable outcomes to alternative methods. We believe the use of a femoral condyle autograft for patellar reconstruction is a safe and simple technique that optimises knee kinematics, without associated donor morbidity.


Tautomeric Effect of Histidine on the Monomeric Structure of Amyloid β-Peptide(1-42).
Tautomeric state of histidine is one of the factors that influence the structural and aggregation properties of amyloid β (Aβ)-peptide in neutral state. It is worth it to uncover the monomeric properties of Aβ(1-42) peptide in comparison with Aβ(1-40) peptide. Our replica-exchange molecular dynamics simulations results show that the sheet content of each tautomeric isomer in Aβ(1-42) monomer is slightly higher than that in Aβ(1-40) monomer except His6(δ)-His13(δ)-His14(δ) (δδδ) isomer, implying higher aggregation tendency in Aβ(1-42), which is in agreement with previous experimental and theoretical studies. Further analysis indicates that (εεε), (εδε), (εδδ), and (δδε) isomers prefer sheet conformation although they are in nondominating states. Particularly, it is confirmed that antiparallel β-sheets of (εδδ) were formed at K16-E22 (22.0-43.9%), N27-A30 except G29 (21.9-40.2%), and M35-I41 except G37 (24.1-43.4%). Furthermore, (εδδ) may be the easiest one to overcome structural transformation due to nonobstructing interactions between K16 and/or L17 and histidine residues. The current study will help to understand the tautomeric effect of Aβ(1-42) peptide to overcome Alzheimer's disease.


Interacting boson problems can be QMA hard.
Computing the ground-state energy of interacting electron problems has recently been shown to be hard for quantum Merlin Arthur (QMA), a quantum analogue of the complexity class NP. Fermionic problems are usually hard, a phenomenon widely attributed to the so-called sign problem. The corresponding bosonic problems are, according to conventional wisdom, tractable. Here, we demonstrate that the complexity of interacting boson problems is also QMA hard. Moreover, the bosonic version of N-representability problem is QMA complete. Consequently, these problems are unlikely to have efficient quantum algorithms.


Analysis of a Chinese population suggests that the TNFB gene is not a susceptibility gene for Graves' disease.
Graves' disease is associated with different HLA genes in different races. The TNFB gene lies between the class I and class II HLA genes and has two alleles, TNFB*1 and TNFB*2. Studies in Caucasians have suggested that the TNFB gene might be a susceptibility gene for Graves' disease. To investigate further the role of TNFB in predisposition to Graves' disease, we determined whether the TNFB disease associations in the Chinese were similar to those in Caucasians. A total of 57 patients with Graves' disease (32 male) were studied. A TNFB gene fragment was amplified from genomic DNA by using the polymerase chain reaction and digested with Nco I to distinguish the TNFB alleles (TNFB*1 and TNFB*2). Genotype frequencies were compared with those in a racially matched group of 92 controls. TNFB*1 homozygosity occurred in 15 (26%) Graves' and 22 (24%) control subjects. TNFB*1/TNFB*2 heterozygosity occurred in 29 (51%) and 48 (52%) and TNFB*2 homozygosity in 13 (23%) and 22 (24%), respectively (NS). There were gender differences in the frequencies of TNFB*1 homozygosity (13 male [41%], 2 female [8%]). TNFB*1/TNFB*2 heterozygosity (13 male [41%], 16 female [64%]) (chi 2 = 7.3, p = 0.02), and TNFB*2 frequency (19 male [59%], 23 female [92%]; pc = 0.04) in Graves' patients. We conclude that the TNFB associations with Graves' disease in the Hong Kong Chinese differ between the genders and from those described in Caucasians. The TNFB gene is not a susceptibility gene for Graves' disease.


Correction to: InRange: Comparison of the Second-Generation Basal Insulin Analogues Glargine 300 U/mL and Degludec 100 U/mL in Persons with Type 1 Diabetes Using Continuous Glucose Monitoring-Study Design.
In the original publication, the timing of baseline CGM assessment was incorrectly stated in the text in two instances; it is correct in Fig. 1.


Conformation-function relationship of vitamin D: conformational analysis predicts potential side-chain structure.
In previous studies, we have grouped regions in space occupied by the vitamin D side chain into four: A, G, EA, and EG. We showed that the receptor (VDR) affinity of 1alpha,25-dihydroxyvitamin D3 derivatives increases, in terms of side-chain region, in the order EG, G, A, and EA. We called this the active space group concept. In the present study, we used this active space group concept to analyze the conformation-activity relationship of about 40 representative potent 1alpha,25-dihydroxyvitamin D3 analogues. We initially listed structural modifications in the side chain of potent vitamin D analogues and estimated their potency factor. Possible side-chain conformations of representative analogues were calculated by the molecular mechanics method and plotted on a dot map compared with the regions A, G, EA, and EG. The cell-differentiating potency of the analogues was correlated with our active space group concept with few exceptions. Among potent analogues with a natural configuration at C(20), the side chains of those with a 22-oxa, 22-ene, 16-ene, or a 18-nor modification were located in front of region EA (termed F). The side chains of the most potent 20-epi-22-oxa-24-homovitamin D analogues were concentrated at the left side of the EA region (L-EA). Thus, the side chains of almost all potent analogues were distributed around the EA region, and potency increased in the order A, F, EA, and L-EA.


Upregulation of transgelin is an independent factor predictive of poor prognosis in patients with advanced pancreatic cancer.
Transgelin is a known actin-binding protein, which plays a role in regulating the functions of smooth muscle cells or fibroblasts. Recent evidence indicates that transgelin is involved in diverse human cancers, yet its role in pancreatic cancer remains unclear. We therefore evaluated the expression characteristics and function of transgelin in pancreatic cancer. Immunohistochemical analysis of benign (n = 30 patients) and malignant (n = 114 patients) pancreatic ductal cells showed significantly higher transgelin staining in malignant cells. Lymph node metastasis (P = 0.026) and diabetes (P = 0.041) were shown to significantly correlate with transgelin protein expression. Patients with high transgelin expression showed a shorter 5-year overall survival and a lower tumor-specific survival than those with low transgelin expression. Multivariate analysis revealed that transgelin was an independent factor affecting pancreatic tumor-specific survival (P = 0.025). In vitro, RNA interference-mediated transgelin knockdown resulted in inhibition of pancreatic cancer cell proliferation, migration and invasion. Depletion of transgelin expression could suppress pancreatic tumorigenicity and tumor growth in vivo, and produce enhanced cytotoxic effects of gemcitabine on pancreatic cancer cells both in vitro and in vivo. Our results indicate that transgelin plays a promoting role in tumor progression, and appears to be a novel prognostic marker for advanced pancreatic cancer.


Assessment of impairment in activities of daily living in mild cognitive impairment using an individualized scale.
Mild impairment in activities of daily living (ADL) can occur in Mild Cognitive Impairment (MCI), but the nature and extent of these difficulties need to be further explored. The Canadian occupational performance measure (COPM) is one of the few individualized scales designed to identify self-perceived difficulties in ADL. The present study investigated impairments in ADL using the COPM in elderly with MCI. A total of 58 MCI patients were submitted to the COPM for studies of its validity and reliability. The COPM proved a valid and consistent instrument for evaluating ADL in elderly MCI patients. A total of 74.6% of the MCI patients reported difficulties in ADL. Of these problems, 41.2% involved self-care, 31.4% productivity and 27.4% leisure. This data further corroborates recent reports of possible functional impairment in complex ADL in MCI.


Bioinformatics analysis of dysregulated exosomal microRNAs derived from oral squamous cell carcinoma cells.
The present study aimed to identify dysregulated exosomal miRNAs associated with diagnostic and therapeutic biomarkers in oral squamous cell carcinoma (OSCC). Microarray analysis was used to compare expression profiles of exosomal miRNAs in the OSCC-derived cell lines HSC-2, HSC-3, Ca9-22, and HO-1-N1 with those in human normal keratinocytes (HNOKs). The identified OSCC-related miRNAs and their potential target genes were analyzed with bioinformatic analyses, and the data were subjected to Ingenuity Pathway Analysis (IPA) to clarify functional networks and gene ontologies of the identified exosomal miRNAs secreted by OSCC cells. Comparison with HNOKs detected 8 upregulated and 12 downregulated miRNAs in OSCC-secreted exosomes. The potential target mRNAs of these dysregulated miRNAs were suggested by IPA, and 6 significant genetic networks were indicated by genetic network analysis. Furthermore, 4 crucial upstream miRNAs-miR-125b-5p, miR-17-5p, miR-200b-3p, and miR-23a-3p-were identified. miR-125b-5p was a central node in the most significant network. Gene ontology analysis showed significant enrichment of genes with cancer-related functions, such as molecular mechanisms of cancer, cell cycle, and regulation of the epithelial-mesenchymal transition. These results provide a comprehensive view of the functions of dysregulated exosomal miRNAs in OSCC, thus illuminating OSCC tumorigenesis and development.


Frequency (pitch) and duration pattern tests.
Compact disc versions of the frequency (pitch) and duration pattern tests are reported. Results are similar to previous reports on these tests using taped materials. Mean performance of normal-hearing young adults for both pattern perception tests was approximately 90 percent. There was no effect of the two presentation levels used in this study. The compact disc version of these tests provides a high-fidelity measure of auditory pattern identification that can be administered easily.


Modelling complex survey data with population level information: an empirical likelihood approach.
Survey data are often collected with unequal probabilities from a stratified population. In many modelling situations, the parameter of interest is a subset of a set of parameters, with the others treated as nuisance parameters. We show that in this situation the empirical likelihood ratio statistic follows a chi-squared distribution asymptotically, under stratified single and multi-stage unequal probability sampling, with negligible sampling fractions. Simulation studies show that the empirical likelihood confidence interval may achieve better coverages and has more balanced tail error rates than standard approaches involving variance estimation, linearization or resampling.


Invisible charginos and neutralinos from gauge boson fusion: a way to explore anomaly mediation.
We point out that vector boson fusion at the Large Hadron Collider (LHC) can lead to useful signals for charginos and neutralinos in supersymmetric scenarios where these particles are almost invisible. The proposed signals are just two forward jets with missing transverse energy. It is shown that, in this way, one can put by far the strongest constraint on the parameter space of a theory with anomaly mediated supersymmetry breaking at the LHC. In addition, scenarios where the lightest neutralinos and charginos are Higgsino-like can give signals of the above type.


C-H functionalization: thoroughly tuning ligands at a metal ion, a chemist can greatly enhance catalyst's activity and selectivity.
This brief essay consists of a few "exciting stories" devoted to relations within a metal-complex catalyst between a metal ion and a coordinated ligand. When, as in the case of a human couple, the rapport of the partners is cordial and a love cements these relations, a chemist finds an ideal married couple, in other words he obtains a catalyst of choice which allows him to functionalize C-H bonds very efficiently and selectively. Examples of such lucky marriages in the catalytic world of ions and ligands are discussed here. Activity of the catalyst is characterized by turnover number (TON) or turnover frequency (TOF) as well as by yield of a target product. Introducing a chelating N,N- or N,O-ligand to the catalyst molecule (this can be an iron or manganese derivative) sharply enhances its activity. However, the activity of vanadium derivatives (with additionally added to the solution pyrazinecarboxylic acid, PCA) as well as of various osmium complexes does not dramatically depend on the nature of ligands surrounding metal ions. Complexes of these metals are very efficient catalysts in oxidations with H2O2. Osmium derivatives are record-holders exhibiting extremely high TONs whereas vanadium complexes are on the second position. Finally, elegant examples of alkane functionalization on the ions of non-transition metals (aluminium, gallium etc.) are described when one ligand within the metal complex (namely, hydroperoxyl ligand HOO(-)) helps other ligand of this complex (H2O2 molecule coordinated to the metal) to disintegrate into two species, generating very reactive hydroxyl radical. Hydrogen peroxide molecule, even ligated to the metal ion, is perfectly stable without the assistance of the neighboring HOO(-) ligand. This ligand can be easily oxidized donating an electron to its partner ligand (H2O2). In an analogous case, when the central ion in the catalyst is a transition metal, this ion changing its oxidation state can donate an electron to the coordinated H2O2 fragment. This provokes the O-O bond rupture in the hydrogen peroxide molecule as is assumed for the role of Fe(2+) ions in the Fenton system.


Regulatory B Cells in Seropositive Myasthenia Gravis versus Healthy Controls.
To find out if the failure in immunotolerance of myasthenia gravis (MG) is a possible aspect of deduction in Breg cells and to characterize B cell subsets in MG. Flow cytometry detection and enzyme-linked immunosorbent assays in peripheral blood films of 10 MG patients and 10 healthy controls (HCs) were performed after isolation of B cells. The CD19+CD5+CD1d+ Breg cells percentages were measured to complement a B cell phenotype assay and frequencies of B cell subsets. The clinical outcome measures and immunological variables of patients with MG were compared with HCs. Patients with MG had relatively lowered percentages of CD19+CD5+CD1d+ Breg cells as compared to HCs. The production of interleukin (IL)-10 and transforming growth factor (TGF)-β1 was relatively lesser in patients with MG than HCs, which were linked with more severe of MG disease status according to Myasthenia Gravis Foundation of America (MGFA) clinical classification. The reduction of cytokine production was more significant for IL-10 than TGF-β1 when compared to HCs. It has been observed that the reduced number of B cells is able to produce IL-10 in MG patients but lesser than compared to HCs. The Bregs reduction mainly was regarded by the severity of disease status, which was highly significant and also by disease duration which was statistically significant as well. The findings of the measurement of B cell phenotype assay and frequencies of B cell subsets between MGs and HCs give us new ideas to develop B cell-mediated therapies of MG such as (1) isolated B cells of MGs could be cultured with steroids, e.g., dexamethasone in vitro to see if it induces the CD19+CD5+CD1d+ Breg cells, (2) it may observe whether induced CD19+CD5+CD1d+ Bregs have higher production of IL-10 and TGF-β1, as both are linked with disease severity, and (3) after completion in vitro steps, through further research in vivo to observe whether it improves the function of MG disease status.


Self-concealment, secrecy, and guilt.
Individuals with a tendency to conceal unflattering information about themselves are more likely to be preoccupied by their secrets and tend to report more negative affect. According to theory, this negative affect is due to self-concealers' conflicting motivation to be authentic in their relationship but fear the negative consequences should they reveal their secrets, which promotes ill-fated attempts to suppress. The purpose of the current study was to test a central component of this model. Two studies of adults who were in a romantic relationship and keeping a secret from their partner (combined N = 635; 67.2% women; Mage = 39.6, SD = 11.9) were surveyed on four biweekly occasions. Multilevel mediation analyses were conducted to test whether preoccupation and suppression mediated the link between self-concealing and negative affect and guilt. The data support the hypotheses. Self-concealers were more preoccupied with and prone to suppress their secret than those low on the trait, which, in turn, predicted greater negative affect and guilt. The findings suggest that self-concealers' insecurities and fear of the relational consequences of disclosure set the stage for the debilitating cycle of suppression and preoccupation that leaves them feeling anxious and guilty.


Plasma concentrations of lidocaine in dogs following lidocaine patch application.
Transdermal absorption of lidocaine was determined by measuring plasma lidocaine concentrations following skin application of 5% lidocaine patches. Two lidocaine patches were placed on the ventral abdominal midline of seven dogs for 72 hours. Lidocaine was detectable in plasma 12 hours after patch application, and it reached steady-state concentrations between 24 and 48 hours. Plasma lidocaine levels decreased dramatically at 60 hours post-application. Low plasma lidocaine concentrations remained for 6 hours after patch removal. No clinically significant side effects were noted.


Repair of an anomalous left coronary artery from the pulmonary artery in a premature neonate.
Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital heart defect. It is typically diagnosed at a few months of age. The infant presents with cardiac failure secondary to left ventricular dysfunction from the coronary steal that develops as pulmonary vascular resistance (PVR) falls. With the diagnosis made, surgical repair is typically performed expeditiously in order to try and restore left ventricular perfusion and stop the ongoing coronary steal. We present an unusual case of a preterm infant undergoing a routine echocardiogram, who was incidentally found to have an ALCAPA. Management strategies between neonatology and cardiology may differ in this setting. In this case, elevated PVR helps to preserve myocardial perfusion prior to surgical repair. Therefore, common neonatal management strategies typically utilized for respiratory distress, elevated PVR, and cardiac dysfunction may have potential for detrimental effects on myocardial perfusion in this specific lesion. This case also emphasizes the importance of identifying the coronary origins as a routine part of a complete pediatric echocardiogram. It also presents a rarely encountered problem: when to repair an ALCAPA in an as yet asymptomatic patient. We believe this to be the youngest and smallest patient reported with the diagnosis and successful surgical correction of an ALCAPA.


Pattern of ophthalmic lesions at two histopathology centres in Ethiopia.
To describe the distribution of ocular, orbital and eyelid lesions that required histopathologic analysis in Ethiopian children and adults. A retrospective study. Tikur Anbessa and Menelik II Teaching hospitals, Addis Ababa, Ethiopia, during 1995 and 1999 period. Two hundred and ninety ophthalmic specimens were examined, 20% of which came from children. Half of the lesions had epithelial origin, about 30% were malignant, 22.6% were benign and 16.4% were potentially malignant. Squamous cell carcinoma was the leading conjunctival (26%), eyelid (33%), orbital (33%) and ocular (20%) lesion among adults and elderly people whereas only 6% of eyelid lesion were basal cell carcinomas. In children the most frequent intra-ocular as well as orbital tumour was retinoblastoma, 39%, followed by miscellaneous benign lesions (24%). More than half of the request forms were incomplete. In Addis Ababa, squamous cell carcinoma and retinoblastoma should be considered when evaluating ophthalmic lesions in adults and children, respectively. Clinicians and pathologists should improve their communication by filling in request forms, providing clear reports and making dialogue.


Detection of Porcine Circovirus 3 in Wildlife Species in Spain.
Porcine circovirus 3 (PCV-3) is the third member of the family Circoviridae, genus Circovirus, able to infect swine. A high prevalence of viral DNA has been recorded in wild boars. Recently, PCV-3 DNA was identified in Italian wild ruminants. Based on these previous results, this study assessed the frequency of PCV-3 DNA detection in free-ranging ruminants and Lagomorpha species in Spain. In addition, the genetic characterization of the PCV-3 PCR-positive samples was performed. A total of 801 serum samples, including red deer (Cervus elaphus, [CE]; n = 108), roe deer (Capreolus capreolus, [CC]; n = 87), Pyrenean chamois (Rupicapra pyrenaica, [RP]; n = 133), Iberian ibex (Capra pyrenaica, [CP]; n = 92), mouflon (Ovis aries, [OA]; n = 91), fallow deer (Dama dama, [DD]; n = 104), European rabbit (Oryctolagus cuniculus, [OC]; n = 101), and European hare (Lepus europaeus, [LE]; n = 85) from Catalonia (northeast Spain) were tested by conventional polymerase chain reaction (PCR) and, when positive, sequenced. Overall, PCV-3 DNA was found in three out of 801 analyzed sera (0.37%) corresponding to one red deer (1/108, 0.9%), one mouflon (1/91, 1.1%), and one fallow deer (1/104, 0.96%). None of the samples collected from Lagomorpha species resulted PCR positive. The partial genome sequences detected in positive samples displayed high identity with some PCV-3 sequences detected in wild boars and domestic pigs (99.7% and 100%, respectively). In conclusion, the present study indicated that free-ranging ruminant and Lagomorpha species are not relevant in the epidemiology of PCV-3 in Spain.


Efficacy and Safety of Lactobacillus plantarum K50 on Lipids in Koreans With Obesity: A Randomized, Double-Blind Controlled Clinical Trial.
Only few studies have investigated the role of probiotics in the development of obesity. We aimed to determine the efficacy and safety of an intake of Lactobacillus plantarum K50 (LPK) on body fat and lipid profiles in people with obesity. This randomized, double-blind, placebo-controlled, clinical trial involved 81 adults with a body mass index of 25-30 kg/m2 who were assigned randomly to a diet including 4 × 109 colony-forming unit of LPK or a placebo. Changes in body fat, anthropometric parameters, and biomarkers of obesity were compared using a linear mixed-effect model. After 12 weeks of treatment, body weight, fat mass, and abdominal fat area did not change significantly in the two groups. However, total cholesterol levels decreased from 209.4 ± 34.4 mg/dL to 203.5 ± 30.9 mg/dL in the LPK group, but increased from 194.7 ± 37.5 mg/dL to 199.9 ± 30.7 mg/dL in the placebo group (P = 0.037). Similarly, triglyceride levels decreased from 135.4 ± 115.8 mg/dL to 114.5 ± 65.9 mg/dL in the LPK group, with a significant difference between groups. LPK supplementation also tended to decrease leptin levels compared with placebo. It also changed the distribution of gut microbiota significantly, with an increase in L. plantarum and a decrease in Actinobacteria, both of whose changes in abundance were correlated with changes in visceral adiposity, with borderline significance. A 12-week consumption of LPK reduced the total cholesterol and triglyceride levels significantly with favorable alterations in microbiota, suggesting potential benefits for controlling blood lipid profiles.


The first mollusk spätzle homolog gene in the clam, Paphia undulate.
Spätzle, is the only identified endogenous Toll receptor ligand, plays a critical role in initiatinge innate immune responses and controlling dorsal-ventral axis formation in Drosophila. Here we identified the first spätzle gene homolog, Pu-Spz, in the marine mollusk Paphia undulate. The full-length of Pu-Spz cDNA is 1248 bp, including an open reading frame (ORF) of 702 bp, a 5'-untranslated region (UTR) of 26 bp and a 3'-UTR of 203 bp. The ORF encodes a 233-amino-acid protein with conserved domains; it includes a putative signal peptide and a C-terminal cystine-knot. Sequence alignment revealed that the cystine-knot domain of Pu-Spz contains six highly conserved Cys residues, which maintain a molecular conformation suitable for Toll receptor binding. Unlike Spätzle, Pu-Spz lacks a seventh Cys residue, which is essential for forming intermolecular disulfide bridge. Phylogenetic analysis revealed that Pu-Spz is closer to the homologs found in crustaceans than to those in the insect branch. Transcript abundance of Pu-Spz was increased after challenging P. undulate with either heat-killed Listeria monocytogenes or heat-killed Vibrio alginolyticus, suggesting Spätzle is involved in P. undulate host defense. Our results demonstrate convergent evolution of the spätzle-Toll system between the mollusk and arthropod lineages.


Dating violence, violence in social networks, anxiety and depression in nursing degree students: A cross-sectional study.
To determine the prevalence and risk factors for dating violence and the correlations between dating violence and violence in social networks, anxiety and depression among nursing students. A cross-sectional and correlational study. This study was conducted with nursing degree students at Spanish university during May 2021. A total of 248 nursing students completed an online survey. The online survey included sociodemographic variables, the Conflict in Adolescent Dating Relationships Inventory, the Social Network Violence Scale and the Hospital Anxiety and Depression Scale. Chi-squared test, Pearson's correlation and logistic regression were used. Of the participants, 13.3% were men and 86.7% were women. A total of 53.2% had experienced and/or perpetrated dating violence. About violence in social networks, 22.2% of the participants had perpetrated it, and 20.2% had been victims of it. Strong correlations were found between experiencing and perpetrating dating violence. Significant associated factors were cohabitation with a partner, alcohol consumption, socioeconomic status and history of dating violence. Dating violence is a serious problem given its high prevalence among the surveyed nursing students, who, as future health professionals, must know how to recognize and react to possible cases of abuse. The study results add to international literature that men and women university nursing students are equally susceptible to intimate partner violence and report similar prevalence of dating violence. Also, dating violence is correlated with increased levels of anxiety and depression. It seems to be necessary to implement training programmes that help minimize the problem and identify possible cases.


Patterns and correlates of adjuvant radiotherapy receipt after lumpectomy and after mastectomy for breast cancer.
To use patient self-report to provide more valid estimates of whether radiotherapy (RT) is underutilized than possible with registry data, as well as to evaluate for disparities and the influence of preferences and provider interactions. We considered 2,260 survey respondents who had nonmetastatic breast cancer, were age 20 to 79 years, were diagnosed between July 2005 and February 2007 in Detroit and Los Angeles, and reported to Surveillance, Epidemiology and End Results (SEER) registries (72% response rate). Survey responses were merged with SEER data. We assessed rates and correlates of RT receipt among all patients with invasive cancer receiving breast-conserving surgery (BCS) and among patients undergoing mastectomy with indications for RT (ie, positive lymph nodes or T3-4 tumors). Among 904 patients undergoing BCS with strong indications for RT, 95.4% received RT, and 77.6% received RT among the 135 patients undergoing mastectomy with strong indications (P < .001). Among 114 patients undergoing BCS with weaker indications (ie, elderly) for RT, 80.0% received treatment, and 47.5% received RT among the 164 patients undergoing mastectomy with weaker indications (T1N1, T2N1, or T3N0 disease; P < .001). On multivariate analysis, surgery type (P < .001), indication strength (P < .001), age (P = .005), comorbidity (P < .001), income (P = .03), patient desire to avoid RT (P < .001), level of surgeon involvement in decision to have radiation (P < .001), and SEER site (P < .001) were significantly associated with likelihood of RT receipt. RT receipt was consistently high across sociodemographic subgroups after BCS but was lower after mastectomy, even among patients with strong indications for treatment, in whom clinical benefit is similar. Surgeon involvement had a strong influence on RT receipt.


Epidemiological, Clinical, and Histopathological Features of Salivary Gland Tumors among 150 Sudanese Patients: 10 Years' Experience.
Salivary gland tumors (SGTs) are serious challenges to pathologists. Herein, we aimed to assess epidemiological and histopathological characteristics of SGTs among Sudanese patients. This retrospective descriptive study was undertaken at The pathology department in Khartoum State between 2008 and 2018. Patient records, histopathological reports, and slides were retrieved; and re-examined by two histopathologists. Diagnoses were reclassified according to the 2017 WHO classification of SGTs. Overall, 150 cases of Sudanese patients with SGT were included (90 [60%] males and 60 [40%] females). Among these, 105 were benign (70%) and 45 were malignant (30%). The parotid glands were the most common site for both benign and malignant tumors (77/150; 51%: 59 benign (76.6%) and 18 malignant [23.4%]). The next common site was the submandibular gland (54 [36%]: 38 benign [70.3%] and 16 malignant [29.7%]), followed by minor salivary glands (19 [12.7%]: 8 benign and 11 malignant [57.9%]). Benign gland entities included pleomorphic adenoma (88/105; 83.7%), oncocytoma (5/105; 4.8%), myoepithelioma (4/105; 3.8%), Whartin tumors (3/105; 2.9%), basal cell adenoma (3/105; 2.9%), and sialolipoma (2/105; 1.9%). Malignant gland entities included adenoid cystic carcinoma (12; 26.7%), mucoepidermoid carcinoma (10; 22,2%), acinic cell carcinoma (6; 13.3%), poorly differentiated carcinoma (4; 8.9%), adenocarcinoma NOS (not otherwise specified) (4; 8.9%), basal cell adenocarcinoma (3; 6.7%), carcinoma ex pleomorphic adenoma (3; 6.7%), polymorphous adenocarcinoma (2; 4.4%), salivary duct carcinoma (1; 2.2%), and epithelial-myoepithelial carcinoma (2.2%). SGTs shared several epidemiological and histopathological features, exhibiting high incidence in the parotid and submandibular glands, lower prevalence in minor glands, and greater male predominance.


A novel zinc finger protein, zic, is involved in neurogenesis, especially in the cell lineage of cerebellar granule cells.
To clarify the mechanism of cerebellar development, we have cloned a gene, named zic, encoding a zinc finger protein that is expressed abundantly in granule cells throughout development of the cerebellum. zic has a significant homology to the zinc finger domain of the Caenorhabditis elegans tra1 gene, the Drosophila cubitus interruptus Dominant gene, and the human GLI oncogene. An in situ hybridization study revealed that zic showed a restricted expression pattern in the granule cells and their putative precursor cells. It is also expressed at an early embryonic stage in the dorsal half of the neural tube. The expression pattern and nuclear localization were confirmed by immunohistochemical study. Furthermore, the bacterially expressed zic protein containing the zinc finger domains bound to the GLI-binding sequence. These findings suggest that zic is one of a number of nuclear factors involved in both differentiation in early development and maintenance of properties of the cerebellar granule cells.


Haemogenic endocardium contributes to transient definitive haematopoiesis.
Haematopoietic cells arise from spatiotemporally restricted domains in the developing embryo. Although studies of non-mammalian animal and in vitro embryonic stem cell models suggest a close relationship among cardiac, endocardial and haematopoietic lineages, it remains unknown whether the mammalian heart tube serves as a haemogenic organ akin to the dorsal aorta. Here we examine the haemogenic activity of the developing endocardium. Mouse heart explants generate myeloid and erythroid colonies in the absence of circulation. Haemogenic activity arises from a subset of endocardial cells in the outflow cushion and atria earlier than in the aorta-gonad-mesonephros region, and is transient and definitive in nature. Interestingly, key cardiac transcription factors, Nkx2-5 and Isl1, are expressed in and required for the haemogenic population of the endocardium. Together, these data suggest that a subset of endocardial/endothelial cells serve as a de novo source for transient definitive haematopoietic progenitors.


Release of arachidonic acid by stimulation of opsonic receptors in human monocytes: the FcgammaR and the complement receptor 3 pathways.
The role of the opsonic receptors FcgammaR and CR3 on the release of arachidonic acid (AA) by human monocytes was studied using IgG-ovalbumin (OVA) equivalence immune complexes (IC), anti-OVA IgG bound to OVA-coupled latex beads, and C3bi-bound IC. Release of AA was produced by IC and latex-OVA beads bound to IgG, whereas binding of C3bi to IC inhibited the ability of IC to release AA. In contrast, coating of zymosan particles with C3bi enhanced AA release as compared with that produced by non-coated particles. Masking of C3bi on C3bi-bound IC by incubation with anti-C3 IgG resulted in the recovery of their ability to release AA, thereby suggesting that binding of C3b by IC reduces their flogogenic effects, whereas opsonization of microbial walls by complement may enhance their proinflammatory potential. The binding/uptake of opsonized zymosan particles was inhibited by anti-CR3 Ab and C3bi-bound IC, but not by beta-glucan, mannan, and anti-Toll-like receptor 2 Ab. These findings show that cooperative engagement of CR3 on both the lectin-like site involved in beta-glucan binding and the I-domain involved in C3bi binding, as it can be observed in the innate immune response, produces AA release, whereas the unique interaction of C3bi-bound IC with the I-domain of CR3, as it may occur in the adaptive immune response, diverts the IC lattice from a productive interaction with FcgammaR linked to AA release.


Quantification of intraluminal motion of surrogate ova in the rabbit oviductal isthmus.
The feasibility of using black polystyrene microspheres as surrogate ova to obtain quantitative information regarding ovum motion in the oviductal isthmus was tested in rabbits. The 175-microns diameter surrogates were instilled into the ampulla at the time of ovulation, and later the oviducts were exposed for direct observation of surrogate movements in the isthmic lumen. With the aid of transillumination, the black spheres were visible through the intact tubal wall and cinematographic records were made to quantify their movements. The frequency of surrogate movements was 5/min at 24, 36 and 48 h after coitus an 10/min at 60 and 72 h. The motion was typically oscillative with individual movements less than 4 mm in length; usually no net displacement occurred during 1-2 h of observation. These preliminary data, when used to test the stochastic model of ovum transport proposed by Verdugo et al. (1980), predicted isthmic transit times of only a few hours. Thus, the long duration of ovum residence in the rabbit isthmus may not be due to a slow transport process governed by random motion.


[Blood levels of somatotropic hormone in patients with various degrees of heart failure].
The hypothesis that in normal pituitary patients (pts) with heart failure the heart is a target-organ of the hypophysis has not be held in due consideration. Aim of the study was: 1) to determine Growth Hormone (GH) plasma levels in pts with various degree of heart failure; 2) to evaluate the relationship between GH, left ventricular mass and some haemodynamic and endocrine parameters of ventricular dysfunction. Blood samples for determination of GH and Atrial Natriuretic Factor (ANF) were collected 24 hours before haemodynamic study. Plasma concentrations of GH and ANF were determined by radio-immuno-assay in 20 normotensive pts (age ranging 31 to 54) without mellitus diabetes in IV (10 pts) and III (10 pts) NYHA FC: Echocardiographic determination of left atrial diameter, end-diastolic and end-systolic left ventricular diameters, index of left ventricular mass (ILVM), were performed. All pts underwent right and left cardiac catheterization and coronary angiography. The pts in IV NYHA FC, Group A, had lower cardiac index (IC) (1.8 +/- 0.4 vs 2.9 +/- 0.1, p < 0.0001) and higher GH and ANF plasma levels than those in III NYHA FC, Group B (4.9 +/- 4.5 vs 0.12 +/- 0.04, p < 0.01; 157.9 +/- 43.9 vs 65.6 +/- 14.6, p < 0.0001). No significant difference was found by comparing in both groups ILVM (212.6 +/- 64.7 vs 192.9 +/- 71.9, NS). GH and ANF plasma levels were 4.1 +/- 5.0 and 113.8 +/- 59.6 in pts with ILVM > or = 200 g/mq and 0.9 +/- 2.7 and 109.7 +/- 57.3 in pts with ILVM < 200 g/mq (no significant statistical difference). We found an high correlation by comparing GH and ANF in group with ILVM > or = 200 g/mq (r = 0.82, p < 0.005) and in group with ILVM < 200 g/mq (r = 0.68, p < 0.05). Our study demonstrated: 1) increased GH plasma levels in pts with severe heart failure; 2) an high correlation between GH and ANF plasma levels in pts with ILVM > or = 200 g/mq.


Cocculina delphinicula sp. nov., a new cocculinid species from whale bone in the East China Sea (Gastropoda: Cocculiniformia).
A new cocculinid species collected from a dolphin skull in the East China Sea is described and assigned to the genus Cocculina Dall, 1882. This new species, Cocculina delphinicula sp. nov., has a medium sized, depressed shell sculptured with regularly spaced concentric growth lines and fine radial threads. The radula has a formula of (ca. 20)+5+1+5+(ca. 20) with a vestigial rachidian, lateral 1 weak but well defined, having an outline that frequently terminates into a small beak-like cusp, laterals 2 and 3 with 3-4 cusps, lateral 4 with a large primary cusp and an outer secondary cusp.


Optimal timing of surgical intervention in patients with acute pancreatitis associated with cholelithiasis.
In evaluating patients with acute pancreatitis, disproportionately high serum amylase values in comparison to physical findings of peritonitis of the upper part of the abdomen and the rapid return to normal values and the lack of a history of alcohol ingestion should be viewed as findings highly indicative of pancreatitis associated with cholelithiasis. Diagnostic roentgenologic procedures can be initiated soon after admission of the patient, with an intravenous cholangiogram or oral cholecystogram, depending upon the feasibility of oral intake, in patients without jaundice. Expectant treatment is both safe and preferable, so that surgical treatment for disease of the biliary tract is performed after the diagnosis is established in the same hospitalization period.


Applied Use of Safety Event Occurrence Control Charts of Harm and Non-Harm Events: A Case Study.
Most hospitals use occurrence reporting systems that facilitate identifying serious events that lead to root cause investigations. Thus, the events catalyze improvement efforts to mitigate patient harm. A serious limitation is that only a few of the occurrences are investigated. A challenge is leveraging the data to generate knowledge. The goal is to present a methodology to supplement these incident assessment efforts. The framework affords an enhanced understanding of patient safety through the use of control charts to monitor non-harm and harm incidents simultaneously. This approach can identify harm and non-harm reporting rates and also can facilitate monitoring occurrence trends. This method also can expedite identifying changes in workflow, processes, or safety culture. Although unable to identify root causes, this approach can identify changes in near real time. This approach also supports evaluating safety or policy interventions that may not be observable in annual safety climate surveys.


Molar-incisor-hypomineralisation impact on developmental defects of enamel prevalence in a low fluoridated area.
This was to study the impact of molar-incisor-hypomineralisations on developmental defects of enamel (DDE) prevalence. Additionally, to present the prevalence of DDE and molar-incisor-hypomineralisations (MIH) in 12-year old children in Bosnia and Herzegovina (BH) who live in an area with low natural fluoride content in the drinking water (less than 0.1 ppm). As a part of the oral health study of 12-year-olds, information about DDE and MIH were collected from a random sample of 560 children. To study the impact of MIH on DDE, a secondary database was developed to determine if and to what extent did MIH affect epidemiological parameters of DDE. The analyses focused on differences in DDE values between the main sample and sub-sample of participants in which those diagnosed with both MIH and DDE were excluded. Research results were analysed using percentages, arithmetic mean value, standard deviation and linear regression. In the main sample MIH prevalence was 12.3%. The DDE prevalence was 32.8% with the highest frequency being demarcated opacities. DDE prevalence, calculated without MIH examinees, was 21.4%. A strong positive correlation was found between MIH and DDE prevalence in different geographic locations (r=0.9, p=0.0008). Molar-incisor-hypomineralisation prevalence has a strong positive correlation with prevalence of developmental defects of enamel. Prevalence of DDE after excluding MIH examinees fell from 32.8% to 21.4%, which was a noticeable difference. Separate registration of these two conditions should be considered.


Hyperbaric oxygen treatment reduces mortality in acute iron intoxication in rats.
Acute iron intoxication is one of the leading causes of overdose morbidity and mortality in children. The toxicity of iron has been postulated to be related to free radical formation and subsequent lipid peroxidation. Hyperbaric oxygen treatment can result in a number of beneficial biochemical, cellular and physiological effects, and has recently been shown to induce cellular protection against ischaemia, and in some cases against free radical formation. In the current study, we aimed to investigate the effects of hyperbaric oxygen treatment on mortality in acute iron intoxication in rats. After iron administration, 57 animals were divided into two groups: a treatment group receiving hyperbaric oxygen treatment (n = 30) and a control group (n = 27), and followed for 48 hr for signs of severe intoxication. In the second part of the study, 21 animals were divided into a treatment group receiving hyperbaric oxygen treatment (n = 10) and a control group (n = 11), and markers of oxidative stress were evaluated. We showed a significant reduction in mortality in hyperbaric oxygen-treated animals from 17 of 27 (62.9%) among untreated rats to 6 of 30 (20%). Surprisingly, in the treatment group, levels of oxidative stress markers were higher. We postulate that hyperbaric oxygen has a potentially beneficial effect in acute iron intoxication.


Naturally Produced Co/CoO Nanocrystalline Magnetic Multilayers: Structure and Inverted Hysteresis.
Cobalt-based multilayers with excellent sequencing are grown via radiofrequency magnetron sputtering with the use of one Co target and natural oxidation. The Co layers are continuous, fully textured {111} and have the face centered cubic structure. At the end of deposition of each Co layer air is let to flow into the vacuum chamber via a fine (leak) valve. The top of Co is oxidized. The oxidized layers consist of cubic CoO crystallites. Near the film surface hexagonal Co(OH)2 is also detected. Magneto-optical Kerr effect hysteresis loops show in-plane magnetized films. The magnetic saturation field in the out-of-plane measurements is large exceeding 12 kOe. This observation supports indirectly the fact that Co is face centered cubic; if it was c-axis textured hexagonal the magnetocrystalline anisotropy would be large resulting in smaller values of the saturation field. As the Co-layer thickness decreases the in-plane loops show reduced remanence, slow approach to magnetic saturation and the out-of-plane loops show inverted hysteresis and/or crossing loop features with sizeable remanence. The effects are discussed with respect to the enhanced orbital magnetic moment of Co and the antiferromagnetic coupling between Co spins at the Co/CoO interface.


Blink reflex in the prediction of outcome of idiopathic peripheral partial facioparesis: follow-up study.
To determine the value of the blink reflex as a predictor of outcome of idiopathic peripheral partial facial paresis. The study included 30 patients suffering from acute idiopathic peripheral facioparesis and 30 age- and sex-matched healthy controls. Patients with symptomatic disease were excluded on the basis of neuroradiologic and laboratory findings. We stimulated the supraorbital foramen and recorded the evoked response from both orbiculares oculi muscles. We measured the ipsilateral early phasic component (R1) and bilateral late tonic component (ipsilateral R2 and contralateral R2) immediately, and a week and 6 months after the first test. In the acute phase of idiopathic peripheral partial facioparesis, the blink reflex showed slightly prolonged latencies and greatly reduced amplitudes of both R1 and R2 and the normal latencies and amplitudes of R2. All subjects showed clinical symptoms and typical electromyographic (EMG) changes, whereas 24 had blink reflex abnormalities. One week after the onset, all patients were still symptomatic and showed EMG changes, but blink reflex abnormalities remained in only 11 patients. Six months after the onset, 21 patients became asymptomatic and showed no EMG changes, 7 had no clinical symptoms but showed chronic neurogenic EMG changes, whereas 2 showed both clinical symptoms and EMG changes. Blink reflex abnormalities were observed in 6 patients. The amplitudes of R1 immediately and one week after the onset were the best predictors of residual motor deficit. Blink reflex is a useful tool for follow-up and recovery prognosis in patients with partial idiopathic facioparesis, especially in the early recovery phase.


Directed evolution of a ring-cleaving dioxygenase for polychlorinated biphenyl degradation.
DoxG, an extradiol dioxygenase involved in the aerobic catabolism of naphthalene, possesses a weak ability to cleave 3,4-dihydroxybiphenyls (3,4-DHB), critical polychlorinated biphenyl metabolites. A directed evolution strategy combining error-prone PCR, saturation mutagenesis, and DNA shuffling was used to improve the polychlorinated biphenyl-degrading potential of DoxG. Screening was facilitated through analysis of filtered, digital imaging of plated colonies. A simple scheme, which is readily adaptable to other activities, enabled the screening of >10(5) colonies/h. The best variant, designated DoxGSMA2, cleaved 3,4-DHB with an apparent specificity constant of 2.0 +/- 0.3 x 10(6) m(-1) s(-1), which is 770 times that of wild-type (WT) DoxG. The specificities of DoxGSMA2 for 1,2-DHN and 2,3-DHB were increased by 6.7-fold and reduced by 2-fold, respectively, compared with the WT enzyme. DoxGSMA2 contained three substituted residues with respect to the WT enzyme: L190M, S191W, and L242S. Structural data indicate that the side chains of residues 190 and 242 occur on opposite walls of the substrate binding pocket and may interact directly with the distal ring of 3,4-DHB or influence contacts between this substrate and other residues. Thus, the introduction of two bulkier residues on one side of the substrate binding pocket and a smaller residue on the other may reshape the binding pocket and alter the catalytically relevant interactions of 3,4-DHB with the enzyme and dioxygen. Kinetic analyses reveal that the substitutions are anti-cooperative.


Progression from impaired fasting glucose to type 2 diabetes mellitus among Chinese subjects with and without hypertension in a primary care setting.
The progression from impaired fasting glucose (IFG) to type 2 diabetes mellitus (T2DM) in Chinese subjects, with and without hypertension, in a primary care setting was unknown. The present retrospective multicenter 5-year (2002-2007) cohort study was performed on IFG subjects attending 23 general outpatient clinics who were identified by their elevated fasting blood glucose laboratory results. Development of T2DM was determined by physician diagnosis of T2DM or starting of oral antidiabetic drugs within 5 years. The relationship between the time of T2DM diagnosis and subject characteristics was assessed by adjusted hazard ratios (aHR) from Cox hazards model. Of the 9161 IFG subjects, 4080 (45%) were men and 5081 (55%) were women. There were 1998 subjects who developed T2DM. The 5-year cumulative incidence was 0.218, whereas the overall annual incidence rate was 5.981/100 person-years. Subjects were more likely to develop T2DM if they were hypertensive (aHR = 1.44; 95% confidence interval [CI] 1.28-1.62; P < 0.001), aged <60 years (aHR = 1.36, 95% CI 1.24-1.49; P < 0.001), female (aHR = 1.18, 95% CI 1.08-1.29; P < 0.001), and had higher fasting glucose levels (6.39 ± 0.49 vs 6.24 ± 0.43 mmol/L in the group that developed T2DM vs the group without T2DM, respectively; aHR = 2.01, 95% CI 1.83-2.20; P < 0.001). Overall, more than one-fifth of IFG subjects in the primary care setting developed T2DM within 5 years. Health care professionals can target interventions to patients with risk factors for disease progression.


Canine insulinomas appear hyperintense on MRI T2-weighted images and isointense on T1-weighted images.
Clinical and imaging diagnosis of canine insulinomas has proven difficult due to nonspecific clinical signs and the small size of these tumors. The aim of this retrospective case series study was to describe MRI findings in a group of dogs with pancreatic insulinomas. Included dogs were presented for suspected pancreatic insulinoma, MRI was used to assist with localization of the primary lesion, and the diagnosis was confirmed with surgical exploratory laparotomy and histopathology. The MRI studies for each dog were retrieved and the following data were recorded: T1-weighted and T2-weighted signal intensities, type of contrast enhancement, size and location of the primary lesion, and characteristics of metastatic lesions (if present). A total of four dogs were sampled. In all patients, the insulinoma displayed high-intensity signal on T2-weighted fat saturation images, similar to human studies. On postcontrast T1-weighted fat saturation images, the tumors were primarily isointense to normal pancreatic tissue, in contrast to human studies where a low-intensity signal is typically identified. Abnormal islet tissue was detected with MRI in all four dogs and metastases were identified in three dogs. Variations in the MRI appearance of primary and metastatic lesions were identified and could have been related to the variation of tissue composition, including the presence of neoplastic cells, hemorrhage, and fibrovascular stroma, and to the transformation of this tissue throughout the disease process.


Medical student appraisal: applications for bedside patient education.
Medical students are often afforded the privilege of counselling patients. In the past resources were limited to pen and paper or anatomic models. The evolution of mobile applications allows for limitless access to resources that facilitate bedside patient education. To evaluate the utility of six applications in patient education and promote awareness of implementing mobile resources in clinical care. Six medical students rotating on various clerkships evaluated a total of six mobile applications. Strengths, limitations, and suggested uses in clinical care were identified. Applications included Meditoons™, VisiblePatient™, DrawMD™, CardioTeach™, Visual Anatomy™, and 360° Patient Education Suite™. Data was generated from narrative responses supplied by each student during their evaluation period. Bedside teaching was enhanced by professional illustrations and animations depicting anatomy and pathophysiology. Impromptu teaching was facilitated, as resources were conveniently available on a student's smartphone or tablet. The ability to annotate and modify images and subsequently email to patients was an extraordinary improvement in provider-patient communication. Universal limitations included small smartphone screens and the novelty of new technology. Mobile applications have the potential to greatly enhance patient education and simultaneously build rapport. Endless opportunities exist for their integration in clinical practice, particularly for new diagnoses, consent for procedures, and at time of discharge. Providers should be encouraged to try new applications and utilize them with patients.


Clinical pharmacology and pharmacokinetic properties of topically applied corticosteroids. A review.
The development of topical corticosteroids since the 1950s has opened new doors for dermatologists previously faced with treating intractable dermatoses, so that the pharmacology of topically applied corticosteroids is now reasonably well described. Manipulation of the steroid molecule has produced compounds with greater lipophilicity, fewer mineralocorticoid properties and high potency. Potency is determined through various techniques, notably the vasoconstrictor assay as well as the mitotic index suppression method and atrophogenic potential assay. The mechanism of activity of corticosteroids is thought to result, at least in part, from binding of the drug to steroid receptors, with resultant effects on the synthesis of proteins responsible for specific effects. Corticosteroids are proposed to alter the inflammatory response, and thus provide therapeutic benefits, via actions on mediator release and function, inflammatory cell function and release of lysosomal enzymes. Disadvantages of corticosteroid activity include the possibility of adrenal suppression, epidermal and dermal thinning, and local effects such as purpura, striae, and steroid-induced rosacea and perioral dermatitis. The cutaneous pharmacokinetics, particularly of absorption of topical corticosteroids, must be examined in parallel with their pharmacodynamic effects to gain a more complete understanding of activity. Many factors can affect percutaneous steroid absorption: drug lipophilicity and solubility, drug concentration, anatomical site, age of the patient, presence of skin disease and use of occlusive dressings will each influence the degree to which topically applied corticosteroids achieve their intended therapeutic results. Cutaneous metabolism is a poorly understood process at present, but one which is acknowledged to have some impact on the biotransformation of corticosteroids applied topically. Thus, although some gaps still persist in present knowledge of the pharmacology and pharmacokinetics of this important class of drugs, there can be no denying the contribution of topical corticosteroids to the therapy of dermatoses.


Identification of mutations that delay somatic or reproductive aging of Caenorhabditis elegans.
Aging is an important feature of animal biology characterized by progressive, degenerative changes in somatic and reproductive tissues. The rate of age-related degeneration is genetically controlled, since genes that influence lifespan have been identified. However, little is known about genes that affect reproductive aging or aging of specific somatic tissues. To identify genes that are important for controlling these degenerative changes, we used chemical mutagenesis to perform forward genetic screens in Caenorhabditis elegans. By conducting a screen focused on somatic aging, we identified mutant hermaphrodites that displayed extended periods of pharyngeal pumping, body movement, or survival. One of these mutations is a novel allele of the age-1 gene. age-1 encodes a phosphatidylinositol-3-kinase (PI3K) that functions in the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway. age-1(am88) creates a missense change in the conserved PIK domain and causes dramatic extensions of the pharyngeal pumping and body movement spans, as well as a twofold extension of the lifespan. By conducting screens focused on reproductive aging in mated hermaphrodites, we identified mutants that displayed increased progeny production late in life. To characterize these mutations, we developed quantitative measurements of age-related morphological changes in the gonad. The am117 mutation delayed age-related declines in progeny production and morphological changes in the gonad. These studies provide new insights into the genetic regulation of age-related degenerative changes in somatic and reproductive tissues.


Prodromal contractions and contractility in the feline bladder.
In the cat there are at least two distinct contractile states of the bladder during urine storage, one when prodromal contractions are present and one when non-micturating contractions are present. It is proposed that prodromal contractions are myogenic. This proposition was examined by comparing prodromal contractions before and after hypogastric nerve section as well as comparing prodromal contractions with the contractions that remain after sectioning of the hypogastric nerves. Key contraction characteristics, such as amplitude, maximum gradient and the variance of the intercontraction interval were not significantly changed by hypogastric nerve section, providing volume effects were corrected for, which suggested that prodromal contractions have a myogenic origin.


The metrics of spatial situation models.
The authors investigated the metrics of spatial distance represented in situation models of narratives. In 3 experiments, a spatial gradient of accessibility in situation models was observed: The accessibility of objects contained in the situation model decreased with increasing spatial distance between the object and the reader's focus of attention. The first 2 experiments demonstrated that this effect of spatial distance was purely categorical rather than Euclidean: Accessibility depended on the number of rooms located between the object and the focus of attention, not on the size of the rooms. Experiment 3 revealed, however, that participants were able to use information about Euclidean distance in a secondary task when necessary. The implications of these results for theories of narrative comprehension and hierarchical versus nonhierarchical theories of spatial memory are discussed.


Differential expression of the epidermal K1 and K10 keratin genes during mouse embryo development.
Induction of genes coding for the K1 and K10 keratins during mouse development was studied by measuring the accumulation of their respective mRNAs in day 10 to 17 embryos using an RNase protection assay. Although these two keratins are coexpressed in the suprabasal layers of the epidermis, it was found that while K1 mRNA was detectable as soon as day 10, K10 mRNA was not detectable before day 12. The expression of these genes at this stage of development was not expected since they are specifically associated with keratinization, a process that does not begin before day 17 of gestation. Histological examination of the epidermis of day 10 to 17 embryos suggests that both genes are induced in cells committed to epidermal differentiation, after stratification has started but before the onset of keratinization. It was also found that the two mRNAs increased in abundance steadily and significantly until day 16 and that, in spite of the expectation that filaments should contain equivalent amounts of each subunit, K1 mRNA remained more abundant than K10 mRNA at all times including in adult epidermis. These observations indicate that the two genes are regulated independently during development.


Postmenopausal osteoporosis: no effect of three years treatment with 1,25-dihydroxycholecalciferol.
The therapeutic effect of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) in postmenopausal osteoporosis was tested in a single blind, randomized prospective study. Thirty-nine women, 50-65 years of age, were treated for three years with 0.5 microgram 1,25(OH)2D3 daily. In a control group, 37 women were given 400 IU vitamin D3 daily. There was no significant difference in annual bone loss from the distal or proximal forearm between the groups. New vertebral fractures were evaluated, and in the treatment group, the annual increase in vertebral fractures was 0.18 +/- 0.387 and in the control group 0.13 +/- 0.330. New long bone fractures were 7 and 5, respectively. None of the observed differences were statistically significant. In the 1,25(OH)2D3 group, 28% had to reduce the dose because of slight hypercalcaemia. We conclude that 1,25(OH)2D3 as used in this study is not effective in the treatment of osteoporosis.


Intrinsic innervation of the gall bladder in the dog.
The gall bladder of eight dogs 3 months old were extracted and studied by the Holme's and Gross-Bielschowsky techniques. The nerves were found to form an extensive network within the wall of the gall bladder. However, 5 plexuses were identified and their arrangement was similar to that in the wall of the intestine. Nerve cells were only found in relation with the myenteric plexus. Moreover, knob-like terminals and circular type of nerve endings were noticed on the muscularis. The findings of the intrinsic innervation of the gall bladder of the dog were compared with that of man, monkey and guinea pig and the significance of that innervation was discussed.


Intraoperative dexamethasone and the risk of secondary posttonsillectomy hemorrhage.
to determine whether intraoperative dexamethasone is a risk factor for secondary posttonsillectomy bleeding. retrospective chart review. tertiary care referral centres in Scotland. the charts of 530 pediatric patients undergoing tonsillectomy were reviewed over a 3-year period (January 2004 to December 2006), and data were collected regarding the use of dexamethasone intraoperatively. Data were analyzed using the SPSS for Windows statistical package (SPSS Inc, Chicago, IL). incidence of secondary posttonsillectomy bleeding. The relative risk of posttonsillectomy bleeding was measured in those receiving dexamethasone. Logistic regression analysis was performed. Thirty-seven episodes of secondary hemorrhage were encountered in 36 children: 9 of 253 (3.6%; 95% CI 1.6-6.7) patients receiving intraoperative dexamethasone compared to 28 of 277 (10.1%; 95% CI 6.8-14.3) not receiving dexamethasone. Six patients had to undergo an emergency reoperation to arrest bleeding, only one of whom had received dexamethasone. When added to a stepwise logistic regression model with age, gender, indication for surgery, surgeon grade, and operative technique, dexamethasone and the presence of obstructive symptoms were the only significant factors influencing the risk of bleeding. The odds ratio indicates that patients with obstructive symptoms (OR 0.16; 95% CI 0.04-0.70) and those receiving dexamethasone were less likely to develop secondary bleeding (OR 0.44; 95% CI 0.20-0.96). based on our study data, the use of intraoperative dexamethasone does not appear to increase the risk of posttonsillectomy bleeding.


Perceived HIV-related physical fatigue, sociodemographic characteristics and physical activity: A cross-sectional study.
To get a deeper understanding of correlates of perceived HIV-related fatigue by exploring its associations with sociodemographic characteristics and physical activity level of HIV-infected people. Previous studies on HIV-related fatigue have mainly focused on physiological and psychological characteristics, but few have considered its associations with sociodemographic variables. In addition, while physical activity has been found to reduce acute fatigue among HIV-infected people, its links with chronic HIV-related fatigue remain to be explored. The study employed an observational and cross-sectional survey design. The manuscript was organised according to STROBE guidelines. A total of 560 people living with HIV in France completed a measure of perceived physical fatigue using the Fatigue Intensity Scale. The predictors targeted sociodemographic characteristics and two measures of individuals' reported level of physical activity. Data were analysed by a stepwise multiple regression model. The results showed that lower age, higher physical activity level and socio-economic status were significantly associated with reduced perceived physical fatigue, explaining 25% of the variance. The results highlighted the importance of considering sociodemographic and lifestyle characteristics to better characterise HIV-related fatigue, in particular in an era where HIV as a chronic illness challenges questions of quality of life throughout increasingly longer lifespans. The results of this study have implications for HIV care professionals in terms of improving strategies for managing chronic fatigue or promoting physical activity according to more specific profiles of HIV-infected people.


Acoustic droplet vaporization for temporal and spatial control of tissue occlusion: a kidney study.
Acoustic droplet vaporization (ADV) has been introduced with the potential application of tumor treatment via occlusion and subsequent necrosis. New Zealand White rabbits were anesthetized, and their left kidney was externalized. An imaging array and single-element transducer were positioned in a tank with direct access to the kidney's vasculature and renal artery. Filtered droplet emulsions (diameter <6 microm) were injected intra-arterially (IA) into the left heart during insonification of the renal artery, and the extent of blood flow reduction by ADV was compared to the untreated right kidney. Flow cytometry (using colored microspheres) of kidney tissue samples and reference blood from the femoral artery allowed the quantitative estimation of regional blood flow. A maximum regional blood flow reduction in the treated region of >90% and an average organ perfusion reduction of >70% was achieved using ADV. After treatment of the left kidney, the control kidney on the contralateral side showed a maximum decrease in regional blood flow of 18% relative to the pre-ADV baseline. Image-based hyper-echogenicity from ADV of IA injections was monitored for approximately 90 minutes, and cortex perfusion was reduced by >60% of its original value for more than 1 hour. This could be enough time for the onset of cell death and possible tumor treatment via ischemic necrosis. Moreover, currently used radiofrequency tissue ablation-based tumor treatment could benefit from ADV due to the decreased heat loss via vascular cooling.


Corticotropin releasing hormone (CRH) in normal and pregnant uterus: physiological implications.
Corticotropin-releasing hormone, is a hypothalamic neuropeptide, responsible not only for the endocrine but also the autonomic, immunological and behavioural responses of mammalian organisms to stress. CRH is also expressed in female reproductive tissues, such as placenta and uterus. Multiple sites within the pregnant uterine cavity express the CRH gene, including the trophoblasts, fetal membranes (chorion, amnion) and decidua. The trophoblastic syncytium appears to be the major source of placental CRH. It is postulated that placental CRH influences the HPA axis of either mother or fetus and participates at the initiation of labour. Recent findings show that human and rat uterus express the CRH gene. Epithelial cells of both species are the main source of endometrial CRH, while stroma does not seem to express it, unless it differentiates to decidua. Estrogens and glucocorticoids inhibit and prostaglandin E2 stimulates the promoter of human CRH gene in transfected human endometrial cells, suggesting that endometrial CRH gene expression is under the control of these agents. Moreover, in rats, endometrial CRH expression is significantly higher at the implantation sites, compared to that at the inter-implantation uterine regions. Given the proinflammatory/vasoregulatory properties of CRH, we hypothesize that endometrial CRH may participate in the regulation of intrauterine phenomena, such as blastocyst implantation, endometrial vascularization and myometrial contractility.


A high-affinity zinc-binding plasma protein in channel catfish (Ictalurus punctatus).
1. Channel catfish (Ictalurus punctatus) have a remarkably high concentration of zinc (Zn) in their blood serum, about 20 micrograms/ml. However, compared to mammals, the concentrations of Zn in their tissues are not remarkable. The serum Zn is dialyzable against a solution containing 1 mM EDTA. 2. Following separation of serum proteins by gel-filtration most of the Zn was recovered in a fraction with the same peak volume of elution for the Zn and protein concentrations and having a molecular weight similar to bovine serum albumin. 3. Binding of Zn to such sites was not changed by Cu2+, Cd2+, Ca2+, or La3+. N-ethylemaleimide (NEM) appeared to decrease binding slightly. 4. Equilibrium dialysis with a Scatchard plot analysis of these data suggested that a single set of binding sites was present on the protein(s) with KD of 2 x 10(-5) M. There were binding sites for 35 x 10(-8) M Zn/mg protein. 5. Parallel equilibrium dialysis measurements using human, rabbit and chicken albumins indicated that the catfish serum protein(s) had a much higher affinity and binding capacity for Zn than the albumins in these species. 6. The catfish Zn serum-binding protein may be an albumin. The possible physiological significance of such a serum protein in freshwater fish is discussed.


The convergent and divergent validity of the Matson Evaluation of Drug Side-effects (MEDS) and the Dyskinesia Identification System: Condensed User Scale (DISCUS).
Medication side-effects such as tardive dyskinesia (TD) are known to occur in individuals with a history of psychotropic drug use. This study aimed to contribute to the development of measures for assessing TD by examining the validity of the Matson Evaluation of Drug Side-effects (MEDS) with the Dyskinesia Identification System: Condensed User Scale (DISCUS) in 163 adults with intellectual disability (ID). To establish convergent validity, the relationship between the MEDS and the DISCUS in identifying TD was examined. To establish divergent validity, the ability of the MEDS to differentiate between TD and other side-effects was investigated. The MEDS demonstrated convergent validity with the DISCUS on the Central Nervous System--Parkinsonism/Dyskinesia (CNS-PD) Subscale. The MEDS showed divergent validity with the DISCUS in cardiovascular and gastrointestinal side-effects, Parkinsonism symptoms (i.e., tremor, mask-like face), dystonia, and akathisia. The MEDS appears to have significant clinical utility in measuring tardive dyskinesia and other medication side-effects in individuals with ID.


Health effects of cadmium exposure in the general environment in Japan with special reference to the lower limit of the benchmark dose as the threshold level of urinary cadmium.
This study investigates renal dysfunction in areas without known environmental cadmium pollution and calculates the threshold level of urinary cadmium. Urinary total protein, beta2-microglobulin (beta2-MG), and N-acetyl-beta-D-glucosaminidase (NAG), used as indicators of renal dysfunction, and urinary cadmium concentration, used as an indicator of cadmium exposure, were measured in two sets of 24-hour urine samples from each of 828 participants (410 men, 418 women), aged 40-59 years and living in three areas without any known environmental cadmium pollution. In multiple regression and logistic regression analyses the association between indicators of cadmium exposure and indicators of renal dysfunction were studied. The lower 95% confidence limit of the dose (benchmark dose) corresponding to a 5% (BMDL5) or 10% (BMDL10) level of each indicator of renal dysfunction above the background level) was calculated as the threshold level of urinary cadmium. With all the expressed units [g creatinine(-1) and day(-1)] in the multiple regression analysis, the partial regression coefficients showed a significant association between urinary cadmium concentration and total protein, beta2-MG, and NAG for both genders, except for total protein for women (g creatinine(-1) and day(-1). The same results were obtained for both genders in the logistic regression analysis. The BMDL10 was 0.6-1.2 microg/g creatinine and 0.8-1.6 microg/day for the men and 1.2-3.6 microg/g creatinine, and 0.5-4.7 microg/day for the women. Cadmium exposure and the levels of the indicators of renal dysfunction were associated among the men and women aged 40-59 years in areas without any known environmental cadmium pollution. The threshold level of urinary cadmium in Japan seems to be almost the same as in Belgium and Sweden.


[Excision and biopsy procedures].
Biopsies and excisions are every-day procedures of the dermatologist. Certain rules have to be followed to fulfil their purpose, mostly a reliable histological diagnosis, and to achieve cosmetically acceptable scars. Most important biopsy techniques are shave and punch biopsies, and fusiform scalpel excisions. In addition to skin and adnexal biopsies, the dermatologist may perform muscle, vessel, testis and minor salivary gland biopsies.


Aiming for a holistic integrated service for men diagnosed with prostate cancer - Definitions of standards and skill sets for nurses and allied healthcare professionals.
To establish a comprehensive set of recommendations for the service structure and skill set of nurses and allied healthcare professionals in prostate cancer care. Using components of formal consensus methodology, a 30-member multidisciplinary panel produced 53 items for discussion relating to the provision of care for prostate cancer patients by specialist nurses and allied healthcare professionals. Items were developed by two rounds of email correspondence in which, first, items were generated and, second, items refined to form the basis of a consensus meeting which constituted the third round of review. The fourth and final round was an email review of the consensus output. The panel agreed on 33 items that were appropriate for recommendations to be made. These items were grouped under categories of "Environment" and "Patient Pathway" and included comments on training, leadership, communication and quality assessment as well as specific items related to prostate diagnosis clinics, radical treatment clinics and follow-up survivor groups. Specialist nurses and allied healthcare professionals play a vital role alongside urologists and oncologists to provide care to men with prostate cancer and their families. We present a set of standards and consensus recommendations for the roles and skill-set required for these practitioners to provide gold-standard prostate cancer care. These recommendations could form the basis for development of comprehensive integrated prostate cancer pathways in prostate cancer centres as well as providing guidance for any units treating men with prostate cancer.


[Pathophysiology of Rett syndrome from the standpoints of clinical characteristics and clinical neurophysiological findings].
The pathophysiology of Rett syndrome (RTT) was discussed by reviewing the characteristic clinical features and neurophysiological studies. The electroencephalography (EEG), sensory evoked potentials (SEP), sleep-wake rhythm (SWR) study and polysomnographical (PSG) study showed age dependent characteristics. The findings in EEG and SEP studies suggested the specific subcortical and cortical involvements taking place during the development. PSG suggested the early dysfunction of the brainstem and midbrain monoaminergic systems; hypoactive serotonin and noradrenaline systems and dopaminergic system associated with receptor supersensitivity. The monoaminergic systems are known to influence the maturation of the higher neuronal systems at specific areas and at the critical developmental stages. Particularly the synaptogenesis of the cerebral cortex are modulated by region or layer specifically from early stage of the development. The age dependent appearance of characteristic clinical features of RTT, and the variation of the clinical severities; e.g. classical, variant, form fruste etc. can be explained by the specific features of these monoaminergic systems. The analysis of the components of rapid eye movement sleep (REM) suggested the onset of RTT lies between 36 gestational weeks to 3-4 months postnatally. The roles of the causative gene, methyl-CpG-binding protein 2 gene (MECP2) are thought to modulate the transcription of the specific target genes which act these area at specific developmental stages.


Antibiotic Resistance in Young Children in Kilosa District, Tanzania 4 Years after Mass Distribution of Azithromycin for Trachoma Control.
Mass administration of azithromycin (MDA) is integral to trachoma control. Recent studies suggest that MDA may increase drug-resistant pathogens, yet findings from prior studies suggest little long-term impact on resistance. This disparity may be linked to differences in pre-MDA community-level resistance patterns. We describe carriage prevalence and antibiotic resistance patterns for Streptococcus pneumoniae (Spn) (nasopharyngeal swab collection), Staphylococcus aureus (SA) (nasopharyngeal swabs), and Escherichia coli (EC) (rectal swabs) in 1,047 children ages 1-59 months in a district with MDA cessation 4 years ago. Antibiotic susceptibility was evaluated by disk diffusion and Etest. The carriage rates for Spn, SA, and EC were 43.5% (455/1,047), 13.2% (138/1,047), and 61.7% (646/1,047), respectively. Resistance to AZM was observed in 14.3%, 29.0%, and 16.6% of the Spn, SA, and EC isolates, respectively. Spn resistance was variable (0-67%) by hamlet. Future analyses will assess the influence of pre-MDA antibiotic resistance patterns on those observed following MDA.


The use of adolescent nonhuman primates to model human alcohol intake: neurobiological, genetic, and psychological variables.
Traits characteristic of type I and type II alcoholism are thought to relate to dysregulated central nervous system serotonin functioning. In this review, we discuss variables associated with high adolescent alcohol consumption and other risk-taking behaviors in a nonhuman primate model. Adolescent primates with low CSF concentrations of the serotonin metabolite 5-HIAA are more impulsive and exhibit increased levels of alcohol consumption. Both genetic and environmental factors contribute to alcohol-seeking behavior in adolescent macaques. Sequence variation within serotonin system genes, for example, a repeat polymorphism in the transcriptional control region of the monoamine oxidase gene (MAOA-LPR), increases the propensity for adolescent males to consume alcohol. Environmental factors, such as early life stress in the form of peer-rearing or early age of exposure to alcohol, are also associated with increased alcohol consumption. Peer-reared females, especially those exposed to alcohol during early adolescence, exhibit increased rates of alcohol consumption compared to those exposed to alcohol later in development. When genetic variables are also considered, there is an interaction between the low activity serotonin transporter gene promoter s allele (rh5-HTTLPR) and rearing condition on alcohol preference in females but not males, suggesting that the interactions between genes and the environment may be sexually dichotomous. By learning more about the interactions between genes, early experience, and alcohol intake in the adolescent nonhuman primate, we may be able to identify factors that contribute to the susceptibility, pathogenesis, and progression of impulse control disorders, such as alcoholism.


Inhibitory effects of caffeine on gustatory plasticity in the nematode Caenorhabditis elegans.
The effects of caffeine on salt chemotaxis learning were investigated using the nematode Caenorhabditis elegans. To estimate the degree of salt chemotaxis learning, nematodes were placed in a mixed solution of NaCl and caffeine, and then the chemotaxis index of NaCl was obtained from the nematodes placed on agar medium after pre-exposure to caffeine concentrations of 0.01, 0.1, 0.3, and 1.0%. Locomotor activity and preference behavior for caffeine were also estimated under these caffeine conditions. Nematodes pre-exposed to 0.3% caffeine showed inhibition of salt chemotaxis learning. Additional experiments indicated that nematodes showed a preference response to the middle concentration of caffeine (0.1%), with preference behavior declining in the 0.3% caffeine condition. Stable locomotor activity was observed under 0.01-0.3% caffeine conditions. These results suggest that salt chemotaxis learning with 0.3% caffeine is useful for investigating the effects of caffeine on learning in nematodes.