Low-energy suspiciously open proximal humerus fracture management in older adult patient: A case report.
Although fractures of the proximal humerus are common among older adults, open fractures following low-energy trauma are exceptionally rare. Prior studies have alluded to the existence of this injury, but there are no detailed reports on its presentation, management, or long-term follow-up. We present the case of a 78-year-old man that sustained a suspiciously open proximal humerus fracture of the dominant hand following a fall down a few stairs. Management consisted of early intravenous antibiotics followed by open reduction and internal fixation with irrigation and debridement. Intraoperative soft tissue assessment revealed a wound extending from bone to skin. The patient suffered no complications, regained full function of his arm, and is pain free. Considering the rarity of this injury and its potential for highly morbid complications, this case serves as a reminder that we should continue to have a low suspicion threshold for open fracture when punctures or lesions are present around proximal humerus fractures, even for low-energy injuries. Prompt and thorough examination, initiation of antibiotics, and surgical intervention are keys to providing best care for this uncommon injury.


Metastasis of Colon Cancer to the Breast.
Breast metastases from extramammary neoplasms are extremely rare, and even more so is metastasis of colon cancer to the breast. Despite its rarity, metastatic disease to the breast is an important diagnostic issue because its treatment differs greatly from that of primary cancer. Proper diagnosis of this rare event requires an accurate clinical history, proper immunohistochemical workup, and a high level of suspicion.


Ventricular arrhythmias in aortic valve stenosis before and after transcatheter aortic valve implantation.
Transcatheter aortic valve implantation (TAVI) is a therapeutic treatment for patients with severe aortic stenosis (AS) at high surgical risk. Although the procedure is associated with a reduction in total mortality, there are no data regarding changing in the incidence of premature ventricular contractions (PVCs) and ventricular arrhythmias (VAs) after TAVI. The aim of this study was to assess the incidence of VAs before and after TAVI. We enrolled 237 patients who underwent TAVI at our centre. Ninety-one patients were excluded for the following reasons: presence of prior permanent pacemaker (PPM) (n = 20), new PPM implant after TAVI (n = 48), death during the follow-up period (n = 16), and lost at follow-up (n = 7). Finally, 146 patients were included in our analysis. The presence of VAs was evaluated in all patients recording a 24 h Holter monitoring before the procedure and after 1 and 12 months. Ventricular arrhythmias were classified according to a modified Lown grading system. Before the procedure, isolates PVCs (grade 1-2 of Lown grading system) were present in 34.9% of patients (n = 51). Complex PVCs (grade 3-4a-4b of Lown grading system) were present in 48.6% of the population (multifocal PVCs in 32 patients, 21.9%; pairs in 25 patients, 17.1%; ventricular tachycardia in 14 patients, 9.6%). One month after the procedure, we observed statistically significant incidence decrease of arrhythmias of grade 3 (from 21.9 to 17.1%) and grade 4 (pairs from 17.1 to 12.3%; ventricular tachycardia from 9.6 to 4.8%). After 12 months, there was a further significant reduction in the frequency and severity of PVCs. In particular, 45.8% of patients had isolates PVCs (<30 in all given hours of monitoring in 45 patients, 30.8%; higher than 30 in any hour of monitoring in 22 patients, 15%) while the frequency of complex arrhythmias was reduced to 16.4% (multifocal PVCs in 13 patients, 9%; couplets 8 patients, 5.5% and ventricular tachycardia in 3 patients, 2.0%). The difference was statistically significant (P < 0.01). This study indicates that VAs are common in patients with AS. We observed a significant decrease in the incidence and severity of PVCs since the first month after TAVI. Furthermore, after 1 year follow-up there was a further and significant reduction in the frequency of complex PVCs. This may be related to the benefits determined by valve replacement on left ventricular function.


Overcoming Limitations in Peer-Victimization Research That Impede Successful Intervention: Challenges and New Directions.
Peer victimization at school is a worldwide problem with profound implications for victims, bullies, and whole-school communities. Yet the 50-year quest to solve the problem has produced mostly disappointing results. A critical examination of current research reveals both pivotal limitations and potential solutions. Solutions include introducing psychometrically sound measures to assess the parallel components of bullying and victimization, analyzing cross-national data sets, and embracing a social-ecological perspective emphasizing the motivation of bullies, importance of bystanders, pro-defending and antibullying attitudes, classroom climate, and a multilevel perspective. These solutions have been integrated into a series of recent interventions. Teachers can be professionally trained to create a highly supportive climate that allows student-bystanders to overcome their otherwise normative tendency to reinforce bullies. Once established, this intervention-enabled classroom climate impedes bully-victim episodes. The take-home message is to work with teachers on how to develop an interpersonally supportive classroom climate at the beginning of the school year to catalyze student-bystanders' volitional internalization of pro-defending and antibullying attitudes and social norms. Recommendations for future research include studying bullying and victimization simultaneously, testing multilevel models, targeting classroom climate and bystander roles as critical intervention outcomes, and integrating school-wide and individual student interventions only after improving social norms and the school climate.


Defective interleukin-2 production and interleukin-2 receptor expression in pulmonary tuberculosis.
The evolution of Mycobacterium tuberculosis as an intracellular pathogen has led to a complex relationship between it and its host, the human mononuclear phagocyte. The products of M. tuberculosis-specific T lymphocytes are essential for macrophage activation for intracellular mycobacterial killing. However, dysfunction cell-mediated immune response to infection with M. tuberculosis may contribute to progressive primary infection or reactivation of endogenous foci of mycobacteria. Th1 cells produce IL-2, which is essential for proper cellular immunity. The aim of this study was to identify the variation in IL-2 activity and soluble IL-2 receptor (IL-2 R) in peripheral blood lymphocyte in patients suffering with pulmonary tuberculosis. A significant decrease in IL-2 and IL-2 receptor level was observed in patients with pulmonary tuberculosis when compared to normal controls. Our results suggested that patients with pulmonary tuberculosis had a defect in IL-2 production. Better understanding of these interactions will allow the development of increasingly specific immune-based interventions for prevention and treatment of tuberculosis.


Low-cost physicochemical treatment for removal of ammonia, phosphate and nitrate contaminants from landfill leachate.
Four low-cost materials, oyster shells, pumice stone, sand and zeolite were employed as adsorbents in an adsorption batch assays investigating the removal of ammonia, phosphate and nitrate from an aqueous solution. These compounds were chosen as they represent typical compounds found in landfill leachate (LFL). Assay performance was evaluated by the Langmuir and Freundlich adsorption isotherms. The top two materials, oyster shells and pumice stone, were employed as adsorbents in a fixed-bed column trial examining the effect of bed height and flow rate on the treatment of a synthetic LFL. The trial concluded that the highest rates of adsorption were achieved using bed heights of 20 cm with a flow rate of 5 mL min-1. After optimization, the system was employed for the treatment of LFL from Powerstown landfill, Carlow, Ireland. Ammonia and nitrate were effectively removed by both adsorption materials resulting in a reduction of influent ammonia and nitrate concentrations to below the national discharge limits set for these compounds of ≤4 mg L-1 and ≤50 mg L-1, respectively. In contrast, although similar high removal efficiencies were observed for phosphate, these rates were not maintained during the test period with overall results indicating reduced phosphate adsorption in comparison to the other compounds tested.


Accelerated formation of alpha-synuclein oligomers by concerted action of the 20S proteasome and familial Parkinson mutations.
A hallmark of Parkinson disease (PD) is the formation of intracellular protein inclusions called Lewy bodies that also contain mitochondria. alpha-Synuclein (alpha Syn) is a major protein component of Lewy bodies, where it is in an amyloid conformation and a significant fraction is truncated by poorly understood proteolytic events. Previously, we demonstrated that the 20S proteasome cleaves alpha Syn in vitro to produce fragments like those observed in Lewy bodies and that the fragments accelerate the formation of amyloid fibrils from full-length alpha Syn. Three point mutations in alpha Syn are associated with early-onset familial PD: A30P, E46K, and A53T. However, these mutations have very different effects on the amyloidogenicity and vesicle-binding activity of alpha Syn, suggesting neither of these processes directly correlate with neurodegeneration. Here, we evaluate the effect of the disease-associated mutations on the fragmentation, conformation, and association reactions of alpha Syn in the presence of the 20S proteasome and liposomes. The 20S proteasome produced the C-terminal fragments from both the mutant and wildtype alpha Syn. These truncations accelerated fibrillization of all alpha-synucleins, but again there was no clear correlation between the PD-associated mutations and amyloid formation in the presence of liposomes. Recent data suggests that cellular toxicity is caused by a soluble oligomeric species, which is a precursor to the amyloid form and is immunologically distinguishable from both soluble monomeric and amyloid forms of alpha Syn. Notably, the rate of formation of the soluble, presumptively cytotoxic oligomers correlated with the disease-associated mutations when both 20S proteasome and liposomes were present. Under these conditions, the wildtype protein was also cleaved and formed the oligomeric structures, albeit at a slower rate, suggesting that 20S-mediated truncation of alpha Syn may play a role in sporadic PD as well. Evaluation of the biochemical reactions of the PD-associated alpha-synuclein mutants in our in vitro system provides insight into the possible pathogenetic mechanism of both familial and sporadic PD.


Monochorionic monoamnionic twins: vaginal delivery.
Monochorionic monoamnionic pregnancies are rare and have a poor obstetric prognosis. A single amniotic sac promotes cord knotting and entanglement with a high risk of fetal anoxia. The response to this risk has been obstetric management consisting of routine cesarean section at 32 weeks of gestation or when pulmonary maturity is attained. This approach is called into question by the series of seven monochorionic monoamnionic pregnancies we present here. Such pregnancies do indeed require increased surveillance to term, but we think it is possible to apply the usual obstetric management of twin pregnancies.


Implications for body weight extremes in solid organ transplantation.
The pharmacokinetic profiles of medications are altered in overweight and underweight patients, but few studies have described these differences in patients with body mass index extremes. As solid organ transplant programs expand their candidate selection criteria to accommodate a growing population of patients with weight extremes, it has become imperative to understand and evaluate the impact weight extremes have on the pharmacokinetics of life-sustaining immunosuppression in this population. This review will describe pharmacokinetic and dosing considerations for weight extremes in solid organ transplant recipients, including changes following bariatric surgeries, non-pharmacologic and pharmacologic management strategies for weight loss and gain, and potential drug-drug interactions with popular weight management products.


Volume changes in hemolytic systems containing resorcinol, taurocholate, and saponin.
Simultaneous measurement of hemolysis, the volume of the intact cells, and the K lost from the intact cells of systems containing resorcinol, sodium taurocholate, and saponin shows that the volume increases may be conspicuously small while the K losses are large, and that the volume increases are un-equal for equal K losses produced by different lysins. In higher concentrations of the same lysins, the critical volume for hemolysis is a function of the nature of the lysin and of its concentration. It is impossible to say whether these observations are compatible with the current "dual mechanism" and "colloid osmotic" hypotheses of hemolysis, in which the swelling of the cell is supposed to result from the lysin having made it cation-permeable. The difficulty to be overcome is that the theory cannot be developed to describe volume changes in finite time unless we know what assumptions to make about the mobilities of K and Na, the forces driving them into and out of the cell, etc. The experimental results do not suggest, however, that any simple set of assumptions would be satisfactory. The conditions which regulate the upper limit of the swelling, i.e. the point at which a swelling phenomenon becomes a hemolytic phenomenon, are functions of the nature of the lysin and sometimes of its concentration. They require to be specified by an independent statement, over and above any statement which may be made about the rate at which swelling occurs in the system. The simplest view of the situation is that the conditions which regulate the critical volume and those which regulate the rate of swelling are both functions, as yet undefined, of the reaction which takes place between the lysin and the structural components of the red cell.


All-trans-retinoic acid activated mast cells via Mas-related G-protein-coupled receptor-X2 in retinoid dermatitis.
Retinoic acid (RA)-induced dermatitis is the most frequent side-effect limiting its widespread use. However, the exact mechanisms triggering dermatitis are not fully understood, including the role of skin mast cells. The newly discovered Mas-related G-protein-coupled receptor-X2 (MRGPRX2) in mast cells mediates pseudoallergic drug reactions in several types of dermatitis. A possible contribution of MRGPRX2 to contact dermatitis induced by RA has hitherto not been examined. To investigate whether all-trans-RA (ATRA) activates mast cells via MRGPRX2/MrgprB2 (the mouse orthologue), contributing to the pathogenesis of retinoid-induced dermatitis. Wild-type (WT) and MrgprB2-/- mice were treated with topical ATRA to observe local inflammation and mast cell degranulation in vivo by the use of haematoxylin and eosin and immunofluorescence staining. Release of histamine and release of β-hexosaminidase were measured and calcium influx was detected in Laboratory of Allergic Disease 2 (LAD2) cells with specific knockdown targeting MRGPRX2 by small interfering RNA (siRNA) and in primary cells from MrgprB2-/- mice. As compared with WT mice, MrgprB2-/- mice showed resistance to ATRA-triggered contact dermatitis and local inflammatory reactions in the paws. ATRA activated mast cells via the MrgprB2 pathway in murine cells, and via the MRGPRX2 pathway in human mast cells. ATRA-induced dermatitis could be achieved by activating mast cells via MRGPRX2/MrgprB2, which may provide a potential therapy target to reduce the side-effect.


Improving clinician-patient communication of health risks when diagnostic test information is imprecise.
Both clinicians and patients experience difficulty with the statistical reasoning required to make inferences about health states on the basis of information derived from diagnostic tests. This problem will grow in importance as we move into the era of personalised medicine where an increasing supply of imprecise diagnostic tests meets an increasing demand to use such tests on the part of intelligent but statistically innumerate clinicians and patients. We describe a user-friendly, interactive, graphical interface for calculating, visualising, and communicating accurate inferences about uncertain health states when diagnostic information (test sensitivity and specificity, and health state prevalence) is imprecise and ambiguous in its application to a specific patient. The software is free, open-source, and runs on all popular PC operating systems (Windows, Mac, Linux).


Cervical spine reoperation rates and hospital resource utilization after initial surgery for degenerative cervical spine disease in 12,338 patients in Washington State.
Patients undergoing surgery for degenerative cervical spine disease may require future surgery for disease progression. We investigated factors related to the rate of additional cervical spine surgery, the associated length of stay, and hospital charges. The was a longitudinal retrospective cohort study using Washington state's 1998 to 2002 state inpatient databases and International Classification of Diseases-Ninth Revision-Clinical Modification (ICD-9) codes to analyze patients undergoing degenerative cervical spine surgery. Multivariate Poisson regression to identify patient and surgical factors associated with reoperation for degenerative cervical spine disease was used. Multivariate linear regressions to identify factors associated with length of stay and hospital charges adjusted for age, sex, year of surgery, primary diagnosis, payment type, discharge status, and comorbidities were also used. A total of 12,338 patients underwent initial cervical spine surgeries from 1998 to 2002; the mean follow-up duration was 2.3 years, and 688 patients (5.6%) underwent a reoperation (2.5% per year). Higher reoperation rates were independently associated with younger patients (P < 0.001) and a primary diagnosis of disc herniation with myelopathy (P = 0.011). Ventral surgery (P < 0.001) and fusion (P < 0.001) were both associated with lower rates of reoperation; however, a high correlation (Spearman's rho = 0.82; P < 0.001) made it impossible to determine which factor was dominant. Longer length of stay was independently associated with nonventral approaches (+1.0 day; P < 0.001) and fusion surgery (+0.8 day; P < 0.001). Greater hospital charges were independently associated with nonventral approaches (+$2900; P < 0.001) and fusion surgery (+$9600; P < 0.001). Patients undergoing surgery for degenerative cervical spine disease undergo reoperations at the rate of 2.5% per year. An initial ventral approach and/or fusion seem to be associated with lower reoperation rates. An initial nonventral approach and fusion were more expensive.


Artificial intelligence to generate medical images: augmenting the cardiologist's visual clinical workflow.
Artificial intelligence (AI) offers great promise in cardiology, and medicine broadly, for its ability to tirelessly integrate vast amounts of data. Applications in medical imaging are particularly attractive, as images are a powerful means to convey rich information and are extensively utilized in cardiology practice. Departing from other AI approaches in cardiology focused on task automation and pattern recognition, we describe a digital health platform to synthesize enhanced, yet familiar, clinical images to augment the cardiologist's visual clinical workflow. In this article, we present the framework, technical fundamentals, and functional applications of the methodology, especially as it pertains to intravascular imaging. A conditional generative adversarial network was trained with annotated images of atherosclerotic diseased arteries to generate synthetic optical coherence tomography and intravascular ultrasound images on the basis of specified plaque morphology. Systems leveraging this unique and flexible construct, whereby a pair of neural networks is competitively trained in tandem, can rapidly generate useful images. These synthetic images replicate the style, and in several ways exceed the content and function, of normally acquired images. By using this technique and employing AI in such applications, one can ameliorate challenges in image quality, interpretability, coherence, completeness, and granularity, thereby enhancing medical education and clinical decision-making.


Exploring volatile organic compound emission from thermally modified wood by PTR-ToF-MS.
Thermal modification of wood is a well-known industrial process performed to increase the durability and dimensional stability or to change the colour of natural wood. The treatment influences many other properties of wood including the emission of volatile organic compounds (VOCs). VOC release ultimately affects the quality of indoor air and the capability of having low VOC emission is often included as a key parameter for the attribution of quality labels. In the present work, wood from six tree species was subjected to different types of treatment and VOC profiling was carried out on both treated and untreated samples by means of PTR-ToF-MS. Different types of thermal treatment were tested, involving either overpressure or vacuum and the effect of different temperature profiles was evaluated. Hardwood and softwood showed different release profiles under all tested conditions: the headspace of softwood was richer in several VOCs, such as terpenes, phenols and C6-C9 aldehydes and carboxylic acids. Upon thermal treatment, terpene emissions decreased, whereas several other VOCs, such as formic acid, formaldehyde, furfural and acetic acid, were released in higher amounts. With its high sensitivity and throughput, PTR-ToF-MS appears to be a very powerful analytical tool, useful in supporting the selection of wood materials for different end uses.


Evaluation of Heat Stress Levels Inside Greenhouses during Summer in Korea.
Farmers working inside greenhouses during summer are at risk of heat-related illness. In this study, we compared the dry-bulb temperatures (DTs) and the wet-bulb globe temperature (WBGT) index inside and outside greenhouses. We then determined the criteria for appropriate working and resting times inside greenhouses. The measurements were performed during the hottest period in 2020 and 2021 for two greenhouses, representative of those commonly found in rural areas. A direct-reading WBGT index meter was used for these measurements, and Automated Synoptic Observing System (ASOS) data were used to obtain regional DT data. DTs inside the greenhouses were significantly higher than the ASOS DTs (p < 0.001). In addition, the August WBGT index inside was significantly higher than that outside the greenhouses (p < 0.001). We found that the temperature during the period between 08:00 and 19:00 exceeded the international threshold of 28 °C for heat-acclimatized workers performing moderate-intensity work, above which heat stress becomes a concern. Our results revealed that the thermal index inside can be significantly higher than that found outside greenhouses. Therefore, when work is required inside greenhouses during the summer, stricter standards and safety measures should be considered.


Cell volume-induced changes in K+ transport across the rat colon.
The effect of cell swelling and cell shrinkage on K+ transport across the rat colonic epithelium was studied by measuring unidirectional fluxes, uptake and efflux of 86Rb+, a marker for K+. Exposure to a hypotonic medium stimulated the secretory, serosa-to-mucosa flux of K+, whereas exposure to a hypertonic medium inhibited the absorptive, mucosa-to-serosa flux of K+ in the distal, but not in the proximal colon. Neither manoeuvre had any effect on the uptake of K+ across the apical or the basolateral membrane. Cell swelling induced a sustained increase in the apical and basolateral K+ efflux from both colonic segments, whereas cell shrinkage reduced the efflux. Ba2+ (10(-2) mol l(-1)) inhibited the swelling-induced stimulation of the apical, quinine (10(-3) mol l(-1)) that of the basolateral K+ efflux in the distal colon. Incubation of the tissue in Ca2+-free buffer or La3+, which blocks Ca2+-influx into the epithelium, strongly reduced the basal K+ efflux across the basolateral membrane. The same was observed with brefeldin A, a blocker of the transport of newly synthesized proteins out of the endoplasmatic reticulum. Swelling-induced K+ efflux, however, was not reduced. In the presence of colchicine, an inhibitor of the polymerization of microtubules, swelling evoked only a transient increase in mucosal efflux, which, especially in the proximal colon, fell after 6 min to the level of the isotonic control period. These results demonstrate that the cell volume is involved in the regulation of transepithelial K+ transport across the rat colonic epithelium and suggest a role of the cytoskeleton in the control of a part of the volume-sensitive K+ channels.


Haemolytic anaemia due to cold agglutinins caused by psittacosis.
A 69-yr-old previously healthy woman, presenting with jaundice and the clinical symptoms of an atypical pneumonia, was hospitalized. Haemolytic anaemia due to cold agglutinins was diagnosed, and erythromycin therapy for a suspected Mycoplasma pneumoniae infection was instituted. Serological testing revealed, however, that the infection was attributable to Chlamydia psittaci. The literature on psittacosis and haematological complications is reviewed. Cold agglutinins are sometimes found in association with psittacosis, but a concomitant haemolytic anaemia is rare.


Rapid and Simultaneous Prediction of Eight Diesel Quality Parameters through ATR-FTIR Analysis.
Quality assessment of diesel fuel is highly necessary for society, but the costs and time spent are very high while using standard methods. Therefore, this study aimed to develop an analytical method capable of simultaneously determining eight diesel quality parameters (density; flash point; total sulfur content; distillation temperatures at 10% (T10), 50% (T50), and 85% (T85) recovery; cetane index; and biodiesel content) through attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and the multivariate regression method, partial least square (PLS). For this purpose, the quality parameters of 409 samples were determined using standard methods, and their spectra were acquired in ranges of 4000-650 cm-1. The use of the multivariate filters, generalized least squares weighting (GLSW) and orthogonal signal correction (OSC), was evaluated to improve the signal-to-noise ratio of the models. Likewise, four variable selection approaches were tested: manual exclusion, forward interval PLS (FiPLS), backward interval PLS (BiPLS), and genetic algorithm (GA). The multivariate filters and variables selection algorithms generated more fitted and accurate PLS models. According to the validation, the FTIR/PLS models presented accuracy comparable to the reference methods and, therefore, the proposed method can be applied in the diesel routine monitoring to significantly reduce costs and analysis time.


In Vivo and In Vitro Genome-Wide Profiling of RNA Secondary Structures Reveals Key Regulatory Features in Plasmodium falciparum.
It is widely accepted that the structure of RNA plays important roles in a number of biological processes, such as polyadenylation, splicing, and catalytic functions. Dynamic changes in RNA structure are able to regulate the gene expression programme and can be used as a highly specific and subtle mechanism for governing cellular processes. However, the nature of most RNA secondary structures in Plasmodium falciparum has not been determined. To investigate the genome-wide RNA secondary structural features at single-nucleotide resolution in P. falciparum, we applied a novel high-throughput method utilizing the chemical modification of RNA structures to characterize these structures. Structural data from parasites are in close agreement with the known 18S ribosomal RNA secondary structures of P. falciparum and can help to predict the in vivo RNA secondary structure of a total of 3,396 transcripts in the ring-stage and trophozoite-stage developmental cycles. By parallel analysis of RNA structures in vivo and in vitro during the Plasmodium parasite ring-stage and trophozoite-stage intraerythrocytic developmental cycles, we identified some key regulatory features. Recent studies have established that the RNA structure is a ubiquitous and fundamental regulator of gene expression. Our study indicate that there is a critical connection between RNA secondary structure and mRNA abundance during the complex biological programme of P. falciparum. This work presents a useful framework and important results, which may facilitate further research investigating the interactions between RNA secondary structure and the complex biological programme in P. falciparum. The RNA secondary structure characterized in this study has potential applications and important implications regarding the identification of RNA structural elements, which are important for parasite infection and elucidating host-parasite interactions and parasites in the environment.


[Automatic classification method of star spectra data based on manifold fuzzy twin support vector machine].
Support vector machine (SVM) with good leaning ability and generalization is widely used in the star spectra data classification. But when the scale of data becomes larger, the shortages of SVM appear: the calculation amount is quite large and the classification speed is too slow. In order to solve the above problems, twin support vector machine (TWSVM) was proposed by Jayadeva. The advantage of TSVM is that the time cost is reduced to 1/4 of that of SVM. While all the methods mentioned above only focus on the global characteristics and neglect the local characteristics. In view of this, an automatic classification method of star spectra data based on manifold fuzzy twin support vector machine (MF-TSVM) is proposed in this paper. In MF-TSVM, manifold-based discriminant analysis (MDA) is used to obtain the global and local characteristics of the input data and the fuzzy membership is introduced to reduce the influences of noise and singular data on the classification results. Comparative experiments with current classification methods, such as C-SVM and KNN, on the SDSS star spectra datasets verify the effectiveness of the proposed method.


Thermophoresis: The Case of Streptavidin and Biotin.
Thermophoretic behavior of a free protein changes upon ligand binding and gives access to information on the binding constants. The Soret effect has also been proven to be a promising tool to gain information on the hydration layer, as the temperature dependence of the thermodiffusion behavior is sensitive to solute-solvent interactions. In this work, we perform systematic thermophoretic measurements of the protein streptavidin (STV) and of the complex STV with biotin (B) using thermal diffusion forced Rayleigh scattering (TDFRS). Our experiments show that the temperature sensitivity of the Soret coefficient is reduced for the complex compared to the free protein. We discuss our data in comparison with recent quasi-elastic neutron scattering (QENS) measurements. As the QENS measurement has been performed in heavy water, we perform additional measurements in water/heavy water mixtures. Finally, we also elucidate the challenges arising from the quantiative thermophoretic study of complex multicomponent systems such as protein solutions.


Multipolar Atom Types from Theory and Statistical Clustering (MATTS) Data Bank: Impact of Surrounding Atoms on Electron Density from Cluster Analysis.
The multipole model (MM) uses an aspherical approach to describe electron density and can be used to interpret data from X-ray diffraction in a more accurate manner than using the spherical approximation. The MATTS (multipolar atom types from theory and statistical clustering) data bank gathers MM parameters specific for atom types in proteins, nucleic acids, and organic molecules. However, it was not fully understood how the electron density of particular atoms responds to their surroundings and which factors describe the electron density in molecules within the MM. In this work, by applying clustering using descriptors available in the MATTS data bank, that is, topology and multipole parameters, we found the topology features with the biggest impact on the multipole parameters: the element of the central atom, the number of first neighbors, and planarity of the group. The similarities in the spatial distribution of electron density between and within atom type classes revealed distinct and unique atom types. The quality of existing types can be improved by adding better parametrization, definitions, and local coordinate systems. Future development of the MATTS data bank should lead to a wider range of atom types necessary to construct the electron density of any molecule.


Pseudo-octahedral nickel(ii) complexes of strongly absorbing benzannulated pincer-type amido ligands: ligand-based redox and non-Aufbau electronic behaviour.
The synthesis, structures and electronic characterization of three strongly coloured, pseudo-octahedral Ni(ii) complexes supported by redox-active diarylamido ligands featuring benzannulated N-heterocyclic donor arms are reported. The S = 1 paramagnets each present two singly occupied molecular orbitals (SOMOs) identified as metal-based by density functional theory (DFT), consistent with solid-state and solution magnetism measurements. Upon applying oxidative potentials, non-Aufbau behaviour leads to the appearance of intense and well-defined absorption features extending into the near IR (NIR). The attribution of these features to the onset of aminyl radical character through ligand-based redox is corroborated by exceptionally strong intervalence charge-transfer (IVCT) transitions ascribed to electronic communication between two Namido moieties across a Ni(ii) bridge.


Proximal humerus fractures: anatomy, diagnosis and management.
Proximal humeral fractures are common with a bimodal distribution and sex discrepancy, affecting younger men and older women. The presentation of a proximal humeral fracture can vary greatly because of this bimodal distribution and the associated differences in mechanism of injury. Initial management should involve assessment of life- and limb-threatening injuries as outlined by the British Orthopaedic Association Standards for Trauma, with particular attention paid to axillary nerve function and vascular status. Initial imaging should involve orthogonal X-rays in three planes to determine fracture characteristics and exclude glenohumeral dislocation. Computed tomography imaging improves interobserver agreement and is the gold standard in determining fracture management. Management depends on fracture pattern, patient functionality and bone stock. Most patients with proximal humeral fractures achieve good functional outcomes via conservative methods (sling support and early, graded mobilisation), although there is a lack of evidence in certain populations, including younger patients. Surgery is required for open fractures and more complex fracture patterns where there is a risk of avascular necrosis of the humeral head, unacceptable impairment of functionality or neurovascular compromise. Surgical techniques can be head-sparing or involve replacement of the humeral head. There are several head-sparing techniques, each with different cost-benefit and complication profiles with no one technique superior to any other. However, improvements in plate technology may render open reduction internal fixation a more suitable technique, particularly in younger patients. Head replacement techniques (hemiarthroplasty and reverse shoulder arthroplasty) are indicated when the risk of avascular necrosis is too high or in older patients with osteoporotic bone. In these patients, reverse shoulder arthroplasty is preferred as it achieves better functional results than hemiarthroplasty. Complication rates vary depending on the fracture configuration and the course of management undertaken.


Relationships among social support, professional empowerment, and nursing career development of male nurses: a cross-sectional analysis.
The purpose of this study is to explore the relationships among social support, professional empowerment, and nursing career development and to identify the significant factors that affect nursing career development among male nurses. A cross-sectional survey design was used with 314 male nurses in Taiwan. Social support and professional empowerment were significantly and positively correlated with nursing career development among male nurses. Social support, professional empowerment, salary, type of institution, type of clinical level, and nursing discipline were identified as factors that significantly influenced nursing career development. Together, they accounted for 55.9% of the total variation. Professional empowerment was the most critical predictor of nursing career development and accounted for 47.7% of the variation. Nursing managers should follow male nurses' empowerment with interest and specifically address professional empowerment to promote male nurses' career development.


Research Progress on Relationship Between Iron Overload and Lower Limb Arterial Disease in Type 2 Diabetes Mellitus.
Iron is one of the most important trace elements in life activities. It participates in a variety of important physiological processes in the body through oxidation-reduction reaction. A large number of studies show that iron overload (IO) is closely related to the progression of diabetes and its various chronic complications. However, the mechanism of iron overload in the pathogenesis of diabetes and the mechanism of iron overload in atherosclerosis (AS) are still controversial, and the relationship between iron overload and diabetic lower extremity arterial disease (LEAD) remains still unclear. Some recent reviews and original research articles suggest further studies to explain the complex relationship between iron metabolism and atherosclerosis. This article reviews the relationship between iron overload and diabetes and its relationship with LEAD, and discusses its mechanisms from various aspects, such as lipid peroxidation induced by iron overload, so as to provide clinical diagnosis and treatment ideas for diabetic lower extremity arterial disease. It is hoped that early evaluation, diagnosis and treatment of LEAD will be inspired.


An interlaboratory comparison programme on radio frequency electromagnetic field measurements: the second round of the scheme.
The second round of an interlaboratory comparison scheme on radio frequency electromagnetic field measurements has been conducted in order to evaluate the overall performance of laboratories that perform measurements in the vicinity of mobile phone base stations and broadcast antenna facilities. The participants recorded the electric field strength produced by two high frequency signal generators inside an anechoic chamber in three measurement scenarios with the antennas transmitting each time different signals at the FM, VHF, UHF and GSM frequency bands. In each measurement scenario, the participants also used their measurements in order to calculate the relative exposure ratios. The results were evaluated in each test level calculating performance statistics (z-scores and En numbers). Subsequently, possible sources of errors for each participating laboratory were discussed, and the overall evaluation of their performances was determined by using an aggregated performance statistic. A comparison between the two rounds proves the necessity of the scheme.


Prenatal diagnosis and molecular cytogenetic characterisation of a small de novo interstitial duplication 16q11.2-q13.
We describe the first prenatally detected case of a small de novo interstitial duplication of chromosome 16q. This chromosomal aberration is extremely rare. Amniocentesis was indicated by advanced maternal age only. Ultrasound examinations of the foetus showed no abnormalities. Conventional and molecular cytogenetic analyses on cultured amniocytes by comparative genomic hybridisation (CGH) and fluorescence in situ hybridisation (FISH) using partial chromosome paints and a locus-specific YAC clone revealed a de novo direct duplication of the chromosomal region 16q11.2-q13 leading to a partial trisomy 16q (46,XX,dup(16)(q11.2q13)). There are only five postnatal reports of comparable duplications involving this chromosomal region. These patients presented with little or no associated dysmorphic features but with significant neurodevelopmental delay and severe behavioural problems. After genetic counselling, the parents opted for termination of pregnancy. Post-mortem examination showed slight facial dysmorphic signs, minor dysgenesis of the ovaries and an atypical outflow of the arteria thyroidea ima.


Pharmacodynamics of cytarabine induced leucopenia: a retrospective cohort study.
Cytarabine is a pyrimidine analogue used to treat a variety of haematological malignancies. There are few data regarding the pharmacodynamics of cytarabine. The only publications regarding this issue cite a biphasic pattern of decline in white blood cell (WBC) counts following low and intermediate doses, in patients with various malignancies, most of them non-haematological. Our purpose was to establish the pharmacodynamics of cytarabine induced leucopenia in acute myeloid leukaemia (AML) patients treated with contemporary cytarabine containing protocols. We conducted a retrospective cohort study, including 56 patients with AML in complete remission who had received 89 cycles of intermediate or high dose cytarabine. Daily counts for WBCs and neutrophils (ANC) were collected during the first 15 days after the initiation of cytarabine administration and pharmacodynamics were analyzed. Further analysis was carried out to correlate between WBC and ANC pharmacodynamics and different cytarabine protocols [high dose cytarabine (HiDAC) vs. intermediate dose cytarabine (IDAC)]. Analysis of blood counts demonstrated a monophasic decline of WBCs and ANCs, unlike a previous depiction of a biphasic pattern. HiDAC was associated with a significantly sharper decline of WBCs than IDAC. Our data support a monophasic decline pattern of WBCs and ANCs following contemporary cytarabine protocols. The decline rate is steeper for patients receiving HiDAC than for those receiving IDAC. These results might help form evidence based guidelines regarding patient monitoring intensity, timing of prophylactic antibacterial and antifungal treatment as well as growth factors' support following cytarabine based consolidation for AML.


Sociodemographic Factors Are Associated with Patient-Reported Outcome Measure Completion in Orthopaedic Surgery: An Analysis of Completion Rates and Determinants Among New Patients.
Patient-reported outcome measures (PROMs) and, specifically, the Patient-Reported Outcomes Measurement Information System (PROMIS), are increasingly utilized for clinical research, clinical care, and health-care policy. However, completion of these outcome measures can be inconsistent and challenging. We hypothesized that sociodemographic variables are associated with the completion of PROM questionnaires. The purposes of the present study were to calculate the completion rate of assigned PROM forms and to identify sociodemographic and other variables associated with completion to help guide improved collection efforts. All new orthopaedic patients at a single academic medical center were identified from 2016 to 2020. On the basis of subspecialty and presenting condition, patients were assigned certain PROMIS forms and legacy PROMs. Demographic and clinical information was abstracted from the electronic medical record. Bivariate analyses were performed to compare characteristics among those who completed assigned PROMs and those who did not. A multivariable logistic regression model was created to determine which variables were associated with successful completion of assigned PROMs. Of the 219,891 new patients, 88,052 (40%) completed all assigned PROMs. Patients who did not activate their internet-based patient portal had a 62% increased likelihood of not completing assigned PROMs (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.58 to 1.66; p < 0.001). Non-English-speaking patients had a 90% (OR, 1.90; 95% CI, 1.82 to 2.00; p < 0.001) increased likelihood of not completing assigned PROMs at presentation. Older patients (≥65 years of age) and patients of Black race had a 23% (OR, 1.23; 95% CI, 1.19 to 1.27; p < 0.001) and 24% (OR, 1.24; 95% CI, 1.19 to 1.30; p < 0.001) increased likelihood of not completing assigned PROMs, respectively. The rate of completion of PROMs varies according to sociodemographic variables. This variability could bias clinical outcomes research in orthopaedic surgery. The present study highlights the need to uniformly increase completion rates so that outcomes research incorporates truly representative cohorts of patients treated. Furthermore, the use of these PROMs to guide health-care policy decisions necessitates a representative patient distribution to avoid bias in the health-care system. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Effect of socio-economic status on the prevalence of dermatophytosis in Madras.
A total of 462 patients living in varying socio-economic conditions were screened for tinea infection. 372/462 (70.7%) were found to be culture positive for dermatophytes. Trichophyton rubrum was the most frequently isolated dermatophyte. 35% of the infected cases were from the very low income group (group-I), 34.2% from low income group (group-II), 23.3% from middle income group (group-III) and 1.8% from moderately rich group (group-IV). Recurrent, chronic and extensive dermatophytosis were found to be most common in group-I (20.3%) and group-II (17.8%), whereas localized infections were common in group-IV (66.6%) and group-III (65.7%). Recurrence chronicity were more frequent in tinea cruris and tinea corporis. The present study suggests that group-I and group-II may be the likely reservoirs of human ringworm infections in Madras.


Photographic polytene chromosome maps for Glossina morsitans submorsitans (Diptera: Glossinidae): cytogenetic analysis of a colony with sex-ratio distortion.
Photographic polytene chromosome maps from trichogen cells of pharate adult Glossina morsitans submorsitans were constructed. Using the standard system employed to map polytene chromosomes of Drosophila, the characteristic landmarks were described for the X chromosome and the two autosomes (L1 and L2). Sex-ratio distortion, which is expressed in male G. m. submorsitans, was found to be associated with an X chromosome (X8) that contains three inversions in each arm. Preliminary data indicate no differences in the fecundity of X(A)X(A) and X(A)X(B) females, but there are indications that G. m. submorsitans in colonies originating from Burkina Faso and Nigeria have genes on the autosomes and (or) the Y chromosome that suppress expression of sex-ratio distortion.


Investigating Effects of Bordered Pit Membrane Morphology and Properties on Plant Xylem Hydraulic Functions-A Case Study from 3D Reconstruction and Microflow Modelling of Pit Membranes in Angiosperm Xylem.
Pit membranes in between neighboring conduits of xylem play a crucial role in plant water transport. In this review, the morphological characteristics, chemical composition and mechanical properties of bordered pit membranes were summarized and linked with their functional roles in xylem hydraulics. The trade-off between xylem hydraulic efficiency and safety was closely related with morphology and properties of pit membranes, and xylem embolism resistance was also determined by the pit membrane morphology and properties. Besides, to further investigate the effects of bordered pit membranes morphology and properties on plant xylem hydraulic functions, here we modelled three-dimensional structure of bordered pit membranes by applying a deposition technique. Based on reconstructed 3D pit membrane structures, a virtual fibril network was generated to model the microflow pattern across inter-vessel pit membranes. Moreover, the mechanical behavior of intervessel pit membranes was estimated from a single microfibril's mechanical property. Pit membranes morphology varied among different angiosperm and gymnosperm species. Our modelling work suggested that larger pores of pit membranes do not necessarily contribute to major flow rate across pit membranes; instead, the obstructed degree of flow pathway across the pit membranes plays a more important role. Our work provides useful information for studying the mechanism of microfluid flow transport across pit membranes and also sheds light on investigating the response of pit membranes both at normal and stressed conditions, thus improving our understanding on functional roles of pit membranes in xylem hydraulic function. Further work could be done to study the morphological and mechanical response of bordered pit membranes under different dehydrated conditions, as well as the related microflow behavior, based on our constructed model.


Unusual foreign body in the nasal cavity of an adult with repaired cleft lip and palate.
Intranasal foreign bodies arising from dental clinical practice, especially in patients with cleft lip and palate (CLP) occur rarely and are very scarce in the literature. This article reports an unusual case of a dental impression material presenting as a foreign body in the nasal cavity of an adult with repaired CLP who presented for dental prosthetic rehabilitation. To our knowledge, this is only the second report presenting nasal foreign body in a cleft patient arising due to a dental impression procedure.


Three cases of severe acute hepatitis after parenteral administration of amiodarone: the active ingredient is not the only agent responsible for hepatotoxicity.
Amiodarone is one of the most effective antiarrhythmic drugs available and is widely prescribed despite several potentially life-threatening side-effects. Hepatotoxicity is the most frequent one during long-term oral therapy: occasionally acute hepatitis necessitates the suspension of treatment but monitoring of a transient increase in serum aminotransferases is usually sufficient; the clinical-morphological pictures of liver cirrhosis have also been reported. Fulminant hepatitis soon after a parenteral load of the drug is far less well described in the literature. Most published cases were reversible after the suspension of treatment. A negative challenge after oral amiodarone exposure suggested that polysorbate 80, a solvent added to the intravenous infusion and already implied in the pathogenesis of a similar syndrome observed in infants, is a more likely cause of this complication. The occurrence of acute hepatitis complicating parenteral amiodarone treatment does not preclude subsequent oral use of the drug: an evidence-based therapeutic behavior now definitively consolidated. Because of the rarity of this diagnosis, we report 3 cases of short-term hepatotoxicity secondary to amiodarone treatment for supraventricular tachyarrhythmias: in 2 male patients with dilated cardiomyopathy and in a female with liver disease. The diagnosis was presumptive and based on a thorough drug history, the temporal relationship, the time-course of liver dysfunction, the exclusion of other causes and on the rapid improvement observed after parenteral amiodarone withdrawal in 2 cases; in no case could we find any other explanation for the liver damage. Since amiodarone is sometimes still an irreplaceable antiarrhythmic drug, we raise the question of whether careful and continuous vigilance should be mandatory in patients receiving the drug or whether it is possible to introduce a pharmaceutical preparation not containing the vehicle that induces acute liver toxicity.


Insufficient sleep among elementary and middle school students is linked with elevated soda consumption and other unhealthy dietary behaviors.
This study examines the extent to which insufficient sleep is associated with diet quality in students taking part in the Massachusetts Childhood Obesity Research Demonstration Project. Data were collected in Fall 2012 for all 4th and 7th grade children enrolled in public schools in two Massachusetts communities. During annual body mass index (BMI) screening, students completed a survey that assessed diet, physical activity, screen time, and sleep. Of the 2456 enrolled students, 1870 (76%) had complete survey data. Generalized estimating equations were used to examine associations between sleep duration and dietary outcomes (vegetables, fruits, 100% juice, juice drinks, soda, sugar-sweetened beverages and water), accounting for clustering by school. Models were adjusted for community, grade, race/ethnicity, gender, television in the bedroom, screen time, and physical activity. In adjusted models, students who reported sleeping < 10 hours/day consumed soda more frequently (β = 0.11, 95% CI: 0.03, 0.20) and vegetables less frequently (β = -0.09, 95% CI: -0.18, -0.01) compared with students who reported ≥ 10 hours/day. No significant associations were observed between sleep duration and fruits, 100% juice, juice drinks or water. In this population, insufficient sleep duration was associated with more frequent soda and less frequent vegetable consumption. Longitudinal research is needed to further examine these relationships.


The Characteristics and Mortality of Chinese Herbal Medicine Users among Newly Diagnosed Inoperable Huge Hepatocellular Carcinoma (≥10 cm) Patients: A Retrospective Cohort Study with Exploration of Core Herbs.
For patients with inoperable huge hepatocellular carcinoma (H-HCC, tumor size ≥10 cm), treatment options are limited. This study aimed to evaluate the characteristics and outcomes of patients with H-HCC who use Chinese herbal medicine (CHM). Multi-institutional cohort data were obtained from the Chang Gung Research Database (CGRD) between 1 January 2002 and 31 December 2018. All patients were followed up for 3 years or until the occurrence of death. Characteristics of CHM users and risk of all-cause mortality were assessed, and core CHMs with potential pharmacologic pathways were explored. Among 1618 patients, clinical features of CHM users (88) and nonusers (1530) were similar except for lower serum α-fetoprotein (AFP) and higher serum albumin levels in CHM users. CHM users had significantly higher 3 year overall survival rates (15.0% vs. 9.7%) and 3 year liver-specific survival rates (13.4% vs. 10.7%), about 3 months longer median survival time, and lower risk of all-cause mortality. Core CHMs were discovered from the prescriptions, including Hedyotis diffusa Willd combined with Scutellaria barbata D.Don, Salvia miltiorrhiza Bunge., Curcuma longa L., Rheum palmatum L., and Astragalus mongholicus Bunge. CHM use appears safe and is possibly beneficial for inoperable H-HCC patients; however, further clinical trials are still required.


[The development of research on the effect of tobacco consumption on the visual organ over the last 200 years].
The purpose of the paper is to assess the development of research in the area of tobacco-related ocular diseases during the last 200 years. Although the first papers about the toxic effect of tobacco on the eye appeared in the beginnings of the XVIIth century, the real interest in this issue arose in the second half of the XIX century. Toxic neuropathy, often called tobacco amblyopia, was recognized as the most common ocular disease related to the use of tobacco. This disorder was described in hundreds of case histories by the most famous Polish and foreign ophthalmologists, for instance Szokalski, Gałezowski, and Sichel, Forster, Eales, DeSchweinitz, Uthoff, Gunn. In the XXth century, and particularly, in its second half, the incidence of tobacco amblyopia decreased, although the consumption of tobacco steadily increased in the same period. This phenomenon confirmed the conviction of the heterogeneous ethiopathogenesis of this disorder, including also alcohol intoxication, malnutrition, and especially vitamin deficiency. At the end of the XXth and at the beginning of the XXIst centuries evidence has been growing that tobacco smoking is a very serious risk factor in cataract, glaucoma, retinal vascular diseases, and most of all age-related macular degeneration. Although the incidence of toxic tobacco amblyopia is much lower than previously, tobacco smoking still remains the most powerful risk factor conducive to various eye diseases. Moreover, smoking being one of the most dangerous risk factors is at the same time the easiest one to eliminate in the prevention and treatment of eye diseases and blindness all over the world.


Identification of two distinct regions of allelic imbalance on chromosome 18Q in metastatic prostate cancer.
Like most cancers, prostate cancer (CaP) is believed to be the result of the accumulation of genetic alterations within cells. Previous studies have implicated numerous chromosomal regions with elevated rates of allelic imbalance (AI), using mostly primary CaPs with an unknown disease outcome. These regions of AI are proposed sites for tumor suppressor genes. One of the regions previously implicated as coding for at least one tumor suppressor gene is the long arm of chromosome 18 (18q). To confirm this observation, as well as to narrow the critical region for this putative tumor suppressor, we analyzed 32 metastatic CaP specimens for AI on chromosome 18q. Thirty-one of these 32 specimens (96.8%) exhibited AI at one or more loci on chromosome 18q. Our analysis using 17 polymorphic markers revealed statistically significant AI on chromosome 18q at 3 markers, D18S35, D18S64 and D18S461. Using these markers as a guide, we have been able to identify 2 distinct minimum regions of AI on 18q. The first region is between the genetic markers D18S1119 and D18S64. The second region lies more distal on the long arm of the chromosome and is between the genetic markers D18S848 and D18S58. To determine if 18q loss is a late event in the progression of CaP, we also examined prostatic intraepithelial neoplasia (PIN) and primary prostate tumors from 17 patients for AI with a subset of 18q markers. We found significantly higher AI in the metastatic samples. Our results are consistent with 18q losses occurring late in CaP progression.


Free-standing gold-nanoparticle monolayer film fabricated by protein self-assembly of α-synuclein.
Free-standing nanoparticle films are of great importance for developing future nano-electronic devices. We introduce a protein-based fabrication strategy of free-standing nanoparticle monolayer films. α-Synuclein, an amyloidogenic protein, was utilized to yield a tightly packed gold-nanoparticle monolayer film interconnected by protein β-sheet interactions. Owing to the stable protein-protein interaction, the film was successfully expanded to a 4-inch diameter sheet, which has not been achieved with any other free-standing nanoparticle monolayers. The film was flexible in solution, so it formed a conformal contact, surrounding even microspheres. Additionally, the monolayer film was readily patterned at micrometer-scale and thus unprecedented double-component nanoparticle films were fabricated. Therefore, the free-floating gold-nanoparticle monolayer sheets with these properties could make the film useful for the development of bio-integrated nano-devices and high-performance sensors.


Identification of multiple sites in the promoter region of the Tetrahymena pyriformis rRNA gene which bind the Escherichia coli catabolite regulatory protein.
The base sequence of the Tetrahymena pyriformis rRNA gene transcription initiation region has been reported (Niles, E. G., Sutiphong, J., and Haque, S. (1981) J. Biol. Chem. 256, 12849-12856). Upstream from the transcription initiation point, a collection of three families of highly conserved repeated sequences were identified, which may play a role in the expression of this gene. One of these families, repeat II, which has 10 members repeated in tandem, was recently observed to be strikingly similar in sequence to the Escherichia coli catabolite regulatory protein recognition site. In order to determine if these sequences can serve as catabolite regulatory protein binding sites, direct binding experiments were undertaken using a combination of the gel electrophoretic mobility alteration assay (Fried, M. G., and Crothers, D. M. (1983) Nucleic Acids Res. 11, 141-158) and DNA footprinting. DNA sequence-specific and cyclic AMP-dependent binding of catabolite regulatory protein to several of the apparent recognition sites has been demonstrated.


Recurrent unexplained hyperammonemia in an adolescent with arginase deficiency.
This report investigates the etiology of recurrent episodic elevations in plasma ammonia in an adolescent male with arginase deficiency as there were concerns regarding pre-analytical and analytical perturbations of ammonia measurements. There were repeated discrepancies between the magnitude of his ammonia levels and the severity of his clinical signs of hyperammonemia. The patient is a fourteen-year-old arginase-deficient male diagnosed at three years of age. Since 2008 (when he reached 10 years of age), there appeared to be an increase in the frequency of hospitalizations with elevated ammonia. A typical emergency visit with initial ammonia of 105 μmol/L (reference interval: 16-47 μmol/L) is illustrated. Pre-analytical and analytical procedures for the patient's sample handling were retrospectively examined. His ammonia levels were compiled since diagnosis. The frequency of his initial or peak ammonia levels greater than two times (94 μmol/L) or four times (188 μmol/L) the upper limit of normal was computed. Student t-test was used to calculate the significance of the differences before 2008 and since 2008. One out of eleven and ten out of 19 hospitalizations had initial ammonia greater than two times normal before and after 2008, respectively. Both the patient's overall ammonia and peak ammonia levels are significantly higher since 2008 (p value <0.001 for both) than those before 2008. To our knowledge, few adolescent males with arginase deficiency experience recurrent episodes of hyperammonemia requiring intravenous nitrogen scavenging agents. We hope that this study provides new insights into the natural history of arginase deficiency and the management of such patients.


Cisplatin augments cytotoxic T-lymphocyte-mediated antitumor immunity in poorly immunogenic murine lung cancer.
Many tumors are poorly immunogenic and resistant to cytotoxic T-lymphocyte-mediated cell lysis. Because cisplatin has been demonstrated to increase tumor cell Fas receptor expression, we hypothesized that cisplatin will enhance cytotoxic T-lymphocyte tumor cell killing and augment the antitumor effect of an active immunotherapy strategy in a poorly immunogenic murine lung cancer model. Lewis lung carcinoma cells were exposed to cisplatin in vitro, and Fas receptor expression and apoptosis in response to an agonistic anti-Fas antibody were quantified using flow cytometry. Wild-type and Fas ligand-deficient mice bearing Lewis lung carcinoma flank tumors were then treated with intraperitoneal cisplatin as well as an intratumoral injection of an adenovirus gene transfer vector encoding CD40 ligand. End points included tumor size, animal survival, and Fas expression (determined using immunofluorescence). Cytotoxicity assays were performed using splenocytes from adenovirus gene transfer vector encoding CD40 ligand-treated animals as effectors and cisplatin-treated Lewis lung carcinoma cells as targets. Cisplatin induced heightened expression of Fas receptor on Lewis lung carcinoma cells in vitro and in vivo and enhanced apoptosis in cells exposed to an agonistic anti-Fas antibody. In vivo, the combination of 1 dose of intraperitoneal cisplatin and intratumoral adenovirus gene transfer vector encoding CD40 ligand inhibited tumor growth and prolonged survival compared with adenovirus gene transfer vector encoding CD40 ligand alone, resulting in a higher cure rate. This effect was lost in Fas ligand-deficient mice. Splenocytes from adenovirus gene transfer vector encoding CD40 ligand-treated wild-type mice lysed cisplatin-treated Lewis lung carcinoma cells more efficiently than untreated Lewis lung carcinoma cells, an effect lost in splenocytes from Fas ligand-deficient mice. Cisplatin augments the antitumor effect of a cytotoxic T-lymphocyte-mediated immunotherapy strategy, resulting in a higher cure rate than seen with immunotherapy alone. This effect is associated with the enhanced ability of cytotoxic T lymphocytes to lyse tumor cells that have been exposed to cisplatin through Fas/Fas ligand interactions.


Novel Characterization of Constipation Phenotypes in ICR Mice Orally Administrated with Polystyrene Microplastics.
Indirect evidence has determined the possibility that microplastics (MP) induce constipation, although direct scientific proof for constipation induction in animals remains unclear. To investigate whether oral administration of polystyrene (PS)-MP causes constipation, an alteration in the constipation parameters and mechanisms was analyzed in ICR mice, treated with 0.5 μm PS-MP for 2 weeks. Significant alterations in water consumption, stool weight, stool water contents, and stool morphology were detected in MP treated ICR mice, as compared to Vehicle treated group. Also, the gastrointestinal (GI) motility and intestinal length were decreased, while the histopathological structure and cytological structure of the mid colon were remarkably altered in treated mice. Mice exposed to MP also showed a significant decrease in the GI hormone concentration, muscarinic acetylcholine receptors (mAChRs) expression, and their downstream signaling pathway. Subsequent to MP treatment, concentrations of chloride ion and expressions of its channel (CFTR and CIC-2) were decreased, whereas expressions of aquaporin (AQP)3 and 8 for water transportation were downregulated by activation of the mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB signaling pathway. These results are the first to suggest that oral administration of PS-MP induces chronic constipation through the dysregulation of GI motility, mucin secretion, and chloride ion and water transportation in the mid colon.


Docking of the proteasomal ATPases' carboxyl termini in the 20S proteasome's alpha ring opens the gate for substrate entry.
The 20S proteasome functions in protein degradation in eukaryotes together with the 19S ATPases or in archaea with the homologous PAN ATPase complex. These ATPases contain a conserved C-terminal hydrophobic-tyrosine-X motif (HbYX). We show that these residues are essential for PAN to associate with the 20S and open its gated channel for substrate entry. Upon ATP binding, these C-terminal residues bind to pockets between the 20S's alpha subunits. Seven-residue or longer peptides from PAN's C terminus containing the HbYX motif also bind to these sites and induce gate opening in the 20S. Gate opening could be induced by C-terminal peptides from the 19S ATPase subunits, Rpt2, and Rpt5, but not by ones from PA28/26, which lack the HbYX motif and cause gate opening by distinct mechanisms. C-terminal residues in the 19S ATPases were also shown to be critical for gating and stability of 26S proteasomes. Thus, the C termini of the proteasomal ATPases function like a "key in a lock" to induce gate opening and allow substrate entry.


Study of hypothermia on cultured neuronal networks using multi-electrode arrays.
Efficient and safe use of hypothermia during various neuro-medical procedures requires sound understanding of low temperature effects on the neuronal network's activity. In this report, we introduce the use of cultivated dissociated neuronal networks on temperature controlled multi-electrode arrays (MEAs) as a simple methodology for studying the long-term effects of hypothermia. The networks exhibit spontaneous activity in the form of synchronized bursting events (SBEs), followed by long intervals of sporadic firing. Through the use of our correlation method, these SBEs can be clustered into sub-groups of similar spatio-temporal patterns. Application of hypothermia to the network resulted in a reduction in the SBE rate, the spike intensity and an increase in inter-neuronal correlations. Within 2h following the cessation of hypothermia, the cultured network returned to its initial spatio-temporal SBE structure. These results suggest that the network survived cold exposure and demonstrate the feasibility of long-term continuous neural network recording during hypothermic conditions.


The Japan Morning Surge-1 (JMS-1) study: protocol description.
Morning blood pressure is reported to be more closely related to hypertensive organ damages such as left ventricular mass index, microalbuminuria and silent cerebral infarcts, than blood pressure at other times of the day. Morning blood pressure may play an important role in the pathogenesis of hypertensive target organ damage. Increased sympathetic nerve activity is reported to be one of the mechanisms of morning hypertension; however, there are no available data that show whether strict home blood pressure control, especially in the morning period, can reduce target organ damage. The Japan Morning Surge-1 (JMS-1) study includes hypertensive outpatients with elevated morning systolic blood pressure (>or=135 mmHg) as assessed by self-measured blood pressure monitoring at home. All enrolled patients are under stable antihypertensive medication status. Exclusion criteria are arrhythmia, chronic inflammatory disease, and taking alpha-blockers or beta-blockers. The target number of patients to be enrolled in the JMS-1 study is 600, and the aim is to evaluate differences in the markers of hypertensive target organ damage, such as brain natriuretic peptide and the urinary albumin excretion/creatinine ratio. All of the patients are randomized to an experimental group or a control group, with randomization to be carried out by telephone interviews with the patients' physicians. In the experimental group, patients begin taking additional antihypertensive medication just before going to bed. This consists of doxazosin 1 mg/day, which then is increased to 2 mg/day and 4 mg/day, with a beta-blocker added after a 1-month interval until the morning systolic blood pressure is controlled to less than 135 mmHg. Patients in the control group continue the treatment they are receiving at the enrollment for 6 months. Blood pressure levels, adverse effects, and hypertensive target organ damage before and after the study are evaluated. In the JMS-1 study, we will evaluate whether strict morning blood pressure control by sympathetic nervous system blockade using an alpha-blocker, doxazosin, and with the addition of a beta-blocker if needed, can reduce hypertensive target organ damage.


Valproate use in the older manic patient.
The authors present a case series of seven older (mean age = 66 years) state hospital patients treated with valproate as an adjunct to conventional medications. The patients had had affective disorder (chiefly bipolar disorder) for an average of 31 years. Most had been hospitalized at the state hospital for several years. Previous unsuccessful treatments had included lithium, carbamazepine, antipsychotics, benzodiazepines, and antidepressants and electroconvulsive therapy in one patient. After 1 month of adjunctive treatment, valproate led to marked improvement in three patients, moderate improvement in two, minimal improvement in one, and no change in one patient with delusional depression. Global Assessment Scale scores increased over baseline an average of 29 points (p = .01). Valproate proved to be safe in these older individuals, many of whom had several medical conditions.


Mental imagery, reasoning, and blindness.
Although reasoning seems to be inextricably linked to seeing in the "mind's eye", the evidence is equivocal. In three experiments, sighted, blindfolded sighted, and congenitally totally blind persons solved deductive inferences based on three sorts of relation: (a) visuo-spatial relations that are easy to envisage either visually or spatially, (b) visual relations that are easy to envisage visually but hard to envisage spatially, and (c) control relations that are hard to envisage both visually and spatially. In absolute terms, congenitally totally blind persons performed less accurately and more slowly than the sighted on all such tasks. In relative terms, however, the visual relations in comparison with control relations impeded the reasoning of sighted and blindfolded participants, whereas congenitally totally blind participants performed the same with the different sorts of relation. We conclude that mental images containing visual details that are irrelevant to an inference can even impede the process of reasoning. Persons who are blind from birth-and who thus do not tend to construct visual mental images-are immune to this visual-impedance effect.


Activities of daily living, chronic medical conditions, and health-related quality of life in older adults.
This study investigated associations between chronic medical conditions, activities of daily living (ADL), and health-related quality of life (HRQOL). Our findings suggest that the number of ADL limitations reported by older adults is associated with their HRQOL. Findings from our analyses also suggest that the association between having multiple comorbid conditions and HRQOL is stronger for those with no ADL limitations than those with at least some limitations. These data will aid practitioners in determining the relative importance of chronic medical conditions and ADL limitations on HRQOL and demonstrate how ADL limitations and comorbid conditions may differentially impact HRQOL.


Structural properties of Pb2MnW(1-x)Re(x)O6 double perovskites.
Pb2MnW(1-x)Re(x)O6 samples have been synthesized and their structure determined by powder x-ray diffraction. These samples undergo a first order structural phase transition between 413 and 445 K depending on the composition. Above this temperature, the samples are cubic. Below the transition temperature, solid solutions are found for x ≤ 0.2 and x ≥ 0.5. The W-rich samples adopt an orthorhombic cell whereas the Re-rich compounds are monoclinic. In the intermediate region, 0.2 < x < 0.5, both phases coexist. X-ray absorption spectra did not reveal significant changes in the local structure for Pb, Mn or Re atoms across the structural phase transition. All the atoms exhibit distorted environments in the whole series. In the case of Pb and W(Re) atoms, the local distortion remains in the high temperature phase. Samples with x ≤ 0.2 also show a sharp discontinuity in the dielectric permittivity at the phase transition temperature indicating the presence of a concomitant electrical ordering in the bulk grains. Such an anomaly in the dielectric constant is not observed for the x ≥ 0.5 samples, compatible with the lack of dipole ordering for this composition range. The different electrical behaviours also explain the differences in the entropy content for the two types of transition.


Neuronal-Activity Dependent Mechanisms of Small Cell Lung Cancer Progression.
Neural activity is increasingly recognized as a critical regulator of cancer growth. In the brain, neuronal activity robustly influences glioma growth both through paracrine mechanisms and through electrochemical integration of malignant cells into neural circuitry via neuron-to-glioma synapses, while perisynaptic neurotransmitter signaling drives breast cancer brain metastasis growth. Outside of the CNS, innervation of tumors such as prostate, breast, pancreatic and gastrointestinal cancers by peripheral nerves similarly regulates cancer progression. However, the extent to which the nervous system regulates lung cancer progression, either in the lung or when metastatic to brain, is largely unexplored. Small cell lung cancer (SCLC) is a lethal high-grade neuroendocrine tumor that exhibits a strong propensity to metastasize to the brain. Here we demonstrate that, similar to glioma, metastatic SCLC cells in the brain co-opt neuronal activity-regulated mechanisms to stimulate growth and progression. Optogenetic stimulation of cortical neuronal activity drives proliferation and invasion of SCLC brain metastases. In the brain, SCLC cells exhibit electrical currents and consequent calcium transients in response to neuronal activity, and direct SCLC cell membrane depolarization is sufficient to promote the growth of SCLC tumors. In the lung, vagus nerve transection markedly inhibits primary lung tumor formation, progression and metastasis, highlighting a critical role for innervation in overall SCLC initiation and progression. Taken together, these studies illustrate that neuronal activity plays a crucial role in dictating SCLC pathogenesis in both primary and metastatic sites.


Comparing the demonstration of freedom from Trichinella infection of domestic pigs by traditional and risk-based surveillance.
Traditionally, the routine artificial digestion test is applied to assess the presence of Trichinella larvae in pigs. However, this diagnostic method has a low sensitivity compared to serological tests. The results from artificial digestion tests in Switzerland were evaluated over a time period of 15 years to determine by when freedom from infection based on these data could be confirmed. Freedom was defined as a 95% probability that the prevalence of infection was below 0.0001%. Freedom was demonstrated after 12 years at the latest. A new risk-based surveillance approach was then developed based on serology. Risk-based surveillance was also assessed over 15 years, starting in 2010. It was shown that by using this design, the sample size could be reduced by at least a factor of 4 when compared with the traditional testing regimen, without lowering the level of confidence in the Trichinella-free status of the pig population.


[Ductal carcinomas in situ].
Presently representing 15 to 30% of new cases of breast cancer, ductal carcinomas in situ do not have specific epidemiological characteristics. The age at which they occur is between 49 and 54 years. The diagnosis is evoked primarily when confronted with an area of micro-calcifications discovered on a mammography. Needle aspiration cytology, useful in cases of palpable abnormalities or infra-clinical masses, is of no interest in isolated micro-calcifications for which surgical biopsy following radiological localisation is the technique of choice. Needle micro-biopsy permits collecting analysable tissue for histological but not cytological examination. Macro-biopsies combine stereotaxic localisation of micro-calcification areas and their excision when isolated. The choice of the method varies depending on the case. Ductal or intra-galactophoric carcinomas are carcinomas of the glactophores that do not infiltrate the connective tissue. They are defined histologically by architectural and cytological characteristics, which differentiate them from lobular carcinomas in situ. They constitute a group of heterogenic lesions not only morphologically but also histologically and with regard to their progression. The aim of treatment is to ensure that the patients have a maximum of chances of cure at the cost of the least possible therapeutic consequences. Mastectomy, treatment of choice for many years, is still recommended in certain situations. In other cases, conservative treatment is possible so long as excision of the micro-calcifications is complete on the post-surgical mammography and, in the case of biopsy excision, that healthy margins of at least 10 millimetres exist. Following surgery, there is no sufficient consensus to propose essential recommendations concerning the place of monitoring alone, irradiation or tamoxifen.


Suicidality and mood disorders in psychiatric emergency patients: Results from SBQ-R.
Patients with mood disorders are at high risk of suicidality, and emergency departments (ED) are essential in the management of this risk. This study aims to (1) describe the suicidal thoughts and behaviours of patients with mood disorders who come to ED; (2) assess the psychometric properties of the Suicidal Behaviours Questionnaire-Revised (SBQ-R) in a psychiatric ED; and (3) determine the best predictors of suicidality for these patients. A total of 300 participants with mood disorders recruited for the Signature Bank of the Institut universitaire en santé mentale de Montréal (IUSMM) were retained. Suicidality was assessed using the SBQ-R. Other clinical and demographic details were recorded. Bivariate analyses, correlations and multivariate regression analyses were conducted. SBQ-R's internal consistency, construct and convergent validities were also tested. In the Patient Health Questionnaire-9 (PHQ-9), 53.3% of the sample stated they had suicidal or self-harm thoughts in the last 2 weeks. The mean score obtained at the SBQ-R was 8.3. Multivariate analysis found that SBQ-R scores were associated with depressive symptoms and substance use, especially alcohol, accounting for 44.3% of the model variance. Cronbach's alpha was 0.81 [0.78, 0.84] and factor loadings for items 1-4 were 0.68, 0.88, 0.54, and 0.85, respectively. The confirmatory factor analysis indicated that the model fit the data well. The SBQ-R is a brief and valid instrument that can easily be used in busy emergency departments to assess suicide risk. Depressive symptoms and alcohol use shall also be assessed, as they are determinants of increased risk of suicidality.


Strategic identities in cyberspace.
This paper aims at describing, according to the recent advances in social psychology and Computer Mediated Communication, how identities are perceived and constructed in cyberspace. All interactions analyzed in this study were performed within "Euroland," a collaborative virtual environment. The interacting community was composed of students, teachers, and researchers working on a transnational educational project. Practices and dialogues within Euroland are analyzed using an ethnographic and conversational method. A sample of discourses and actions that occurred during 8 months of time, selected according to the research aims, was analyzed. During online connections, users were personified by an "Avatar." Avatars are able to walk, fly, and look around the virtual world. They are also able to build and manipulate three-dimensional objects, perform virtual actions, and chat with other connected users. Results showed that "Eurolanders" showed and constructed their identities using strategic "positioning" depending on the interactive situation. Identities are thus dynamic and strongly related to the context, created and constantly recreated by the users. It is concluded that specific features offered by the Euroland environment are exploited by the users as resources to play with, while moving from one strategic positioning to another. Cyber identities involve resources given by specific technological tools and by community. The cyber-identity construction process seems to be highly congruent to the advances in the dialogical perspective in psychology, where identities are considered in their conceptualizations as multiple, "multivoiced," "positioned," and context-dependent.


Development of a compact efficient 10 Hz 20 TW Ti:sapphire laser system with a 1 kHz regenerative amplifier.
We have constructed a compact efficient Ti:sapphire laser system that generates 30 fs, 630 mJ pulses at a repetition rate of 10 Hz. A new geometry for a single-stage multipass power amplifier is proposed that greatly weakens and even makes use of thermal lensing. Such geometry can realize high output in a single-stage power amplifier; otherwise at least two-stage power amplifiers are required. The new configuration simplifies the laser system and reduces the cost. The key point in this design is that the beam spot size evolution is considered in combination with the pulse amplification.


[Diffusion-weighted imaging of acute vertebral compression: Differential diagnosis of benign versus malignant pathologic fractures].
Our purpose was to assess the value of diffusion-weighted steady-state free precession (SSFP) sequence for differentiating between benign and pathologic compression fractures. Forty-nine patients with 63 acute vertebral compression fractures caused by osteoporosis (n = 23), trauma (n = 7), malignancy (n = 30), infection (n = 3) were examined with a diffusion-weighted SSFP sequence (diffusion gradient strength; 23 mT/m, diffusion pulse length 5 ms), T1-weighted turbo spin-echo sequence, and short-inversion-time (TI 150 ms) T2-weighted turbo inversion recovery sequence. The signal intensity characteristics were analyzed qualitatively and quantitatively for all sequences. Statistical analysis was performed with the Student's t test. In diffusion-weighted MR imaging, benign osteoporotic and traumatic fractures were hypo- to isointense to adjacent normal vertebral bodies. Pathologic and infectious compression fractures were hyperintense to normal vertebral bodies. Pathologic vertebral fractures had positive bone marrow contrast ratios at diffusion-weighted imaging, whereas non infectious benign vertebral fractures had negative values (p < 0.001). The difference in bone marrow contrast ratios for benign and pathologic compression fractures at T1-weighted TSE and T2-weighted turbo IR was not significant (p > 0.01). Diffusion-weighted SSFP sequence provides unique information that significantly impacts the accuracy of radiologic diagnosis. Diffusion-weighted SSFP sequence may allow the differentiation of acute benign osteoporotic fractures from malignant compression fractures. Acute benign osteoporotic or traumatic fractures show hypointense or isointense signal on diffusion-weighted sequences that reflects persistent free water proton mobility. Malignant compression fractures show hyperintensity compared with normal surrounding bone marrow probably due to altered water proton mobility within the neoplasm.


[Assessment of hydration on the stratum corneum and the influencing factors in neonates].
The study was conducted to investigate the skin hydration level in various body sites and identify the influencing factors in neonates. An exploratory comparison study was designed to measure the stratum corneum hydration, using a National DM-R2 on the forehead, abdomen, buttocks, and the back of the hands and feet of 198 neonates including 92 premature infants. The results showed 32.7%-36.5% of stratum corneum hydration for all sites. Premature infants revealed a higher hydration level on the peripheral sites (dorsal hand and feet) than those of the full-term infants, possibly resulting from therapeutic regimens including an incubator or radiant warmer. Infants in an incubator showed a higher hydration level than those in radiant warmers, suggesting more attention to fluid management for infants in the open environment. In addition, all stratum corneum hydration measurements except one, from the forehead, showed a positive correlation with postnatal age in full-term infants while showing no relation to any measurements in premature infants. The study demonstrated the very low skin hydration levels in hospitalized neonates, particularly in premature neonates with more susceptible skin hydration instability despite therapeutic interventions for fluid balance. More vigilant fluid management is imperative in neonates, particularly those in the open environment.


Magnetic resonance imaging assessment of ventricular dyssynchrony: current and emerging concepts.
Despite the numerous documented benefits of cardiac resynchronization therapy (CRT), a significant proportion of patients undergoing CRT do not demonstrate symptomatic or morphologic improvement, triggering the search to improve targeting of this therapy. Many studies now support direct assessment of mechanical dyssynchrony as a method to better identify CRT responders. Among the methods used, echo-Doppler imaging has taken center stage and is covered in other articles in this special issue; however, these methods have several inherent limitations, and other alternatives are also being explored such as magnetic resonance imaging (MRI). This review discusses the concepts and clinical use of MRI methods for quantitative assessment of mechanical dyssynchrony, highlighting newer acquisition and analysis methods and focusing on how the data can be synthesized into robust indexes of dyssynchronous heart failure.


Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6.
Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of drugs such as bupropion, efavirenz, propofol, and selegiline, among others. More than 200 commonly prescribed drugs and other xenobiotics were examined for their ability to inhibit CYP2B6-mediated bupropion hydroxylase activity. Thirty compounds were found exhibiting greater than 50% inhibition at 30 microM. Inhibitors of CYP2B6 were identified from a wide variety of therapeutic classes. The 2 platelet aggregation inhibitors, clopidogrel and ticlopidine, were both identified as potent inhibitors (IC50 = 0.0206 and 0.149 microM, respectively). Other inhibitors (IC50 < 1 microM) included clotrimazole, itraconazole, sertraline, and raloxifene. These in vitro data were used along with clinical pharmacokinetic information in the prediction of potential drug-drug interactions that could occur by inhibition of CYP2B6. Although few drugs tested are expected to cause drug interactions, clopidogrel and ticlopidine were identified as being of concern as potential inhibitors of clinical relevance. These findings are discussed in context to potential drug interactions that could be observed between these agents and drugs for which CYP2B6 is involved in metabolism.


Assessment of osteoporosis using standard radiographs of the wrist.
This study evaluated the ability of the orthopaedic surgeon to radiographically assess bone density in the wrist with sufficient accuracy to determine which patients require treatment for osteoporosis. Thirty-eight patients with unilateral distal radius fractures, 30 of whom were female, were included in this study. The mean age was 55 years (range 45 to 82). Standard radiographs of the fractured and normal wrists were taken. Dual energy x-ray absorptiometry was performed on the normal distal radius of all patients within 1 week of their injury. The radiographs were viewed in blinded randomized fashion on two separate occasions by three orthopaedic surgeons and once by a fourth. The participants were required to determine the presence of osteoporosis. Visual analog scales (VAS) were used to evaluate (1) porosity, (2) cortical thickness, (3) trabecular thickness, and (4) the number of trabeculae in the ultradistal radius. Intraobserver agreement assessing osteoporosis averaged 81% (kappa of 0.5393). VAS assessment was unreliable for all four parameters. Radiographic determination of osteoporosis had a specificity of 61% and a sensitivity of 61% using x-rays of the uninjured wrist. We conclude that orthopaedic surgeons cannot predict with sufficient accuracy using plain x-rays whether a patient is significantly osteoporotic.


The application of reporter gene assays for the detection of endocrine disruptors in sport supplements.
The increasing availability and use of sports supplements is of concern as highlighted by a number of studies reporting endocrine disruptor contamination in such products. The health food supplement market, including sport supplements, is growing across the Developed World. Therefore, the need to ensure the quality and safety of sport supplements for the consumer is essential. The development and validation of two reporter gene assays coupled with solid phase sample preparation enabling the detection of estrogenic and androgenic constituents in sport supplements is reported. Both assays were shown to be of high sensitivity with the estrogen and androgen reporter gene assays having an EC(50) of 0.01 ng mL(-1) and 0.16 ng mL(-1) respectively. The developed assays were applied in a survey of 63 sport supplements samples obtained across the Island of Ireland with an additional seven reference samples previously investigated using LC-MS/MS. Androgen and estrogen bio-activity was found in 71% of the investigated samples. Bio-activity profiling was further broken down into agonists, partial agonists and antagonists. Supplements (13) with the strongest estrogenic bio-activity were chosen for further investigation. LC-MS/MS analysis of these samples determined the presence of phytoestrogens in seven of them. Supplements (38) with androgen bio-activity were also selected for further investigation. Androgen agonist bio-activity was detected in 12 supplements, antagonistic bio-activity was detected in 16 and partial antagonistic bio-activity was detected in 10. A further group of supplements (7) did not present androgenic bio-activity when tested alone but enhanced the androgenic agonist bio-activity of dihydrotestosterone when combined. The developed assays offer advantages in detection of known, unknown and low-level mixtures of endocrine disruptors over existing analytical screening techniques. For the detection and identification of constituent hormonally active compounds the combination of biological and physio-chemical techniques is optimal.


[Study of correlation between urinary IL-6 level and mesangial lesion in childhood onset IgA nephropathy].
In the present study, urinary IL-6 levels in 28 patients with IgA nephropathy (IgAN), 10 patients with idiopathic minimal change nephrotic syndrome (IMCNS) and 11 normal controls were measured using by an ELISA method to clarify the role of IL-6 as an autocrine growth factor of mesangial cells. Spot urine was centrifuged at 1000 rpm for 10 minutes at 4 degrees C and the supernatant was utilized as samples. The patients with IgAN were classified into three groups, group I (18 patients); minor glomerular abnormalities, group II (5 patients); focal segmental lesions, group III (5 patients); diffuse glomerulonephritis, according to the WHO classification of glomerular diseases. Geometric mean +/- S.E. of urinary IL-6 was 1.619 +/- 0.075 in patients with IgAN (group I; 1.432 +/- 0.078, group II; 1.920 +/- 0.181 and group III; 1.987 +/- 0.055), 0.681 +/- 0.174 in IMCNS and 0.506 +/- 0.181 in normal controls, respectively. Urinary IL-6 levels were significantly elevated in patients with IgAN than in IMCNS and normal controls, but did not necessarily reflect the severity of mesangial lesions. Some patients with prominent segmental mesangial proliferation in group II showed much higher urinary IL-6 levels than those in group III. Elevated urinary IL-6 levels in group II may be involved in higher activity of mesangial proliferation, and the decreased production of IL-6 observed in some patients of group III may related to advanced glomerular sclerosis. The results suggests that IL-6 plays an important role as a mesangial proliferative growth factor in IgAN and that measurement of urinary IL-6 levels by an ELISA method is a useful method to estimate the degree of mesangial proliferation and disease activities easily and noninvasively in patients with IgAN.


Immune suppression and isolated severe head injury: a significant clinical problem.
In the developed world, trauma is the principal cause of death under the age of 40 and is the third largest overall killer. In the UK, approximately 25,000 people die each year as a result of major injury, 25% as a result of head injuries alone. Despite improved diagnosis and management, infection remains the commonest complication in those patients surviving the initial injury. Some 5% are reported to die as a result of septic complications. Prolonged periods of intensive care and respiratory support predispose to infective respiratory complications. These patients in the absence of significant systemic injury and, as a result of severe head injury, are unable to mount an effective immune response. This literature review examines the changes that have been reported to occur in the immune system following isolated severe head injury and explores the relationship these changes may have to the increased development of infective complications.


Refractive index and diameter determinations of step index optical fibers and preforms.
A new method to determine the index of refraction in combination with the diameter of the cores of stepindex optical fibers and preforms is presented. The technique is based on an analysis of the backscattered light when a beam from a cw laser impinges transversely upon the fiber or preform. A geometrical-optics analysis shows that, under appropriate assumptions, a combination of the refractive indexes and the radii of the core and cladding can be determined from unique characteristics of the backscattered radiation pattern. The theory is compared to experimental observations with excellent agreement.


Neuromuscular defects and breathing disorders in a new mouse model of spinal muscular atrophy.
Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein leading to muscle paralysis and respiratory failure. In mouse, introducing the human SMN2 gene partially rescues Smn(-)(/)(-) embryonic lethality. However current models were either too severe or nearly unaffected precluding convenient drug testing for SMA. We report here new SMN2;Smn(-/-) lines carrying one to four copies of the human SMN2 gene. Mice carrying three SMN2 copies exhibited an intermediate phenotype with delayed appearance of motor defects and developmental breathing disorders reminiscent of those found in severe SMA patients. Although normal at birth, at 7 days of age respiratory rate was decreased and apnea frequency was increased in SMA mice in parallel with the appearance of neuromuscular junction defects in the diaphragm. With median survival of 15 days and postnatal onset of neurodegeneration, these mice could be an important tool for evaluating new therapeutics.