E6AP and calmodulin reciprocally regulate estrogen receptor stability.
Estrogen promotes the proliferation of human breast epithelial cells by interacting with the estrogen receptor (ER). Physiological responses of cells to estrogen are regulated in part by degradation of the ER. Previous studies revealed that calmodulin binds directly to the ER, thereby enhancing its stability. Consistent with these findings, cell-permeable calmodulin antagonists dramatically reduced the number of ER in MCF-7 human breast epithelial cells. Here we investigated the molecular mechanism by which calmodulin attenuates ER degradation. MG132 and lactacystin, inhibitors of the ubiquitin-proteasome pathway, prevented the calmodulin antagonist CGS9343B from reducing the amount of ER in MCF-7 cells. In contrast, protease inhibitors afforded no protection. Moreover, CGS9343B enhanced ER ubiquitination. A point mutant ER construct that is unable to bind calmodulin, termed ERDeltaCaM, is ubiquitinated to a greater extent than wild type ER. The ubiquitin-protein isopeptide ligase E6-associated protein (E6AP) associated with and promoted the degradation of ER. The possible convergence of calmodulin and E6AP on ER degradation was examined. ERDeltaCaM bound E6AP with higher affinity than that of wild type ER. Moreover, calmodulin attenuated the in vitro interaction between ER and E6AP in a Ca(2+)-dependent manner. Collectively, our data reveal that E6AP is a component of ER degradation via the ubiquitin-proteasome pathway and that Ca(2+)/calmodulin modulates this degradation mechanism. These results have potential implications for the development of selectively targeted therapeutic agents for breast cancer.


Fast and high yield post-synthetic modification of metal-organic frameworks by vapor diffusion.
Vapor-phase post-synthetic modification (VP-PSM) is herein described. VP-PSM is a tool that overcomes limitations of standard PSM methods by giving a higher yield in short reaction times and will give more flexibility in designing metal-organic frameworks with functionalization for chemical and physical applications.


Developing chemically modified redox-responsive proteins as smart therapeutics.
The conditional control of protein function in response to the physiological changes of diseased cells is essential to develop smart protein therapeutics. Herein, we report a redox-responsive chemical modification of a protein by conjugating an intracellular glutathione (GSH)-cleavable ligand, NSA, onto a protein residue. We demonstrated that the NSA conjugation of Ribonuclease A (RNase A) enabled the control of the protein function by GSH in an aqueous solution and living cells, with extended applications for targeted cancer therapy using a lipid nanoparticle-based intracellular protein delivery strategy.


Incidence of psychotic disorders in immigrant groups to The Netherlands.
Previous reports on the incidence of schizophrenia in immigrant groups to The Netherlands were based on hospital data. To compare the incidence of psychotic disorders in the immigrant groups to that in natives. Two-year first-contact incidence study in The Hague. The risks of schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV criteria) were increased for subjects born in Morocco (gender and age-adjusted relative risk=4.5; 95% Cl 1.4-8.5), Surinam (relative risk=3.2; 1.8-5.7), The Netherlands Antilles (relative risk=2.9; 0.9-9.5) and other non-Western countries (relative risk=2.4; 1.3-4.7). This risk was also increased for Moroccans (relative risk=8.0; 2.6-24.5) and Surinamese (relative risk=5.5; 2.5-11.9) of the second generation. The risks for Turkish immigrants, first or second generation, and for immigrants from Western countries were not significantly increased. This study indicates that the incidence of schizophrenia is increased in several, but not all, immigrant groups to The Netherlands. It is possible that factors associated with a process of rapid westernisation precipitate schizophrenia in people who are genetically at risk.


New anti-seizure medication for elderly epilepsy patients - a critical narrative review.
Introduction: The number of elderly patients with epilepsy is growing in resource rich countries due to demographic changes and increased longevity. Management in these patients is challenging as underlying etiology, co-morbidities, polypharmacy, age-related pharmacokinetic and pharmacodynamic changes need to be considered.Areas covered: Lacosamide, eslicarbazepine acetate, brivaracetam, and perampanel have been approved in the USA and Europe for monotherapy and/or adjunctive treatment of seizures in the last few years. The authors review the pharmacological properties and safety profile of these drugs and provide recommendations for their use in in the elderly.Expert opinion: There are only limited data available on more recent antiseizure medications (ASMs). Drugs with a low risk of interaction (lacosamide, brivaracetam) are preferred choices. Once daily formulations (perampanel and eslicarbazepine acetate) have the advantage of increased compliance. Intravenous formulations (brivaracetam and lacosamide) are useful in emergency situations and in patients who have difficulties to swallow. Dose adjustments are necessary for all ASMs used in the elderly with slow titration and lower target doses than in the regulatory trials. The adverse event profile does not significantly differ from that found in the general adult population.


A SERS-based sandwich assay for ultrasensitive and selective detection of Alzheimer's tau protein.
In this study, a simple and highly selective homogeneous sandwich assay was developed for fast and ultrasensitive detection of the tau protein using a combination of monoclonal antitau functionalized hybrid magnetic nanoparticles and polyclonal antitau immobilized gold nanoparticles as the recognition and surface-enhanced Raman scattering (SERS) component, respectively. The magnetic silica particles were first coated with poly(2-hydroxyethyl methacrylate) via surface-mediated reversible addition-fragmentation chain transfer (RAFT) polymerization and then biofunctionalized with monoclonal antitau, which are both specific for tau and can be collected via a simple magnet. After separating tau from the sample matrix, they were sandwiched with the SERS substrate composed of polyclonal antitau and 5,5-dithiobis(2-dinitrobenzoic acid) on gold nanoparticles. The correlation between the tau concentration and SERS signal was found to be linear within the range of 25 fM to 500 nM. The limit of detection for the sandwich assay is less than 25 fM. Moreover, the sandwich assay was also evaluated for investigating the tau specificity on bovine serum albumin and immunoglobulin G.


Inhibition of histone deacetylase causes reduction of appressorium formation in the rice blast fungus Magnaporthe oryzae.
Post-translational modifications (PTMs) are important for cellular functions. The regulation of histone acetyltransferases (HATs) and histone deacetylases (HDACs) is one of important PTMs for epigenetic control, protein activity and protein stability. The regulation of acetylation of the N-terminal histone tails of core histone affects gene expression. Two class I HDAC genes and two class II HDAC genes have been identified in the Magnaporthe oryzae genome. Treatment with Rpd3/Hda1 family (classical) HDAC inhibitor inhibited the appressorium differentiation of M. oryzae. Treatment with trichostatin A, a classical HDAC inhibitor, also decreased pathogenesis. Furthermore, analyses of HDAC mutants indicated that MoHda1 and MoHos2 were required for vegetative growth and conidiation, and MoHos2 was required for appressorium formation. Disruption MoRPD3 was unsuccessful, as in the case with Aspergillus nidulans RpdA. These data indicated that HDACs have important roles in the asexual differentiation of M. oryzae.


The clinical application of pain neuroscience, graded motor imagery, and graded activity with complex regional pain syndrome-A case report.
Chronic Regional Pain Syndrome (CRPS) is a condition that physical therapists may encounter in an outpatient orthopedic setting. In physical therapy (PT) treatment of CRPS addresses pain and the changes observed in the brain through the use of graded motor imagery (GMI). A 57-year-old female presented to an outpatient PT clinic with CRPS type 1. Complicating psychosocial factors such as kinesiophobia and catastrophization were present. The patient engaged in a treatment plan including GMI: pain neuroscience education (PNE), laterality training, motor imagery, and mirror training. As symptoms improved, graded functional exposure and functional restoration occurred. The patient was seen for a total of 26 visits over a 9-month period. FAAM measures exceeded reported clinically important change that was sustained at two-year follow-up. Long term outcomes showed no functional deficits related to her foot or ankle and minimal to no catastrophizing and fear avoidance behaviors. This case report showcases the use of GMI with a patient with CRPS type 1 in an outpatient orthopedic clinic. Clinicians may consider the use of GMI to progress a patient toward maximal functional gains.


The role of amygdala and hypothalamus in GABAA antagonist bicuculline-induced cardiovascular responses in conscious rats.
gamma-Aminobutyric acid (GABA) is known to play an important role in the central control of cardiovascular functions. GABAergic agonists and antagonists elicit blood pressure and heart rate changes when injected into the brain. It was demonstrated here that bicuculline methiodide (BMI), a GABAA antagonist, caused dose-dependent increases in both blood pressure and heart rate in conscious rats when injected intracerebroventricularly. The roles of the central nucleus of the amygdala (CeA), the paraventricular nucleus (PVN) and the dorsomedial nucleus (DMH) of the hypothalamus in BMI-induced blood pressure and heart rate changes were investigated in this study. The pressor effect of BMI was significantly attenuated by the electrolytic ablation of DMH and PVN, whereas it was only slightly, but insignificantly reduced by CeA lesions. The microinjection of BMI into the DMH and the PVN elicited significant pressor and tachycardic responses whereas only a slight increase was observed in rats injected BMI into the CeA. The BMI-induced increases in both blood pressure and heart rate were more prominent when given into the DMH. These results indicate that the DMH plays an important role in GABAergic control of cardiovascular functions. The PVN and CeA seem to have a minor part in this respect.


Enhancement of visual attention precedes the emergence of novel metaphor interpretations.
Emergence of creative ideas often involves sudden linking of unrelated ideas. Here we demonstrate that the production of insights about novel metaphor was preceded by prolonged visual inspection of metaphorical sentences. The participants made free spoken responses in a task requiring the generation of semantic interpretations about visually presented sentences, where gaze locations were continuously monitored. We found that creative interpretations were primarily generated from novel metaphorical expressions, rather than from conventional expressions. Moreover, presented words within novel metaphors were visually inspected for longer periods specifically before creative interpretations were produced. Interestingly, prolonged gazes occurred several seconds (∼8 s) prior to the generation of creative interpretations, particularly, in the case of the topic word within the metaphor. These results demonstrate latent cognitive process meditating the emergence of insights, and suggest that the prior visual inspection prompted the semantic representation of the metaphorical sentences, which eventually facilitates creative ideas.


Effect of temperature on the electron paramagnetic resonance spectrum of irradiated alanine.
Polycrystalline samples of the amino acid L-alpha-alanine have been irradiated with X rays at both room temperature and higher temperatures. The electron paramagnetic resonance (EPR) spectra of alanine powder irradiated at room temperature are dominated by the well-known room-temperature-stable alanine radical CH3C*HCOOH. Upon heating of room-temperature-irradiated alanine powder, a strong decay of the signal was observed, and the features of the spectrum recently ascribed to a second stable radical in alanine irradiated at room temperature become more pronounced, providing an experimental isolation of this second alanine radical. In combination with the high-temperature experiments, a multivariate statistical decomposition method, maximum likelihood common factor analysis, was used to determine the number of components in irradiated alanine powder which behave differently as a function of temperature. The EPR components found in the present study are compared with simulations using earlier EPR and ENDOR single-crystal data.


ELISA-Based Detection System for Protein S K196E Mutation, a Genetic Risk Factor for Venous Thromboembolism.
Protein S (PS) acts as a cofactor for activated protein C in the plasma anticoagulant system. PS Lys196-to-Glu (K196E) mutation is a genetic risk factor for venous thromboembolism in Japanese individuals. Because of the substantial overlap in PS anticoagulant activity between KK (wild-type) and KE (heterozygous) genotypes, it is difficult to identify PS K196E carriers by measuring PS activity. Here, we generated monoclonal antibodies specific to the PS K196E mutant and developed a simple and reliable method for the identification of PS K196E carriers. We immunized mice with a keyhole limpet hemocyanin-conjugated synthetic peptide with Glu196. The hybridoma cells were screened for the binding ability of the produced antibodies to recombinant mutant EGF-like domains of PS (Ile117-Glu283). We obtained three hybridoma cell lines producing PS K196E mutation-specific antibodies. We established a sandwich enzyme-linked immunosorbent assay (ELISA) system in which the PS K196E mutation-specific monoclonal antibody was used as a detection antibody. We measured human plasma samples by using this system and successfully discriminated 11 individuals with the KE genotype from 122 individuals with the KK genotype. The ELISA system using the PS K196E mutation-specific antibody is a useful tool for the rapid identification of PS K196E carriers, who are at a higher risk for venous thromboembolism.


Feeding dynamics and ecomorphology of Oligosarcus jenynsii (Gunther, 1864) and Oligosarcus robustus (Menezes, 1969) in the Lagoa Fortaleza, southern Brazil.
Oligosarcus jenynsii and Oligosarcus robustus are fishes of Characidae family that occur in Rio Grande do Sul, Uruguay and northern Argentina. This work purported to study the feeding dynamics (repletion and hepatosomatic indexes and condition factor) over time, and to investigate the coexistence of these two species by evaluating the partition of resources using qualitative and quantitative analyses of diet, temporal and spatial segregation throughout the water column and some ecomorphological aspects of the species in the Lagoa Fortaleza. Specimens were sampled monthly, from May 2000 to April 2001 during 24 h/month, using stationary gill nets of different mesh sizes. The records of each individual included total and standard length; total, stomach and liver weight; sex and stomach repletion. The variation of the mean values of repletion index and relative frequencies of stomach repletion stages indicate that O. jenynsii and O. robustus do not present seasonal differences in feeding intensity. The hepatosomatic index shows an allocation of energy to the liver during every period except reproduction, when part of the energy is used for gonad maturation. The estimated condition factor for both species reveals an increase in the reproductive period, evidencing the influence of gonads upon the condition of the fish. The diet analysis revealed that O. robustus is piscivorous, whereas O. jenynsii is a generalist carnivore, tending to piscivory as well. The active period of O. robustus is more concentrated at sunrise and sunset, whereas O. jenynsii is continually active, a characteristic related to hunting for prey. The ecomorphological analysis revealed differences between the two species in the dimensions of the mouth. Evidence suggests that the species coexist, sharing food sources, differing in oral morphology but ingesting similar prey, possibly because food is not a limiting factor in the environment.


Genome Sequencing and Analysis of the Postharvest Fungus Penicillium expansum R21.
Blue mold is the vernacular name of a common postharvest disease of stored apples, pears, and quince that is caused by several common species of Penicillium This study reports the draft genome sequence of Penicillium expansum strain R21, which was isolated from a red delicious apple in 2011 in Pennsylvania.


Skin assessment in adults.
The skin has often been described in fictional literature as the window to the soul. It is the largest organ in the body and integral to both physical and psychosocial health. A complete skin assessment is essential for holistic care and must be completed by nurses and other health professionals on a regular basis. Providing patients and relatives with information on good skin hygiene can improve skin integrity and reduce the risk of pressure damage and skin tears.


Magnetic resonance imaging and expression of vascular endothelial growth factor in hepatocellular nodules in cirrhosis and hepatocellular carcinomas.
We summarized and discussed our previous research results on correlation between magnetic resonance (MR) imaging findings and vascular endothelial growth factor (VEGF) expression in benign or borderline hepatocellular nodules in cirrhosis, hepatocellular carcinomas (HCCs), and in the surrounding liver. Magnetic resonance images were retrospectively correlated quantitatively and qualitatively with VEGF expression in hepatic nodules and in the surrounding liver. By immunohistochemistry, hepatic nodules with moderate to strong immunoreactivity for VEGF showed higher T1 signal intensity, and those with intense immunoreactivity for VEGF showed higher T2 signal intensity. By Western blotting, HCC-to-liver contrast-to-noise ratio correlated with VEGF indices (VEGFs) of hepatocellular carcinomas inversely on opposed-phase T1-weighted, directly on T2-weighted, and marginally and inversely on gadolinium-enhanced hepatic arterial-phase images. On T2-weighted images, standard-deviation ratio of hepatocellular carcinomas correlated directly with VEGFs of hepatocellular carcinomas. Heterogeneities of hepatocellular carcinomas on MR images correlated directly with VEGFs of HCCs on opposed-phase T1-weighted, T2-weighted, hepatic arterial-phase, and equilibrium-phase images. Our results may reflect that MR signal intensity, hepatic arterial vascularity, and heterogeneity of hepatocellular nodules on MR images are closely related to the intensity of VEGF expression as up-regulated by hyper- or hypoxia in the nodules. Gadolinium-enhanced MR imaging may be useful to monitor ischemic state of hepatocelluar nodules. Although real impacts of our results on radiologic practice have been still debatable, we believe that our results may help future radiologic practice in conjunction with biomolecular or genetic treatments for hepatocellular carcinomas.


Molecular Design and Property Prediction of Sterically Confined Polyimides for Thermally Stable and Transparent Materials.
To meet the demand for next-generation flexible optoelectronic devices, it is crucial to accurately establish the chemical structure-property relationships of new optical polymer films from a theoretical point of view, prior to production. In the current study, computer-aided simulations of newly designed poly(ester imide)s (PEsIs) with various side groups (⁻H, ⁻CH₃, and ⁻CF₃) and substituted positions were employed to study substituent-derived steric effects on their optical and thermal properties. From calculations of the dihedral angle distribution of the model compounds, it was found that the torsion angle of the C⁻N imide bonds was effectively constrained by the judicious introduction of di-, tetra-, and hexa-substituted aromatic diamines with ⁻CF₃ groups. A high degree of fluorination of the PEsI repeating units resulted in weaker intra- and intermolecular conjugations. Their behavior was consistent with the molecular orbital energies obtained using density functional theory (DFT). In addition, various potential energy components of the PEsIs were investigated, and their role in glass-transition behavior was studied. The van der Waals energy (EvdW) played a crucial role in the segmental chain motion, which had an abrupt change near glass-transition temperature (Tg). The more effective steric effect caused by ⁻CF₃ substituents at the 3-position of the 4-aminophenyl group significantly improved the chain rigidity, and showed high thermal stability (Tg > 731 K) when compared with the ⁻CH₃ substituent at the same position, by highly distorting (89.7°) the conformation of the main chain.


Dissymmetric gemini surfactants generated by disulfide exchange in mixed micelles.
We found the generation of dissymmetric gemini surfactants from symmetric ones in aqueous micelle solutions of gemini surfactants with a spacer containing disulfide linkage. The equilibrium was attained during 5 h incubation at 25 degrees C with 1:2 ratio of symmetric to dissymmetric ones when the total concentrations were sufficiently high compared with monomer concentrations. The generation of dissymmetric form is attributed to the disulfide exchange between the spacer chains, which occurs in the mixed micelles of gemini surfactants with different hydrocarbon chains. The pseudo-phase separation model for micellization was successfully used to predict not only the cmc of binary and ternary mixtures composed of symmetric and dissymmetric gemini surfactants but also the monomer concentrations after the equilibrium. Reversibility of the disulfide exchange was ascertained by the generation of symmetric gemini surfactants from dissymmetric ones.


Association of dementia with death after ischemic stroke: A two-year prospective study.
The association between dementia and the risk of death after ischemic stroke was investigated. Neurological, neuropsychological and functional assessments were evaluated in 619 patients with acute ischemic stroke. Dementia was diagnosed at admission and at three months after stroke onset. The patients were scheduled for a two-year follow-up after the index stroke. The Kaplan-Meier survival and Cox proportional hazards regression analyses were used to estimate the cumulative proportion of survival, and the association between dementia and risk of death after stroke. In total, 146 patients (23.6%) were diagnosed with dementia after stroke. The cumulative proportion of surviving cases was 49.3% in patients with dementia after a median follow-up of 21.2±5.6 months, and 92.5% in patients without dementia. Multivariate analysis revealed that dementia (HR, 7.21; 95% CI, 3.85-13.49) was associated with death, independent of age, atrial fibrillation, previous stroke and NIH stroke scale. In conclusion, the mortality rate is increased in stroke patients with dementia. Dementia is an important risk factor for death after stroke, independent of age, atrial fibrillation, previous stroke, and the severity of the stroke.


Inhibition of neutrophil migration by hemopexin leads to increased mortality due to sepsis in mice.
The reduction of neutrophil migration to the bacterial focus is associated with poor outcome in sepsis. The objective of this study was to identify soluble substances in the blood of septic mice that inhibit neutrophil migration. A pool of serum obtained from mice 2 hours after the induction of severe sepsis by cecal ligation and puncture inhibited the neutrophil migration. The proteins with inhibitory activity on neutrophil migration were isolated by Blue-Sepharose chromatography, high-performance liquid chromatography, and electrophoresis, and identified by mass spectrometry. Hemopexin was identified as the serum component responsible for the inhibition of neutrophil migration. In sepsis, the pretreatment of wild-type mice with hemopexin inhibited neutrophil migration to the focus of infection and decreased the survival rate from 87.5 to 50.0%. Hemopexin-null mice subjected to severe sepsis presented normal neutrophil migration, low bacteremia, and an improvement of 40% in survival rate. Moreover, hemopexin inhibited the neutrophil chemotaxis response evoked by C5a or macrophage inflammatory protein-2 and induced a reduction of CXCR2 and L-selectin as well as the up-regulation of CD11b expression in neutrophil membranes. The inhibitory effect of hemopexin on neutrophil chemotaxis was prevented by serine protease inhibitors or ATP. In addition, serum levels of ATP were decreased 2 hours after severe sepsis. These data demonstrate for the first time the inhibitory role of hemopexin in neutrophil migration during sepsis and suggest that the therapeutic inhibition of hemopexin or its protease activity could improve neutrophil migration to the focus of infection and survival in sepsis.


Tissue oxygenation during management of cerebral perfusion pressure with phenylephrine or vasopressin.
Phenylephrine is often used for management of cerebral perfusion pressure after traumatic brain injury, but can have undesirable actions. Few studies have evaluated alternatives. The hypothesis was that arginine vasopressin was as effective as phenylephrine for maintaining tissue oxygenation during cerebral perfusion pressure management. Prospective randomized, blinded animal study. University laboratory. Thirty-five anesthetized swine (46 +/- 1 kg). Blunt trauma to the head and bilateral chests (estimated injury severity score was 25-32) was followed by hypoventilation. Resuscitation was divided into phases to simulate treatment in a typical prehospital, emergency room, and intensive care unit. For 30-45 mins postinjury, 1 L of normal saline was administered. For 45-120 mins, normal saline maintained systolic blood pressure >100 mm Hg plus mannitol for intracranial hypertension. After 120 mins, phenylephrine or arginine vasopressin was titrated to cerebral perfusion pressure >70 mm Hg (randomized and blinded) plus normal saline to maintain filling pressure >12 mm Hg plus glucose to maintain normoglycemia. Mortality rate was 37% (13 of 35) within 2 hrs. Before resuscitation, mean arterial pressure was 61 +/- 5 mm Hg, heart rate was 110 +/- 6 beats/min, PaO2 was 46 +/- 2 mm Hg, and lactate was 5.0 +/- 0.4 mM. Intracranial pressure increased from 8 +/- 1 mm Hg to 20 +/- 1 mm Hg and brain tissue PO2 decreased from 19 +/- 1 mm Hg to 8 +/- 1 mm Hg. Resuscitation corrected most variables, as well as mixed venous, renal, portal, and muscle oxygen saturations, but 90% (20 of 22) required pressor support. After 6 hrs with either pressor, hemodynamics were stable. However, with phenylephrine vs. arginine vasopressin, intracranial pressure averaged >10 mm Hg higher and brain tissue PO2 was 6 mm Hg lower, whereas tissue oxygen saturations were >10% higher in the shoulder and hindlimb muscles (all p < 0.05). Arginine vasopressin was as effective as phenylephrine for maintaining cerebral perfusion pressure, but intracranial pressure and brain tissue oxygenation were improved at the expense of the periphery.


A rheological approach to identify efficient biopolymer producing bacteria.
This study investigates the relationship between collective motion and propulsion of bacterial consortia and their biopolymer production efficiency. Rheological tests were conducted for suspensions of two different methanotrophic bacterial consortia obtained after enrichment of sediment samples from mangrove sites in Brazil. We considered the linear viscoelasticity region and analyzed the values of storage and loss moduli as functions of days of cultivation, for different values of the volume fraction. The suspensions' rheological behaviors reflected the bacterial growth stage. We found that the formation of structures over time in some types of consortia can hinder the movement of bacteria in the search for nutrients. The change in complex viscosity of the two consortia followed a different and rich behavior that appears to be closely related to their capacity to capture methane. Our analysis showed a possible correlation between collective motion, viscosity reduction, and biopolymer production. The pieces of evidence from this study suggest that the efficiency of bacterial motion is directly related to biopolymer production, and this could facilitate the process of identifying the best consortium of biopolymer producing bacteria.


Examination of the melatonin hypothesis in women exposed at night to EMF or bright light.
It has been hypothesized that the increased incidence of breast cancer in industrial societies is related to greater exposure to power-frequency electric and magnetic fields (EMF) and/or the presence of high levels of light at night (LAN). EMF and LAN are said to reduce circulating levels of the hormone melatonin which, in turn, allows estrogen levels to rise and stimulate the turnover of breast epithelial stem cells and increase the risk for malignant transformation. Three laboratory-based studies, in which a total of 53 healthy young women were exposed at night to EMF or to LAN under controlled exposure conditions, were performed to determine whether such exposures reduce melatonin and are associated with further alterations in estrogen. All-night exposure to industrial-strength magnetic fields (60 Hz, 28.3 microT) had no effect on the blood levels of melatonin or estradiol. In contrast, nocturnal melatonin levels were profoundly suppressed, and the time of peak concentration was significantly delayed in women exposed to LAN, regardless of whether they were in the follicular or luteal phase of the menstrual cycle. These changes, however, were not associated with alterations in point-for-point matching measures of estradiol. Women who chronically secrete high or low amounts of melatonin each night (area-under-curve range: 86-1,296 pg/mL) also did not differ in their blood levels of estradiol. Taken together, these results are consistent with a growing body of evidence which generally suggests that environmental EMF exposure has little or no effect on the parameters measured in this report.


Dexamethasone Suppresses Palatal Cell Proliferation through miR-130a-3p.
Cleft lip with or without cleft palate (CL/P) is one of the most common congenital birth defects. This study aims to identify novel pathogenic microRNAs associated with cleft palate (CP). Through data analyses of miRNA-sequencing for developing palatal shelves of C57BL/6J mice, we found that miR-449a-3p, miR-449a-5p, miR-449b, miR-449c-3p, and miR-449c-5p were significantly upregulated, and that miR-19a-3p, miR-130a-3p, miR-301a-3p, and miR-486b-5p were significantly downregulated, at embryonic day E14.5 compared to E13.5. Among them, overexpression of the miR-449 family (miR-449a-3p, miR-449a-5p, miR-449b, miR-449c-3p, and miR-449c-5p) and miR-486b-5p resulted in reduced cell proliferation in primary mouse embryonic palatal mesenchymal (MEPM) cells and mouse cranial neural crest cell line O9-1. On the other hand, inhibitors of miR-130a-3p and miR-301a-3p significantly reduced cell proliferation in MEPM and O9-1 cells. Notably, we found that treatment with dexamethasone, a glucocorticoid known to induce CP in mice, suppressed miR-130a-3p expression in both MEPM and O9-1 cells. Moreover, a miR-130a-3p mimic could ameliorate the cell proliferation defect induced by dexamethasone through normalization of Slc24a2 expression. Taken together, our results suggest that miR-130-3p plays a crucial role in dexamethasone-induced CP in mice.


Resistance to Marek's disease herpesvirus-induced lymphoma is multiphasic and dependent on host genotype.
Genotype-dependent differences in Marek's disease (MD) susceptibility were identified using 14-day-old line N and 6(1) (resistant) and 151 and 7(2) (susceptible) inbred chickens infected with HPRS-16 MD virus (MDV). All line 72 chickens developed progressive MD. Line 15I had fluctuating MD-specific clinical signs and individuals recovered. A novel histologic scoring system enabled indices to be calculated for lymphocyte infiltration into nonlymphoid organs. All genotypes had increased mean lesion scores (MLSs) and mean total lesion scores after MDV infection. These differed quantitatively and qualitatively between the genotypes. Lines 6(1) and 7(2) had a similar MLS distribution in the cytolytic phase, although scores were greater in line 7(2). At the time lymphomas were visible in line 7(2), histologic lesions in line 6(1) were regressing. AV37+ cells were present in similar numbers in all genotypes in the cytolytic phase, suggesting that neoplastically transformed cells were present in all genotypes regardless of MD susceptibility. After the cytolytic phase, AV37+ cell numbers increased in lines 7(2) and 15I but decreased in lines 6(1) and N. In the cytolytic and latent phases, in all genotypes, most infiltrating cells were CD4+. After this time, line 7(2) and 15I lesions increased in size and most cells were CD4+; line 6(1) and N lesions decreased in size and most cells were CD8+. In all genotypes, AV37 immunostaining was weak in lesions with many CD8+ cells, suggesting that AV37 antigen expression or AV37+ cells were controlled by CD8+ cells. The rank order, determined by clinical signs and pathology, for MD susceptibility (highest to lowest) was 7(2) > 15I > 6(1) > N.


Stress, social support, and college adjustment among Latino students.
This study examined the role of social support and stress on adjustment to college among Latino students. Measures of social support, stress, and adjustment to college were obtained from 77 Latino college students. Social support was positively associated with adjustment and negatively associated with stress. A negative relationship was found between stress and adjustment in bivariate analyses indicating that exposure to stress interferes with adequate adjustment. However, stress did not significantly contribute to adjustment when included with social support in multivariate analyses. The functional nature of support was also examined in this study. Emotional support was associated with better overall and academic adjustment and less stress than instrumental support. there was a significant negative relationship between support from friend/other and stress. Finally, support from friend/other was negatively correlated with stress from exposure to racism. Implications of the study in terms of future research and college programs for Latino students are discussed.


Metabolic immune restraints: implications for anticancer vaccines.
Metabolic immune restraints belong to a highly complex network of molecular mechanisms underlying the failure of naturally occurring and therapeutically induced immune responses against cancer. In the light of the disappointing results yielded so far with anticancer vaccines in the clinical setting, the dissection of the cascade of molecular events leading to tumor immune escape appears the most promising way to develop more effective immunotherapeutic strategies. Here we review the significant advances recently made in the understanding of the tumor-specific metabolic features that contribute to keep malignant cells from being recognized and destroyed by immune effectors. These mechanistic insights are fostering the development of rationally designed therapeutics aimed to revert the immunosuppressive circuits and thus to enhance the effectiveness of anticancer vaccines.


Body fatness during childhood and adolescence and breast density in young women: a prospective analysis.
Overweight and obesity in childhood and adolescence are associated with reduced breast cancer risk, independent of adult body mass index (BMI). These associations may be mediated through breast density. We prospectively examined associations of early life body fatness with adult breast density measured by MRI in 182 women in the Dietary Intervention Study in Children (DISC) who were ages 25-29 at follow-up. Height, weight, and other factors were measured at baseline (ages 8-10) and annual clinic visits through adolescence. We used linear mixed-effects models to quantify associations of percent breast density and dense and non-dense breast volume at ages 25-29 with quartiles of age-specific youth body mass index (BMI) Z-scores, adjusting for clinic, treatment group, current adult BMI, and other well-established risk factors for breast cancer and predictors of breast density. We observed inverse associations between age-specific BMI Z-scores at all youth clinic visits and percent breast density, adjusting for current adult BMI and other covariates (all p values <0.01). Women whose baseline BMI Z-scores (at ages 8-10 years) were in the top quartile had significantly lower adult breast density, after adjusting for current adult BMI and other covariates [least squares mean (LSM): 23.4 %; 95 % confidence interval (CI): 18.0 %, 28.8 %] compared to those in the bottom quartile (LSM: 31.8 %; 95 % CI: 25.2 %, 38.4 %) (p trend <0.01). Significant inverse associations were also observed for absolute dense breast volume (all p values <0.01), whereas there were no clear associations with non-dense breast volume. These results support the hypothesis that body fatness during childhood and adolescence may play an important role in premenopausal breast density, independent of current BMI, and further suggest direct or indirect influences on absolute dense breast volume. NCT00458588 ; April 9, 2007.


[Radiological evaluation of breasts reconstructed with lipomodeling].
We have been using the lipomodeling technique since 1999 in order to improve the form and the volume of the breasts reconstructed with latissimus dorsi flap. During several recent years this technique has known a considerable development and its results are quite attractive. At the same time, the breast imaging remains to be a fundamental mean of cancer control. The knowledge of radiological manifestations of the implanted fat tissue is very important. The aim of this study was to evaluate the imaging aspects of lipomodeling in breasts reconstructed with latissimus dorsi flap, using three types of explorations: ultrasound, radiological mammography and MRI. A total of 30 patients were included into the study with average age of 51 years. All of these patients underwent a breast reconstruction using a latissimus dorsi flap with lipomodeling, which average volume reached 165 cc. Four of the patient had a bilateral breast reconstruction. Three modes of imaging (ultrasound, mammography and MRI) were performed a year after the surgery. In 20 patients the imaging findings proved to be normal (in total 34 breasts). An image of fat tissue was revealed in 14 cases and some benign microcalcifications were found in 4 patients. A suspicious tissular image was discovered in one patient, who later underwent a biopsy. The result was a benign giant cell granuloma. In conclusion, the lipomodeling technique does not affect the postoperative follow-up of the patients with breast cancer and an imaging controlled biopsy is possible in case of any doubt. At present, some additional studies are underway evaluating the fat tissue transplants in normal breasts, in order to widen its indications in the plastic breast surgery.


A special pool project for rehabilitation of hip and knee arthroprosthesis.
The use of ankle or knee arthroprostheses is increasing and proper rehabilitation is needed after the surgery. We have designed a special pool where normal gait can take place under partly unweighted conditions, thus improving quality of therapy and reducing the length of stay. Underwater TV recording permits daily gait analysis. Data are provided on pool shape, length and depth of the walkway, water conditions, safety and other facilities. The cost has been compared to commercial pools of the same type. The design permits accurate definition of stride parameters during rehabilitation which enables the programme to be optimized. The pool is cheaper than commercial ones but offers many more research possibilities. The Authors are glad to share their expertise freely upon request.


Endoreplication in Anemia phyllitidis coincides with the development of gametophytes and male sex.
Analyses of DNA content using fluorescence microcytophotometry showed that development of Anemia phyllitidis gametophytes coincided with endoreduplication process. The level of this process shown by the number of endopolyploid cells studied at the I-V arbitrarily established cellular gametophyte stages, was 3%, while at the VI-VII and VII* (male stages) were 10.5 and 4%, respectively. This process coincided with decreased mitotic activity of cells and concerned the cells with their profile area between 1100 and 13,000 microm(2). However, the correlation between cell size and its polyploidisation level was detected only for 12% of these cells. Endoreduplication during development of A. phyllitidis gametophytes seems to be connected with the end of cell cycle followed by the exit of cells from the cell cycle and with subsequent switch of proliferation to the postmitotic differentiation and/or to the endocycle. Endoreplication of A. phyllitidis gametophytes is a function of age, size and number of cells as well as type of gametophyte morphogenesis, which probably maintains the functional copies of genes whose number is restricted by elimination of cells from gametophytes by their death.


Enhanced photocatalytic activity of titanium oxide nanotubes after heating treatment.
Titanium oxide nanotubes were obtained by an electrochemical anodization method. Scanning electron microscope results demonstrate that the diameter of the tubes is about 120 nm and the length of the tubes is around 13 microm. Transmission electron microscope results indicate that the nanotubes are assembled by numerous nanoparticles and tube-like structure remains well after heat treatment at 400-600 degrees C. The photocatalysis performance of the nanotubes was evaluated in terms of the decomposition rate of methyl orange under UV irradiation. The results show that the photocatalytic activity was enhanced through the heating treatment of the nanotubes, and the nanotubes heated at 600 degrees C exhibits the best photocatalytic activity. X-ray diffraction patterns indicate that there is no phase transformation during the heat treatment. Therefore, the enhanced activity can be attributed to the improvement of nanotubes crystallinity, which may provide more insights about the effect of the crystallinity on the photocatalytic performance.


Prednisone inhibits the IL-1β-induced expression of COX-2 in HEI-OC1 murine auditory cells through the inhibition of ERK-1/2, JNK-1 and AP-1 activity.
Hearing loss can be induced by multiple causes, including cochlear inflammation. Prednisone (PDN) is a well-known steroid clinically used in the treatment of hearing loss. In the present study, we investigated the inhibitory effects and the mechanisms of action of PDN on the expression of cyclooxygenase (COX)-2, an inflammatory enzyme involved in the production of prostaglandins (PGs), in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells (a murine auditory cell line) treated with the inflammatory cytokine, interleukin (IL)-1β. The exposure of HEI-OC1 cells to IL-1β increased COX-2 protein and mRNA expression, COX-2 promoter-driven luciferase activity and COX-2 enzymatic activity [as indicated by the increased production of prostaglandin E2 (PGE2), a major COX-2 metabolite]. However, PDN markedly inhibited the IL-1β-induced COX-2 protein and mRNA expression, COX-2 promoter activity and PGE2 production in the HEI-OC1 cells without affecting COX-2 protein and mRNA stability. PDN further inhibited the IL-1β-induced activation of extracellular signal-regulated kinase (ERK)-1/2 and c-Jun N-terminal kinase (JNK)-1, but had no effect on the cytokine-induced activation of p38 MAPK and proteolysis of IκB-α, a nuclear factor-κB (NF-κB) inhibitory protein. PDN also partially suppressed the IL-1β‑induced activation of activator protein (AP)-1 (but not that of NF-κB) promoter-driven luciferase activity. Of note, the inhibitory effects of PDN on the IL-1β-induced expression of COX-2 and the activation of ERK-1/2 and JNK-1 in the HEI-OC1 cells were significantly diminished by RU486, a glucocorticoid receptor (GR) antagonist, suggesting that PDN exerts its inhibitory effects through GR. To the best of our knowledge, our study demonstrates for the first time that PDN inhibits the IL-1β-induced COX-2 expression and activity in HEI-OC1 cells by COX-2 transcriptional repression, which is partly associated with the inhibition of ERK-1/2, JNK-1 and AP-1 activation.


Review of Laser Therapy in Cardiovascular Diseases.
Introduction: In recent years, there has been a rise in laser therapy for the treatment of cardiovascular diseases. Methods: This paper attempted to represent recent advances in laser therapy in cardiovascular tissue repairs. Three standard techniques have been explicitly described here in cardiovascular tissue repairs by laser. Results: One of the advantages of using laser therapy in cardiovascular diseases is its non-invasiveness. It also reduces the treatment process pain and prevents massive surgical incisions and bleeding throughout the operation. Laser therapy can ensure an alternative method to treat the ischemic region of the heart and creating anastomosis of vessels. Conclusion: With professional technologies and endoscopic surgery method development, the role of using lasers has become much more precise and more transparent in cardiovascular diseases.


Correlation of microscopic and mitochondrial DNA hair comparisons.
Expert opinions regarding the microscopic comparison of human hairs have been accepted routinely in courts for decades. However, with the advent of mitochondrial DNA (mtDNA) sequencing, an assessment can be made of the association by microscopic hair comparisons in casework between a questioned hair and reference hairs from an individual. While each method can be used separately, the two analytical methods can be complementary and together can provide additional information regarding source association. Human hairs submitted to the FBI Laboratory for analysis between 1996 and 2000 were reviewed. Of 170 hair examinations, there were 80 microscopic associations; of these, only nine were excluded by mtDNA. Importantly, 66 hairs that were considered either unsuitable for microscopic examinations or yielded inconclusive microscopic associations provided mtDNA results. Only six hairs did not provide sufficient mtDNA, and only three yielded inconclusive results. Consistency was observed in exculpatory results with the two procedures. This study demonstrates the utility of microscopic hair examinations and the strength of combining microscopic analysis with mtDNA sequencing.


Dynamics in the isotropic phase of nematogens using 2D IR vibrational echo measurements on natural-abundance 13CN and extended lifetime probes.
The long time scale orientational relaxation of nematogens in the isotropic phase is associated with the randomization of pseudonematic domains, which have a correlation length that grows as the isotropic-to-nematic phase transition temperature is approached from above. Here we begin to address the fast dynamics of the nematogen molecules within the domains using two-dimensional infrared (2D IR) vibrational echo experiments. The problems of performing ultrafast IR experiments in pure liquids are discussed, and solutions are presented. In addition, the issue of short vibrational lifetimes, which limit the ability of 2D IR experiments to examine dynamics over a wide range of times, is addressed. The experiments were performed on the nematogen 4-cyano-4'-pentylbiphenyl (5CB), with the CN stretch initially used as the vibrational probe. Although the CN stretch has a small transition dipole, because the sample is a pure liquid it is necessary to use an exceedingly thin sample to perform the experiments. The small sample volume leads to massive heating effects that distort the results. In addition, the high concentration in the pure liquid can result in vibrational excitation transfer that interferes with the measurements of structural dynamics, and the CN vibrational lifetime is very short (3.6 ps). These problems were overcome by performing the experiments on the natural-abundance (13)CN stretch (5(13)CB), which greatly reduced the absorbance, eliminating the heating problems; also, this stretch has a longer lifetime (7.9 ps). Experiments were also performed on benzonitrile, which showed that the heating problems associated with pure liquids are not unique to 5CB. Again, the problems were eliminated by conducting measurements on the (13)CN stretch, which has an even longer lifetime (20.2 ps) compared with the (12)CN stretch (5.6 ps). Finally, to extend the range of the dynamical measurements, 4-pentyl-4'-thiocyanobiphenyl (5SCB) was synthesized and studied as a dilute solute in 5CB. The CN stretch of 5SCB has a vibrational lifetime of 103 ps, which permits dynamical measurements to 200 ps, revealing the full range of fast structural dynamics in the isotropic phase of 5CB. It is shown that the 5SCB probe reports essentially the same dynamics as 5(13)CB on the short time scale that is observable with the 5(13)CB vibrational probe.


[Animal models of hypoxic-ischemic encephalopathy].
This review presents the animal models more widely used to study neurological and neuropathological outcomes of perinatal asphyxia. Methods used to induce hypoxia/ischemia in fetal and newborn non-human primates, lambs, piglets and rodents are concisely described, reporting the more relevant neuropathological and behavioural findings. In line with human observational data, experimental studies indicate that motor behaviour and attentional/cognitive abilities are among those behavioural regulations more significantly affected by perinatal asphyxia.


Extending the IEEE 802.15.4 security suite with a compact implementation of the NIST P-192/B-163 elliptic curves.
Typically, commercial sensor nodes are equipped with MCUsclocked at a low-frequency (i.e., within the 4-12 MHz range). Consequently, executing cryptographic algorithms in those MCUs generally requires a huge amount of time. In this respect, the required energy consumption can be higher than using a separate accelerator based on a Field-programmable Gate Array (FPGA) that is switched on when needed. In this manuscript, we present the design of a cryptographic accelerator suitable for an FPGA-based sensor node and compliant with the IEEE802.15.4 standard. All the embedded resources of the target platform (Xilinx Artix-7) have been maximized in order to provide a cost-effective solution. Moreover, we have added key negotiation capabilities to the IEEE 802.15.4 security suite based on Elliptic Curve Cryptography (ECC). Our results suggest that tailored accelerators based on FPGA can behave better in terms of energy than contemporary software solutions for motes, such as the TinyECC and NanoECC libraries. In this regard, a point multiplication (PM) can be performed between 8.58- and 15.4-times faster, 3.40- to 23.59-times faster (Elliptic Curve Diffie-Hellman, ECDH) and between 5.45- and 34.26-times faster (Elliptic Curve Integrated Encryption Scheme, ECIES). Moreover, the energy consumption was also improved with a factor of 8.96 (PM).


[An investigation of the mode of local spreading of biliary tract carcinoma to microvascular and neural structure].
To understand the spreading mode of extrahepatic bile duct carcinoma and gallbladder carcinoma, 170 specimens (86 of which had gallbladder carcinoma while the remaining 84 had extrahepatic bile duct carcinoma) were histo-pathologically studied. In addition, experiments utilizing a canine model were also concurrently conducted in order to gain a greater understanding of relationship between micrometastasis of extrahepatic bile duct carcinoma and microstructures of lymphatics, veins and nerves of biliary tract. The results were as follows: 1) Invasion of the local lymphatics, veins and nerves was found to increase as the grade of tumor penetration into the wall of the biliary tract increased. In addition, it was observed in cases of extrahepatic bile duct carcinoma, a high rate of lymphatic involvement when tumor invasion involved the fibrous muscle layer. However, in cases of gallbladder carcinoma there was no lymphatic involvement even though it also had tumor invasion of the proper muscular layer. 2) In the case of gallbladder carcinoma, correlation of the micrometastasis to lymphatics, veins and nerves was seen, but in cases of extrahepatic bile duct carcinoma, no relationship to micrometastasis of veins and nerves was observed. 3) Anatomically, the study noted rich networks of lymphatics and nerves in the hepatoduodenal ligament. Thus, the rate of micrometastasis to these lymphatics and nerves was more extensive than the observed positive rate of the micrometastasis to veins. 4) Although no direct relationship between nerves and lymphatics was found, it was noted that perineural space was extended in the cases with lymph stasis. There was a network of blood-vessels of nerves and the pericholedocal vascular plexus in the hepatoduodenal ligament. Perineural invasion of carcinoma cells account for the anatomical distribution the surrounding lymphatics and veins. In conclusion, the localization and distribution of micrometastasis from extrahepatic bile duct carcinoma to the involved lymphatics, veins and nerves structures seemed to correlate to the microanatomy of the biliary.


Journal club as a supplement to the undergraduate biochemistry laboratory.
After purification of lysozyme, our biochemistry students write a research proposal that outlines a strategy for studying this enzyme after alteration by site-directed mutagenesis. Despite a literature search that yielded a wealth of background information, students were often overwhelmed by the assignment because they were not familiar with advanced techniques of protein analysis. We therefore developed a series of journal clubs in which teams of students present methods and data found in papers dealing with lysozyme. The five topics for journal clubs include; substrate binding and mechanism; spectroscopic techniques; stability analysis; two-dimensional NMR; and X-ray crystallography. After the adoption of the group talks, the quality of the research proposals improved immensely and students found the assignment to be an educationally rewarding exercise.


Endogenous Inactivators of Arginase, l-Arginine Decarboxylase, and Agmatine Amidinohydrolase in Evernia prunastri Thallus.
Arginase (EC 126.96.36.199), l-arginine decarboxylase (EC 188.8.131.52), and agmatine amidinohydrolase (EC 220.127.116.11) activities spontaneously decay in Evernia prunastri thalli incubated on 40 millimolar l-arginine used as inducer of the three enzymes if dithiothreitol is not added to the media. Lichen thalli accumulate both chloroatranorin and evernic acid in parallel to the loss of activity. These substances behave as inactivators of the enzymes at a range of concentrations between 2 and 20 micromolar, whereas several concentrations of dithiothreitol reverse, to some extent, the in vitro inactivation.


Development and validation of a voice-of-the-patient measure of cognitive concerns experienced by people living with HIV.
People living with HIV may experience some degree of mild cognitive impairment. They are best placed to report on their cognitive symptoms, but no HIV-specific questionnaire exists to elicit these concerns. This study aimed to validate a set of items to form a measure METHODS: 48 items were tested on an initial sample of 204 people with HIV. Rasch analysis was used to identify those that fit a hierarchical continuum. The hierarchy was validated on a new sample of 703 people with HIV and a sample of 484 people without HIV. 18 items fit the model and formed the Communicating Cognitive Concerns Questionnaire (C3Q). The items spanned the full range of cognitive ability, distinguished between people working and not working, and correlated with other self-report outcomes such as mental health (0.56) and work productivity (0.60), although showed a low correlation with cognitive test performance. The C3Q is the first questionnaire specifically developed for use among people with HIV. While not strongly associated with cognitive test performance, it reflects real-life concerns of people and is associated with mood, work, and work productivity. It is a needed step in assessing cognition in this population.


Circadian tryptophan hydroxylase levels and serotonin release in the suprachiasmatic nucleus of the rat.
Serotonin (5-HT) plays an important role in the regulation of the time-keeping system in rodents. In the present study, we have investigated the interplay between the rhythms of 5-HT synthesis and release in the suprachiasmatic nuclei (SCN) of the rat. The quantitative distribution of tryptophan hydroxylase (TpH) protein was used as an index of 5-HT synthesis, in perikarya and terminals areas. In the raphe medianus, the maximal levels of TpH was reached in the early daytime period, followed by a decrease before the onset of darkness. Conversely, in the axon terminals of the SCN the highest levels of TpH were found before the onset of the dark-period. Furthermore, TpH amount in SCN displays variations depending on the anatomical area of the SCN. Extracellular 5-HT peaked at the beginning of the night, as evidenced by in vivo microdialysis in the SCN. The 5-HT metabolite, 5-HIAA, presented a similar pattern, but the acrophase occurred in the middle of the dark period. These results suggest that TpH is transported from the soma to the nerve terminals in which 5-HT is synthesized during daytime. This would fill the intracellular stores of 5-HT to provide for its nocturnal release.


Alleviation of intrasteric inhibition by the pathogenic activation domain mutation, D444N, in human cystathionine beta-synthase.
Human cystathionine beta-synthase is a heme protein that catalyzes the condensation of serine and homocysteine to form cystathionine in a pyridoxal phosphate-dependent reaction. Mutations in this enzyme are the leading cause of hereditary hyperhomocysteinemia with attendant cardiovascular and other complications. The enzyme is activated approximately 2-fold by the allosteric regulator S-adenosylmethionine (AdoMet), which is presumed to bind to the C-terminal regulatory domain. The regulatory domain exerts an inhibitory effect on the enzyme, and its deletion is correlated with a 2-fold increase in catalytic activity and loss of responsiveness to AdoMet. A mutation in the C-terminal regulatory domain, D444N, displays high levels of enzyme activity, yet is pathogenic. In this study, we have characterized the biochemical penalties associated with this mutation and demonstrate that it is associated with a 4-fold lower steady-state level of cystathionine beta-synthase in a fibroblast cell line that is homozygous for the D444N mutation. The activity of the recombinant D444N enzyme mimics the activity of the wild-type enzyme seen in the presence of AdoMet and can be further activated approximately 2-fold in the presence of supraphysiolgical concentrations of the allosteric regulator. The mutation increases the K(act) for AdoMet from 7.4 +/- 0.2 to 460 +/- 130 microM, thus rendering the enzyme functionally unresponsive to AdoMet under physiological concentrations. These results indicate that the D444N mutation partially abrogates the intrasteric inhibition imposed by the C-terminal domain. We propose a model that takes into account the three kinetically distinguishable states that are observed with human cystathionine beta-synthase: "basal" (i.e., wild-type enzyme as isolated), "activated" (wild-type enzyme + AdoMet or the D444N mutant as isolated), and superactivated (D444N mutant + AdoMet or wild-type enzyme lacking the C-terminal regulatory domain).


Can Serum Thyroglobulin Levels Help to Identify the Involved Neck Compartment of Differentiated Thyroid Carcinoma?
We aimed to evaluate the predictive ability of serum thyroglobulin (Tg) levels on the localization of the metastatic lymph node compartments in locoregional metastases of papillary thyroid cancer (PTC). This retrospective study included 143 patients who underwent neck dissections for a total of 172 for persistent/recurrent locoregional PTC. They were grouped according to the localization of lymph node metastasis (LNM): Central (C-LNM), Lateral (L-LNM), both central and lateral LNM (C+L LNM). To confirm that the Tg cutoff discriminated LNM localizations, the sample was categorized as suppressed (<0.1 mU/l) or non-suppressed (>0.1 mU/l) according to TSH and ROC analysis. Mixed-effects models were used to investigate the effect of LNM localization on Tg levels and to eliminate the confounding effects of TSH, tumor burden (defined as the number and the largest diameter of LNM), and RAI. Mean Tg levels were 1.43 μg/l for C-LNM (n=47), 3.7 μg/l for L-LNM (n=99), and 8.60 μg/l for C+L LNM (n=26). Independent of TSH, tumor burden and RAI, the mean Tg levels of L-LNM and C+L LNM groups were not significantly different, while that of C-LNM was significantly lower than those of L-LNM and C+L LNM. To discriminate C-LNM from L-LNM and C+L LNM in patients with TSH>0.1 mU/l, the optimal cutoff for Tg was 1.05 μg/l (sensitivity=74.7%, specificity=70.4%, PPV=87.7%). L-LNM increases serum Tg levels more than C-LNM in persistent/recurrent locoregional nodal disease of PTC. Tg above 1.05 μg/l may indicate lateral LNM. Tg may be an important marker for the localization of LNM in the neck.


A class discovery and class prediction approach to histopathological classification of mammographic screen detected columnar cell lesions of the breast.
Columnar cell lesions (CCLs) of the breast have been increasingly recognised in biopsies taken to investigate mammographic screen detected microcalcification. The aim of this study was to identify distinct CCL subtypes by systematic analysis of histopathology. Hierarchical cluster analysis was performed based on the profile of histopathological features in 102 screen detected CCLs. Features assessed included nuclear morphology, acinar dilatation, epithelial cell hyperplasia, cell crowding, apical snout formation and intraluminal secretion. The stability of this classification was tested in an independent cohort of 32 cases. The histopathology of screen detected CCLs was extremely variable. Hierarchical cluster analysis identified two subclasses: Class 1 (34/102, 33%) characterised by absence of nuclear atypia and less pronounced hyperplasia; and Class 2 (68/102, 67%) that were generally more atypical. Ki-67 scores were significantly lower for Class 1 CCLs (p < 0.001). In the independent cohort of 32 cases, Class 1 cases were clearly distinguished from Class 2, indicating that these were stable phenotypes amongst screen detected CCLs. The histopathological features of CCLs diagnosed at screening are extremely heterogeneous. Using a systematic approach, we have devised a broad classification system that delineates a category of less atypical CCLs that could form a basis for future studies.


Pharmacokinetics of trazodone and its major metabolite m-chlorophenylpiperazine in plasma and brain of rats.
Sprague-Dawley rats were used as models for single trazodone administration (males), continuous adminstration and dose proportionality experiments (males, females, pregnant females). Plasma and brain tissue were analysed for trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP). Fetal exposure to trazodone and m-CPP was assessed and differences in their steady-state plasma concentration were sought between adult males and females. Both trazodone and m-CPP rapidly appeared in plasma and brain tissue following a single intraperitoneal trazodone dose with brain concentrations exceeding those in plasma. Plasma concentrations of m-CPP were lower than those of trazodone but exceeded them in brain tissue. Chronic administration using osmotic mini-pumps revealed a significant linear relationship between trazodone concentration in plasma and brain at steady-state (r=0.96, p<0.0001). No simple relationship was found between plasma and brain tissue concentration for m-CPP. In contrast to observations following single trazodone administration, m-CPP concentrations at steady-state were lower than trazodone concentrations in brain tissue, suggesting a lack of stationarity in the disposition of trazodone over time. No significant differences in plasma or brain tissue drug concentrations relative to administered trazodone dose were observed between male and female rats, nor between pregnant and non-pregnant females. Trazodone and m-CPP were both detected in fetal and placental tissues, with placenta having the highest concentrations. The data suggest that neuropharmacological studies of trazodone could yield different results depending upon the route and schedule of drug administration. Maternally administered trazodone, like many other antidepressants, is distributed to fetal tissues in rodents, reaffirming the need for caution in treating pregnant women with psychoactive drugs.


Sodium iodide symporter in health and disease.
Radioiodine-concentrating activity in thyroid tissues has allowed the use of radioiodine as a diagnostic and therapeutic agent for patients with thyroid disorders such as well-differentiated thyroid cancer. However, some extrathyroidal tissues also take up radioiodine, contributing to unwanted side effects of radioiodine therapy. Now that the molecule that mediates radioiodine uptake, the sodium iodide symporter (NIS), has been cloned and characterized, it may be possible to develop novel strategies to differentially modulate NIS expression and/or activity, enhancing it in target tissues and impeding it in others. In addition to restoring NIS expression/activity to ensure sufficient radioiodine uptake for the diagnosis and treatment of advanced thyroid cancers, we envision that it may be possible to selectively increase or confer NIS expression/activity in tumors of nonthyroidal tissues to facilitate the use of radioiodine in their diagnosis and treatment. We also consider the molecular basis of thyroid and nonthyroid disorders that may be complicated by NIS deregulation. Finally, we explore the use of NIS as an imaging reporter gene to monitor the expression profile of the transgene in transgenic mouse animal models and in patients undergoing gene therapy clinical trials.


Changes in the fabric and compliance tensors of cancellous bone due to trabecular surface remodeling, predicted by a digital image-based model.
Fabric and compliance tensors of a cube of cancellous bone with a complicated three-dimensional trabecular structure were obtained for trabecular surface remodeling by using a digital image-based model combined with a large-scale finite element method. Using mean intercept length and a homogenization method, the fabric and compliance tensors were determined for the trabecular structure obtained in the computer remodeling simulation. The tensorial quantities obtained indicated that anisotropic structural changes occur in cancellous bone adapting to the compressive loading condition. There were good correlations between the fabric tensor, bone volume fraction, and compliance tensor in the remodeling process. The result demonstrates that changes in the structural and mechanical properties of cancellous bone are essentially anisotropic and should be expressed by tensorial quantities.


Accountability systems and instructional approaches in youth volleyball training.
The purpose of this study was to examine accountability systems operating in youth volleyball training sessions and to understand how those systems vary according to the instructional tasks and the nature of the information provided by coaches. Additionally, the interactive effect of the players' age group on accountability systems and instructional tasks will be inspected. Twenty-eight youth volleyball coaches (for under 14s and under 18s) were observed, one training session each. Systematic observation strategies were used to describe and analyse task presentation and task structure during practice. Results convey that the accountability systems implemented by coaches were mainly implicit and governed by opportunity rather than explicit performance criteria imparted in task presentation. Remarks on the quality of performance only occurred during ongoing practice. More often than not coaches showed no reaction when athletes did not accomplish the tasks, failing to convey consequential expectancy-demand-monitoring messages. The instructional approach was predominantly composed of informing tasks, of technical nature and general information, which can reflect a technique and generalist coach profile. These results indicate the presence of weak and ambiguous accountability system, also corroborated by positive correlations of extending tasks with the category without exigency task presentation as well as with no reaction to unaccomplished tasks. There were no notorious differences in accountability behaviours between players' age group. Key pointsAccountability systems implemented by coaches were mainly implicit and governed by opportunity rather than explicit performance criteria imparted in task presentation. Only during practice, coaches remark the performance quality, followed by participation/effort.The instructional approach was predominantly composed of informing tasks, of technical nature and general information, which can reflect a technique and generalist coach profile.In general, coaches did not differentiate accountability behaviours according to the players' age group.


Significant cancer prevention factor extraction: an association rule discovery approach.
Cancer is increasing the total number of unexpected deaths around the world. Until now, cancer research could not significantly contribute to a proper solution for the cancer patient, and as a result, the high death rate is uncontrolled. The present research aim is to extract the significant prevention factors for particular types of cancer. To find out the prevention factors, we first constructed a prevention factor data set with an extensive literature review on bladder, breast, cervical, lung, prostate and skin cancer. We subsequently employed three association rule mining algorithms, Apriori, Predictive apriori and Tertius algorithms in order to discover most of the significant prevention factors against these specific types of cancer. Experimental results illustrate that Apriori is the most useful association rule-mining algorithm to be used in the discovery of prevention factors.


[Emission Characteristics of Gas-and Particle-Phase Polycyclic Aromatic Hydrocarbons from Cooking].
Polycyclic aromatic hydrocarbons (PAHs) play a key role in the formation of secondary organic areole and ozone. This study sampled three commercial Chinese restaurants and a food plant in Shenzhen to analyze the emission characteristics of PAHs, especially the alkyl PAHs in both gas and particle phases. The results showed that the ρ(total PAHs)in the particle and gas phase were (1381.6±140.5) ng·m-3, (1030.2±116.4) ng·m-3, (908.3±111.9) ng·m-3, and (838.0±93.5) ng·m-3 in the food plant, Sichuan, Cantonese, and Zhejiang restaurants, respectively. More than 60% of the PAHs were distributed in the gas phase, especially the lower molecular weight PAHs (lower than Chrysene). The gas phase proportion of naphthalene was the highest, with over 75% of it distributed in the gas phase. However, the PAHs with a higher molecular weight than that of benzo(b)fluorescence were mainly distributed in the particle phase. The total concentration of alkyl PAHs emitted from cooking was much lower than that of the corresponding parent PAHs, and the distribution characteristics of alkyl PAHs were quite different from those of other emission sources. The linear fitting of lgKp and lgPL showed that the slopes of the three commercial restaurants ranged from -0.25 to -0.28, whereas for the food plant, the value was -0.18, which indicates that the gas-particle partitioning of PAHs were not in equilibrium.


Dissociation between steroid receptor expression and cell proliferation in the human breast.
We have shown previously that estradiol stimulates cell proliferation and progesterone receptor (PgR) synthesis in luminal epithelial cells of the normal human breast. Approximately 10-15% of luminal epithelial cells within the normal breast express immunodetectable estrogen receptor (ER), but little is known about their distribution within lobules and their organization in relation to the smaller population of proliferating cells. Using normal human breast tissue, we show that ER-positive cells are distributed evenly throughout the mammary epithelium. Using double antibody immunofluorescence, we show that 96% of steroid receptor-positive cells synthesize both ER and PgR (n = 25). Double labeling with antibodies to either ER or PgR coupled with either [3H]thymidine histoautoradiography or with antibodies to the Ki67 proliferation antigen indicates that dividing cells are separate from those expressing the receptors (although they are often in close proximity). However, in contrast to the normal human breast, two-thirds of ER-positive human mammary tumors examined (n = 19) have a high proportion of dividing cells that are ER positive. These data are consistent with the hypothesis that cells in normal human breast epithelium are hierarchical in organization and support a model in which proliferation of ER-negative cells is controlled by paracrine factors released from ER-positive cells under the influence of estradiol. This organization may be disrupted in some tumors.


Review of factors that influence the abundance of ions produced in a tandem mass spectrometer and statistical methods for discovering these factors.
Proteomic technologies are important because they link genes, proteins and disease. The identification of proteins and peptides has been revolutionized in the last decade by the use of mass spectrometry. This method is highly sensitive and much faster than the chemical reactions used previously because it can fragment peptides in seconds rather than in hours or days. Proteins are digested with an enzyme, usually trypsin, and the resulting peptides are fragmented in a tandem mass spectrometer (MS/MS). The masses of the fragment ions formed in the MS/MS can be used to identify the sequence of amino acids in the peptides. However, a number of different factors have been found to influence the amount of the various types of fragment ion formed. In this article, we review these factors and their interrelation together with the statistical methods used to discover them. Information on the number of fragment ions formed is at present underused in peptide identification algorithms, and fully utilizing this information could improve current algorithms.


Clinical leadership project.
Nurse educators seek innovative strategies to maximize student learning in the classroom and clinical settings. Students enrolled in a nursing leadership and management course often find they spend more clinical time observing leaders than practicing the necessary skills to lead others in the provision of nursing care. In addition, opportunities to explore the nurse educator role often do not exist in baccalaureate nursing education, despite the shortage of nurse educators. An experience was developed in a baccalaureate nursing program to give senior students, under supervision of faculty, the opportunity to lead and evaluate lower-level students providing patient care in the clinical setting and to experience the role of nursing faculty. Feedback from senior students was positive, and students noted increased proficiency in leadership ability and critical thinking. Student interest in the nurse educator role was also enhanced. Program expansion and evaluation with faculty, clinical staff, and patients are planned.


Prevention of postsurgery-induced abdominal adhesions by electrospun bioabsorbable nanofibrous poly(lactide-co-glycolide)-based membranes.
The objective of this study was to evaluate the efficacy of nonwoven bioabsorbable nanofibrous membranes of poly(lactideco-glycolide) for prevention of postsurgery-induced abdominal adhesions. Recent reports indicated that current materials used for adhesion prevention have only limited success. Studies on other bioabsorbable materials using a new fabrication technique demonstrated the promising potential of generating an improved and inexpensive product that is suitable for a variety of surgical applications. All rats underwent a midline celiotomy. The cecum was identified and scored using an abrasive pad until serosal bleeding was noted on the anterior surface. A 1 x 1 cm of abdominal wall muscle was excised directly over the cecal wound. The celiotomy was then closed in 2 layers immediately (control) after a barrier was laid in between the cecum and the abdominal wall. All rats underwent a second celiotomy after 28 days to evaluate the extent of abdominal adhesions qualitatively and quantitatively. Cecal adhesions were reduced from 78% in the control group to 50% in the group using biodegradable poly(lactide-co-glycolide) (PLGA) nonwoven nanofibrous membranes (n = 10, P = 0.2) and to 22% in the group using membranes containing PLGA and poly(ethylene glycol)/poly(D,L-lactide) (PEG-PLA) blends (n = 9, P = 0.03). Electrospinning method also enabled us to load an antibiotic drug Cefoxitin sodium (Mefoxin; Merck Inc., West Point, PA) with high efficacy. The electrospun PLGA/PEG-PLA membranes impregnated with 5 wt% cefoxitin sodium, which amounts to approximately 10% of the systemic daily dose typically taken after surgery in humans, completely prevented cecal adhesions (0%) in rats. Electrospun nonwoven bioabsorbable nanofibrous membranes of poly(lactide-co-glycolide) were effective to reduce adhesions at the site of injury using an objective rat model. The membrane acted as a physical barrier but with drug-delivery capability. The combined advantages of composition adjustment, drug-loading capability, and easy placement handling (relatively hydrophobic) make these membranes potentially successful candidates for further clinical evaluations.


Capillary electrophoretic development of aptamers for a glycosylated VEGF peptide fragment.
The emergence of functional genomics and proteomics has added to the growing need for improved analysis methods that can detect and distinguish between protein variants resulting from allelic variation, mutation, or post-translational modification. Aptamers, single-stranded DNA or RNA molecules that fold into three-dimensional structures conducive to binding targets, have become an attractive alternative to antibodies for this type of analysis. Although aptamers have been developed for a wide range of target species, very few sequences have been identified that bind selectively to proteins with specific post-translational modifications. Using capillary electrophoresis-based selection, we have developed DNA aptamer sequences that selectively bind an N-glycosylated peptide fragment of vascular endothelial growth factor (VEGF). The selection method incorporates alternating positive- and counter-selection steps in free solution in order to obtain aptamers with both high affinity toward the glycosylated target and high selectivity versus a non-glycosylated variant. Affinity capillary electrophoresis and surface plasmon resonance binding assays indicate these sequences have low-µM dissociation constants and preferentially bind the glycosylated peptide with as much as 50-fold specificity. Such aptamers could serve as tools for rapid and simple monitoring of disease-linked functional changes in proteins, with potential applications in drug screening and disease diagnosis.


Erythrocyte L-arginine uptake in peritoneal dialysis patients: systems y and y+ L.
L-Arginine is the substrate for nitric oxide synthesis and may enter cells by the y+ and y+ L transport systems. Peritoneal membrane characteristics may depend on vascular function and the L-arginine-nitric oxide pathway. In a cross-sectional study, we evaluated erythrocyte L-arginine uptake in stable peritoneal dialysis (PD) patients with various categories of peritoneal transport function. We used 14C as a marker and N-ethyl-maleimide as an inhibitor of the y+ system to measure maximal uptake capacity (Vma in ulmol/L cell/h) and the half-saturation constant (Km in micromol/L) in erythrocytes. The sample consisted of 41 patients (mean age: 50 +/- 17 years; 5 with diabetes; 18 men). Mean dialysate-toplasma creatinine (D/P(Cr)) was 0.62 +/- 0.14. Peritoneal membrane transport was classified as high, high-average, low-average, or low in 10, 11, 11, and 9 patients, respectively. Mean y+ L Vmax, was 208 +/- 111 micromol/L cell/h, 494 +/- 893 micromol/L cell/h, 222 +/- 59 micromol/L cell/h, and 193 +/- 63 umol/L cell/h [p = 0.404, analysis of variance (ANOVA)] for the high, high-average, low-average, and low transporters respectively. Similarly, mean y+ Vmax was 963 +/- 1034 micromol/L cell/h 843 +/- 366 micromol/L cell/h, 639 +/- 254 micromol/L cell/h, and 774 +/- 378 micromol/L cell/h (p = 0.647, ANOVA). As with Vmax, the y+ L Km and y+ Km values were not significantly different between the various peritoneal transport categories. A negative correlation was observed between y+ Vmax and Kt/V (r = -0.393, p = 0.011). Erythrocyte uptake of L-arginine does not vary with peritoneal membrane transport characteristics, but maximal L-arginine uptake capacity is higher in patients with a lower Kt/V.


The correlates of unemployment and its association with quality of life in cervical cancer survivors.
Little is known regarding cervical cancer survivors' employment status, which represents social integration of cancer survivors as a pivotal domain of long-term quality of life. The goal of this study was to assess the correlates of unemployment and evaluate the impact on the comprehensive quality of life in cervical cancer survivors. We enrolled 858 cervical cancer survivors from the gynecologic oncology departments of multi-centers in Korea. Factors associated with unemployment were identified using multivariate logistic regression analyses. We assessed different health-related quality of life domains with multivariate-adjusted least-square means between cervical cancer survivors who currently work and do not. After diagnosis and treatment, the percentage of unemployed survivors increased from 50.6% to 72.8%. Lower income (adjusted odds ratio [aOR], 1.97; 95% confidence interval [CI], 1.38 to 2.81), medical aid (aOR, 1.58; 95% CI, 1.05 to 2.38), two or more comorbidities (aOR, 1.80; 95% CI, 1.12 to 2.90), current alcohol drinkers (aOR, 2.33; 95% CI, 1.54 to 3.52), and employed at the time of diagnosis (aOR, 10.72; 95% CI, 7.10 to 16.16) were significantly associated with unemployment. Non-working groups showed significant differences with respect to physical functioning, role functioning, depression, and existential well-being. The proportion of unemployed cervical cancer survivors seems to increase, with low-income status and the presence of medical aid negatively being associated with employment, in addition to other comorbidities and previous working status. Effort should be made to secure the financial status of cervical cancer survivors.


A neuromagnetic study of movement-related somatosensory gating in the human brain.
Neuromagnetic fields from the left cerebral hemisphere of five healthy, right-handed subjects were investigated under three different experimental conditions: (1) electrical stimulation of the right index finger (task S); (2) voluntary movement of the same finger (M); (3) M+S condition, consisting of voluntary movements of the right index finger triggering the electrical stimulus at the very beginning of the electromyogram. The three conditions were administered in random order every 5-8 s. In addition, the task somatosensory evoked fields (task SEFs) gathered during condition (1) were compared with control SEFs recorded at the beginning of the experiment during rest. In all subjects the overlay of somatosensory stimulation on movement provoked a decrement in brain responsiveness (gating) as determined by the amplitude of gated SEFs. The latter was found as the difference between the neuromagnetic fields during M+S condition (overlaying of movement and sensory stimulation) minus neuromagnetic fields under M condition (M only). The gating effect was found to begin approximately 30 ms after movement onset, and to last for the whole period of the ongoing movement. The theoretical locus of gating was estimated by dipole localisation of the difference between task SEFs and gated SEFS using a moving dipole model. The site of the "early" gating effect (< 40 ms) was found to be more anteriorly located than the "later" (> 40 ms) gating effect. The task SEFs were found to be larger (significant after 30 ms) than the control SEFs elicited under the basal condition. The results are discussed with respect to timing, mechanism (centrifugal and centripetal), locus and selectivity of gating. In addition, the results are discussed with regard to clinical application (measuring attentional deficits in patients with impairments of higher mental functions and measuring gating deficits in patients with disturbed sensorimotor integration.


Ratchet-induced segregation and transport of nonspherical grains.
We consider through simulations the behavior of elongated grains on a vibrating ratchet-shaped base. We observe differences in layer velocity profile and in net grain velocity for grains that are composed of one, two, or three collinear spheres. In the case of mixtures of different species of grains, we demonstrate layer-by-layer variation in the average velocity as well as layer segregation of species, and show that horizontal separation of the species can be achieved using this geometry. We also find that the addition of a small number of shorter grains to a sample of long grains provides a lubrication effect that increases the velocity of the long grains.


Oral fluid and plasma cannabinoid ratios after around-the-clock controlled oral Δ(9)-tetrahydrocannabinol administration.
Oral fluid (OF) testing is increasingly important for drug treatment, workplace, and drugged-driving programs. There is interest in predicting plasma or whole-blood concentrations from OF concentrations; however, the relationship between these matrices is incompletely characterized because of few controlled drug-administration studies. Ten male daily cannabis smokers received around-the-clock escalating 20-mg oral Δ(9)-tetrahydrocannabinol (THC, dronabinol) doses (40-120 mg/day) for 8 days. Plasma and OF samples were simultaneously collected before, during, and after dosing. OF THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC (THCCOOH) were quantified by GC-MS at 0.5-μg/L, 0.5-μg/L, and 7.5-ng/L limits of quantification (LOQs), respectively. In plasma, the LOQs were 0.25 μg/L for THC and THCCOOH, and 0.5 μg/L for 11-hydroxy-THC. Despite multiple oral THC administrations each day and increasing plasma THC concentrations, OF THC concentrations generally decreased over time, reflecting primarily previously self-administered smoked cannabis. The logarithms of the THC concentrations in oral fluid and plasma were not significantly correlated (r = -0.10; P = 0.065). The OF and plasma THCCOOH concentrations, albeit with 1000-fold higher concentrations in plasma, increased throughout dosing. The logarithms of OF and plasma THCCOOH concentrations were significantly correlated (r = 0.63; P < 0.001), although there was high interindividual variation. A high OF/plasma THC ratio and a high OF THC/THCCOOH ratio indicated recent cannabis smoking. OF monitoring does not reliably detect oral dronabinol intake. The time courses of THC and THCCOOH concentrations in plasma and OF were different after repeated oral THC doses, and high interindividual variation was observed. For these reasons, OF cannabinoid concentrations cannot predict concurrent plasma concentrations.


[Analysis of qualifications of medical and health institutions and certified doctors for providing occupational disease diagnosis in China].
To investigate the qualifications and current situations of the medical and health institutions and certified doctors for providing occupational disease diagnosis in China and to provide a reference for developing relevant policies. Work reports and questionnaires survey were used to investigate the qualifications of all medical and health institutions and certified doctors for providing occupational disease diagnosis in China and their acceptance and diagnosis of occupational disease cases from 2006 to 2010. The rate for the work reports was 100%, and the response rate for the questionnaires was 71.0%. By the end of 2010, in the 31 provincial-level regions (excluding Hong Kong, Macao, and Taiwan) in China, there had been 503 medical and health institutions which were qualified for providing occupational disease diagnosis, including 207 centers for disease control and prevention, accounting for 41.2%, 145 general hospitals, accounting for 28.8%, 69 enterprise-owned hospitals, accounting for 13.7%, and 64 institutes or centers for occupational disease prevention and control, accounting for 12.7%; 4986 certified doctors got the qualification for providing occupational disease diagnosis, with 9.4 certified doctors on average in each institution, and there was 0.65 certified doctor per 100 000 employees. In addition, 16.5% of the institutions got all the qualifications for diagnosing 9 occupational diseases, and 17.1% of the institutions got the qualification for diagnosing one occupational disease. Each certified doctor accepted diagnosis of 16.8 cases of occupational diseases on average every year. A national occupational disease diagnosis network has been established in China, but the imbalance in regional distribution and specialty programs still exists among the qualified medical and health institutions and certified doctors. It is essential to further strengthen the development of regional qualified medical and health institutions and training of qualified doctors.


Placental pathology for the nineties.
Examination of the placenta in a problem pregnancy is potentially very valuable, yielding information about the nature and duration of processes occurring in gestation. Such evaluation requires thoughtful gross examination, careful sectioning, and an understanding of the basic microscopic changes in a variety of pathologic processes. As there are very few absolute associations in placental pathology, it is most important to appreciate the range of normal in assessing the potential importance of lesions. This chapter has tried to provide the essential relevant material, with emphasis on commonly encountered problem areas, and a variety of topics potentially related to maternal and fetal morbidity and mortality.


Polysomnographic characteristics of a referred sample of children with sickle cell disease.
To describe polysomnographic parameters and their clinical correlates in a referred sample of children with sickle cell disease (SCD). This was a retrospective medical record review of 55 consecutive children aged 2-18 years with SCD (hemoglobin [Hb] SS and Hb SC genotypes) undergoing polysomnography for evaluation of sleep disordered breathing. Polysomnography values were compared between SCD genotypes, 4 age groups, and adenotonsillectomy status using descriptive and nonparametric statistics. Obstructive sleep apnea (OSA) was diagnosed in 38/55 (69%) children. Polysomnographic parameters differed significantly between Hb SS and Hb SC genotypes only on arterial oxyhemoglobin saturation (SpO2; 95.2 +/- 3.8 vs. 98.0 +/- 0.8, respectively, p < 0.01) and percent of sleep time below SpO2 90% (T90; 8.0 +/- 22.0 vs. 0.01 +/- 0.02, respectively, p < 0.05). Increasing age was associated with decreasing SpO2 (rho = -0.282, p < 0.05), obstructive apnea-hypopnea index (OAHI; rho = -0.364, p < 0.01), total arousal index (rho -0.272, p < 0.05) and respiratory arousal index (rho = -0.349, p < 0.01). Periodic limb movements in sleep (PLM) averaged 4.7 +/- 8.8/h, with a PLM index > 5/h in 5/17 children without OSA. Post- adenotonsillectomy, 8/10 children had OSA, but compared to untreated OSA-positive children they had a lower mean OAHI (4.4 +/- 5.5 vs. 8.9 +/- 12.5) and a lower T90 (1.6 +/- 4.2 vs. 9.2 +/- 24.9). Both OSA and PLMs were common in children with SCD. Children with Hb SS experienced more severe nocturnal oxygen desaturation than did those with Hb SC. Post-adenotonsillectomy, most children had OSA, although they experienced fewer obstructive respiratory events and less severe nocturnal oxygen desaturation than did untreated OSA-positive children.


Gold-catalyzed intramolecular diazo coupling: an efficient macrocyclization towards cyclic olefins.
A gold-catalyzed intramolecular coupling of diazo compounds to produce cyclic olefins has been well established. The medium and large sized membered olefins were obtained in moderate to good yields. Notably, the Z/E selectivity of the olefins highly depended on the ring size. Furthermore, this investigation indicated that the structure of the phosphorous ligand binding to the gold centre played a vital role in the reaction efficiency. Also, high dilution of the reaction mixture is not needed.


Microscopic and macroscopic stress with gravitational and rotational forces.
Many recent papers have questioned Irving and Kirkwood's atomistic expression for stress. In Irving and Kirkwood's approach both interatomic forces and atomic velocities contribute to stress. It is the velocity-dependent part that has been disputed. To help clarify this situation we investigate (i) a fluid in a gravitational field and (ii) a steadily rotating solid. For both problems we choose conditions where the two stress contributions, potential and kinetic, are significant. The analytic force-balance solutions of both these problems agree very well with a smooth-particle interpretation of the atomistic Irving-Kirkwood stress tensor.


Neurocognitive performance in first-episode and chronic schizophrenic patients.
Previous research on neuropsychological disturbances in first-episode and chronic schizophrenic patients has provided mixed results which can be partially attributed to methodological inconsistencies. For the present study, 70 schizophrenic patients (40 with chronic and 30 with first-episode schizophrenia) were compared to 30 healthy controls on a large battery of neuropsychological tests. Special attention was paid to potential confounds such as differences in psychopathology, age and educational level between the schizophrenic sub-samples. Healthy controls performed better than both first-episode and chronic patients in almost all cognitive domains (P < 0.01), while the patient samples did not differ in any of the tasks. Results were confirmed in a second series of analyses in which patient subgroups were equated for sociodemographic background variables. The present results confirm recent data collected in longitudinal studies, thus, lending further support for a neurodevelopmental model of schizophrenia. It is suggested that neuropsychological disturbances occur early in schizophrenia and do not worsen in the course beyond age-related decrement. Possible reasons why previous research has produced contradictory findings are discussed.


Low Level of Haptoglobin in Lupus.
Haptoglobin levels are measured in systematic lupus erythematosus patients as part of the workup for anemia, with low levels indicating hemolysis. Haptoglobin is an acute phase protein. We present 2 lupus patients who were found to have low haptoglobin levels in the absence of other evidence of hemolysis.


Physical mapping of 20 unmapped fragments of the btau_4.0 genome assembly in cattle, sheep and river buffalo.
The recent advances in sequencing technology and bioinformatics have revolutionized genomic research, making the decoding of the genome an easier task. Genome sequences are currently available for many species, including cattle, sheep and river buffalo. The available reference genomes are very accurate, and they represent the best possible order of loci at this time. In cattle, despite the great accuracy achieved, a part of the genome has been sequenced but not yet assembled: these genome fragments are called unmapped fragments. In the present study, 20 unmapped fragments belonging to the Btau_4.0 reference genome have been mapped by FISH in cattle (Bos taurus, 2n = 60), sheep (Ovis aries, 2n = 54) and river buffalo (Bubalus bubalis, 2n = 50). Our results confirm the accuracy of the available reference genome, though there are some discrepancies between the expected localization and the observed localization. Moreover, the available data in the literature regarding genomic homologies between cattle, sheep and river buffalo are confirmed. Finally, the results presented here suggest that FISH was, and still is, a useful technology to validate the data produced by genome sequencing programs.


Surgical treatment of deep burns.
The results are presented of the treatment of 168 patients aged 1 to 60 yr with deep burns. The use of active surgical tactics in patients with deep and extensive burns was tested. It was found that the application of a method of active surgical tactics, in combination with different approaches of wound covering such as "combined auto- and allografting", "combined auto- and porcine-skin grafting", and "combined autografting with cultivated allofibroblast cell culture usage", reduced purulent-septic complications and improved the results of treatment.