Diagnostic utility of hepatocyte nuclear factor 1-beta immunoreactivity in endometrial carcinomas: lack of specificity for endometrial clear cell carcinoma.
Hepatocyte nuclear factor 1-beta (HNF1β) has recently emerged as a relatively sensitive and specific marker for ovarian clear cell carcinoma. The purpose of this study is to assess the diagnostic utility of this marker for endometrial clear cell carcinoma. Immunohistochemical analysis was performed on 75 endometrial tissues using a goat polyclonal antibody raised against a peptide mapping at the C-terminus of human HNF1β protein. The 75 cases included 15 clear cell carcinomas, 20 endometrioid carcinomas, 15 endometrial serous carcinomas/uterine papillary serous carcinomas, 20 cases of normal endometrium, 2 cases of clear cell metaplasia, and 3 cases of Arias Stella reaction. Staining interpretations were based on a semiquantitative scoring system, a 0 to 12+ continuous numerical scale that was derived by multiplying the extent of staining (0 to 4+ scale) by the intensity of staining (0 to 3+ scale) for each case. HNF1β expression was found to be present in a wide spectrum of tissues. Twenty-seven (54%) of the 50 carcinomas displayed at least focal nuclear HNF1β expression, including 11 (73%) of 15, 9 (60%) of 15, and 7 (35%) of 20 clear cell, serous, and endometrioid carcinomas, respectively. The average nuclear staining scores for clear cell carcinomas, endometrioid carcinomas, and serous carcinomas were 5.2, 1.4, and 4.1, respectively. Clear cell carcinomas and endometrioid carcinomas displayed statistically significant differences regarding their nuclear staining scores (P = 0.0027), but clear cell carcinomas and endometrial serous carcinomas did not (P = 0.45). The calculated sensitivity of any nuclear HNF1β expression in classifying a carcinoma as being of the clear cell histotype was 73%, whereas the specificity was 54%. Nineteen of 20 normal endometrium samples displayed at least focal nuclear expression of HNF1β, and this expression was often diffuse. The 5 cases of benign histologic mimics of clear cell carcinomas (Arias Stella reaction and clear cell metaplasia) displayed some degree of HNF1β immunoreactivity, with an average nuclear staining score of 7.3. We conclude that although HNF1β is frequently expressed in clear cell carcinomas, it should be used with caution as a diagnostic marker because of its lack of specificity. It neither distinguishes endometrial serous carcinomas from clear cell carcinomas nor clear cell carcinomas from its benign mimics. The greatest diagnostic utility of HNF1β expression may be in a supportive evidentiary role favoring clear cell carcinoma when the principal differential diagnostic consideration is endometrioid carcinoma.


No effect of the hemoglobin solution HBOC-201 on the response of the rat R1H tumor to fractionated irradiation.
Tumor hypoxia is regarded as one important underlying feature of radioresistance. The authors report on an experimental approach to improve tumor response to radiation by combining fractionated irradiation with HBOC-201, an ultrapurified polymerized hemoglobin solution, which is currently used in clinical phase II/III trials as alternative oxygen carrier and proved to be highly effective in tissue oxygenation (tpO(2)). Subcutaneously growing rhabdomyosarcoma R1H tumors of the rat were treated with either 40 Gy (2 Gy/fraction, 20 fractions in 2 weeks, ambient) followed by graded top-up doses (clamped) alone, or in combination with HBOC-201, or with HBOC-201 plus carbogen (95% O(2) + 5% CO(2)). Local tumor control (TCD50%) and growth delay were used as endpoints. In addition, the effect of HBOC-201 alone or in combination with carbogen on the tpO(2) of tumor and muscle was determined using a flexible stationary probe (Licox, GMS). TCD50% values of 119 Gy (95% confidence interval 103;135), 111 Gy (84;138), and 102 Gy (83;120) were determined for tumors irradiated alone, in combination with HBOC-201, and with HBOC-201 plus carbogen, respectively. Although the dose-response curves showed a slight shift to lower doses when HBOC-201 or HBOC-201 plus carbogen was added, the differences in TCD50% were not statistically significant. No effect was seen on the growth delay of recurrent tumors. HBOC-201 alone did not effect tumor or muscle tpO(2). In combination with carbogen the mean tpO(2) of muscle raised from 23.9 mmHg to 59.3 mmHg (p < 0.05), but this effect was less pronounced than the increase in tpO(2) by carbogen alone. Low-dose application of HBOC-201 does not improve the response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation.


Gas exchange responses to constant work-rate exercise in patients with glycogenosis type V and VII.
During constant work-rate exercise above the lactic acidosis threshold, oxygen consumption fails to plateau by 3 minutes, but continues to rise slowly. This slow component correlates closely with the rise in lactate in normal subjects. We investigated if oxygen consumption during constant work-rate exercise could rise after 3 minutes in the absence of a rise in lactate. We studied five patients with McArdle's disease, one patient with phosphofructokinase deficiency and six normal subjects. Subjects performed two 6-minute duration constant work-rate exercise tests at 40 and 70% of peak oxygen consumption. During low-intensity exercise, oxygen consumption reached steady state by 3 minutes in both groups. Lactate rose slightly in control subjects but not in patients. During high-intensity exercise, oxygen consumption rose from the third to the sixth minute by 144 (21-607) ml/minute (median and range) in control subjects and by 142 (73-306) ml/minute in patients (p = not significant, Mann-Whitney U test). Over the same period, lactate (geometric mean and range) rose from 2.68 (1.10-5.00) to 5.39 (2.70-10.00) mmol/L in control subjects, but did not rise in patients (1.20 [0.64-1.60] to 0.70 [0.57-1.20] mmol/L). We conclude that the slow component of oxygen consumption during heavy exercise is not dependent on lactic acidosis.


Testosterone and the decline of sexual behavior in aging male rats.
This experiment was designed to elucidate the role of testosterone in the decline of sexual behavior in aging males. Old (25 months) and middle-aged (10 months) male rats were given six tests (30-min long) of sexual behavior. The old males then were divided into two groups: intact and castrated with testosterone treatment. The middle-aged males were divided into three groups: intact, castrated with testosterone present all the time, and castrated with testosterone present only when tested. The old males were given another set of six tests 1 week after the operation (when 27.5 months old), and the middle-aged males were given three more sets of six tests 8, 26, and 39 weeks after the operation (when 15, 19, and 22.5 months old, respectively). Blood drawn after each test set was assayed for testosterone. The middle-aged intact males had higher levels of testosterone than the old intact males, and the testosterone-treated castrated males, whether middle-aged or old, had higher levels than the intact males. The presence of higher levels at the time of testing resulted in increased rates of mounting and intromitting in old males and an attenuated decline in the mount rate and percentage of tests with intromissions in middle-aged males. The middle-aged castrated males with continuous testosterone differed from the middle-aged castrated males with periodic testosterone only in the mount-intromission interval; the former group had a longer interval. It was concluded that testosterone, in general, does not prevent or reverse the decline in sexual performance of aging male rats and that the degree and rate of decline do not depend on whether or not testosterone is continuously present.


An unusual finding of massive pulmonary embolism in a patient during treatment with high-dose ibuprofen.
Non-steroidal anti-inflammatory drugs have been associated with an increased risk of venous thromboembolism. We report for the first time, the case of a patient who developed massive pulmonary embolism after a long period of treatment with high doses of ibuprofen. A 65-year-old woman was admitted with severe dyspnea while on treatment with high doses of ibuprofen for diffuse spine pain due to arthrosis. A spiral computed tomography showed a massive pulmonary embolism. No other explanation for the thromboembolic disorder was found. She was successfully treated with therapeutic doses of low-molecular-weight heparin followed by rivaroxaban. Ibuprofen was discontinued and replaced by tramadol. High-dose ibuprofen is likely to have accounted for the life-threatening thromboembolic disorder.


[Determination of oxygenates in methanol-to-olefin gasoline byproducts and methanol-to-gasoline product with solid phase extraction-gas chromatography].
Silica solid phase extraction (SPE) column was used for sample pretreatment to enrich the target analytes and simplify background. Due to its high efficiency, reliability and simplicity, the technique has been widely used in many fields. The byproduct gasoline of methanol-to-olefin (MTO) and the product of methanol-to-gasoline (MTG) mainly consist of hydrocarbons along with small amounts of oxygenates. Trace amounts of oxygenates are hard to identify because of their complex hydrocarbon components. With the SPE technique, the samples were separated into two major classes, oxygenates and hydrocarbons. Oxygenates were then determined with gas chromatography-mass spectrometry (GC-MS). The elution conditions of the silica solid phase extraction column were optimized with the standard sample. Under the optimized elution conditions, the hydrocarbons were first eluted from the SPE column with 5 mL dichloromethane, the oxygenates were then eluted with 3 mL acetonitrile. The recoveries of standard samples were tested before and after pretreatment. The standard recoveries were 87.7%-95.3%. The oxygenates except methanol and ethanol were then quantified by gas chromatography-flame ionization detection (GC-FID) and internal standard method. Methanol and ethanol were then quantified by extracting characteristic ion chromatograms and external standard method. The results show that the oxygenates of MTO byproduct gasoline and MTG product mainly consist of ketones and aldehydes. The method improves the sensitivities of the target compounds and reduces the interference of the background.


Effects on ionized calcium of a correction of acidosis with alkalinizing agents. A rational basis for the administration of calcium in cardiac resuscitation.
The effects on the ionized calcium concentration of a correction of various forms of acidosis with sodium bicarbonate or (tris-hydroxymethyl)aminomethane (THAM) were investigated in vitro in human plasma. Calculation of least square regression equations of ionized calcium (m mol) on pH yielded the following regression coefficients: hydrochloric acidosis: -0.65 +/- 0.06; lactic acidosis: -0.27 +/- 0.05; hydrochloric acidosis corrected with sodium bicarbonate: -0.65 +/- 0.02; lactic acidosis corrected with sodium bicarbonate: -0.51 +/- 0.03. The results indicate that after correction of lactic acidosis the ionized calcium concentration will be below the control values while pH is restored to the normal range. This effect is even more pronounced when THAM is used. The findings point to the need for calcium administration in cardiac resuscitation.


Occupational exposome: a network-based approach for characterizing Occupational Health Problems.
Surveillance of work-related diseases and associated exposures is a major issue of public health, in particular for identifying and preventing new threats for health. In the occupational health context, the French national occupational disease surveillance and prevention network (RNV3P) have constructed a growing database that records every year all Occupational Health Problems (OHPs) diagnosed by a network of physician specialists. The network aims to provide and develop an expertise on the disease-exposure relationships, and uses the RNV3P database for developing the surveillance of OHPs and for the detection of emerging associations between diseases and occupational exposures. In this paper, we have developed the theoretical framework of the occupational exposome, defined as a network of OHPs linked by similar occupational exposures, as a novel approach which allows to characterize and to analyze the disease-exposure associations reported in the RNV3P database in the form of a relational network. Next, the occupational exposome is structured in terms of occupational exposure groups which constitute informative sub-sets of hazards considered as the backbone tree spectrum of the occupational exposures potentially related to a disease. To illustrate the wide possibilities of this method, the exposome approach is applied to the RNV3P database's sample of Non-Hodgkin Lymphomas (NHLs). As a result, we found that the NHL occupational exposome could be described in terms of 86 embedded exposure groups, defined as a set of OHPs sharing at least one component of the occupational multi-exposure. For example, "organic solvents and thinners" is the most represented hazards related to NHLs, but is also co-associated to "benzene", "ionizing radiations" or "agricultural products". From the knowledge stored in the database by physician experts, the occupational exposome constitutes a decisive step towards the evolving monitoring of multi-exposure associated to a given disease.


Response of the law to developments in genetics.
In this article, first of all the potential role of the law with regard to complex developments like those in genetics is examined; a distinction is made between substantive law (for example prohibitions) and procedural law (for example licensing systems), and between statutory and voluntary regulation. In Europe, in particular the parliament of the European Union has called for legislation. Although several European countries have prepared legislation relating to particular aspects (for instance embryo research, genetic screening, use of genetic tests in employment and insurance), in general the response would seem cautious. When legislation is envisaged the outcome of the lawmaking process is not always predictable because of moral pluralism and political pressures. Legislating in this field is hard also for other reasons, such as the pace of development and the difficulty to assess the social consequences of developments. Other problems are the similarity or difference between genetic information and conventional medical information, and the fact that the developments in genetics lay bare more general deficiencies in the social system. With regard to many developments, the response of the law in the immediate future should be to monitor rather than to ban; where possible, self-regulation should be preferred over statutory regulation, and general laws over genetic specific laws. An international level, common principles should be adopted to serve as a framework for national legislation. Nevertheless, in some areas legislation may already be needed: in particular where genetic technologies or their results are being applied outside the regular health care setting, for instance in the form of population screening or testing for insurance purposes.


Increasing incidence of diabetes after gestational diabetes: a long-term follow-up in a Danish population.
To study the incidence of diabetes among women with previous diet-treated gestational diabetes mellitus (GDM) in the light of the general increasing incidence of overweight and diabetes and to identify risk factors for the development of diabetes. Women with diet-treated GDM during 1978-1985 (old cohort, n = 241, also followed up around 1990) or 1987-1996 (new cohort, n = 512) were examined in 2000-2002. Women were classified by a 2-h, 75-g oral glucose tolerance test according to the World Health Organization criteria or an intravenous glucagon test supplemented by measurement of GAD antibodies. Historical data from index-pregnancy and anthropometrical measurements were collected. A total of 481 (63.9%) women were examined (median 9.8 years [interquartile range 6.4-17.2]) after index pregnancy. Diabetes and impaired glucose tolerance (IGT)/impaired fasting glucose were present in 40.0 and 27.0% of women, respectively. In the new cohort, 40.9% had diabetes compared with 18.3% in the old cohort at the 1990 follow-up (P < 0.0005). Prepregnancy BMI was significantly higher in the new compared with the old cohort (26.0 [22.5-30.8] vs. 22.9 kg/m2 [20.2-28.0], P < 0.0005). Among others, new-cohort membership, prepregnancy overweight (BMI > or = 25 kg/m2), and IGT postpartum were identified as independent predictors of diabetes by multiple logistic regression analyses. The incidence of diabetes among Danish women with previous diet-treated GDM was very high and had more than doubled over a 10-year period. This seems to be due to a substantial increase in BMI in women with GDM.


Peripheral ameloblastoma with potentially malignant features: report of a case with special regard to its keratin profile.
A peripheral ameloblastoma with atypical features occurring on the left maxillary alveolar ridge of 40-year-old man is described, along with an immunohistochemical profile of its cytokeratin (CK). The lesion apparently originated from the surface gingival epithelium. The tumor nests or strands were highly cellular with a variable degree of squamous differentiation and microcyst formation. Occasional mitotic figures and dystrophic calcification, both of which are not seen in conventional ameloblastomas, were also observed. The tumor infiltrated deep into the alveolar mucosa, including the periodontal ligament, and showed histological and topographical evidence of atypism, resulting in resorption of the underlying alveolar bone. On the CK immunohistochemistry, CK19 was demonstrated in all the types of neoplastic epithelia, including microcyst-forming cells, densely packed round or spindle cells within the tumor nests, cells with squamous metaplasia, and peripheral tall columnar cells. The CK immunohistochemical findings suggest the lesion's cell of odontogenic origin; they may reflect an immature phenotypic expression of cell differentiation in the odontogenic epithelia during the tumor growth in the gingival mucosa.


Phosphatidylserine expression on the platelet membrane of patients with myeloproliferative disorders and its effect on platelet-dependent thrombin formation.
Recently, the asymmetric distribution of phospholipids in eukaryotic cell membranes has been appreciated and been found to be dependent on the activity of a number of enzymes. The expression of phosphatidylserine (PS), a negatively charged phospholipid, on the platelets of patients with polycythemia vera (P vera) and essential thrombocythemia (ET) was compared to that in normal individuals. The effect of platelet aggregation on PS expression was determined. Exposure of PS on platelets obtained from patients with P vera and ET and from age- and sex-matched healthy volunteers was measured by fluorescein-labeled Annexin V binding to platelets and by the platelets' thrombin-generating capacity determined by the prothrombinase assay. PLatelet prothrombinase activity (mean +/- standard deviation [SD]), as measured by thrombin generation, was 2.32+/-2.2 micro/mL in the P vera group and 1.55+/-1.0 micro/mL in the control group (p=0.3). PS expression as measured by Annexin V binding (mean +/- SD) was 2.6+/-2.4 % in the P vera group versus 1.55+/-1.2% among controls (p=0.03). In the ET group, prothrombinase activity (mean +/- SD) was 1.0+/-0.6 micro/mL and 2.1+/-0.9 micro/mL in the control group (p=0.006). Annexin V binding (mean +/- SD) was 4.8+/-4.2% in the ET group and 2.77+/-2.1% among control subjects (p=0.09). When the prothrombinase assay was performed after addition of adenosine diphosphate (ADP) to the platelets, there was a significant increase in thrombin generation in the myeloproliferative disorder (MPD) group (3.1+/-2.0 micro/mL) compared to the thrombin generated by unstimulated myeloproliferative disorder platelets (2.07+/-1.69 micro/mL) (p=0.0006). An increase in thrombin generation was seen in the ADP-stimulated platelet samples in all ten paired samples studied. Likewise, the addition of ADP to control platelets increased thrombin generation from 2.0+/-1.0 micro/mL in unstimulated platelets to 4.3+/-1.6 micro/mL in ADP-treated platelets (p=0.0006). Thrombin generation increased in all of the ADP-stimulated platelet samples compared to the untreated platelets. There was however, no difference in the increased thrombin generation when ADP-stimulated platelets from MPD patient and control subjects were compared (p=0.3). Results indicate that some patients with MPDs may show increased PS expression on platelet surface. When analyzed overall, there was a tendency toward greater PS expression in the P vera and ET patient groups; however, the increase did not reach statistical significance. This increase was noted in both the prothrombinase assay the Annexin V binding assay. We have also shown that stimulation of platelets by addition of the agonist ADP results in enhanced PS expression, which appears increase the thrombogenic potential of the platelets as demonstrated by the enhanced thrombin generation demonstrated by these platelets in the prothrombinase assay. There was no difference in the degree of PS expression in response to ADP stimulation between MPD and control platelets. Results show that PS expression and platelet-dependent thrombin generation is variable in patients with MPDs. This expression is increased after platelet aggregation occurs. The role of PS expression in the thromboembolic complications of MPD patients should be studied further.


Phototherapeutic keratectomy: who are the best candidates and how do you treat them?
To discuss the primary types of lesions most amenable to excimer laser phototherapeutic keratectomy (PTK) and the specific techniques to best treat each of these disorders. Elevated and anterior stromal lesions respond best to PTK. PTK can also be used to effectively treat recurrent erosions. Smoothing agents and intraoperative mitomycin C can be helpful for certain disorders. The preoperative evaluation is very important in order to establish whether the eye is a good candidate for excimer laser PTK. Careful slit lamp evaluation and ancillary testing can not only determine how good a candidate they are but just as importantly, the best surgical approach. Surgeons and patients need to understand the limitations of PTK for proper informed consent. PTK is a minimally invasive procedure that is often successful in delaying or avoiding more aggressive corneal surgeries.


[Fetal programming and the etiology of osteoporosis].
Osteoporosis is a multifactorial skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased risk of fracture. Peak bone mass is an important predictor of later risk of osteoporosis. Epidemiological studies revealed that the risk of osteoporosis might be modified by exposure to environmental factors during intrauterine life and early postnatal period. This review summarizes the influence of fetal programming on the development of osteoporosis based on the epidemiological studies and potential mechanisms of epigenetic regulation of gene expression.


Human chromatid ultrastructure: new observations with scanning and transmission electron microscopy.
Two new observations have been made on human chromatid/chromosome ultrastructure using both scanning and transmission electron microscopy (SEM, TEM). A bipartite, apparently half-chromatid-like structure was observed in whole human chromosomes studied with SEM and in longitudinally sectioned chromosomes analyzed with TEM. In addition, we also observed a zipper-like configuration as the parallel sister chromatids separated likely due to the supercoiled structure of the chromosome and chromatid. It is possible that either or both of these new observations resulted from our (improved) method of preparing the chromosomes for SEM and TEM.


Normal biochemistry values in baboons (Papio C. cinocephalus).
1. Analysis of biochemical parameters was carried out on material pooled from 10 baboons, adult male and female, of the Papio c. cinocephalus strain. 2. The values determined were for the common metabolites and enzymes utilized for specific studies in general metabolism (urea, glucose, cholesterol, phospholipids, bilirubin, uric acid, creatinine, alkaline phosphatase, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactic dehydrogenase, leucine amino peptidase, gamma glutamyl transpeptidase, total creatine kinase and amylase). Total protein and its fractions (ratio albumin/globulin, albumin, alpha 1-globulin and alpha 2-globulin) were also determined. 3. Results of these studies were compared with values for normal human adults. 4. The differences obtained between the respective ranges can be explained by the different physiology of the two species and, possibly, may also be caused by the use of human substrates in the enzyme assays. 5. Through the determination of normal values for the baboon, this study provides values for this species as an experimental animal in biomedical research.


Lateral tilt for caesarean section.
When pregnant women near term lie in the supine position the uterus can compress the inferior vena cava, interfering with venous return to the heart. This can result in hypotension, reduced placental perfusion and decreased fetal oxygenation. The objective of this review was to assess the effects on the fetus or newborn of lateral tilt at caesarean section compared to the operation carried out with the mother in the supine position. We searched the Cochrane Pregnancy and Childbirth Group trials register. Randomised or quasi-randomised trials of lateral tilt (10 to 15 degrees) compared to supine position during caesarean section in pregnant women undergoing elective or emergency caesarean section. Trial quality assessment and data extraction were done by one reviewer. Three trials involving 293 women were included. The trials were all methodologically poor. There were fewer low Apgar scores when lateral tilt was used, and pH measurements and oxygen saturation appeared to be better when tilt was used. There is not enough evidence from these trials to evaluate use of lateral tilt during caesarean section.


Effects of porcine pancreatic enzymes on the pancreas of hamsters. Part 1: basic studies.
Porcine pancreatic enzymes (PPE) extracted from glandular stomach has been used for the treatment of pancreatic cancer patients. Unfortunately, no information is available on the in vitro and in vivo effect on the pancreas and other tissues. We used Syrian Golden hamsters, a unique pancreatic cancer model, to obtain basic information on PPE for its eventual use for the treatment of pancreatic cancer. PPE was used in different concentrations in vitro and in vivo. The stability of the enzyme in the water solution was investigated. It was given to the hamsters by gavage in concentrations of 1g/kg and 400 mg/kg for short periods and in aqueous solution for 65 days. Plasma enzyme and insulin, the size of islets and the number of the insulin cells per islet were examined. The enzyme activity of PPE was maintained in water solution for at least 24 hours. Due to its content of calcium chloride it showed a high toxicity to normal and malignant hamster pancreatic cancer cells and human pancreatic cancer cell lines in vitro. PPE did not alter the plasma pancreatic enzyme levels regardless of the dose, duration and application route. On the contrary, PPE reduced their levels significantly. Remarkably, it also reduced the level of insulin, the size of the islets and the number of insulin cells in the islets significantly. The results imply that PPE does not enter the blood circulation but it appears to slow down the function of both the exocrine and endocrine pancreas.


Muscle strength testing in Parkinson's disease.
Isotonic muscle strength measured by a quantitative technique was decreased in early Parkinson's disease compared to age-matched controls. Weakness was present both on the affected and unaffected side in hemiparkinsonism. Similar degrees of weakness occurred in limbs with tremor or rigidity. Muscle weakness appears to be a primary symptom of Parkinson's disease which may relate to disturbed motor programming due to basal ganglia dysfunction.


Species-genetic diversity correlations in habitat fragmentation can be biased by small sample sizes.
Predicted parallel impacts of habitat fragmentation on genes and species lie at the core of conservation biology, yet tests of this rule are rare. In a recent article in Ecology Letters, Struebig et al. (2011) report that declining genetic diversity accompanies declining species diversity in tropical forest fragments. However, this study estimates diversity in many populations through extrapolation from very small sample sizes. Using the data of this recent work, we show that results estimated from the smallest sample sizes drive the species-genetic diversity correlation (SGDC), owing to a false-positive association between habitat fragmentation and loss of genetic diversity. Small sample sizes are a persistent problem in habitat fragmentation studies, the results of which often do not fit simple theoretical models. It is essential, therefore, that data assessing the proposed SGDC are sufficient in order that conclusions be robust.


Vestibular and other balance disorders in multiple sclerosis. Differential diagnosis of disequilibrium and topognostic localization.
Disorders of balance and equilibrium are common in multiple sclerosis (MS). This article reviews areas of central nervous system anatomy that may be involved in MS disequilibrium as well as the role of clinical examination, electrophysiologic testing, and magnetic resonance imaging in the diagnosis and assessment of vestibular dysfunction in MS patients. Relevant literature is reviewed and a case history is presented.


The miR-27a-3p/USP25 axis participates in the pathogenesis of recurrent miscarriage by inhibiting trophoblast migration and invasion.
Insufficient invasion ability of trophoblasts might be associated with the development of recurrent miscarriage (RM). Ubiquitin-specific protease 25 (USP25) can regulate the processes of invasion and migration in different types of cancer cells. However, the effect of USP25 on trophoblasts and its roles in the development of RM are unknown. In this study, we first analyzed the USP25 expression in placental villous tissues from RM patients, and then assessed the roles of USP25 in epithelial-to-mesenchymal transition (EMT), invasion and migration of trophoblasts. Furthermore, bioinformatics prediction and luciferase reporter assay were used to explore the mechanism of microRNA on USP25 expression, and regulation of USP25 expression in trophoblasts was assessed following transfection with microRNA mimics or inhibitor. The results showed that the expression of USP25 in the placental villous tissues was downregulated in RM patients. Knockdown of USP25 suppressed the EMT process, the invasion and migration capability of trophoblast cells, while overexpression of USP25 exhibited opposite results. Mechanistically, miR-27a-3p could regulate USP25 expression by binding to the 3'-untranslated region of USP25 in trophoblasts. Quantitative real-time polymerase chain reaction results found the expression of miR-27a-3p were negatively related to USP25 in RM patients. MiR-27a-3p mimics inhibited but miR-27a-3p inhibitor enhanced the migration and invasion capability of trophoblasts. Furthermore, sh-USP25 counteracted the promotion of invasion and migration mediated by the miR-27a-3p inhibitor. Taken together, these data indicate that USP25 downregulation by miR-27a-3p contributes to the EMT process, thereby inhibiting the migration and invasion of trophoblast cells, and these findings might provide potential biomarkers for RM.


Levels of monocyte reactive oxygen species are associated with reduced natural killer cell activity in major depressive disorder.
Major depressive disorder (MDD) is associated with reductions in natural killer cell activity (NKCA), however the mechanism(s) mediating reduced NKCA in MDD has yet to be determined. In light of evidence that MDD is associated with an inflammatory immune response, we propose that reactive oxygen species (ROS), generated by inflammatory leukocytes (monocytes and/or neutrophils), may mediate the suppression of NKCA in MDD. Intracellular levels of monocyte ROS were significantly associated with reductions in NKCA in outpatients (n = 15) diagnosed with MDD. Sleep disturbance was also significantly correlated with reductions in NKCA. Elevated levels of ROS may be an additional characteristic of a subset of depressed patients in whom an inflammatory response persists and elevations in ROS may, in part, mediate the associations observed between MDD, cardiovascular disease, and cancer.


Resveratrol Prevents Tumor Growth and Metastasis by Inhibiting Lymphangiogenesis and M2 Macrophage Activation and Differentiation in Tumor-associated Macrophages.
Antitumor and antimetastatic effects of resveratrol on tumor-induced lymphangiogenesis through the regulation of M2 macrophages in tumor-associated macrophages currently remain unknown. Therefore, we herein examined the effects of resveratrol on M2 macrophage activation and differentiation, and those of resveratrol-treated condition medium (CM) in M2 macrophages on vascular endothelial cell growth factor (VEGF)-C-induced migration, invasion, and tube formation by human lymphatic endothelial cells (HLECs). Resveratrol (50 μM or 5-50 μM) inhibited the production of interleukin-10 and monocyte chemoattractant protein-1 in M2 macrophages, whereas it promoted that of transforming growth factor-β1. Resveratrol (25 and 50 μM) inhibited the phosphorylation of signal transducer and activator of transcript 3 without affecting its expression in the differentiation process of M2 macrophages. Furthermore, resveratrol-treated CM of M2 macrophages inhibited VEGF-C-induced HLEC migration, invasion, and lymphangiogenesis. Resveratrol (25 mg/kg, twice daily) inhibited tumor growth and metastasis to the lung and also reduced the area of lymphatic endothelial cells in tumors (in vivo). These results suggest that the antitumor and antimetastatic effects of resveratrol were partly due to antilymphangiogenesis through the regulation of M2 macrophage activation and differentiation.


Ecotoxicity of the veterinary pharmaceutical ivermectin tested in a soil multi-species (SMS) system.
The present study tests the effect of antiparasitic compound ivermectin in a constructed food-web system, a soil multi-species (SMS) higher tier test system. Mutualism, competition and predation within the SMS system were introduced by the addition of five collembolan species, one enchytraeid and a predatory mite species. Bait lamina sticks were incorporated as a measure of functional toxicity, attempting to the integrated feeding activity of the invertebrates. The study showed that on the community level all treatments were significantly affecting the community abundance and composition and that the decrease in abundance corresponded well with increasing exposure concentration for all species. Since all concentrations had significant adverse effect on the community structure, the community-based no-effect-concentration is below the lowest test concentration of 0.25 mg kg(-1), whereas the EC10 for the individual species were as low as 0.05 mg kg(-1). The bait lamina respond was only affected at the highest exposure concentration.


Rapid 90Sr/90Y determination in water samples using a sequential injection method
We have developed a semiautomatic procedure based on a sequential injection method for 90Sr/90Y determination that allows their radiochemical separation in about 30 min. The method has been tested using 90Sr/90Y solutions with activities lower than 12 Bq. The source is eluted in a pH = 6.5 medium through a MnO2-impregnated cotton filter, where 9OY is preconcentrated in preference by adsorption. 90Y is extracted from the column with hydroxylamine, some 90Sr in the leached solution has also been found. After the radiochemical separation, the total beta-activity of the leached solution has been determined using a low background alpha-beta proportional counter and, assuming the presence of 90Sr and 90Y at t = 0, the solution of the Bateman equations allows the initial concentration of both isotopes to be obtained. We have verified that the addition of some ions usually found in water samples (Cl-, HCO3-, NO3-, SO4(2-), Ca2+, Mg2+) does not interfere with the yield of the radiochemical process, (90 +/- 10)%. The method has been applied to 90Sr/90Y determination in mineral waters, and even in thermal waters, where the salt concentration can be about 3500 mg/l, the radiochemical yield remains greater than 80%.


Synthetic DNA filaments: from design to applications.
Natural filaments, such as microtubules and actin filaments, are fundamental components of the cell. Despite their relatively simple linear structure, filaments play a number of crucial roles in living organisms, from scaffolding to cellular adhesion and motility. The mechanical properties of natural filaments mostly rely on the structural features of the component units and on the way they are connected together, thus providing an ideal molecular model for emulation purposes. In this review, we describe the progresses done in this field using DNA for the rational design of synthetic filamentous-like materials with tailored structural and physical characteristics. We firstly survey the strategies that have been adopted until now for the construction of individual DNA building components and their programmable self-assembly into linear oligomeric structures. We then describe the theoretical models of polymer elasticity applied to calculate the bending strength of DNA filaments, expressed in terms of persistence length. Finally, we report some of the most exciting examples of truly biomimetic DNA filaments, which are capable of mimicking not only the sophisticated structural features of their natural counterparts but also their responsiveness to external stimuli, thus resulting in active motion and growing networks between distant loci.


Evaluation of a pulse oximeter during profound hypothermia. An assessment of the Biox 3700 during induction of hypothermia before cardiac surgery in paediatric patients.
The accuracy of the Ohmeda Biox 3700 pulse oximeter was evaluated in 10 paediatric patients, deliberately surface cooled to 25 degrees C in preparation for cardiac surgery, by comparing the arterial oxygen saturation results obtained from an Ohmeda Biox 3700 and a Radiometer OSM-2 Hemoximeter. Though there was a good correlation between the two series of results, the arterial oxygen saturation was over-estimated by the pulse oximeter compared to the OSM-2 Hemoximeter in the temperature range 36 degrees to 30 degrees C and under-estimated below 30 degrees C. These differences were greatest when the initial saturations were low.


Photoaffinity labeling with the activator IMP and site-directed mutagenesis of histidine 995 of carbamoyl phosphate synthetase from Escherichia coli demonstrate that the binding site for IMP overlaps with that for the inhibitor UMP.
Photoaffinity labeling with IMP was used to attach covalently this activator to its binding site of Escherichia coli carbamoyl phosphate synthetase. We now identify histidine 995 of the large enzyme subunit as the amino acid that is cross-linked with IMP. The identification was carried out by comparative peptide mapping in two chromatographic systems of peptides differentially labeled with [3H]IMP and with the labeled inhibitor [14C]UMP, followed by automated Edman degradation and radiosequence analysis. Site-directed substitution of His995 by alanine confirmed His995 to be the only amino acid in the protein forming a covalent adduct with IMP. The His995Ala mutant protein was soluble and active and exhibited normal kinetics for the activator ornithine and for the substrates in the presence of ornithine. However, the mutation selectively induced changes in the activation by IMP and the inhibition by UMP, and it abolished the photolabeling of the enzyme by IMP without affecting the photolabeling by the inhibitor UMP. Since UMP is cross-linked to Lys993 [Cervera, J., et al. (1996) Biochemistry 35, 7247-7255] only two residues upstream of the site of IMP labeling, the results provide structural evidence for earlier proposals which suggested that UMP and IMP bind in a single or overlapping site. The two residues are within the region previously proposed as the binding fold for the nucleotide effectors. In the crystal structure of the enzyme, Lys993 and His995 are exposed and line a crevice where a Pi molecule was found [Thoden, J. B., et al. (1997) Biochemistry 36, 6305-6316]. UMP and IMP appear to bind in this crevice, possibly toward the C-side of the beta-sheet in a Rossman fold. Their binding in this site is consistent with the selectivity of adduct formation of UMP with Lys993 and of IMP with His995. It is also consistent with the nonessentiality of His995 for the binding, since the interactions with other residues that line the crevice must contribute a large part of the binding energy. The lack of an effect of the mutation on the activation by ornithine is consistent with the binding of this activator in a separate site in the protein.


Switchable C-H Functionalization of N-Tosyl Acrylamides with Acryloylsilanes.
A controllable Rh-catalyzed protocol to access alkylation and alkenylation-annulation of N-tosyl acrylamide with acryloyl silane is reported. In contrast to the directing group or catalyst-dependent divergent sp2 C-H alkylation/alkenylation, the intrinsic property of acryloylsilane allows the switchable reaction manifold, thereby affording either alkylation or annulation products with slight modification of the reaction conditions.


[Expression of human prp gene in prokaryotic cells using GST fusion protein expression system].
To study the biological features of cell-surface protein PrPc, which is thought to be involved in the prion-associated diseases after converting to a proteinase-resistant isoform PrPSc posttranslationally, and to establish an effective immunologic diagnostic method using PrPc as antigen. Amplifying and cloning the human prp gene from lymphocytes of two normal Chinese, after confirmed by DNA sequence analysis, the genes were separately subcloned into a GST-fusion expression plasmid. Sequence analysis showed that one contatined a point mutation that induced the 65th amino acid "Trp" inverting to a stop codon "TAG", whereas the other had the same sequence as the published standard prp gene. Both the standard and the mutated prp genes were separately subcloned into a GST fusion protein expression vector and expressed in the prokaryotic cells effectively. Western blot assay revealed that both of them expressed GST-PrP fusion proteins and could be recognized by PrP specific monoclonal antibody. It suggests that human PrP protein can be expressed in the GST fusion protein expression system and the expressed proteins hold good immune-reactivity.


Cystoid macular edema from cancer-associated retinopathy.
This article reviews the diagnosis and management of a patient with cancer-associated retinopathy (CAR) secondary to small cell lung cancer who developed a rare presentation of CAR, cystoid macular edema (CME). CAR is a rare cause of unexplained, often rapid, visual acuity and visual field loss. A 67-year-old man with a recent history of photopsias and simultaneous dimming of vision presented to our clinic. Four months before, he had been diagnosed with small cell lung cancer. Retinal examination was normal, but the visual field was severely constricted. He was referred for an electroretinogram and an evaluation by a retina specialist because of a strong suspicion of CAR, which was confirmed. Despite a lack of strong clinical evidence for the treatment of CAR, and no clinical recommendations for CME found in CAR, our patient's CME was initially treated with diclofenac QID and, subsequently, a sub-tenon injection of triamcinolone. Since his diagnosis of CME, he has been chronically managed with diclofenac QID to treat his edema, with relatively stable visual acuity. His visual fields remain highly constricted. CAR is a rare form of painless bilateral vision loss in patients with a history of cancer. Our patient developed CME from his CAR, and was treated with diclofenac and sub-tenon injections of triamcinolone. Despite potential options for treatment, none have demonstrated much efficacy, and the visual prognosis is typically poor.


Immediate and 12-Month Outcomes of Ischemic Versus Nonischemic Functional Mitral Regurgitation in Patients Treated With MitraClip (from the 2011 to 2012 Pilot Sentinel Registry of Percutaneous Edge-To-Edge Mitral Valve Repair of the European Society of Cardiology).
In literature, there are limited data comparing ischemic mitral regurgitation (I-MR) versus nonischemic MR regarding outcomes after percutaneous "edge-to-edge" repair. We aimed to describe the early and 12-month results after MitraClip device implantation regarding the 2 etiologies. From January 2011 to December 2012, the Transcatheter Valve Treatment Sentinel Pilot Registry included 452 patients with MR who underwent MitraClip procedure in 25 centers across Europe. The prevalent etiology was I-MR (235 patients, 52.0%). I-MR group had a significantly higher proportion of men (74.9 vs 59.9%, p <0.001) and surgical risk (logistic EuroSCORE 24.8 ± 18.2 vs 18.8 ± 16.3, p <0.001). Acute procedural success was high (96%) and similar between groups (p = 0.48). Patients with I-MR required a higher, albeit not significant, number of clips to reduce MR (p = 0.08). Inhospital mortality was low (2.0%) without significant differences between etiologies. The estimated 1-year mortality and rehospitalization rates were 15.0% and 25.8%, respectively, without significant differences between groups. Paired echocardiographic data showed a persistent improvement of MR at 1 year in both etiologies. Despite a significant overall reverse atrial remodeling after clip, there were no significant changes in left ventricular volumes. In conclusion, this large independent cohort showed that percutaneous "edge-to-edge" therapy was associated with early- and long-term improvement of MR severity and functional condition both in patients with I-MR and nonischemic MR. There were no significant differences between the 2 etiologies regarding survival and freedom from rehospitalization due to heart failure at the 1-year follow-up.


Etiology of Neuromuscular Fatigue After Repeated Sprints Depends on Exercise Modality.
To compare neuromuscular fatigue induced by repeated-sprint running vs cycling. Eleven active male participants performed 2 repeated-maximal-sprint protocols (5×6 s, 24-s rest periods, 4 sets, 3 min between sets), 1 in running (treadmill) and 1 in cycling (cycle ergometer). Neuromuscular function, evaluated before (PRE); 30 s after the first (S1), the second (S2), and the last set (LAST); and 5 min after the last set (POST5) determined the knee-extensor maximal voluntary torque (MVC); voluntary activation (VA); single-twitch (Tw), high- (Db100), and low- (Db10) frequency torque; and maximal muscle compound action potential (M-wave) amplitude and duration of vastus lateralis. Peak power output decreased from 14.6 ± 2.2 to 12.4 ± 2.5 W/kg in cycling (P < .01) and from 21.4 ± 2.6 to 15.2 ± 2.6 W/kg in running (P < .001). MVC declined significantly from S1 in running but only from LAST in cycling. VA decreased after S2 (~-7%, P < .05) and LAST (~-9%, P < .01) set in repeated-sprint running and did not change in cycling. Tw, Db100, and Db10/Db100 decreased to a similar extent in both protocols (all P < .001 post-LAST). Both protocols induced a similar level of peripheral fatigue (ie, low-frequency peripheral fatigue, no changes in M-wave characteristics), while underlying mechanisms probably differed. Central fatigue was found only after running. Findings about neuromuscular fatigue resulting from RS cycling cannot be transferred to RS running.


Amino acid incorporation during morphine intoxication Electrophoretic separation of extracellular proteins from a brain stem astroglial and neuronal containing co-cultivation system.
Extracellular proteins from brain stem astroglial enriched primary cultures were resolved with gel electrophoresis after labelling the cultures with (3)H/(14)C (experimental/control) valine. A protein fraction with a subunit molecular weight (mol. wt) of approx. 40,000 increased in (3)H/(14)C valine labelling after incubating the cultures for 1 h in 10(?6) or 10(?5) M morphine or after incubation for 4 h in 10(?7)M morphine. After incubating the cultures for up to 4 h in 10(?6) or 10(?5)M morphine proteins with subunits of mol. wt: ?15,000, 40,000 and 80,000 increased in labelling while subunits with mol. wt: ?65,000 and 100,000 decreased in labelling. After co-cultivating the astroglial-enriched primary brain stem cultures for 1 week with fetal (neuronal containing) brain stem cultures, incubation in 10(?) or 10(?6)M morphine for 1 h increased extracellular (3)H/(14)C labelling of electrophoretically resolved material with mol. wt ?15,000 and 40,000. After incubation in the same concentrations for 2 h an additional 80,000 mol. wt fraction increased in (3)H/(14)C labelling. After incubation in 10(?6)M morphine for 4 h the same result as above was obtained, the changes in the 15,000 and 80,000 mol. wt fractions being blocked by prior addition of 10(?6)M naloxone hydrochloride. Incubation in 10(?5)M morphine did not result in significant changes in the co-cultivation system used. It is suggested that extracellular proteins, mainly astroglial-derived, might serve functions during morphine intoxication. Co-cultivation of astroglial-enriched and neuronal containing cultures might be one model system to study macromolecular communication between these cell types.


Is sequential free flap safe in oral cancer reconstruction in the same patient? An outcome and complication analysis.
Sequential free flap reconstruction in patient with head and neck cancer can provide reliable and effective wound coverage. Only a few studies have reported on the outcome and complications analysis but without consensus on the recipient vessels and flap chosen. Herein, we presented the outcome and analysed the risk factors for complications in sequential free flap reconstruction. Patients who had sequential free tissue transfers due to cancer recurrence, second primary cancer, or secondary correction of the soft tissue contractures and volume deficits were all included. Variables extracted included demographics, comorbidities, free flap characteristics, infection, dehiscence and flap necrosis rates. In total, 40 patients with 92 free flaps were analyzed; 42 initial and 50 sequential free flaps. The most common recipient vessels for sequential flap were contralateral superficial thyroid vessels (68%). The most common flap for both initial and sequential free flap was anterolateral thigh flap (64.3 and 62%). The success rate of sequential free flap was 92.0 compared to 92.9% for initial free flap, which showed no significant difference. Female was independently associated with delayed wound healing with an odds ratio of 90.91 (95% confidence interval 0.001-0.17, P = 0.001), as well as diabetes with an odds ratio of 31.14 (95% confidence interval 2.60-373.19, P = 0.007). Sequential free flap was not a risk factor for any complication. Sequential free flap is a reliable method for head and neck surgery without more complication rate comparing to initial free flap reconstruction. More attentions should be paid on patients with preferential risk for certain complications.


AP-1 and ATF-2 are constitutively activated via the JNK pathway in Theileria parva-transformed T-cells.
Bovine T-cells infected by the protozoan parasite Theileria parva undergo lymphoblastoid transformation, and proliferate in an uncontrolled manner. While it has been established that the transcription factor NF-kappa B is constitutively activated in T. parva-infected T-cells, little is known about other transcription factors such as AP-1 and ATF-2. We demonstrated increased binding activity to the AP-1 and CREB/ATF-2 consensus binding sites and show that the AP-1 complex is composed of c-Jun, JunD, c-Fos, and ATF-2. The transcription factors c-Jun and ATF-2 are constitutively phosphorylated in a parasite-dependent manner. Both transcription factors can be phosphorylated by jun-NH2-terminal kinase (JNK), but ATF-2 is also a substrate for p38. We determined whether p38 is activated in T. parva-infected cells. Immunoblot analysis and inhibitor studies indicate that JNK, but not p38, is involved in ATF-2 phosphorylation. Based on these results and previous studies, we conclude that parasite interference with mitogen-activated protein kinase pathways is restricted to constitutive activation of JNK.


Efficacy of theophylline and its N-7-substituted derivatives in experimentally induced bronchial asthma in the guinea-pig.
A study has been made of the bronchospasmolytic actions of theophylline and some ot its N-7-substituted derivatives administered by i.v infusion in anaesthetized guinea pigs, in which experimental bronchial asthma was induced by i.v. administration of histamine, 5-hydroxytryptamine and bradykinin. Bronchoconstriction was measured as changes in tidal volume, airflow rate, intrapleural pressure fluctuations and respiratory frequency. Dynamic lung compliance and pulmonary resistance was computed and recorded simultaneously. In addition blood pressure and heart rate were recorded. Theophylline, proxyphylline, diprophylline and etophylline when given alone had hardly an effect on lung function; relatively high doses of the drugs caused a fall in blood pressure and an increase in heart rate. Acephylline infusion in relatively high doses produced a decrease of dynamic lung compliance and an increase of pulmonary resistance. Some animals died. Theophylline, proxyphylline, diprophylline and etophylline were effective in reducing the mediator-induced bronchoconstriction. Protective effects correlated considerably (R = 0.75-0.82) with the plasma concentrations. The magnitude of these protective effects increased with the plasma concentration. Effective doses of proxyphylline, diprophylline and etophylline were much higher than those of theophylline. Acephylline was completely inactive in reversing the mediator-induced bronchoconstriction. At relatively high doses it increased the bronchoconstrictive effects of the mediators. It is concluded that diprophylline, proxyphylline and etophylline, like theophylline, are highly effective bronchospasmolytics, but does of the individual drugs must be adjusted according to the derivative used. Theophylline is by far the most effective of the four compounds. On the basis of this study and recent pharmacokinetic data in man the therapeutic value of acephylline in asthmatics seems doubtful.


[Clinical and rhino-manometric evaluation of flunisolide in treatment of seasonal allergic rhinitis].
24 patients with seasonal allergic rhinitis (SAR) were observed. Persons with nasal obstruction caused by other mechanisms than allergy to pollens were excluded. The increase of nasal resistance and complaints after begin of pollen season was statistically significant. The clinical efficacy of topical flunisolide in patients with SAR was evaluated. The significant building of symptoms scores and increase of rhinomanometric measured nasal patency were noted.


Analysis of gender effects on pain perception and symptom presentation in temporomandibular pain.
Based on clinical populations, chronic orofacial pain of temporomandibular disorders (TMD) occurs more frequently (range: 2:1 to 9:1) in women than men. The reasons for this difference are not clear. The present study evaluated symptom presentation, sensitivity to pain, personality, and illness behavior in 2 samples of patients suffering with orofacial pain. Also, pain responses were studied in pain-free volunteers, controlling for experimenter-gender effects. The results showed few gender differences based on ratings of chronic or experimental pain, pain-related illness behavior, and personality. The higher ratio of women versus men seeking TMD care is consistent with greater health awareness or interest in symptoms by women than by men.


Blind persons navigate in virtual reality (VR); hearing and feeling communicates "reality".
Can Virtual Reality (VR) developments in audio navigation for blind persons support therapies for all? Working with Crystal River Engineering we are developing navigable Virtual Reality worlds for blind users, using spatialized audio [1], [2]. All persons, however, use specialized channels, such as: visual, aural, and kinetic learning senses. Predominantly visual VR worlds and health informatics models from World Wide Webs, may be downloaded, tailored, augmented, and delivered to each of these learning senses using VR. We are also testing a proof of concept system with Boston Dynamics which downloads 3-dimensional, satellite-derived map models from the World Wide Web, and makes them navigable by "feeling" the terrain using haptic (tactual or force feedback to your hand) robotic interfaces. Ultimately, these multi-sensory VR access methods: sight, localization by audio, and "feeling" of data sets could open up the World Wide Web to individuals with sight impairments. This could also, however, benefit government, businesses, universities, and (elementary) education. It could contribute more powerful communications, education, and medical simulation applications on the World Wide Web. This work is part of government technology transfer to telemedicine, (elementary) education, disabilities access to the Web, and new Internet access and productivity efforts under Vice President Gore's National Performance Review.


A Novel 3,4-Secocycloartane Triterpene, Bearing a Tetrahydropyran Moiety, from Pasaniaformosana Leaf.
Bioassay guided fractionation against a-glucosidase and separation of the ethanolic extract of Pasania formosana leaf by chromatographic methods led to the isolation of a novel secocycloartane triterpene. This compound, named pasasecocycloartenoic acid, was elucidated as 21,24(R)-epoxy-25-hydroty-3;4- secocycloart-4(28)-en-3-oic acid through analysis of 1D and 2D NMR spectra and on the basis of HRESIMS data. The compound showed weak activity against α-glucosidase, but its poor solubility hampered the bioassay.


In silico allergenicity prediction of several lipid transfer proteins.
Non-specific lipid transfer proteins (nsLTPs) are common allergens and they are particularly widespread within the plant kingdom. They have a highly conserved three-dimensional structure that generate a strong cross-reactivity among the members of this family. In the last years several web tools for the prediction of allergenicity of new molecules based on their homology with known allergens have been released, and guidelines to assess potential allergenicity of proteins through bioinformatics have been established. Even if such tools are only partially reliable yet, they can provide important indications when other kinds of molecular characterization are lacking. The potential allergenicity of 28 amino acid sequences of LTPs homologs, either retrieved from the UniProt database or in silico deduced from the corresponding EST coding sequence, was predicted using 7 publicly available web tools. Moreover, their similarity degree to their closest known LTP allergens was calculated, in order to evaluate their potential cross-reactivity. Finally, all sequences were studied for their identity degree with the peach allergen Pru p 3, considering the regions involved in the formation of its known conformational IgE-binding epitope. Most of the analyzed sequences displayed a high probability to be allergenic according to all the software employed. The analyzed LTPs from bell pepper, cassava, mango, mungbean and soybean showed high homology (>70%) with some known allergenic LTPs, suggesting a potential risk of cross-reactivity for sensitized individuals. Other LTPs, like for example those from canola, cassava, mango, mungbean, papaya or persimmon, displayed a high degree of identity with Pru p 3 within the consensus sequence responsible for the formation, at three-dimensional level, of its major conformational epitope. Since recent studies highlighted how in patients mono-sensitized to peach LTP the levels of IgE seem directly proportional to the chance of developing cross-reactivity to LTPs from non-Rosaceae foods, and these chances increase the more similar the protein is to Pru p 3, these proteins should be taken into special account for future studies aimed at evaluating the risk of cross-allergenicity in highly sensitized individuals.


Religiosity and Health-Related Quality of Life: A Cross-Sectional Study on Filipino Christian Hemodialysis Patients.
This study aimed to measure the religiosity and health-related quality of life of Filipino Christian HD patients. A cross-sectional study of 100 HD patients was conducted. The Duke University Religion Index and the Ferrans and Powers QLI Dialysis Version-III were used. Data were analyzed using descriptive statistics and Pearson r correlation. Attendance to organizational religious activities and NORA were found to be correlated with some of the dimensions of HRQoL. Intrinsic religiosity showed a strong, positive correlation with HRQoL. It is essential to attend to and nourish their religious needs. Holistic approach in providing care to HD patients, with emphasis on spiritual care, is encouraged to improve their total health.


Selective enrichment and characterization of Roseospirillum parvum, gen. nov. and sp. nov., a new purple nonsulfur bacterium with unusual light absorption properties.
A new type of phototrophic purple bacterium, strain 930I, was isolated from a microbial mat covering intertidal sandy sediments of Great Sippewissett Salt Marsh (Woods Hole, Mass., USA). The bacterium could only be enriched at a wavelength of 932 (+/- 10) nm. Cells were vibrioid- to spirilloid-shaped and motile by means of bipolar monotrichous flagellation. The intracytoplasmic membranes were of the lamellar type. Photosynthetic pigments comprised bacteriochlorophyll a and the carotenoids spirilloxanthin and lycopenal. The isolated strain exhibited an unusual, long-wavelength absorption maximum at 911 nm. Sulfide or thiosulfate served as electron donor for anoxygenic phototrophic growth. During growth on sulfide, elemental sulfur globules formed outside the cells. Elemental sulfur could not be further oxidized to sulfate. In the presence of sulfide plus bicarbonate, fructose, acetate, propionate, butyrate, valerate, 2-oxoglutarate, pyruvate, lactate, malate, succinate, fumarate, malonate, casamino acids, yeast extract, L(+)-alanine, and L(+)-glutamate were assimilated. Sulfide, thiosulfate, or elemental sulfur served as a reduced sulfur source for photosynthetic growth. Maximum growth rates were obtained at pH 7.9, 30 degrees C, 50 micromol quanta m-2 s-1 of daylight fluorescent tubes, and a salinity of 1-2% NaCl. The strain grew microaerophilically in the dark at a partial pressure of 1 kPa O2. The DNA base composition was 71.2 mol% G + C. Sequence comparison of 16S rRNA genes indicated that the isolate is a member of the alpha-Proteobacteria and is most closely related to Rhodobium orientis at a similarity level of 93.5%. Because of the large phylogenetic distance to known phototrophic species of the alpha-Proteobacteria and of its unique absorption spectrum, strain 930I is described as a new genus and species, Roseospirillum parvum gen. nov. and sp. nov.


[Therapeutic effect of liposome on II degree burn wound].
To study the therapeutic effect of Suyuping in which liposome is the main constituent on II degree burn wound. From October 1998 to October 1999, 42 cases with II degree burn wound were adopted in this study. Among them, there were 30 males and 12 females, the average wound area was (23.4 +/- 9.7)%. The wounds on the left side of body were managed with sulfadiazine argentum(SD-Ag) while that on the right side with Suyuping. Healing and other situation about the burn wounds were observed and recorded at times. Forty-two patients completely healed when discharged from hospital. The average wound area managed with Suyuping was (11.2 +/- 7.3)% and the area with SD-Ag was (9.4 +/- 5.8)%. The mean healing time of Suyuping group was(18.4 +/- 4.7) days while that of SD-Ag was (23.5 +/- 7.9) days, there was significant difference(P < 0.05). Suyuping group presented few wound pain, allergy, bleeding and the side effect was less. Suyuping can accelerate wound healing and attenuate wound pain, allergy and bleeding, it is a potential and specific topical agent for treating II degree burn wound.


Alpinia galanga extracts downregulate interleukin-1β-induced matrix metalloproteinases expression in human synovial fibroblasts.
Alpinia galanga has been used as alternative medicine for anti-rheumatic activities. However, the precise action of the extract on arthritic diseases is not yet fully understood. In this study, we investigated the effects of A. galanga extracts on the expression of genes involved in catabolic activities in an interleukin-1β (IL-1β)-induced human synovial fibroblast as an inflammatory model. Confluent primary human synovial fibroblasts were treated for 24 h with A. galanga hexane extracts in the presence of recombinant human IL-1β. MMPs in the culture medium were monitored by gelatin zymography. Total RNA was isolated from the cell lysate and analyzed via semi-quantitative RT-PCR. After treatment with A. galanga extracts, MMP-2 activity in the culture medium was significantly reduced. In addition, MMP-1, MMP-3, MMP-13, and Cox-2 expression were downregulated. These data suggest that the decrease of gene expression and production of MMPs in synovial fibroblasts against inflammatory stimuli could be due to the effects of the A. galanga extracts. Therefore, A. galanga extracts might be a promising therapeutic agent for arthritis.


Mutational analysis of the STAT6 SH2 domain.
The SH2 domain of the STAT family of transcription factors is essential for STAT binding to phosphorylated cytoplasmic domains of activated cytokine receptors. Furthermore, the same domain mediates dimerization of activated STAT monomers, a prerequisite for DNA binding by this family of proteins. To identify amino acid residues within the STAT protein that mediate these various interactions, we have carried out an extensive mutational analysis of the Stat6 SH2 domain. Recombinant proteins carrying C-terminal deletions or double alanine substitutions were expressed in mammalian and insect cells and assayed for DNA binding, transcription activation, tyrosine phosphorylation, and the ability to interact with a tyrosine-phosphorylated peptide derived from the interleukin-4 receptor signaling chain. From these studies, we have identified amino acids that are required for both DNA binding and interleukin-4 receptor interaction, as well as residues that when mutated impair only one of the two functions. Our results suggest that the structural homology between the SH2 domain of Stat6 and that of the distantly related Src protein may be higher than predicted on the basis of primary amino acid sequence comparisons. However, the two types of SH2 domains may differ at their C-terminal ends.


Do miniscrews remain stationary under orthodontic forces?
Miniscrews have been used in recent years for anchorage in orthodontic treatment. However, it is not clear whether the miniscrews are absolutely stationary or move when force is applied. Sixteen adult patients with miniscrews (diameter = 2 mm, length = 17 mm) as the maxillary anchorage were included in this study. Miniscrews were inserted on the maxillary zygomatic buttress as a direct anchorage for en masse anterior retraction. Nickel-titanium closed-coil springs were placed for the retraction 2 weeks after insertion of the miniscrews. Cephalometric radiographs were taken immediately before force application (T1) and 9 months later (T2). The cephalometric tracings at T1 and T2 were superimposed for the overall best fit on the structures of the maxilla, cranial base, and cranial vault to determine any movement of the miniscrews. The miniscrews were also evaluated clinically for their mobility (0: no movement, 1: < or =0.5 mm, 2: 0.5-1.0 mm, 3: >1.0 mm). The mobility of all miniscrews was 0 at T1 and T2. On average, the miniscrews tipped forward significantly, by 0.4 mm at the screw head. The miniscrews were extruded and tipped forward (-1.0 to 1.5 mm) in 7 of the 16 patients. Miniscrews are a stable anchorage but do not remain absolutely stationary throughout orthodontic loading. They might move according to the orthodontic loading in some patients. To prevent miniscrews hitting any vital organs because of displacement, it is recommended that they be placed in a non-tooth-bearing area that has no foramen, major nerves, or blood vessel pathways, or in a tooth-bearing area allowing 2 mm of safety clearance between the miniscrew and dental root.


[Assessment of cardiorespiratory functions in patients receiving suggestive psychotherapy].
It is shown that suggestive psychotherapy based on verbal suggestions provides a tool for individual correction of the patient's functional state. It reduces sympathetic and promotes parasympathetic influences, decreases high initial level of psychoemotional tension, and normalizes relationship between cardiac and respiratory rhythms. Also, suggestive psychotherapy has beneficial effect on the psychological sphere and subjective feeling of well-being, reduces anxiety, strengthens the sense of confidence and hope for a cure.


Relationship of blood EG2+ eosinophils in patients with bronchial asthma.
The presence of eosinophils in peripheral blood has been previously associated with different degrees of activity in the evolution of disease in asthmatics. The eosinophil cationic protein is a mediator released by the eosinophils when they are activated due to various stimuli. The monoclonal antibody EG2 binds to human ECP, the epitopes which EG2 recognizes is only present in the secreted form of ECP, hence it only stains eosinophils which are undergoing activation and/or secretion. Flow cytometry was used to measure the level of eosinophils stained by the monoclonal antibody EG2 (eosinophil EG2+) in the peripheral blood of subjects with unstable extrinsic bronchial asthma, stable extrinsic bronchial asthma and healthy control group. A statistically significant higher level of eosinophil EG2+ was found in the group with unstable asthma than in either the group with stable asthma or the group of healthy subjects (p < 0.0002). No difference was found between the patients with stable asthma and the control group. The level of eosinophil EG2+ in peripheral blood, measured by flow cytometry, could be used as an indicator of inflammatory activity in patients suffering from bronchial asthma.


[Immediate evaluation of continuous medical education].
To analyse the results of the immediate evaluation of an European teaching session using a questionnaire provided by the French College of anaesthesiologists. Open evaluation. Questionnaires completed after each topic by 50 participants of an European course including 15 lectures were collected. The types of professional exercise and the medical practise reliable to the different topics were pointed out. The evaluation included 4 items noted from 1 to 10: new information for medical practise, definition of pedagogic objectives, quality of means used for teaching, interest for the treated subject. The global mean score for each item and for each speaker was calculated. Results were compared according to the professional mode of exercise, the own medical practise and the project to modify it in the future. Scores affected to items were significantly lower for participants exercising in PSPH compared to general and university hospitals and private clinics (p < 0.001). New information was better found in case of poor or absence of practise, but interest was improved when medical practise was frequent. 2/3 of the participants projected to modify their practise after the session. The analysis of medical evaluation should allow to determine an acceptable zone of quality which may be useful for accreditation. However, distorting results according to the professional mode of exercise and the own medical practise should encourage the development of adapted continuous medical education. Delayed evaluation may be necessary to objective the putative benefits of CME on medical practise.


Phosphate uptake inLemna gibba G1: energetics and kinetics.
Phosphate uptake was studied by determining [(32)P]phosphate influx and by measurements of the electrical membrane potential in duckweed (Lemna gibba L.). Phosphate-induced membrane depolarization (ΔE m ) was controlled by the intracellular phosphate content, thus maximal ΔE m by 1 mM H2PO 4 (-) was up to 133 mV after 15d of phosphate starvation. The ΔE m was strongly dependent on the extracellular pH, with a sharp optimum at pH 5.7. It is suggested that phosphate uptake is energized by the electrochemical proton gradient, proceeding by a 2H(+)/H2PO 4 (-) contransport mechanism. This is supported also by the fusicoccin stimulation of phosphate influx. Kinetics of phosphate influx and of ΔE m , which represent mere plasmalemma transport, are best described by two Michaelis-Menten terms without any linear components.


Genetically Encoded Azide Containing Amino Acid in Mammalian Cells Enables Site-Specific Antibody-Drug Conjugates Using Click Cycloaddition Chemistry.
Antibody-drug conjugates (ADC) have emerged as potent antitumor drugs that provide increased efficacy, specificity, and tolerability over chemotherapy for the treatment of cancer. ADCs generated by targeting cysteines and lysines on the antibody have shown efficacy, but these products are heterogeneous, and instability may limit their dosing. Here, a novel technology is described that enables site-specific conjugation of toxins to antibodies using chemistry to produce homogeneous, potent, and highly stable conjugates. We have developed a cell-based mammalian expression system capable of site-specific integration of a non-natural amino acid containing an azide moiety. The azide group enables click cycloaddition chemistry that generates a stable heterocyclic triazole linkage. Antibodies to Her2/neu were expressed to contain N6-((2-azidoethoxy)carbonyl)-l-lysine at four different positions. Each site allowed over 95% conjugation efficacy with the toxins auristatin F or a pyrrolobenzodiazepine (PBD) dimer to generate ADCs with a drug to antibody ratio of >1.9. The ADCs were potent and specific in in vitro cytotoxicity assays. An anti Her2/neu conjugate demonstrated stability in vivo and a PBD containing ADC showed potent efficacy in a mouse tumor xenograph model. This technology was extended to generate fully functional ADCs with four toxins per antibody. The high stability of the azide-alkyne linkage, combined with the site-specific nature of the expression system, provides a means for the generation of ADCs with optimized pharmacokinetic, biological, and biophysical properties.


Stereoselective Chiral Recognition of Amino Alcohols with 2,2'-Dihydroxybenzil.
2,2'-Dihydroxybenzil is demonstrated to be a highly diastereoselective stereodynamic receptor for the chiral recognition of amino alcohols. The receptor by forming diimine compounds with amino alcohols showed good (11:1) to excellent (>50:1) diastereoselectivity in chloroform. The existence of intramolecular hydrogen bonding with amino alcohols only in an axial conformer is demonstrated by 1H NMR and CD spectroscopy, X-ray crystallography, and DFT computations. The exciton chirality method can be used with diazo-attached 2,2'-dihydroxybenzil.


Intestinal helminth fauna of bottlenose dolphin Tursiops truncatus and common dolphin Delphinus delphis from the western Mediterranean.
We report on the intestinal helminth fauna of 15 bottlenose dolphins Tursiops truncatus and 6 short-beaked common dolphins Delphinus delphis from the western Mediterranean. Eight helminth species were found in bottlenose dolphin, i.e., the digeneans Synthesium tursionis, Brachycladium atlanticum, and Pholeter gastrophilus, the nematode Anisakis sp., and the cestodes Tetrabothrius forsteri, Diphyllobothrium sp., Strobilocephalus triangularis, and tetraphyllidean plerocercoids. Brachycladium atlanticum, S. triangularis , and tetraphyllidean plerocercoids are new host records. No T. forsteri had previously been reported in Mediterranean bottlenose dolphins. Three species of helminths were recorded in the common dolphin, i.e., the digenean Synthesium delamurei (which was a new host record), and the cestodes T. forsteri and tetraphyllidean plerocercoids. The intestinal helminth communities of bottlenose and common dolphins are depauperate, similar to that of other cetacean species, but those from bottlenose dolphins harbored a higher number of helminth species. This study supports the notion that oceanic cetaceans, such as common dolphins, have a comparatively poorer helminth fauna than that of neritic species, such as bottlenose dolphins, because the likelihood of parasite recruitment is decreased.


Glycylproline dipeptidyl aminopeptidase and gamma-glutamyl transpeptidase in human hepatic cancer and embryonal tissues.
Changes of glycylproline dipeptidyl aminopeptidase (GPDA) and gamma-glutamyl transpeptidase (gamma-GTP) activities and their subcellular distributions were compared in human hepatic cancer and embryonal tissues. The activity of GPDA in cancer tissues was significantly higher than that found in healthy liver, though there were no significant differences between fetal and adult livers. The placenta, however, had the highest GPDA activity. The activity of gamma-GTP, on the other hand, was increased significantly not only in cancer tissues but also in live tissues adjacent to the tumor, and it was higher in the fetal liver but much lower in the placenta. Subcellular distribution of GPDA was also different from that of gamma-GTP in cancer tissues, especially after postmortem changes. These results suggest the possibility that GPDA has carcinoembryonic characters similar to gamma-GTP, but the mechanisms, whereby serum activities of these two enzymes were increased in hepatocellular carcinoma patients, are different from each other.


[A case of embolic infarction originating from extracranial vertebral artery stenosis by cervical spondylosis at C5/6: its pathogenesis and surgical treatment].
We report a case of right brainstem and cerebellar infarction induced by head rotation. The infarction was due to an artery to artery embolism originating from extracranial vertebral artery stenosis resulting from C5-6 cervical spondylosis. A-64-year-old man with cervical spondylosis experienced swallowing difficulty and vertigo while eating dinner. Neurological examination at admission indicated lateral medullary syndrome (Wallenberg syndrome). MRI (FLAIR) revealed multiple high-intensity signal areas in the right lateral medulla and the cerebellar hemisphere in the territory of the posterior inferior cerebellar artery (PICA). Right vertebral angiogram demonstrated marked stenosis in the neutral position and occlusive changes with head rotation to the right (30 degrees) at C5-6. Rotation induced substantially delayed filling of the right vertebral artery. To remedy this, we resected the osteophyte, fused the uncovertebral joint and connective tissue adhering tightly to the right vertebral artery at C5-6 level, and unroofed the transverse foramens at C5 and C6. Post-operative angiogram confirmed the disappearance of marked stenosis and improved antegrade filling of the right vertebral artery. In the present report, the pathogenesis and surgical treatment of this particular case are discussed.


[Effect of acute exposure to SO2 on cellular defense mechanisms in the lung (pilot study)].
Sulphur dioxide is one of the most important and most frequent atmospheric pollutant of our environmental setting. In presented pilot-study we describe the influence of acute exposure to sulphur dioxide on alveolar macrophages of guinea pigs. The alveolar macrophages represent the main part of mononuclear phagocytic system, which is responsible for the defence of respiratory tract against foreign compounds. The experimental animals were exposed over three hours to sulphur dioxide with the concentration of about 400 ppm. After exposure we did not find significant changes in phagocytic activity of alveolar macrophages.


Validity evaluation of recently published diabetes risk scoring models in a general Chinese population.
The study aimed to assess the validity of some recently published diabetes risk scoring models in a general Chinese population. In 2007, there was a re-examination of 711 individuals who were originally examined in 1992. Since 24 individuals had diabetes in 1992, 687 individuals were available for analysis. Validity was assessed with area under the receiver operating characteristic curve (AROC), and we assessed seven prospective and four cross-sectional models. When applied to our population, AROCs tended to be higher in Asian models than in non-Asian models (average AROCs 0.694±0.034 vs. 0.667±0.040, p=0.258), and those tended to be higher in prospective models than in cross-sectional models (average AROCs 0.695±0.028 vs. 0.652±0.042, p=0.072). A prospective model from Taiwan performed best (AROC 0.749; 95% CI 0.691-0.807). In conclusion, diabetes risk scoring models could not always be generalized from one population to another before validation. Asian models might be more suitable for Asian populations than non-Asian models, and prospective models might be more suitable for predicting future diabetes than cross-sectional models. When applied to our population, a prospective model from Taiwan performed best, and widespread application might be considered in the population.


Sucralfate suppresses Helicobacter pylori infection and reduces gastric acid secretion by 50% in patients with duodenal ulcer.
The mechanism(s) by which sucralfate heals duodenal ulcers remains unclear. The aim of this study was to determine the effect of sucralfate on Helicobacter pylori infection and on the accompanying hypersecretion of gastric acid the infection induces in patients with duodenal ulcer. Basal and gastrin-releasing peptide (GRP) stimulated gastrin release and acid secretion. H. pylori density, gastric urease activity, and severity of gastritis were studied in patients with duodenal ulcer who were positive for H. pylori before, during, and after 4 weeks' treatment with sucralfate (2 g twice daily). The density of H. pylori decreased by 70% during sucralfate treatment and returned to the pretreatment level after discontinuation of therapy. This suppression of H. pylori infection was accompanied by an 80% decrease in gastric urease activity. GRP-stimulated plasma gastrin concentrations, GRP-stimulated acid output, and basal acid output all decreased by approximately 50% during sucralfate therapy and returned to pretreatment levels after treatment was discontinued. These findings indicate that sucralfate markedly suppresses H. pylori infection and the accompanying hypersecretion of acid the infection induces in patients with duodenal ulcer. These effects are likely to be important mechanisms by which the drug promotes duodenal ulcer healing.


The use of imatinib mesylate has no adverse effects on the heart function. Results of a pilot study in patients with chronic myeloid leukemia.
To investigate cardiac effects of imatinib at an extended follow-up (median 12.4 months), 12 chronic myeloid leukemia patients underwent cardiac screening. No significant changes on the frequency of cardiovascular signs and symptoms, electrocardiographic abnormalities, echocardiographic measurements and BNP levels were observed. Median ejection fraction was 67% at baseline versus 68% at follow-up (median intra-patient change 0.5%). Median BNP levels were 8.3 versus 7.3pg/mL (median intra-patient change 0.2pg/mL). Troponin I measures were below the lower limit of detection, whereas strain measures were similar to healthy control. This pilot study suggests that it is probably safe to perform cardiac monitoring on an annual basis.


Transurethral prostatectomy: analysis and comparison of four clinical series.
Charts of 302 patients from four groups who had transurethral prostatectomy were reviewed with respect to patient characteristics and complications. The four groups were similar in average age and amount of tissue resected. Patients from the University of Alabama Hospital and Veterans Administration Hospital tended to have more associated illnesses than patients in the two private practices. Bleeding, the most frequently seen intraoperative and immediate postoperative complication, occurred most often in the University of Alabama Hospital series and in patients with prostates weighing more than 45 gm. Incontinence, the most frequent long-term complication, occurred most often in patients from the Veterans Administration Hospital. Complications and characteristics are compared with those in previously reported series of patients having transurethral prostatectomy and with those of the American Urological Association cooperative study.


Anatomy of the long head of biceps femoris: An ultrasound study.
Hamstring strains, particularly involving the long head of biceps femoris (BFlh) at the proximal musculotendinous junction (MTJ), are commonly experienced by athletes. With the use of diagnostic ultrasound increasing, an in-depth knowledge of normal ultrasonographic anatomy is fundamental to better understanding hamstring strain. The aim of this study was to describe the architecture of BFlh, using ultrasonography, in young men and cadaver specimens. BFlh morphology was examined in 19 healthy male participants (mean age 21.6 years) using ultrasound. Muscle, tendon and MTJ lengths were recorded and architectural parameters assessed at four standardised points along the muscle. Measurement accuracy was validated by ultrasound and dissection of BFlh in six male cadaver lower limbs (mean age 76 years). Intra-rater reliability of architectural parameters was examined for repeat scans, image analysis and dissection measurements. Distally the BFlh muscle had significantly (P < 0.05) shorter fascicles and larger pennation angles than proximal sites. Agreement between ultrasound and dissection (cadaver study) was excellent for all architectural parameters, except pennation angle (PA), and MTJ length. All other measures demonstrated good-excellent repeatability. BFlh is not uniform in architecture when imaged using ultrasound. It is likely that its distal-most segment is better suited for force production in comparison to the more proximal segments, which show excursive potential, traits which possibly contribute to the high rate of injury at the proximal MTJ. The data presented in this study provide specific knowledge of the normal ultrasonographic anatomy of BFlh, which should be of assistance in analysing BFlh injury via imaging. Clin. Anat. 29:738-745, 2016. © 2016 Wiley Periodicals, Inc.


[Strategies of surgical and comprehensive management of breast cancer patients with local regional recurrence].
Breast conserving surgery and sentinel lymph node biopsy are widely used in early breast cancer treatment. Right now, the mode of local regional recurrence (LRR) has significantly changed and the rate of ipsilateral breast tumor recurrence and axillary lymph node recurrence are steadily increasing. Due to its relatively low incidence of LRR compared with distant metastasis, inconsistent of pre-recurrence treatment, difficulty in surgical treatment, and few prospective clinical studies, there are rising new challenges for clinical management of LRR patients. In this article, based on new theory of LRR, clinical diagnosis and treatment progress, and our own clinical practice experience for LRR breast cancer patients, we propose that we should make pathological diagnosis and do systemic evaluation for LRR disease, then considering it as a curable disease, and integrating local and systemic comprehensive treatment for LRR patients, thus to improve their disease outcome.


Outstanding performance of configuration interaction singles and doubles using exact exchange Kohn-Sham orbitals in real-space numerical grid method.
To assess the performance of multi-configuration methods using exact exchange Kohn-Sham (KS) orbitals, we implemented configuration interaction singles and doubles (CISD) in a real-space numerical grid code. We obtained KS orbitals with the exchange-only optimized effective potential under the Krieger-Li-Iafrate (KLI) approximation. Thanks to the distinctive features of KLI orbitals against Hartree-Fock (HF), such as bound virtual orbitals with compact shapes and orbital energy gaps similar to excitation energies; KLI-CISD for small molecules shows much faster convergence as a function of simulation box size and active space (i.e., the number of virtual orbitals) than HF-CISD. The former also gives more accurate excitation energies with a few dominant configurations than the latter, even with many more configurations. The systematic control of basis set errors is straightforward in grid bases. Therefore, grid-based multi-configuration methods using exact exchange KS orbitals provide a promising new way to make accurate electronic structure calculations.


Assessment of heavy metal contamination in Candarli Gulf sediment, Eastern Aegean Sea.
Concentrations of selected heavy metals (Fe, Mn, Ni, Cu, Zn, Pb, Hg, Cr, Al, and As) in surface sediments from 18 stations in the Candarli Gulf were studied in order to understand current metal contamination due to urbanization and economic development in Candarli region, Turkey. The sediment samples were collected by box corer in Candarli Gulf in 2009 to assess heavy metal pollution. Heavy metal concentrations in surface sediment varied from 1.62% to 3.60% for Fe, 0.38-2.53% for Al, 173-1,423 for Mn, 8-100 for Ni, 3-46 for Cu, 55-119 for Zn, 16-138 for Pb, 0.2-6.3 for Hg, 16-71 for Cr, and 11-37 mg kg( -1) for As. This study showed that the concentrations of Mn, Ni, Zn, Pb, Hg, and Cr in the surface sediment layers were elevated when compared with the subsurface layers. Both metal enrichment and contamination factors show that Hg, Zn, and Pb contamination exists in the entire study area and contamination of other metals is also present in some locations depending on the sources.


Treatment of psoriasis with topical nitrogen mustard.
With the advent of various new methods of treating psoriasis, it is necessary to remind physicians to consider an agent that is easy to administer, locally effective, relatively inexpensive, not time-consuming and without systemic toxic effects. Nineteen patients were treated with topical nitrogen mustard between 1972 and 1976, and only five developed sufficient contact sensitization to warrant stopping medication.


The patient with diabetes mellitus: etiology, epidemiology, principles of medical management, oral disease burden, and principles of dental management.
Diabetes mellitus is an etiologically and clinically heterogeneous group of metabolic disorders that share the commonality of hyperglycemia. Long-term hyperglycemia produces tissue damage, which ultimately manifests as microvascular and macrovascular disease, and neuropathy. The presence of macrovascular disease should alert clinicians to the possibility that the patient may have coronary artery disease, particularly because coronary artery disease and myocardial ischemia are likely to be silent. Elderly patients with diabetes mellitus are also more likely to develop congestive heart failure. Patients with unstable coronary syndromes, decompensated heart failure, and symptomatic cardiac arrhythmias are at increased risk of perioperative cardiovascular complications (myocardial infarction, heart failure, and sudden death) while undergoing noncardiac procedures. In addition, clinicians must avoid the risk of hypoglycemic episodes. Oral health care providers can expect to be called upon to care for patients with this progressively debilitating disease. To provide competent care to patients with diabetes mellitus, dental clinicians must understand the disease, its treatment, and the impact the disease and its treatment may have on the patient's ability to undergo and respond to dental care.


A method to quantify alteration of knee kinematics caused by changes of TKR positioning.
Few in-vitro studies have investigated changes in kinematics caused by total knee replacement (TKR) implantation. The advent of surgical navigation systems allows implant position to be measured accurately and the effects of alteration of TKR position and alignment investigated. A test rig and protocol were developed to compare the kinematics of TKR-implanted knees for different femoral component positions. The TKR was implanted and the component positions documented using a navigation system. The quadriceps was tensed and the knees were flexed and extended manually. Torques and drawer forces were applied to the tibia during knee flexion-extension, while recording the kinematics with the navigation system. The implant was removed and replaced on an intramedullary fixation that allowed proximal-distal, and internal-external rotation of the femoral component without conducting a repeated arthrotomy on the knee. The implant was repositioned using the navigation system to reproduce the previously achieved normally navigated position and the kinematics were recorded again. The recorded kinematics of the knee were not significantly different between both normal implantation and intramedullary remounting for tibial internal-external rotation, varus-valgus angulation, or posterior drawer, at any angle of knee flexion examined. Anterior drawer was increased approximately 2.5mm across the range 20-35 degrees knee flexion (p<0.05), but was otherwise not significantly different. This method of navigating implant components and of moving them within the closed knee (thus avoiding artefactual effects of repeated soft tissue manipulations) can now be used to quantify the effect on kinematics of alteration of the position of the femoral component.


Percutaneous Treatment of Multiple Recurrent Thromboembolization from a Descending Thoracic Aortic Intimal Sarcoma.
Aortic intimal sarcomas are rare tumors that may result in distal embolic ischemia. Here, we present a patient who presented with crescendo lower extremity and mesenteric ischemic events from malignant macroembolism. Management with percutaneous pharmacomechanical thromboembolectomy enabled restoration of distal perfusion and minimally invasive collection of tumor sample to confirm the suspected diagnosis of aortic sarcoma. The patient underwent definitive aortectomy and reconstruction and is recovering well.


Devastating scalp infections.
The treatment of scalp wounds is occasionally complicated by infection. Although infected scalp wounds are generally limited and readily treated, they can progress to devastating proportions if not promptly and aggressively managed. This report highlights three such cases of severe infection: extensive subgaleal abscess, fatal necrotizing fasciitis, and widespread carbunculosis. The authors emphasize the need for proper assessment of scalp wounds, meticulous cleansing and closure of all fresh wounds, definitive drainage of newly infected wounds, and adherence to sound surgical principles in managing these wounds.


A direct real-time spectroscopic investigation of the mechanism of open complex formation by T7 RNA polymerase.
Initiation of transcription occurs through a series of steps starting with the binding of RNA polymerase to a promoter DNA and formation of a closed complex. The closed complexes, then isomerize to open complexes. In the open complexes a portion of the promoter DNA is unwound. Using fluorescence spectroscopy, we have investigated in real-time the mechanism of unwinding of promoter DNA during the transition from closed to open complexes of T7 RNA polymerase. We synthesized DNA templates containing the fluorescent base analog 2-aminopurine in place of adenine at specific positions in a T7 RNA polymerase promoter. We located the 2-aminopurine residues in the presumed melting domain of the promoter at -1, -4, and at -6. The fluorescence of 2-aminopurine increases when the DNA goes from a double-stranded form to a single-stranded form. By spectroscopically monitoring the increase in fluorescence of 2-aminopurine in DNA-T7 RNA polymerase complexes, we obtained kinetic and thermodynamic information for DNA unwinding. In the presence of the initiating nucleotide GTP, conformational transitions in the polymerase-promoter complex leading to strand opening were slower than in its absence. The rate of base pair disruption at -1, -6, and at -4 was also slower in the presence of GTP than in its absence. At 37 degrees C, base pair disruption occurred first at -1 followed by -6 and finally at -4. Open complex formation was temperature-sensitive. Temperature effects at -1, -6, and at -4 were consistent with this order of base pair disruption. The apparent activation energies (Ea) for base pair disruption around -1 and -6 were 14 kcal mol-1 and 50 kcal mol-1, respectively, also suggesting this order of base pair disruption. Transcription initiation assays using G-ladder synthesis revealed that initiation rates were almost the same on all three templates containing the modified base. Unlike strand opening, we did not observe lag times for G-ladder synthesis. We suggest that facile base pair disruption at -1 is sufficient for transcription initiation. Based on these data, it is proposed that the polymerase makes contacts at or near -1 and -6 resulting in untwisting of these base pairs thus creating at least two base pair disruption events at -1 and at -6, which are followed by bidirectional propagation to -4.