Methyl prednisolone acetate modulation of infection and subsequent pulmonary pathology in hamsters exposed to parainfluenza-1 virus (Sendai).
Parainfluenza-1 virus (PI-1) has a wide host range; the disease process observed varies with the age, previous exposure, and species. This study was performed to determine possible effects of the corticosteroid methyl prednisolone acetate (MPA) on PI-1 infection in hamsters. Hamsters serologically negative for PI-1 were exposed to virus alone or were exposed to virus the day after pretreatment with a single subcutaneous injection of MPA. Serum antibodies to PI-1 were present in virus-only exposed hamsters by Day 8 and increased up to Day 20. PI-1 was recovered from lungs of virus-only exposed hamsters on Day 2 to 8. Virus antigen was detected by immunocytochemistry on Days 2 to 10 in lungs of virus-only exposed hamsters. Virus-associated lesions in these hamsters began as acute bronchiolar epithelium degeneration and necrosis on Day 4 and were foci of fibrosis by Days 12 to 20. Hamsters exposed to virus after MPA treatment developed no antibodies to virus, had no virus detectable by plaque assays or immunocytochemistry, and had no pulmonary lesions. Hamsters treated with MPA had decreased total lymphocyte counts up to Day 20 after treatment. Treatment of hamsters with MPA one day prior to PI-1 virus exposure is associated with no detectable evidence of viral infection. Humoral and cellular immunity mediated by MPA-sensitive lymphocytes may mediate some of the manifestations of PI-1 pulmonary disease.


[Bcl-2 inhibits p53-induced apoptosis after genotoxic damage by inhibitors of nuclear import of p53].
The tumor suppressor gene p53 in overexpressed in 50% of colorectal carcinomas and is an interesting target for gene therapeutic approaches. Furthermore the protooncogen bcl-2 is known to inhibit p53 induced apoptosis and is expressed in some colorectal carcinomas. In this study mechanism of bcl-2 cell death inhibition after p53 induction were evaluated. The human colon carcinoma cell line RKO posses wild-type p53 and also expresses bcl-2 protein. RKO cells were treated with liposomal bcl-2 antisense oligonucleotides (AS), control oligonucleotides (CO) and empty liposomes (EL) resulting in decreased bcl-2 expression. After induction of p53 with gamma-irradiation p53 protein expression was induced in AS, CO and EL pretreated cells. Microscopy and immunoblotting was used to characterize subcellular localization of p53 protein. Further p53 subcellular localisation was examined after p53 transfer of wt p53 cDNA in three bcl-2 expressing cell lines. Most of the p53 protein remained localized in the cytosol and apoptosis was decreased in bcl-2 expressing cells assessed by flow cytometric analysis (Ao). Our data suggests that bcl-2 is able to modulate transmembrane trafficking of p53. This resulted in inhibition of cell death implicating that bcl-2 function is involved in regulation of transmembrane gradients.


Quantitative studies of single-cell properties in monkey striate cortex. III. Spatial frequency.
1. The response properties of single cells in monkey striate cortex were examined using moving bars, square-wave gratings, and sine-wave gratings. 2. The moving of cells studied were not selective for bar width or for the spatial frequency of square-wave gratings. 3. Most cells responded selectively to the spatial frequency of the sine-wave gratings. 4. The spatial frequency of the sine-wave grating eliciting the optimal response could not be predicted from the organization of the receptive field of each cell as determined by stationary or moving stimuli. 5. The sharpness of spatial-frequency selectivity is only slightly more pronounced in S-type cells than in CX-type cells. 6. S-type and CX-type cells differ significantly in the temporal modulation of their discharges to gratings. S-type cells discharge in sharp bursts to each cycle which traverses the receptive field. CX-type cells discharge in a rather continuous fashion. This measure can be used reliably to classify cells as S or CS type.


Diet does not predict incidence or prevalence of non-insulin-dependent diabetes in Nauruans.
Cross-sectional and longitudinal relationships between diet and non-insulin-dependent diabetes (NIDDM) were assessed in Nauruan adults to determine if a particular component of the diet contributed to the high prevalence of NIDDM in this population. In 1982, 24-h dietary recall data were collected from 430 Nauruans over the age of 20, who were participating in a noncommunicable disease (NCD) survey. In 1987 a follow-up survey was performed which included 350 of the subjects from whom dietary data was obtained. Neither cross-sectional nor longitudinal analyses showed any statistically significant associations between any of the specific dietary components studied and NIDDM prevalence or incidence. However, when nutrient intakes were adjusted for energy intake it appeared that the age- and body-mass-index (BMI)-corrected mean intakes of total fat, total carbohydrates, alcohol, sugar and monounsaturated fat were slightly higher in the seven incident cases than in those who remained healthy, while intakes of protein, fibre and cholesterol were lower. Despite the inability to demonstrate an association between NIDDM risk and nutrient intake at the individual level, Nauruans as a population have total energy intakes 115-135% greater than recommended for maintenance of healthy weight, protein intakes about 250% of that required, sugar intakes about twic 1000 e the recommended, fibre intakes only about 30% of current recommended levels and in men a mean alcohol intake more than three times the recommended level. This adverse diet undoubtedly contributes to the high prevalence of obesity in the population and hence, even if there are no direct dietary effects, to the risk of NIDDM and other diet-related diseases.


Recruitment and differentiation of intramuscular preadipocytes in stromal-vascular cell cultures derived from neonatal pig semitendinosus muscles.
The present study examined the influence of dexamethasone (DEX) treatment on preadipocyte recruitment and expression of CCAAT/enhancing binding protein-alpha (C/EBPalpha) and peroxisome proliferator-activated receptor-gamma (PPARgamma) proteins in stromal-vascular (SV) cell cultures derived from neonatal subcutaneous adipose tissue and semitendinosus muscles. One adipose tissue SV cell culture and one semitendinosus muscle SV cell culture were established from each of six young pigs (5 to 7 d of age). Conventional SV cell-culture procedures were used to digest adipose and muscle tissue and to harvest and culture adipose and muscle SV cells. Muscles were digested after the removal of all visible connective tissue from the excised muscle. One hour after seeding, muscle SV cell cultures were rinsed and refed new media to remove debris and insoluble muscle protein. The SV cell cultures were double-stained for lipid and the AD-3 antibody, a preadipocyte marker, at 1, 3, and 6 d and were double-stained for lipid and C/EBPalpha or PPARgamma at d 6. Preadipocytes were randomly distributed and not clustered after 1 d in muscle and adipose SV cultures. Regardless of treatment, relative and absolute fat cell numbers were lower (P < 0.05) in muscle than in adipose-SV cell cultures. The DEX treatments produced similar magnitudes of increase in relative and absolute preadipocytes and adipocytes in muscle- and adipose-SV cultures. Several extracellular matrix substrata had no influence on adipogenesis in muscle-SV cell cultures. These studies indicate that muscle-SV cultures are characterized by a low number of adipocytes under basal conditions and a low number of glucocorticoid-responsive preadipocytes.


iPTF16geu: A multiply imaged, gravitationally lensed type Ia supernova.
We report the discovery of a multiply imaged, gravitationally lensed type Ia supernova, iPTF16geu (SN 2016geu), at redshift z = 0.409. This phenomenon was identified because the light from the stellar explosion was magnified more than 50 times by the curvature of space around matter in an intervening galaxy. We used high-spatial-resolution observations to resolve four images of the lensed supernova, approximately 0.3 arc seconds from the center of the foreground galaxy. The observations probe a physical scale of ~1 kiloparsec, smaller than is typical in other studies of extragalactic gravitational lensing. The large magnification and symmetric image configuration imply close alignment between the lines of sight to the supernova and to the lens. The relative magnifications of the four images provide evidence for substructures in the lensing galaxy.


Emigration patterns of cancer cases in Alberta, Canada.
Cancer registries are a unique source of data for population-based analysis of survival of cancer cases, but information on current vital status is essential. This paper describes a method to determine the last known vital status of cases and the emigration pattern of cancer cases diagnosed in Alberta. Data from the Alberta Cancer Registry (ACR) for the years 1985 1993 (83,446 cases), were linked to the Alberta Health Care Insurance Plan (AHCIP) registration file to identify cases that had left the province, and the date they emigrated. Ninety-nine percent of the ACR cases linked correctly to the AHCIP registration file. Three percent of cases had left Alberta by March 1998; For the first five years of follow-up between 0.6% and 0.8% of cases alive at the beginning of each year of follow-up left the province in the succeeding year. Seven percent of those diagnosed under 45 years of age left the province compared to less than 2% of those aged 65 and over. There was no difference in emigration patterns between the sexes. The cancer sites with good prognosis tended to have the highest proportion of emigrants.


A comparative evaluation of snail sampling and cercariometry to detect Schistosoma mansoni transmission in a large-scale, longitudinal field-study in Machakos, Kenya.
In an operational Schistosoma mansoni field-study in an area about 20 km 2 (population approximately 8000), transmission detection by simple snail sampling was compared with cercariometry. Between 1985 and 1987, 62 field sites were sampled at fortnightly intervals. Of a total of 2758 field observations, 89.8% gave full snail data; 64.4% full cercarial data; and 61.7% complete data for both methods. The complete data sets showed significant but not strong correlations between Biomphalaria pfeifferi (total and infected with S. mansoni or other trematodes) and cercarial (S. mansoni and non-human) recoveries. Non-human (but not S. mansoni) cercarial recovery decreased with deteriorating cercariometry filter quality. Both snail and cercarial recoveries diminished significantly with increasing water flows at the time of collection. Many samples yielded infected snails or cercariae, but not both, and neither method detected significantly more transmission sites. The method of choice for detecting transmission in a large-scale field-study depends on logistical and financial considerations. Relatively simple snail sampling allows quick, cheap and widespread data collection adequate for most purposes but more complicated cercariometry is still valuable for specific, small-scale studies.


Effects of superovulation, culture and microinjection on development of rabbit embryos in vitro.
Factors influencing the developmental potential of cultured rabbit zygotes and their ability to incorporate and integrate the WAP-hPC (human protein C) gene were investigated. Rabbit zygotes (n = 1053) were recovered from both superovulated and nontreated New Zealand White females. The hormonal treatment of rabbit donors resulted in a doubling of the number of recovered ova per donor when compared with the nontreated group (18 vs 9 ova). However, the quality of recovered zygotes (presence of both pronuclei) was significantly better in the nontreated group (99 vs 88%, Experiment 1). The effect of various culture media on the development of rabbit zygotes in vitro was evaluated after incubation under CO2-free conditions (Experiment 2). In serum-free, growth factor-supplemented medium (BSEITS, DME/F12, 1.5% BSA, EGF, insulin, transferrin and sodium selenite) the percentage of morula/blastocyst stage embryos was significantly higher (88%) than in DME/FCS, (DME/F12, 10% fetal calf serum, 59%) or the control group (DME/F12, 1.5% BSA, 25%). In Experiment 3, zygotes were microinjected with the WAP-hPC gene and were examined after 72 h of culture. Zygote cleavage and the percentage of morula/blastocyst stage intact embryos were higher (79 and 58%, respectively) than in microinjected embryos (31.0 and 21.5%, respectively). Summarized data of the PCR assay of microinjected zygotes demonstrated positive signals for the integration of the WAP-hPC gene in 6.6% (34 of 515) of all the microinjected zygotes.


J-aggregates in vapor deposited films of a bisazomethine dye.
This is the first report of J-aggregate formation of a non-ionic bisazomethine dye in vapor deposited films; this dye allows us to prepare easily large homogeneous and very stable J-aggregate thin films and to investigate intrinsic properties of low-dimensional Frenkel excitons.


The effect of mutations in the uvrD cistron of Escherichia coli on repair resynthesis.
The resynthesis step of the excision repair pathway has been examined in Escherichia coli K12 strains isogenic except for mutations in the uvrD cistron. Strains mutant at the uvrD3, uvrD101, uvrE156, and recL152 loci exhibited slight but distinct differences in their response to ultraviolet radiation. The repair capacity of the uvrD101 mutant was given special attention. Repair resynthesis in this mutant was saturated at fluences greater than about 20 J/m2. Isopycnic analysis of repaired deoxyribonucleic acid from this strain revealed a two-fold increase over its wild-type counterpart in the amount of repair replication performed after a dose of 15 J/m2. Sedimentation velocity analysis of DNA after selective photolysis of bromouracil-containing repaired regions showed that the uvrD101 mutation exerted its primary effect on the long-patch component of excision repair. The uvrD101 mutant performed long-patch repair at a larger number of sites than the number repaired by this mode in the wild-type strain; these patches were more extensive in length than the long-patch component in wild-type.


A new technique to correct vascular steal secondary to hemodialysis grafts.
Three patients are described who developed symptomatic steal distal to hemodialysis grafts, documented by angiodynography. Intraoperatively, the graft was plicated to increasing depths while using angiodynography over the radial and ulnar artery. When the flow became antegrade, the plication was stopped, resulting in salvageable grafts. Using the technique, all three patients had long use of the graft after the steal was corrected.


Class I major histocompatibility complex antigen expression on early murine trophoblast and its induction by lymphokines in vitro. II. The role of gamma interferon in the responses of primary and secondary giant cells.
The induction of paternal Class I and II MHC antigens by crude lymphokine preparations or purified recombinant gamma interferon was investigated on (C57BL/6J X CBA/H)F1 primary and secondary trophoblast giant cell outgrowths from 3.5-day post-coital (pc) blastocyst and 7.5-day pc ectoplacental cone preparations, respectively, using sensitive immunogold labelling techniques and electron microscopy. Class I MHC (but not Class II) antigens could readily be induced on secondary trophoblast giant cells, by incubation in vitro with gamma interferon for 40 h. However, repeated attempts to induce detectable MHC antigens on primary trophoblast giant cells failed. Mock-treated (C57BL/6J X CBA/H)F1 secondary trophoblast giant cell control preparations failed to express detectable MHC antigens. These findings suggest that, at the time of implantation, there is a time window during which MHC antigens are neither expressed constitutively nor are inducible by soluble factors which normally modulate cell surface MHC antigen concentration.


Effector studies of 3'-azidothymidine nucleotides with human ribonucleotide reductase.
The 5'-mono-, di- and triphosphate derivatives (N3dTMP, N3dTDP and N3dTTP respectively) of 3'-azidothymidine (N3dThd), a new drug for the treatment of the acquired immune deficiency syndrome (AIDS), were synthesized. The abilities of these analog nucleotides to mimic the effector properties of the corresponding thymidine nucleotides with human ribonucleotide reductase were studied. Surprisingly, the mode of inhibition of CDP reduction by dTTP and dTDP was found to be competitive versus CDP. The Ki values were 22 and 78 microM respectively. Inhibition by N3dTTP and N3dTDP was considerably weaker, with Ki values of 1200 and 550 microM. Neither dTMP nor N3dTMP produced significant inhibition at concentrations up to 500 microM. dTTP was an essential activator for GDP reduction. In the presence of the accessory activator, ATP, the activation constant for dTTP was 7.8 microM. N3dTTP was neither an activator of GDP reduction nor an inhibitor of the activation by dTTP. In view of the intracellular concentrations of these analog nucleotides reached after incubations with N3dThd [Furman et al., Proc. natn. Acad. Sci. U.S.A. 83, 8333 (1986)] and the weakness of their interactions with ribonucleotide reductase, it is unlikely that the antiviral or toxic effects of N3dThd can be attributed to direct effects on this enzyme. The possible indirect effects caused by alterations in the pools of the natural effectors are discussed.


Corpus-predominant gastritis as a risk factor for false-negative 13C-urea breath test results.
Urea breath test sensitivity seems affected by increased intragastric acidity during therapy with antisecretory drugs. Intragastric pH is increased in patients with corpus gastritis with/without atrophy. To test the hypothesis that urea breath test results may also be affected by this gastritis phenotype. 123 untreated patients underwent gastroscopy plus biopsies and intragastric pH measurement. The study included 82 endoscopically proven Helicobacter pylori-positive patients who were offered urea breath test with an acidic meal. Histological findings, urea breath test results and intragastric pH were compared in 66 of the subjects. 21 of 66 (31.8%) patients had a false-negative urea breath test. In these patients corpus-predominant gastritis (85.7% vs. 37.7%; P = 0.0004) and fundic atrophy (66.6% vs. 17.7%; P = 0.0001) were more frequent than in patients with true-positive urea breath test. Intragastric pH was higher in false-negative patients (mean 6.3 vs. 4.4; P = 0.001). In a multivariate analysis, the only risk factor for a false-negative urea breath test was the presence of corpus-predominant gastritis (OR = 5.6; 95% CI: 1.1-27). There was a negative correlation between the intragastric pH and the delta over baseline values (r = -0.378; P = 0.0023). Our results support the hypothesis that the pattern of gastritis can affect the sensitivity of urea breath test, and suggest that patients with corpus-predominant gastritis have a high risk of false-negative urea breath test results.


Phylogeography of cliff-dwelling relicts with a highly narrow and disjunct distribution in the western Mediterranean.
The high biodiversity in the Baetic-Rifan hotspot of Mediterranean region is shaped by complex geological and climatic histories and has been a subject of recent intensive studies. However, very little is known about phylogenetic and biogeographic history of three rare and critically endangered cliff-dwelling species of Sonchus in section Pustulati in this region. We investigated the genetic variation and phylogenetic relationships of populations based on nuclear (ITS/ETS) and plastid (3'trnL-ndhJ/psaI-accD) DNA sequences, and amplified fragment length polymorphisms (AFLPs). We performed a Bayesian relaxed molecular clock analysis with ITS data to estimate divergence times for major lineages. ITS/ETS and AFLP phylogenies showed high concordance and contrasted with cpDNA data. The divergence between S. masguindalii and S. fragilis was dated at 5.48 Ma, between S. fragilis and S. pustulatus at 3.89 Ma, and between the Baetic and Rifan S. pustulatus at 1.18 Ma. Within each distribution area, AFLP data showed a relatively high genetic structuring and moderate genetic diversity, the latter being impoverished in the Baetic populations. Our results further confirm the hybrid origin of S. pustulatus, a critically endangered species. The origin and diversification of lineages appear to have occurred on the temporary land bridge that joined Iberian and North Africa during the Messinian Salinity Crisis (5.96-5.33 Ma) and the subsequent Zanclean flood that progressively refilled the Mediterranean Basin (5.33-3.60 Ma). The only Baetic populations of S. pustulatus most likely originated from the Rifan ones.


Plasma adiponectin is an independent predictor of type 2 diabetes in Asian indians.
Adiponectin, secreted by fat cells, has regulatory functions on energy metabolism. Its low levels are predictive of future development of diabetes. Because no studies on the regulatory role of adiponectin in glucose homeostasis in Asian Indians exist, this analysis was performed to determine the prospective association of adiponectin and diabetes in subjects with impaired glucose tolerance (IGT). Baseline values of plasma adiponectin, results of anthropometry, fasting and 2-h plasma glucose levels, HbA(1c), results of lipid profile, and insulin resistance were analyzed in 91 subjects with IGT (53 men and 38 women) in a primary prevention study. Reassessment of glucose tolerance was performed during 1-year review. The predictive nature of adiponectin for development of diabetes was assessed using univariate and multiple logistic regression analyses. A control group comprising healthy, normoglycemic individuals was used for comparison. At follow-up, diabetes had developed in 25 of the 91 study subjects. The mean baseline adiponectin level was lower in the diabetic subjects than in the nondiabetic subjects (11.3 +/- 5.5 vs. 16.7 +/- 7.6 micro g/ml, P = 0.0017). Low adiponectin level was a strong predictor of future development of diabetes, and HbA(1c) also showed a positive predictive association. Women had higher adiponectin levels (16.4 +/- 6.1 micro g/ml) than men (13.9 +/- 7.6 micro g/ml) (P = 0.035). In Asian Indians, low plasma adiponectin level was predictive of future development of diabetes.


Effect of high ambient temperature on the lipids and on the activity of enzymes of rat liver microsomes.
The work has been aimed at determining the content of cholesterol and selected phospholipids (phosphatidyl choline, phosphatidyl ethanolamine, phosphatidylserine, and phosphatidylinositol) in rats' liver microsomes subjected to single and repeated exposure to an increased ambient temperature. Simultaneously, under the same experimental conditions, NADH activities--cyt. c. reductase and glucoso-6-phosphatase-in liver microsomal fractions were determined. In the experiments--a thermal chamber with controlled temperature, continual airflow and controllable humidity coming to 47-65% was used. Rats were subject to 6-hr exposure to the temperature of 21 degrees C, 28 degrees C, and 35 degrees C singly or for 3 and 6 consecutive days. In the experimental arrangements applied, no significant changes in the content of test phospholipids and cholesterol were found. The slight increase in the PC/PE relation under the effect of 28 degrees C and 35 degrees C for 6 consecutive days was not statistically significant. Cholesterol content in rats subjected to 35 degrees C for 6 days, 6 hrs daily, was higher--compared to the control group exposed to 21 degrees C--by about 15%, this differences being not statistically significant, either. The activities of NADH: cyt. c. reductase and glucoso-6-phosphatase in result of rats' single, 3- or 6-fold exposure to an increased temperature exhibit a level approximating the activity of those enzymes in controls. The lowest activities were observed in rats subjected to 35 degrees C for 6 consecutive days, 6 hrs daily.(ABSTRACT TRUNCATED AT 250 WORDS)


Self-disclosure in psychotherapy supervisors: gender differences.
This article will explore the possible reasons for gender differences found in self-disclosure in psychotherapy supervisors. Trainees and supervisors in the Brown University Department of Psychiatry and Human Behavior completed a questionnaire that asked about the appropriateness of the actions of a psychotherapy supervisor. On three items, male and female supervisors differed significantly in their perceptions of appropriate boundaries. These items were: interacting with the resident alone outside of supervision e.g. playing tennis (p = .0005), publishing identifiable content of supervision discussions with resident's consent (p = .0006), and disclosing the supervisor's prior struggles with substance abuse (p = .0008). Female supervisors answered "never" to these items in greater numbers than the male supervisors, who, for the most part answered "occasionally". Traditional gender role behaviors and differential gender socialization patterns are possible reasons for the gender difference in perception of boundaries by supervisors.


Photolysis of alpha-azidoacetophenones: trapping of triplet alkyl nitrenes in solution.
[reaction: see text] Selective excitation of the ketone chromophore in alpha-azidoacetophenones, 1, leads to intramolecular triplet energy transfer to the azido group, which forms the corresponding triplet alkyl nitrene, 2. Azides 1 also undergo alpha-cleavage to form benzoyl and methyl azido radicals in competition with nitrene formation. Thus the major photoproduct, 2-benzoylamino-1-phenylethanone, 3, comes from trapping of 2 with a benzoyl radical. This appears to be the first observation of bimolecular trapping of triplet alkyl nitrenes in solution.


Trends in in-hospital mortality following acute myocardial infarction (AMI) in Victoria, 1987-1994.
Death rates from coronary hearts disease have exhibited remarkable declines in most industrialised countries. Cardiovascular mortality has been the subject of extensive research and we considered it important to analyse recent local population based data on hospital outcomes of acute myocardial infarction (AMI). To document the trends in in-hospital mortality from AMI in Victoria from 1987-1994. This was a retrospective analysis of data from the Victorian Inpatient Minimum Database relating to all public acute care hospitals. All separations recording a principal diagnosis 410 (AMI) were selected. Changes in distribution of AMI separations, in-hospital mortality, and changes in length of stay were examined. The mean age of women admitted was 72 years compared with 64 years for men. Women comprised around a third of the overall sample but the proportion varied from 13% in those under 50 years to 57% among those aged 80 years and over. A striking decline in mortality was observed throughout the eight year period. The relative age adjusted decline was 33.5% (40% in males and 26% in females) with rates remaining higher in women. This decline occurred despite the increasing representation of those aged over 80 years. There was a significant decline in the mean length of stay (1.8 days) over the eight year period but this is likely to have had only minimal impact on mortality rates. We have documented welcome declines in in-hospital mortality from AMI that are not an artefact of declining lengths of stay. Our observations parallel those in similar overseas studies. Large changes in medical management have taken place from the mid 1980s and may be partly responsible, but a change in disease process cannot be ruled out.


The current role of microsurgery for posterior circulation aneurysms: a selective approach in the endovascular era.
During the past decade, management of posterior circulation aneurysms has shifted away from microsurgery. Currently, microsurgical clipping is considered a primary, competitive alternative to endovascular coiling, or more commonly, a secondary alternative when endovascular therapy is unfavorable. We present a large, multidisciplinary team experience with posterior circulation aneurysms in an institution that continues to use microsurgery as a primary treatment modality for selected aneurysms. During a 9-year period, 217 patients with 228 posterior circulation aneurysms were treated microsurgically; they included 106 basilar bifurcation, 27 posterior cerebral artery, 23 superior cerebellar artery, eight anteroinferior cerebellar artery, five basilar trunk, 47 posteroinferior cerebellar artery, and 12 vertebral artery aneurysms. Overall, 81% of patients presented with hemorrhage, and 33% of the aneurysms were large or giant in size. Direct clipping was performed in 75% of cases, and the overall rate of angiographic aneurysm obliteration was 98.1%. Sixteen patients (7.4%) died after surgery, 25 patients (11.5%) experienced transient neurological deterioration, and 17 patients (7.8%) experienced permanent neurological deterioration. At late follow-up (mean duration, 13.6 mo), 144 patients had good outcomes (Glasgow Outcome Scale scores of 5 or 4, 66%), and 184 patients (85%) either improved or were unchanged relative to their preoperative baseline. Overall, mean Glasgow Outcome Scale scores improved from 3.60 to 3.97. Despite increasing reliance on endovascular therapy with posterior circulation aneurysms, there is a role for microsurgical therapy. Microsurgery remains a competitive, primary therapy for superior cerebellar artery, P1 posterior cerebral artery, distal anteroinferior cerebellar artery, and posteroinferior cerebellar artery aneurysms. Microsurgery has become a secondary therapy for P2 posterior cerebral artery, basilar trunk, proximal anteroinferior cerebellar artery, vertebrobasilar junction, and vertebral artery aneurysms when endovascular therapy is unfavorable. The preferred therapy for basilar bifurcation aneurysms remains unclear. Collaborative, multidisciplinary teams are strengthened and results are improved by offering competitive treatment alternatives for patients to consider and select. Rather than abandoning the posterior circulation prematurely, aneurysm surgeons should maintain technical proficiency with these lesions.


Alcohol, calorie intake, and adiposity in overweight men.
The relation of alcohol use to calorie intake and adiposity was studied in 155 non-smoking, overweight men. Alcohol use and calorie intake were assessed by 7-day dietary record, and body composition was determined by hydrostatic weighing. Increased intake of food calories (i.e., non-ethanol calories only) on alcohol-drinking days was compensated for by decreased food consumption on non-drinking days of the week. Added alcohol calories were not offset during the week and resulted in a surplus intake of over 4,000 kcal/wk for men in the highest drinking group. Although alcohol calories were "added" to food intake, alcohol use was unrelated to level of adiposity. This finding was not accounted for by concomitant differences in exercise status. Basal metabolic rate, however, was elevated in men imbibing one or more "drinks" per day (as compared to abstainers and light-drinkers). Increased basal energy expenditure may have partially offset the alcohol calories of men at lower levels of alcohol intake, but it did not substantially offset the large calorie surplus seen at higher levels of consumption. Our results support recent speculation that alcohol consumption may not be as "fattening" as traditionally believed.


Lipid peroxidation and changes in cytochrome c oxidase and xanthine oxidase activity in organophosphorus anticholinesterase induced myopathy.
A possible role of radical oxygen species (ROS) initiated lipid peroxidation in diisopropylphosphorofluoridate (DFP)-induced muscle necrosis was investigated by quantifying muscle changes in F2-isoprostanes, novel and extremely accurate markers of lipid peroxidation in vivo. A significant increase in F2-isoprostanes of 56% was found in the diaphragm of rats 60 min after DFP-induced fasciculations. As possible source of ROS initiating lipid peroxidation, the cytocrome-c oxidase (Cyt-ox) and xanthine dehydrogenase-xanthine oxidase (XD-XO) systems were investigated. Within 30 min of onset of fasciculations Cyt-ox activity was reduced by 50% from 0.526 to 0.263 mumol/mg prot/min and XO activity increased from 0.242 to 0.541 mumol/mg prot/min. Total XD-XO activity was unchanged, indicating a conversion from XD into XO. In rats pretreatment with the neuromuscular blocking agent d-tubocurarine, prevented DFP-induced fasciculations, increases in F2-isoprostanes and changes in Cyt-ox or XD-XO. The decrease in Cyt-ox and increase in XO suggest that ROS are produced during DFP induced muscle fasciculations initiating lipid peroxidation and subsequent myopathy.


[Microsomal oxidative metabolism in the liver of rats treated with vinorelbine: evaluation through antipyrine elimination].
Determination of the metabolic efficiency of the liver in neoplastic diseases in patients receiving highly toxic drugs is of great practical importance. The effect of vinorelbine on the metabolic efficiency of the liver was evaluated by means of phenazone kinetics in rats. The test was compared with a battery of tests routinely used whenever hepatic dysfunction is suspected. Vinorelbine was administered to the rats and the pharmacokinetic parameters of antipyrine were compared with those in control rats. A statistically significant prolongation of the elimination half-life, as well as a decrease in the elimination constant and clearance of antipyrine were found in the rats receiving the anticancer drug in comparison with controls (p < 0.01). Statistically significant correlations were found between the elimination half-life of antipyrine and serum albumin values (p < 0.01) and prothrombin time (p < 0.001). Determination of antipyrine pharmacokinetics allows early detection of vinorelbine-induced hepatic dysfunction, with a sensitive scale.


Oncofetal expression of glutathione S-transferase placental form in human stomach carcinomas.
The content of glutathione S-transferase placental form (GST-pi) was immunohistochemically analyzed in 100 cases of human stomach carcinoma of various histological types and compared with the content in the stomach mucosa of the human fetus, infant and adult. High levels of GST-pi content were demonstrated in all stomach carcinomas except for signet ring cell carcinomas. High levels were also present in surface mucous cells and glandular cells of the stomach from a fetus aged 18 weeks, whereas only the parietal cells of fundic glands in the adult stomach showed slight staining for GST-pi. These results indicate that the phenotypic expression of GST-pi in human stomach carcinoma is oncofetal in character.


Bovine nasal granuloma: a review.
The literature on granulomatous nasal diseases of cattle is reviewed, with emphasis on nasal granuloma, a disease of unknown cause which is enzootic in Australian dairy cattle. It is concluded that on available evidence the disease is most probably a form of allergic rhinitis.


Coping self-efficacy as a mediator between catastrophizing and physical functioning: treatment target selection in an osteoarthritis sample.
The purpose of this study was to assess the relative effects of coping self-efficacy and catastrophizing on physical functioning. Over a 9-month period, studying changes in self-efficacy as possible mediator between catastrophizing changes and physical functioning changes might provide evidence for the most promising treatment target. Data came from a randomized, longitudinal controlled trial comparing exercise, self-management and the two combined to treat 254 individuals with early knee osteoarthritis. A secondary analysis using a bootstrapped linear mixed-effects mediational model produced estimates of both the direct and indirect effects. Results indicated that self-efficacy partially mediated the effect between catastrophizing and physical functioning suggesting that self-efficacy was the more direct treatment target compared to catastrophizing. Treatments targeting both self-efficacy and catastrophizing may have greater impact on physical functioning compared to treatments that focus on only one.


Akhmediev breathers and Peregrine solitary waves in a quadratic medium.
I investigate the formation of optical localized nonlinear structures, evolving upon a non-zero background plane wave in a dispersive quadratic medium. I show the existence of quadratic Akhmediev breathers and Peregrine solitary waves in the regime of cascading second-harmonic generation. This finding opens a novel path for the excitation of extreme rogue waves and for the description of modulation instability in quadratic nonlinear optics.


Changing Criminal Attitudes Among Incarcerated Offenders: Initial Examination of a Structured Treatment Program.
The present study investigated the effect of a criminal attitude treatment program to changes on measured criminal attitudes and postprogram recidivism. The criminal attitude program (CAP) is a standardized therapeutic curriculum consisting of 15 modules offering 44 hr of therapeutic time. It was delivered by trained facilitators to a total of 113 male offenders incarcerated in one of five state correctional institutions. Pretreatment and posttreatment comparisons were made on standardized measures of criminal attitudes, response bias, and motivation for lifestyle changes. Results found statistically significant lower criminal attitudes at posttreatment that were unaffected by response bias. There were also increases in motivation for lifestyle changes, but these did not reach statistical significance. Fifty-seven participants were released into the community following the program and were eligible for recidivism analyses. Comparisons between participants who completed the CAP and those who did not complete the CAP revealed 7% lower rearrest among CAP completers. Although preliminary, these results indicate that the CAP had a positive effect on changes to criminal attitudes and recidivism. The findings are discussed in terms of conceptual and practical considerations in the assessment and treatment of criminal attitudes among offenders.


Reactions of [Cu(X)(BPEP-Ph)] (X = PF6, SbF6) with silyl compounds. Cooperative bond activation involving non-coordinating anions.
Bond activation of silyl compounds, assisted by the cooperative action of non-coordinating anions, is achieved using Cu(I) complexes coordinated with a PNP-pincer type phosphaalkene ligand, [Cu(X)(BPEP-Ph)] (X = PF6 (1a), SbF6 (1b); BPEP-Ph = 2,6-bis[1-phenyl-2-(2,4,6-tri-tert-butylphenyl)-2-phosphaethenyl]pyridine). Complexes 1a and 1b react with Me3SiCN to form Me3SiF and Cu(i) cyanide complexes of the formula [Cu(CN-EF5)(BPEP-Ph)] (E = P (2a), Sb (2b)), in which the CN ligand is associated with the EF5 group arising from EF6(-). Formation of the intermediary isonitrile complex [Cu(CNSiMe3)(BPEP-Ph)](+)SbF6(-) (3b) is confirmed by its isolation. Thus, a two-step reaction process involving coordination of Me3SiCN, followed by nucleophilic attack of SbF6(-) on the silicon atom of 3b is established for the conversion of 1b to 2b. Complex 1b cleaves the H-Si bond of PhMe2SiH as well. The isolation and structural identification of [Cu(BPEP-Ph)](+)BAr(F)4(-) (1c) (BAr(F)4 = B{3,5-(CF3)2C6H3}4) as a rare example of a T-shaped, three-coordinated Cu(i) complex is reported.


The role of sex steroids in the oxytocin hormone system.
The sex steroids and the peptide hormone oxytocin are both ancient modulators of the reproductive system of most metazoan species responsible for tissue differentiation and acute events respectively. In vivo experimentation implies estrogenic control of both the oxytocin (OT) gene and that for its receptor (OTR). Yet neither gene promoter appears able to bind classic estrogen-dependent nuclear receptors (ER) in vitro. The literature is confused by some transfected cell culture experiments which suggest that the human and rat OT gene promoter can be regulated by both ER alpha and ER beta through a major hormone response element at -160 bp upstream of the transcription start site. These findings depended, however, upon the presence of a high molar excess of the nuclear estrogen receptor. The current consensus suggests that the sex steroids are acting indirectly on both the OT and OTR genes, possibly involving intermediate transcription factors or cofactors. They may also act upon the OTR at the cell membrane, though more study is needed before the few current observations can be generalized. Due to the OT system being so ancient and fundamental to all aspects of reproduction, it is likely that the mechanisms by which the sex steroids influence this system are going to be of general importance to many other basic aspects of reproductive control.


Neuropsychiatric decision making: designing nonbinary diagnostic tests.
Most diagnostic tests used in medicine, science, and technology are nonbinary: they are based on quantification of a variable that has a range of possible values. In this article, the authors describe how such tests are designed and characterized. They shall use the concepts developed here in future articles that describe how diagnostic techniques are operationalized for clinical settings.


Immobilized cytochrome c bound to cardiolipin exhibits peculiar oxidation state-dependent axial heme ligation and catalytically reduces dioxygen.
Mitochondrial cytochrome c (cytc) plays an important role in programmed cell death upon binding to cardiolipin (CL), a negatively charged phospholipid of the inner mitochondrial membrane (IMM). Although this binding has been thoroughly investigated in solution, little is known on the nature and reactivity of the adduct (cytc-CL) immobilized at IMM. In this work, we have studied electrochemically cytc-CL immobilized on a hydrophobic self-assembled monolayer (SAM) of decane-1-thiol. This construct would reproduce the motional restriction and the nonpolar environment experienced by cytc-CL at IMM. Surface-enhanced resonance Raman (SERR) studies allowed the axial heme iron ligands to be identified, which were found to be oxidation state dependent and differ from those of cytc-CL in solution. In particular, immobilized cytc-CL experiences an equilibrium between a low-spin (LS) 6c His/His and a high-spin (HS) 5c His/- coordination states. The former prevails in the oxidized and the latter in the reduced form. Axial coordination of the ferric heme thus differs from the (LS) 6c His/Lys and (LS) 6c His/OH(-) states observed in solution. Moreover, a relevant finding is that the immobilized ferrous cytc-CL is able to catalytically reduce dioxygen, likely to superoxide ion. These findings indicate that restriction of motional freedom due to interaction with the membrane is an additional factor playing in the mechanism of cytc unfolding and cytc-mediated peroxidation functional to the apoptosis cascade.


Photoacoustic phase study on the frequency dependence of phase angle and triplet state lifetime of Nd(III)-acetylacetonate.
The amplitude and phase of the photoacoustic (PA) signal generated in the rare earth complex powder of Nd(III)-acetylacetonate (Nd(AA)3) were examined. By using the reasonably simplified formula about phase angle at the wavelengths assigned to pi-pi* transition of ligand and f-f transitions of Nd3+, the instrumental contribution to phase angle at different chopping frequency was calculated. The frequency dependence of sample phase angle, the relative phase angle shift caused by instrumental factors and the calculation of triplet state lifetime of sample under study were also discussed. Being independent of sample, the instrumental contribution to phase angle was regarded as a parameter representing the situations of instruments and measurement and it became an approach to calculate the relaxation time of ligand in rare earth complex.


Is self-esteem an important outcome in hyperactive children?
Using a prospective design, this study examined (a) whether hyperactive children suffer from low self-esteem as adolescents; (b) whether low self-esteem is associated with poor functioning in adolescence; (c) whether hyperactive children exhibit a positive illusory bias, in which self-esteem is independent of level of functioning; and (d) whether self-esteem in adolescence is associated with poor functioning in adulthood. Subjects were 65 children diagnosed as hyperactive in childhood, and 62 matched controls sampled from a medical clinic. After controlling for current mental disorder, the hyperactive cohort reported lower self-esteem in adolescence, was judged by clinicians to have lower levels of overall adjustment in adolescence, and had lower educational achievement and occupational rank in adulthood, as compared to controls.


Ecotoxicological evaluation of diethanolamine using a battery of microbiotests.
In order to investigate the potential ecotoxicity of diethanolamine (DEA), a battery of model systems was developed. DEA is widely used as a chemical intermediate and as a surface-active agent in cosmetic formulations, pharmaceuticals and agricultural products. DEA was studied using ecotoxicological model systems, representing four trophic levels, with several bioindicators evaluated at different exposure time periods. The battery included bioluminescence inhibition of the bacterium Vibrio fischeri, growth inhibition of the alga Chlorella vulgaris and immobilization of the cladoceran Daphnia magna. Cell morphology, total protein content, neutral red uptake, MTS metabolization, lysosomal function, succinate dehydrogenase activity, G6PDH activity, metallothionein levels and EROD activity were studied in the hepatoma fish cell line PLHC-1, derived from Poeciliopsis lucida. The systems most sensitive to DEA were both D. magna and V. fischeri, followed by C. vulgaris and the fish cell line PLHC-1. The most prominent morphological effect observed in PLHC-1 cultures exposed to DEA was the induction of a marked steatosis, followed by death at high concentrations, in some cases by apoptosis. The main biochemical modification was a nearly three-fold increase in metallothionein levels, followed by the stimulations of lysosomal function and succinate dehydrogenase and G6PDH activities. Judging by the EC(50) values in the assay systems, DEA is not expected to produce acute toxic effects in the aquatic biota. However, chronic and synergistic effects with other chemicals cannot be excluded.


The effect of need-based spiritual/religious intervention on spiritual well-being and anxiety of elderly people.
Anxiety and spiritual distress are the most common problems among the patients admitted in intensive care units. The elderly are more vulnerable to this problem due to impairment of their adaptation mechanisms. Hence, helping to reduce anxiety is one of the most effective nursing interventions. Therefore, this study aimed at investigating the effect of need-based spiritual/religious interventions on spiritual well-being (SWB) and anxiety of the elderly admitted to coronary care unit (CCU). This quasi-experimental study with pre- and posttest control group design was conducted on 66 patients admitted to CCU of Imam Reza hospital in Lar, southern Iran, in 2014. After obtaining informed consents, the data were collected using the Spielberger State-Trait Anxiety Inventory, the SWB Scale, and a demographic questionnaire. The questionnaires were completed through interviewing the patients before and after the intervention. The participants of the intervention group underwent 60- to 90-minute sessions of spiritual and religious need-based interventions for 3 consecutive days. The results showed a significant increase in the mean scores of SWB in the intervention group after the intervention (P = .001). Also, a significant decrease was found in mean scores of trait and state anxiety in the intervention group in comparing to control group (P < .001). Moreover, a significant correlation was observed between the mean scores of SWB and state and trait anxiety. Spiritual/religious interventions could enhance SWB and reduce anxiety in the elderly admitted to CCU.


Inducing mechanism of biological phosphorus removal driven by the aerobic/extended-idle regime.
Recently, it was found that excess phosphorus (Pi) removal could be achieved in activated sludge with an aerobic/extended-idle (AEI) process. In this study, batch tests were performed to further reveal the inducing mechanism of Pi removal involved in the AEI process. Unlike the classical anaerobic/aerobic process where an anaerobic Pi release along with a significant polyhydroxyalkanoate (PHA) accumulation drives polyphosphate (poly-P) accumulating organisms (PAOs) to over-store Pi as poly-P, an idle Pi release accompanied by a low-idle PHA production, which is usually considered to be detrimental for biological Pi removal, was observed to induce some cells to effectively uptake Pi in excess of metabolic requirement in the AEI process. With the increase of idle Pi release, Pi removal efficiency linearly increased. The results also showed that a long idle period with a low level of intracellular glycogen could significantly increase Pi release contents, thus remarkably enhancing Pi removal performances. Fluorescence in situ hybridization analysis further revealed that activated sludge in the AEI process contained 37.6% of Accumulibacter (PAOs) and 28.2% of Competibacter and Defluviicoccus-related organisms (glycogen accumulating organisms). This study revealed an actually existent, yet previously unrecognized, inducing mechanism of poly-P accumulation, and this mechanism behind the AEI regime may provide a scientific basis for the development of an alternative strategy for Pi removal from wastewaters.


Circadian disruption of body core temperature and rest-activity rhythms after general (propofol) anesthesia in rats.
General anesthesia is commonly associated with sleep disorders, fatigue, drowsiness, and mood alterations in patients. The authors examined whether general (propofol) anesthesia can impact the circadian temporal structure by disturbing circadian rest-activity and body temperature rhythms under normal light-dark conditions (light-dark 12:12 h) in rats. A group of rats was anesthetized with propofol, and another was injected with 10% Intralipid, which was used as a control lipidic solution. The authors examined six groups of rats according to the Zeitgeber time of intraperitoneal administration (ZT6, ZT10, ZT16) and the substance injected (propofol or Intralipid). On the day after anesthesia, propofol induced a significant 60- to 80-min phase advance of both rest-activity and body temperature rhythms. A significant 45- to 60-min phase advance of body temperature and a significant 20-min phase advance of rest-activity were still observed on the second day after anesthesia. The amplitudes of both rest-activity and body temperature rhythms were decreased on the first and second days after anesthesia. The 24-h mean rest-activity rhythm was decreased on the day after anesthesia, whereas the 24-h mean body temperature rhythm was not modified. The results demonstrate the disturbing effects of propofol anesthesia on the circadian time structure in rats under normal light conditions.


Tumor angiogenesis: pathophysiology and implications for contrast-enhanced MRI and CT assessment.
The process of tumor neoangiogenesis plays a central role in the growth and spread of tumors. It is currently a leading theme in oncology, and many new drugs targeting the tumor neoangiogenic process are under development. Expanding tumors become hypoxic and tumor cells express transcription factors, such as the hypoxia-inducible factor (HIF), which induce the release of proangiogenic growth factors such as vascular endothelial growth factors (VEGF) and transforming growth factors that promote the formation of new capillaries by recruiting, activating, and stimulating endothelial cells. Activated endothelial cells secrete matrix metalloproteases, which degrade the basement membrane and the extracellular matrix, and adhesion receptors such as integrins alphavbeta(3), which allow their migration into the extracellular matrix toward the tumor cells. The newly grown vessels are immature and differ from normal capillaries. They are tortuous and irregular, resulting in poorly efficient perfusion, they are leaky (especially to macromolecules), and they are independent of the normal mechanisms of regulation of the capillary blood flow. Moreover, tumor microcirculation is heterogeneous. Evaluation of angiogenesis can be used as a prognostic marker to evaluate the aggressiveness of tumor and as a potential predictive marker of antiangiogenic treatment response. Histopathologic techniques of microvascular density indexes require invasive tissue sampling and need to be standardized. Hemodynamic characteristics of immature neovessels can be noninvasively assessed by dynamic contrast-enhanced magnetic resonance imaging or computed tomography. Tissue enhancement depends on arterial input function, kinetic of distribution of blood into the capillary bed, leakage across the capillary walls, and volume of the interstitial space. Pharmacodynamic models allow the evaluation of microvascular parameters of tissue blood flow, tissue blood volume, tissue interstitial volume, mean transit time, and permeability by surface of capillary wall. Methods based on dynamic contrast enhancement have been shown to correlate with conventional outcome methods such as histopathologic studies and survival. Radiologists must be convinced that, by using this emerging and promising approach, it is becoming possible to gain functional information during routine tumor imaging.


BrFLC5: a weak regulator of flowering time in Brassica rapa.
A splicing site mutation in BrFLC5, a non-syntenic paralogue of FLOWERING LOCUS C, was demonstrated to be related to flowering time variation in Brassica rapa. Flowering time regulation in Brassica rapa is more complex than in Arabidopsis, as there are multiple paralogues of flowering time genes in B. rapa. Brassica rapa contains four FLOWERING LOCUS C (FLC) genes, three of which are syntenic orthologues of AtFLC, while BrFLC5 is not. BrFLC1, BrFLC2, and BrFLC3 have been reported to be involved in flowering time regulation. However, BrFLC5 has thus far been deemed a pseudogene. We detected two alternative splicing patterns of BrFLC5 resulting from a nucleotide mutation (G/A) at the first nucleotide of intron 3 (named as Pi3+1(G/A)). Genotyping of BrFLC5Pi3 + 1(G/A) for 301 B. rapa accessions showed that this single nucleotide polymorphism was significantly related to flowering time variation (p < 0.001). In the collection, the frequency of the functional G allele (35.2%) was much lower than that of the nonfunctional A allele (59.1%); however, the frequency of the G allele was very high among the turnips (83.6%). An F2 population segregating at this locus was developed to analyze the genetic effect of BrFLC5. The result showed that the G allele individuals began to bolt two days later than the A allele individuals, indicating that BrFLC5 is a weak regulator of flowering time. BrFLC5 was expressed at the lowest level among the three analyzed BrFLCs. The late allele (G allele) was dominant to the early allele (A allele) at the BrFLC5 locus, which was in contrast to that of BrFLC1 and BrFLC2. This characteristic suggests that BrFLC5 would be more efficient for breeding premature bolting resistance in B. rapa.


A preliminary investigation of serum folate concentrations in sows during pregnancy and at weaning.
The mean serum folate concentrations of Large White sows were compared between one group of 13 animals, 43-80 days pregnant and another group of 9 animals at weaning when the litters were 28-30 days old. The mean concentration was higher in sows at weaning (p<0.05) and the lowest levels were found in sows no more than 51 days pregnant (p<0.05).


[New anticoagulants - direct factor Xa-inhibitors].
The direct oral factor Xa-inhibitors are at present in clinical use as antithrombotics, after their efficiency and safety have been proved in clinical studies. Three products are actually in the market, rivaroxaban (Xarelto®) apixaban (Eliquis®) and edoxaban (Lixiana®). Efficacy and safety have been tested for rivaroxaban and apixaban in large study programmes with more than 60'000 patients each. For edoxaban large phase III studies are under way. Based on these data rivaroxaban was registered in the EU and CH for primary prophylaxis against thrombosis after major orthopaedic surgery, such as hip- and knee-joint protheses, for treatment and prophylaxis of deep vein thrombosis and pulmonary embolism and for prophylaxis against thromboembolic stroke in patients with atrial fibrillation. Apixaban is presently registered in the EU and CH for prophylaxis against thrombosis after major orthopaedic surgery, Edoxaban is registered only in Japan for the same indication. These products have been shown to be non-inferior or superior compared with vitamin K antagonists or low-molecular weight heparins, they are administered once or twice a day, they do not need laboratory monitoring. But they have disadvantages also, they depend on renal clearance, they can interact with other medicaments and they lack a specific antidote. In total, though, they are considered as a progress for the appropriate patients in terms of quality of treatment.


The effect of rear-seat overloading in a car crash: pathological and kinematics evidences.
Seat belts have been shown to decrease the incidence of lethal lesions to the head, chest, and abdomen. Since the introduction of seat belts, it is reported that the incidence of traumatic lesions in these body parts is reduced. In the meantime, the characteristic lesions to the chest and abdomen caused by the use of seat belts are described (J Trauma. 2007;62(6):1473-1480).Reported is a peculiar case of an oblique front-to-rear car collision, in which overloading of the rear seat with packages pushed forward the passenger front seat in an abnormal way, causing fatal thoracic and abdominal lesions.The authors underline that the seat belt protection device is defeated if front seats are damaged by heavy unanchored bags on the rear seat or on the rear parcel shelf of a motor vehicle.


Identification of naturally occurring trans, trans delta 5,9 fatty acids from the sponge Plakortis halichondroides.
The first trans fatty acids from a sponge have been isolated from Plakortis halichondroides. The sponge was shown to contain the iso acids (5E,9E)-19-methyl-5,9-eicosadienoic, (5E,9E)-20-methyl-5,9-heneicosadienoic and (5E,9E)-21-methyl-5,9-docosadienoic acid, as well as the anteiso acids (5E,9E)-19-methyl-5,9-heneicosadienoic and (5E,9E)-20-methyl-5,9-docosadienoic acid together with the straight chain (5E,9E)-5,9-docosadienoic acid. The acids were shown by gas chromatography, Fourier transform infrared and 13C nuclear magnetic resonance to contain the trans configuration. An eicosadienoic acid, namely (6E,14E)-6,14-eicosadienoic acid, and 12-methyl-5-octadecenoic acid were also identified in a sponge for the first time. The fatty acids were shown to be the principal constituents of phosphatidylethanolamine and phosphatidylcholine. No sterols were found in the sponge. The results presented in this work should be helpful in taxonomy of Homoscleromorpha.


Changes in sexual activity and risk behaviors among PLWHA initiating ART in rural district hospitals in Cameroon -- data from the STRATALL ANRS 12110/ESTHER trial.
The continued scaling-up of antiretroviral therapy (ART) in Sub-Saharan Africa provides an opportunity to further study its impact on sexual behaviors among people living with HIV/AIDS (PLWHA). We explored time trend and correlates of sexual activity among PLWHA initiating ART in Cameroon and compared sexual risk behaviors between patients sexually active before and after initiating ART and those resuming sexual activity after ART initiation. Analyses were based on longitudinal data collected within the randomized trial (n=459) conducted in nine rural district hospitals in Cameroon. Sexual activity was defined as reporting at least one sexual partner during the previous 3 months. Inconsistent condom use (ICU) was defined as reporting to have "never," "sometimes," or "nearly always" used condoms at least once with a partner(s) either HIV-negative or of unknown HIV status during the same period. Mc Nemar tests were used to assess time trend, while mixed-effect logistic regressions were conducted to analyze the effect of time since ART initiation on sexual activity. The proportion of sexually active patients significantly increased over time: from 31.8% at baseline to 40.2 and 47.1% after 6 and 12 months of ART, respectively (p=0.001), to 55.9% after 24 months (p=0.02). After adjustment for behavioral and psychosocial factors, time since ART initiation was independently associated with reporting sexual activity (AOR [95% CI]=1.30 [1.17-1.46] per 6-month increase, p=0.001). ICU was more frequent among patients sexually active both before and after ART initiation than among those who resumed sexual activity after ART initiation (82 vs. 59%, p<B0.001). To conclude, while ART initiation fosters resumption of sexual activity in patients who are inactive before starting treatment; unsafe sexual behaviors remain less frequent in this population than in patients who are already sexually active before starting ART. Risk reduction programs should be reinforced among PLWHA in the context of ART scaling-up.


Implementation of advanced Optimum Contribution Selection in small-scale breeding schemes: prospects and challenges in Vorderwald cattle.
Vorderwald cattle are a regional cattle breed from the Black Forest in south western Germany. In recent decades, commercial breeds have been introgressed to upgrade the breed in performance traits. On one hand, native genetic diversity of the breed should be conserved. On the other hand, moderate rates of genetic gain are needed to satisfy breeders to keep the breed. These goals are antagonistic, since the native proportion of the gene pool is negatively correlated to performance traits and the carriers of introgressed alleles are less related to the population. Thus, a standard Optimum Contribution Selection (OCS) approach would lead to reinforced selection on migrant contributions (MC). Our objective was the development of strategies for practical implementation of an OCS approach to manage the MC and native genetic diversity of regional breeds. Additionally, we examined the organisational efforts and the financial impacts on the breeding scheme of Vorderwald cattle. We chose the advanced Optimum Contribution Selection (aOCS) to manage the breed in stochastic simulations based on real pedigree data. In addition to standard OCS approaches, aOCS facilitates the management of the MC and the rate of inbreeding at native alleles. We examined two aOCS strategies. Both strategies maximised genetic gain, while strategy (I) conserved the MC in the breeding population and strategy (II) reduced the MC at a predefined annual rate. These two approaches were combined with one of three flows of replacement of sires (FoR strategies). Additionally, we compared breeding costs to clarify about the financial impact of implementing aOCS in a young sire breeding scheme. According to our results, conserving the MC in the population led to significantly (P < 0.01) higher genetic gain (1.16 ± 0.13 points/year) than reducing the MC (0.88 ± 0.10 points/year). In simulation scenarios that conserved the MC, the final value of MC was 57.6% ± 0.004, while being constraint to 58.2%. However, reducing the MC is only partially feasible based on pedigree data. Additionally, this study proves that the classical rate of inbreeding can be managed by constraining only the rate of inbreeding at native alleles within the aOCS approach. The financial comparison of the different breeding schemes proved the feasibility of implementing aOCS in Vorderwald cattle. Implementing the modelled breeding scheme would reduce costs by 1.1% compared with the actual scheme. Reduced costs were underpinned by additional genetic gain in superior simulation scenarios compared to expected genetic gain in reality (+4.85%).


Simulated anchoring of a nematic liquid crystal at a polymer surface.
Liquid-crystal anchoring at a polymer surface arises from interactions at several different length scales. At the molecular level, a liquid-crystal molecule may tend to align with the substrate polymer chain, while at the nanometer length scale grooves can exist that arise from the periodic repeat structure of a polymer chain or from nanometer-scale undulations due to surface stresses. On a still longer scale there is the secondary effect of grooves or surface inhomogeneities. We have performed a total of more than 900 ns of atomistic molecular dynamics simulations in order to study the relative importance of the molecular-level interaction and the topography of the polymer surface in liquid-crystal anchoring. Substrates were constructed in which grooves were induced along a direction perpendicular to the constituent molecular chains. In the results presented for the case of 32 5CB molecules on a poly(vinyl alcohol) substrate, the liquid-crystal director orientation appeared to be determined principally by the substrate chain orientation. Only for the deepest grooves did the director align along the grooves and perpendicular to the substrate molecular chain direction.


Solvent tuned single molecule dual emission in protic solvents: effect of polarity and H-bonding.
Phen-PENMe2 has recently been proposed as a promising new molecule displaying solvent-tuned dual emission, highlighting an original and newly-described charge transfer model. The study of the photophysical behaviour of this molecule was extended to include protic solvents. The effects of polarity and hydrogen bonding lead to an even more evident dual emission associated with a large multi-emission band in some solvents like methanol, highlighting Phen-PENMe2 as a promising candidate for white light emission.


Practical strategies for implementing continuous quality improvement.
The strategies for implementing these components will vary for individual health care organizations. It should be apparent that implementation of continuous improvement theories is a complex undertaking which requires a long-term effort to be successful and improve performance.


Towards the integration of matrix assisted laser desorption ionisation mass spectrometry imaging into the current fingermark examination workflow.
A wide range of fingermark enhancement techniques (FET) is currently employed to visualise latent fingermarks at crime scenes. However, if smudged, partial, distorted or absent in the National Fingerprint Database, crime scene marks may be not useful for identification purposes. In these circumstances, a technology enabling chemical imaging of both endogenous and exogenous species contained within the fingermark could provide additional and associative investigative information, to profile the suspect's activities prior to the crime. Matrix Assisted Laser Desorption Ionisation Mass Spectrometry Imaging (MALDI MSI) has proven to be such a technique, enabling investigative information to be gathered, for example, on what substances the donor has come in contact with and what they have ingested. Nonetheless, to be employed, MALDI MSI has to be validated and its compatibility with FET tested for integration into the standard fingermark examination workflow. For the first time, a direct comparison has been made between the efficiency of a range of FET and MALDI MSI under different conditions. This information will build towards validation of the technology. Also, for the first time, MALDI MSI has been successfully employed as a sequential step following fingermark enhancement using many of the currently employed FET. Additionally, known enhancers have been "re-visited" by combining them with a MALDI matrix, providing both improved fingermark development and chemical species detection via MALDI MSI. The result reported here are good indication in favour of the integration of MALDI MSI into the current fingermark examination workflow for gathering additional investigative information.


Clinical manifestations of acute rejection in renal allograft recipients receiving cyclosporin-A therapy.
Cyclosporin-A-treated renal allograft recipients have demonstrated an improved graft survival rate, when compared to that of patients treated with conventional azathioprine and steroid therapy. Cyclosporin-A has been used for immunosuppressive therapy after renal transplantation at the National Taiwan University Hospital since November 1985. Since then, the one-year graft survival rate has been 78%, and the patient survival rate is 91%. At our service, acute rejection is confirmed mainly by an increase in the serum creatinine level of 0.5 mg% per day and a subsequent return of kidney function to normal after pulse steroid therapy. Twenty patients receiving cyclosporin-A and suffering from acute rejection episodes were chosen for comparison with 18 patients receiving conventional azathioprine and steroid therapy. Compared to conventional therapy, the classical systemic manifestations of rejection, such as malaise, lethargy, apathy, general weakness, vague discomfort, increase in body weight, swelling of graft with tenderness, were all more mild and less frequent in the cyclosporin-A-treated group. Episodes of rejection appeared earlier and the duration of rejection was shorter than in those of the conventional group. The urinary sodium concentration and the ratio of urine urea nitrogen to blood urea nitrogen were reliable references during the acute rejection episode in the conventional group, but it cannot be used as indices in the cyclosporine group. These findings can help us understand the changes which occurred in acute rejection in patients who receive renal transplantation during the cyclosporine era.


Enterohepatic circulation: physiological, pharmacokinetic and clinical implications.
Enterohepatic recycling occurs by biliary excretion and intestinal reabsorption of a solute, sometimes with hepatic conjugation and intestinal deconjugation. Cycling is often associated with multiple peaks and a longer apparent half-life in a plasma concentration-time profile. Factors affecting biliary excretion include drug characteristics (chemical structure, polarity and molecular size), transport across sinusoidal plasma membrane and canniculae membranes, biotransformation and possible reabsorption from intrahepatic bile ductules. Intestinal reabsorption to complete the enterohepatic cycle may depend on hydrolysis of a drug conjugate by gut bacteria. Bioavailability is also affected by the extent of intestinal absorption, gut-wall P-glycoprotein efflux and gut-wall metabolism. Recently, there has been a considerable increase in our understanding of the role of transporters, of gene expression of intestinal and hepatic enzymes, and of hepatic zonation. Drugs, disease and genetics may result in induced or inhibited activity of transporters and metabolising enzymes. Reduced expression of one transporter, for example hepatic canalicular multidrug resistance-associated protein (MRP) 2, is often associated with enhanced expression of others, for example the usually quiescent basolateral efflux MRP3, to limit hepatic toxicity. In addition, physiologically relevant pharmacokinetic models, which describe enterohepatic recirculation in terms of its determinants (such as sporadic gall bladder emptying), have been developed. In general, enterohepatic recirculation may prolong the pharmacological effect of certain drugs and drug metabolites. Of particular importance is the potential amplifying effect of enterohepatic variability in defining differences in the bioavailability, apparent volume of distribution and clearance of a given compound. Genetic abnormalities, disease states, orally administered adsorbents and certain coadministered drugs all affect enterohepatic recycling.


Serological evidence of bluetongue in game animals in Botswana.
Using the Agar Gel Precipitin technique the sera of 397 African buffalo (Syncerus caffer) and 90 sera of other common game species were examined for bluetongue antibodies. Of the adult buffalo 283 out of 325 (87 per cent) were positive. Buffalo calves were positive in 25 out of 72 cases (35 per cent). Positive reactions were also recorded in lechwe (Kobus leche), tsessebe (Damaliscus lunatus), red hartebeeste (Alcelaphus buselaphus), gemsbok (Oryx gazella), sable (Hippotragus niger) and impala (Aepyceros melampus).


Subtle ligand effects in oxidative photocatalysis with iridium complexes: application to photopolymerization.
Iridium(III) complexes were designed and evaluated as efficient photoinitiators of polymerization reactions in combination with iodonium salts and silanes. Mechanistically, these reactions were shown to proceed through oxidative photoredox catalysis, generating aryl and silyl radicals under very soft irradiation conditions (blue LED, xenon lamp, and even sunlight). These radicals can initiate the free radical polymerization of acrylates or can be oxidized during the catalytic cycle to promote the ring-opening polymerization of epoxy monomers. Remarkably, both the (photo)chemical reactivity and the practical efficiency are dramatically affected by the ligands. In addition, the central role played by the oxidation ability of the excited state of the photocatalyst is discussed.


Expression of the Thy-1 antigen in long-term cultures of embryonic mouse spinal cord.
Immunofluorescent studies of the Thy-1 antigen in cultures of mouse spinal cord demonstrated positivity on the surfaces of a fraction of neurons and glia. Positivity was evident by one week and increased slowly over the lifespan of the cultures, often several months. Thy-1 positivity was most apparent in regions of clustering of neurons and glia. Neuroglial clusters were identified by morphologic appearance; the identity of astrocytes was confirmed by immunofluorescent staining of glial fibrillary acidic protein.


[Management and clinical outcome in patients over 80 years with rectal cancer treated between 2006 and 2008 in Southern France (PACA region)].
Rectal cancer is increasingly prevalent in elderly patients. Their clinical history and outcome after treatment are poorly described. This retrospective study was undertaken to provide more data and to compare therapeutic strategies to the standard of care for younger patients. Patients concerned were aged 80 years or older, with a rectal cancer diagnosed between 2006 and 2008 and treated in Provence-Alpes-Côte-d'Azur (PACA), irrespective of stage and treatment of the disease. Overall survival and relapse-free-survival were correlated with patients' characteristics and treatment. The adopted therapeutic strategy was then compared to the standard-of-care for younger patients. With a median follow-up of 36 months, among the 160 patients included, the 3-year overall survival and relapse-free survival were 59.2% and 76.6%, respectively for the 117 patients who received a treatment with curative intent. In the multivariate analysis, node status and surgery independently influenced overall survival, while relapse-free survival was influenced by age, N status, and gender. For T0-T2 tumours, patients were treated similarly to younger patients with an overall survival of 83.6% and a relapse-free survival of 95.2%. For T3-T4 tumours, the 3-year relapse-free survival was 65%, even with a less aggressive strategy. Surgical resection after evaluation using the Comprehensive Geriatric Assessment (CGA) test should be the standard treatment for localized rectal cancer (T0-T2) in elderly patients, as it is in younger patients. For locally advanced lesions (T3-T4), results obtained after a conservative approach suggest that a non-surgical strategy can be used in elderly patients.


Distribution of enterotoxin genes among carriage- and infection-associated isolates of Staphylococcus aureus.
To compare the distribution of genes encoding classical and newly described enterotoxins among Staphylococcus aureus, associated with carriage and infection. Forty-five nasal isolates from carriers and 42 clinical isolates were included. The genes sea to see and seg to sei as well as sem, sen, seo and seu were tested using multiplex and conventional PCR. The most frequently found toxin genes were egc-related genes, in particular the combination seg and sei (n = 55, 63.1%), followed by sen and seu (n = 54, 62.1%), sem (n = 51, 58.6%) and seo (n = 48, 55.2%). Significant differences were found for seg and sei combination (33 of the nasal vs 22 of the infection isolates, P = 0.048) as well as for the genes sem (P = 0.004), sen (P = 0.029) and seo (P = 0.032). Regarding the classical toxin genes no significant differences between the two groups of isolates were found. Significant differences between infection and carriage strains were found only for the egc-related genes, which were more common in the nasal isolates. The egc-related enterotoxin genes seem to be more prevalent in carriage- than in infection-associated S. aureus isolates. The possible contribution of egc-related genes in determining the potential for nasal carriage requires further investigation.


Intrapartum detection of Group B streptococci colonization by rapid PCR-test on labor ward.
Group B streptococci (GBS) may lead to early onset neonatal sepsis with severe morbidity and mortality of newborns. Intrapartum detection of GBS is needed. The objective was to compare a PCR-based test performed in the laboratory versus labor ward. 300 patients were included prospectively. In phase I, swabs were analyzed by selective culture and rapid PCR in the laboratory. In phase II, swabs were analyzed accordingly, but the PCR test was conducted in labor ward. Test performances were analyzed and compared. In phase I the rapid PCR test had a sensitivity of 85.71% and a specificity of 95.9%. The GBS colonization rate was 18.67%. Overall 8.5% of the PCR results were invalid. In phase II the PCR test showed a sensitivity of 85.71% and a specificity of 95.65%. The GBS colonization rate was 23.3%. Overall 23.5% of swabs tested with PCR were invalid. Initiation of specific, short 2-hour training for operating personnel in the labor ward reduced the invalid test rate to 13.4%. The rapid PCR-based test yields adequate results to identify GBS colonization when performed in labor ward. In order to reduce the number of invalid tests a short training period is needed.


Primary peripheral T cell lymphoma in a kidney transplant under immunosuppression with cyclosporine A.
A 56-year-old patient received a cadaveric renal allograft because of primary cystic kidney disease. The donor was a 28-year-old man who died from head trauma. No other major illnesses were present at the time of transplantation. Immunosuppression was performed with cyclosporine A and steroids. After 3 months, the patient presented with fever and abdominal pain which was located in the region of the allograft. Ultrasonography demonstrated a tumor mass at the renal transplant hilus that was suspected to be an infected hematoma. Kidney biopsy from the cortex revealed only severe morphologic signs of cyclosporine A toxicity which was due to high cyclosporine A levels during the first 2 months after transplantation. The patient died from pulmonary embolism 6 months posttransplant. Histologic evaluation of the tumor specimens obtained at autopsy showed an extensive infiltration of the renal hilus and the medulla by a peripheral T cell lymphoma of the large-cell type. The T cell origin was confirmed by immunohistochemistry using the T cell-associated monoclonal antibodies UCHL-1 and MT1.


Three-dimensional imaging of atomic four-body processes.
To understand the physical processes that occur in nature we need to obtain a solid concept about the 'fundamental' forces acting between pairs of elementary particles. It is also necessary to describe the temporal and spatial evolution of many mutually interacting particles under the influence of these forces. This latter step, known as the few-body problem, remains an important unsolved problem in physics. Experiments involving atomic collisions represent a useful testing ground for studying the few-body problem. For the single ionization of a helium atom by charged particle impact, kinematically complete experiments have been performed since 1969 (ref. 7). The theoretical analysis of such experiments was thought to yield a complete picture of the basic features of the collision process, at least for large collision energies. These conclusions are, however, almost exclusively based on studies of restricted electron-emission geometries. Here, we report three-dimensional images of the complete electron emission pattern for the single ionization of helium by the impact of C6+ ions of energy 100 MeV per a.m.u. (a four-body system) and observe features that have not been predicted by any published theoretical model. We propose a higher-order ionization mechanism, involving the interaction between the projectile and the target nucleus, to explain these features.


Safety of levonorgestrel 52 mg intrauterine system compared to copper intrauterine device: a population-based cohort study.
To compare the risk of all-cause death, hospitalizations (any cause), ectopic pregnancy, pelvic inflammatory disease or infection, uterine perforation, device removal, neuro-psychiatric drugs initiation, or new psychiatric visit(s) between levonorgestrel (LNG) 52 mg intrauterine system (IUS) and copper intrauterine device (IUD) users in France. We identified a historical cohort of women aged 20-55 years with a first dispensing of either LNG 52 mg IUS or copper-IUD between January 1, 2010, and December 31, 2014, in the French National Claims database, SNDS. We used propensity score matching to balance the two groups on baseline sociodemographic and clinical characteristics to minimize confounding. We estimated Cox proportional hazards models to compare health outcomes between LNG 52 mg IUS and copper-IUDs users. We matched 9318 LNG 52 mg IUS users (mean age 36.2±6.8 years) to 10,185 copper-IUD users (mean age 35.4±7.1 years). After matching and age-adjustment, LNG 52 mg IUS users had a slightly higher risk of anxiolytic drugs initiation (HR 1.08, 95%CI 1.01-1.15) and device removal (HR 1.05, 95%CI 1.01-1.10) compared to copper-IUD users, with no differences for other studied outcomes. French IUS users report slightly more anxiolytic treatment initiation and IUD removal compared to copper-IUD users. These results are consistent with a potential pharmacovigilance signal of anxiety-related disorders in LNG 52 mg IUS users. In French LNG 52 mg IUS users, there was slightly more anxiolytic treatment initiation and IUD removal compared to copper-IUD users. No risk difference was found for all-cause death, hospitalizations, ectopic pregnancy, pelvic disorders, and uterine perforation. We cannot exclude that the associations are related to differences in characteristics of women who chose each type of type of IUD.


Endolymphatic hydrops as a cause of audio-vestibular manifestations in relapsing polychondritis.
Relapsing polychondritis (RP) is characterized by inflammation and subsequent degeneration of cartilage. We report a 61-year-old woman who had RP with audio-vestibular manifestations. She was also diagnosed as having a myelofibrosis with myeloid metaplasia (MMM). Bilateral endolymphatic hydrops (EH) was confirmed by dominant -SP/AP of the electrocochleogram (ECochG). When thalidomide and prednisolone were prescribed for the treatment of MMM, symptoms of RP -- including the inner ear dysfunction -- were ameliorated. Isosorbide, one of the osmotic diuretics commonly used for the treatment of Meniere's disease (MD) in Japan, was also effective in keeping her free from inner ear dysfunction. This is the first report to confirm the existence of EH in a patient with RP with audio-vestibular manifestations. We suppose that an immunological imbalance due to MMM, in conjunction with a specific immunogenetic background, may have played a role in the pathogenesis of RP and the formation of EH in this patient.


[Immunotherapy of sepsis and septic shock].
An extraordinary advance in basic sciences and technology did not reduce high lethality rate of the septic shock patients. The lethality rate of those patients was and still is around 50%. A new knowledge about a role of an inflammatory response on the infection in the later fatal course of the septic patients, led to the new approach in the treatment. A trial to block an endotoxin, cytokines, especially TNF and IL-1, as well as some other substances, in experimental models of sepsis, in spite of inconsistent results, is promising. A clinical experiences are disappointing, at first because of our still poor knowledge about various cytokines cascade, feedback mechanisms, cellular protective mechanisms, etc. The new chapter on the treatment of that highly lethal syndrome is open, though a final achievement of that approach is not clear till now.


Non-linear PCA: a missing data approach.
Visualizing and analysing the potential non-linear structure of a dataset is becoming an important task in molecular biology. This is even more challenging when the data have missing values. Here, we propose an inverse model that performs non-linear principal component analysis (NLPCA) from incomplete datasets. Missing values are ignored while optimizing the model, but can be estimated afterwards. Results are shown for both artificial and experimental datasets. In contrast to linear methods, non-linear methods were able to give better missing value estimations for non-linear structured data. We applied this technique to a time course of metabolite data from a cold stress experiment on the model plant Arabidopsis thaliana, and could approximate the mapping function from any time point to the metabolite responses. Thus, the inverse NLPCA provides greatly improved information for better understanding the complex response to cold stress. scholz@mpimp-golm.mpg.de.


Genomic Characterization of a Metastatic Alveolar Rhabdomyosarcoma Case Using FISH Studies and CGH+SNP Microarray Revealing FOXO1-PAX7 Rearrangement with MYCN and MDM2 Amplification and RB1 Region Loss.
Rhabdomyosarcomas (RMS) are rare, heterogeneous, soft tissue sarcomas and a common type of childhood malignancy with a distinct histomorphology. At the molecular level, alveolar rhabdomyosarcoma (ARMS), a subtype of RMS, harbors a signature genetic makeup characterized by specific translocations. The type of translocation and associated genetic aberrations correlate with disease progression, hence we used multiple molecular modalities including high-resolution array comparative genomic hybridization to explore the oncogenic gene fusion and associated copy number variations in a case of metastatic ARMS. We describe a case where traditional cytogenetic and molecular methods yielded inconclusive results in detecting the FOXO1 gene rearrangement. However, microarray analysis identified the essential FOXO1-PAX7 aberration and additional submicroscopic genomic alterations, including amplification of MYCN and MDM2 and deletion of RB1.


Re-expression of disease-characteristic features of non-bullous congenital ichthyosiform erythroderma (CIE) after grafting of the pathological keratinocyte cultures to athymic mice.
Epidermal keratinocytes separated from skin lesions of non-bullous congenital ichthyosiform erythroderma were investigated in an attempt at experimental reproduction of this keratinization disorder. In vitro studies on growth and differentiation of pathological keratinocytes isolated from the influence of the host's dermal and humoral components were performed using the immersed epidermal cell culture technique. Ten to 25-day-old confluent and stratified cultures were examined by means of photonic and electron microscopy, and stained with various differentiation markers for indirect immunofluorescence studies. The cultured epidermis showed low-grade differentiation and no clear-cut evenly distributed signs of the original disease. Grafting on congenitally athymic nude mice allowed further differentiation of the epidermal sheets and re-expression of the histologic and ultrastructural features of non-bullous congenital ichthyosiform erythroderma. Thus, the purely epidermal origin of this particular form of autosomal recessive ichthyosis could be confirmed. Large amounts of pathological keratinocytes generated from small skin biopsies may be used for experimental purposes after grafting on several athymic animals.


The origin, migration and fine morphology of human primordial germ cells.
Human primordial germ cells (PGCs) were observed ultrastructurally in stages from their endodermal to gonadal locations. Primitive PGCs in the hind-gut epithelium of the 4-week embryo, were recognized as well demarcated cells from the neighboring cells. At the time fo separation, the basal lamina of the epithelium was broken, then, through the gap so opened, the PGCs started to escape into the outer mesenchyme. In embryos at five weeks, PGCs were in the migration stage, and were found in the dorsal mesentery, at the coelomic angle and in the forming germinal ridge. In embryos at six weeks or later, almost all PGCS were accumulated in the gonad. The PGC was characterized by its large size and the large and round nucleus with conspicuous nucleolus, and by the presence of abundant glycogen particles and a considerable number of lipid droplets in the cytoplasm. Alkaline phosphatase activity was demonstrated selectively on the plasma membrane of the PGC. The shape of PGC was irregular, often had pseudopodia in PGCs in the separation and migration stages, suggesting their amoeboid movement in vivo, but was generally round or elliptic in PGCs in the settlement stage. The PGC was usually surrounded by and in close association with adjacent somatic cells.


A new beta-1,2-N-acetylglucosaminyltransferase that may play a role in the biosynthesis of mammalian O-mannosyl glycans.
Recent studies have shown that O-mannosyl glycans are present in several mammalian glycoproteins. Although knowledge on the functional roles of these glycans is accumulating, their biosynthetic pathways are poorly understood. Here we report the identification and initial characterization of a novel enzyme capable of forming GlcNAc beta 1-2Man linkage, namely UDP-N-acetylglucosamine: O-linked mannose beta-1,2-N-acetylglucosaminyltransferase in the microsome fraction of newborn rat brains. The enzyme transfers GlcNAc to beta-linked mannose residues, and the formed linkage was confirmed to be beta 1-2 on the basis of diplococcal beta-N-acetylhexosaminidase susceptibility and by high-pH anion-exchange chromatography. Its activity is linearly dependent on time, protein concentration, and substrate concentration and is enhanced in the presence of manganese ion. Its activity is not due to UDP-N-acetylglucosamine: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GnT-I) or UDP-N-acetylglucosamine: alpha-6-D-mannoside beta-1,2-D-acetylglucosaminyltransferase II (GnT-II), which acts on the early steps of N-glycan biosynthesis, because GnT-I or GnT-II expressed in yeast cells did not show any GlcNAc transfer activity against a synthetic mannosyl peptide. Taken together, the results suggest that the GlcNAc transferase activity described here is relevant to the O-mannosyl glycan pathway in mammals.


Motor coordination. Watching the brain think.
Recording from populations of neurons in motor areas of the cerebral cortex has brought us a step closer to understanding how we control the movement of our own bodies.


Analyzing the effect of laparoscopy duration time on peroperative gastroesophageal reflux
Intraabdominal pressure (IAP) is one of the main reasons for gastroesophageal reflux (GER). This study investigates whether IAP during laparoscopic surgery leads to GER in a time-dependent manner. In a laparoscopy model, 15 mmHg IAP was created in 8 Wistar albino rats in the Trendelenburg position (TP). A 5 mm laparotomy was performed in the left lower abdominal region, and a 6 Fr catheter was placed intraabdominally. Air was insufflated into the abdominal cavity, and the pressure was kept constant at 15 mmHg. Esophageal pH alterations were measured by pH sticks for 4 h every 30 min. The basal median esophageal pH value was 9 (8–10), the value after placing the catheter was 9 (7–10) (P = 0.47), and the median pH value after placing the subjects in TP was 9 (8–10) (P = 0.70). In our experimental model, esophageal pH values were found to decrease significantly at the 150th minute in TP and at 15 mmHg IAP (P < 0.05). Two rats died: one at the 120th minute and the other at the 240th minute (P > 0.05) Esophageal pH values decreased and continued to remain low following IAP increase and TP in this experimental rat model. Prolonged laparoscopic procedures can particularly lead to GER that requires instant recognition and rapid and appropriate intervention.


Self-examination therapy as an adjunct treatment for depressive symptoms in substance abusing patients.
To determine the efficacy of Self-Examination Therapy as an adjunct treatment for depressive symptoms in substance abusing patients, 28 adult male volunteers from a substance abuse unit at a VA Medical Center were randomly assigned to either Self-Examination Therapy or a Current Events comparison group. Analyses indicated that participants in Self-Examination Therapy showed significantly greater improvement in depressive symptoms and overall psychopathology than participants in the Current Events comparison group. These results suggest that Self-Examination Therapy is a viable adjunct treatment for substance abusers, particularly those with depressive symptoms.


[Polyglandular type I autoimmune syndrome].
Two HLA-identical sisters have developed the full picture of type I polyglandular autoimmune syndrome over a period of 12 years. Both girls have hypoparathyroidism and Addison's disease. One of them additionally developed diabetes mellitus, hypergonadotropic hypogonadism and hypothyroidism. Autoantibodies to the adrenal, parathyroid and thyroid glands are present in both patients, as well as antinuclear antibodies. HLA associations have been described recently for the type I polyglandular autoimmune syndrome, but this could not be confirmed in the present two cases. Although we assume that the same genetic defect is present in both girls, additional factors to the genetic disposition are important for the clinical expression of the disease. The linkage of the disease-causing gene with the HLA region is not very close.


Spontaneous Regression of Pulmonary Nodules Presenting as Epstein-Barr Virus-related Atypical Infectious Mononucleosis.
Pulmonary nodules associated with Epstein-Barr virus (EBV)-related atypical infectious mononucleosis have rarely been described. A 12-year-old Japanese boy, upon admission, revealed multiple small round nodules (a total of 7 nodules in 4 to 8 mm size) in the lungs on computed tomography. The hemorrhagic pharyngeal tonsils with hot signals on 18F-fluorodeoxyglucose-positron emission tomography-computed tomography were biopsied revealing the presence of EBV-encoded small nuclear RNA (EBER)-positive cells; however, no lymphoma was noted. The patient was diagnosed as having atypical EBV-infectious mononucleosis associated with primary EBV infection. Pulmonary nodules markedly reduced in numbers and sizes spontaneously over a 2-year period. Differential diagnosis of pulmonary nodules in childhood should include atypical EBV infection.


Clinical outcome and paravalvular leakage of the new balloon-expandable Edwards Sapien 3 valve in comparison to its predecessor model (Edwards Sapien XT) in patients undergoing transfemoral aortic valve replacement.
The aim of this study was to compare the 30-day procedural, clinical and echocardiographic outcome of the new balloon-expandable Edwards Sapien 3 (ES3) valve with the Edwards Sapien XT (ESXT). Post-implant paravalvular leaks (PVL) after transfemoral aortic valve replacement (TAVR) resulting in residual aortic regurgitation (AR) are a major limitation for long term outcome. New TAVR-devices have to eliminate this problem. Transfemoral TAVR was performed in 209 consecutive intermediate-high-risk surgical patients (pts) with symptomatic aortic stenosis (ESXT n = 102, ES3 n = 107). Transthoracic echocardiography (TTE) and 3-dimensional computed tomography were used for valve size selection. Primary endpoint of the study was none/trace AR derived by TTE 30-days after TAVR. All pts underwent successfully TAVR with a combined device success of 100/102 (99%) in ESXT and 107/107 (100%) in ES3 pts. Fluoroscopy time (ESXT 11.8 ± 0.5 min vs. ES3 10.0 ± 0.5 min, P = 0.003) and contrast (ESXT 188.9 ± 5.6 mL vs. ES3 170.4 ± 4.7 mL, P = 0.04) were significantly lower in ES3 patients. 30-day clinical events did not differ. Transvalvular mean pressure gradients were significantly reduced to 7.4 ± 0.8 mmHg after ESXT and to 10.1± 0.4 mmHg after ES3 implantation. After 30 days none/trace AR was found in 34.3% (n = 35) of all ESXT pts in contrast to 89.7% (n = 96) of all ES3 patients. Moderate-to-severe AR was found rarely (ESXT 2.9% vs. ES3 0%, P = 0.073). Although there was no significant difference in 30 day mortality, the newer ES3 valve reduced significantly residual paravalvular leakage. © 2016 Wiley Periodicals, Inc.


Development in and challenge for traditional Chinese medicine in Australia.
Demand for and use of Traditional Chinese Medicine (TCM) has been growing steadily in Australia. This article outlines the growth of TCM in usage, research capacity, and availability of tertiary training. However, there are continuing challenges, institutional recognition of TCM is lagging behind consumer demand, and there is little TCM practiced in the Australian public health system. This article suggests some possible reasons. The tools of evidence-based medicine (EBM) have the potential to provide a bridge between, and a common language for, TCM and Western biomedicine (WB) researchers and practitioners. While there is no sign of a slowing in consumer demand for TCM services, EBM has the potential to increase the legitimacy and institutional recognition of TCM, thereby encouraging the integration of TCM into the Australian health care system.