Disturbance maintains alternative biome states.
Understanding the mechanisms controlling the distribution of biomes remains a challenge. Although tropical biome distribution has traditionally been explained by climate and soil, contrasting vegetation types often occur as mosaics with sharp boundaries under very similar environmental conditions. While evidence suggests that these biomes are alternative states, empirical broad-scale support to this hypothesis is still lacking. Using community-level field data and a novel resource-niche overlap approach, we show that, for a wide range of environmental conditions, fire feedbacks maintain savannas and forests as alternative biome states in both the Neotropics and the Afrotropics. In addition, wooded grasslands and savannas occurred as alternative grassy states in the Afrotropics, depending on the relative importance of fire and herbivory feedbacks. These results are consistent with landscape scale evidence and suggest that disturbance is a general factor driving and maintaining alternative biome states and vegetation mosaics in the tropics.


Enhancement of CD4+ T Cell Function as a Strategy for Improving Antibiotic Therapy Efficacy in Tuberculosis: Does It Work?
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) remains a major public health problem worldwide due in part to the lack of an effective vaccine and to the lengthy course of antibiotic treatment required for successful cure. Combined immuno/chemotherapeutic intervention represents a major strategy for developing more effective therapies against this important pathogen. Because of the major role of CD4+ T cells in containing Mtb infection, augmentation of bacterial specific CD4+ T cell responses has been considered as an approach in achieving this aim. Here we present new data from our own research aimed at determining whether boosting CD4+ T cell responses can promote antibiotic clearance. In these studies, we first characterized the impact of antibiotic treatment of infected mice on Th1 responses to major Mtb antigens and then performed experiments aimed at sustaining CD4+ T cell responsiveness during antibiotic treatment. These included IL-12 infusion, immunization with ESAT-6 and Ag85B immunodominant peptides and adoptive transfer of Th1-polarized CD4+ T cells specific for ESAT-6 or Ag85B during the initial month of chemotherapy. These approaches failed to enhance antibiotic clearance of Mtb, indicating that boosting Th1 responses to immunogenic Mtb antigens highly expressed by actively dividing bacteria is not an effective strategy to be used in the initial phase of antibiotic treatment, perhaps because replicating organisms are the first to be eliminated by the drugs. These results are discussed in the context of previously published findings addressing this concept along with possible alternate approaches for harnessing Th1 immunity as an adjunct to chemotherapy.


Core-shell LiFePO4 /carbon-coated reduced graphene oxide hybrids for high-power lithium-ion battery cathodes.
Core-shell carbon-coated LiFePO4 nanoparticles were hybridized with reduced graphene (rGO) for high-power lithium-ion battery cathodes. Spontaneous aggregation of hydrophobic graphene in aqueous solutions during the formation of composite materials was precluded by employing hydrophilic graphene oxide (GO) as starting templates. The fabrication of true nanoscale carbon-coated LiFePO4 -rGO (LFP/C-rGO) hybrids were ascribed to three factors: 1) In-situ polymerization of polypyrrole for constrained nanoparticle synthesis of LiFePO4 , 2) enhanced dispersion of conducting 2D networks endowed by colloidal stability of GO, and 3) intimate contact between active materials and rGO. The importance of conducting template dispersion was demonstrated by contrasting LFP/C-rGO hybrids with LFP/C-rGO composites in which agglomerated rGO solution was used as the starting templates. The fabricated hybrid cathodes showed superior rate capability and cyclability with rates from 0.1 to 60 C. This study demonstrated the synergistic combination of nanosizing with efficient conducting templates to afford facile Li(+) ion and electron transport for high power applications.


[Inhibition of thrombocyte aggregation by F(ab')2-fragments of monoclonal antibodies FraMon (CRC64) to glycoproteins IIb-IIIa].
To study the effects of F(ab')2 fragments of the monoclonal antibody (monAB) FRaMon against glycoproteins (GP) IIb-IIIa on platelet aggregating activity in vitro and after injection to healthy volunteers. In vitro experiments were performed to study effects of F(ab')2 and Fab fragments of FRaMon on platelet aggregation (PA) and 14C-serotonin secretion and characteristics of 125I-labelled F(ab')2 and Fab FRaMon binding to platelets. In vivo effects of F(ab')2 FRaMon (preparation FRAMON) were studied upon its bolus i.v. injection to 10 healthy volunteers at the doses of 0.025-0.2 mg/kg. PA was registered before and 1, 6, 12, 24 hours and 3 and 12-15 days after FRAMON injection. FRAMON binding to platelets in the vascular bed was evaluated by inhibition of 125I-FRAMON in vitro binding to platelets obtained from volunteers. Development of antibodies against FRAMON was evaluated by ELISA two weeks after FRAMON injection. In vitro F(ab')2 FRaMon completely blocked PA induced by ADP and thrombin at the concentrations < 4 and < 7.5 mcg/ml, respectively, and revealed higher inhibitory capacity than Fab FRaMon. F(ab')2 FRamon also inhibited 14C-serotonin secretion from ADP-activated platelets. F(ab')2 FRamon interacted with two GP IIb-IIIa molecules on one platelet and bound to platelets more tightly than Fab FRaMon. F(ab')2 FRaMon (preparation FRAMON) bolus i.v. injection to healthy volunteers at the doses of 0.025-0.2 mg/kg did not induce any signs of individual intolerance, including allergic reactions, bleeding and thrombocytopenia. FRAMON at 0.2 mg/kg almost completely inhibited ADP-induced PA of volunteer's platelets 1 h after injection and by more than 70% at 12 h and by more than 50% at 24 h after injection. PA ability recovered to normal 3 days after injection. Antibodies against FRAMON were detected in 1 out of 10 volunteers. F(ab')2 fragments of monAB FRaMon effectively inhibited aggregating ability both in vitro and after injection to healthy volunteers and could be suggested as a basis for development of a new GP IIb-IIIa antagonist.


Prostate cancer: epidemiology and screening.
The challenge continues-to find better methods of screening for prostate cancer, of determining who should undergo needle biopsy, and of predicting who will fail initial therapy. Investigators are looking at the value of neural networks and an array of markers to provide improved screening and prognostic information.


Expression of CR1 and CR2 complement receptors following Epstein-Barr virus infection of Burkitt's lymphoma cell lines.
Epstein-Barr virus (EBV) infection of human B lymphocytes involves a specific receptor closely associated with, or identical to, the C3d complement receptor, CR2. Thus, 25 out of 29 EBV-positive Burkitt's lymphoma (BL) cell lines but none of 15 EBV-negative BL lines were found to express C3 receptors. Furthermore, in vitro infection with EBV of six EBV-negative cell lines resulted in the expression of C3 receptors in association with that of EBV-determined nuclear antigen (EBNA). Rosette assays using erythrocytes coated with human C3b, C3bi, and C3d, inhibition of rosette formation with anti-receptor antibodies, and flow cytometry analysis of stained cells demonstrated that EBV-converted lines expressed C3b and C3d receptors, CR1 and CR2. Anti-receptor antibodies recognized an average of 40,700 anti-CR1 and 140,000 anti-CR2 binding sites on an EBV-converted line (BL41/B95), whereas no specific binding occurred on the corresponding EBV-negative (BL41) cells. Because CR1 and CR2 are involved in B-cell proliferation and/or differentiation, enhanced expression of C3 receptors following the interaction between EBV and B cells and/or subsequent infection of the cells by EBV may provide a basis for positive control of B lymphocyte proliferation by EBV.


Expression of p53 in colorectal carcinoma: correlation with clinicopathologic features.
The p53 gene mutation is closely related to carcinogenesis in most malignant diseases. The main function of wild p53 protein is to maintain the integrity of genes by detecting mutations and preventing the division of cells with damaged DNA. The mutated form of p53 protein is overexpressed due to an extended half-life and can be easily detected by immunohistochemistry. To estimate the frequency of p53 protein overexpression in colorectal carcinoma and its correlation with some clinicopathologic variables. One hundred paraffin-preserved colorectal carcinoma samples were collected randomly from patients undergoing tumor resection from April 1995 through April 2001 in Omid Hospital, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. The overexpression of p53 protein was studied using a monoclonal antibody (clone DO-7; Dako). The number of cells stained were classified semiquantitatively as (-): <5% positive cells, (+): 5 - 25% positive cells, (++): 25 - 75% positive cells, and (+++): >75% positive cells. Clinicopathologic data including gender, age, tumor location, histologic type, and stage (Astler-Coller) were collected from the files maintained at the Department of Pathology. The correlation between p53 protein overexpression and each variable was evaluated using Chi-square analysis. p53 staining was positive in 59 of 100 specimens. Out of these 100 specimens, 16 were weekly (+), 16 moderately (++), and 27 intensely (+++) positive for p53 protein over-expression. There was no significant correlation between p53 staining and gender (P = 0.34), age (< 40 vs. > or = 40 yr; P = 0.74), site of tumor (right vs. left colon and rectum; P = 0.26), pathologic type (mucinous vs. nonmucinous; P = 0.63), and stage of the disease (P = 0.12). Considering the p53 protein overexpression in a relatively high percentage of patients, it seems that p53 mutation plays an important role in development of colorectal carcinoma. There was no significant association between p53 protein expression and some common clinicopathologic variables such as age, gender, site of tumor, pathologic type, and stage of the disease.


Flavonoid silybin improves the response to radiotherapy in invasive bladder cancer.
Conservative treatment for invasive bladder cancer (BC) involves a complete transurethral tumor resection combined with chemotherapy (CT) and radiotherapy (RT). The major obstacles of chemo-radiotherapy are the addition of the toxicities of RT and CT, and the recurrence due to RT and CT resistances. The flavonoid Silybin (Sb) inhibits pathways involved in cell survival and resistance mechanisms, therefore the purpose of this paper was to study in vitro and in vivo, the ability of Sb to improve the response to RT, in two murine BC cell lines, with different levels of invasiveness, placing emphasis on radio-sensitivity, and pathways involved in radio-resistance and survival. In vitro, Sb radio-sensitized murine invasive cells through the inhibition of RT-induced NF-κB and PI3K pathways, and the increase of oxidative stress, while non-invasive cells did not show to be sensitized. In vivo, Sb improved RT-response and overall survival in invasive murine tumors. As Sb is already being tested in clinical trials for other urological cancers and it improves RT-response in invasive BC, these results could have translational relevance, supporting further research.


Patients' perspectives on how idiopathic pulmonary fibrosis affects the quality of their lives.
Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease with a survival of only three to five years from the time of diagnosis. Due to a paucity of studies, large gaps remain in our understanding of how IPF affects the quality of patients' lives. In only one other study did investigators ask patients directly for their perspectives on this topic. Further, currently there is no disease-specific instrument to measure health-related quality of life (HRQL) in patients with IPF. A carefully constructed measurement instrument, sensitive to underlying change, is needed for use in clinical trials and longitudinal studies of patients with IPF. Before developing such an instrument, researchers must improve their understanding of the relevant effects of IPF on patients' lives. On a broader scale, to provide the best care for people with IPF, clinicians must appreciate--from patients' perspectives--how this disease affects various aspects of their lives. We used focus groups and individual in-depth interviews with 20 IPF patients to collect their perspectives on how IPF affects their lives (with a focus on the quality of their lives). We then analyzed these perspectives and organized them into a conceptual framework for describing HRQL in patients with IPF. Next, we examined how well certain existing measurement instruments--which have been administered to IPF patients in prior studies--covered the domains and topics our patients identified. In our framework, we identified 12 primary domains: symptoms, IPF therapy, sleep, exhaustion, forethought, employment and finances, dependence, family, sexual relations, social participation, mental and spiritual well-being, mortality. Each domain is composed of several topics, which describe how IPF affects patients' lives. When we compared the content of our conceptual framework with the existing instruments, we found the coverage of the existing instruments to be inadequate for several reasons, including they may tap general areas of QOL or HRQL but not some areas that appear to be most directly affected by IPF, and they include items that are relevant to symptoms and effects of other respiratory diseases but not IPF. Collecting patients' perspectives and developing an organized inventory of the relevant effects of IPF on patients' lives provides valuable information for improving our understanding of the impact of this disease on patients and their loved ones. We believe our findings will help alert clinicians and researchers to IPF patients' experiences and concerns. Based on the comparison or our conceptual framework with the content of four existing instruments, it would appear that developing an IPF-specific measurement instrument is justified. Our conceptual framework for describing health-related quality of life in patients with IPF lays a solid foundation for constructing such an instrument.


Pharmacokinetic and pharmacodynamic comparative study of zofenopril and enalapril in healthy volunteers.
Zofenopril calcium (CAS 81938-43-4) is a new angiotensin converting enzyme (ACE) inhibitor, which in addition to the typical activity of the class, proved to possess a specific cardioprotective effect due also to the presence of the sulfhydryl group. In this trial zofenopril calcium and enalapril maleate (CAS 76095-16-4) were given to 20 healthy volunteers of both sexes in repeated dose regiment at two dose levels: 30 mg and 60 mg zofenopril calcium and 10 mg and 20 mg enalapril maleate. The study was conducted according to a two-period, two-sequence, crossover design, with washout. ACE activity in serum and zofenopril, zofenoprilat, enalapril and enalaprilat plasma concentrations were determined during and on the last day of the two study periods. Both zofenopril and enalapril were extensively converted through hydrolysis to their active metabolites zofenoprilat and enalaprilat, respectively. Zofenopril exhibited a complete and a more rapid hydrolysis rate compared to enalapril, which is reflected by the higher metabolite to parent drug ratio of Cmax and AUCss, tau showed by this compound. Even though only two dose levels were investigated in this trial, the pharmacokinetics of both drugs seem to be linear. In line with previous trials, both compounds at both dose levels investigated produced complete or almost complete inhibition of ACE activity in serum, for a period lasting 6-8 h after administration, the inhibition being still relevant 24 h thereafter. The tolerability of the two drugs at both dose levels proved to be very good as demonstrated by subjective and objective symptoms, by the absence of relevant adverse events, and by laboratory biochemical parameters and vital signs evaluated before and after the trial. Blood pressure showed a fairly decreasing trend with both the drugs, systolic and diastolic blood pressure values being however within normal range in all the subjects. In no case symptoms of hypotension were experienced. In conclusion, zofenopril calcium and enalapril maleate show very good tolerability and appear to exert similar activity on serum ACE. The main difference in the pharmacokinetics of the two compounds is the conversion from pro-drug to the active metabolite which is faster with zofenopril.


Statins and autoimmunity: State-of-the-art.
HMG-CoA reductase inhibitors, or statins, are potent plasma LDL-cholesterol (LDL-c) lowering agents. Since the introduction of the first statin, lovastatin, in 1987, accumulating evidence showed that non-cholesterol lowering effects play an important role in their efficacy to reduce atherosclerotic cardiovascular disease (ASCVD). Thus, these non-LDL-c lowering properties could benefit patients with immune-mediated diseases. Statins and their associated immune-modulating roles have recently received much attention. Different statins have been administered in various experimental and clinical studies focused on autoimmunity. The results indicate that statins can modulate immune responses through mevalonate pathway-dependent and -independent mechanisms. The anti-inflammatory and immune-modulating effects include cell adhesion, migration of antigen presenting cells, and differentiation, as well as activation, of T-cells. In various autoimmune diseases (e.g. rheumatoid arthritis, lupus, and multiple sclerosis), promising results have been obtained to date.


Ethnic disparities in educational and occupational gradients of estimated cardiovascular disease risk: The Healthy Life in an Urban Setting study.
European societies are becoming increasingly ethnically diverse. This may have important implications for socio-economic inequalities in health due to the often disadvantaged position of ethnic minority groups in both socio-economic status (SES) and disease, especially cardiovascular disease (CVD). The aim of this study was to determine whether the socio-economic gradient of estimated CVD risk differs between ethnic groups. Using the Healthy Life in an Urban Setting study, we obtained data on SES and CVD risk factors among participants from six ethnic backgrounds residing in Amsterdam. SES was measured using educational level and occupational level. CVD risk was estimated based on the occurrence of CVD risk factors using the Dutch version of the systematic coronary risk evaluation algorithm. Ethnic disparities in socio-economic gradients for estimated CVD risk were determined using the relative index of inequality (RII). Among Dutch-origin men, the RII for estimated CVD risk according to educational level was 6.15% (95% confidence interval [CI] 4.35-7.96%), indicating that those at the bottom of the educational hierarchy had a 6.15% higher estimated CVD risk relative than those at the top. Among Dutch-origin women, the RII was 4.49% (CI 2.45-6.52%). The RII was lower among ethnic minority groups, ranging from 0.83% to 3.13% among men and -0.29% to 5.12% among women, indicating weaker associations among these groups. Results were similar based on occupational level. Ethnic background needs to be considered in associations between SES and disease. The predictive value of SES varies between ethnic groups and may be quite poor for some groups.


Biallelic losses of 13q do not confer a poorer outcome in chronic lymphocytic leukaemia: analysis of 627 patients with isolated 13q deletion.
Losses in 13q as a sole abnormality confer a good prognosis in chronic lymphocytic leukaemia (CLL). Nevertheless, its heterogeneity has been demonstrated and the clinical significance of biallelic 13q deletions remains controversial. We compared the clinico-biological characteristics of a series of 627 patients harbouring isolated 13q deletions by fluorescence in situ hybridization (FISH), either monoallelic (13q × 1), biallelic (13q × 2), or the coexistence of both clones (13qM). The most frequent 13q deletion was 13q × 1 (82·1%), while 13q × 2 and 13qM represented 8·6% and 9·3% of patients respectively. The median percentage of altered nuclei significantly differed across groups: 55%, 72·5% and 80% in 13q × 1, 13q × 2 and 13qM (P < 0·001). However, no significant differences in the clinical outcome among 13q groups were found. From 84 patients with sequential FISH studies, eight patients lost the remaining allele of 13q whereas none of them changed from 13q × 2 to the 13q × 1 group. The percentage of abnormal cells detected by FISH had a significant impact on the five-year cumulative incidence of treatment and the overall survival, 90% being the highest predictive power cut-off. In conclusion, loss of the remaining 13q allele is not enough to entail a worse prognosis in CLL. The presence of isolated 13q deletion can be risk-stratified according to the percentage of altered cells.


Post-treatment imaging of liver tumours.
In the past few years, great improvements have been made to achieve local tumour control of primary liver malignancies and liver metastases. For hepatocellular carcinoma (HCC), transarterial chemoembolisation (TACE) and tumour ablation techniques, including percutaneous ethanol injection (PEI), radiofrequency ablation (RF), and laser-induced interstitial thermotherapy (LITT) have been developed. For colorectal liver metastases, surgery is still the standard technique in localised disease, although percutaneous RF ablation has gained considerable acceptance. In patients with widespread disease, chemotherapy with new drugs offers improved survival. Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) are the modalities of choice to evaluate treatment response. The present review demonstrates imaging findings of complete and incomplete tumour control after intervention as well as the imaging spectrum of complications. Imaging guidelines according to the World Health Organization and Response Evaluation Criteria In Solid Tumors (RECIST) for assessment of chemotherapy response are presented.


Specialized Metabolites of the Lichen Vulpicida pinastri Act as Photoprotective Agents.
The extreme resiliency of lichens to UV radiations makes them an interesting model to find new photoprotective agents acting as UV-blockers and antioxidant. In this research, using a new in vitro method designed to overcome the shortage of material associated to many studies dealing with natural products, we show that the three major compounds isolated from the lichen Vulpicida pinastri, vulpinic acid, pinastric acid and usnic acid, were UV blocker agents. Antioxidant assays evidenced superoxide anion scavenging activity. Combination of the most promising compounds against UVB and UVB radiations, usnic acid, vulpinic acid and pinastric acid, increased the photoprotective activity. At the same time, they were found not cytotoxic on keratinocyte cell lines and photostable in the UVA and UVB ranges. Thus, lichens represent an attractive source to find good candidate ingredients as photoprotective agents. Additionally, the uncommon scalemic usnic acid mixture in this Vulpicida species was proven through electronic circular dichroism calculation.


Three-dimensional plasmonic photoanodes based on Au-embedded TiO(2) structures for enhanced visible-light water splitting.
Plasmon-assisted visible light photocatalysis presents a possible solution for direct solar-to-fuel production. Here we investigate the plasmon-enhanced photocatalytic water splitting using different TiO2/Au electrode structures. Experimental data demonstrates that the Au embedded in TiO2 (Au-in-TiO2) electrode greatly outperforms the Au sitting on TiO2 (Au-on-TiO2) electrode. Numerical simulation shows that the local electric field is very intense in the semiconductor near Au nanoparticles, which causes the enhancement of electron-hole pair generation. A 3D Au-embedded TiO2 structure is thus proposed to further improve the light absorption and photocatalytic performance.


Antioxidant vitamin levels in plasma and low density lipoprotein of obese girls.
To investigate the antioxidant status of obese children, we analyzed beta-carotene and alpha-tocopherol levels in plasma and low density lipoprotein (LDL). We also analyzed the fatty acid composition of LDL as a substrate for oxidative stress. The plasma beta-carotene and alpha-tocopherol levels were relatively lower in obese girls than in normal controls. However, the plasma alpha-tocopherol/lipids ratio was significantly lower in obese girls than in normal controls. Both LDL beta-carotene and LDL alpha-tocopherol levels were significantly lower in obese girls than in normal controls, although no obvious differences were observed in plasma levels. In obese girls LDL contained more polyunsaturated fatty acid (PUFA) compared with normal controls. When the peroxidizability index (PI) was calculated to estimate the susceptibility of lipids to oxidative stress, obese girls had significantly higher PI values than normal controls. Both the LDL beta-carotene/PI ratio and the LDL alpha-tocopherol/PI ratio were significantly lower in obese girls than in normal controls. These results indicate the increased susceptibility of LDL to oxidative stress in obese girls which may promote atherosclerosis later in life.


Clinical use of an improved processed bovine cartilage for contour defects.
We have combined irradiation with a new chemical processing to cross-link the collagen of bovine cartilage, thereby stabilizing the collagen molecule and rendering it antigenically inert and dimensionally stable. Irradiated allograft cartilage has been successfully used for repair of facial contour defects since the 1950s, but the usefulness of this material has been limited by lack of availability. Chemically processed bovine cartilage had previously been used, but the implants were subject to slow degradation and were usually absorbed completely within 2 years. After first testing this new material on rabbits and primates, we experimentally placed 40 implants in 28 patients over the course of 3 years. Thirty-six of these implants have survived without change in size or shape for more than 1 year, 20 of these for more than 2 years. In 2 cases, full or partial absorption of the implants occurred secondary to operative infection. In another case 2 implants were lost, probably because of infection. In the absence of infection, neither primary nor second-set provocative implant tests of processed irradiated bovine cartilage elicit any foreign body reaction, either cellular or noncellular. The material performs well aesthetically and appears to undergo no absorption during the 1- to 4-year follow-up observed to date. The period of follow-up of 1 to 4 years reported here may be insufficient to reach a definitive conclusion that no very slow absorption of processed irradiated bovine cartilage implants occurs. It is noteworthy, however, that half of the implants have already survived with no apparent absorption for a period longer than that at which nonirradiated bovine cartilage implants would be expected to have been absorbed completely. This result suggests that any absorption that may occur, other than that associated with infection, takes place at a rate so slow as to be unobservable in anything but the very long run. We believe that this evidence of the long-term survivability of processed irradiated bovine cartilage, together with its excellent performance aesthetically and the fact that it can be made readily available commercially, indicates that it may represent an effective implant material for repair of contour defects.


Detection of Pol IV/RDR2-dependent transcripts at the genomic scale in Arabidopsis reveals features and regulation of siRNA biogenesis.
Twenty-four-nucleotide small interfering (si)RNAs are central players in RNA-directed DNA methylation (RdDM), a process that establishes and maintains DNA methylation at transposable elements to ensure genome stability in plants. The plant-specific RNA polymerase IV (Pol IV) is required for siRNA biogenesis and is believed to transcribe RdDM loci to produce primary transcripts that are converted to double-stranded RNAs (dsRNAs) by RDR2 to serve as siRNA precursors. Yet, no such siRNA precursor transcripts have ever been reported. Here, through genome-wide profiling of RNAs in genotypes that compromise the processing of siRNA precursors, we were able to identify Pol IV/RDR2-dependent transcripts from tens of thousands of loci. We show that Pol IV/RDR2-dependent transcripts correspond to both DNA strands, whereas the RNA polymerase II (Pol II)-dependent transcripts produced upon derepression of the loci are derived primarily from one strand. We also show that Pol IV/RDR2-dependent transcripts have a 5' monophosphate, lack a poly(A) tail at the 3' end, and contain no introns; these features distinguish them from Pol II-dependent transcripts. Like Pol II-transcribed genic regions, Pol IV-transcribed regions are flanked by A/T-rich sequences depleted in nucleosomes, which highlights similarities in Pol II- and Pol IV-mediated transcription. Computational analysis of siRNA abundance from various mutants reveals differences in the regulation of siRNA biogenesis at two types of loci that undergo CHH methylation via two different DNA methyltransferases. These findings begin to reveal features of Pol IV/RDR2-mediated transcription at the heart of genome stability in plants.


Associations between the repressive adaptive style and self-reported hope in Mexican American and Euro-American children.
A large literature has examined the associations between Weinberger, Schwartz, and Davidson's (1979) repressive adaptive style (RAS) construct and various self-report measures of distress or unpleasant emotional states in adults and children. Fewer investigations have examined the role of RAS in self-reported positive psychology constructs. In this investigation, we used Weinberger et al.'s (1979) categorical typology to examine the associations between adaptive style and hope in Euro-American (n = 60) and Mexican American (n = 49) children (M age = 11.4 years) who were students at 1 of 3 parochial schools in a large Midwestern city. Partially supporting the hypotheses, a univariate 2 (ethnic group) x 2 (repressor group) analysis of variance indicated a significant main effect for adaptive style group but no significant main effect for ethnic group and no significant interaction effect. Results extend the literature on the associations between adaptive style and self-report instruments and indicate that (similar to self-reported measures of distress) self-reported hope may be subject to social desirability bias.


Radiological changes in infantile dissecting anterior communicating artery aneurysm treated endovascularly. A case report and five-year follow-up.
Intracranial aneurysms are extremely rare in infants, and to our knowledge only seven infants treated for ruptured spontaneous dissecting aneurysms have been reported. Good outcomes have been achieved with endovascular treatment of infantile aneurysm. We the endovascular treatment of a one-month-old girl for ruptured dissecting aneurysm located in the anterior communicating artery, and the unique radiological changes that were observed during the perioperative and follow-up periods. These changes suggest that blood coagulation and fibrinolytic response play a part in the repair and healing processes of dissecting aneurysms. Careful neuroradiological surveys are needed for pediatric dissecting aneurysms treated endovascularly.


Stress, Emotions, and Motivational States Among Traditional Dancers in New Zealand and Japan.
This study used a reversal theory framework to examine motivational dominance and changes in motivational state, arousal, stress, and emotions among members of traditional Japanese (Nihon Odori Sports Science (NOSS)) and New Zealand (Kapa Haka) dance groups. Eighty-four participants (50 in Japan and 34 in New Zealand) completed questionnaires on each variable before and after a dance class. The findings indicated that the Kapa Haka dancers were significantly more playful and arousal-seeking than the NOSS dancers. They also reported higher overall arousal, preferred arousal, and effort during performance while the NOSS dancers became more serious afterward. Data on emotions matched those of arousal in that the Kapa Haka dancers felt significantly more excited and provocative after the session. The NOSS dancers were more relaxed and placid, both overall and after dancing. These patterns were consistent with the dancers' respective motivational states and motivational dominance, and suggest that both dances can be effective in reducing negative affect. They also suggest that psychological effects are dependent upon performers' personal and cultural affiliation with the two dance forms.


An inverse association between plasma benzoxazinoid metabolites and PSA after rye intake in men with prostate cancer revealed with a new method.
Prostate cancer (PC) is a common cancer among men, and preventive strategies are warranted. Benzoxazinoids (BXs) in rye have shown potential against PC in vitro but human studies are lacking. The aim was to establish a quantitative method for analysis of BXs and investigate their plasma levels after a whole grain/bran rye vs refined wheat intervention, as well as exploring their association with PSA, in men with PC. A quantitative method for analysis of 22 BXs, including novel metabolites identified by mass spectrometry and NMR, was established, and applied to plasma samples from a randomized crossover study where patients with indolent PC (n = 17) consumed 485 g whole grain rye/rye bran or fiber supplemented refined wheat daily for 6 wk. Most BXs were significantly higher in plasma after rye (0.3-19.4 nmol/L in plasma) vs. refined wheat (0.05-2.9 nmol/L) intake. HBOA-glc, 2-HHPAA, HBOA-glcA, 2-HPAA-glcA were inversely correlated to PSA in plasma (p < 0.04). To conclude, BXs in plasma, including metabolites not previously analyzed, were quantified. BX metabolites were significantly higher after rye vs refined wheat consumption. Four BX-related metabolites were inversely associated with PSA, which merits further investigation.


Thyroid homeostasis in mother-child pairs in relation to maternal iodine status: the MISA study.
Iodine deficiency during pregnancy may influence maternal and foetal thyroid function with the risk of causing neurocognitive and psychomotor deficits in the offspring. The objective of this study was to assess iodine status in pregnant women from Northern Norway and to investigate the influence of iodine status on maternal and infant thyroid function. Women from the Northern Norway Mother-and-Child contaminant Cohort Study (MISA) donated a blood and urine sample at three visits during their pregnancy and postpartum period (in second trimester, 3 days and 6 weeks after delivery. N=197). Women were assigned to iodine status groups according to urine iodine concentrations (UICs) in second trimester and mixed effects linear models were used to investigate potential associations between iodine status and repeated measurements of thyroid-stimulating hormone (TSH), thyroid hormones (THs), TH-binding proteins and thyroid peroxidase antibodies. Associations between maternal iodine status and TSH in heel prick samples from the infants were investigated with linear regression. Median UIC in second trimester was 84 μg/l (range 18-522) and 80% had UIC below recommended level (<150 μg/l). Iodine-deficient women had higher concentrations of T3, FT3 and FT4 (estimated differences (confidence intervals) of 0.10 nmol/l (0.01, 0.17), 0.16 pmol/l (0.05, 0.26) and 0.45 pmol/l (0.10, 0.78), respectively) compared with iodine-sufficient women. The concentrations varied within normal reference ranges, but the majority of women with subclinical hypothyroidism were iodine deficient. Maternal iodine status did not influence infant TSH concentrations. This study indicate iodine deficiency among pregnant women in Norway. Iodine status during pregnancy influences maternal thyroid homeostasis and is therefore a risk factor for foetal and infant development.


Point mutations in the 23 S rRNA genes of four lincomycin resistant Nicotiana plumbaginifolia mutants could provide new selectable markers for chloroplast transformation.
Experiments designed to establish stable chloroplast transformation require selectable marker genes encoded by the chloroplast genome. The antibiotic lincomycin is a specific inhibitor of chloroplast ribosomal activity and is known to bind to the large ribosomal subunit. We have investigated a defined region of the chloroplast 23 S rRNA genes from four lincomycin resistant Nicotiana plumbaginifolia mutants and from wild-type N. plumbaginifolia. The mutants LR415, LR421 and LR446 have A to G transitions at positions equivalent to the nucleotides 2058 and 2059 in the Escherichia coli 23 S rRNA. The mutant, LR400, possesses a G to A transition at a position corresponding to nucleotide 2032 of the E. coli 23 S rRNA.


Entertaining and instructing the public: John Zahorsky's 1904 incubator institute.
In 1904 American physician John Zahorsky managed an incubator institute at the Louisiana Purchase Expositiioon in St. Louis, Missouri. For Zahorsky the incubator became a focal point for organizing medical care, for evaluating existing practices and for developing new ones. His efforts resulted in markedly improved survival rates for premature infants. Despite his success, however, his findings never became part of the medical literature on prematurity. Zahorsky himself believed that physicians dismissed his work because of his association with showmen. This paper also suggests that his were not practical findings. The incubator was too heavy to be used for home births among middle class families and the equipment and nursing care were too expensive to be used with hospitalized infants from tenements. Zahorsky recognized that the incubator somehow diminished the humanity of premature infants, for parents sometimes did not reclaim infants lent to the exhibit. The infant on exhibit became a commodity at a time when babies were offered for sale by advertisement. The incubator institute illustrated the prevailing sensibility about infants, one context in which medical research took place, and the relationships among commerce, entertainment, medical practices, and medical science in the United States early in the twentieth century.


Preparation, Characterization and Application of Multi-Mode Imaging Functional Graphene Au-Fe3O4 Magnetic Nanocomposites.
Nanomaterials extensively studied by nanotechnology scientists have been extensively applied in biomedicine, chemistry, physics and other fields nowadays. Magnetic nanoparticles, surpassing nano applications, are found to possess many advantages over nonmagnetic nanomaterials. Graphene oxide (GO), in particular, draws growing scholarly attention due to its large surface area, good water solubility and biocompatibility, rich surface functional group and easy-to-modify property. In this paper, we modify the Polyethylene mide (PEI) molecule on the surface of GO to increase its biocompatibility. The Au-Fe3O4 nanoparticles and folic acid molecules on the ligand make the resulting composite applicable both in magnetic resonance imaging and in cancer cell targeting. In addition, the π-π accumulation of doxorubicin used to load the anticancer drug can release the drug under the acid condition of the cancer cells, detect the cancer cells by fluorescence and realize the multi-mode detection of cancer cells.


Intravenous immunoglobulin for recurrent unexplained pregnancy loss: a case report.
Recurrent unexplained pregnancy loss plagues obstetricians. Many therapies are controversial, including intravenous immunoglobulin (IVIG). There have been limited studies to support or oppose its use. A 33-year-old woman, gravida 12, para 0, 2, 10, 1, with normal laboratory values and normal parental karyotypes, unsuccessfully tried many different accepted therapies for recurrent pregnancy loss. She tried IVIG with the last pregnancy and achieved delivery of a viable, male infant at 32 weeks' gestation. For many cases of unexplained recurrent pregnancy loss, IVIG may not be the answer. However, this case may demonstrate a limited role for IVIG in the treatment of recurrent pregnancy loss with repeated maternal floor infarction of the placenta. Deciding whether or not to use IVIG should not be the question; the real question may be when to use it.


IL-12p40 is essential for the down-regulation of airway hyperresponsiveness in a mouse model of bronchial asthma with prolonged antigen exposure.
We previously reported a mouse model of bronchial asthma showing eosinophilic inflammation, but not airway hyperresponsiveness (AHR), after prolonged antigen exposure. This model showed an increase of IL-12 in the lung. The aim of this study was to investigate the role of IL-12p40 in a murine asthma model with prolonged antigen exposures. An ovalbumin (OVA)-induced asthma model was first established in wild-type (WT) and IL-12p40-deficient (IL-12p40(-/-)) mice. Both strains of mice were further exposed to either OVA (prolonged exposure group) or phosphate-buffered saline (positive control group) 3 days per week for 3 weeks. During week 4, both groups of mice were given a final challenge with OVA. Prolonged antigen exposures resulted in marked suppression of airway eosinophilia in both WT and IL-12p40(-/-) mice. However, AHR persisted in IL-12p40(-/-) but not in WT mice. There were no significant differences of IL-5, IL-13 or IFN-gamma levels in bronchoalveolar lavage fluid between WT and IL-12p40(-/-) mice. The hydroxyproline content of the lung and peribronchial fibrosis were, however, significantly increased in IL-12p40(-/-) mice. The results suggest that endogenous IL-12p40 is essential for inhibition of AHR and peribronchial fibrosis, but not eosinophilic inflammation, in a murine asthma model with prolonged antigen exposures.


Fungal-mediated multitrophic interactions--do grass endophytes in diet protect voles from predators?
Plant-associated micro-organisms such as mycotoxin-producing endophytes commonly have direct negative effects on herbivores. These effects may be carried over to natural enemies of the herbivores, but this has been rarely explored. We examined how feeding on Neotyphodium endophyte infected (E+) and endophyte free (E-) meadow ryegrass (Scherodonus pratensis) affects body mass, population size and mobility of sibling voles (Microtus levis), and whether the diet mediates the vulnerability of voles to least weasel (Mustela nivalis nivalis) predation. Because least weasels are known to be olfactory hunters, we also examined whether they are able to distinguish olfactory cues of voles fed on E+ and E- diets. Neither body mass of voles nor population size differed between diets. However, contrary to our prediction, least weasels preyed more often on voles fed with E- grass than on voles fed with E+ grass. The mobility of voles fed on E+ grass was reduced compared to voles fed on E- grass, but this effect was unrelated to risk of predation. Least weasels appeared unable to distinguish between excrement odours of voles between the two treatments. Our results suggest that consumption of endophytic grass is not directly deleterious to sibling voles. What's more, consumption of endophytes appears to be advantageous to voles by reducing risk of mammalian predation. Our study is thus the first to demonstrate an effect of plant-associated microbial symbionts on herbivore-predator interactions in vertebrate communities.


Reaction of Laser-Ablated Uranium and Thorium Atoms with H2Se: A Rare Example of Selenium Multiple Bonding.
The compounds H2ThSe and H2USe were synthesized by the reaction of laser-ablated actinide metal atoms with H2Se under cryogenic conditions following the procedures used to synthesize H2AnX (An = Th, U; X = O, S). The molecules were characterized by infrared spectra in an argon matrix with the aid of deuterium substitution and electronic structure calculations at the density functional theory level. The main products, H2ThSe and H2USe, are shown to have a highly polarized actinide-selenium triple bond, as found for H2AnS on the basis of electronic structure calculations. There is an even larger back-bonding of the Se with the An than found for the corresponding sulfur compounds. These molecules are of special interest as rare examples of multiple bonding of selenium to a metal, particularly an actinide metal.


Adolescent parricide: a comparison with other adolescent murder.
The authors examined the available data for 10 adolescents who had been charged with parricide and compared these with data for matched groups of 10 adolescents charged with murdering another relative or a close acquaintance and 10 charged with murdering a stranger. They found significant differences between parricidal adolescents and other homicidal adolescents on personality, family, social, and follow-up adjustment variables.


Genetic control of yeast mannan structure: mapping genes mnn2 and mnn4 in Saccharomyces cerevisiae.
Two mutations concerned with mannan biosynthesis in the yeast Saccharomyces cerevisiae have been mapping. The mnn2 mutation, which affects the addition to the polysaccharide backbone of the first side-chain D-mannose unit in alpha1-leads to2 linkage, was located on chromosome II linked to the centromere and the gall locus. The mn4 locus, which regulates the synthesis of mannosylphosphate groups on the mannan side chains, was placed on chromosome XI near trp3 and ural and a locus previously reported to regulate the ability of a S. diastaticus strain to bind alcian blue (Friis and Ottolenghi, 1970). The mnn4 mutant also fails to bind alcain blue, but the gene responsible for alcian blud binding in this strain segregates independently from the dye-binding locus of S. diastaticus, and therefore must be a different gene. A diploid heterozygous for mnn4 fails to bind dye, indicating dominance of this mutant genotype. The alcian blue dye binding locus dbll, reported to Friis and Ottolenghi (1970), is also dominant. Thus, there are at least two independent genes that control the formation of the mannosylphosphate units in the mannan side chains, and both have the property of dominance in the mutant form.


New Insights into the Role of the Surrounding Medium Temperature in the Under-Liquid Wetting of Solid Surfaces.
The wetting of a solid surface by a liquid droplet under a liquid medium at elevated temperatures depends not only on the solid-drop and drop-medium interfacial tensions (IFTs) but also on the temperature dependency of the IFT of the surrounding medium. Previous studies have shown either a decreasing or nearly invariant trend of wettability with an increase in temperature. However, much of the research up to now has only focused on the evaluation of solid wettability in air or vapor, and no model has been proposed to predict the variation of solid wettability at high temperatures under a liquid medium. Here, we developed a theoretical framework and a novel experimental approach to evaluate the high-temperature solid-liquid-liquid wettability. We investigated the wettability of different polymeric and nonpolymeric surfaces, namely, glass, silicon wafer, poly(methyl methacrylate) (PMMA), and polytetrafluoroethylene (PTFE), for a wide range of polar and nonpolar probe droplets under water (as a liquid medium) at temperatures up to 90 °C. The experimental results revealed that the nonpolymeric highly polar solid surfaces, that is, glass and silicon wafer, showed a sharp increase in their contact angle with the probe droplets at elevated temperatures. Between the two polymeric surfaces, PMMA showed a decreasing trend of the contact angle over the variation of temperatures, while in the case of PTFE, no specific trend was observed. The predictions of our theoretical model were in good agreement with the experimental observations with less than ±25% deviation.


Cognitive-behavioral characteristics and developmental trajectories in children with deletion 11qter (Jacobsen syndrome), and their relation to deletion size.
Subtelomeric deletions represent an important class of abnormalities to be considered when investigating genetic links to intellectual disability (ID). One subtelomeric deletion found on the long arm of chromosome 11q produces a characteristic phenotype that includes ID and is often referred to as Jacobsen syndrome (JBS). Previously, researchers found an inverse relationship between IQ and deletion size. While useful, IQ does not provide a comprehensive picture of the cognitive-behavioral strengths and weaknesses in JBS, nor does it reveal how the profiles evolve as these individuals age. One purpose of this study was to confirm the relationship between IQ or adaptive behavior (DQ) and deletion size. We also examined cognitive-behavioral profiles of children with JBS and the extent to which they changed over time. Initially, at T1, we examined 10 children, ages 5-20 years, diagnosed with JBS. Cognitive ability was assessed with the Stanford-Binet (4th Edition). Adaptive behavoir was evaluated with the Vineland Adaptive Behavior Scales (VABS). Eight children were reassessed 2 years later (T2). Results show a negative but non-significant correlation between IQ and deletion size. There was no statistically significant relationship between DQ and deletion size. As for our second aim, IQ and DQ scores were stable from T1 to T2. Cognitive profiles were not significantly different from T1 to T2. However, there were significant changes in adaptive behavior domain scores from T1 to T2. Lack of a significant relationship between cognitive-behavioral measures and deletion size, as well as changes in cognitive-behavioral profiles are discussed.


Mild mitochondrial depolarization is involved in a neuroprotective mechanism of Citrus sunki peel extract.
Mitochondrial membrane potential (∆Ψm ) contributes to determining a driving force for calcium to enter the mitochondria. It has been demonstrated that even a small mitochondrial depolarization is sufficient to prevent mitochondrial calcium overload and the subsequent apoptosis. Therefore, mild mitochondrial depolarization has been recently evaluated as a novel mechanism of neuroprotection via inhibiting neurotoxic mitochondrial calcium overload during neuronal insults. In the present study, using both real-time recording and flow cytometric analyses of ∆Ψm , we demonstrated that ethanolic peel extract of Citrus sunki Hort. ex Tanaka (CPE) and its active compounds are capable of inducing a mild mitochondrial depolarization. Polymethoxylated flavones such as nobiletin and tangeretin were found as the active compounds responsible for CPE effects on ∆Ψm . Neuronal viability was significantly increased in a dose-dependent manner by CPE treatment in H2 O2 -stimulated HT-22 cells as an in vitro neuronal insult model. CPE treatment significantly inhibited H2 O2 -induced apoptotic processes such as chromatin condensation, caspase 3 activation and anti-poly (ADP-ribose) polymerase (PARP) cleavage. CPE treatment significantly blocked mitochondrial calcium overload in H2 O2 -stimulated HT-22 neurons as indicated by rhod-2 acetoxymethyl ester. Taken together, our findings suggest that CPE and its active compounds may be considered as promising neuroprotective agents via inducing a mild mitochondrial depolarization.


Toxic effects of orimulsion on rainbow trout Oncorhynchus mykiss.
Orimulsion (stable emulsion of natural bitumen and water) is a new imported industrial fuel in Lithuania. No data on its toxicity to fish is freely available. The aim of this study was to investigate sensitivity of rainbow trout (Oncorhynchus mykiss) to acute and chronic toxicity of orimulsion and to estimate the Maximum Acceptable Toxicant Concentration (MATC) of orimulsion to fish. Laboratory tests were conducted on rainbow trout in all stages of development (embryos, larvae, adults). Acute toxicity (96-hour duration) and long-term (28 or 60-day duration) tests evaluating the wide range spectrum of biological indices were performed under semi-static conditions. Median lethal concentration (96-hour LC50) values and their 95% confidence intervals derived from the tests were: 0.1 (0.09-0.12) to embryos, 0.06 (0.05-0.07) to larvae and 2.22 (2.02-2.43) to adult fish, and 28-day LC50 to adult fish was found to be 0.26 (0.21-0.32) g/l of total orimulsion respectively. The acute toxicity of orimulsion to rainbow trout can be characterised by a narrow zone of toxic effect and a sharp boundary between lethal and sublethal concentrations. The lowest 'safe' or 'no-effect' concentration values of total orimulsion obtained in long-term tests were equal to 0.09 g/l to adult fish, 0.019 g/l to embryos, and 0.0017 g/l to larvae. Proposed value of 'application factor' for orimulsion was found to be equal to 0.03. Since orimulsion has the property to disperse in all water volume, its toxic effect on fish can be characterised by the combined effects of dispersion and water-soluble-fraction. Maximum Acceptable Toxicant Concentration (MATC) of 0.0017 g/l of total orimulsion to fish was derived from long-term tests based on the most sensitive parameter of rainbow trout larvae (relative mass increase at the end of the test). According to substance toxicity classification accepted for Lithuanian inland waters, orimulsion can be referred to substances of 'moderate' toxicity to fish. For prediction and evaluation of toxic impact of orimulsion accident spills on fish, some recommendations should be given. Since orimulsion has the property to disperse in all water volume during short time periods, the amounts of both spilled orimulsion and polluted water should be ascertained. Once both parameters are known, the real concentration of orimulsion in the water body must be determined. Then this concentration must be compared with 'safe' concentration to fish. By use of 'application factor' 0.03, approximate MATC for other fish species can be estimated when only acute toxicity data (96-hour LC50 value) is available.


Measuring contact area in a sliding human finger-pad contact.
The work outlined in this paper was aimed at achieving further understanding of skin frictional behaviour by investigating the contact area between human finger-pads and flat surfaces. Both the static and the dynamic contact areas (in macro- and micro-scales) were measured using various techniques, including ink printing, optical coherence tomography (OCT) and Digital Image Correlation (DIC). In the studies of the static measurements using ink printing, the experimental results showed that the apparent and the real contact area increased with load following a piecewise linear correlation function for a finger-pad in contact with paper sheets. Comparisons indicated that the OCT method is a reliable and effective method to investigate the real contact area of a finger-pad and allow micro-scale analysis. The apparent contact area (from the DIC measurements) was found to reduce with time in the transition from the static phase to the dynamic phase while the real area of contact (from OCT) increased. The results from this study enable the interaction between finger-pads and contact object surface to be better analysed, and hence improve the understanding of skin friction.


Comparison of functional MR imaging guidance to electrical cortical mapping for targeting selective motor cortex areas in neuropathic pain: a study based on intraoperative stereotactic navigation.
To assess the concordance between data from functional MR imaging (fMRI) guidance and the intraoperative electrical cortical mapping (iCM) in targeting selective motor cortex areas in refractory neuropathic pain. Twenty-one patients (11 women and 10 men; mean age, 55.6 years) with refractory central (ischemic, 8 cases) and neuropathic pain (trigeminal neuropathy, 6 cases; syrinx/amputation/plexus trauma, 7 cases) underwent surgery for the implantation of an epidural electrode for chronic motor cortex stimulation (MCS) with general anesthesia and a frameless neuronavigation system used for the image-guided targeting procedure. All patients were studied by preoperative fMRI and epidural iCM with somatosensory evoked potentials and motor cortex stimulodetection. fMRI investigated systematically motor tasks of both hands and that related to the somatic area (foot or tongue) affected by pain. fMRI data were analyzed with the Statistical Parametric Mapping99 software (initial analysis threshold [AT] corresponding to P < .001), registered in the neuronavigation system and correlated intraoperatively with iCM. Matching of fMRI and iCM was specifically examined, focusing the study on hand mapping. Concordance between contours of fMRI activation area and iCM in precentral gyrus (mean distance, 3.8 mm) was found in 20/21 patients (95%). Because precision of iCM was suboptimal in 7 patients, concordance for more restrictive values of the AT (P < .0001) was found in only 13 of these 20 patients. Concordance was not found in one patient, as result of image distortion and residual motion artifact. In this study, fMRI guidance provides information that matches those of an independent functional method. These data illustrate the functional accuracy of fMRI guidance for the operative targeting of selective motor cortex areas in neuropathic pain.


Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12.
Colorectal cancer (CRC) is a common malignant tumor in the digestive tract, and 30%-85% of CRCs express epidermal growth factor receptors (EGFRs). Recently, treatments using cetuximab, also named C225, an anti-EGFR monoclonal antibody, for CRC have been demonstrated to cause an S492R mutation in EGFR. However, little is known about the biological function of S492R EGFR. Therefore, we attempted to elucidate its biological function in CRC cells and explore new treatment strategies for this mutant form. Our study indicated that EGFR and S492R EGFR accelerate the growth of CRC cells in vitro and in vivo and monoclonal antibody CH12, which specifically recognizes an EGFR tumor-specific epitope, can bind efficiently to S492R EGFR. Furthermore, mAb CH12 showed significantly stronger growth suppression activities and induced a more potent antibody-dependent cellular cytotoxicity effect on CRC cells bearing S492R EGFR than mAb C225. mAb CH12 obviously suppressed the growth of CRC xenografts with S492R EGFR mutations in vivo. Thus, mAb CH12 may be a promising therapeutic agent in treating patients with CRC bearing an S492R EGFR mutation.


Alternative splicing of exons in the alpha1 subunit of the rat testis L-type voltage-dependent calcium channel generates germ line-specific dihydropyridine binding sites.
Cell-specific isoforms of the alpha1 subunit of the L-type voltage-dependent calcium channel (VDCC) have unique pharmacological reactivities. Prior sequence analysis of nucleotide bases 3908-6077 of the VDCC alpha1 subunit expressed in rat testis differed from cardiac sequences only in a 84 base pair region corresponding to exons 31/32 encoding a putative dihydropyridine binding region. We now report that sequence analysis of bases 3048-3936 identifies a second difference between the rat testis and rat cardiac alpha1 sequence in a 60 base pair region corresponding to exons 21/22 and encoding another putative dihydropyridine binding site. Variable VDCC exons 21/22 and 31/32 and their linking introns were sequenced using genomic DNA from rat lung as template, providing evidence that the rat testis and cardiac alpha1 isoforms are products of the same gene. Reverse transcription in-situ polymerase chain reaction (PCR) with frozen sections of rat testis was carried out with primers identifying the testis-specific exon 32 of the VDCC alpha1 subunit. PCR products were confined to seminiferous tubules and were associated with the germ cell lineage from Type A spermatogonia to mature spermatozoa. Close coupling of testis alpha1 VDCC gene transcription and translation was established by in-situ immunolabelling of serial frozen sections with a monoclonal antibody (IIF7) directed against epitopes on rabbit skeletal muscle L-type VDCC alpha1. Western blot analysis of rat proteins extracted from heart, skeletal muscle, testis and spermatozoa which were reactive with the IIF7 antibody detected primarily 175-220 kDa proteins in the size range of VDCC. These data unequivocally demonstrate that an L-type VDCC is expressed in rat testis and that VDCC isoforms from rat testis and heart differ in deduced amino acid composition in and around potential binding sites for calcium channel blocking drugs such as the dihydropyridines.


Carnitine palmitoyltransferase I (CPT I) activity and its regulation by malonyl-CoA are modulated by age and cold exposure in skeletal muscle mitochondria from newborn pigs.
Whole-body lipid utilization is progressively enhanced during the first postnatal day in pigs, especially during cold exposure and muscular shivering thermogenesis. This study was designed to examine early postnatal changes in fatty acid oxidation potential, carnitine palmitoyltransferase I activity and regulation by malonyl-CoA in skeletal muscle mitochondria isolated from newborn and 5-d-old piglets. At 5 d of life, pigs were maintained for a 4-h period in thermoneutral (30 degreesC) or cold (20 degreesC) conditions. Intermyofibrillar and subsarcolemmal mitochondria were isolated from longissimus dorsi and rhomboïdeus muscles. In subsarcolemmal mitochondria, carnitine palmitoyltransferase I activity increased with age (P < 0.01) and was 80% lower (P < 0.001) than in intermyofibrillar mitochondria. Intermyofibrillar mitochondria had high enzyme activities and fatty acid oxidation potential from birth. The fatty acids 16:0, 18:1(n-9) and 18:2(n-6) were oxidized at a higher rate than 18:0 (-37%) and 8:0 (-55%). Sensitivity of carnitine palmitoyltransferase I to malonyl-CoA inhibition and malonyl-CoA levels decreased by 47% (P < 0.05) and 33% (P < 0.01) with age, respectively. After 4 h of cold exposure, sensitivity of carnitine palmitoyltransferase I to malonyl-CoA was unaffected in the rhomboideus and tended to be greater (P < 0.06) in longissimus dorsi muscle. Malonyl-CoA levels were lower (P < 0.05) in the rhomboideus and were unaffected in longissimus dorsi muscle. These results demonstrate that fatty acid oxidation is effective from birth in isolated intermyofibrillar mitochondria. The postnatal enhancement of fatty acid utilization observed in vivo can be explained, at least in part, by a rise in carnitine palmitoyltransferase I activity in subsarcolemmal mitochondria and a modulation of its activity by malonyl-CoA in intermyofibrillar mitochondria.


A New Phytosanitary Method to Reduce the Ascospore Potential of Venturia inaequalis.
Ascospores of Venturia inaequalis, released from pseudothecia in overwintered, infected apple leaves, serve as the primary inoculum for apple scab. In this study, we tested a new sanitation strategy to reduce ascospore inoculum under orchard conditions over three overwintering periods. After leaf fall, nutrient media containing different concentrations of degraded casein or a yeast extract from Saccharomyces cerivisiae were applied to leaf litter infected with apple scab. The application of 30 and 60% yeast extract showed the greatest efficacy, and significantly reduced ascospore discharge by 99% (P < 0.01) in 2013 and 2014. The efficacy of the treatments did not differ from treatment with 5% urea (P > 0.05). Leaf litter decay was accelerated in the plots treated with yeast extract compared with untreated control plots. Moreover, apple leaves treated with yeast extract had completely decayed due to earthworm activity before ascospore maturity. In comparison, up to 26% of the leaves in untreated control plots had not decayed. These results suggest that the treatment of leaf litter with yeast extract can almost completely eliminate apple scab inoculum in the course of the whole primary season. These sanitation practices may be beneficial for both organic and conventional cultivation. The reduced infection pressure may allow growers the usage of fungicides with lower efficacy or to reduce the number of applications needed to manage apple scab in spring.


The typical presentation of an atypical pathogen during an outbreak of Legionnaires' disease in Vila Franca de Xira, Portugal, 2014.
An outbreak of Legionella pneumophila serogroup 1, with 403 cases was identified on the 7th November 2014 in Vila Franca de Xira, Portugal. Outbreak source was the wet cooling system of a local factory. Hospital Pulido Valente was one of the hospitals receiving patients with Legionnaires' disease (LD). We describe the clinical findings and diagnostic methods used among the 43 confirmed or probable cases admitted to our department. 60.5% were male, mean age was 56.1±13.5 years and tobacco smoking was the most frequent risk factor (76.7%). All patients had fever, 62.8% ≥39.5°C, 72.1% had chills and myalgia/arthralgia and 62.8% had dry cough. Extra pulmonary symptoms were frequent: confusion and headache occurred in 34.9% and gastrointestinal symptoms in 20.9%. High C-Reactive Protein (55.8% ≥30mg/dL) and hyponatremia (62.8%) were the laboratorial abnormalities most commonly found. Hypoxemia occurred in 55.8% and hypocapnia in 93%. Urinary Antigen Test (UAT) was positive in 83.7% of the cases. Although not specific, a combination of risk factors, symptoms and laboratory findings can be highly suggestive of LD, even in an outbreak. This should prompt diagnosis confirmation. Routine use of UAT in less severe cases of community acquired pneumonia might contribute to earlier diagnosis.


[Congenital absence of the portal vein in an adult woman with liver tumor].
A 30-years-old Japanese woman with a liver tumor was found to have congenital absence of the portal vein (CAPV). Both three-dimensional CT and angiography revealed that the superior mesenteric vein and splenic vein flowed into inferior vena cava and there was us portal vein, CAPV is an extremely rare congenital anomaly and liver tumor. Most cases on diagnosed in childhood, although this case was found in on adult. We reviewed the literature on reported CAPV cases.


[Population aging and health information from the National Household Sample Survey: contemporary demands and challenges. Introduction].
This article examines the new demographic and epidemiological reality in Brazil, based on data collected and organized in the Health Supplement of the National Household Sample Survey (PNAD-Health). It highlights the urgency of changes and innovations in health care paradigms for the elderly population with a preventive approach based on comprehensive education and care. As key concepts, the article emphasizes the need to preserve autonomy, participation, care, self-satisfaction, and the possibility of elder citizens being active in various social contexts. It also discusses the contribution by various authors to the discussion forum on Human Aging and the National Household Sample Surveys, coordinated by Cadernos de Saúde Pública/Reports in Public Health, featuring studies on access to and utilization of health services by the elderly, the epidemiological pattern of breast cancer in elderly women, and the validity of using proxy respondents in research on self-perceived health status, concluding that the PNAD data are consistent and can be used by the scientific community.


A study of nurse scheduling in Japan.
Scheduling nurses to staff shifts is a major problem in hospitals. The necessity of maintaining a certain level of service and skill in the makeup of every shift, while balancing the workload among the nurses involved, is incredibly difficult. It is often impossible to develop a schedule which satisfies all the requirements despite the time and resources spent in the effort. This paper summarizes all our published research on nurse scheduling to date. The difficulties realized by our two investigations in Japan are shown first, together with a resulting scheduling problem. The nurse scheduling model based on the results is then described. In this model, all constraints are divided into two essentially different types; that which maintains a certain level of skill for each shift ('shift constraints') and that which concerns the workload for each nurse ('nurse constraints'). By classifying the constraints in this manner, we can determine what is affected by a specific constraint when the constraint is not satisfied. We developed efficient algorithms while taking advantage of the structure of this model. Finally, it is shown that our algorithm can solve this problem for a 2-shift system efficiently.


Rubber band ligation of hemorrhoids.
Hemorrhoids are frequently seen by family physicians. Prolapse and painless bleeding are the symptoms most commonly experienced by patients with internal hemorrhoids. These areas of chronically enlarged rectal tissue arise above the dentate line and are amenable to treatment by rubber band ligation. The procedure is safe and effective, and can be performed in the physician's office. Contraindications include infection, chronic liver or bowel disease, clotting disorders and significant thrombosis.


MYPATH: A novel mindfulness and yoga-based peer leader intervention to prevent violence among youth experiencing homelessness.
Young adults experiencing homelessness (YAEH) are at elevated risk for violence victimization and perpetration. However, there are no evidence-based violence prevention interventions for homeless populations. This study is an evaluation of a novel mindfulness-based peer-leader intervention designed to reduce violence and improve mindfulness in YAEH. A social network of YAEH receiving services at a drop-in agency was recruited in Summer 2018 (n = 106) and peer-leaders identified at baseline (n = 12). Peer leaders were trained in mindfulness and yoga skills during a 1-day intensive workshop and seven 1-h weekly follow-up workshops and encouraged to share their knowledge with in-network peers. Postintervention data were collected 2 and 3 months after baseline. Two one-way repeated-measures analyses of variance (ANOVAs) tested differences in means for mindfulness and fighting. ANOVA models showed significant increases in group mean mindfulness F(2, 110) = 3.42, p < 0.05 and significant decreases in group mean violent behavior F(2, 112) = 5.23, p < 0.01 at the network level. Findings indicate a network-based, peer-leader model can be effective for influencing complex, socially conditioned attitudes and behaviors among YAEH. Additional advantages of the peer-leader model include relatively few direct-service person-hours required from providers and convenience to participants able practice skills in their relevant social contexts.


Genetically Encoded Double-Stranded DNA-Based Nanostructure Folded by a Covalently Bivalent CRISPR/dCas System.
DNA nanotechnology has been widely employed in the construction of various functional nanostructures. However, most DNA nanostructures rely on hybridization between multiple single-stranded DNAs. Herein, we report a general strategy for the construction of a double-stranded DNA-ribonucleoprotein (RNP) hybrid nanostructure by folding double-stranded DNA with a covalently bivalent clustered regularly interspaced short palindromic repeats (CRISPR)/nuclease-dead CRISPR-associated protein (dCas) system. In our design, dCas9 and dCas12a can be efficiently fused together through a flexible and stimuli-responsive peptide linker. After activation by guide RNAs, the covalently bivalent dCas9-12a RNPs (staples) can precisely recognize their target sequences in the double-stranded DNA scaffold and pull them together to construct a series of double-stranded DNA-RNP hybrid nanostructures. The genetically encoded hybrid nanostructure can protect genetic information in the folded state, similar to the natural DNA-protein hybrids present in chromosomes, and elicit efficient stimuli-responsive gene transcription in the unfolded form. This rationally developed double-stranded DNA folding and unfolding strategy presents a new avenue for the development of DNA nanotechnology.


Fast domain wall propagation under an optimal field pulse in magnetic nanowires.
We investigate field-driven domain wall (DW) propagation in magnetic nanowires in the framework of the Landau-Lifshitz-Gilbert equation. We propose a new strategy to speed up the DW motion in a uniaxial magnetic nanowire by using an optimal space-dependent field pulse synchronized with the DW propagation. Depending on the damping parameter, the DW velocity can be increased by about 2 orders of magnitude compared to the standard case of a static uniform field. Moreover, under the optimal field pulse, the change in total magnetic energy in the nanowire is proportional to the DW velocity, implying that rapid energy release is essential for fast DW propagation.


Recombinant Adeno-Associated Viral Integration and Genotoxicity: Insights from Animal Models.
Currently, clinical gene therapy is experiencing a renaissance, with new products for clinical use approved in Europe and clinical trials for multiple diseases reporting positive results, especially those using recombinant adeno-associated viral (rAAV) vectors. Amid this new success, it is prudent to recall that the field of gene therapy experienced tragic setbacks in 1999 and 2002 because of the serious adverse events related to retroviral and adenoviral gene delivery in two clinical trials that resulted in the death of two patients. In both cases, the toxicity observed in humans had been documented to occur in animal models. However, these toxicities were either undetected or underappreciated before they arose in humans. rAAVs have been tested extensively in animals and animal models of disease, largely without adverse events, except for transient elevation in liver enzymes in some patients. However, a small but growing number of murine studies have documented that adeno-associated viral gene delivery can result in insertional mutagenesis. Herein, the aggregate data are reviewed from multiple murine studies where genotoxicity associated with rAAV treatment has been observed. The data emphasize the need for a proactive position to evaluate the potential risks and possible solutions associated with AAV-mediated gene therapy.


CaMKII-mediated phosphorylation of the myosin motor Myo1c is required for insulin-stimulated GLUT4 translocation in adipocytes.
The unconventional myosin Myo1c has been implicated in insulin-regulated GLUT4 translocation to the plasma membrane in adipocytes. We show that Myo1c undergoes insulin-dependent phosphorylation at S701. Phosphorylation was accompanied by enhanced 14-3-3 binding and reduced calmodulin binding. Recombinant CaMKII phosphorylated Myo1c in vitro and siRNA knockdown of CaMKIIdelta abolished insulin-dependent Myo1c phosphorylation in vivo. CaMKII activity was increased upon insulin treatment and the CaMKII inhibitors CN21 and KN-62 or the Ca(2+) chelator BAPTA-AM blocked insulin-dependent Myo1c phosphorylation and insulin-stimulated glucose transport in adipocytes. Myo1c ATPase activity was increased after CaMKII phosphorylation in vitro and after insulin stimulation of CHO/IR/IRS-1 cells. Expression of wild-type Myo1c, but not S701A or ATPase dead mutant K111A, rescued the inhibition of GLUT4 translocation by siRNA-mediated Myo1c knockdown. These data suggest that insulin regulates Myo1c function via CaMKII-dependent phosphorylation, and these events play a role in insulin-regulated GLUT4 trafficking in adipocytes likely involving Myo1c motor activity.


Microdrop-Assisted Microdomain Hydrophilicization of Superhydrophobic Surfaces for High-Efficiency Nucleation and Self-Removal of Condensate Microdrops.
Superhydrophobic-hydrophilic hybrid surfaces have attracted intensive interest because of their significant academic and commercial values. However, almost all reported microdomain hydrophilicization methods rely on costly micropatterning techniques that need special instruments. Here, we report a microdrop-assisted method for microdomain hydrophilicization of a low-adhesive superhydrophobic surface and demonstrate its utility in high-efficiency nucleation and self-removal of condensate microdrops. Micrometer-sized fogdrops containing polyvinyl alcohol molecules can be selectively captured by breath figures of superhydrophobic surfaces with specific sizes and spatial distributions and can be converted into desired hydrophilic microdomains after thermal evaporation. After exploring the influence of hydrophilic microdomains' distributions and sizes to surface wettability, adhesion, and condensation dynamics, we achieved an optimal hybrid surface, which possesses 240% average microdrop density, 387% microdrop self-removal rate, and 75% average microdrop diameter as compared to the contrast superhydrophobic surface with uniform chemistry nature. This method is dispensed with special equipment, easy to implement, very cheap, and eco-friendly, which would help develop other superhydrophobic-hydrophilic hybrid surfaces with different functions such as water harvesting, dehumidification, and heat exchange.


[Methodological mistakes and contradictions in the ederal clinical recommendations on addiction medicine].
Methodological mistakes and contradictions in the Federal clinical recommendations on therapy of addictive disorders are analyzed. It is noted that the recommendations aren't based on the principles of evidence-based medicine; ignore achievements of world addiction medicine and necessity of using drugs with the proved efficacy; are accepted in the conditions of refusal of scientific collegiality; contradict the instructions on the use of medicines and contain a large number of controversial theoretical issues.


Synthesis and characterization of antibacterial carboxymethyl cellulose/ZnO nanocomposite hydrogels.
In this study, carboxymethyl cellulose/ZnO nanocomposite hydrogels have been synthesized through the in situ formation of ZnO nanoparticles within swollen carboxymethyl cellulose hydrogels. The formation of ZnO nanoparticles in the hydrogels was confirmed using X-ray diffraction, UV-vis spectroscopy and scanning electron microscopy (SEM) studies. SEM micrographs revealed the formation of ZnO nanoparticles with size range of 10-20 nm within the hydrogel matrix. The prepared nanocomposite hydrogels showed a pH and salt sensitive swelling behavior. The ZnO nanocomposite hydrogels have rather higher swelling in different aqueous solutions in comparison with neat hydrogel. The nanocomposite hydrogels demonstrated antibacterial effects against Escherichia coli and Staphylococcus aureus bacteria. The developed carboxymethyl cellulose/ZnO nanocomposite hydrogels can be used effectively for biomedical application.


[Interferon alpha antibodies show no cross reactions with typical autoantibodies].
Patients treated with natural human interferon alpha develop anti-interferon antibodies (IFN-AB) only in very rare cases. By contrast, patients with autoimmune disorders are able to generate high-titered IFN-AB against endogenous interferon alpha. One explanation for the development of auto-IFN-AB could be cross-reactivity with typical autoimmune antigens. We investigated the cross-reactivity of 3 high-titered IgG IFN-AB of female autoimmune patients (aged 32, 36, 74 years; two severe cases of SLE, one case of autoimmune thyroiditis) as well as 25 low-titered natural IgM IFN-AB of healthy blood donors (aged 19-48 years). Typical autoimmune antigens including dsDNA, ENA, as well as natural interferon beta and recombinant interferon gamma are not able to inhibit binding of IFN-AB to interferon alpha in an ELISA test system. Preincubation of sera containing either dsDNA antibodies (dsDNA-AB) (24 patients), thyroid peroxidase (TPO-AB) (9 patients) or thyroglobulin (TG-AB) (12 patients) with interferon alpha resulted in no change in the respective autoantibody titer. These data suggest that there is no cross-reactivity between IFN-alpha-AB and dsDNA-AB, TPO-AB or TG-AB. Thus, an explanation for the occurrence of IFN-AB in autoimmune disorders cannot be found in a cross-reaction between interferon alpha with typical autoimmune antigens.


Histochemical modifications induced "in vitro" by electromagnetic stimulation of growing bone tissues.
The histochemical modifications induced on a mouse limb bud culture system by electromagnetic stimulation have been investigated using mucopolysaccharide (MPS) staining methods. An increase in the amount of MPS with cartilage has been observed. This difference is more obvious on the more distal segments of the limb, i.e. on the youngest structures. These observations are correlated with some modifications observed in the enzymatic activities of acid phosphatase and of beta glucuronidase.


An investigation of the factor structure of the beck depression inventory-II in anorexia nervosa.
Symptoms of depression frequently co-occur with eating disorders and have been associated with negative outcomes. Self-report measures such as the Beck Depression Inventory-II (BDI-II) are commonly used to assess for the presence of depressive symptoms in eating disorders, but the instrument's factor structure in this population has not been examined. The purposes of this study were to explore the factor structure of the BDI-II in a sample of individuals (N = 437) with anorexia nervosa undergoing inpatient treatment and to examine changes in depressive symptoms on each of the identified factors following a course of treatment for anorexia nervosa in order to provide evidence supporting the construct validity of the measure. Exploratory factor analysis revealed that a three-factor model reflected the best fit for the data. Confirmatory factor analysis was used to validate this model against competing models and the three-factor model exhibited strong model fit characteristics. BDI-II scores were significantly reduced on all three factors following inpatient treatment, which supported the construct validity of the scale. The BDI-II appears to be reliable in this population, and the factor structure identified through this analysis may offer predictive utility for identifying individuals who may have more difficulty achieving weight restoration in the context of inpatient treatment. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.


[Complex angiographic diagnosis of space-demanding processes in the kidney including renocystography].
Issuing from the experiences of the complex angiorgraphic diagnostics of space-demanding processes of the kidneys in 400 patients value and sequence of different angiographic methods including renocystography are discussed. The diagnostic certainty in hypo- and avascular tumours by the renal phlebography and in cystic processes is essentially increased by percutaneous puncture. In malignant tumours before operation the judgement of the endovenous extension is always to be demanded, which is most certainly achieved by direct venography. A diagnostic step programme is proposed, to make possible the rational use of the methods.


Orbital Atherectomy Plaque Modification Assessment of the Femoropopliteal Artery Via Intravascular Ultrasound (TRUTH Study).
The Tissue Removal Assessment with Ultrasound of the SFA and Popliteal (TRUTH) study assessed the performance of the orbital atherectomy system (OAS) to treat femoropopliteal arteries, including determining its effect on plaque removal. Patients with symptomatic femoropopliteal peripheral arterial disease were treated with the OAS followed by adjunctive balloon angioplasty (BA). Intravascular ultrasound (IVUS) images were collected pre- and post-OAS and post-OAS BA. Patients were followed through 12 months post-procedure. Twenty-nine lesions were treated with OAS-BA in 25 patients. The mean maximum balloon inflation pressure was 5.2 ± 1.2 atm. Virtual histology IVUS (VH-IVUS) analysis revealed at the maximum calcium ablation site that calcium reduction was responsible for 86% of the lumen area increase. The minimum lumen area increased from 4.0 mm(2) to 9.1 mm(2) (<.0001), and the percentage of area stenosis decreased from 76.9% to 43.0% (<.0001) after OAS-BA. At 12 months, the target lesion revascularization rate was 8.2%, and ankle-brachial index and Rutherford classification improved significantly from baseline through follow-up. The VH-IVUS analysis reveals that OAS modifies the calcified component of the plaque burden. It is hypothesized that calcium modification by OAS changes the lesion compliance, allowing for low pressure adjunctive BA. The clinical outcomes were favorable through 12-month follow-up.


Electrospun composite nanofiber fabrics containing uniformly dispersed antimicrobial agents as an innovative type of polymeric materials with superior antimicrobial efficacy.
Herein we report that electrospun composite nanofiber fabrics containing uniformly dispersed antimicrobial agents and having large surface-to-mass ratios are an innovative type of antimicrobial polymeric materials with durable, nonleachable, and biocompatible characteristics, and more importantly, superior antimicrobial efficacy. Specifically, electrospun cellulose acetate (CA) nanofiber fabrics containing an N-halamine antimicrobial agent of bis(N-chloro-2,2,6,6-tetramethyl-4-piperidinyl) sebacate (Cl-BTMP) were prepared and evaluated; the results of antimicrobial efficacy indicated that the electrospun composite nanofiber fabrics substantially outperformed the control samples that were solution-cast films containing identical amounts of CA and Cl-BTMP. Additionally, the results of trypan blue assay test suggested that the electrospun composite nanofiber fabrics also had excellent mammal cell viability. The developed electrospun composite nanofiber fabrics with superior antimicrobial efficacy are expected to find vital applications in biomedical, hygienic, and many other fields.


Ventricular discrepancy as a sonographic sign of coarctation of the fetal aorta: how reliable is it?
The purpose of this study was to assess the predictive value and sensitivity of discrepant ventricular size for fetal aortic coarctation. Postnatal follow-up data were obtained in 42 fetuses in whom ventricular size discrepancy (left ventricle smaller than right ventricle) was recognized on an obstetrical sonogram. Additionally, from postnatal records, we identified infants with coarctation who had had an obstetrical sonogram after 16 weeks. Fourteen of the 42 fetuses had coarctation or other aortic arch obstruction after birth (33% positive predictive value). Eight (62%) of 13 fetuses with ventricular discrepancy recognized before 34 weeks had coarctation, compared with six (21%) true positive cases among 29 recognized after 34 weeks (P = 0.01, Fisher's exact test). Of 21 infants with coarctation, ventricular discrepancy had been recognized by prenatal sonography in 13 (62% sensitivity). Ventricular discrepancy has moderate sensitivity and mediocre positive predictive value for coarctation. The limitations of this finding for diagnosing coarctation, particularly a higher false positive rate after 34 weeks, must be recognized, but it is still a useful sign to identify this potentially ductus-dependent lesion.


Dietary orotic acid increases 1 ,2-diacylglycerol level and lowers superoxide dismutase activity in rat liver.
The effects of the dietary addition of orotic acid were studied on lipid levels in the rat liver and serum, 1,2-diacylglycerol levels in some organs, activities of antioxidant liver enzymes (superoxide dismutase, glutathione peroxidase, and catalase), and serum enzyme activities (ornithine carbamoyltransferase and alanine aminotransferase), after feeding for 0, 7, 14, and 21 d, respectively. Rats on the orotic acid diet accumulated more liver total lipids, triacylglycerol, and phospholipids than those on the basal diet. However, the levels of serum triacylglycerol and phospholipids of those rats were markedly decreased after 7, 14, and 21 d on the diet. Dietary orotic acid increased the 1,2-diacylglycerol levels in the liver of rats fed for 14 or 21 d, but not in the ileum of small intestine, vastus lateralis muscle, and heart. The addition of orotic acid lowered the activities of liver total and Cu,Zn-superoxide dismutase after feeding for 7, 14, and 21 d. The serum ornithine carbamoyltransferase activity after 14, and 21 d and that of serum alanine aminotransferase after 7, 14, and 21 d were increased. These data suggested that the increase in the activities of serum enzymes tested may result from liver damage induced by the marked accumulation of liver lipids and possibly from the increased superoxide anion because of the decreased activities of hepatic superoxide dismutase by orotic acid feeding.


[The treatment of binge eating disorder - a review].
The binge eating disorder is a relatively new type of eating disorders, which was first described in 1992, and became a distinct nosological entity in the system of DSM-5 in 2013. Its central symptom is the binge, which is not followed by compensatory behaviours as in bulimia nervosa. Therefore, the patients are generally obese. The prevalence of the disorder is 1-3% in the general population, but much higher in help-seeking obese subjects. The two main goals of the therapy is body weight reduction, and the cessation of binges. In the pharmacotherapy of binge eating disorder the antidepressants are recommended mainly in the case of unsuccessful psychotherapy, and in treating comorbid depression. In the field of psychotherapy data are available mainly on the effectiveness of cognitive behavioural therapy, dialectic behaviour therapy, behavioural weight loss, and interpersonal therapy. Effectivity studies on new therapeutic methods and treatment combinations are needed as well as long term follow-up studies.


Decoding the substrate supply to human neuronal nitric oxide synthase.
Nitric oxide, produced by the neuronal nitric oxide synthase (nNOS) from L-arginine is an important second messenger molecule in the central nervous system: It influences the synthesis and release of neurotransmitters and plays an important role in long-term potentiation, long-term depression and neuroendocrine secretion. However, under certain pathological conditions such as Alzheimer's or Parkinson's disease, stroke and multiple sclerosis, excessive NO production can lead to tissue damage. It is thus desirable to control NO production in these situations. So far, little is known about the substrate supply to human nNOS as a determinant of its activity. Measuring bioactive NO via cGMP formation in reporter cells, we demonstrate here that nNOS in both, human A673 neuroepithelioma and TGW-nu-I neuroblastoma cells can be fast and efficiently nourished by extracellular arginine that enters the cells via membrane transporters (pool I that is freely exchangeable with the extracellular space). When this pool was depleted, NO synthesis was partially sustained by intracellular arginine sources not freely exchangeable with the extracellular space (pool II). Protein breakdown made up by far the largest part of pool II in both cell types. In contrast, citrulline to arginine conversion maintained NO synthesis only in TGW-nu-I neuroblastoma, but not A673 neuroepithelioma cells. Histidine mimicked the effect of protease inhibitors causing an almost complete nNOS inhibition in cells incubated additionally in lysine that depletes the exchangeable arginine pool. Our results identify new ways to modulate nNOS activity by modifying its substrate supply.


[The Rehabilitation in Pain Clinic].
Rehabilitation is becoming an important field of care at pain clinics designed to alleviate pain. Exercise and physical therapies are widely used in rehabilitation, and exercise therapy in particular is considered a treatment that should be actively incorporated. Intervention must continue to be provided after ascertaining whether exercise therapy is within the scope of pain clinicians themselves, or whether it should be offered in collaboration with physical therapists. This can be achieved by deepening knowledge of exercise therapy and investigating how it should be offered depending on the disease. Focus should be placed on abnormal posture and exercise, as well as secondary pain. Visualizing movement and building up associated sensorimotor experiences are also considered important. To achieve this, cooperation between physiatrists and physical therapists, they must deepen and exchange understanding and knowledge with each other.


Donor Shortage in Germany: Impact on Short- and Long-Term Results in Liver Transplantation.
With slightly more than 10 donors per million inhabitants, Germany belongs to the underdeveloped countries in Europe with regard to organ donation. Organ shortage is supposed to promote the usage of organs which are declined in case of less pronounced scarcity. This may result in deteriorated graft and patient survival. In the light of this situation, data on the centers' procedures and outcome of liver transplantation in Germany is presented based upon reports of Eurotransplant, the German Institutions for Quality Assessment, and the Deutsche Stiftung Organtransplantation. Surprisingly, along with an increasing organ scarcity, the outcome during waiting time and after transplantation has been improved. The 1- and 3-year patient survival improved by 7 and 9%, respectively. Reasons for this unexpected development are discussed.


Low Utility of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography for Detecting Hepatocellular Carcinoma in Patients Before Liver Transplantation.
Our program routinely used fluorodeoxyglucose-positron emission tomography/computed tomography as part of the liver transplant evaluation of patients with hepatocellular carcinoma. The aim of this study was to evaluate the role of this imaging modality in the pretransplant work-up. This was a retrospective chart review of our liver transplant database from January 2011 to December 2014 for all patients with hepatocellular carcinoma who underwent a liver transplant. Collected data included age, sex, cause of liver disease, imaging modality, fluorodeoxyglucose-positron emission tomography/computed tomography results, explant tissue analysis, type of transplant, and transplant outcome. During the study period, 275 liver transplants were performed. Fifty-three patients had hepatocellular carcinoma; 41 underwent fluorodeoxyglucose-positron emission tomography/computed tomography. Twenty-nine patients underwent living-donor liver transplant, and 12 patients underwent deceased-donor liver transplant. One of the 41 patients with negative FDG-imaging results had no evidence of hepatocellular carcinoma in the explant and was excluded from the study. The patients' average age was 58 years (range, 22-72 y), and 28 patients were men. The cause of liver disease was hepatitis C virus in 24 patients, cryptogenic cirrhosis in 12 patients, and hepatitis B virus in 5 patients. One patient had no hepatocellular carcinoma on explants and was excluded from the study. Twenty-five patients had hepatocellular carcinoma that met the Milan criteria, 7 were within the UCSF (University of California, San Francisco) criteria, and 8 exceeded the UCSF criteria. Of the 40 patients, 11 had positive fluorodeoxyglucose-positron emission tomography/computed tomography results (27.5%) with evidence of hepatocellular carcinoma in the explant; the remaining 29 patients (72.5%) had negative results. The fluorodeoxyglucose-positron emission tomography/computed tomography results were positive in 16% (4 of 21) of patients who met the Milan criteria, 28% (2 of 7) of patients who met the UCSF criteria and 62% (5 of 8) of patients who exceeded the UCSF criteria. Fluorodeoxyglucose-positron emission tomography/computed tomography has a low degree of use in patients with hepatocellular carcinoma that falls within the Milan criteria and should not be routinely used as part of the liver transplant work-up.


Mortality from accidental falls among the elderly in the United States, 1962-1988: demonstrating the impact of improved trauma management.
Falls in elderly persons primarily occur because of increasing intrinsic frailty rather than extrinsic environmental hazards. Thus declining mortality from accidental falls in the elderly predominantly reflects improved trauma management rather than injury prevention. Mortality attributed to accidental falls among individuals aged 60 to 85 years in the United States from 1962 through 1988 was analyzed using the Strehler-Mildvan modification of the Gompertz relationship of aging and mortality. This method of analysis can be used to define a disorder-specific age at which etiopathogenic influences are directly proportional to the mortality rate. From 1962 through 1988, the mortality rates (per 100,000) from accidental falls in the United States declined 63.5% (from 165.6 to 60.4) among men at age 83.4 years, and declined 76.3% (from 86.2 to 20.4) among women at age 77.5 years. This analysis suggests that trauma management, at the population level, was 2.74 times more effective in men and 4.22 times more effective in women at reducing mortality from accidental falls among the elderly in 1988 than in 1962.