Doppler echocardiographic assessment of left ventricular filling pressures in elderly patients with moderate/severe aortic stenosis.
Doppler-derived mitral inflow indices reflect left ventricular (LV) filling pressures but often vary with age. Diastolic filling is impaired in LV pressure overload states. The objective of this study was to determine the influence of age on the relationship between mitral inflow indices and LV filling pressures in patients with aortic stenosis. The authors studied 57 consecutive patients (age, 77 years; 52% male) with moderate to severe aortic stenosis (aortic valve area < or =1.0 cm(2)) on cardiac catheterization and echocardiographic studies performed within 48 hours of catheterization. Patients with atrial fibrillation, aortic insufficiency, mitral stenosis, and paced rhythm were excluded. Echocardiographic variables obtained from five cardiac cycles were: E/A ratio and deceleration time (DT). Patients were subclassified by age (< and > or =75 years), ejection fraction ([EF] < and > or =50%), and coronary artery disease (CAD). Pulmonary capillary wedge pressure (PCWP) correlated with DT (r=-0.86; p=0.001) and with E/A (r=0.7; p=0.001) more strongly than did LV end-diastolic pressure. Age did not alter the relationship between DT and PCWP (r=-0.92; p=0.001 for < 75 years vs. r=-0.83; p=0.001 for > or =75 years). PCWP was predicted by the equation PCWP=-0.10DT+43, regardless of age. EF also had little influence on the correlation between PCWP and DT (r=-0.80; p=0.001 for EF < 50% vs. r=-0.94; p=0.001 for EF > or =50%). Similarly, there were no significant differences between the regression equations and correlations between the CAD and no-CAD groups: for CAD patients, PCWP=41.8-0.10DT; p < 0.0001; r=-0.84 (p < 0.0001). For no-CAD subjects, PCWP=46.2-0.12DT; p < 0.0001; r=20.92 (p < 0.0001). In patients with significant aortic stenosis, DT correlated strongly with PCWP but not with LV end-diastolic pressure. This relationship was independent of age, CAD, or EF.


Antibiotic use as an inducer of resistant urinary tract infections.
Urinary tract infection is second in frequency only to respiratory infection as an indication for antimicrobial chemotherapy. As a result, a significant proportion of both domiciliary and hospital patient populations are exposed to chemotherapy which, in turn, may act as a potent selection pressure for development of resistance mediated by intrinsic mechanisms or acquisition of R-plasmids or transposons. The widespread use of broad spectrum agents has encouraged the development of such resistance in enterobacteria, notably but not exclusively amongst the Klebsiella-Enterobacter-Serratia group, leading to the creation of patient reservoirs of multiply-antibiotic-resistant bacteria. Such situations occur frequently in urological units, amongst catheterised individuals receiving chemotherapy, and, via cross-infection, may rapidly spread to other units and other hospitals. The use of antibiotic combinations, such as co-trimoxazole, may not prevent such problems, which are however amenable to policies which restrict, either selectively or globally, antibiotic use. Such policies can be expected to control the spread of multiply-antibiotic-resistant infection.


Sex-Specific Association between Metabolic Abnormalities and Elevated Alanine Aminotransferase Levels in a Military Cohort: The CHIEF Study.
The association of metabolic syndrome (MetS) components with elevated serum alanine aminotransferase (ALT) levels, a marker of hepatic injury, may differ between men and women. However, the sex-specific association in a military young population which has a low prevalence of MetS was unclear. We conducted a cross-sectional examination in 6738 men and 766 women, aged 18-50 years, from the cardiorespiratory fitness study in armed forces (CHIEF) in eastern Taiwan. The components of MetS were defined according to the updated International Diabetes Federation (IDF) ethnic criteria for Asians. Elevated ALT levels were defined as ≥40 U/L for both sexes and ≥30 U/L for women alternatively. Multivariate logistic regression analysis was performed to determine the sex-specific association between MetS components and elevated ALT. The prevalence of MetS and elevated ALT in men were 11.9% and 12.7% respectively, and in women were 3.5%, and 3.8% respectively. In men, high-density lipoprotein < 40 mg/dL, blood pressures ≥ 130/85 mmHg, serum triglycerides ≥ 150 mg/dL, and waist size ≥ 90 cm were associated with elevated ALT (odds ratios (OR) and 95% confidence intervals: 1.59 (1.34-1.90), 1.40 (1.19-1.65), 2.00 (1.68-2.39), and 1.68 (1.38-2.04); all p < 0.001); whereas in women, only fasting plasma glucose ≥ 100 mg/dL was associated with elevated ALT ≥ 40 U/L (OR: 7.59 (2.35-24.51), p = 0.001) and ALT ≥ 30 U/L (2.67 (0.89-7.95), p = 0.08). Our findings suggest that the relationship between metabolic abnormalities and elevated ALT may differ by sex, possibly due to the MetS more prevalent in young adult men than in women.


Lithium carbonate pre-treatment in 131-I therapy of hyperthyroidism.
The aim of the present work was to investigate the influence of lithium carbonate on the kinetics of radioiodine in the thyroid gland, and the long-lasting effect of radioiodine therapy pre-treated with lithium carbonate in patients with different types of hyperthyreosis and low baseline 24-h thyroidal radioactive iodine uptake (RAIU). The examinations were performed in two groups of patients: in a control group with RAIU 〉 30% and in patients with RAIU 〈 30%. All groups were comparable with regard to age, sex, duration and type of disease (Graves' disease, autonomous node, multinodular goitre). The control group was treated (without lithium) according to described protocol. The second group was pre-treated with lithium carbonate in a dose of 1.0 g/day for 6 days before radioiodine and 3 days thereafter. A significant increase in iodide uptake in the thyroid gland was observed during intake of lithium carbonate in 106 out of 128 patients. A decrease of T(3), FT(3), T(4), and FT(4) levels and no significant changes in concentration of TSH were observed as an effect of lithium carbonate treatment. Three years of follow-up show that the results of radioiodine therapy with short lasting lithium carbonate intake are better in the first year and are similar in the second and third years in comparison to the control group. Lithium pre-treatment in hyperthyroid patients with low baseline uptake of radioiodine can increase iodine retention in the thyroid gland independently of the primary disease and permits the use of lower doses of radiation in the therapy.


Study of extra wide coherent optical combs generated by a QW-based integrated passively mode-locked ring laser.
We present an investigation of an InP quantum-well-based integrated extended cavity passively mode-locked laser which shows extra broad frequency comb generation. The ring laser was characterized in frequency and time domains for a range of the current levels injected in the semiconductor optical amplifier. The study showed an increase of the bandwidth to over 40 nm at the -20 dB level. The coherence between the longitudinal modes in the wide comb is demonstrated by the characterization of a spectrally filtered signal in time and RF domains. The relative time delay across the optical comb was measured.


Genetic basis of hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) was the first cardiovascular disorder in which a genetic basis was identified. The disease is characterized by a marked thickening of the left ventricle and is the most common structural cause of sudden cardiac death in those aged under 35 years. HCM is primarily a disease of the sarcomere with over 250 mutations identified currently within 13 sarcomere-related genes. At present, genetic screening is available for the genes shown to cause HCM most frequently, with a mutation pick-up rate of up to 60%. Current research is focused on the identification of additional causative genes and elucidation into signaling mechanisms involved in HCM pathogenesis, as well as investigation of modifying factors that can alter the clinical phenotype in HCM. The unifying goal of these studies is to improve our understanding of disease pathogenesis in HCM, thereby facilitating the process of new diagnostic and therapeutic approaches in patients, ultimately leading to disease prevention and possible curative treatment.


[Lesiones de mucosa bucal. Factores asociados en población infantil].
there are few systematic studies reporting the prevalence of oral mucosal lesions in children. The reported prevalence is ranging from 4.1 % to 52.6 %, probably due to differences in methodology and population. The aim was to identify the prevalence of oral mucosal lesions in children population. a cross, descriptive, retrospective study in children who attended the dental clinic San Lorenzo Atemoaya was done (January 2006-July 2009); the data was obtained from medical records. Oral mucosal lesions were recorded. Descriptive analysis and unconditional logistic regression were conducted. the sample was 367; there were 200 males (54.5 %). The median age was six years. The prevalence of oral mucosal lesions was 66.2 %. The most common lesions were cheilitis simple (41.1 %), melanotic macule (18.3 %), petechiae (16.9 %) and traumatic ulcer (12 %), without difference between sexes. The sucking lip was associated with cheilitis simple (OR 1.7, p = 0.013) and recurrent ulcers with onychophagia (OR 15.75, p = 0.026). it was observed a higher prevalence of oral mucosal lesions in children than reported in other papers. Association is confirmed between parafunctional habits and oral mucosal lesions.


Neurons from fetal rat brains contain functional luteinizing hormone/chorionic gonadotropin receptors.
Adult and neonatal rat brains contain functional LH/hCG receptors. These findings have led us to hypothesize that the fetal rat brain may also contain these receptors. To test this hypothesis, we isolated neurons from 19-day-old fetal rat brains and cultured them in chemically defined serum-free medium. The reverse transcription polymerase chain reaction amplified an expected 256-base pair size LH/hCG receptor fragment that could hybridize with a full-length LH/hCG receptor cDNA in Southern blotting. Northern blotting demonstrated that neurons contained a major 2.6 kilobase (kb) and a minor 4.3 kb transcript. Immunocytochemistry demonstrated that the neurons contained LH/hCG receptor immunostaining. Western immunoblotting showed that neurons contained an 80-kDa receptor protein that increased to a maximal level on Day 3 of culture and then gradually decreased until the 9th day of culture. Culturing neurons for 3 days in the presence of highly purified hCG resulted in a dose-dependent increase in the outgrowth of neurite processes and total cellular protein and a decrease in DNA fragmentation as compared to values in the corresponding controls. At the maximally effective hCG concentration, the number of neurite-bearing cells was increased by 53% and the total cellular protein by 60%, and DNA fragmentation decreased by 31%. In summary, this is the first study to demonstrate the presence of LH/hCG receptors and neurotrophic effects of hCG in fetal rat brain neurons. These findings imply that locally produced gonadotropins may possibly play a role in the growth and development of the fetal brain.


Draft Genome Sequence of Hoeflea sp. Strain BAL378, a Potential Producer of Bioactive Compounds.
Some phytoplankton-associated marine bacteria produce bioactive compounds. Members of the genus Hoeflea may be examples of such bacteria; however, data describing their metabolisms are scarce. Here, we report the draft genome sequence of Hoeflea sp. strain BAL378, a putative producer of bacteriocins, polyketides, and auxins, as demonstrated by genome mining.


Effectiveness of Convalescent Plasma Therapy in Severe or Critically Ill COVID-19 Patients: A Retrospective Cohort Study.
Coronavirus disease-2019 (COVID-19) is a novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); there are few specific treatments. Convalescent plasma (CP), donated by people who have recovered from COVID-19, is an investigational therapy for severe or critically ill patients with COVID-19. This retrospective cohort study evaluated the effectiveness of CP therapy in patients with severe or life-threatening cases of COVID-19 at two hospitals in Seoul, Korea, between May and September 2020. Clinical outcomes were evaluated in 20 patients with CP therapy in a descriptive manner. Additionally, the changes in cycle threshold (Ct) values of 10 patients with CP therapy were compared to those of 10 controls who had the same (±0.8) initial Ct values but did not receive CP. Of the 20 patients (mean age 66.6 years), 18 received high-dose oxygen therapy using mechanical ventilators or high-flow nasal cannulas. Systemic steroids were administered to 19 patients who received CP. The neutralizing antibody titers of the administered CP were between 1:80 and 1:10240. There were two ABO-mismatched transfusions. The World Health Organization ordinal scale score and National Institutes of Health severity score improved in half of the patients within 14 days. Those who received CP showed a higher increase in Ct values at 24 h and 72 h after CP therapy compared to controls with similar initial Ct values (p=0.002). No transfusion-related side effects were observed. CP therapy may be a potential therapeutic option in severe or critically ill patients with COVID-19.


Saliva composition and caries development during protein deficiency and beta-receptor stimulation or inhibition.
We tested the hypothesis that a low protein diet (5%) would change the conditions for synthesis and release of protein from the salivary secretory cells and increase caries development. In addition, we tested whether the simultaneous use of a beta-adrenoceptor agonist or antagonist had an additive effect. After an experimental period of nine weeks the animals fed the 5% protein diet had lower body weights, saliva secretion rates and total protein secreted per minute than a control group fed a 20% protein diet. There were greater numbers of cariogenic streptococci on the teeth and the caries scores were higher in the rats fed the low protein diet than in the rats in the control group. The beta-receptor agonist, isoproterenol, given to rats fed the 20% protein diet, caused a reduction in protein concentration and amylase activity in saliva and a slight increase in caries development. Propranolol had no effect on either saliva composition or caries development.


Evidence that adenine nucleotides modulate nucleoside-transporter function. Characterization of uridine transport in chromaffin cells and plasma membrane vesicles.
Uridine transport was investigated in cultured chromaffin cells and plasma membrane vesicles from chromaffin tissue. In intact cells, the kinetic parameters for uridine uptake were Km 150 +/- 45 microM, and Vmax 414 +/- 17 pmol . 10(6) cells-1 . min-1. This low affinity for uridine and its inhibition by low concentrations of nitrobenzylthioinosine (Ki 3 nM) and dipyridamole (Ki 54 nM) are consistent with a facilitated diffusion nucleoside transport system. The IC50 value for the adenosine transport inhibition by uridine was very high (240 microM), agreeing with the relative affinities of these nucleosides in the chromaffin cell nucleoside transport system, which was 150-fold higher for adenosine than for uridine. Uridine was significantly metabolized in chromaffin cells but not in plasma membrane vesicles. The affinity of uridine transport measured in these membrane vesicles was reproducible and similar to the affinity found for intact cells with a Km value of 185 +/- 11 microM and a Vmax value of 4.24 +/- 0.10 pmol . mg protein-1 . s-1. These membrane preparations were employed to investigate the regulatory action of ATP and other nucleotide analogues on nucleoside transport. ATP increased the Vmax value but the Km value was not significantly modified. Adenosine 5'-[beta,gamma-imino]triphosphate, 1,N6-ethenoadenosine 5'-triphosphate, and adenosine(5')-tetraphospho(5')adenosine(Ap4A) at 100 microM were able to mimic the ATP effect. These results agree with a regulatory role of ATP, and the uridine transport on chromaffin plasma membrane vesicles is a good model for analyzing the nucleoside-transporter function and regulation.


[Analysis of a weight loss program with meal replacement products on weight and biochemical markers in overweight or type I obese patients].
There are scarce data about the efficacy and security of meal replacement products as a strategy to weight loss. To evaluate the efficacy and safety of a weight loss program that includes meal replacement products. We evaluated the effect of a hypocaloric diet versus a hypocaloric diet that includes meal replacement products in 55 overweight or type I obese patients. Patients were distributed to a control group (hypocaloric diet) or an intervention group (hypocaloric diet with meal replacement products) during 8 weeks. We registered anthropometric data, smoke habit and level of physical activity. We also studied biochemical parameters at the beginning of the study, at 4th week of the study and at the end of the same. The control group lost 3.97 kg, while in the intervention group we observed a loss of 4.44 kg. These differences were not statistically significant between groups. Other anthropometric parameters as waist and hip perimeters diminished also in both groups, without differences between them. We observed also a statistically significant decrease (p=0.041) in the values of triglycerides, without differences between groups again. Meal replacement products were as effective and safe to lose weight and to modify other anthropometric parameters in a controlled dietetic program as a conventional dietetic treatment without meal replacement products.


Hydrodynamics of the new Medos aortic cannula.
Postoperative neurologic complications in cardiac surgery patients are considered to be associated with the design of an aortic cannula and its hydrodynamic profile. To gain knowledge about the hydrodynamics of a new cannula type, based on the integration of a helical stator in its tip, was the aim of the present study. Pressure gradients and back pressures of the new Medos aortic cannula were measured and compared with a commonly used single-stream cannula at varying flow rates in a mock circulation. Additionally, flow visualization was performed by ink injection. Pressure gradients across the Medos cannula were 25.5-31.8% lower at all flow rates measured when compared to the reference cannula. Back pressures of the Medos cannula were 64.1-67.9% lower than reference back pressures. The Medos cannula provides improved hydrodynamic characteristics, probably reducing the risk of atherosclerotic embolism and cerebral malperfusion by avoidance of high back pressures and sandblasting effect.


Sequence homology: a poor predictive value for profilins cross-reactivity.
Profilins are highly cross-reactive allergens which bind IgE antibodies of almost 20% of plant-allergic patients. This study is aimed at investigating cross-reactivity of melon profilin with other plant profilins and the role of the linear and conformational epitopes in human IgE cross-reactivity. Seventeen patients with melon allergy were selected based on clinical history and a positive skin prick test to melon extract. Melon profilin has been cloned and expressed in E. coli. The IgE binding and cross-reactivity of the recombinant profilin were measured by ELISA and inhibition ELISA. The amino acid sequence of melon profilin was compared with other profilin sequences. A combination of chemical cleavage and immunoblotting techniques were used to define the role of conformational and linear epitopes in IgE binding. Comparative modeling was used to construct three-dimensional models of profilins and to assess theoretical impact of amino acid differences on conformational structure. Profilin was identified as a major IgE-binding component of melon. Alignment of amino acid sequences of melon profilin with other profilins showed the most identity with watermelon profilin. This melon profilin showed substantial cross-reactivity with the tomato, peach, grape and Cynodon dactylon (Bermuda grass) pollen profilins. Cantaloupe, watermelon, banana and Poa pratensis (Kentucky blue grass) displayed no notable inhibition. Our experiments also indicated human IgE only react with complete melon profilin. Immunoblotting analysis with rabbit polyclonal antibody shows the reaction of the antibody to the fragmented and complete melon profilin. Although, the well-known linear epitope of profilins were identical in melon and watermelon, comparison of three-dimensional models of watermelon and melon profilins indicated amino acid differences influence the electric potential and accessibility of the solvent-accessible surface of profilins that may markedly affect conformational epitopes. Human IgE reactivity to melon profilin strongly depends on the highly conserved conformational structure, rather than a high degree of amino acid sequence identity or even linear epitopes identity.


Genetic background of anticyclic citrullinated peptide autoantibody production in Hungarian patients with rheumatoid arthritis.
Polymorphisms of the peptidylarginine deiminase 4 (PADI4) gene encoding for the isoenzyme that converts arginyl into citrullyl residues have been shown to contribute to susceptibility to rheumatoid arthritis (RA), depending on the population studied. We aimed at determining whether PADI4 single nucleotide polymorphisms (SNPs) are associated with RA in a Hungarian population. The relationship between anticyclic citrullinated peptide (anti-CCP) production and HLA-DRB1 alleles encoding the shared epitope (SE) was also investigated. DNA samples were obtained from RA (n = 261) patients and from control donors (n = 120). HLA-DRB1 genotyping was carried out by polymerase chain reaction (PCR) with sequence-specific priming. PAD4_92 G/C and PAD4_104 T/C SNPs were genotyped using real-time PCR allele discrimination. Autoantibodies against CCP were detected by ELISA. All healthy controls tested anti-CCP negative, whereas 171 (66%) RA patients were anti-CCP positive. No significant difference in allele or genotype frequencies were found between RA patients and controls for any of the PADI4 SNPs. Anti-CCP seropositivity was unrelated to these two SNPs. No association was found between any of the PADI4 SNPs and HLA-DRB1 subtypes. Presence of the HLA-RB1 SE alleles was significantly associated with anti-CCP seropositivity; HLA-DRB1*0401 and HLA-DRB1*1001 carriers showed the strongest association. In conclusion, our data suggest that polymorphisms of the PADI4 gene are not associated with rheumatoid arthritis and are unlikely to be responsible for the presence of anti-CCP autoantibodies in a white Hungarian population. HLA-DRB1 SE alleles, however, may significantly contribute to the genetic determination of anti-CCP production in Hungarian patients with RA.


Kernel-Based Distance Metric Learning for Supervised k -Means Clustering.
Finding an appropriate distance metric that accurately reflects the (dis)similarity between examples is a key to the success of k -means clustering. While it is not always an easy task to specify a good distance metric, we can try to learn one based on prior knowledge from some available clustered data sets, an approach that is referred to as supervised clustering. In this paper, a kernel-based distance metric learning method is developed to improve the practical use of k -means clustering. Given the corresponding optimization problem, we derive a meaningful Lagrange dual formulation and introduce an efficient algorithm in order to reduce the training complexity. Our formulation is simple to implement, allowing a large-scale distance metric learning problem to be solved in a computationally tractable way. Experimental results show that the proposed method yields more robust and better performances on synthetic as well as real-world data sets compared to other state-of-the-art distance metric learning methods.


Reproductive ability of workmen occupationally exposed to lead.
The reproductive ability of 150 men occupationally exposed to lead were studied by clinical and toxicological analysis. Subjects were divided into four groups: lead-poisoned workmen (23) and those showing a moderate (42), slight (35), or physiologic absorption (50). Findings show that (1) Lead poisoning as well as moderate increased absorption of lead decrease the fertile ability of men. An increased frequency of asthenospermia, hypospermia, and teratospermia have objectified the decrease. (2) Slight increased or physiologic absorption of lead do not significantly influence the fertile ability of workmen. (3) Hypofertility induced by lead is due, perhaps, to its direct toxic effect on the gonads, as no interference with the hypothalamopituitary axis were evidenced.


Illnesses associated with Escherichia coli O157:H7 infections. A broad clinical spectrum.
To describe the spectrum of illnesses associated with Escherichia coli O157:H7 infections. Described an outbreak that showed the broad spectrum of these infections. Reviewed the clinical findings in the other eight major outbreaks reported between 1982 and 1986. Also reviewed reports of sporadic cases. Outbreaks in communities, nursing homes, a day care center, and a kindergarten. Persons identified in outbreaks of E. coli O157:H7 infections. Escherichia coli O157:H7 infection causes bloody diarrhea (hemorrhagic colitis), nonbloody diarrhea, the hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Infection can be asymptomatic, can involve extraintestinal sites, and can be fatal. Bloody diarrhea is the commonest symptom. Most patients have severe abdominal cramps; fever is documented in less than half. Findings from fecal leukocyte examinations often suggest a noninfectious cause. Results of radiologic and colonoscopic examinations can be consistent with a diagnosis of inflammatory bowel disease or ischemic colitis. Patients at the extremes of age are at increased risk for E. coli O157:H7-associated diarrhea, the hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and death. Antimicrobial agents have not been shown to modify the illness, but there are few data on individual agents. Infection with E. coli O157:H7 should be considered in all patients with bloody diarrhea, the hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura because the infection can masquerade as gastrointestinal bleeding of noninfectious cause, the antecedent diarrhea may be resolved and forgotten by the time the hemolytic uremic syndrome or thrombotic thrombocytopenic purpura is diagnosed, and the detection of E. coli O157:H7 requires specific stool culture techniques.


The diurnal rhythm of plasma aldosterone, plasma renin activity, plasma cortisol and serum growth hormone and subnormal responsiveness of aldosterone to angiotensin-II in the patients with normotensive acromegaly.
The diurnal rhythm of plasma aldosterone concentration (PA), plasma renin activity (PRA), plasma cortisol (PC) and serum growth hormone (GH) were examined in 5 cases of normotensive acromegaly and the results were compared with the observations in normal subjects. Moreover, the response of PA to angiotensin-II infusion was studied in 6 cases of normotensive acromegaly. A normal diurnal rhythm with the lowest values in the evening or midnight and the highest values in the morning was observed in 3 of 5 cases in PA and 3 of 4 cases in PC. On the other hand, no apparent rhythm of GH was observed in any cases and that of PRA in 4 of 5 cases. Although there was a significant positive correlation between PA and PC, no significant correlation was demonstrated between PA and PRA. The response of PA to angiotensin-II fusion was significantly suppressed in normotensive acromegaly as compared to the normal subjects in spite of normal levels of PRA except for 1 case. The above observations were interpreted to suggest that the aldosterone regulation system is slightly altered in a certain number of patients with normotensive acromegaly in contrast to the normal subjects in which PRA is the main contributing factor. The low PA and suppressed response of PA toangiotensin-II infusion may suggest the defective action of angiotensin-II infusion on the adrenal gland.


Carotenoids and cancer: an update with emphasis on human intervention studies.
This article gives an overview of the current state of knowledge on the cancer preventive potential of carotenoids. Numerous retrospective and prospective epidemiological studies have shown that a high intake of carotenoid-rich fruits and vegetables is associated with a decreased risk of cancer at a number of common sites. For several other cancer sites, however, the epidemiological evidence is not very consistent. A number of mechanisms for the cancer preventive properties of carotenoids have been proposed. Conversion to retinol, possibly in posthepatic tissues, would allow an effect on cellular differentiation and proliferation, and on cell-to-cell communication. Antioxidant functions could prevent free radical-induced damage to cellular DNA and other macromolecules. Immunomodulatory effects could enhance immune surveillance in tumorigenesis. In addition, non-retinol-mediated effects of carotenoids on metabolism of carcinogens and cell-to-cell communication have been shown. Observational epidemiology cannot resolve whether associations are due to a specific carotenoid, or to an associated factor in fruits and vegetables, whereas interpretation of animal studies is hampered by uncertainties in extrapolation between species, more so because the metabolism of carotenoids in most animals differs notably from that in humans. Human intervention studies on biomarkers related to cancer risk and on cancer incidence are, therefore, necessary. Human intervention studies performed so far suggest that beta-carotene can affect carcinogenesis, though not at all stages and not at all cancer sites. Implications for future human intervention research are discussed.


Induction of the autoantigen proliferating cell nuclear antigen in T lymphocytes by a mycobacterial antigen.
Mycobacteria have been implicated in the pathogenesis of autoimmunity. To determine the potential effect of mycobacterial antigens on peripheral blood mononuclear cells (PBMC), we analyzed PBMC incubated with the acetone-precipitable fraction of Mycobacterium tuberculosis (APMT) for changes in cellular protein expression. Two-dimensional gel analysis showed induction of a 36-kD polypeptide identified as proliferating cell nuclear antigen (PCNA), a known autoantigen, after incubation with AP-MT. PCNA plays a role in cell proliferation and is expressed as a late growth regulated factor. However, its synthesis in response to AP-MT was induced as an early event. The early induction of PCNA was regulated at a posttranscriptional level and was restricted to T cells. Treatment of PBMC with known T cell mitogens, namely PHA, anti-CD3 antibodies, and staphylococcal superantigens failed to induce an early PCNA increase. The distinct characteristics of the AP-MT effect on PCNA expression suggest a separate mechanism of induction in response to AP-MT, compared with the late increase observed in response to mitogens. The induction of PCNA in response to mycobacterial antigens may represent a pathogenically relevant mechanism in autoimmunity.


Veritas filia temporis: The origins of the idea of scientific progress.
The article provides insight into the epistemological and anthropological aspect of the origination of the idea of scientific progress. It focuses on the relationship between individual's limited lifetime and the immensity of nature. The basic assumption is that the idea of scientific progress offers a solution of the epistemological problem stemming from the finding that there is no (teleological) coincidence between human cognitive abilities and the extent of nature. In order to facilitate the understanding of the origin of the idea of scientific progress, I propose distinction between the descriptive and prescriptive concepts of progress. While the descriptive notion of progress expresses the cumulative character of scientific knowledge and the superiority of the present over preceding generations, the prescriptive concept pertains to progressivist epistemology directing scientific research at the future development of knowledge. This article claims that the prevalent concept in Antiquity was the descriptive concept of scientific progress. The prescriptive notion had developed only in ancient astronomy. Early modern science was faced with similar issues as ancient astronomy - mainly the empirical finding related to the inexhaustible character of nature. Consequently to the introduction of the idea of progress, the progress of sciences became a purpose in itself - hence becoming infinite.


Proliferation of CD4CD25Foxp3 regulatory T lymphocytes in ex vivo expanded ascitic fluid from primary and recurrent ovarian carcinoma.
Regulatory T lymphocytes evoke the immune tolerance by suppressing and inactivating cytotoxic T lymphocytes. The objective of this study was to compare the proportion of regulatory T lymphocytes, precisely defined as CD4(+)CD25(high+)Foxp3(+) T lymphocytes, in primary and recurrent ovarian carcinoma before and after ex vivo expansion of ascites with interleukin-2 (IL-2). Ascitic fluid samples were obtained from 26 patients with ovarian carcinoma. Lymphocytes were isolated from ascites and cell markers were analyzed by flow cytometry using anti-CD3/CD4/CD8/CD16/CD56/CD25 and anti-Foxp3 antibodies. Lymphocytes were incubated for 2 to 3 weeks and expanded ex vivo by IL-2 stimulation and their phenotypes were analyzed by flow cytometry. Following ex vivo expansion, ascitic fluid lymphocytes increased by a greater extent in the recurrent group than in the primary group. The proportion of ex vivo-expanded lymphocytes changed as follows; CD4(+) T lymphocytes increased, CD8(+) T lymphocytes decreased, and the proportion of CD3(-)CD16(+)56(+) NK cells was unchanged. The proportion of CD4(+)CD25(high+)Foxp3(+) regulatory T lymphocytes in CD4(+) T lymphocytes increased after ex vivo expansion in both groups, but to a greater degree in the recurrent group. This study showed that regulatory T lymphocytes, neither cytotoxic T lymphocytes nor NK cells, were extensively increased after ex vivo expansion, especially in recurrent ovarian carcinoma. These results may provide information that helps to guide the future development of adoptive immunotherapy against ovarian carcinoma.


On-line three-dimensional coordinate measurement of dynamic binocular stereo vision based on rotating camera in large FOV.
A dynamic binocular stereo vision (DBSV) based on a non-zoom rotating camera in a large field of view (FOV) is established herein. A novel two-point method is proposed to estimate the initial parameters of the camera quickly. The intrinsic parameters and roll angle of each camera remains constant, and the pitch and yaw angles after the camera rotates are directly estimated from output of high-precision two-axes platform, which makes it possible that three-dimensional (3D) coordinate can be measured online after rotation. Moreover, a target matching algorithm based on moving DLT is proposed to achieve automatic alignment of the camera. The accuracy of 3D coordinate measurement is evaluated on various synthetic and real data, and the DBSV is suitable for occasions where extremely high accuracy is not required in large FOV.


Soft tissue molding technique in cleft lip and palate patient using laser surgery in combination with orthodontic appliance: A case report.
Although surgical treatment protocols for cleft lip and palate patients have been established, many patients still have some soft tissue defects after complete healing from surgical interventions. These are excess soft tissue, high attached fraena and firmed tethering scares. These soft tissue defects resulted shallowing of vestibule, restricted tooth movement, compromised periodontal health and trended to limit the maxillary growth. The aim of this case report was to present a method of correcting soft tissue defects after conventional surgery in cleft lip and palate patient by using combined laser surgery and orthodontic appliance. A bilateral cleft lip and palate patient with a clinical problem of shallow upper anterior vestibule after alveolar bone graft received a vestibular extension by using CO2 laser with ablation and vaporization techniques at 4 W and continuous wave. A customized orthodontic appliance, called a buccal shield, was placed immediately after surgery and retained for 1 month to 3 months until complete soft tissue healing. The procedures were performed 2 episodes. Both interventions used the same CO2 laser procedure. The first treatment resulted in partial re-attachment of soft tissue at surgical area. The second laser operation with the proper design of buccal shield providing passive contact with more extended flange resulting in a favorable outcome from 1 year follow up. Then the corrective orthodontic treatment could be continued effectively. The CO2 laser surgery was a proper treatment for correcting soft tissue defects and the design of buccal shield was a key for success in molding surgical soft tissue.


Mass-forming extramedullary hematopoiesis in multiple myeloma: 18F-FDG PET/CT is useful in excluding extramedullary myeloma involvement.
Extramedullary hematopoiesis (EMH), a benign condition, is usually observed in patients with hematologic disorders. We report the first case of mass-forming EMH detected on a 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scan in a patient with multiple myeloma (MM). A 58-year-old woman underwent workup for bicytopenia, and was diagnosed with MM based on the results of bone marrow aspiration and serum protein electrophoresis. An 18F-FDG PET/CT scan revealed a paravertebral mass with mild FDG avidity, suggesting a tumorous condition. Biopsy was performed to exclude malignancy and the mass was eventually confirmed as EMH. Differential diagnosis of a mildly FDG-avid paravertebral mass in MM should include EMH.


Analysis of frequency quadrupling using a single Mach-Zehnder modulator for millimeter-wave generation and distribution over fiber systems.
We comprehensively investigate three modulation techniques for the generation of millimeter-wave (mm-wave) using optical frequency quadrupling with a dual???electrode Mach-Zehnder modulator (MZM), i.e. Technique-A, Technique-B and Technique-C. For Technique-A, an RF signal drives the two electrodes of the MZM with maximum transmission bias, and this MZM is used for both the mm-wave generation and signal modulation. Technique-B is the same as Technique-A, but 180(0) phase shift between the two electrodes is applied. Technique-C is the same as Technique-B, but the MZM is only used for the mm-wave generation without signal modulation. It is found that Technique-B and Technique-C are better for frequency quadrupling than frequency doubling, tripling and sextupling. Both theoretical analysis and simulation show that the generated mm-wave suffers from constructive/destructive interaction due to fiber chromatic dispersion in Technique-A. However, the generated mm-wave is almost robust to fiber chromatic dispersion in Technique-B and Technique- C. It is found that Technique-C is the best in the quality of the generated mm-wave, especially when poor optical filtering is used. In addition, we develop a theory for calculation of Q-factor for mm-wave generation using the three modulation techniques. We consider an RF at 7.5 GHz and obtain an mm-wave at 30 GHz as an example, i.e. a frequency quadrupler. We evaluate the generation and distribution in terms of system Q-factor. The impact of RF modulation index, chromatic dispersion, MZM extinction ratio and optical filtering on Q-factor are investigated.


[Crisis of the scientific communication].
Scientific communication is undergoing radical changes. The increasingly high prices of scientific journals and other barriers limiting their accessibility are important reasons. On the internet, it is possible to archive and publicize articles with open access, thereby speeding up scientific communication and achievements. Thousands of researchers around the world and many institutions are in favour of open access, while commercial publishers fear losing their profits. The new open-access journals have a low impact factor, which is impending the transformation of the publication system.


Identification of the structural gene and nonsense alleles for adenylate cyclase in Saccharomyces cerevisiae.
Tetraploid strains of Saccharomyces cerevisiae carrying different dosages of the CYR1+ gene have been constructed. Adenylate cyclase activity observed in these tetraploid strains was proportional to the dosage of the active CYR1+ gene. Of the 57 mutants requiring adenosine 3',5'-monophosphate for growth at 35 degrees C, two allelic temperature-sensitive cyr1 mutants produced thermolabile adenylate cyclase. Crude extract and plasma membrane fraction of cyr1 mutant cells had no adenylate cyclase activity when assayed with GTP or 5'-guanylyl imidodiphosphate in the presence of Mn2+ or Mg2+. Plasma membrane and Lubrol-soluble plasma membrane fractions obtained from the temperature-sensitive cyr1 mutant were thermolabile compared with those from the wild-type strain. Three cyr1 mutants carried nonsense mutations susceptible to ochre (UAA) suppressors, SUP3 and SUP-o, and had no detectable level of adenylate cyclase activity. It is concluded that the cyr1 mutants carry lesions in the structural gene for adenylate cyclase.


Furazolidone-based triple therapy for H pylori gastritis in children.
To evaluate the furazolidone-based triple therapy in children with symptomatic H pylori gastritis. A prospective and consecutive open trial was carried out. The study included 38 patients with upper digestive symptoms sufficiently severe to warrant endoscopic investigation. H pylori status was defined based both on histology and on positive (13)C-urea breath test. Drug regimen was a seven-day course of omeprazole, clarithromycin and furazolidone (100 mg, 200 mg if over 30 kg) twice daily. Eradication of H pylori was assessed two months after treatment by histology and (13)C -urea breath test. Further clinical evaluation was performed 7 d, 2 and 6 mo after the treatment. Thirty-eight patients (24 females, 14 males) were included. Their age ranged from 4 to 17.8 (mean 10.9 +/- 3.7) years. On intent-to-treat analysis (n = 38), the eradication rate of H pylori was 73.7% (95% CI, 65.2%-82%) whereas in per-protocol analysis (n = 33) it was 84.8% (95% CI, 78.5%-91%). All the patients with duodenal ulcer (n = 7) were successfully treated (100% vs 56.2% with antral nodularity). Side effects were reported in 26 patients (68.4%), mainly vomiting (14/26) and abdominal pain (n = 13). Successfully treated dyspeptic patients showed improvement in 78.9% of H pylori-negative patients after six months and in 50% of H pylori-positive patients after six months of treatment. Triple therapy with furazolidone achieves moderate efficacy in H pylori treatment. The eradication rate seems to be higher in patients with duodenal ulcer.


Self-reported benefit, sound perception, and quality-of-life in patients with auditory brainstem implants (ABIs).
The majority of the patients used their auditory brainstem implants (ABIs) all the time, reporting that he/she would make the decision to receive an implant again if the decision were reconsidered. The findings support that the ABI is a valuable treatment in patients with type 2 neurofibromatosis (NF2) and in children with congenital inner ear and nerve anomalies or cochlear ossification. To evaluate the patients who underwent ABI implantation in Uppsala during 1993-2013. This study analyzed patients' implant use, perception of environmental sounds, perceived benefit from the implant, and quality-of-life (QoL). The NF2-patients (n = 20) comprised the majority of the patients, and there were a few non-NF2 pediatric patients (n = 4). The exclusion criteria included deceased patients (n = 4) and patients with no hearing sensations from the implant, or those with an inactivated ABI (n = 2). The data were collected from a questionnaire survey. Eleven adult patients and two pediatric patients answered the questionnaires. Eight of the adult patients used their implants 'always'. The two children always used their implants. Hearing problems had the largest negative effect on the QoL. The non-users and the users scored equally on the NFTI-QoL.


Effect of pro-inflammatory interleukin-17A on epithelial cell phenotype inversion in HK-2 cells in vitro.
Renal interstitial fibrosis (RIF) is a pathological change common to a variety of chronic renal diseases, ultimately progressing to end-stage renal failure. It is believed that epithelial cell phenotype inversion plays an important role in RIF, which is characterized by expression of the mesenchymal maker α-SMA, loss of the epithelial maker E-cadherin, and enhanced secretion of extracellular matrix. IL-17, a newly discovered pro-inflammatory cytokine, has recently been reported to play an important role in tissue fibrosis, involving pulmonary, liver, intestine and skin tissues. This study aimed to investigate whether IL-17A, a member of the IL-17 family, can induce epithelial cell phenotype inversion, and to explore the molecular mechanism of this phenotype inversion, in vitro. HK-2 cells were cultured and incubated with IL-17A. Cell proliferation was measured by CCK-8 assay, and the secretion of types I and III collagen was detected by ELISA in dose-dependent and time-dependent experiments. To find out whether IL-17A can induce epithelial cell phenotype inversion, HK-2 cells were stimulated with 80 ng/mL of IL-17A and 10 ng/mL of TGF-β1 as a positive control, for 72 h. To explore the potential signaling pathway, anti-TGF-β1 antibody was added before IL-17A treatment. At the same time, anti-TGF-β1 antibody alone was added to the medium as the negative control group. The expression of types I and III collagen, α-SMA and E-cadherin proteins, and mRNA was measured by real-time PCR, western blotting and immuno-histochemistry. IL-17A promoted the proliferation of HK-2 cells and secretion of types I and III collagen in a dose-dependent and time-dependent manner. Compared with the normal control, IL-17A could stimulate the expression of α-SMA, types I and III collagen, and suppressed the expression of E-cadherin in HK-2 cells. Incubation of IL-17A with TGF-β1 antibody decreased significantly the expression of α-SMA, but increased the expression of E-cadherin in HK-2 cells. Our results suggest that IL-17A might promote the proliferation of HK-2 cells and secretion of extracellular matrix, and induce epithelial cell phenotype inversion via a TGF-β1-dependent pathway. Blocking the pro-inflammatory cytokine IL-17A might be a potential target for the treatment of fibrotic kidney disease.


End-of-life care and social work education: what do students need to know?.
Social workers are major service providers to people who are facing end-of-life issues including the terminally ill and their families. Yet, exemplary models for social work education and intervention methods are limited in rural states. A statewide survey conducted in Kentucky found only two social work courses dedicated to end-of-life care currently being offered by accredited undergraduate and graduate institutions. Another statewide survey found that many hospice social workers are relatively inexperienced and have a need and desire for more education on death, dying and loss. Also, unique cultural, economic and geographic areas, such as Appalachia are enigmas when it comes to the provision of end-of-life care. This partnership provides a varied perspective on delivery of end-of-life care services with an emphasis on social work interventions and education.


Ryanodine receptors are part of the myospryn complex in cardiac muscle.
The Cardiomyopathy-associated gene 5 (Cmya5) encodes myospryn, a large tripartite motif (TRIM)-related protein found predominantly in cardiac and skeletal muscle. Cmya5 is an expression biomarker for a number of diseases affecting striated muscle and may also be a schizophrenia risk gene. To further understand the function of myospryn in striated muscle, we searched for additional myospryn paralogs. Here we identify a novel muscle-expressed TRIM-related protein minispryn, encoded by Fsd2, that has extensive sequence similarity with the C-terminus of myospryn. Cmya5 and Fsd2 appear to have originated by a chromosomal duplication and are found within evolutionarily-conserved gene clusters on different chromosomes. Using immunoaffinity purification and mass spectrometry we show that minispryn co-purifies with myospryn and the major cardiac ryanodine receptor (RyR2) from heart. Accordingly, myospryn, minispryn and RyR2 co-localise at the junctional sarcoplasmic reticulum of isolated cardiomyocytes. Myospryn redistributes RyR2 into clusters when co-expressed in heterologous cells whereas minispryn lacks this activity. Together these data suggest a novel role for the myospryn complex in the assembly of ryanodine receptor clusters in striated muscle.


Future Directions of Research and Care for Urinary Incontinence: Findings from the National Institute of Diabetes and Digestive and Kidney Diseases Summit on Urinary Incontinence Clinical Research in Women.
Female urinary incontinence is prevalent, costly and morbid. Participants in a NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) sponsored summit reviewed findings from NIH (National Institutes of Health) funded clinical research on urinary incontinence in women and discussed the future of urinary incontinence research. The NIDDK convened the Summit on Urinary Incontinence Clinical Research in Women on March 14, 2014. Participants representing a broad range of clinical expertise reviewed completed NIH sponsored urinary incontinence related studies, including results from community based epidemiological studies such as the BACH (Boston Area Community Health) Survey and from randomized clinical trials such as PRIDE (Program to Reduce Incontinence by Diet and Exercise), and studies conducted by the Pelvic Floor Disorders Network and the Urinary Incontinence Treatment Network. BACH Survey results improved our understanding of precursors, incidence, prevalence and natural history of urinary incontinence in a diverse group of women. The Pelvic Floor Disorders Network study found that anticholinergic medications and onabotulinumtoxinA are efficacious for treating urge urinary incontinence, and Burch colposuspension and retropubic mid urethral polypropylene slings are efficacious for decreasing stress urinary incontinence following pelvic organ prolapse surgery in women with potential stress urinary incontinence. The Urinary Incontinence Treatment Network study found that fascial slings were better than colposuspension, and that retropubic and transobturator mid urethral polypropylene slings were equivalent for stress urinary incontinence. In patients with stress urinary incontinence a preoperative urodynamic study was noninferior to basic office examinations for surgical outcome. The addition of behavioral intervention did not allow female patients to discontinue antimuscarinics for urge urinary incontinence. PRIDE showed that modest weight reductions significantly decreased urinary incontinence. Strategies for future research on urinary incontinence should include a focus on early disease, risk factor identification, better phenotyping, incorporation of new technologies, patient centered research and prevention.


Microinjected Xenopus oocytes synthesize active human plasminogen activator.
Induction of synthesis of the protease plasminogen activator (PA) by hormones, oncogenic viruses and tumor promoters occurs at the transcription level. A novel bioassay for PA messenger RNA was developed to study the regulation of PA synthesis and the genetic elements involved in it. Poly(A)-containing RNA from HEp-3, a PA-rich tumor of human origin, was found to direct the synthesis of a new proteolytic activity when microinjected into Xenopus oocytes. Newly synthesized protease can be detected within a few hours after microinjection of minute quantities of unfractionated mRNA. The new enzymatic activity is indistinguishable from human PA: it is absolutely dependent on human plasminogen; it is neutralized by serum raised against urokinase, the human urinary PA; and it comigrates with urokinase and HEp-3 PA in gel electrophoresis, exhibiting a molecular weight of 60,000.


Deletion of AcMNPV ac146 eliminates the production of budded virus.
Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac146 is a highly conserved gene in the Alpha- and Betabaculovirus genera that has an unknown function. Northern blot analysis and transcript mapping showed that ac146 is transcribed at late times post infection as a 1.2 kb mRNA. To determine the role of ac146 in the baculovirus life cycle ac146 knock out viruses were constructed. Transfection and plaque assays showed that all the ac146 deletions produced a single cell phenotype indicating that no infectious budded virus (BV) was produced, however occlusion bodies were formed. The lack of BV production was confirmed by viral titration utilizing both qPCR and TCID₅₀. Analysis of BV and occlusion derived virus (ODV) revealed that AC146 is associated with both forms of the virus and is modified specifically in ODV. This study therefore demonstrates that AC146 is a late virion associated protein and is essential for the viral life cycle.


Effect of vigabatrin on seizure control and safety profile in different subgroups of children with epilepsy.
To evaluate the efficacy and safety of vigabatrin in pediatric epilepsy. We retrospectively reviewed patients with epilepsy treated with vigabatrin over a 2-year period at a pediatric tertiary center. We assessed the relationship between seizure frequency, etiology, vigabatrin dose, adverse events, medication discontinuation reasons, and electroencephalography (EEG) characteristics. One hundred three patients followed at Boston Children's Hospital were treated with vigabatrin and had complete medical records. Within the follow-up interval, 69 (67%) of 103 patients had discontinued vigabatrin therapy. Two patients (1.9%) died during therapy for unknown reasons. Median age at vigabatrin initiation was 8 months (interquartile range [IQR] 5-15). Median starting dose was 48.1 mg/kg per day (IQR 29.8-52.3) with a median target of 100 mg/kg (IQR 81.9-107.9). Median treatment duration was 12.1 months (n = 89, IQR 5.0-22.9) overall, and 13.3 months (IQR 5.2-23.2) for patients who discontinued vigabatrin. The most common reasons for discontinuation were controlled seizures in 31 (43.7%) of 71 and unsatisfactory therapeutic effect in 23 (32.4%) of 71. Median percent seizure reduction from baseline to first follow-up was 83.3% (IQR 27.4-99.8) and 96.7% (IQR 43.3-100) to last follow-up. Twenty-four (38.7%) of 62 patients with a follow-up posttreatment remained seizure-free. Four patients who had initially achieved seizure freedom relapsed. Patients with structural/metabolic etiology had greater median percent seizure reduction at first follow-up than patients with genetic etiology (98.7% vs. 61.4%, respectively, p = 0.001). Hypsarrhythmia resolved after therapy in 18 of 20 (90%, 95% confidence interval [CI] 70-97) patients with pretreatment hypsarrhythmia, and 2 patients presented with hypsarrhythmia posttreatment. Risk of having hypsarrhythmia was reduced by 32% (95% CI 14.9-49.1) posttreatment. Vigabatrin is efficacious in all seizure types and resolved hypsarrhythmia in most patients. In this series with a median treatment duration of 12.1 months, vigabatrin had a good safety profile with a low rate of discontinuation due to nonophthalmologic and ophthalmologic adverse effects.


[Wide-spread subcutaneous emphysema after third molar extraction. Case report].
Two days after wisdom teeth removal an eighteen-year-old man complained of a painful subcutaneous neck emphysema. CT scans showed that the air collections were expanding close to the mediastinum. A conservative intravenous medication with broadspectrum antibiotics was administered and within three days the symptoms resolved completely without any surgical intervention. Subcutaneous emphysema after dental treatment can develop into infectious, potentially lethal fasciitis and mediastinitis. Therefore it must be thoroughly examined and immediately operated on, if suspicious of an infection.


Effects of cardiac-restricted overexpression of the A(2A) adenosine receptor on adriamycin-induced cardiotoxicity.
Activation of the A(2A) adenosine receptor (A(2A)R) has been shown to be cardioprotective. We hypothesized that A(2A)R overexpression could protect the heart from adriamycin-induced cardiomyopathy. Transgenic (TG) mice overexpressing the A(2A)R and wild-type mice (WT) were injected with adriamycin (5 mg.kg(-1).wk(-1) ip, 4 wk). All WT mice survived adriamycin treatment while A(2A)R TG mice suffered 100% mortality at 4 wk. Telemetry showed progressive prolongation of the QT interval, bradyarrhythmias, heart block, and sudden death in adriamycin-treated A(2A)R TG but not WT mice. Both WT and A(2A)R TG demonstrated similar decreases in heart function at 3 wk after treatment. Adriamycin significantly increased end-diastolic intracellular Ca(2+) concentration in A(2A)R TG but not in WT myocytes (P < 0.05). Compared with WT myocytes, action potential duration increased dramatically in A(2A)R TG myocytes (P < 0.05) after adriamycin treatment. Expression of connexin 43 was decreased in adriamycin treated A(2A)R TG but not WT mice. In sharp contrast, A(2A)R overexpression induced after the completion of adriamycin treatment resulted in no deaths and enhanced cardiac performance compared with WT adriamycin-treated mice. Our results indicate that the timing of A(2A)R activation is critical in terms of exacerbating or protecting adriamycin-induced cardiotoxicity. Our data have direct relevance on the clinical use of adenosine agonists or antagonists in the treatment of patients undergoing adriamycin therapy.


Genetic evaluation of somatic cell scores for United States dairy cattle.
Increases in milk yield from genetic selection may be accompanied by correlated increases in genetic susceptibility to clinical mastitis and somatic cells. Unlike clinical mastitis, somatic cell scores can be easily determined and recorded and are related to milk loss from subclinical mastitis. Selection against high somatic cell scores should decrease incidence of clinical mastitis and provide direct economic benefits through higher milk quality premiums. Genetic evaluation for lactation means of linear somatic cell scores has been implemented by USDA and parallels that for yield traits. Because additive genetics accounts for only about 10% of differences in somatic cell scores among cows, more information is needed for the same degree of confidence in genetic estimates as for yield. Only 80% of DHIA cows currently have somatic cell records. Thus, reliabilities of somatic cell evaluations are smaller than those for yield traits. Most progress in selection for lower somatic cell scores will come through sires of cows considered as bull dams. Somatic cell evaluations may best be reported through an economic index with a small amount of emphasis on somatic cell score relative to yield traits. Greater emphasis on somatic cell scores would decrease genetic gain in yield traits, which are economically more important.


Effect of sufentanil on intracranial pressure in neurosurgical patients.
The effects of sufentanil on intracranial pressure, mean arterial pressure, cerebral perfusion pressure and heart rate were studied in 20 neurosurgical intensive care unit patients. Epidural intracranial pressure probes were implanted in patients who suffered head injury, intracerebral haemorrhage or underwent tumour resection. Sufentanil was given intravenously in sequential doses of 0.5, 1.0 and 2.0 micrograms/kg. Fifteen minutes elapsed after each dose. The patients were allocated to either group 1 (baseline intracranial pressure less than 20 mmHg) or group 2 (baseline intracranial pressure greater than 20 mmHg). Intracranial pressure did not change significantly in either group. Therefore the falls in mean arterial pressure with the highest dose in both groups and with 1.0 micrograms/kg in group 2, closely reflect corresponding reductions in cerebral perfusion pressure. As sufentanil in itself exerts no effects on intracranial pressure, concomitant haemodynamic changes are the critical factor for an adequate cerebral perfusion pressure.


Laser-Treated Surfaces for VADs: From Inert Titanium to Potential Biofunctional Materials.
Objective. Laser-treated surfaces for ventricular assist devices. Impact Statement. This work has scientific impact since it proposes a biofunctional surface created with laser processing in bioinert titanium. Introduction. Cardiovascular diseases are the world's leading cause of death. An especially debilitating heart disease is congestive heart failure. Among the possible therapies, heart transplantation and mechanical circulatory assistance are the main treatments for its severe form at a more advanced stage. The development of biomaterials for ventricular assist devices is still being carried out. Although polished titanium is currently employed in several devices, its performance could be improved by enhancing the bioactivity of its surface. Methods. Aiming to improve the titanium without using coatings that can be detached, this work presents the formation of laser-induced periodic surface structures with a topology suitable for cell adhesion and neointimal tissue formation. The surface was modified by femtosecond laser ablation and cell adhesion was evaluated in vitro by using fibroblast cells. Results. The results indicate the formation of the desired topology, since the cells showed the appropriate adhesion compared to the control group. Scanning electron microscopy showed several positive characteristics in the cells shape and their surface distribution. The in vitro results obtained with different topologies point that the proposed LIPSS would provide enhanced cell adhesion and proliferation. Conclusion. The laser processes studied can create new interactions in biomaterials already known and improve the performance of biomaterials for use in ventricular assist devices.


Seed-Specific Expression of AtLEC1 Increased Oil Content and Altered Fatty Acid Composition in Seeds of Peanut (Arachis hypogaea L.).
Peanut (Arachis hypogaea L.) is one of the major oil crops and is the fifth largest source of plant oils in the world. Numerous genes participate in regulating the biosynthesis and accumulation of the storage lipids in seeds or other reservoir organs, among which several transcription factors, such as LEAFY COTYLEDON1 (AtLEC1), LEC2, and WRINKLED1 (WRI1), involved in embryo development also control the lipid reservoir in seeds. In this study, the AtLEC1 gene was transferred into the peanut genome and expressed in a seed-specific manner driven by the NapinA full-length promoter or its truncated 230-bp promoter. Four homozygous transgenic lines, two lines with the longer promoter and the other two with the truncated one, were selected for further analysis. The AtLEC1 mRNA level and the corresponding protein accumulation in different transgenic overexpression lines were altered, and the transgenic plants grew and developed normally without any detrimental effects on major agronomic traits. In the developing seeds of transgenic peanuts, the mRNA levels of a series of genes were upregulated. These genes are associated with fatty acid (FA) biosynthesis and lipid accumulation. The former set of genes included the homomeric ACCase A (AhACC II), the BC subunit of heteromeric ACCase (AhBC4), ketoacyl-ACP synthetase (AhKAS II), and stearoyl-ACP desaturase (AhSAD), while the latter ones were the diacylglycerol acyltransferases and oleosins (AhDGAT1, AhDGAT2, AhOle1, AhOle2, and AhOle3). The oil content and seed weight increased by 4.42-15.89% and 11.1-22.2%, respectively, and the levels of major FA components including stearic acid, oleic acid, and linoleic acid changed significantly in all different lines.


Triage of women with ASCUS and LSIL cytology: use of qualitative assessment of p16INK4a positive cells to identify patients with high-grade cervical intraepithelial neoplasia.
The identification of a small percentage of high-grade cervical intraepithelial neoplasias (HGCIN) among patients with minor cytological abnormalities (atypical squamous cells of undetermined significance [ASCUS] and/or low-grade squamous intraepithelial lesions [LSIL] group) is a major problem in cytology-based cervical cancer screening. The authors investigated the efficacy of p16INK4a as a biomarker to identify samples of patients with HGCIN among those with an ASCUS or LSIL result in Papanicolaou cytology. Consecutive liquid-based cytology specimens of 137 ASCUS and 88 LSIL results were selected from gynecologists who adopted a triage regimen with biopsy under colposcopy 2 months later, independent of the p16INK4a result. p16INK4a stained slides were prepared and independently read by 2 observers, who used a recently described score to categorize p16INK4a stained squamous cells. The endpoint of the study was detection of a biopsy-confirmed HGCIN. The overall sensitivity and specificity of p16INK4a positive cells with a nuclear score >2 for diagnosis of HGCIN in ASCUS and LSIL cases combined was 96% and 83%, respectively. The sensitivity and specificity in the ASCUS group was 95% and 84%, and 100% and 81% in the LSIL group, respectively. Two observers had a high concordance in assessing p16INK4a stained cells (kappa value of 0.841). These data suggested that the use of p16INK4a as a biomarker combined with nuclear scoring of p16INK4a positive cells in cervical cytology to triage ASCUS and/or LSIL cases allows identification of HGCIN with good sensitivity and specificity.


Depression and its pharmacological management.
Clinical factors of importance in the treatment of primary affective disorder with antidepressants are reviewed, and the selection of drugs is discussed on both clinical and biological grounds. Two recently validated neuro-endocrine tests used in the assessment of major depressive disorder are referred to, and research trends with regard to the neurobiology of these disorders are commented upon.


Sweat testing for heroin and metabolites in a heroin maintenance program.
Recent advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional biological materials such as sweat. In a study conducted during a heroin maintenance program, 14 subjects had sweat patches applied, then received intravenously two or three doses of heroin hydrochloride ranging from 80 to 1000 mg/day. The sweat patch was applied 10 min before the first dosage and removed approximately 24 h later, minutes before the next dosage. Absorbent pads were stored at -20 degrees C in plastic tubes until analysis. The target drugs were extracted in 5 mL of acetonitrile in the presence of 100 ng each of heroin-d9, 6-acetylmorphine-d3, and morphine-d3. After agitation for 30 min, the acetonitrile solution was divided into two portions: 2 mL for heroin testing and the remainder for testing for the other compounds. After evaporation, the residue of the first portion was reconstituted in 35 microL of acetonitrile; the second was derivatized by silylation with 40 microL of N,O-bis(trimethylsilyl)trifluoroacetamide containing 10 mL/L trimethylchlorosilane. Drugs were analyzed by GC-MS in electron impact mode. Concentrations (nanograms per patch) ranged from 2.1 to 96.3 for heroin, 0 to 24.6 for 6-acetylmorphine, and 0 to 11.2 morphine. Except in one case, heroin was the major drug present in sweat, followed by 6-acetylmorphine and morphine. We observed no correlation between the doses of heroin administered and the concentrations of heroin measured in sweat.


Sociodemographic Disparities in Mercury Exposure from United States Coal-Fired Power Plants.
Hazardous air pollutants emitted by United States (U.S) coal-fired power plants have been controlled by the Mercury and Air Toxics Standards (MATS) since 2012. Sociodemographic disparities in traditional air pollutant exposures from U.S. power plants are known to occur but have not been evaluated for mercury (Hg), a neurotoxicant that bioaccumulates in food webs. Atmospheric Hg deposition from domestic power plants decreased by 91% across the contiguous U.S. from 6.4 Mg in 2010 to 0.55 Mg in 2020. Prior to MATS, populations living within 5 km of power plants (n = 507) included greater proportions of frequent fish consumers, individuals with low annual income and less than a high school education, and limited English-proficiency households compared to the US general population. These results reinforce a lack of distributional justice in plant siting found in prior work. Significantly greater proportions of low-income individuals lived within 5 km of active facilities in 2020 (n = 277) compared to plants that retired after 2010, suggesting that socioeconomic status may have played a role in retirement. Despite large deposition declines, an end-member scenario for remaining exposures from the largest active power plants for individuals consuming self-caught fish suggests they could still exceed the U.S. Environmental Protection Agency reference dose for methylmercury.


Attenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit Hyperactivity Disorder.
It is unclear whether attention deficit hyperactive disorder (ADHD) is a hypodopaminergic or hyperdopaminergic condition. Different sets of data suggest either hyperactive or hypoactive dopamine system. Since indirect methods used in earlier studies have arrived at contradictory conclusions, we directly measured the tonic and phasic release of dopamine in ADHD volunteers. The tonic release in ADHD and healthy control volunteers was measured and compared using dynamic molecular imaging technique. The phasic release during performance of Eriksen's flanker task was measured in the two groups using single scan dynamic molecular imaging technique. In these experiments volunteers were positioned in a positron emission tomography (PET) camera and administered a dopamine receptor ligand (11)C-raclopride intravenously. After the injection PET data were acquired dynamically while volunteers either stayed still (tonic release experiments) or performed the flanker task (phasic release experiments). PET data were analyzed to measure dynamic changes in ligand binding potential (BP) and other receptor kinetic parameters. The analysis revealed that at rest the ligand BP was significantly higher in the right caudate of ADHD volunteers suggesting reduced tonic release. During task performance significantly lower ligand BP was observed in the same area, indicating increased phasic release. In ADHD tonic release of dopamine is attenuated and the phasic release is enhanced in the right caudate. By characterizing the nature of dysregulated dopamine neurotransmission in ADHD, the results explain earlier findings of reduced or increased dopaminergic activity.


[Increased HDL-cholesterol level improves the prognosis in patients with coronary vasospasm].
Cardiovascular events were analyzed in the subset of 49 consecutive patients with vasospastic coronary artery disease who underwent diagnostic coronary arteriography from December, 1987 to March, 1991 to confirm coronary artery spasm during anginal attacks. During the follow-up period (30 +/- 14 months, mean +/- SEM), seven patients had cardiovascular accidents including acute myocardial infarction, unstable angina, and stroke (group A), while the remaining 42 patients were event-free (group B). Current smokers at the end of the follow-up period were more common in group A (71%) than in group B (12%) (p < 0.01). Serum total-cholesterol, low density lipoprotein cholesterol, and triglyceride levels were not significantly different between the two groups before or after the follow-up period. The baseline high-density lipoprotein cholesterol (HDL-C) level also did not differ between group A (32.5 +/- 8.3 mg/dl) and group B (41.0 +/- 12.9 mg/dl). However, the HDL-C level significantly increased during the follow-up period in group B (delta HDL-C 6.1 +/- 9.4 mg/dl) (p < 0.01), but not in group A (delta HDL-C -3.3 +/- 7.2 mg/dl). The HDL-C level at the end of the follow-up period in group A (29.2 +/- 9.0 mg/dl) was significantly lower than in group B (47.1 +/- 11.5 mg/dl) (p < 0.01). Cardiovascular accidents were significantly more common in current smokers (50%) (p < 0.01) than in current nonsmokers (5%) after the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)


Short interferon and ribavirin treatment for HCV genotype 2 or 3 infection: NORDynamIC trial and real-life experience.
Interferon-free therapy for hepatitis C virus (HCV) infection is costly, and therefore patients with advanced fibrosis are prioritized. Although coupled with considerable side effects, a large proportion of genotype 2/3 infected patients achieve a sustained virological response (SVR) following interferon-based therapy. The present study evaluates experimental clinical trial and verifying real-life data with the aim of identifying patients with a high likelihood of favorable outcome following short interferon-based treatment. The impact of established response predictors, e.g. age, ITPA and IL28B genetic variants, IP-10, liver histopathology and early viral kinetics on outcome was evaluated among HCV genotype 2/3 infected patients enrolled in the NORDynamIC trial. Similarly outcome was evaluated among Finnish and Swedish real-life genotype 2/3 infected patients treated for 12-16 weeks in accordance with national guidelines. In the NORDynamIC trial, age < 40 years or achieving HCV RNA < 1000 IU/mL day 7 were highly predictive of favorable outcome following 12 weeks therapy. Among 255 Finnish real-life patients below the age of 40 years treated for 12 weeks with interferon and ribavirin, 87% of HCV genotype 2 and 79% of genotype 3 infected patients achieved SVR, and among 117 Swedish real-life patients treated for 12-16 weeks, 97% of HCV genotype 2 and 94% of genotype 3 infected achieved SVR. Short interferon-based therapy offers a high likelihood of achieving SVR for selected HCV genotype 2/3 infected patients, and is an acceptable option given that a thorough discussion of the side effects is provided prior to initiation.


Allele-specific HLA-B*15 typing by PCR-SSP and its application to four distinct ethnic populations.
We present a set of primer mixes for the allele-specific typing of the HLA-B*15 group by PCR-SSP. The set comprises 46 primer mixes which are designed to unequivocally resolve all but two of the 666 possible combinations of the B*15 alleles, B*1501-37 (B*1536 sequence unavailable). A core subset of 34 of the 46 mixes can be used alone to give a high resolution B*15 typing set. This allows for the identification of each B*15 allele when present as the only B*15 allele and the majority of the possible B*15 homozygotic combinations. The method was validated using reference DNA samples and the B*15 allele frequency in 4 distinct ethnic populations was investigated. The results show that these populations contain predominantly mutually exclusive sets of B*15 alleles.


In Situ Synthesis Strategy for Hierarchically Porous Ni2P Polyhedrons from MOFs Templates with Enhanced Electrochemical Properties for Hydrogen Evolution.
The development of highly active and stable noble metal-free electrocatalysts of hydrogen evolution reaction (HER) under both acidic and basic conditions for renewable-energy conversion techniques is of great significance. Herein, a practical in situ synthesis strategy for a three-dimensional Ni2P polyhedron with a hierarchically porous structure was presented, which was efficiently obtained from a nickel centered metal-organic frameworks (MOF-74-Ni) by direct low-temperature phosphorization. The as-prepared Ni2P polyhedron showed a high BET surface area (175.0 m2·g-1), hierarchically porous property, and outstanding metal dispersion, which well inherited the morphology and porosity of its MOF precursor. Compared with Ni2P particles obtained from a nonporous precursor, the as-prepared Ni2P polyhedron used as electrocatalyst exhibited excellent electrocatalytic performance toward the HER, with a low overpotential of 158 mV to produce the cathodic current density of 10 mA cm-2. A small Tafel slope of 73 mV per decade is obtained for Ni2P polyhedron, which revealed a Volmer-Heyrovsky mechanism during the HER. In addition, benefiting from the structural stability, the porous Ni2P polyhedron used as a electrocatalyst showed satisfactory long-term durability for the HER in acidic media.


Revisiting Recent Tissue Engineering Technologies in Alveolar Cleft Reconstruction.
Tissue engineering and regenerative medicine have received significant attention in treating degenerative disorders and presented unique opportunities for researchers. The latest research on tissue engineering and regenerative medicine to reconstruct the alveolar cleft has been reviewed in this study. Three approaches have been used to reconstruct alveolar cleft: Studies that used only stem cells or biomaterials and studies that reconstructed alveolar defects by tissue engineering using a combination of stem cells and biomaterials. Stem cells, biomaterials, and tissue-engineered constructs have shown promising results in the reconstruction of alveolar defects. However, some contrary issues, including stem cell durability and scaffold stability, were also observed. It seems that more prospective and comprehensive studies should be conducted to fully clarify the exact dimensions of the stem cells and tissue engineering reconstruction method in the therapy of alveolar cleft.


Left-Behind Children's Subtypes of Antisocial Behavior: A Qualitative Study in China.
As a result of the recent decades of urbanization and industrialization, millions of people have migrated to cities in search of better work opportunities in China. Meanwhile, their children have often been left behind in the care of other family members. To classify the subtypes of antisocial behavior of the left-behind children, this qualitative study interviewed a total of 71 participants, including five groups: left-behind children, parents, teachers, principals and community workers. The findings showed that left-behind children's antisocial behavior is manifested as the type of limited adolescent antisocial behavior, and the three subtypes of left-behind children's antisocial behavior were rule-breaking behavior, delinquent behavior and criminal behavior. In addition, the development of children's antisocial behavior could range from general violations to delinquent behaviors and even to criminal behaviors.


The Evolution of the Wechsler Memory Scale: A Selective Review.
In clinical use since 1940, the Wechsler Memory Scale was formally introduced to the psychological community in 1945 . By 1946, it ranked 90th out of the 100 most frequently used psychological tests. By 1969, it was the 19th most used psychological test and the 2nd most used test of memory. By 1982, it was the 12th most used test and the most used memory test-a popularity it continues to enjoy. The present article will briefly trace the origin of the Wechsler Memory Scale and examine its evolution across the revisions that appeared in 1987 , 1997 , and 2009 . Issues with norming and standardization, as well as reliability and validity, will be summarized. It is argued that the test continues to have several serious shortcomings, including a lack of anchoring in an explicit neuroanatomical theory of memory and an underlying factor structure that appears to have changed little despite changes in the manifest structure and content of the test.


Update in mild traumatic brain injury.
There has been concern for many years regarding the identification of patients with mild traumatic brain injury (TBI) at high risk of developing an intracranial lesion (IL) that would require neurosurgical intervention. The small percentage of patients with these characteristics and the exceptional mortality associated with mild TBI with IL have led to the high use of resources such as computerised tomography (CT) being reconsidered. The various protocols developed for the management of mild TBI are based on the identification of risk factors for IL, which ultimately allows more selective indication or discarding both the CT application and the hospital stay for neurological monitoring. Finally, progress in the study of brain injury biomarkers with prognostic utility in different clinical categories of TBI has recently been incorporated by several clinical practice guidelines, which has allowed, together with clinical assessment, a more accurate prognostic approach for these patients to be established.


[Prevention and treatment of cytomegalovirus infections after graft of allogenic bone marrow].
Cytomegalovirus (CMV) infection is the most frequent cause of lethal infection after bone marrow transplantation. Viremia occurs in 50% of patients seropositive for CMV before transplantation. Interstitial pneumonitis due to CMV occurs in 10% to 20% of patients with 85% mortality. It is known that CMV infection is due to host reactivation of latent CMV infection or to the transmission of the virus by the marrow donor or by blood transfusions. Treatment of CMV infection has been disappointing in the past. All attempts to treat CMV pneumonia with available agents have failed. Recent studies have indicated the usefulness of prophylactic measures and the early treatment of CMV infections. The use of hyperimmune gammaglobulins has given contradictory results. The selection of seronegative marrow donors or blood donors is useful only if the recipient is seronegative. New antiviral drugs have been used recently in preliminary clinical trials. In preliminary studies a guanosine analogue similar to Acyclovir (DHPG Synthex or BWB 759 U Wellcome) has given reasonable hope of disease cure if it is used early before the occurrence of pneumonia. Phosphonoformate (Foscarnet) has also been shown to be active against CMV infection. Both drugs have good antiviral and clinical action in immunosuppressed patients but the results have been disappointing in cases of pneumonia. Relapse occurs frequently after cessation of the treatment and attempts are being made to use maintenance therapy.


Short-term caloric restriction and sites of oxygen radical generation in kidney and skeletal muscle mitochondria.
Mitochondrial free radical generation is believed to be one of the principal factors determining aging rate, and complexes I and III have been described as the main sources of reactive oxygen species (ROS) within mitochondria in heart, brain, and liver. Moreover, complex I ROS generation of heart and liver mitochondria seems especially linked to aging rate both in comparative studies between animals with different longevities and in caloric restriction models. Caloric restriction (CR) is a well-documented manipulation that extends mean and maximum longevity. One of the factors that appears to be involved in such life span extension is the reduction in mitochondrial free radical generation at complex I. We have performed two parallel investigations, one studying the effect of short-term CR on oxygen radical generation in kidney and skeletal muscle (gastrocnemius) mitochondria and a second one regarding location of mitochondrial ROS-generating sites in these same tissues. In the former study, no effect of short-term caloric restriction was observed in mitochondrial free radical generation in either kidney or skeletal muscle. The latter study ruled out complex II as a principal source of free radicals in kidney and in skeletal muscle mitochondria, and, similar to previous investigations in heart and liver organelles, the main free radical generators were located at complexes I and III within the electron transport system.


Antimicrobial activity of various ethanolic plant extracts against pathogenic multi drug resistant Candida spp.
A total of 50 Candida isolates were isolated and identified from clinical specimens and these were tested for resistance to various antifungal drugs. It was observed multi-drug resistance in all candida isolates by 84%, 62%, 60%, 76%, 46, 30%, and 22% against fluconazole, clotrimazole, Amphotericin B, itraconazole, ketoconazole, miconazole and nystatin tested respectively. The isolates, which were found to be resistant to antifungal drugs were selected and subjected to antifungal testing against six ethanolic plants, extract namely Azadiracta indica, Allium sativum, Cordia dichotoma Ocimum sanctum, Syzygium cumini and Trigonella foenum grecum. All the plant extracts tested were found to effective against all MDR Candida isolates with inhibition zone ranging from 10- 18mm in diameter. Ethanolic extract of Allium sativum was observed most effective against the isolates among all the plants extracts tested. The minimum inhibitory concentration (MIC) of all ethanolic plant extract was recorded ranging from 1.56-25mg/ml against MDR candida isolates. Phytochemical analysis of the alcoholic plant extracts revealed the presence of alkaloid, flavanoid, glycosoid, phenol; phenol, tannins, saponins in all the plants studied. The present study may be successful in identifying the plants with different antimicrobial activity. These plants containing various phytochemicals may be exploited in the treatment of infectious diseases caused by drug-resistant microorganisms.


On the encapsulation of nickel clusters by molecular nitrogen.
The structures and energetic effects of molecular nitrogen adsorbates on nickel clusters are investigated using an extended Huckel model coupled with two models of the adsorbate-nickel interaction. The potential parameters for the adsorbates are chosen to mimic experimental information about the binding strength of nitrogen on both cluster and bulk surface phases of nickel. The first model potential is a simple Lennard-Jones interaction that leads to binding sites in holes defined by sets of near-neighbor nickel atoms. The second model potential has a simple three-body form that forces the model nitrogen adsorbates to bind directly to single nickel atoms. Significant rearrangement of the core nickel structures are found in both models. A disconnectivity graph analysis of the potential energy surfaces implies that the rearrangements arise from low transition state barriers and the small differences between available isomers in the nickel core.


[Surgical results of T4 lung cancer invading left atrium and great vessels].
To analyzed the indication and prognostic factors of surgical treatment of lung cancer invading left atrium and great vessels (T4). We retrospectively reviewed the database of 136 T4 lung cancer (tumors invading left atrium and great vessels) patients who received surgical treatment in Cancer Hospital of Chinese Academy of Medical Science (CAMS) from September 1981 to January 2007. There are 114 men and 22 women, the median age was 58 years (range 28 - 76). All patients were divided into three subgroups according to the invading site: tumor invading left atrium group, tumor invading superior vena cava group and tumor invading pulmonary artery group. All patients were divided into two subgroups according to the character of operation: complete resection group and incomplete resection group. Patients were divided into three subgroups according to pathological lymph node status: N0, N1 and N2 group. One hundred and thirty six lung cancer patients received resection of primary lesions plus arterioplasty of pulmonary artery (PA) (n = 83) and/or angioplasty of superior vena cava (SVC) (n = 21) and/or partial resection of left atrium (LA) (n = 32). Complete resection was possible in 120 patients and 16 patients underwent incomplete resection. Five-year survival was 43.0% for entire group, 52. 8% for PA group, 18.2% for SVC group and 18.4% for LA group. Factors significantly influencing the overall 5-year survival were the pathologic N status (5-year survival 15.1% for N2, 5-year survival 44.9% for N1, 5-year survival 74% for N0 group; N2 versus N1 versus N0, P = 0.028) and the completeness of resection (5-year survival 37.5% for complete resection, 5-year survival 22.4% for incomplete resection group; complete versus incomplete, P = 0.042). Pathological lymph node status but not histology and character of operation was an independent prognostic factor using Cox regression analysis (P = 0.01, RR = 1.923, 95% CI: 1.172 -3. 157). Pathological lymph node status is an independent prognostic factor for T4 lung cancer. Patients with pathological N0-1 lung cancer invading left atrium and great vessels (T4) may benefit from surgical treatment. In the preoperative workup, every possible effort should be made to achieve a careful evaluation of mediastinal lymph noda status. Compared with incomplete resection group, complete resection group may have a better prognosis. Tumor invading extrapericardial PA may be defined as T2.


Angiotensin I-converting enzyme inhibitor activity of nutritive plants in KwaZulu-Natal.
Traditional herbal remedies still form an integral part of South African culture, hence necessitating reports on the scientific rationale for their uses. Organic and aqueous extracts from 16 nutritive plants found in KwaZulu-Natal, South Africa were screened for angiotensin I-converting enzyme (ACE) inhibitory activity using a fluorometric enzyme assay. A plant was considered to have potential antihypertensive properties if it inhibited the ACE enzyme and thus the conversion of angiotensin I to angiotensin II by greater than 50%. Eight of the 16 plants screened demonstrated ACE inhibitory activity and satisfied these criteria. These eight plants were then subjected to a gelatin salt block test for tannins to show that the ACE inhibitory activities were not due to the presence of tannins, as tannins also inhibit ACE activity. The plants that showed ACE inhibitory activity were Amaranthus dubius, Amaranthus hybridus, Asystasia gangetica, Galinsoga parviflora, Justicia flava, Oxygonum sinuatum, Physalis viscosa, and Tulbaghia violacea. T. violacea in particular shows promise with regards to ACE inhibition as in vivo administration of this extract showed only a 2.2% increase in maximum mean arterial pressure when compared to the 14.5% increase observed in the control group after co-administration with exogenous Ang I.


Species identification of Enterococcus spp: Whole genome sequencing compared to three biochemical test-based systems and two Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) systems.
Here, we evaluated the performance of two commercial MALDI-TOF MS systems and three biochemical-based systems and compared them to WGS as the gold standard for identifying isolates of vancomycin-resistant enterococci (VRE). A total of 87 VRE clinical isolates were included. The mass spectrometers were the Microflex system with Biotyper software 3.1 and the Vitek MS system. The biochemical-based systems included the Vitek 2, Phoenix, and MicroScan WalkAway systems. WGS was performed on an Illumina MiSeq instrument using the MiSeq v3 reagent kit. Vancomycin resistance was determined according to CLSI criteria. Among the 87 VRE, 71 and 16 were identified as Enterococcus faecium and Enterococcus faecalis by WGS. All 71 E faecium were correctly identified by both mass spectrometers, as well as the Vitek 2 and Phoenix instruments. However, only 51 E faecium isolates were correctly identified by the MicroScan system. The most frequent misidentification was Enterococcus casseliflavus (n = 20). For vancomycin-resistant E faecium, the Microflex Biotyper system had the highest sensitivity (85.54%), and all instruments (except for the Microscan) had a 100% specificity and PPV. Up to 87% of E faecalis isolates were misidentified by VITEK MS and VITEK2, 81% by Microscan and Phoenix, and 75% by Bruker biotyper. As the coverage of type strain-genome sequence database continues to grow and the cost of DNA sequencing continues to decrease, genome-based identification can be a useful tool for diagnostic laboratories, with its superior accuracy even over MALDI-TOF and database-driven operations.


Explaining the effects of floral density on flower visitor species composition.
Floral density often influences the species composition of flower visitors. This variation in visitor species composition could have significant effects on pollination success and plant fitness but is poorly understood, especially in the many pollination guilds dominated by nonterritorial species. This article presents a foraging model that explores how flower visitors with diverse traits should distribute themselves across resource patches differing in floral density. The model predicts that species with low flower search speeds and low flower handling costs compared to those of competitors will usually dominate dense flower patches. In addition, among flower visitors that have lower energy expenditure rates while handling flowers than while traveling, species maximizing energetic efficiency are typically associated with dense flower patches, whereas those maximizing net rate of energy intake are associated with sparse patches. The model is able to predict some key aspects of a previously observed effect of floral density on species composition of flower visitors to the yellowflower tarweed (Holocarpha virgata). By providing insights into how flower visitors' traits shape the effects of floral density on the species composition of flower visitors, this study makes an important step towards understanding how pollinator diversity influences relationships between plant density and plant fitness.


Zinc-catalyzed cycloisomerizations. Synthesis of substituted furans and furopyrimidine nucleosides.
5-Endo-dig cycloisomerization of 1,4- and 1,2,4- mostly aryl-substituted but-3-yn-1-ones in the presence of a catalytic amount of zinc chloride etherate (10 mol %) in dichloromethane at room temperature gave 2,5-di- and 2,3,5-trisubstituted furans in high yields (85-97%). DSC studies confirmed that a solely thermal process does not take place. A relevant catalytic process, employing mu-oxo-tetranuclear zinc cluster Zn4(OCOCF3)6O, yielded bicyclic furopyrimidine nucleosides, when starting from acetyl-protected 5-alkynyl-2'-deoxyuridines (85-86%). Furopyrimidine was deprotected or simultaneously converted into pyrrolopyrimidine nucleoside. The time/concentration dependence for the reaction of 1-phenyl-4-(4-methylphenyl)butynone to 2-(4-methylphenyl)-5-phenylfuran displayed first-order kinetics with the rate dependent on catalyst concentration. The plot of ln k(obs) versus ln[ZnCl2] indicated first-order cycloisomerization, as referred to ZnCl2 concentration, using both NMR and UV-vis reaction monitoring. The crystal structure of propyl furopyrimidine nucleoside (orthorhombic, P2(1)2(1)2(1), a/b/c = 5.684(2)/6.682(2)/36.02(2) A, Z = 4) shows C2'- endo deoxyribose puckering, and the base is found in the anti position in crystalline form.


[Expression of ribosomal genes under the action of 5-azacytidine in the African green monkey RAMT cell line].
The use of cytosine analogue--5-Azacytidine(5AzaC), derepression of ribosomal genes has been studied in one of organising chromosomes in the African green monkey RAMT cell line in which the nucleolar organizer region (NOR) in parental cells was active. The effect of 5AzaC on the functional state of NOR was assessed by the length of the secondary constriction in this chromosome and by the intensity of Ag-staining of NOR. 5AzaC was added to the cell culture at concentrations 2-16 M, either immediately after the cell passage or at the 24th h from the beginning of cell cultivation for the following 17-34 hours. As a control the cells cultivated in the absence of 5AzaC were used. Comparison of control cells with those treated with 5AzaC showed: 1) increase of the length of the second constriction in the chromosome with the initial inactive NOR in the 5AzaC--treated cells; 2) a marked increase of the intensity of NOR's Ag-staining in the same chromosome after incorporation of 5-AzaC into DNA. The conclusion about the methylation of cytosine bases in the DNA of ribosomal genes in one NOR organising chromosomes in RAMT cell line was made.


Effect of Third-generation Dual-source CT Technology on Image Quality of Low-dose Chest CT.
Objective To evaluate the image quality and radiation dose of third-generation dual-source CT with tin filtration for spectral shaping and iterative reconstructions.Methods Thirty-five patients underwent low-dose CT (LDCT) for lung cancer screening on second-generation dual-source CT and follow-ups on third-generation dual-source CT. Image quality and radiation dose were compared between the two examinations.ResultsThe radiation dose of third-generation dual-source CT [dose-length product (DLP)(49.7±18.2)mGy·cm, effective dose (ED)(0.73±0.26)mSv] was lower than second-generation dual-source CT [DLP (86.37±13.44) mGy·cm, ED(1.20±0.42)mSv](t=6.01, P=0.000;t=6.57, P=0.000). The objective image noise of second-generation dual-source CT [(25.7±2.9)HU] was higher than that of third-generation dual-soure CT[(18.6±4.2)HU](t=5.24,P=0.000).The subjective image noise of second-generation dual-source CT [(4.60±0.49)scores] was significantly lower than that of third-generation dual-source CT [(4.80±0.40)scores] (t=4.15, P=0.000). Conclusion Chest CT for the detection of pulmonary nodules can be performed with third-generation dual-source CT that produces high image quality and low radiation dose when using a stellar infinity detector with spectral shaping.


Baroreceptor effects on renal and adrenal nerve activity.
Spontaneous efferent discharges were recorded from nerve filaments dissected from adrenal and renal nerve bundles in the rabbit. Raising of the systemic blood pressure or stimulation of the depressor nerve caused a decrease in discharge rate in these nerve filaments. Portal vein occlusion or elevation of mesenteric venous pressure caused a depression of activity in these nerves. It is suggested that adrenal and renal sympathetic nerve cells receive inputs from baroreceptors in the systemic arterial system and from mechanoreceptors in the portal and mesenteric veins that cause reflex inhibition of activity in these nerve cells.