Herbal products and conventional medicines used by community-residing older women.
There is a risk of interaction between herbal products and conventional medications, therefore, more needs to be known about the use of herbals by older persons. The purpose of this research was to explore the use of herbal products for medicinal purposes and to compare differences in the demographic characteristics and health status of herbal product users and nonusers among community-dwelling older women. In 1998, a random sample of 86 women aged 65 years and older who lived independently in a North Central Florida county was selected. Names were obtained from the Florida State Department of Highway Safety and Motor Vehicles. Structured interviews using questionnaires were completed for 86 subjects. The interview questionnaire addressed health status and the use of conventional medicines, use of herbal products, and demographic data. Findings indicated that herbal products were used by 45% of the sample in the previous 12 months. The average number of herbal products used by the 45% was 2.5. Herbal products were used to prevent health problems (41%), to treat illness (23%), and for both prevention and treatment (36%). The women reported using an average of 3.2 prescribed medicines and 3.8 nonprescribed medicines. No differences in demographic characteristics and health status were found for users and nonusers of herbal products except that herbal product users were more concerned with memory problems than nonusers. No difference in perceived seriousness of memory problems existed between the two groups. It is important for health care providers to be knowledgeable about the use of herbal products to provide comprehensive health care to older women.


A computational model of the effect of symplastic growth on cell mechanics in a linear leaf blade.
The epidermis of a linear leaf, as in Poaceae, is established by parallel files of cells originating from the leaf base. Their feature is symplastic growth where neighboring cell walls adhere and do not slide along each other. We developed a simple mechanical cell-based model for symplastic growth of linear leaf blade. The challenge is to determine what restrictions on cell size symplastic growth creates compared to the free growing cells. We assume an unidirectional growing cell ensemble starting from a meristem-like layer of generative cells and then generating parallel cell rows from every cell of the initial layer. Each cell is characterized by its growth function, and growth of the whole leaf blade is accompanied by mutual adjustment between all the cells. Cells divide once they have reached a threshold area. A mathematical model and its implementation are proposed for computational simulation of 1D symplastic growth of tissues. The question analyzed is how a cell grows in a plant tissue if there is a mechanism for regulating the growth of an isolated growing cell and the behavior of the cell wall matter is elastoplastic. The results of the simulation of linear leaf blade growth are compared to those for a free-growing cell population.


Factors influencing the implementation of the guideline triage in emergency departments: a qualitative study.
The objectives are: (1) to identify factors that influence the implementation of the guideline Triage in emergency departments [2004] in emergency departments in the Netherlands, and (2) to develop tailored implementation strategies for implementation of this guideline. Guideline dissemination is no guarantee for guideline implementation. In 2004 the guideline Triage in Emergency Departments was disseminated in Dutch hospitals. Guideline revision was scheduled in 2008. Prior to the revision, factors which influenced the implementation of the guideline [2004] were studied to be addressed at the implementation of the revised guideline. This is an exploratory study using a qualitative design including: a questionnaire sent to all emergency departments in the Netherlands (n = 108): four focus group interviews, including nurses and ward managers and in-depth interviews with ward managers and doctors. Based on the results, tailored implementation strategies and activities were suggested which target the identified influencing factors. Various factors at individual, social context and organisational level were identified as influencing the implementation of the 2004 version of the guideline, namely: level of knowledge; insight and skills; work preferences; motivation and/or commitment; support; informed doctors; preliminary work and arrangements for implementation; description of tasks and responsibilities; workload and resources. Ward managers, nurses and doctors mentioned similar as well as different factors. Consequently, tailored implementation strategies and activities related to education, maintenance of change, motivation and consensus-building, information, organisation and facilitation were suggested. Nurses, ward managers and doctors broadly indicated similar influencing factors, although the importance of these factors differed for the different groups. For nurses, resistance and lack of resources are most important, ward managers mentioned culture and doctors the availability of doctors at the emergency department. Insight into the barriers for implementation and tailoring implementation strategies to these barriers improves the implementation.


Molecular evolution of the mtDNA encoded rps3 gene among filamentous ascomycetes fungi with an emphasis on the Ophiostomatoid fungi.
The mitochondrial ribosomal protein S3 (rps3) gene within the fungi is extremely diverse in location and organization, some versions of this gene have been incorporated into a group I intron, others appear to have gained large insertions, microsatellite expansions, or have been invaded by homing endonucleases. Among the ascomycetes fungi the group I intron encoded version of rps3 appears to have a rather complex evolutionary history including first the acquisition of rps3 by a group I intron (mL2449), the loss of the mL2499 intron and the establishment of rps3 as a free-standing gene, and the eventual loss of the intron derived version of rps3.


Predictors of cardiovascular death in patients with a left ventricular restrictive filling pattern of the mitral inflow.
The survival, clinical and echocardiographic variables and the predictors of cardiovascular death were determined for a group of 168 patients (mean age 63+/-13 years; 65 females; mean left ventricular ejection fraction 32+/-10%) with restrictive filling of the left ventricle and depressed systolic function after a mean follow-up period of 2.7+/-1 years. Shorter deceleration time (DT) of the mitral inflow was the only variable significantly different between survivors and nonsurvivors (p<0.05) and the only predictor of death found by multivariate logistic regression analysis (odds ratio 2.2, 95% confidence interval 1.7-3.6). In this patient population, a DT of the early wave of the mitral inflow <140 ms identified the patients with the highest risk of cardiac death. DT is a practical echocardiographic parameter for risk stratification of patients with significant left ventricular systolic dysfunction and restrictive filling of the left ventricle.


[Effect of the chemical structure of low molecular weight hapten carriers on immunoreactivity].
Patients with demonstrated contact dermatitis to DNCB (dinitrochlorobenzene) were patch-tested using various dinitrophenyl (DNP) derivatives. These investigations revealed the varying sensitivities to the structural isomers DNP-L-alpha-alanine (59% positive) and DNP-beta-alanine (4% positive). These results are discussed both in connection with various sensitivity rates to other DNP compounds and published findings from the literature concerning the influence of structural factors on immune reactivity.


Detection of Agr-Type Autoinducing Peptides Produced by Staphylococcus aureus.
Strains of the Gram-positive pathogen Staphylococcus aureus can be divided into four quorum sensing (QS) groups. Membership of each group is defined by the amino acid sequence of the autoinducing peptide (AIP) QS signal molecule that is encoded within the agrBDCA genetic locus and specifically within agrD. This chapter describes the use of simple, in-cell, lux-based, bio-reporters that can be used to identify/confirm the specific agr group to which a particular S. aureus isolate belongs, as well as to assess the timing and quantity of AIP produced.


Exercise-induced ST segment elevation in a patient with effort angina pectoris and normal coronary arteries.
A 32 year old woman who complained of exercise-induced chest pain was found to have widespread elevation of the ST segment of the electrocardiogram during exercise testing. Coronary angiography demonstrated no obstructive lesions and no evidence of coronary artery spasm despite ergonovine administration, bicycle ergometry and rapid atrial pacing. Exercise thallium-201 scintigraphy demonstrated no perfusion defects despite ST segment elevation. Radionuclide blood pool imaging revealed a slight decrease in ejection fraction with exercise. The available evidence raises the possibility of small vessel coronary artery disease, either structural or vasotonic, as a cause of this patient's symptoms.


Clinical Outcomes of Patients with Small Rectal Neuroendocrine Tumors Treated Using Endoscopic Submucosal Resection with a Ligation Device.
The therapeutic strategies for small rectal neuroendocrine tumors (NETs) have not been standardized. We examined the efficacy and safety of endoscopic submucosal resection with a ligation device (ESMR-L) and the long-term outcomes after endoscopic treatment. A total of 181 patients with rectal NETs <10 mm who were treated between May 2002 and May 2017 were retrospectively enrolled. All the lesions had been resected using ESMR-L, and the follow-up strategies were determined according to the pathological examinations. The long-term outcomes after a 53-month follow-up period were also evaluated. R0 resection was achieved in 180 cases (99.4%). Lymphovascular invasion was confirmed in 67 cases (37.0%), while a curative resection was achieved in 114 cases (63.0%). One perforation (0.6%) and 11 cases with delayed bleeding (6.1%) were observed. A multivariate logistic regression analysis revealed that a tumor size > 5 mm (OR 2.06; 95% CI 1.04-4.08, p = 0.04) was a significant independent predictor of the presence of lymphovascular invasion. Of the 67 patients with non-curative resections, 11 patients underwent additional surgery; lymph node metastasis was confirmed in 2 cases (18.2%). No local or distant metastases were observed during the follow-up period in 77 patients with a curative resection, 9 patients who received additional surgery, and 50 patients with non-curative resections. ESMR-L is an easy, safe and effective treatment for rectal NETs <10 mm in diameter, and the prognosis of patients seems to be good, despite a relatively high rate of lymphovascular invasion.


Influx of 22Na through acetylcholine receptor-associated Na channels: relationship between 22Na influx, 45Ca influx and secretion of catecholamines in cultured bovine adrenal medulla cells.
The effects of carbachol, veratridine and high K on the influx of 22Na were investigated in relation to the influx of 45Ca and the secretion of catecholamines in cultured bovine adrenal medulla cells, in which stimulation of nicotinic but not muscarinic acetylcholine receptor causes the secretory response. (1) Carbachol caused a rapid influx of 22Na, influx of 45Ca and secretion of catecholamines, all of which occurred within 1 min and leveled off thereafter. Influx of 45Ca and secretion of catecholamines caused by carbachol were not inhibited by tetrodotoxin, but were greatly reduced in Na-free medium. Nicotine evoked an influx of 22Na and it was antagonized by hexamethonium and d-tubocurarine but not by tetrodotoxin. Muscarine had no effect on 22Na influx. The concentration-response curve of carbachol for 22Na influx was quite similar to that for 45Ca influx. (2) Veratridine induced a sustained influx of 22Na, influx of 45Ca and secretion of catecholamines, all of which were antagonized by tetrodotoxin. Influx of 45Ca and secretion of catecholamines due to veratridine were not observed in Na-free medium. (3) High K caused an influx of 45Ca and secretion of catecholamines but did not cause an influx of 22Na. High K-induced influx of 45Ca and secretion of catecholamines were not inhibited by tetrodotoxin nor by Na removal. (4) Magnesium, an inhibitor of voltage-dependent Ca channels, inhibited the influx of 45Ca and secretion of catecholamines caused by carbachol, veratridine and high K. These results indicate that cultured bovine adrenal medulla cells have at least three distinct ion channels: (1) nicotinic acetylcholine receptor-associated Na channels which are not inhibited by tetrodotoxin, (2) voltage-dependent Na channels which are kept activated by veratridine and inhibited by tetrodotoxin and (3) voltage-dependent Ca channels. Influx of Ca through voltage-dependent Ca channels is the common ionic event for the secretion of catecholamines caused by either carbachol, veratridine or high K. It seems that the influx of Na through acetylcholine receptor-associated Na channels as well as voltage-dependent Na channels, activates voltage-dependent Ca channels which triggers the secretion of catecholamines.


Lovastatin protects keratinocytes from DNA damage-related pro-apoptotic stress responses stimulated by anticancer therapeutics.
Oral mucositis (OM) is a relevant adverse effect of anticancer therapy involving ionizing radiation (IR) and doxorubicin (Doxo). Because DNA damage of keratinocytes is causative for the pathogenesis of OM, we aim to identify pharmacological measures for geno- and cytoprotection of keratinocytes. We investigated the influence of the lipid-lowering drug lovastatin on cell death, proliferation and DNA damage response (DDR) mechanisms of human keratinocytes following treatment with IR and Doxo. Lovastatin protected keratinocytes from the cytotoxic and genotoxic effects of IR and Doxo as shown by a diminished induction of apoptosis as well as a reduced formation and slightly improved repair of DNA damage following Doxo and IR treatment, respectively. Lovastatin selectively blocked the activation of Chk1 and ATR kinases following treatment with IR, Doxo and the ribonucleotide reductase inhibitor hydroxyurea, indicating that the statin antagonizes ATR/Chk1-regulated replicative stress responses. Part of the cytoprotective activity of lovastatin seems to rest on a delayed entry of lovastatin treated cells into S-phase. Yet, because the statin also protected non-proliferating keratinocytes from IR- and Doxo-induced cytotoxicity, cell cycle independent protective mechanisms are involved, too. Lovastatin attenuates pro-toxic DNA damage-related responses of keratinocytes stimulated by OM-inducing anticancer therapeutics. The data encourage forthcoming in vivo and clinical studies addressing the usefulness of statins in the prevention of OM.


[Effect of neonatal castration on the capacity of the cerebral neurons in the septal complex of male rats to bind sex steroids].
The influence of neonatal castration on neuron capacity to bind septal dorsal, lateral and medial nuclei, Brock's diagonal fold nucleus and terminal streak bed nucleus of radiolabeled sex steroids (3H-testosterone and 3H-estradiol) was studied. Neonatal castration performed on the 1st day of male postnatal life raised the capacity of brain septal complex neurons to uptake sex steroids, mainly 3H-testosterone. The strategic position of the septal complex in the brain and the presence of neurons taking up actively sex steroids indicated an important role of this structure of the limbic system of the brain in the formation of neural mechanisms in the regulation of sex functions in male rats.


Acute care patients discuss the patient role in patient safety.
Patient safety has been a highly researched topic in health care since the year 2000. One strategy for improving patient safety has been to encourage patients to take an active role in their safety during their health care experiences. However, little research has shed light on how patients view their roles. This study attempted to address this deficit by inductively exploring the results of a qualitative study in which patients reported their ideas about what they believe their roles should be. Patients with an overnight stay in the previous 90 days at one of three hospitals were surveyed using a mailing methodology. Of 1,040 respondents, 491 provided an open-ended response regarding what they believe the patient role should be. Qualitative analysis found several prominent themes. The largest proportion of responses (23%) suggested that patients should follow instructions given by care providers. Other prominent themes were that patients should ask questions and become informed about their conditions and treatments, and many implied that they should expect competent care. Our results suggest that patients believe they should be able to trust that they are being provided competent care, as opposed to assuming a leadership role in their safety. Our results suggest that engaging patients in safety efforts may be complex, requiring a variety of strategies. Managers must provide environments conducive to staff and patient interactions to support patients in this effort. Different types of patients may require different engagement strategies.


The effects of four acidifying sprays, vinegar, and water on canine cutaneous pH levels.
This study determined the extent and duration of cutaneous acidification caused by a single application of four acidifying sprays, vinegar, and water. Multivariate repeated measures analysis of variance revealed a significant difference between the six sprays (F = 15.3; P < or = 0.001). Linear contrast tests showed that the effects of the acidifying sprays were significantly different from vinegar and water (F = 6.0; P < or = 0.001), and vinegar was significantly different from water (F = 13.8; P < or = 0.001). The acidifying sprays decreased cutaneous pH to < 6.0 for a mean range of 50 to 65 hours, while vinegar did so for a mean of 12 hours.


[Effects of ET-1 on isolated perfused rat liver and vascular rings at two stages of cirrhosis].
To investigate the effects of ET-1 on isolated perfused rat liver and vascular rings at early and late stages of cirrhosis. Liver cirrhosis was induced by an intraperitoneal injection of 50% CCl(4) (0.3 ml/100 g, twice a week). In the 9th and 14th weekend after injecting CCl(4), the isolated perfused liver and vascular rings were performed to evaluate effects of four concentrations of ET-1 on early and late stages of cirrhosis. The Ppv of L-HC group at baseline was higher than that of E-HC group, both were higher than that of the controls. However, there showed no differences on Phv in these groups. With the concentration of ET-1 increasing, PVP was elevated accordingly in E-HC and L-HC group. L-HC group showed higher PVP compared with E-HC group, both were higher than the controls. While in isolated vascular rings, with the deteriorating of cirrhosis, the cumulative response curves showed right-shift. 0.1 nmol/L ET-1 showed mild relaxation on vascular rings in L-HC group. ET-1 can increase the PVP, especially with the deterioration of cirrhosis, there showed higher reaction compared with normal controls. The vascular rings showed low response on the contrary. So ET-1 plays an important role in the pathogenesis of portal hypertension. In view of its different roles on liver and vascular rings at early and late stages, administration of different selective antagonist of ET receptor at different stages of cirrhosis should be well considered.


In vitro and in vivo evaluation of the indoloquinone EO-9 (NSC 382 459) against human small cell carcinoma of the lung.
As the indoloquinone EO-9 has previously shown activity in several tumor model systems it was evaluated against four human small cell lung cancer cell lines by the clonogenic assay. In two cell lines (Nyh and Tol), exponential dose-response curves were achieved with both 1 h and continuous exposure, whereas no cell kill was obtained in the other two cell lines (69 and 592) when tested with 1 h incubation up to 0.25 microgram/ml. When the cells were exposed to drug in vitro, flow cytometric DNA analysis showed perturbations in the cell cycle distribution of the most sensitive cell line (Tol) at a lower EO-9 concentration than in the less sensitive cel line (592). This in vitro predicted difference in EO-9 sensitivity between two of the cell lines (592 and Tol) was confirmed when the cell lines were heterotransplanted to nude mice.


Serum changes of Ferroxidases and iron-binding capacity in pregnancy.
Serum changes of Ferroxidase I and II well as the total iron binding capacity (TIBC) and unsaturated iron binding capacity (UIBC) were measured throughout their gestation in 32 normal pregnant women. Significantly higher concentrations for all the above mentioned parameters were found as pregnancy advanced. Moreover, a significant and positive correlation between the weeks of gestation and a) serum Ferroxidase I (r:0.568 p < 0.001), d) serum Ferroxidase II (r:0.619 p < 0.001), c) serum TIBC (r:0.549 p < 0.01), and d) serum UIBC (r:0.424 p < 0.05) was found. The parallel serum changes of both ferroxidase with those of TIBC and UIBC are also shown in this study. The correlation of Ferroxidase I with TIBC (r:0.734 p < 0.001) and UIBC (r:0.536 p < 0.01) as that of Ferroxidase II with TIBC(r:0.634 p < 0.001) and UIBC (r:0.513 p < 0.01) was significant and positive. In conclusion, serum Ferroxidase I and II are progressively increased with serum TIBC and UIBC as pregnancy advances.


Expression of CD44v3 protein in human endothelial cells in vitro and in tumoral microvessels in vivo.
The most universal angiogenic cytokines (VEGF, bFGF, HGF) are all heparin-binding proteins, the function of which is dependent on cell surface heparan sulfate proteoglycans (HSPG). Several proteoglycans have been demonstrated in endothelial cells, but only glypican-1 from the cell surface HSPG subfamily was documented at protein level. Here, we show that CD44v3 is expressed in human immortalized endothelial cells [anchorage-dependent human umbilical vein endothelial cells (HUVEC) and anchorage-independent Kaposi sarcoma (KS-Imm)] at mRNA and protein level, but is absent from the primary culture of human brain microvascular endothelial cells. We have shown that CD44v3 has a large cytoplasmic pool in endothelial cells, but a limited surface expression, mainly at filopodia, colocalized with MMP-2. Angiogenic factors like VEGF or bFGF did not affect surface detection of CD44v3 suggesting a constitutive expression. The putative functional role for endothelial cell surface CD44v3 was identified in chemotaxis assay when anti-CD44v3 antibody pretreatment proved to be inhibitory for HUVEC. Furthermore, we provided evidence for the CD44v3 protein expression in human endothelial cells in vivo in peritumoral microvessels of both human melanoma and glottic cancers, suggesting a role for this part-time heparan sulfate proteoglycan in tumor induced angiogenesis.


Schizotrypanum in British bats.
Two species of Schizotrypanum, T. (S.) dionisii and T. (S.) vespertilionis, were identified from British bats. Laboratory studies on stocks of isolated trypanosomes from 5 species of bat (Pipistrellus pipistrellus, Nyctalus leisleri, N. noctula, Eptesicus serotinus and Myotis brandti) indicated that the predominant species was T. d. dionisii. Collections and dissection of the bat bug Cimex pipistrelli from bat roosts revealed flagellate infection in a total of 12 out of 20 bugs; 7 of these bugs had metacyclic trypanosomes present. C. pipistrelli and the human bed bug, C. lectularius were reared in the laboratory and allowed to feed on wild-caught bats known to be infected with T. d. dionisii. Development occurred in both species of Cimex. Cimex spp. could be used to detect subpatent Schizotrypanum infections by xenodiagnosis. This technique was used to test the parasitological status of bats collected in the wild or reared in captivity. On a single occasion an apparent transmission of T. d. dionisii to an uninfected (by xenodiagnosis) laboratory reared bat was achieved. A stock of Schizotrypanum isolated from a wild-caught C. pipistrelli collected in a N. leisteri roost was identified by DNA buoyant density centrifugation as T. (S.) vespertilionis. A P. pipistrellus known to be infected with T. d. dionisii was found to have cyst-like structures in thoracic skeletal muscle containing amastigotes. The study provided the strongest evidence yet that C. pipistrelli is the vector of Schizotrypanum in British bats.


Is elective surgery traumatic for children and their parents?
The emotional consequences of elective surgery to children and to their parents have not been sufficiently studied. The aim of the present study was to prospectively assess the prevalence and severity of post-traumatic, anxiety and depressive symptoms in this population. Forty children and adolescents consecutively admitted for elective surgery in a general hospital participated in the study. Their parents were also assessed. The assessments were made on the day of admission and surgery, and 1 and 6 months after the surgery. Minor post-traumatic symptoms of the children were noted at the first and second assessments, decreasing significantly at the 6-month assessment. Further, the prevalence of children with elevated post-traumatic symptoms decreased significantly between the first and second assessments. Parents scored highest for anxiety and depression at the first assessment. Their symptoms, however, decreased significantly within 1 month. A significant decrease between the first and second assessments was also noted in the prevalence of parents with elevated anxiety symptoms. At the 1- and 6-month follow-up assessments, there was a significant correlation between the children's symptoms and their parents'. Mild post-traumatic symptoms may accompany paediatric elective surgery and persist for at least 1 month. Parents may also manifest anxiety and depressive symptoms, which may diminish earlier, that is, immediately after the surgery or within 1 month.


Role of magnesium in the (Ca2+ + Mg2+)-stimulated membrane ATPase of human red blood cells.
(Ca2+ + Mg2+)-stimulated ATPase of human red cell membranes as a function of ATP concentration was measured at fixed Ca2+ concentration and at two different but constant Mg2+ concentrations. Under the assumption that free ATP rather than Mg-ATP is the substrate, a value for Km (for ATP) of 1-2 micron is found which is in good agreement with the value obtained in the phosphorylation reaction by A.F. Rega and P.J. Garrahan (1975. J. Membrane Biol. 22:313). Mg2+ increases both the maximal rate and the affinity for ATP, whereas Ca2+ increases the maximal rate without affecting Km for ATP. As a by-product of these experiments, it was shown that after thorough removal of intracellular proteins the adenylate kinase reaction at approximately 1 mM substrate concentration is several times faster than maximal rate of (Ca2+ + Mg2+)ATPase in red cell membranes.


Antiangiogenic mechanisms of diet-derived polyphenols.
Accumulating evidence demonstrates that polyphenols in natural products are beneficial against human lethal diseases such as cancer and metastasis. The underlying mechanisms of anti-cancer effects are complex. Recent studies show that several polyphenols, including epigallocatechin-3-gallate (EGCG) in green tea and resveratrol in red wine, inhibit angiogenesis when administrated orally. These polyphenols have direct effects on suppression of angiogenesis in several standard animal angiogenesis models. Because angiogenesis is involved in many diseases such as cancer, diabetic retinopathy and chronic inflammations, the discovery of these polyphenols as angiogenesis inhibitors has shed light on the health beneficial mechanisms of natural products, which are rich in these molecules. At the molecular level, recent studies have provided important information on how these molecules inhibit endothelial cell growth. Perhaps the greatest therapeutic advantage of these small natural molecules over large protein compounds is that they can be administrated orally without causing severe side effects. It is anticipated that more polyphenols in natural products will be discovered as angiogenesis inhibitors and that these natural polyphenols could serve as leading structures in the discovery of more potent, synthetic angiogenesis inhibitors.


Effect of pH on the denitrifying enzyme activity in pasture soils in relation to the intrinsic differences in denitrifier communities.
The effects of pH on denitrifying enzyme activity (DEA) and on the ratio of the denitrification products, N(2)O and N(2), were determined in three pasture soils differing in cattle impact. The linkage between intrinsic differences in the denitrifying communities and pH effects on relative N(2)O production was also assessed. Soil pH values were adjusted just before DEA determination to obtain soil slurries with a range of pH values. The intrinsic differences in the denitrifier communities were assessed by measuring the kinetic constants of NO(3)(-) and N(2)O reductions. DEA for all three soils was highest at pH 8.4, regardless of native soil pH. Because DEA has typically been measured at native soil pH, our results suggest that DEA might have been underestimated in many previous studies. Further, relative N(2)O production at different pH values did not differ among the soils, even though the denitrifier communities differed in their intrinsic capability to reduce NO(3)(-) all the way to N(2), suggesting that the ratio of denitrification products (N(2)O and N(2)) is pH-specific rather than soil-specific. This suggests that manipulations of soil pH will alter N(2)O fluxes from agricultural soils.


[Microbiology and epidemiology of Yersinia infections].
Eleven species are actually recognized within the genus Yersinia of which three--Y. pestis, Y. pseudotuberculosis, and certain serovars of Y. enterocolitica--are important infectious organisms for humans and warm-blooded animals. The causative agents of yersiniosis, Y. pseudotuberculosis and Y. enterocolitica, occur world-wide in areas of moderate and subtropical climate. Asymptomatically infected warm-blooded animals, causing environmental contamination, are the most important factors for the epidemiology of yersiniosis; apathogenic Yersinia species and serovars, on the other hand, are largely adapted to environmental conditions and, with regard to their ecology, independent from warm- or cold-blooded host organisms. The agents are usually transmitted by the oral route with food-stuffs as the most important vehicle of human yersiniosis. For their isolation, enrichment procedures and selective media have been developed. The organisms are identified by biochemical reactions and can be differentiated by serological and, in case of Y. enterocolitica, also by phage-typing methods. The differentiation of pathogenic and apathogenic strains is of diagnostic importance and should be routinely performed; simple tests are available for this purpose. Demonstration of antibodies against cell-wall-associated (lipopolysaccharide) or plasmid-encoded (protein) antigens may confirm the diagnosis if the causative agents failed to be isolated.


The HIV-1 Pr55 gag polyprotein binds to plastidial membranes and leads to severe impairment of chloroplast biogenesis and seedling lethality in transplastomic tobacco plants.
Chloroplast genetic engineering has long been recognised as a powerful technology to produce recombinant proteins. To date, however, little attention has been given to the causes of pleiotropic effects reported, in some cases, as consequence of the expression of foreign proteins in transgenic plastids. In this study, we investigated the phenotypic alterations observed in transplastomic tobacco plants accumulating the Pr55(gag) polyprotein of human immunodeficiency virus (HIV-1). The expression of Pr55(gag) at high levels in the tobacco plastome leads to a lethal phenotype of seedlings grown in soil, severe impairment of plastid development and photosynthetic activity, with chloroplasts largely resembling undeveloped proplastids. These alterations are associated to the binding of Pr55(gag) to thylakoids. During particle assembly in HIV-1 infected human cells, the binding of Pr55(gag) to a specific lipid [phosphatidylinositol-(4-5) bisphosphate] in the plasma membrane is mediated by myristoylation at the amino-terminus and the so-called highly basic region (HBR). Surprisingly, the non-myristoylated Pr55(gag) expressed in tobacco plastids was likely able, through the HBR motif, to bind to nonphosphorous glycerogalactolipids or other classes of lipids present in plastidial membranes. Although secondary consequences of disturbed chloroplast biogenesis on expression of nuclear-encoded plastid proteins cannot be ruled out, results of proteomic analyses suggest that their altered accumulation could be due to retrograde control in which chloroplasts relay their status to the nucleus for fine-tuning of gene expression.


Histidine sensitive variant of the blue-green alga Nostoc muscorum: response to corepressors of histidine biosynthesis.
A model has been proposed to account for growth inhibition by L-histidine in a variant strain of Nostoc muscorum. This strain has been characterized for its response to 3-amino-1,2,4-triazole and 1,2,4-triazole-3-alanine known to act as false core-pressors of the histidine biosynthesis genes. The histidine sensitive strain retained its sensitivity to triazole alanine while the inhibitory effects of aminotriazole were much reduced indicating a change in regulation of his genes. The probable interactions between nif and his genes in cyanobacteria (blue-green algae) have been discussed.


Parameters affecting the determination of mercury by anodic stripping voltammetry using a gold electrode.
The electrochemical determination of aqueous Hg(II) by anodic stripping voltammetry (ASV) at a solid gold electrode is described. The aim of this work is to optimise all factors that can influence this determination. Potential wave forms (linear sweep, differential pulse, square wave), potential scan parameters, deposition time, deposition potential and surface cleaning procedures were examined for their effect on the mercury peak shape and intensity. Five supporting electrolytes were tested. The best responses were obtained with square wave potential wave form and diluted HCl as supporting electrolyte. Electrochemical and mechanical surface cleaning, aimed at removing the amount of mercury deposited onto the gold surface, were necessary for obtaining a good performance of the electrode. Response linearity, repeatability, accuracy and detection limit were also evaluated.


Decreased plasma adiponectin levels in young obese males.
Plasma adiponectin levels are reduced in middle-aged obesity and in patients with type 2 diabetes and coronary artery disease. The purpose of this study was to investigate the effects of early-aged obesity on plasma adiponectin level. Twenty-six male college students (19.2 +/- 1.1 years, obese group: n = 15, [body mass index > 25, percent body fat > 25%], non-obese group: n = 11) participated in the present study. We measured anthropometric parameters and plasma adiponectin and leptin level. Plasma adiponectin levels in the obese group were significantly lower than those in the non-obese group (obese: 4.7 +/- 2.0 micro g/ml, non-obese: 6.8 +/- 2.2 micro g/ml, p < 0.05). On the other hand, plasma leptin levels in the obese group were significantly higher than those in the non-obese group (obese: 8.4 +/- 3.2 ng/ml, non-obese: 2.6 +/- 2.1 ng/ml, p < 0.001). Plasma adiponectin levels were significantly correlated with body weight (r = -0.415, p < 0.05) and percent body fat (r = -0.412, p < 0.05). Stepwise multiple regression analysis revealed that percent body fat was a significant independent predictor of plasma adiponectin level (r = 0.406, p < 0.05). These results show that obesity is associated with reduced plasma adiponectin even in young subjects.


Declining complication rates with flow diversion of anterior circulation aneurysms after introduction of the Pipeline Flex: analysis of a single-institution series of 568 cases.
OBJECTIVEThe second-generation Pipeline embolization device (PED), Flex, has several design upgrades, including improved opening and the ability to be resheathed, in comparison with the original device (PED classic). The authors hypothesized that Flex is associated with a lower rate of major complications.METHODSA prospective, IRB-approved, single-institution database was analyzed for all patients with anterior circulation aneurysms treated by flow diversion. The PED classic was used from August 2011 to January 2015, and the Pipeline Flex has been used since February 2015.RESULTSA total of 568 PED procedures (252 classic and 316 Flex) were performed for anterior circulation aneurysms. The average aneurysm size was 6.8 mm. Patients undergoing treatment with the Flex device had smaller aneurysms (p = 0.006) and were more likely to have undergone previous treatments (p = 0.001). Most aneurysms originated along the internal carotid artery (89% classic and 75% Flex) but there were more anterior cerebral artery (18%) and middle cerebral artery (7%) deployments with Flex (p = 0.001). Procedural success was achieved in 96% of classic and 98% of Flex cases (p = 0.078). Major morbidity or death occurred in 3.5% of cases overall: 5.6% of classic cases, and 1.9% of Flex cases (p = 0.019). On multivariate logistic regression, predictors of major complications were in situ thrombosis (OR 4.3, p = 0.006), classic as opposed to Flex device (OR 3.7, p = 0.008), and device deployment in the anterior cerebral artery or middle cerebral artery as opposed to the internal carotid artery (OR 3.5, p = 0.034).CONCLUSIONSFlow diversion of anterior circulation cerebral aneurysms is associated with an overall low rate of major complications. The complication rate is significantly lower since the introduction of the second-generation PED (Flex).


Feline heartworm (Dirofilaria immitis) infection: a statistical elaboration of the duration of the infection and life expectancy in asymptomatic cats.
A study was conducted to assess the duration and the outcome (self-cure or death) of feline heartworm infection and the life expectancy of infected cats. To be included in the study, cats had to be positive for heartworm antibody (Ab) and heartworm antigen (Ag) and had to demonstrate the presence of worms by echocardiography. Self-cure was defined as (1) negative for heartworm Ag and (2) no further visualization of worms by echocardiography. Of the 1962 eligible cats, 364 (18.5%) were positive for heartworm Ag and 131 were positive for heartworm Ag and for echocardiography diagnosis (prevalence 6.7%). None of the cats was microfilaremic. Of 43 asymptomatic cats included into the follow-up study with owners' consent, 34 (79%) self-cured and nine (21%) died. Eleven (26%) cats remained asymptomatic and self cured within 21-48 months, 23 (53%) showed symptoms but self-cured within 18-49 months, 6 (14%) died within 8-41 months of follow-up and 3 (7%) suddenly died after 38-40 months, which was related to heartworm infection. The probability for death or sudden death increased significantly with age at diagnosis, but no difference was detected by gender, survival time after diagnosis, or the presence or absence of symptoms. The presence/absence of symptoms showed significant interaction with the age at diagnosis (i.e., symptomatic cats showed increasing duration of heartworm infection along with age at diagnosis compared to that for asymptomatic cats. Heartworm-infected cats survived significantly longer than heartworm-negative cats affected by hypertrophic cardiomyopathy, chronic renal failure, or neoplastic diseases.


A path analysis on correlates of consumer trust in online health information: evidence from the health information national trends survey.
Many people look for health information online, and the Internet is the third most trusted health information source. What implications does this trust have on consumer health? Not much research has been done in this area. This study explored various health-related correlates of consumer trust in online health information, including Internet use for health, self-efficacy belief in managing one's own health, negative emotions, and subjective health status. The 2007 Health Information National Trends Survey data were analyzed. Results showed that controlling for demographics, trust in online health information was directly related to both Internet use for health and the self-efficacy belief, and was indirectly associated with negative emotions; the latter two factors in turn were associated with self-rated health.


Polymerase chain reaction for the detection of bacteremia.
Analysis of blood by polymerase chain reaction (PCR) is a more rapid and sensitive method to detect bacteremia than blood culture. The PCR was performed on blood obtained from patients during blood culture draws and on blood from normal volunteers. Eighty-seven patients provided 125 blood samples for blood culture comparison with PCR. Specific PCR primers for Staphylococcus aureus and Escherichia coli that targeted conserved regions common to gram-positive and gram-negative bacteria were used. Selective stringency conditions identified other gram-positive and gram-negative bacteria. The blood culture agreed with the PCR in 93 of the 125 patient specimens (74%). In 29 of these specimens the PCR was positive yet the blood culture was negative. When clinical information was included with positive blood culture to define sepsis in these patients and their specimens were added to the positive blood cultures the statistical accuracy of PCR was 93 per cent. Only three of the 78 specimens with negative PCR had positive blood cultures. The PCR was negative in all but one of the 50 volunteers. PCR is more sensitive than blood culture, and it can quickly rule out bacteremia.


Renin-angiotensin-aldosterone blockade for cardiovascular disease prevention.
The renin-angiotensin-aldosterone system (RAAS) plays a significant role in pathophysiology of multiple disease states. RAAS blockade is beneficial in patients with hypertension, acute myocardial infarction, chronic heart failure, stroke, and diabetic renal disease. RAAS blockade with the combination angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) has demonstrated conflicting results in recent clinical trials. This article reviews the latest evidence of isolated ACEI or ARB use, their combination, and the role of aldosterone blockers and direct renin inhibitors in patients at risk, and makes recommendations for their use in the prevention of morbidity and mortality in cardiovascular disease.


Endoscopic finding of an intramural haemorrhage in the duodenum under anticoagulant therapy with phenprocoumon.
We report a case of intramural haemorrhage in the duodenum, which was diagnosed by endoscopy and clinical findings. The typical endoscopic findings are described and illustrated. Different causes of intramural haemorrhage of the gut are discussed.


Intradural spinal teratoma: evidence for a dysembryogenic origin. Report of four cases.
Intradural spinal teratoma is a rare tumor that can be associated with dysraphic defects. Although the origin of these tumors is traditionally thought to be secondary to primordial germ cells misplaced early in embryogenesis, the pathogenesis of intraspinal teratoma remains unclear. The authors present a series of patients in whom an intradural teratoma arose at the same site as a developmental spinal cord abnormality, including a split cord malformation, myelomeningocele, and lipomyelomeningocele. It is postulated that these lesions were the result of a dysembryogenic mechanism and were not neoplastic.


Protein-coated poly(L-lactic acid) fibers provide a substrate for differentiation of human skeletal muscle cells.
Tissue engineering represents a potential method for repairing damaged skeletal muscle tissue. Extracellular matrix (ECM) proteins were evaluated for their ability to aid in cell attachment, whereas a poly(L-lactic acid) (PLLA) fiber scaffold was tested as a substrate for the differentiation of human skeletal muscle cells. In comparison to uncoated or gelatin-coated PLLA films, cell attachment increased significantly (p < 0.001) on PLLA films coated with ECM gel, fibronectin, or laminin. Myoblasts differentiated into multinucleated myofibers on ECM gel-coated PLLA fibers, and expressed muscle markers such as myosin and alpha-actinin. Oligonucleotide microarray analysis showed similar gene expression profiles for human skeletal muscle cells on ECM gel-coated PLLA fibers as to that observed for myofibers on tissue culture plates. Therefore, PLLA fibers coated with ECM proteins provide a scaffold for the development of skeletal muscle tissue for tissue engineering and cell transplantation applications.


alpha-(3,4-dimethyoxyphenyl)-3,4-dihydro-6,7-dimethoxy-alpha- [(4-methylphenyl)thio]-2(1H)-isoquinolineheptanenitrile (CL 329,753): a novel chemosensitizing agent for P-glycoprotein-mediated resistance with improved biological properties compared with verapamil and cyclosporine A.
Agents that inhibit P-glycoprotein may restore sensitivity to some antitumor drugs in cancer patients. Optimization of the specificity and potency of one class of chemosensitizing agents related to verapamil has led to the identification of alpha-(3,4-dimethyoxyphenyl)-3,4-dihydro-6, 7-dimethoxy-alpha-[(4-methylphenyl) thio]-2(1H)-isoquinolineheptanenitrile, designated CL 329,753. In vitro, 0.1 to 2.0 microM CL 329,753 restored sensitivity to drugs in the multidrug resistance (MDR) phenotype in cell lines that overexpress P-glycoprotein. CL 329,753 was greater than 10-fold more potent and efficacious than cyclosporine A or verapamil in vitro, particularly in cells that express high levels of P-glycoprotein. The enhanced activity of CL 329,753 may be related to its inability to be transported by P-glycoprotein, since low drug accumulation of cyclosporine or verapamil but not CL 329,753 was found in P-glycoprotein-containing cells, yet all three agents inhibited vinblastine binding to membranes containing P-glycoprotein and inhibited photoaffinity labeling of P-glycoprotein. In vivo, CL 329,753 resensitized drug-resistant tumors to vinblastine or doxorubicin in an ascitic or solid tumor model, respectively. No alteration in the plasma pharmacokinetic profile of doxorubicin by CL 329,753 has been found. Furthermore, the compound had 70-fold less calcium channel antagonistic activity compared with verapamil.


[The different ways of expressing the results of the monoxide test in steady state: discussion and proposition of reference values for epidemiological studies (author's transl)].
The results of the steady state carbon monoxide test can be expressed quantitatively as the amount of CO absorbed by the lung per minute and per 1 mm Hg pressure difference (TCO; ml/min/mm Hg) or as the ratios between partial pressures of CO (FICO, FECO, FACO), fractional untake coefficient (Formula: see text), From measurements taken in 141 non-smokers (mean age 47.43 +/- 6.4 years), 60 ex smokers (mean age 45.73 +/- 5.29 years) and 322 smokers (mean age 46.65 +/- 5.5 years), TCO and fractional uptakes were calculated and discussed. Considering the fact that mean TCO had a larger standard deviation that mean FUCO and that TCO had a non-Gaussian distribution, the authors chose to express the results of the test in fractional uptakes. Equations are proposed to calculated fractional uptakes.


Achiral and chiral PNP-pincer ligands with a carbazole backbone: coordination chemistry with d8 transition metals.
Two new monoanionic PNP pincer type ligands have been synthesized, the achiral 3,6-di-tert-butyl-1,8-bis((diphenyl-phosphino)methyl)-9H-carbazole CbzdiphosH (5) and the chiral 3,6-di-tert-butyl-1,8-bis(((2R,5R)-2,5-diphenylphospholan-1-yl)methyl)-9H-carbazole CbzdipholH (7), both of which were initially prepared as their borane complexes. The synthesis of CbzdiphosH is based on the reaction between the key intermediate 1,8-bis(bromomethyl)-3,6-di-tert-butyl-9H-carbazole (3) and lithium diphenylphosphide-borane complex. The chiral ligand CbzdipholH was prepared by treating 3 with lithium (2R,5R)-2,5-diphenylphospholanide-borane complex and subsequent deprotection with diethylamine. The complexation of the two ligands with nickel, palladium and rhodium was investigated, for which the conformational behavior of the ligands was found to be different. Although the arrangement of the donor atoms in all crystallographically characterized complexes is approximately square planar, the carbazole plane in Cbzdiphos complexes is inclined relative to the coordination plane. On the other hand, a helical twist is observed in Cbzdiphol complexes.


Hematopoietic cell formation in leech wound healing.
The angiogenic process in vertebrates and hirudineans has been compared. The leech Hirudo medicinalis, subjected to an angiogenic stimulus (surgical explant or cytokine treatment) responds, as a vertebrate, with the formation of an extensive network of new vessels accompanied by the production of circulating cells. The reviewed data confirm the surprising similarity between hirudinean and vertebrate processes in wound healing, and suggest that basic common events such as antigenic expressions of endothelial and hemopoietic cells, cytokine secretion and regulation as well as extracellular matrix interactions, are conserved and extended across diverse species, tissues and developmental phases.


Current concepts in the idiopathic inflammatory myopathies: polymyositis, dermatomyositis, and related disorders.
Idiopathic inflammatory myopathy, a category encompassing polymyositis, dermatomyositis, and a number of other disorders, is very uncommon, but has been the focus of intense study in the Arthritis and Rheumatism Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases for the past several years. We describe the clinical picture, stressing the need for biopsy to ensure correct diagnosis. It is especially important to recognize the treatment-resistant variant, inclusion body myositis. The extraskeletal manifestations, particularly the cardiopulmonary, oropharyngeal, gastrointestinal, and endocrine involvement, are described. The cardiopulmonary involvement, especially interstitial lung disease, arrhythmias, and cardiac failure, may dominate the clinical picture. The known causes are varied, and include drugs, toxins, and some infectious agents, however, in most cases a cause cannot yet be identified. Circumstantial evidence suggests that picornaviruses may initiate some cases in humans, and a very similar disease in mice caused by a picornavirus is actively under study. Studies of autoantibodies and cellular immune function support a central role for disordered immunity in the pathogenesis. The myositis-specific autoantibodies, especially those directed at certain enzymes important in protein synthesis (the aminoacyl-transfer RNA synthetases), are found in a clinically distinct subset of patients. Although most patients respond initially to corticosteroids, cytotoxic drugs are sometimes added when steroid toxicity or refractoriness develops. We describe several newer therapies under study for such cases and outline future directions in research.


Metabolic and endocrine changes during the reproductive cycle of dermatophagic caecilians in captivity.
The amphibian order Gymnophiona is poorly known, and studies about their reproduction are mainly comparative and descriptive, focusing on the structure of testes, ovaries and oviducts. However, to understand the reproductive processes, including those of the oviparous dermatophagic species, it is important to know the dynamics of storage and mobilization of energetic substrates to gonads and skin during the reproductive cycle of males and females, as well as the endocrine control associated. For the present study, total lipids and proteins were measured during the annual cycle in the plasma, liver, muscle, testes, ovaries and skin of Siphonops annulatus in captivity. Plasma levels of gonadal steroids (estradiol, testosterone and progesterone) were quantified by radioimmunoassay. Histological analyses of ovaries and testes were performed to classify the maturation stages of the animals during the reproductive cycle. Gonadal maturation in males and females of S. annulatus was accompanied by metabolic changes in reserve tissues, which supported gonadal development and prepared the females' epidermis for skin feeding by the offspring. Even in confinement conditions, females and males synchronized the reproductive period. However, due to the absence of environmental cues in captivity inadequate levels of the hormones responsible for gamete release were triggered, leading to a lack of reproductive success.


The role of liver resection in patients with metastatic breast cancer: a systematic review examining the survival impact.
Approximately 10% of breast cancer patients will present with solid organ metastases, while up to 30% will develop metastatic disease during their treatment course. Liver metastases are usually treated with systemic chemotherapy. Although colorectal liver metastases are routinely resected, this is not yet the standard of care for breast cancer-related liver metastases. This review examines the evidence for resection of breast cancer-related liver metastases. A systematic review identified 25 articles for inclusion, 12 papers concerning patients with isolated liver metastases, and 13 papers concerning patients with extrahepatic metastases. Data from 1080 patients were included. Two hundred eighty patients underwent hepatic resections for breast cancer-associated metastases with no extrahepatic metastases. Reported 5-year survival ranged from 24.6 to 78%. Median overall survival ranged from 29.5 to 116 months. For patients with oligometastatic disease undergoing resection, 5-year survival ranged from 21 to 57%, with median overall survival ranging from 32 to 58 months. Reported 30-day morbidity ranged from 14 to 42% for isolated and multiple metastases. Hepatic resection can be considered in the management of breast cancer patients with isolated liver metastases as well as those with oligometastatic disease.


Transcutaneous blood gas monitoring during neonatal intensive care.
To evaluate the accuracy in transcutaneous (Tc) blood gas monitoring in newborn infants, including extremely low birth weight infants, during neonatal intensive care. Tc PO(2) /PCO(2) was monitored in the neonatal intensive care unit (NICU) during stable infant conditions. In comparison, simultaneous arterial PO(2) and PCO(2) was measured. Sixty measurements were taken in 46 infants with median (range) birth weight of 0.93 (0.53-4.7) kg and at median (range) age of 8.5 (1-44) days. Comparison of measurements was performed using Bland-Altman plots, and the mean (95% CI) of the difference was calculated. Comparison was also performed in relation to body weight, postnatal age and oxygen requirement. The mean (95% CI) difference in PO(2) (TcPO(2)-aPO(2)) was 0.3 (-0.2-0.9) kPa, and the corresponding difference in PCO(2) (TcPCO(2)-aPCO(2)) was 0.4 (0.03-0.8, p < 0.05) kPa. Some differences were related to body weight, age and oxygen requirement, but these differences were small. There was good agreement between TcPO(2)/TcPCO(2) and corresponding arterial measurements. The mean difference between the methods was small and clinically acceptable in a current NICU. Tc blood gas monitoring could be recommended as a valuable complement for blood gas monitoring also in extremely low birth weight infants.


Colon PillCam: why not just take a pill?
This review article deals with the clinical value of capsule endoscopy for visualization of the colon. Since its introduction in 2006, the colon capsule endoscopy underwent major technological improvements. The improved performance of colon capsule endoscopy is reviewed based on three multicenter prospective studies. Screening patients for colonic adenomatous polyps is reasonable in patients who are unwilling to undergo conventional colonoscopy. Another prospective study proved that colon capsule endoscopy is effective in incomplete colonoscopy. Colon capsule endoscopy was shown to be superior to virtual colonography in the evaluation of patients with incomplete colonoscopy. Further improvements are expected in colon capsule endoscopy.


Effects of TGF-beta and TGF-beta neutralizing antibodies on fibroblast-induced collagen gel contraction: implications for proliferative vitreoretinopathy.
The main cause of failure after retinal reattachment surgery is proliferative vitreoretinopathy (PVR), in which contractile fibrocellular membranes form on the retinal surface and vitreous base. Recently, elevated levels of transforming growth factor-beta 2 (TGF-beta 2) were measured in the vitreous of patients with PVR, suggesting a possible association with the disease. Because neutralizing TGF-beta may prove useful in controlling this blinding disease process, the authors examined the effect of anti-TGF-beta 1 and TGF-beta 2 antibodies in TGF-beta-mediated fibroblast-induced collagen gel contraction. Rabbit dermal fibroblasts were combined with type I collagen in an in vitro model of collagen gel contraction. The authors evaluated the effect of TGF-beta 1, TGF-beta 2, and their antibodies on fibroblast-induced gel contraction. TGF-beta 1 and TGF-beta 2 equally enhanced gel contraction to an average of 6% to 7% of the control area by day 4. In contrast, gels without TGF-beta contracted only to an average of 38% of the control gels. Several anti-TGF-beta antibodies neutralized this TGF-beta-enhanced contraction, whereas control IgGs had no effect. A dose-dependent response was detected with TGF-beta 1, TGF-beta 2, and anti-TGF-beta. Because TGF-beta levels have been shown to correlate with the severity of PVR, the neutralizing action of anti-TGF-beta on TGF-beta-mediated contraction may offer further insights into the structure and function of PVR membranes and may provide clues to possible therapeutic solutions for controlling this disease process.


Psychomotor and cognitive performance in nonapneic snorers: preliminary findings.
Snoring is a common phenomenon and a primary symptom in obstructive sleep apnea syndrome, a sleep-related breathing disorder in which neuropsychological function is reported to be impaired. The first purpose of the present study was to compare cognitive and motor function in 25 heavy nonapneic snorers and 26 sleep apneics. As the basis for impairments in heavy nonapneic snorers is still unclear, the influence of nighttime breathing disturbances and morning alertness, respectively, on daytime performance was evaluated too. Nonapneic snorers exhibit more slow wave sleep and tend to have fewer changes in sleep stage than sleep apnea patients, but values for other sleep variables are similar. Snorers also show comparable alertness. Deficits in immediate visual memory and in visuospatial reasoning are not found. However, there are some indications that snorers show decreased manual dexterity and eye-hand coordination for the nonpreferred hand and that they have deficits in focused attention. In addition, snorers may show difficulties in finger-tapping speed. These performance measures tend to be associated with reduced morning alertness, except for the score on focused attention which has a tendency to be related to the nocturnal breathing disturbances.


The international standard for human interleukin-2. Calibration by international collaborative study.
Three lyophilized preparations of interleukin-2 coded 86/500, 86/564 and 86/504 have been evaluated in an international collaborative study for their suitability as an international standard. All of the preparations performed well in the different bioassay systems included in the study, and showed excellent stability on accelerated temperature degradation. Material similar to that in preparation 86/504 has served well as an interim reference reagent for interleukin-2 for 3 years. Therefore with the agreement of the study participants and the authorization of the Expert Committee on Biological Standardization of the World Health Organization, the preparation coded 86/504 was established in 1987 as the 1st international standard for interleukin-2, with a defined potency of 100 IU/ampoule.


Management and outcome of complex hypospadias repairs.
Repeated attempts at surgical repair of hypospadias may leave the penis scarred, hypovascular and shortened. We report on the clinical outcomes of our repaired complex hypospadias cases, often referred to as hypospadias cripples. We evaluated the records of 137 children and young adults from January 1980 through December 2002 who were referred to us after multiple unsuccessful hypospadias repairs. The records of 11 patients were inadequate. The ages of the remaining 126 patients ranged from 14 months to 35 years. The number of prior surgical procedures ranged from 2 to 23. Of the 126 cases 98 (78%) were repaired in a single stage (group 1) and 28 (22%) underwent multistage repairs (group 2). Major complications occurred in 17 cases (17%) in group 1 and in 2 (7%) in group 2. Major complications included repair breakdown, stricture, diverticulum and multiple fistulas. Minor complications occurred in 9 (9%) cases in group 1 and in 4 (14%) in group 2. Minor complications included a single small urethrocutaneous fistula, skin tethering, inclusion cysts and glandular irregularity. Urethral substitution using skin grafts and/or bladder mucosa resulted in a high complication rate of 32% and 37%, respectively, whereas use of buccal mucosa resulted in a 15% complication rate. Preoperative psychological counseling and discussion with other parents or patients were helpful. We no longer use free skin grafts and/or bladder mucosa for urethral substitution. Waterproofing the urethral tube was performed using either a dartos or tunica vaginalis flap. When the quality of the tissues was poor or severely scarred a 2-stage repair was performed. When resurfacing the penis local skin flaps may be insufficient or unreliable, and rotation of scrotal skin flaps or burial of the penis in the scrotum (Cecil-Culp) offers dependable skin coverage.


Immunologic regulator and effector functions in perimyocarditis, postmyocarditic heart muscle disease and dilated cardiomyopathy.
In acute perimyocarditis we found that OKIAI-positive cells were increased, and in dilated cardiomyopathy OKMI-positive cells were increased. No significant alteration in suppressor T cell activity was observed in our patients with either disease. The characteristic immunofluorescent pattern in carditis and postmyocarditic heart disease is the presence of antimyolemmal antibodies with intact rat and human cardiocytes in titers of 1:40-1:320 as antigens. The antimyolemmal fluorescence can be absorbed with the respective causative virus in Coxsackie B, influenza, mumps and EBV-myocarditis, indicating that the antibodies are a cross-reactive. AMLA-positive sera induce cytolysis of vital rat cardiocytes in vitro, suggesting that the antibodies are of pathogenetic relevance. Cytolytic serum activity could be absorbed out with the respective virus. Immunohistologic specimens obtained from patients with carditis demonstrate the fixation of IgG and IgM antibodies; IgG antibodies also occur in dilated cardiomyopathy and coronary artery disease. In dilated postmyocarditic heart disease both antimyolemmal fluorescence and cytolytic activity are preserved at a lower level when compared to carditis. These antibodies can also fix complement. In the acute phase of carditis circulating immune complexes can be demonstrated. Cellular effector mechanisms against vital cardiocytes were maintained or even slightly enhanced in carditis, postmyocarditic and primary dilated cardiomyopathy. In vitro NK cell activity against K 562, however, was decreased. This is compatible with a sustained target-specific cytotoxicity whereas reduced NK cell activity may indicate impairment of this effector organ.


Biomimetic Assembly of Vascular Endothelial Cells and Muscle Cells in Microgrooved Collagen Porous Scaffolds.
Porous scaffolds can be used to engineer three-dimensional (3D) tissues for tissue repair. Coculture of vascular endothelial cells and the cells of target tissue in porous scaffolds is promising to engineer vascularized tissue. However, it is difficult to induce regeneration of anisotropic tissues such as muscle and nerve that have well-aligned cells, blood vessels, and extracellular matrix (ECM) by using conventional porous scaffolds with homogeneous pore structures. In this study, we developed collagen porous scaffolds with parallel and concave microgrooves by using micropatterned ice template and freeze drying. Vascular endothelial cells and skeletal muscle myoblasts were cocultured on the microgrooved collagen scaffolds and control collagen scaffolds without micropattern structure. When the two types of cells were seeded at a proper ratio and concentration, the 3D microgrooved collagen scaffolds triggered spontaneous cell assembly into anisotropic muscle bundles with well-aligned tubule-like structure. Muscle cells were highly aligned in the tissue bundles, showing high expression of myosin heavy chain and incorporating the aligned tubule structure of vascular endothelial cells. Micropatterned porous scaffolds with microgrooves enabled engineering of anisotropic tissue with well-ordered tubules and could provide a platform for the study of cell assembly in micropatterned material environment.


Feeling the force: how pollen tubes deal with obstacles.
Physical forces are involved in the regulation of plant development and morphogenesis by translating mechanical stress into the modification of physiological processes, which, in turn, can affect cellular growth. Pollen tubes respond rapidly to external stimuli and provide an ideal system to study the effect of mechanical cues at the single-cell level. Here, pollen tubes were exposed to mechanical stress while monitoring the reconfiguration of their growth and recording the generated forces in real-time. We combined a lab-on-a-chip device with a microelectromechanical systems (MEMS)-based capacitive force sensor to mimic and quantify the forces that are involved in pollen tube navigation upon confronting mechanical obstacles. Several stages of obstacle avoidance were identified, including force perception, growth adjustment and penetration. We have experimentally determined the perceptive force threshold, which is the force threshold at which the pollen tube reacts to an obstacle, for Lilium longiflorum and Arabidopsis thaliana. In addition, the method we developed provides a way to calculate turgor pressure based on force and optical data. Pollen tubes sense physical barriers and actively adjust their growth behavior to overcome them. Furthermore, our system offers an ideal platform to investigate intracellular activity during force perception and growth adaption in tip growing cells.


The extracellular domain of the neurokinin-1 receptor is required for high-affinity binding of peptides.
The neurokinin-1 receptor binds neurokinin peptides with the potency order of substance P > substance K > neurokinin B. Elucidating the molecular basis of differential peptide selectivity will require the localization of the binding domain on the receptor. In the present report, mutagenesis and heterologous expression experiments reveal that a segment of the extracellular N-terminal sequence of the neurokinin-1 receptor is required for the high-affinity binding of substance P and related peptide agonists. Substitution of amino acid residues in the N-terminal region of the receptor affects the binding affinity of both intact peptides and a C-terminal substance P "analog", but not of a nonpeptide antagonist. Glycosylation of the receptor does not change the peptide binding affinity. In addition, substitution of the valine-97 residue in the rat neurokinin-1 receptor by a glutamate residue increases the binding affinity of neurokinin B but not substance P or substance K, suggesting that the second extracellular segment is involved in peptide selectivity. These results indicate that the extracellular domains of neurokinin-1 receptor play a critical role in peptide binding.


Primer on imaging technologies for cancer.
Medical images represent maps of the spatial distribution of tissue properties. Each modality probes a specific set of tissue properties such as x-ray attenuation for computed tomography, transmission of sound for ultrasound, and the rate of glucose uptake for fluorodeoxyglucose-positron emission tomography. Understanding the basic principal underlying each modality is important for developing approaches to utilize imaging in cancer research and clinical care. In addition, each modality has specific challenges related to reliable quantitation that are important to appreciate.


Aging effects on the startle response and startle plasticity in Fischer F344 rats.
The effects of aging on acoustic and airpuff startle reactivity, acoustic and airpuff startle habituation, acoustic and cross-modal (light-acoustic) prepulse inhibition (PPI), and fear-potentiated startle (FPS) were examined using 3- (Y: young), 11- (AD: adult), 17- (MA: middle-aged), and 22- (O: old) month-old Fischer F344 rats. AD rats had the highest acoustic startle reactivity with the Y and MA rats showing smaller and comparable startle levels. The O rats had diminished startle reactivity, with over a 65% reduction in responding. Airpuff startle reactivity was comparable in the Y and AD groups, while the MA and O groups had 40% and 80% reductions in airpuff startle respectively. There was an age-related increase in airpuff startle habituation. Acoustic and cross-modal PPI were reduced significantly in O rats when compared to other age groups. Finally, there were no effects of age on FPS. In summary, these studies suggest that in Fischer F344 rats, there are age-associated differences in startle reactivity, startle habituation, and PPI, but no aging effect on FPS.


Chemical fossils: the geological fate of steroids.
Steroids are used to illustrate some of the significant advances that have been made in recent years in understanding the biological origin and geological fate of the organic compounds in sediments. The precursor sterols are transformed, initially by microbial activity and later by physicochemical constraints, into thermodynamically more stable saturated and aromatic hydrocarbons in mature sediments and petroleums. The steps in this transformation result in a complex web linking biogenesis, diagenesis, and catagenesis. Indeed, the complexity and variety of biological lipids such as the steroids are evidently matched in the corresponding geolipids. The extent of preservation of the biochemical imprint in the structures and stereochemistry of these geolipids, even over hundreds of millions of years, is startling, as is the systematic and sequential nature of the geochemical changes they evidently undergo. This new understanding of molecular organic geochemistry has applications in petroleum geochemistry, where biological marker compounds are valuable in the assessment of sediment maturity and in correlation work.


Birth outcomes of women with celiac disease: a nationwide historical cohort study.
We aimed to examine birthweight, low birthweight (<2500 g), and intrauterine growth retardation in offspring of women with celiac disease in relation to their first hospitalization for the disease. This was a historical cohort study based on The Danish Medical Birth Registry data of celiac women discharged from Danish hospitals from 1977-1992. The study included 211 newborns to 127 mothers with celiac disease, and 1260 control deliveries. Before celiac women were first hospitalized the mean birthweight of their newborns was 238 g (95% confidence interval [95% CI] = 150, 325 g) lower than that of the control women, after adjustment for potential confounders. After the first hospitalization the mean birthweight for newborns of diseased women was higher than that of controls, by 67 g (95% CI = -88, 223 g) after adjustment for potential confounders. Before celiac women were first hospitalized we found an increased risk of low birthweight (odds ratio [OR] = 2.6, 95% CI = 1.3-5.5) and intrauterine growth retardation (OR = 3.4, 95% CI = 1.6-7.2). After celiac women were first hospitalized we found no increased risk of low birthweight and no babies with intrauterine growth retardation. Offspring of mothers with celiac disease had lower birthweight than expected and more than a three-fold higher risk of intrauterine growth retardation when birth occurred before the first hospitalization for the disease. After the mother's first hospitalization the birthweight was similar to controls and no increased risk of low birthweight was seen. Our study indicates that treatment of celiac women is important in the prevention of fetal growth retardation.


Side-chain effect on the structural evolution and properties of poly(9,9-dihexylfluorene-alt-2,5-dialkoxybenzene) copolymers.
The structural evolution and properties of poly(9,9-dihexylfluorene-alt-2,5-dialkoxybenzene) with different lengths of alkoxy side chains on phenylene have been systematically investigated by means of thermogravimetric analysis (TGA), X-ray diffraction (XRD), differential scanning calorimetry (DSC), polarizing light microscopy (PLM), atomic force microscopy (AFM), and cyclic voltammetry (CV) techniques. The polymer self-organizes into a lamellar structure consisting of both two- and one-layer packing, and the two-layer packing style is the dominant structure. In addition, the two-layer and one-layer packing structures also accompany the presence of planar stacking and/or crystalline and noncrystalline structures, thus maintaining the stability of the packing. PF6OC6 shows three ordered phases (two crystalline phases and one nematic phase) during the heating process. With further increase of the length of alkoxy side chains, only two ordered phases (one crystalline phase and one nematic phase) are observed and the polymers show a melting-recrystallization phenomenon, which is steadily inhibited as the length of the alkoxy side chains increases. The optical and electrochemical properties of the polymers do not exhibit noticeable dependence on the length of the alkoxy side chains. However, the thermal stability, the vibronic structures, and the full width at half-maximum (fwhm) in photoluminescence spectra of the films gradually decrease, and the oxidation onset potentials and the corresponding HOMO energy levels slightly increase with increasing length of alkoxy side chains on phenylene. These results indicate that the length variation of alkoxy side chains does not change the electronic structure of the polymer backbones, but remarkably affects the microphase separation between the flexible side chains and the conjugated backbones.


Mild iron overload effect on rat liver nuclei.
A single injection of iron-dextran significantly increased iron content in plasma, whole liver, cellular cytosol and liver nuclei. In vitro nuclear rate of Fe(3+)-EDTA reduction was not affected by the treatment. Membrane-bound enzymatic activities in the nuclei were measured after iron overload. Both NADPH- and NADH-dependent cytochrome c reductases were slightly decreased after iron overload, but cytochrome P450 was undetectable after 6 h of iron supplementation. The contents of lipid- and water-soluble antioxidants were measured in isolated nuclei from control and iron-overloaded rats. alpha-Tocopherol and beta-carotene co-elutant were decreased by 40% and 83%, respectively after 6 h of treatment. Nuclear glutathione content was not affected. The rate of generation of superoxide anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical-like species by isolated rat liver nuclei, were decreased by 50%, 40% and 60%, respectively after 6 h of iron supplementation. An identical qualitative response to iron overload was observed with NADPH and NADH. The inactivation of nuclear cytochrome P450, the significant loss in lipid-soluble antioxidants (alpha-tocopherol and beta-carotene) and the decrease in enzyme-dependent oxygen radical generation, suggest that the increase in catalytic active iron induced by iron overload could affect the cellular nuclei functionality.


Receptor binding by an H7N9 influenza virus from humans.
Of the 132 people known to have been infected with H7N9 influenza viruses in China, 37 died, and many were severely ill. Infection seems to have involved contact with infected poultry. We have examined the receptor-binding properties of this H7N9 virus and compared them with those of an avian H7N3 virus. We find that the human H7 virus has significantly higher affinity for α-2,6-linked sialic acid analogues ('human receptor') than avian H7 while retaining the strong binding to α-2,3-linked sialic acid analogues ('avian receptor') characteristic of avian viruses. The human H7 virus does not, therefore, have the preference for human versus avian receptors characteristic of pandemic viruses. X-ray crystallography of the receptor-binding protein, haemagglutinin (HA), in complex with receptor analogues indicates that both human and avian receptors adopt different conformations when bound to human H7 HA than they do when bound to avian H7 HA. Human receptor bound to human H7 HA exits the binding site in a different direction to that seen in complexes formed by HAs from pandemic viruses and from an aerosol-transmissible H5 mutant. The human-receptor-binding properties of human H7 probably arise from the introduction of two bulky hydrophobic residues by the substitutions Gln226Leu and Gly186Val. The former is shared with the 1957 H2 and 1968 H3 pandemic viruses and with the aerosol-transmissible H5 mutant. We conclude that the human H7 virus has acquired some of the receptor-binding characteristics that are typical of pandemic viruses, but its retained preference for avian receptor may restrict its further evolution towards a virus that could transmit efficiently between humans, perhaps by binding to avian-receptor-rich mucins in the human respiratory tract rather than to cellular receptors.


Plagiarism: using a collaborative approach in an online allied health professions course.
The purpose of the study was to evaluate the effectiveness of interventions to increase the awareness and understanding of plagiarism among undergraduate students enrolled in an online allied health professions course in a community college in the Midwestern United States. The results suggested that the interventions were effective in educating students about how to avoid plagiarism.


Histopathology and ultrastructure of tumours and tumour-like lesions of bone.
The monograph summarizes the most important data and experience based on the clinicopathological analysis, histological and histoenzymatic examinations of more than 1000 primary tumours and 400 tumour-like lesions of bones. The diagnosis of them has been based on the WHO classification of bone tumours which appeared to be the best in meeting the needs of diagnostic practice. However, in our collection of cases also occurred such cases which did not fit into the WHO diagnostic scheme. They included lesions the separate existence of which could be proved only recently or has remained the matter of discussion, such as periosteal osteosarcoma, clear-cell and dedifferentiated chondrosarcoma, malignant fibrous histiocytoma, the so-called parachordoma, resorptive giant-cell granuloma, reactive periostitis of tubular bones of hands and feet, and the tibial lesion reminiscent of cementifying fibroma. In the majority of types of the tumours and tumour-like lesions of bones electron microscopical examination was carried out (203 cases), the results of which are presented here in a considerable extent. On the one hand, electron microscopy facilitated the diagnosis in some cases, and, on the other hand, it proved as extremely important in solving the problems of histogenesis of some of the lesions.


Tuning Mobility Separation Factors of Chemical Warfare Agent Degradation Products via Selective Ion-Neutral Clustering.
Combining experimental data with computational modeling, we illustrate the capacity of selective gas-phase interactions using neutral gas vapors to yield an additional dimension of gas-phase ion mobility separation. Not only are the mobility shifts as a function of neutral gas vapor concentration reproducible, but also the selective alteration of mobility separation factors is closely linked to existing chemical functional groups. Such information may prove advantageous in elucidating chemical class and resolving interferences. Using a set of chemical warfare agent simulants with nominally the same reduced mobility values as a test case, we illustrate the ability of the drift-gas doping approach to achieve separation of these analytes. In nitrogen, protonated forms of dimethyl methyl phosphonate (DMMP) and methyl phosphonic acid (MPA) exhibit the reduced mobility values of 1.99 ± 0.01 cm2 V-1s-1 at 175 °C. However, when the counter current drift gas of the system is doped with 2-propanol at 20 μL/h, full baseline resolution of the two species is possible. By varying the concentration of the neutral modifier, the separation factor of the respective clusters can be adjusted. For the two species examined and at a 2-propanol flow rate of 160 μL/h, MPA demonstrated the greatest shift in mobility (1.58 cm2V-1s-1) compared the DMMP monomer (1.63 cm2V-1s-1). Meanwhile, the DMMP dimer experienced no change in mobility (1.45 cm2V-1s-1). The enhancement of separation factors appears to be brought about by the differential clustering of neutral modifiers onto different ions and can be explained by a model which considers the transient binding of a single 2-propanol molecule during mobility measurements. Furthermore, the application of the binding models not only provides a thermodynamic foundation for the results obtained but also creates a predictive tool toward a quantitative approach.


Immigrants in community colleges.
Immigrant youth and children of immigrants make up a large and increasing share of the nation's population, and over the next few decades they will constitute a significant portion of the U.S. workforce. Robert Teranishi, Carola Suárez-Orozco, and Marcelo Suárez-Orozco argue that increasing their educational attainment, economic productivity, and civic engagement should thus be a national priority. Community colleges offer one particularly important venue for achieving this objective. Because they are conveniently located, cost much less than four-year colleges, feature open admissions, and accommodate students who work or have family responsibilities, community colleges are well suited to meet the educational needs of immigrants who want to obtain an affordable postsecondary education, learn English-language skills, and prepare for the labor market. The authors explore how community colleges can serve immigrant students more effectively. Already, more immigrant students attend community colleges than any other type of post-secondary institution. But community colleges could attract even more immigrant students through outreach programs that help them to apply and to navigate the financial aid system. Federal reforms should also allow financial aid to cover tuition for English as a Second Language courses. Community colleges themselves could raise funds to provide scholarships for immigrants and undocumented students. Although there are many good ideas for interventions that can boost enrollment and improve the performance of immigrant students in community colleges, rigorous research on effective programs is scant. The research community and community colleges need to work together closely to evaluate these programs with a view toward what works and why. Without such research, policy makers will find it difficult to improve the role of community colleges in increasing the educational achievement of immigrant students.


Relationships among parents' economic stress, parenting, and young children's behavior problems.
In a time of economic recession, identifying how economic stress may be related to parenting stress, to the parenting behaviors used by mothers and fathers, and to young children's behavior problems may provide insight into interventions that may best assist families through their own economic crises. As part of this study, 124 culturally diverse parents with young children who ranged in age from 2- to 6-years rated their own economic, life, and parenting stress; their parenting behaviors; and their young children's behavior problems. Hierarchical regression analyses suggested that negative economic events and parenting stress provide unique incremental variance in predicting young children's internalizing problems, whereas life stress and parenting stress provide unique incremental variance in predicting young children's externalizing problems. With closer examination, parenting stress fully mediated the relationship between parents' financial cutbacks and young children's internalizing problems and the relationship between parents' negative economic events and young children's externalizing problems. These findings suggested that these variables are important to examine collectively.


Visfatin and Rheumatoid Arthritis: Pathogenetic Implications and Clinical Utility.
Analysis and generalization of data related to visfatin involvement in the pathogenesis of inflammation at various stages of rheumatoid arthritis. Visfatin is an adipocytokine which has been also identified in non-adipose tissues. It influences directly on maturation of B cells, which are involved in autoantibody production and T cell activation. Visfatin can promote inflammation via regulation of pro-inflammatory cytokines including TNF, IL-1β and IL-6. Concentration of circulating visfatin in rheumatoid arthritis patients is higher comparing to healthy individuals. Several studies suggest that visfatin level is associated with rheumatoid arthritis activity, and its elevation may precede clinical signs of the relapse. In murine collagen-induced arthritis visfatin levels were also found to be elevated both in inflamed synovial cells and in joint vasculature. Visfatin blockers have been shown to confer fast and long-term attenuation of pathological processes; however, most of their effects are transient. Other factors responsible for hyperactivation of immune system can participate in this process at a later stage. Treatment of rheumatoid arthritis with combination of these blockers and inhibitors of other mediators of inflammation can potentially improve treatment outcomes comparing to current therapeutic strategies. Recent advances in the treatment of experimental arthritis in mice as well as application of emerging treatment strategies obtained from oncology for rheumatoid arthritis management could be a source of novel adipokine-mediated anti-rheumatic drugs. The ongoing surge of interest in anticytokine therapy makes further study of visfatin highly relevant as it may serve as a base for innovational RA treatment.


Induction, management, and complications of streptozotocin-induced diabetes mellitus in rhesus monkeys.
Diabetes mellitus (DM) model using streptozotocin (STZ) which induces chemical ablation of β cell in the pancreas has been widely used for various research purposes in non-human primates. However, STZ has been known to have a variety of adverse effects such as nephrotoxicity, hepatotoxicity, and even mortality. The purpose of this study is to report DM induction by STZ, toxicity associated with STZ and procedure and complication of exogenous insulin treatment for DM management in rhesus monkeys (Macaca mulatta) that are expected to be transplanted with porcine islets within 2 months. Streptozotocin (immediately dissolved in normal saline, 110 mg/kg) was slowly infused via central catheter for 10 minutes in 22 rhesus monkeys. Clinical signs, complete blood count and blood chemistry were monitored to evaluate toxicity for 1 week after STZ injection. Monkey basal C-peptides were measured and intravenous glucose tolerance test was performed to confirm complete induction of DM. Exogenous insulin was subcutaneously injected to maintain blood glucose in diabetic rhesus monkeys and the complications were recorded while in insulin treatment. Severe salivation and vomiting were observed within 1 hour after STZ injection in 22 rhesus monkeys. One monkey died at 6 hours after STZ injection and the reason for the death was unknown. Pancreatitis was noticed in one monkey after STZ injection, but the monkey recovered after 5 days by medical treatment. Serum total protein and albumin decreased whereas the parameters for the liver function such as aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase significantly increased (P<.05) after STZ injection, but they were resolved within 1 week. Azotemia was not observed. Monkey fasting C-peptide levels after STZ injection were <0.1 ng/mL in 18 rhesus monkeys, but 0.34, 0.22, 0.16 ng/mL in three monkeys, respectively. The value of daily insulin requirement was 0.92±0.26IU/kg/d (range=0.45-1.29) in the monkeys. Diabetic ketoacidosis was observed in one rhesus monkeys, but the monkey recovered after 24 hours by fluid and insulin treatment. Streptozotocin was effective for inducing DM in rhesus monkeys, but various adverse effects such as pancreatitis, liver toxicity or death were observed. Therefore, careful and suitable medical managements should be implemented to eliminate the risks of mortality and severe adverse effects.


A Brief Communication on Circulating PD-1-positive T-Regulatory Lymphocytes in Melanoma Patients Undergoing Adjuvant Immunotherapy With Nivolumab.
Upregulation of T-regulatory lymphocytes (Tregs) is one of numerous immune escape mechanisms of malignancies. In the present pilot study we aimed to study the effect of adjuvant nivolumab during the initiation of treatment on circulating Tregs subpopulations in patients with stage III melanoma. We subsequently recruited patients with stage III melanoma who had the indication for adjuvant anti-programmed death 1 (PD-1) treatment with nivolumab. Blood collections were performed before the initiation of nivolumab and before every 2-week therapy cycle. Flow cytometry was performed for the determination of circulating CD4CD25highCD127PD-1(PD-1Tregs) and CD4CD25highCD127CTLA-4 (CTLA-4Tregs) Treg populations. Circulating PD-1Tregs [18.1% (range, 2.9%-41.7%) vs. 4.2% (0.4%-9.8%), P=0.0001] significantly decreased after the first cycle of immunotherapy and maintained decreased during a 3-month course of treatment. By contrast, CTLA-4Tregs significantly increased after the first nivolumab dose when compared with CTLA-4Tregs before the second treatment [0.75 (0-45.5) vs. 2.1 (0.1-90.8), P=0.0002]. Blood levels of PD-1Tregs and CTLA-4Tregs remained more or less decreased and increased during a 3-month therapy with nivolumab, respectively. Data of PD-1Tregs as well as CTLA-4Tregs was not significantly associated with frequencies of immune-related adverse events (P<0.05). In conclusion, we have demonstrated that circulating PD-1Tregs of melanoma patients in stage III rapidly and continuously decline after the initiation of adjuvant treatment with the PD-1 blocking antibody nivolumab. By contrast, this decline is paralleled with an increase of CTLA-4Tregs. The expression of PD-1 and CTLA-4 on Tregs might be a potential biomarker for the efficacy of immune checkpoint blockade in melanoma.


Bacterial community structure analyses to assess pollution of water and sediments in the Lake Shkodra/Skadar, Balkan Peninsula.
Lake Skadar is the largest lake of the Balkan Peninsula, located along the Montenegro-Albanian border. The unique features of the lake and wide range of endemic, and rare or endangered plant and animal species, resulted in the classification of the Skadar as a wetland site of international significance. In spite of its importance, the lake is influenced by inflowing waters from the river Moraca and other regional rivers contaminated by the industry, municipal and agricultural activities in the area. Therefore, the lake has been the subject of various physical, chemical, biological and toxicological examinations. However, community-level analyses are most relevant to assess the effect of stressors on aquatic ecosystems. In the present study, bacterial community structure among differently polluted sites of the lake was compared using a genetic fingerprinting technique. Water and sediment samples were collected from five differently polluted sampling sites on the Lake Skadar in spring and autumn of the same year. The bacterial community structure in the samples was characterized and compared by temporal temperature gel electrophoresis (TTGE) analysis of polymerase chain reaction-amplified bacterial 16S rRNA genes. The TTGE analysis resulted in many distinguishable and reproducible band patterns, allowing a reliable comparison of bacterial communities among sampling sites. Results on the bacterial community structure revealed that three of the selected locations can be considered as sites that have not shown any pollution degradation determined by our method, due to similar structure of a bacterial community in the sediment samples. On the other hand, significant shifts in the bacterial community structure in the mouth of the rivers Moraca and Plavnica were shown. Since the results coincide with some of the bioassays and chemical analysis performed previously, the changes in bacterial community structure are explained as an effect of antropogenic pollution on the lake ecosystem by waters of the river Moraca and the stream Plavnica. The TTGE has proven to be an efficient and reliable method to monitor bacterial dynamics and community shifts in aquatic environments, especially in sediments. Within the variety of environmental quality assessments, the use of TTGE analyses from bacterial communities is strongly recommended, particularly as an initial investigation. However, in any conclusion on the state of the environment, the TTGE results should be combined to some other biological, chemical and hydrological data. Since prokaryotes are a crucial group of organisms in the biosphere, the ecosystem function studies are largely based on bacterial communities. Therefore, bacterial community structure analysis should be a part of an integrated weight of evidence approach in pollution assessment. In case of Triad approach, consisting of chemical analyses, bioassays, and community studies in the field, the TTGE bacterial community structure analyses should be placed in the later Triad leg. In comparison to other community studies, based on various biotic indices, the TTGE bacterial community analysis has proven to be very sensitive, reliable and less time consuming.


Redo carotid endarterectomy versus primary carotid endarterectomy.
Several authorities have recently advocated carotid stenting for recurrent carotid stenosis because of the perception that redo surgery has a higher complication rate than primary carotid endarterectomy (CEA). This study compares the early and late results of reoperations versus primary CEA. All reoperations for recurrent carotid stenosis performed during a recent 7-year period by a single vascular surgeon were compared with primary CEA. Because all redo CEAs were done with polytetrafluoroethylene (PTFE) or vein patch closure, we only analyzed those primary CEAs that used the same patch closures. A Kaplan-Meier life-table analysis was used to estimate stroke-free survival rates and freedom from >/=50% recurrent stenosis. Of 547 primary CEAs, 265 had PTFE or saphenous vein patch closure, and 124 reoperations had PTFE or vein patch closure during the same period. Both groups had similar demographic characteristics. The indications for reoperation and primary CEA were symptomatic stenosis in 78% and 58% of cases and asymptomatic >/=80% stenosis in 22% and 42% of cases, respectively (P<0.001). The 30-day perioperative stroke and transient ischemic attack rates for reoperation and primary CEA were 4.8% versus 0.8% (P=0.015) and 4% versus 1.1%, respectively, with no perioperative deaths in either group. Cranial nerve injury was noted in 17% of reoperation patients versus 5.3% of primary CEA patients; however, most of these injuries were transient (P<0.001). Mean hospital stay was 1.8 days for reoperation versus 1.6 days for primary CEA. Cumulative rates of stroke-free survival and freedom from >/=50% recurrent stenosis for reoperation and primary CEA at 1, 3, and 5 years were 96%, 91%, and 82% and 98%, 96%, and 95% versus 94%, 92%, and 91% and 98%, 96%, and 96%, respectively (no significant differences). Reoperation carries higher perioperative stroke and cranial nerve injury rates than primary CEA. However, reoperations are durable and have stroke-free survival rates that are similar to primary CEA. These considerations should be kept in mind when carotid stenting is recommended instead of reoperation.