Long-term resistance training is associated with reduced circulating levels of IL-6, IFN-γ and TNF-α in elderly women.
The increase in inflammatory activity associated with aging is a characteristic of chronic disease processes that accounts for most of the mortality in the elderly. Resistance training (RT) has been shown to promote metabolic and functional benefits in this population. The objective of this study was to investigate the association between long-term RT and circulating levels of the proinflammatory mediators IL-6, TNF-α and IFN-γ in elderly women. This cross-sectional study included 54 older outpatients divided into a group that underwent RT (n = 28) for an average of 8.6 ± 0.3 months and a sedentary group (n = 26). Measurements were taken only at the end of the intervention, and cytokine values were log-transformed. Dietary intake was controlled as a confounding factor. The RT group presented reduced levels of log₁₀IFN-γ (approx. 45%; p = 0.003), log₁₀IL-6 (approx. 30%; p = 0.002) and log₁₀TNF-α (approx. 22%; p = 0.036). Total caloric intake and systolic arterial blood pressure were significantly lower in the RT group (p = 0.001 and p = 0.022, respectively). Pearson's product moment correlation test revealed a negative association between the fat-free mass (FFM) index and log-transformed IL-6 levels (p = 0.03; n = 54) and a trend towards significance for the correlation between the FFM index and log₁₀IFN-γ (p = 0.05; n = 54). Long-term, moderate-intensity RT in elderly women is associated with lower circulating levels of cytokines that are potentially implicated in disorders associated with physical inactivity and aging.


Relationships of working conditions and individual characteristics to occupational injuries: a case-control study in coal miners.
This study assessed the relationship of age, poor perception of working condition, poor safety environment, poor management and supervision, risk-taking behavior, emotional instability, negative job involvement, job dissatisfaction, job stress, and poor safety performance of workers to occupational injuries. This case-control study was conducted on 202 male coal miners with at least one occupational injury during a five-year period and 202 male controls with no occupational injury, matched on the job. A standardized questionnaire administered by individual interviewers was used. Data were analysed by the logistic regression method. For all workers combined, the factors with significant adjusted odds ratios (ORs) found were: 30-45 and >45 yr age groups (OR vs. <30 yr age group: 1.80, 95% CI 1.02-3.17 and 2.59, 1.38-4.85 respectively), poor perception of working conditions (1.61, CI 1.00-3.18), emotional instability (2.33, 1.04-5.22), job stress (1.83, 1.00-3.46) and poor safety performance of workers (3.10, 1.45-6.63). No significant interaction was found between these risk factors and the job. It was concluded that older age, poor perception of work conditions, poor work environment, and human behavioral factors played significant roles in occupational injuries. This information would help in implementing preventive programs to improve working conditions and management quality and to help the workers to develop positive psychological traits, but workers with negative traits such as emotional instability and older workers should be employed in less demanding jobs.


X-linked dominant inheritance of partial phosphorylase kinase deficiency in mice.
A new mouse strain, the V strain, with a partial deficiency of phosphorylase kinase has been established. The deficiency is caused by an X-linked dominant gene (PhKc). Muscle extracts of homozygous and heterozygous females and hemizygous males have about 25% of the activity found in extracts of normal (C3H/HeHan) mice. This dominant phosphorylase kinase deficiency of the new V strain is different from that of the I-strain mice with the X-linked recessive deficiency of skeletal muscle phosphorylase kinase. The muscle extracts of V-strain and normal mice contain the same phosphorylase phosphatase activity of about 1 U/mg. Heart and liver extracts from V mice contained about 50% and 66%, respectively, of the phosphorylase kinase activity compared to that found in the same organs from the normal mice. The glycogen content of the skeletal muscle of the V strain was normal, i.e., 0.9 mg/g. Phosphorylase kinase was purified from the skeletal muscle of the V strain by (a) hydrophobic chromatography on methylamine Sepharose, (b) ammonium sulfate precipitation, and (c) gel filtration of Sepharose 4B. The enzyme has a similar structure to the normal murine and rabbit skeletal muscle enzyme, except that the proportion of the subunits differs. The molar ratio of the subunits of the V strain mice is (alpha + alpha'):beta:gamma=0.54:1:1.169, in comparison with that of the rabbit (alpha + alpha'):beta:gamma=1.1:1.0:1.0 and that of normal murine enzyme 0.9:1.0:0.7.


[Predictive genetic investigations. Individualization of diagnosis and treatment in families with multiple endocrine neoplasia type II].
When multiple endocrine neoplasia type 2 (MEN2) is suspected, genetic tests are at the centre of screening procedures. It was the aim of this study to compare the diagnostic value of molecular biological investigations with that of conventional biochemical tests. The study cohort consisted of all 144 patients cared for in our department since 1990 with the suspected diagnosis of MEN2 (evidence of a medullary thyroid carcinoma [MTC]), coexistence of two MEN2 tumours or a family history of MEN2. 14 of the 144 patients (from 12 families) were already known to have an hereditary MTC, while the remaining 130 had been referred for further diagnostic investigations. An hereditary MTC was diagnosed in 22 of the 130 patients, a sporadic MTC in 32, while no definitive classification was possible in 20 MTC patients without a positive family history and on whom no mutation analysis had been performed. MEN2 was excluded in 56 family members. All 22 patients with newly diagnosed MTC had abnormally high calcitonin levels. A germ-line mutation in the RET proto-oncogene was found in 8 of the 9 families who had undergone molecular biological tests. The investigate results led to a thyroidectomy in 19 of the 22 patients with hereditary MTC; in all of them the surgical specimen showed C-cell hyperplasia and/o MTC. These results emphasize the importance of genetic tests in family screening. Preoperative measurement of calcitonin remains essential in MEN2 families in whom a germ-line mutation is not known. The choice of the appropriate diagnostic test must be individualized to the particular patients so that optimal results are obtained.


Interplay Between SIRT-3, Metabolism and Its Tumor Suppressor Role in Hepatocellular Carcinoma.
Sirtuins (SIRT), first described as nicotinamide adenine dinucleotide (NAD+)-dependent type III histone deacetylases, are produced by cells to support in the defense against chronic stress conditions such as metabolic syndromes, neurodegeneration, and cancer. SIRT-3 is one of the most studied members of the mitochondrial sirtuins family. In particular, its involvement in metabolic diseases and its dual role in cancer have been described. In the present review, based on the evidence of SIRT-3 involvement in metabolic dysfunctions, we aimed to provide an insight into the multifaceted role of SIRT-3 in many solid and hematological tumors with a particular focus on hepatocellular carcinoma (HCC). SIRT-3 regulatory effect and involvement in metabolism dysfunctions may have strong implications in HCC development and treatment. Research literature widely reports the relationship between metabolic disorders and HCC development. This evidence suggests a putative bridge role of SIRT-3 between metabolic diseases and HCC. However, further studies are necessary to demonstrate such interconnection.


Cloning, mapping and characterization of a genomic copy of the Lipomyces kononenkoae alpha-amylase-encoding gene (LKA1).
The expression in Saccharomyces cerevisiae and Schizosaccharomyces pombe of a cDNA copy of the Lipomyces kononenkoae IGC4052B alpha-amylase gene (LKA1), linked to the phosphoglycerate kinase gene (PGK1) promoter, resulted in the extracellular production of biologically active alpha-amylase (LKA1). However, transformation of S. cerevisiae and Schiz. pombe with a cosmid clone containing the complete genomic copy of LKA1, expressed from its native promoter, did not result in secretion of active alpha-amylase by any of the transformants. When the cDNA copy of LKA1 was expressed in S. cerevisiae under control of the wild-type L, kononenkoae promoter, biologically active alpha-amylase was secreted into the culture medium, indicating the recognition of the LKA1 promoter in S. cerevisiae. Sequence analysis of the GC-rich LKA1 promoter revealed canonical sequences that are homologous to the TATAAA, CAAT and CCAAT boxes and GCN4-binding sites that are present in several promoter sequences of S. cerevisiae. Primer extension analysis of LKA1 transcripts in L. kononenkoae indicated major initiation sites at nucleotides -64 and -65. S. cerevisiae and Schiz. pombe cells transformed with a plasmid containing the open reading frame of the genomic copy of LKA1, linked to the PGK1 promoter, did not produce alpha-amylase. Polymerase chain reaction mapping and sequence analysis revealed the presence of a 61-bp intron in the genomic copy of LKA1 that impaired synthesis of biologically active alpha-amylase in S. cerevisiae and Schiz. pombe. This intron contains donor, acceptor and branch sequences that correlate with the consensus sequences identified in the introns of split genes from Schiz. pombe and mammals. Pulsed-field gradient gel electrophoresis resolved at least eight chromosomal DNAs for L. kononenkoae IGC4052B and chromoblot analysis indicated that LKA1 is located on the second smallest chromosome, designated chromosome II.


The development of a new hemoperfusion column: the filmadsorber.
A hemoperfusion system has been developed in which very small charcoal particles (average diameter 40 micrometers) are embedded and immobilized in a collodion film (Filmadsorber). In vitro studies revealed that the absorption of bile acids by these small charcoal particles is superior to that by larger ones (size: 0.5 to 5 mm) as used in commercially available adsorbers. In vivo studies confirmed these results: dogs with ligated bile ducts were subjected to hemoperfusion through different types of charcoal adsorbers. Bile acid clearances of filmadsorbers containing less charcoal than the commercials were significantly higher.


Chloroquine-sensitive transplasmalemma electron transport in Tetrahymena pyriformis: a hypothesis for control of parasite protozoa through transmembrane redox.
Plasma membrane electron transport was studied in a protozoan cell, Tetrahymena pyriformis, by assaying transmembrane ferricyanide reduction and the reduction of iron compounds. The rates of ferricyanide reduction varied between 0.5 and 2.5 mumol/g dry wt. per min, with a pH optimum at 7.0-7.5. Other active non-permeable electron acceptors, with redox potentials from +360 to -125 mV, were cytochrome c, hexaammine ruthenium chloride, ferric-EDTA, ammonium ferric citrate, and indigo di-, tri- and tetrasulfonates. It was found that Tetrahymena cells can reduce external electron acceptors with redox potentials at pH 7.0 down to -125 mV. Ferricyanide stimulates ciliary action. Transmembrane ferricyanide reduction by Tetrahymena was not inhibited by such mitochondrial inhibitors as antimycin A, 2-n-heptyl-4-hydroxyquinoline N-oxide, or potassium cyanide, but it responded to inhibitors of glycolysis. Transmembrane ferricyanide reduction by Tetrahymena appears to involve a plasma membrane electron transport chain similar to those of other animal cells. As in other cells, the transmembrane electron transport is associated with proton release which may be involved in internal pH control. The transmembrane redox system differs from that of mammalian cells in a 20-fold greater sensitivity to chloroquine and quinacrine. The Tetrahymena ferricyanide reduction is also inhibited by chlorpromazine and suramin. Sensitivity to these drugs indicates that the transplasma membrane electron transport and associated proton pumping may be a target for drugs used against malaria, Trypanosomes and other protozoa.


Phenothiazine-induced ventricular tachycardia following acute overdose.
The chronic use of phenothiazine is known to result in ventricular arrhythmias in certain patients. The occurrence of cardiac abnormalities following acute phenothiazine overdose is less well documented. Phenothiazine-induced ventricular tachycardia, when it occurs in the overdose situation, may be refractory to conventional antiarrhythmic drugs. We present a case in which the usual therapy was unsuccessful. Only after a transvenous pacemaker was inserted was the patient's condition reversed.


Farmers' knowledge, attitudes, and practices with respect to rodent management in the upland and lowland farming systems of the Lao People's Democratic Republic.
Rodents are a serious constraint to poor farmers in the upland and lowland farming systems of the Lao People's Democratic Republic and have been described as the pest they have least control over. To better understand these problems a baseline survey of farmers was conducted to assess their knowledge, attitudes, and practices with respect to rodent management. A structured survey was conducted in 12 villages across Luang Namtha, Luang Prabang, and Houaphan provinces. Twenty farmers from each village were interviewed (a total of 240 farmers). Farmers noted that the main factor limiting production was pests (70%), with rats identified as the most important pest (98%). The mean yield loss was estimated at 19% (range 0-100%). Trapping and rodenticides were commonly used by farmers. Farmers believed that it was important to control rats and believed that rats could only be controlled if farmers worked together. However, 65% of farmers conducted rodent control by themselves, and 92% of farmers believed that rodenticides were harmful to the environment. The main constraints identified were the high cost of some control methods and the need to get farmers to work together as a community.


Propionibacterium acnes, a resident of lipid-rich human skin, produces a 33 kDa extracellular lipase encoded by gehA.
Five independent clones of the Propionibacterium acnes P-37 lipase gene (gehA) were obtained in Escherichia coli, and the gene was localized to a 2.75 kb Xhol fragment by subcloning. The five clones were shown to contain the same gene by Southern blotting with a DIG-labelled probe to gehA. The nucleotide sequence of gehA was determined, and shown to contain a single ORF of 1017 kb, encoding a protein of 339 amino acids. The predicted molecular mass was 36 kDa. A 33 kDa (PAGE) radiolabelled polypeptide was detected from E. coli minicell preparations harbouring gehA, which could correspond to GehA after cleavage of the putative 26 amino acid residue signal peptide. gehA was overexpressed in E. coli under the control of the bacteriophage T7 promoter, and the corresponding polypeptide was found to be present in insoluble aggregates. Active lipase was produced when the overexpressing strain was incubated at a reduced temperature in the presence of sucrose. Purification of lipase from P. acnes culture supernatant fluids confirmed the production of a 33 kDa (PAGE) lipase.


Structural changes in a cryo-cooled protein crystal owing to radiation damage.
The high intensity of third-generation X-ray sources, along with the development of cryo-cooling of protein crystals at temperatures around 100 K, have made it possible to extend the diffraction limit of crystals and to reduce their size. However, even with cryo-cooled crystals, radiation damage becomes a limiting factor. So far, the radiation damage has manifested itself in the form of a loss of overall diffracted intensity and an increase in the temperature factor. The structure of a protein (myrosinase) after exposure to different doses of X-rays in the region of 20 x 10(15) photons mm(-2) has been studied. The changes in the structure owing to radiation damage were analysed using Fourier difference maps and occupancy refinement for the first time. Damage was obvious in the form of breakage of disulfide bonds, decarboxylation of aspartate and glutamate residues, a loss of hydroxyl groups from tyrosine and of the methylthio group of methionine. The susceptibility to radiation damage of individual groups of the same kind varies within the protein. The quality of the model resulting from structure determination might be compromised owing to the presence of radiolysis in the crystal after an excessive radiation dose. Radiation-induced structural changes may interfere with the interpretation of ligand-binding studies or MAD data. The experiments reported here suggest that there is an intrinsic limit to the amount of data which can be extracted from a sample of a given size.


Quantitation of rat cerebral blood flow using 99mTc-HMPAO.
Technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) is potentially useful for the assessment of cerebral blood flow (CBF) in small animals. In this paper, a procedure for quantitation of rat CBF using 99mTc-HMPAO was determined. Biodistribution of 99mTc-radioactivity in normal rats was determined after intravenous administration of 99mTc-HMPAO. Acetazolamide treated rats were intravenously administered with the mixture of 99mTc-HMPAO and N-isopropyl-[125I]iodoamphetamine ([125I]IMP), and arterial blood was then collected for 5min. After blood sampling, the brain radioactivity concentration was measured with the auto-well γ counter. The brain radioactivity concentration after intravenous administration of 99mTc-HMPAO was steady from 14s to 60min post-injection. A double tracer experiment using 99mTc-HMPAO and [125I]IMP showed that 19s was the average of the optimal integration interval of arterial blood 99mTc-radioactivity concentration to obtain CBF values measured by 99mTc-HMPAO identical to those determined by [125I]IMP. The CBF value determined by 99mTc-HMPAO, calculated by dividing the brain radioactivity concentration at 5min post-injection by the integrated arterial blood radioactivity concentration until 19s post-injection, was well correlated with CBF as determined by [125I]IMP. These results suggest that the CBF quantitation procedure described in this paper could be useful for rat CBF assessment.


Identification and expression analysis of chitinase genes related to biotic stress resistance in Brassica.
Brassica is a very important vegetable group because of its contribution to human nutrition and consequent economic benefits. However, biotic stress is a major concern for these crops and molecular biology techniques offer the most efficient of approaches to address this concern. Chitinase is an important biotic stress resistance-related gene. We identified three genes designated as Brassica chitinase like protein (BrCLP1), BrCLP2 and BrCLP3 from a full-length cDNA library of Brassica rapa cv. Osome. Sequence analysis of these genes confirmed that BrCLP1 was a class IV chitinase, and BrCLP2 and BrCLP3 were class VII chitinases. Also, these genes showed a high degree of homology with other biotic stress resistance-related plant chitinases. In expression analysis, organ-specific expression of all three genes was high except BrCLP1 in all the organs tested and BrCLP2 showed the highest expression compared to the other genes in flower buds. All these genes also showed expression during all developmental growth stages of Chinese cabbage. In addition, BrCLP1 was up-regulated with certain time of infection by Pectobacterium carotovorum subsp. carotovorum in Chinese cabbage plants during microarray expression analysis. On the other hand, expression of BrCLP2 and BrCLP3 were increased after 6 h post inoculation (hpi) but decreased from 12 hpi. All these data suggest that these three chitinase genes may be involved in plant resistance against biotic stresses.


Supramolecular host-guest pseudocomb conjugates composed of multiple star polycations tied tunably with a linear polycation backbone for gene transfection.
A series of novel supramolecular pseudocomb polycations (l-PGEA-Ad/CD-PGEAs) were synthesized by tying multiple low-molecular-weight β-cyclodextrin (CD)-cored, ethanolamine-functionalized poly(glycidyl methacrylate) (PGEA) star polymers (CD-PGEAs) with an adamantine-modified linear PGEA (l-PGEA-Ad) backbone via the host-guest interaction. The pseudocomb carriers were studied in terms of their DNA binding capabilities, cytotoxicities, and gene transfection efficiencies in the HepG2 and HEK293 cell lines. The pseudocomb l-PGEA-Ad/CD-PGEAs exhibited better plasmid DNA-condensing abilities than their counterparts, CD-PGEA and l-PGEA. Meanwhile, the pseudocomb carriers displayed low cytotoxicity, similar to CD-PGEA and l-PGEA. Moreover, the gene transfection efficiencies of the pseudocomb carriers were much higher than those of CD-PGEA and l-PGEA at various PGEA nitrogen/DNA phosphate molar ratios. Such supramolecular preparation of pseudocomb gene carriers could provide a flexible approach for adjusting the structure and functionality of supramolecular polymers via the proper use of non-covalent interactions.


Selective Action of N-Arachidonoyl Dopamine on Viability and Proliferation of Stromal Cells from Eutopic and Ectopic Endometrium.
We performed a comparative study of the cytotoxic effect of endocannabinoid N-arachidonoyl dopamine (AA-DA) on cultured stromal cells of ectopic and eutopic endometrium. It was found that AA-DA in the concentration range of 1-20 μM produces more selective cytotoxic effect on the stromal cells of the ectopic endometrium due to interaction with cannabinoid type 1 receptor. In concentrations below 1 μM, AA-DA stimulated the proliferation of stromal cells of the eutopic endometrium and did not affect the division of ectopic endometrium cells. This effect was realized due to its interaction with cannabinoid type 2 receptor.


[Effect of sodium diethyldithiocarbamate on embryogenesis in mice].
Sensitivity of mouse embryos (8-11 days old) to sodium diethyldithiocarbamate (SDDC), inhibitor of dopamine -beta-hydroxylase, has been investigated. SDDC produces certain anomalies in development of the CNS, facial skull, mandible , extremities and others. It is possible that the base of the mechanism, stimulating development of these anomalies, together with the other causes, can be some disturbances in catecholamine metabolism. This, in its turn, can result in disorders of cell interactions via neurotransmitters during active morphogenetic processes.


The modular construction of the neuropil in the substantia gelatinosa of the cat's spinal cord. A computer aided analysis of Golgi specimens.
Golgi impregnated spinal cord sections cut in the sagittal plane were used to study the branching pattern, terminal structure and orientation features of terminal axon arborizations in the substantia gelatinosa (lamina II) of the cat. The histological description of the arborizations was supplemented with computer aided quantitative three-dimensional analysis. Six types of axon arborizations could be distinguished among the 31 arborizations collected from C4 and L4 spinal segments. One type was tentatively identified as terminals of non-myelinated primary afferent fibres (Class I arborizations), while the others (Class II arborizations) were suggested to belong to thin myelinated primary afferent fibres, to descending tract fibres and to spinal interneurons. Arborizations differed in branching pattern and in the thickness of the branches. They possessed several terminal and en passant thickenings (up to 75) which were interpreted as presynaptic sites. The arborizations were confined to long and narrow sagittal sheets of the neuropil. These sheets were tilted from the sagittal plane but their rostro-caudal axis lined up exactly parallel to the axis of the spinal cord. The dimensions of the elongated brick-shaped territories encompassing the presynaptic sites of the arborizations were measured. The average values of 10 Class I trees were 526 micrometer in length, 53 micrometer in dorso-ventral direction and 17 micrometer in width (medio-lateral dimension). Class II trees were generally shorter but wider. Trees were found occasionally to arborize in two adjacent sheets. Arborizations with partially or totally overlapping branches were frequently seen.


Bovine papillomaviral gene expression in equine sarcoid tumours.
The sarcoid is a benign locally invasive dermal fibroblastic lesion, commonly affecting horses and donkeys. The aetiology of the equine sarcoid is equivocal. Bovine papillomaviral (BPV) DNA (type 1/2) is frequently demonstrable in equine sarcoid tumour biopsies. However, the exact role of the virus in the disease process and its contribution to the phenotypic differences in sarcoids is not known. It was sought to assess the transcriptional activity of BPV-1 found in sarcoid tissues. Of 20 tumours examined, 18 were positive for E2 expression and ten positive for L1 expression. Viral oncogenes E5, E6 and E7 transcripts were detected in 16, nine and 12 tumours, respectively. This study demonstrates BPV gene expression in equine sarcoids and provide the first evidence for a direct involvement of the virus in the pathogenesis of sarcoids.


Managing type 2 diabetes: balancing HbA1c and body weight.
Most patients with type 2 diabetes present with comorbid overweight or obesity. Reaching and maintaining acceptable glycemic control is more difficult in overweight and obese patients, and these conditions are associated with increased risk for cardiovascular and other diseases. Glycemic management for these patients is complicated by the fact that insulin and many of the oral medications available to treat type 2 diabetes produce additional weight gain. However, an increasing number of therapeutic options are available that are weight neutral or lead to weight loss in addition to their glycemic benefits. This article evaluates the evidence from clinical trials regarding the relative glycemic benefits, measured in terms of glycated hemoglobin change, versus the impact on body weight of each medication currently approved for type 2 diabetes. In general, the sulfonylureas, thiazolidinediones, and D-phenylalanine derivatives have been shown to promote weight gain. The dipeptidyl peptidase-4 inhibitors are weight neutral, while the biguanides, incretin mimetics, and amylin mimetics promote weight loss. Trials examining the glycemic benefits of the weight loss agents orlistat and sibutramine are also examined. Awareness of this evidence base can be used to inform medication selection in support of weight management goals for patients with type 2 diabetes.


Non-invasive laboratory diagnosis of deep venous thrombosis.
Both legs of 52 patients, in whom deep thrombosis was clinically suspected in one leg, were investigated. Out of the 52 legs used as a control, without suspected deep venous thrombosis, two were found to have deep venous thrombosis. Laboratory findings revealed that deep venous thrombosis was not present in 25% of the cases suspected. The patients in this group did not require venogram and were not treated. Nineteen suspected legs (36.5%) were proved negative not only by the laboratory method but also by venography.


Interventional radiology in infants and children: clinical and technical aspects.
The authors performed 53 extravascular interventional procedures in 47 pediatric patients between July 1981 and September 1983. Except for transhepatic cholangiography in patients without intrahepatic biliary dilatation, the success rate was high. There were few complications, and none that were life-threatening or required surgery. More than 90% of procedures were performed without general anesthesia. Factors essential to safe and successful intervention in infants, children, and adolescents, in the authors' opinion, include (a) active involvement by the radiologist, (b) guidance by real-time imaging, (c) careful matching of needles, catheters, and guide wires to patient size, and (d) adequate sedation and analgesia.


[Analyzing a nursing information system in terms of Lewin's change theory].
The ever increasing are of information technology has deeply influenced, indeed changed our lives. Under its impact, healthcare institutions have constantly changed to improve the quality of patient care. Enterprise management has become a major focus of hospitals, and the development of nursing information systems has accelerated in line with this worldwide trend. The purpose of this study is to apply Lewin's change theory in analyzing a nursing information system, as well as to explore issues regarding challenges that such systems will present to managers and staff and the strategies that can be applied in order to set up the infrastructure for future nursing information systems.


Induction of immune response and anti-tumor activities in mice with a DNA vaccine encoding human mucin 1 variable-number tandem repeats.
Mucin 1 (MUC1) is a tumor-associated antigen that carries the important variable-number tandem repeat (VNTR) epitopes for inducing cytotoxic T lymphocytes. Such a property makes MUC1 VNTR potentially attractive for immunotherapy. This study explored the possibility of developing an efficient anti-tumor vaccine strategy using the specific antitumor immunity induced by the MUC1 VNTR DNA vaccine combined with the adjuvant effect of a plasmid expressing murine interleukin-2 (IL-2). The results showed that the MUC1 VNTR DNA vaccine successfully induced both humoral and cellular immune responses against MUC1 VNTR in mice. The effect could be obviously enhanced by increasing the number of tandem repeats, the number of immunizations, and by co-administration of the cytokine plasmid. The growth of MUC1-expressing (MUC1(+)) tumors was significantly inhibited in mice immunized with the MUC1 VNTR DNA vaccine combined with the IL-2 plasmid, both before and after tumor challenge. A much larger percentage of the immunized mice survived tumor challenge than the non-immunized mice. The combination of the MUC1 VNTR DNA vaccine and the IL-2 adjuvant plasmid provides an attractive alternative for prophylactic and therapeutic vaccinations against MUC1(+) tumors.


Magnesium and zinc potentiate ethanol inhibition of N-methyl-D-aspartate-stimulated nitric oxide synthase in cortical neurons.
The coupling of calcium mobilizing receptors to nitric oxide (NO) formation was examined in cerebral cortical cultures. Of the various agents tested, only glutamate, depolarization with KCl and the calcium ionophore ionomycin stimulated nitric oxide synthase (NOS) activity. Characterization of the glutamate response revealed that the ionotropic glutamate receptor agonists N-methyl-D-aspartate (NMDA), kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic all stimulated NOS activity with a relative maximal efficacy of NMDA > kainate > alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic. Ethanol, Mg++ and Zn++ produced a concentration-dependent inhibition of NMDA stimulation of NOS. The Mg++ inhibition was reversed by increasing concentrations of NMDA, whereas Zn++ inhibition was not. Ethanol (100 mM) produced an apparent competitive type inhibition as seen by a parallel right-shift in the NMDA concentration-response curve. However, ethanol inhibition was dependent upon the presence of Mg++ and/or Zn++ in a concentration-related manner. Whereas 100 mM ethanol did not significantly inhibit NMDA stimulation of NOS activity in the absence of Mg++ and Zn++, inclusion of a combination of these cations increased the sensitivity to ethanol such that the NMDA response was completely blocked by 100 mM ethanol (IC50 approximately 30 mM). The potency for inhibition of NMDA stimulation of NOS by several short-chain alcohols followed their hydrophobicity profile and showed a similar dependency upon Mg++ for inhibition, alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic, but not kainate, stimulation of NOS was also inhibited by ethanol (100 mM).(ABSTRACT TRUNCATED AT 250 WORDS)


[Ruptured aneurysm of pancreaticoduodenal artery, report of two cases].
We describe two cases of ruptured areurysm of pancreaticoduodenal artery (PDA), whose chief complaints were right upper abdominal pain. They were diagnosed to retroperitoneal hematoma around the duodenum and the uncus of the pancreas by Computed tomography and aneurysm of pancreaticoduodenal artery by Angiography. The patients underwent a coil embolization of the eneurysms, one ending to successful, the other to unsuccessful, so, underwent pancreatioduodenectomy. In our both cases, no history of chronic pancreatitis, trauma, infection and connective tissue disorders, and celiac axis stenosis or occulusion, were found. We reviewed 71 case repotrs of PDA aneurysm in Japanese literature and the treatment of PDA aneurysm.


A Mixed Methods Review of Education and Patient Navigation Interventions to Increase Breast and Cervical Cancer Screening for Rural Women.
Reviews have assessed studies of breast and cervical cancer screening access and utilization for rural women, but none analyze interventions to increase screening rates. A mixed methods literature search identified studies of breast and/or cervical cancer prevention education and patient navigation interventions for rural women. Rural areas need greater implementation and evaluation of screening interventions as these services address the challenges of delivering patient-centered cancer care to un-/underserved communities. The lack of intervention studies on breast and cervical cancer education and patient navigation programs compared to urban studies highlights the need for validation of these programs among diverse, rural populations.


Copper(I)-Catalyzed Kinetic Resolution of N-Sulfonylaziridines with Indoles: Efficient Construction of Pyrroloindolines.
The first Lewis acid catalyzed [3 + 2] annulation of indoles and 2-aryl-N-tosylaziridines was realized by using copper(I)/chiral diphosphine complexes as a catalyst. With this method, a variety of uniquely substituted chiral pyrroloindolines bearing multiple contiguous stereogenic centers were facilely accessed in a straightforward, high-yielding, and highly stereoselective way under mild conditions.


Plan in a pack.
Children who have used the new My Asthma packs say their compliance with medication has improved.


Statistical characterizers of transport in communication networks.
We identify the statistical characterizers of congestion and decongestion for message transport in model communication lattices. These turn out to be the travel time distributions, which are Gaussian in the congested phase, and logarithmic normal in the decongested phase. Our results are demonstrated for two-dimensional lattices, such the Waxman graph, and for lattices with local clustering and geographic separations, gradient connections, as well as for a one-dimensional ring lattice with random assortative connections. The behavior of the distribution identifies the congested and decongested phase correctly for these distinct network topologies and decongestion strategies. The waiting time distributions of the systems also show identical signatures of the congested and decongested phases. The distributions are explained using a stochastic differential equation to model the transport.


Ocular manifestations in Japanese patients with human immunodeficiency virus infection.
The ocular manifestations in 65 Japanese human immunodeficiency virus (HIV)-seropositive patients were examined. Based on the cumulative totals, 22 of the cases had acquired immunodeficiency syndrome (AIDS), 17 had AIDS-related complex (ARC), and 35 were asymptomatic carriers (AC), including 4 AIDS cases who had progressed from ARC and 5 ARC cases from AC. Seventy-seven percent of the AIDS cases had ocular manifestations, including cotton-wool spots (50%), retinal hemorrhages (59%), cytomegalovirus retinitis (46%) and pupil abnormalities (14%). The ocular signs were also seen in 71% of the ARC cases and 37% of the AC cases. In Japanese HIV-seropositive patients, ocular manifestations are also as common as in Western HIV-seropositive patients.


[To evaluate the role of OLT on splenomegaly of portal hypertension by the radiological changes of splenic morphology and collaterals].
To explore the effect of orthotopic liver transplantation (OLT) on portal hypertension by observing the radiological changes of splenic volume and collaterals before and after OLT. In our hospital 56 patients performing OLT due to cirrhosis, portal hypertension and splenomegaly were classified into five groups according to their following-up time: A (≤3 months), B (>3-6 months), C (>6-12 months), D (>12-24 months), and E (>24 months). Twenty health people were chose as control group (F). The splenic width, thickness, length, volume, diameter of portal and splenic vein and collaterals were measured and observed in every patient of six groups before and after OLT respectively. After OLT, the splenic volume decreased by 25.4%, 27.8%, 21.9%, 25.2%, 27.7% in five groups respectively, which was still larger than the normal group (P<0.05). Gastroesophageal varices in 31 cases (81.6%, 31/36) became normal after OLT. The opened umbilical vein disappeared and the retroperitoneal varices persisted in five cases after OLT. Splenomegaly and opened collaterals can be relieved by OLT effectively. The splenic volume didn't change obviously until it decreased by 25% in the three months after OLT. Gastroesophageal varices can be removed in most of patients after OLT. The splenomegaly could last paralled with the splenic vein and retroperitoneal varices after OLT. After OLT, correct disposal of splenic and collateral changes could improve the success rate and the long-term treatment effect of OLT.


Prospective comparison of unstable angina versus non-Q wave myocardial infarction during antithrombotic therapy. Antithrombotic Therapy in Acute Coronary Syndromes Research Group.
This study was designed to compare the response of unstable angina and non-Q wave myocardial infarction during treatment with antithrombotic therapy. Antithrombotic therapy is beneficial in patients with these two coronary syndromes. In a multicenter trial of antithrombotic therapy in unstable angina or non-Q wave myocardial infarction, 358 patients admitted within 48 h of chest pain were randomized to antithrombotic therapy with either 1) aspirin alone, or 2) aspirin plus heparin followed by aspirin plus warfarin, and were prospectively followed up for 12 weeks. Admission cardiac enzyme analyses revealed unstable angina in 268 patients and non-Q wave myocardial infarction in 62. Given an event rate of about 25%, this study has a power of 80% to detect a 50% difference between the two groups. Patients with unstable angina and non-Q wave myocardial infarction were similar with regard to age, gender, coronary risk factors and prior antianginal medication. Primary end points at 12 weeks were recurrent ischemia, infarction and death. [table: see text] In the non-Q wave group, all infarctions and death occurred within the 1st week. Patients with unstable angina or non-Q wave myocardial infarction on antithrombotic therapy have a similar total number of ischemic events by 12 weeks. However, despite maximal medical therapy with antianginal and antithrombotic medication, patients with non-Q wave infarction have a significantly higher rate of reinfarction and death.


Evaluation of dental injury following endotracheal intubation using the Periotest technique.
The hazards of damage to teeth and their periodontal attachment during tracheal intubation are well known. Dental trauma represents the commonest single reason for complaints against anesthesiologists. In order to predict the possible risk of perianesthetic iatrogenic tooth luxation we evaluated the use of a measuring method (Periotest technique), being well established for the diagnosis of periodontal disease. In 120 patients undergoing elective surgery, we compared the amount of tooth mobility before and after general anesthesia to different scores assessing the difficulty of tracheal intubation. Furthermore, the level of work experience of the intubating anesthetist was compared with the degree of postoperative tooth mobility. Changes of periodontal attachment could not be detected by the Periotest technique. The Periotest technique does not seem to have the ability to detect early periodontal changes associated with endotracheal intubation.


Conversion to Gastric Bypass After Either Failed Gastric Band or Failed Sleeve Gastrectomy.
Roux-en-Y gastric bypass (RYGB) is still considered the gold standard in bariatric surgery. Before, adjustable gastric banding (AGB) was regarded as an alternative; nowadays, sleeve gastrectomy (SG) is a more favorable alternative. In case of unsatisfactory results, RYGB is often performed as a secondary procedure. Conversion of an AGB is associated with a high risk of complications; the hypothesis was that this would be less after conversion of an SG. All patients undergoing conversion to RYGB after AGB or SG between 2005 and 2012 were included for retrospective analysis. Patient characteristics, operative details, postoperative complications, the relief of complaints, weight loss, reasons for failure, and evolution of known comorbidities up to 2 years were analyzed. A total of 178 patients were included (79.8 % female): AGB 110 (61.8 %) versus SG 68 (38.2 %). Main reasons for conversion were weight regain/insufficient weight loss (48.4 %) or dysphagia/reflux complaints (39.9 %). Surgical complications were found in 19 patients (AGB 13 vs SG 6; p = 0.530). Infectious complications occurred in 13 patients (AGB 11 vs SG 2; p = 0.135). Total body weight loss was equal between groups after 2 years (AGB 31.6 ± 11.0 % vs SG 31.6 ± 12.0 %; p = 0.998). Similar results were found in a subgroup analysis on patients undergoing conversion for additional weight loss (AGB 31.7 ± 11.7 % vs SG 27.0 ± 13.1 %; p = 0.173). Conversion to RYGB after failed AGB or SG showed comparable short-term results in terms of postoperative complications and weight loss.


[A case of both cryptococcal pneumonia and meningitis with idiopathic CD4+T-lymphocytopenia followed up over a long time].
A 62-year-old man had felt cold-like symptoms for 2 months. He visited a clinic for a health check in late July 1998 and chest X-ray film showed an infiltrative shadow in the left middle and lower lung fields. Next day he had a fever of 38.3 degrees C and felt breathless. Six days thereafter he had a cough, thick head and felt fatigue. Chest X-ray films showed other infiltrative shadows in the bilateral upper lung fields. He worked in a race track and was exposed to pigeons and seabirds at that time. Culture of sputum grew Cryptococcus neoformans. He was admitted and was treated with intravenous antifungal drugs. Cerebrospinal fluid examination revealed positive Indian ink stain for C. neoformans. The CD4 + T-lymphocyte count and CD8 + T-lymphocyte count were 143.4 cells/mm3 and 1288.8 cells/mm3 respectively, but without HIV infection. Cryptococcal pneumonia and meningitis with Idiopathic CD4 + T-lymphocytopenia was diagnosed. After induction therapy, the symptoms improved but abnormal shadows remained on chest X-ray films. Maintenance therapy has been continued at doses of 200 mg/day of fluconazole for 10 years. He has had no symptoms, but the abnormal X-ray shadow has persisted and the CD4 count has remained low during the same period.


How to choose the training data for neural network medical diagnosis systems.
This paper presents a research work on the generalization capability of Multilayers Feedforward Neural Networks with Backpropagation under the point of view of training data. The research is focused on the case of neural networks medical diagnosis systems and it is shown through 3-D plots of the neural network performance an appropriate way to select the training data distribution which should be used for the design of the neural network. A real world distribution which can be obtained by randomly sampling a medical data base is more appropriate than an equal distribution which is the normally used distribution in the bibliography. The results are presented by using a medical diagnosis data base: different diagnosis of one main symptom: vaginal discharge of non-menstruating women.


Development and Validation of a Qualitative Method for Target Screening of 448 Pesticide Residues in Fruits and Vegetables Using UHPLC/ESI Q-Orbitrap Based on Data-Independent Acquisition and Compound Database.
A semiautomated qualitative method for target screening of 448 pesticide residues in fruits and vegetables was developed and validated using ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC/ESI Q-Orbitrap). The Q-Orbitrap Full MS/dd-MS2 (data dependent acquisition) was used to acquire product-ion spectra of individual pesticides to build a compound database or an MS library, while its Full MS/DIA (data independent acquisition) was utilized for sample data acquisition from fruit and vegetable matrices fortified with pesticides at 10 and 100 μg/kg for target screening purpose. Accurate mass, retention time and response threshold were three key parameters in a compound database that were used to detect incurred pesticide residues in samples. The concepts and practical aspects of in-spectrum mass correction or solvent background lock-mass correction, retention time alignment and response threshold adjustment are discussed while building a functional and working compound database for target screening. The validated target screening method is capable of screening at least 94% and 99% of 448 pesticides at 10 and 100 μg/kg, respectively, in fruits and vegetables without having to evaluate every compound manually during data processing, which significantly reduced the workload in routine practice.


Particle stability in polymer-assisted reverse colorimetric DNA assays.
"Reverse" colorimetric DNA detection by the formation of core-shell particles upon DNA hybridization is described. Specifically, the assay is based on a strategy to covalently link polymer reaction initiators to suspended nanoparticles upon DNA hybridization. These initiators then prompt polymer chain growth to form a thick polymer shell outside of particles, acting as the physical barrier to keep Au particles apart. Particles without DNA hybridization aggregate, accompanied by a pronounced solution color change from red to blue. The focus of this report is to address reaction kinetics of two co-occurring processes: polymer growth and particle aggregation during the reverse colorimetric DNA assay. The results show that Cu ions used as the polymerization catalyst bind strongly to the bases in DNA molecules, resulting in crosslinking of DNA-attached gold nanoparticles and their subsequent precipitation. Both Cu-ion-assisted particle aggregation and polymer growth are found to depend strongly on Cu ion concentration, salt concentration, and reaction temperature. Under the optimized conditions, faster polymer chain growth on the surface overcomes particle aggregation and preserves particle stability via steric stabilization.


Platelet-rich fibrin in treatment of periapical lesions: a novel therapeutic option.
In the present case of a 35-year old patient, platelet-rich fibrin, which is an autologous platelet concentrate, was used to fill the osseous defect following surgery. The case was assessed both clinically and radiographically for a period of 9 months.


Effects on adult cognitive function after neonatal exposure to clinically relevant doses of ionising radiation and ketamine in mice.
Radiological methods for screening, diagnostics and therapy are frequently used in healthcare. In infants and children, anaesthesia/sedation is often used in these situations to relieve the patients' perception of stress or pain. Both ionising radiation (IR) and ketamine have been shown to induce developmental neurotoxic effects and this study aimed to identify the combined effects of these in a murine model. Male mice were exposed to a single dose of ketamine (7.5 mg kg-1 body weight) s.c. on postnatal day 10. One hour after ketamine exposure, mice were whole body irradiated with 50-200 mGy gamma radiation (137Cs). Behavioural observations were performed at 2, 4 and 5 months of age. At 6 months of age, cerebral cortex and hippocampus tissue were analysed for neuroprotein levels. Animals co-exposed to IR and ketamine displayed significant (P≤0.01) lack of habituation in the spontaneous behaviour test, when compared with controls and single agent exposed mice. In the Morris Water Maze test, co-exposed animals showed significant (P≤0.05) impaired learning and memory capacity in both the spatial acquisition task and the relearning test compared with controls and single agent exposed mice. Furthermore, in co-exposed mice a significantly (P≤0.05) elevated level of tau protein in cerebral cortex was observed. Single agent exposure did not cause any significant effects on the investigated endpoints. Co-exposure to IR and ketamine can aggravate developmental neurotoxic effects at doses where the single agent exposure does not impact on the measured variables. These findings show that estimation of risk after paediatric low-dose IR exposure, based upon radiation dose alone, may underestimate the consequences for this vulnerable population.


[Results of the Sanitary and Epidemiologic Service studies on the effects of lead on health status of workers].
The article covers through studies concerning causes of environmental pollution and workers' health state in order to specify prophylactic measures.


Neurocysticercosis: A case report and brief review.
Neurocysticercosis (NCC) is one of the seven neglected endemic zoonoses targeted by the World Health Organization. It is considered a common infection of the nervous system caused by the Taenia solium and is known to be the primary cause of preventable epilepsy in many developing countries. NCC is commonly resulted by the ingestion of Taenia solium eggs after consuming undercooked pork, or contaminated water. The parasite can grow in the brain and spinal cord within the nervous system, causing severe headache and seizures beside other pathological manifestations. Immigration and international travel to endemic countries has made this disease common in the United States. NCC can be diagnosed with computed tomography and magnetic resonance imaging of the brain. The treatment of the NCC including cysticidal drugs (e.g., albendazole and praziquantel), and neurosurgical procedure, depending upon the situation. A patient of Asian origin came to our clinic with complaints of dizziness, headaches and episodes seizures for the past twelve years without proper diagnosis. The computed tomography and magnetic resonance imaging scans indicated multilobulated cystic mass in the brain with the suspicion of neurocysticercosis.


Is Perioperative Fluid and Salt Balance a Contributing Factor in Postoperative Worsening of Obstructive Sleep Apnea?
An understanding of the potential mechanisms underlying recurrent upper airway collapse may help anesthesiologists better manage patients in the postoperative period. There is convincing evidence in the sleep medicine literature to suggest that a positive fluid and salt balance can worsen upper airway collapse in patients with obstructive sleep apnea through the redistribution of fluid from the legs into the neck and upper airway while supine, in a process known as "rostral fluid shift." According to this theory, during the day the volume from a fluid bolus or from fluid overload states (i.e., heart failure and chronic kidney disease) accumulates in the legs due to gravity, and when a person lies supine at night, the fluid shifts rostrally to the neck, also owing to gravity. The fluid in the neck can increase the extraluminal pressure around the upper airways, causing the upper airways to narrow and predisposing to upper airway collapse. Similarly, surgical patients also incur large fluid and salt balance shifts, and when recovered supine, this may promote fluid redistribution to the neck and upper airways. In this commentary, we summarize the sleep medicine literature on the impact of fluid and salt balance on obstructive sleep apnea severity and discuss the potential anesthetic implications of excessive fluid and salt volume on worsening sleep apnea.


Changes in MicroRNA Expression During Maturation of the Bovine Corpus Luteum: Regulation of Luteal Cell Proliferation and Function by MicroRNA-34a.
The corpus luteum (CL) develops from the remnants of the ovulatory follicle and produces progesterone, required for maintenance of pregnancy in mammals. The differentiation of granulosal and thecal cells into luteal cells is accompanied by hypertrophy and hyperplasia of cells. As the CL matures, growth ceases and in ruminants, the tissue acquires the ability to undergo regression in response to prostaglandin F2alpha. The regulators of this transition are poorly understood. MicroRNA, which are posttranscriptional regulators of tissue development and function, are expressed in the CL. However, the pattern of their expression and their function during the transition from developing to functional CL is not known. The objectives of this study were to profile the expression of miRNA in developing versus mature bovine CL and determine effects of miRNA on bovine luteal cell survival and function. Knockdown of Drosha in midcycle (MC) luteal cells decreased progesterone and increased luteal cell apoptosis in the presence or absence of proinflammatory cytokines. Microarray analysis demonstrated that a greater number of miRNA were expressed in MC compared to D4 CL. Ingenuity pathway analysis (IPA) predicted that D4-specific miRNA regulate pathways related to carbohydrate metabolism, while MC-specific miRNA regulate pathways related to cell cycle and apoptosis signaling. Both predictions are consistent with a switch in the CL from a growing phase to a maintenance phase. One of the MC specific miRNA, miR-34a, was selected for further analysis. Increased concentrations of miR-34a in MC luteal cells resulted in decreased luteal cell proliferation, increased progesterone production, and inhibition of Notch1 and YY1 translation, but had no effect on luteal cell apoptosis. In conclusion, these data support a role for miRNA in general, and miR-34a in particular, in luteal formation and function.


Detection of the hippocampal formation asymmetry in patients with posttraumatic stress disorder.
The goal of this work was to analyze asymmetry of hippocampal formation in PTSD patients. The objects of the analysis were 10 MRI scans of patients with PTSD with established cognitive function damage. MRI scans were obtained using MAGNET IMPACT SIEMENS 1,0 TESLA in T1 and T2 relaxation. The measurement of hippocampal formation dimensions, and comparisons between the right and the left side were done using evaluate - distance program on the MRI instrument of the Institute of Radiology at Sarajevo Clinics Center. We tested 20 patients with PTSD 49,9 years of average age with standard deviation of 4,62 years. Based on the analysis of our results regarding the size of hippocampal formation in all the three projections (axial, coronal and sagital), in the group of patients with PTSD, we can the make the following observations: 1. In axial slice the length of hippocampal formation measured on the left and right side is significantly asymmetric in all patients. In the sagital slice, the hippocampal formation measured on the left side is in many cases longer than in the right - 50 %. In coronal slice no significant differences were found in the proportion of patients according to symmetry/asymmetry of hippocampal formation width on the left and right. 2. The difference in average size of hippocampal formation between the left and right side measured in axial and coronal slices is not statistically significant, but it is significant in sagitall slice. So, the results of this new research, showed smaller hippocampal dimensions in PTSD as measured using MRI. We have to be careful about what projection we are refusing to as being watched hippocampal formation because the results will depend on that. We suggest that future studies be done in more projections because of the importance of statistically significant conclusions. MRI - volumetric measurements have their value.


[Preoperative analysis of vital lung capacity in female patients with flattened thyrotoxicosis].
Unbalanced hyperthyroidism leads to the feeling of dyspnea and to the decrease of vital lung capacity. Efficacious treatment of thyrotoxicosis relieves mentioned disorders and brings normalization of ventilation parameters. The main issue of this research was the analysis of vital lung capacity in female patients with properly treated hyperthyroidism and comparison of values of these parameters among patients with balanced thyrotoxicosis, non-toxic goitre and with non-thyroid disorders. Research was conducted on 300 randomized female-patients (ASA I, II), aged 18 to 47 with surgically treated hyperthyroidism, non-toxic goitre or non-thyroid disorders. Vital lung capacity (VLC) was analyzed as absolute values and as a percent of predicted values. Statistical analysis revealed that patients in specified groups did not differ in age, weight and frequency of belonging to both ASA categories. Vital lung capacity and percent of predicted values were not significantly different in all groups. Vital lung capacity of female-patients with balanced hyperthyroidism did not differ significantly from vital lung capacity of patients with non-toxic goitre and non-thyroid disorders.


Distribution of DTHS3 satellite DNA across 12 bivalve species.
In this study, characterization of DTHS3 satellite DNA (satDNA) was further expanded within the class Bivalvia. Monomer variants of DTHS3 satDNA were compared in 12 bivalve species belonging to two different subclasses, Heterodonta and Pteriomorphia. This satDNA, whose age is estimated to a minimum of 516 Ma, is contributing to the concept of the dual character of satDNA sequences: their sequence preservation throughout long evolutionary periods and generation of species-specific variants of the same satDNA family.


Water-catalyzed gas-phase hydrogen abstraction reactions of CH3O2 and HO2 with HO2: a computational investigation.
The gas-phase hydrogen abstraction reactions of CH(3)O(2) and HO(2) with HO(2) in the presence and absence of a single water molecule have been studied at the CCSD(T)/6-311++G(3d,2p)//B3LYP/6-311G(2d,2p) level of theory. The calculated results show that the process for O(3) formation is much faster than that for (1)O(2) and (3)O(2) formation in the water-catalyzed CH(3)O(2) + HO(2) reaction. This is different from the results for the non-catalytic reaction of CH(3)O(2) + HO(2), in which almost only the process for (3)O(2) formation takes place. Unlike CH(3)O(2) + HO(2) reaction in which the preferred process is different in the catalytic and non-catalytic conditions, the channel for (3)O(2) formation is the dominant in both catalytic and non-catalytic HO(2) + HO(2) reactions. Furthermore, the calculated total CVT/SCT rate constants for water-catalyzed and non-catalytic title reactions show that the water molecule doesn't contribute to the rate of CH(3)O(2) + HO(2) reaction though the channel for O(3) formation in this water-catalyzed reaction is more kinetically favorable than its non-catalytic process. Meanwhile, the water molecule plays an important positive role in increasing the rate of HO(2) + HO(2) reaction. These results are in good agreement with available experiments.


Effect of taurine on calcium paradox and ischemic heart failure.
The loss of mechanical function in rat hearts subjected to either the calcium-paradox or global ischemia heart failure models was found to correlate with decreases in myocardial taurine levels. Therefore, the effect of taurine treatment was assessed in the two failure procedures. The presence of taurine protected against loss of mechanical function resulting from the calcium paradox and prevented both the large decline in sarcolemmal ATPase activities and the increase in sarcolemmal calcium binding normally associated with this model. Parallel studies on reperfused, taurine-untreated ischemic hearts showed only minor changes in these sarcolemmal functions. Taurine treatment normalized the slight increase in calcium binding associated with ischemia, but had no observable effect on recovery of mechanical function. Although taurine returns selected parameters of the sarcolemma toward normal in both models, it only improves mechanical function in the paradox model. This suggests that calcium paradox-induced heart failure is more closely associated with sarcolemmal dysfunction than ischemic heart failure.


Seroprevalence of herpes simplex virus type 1 and type 2 in selected German populations-relevance for the incidence of genital herpes.
This study was carried out to determine the prevalence of antibodies to herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) in selected German populations, such as blood donors, hospital patients, and human immunodeficiency virus (HIV)-seropositive individuals. Serum samples collected between 1996 and 1998 were tested by enzyme immunoassays using monoclonal antibody-selected native gG1 and gG2 as antigens and an immunoblot using type-specific recombinant glycoproteins. Equivocal results were resolved by an "in-house" Western blot assay. The prevalence of HSV-1 antibodies increased steadily with age and reached high levels of >/=88% among subjects 40 years of age or older. In the sample of patients and blood donors, the HSV-2 seroprevalence was 12.8% (95% CI = 11.9-13.8%). About 81% of the HSV-2 seropositive subjects were coinfected with HSV-1. When adjusted for age, there was no difference in the HSV-2 seroprevalence between hospital patients and blood donors. The HSV-2 seroprevalence was significantly higher among women (15%) than among men (10.5%), yielding a female : male odds ratio of 1.5 for hospital patients and of 1.67 for blood donors. Among the HIV-infected population, 91.1% were seropositive for HSV-1 and 47.9% for HSV-2. HIV-infected women have a significantly higher risk of HSV-2 infection than men (odds ratio [OR] = 3.22; 95% confidence ratio [CI] 1.99-5.20). In conclusion, although the rate of infections with HSV-2 is relatively low in the German population, attention should be given to the further development in adolescents, especially in view of a possible decrease of HSV-1 seroprevalence in childhood.


How do depressive symptoms in husbands and wives relate to the interpersonal dynamics of marital interactions?
We investigated how depressive symptoms in husbands and wives may affect patterns of interpersonal behavior during marital conflict discussions. Using the Continuous Assessment of Interpersonal Dynamics (CAID) approach, observers rated moment-to-moment levels of dominance and affiliation for each partner, from which dynamic indices were derived, including the slopes for each partner and the degree of rhythmic entrainment between partners. Results supported predictions that the wife's depressive symptoms would be related to alterations in the dynamics of dominance, whereas the husband's depressive symptoms would be related to alterations in the dynamics of affiliation. For example, the higher the husband's depressive symptoms, the less affiliative both the wife and husband became over the interaction and the less entrained the partners were on affiliation. The results shed new light on gender differences in the impact of depressive symptoms on the management of marital disagreements. (PsycINFO Database Record


Building healthy communities in the 21st century.
A profound set of changes is occurring all around us in health care. Many of our organizations are going through a merger or consolidation; some are struggling to grow their net revenue; some are prospering in the new competitive environment; others are trying to figure out just how to survive. Our task is to create health care organizations that work, especially in a world where everything constantly seems up in the air. We know that fundamental change is required. The changes that effect our health care organizations can often times have a profound effect on our communities.


Beta-nitrostyrene derivatives as potential antibacterial agents: a structure-property-activity relationship study.
A multidisciplinary project was developed, combining the synthesis of a series of beta-nitrostyrene derivatives and the determination of their physicochemical parameters (redox potentials, partition coefficients), to the evaluation of the corresponding antibacterial activity. A complete conformational analysis was also performed, in order to get relevant structural information. Subsequently, a structure-property-activity (SPAR) approach was applied, through linear regression analysis, aiming at obtaining a putative correlation between the physicochemical parameters of the compounds investigated and their antibacterial activity (both against standard strains and clinical isolates). The beta-nitrostyrene compounds displayed a lower activity towards all the tested bacteria relative to the beta-methyl-beta-nitrostyrene analogues. This was observed particularly for the 3-hydroxy-4-methoxy-beta-methyl-beta-nitrostyrene (IVb) against the Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium). The SPAR results revealed the existence of a clear correlation between the redox potentials and the antibacterial activity of the series of beta-nitrostyrene derivatives under study.


Synthesis of 5-fluorouracil-imprinted polymers with multiple hydrogen bonding interactions.
The antitumor active compound 5-fluorouracil (5-FU) was used as a target molecule and 5-FU-imprinted polymers were synthesized using 2,6-bis(acrylamido)pyridine and/or 2-(trifluoromethyl)acrylic acid as functional monomers. The 5-FU-imprinted polymers showed a higher affinity for 5-FU than that for 5-FU derivatives. By using both functional monomers simultaneously, the affinity and separation for 5-FU were improved.


PARAFAC modeling of fluorescence excitation-emission spectra for rapid assessment of compost maturity.
Assessment of compost maturity is crucial for achieving high quality compost in order to guarantee its marketability. In this context, a novel technique that combines fluorescence excitation-emission matrices (EEMs) with parallel factor (PARAFAC) analysis to assess compost maturity is presented. A total of 60 fluorescence EEMs of composts were successfully decomposed into a three-factor model using PARAFAC analysis. Components 1 [excitation/emission (Ex/Em) wavelengths=(230, 330)/410] and 2 [Ex/Em wavelengths=(250, 350)/450] were attributable to humic-like and fulvic-like substances, whereas component 3 [Ex/Em wavelengths=(220, 280)/340] belonged to protein-like substances. Pearson correlation analysis between the common maturity indices and log scores of three components demonstrated that components 1 and 3 are more suitable to assess compost maturity than component 2. These results reveal that EEM-PARAFAC could be applied as a valuable tool for assessing compost maturity, given its high sensitivity and selectivity.


Detecting recombination and diversifying selection in human alpha-papillomavirus.
Intragenic recombination and selection analyses were performed in DNA sequences of human alpha-papillomavirus. Recombination was estimated and the corresponding breakpoints obtained by re-analyzing data grouped by phylogenetic and epidemiological criteria, using different alignment methods. Diversifying or positive selection has been scarcely studied in these viruses probably due to the high divergence rates. We have applied maximum likelihood, empirical Bayesian and maximum parsimony methods to detect the presence of positive selection. Within the HPV 16 type, significant positive selection was detected at the time of the separation of the African 1 and African 2 branches from the other populations. At the inter-type level, positive selection can be traced in some codons of the gene L2 of the high and low risk groups. These results indicate that positive selection could have been important in the evolution of HPV both at inter- and intra-type levels.


Letter to the Editor: Thrombocytopenia After Sutureless Aortic Valve Implantation: Does It Really Matter?
Despite the limited clinical relevance of thrombocytopenia after bioprosthetic aortic valve replacement (AVR), the postoperative depletion of platelet count continues to attract the attention of many authors. The development of thrombocytopenia has been evaluated either in patients receiving a sutureless bioprosthesis (1,2) or in those undergoing transcatheter aortic valve implantation, where cardiopulmonary bypass bears little or no relation to this phenomenon (3). Recently, Sánchez et al. (1) have published their findings on this topic, but their limited experience with the devices used makes their study of doubtful interest. Over three years, 27 patients were implanted with a sutureless bioprosthetic valve and were compared with 50 patients receiving a stented aortic valve. No risk factors that may have predisposed to platelet dysfunction were described in either group.Mortality and number of units of transfused red blood cells also seems to be extremely high for a patient population undergoing elective isolated AVR: it is not clear whether bleeding complications occurred in any patients and re-thoracotomy could not be performed, or whether more liberal transfusion protocols were used. In addition, platelet transfusions in patients from the sutureless group could represent a bias that renders the comparison of postoperative mean platelet volume and platelet distribution width between groups unreliable. It would have been more appropriate to consider postoperative echocardiographic findings because, in case of suboptimal placement of the prosthesis, paravalvular leakage may cause severe hemolysis and thrombocytopenia. At present, clinical data can be derived from other case series (4). At our Center, over a six-year period, AVR was performed using a sutureless, stentless, or stented bioprosthesis in 432, 193, and 180 patients, respectively, with all devices being supplied by the same manufacturer. Perioperative trends in platelet count after sutureless AVR did not show progression towards thrombocytopenia as occurs after stentless AVR (5), but compared favourably with conventional stented AVR (Fig. 1), where platelet depletion has no clinical relevance. Figure 1: Perioperative trends in platelet count after aorticvalve replacement with the sutureless Perceval, stentlessSolo, and stented Crown bioprosthetic valves.References1. Sánchez E, Corrales JA, Fantidis P, Tarhini IS, Khan I, Pineda T, González JR. Thrombocytopenia after aortic valve replacement with Perceval S sutureless bioprosthesis. J Heart Valve Dis 2016;25:75-812. Jiritano F, Cristodoro L, Malta E, Mastroroberto P. Thrombocytopenia after sutureless aortic valve implantation: Comparison between Intuity and Perceval bioprostheses. J Thorac Cardiovasc Surg 2016;152:1631-16333. McCabe JM, Huang PH, Riedl LA, et al. Incidence and implications of idiopathic thrombocytopenia following transcatheter aortic valve replacement with the Edwards Sapien® valves: A single center experience. Catheter Cardiovasc Interv 2014;83:633-6414. Santarpino G, Fischlein T, Pfeiffer S. A word of caution is needed before uttering a word of caution: Thrombocytopenia and sutureless valves. Heart Surg Forum 2016;19:E1695. Pozzoli A, De Maat GE, Hillege HL, Boogaard JJ, Natour E, Mariani MA. Severe thrombocytopenia and its clinical impact after implant of the stentless Freedom Solo bioprosthesis. Ann Thorac Surg 2013;96:1581-1586.


[Recurrent losses of consciousness in anaphylactic reactions].
Within one year a 36-year-old man had three episodes of loss of consciousness associated with a fall in blood pressure. No cause was established despite repeated hospital admissions. But an anaphylactic reaction was suspected as the cause after yet another syncope when the administration of antihistamines and steroids had quickly improved the patient's state. In retrospect it became clear that the loss of consciousness had occurred after the eating of bananas. Total IgE level was 695 kU/l and there was marked sensitization to bananas (IgE radio-allergosorbent test [RAST] class 2) and latex (IgE RAST class 2), confirmed by marked immediate-type reactions to these substances in the prick test. Dietary advice was given and the significance of the latex sensitization explained. The patient was given an allergy pass and drugs for emergency use. Anaphylactic reaction should be included in the differential diagnosis of loss of consciousness of uncertain cause. The prognosis of such a reaction is excellent only if treated at once. Both diagnosis and treatment are relatively simple.


Synthesis of 1-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)semi-carbazides and their transformation into 4-chloro-2-mercapto-N-(4,5-dihydro-5-oxo-4-phenyl-1H-1,2,4-triazol-3-yl)benzenesulfonamides as potential anticancer and anti-HIV agents.
Synthesis of a series of 1-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)semicarbazides (6-16) and 4-chloro-2-mercapto-N-(4,5-dihydro-5-oxo-4-phenyl-1H-1,2,4-triazol-3-yl)benzenesulfonamides (17-22) were reported. Compounds 7-9, 17, 19-22 were tested at the US National Cancer Institute for their in vitro anticancer and anti-HIV activities. Results of anticancer screening showed moderate activity of 21 and 22, while 19 was found to have encouraging anti-HIV activity at EC(50) = 28.8 microM.


Mycophenolate mofetil in the treatment of IgA nephropathy: a systematic review.
The aim of this study was to determine the effectiveness of mycophenolate mofetil (MMF) in IgA nephropathy (IgAN). A search through Cochrane Library, EMBASE and PubMed was carried out. Randomised controlled trials (RCTs), which compared MMF with conventional treatments, were identified. Patients' baseline, treatment strategies and study end-points were compared. Four RCTs (168 patients) were selected. All patients had histologically-confirmed IgAN and proteinuria greater than 1 g/day. The follow-up duration ranged from 1.5 to 3.0 years. MMF was used at a titrated dose of 1-2 g/day. In the two trials with subjects having moderate to high risk for progressive disease, MMF did not demonstrate any significant difference in retarding the decline in renal function and proteinuria reduction. One trial concluded that there was a trend towards worse outcomes when MMF was used in moderately-advanced disease. Only one trial involving subjects with less advanced disease (reflected by a favourable histological grade) showed a significant decrease in proteinuria in the MMF-treated group. No serious adverse events occurred in all the four trials using MMF. No benefit was seen in moderately-advanced IgAN treated with MMF. In a selected group of patients with less advanced disease, MMF was effective in proteinuria reduction. Larger randomised studies are needed to confirm or reject these results.


Stability of diluted heparin sodium stored in plastic syringes.
The stability of heparin diluted in 0.9% sodium chloride injection and stored in plastic syringes for a three-week period was studied. Heparin activity was assayed by the activated partial thromboplastin time (APTT) method. Heparin sodium (25,000 units/ml) was diluted to 500 units/ml and stored in 50-ml polypropylene syringes. Concentrations were compared in two brands of syringes stored at room temperature in the dark. In another experiment controlled for order-related assay errors, heparin was stored in one brand by syringe at either 0-4 degrees C or room temperature. There was a statistically decrease in heparin activity over three weeks in both syringes and at both 0-4 degrees C and room temperature. However, the overall drop in activity was only about 8%. Analysis of covariance confirmed significant regression with time at both temperatures. An unexpected finding was that heparin at 500 units/ml consistently assayed higher than this value. A study of the effect of glass and plastic showed that when heparin was diluted into either a glass or plastic container, there was significantly less heparin activity in the glass containers within two hours. One possible explantation for this phenomenon is absorption of heparin to glass surfaces. It was concluded that heparin can be stored in polypropylene syringe for up to three weeks without refrigeration. However, once diluted, heparin should not be stored in glass containers.


Megalencephalic leukoencephalopathy with subcortical cysts.
Megalencephalic leukoencephalopathy with subcortical cysts is one of the newly described white-matter disorders for which recognition has been brought about by advances in imaging technology. The essential diagnostic features include megalencephaly noted in infancy, motor disability in the form of spasticity, ataxia, occasional seizures, mild cognitive decline, and slow progression. Magnetic resonance imaging (MRI) shows bilateral extensive white-matter changes with cysts in the temporal regions. Based on the clinical and MRI features, megalencephalic leukoencephalopathy with subcortical cysts can be distinguished from other conditions (ie, Alexander's disease, Canavan's disease, glutaricaciduria type I) that present in infancy with megalencephaly. Megalencephalic leukoencephalopathy with subcortical cysts is an autosomal recessive disorder, and mutations in the MLC1 gene have now been shown to cause this condition. Several genotypic and phenotypic variations have been described. In India, megalencephalic leukoencephalopathy with subcortical cysts occurs predominantly in the Agarwal community. A common mutation in the MLC1 gene has been seen in 31 Agarwal patients, which suggests a founder effect.


The role of aromatherapy massage in reducing anxiety in patients with malignant brain tumours.
Research suggests that aromatherapy massage (AM) is increasingly being used by cancer patients, especially in the palliative care setting, although few studies have assessed its effectiveness. I wanted to find out whether AM reduces anxiety in patients with a primary malignant brain tumour attending their first follow-up appointment after radiotherapy. Eight patients were recruited to the study, which comprised three methods of data collection: the measurement of physical parameters; the completion of Hospital Anxiety and Depression Scales (HADS); and semi-structured interviews. The results from HADS did not show any psychological benefit from AM. However, there was a statistically significant reduction in all four physical parameters, which suggests that AM affects the autonomic nervous system, inducing relaxation. This finding was supported by the patients themselves, all of whom stated during interview that they felt 'relaxed' after AM. Since these patients are faced with limited treatment options and a poor prognosis, this intervention appears to be a good way of offering support and improving quality of life.


Health-related quality of life of pediatric patients receiving allogeneic stem cell or bone marrow transplantation: results of a longitudinal, multi-center study.
The results of a 5-year longitudinal prospective study about the health-related quality of life (HRQL) of pediatric patients receiving allogeneic bone marrow or stem cell transplantation (BMT) are described. The patients' HRQL was assessed twice before, and five times after BMT, the end point being 1 year after BMT. For the measurement of HRQL, standardized questionnaires were completed by patients, parents and physicians. The final sample consisted of 68 patients aged 4-18 years, of which 19 were lost in the course of the study owing to relapse, transplant rejection and/or death. The worst HRQL was seen shortly after transplant and HRQL thereafter improved steadily, although the improvement was not always linear and not all patients drew benefit from this average positive evolution. Compromised emotional functioning, a high level of worry and reduced communication during the acute phase of treatment had a negative impact on HRQL 1 year after BMT. Nausea and pain during the acute phase of treatment did not have an effect on later HRQL. The interobserver agreement of HRQL reports between parents and their children was moderate to good, and generally better than child-physician and parent-physician agreement.


Efficiency of combinative salicylic acid and chitosan preharvest-treatment on antioxidant and phytochemicals of ready to eat daikon sprouts during storage.
Effects of salicylic acid (SA), chitosan and combinative SA and chitosan (SA + Chitosan) preharvest-treatments on bioactive compounds improvement of daikon sprouts during cold storage (5 ± 1 °C) were investigated. In preliminary experiment, 2.0 mM SA and 0.1% chitosan treatments were best concentration in improving antioxidant activity and bioactive compounds of the sprouts during storage. In the main experiment, the effects of SA + Chitosan treatment on visual appearance, antioxidant activity, phytochemicals and antioxidant enzymes of the sprouts were monitored during storage. Visual appearance and pigments contents did not significantly change throughout storage. SA + Chitosan treated sprouts contained total phenols, ascorbic acid, antioxidant enzymes and antioxidant activity higher that control. Compared to SA and chitosan, SA + Chitosan enhanced total phenols, ascorbic acid, catalase activity and free radical scavenging activity during storage. In conclusion, SA + Chitosan could be a good mean enhancing phytochemicals of daikon sprouts during cold storage.


Neuroenteric cyst of the anterior cranial fossa: case report and review of the literature.
A case of intradural neuroenteric cyst located in the anterior cranial fossa is presented. The cyst caused anosmia and progressive personality changes in an elderly woman. The patient underwent bifrontal craniotomy with evacuation of cyst contents and removal of the cyst wall. Incidence, classification, histopathology, and histogenesis of neuroenteric cysts are discussed with review of the literature.


Proof of Concept: Design and Initial Evaluation of a Device to Measure Gastrointestinal Transit Time.
Chronic constipation and gastrointestinal motility disorders constitute a large part of a gastroenterology practice and have a significant impact on a patient's quality of life and lifestyle. In most cases, medications are prescribed to alleviate symptoms without there being an objective measurement of response. Commonly used investigations of gastrointestinal transit times are currently limited to radiopaque markers or electronic capsules. Repeated use of these techniques is limited because of the radiation exposure and the significant cost of the devices. We present the proof of concept for a new device to measure gastrointestinal transit time using commonly available and inexpensive materials with only a small amount of radiotracer. Methods: We assembled gelatin capsules containing a 67Ga-citrate-radiolabeled grain of rice embedded in paraffin for use as a point-source transit device. It was tested for stability in vitro and subsequently was given orally to 4 healthy volunteers and 10 patients with constipation or diarrhea. Imaging was performed at regular intervals until the device was excreted. Results: The device remained intact and visible as a point source in all subjects until excretion. When used along with a diary of bowel movement times and dates, the device could determine the total transit time. The device could be visualized either alone or in combination with a barium small-bowel follow-through study or a gastric emptying study. Conclusion: The use of a point-source transit device for the determination of gastrointestinal transit time is a feasible alternative to other methods. The device is inexpensive and easy to assemble, requires only a small amount of radiotracer, and remains inert throughout the gastrointestinal tract, allowing for accurate determination of gastrointestinal transit time. Further investigation of the device is required to establish optimum imaging parameters and reference values. Measurements of gastrointestinal transit time may be useful in managing patients with dysmotility and in selecting the appropriate pharmaceutical treatment.


Orientation restraints in molecular dynamics simulations using time and ensemble averaging.
In this article we present methodology for simulating protein dynamics while imposing restraints derived from NMR measurements on partially ordered molecules. Such measurements may include residual dipolar couplings and chemical-shift anisotropies. We define a restraint potential for use in molecular dynamics and energy minimization. The presented potential is consistent with the simultaneously optimized molecular order tensor. Restraining can be performed with time and ensemble averaging. We performed a large number of molecular dynamics simulations of the histidine containing phosphocarrier protein with restraints on backbone N-H vector orientations derived from residual dipolar couplings. From these simulations it is evident that the use of time- or ensemble-averaged restraints is essential to leave the fluctuations of the restrained vectors unaffected. Without averaging the fluctuations of the restrained vectors are reduced significantly. This also has the effect of decreasing the apparent molecular order-parameter tensor.


Behavioral screening for nightblindness mutants in zebrafish reveals three new loci that cause dominant photoreceptor cell degeneration.
Here we report three dominant nightblindness mutations in zebrafish: nightblindness e (nbe), nightblindness f (nbf) and nightblindness g (nbg). The mutants were isolated in the F1 generation of N-ethyl-N-nitrosourea (ENU) mutagenized zebrafish using a behavioral assay based on visually mediated escape responses. Subsequently, electroretinographic (ERG) recordings were made, and histological sections were screened for degenerative processes. For each mutant line, correlation analysis between behavioral, ERG and histological parameters was performed, and their relationships were determined by either calculating the Pearson correlation coefficient or by ANOVA. nbe is characterized by severe rod outer segments (ROS) degeneration. The degeneration correlates weakly with behavioral threshold and ERG b-wave amplitude, however, behavioral threshold correlates strongly with ERG b-wave. nbf is characterized by a dual histological pathology: patchy ROS-degeneration and 'gaps' homogeneously distributed over the outer nuclei layer (ONL) and between cone outer segments (COS). The correlations between histological pathology and behavioral threshold, and between behavioral threshold and ERG b-wave amplitude are obvious, but the correlation between histology and b-wave amplitude is less prominent. nbg is characterized by moderate ROS degeneration and moderate correlation between histology and behavioral threshold. Interestingly, behavioral threshold correlated inversely with ERG b-wave amplitude and threshold. Thus, contrary to what is normally seen in other nightblindness mutants, in nbg, the fish with the lowest behavioral threshold had the smallest b-waves amplitudes and the highest b-wave threshold. In our interpretation, the major impairment in nbe is photoreceptor-specific. In nbf, both photoreceptor degeneration and altered post-photoreceptor signaling are responsible for the behavioral deficit. In nbg, we find hypersensitivity at a post-photoreceptoral level concurrently with behavioral impairment.


Effectiveness of Integrated Simulation and Clinical Experiences Compared to Traditional Clinical Experiences for Nursing Students.
The focus of this research study was the evaluation of the effectiveness of using high-fidelity simulations to replace 50 percent of traditional clinical experiences in obstetrics, pediatrics, critical care, and mental health nursing. Increasing student admissions to nursing programs require additional clinical learning opportunities to accommodate extra students. Three schools with associate degree nursing programs partnered to identify, implement, and evaluate a creative solution to this dilemma. The resulting quasi-experimental study investigated if substituting half of the conventional clinical experiences with simulations was as effective as traditional clinical activities in obstetrics, pediatrics, mental health, and critical care. One hour of simulation counted for two hours of clinical time. RESULTS Findings indicated combining simulations with conventional clinical experiences resulted in significantly higher scores on the pre-graduation exit exam than traditional clinical experiences alone. Findings have implications for articulation and basic students in associate degree nursing programs.


Adjuvant chemohormonal therapy of high risk prostate carcinoma. Ten year results.
Patients with T3 and/or N1 prostate carcinoma have poor cure rates. The authors sought to improve the relapse free, cancer specific survival of these patients by adding chemohormonal therapy to radiation. Twenty-five men with clinical Stage III positive seminal vesicles or positive nodes received six courses of vinblastine, doxorubicin, and mitomycin with simultaneous radiation and permanent androgen deprivation. Prostate specific antigen (PSA) testing was the sole criterion for relapse. Median followup was 10.5 years. Treatment was well tolerated. Patients received 91-95% of each drug and all planned radiation. At 10 years the cumulative relapse free rate determined by continuously undetectable PSA levels was 73%, and the cumulative cancer specific survival was 81%. Of node-positive patients, 82% were relapse-free at 10 years. The addition of chemotherapy to hormonal and radiation therapy is feasible and is accepted by most men when they are openly informed of their prognosis with conventional therapy. Results in the current small series appear excellent and may be superior to radiation plus hormones alone. Larger randomized studies are warranted.


Association of alpha-synuclein and mutants with lipid membranes: spin-label ESR and polarized IR.
Alpha-synuclein is a presynaptic protein, the A53T and A30P mutants of which are linked independently to early-onset familial Parkinson's disease. The association of wild-type alpha-synuclein with lipid membranes was characterized previously by electron spin resonance (ESR) spectroscopy with spin-labeled lipids [Ramakrishnan, M., Jensen, P. H., and Marsh, D. (2003) Biochemistry 42, 12919-12926]. Here, we study the interaction of the A53T and A30P alpha-synuclein mutants and a truncated form that lacks the acidic C-terminal domain with phosphatidylglycerol bilayer membranes, using anionic phospholipid spin labels. The strength of the interaction with phosphatidylglycerol membranes lies in the order: wild type approximately truncated > A53T > A30P > fibrils approximately 0, and only the truncated form interacts with phosphatidylcholine membranes. The selectivity of the interaction of the mutant alpha-synucleins with different spin-labeled lipid species is reduced considerably, relative to the wild-type protein, whereas that of the truncated protein is increased. Polarized infrared (IR) spectroscopy is used to study the interactions of the wild-type and truncated proteins with aligned lipid membranes and additionally to characterize the fibrillar form. Wild-type alpha-synuclein is natively unfolded in solution and acquires secondary structure upon binding to membranes containing phosphatidylglycerol. Up to 30-40% of the amide I band intensity of the membrane-bound wild-type and truncated proteins is attributable to beta-sheet structure, at the surface densities used for IR spectroscopy. The remainder is alpha-helix and residual unordered structure. Fibrillar alpha-synuclein contains 62% antiparallel beta-sheet and is oriented on the substrate surface but does not interact with deposited lipid membranes. The beta-sheet secondary-structural elements of the wild-type and truncated proteins are partially oriented on the surface of membranes with which they interact.


Cyclic AMP and Ca2+ as regulators of zygote formation in the cellular slime mold Dictyostelium mucoroides.
To analyze the mechanism of the sexual process (macrocyst formation) in the cellular slime mold Dictyostelium mucoroides-7 (Dm7), the effects of 3',5'-cyclic adenosine monophosphate (cAMP), conditioned medium (CM) factors, and various ions including Ca2+ on zygote formation were examined. The application of cAMP was found to inhibit the sexual cell fusion. In addition, the activity of fusion inhibitor(s) contained in CM was heat stable and lost by phosphodiesterase (PDE)-treatment, thus indicating that cAMP is the inhibitor, being in contrast to ethylene as a fusion activator. Pulse experiments using two cAMP analogues, 2'-deoxy-cAMP and 8-bromo-cAMP suggested that the signal transduction system through the cell surface cAMP receptor is of particular importance for regulation of the sexual fusion process. Among several ions having effects on zygote formation, Ca2+ seemed to be necessary both for the acquisition of fusion competence and for cell fusion itself. In the presence of Ca2+, K+ and Na+ had the opposite effects on zygote formation; K+ was stimulative, while Na+ inhibitory. The significance of these findings is discussed in relation to the regulatory mechanism of zygote formation.


Molecular modelling of cytochrome CYP1A1: a putative access channel explains differences in induction potency between the isomers benzo(a)pyrene and benzo(e)pyrene, and 2- and 4-acetylaminofluorene.
The present studies were undertaken to provide a rationale for the observation that benzo(a)pyrene and 2-acetylaminofluorene induce the hepatic CYP1A1 protein, whereas their non-carcinogenic isomers benzo(e)pyrene and 4-acetylaminofluorene are, at best, relatively very weak inducers. Using amino acid sequence alignment, a molecular model of the CYP1A1 was constructed by analogy to CYP101, the bacterial protein for which the 3-dimensional structure is known from X-ray crystallographic analysis. The putative structure of the active site of the CYP1A1 protein shows the presence of two phenylalanine residues preferentially aligned in parallel orientation, presumably functioning as a 'sieve' for planar molecules, the established substrates of CYP1A1. The molecular dimensions of this putative access channel show a width and depth of 8.321 and 3.261 A, respectively. The width of 4-acetylaminofluorene, 8.794 A, and benzo(e)pyrene, 9.153 A, precludes their passage through this channel access in contrast to benzo(a)pyrene and 2-acetylaminofluorene having a width of 7.150 and 5.283 A, respectively, explaining their difference in CYP1A1 induction potential.


Targeting Brucella melitensis with polymeric nanoparticles containing streptomycin and doxycycline.
Treatment and eradication of intracellular pathogens such as Brucella is difficult because infections are localized within phagocytic cells and most antibiotics, although highly active in vitro, do not actively pass through cellular membranes. Thus, an optimum strategy to treat these infections should address targeting of active drugs to the intracellular compartment where the bacteria replicate, and should prolong the release of the antibiotics so that the number of doses and associated toxicity can be reduced. We incorporated streptomycin and doxycycline into macromolecular nanoplexes with anionic homo- and block copolymers via cooperative electrostatic interactions among the cationic drugs and anionic polymers. The approach enabled simultaneous binding of both antibiotics into the nanoplexes, and their use resulted in an improvement in performance as compared with the free drugs. Administration of two doses of the nanoplexes significantly reduced the Brucella melitensis load in the spleens and livers of infected BALB/c mice. The nanoplexes were more effective than free drugs in the spleens (0.72-log and 0.51-log reductions, respectively) and in the livers (0.79-log and 0.42-log reductions, respectively) of the infected mice. Further research regarding the design of optimum nanoplex structures will be directed towards alterations in both the core and the shell properties to investigate the effects of the rates and pathways of entry into immune cells where the brucellae replicate.


Immunochemical identification of antigens of Brucella melitensis by means of CRIE.
A crude extract of Brucella melitensis was obtained by sonication, centrifugation and dialysis, and analyzed by quantitative immunoelectrophoresis. CIE analysis, using a high titer purified rabbit antibody anti-brucella fraction, showed that the Brucella melitensis extract contained at least 22 antigens that all moved towards the anode. The antigens of the crude extract able to interact with IgG of patients affected by brucellosis, were identified by means of CRIE using sheep 125I-anti human IgG. Fifteen sera of patients affected by brucellosis were analyzed by CRIE and three (Ag6, Ag12, Ag15) of the 22 antigens were able to bind specific human IgG to their corresponding immunoprecipitates. Ag6 was the only one present after one day of the CRIE plate exposure. After treatment of brucellosis patients with antibiotics for two weeks, the three antigens were still able to bind the specific IgG, after two months of treatment the antigens were reduced to two (Ag6, Ag15), while after ten months only one antigen (Ag6) was still able to bind specific human IgG. The brucellosis titer determined with common methods gave normal values after ten months of therapy. These results suggest that Ag6 is the most important antigen specific for human IgG. A preliminary determination of the molecular weight range of these antigens was carried out by a combination of size exclusion chromatography and CIE analysis. The Kav values were all above 66 kD.