Effect of using triclosan-impregnated suture for incisional closure on surgical site infection and inflammation following tibial plateau leveling osteotomy in dogs.
To compare surgical site infection and inflammation rates between the use of nonimpregnated (polydioxanone and poliglecaprone 25) versus triclosan-impregnated (polydioxanone and poliglecaprone 25) suture for incisional closure in dogs undergoing a standardized orthopedic procedure (tibial plateau leveling osteotomy [TPLO]). Retrospective cohort study. 283 dogs that underwent TPLO between November 2005 and December 2009. Medical records were reviewed for age; body weight; body condition score; use of propofol; perioperative and postoperative administration of antimicrobials; presence of a preoperative infection; use of a jig; technique of joint exploration; type of suture material (triclosan impregnated vs nonimpregnated) used to close the pes anserinus, subcutaneous layer, and subcuticular layer; use of staples or suture to close the skin; and surgery and anesthesia durations. The outcome variables were surgical site inflammation and infection. Rates of infection and inflammation did not differ between surgeries for which triclosan-impregnated suture was used (n = 159 [8.8%, and 18.8%, respectively]) and those for which nonimpregnated suture was used (112 [10.7% and 15.2%, respectively]). The use of staples, compared with suture, to close the skin significantly decreased the inflammation rate. Compared with in vitro conditions, in vivo conditions (where the environment is not controlled and triclosan may elute more quickly from the suture) may decrease the antibacterial effectiveness of triclosan-impregnated suture. On the basis of our findings, triclosan-impregnated sutures did not seem to provide an additional benefit for clinical use and cannot be strongly recommended for elective orthopedic procedures in veterinary medicine.


Specific combinations of ion channel inhibitors reduce excessive Ca2+ influx as a consequence of oxidative stress and increase neuronal and glial cell viability in vitro.
Combinations of Ca2+ channel inhibitors have been proposed as an effective means to prevent excess Ca2+ flux and death of neurons and glia following neurotrauma in vivo. However, it is not yet known if beneficial outcomes such as improved viability have been due to direct effects on intracellular Ca2+ concentrations. Here, the effects of combinations of Lomerizine (Lom), 2,3-dioxo-7-(1H-imidazol-1-yl)6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]acetic acid monohydrate (YM872), 3,5-dimethyl-1-adamantanamine (memantine (Mem)) and/or adenosine 5'-triphosphate periodate oxidized sodium salt (oxATP) to block voltage-gated Ca2+ channels, Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, NMDA receptors and purinergic P2X7 receptors (P2X7R) respectively, on Ca2+ concentration and viability of rat primary mixed cortical (MC) cultures exposed to hydrogen peroxide (H2O2) insult, were assessed. The contribution of ryanodine-sensitive intracellular stores to intracellular Ca2+ concentration was also assessed. Live cell calcium imaging revealed that a 30min H2O2 insult induced a slow increase in intracellular Ca2+, in part from intracellular sources, associated with loss of cell viability by 6h. Most combinations of inhibitors that included oxATP significantly decreased Ca2+ influx and increased cell viability when administered simultaneously with H2O2. However, reductions in intracellular Ca2+ concentration were not always linked to improved cell viability. Examination of the density of specific cell subpopulations demonstrated that most combinations of inhibitors that included oxATP preserved NG2+ non-oligodendroglial cells, but preservation of astrocytes and neurons required additional inhibitors. Olig2+ oligodendroglia and ED-1+ activated microglia/macrophages were not preserved by any of the inhibitor combinations. These data indicate that following H2O2 insult, limiting intracellular Ca2+ entry via P2X7R is generally associated with increased cell viability. Protection of NG2+ non-oligodendroglial cells by Ca2+ channel inhibitor combinations may contribute to observed beneficial outcomes in vivo.


[An overview of the definition and implementation of the Brazilian National Policy on Health Data and Information Technology].
The This qualitative study aimed to analyze the development and implementation of the Brazilian National Policy on Health Data and Information Technology (NPIIH). We analyzed documents and applied an online questionnaire to the experts involved in developing the policy. The data were submitted to content analysis using the categorical thematic modality. The PNIIS is the target of debate and proposals at various levels. Provisions have appeared in parallel to regulate measures on health data and information technology. Community participation in developing this policy and the convergence of laws, standards, resolutions, and policy-making levels in a common and broadly acknowledged and enforced policy are challenges, in addition to linking the public and private sectors. The study concludes that the National Policy on Health Data and Information Technology is making gradual progress, predominantly in theoretical debates, revisions, and updates. There are numerous challenges for its implementation and a prevailing need for legitimation.


Fuel utilization and glucose hyperalimentation after liver resection.
Clinical studies and experiments in rats were carried out to elucidate changes in fuel utilization after hepatectomy. In addition, the effect of glucose hyperalimentation on energy metabolism in the liver remnant was studied. Respiratory quotient (RQ) and substrate oxidation rate for fat and glucose were evaluated by indirect calorimetry in eight patients who had undergone liver resection. Patients had a reduced nonprotein RQ of approximately 0.85 and a reduced ratio of glucose to fat oxidation of approximately 2.0 on the 1st and 2nd postoperative days. After 80% hepatectomy, rats received either 30 kcal.kg-1.day-1 (group 1) or 200 kcal.kg-1.day-1 (group 2) of glucose for 48 h. In both rat groups, hepatic mitochondrial ATP synthesis 12 and 24 h after hepatectomy was accelerated when palmitic acid was used as the substrate and suppressed when pyruvate was used compared with sham-operated groups. This suggests that the energy substrate of the remnant liver was principally fatty acids rather than glucose, which seems to occur also in humans. Hepatic energy charge was within normal limits in group 1 (0.862 +/- 0.008) but decreased significantly in group 2 (0.818 +/- 0.006, p < 0.01) 12 h after hepatectomy. An abundance of glucose in the early postoperative period therefore caused a hepatic energy derangement by suppressing endogenous fat oxidation. This suppression was corroborated by the findings of lower immunoreactive glucagon and nonesterified fatty acid concentration in group 2. Therefore, glucose hyperalimentation in the early postoperative period after liver resection is not recommended.


Sequence of alcohol-induced initial changes in plasma lipoproteins (VLDL and HDL) and lipolytic enzymes in humans.
The sequence of alterations in the concentration and composition of different plasma lipoproteins following alcohol intake is not known. We therefore monitored the concentrations of cholesterol, triglycerides, phospholipids, and proteins in the major lipoprotein fractions (VLDL, LDL, HDL2, and HDL3) in ten nonalcoholic healthy male volunteers who were given 5.5 g of alcohol per kilogram of body weight during 21/2 days (a weekend). In addition, lipoprotein lipase activity was measured in post-heparin plasma and in adipose tissue and hepatic lipase activity was measured in post-heparin plasma before and after the experiment. in a separate control experiment, the same subjects received meals and liquids without alcohol. Blood alcohol levels remained below 1.5 g/L. Alcohol caused a progressive increase in the fasting VLDL triglyceride and phospholipid concentrations, both of which were doubled during the experiment (P less than 0.001). In contrast, the VLDL cholesterol levels remained unchanged until the third morning, when there was a slight increase. The LDL triglyceride and phospholipid concentrations also rose without simultaneous changes in the LDL cholesterol concentration. Consistent with these changes, the HDL cholesterol concentration showed no response to alcohol during the experiment, but the HDL phospholipid level rose from 76 to 99 mg/dL (P less than 0.001). This was reflected as an increase in the HDL2 concentration from 124 to 158 mg/dL (P less than 0.01), whereas no change occurred in the HDL3 level. The increment of HDL2 concentration was due to a rise of its triglycerides, phospholipids, and apoproteins A-I and A-II but not to a rise of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)


Structural modelling of substrate binding and inhibition in penicillin V acylase from Pectobacterium atrosepticum.
Penicillin V acylases (PVAs) and bile salt hydrolases (BSHs) have considerable sequence and structural similarity; however, they vary significantly in their substrate specificity. We have identified a PVA from a Gram-negative organism, Pectobacterium atrosepticum (PaPVA) that turned out to be a remote homolog of the PVAs and BSHs reported earlier. Even though the active site residues were conserved in PaPVA it showed high specificity towards penV and interestingly the penV acylase activity was inhibited by bile salts. Comparative modelling and docking studies were carried out to understand the structural differences of the binding site that confer this characteristic property. We show that PaPVA exhibits significant differences in structure, which are in contrast to those of known PVAs and such enzymes from Gram-negative bacteria require further investigation.


Measurement invariance of the Mini Asthma Quality of Life Questionnaire across African-American and Latino adult asthma patients.
This study tested the factorial and measurement invariance of the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) in a sample of Latino and African-American asthmatic patients. We used confirmatory factor analyses (CFA) to examine data from adult outpatients diagnosed with asthma (n = 265). We proceeded by examining the original factor structure of the MiniAQLQ in the whole sample. We then determined whether the factor structure supported by the data was invariant across African-American and Latino patients by testing a series of nested models. Results revealed that a three-factor structure model that combined the emotional function and symptom domains had the best fit to the whole sample (chi (2)(91) = 99.83, P = 0.08). Analysis using a MIMIC model among Latino participants indicated that survey language did not influence item functioning (chi (2)(93) = 103.29, P = 0.22). Multi-group CFA showed that both the structure and the meaning of the items were invariant across Africa-American and Latino participants. Scalar and strict measurement invariance was supported for 11 out of 15 items. These data suggest that structure of the MiniAQLQ needs to be reassessed. Additional research needs to examine whether elimination of current items or inclusion of new items can ensure that constructs are measured without bias across different ethnic groups.


The investigation of circulating microRNAs associated with lipid metabolism in childhood obesity.
Childhood obesity is an increasing health challenge related to increased risk of chronic diseases. microRNAs (miRNAs) are noncoding short RNA molecules regulating multiple biological processes linked to obesity. We aimed at evaluating the association between circulating miRNA levels and lipid metabolism in obese and non-obese children and adolescents. By constituting study group, 45 obese children and adolescents were recruited. To perform comparisons with study group, 41 lean controls were matched for age and sex. Using real-time quantitative PCR analysis, circulating miRNAs were evaluated in both groups. Circulating miR-335 (P < 0.001), miR-143 (P = 0.001) and miR-758 (P = 0.006) in obese children were significantly lower than those of controls. However, circulating miR-27 (P = 0.032), miR-378 (P < 0.001) and miR-370 (P = 0.045) in obese children were significantly higher, compared with those of controls. In addition, circulating miR-33 in obese children was higher than those of controls, but no significant difference was present (P = 0.687). Our findings showed that a significant association is present between circulating miR-370, miR-33, miR-378, miR-27, miR-335, miR-143 and miR-758 values, and childhood obesity. Low levels of miR-335, miR-143 and miR-758, and high levels of miR-27, miR-378, miR-33 and miR-370 may have been responsible for elevated triglycerides and low-density lipoprotein (LDL-C) levels, and low level of high-density lipoprotein (HDL-C) in obese subjects. Therefore, miRNAs may be a good novel biomarker for childhood obesity.


Hemodynamic changes during posterior epilepsies: an EEG-fNIRS study.
Posterior epilepsies are mainly characterized clinically by visual symptoms. Functional near-infrared spectroscopy (fNIRS) is an emerging non-invasive imaging technique that has the potential to monitor hemodynamic changes during epileptic activity. Combined with electroencephalography (EEG), 9 patients with posterior epilepsies were recorded using EEG-fNIRS with large sampling (19 EEG electrodes and over 100 fNIRS channels). Spikes and seizures were carefully marked on EEG traces, and convolved with a standard hemodynamic response function for general linear model (GLM) analysis. GLM results for seizures (in 3 patients) and spikes (7 patients) were broadly sensitive to the epileptic focus in 7/9 patients, and specific in 5/9 patients with fNIRS deoxyhemoglobin responses lateralized to the correct lobe, and to plausible locations within the occipital or parietal lobes. This work provides evidence that EEG-fNIRS is a sensitive technique for monitoring posterior epileptic activity.


The effects of aging on sexuality.
A variety of myths prevail about sexuality and aging, many of which are accepted by the elderly themselves. How aging actually affects sexuality is explored here, as is the social worker's potential role in educating and supporting elderly clients in regard to sexual issues.


[Inadequate care by family caregiver of frail elderly living at home].
In order to elucidate the present situation and background of inadequate care of frail elderly living at home by family caregivers, a questionnaire survey was performed on family caregivers. A total of 408 family caregivers were analyzed. The major results of this survey were as follows; 1. Thirty two percent of caregivers were associated with inadequate care. The percentage of main details of inadequate care were "ignoring" was 19%, "the infliction of mental anguish (e.g. insulting or verbal aggression)" was 14% and "physical injury (e.g. slap, pinch or kick)" was 8%. 2. As a result of the analysis of answers to open-ended questions by caregivers, the reason for inadequate care were classified roughly into three groups as follows; 1. stress and feelings of the caregiver 2. behavior or characteristics of the elderly 3. human relationship between the caregiver and the elderly or the caregiver and the relatives. 3. Frequency of caregiver's emotion of animosity to elderly were "often" was 3.9%, "sometimes" was 18.1%, "occasionally" was 39.2%, "rarely" was 22.5%, "none" was 11.5%. The main reason for animosity were "elderly happened to be angry or complained", "not able to understand caregivers talk", "irritated due to being busy" or "there is no feeling of appreciation in the elderly". 4. The relation of inadequate care and emotion of animosity was large (chi 2 test, P < 0.0001) and correlation of degree of animosity and experience of inadequate care was linear.


Bacterial production of short-chain organic acids and trehalose from levulinic acid: a potential cellulose-derived building block as a feedstock for microbial production.
Levulinic acid (LA) is a platform chemical derived from cellulosic biomass, and the expansion of LA utilization as a feedstock is important for production of a wide variety of chemicals. To investigate the potential of LA as a substrate for microbial conversion to chemicals, we isolated and identified LA-utilizing bacteria. Among the six isolated strains, Pseudomonas sp. LA18T and Rhodococcus hoagie LA6W degraded up to 70 g/L LA in a high-cell-density system. The maximal accumulation of acetic acid by strain LA18T and propionic acid by strain LA6W was 13.6 g/L and 9.1 g/L, respectively, after a 4-day incubation. Another isolate, Burkholderia stabilis LA20W, produced trehalose extracellularly in the presence of 40 g/L LA to approximately 2 g/L. These abilities to produce useful compounds supported the potential of microbial LA conversion for future development and cellulosic biomass utilization.


Synthesis, spectroscopic characterisation and structure of the first chiral heteroleptic bis(phthalocyaninato) rare earth complexes.
Treatment of MIII(Pc)(acac) (M = Sm, Eu, Gd; Pc = phthalocyaninate; acac = acetylacetonate), generated in situ, with 3-(3-pentyloxy)phthalonitrile in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in n-pentanol affords racemic mixtures of the chiral double-deckers MIII(Pc)[Pc(OC5H11)4] [Pc(OC5H11)4 = 1,8,15,22-tetrakis(3-pentyloxy)phthalocyaninate], which have been spectroscopically and structurally characterised.


The survival of Ostertagia circumcincta and Trichostrongylus colubriformis in faecal culture as a source of bias in apportioning egg counts to worm species.
When cultured alone or concurrently with Trichostrongylus colubriformis in sheep faeces, Ostertagia circumcincta produced fewer infective larvae per 100 eggs than did T. colubriformis. Averaged over five trials 60% of T. colubriformis eggs were recovered as infective larvae while for O. circumcincta the figure was only 39%. This result was observed for two strains of O. circumcincta and was independent of when larvae were harvested from culture (days 6-10 at 25 degrees C). The mortalities of both species occurred at the first and second larval stages. These observations are of concern when using larval differentiation from faecal culture to make quantitative estimates of worm egg numbers for each species present. Species such as T. colubriformis which have a low mortality during culture are likely to have their egg numbers overestimated when cultured with a species, like O. circumcincta, that suffers high mortality in culture.


Absorption of pancreatic lipase from the duodenum into lymphatics.
A significantly higher lipase activity was measured in the duodenal lymph samples of 15 dogs than in each of corresponding arterial blood plasma samples collected prior to, during and after maximal hormonal stimulation of pancreatic secretion. The result may be evaluated as a sign of pancreatic lipase absorption by the duodenum into lymphatics.


Steroidal glycosides from the aerial part of Asclepias incarnata.
The aerial part of Asclepias incarnata afforded 34 pregnane glycosides. These were confirmed to have lineolon, isolineolon, ikemagenin, 12-O-nicotinoyllineolon, deacylmetaplexigenin, metaplexigenin, rostratamine, 12-O-acetyllineolon, 15beta-hydroxylineolon and 15beta-hydroxyisolineolon moieties as their aglycones, and 2.6-dideoxyhexopyranose, glucopyranose and allopyranose as the corresponding sugar constituents. Their structures were determined using both spectroscopic and chemical methods.


Epidemiology of respiratory syncytial virus infection and its effect on children with heart disease in Hong Kong: a multicentre review.
There is no guideline in Hong Kong regarding respiratory syncytial virus (RSV) immunoprophylaxis for children with heart disease because of a lack of local data on RSV infection. Therefore, this study evaluated the epidemiology and impact of RSV infection on children with heart disease in Hong Kong, with the goal of providing recommendations regarding RSV immunoprophylaxis. This multicentre retrospective case-control study on paediatric RSV infection was conducted in four local regional hospitals from 2013 to 2015. The patients' demographic and clinical data were retrieved and analysed. There were 3538 RSV hospitalisations during the study period, and the mortality rate was 0.14%. Some RSV seasonality was present in Hong Kong, primarily in spring and summer. Respiratory syncytial virus infection was positively correlated with relative humidity and negatively correlated with wind speed and atmospheric pressure. Patients with heart disease had a more severe outcome than those without, including longer median hospital stay (4 vs 2 days, P<0.001), higher complication rate (28.6% vs 9.8%, P<0.001), and higher rates of intensive care (11.6% vs 1.4%, P<0.001) and mechanical ventilation (3.6% vs 0.4%, P=0.003). Complications in non-cardiac patients included myocarditis and Kawasaki disease. Predictors of severe RSV infection in patients with heart disease were heart failure, pulmonary hypertension, and severe airway abnormalities associated with congenital heart disease. Respiratory syncytial virus infection occurs mainly in spring and summer in Hong Kong, and is related to meteorological conditions. Respiratory syncytial virus infection poses a heavy disease burden on children with heart disease. A local guideline on RSV immunoprophylaxis for these children is therefore needed.


Why is health relatively poor on Sri Lanka's tea estates?
The mountainous interior of Sri Lanka is one of the world's great tea-producing areas. The labour force on the tea estates consists of a population which has migrated from Tamil Nadu, in southern India, over the last one hundred years. This migrant population is known as 'Indian Tamils' and is largely drawn from the two largest Harijan castes of agricultural labourers in Tamil Nadu. On the now government owned estates, they have formed a kind of industrial proletariat, living in long estate line housing where each family has one or two rooms. The women, who are the tea pickers, work longer hours than do the men. The Indian Tamils have been characterized by markedly higher mortality than the indigenous population (Sinhalese, Sri Lankan Tamils and Moors). This paper reports a research program which was carried out in 1987 and which employed both anthropological and demographic survey techniques in an attempt to explain these higher mortality levels. The research identified the origins of higher mortality, both in limited access to health provision and in the social characteristics and economic circumstances of the community.


A review of interventions to reduce mechanical restraint and seclusion among adult psychiatric inpatients.
This review examines the nature and effectiveness of interventions to reduce the use of mechanical restraint and seclusion among adult psychiatric inpatients. Thirty-six post-1960 empirical studies were identified. The interventions were diverse, but commonly included new restraint or seclusion policies, staffing changes, staff training, case review procedures, or crisis management initiatives. Most studies reported reduced levels of mechanical restraint and/or seclusion, but the standard of evidence was poor. The research did not address which programme components were most successful. More attention should be paid to understanding how interventions work, particularly from the perspective of nursing staff, an issue that is largely overlooked.


Autologous bacteria induce chemotaxis of peripheral blood mononuclear cells (MNC) from non-atopic asthmatics.
The chemotactic response of peripheral blood MNC from healthy subjects and non-atopic asthmatics against the respective pathogen isolated and cultured from sputum of individual patients was investigated. We found that the wide range of concentrations of autologous bacteria induced chemotaxis of MNC from asthmatics but showed no influence on MNC from healthy subjects. This finding might explain the mechanism of lymphocyte accumulation in the lungs of non-atopic asthmatics.


Prevalence of Giardia spp. infection in pre-weaned and weaned calves in relation to management factors.
Two hundred and forty calf faecal samples from 16 Malaysian farms were screened by PCR for Giardia spp. The overall prevalence was 12.5% and the overall farm prevalence was 68.8% (11/16 farms). The prevalence in pre-weaned and weaned calves was 16.7% and 8.3%, respectively. Sequence analysis of 25 isolates identified all as G. duodenalis assemblage E. Management factors associated with an increased risk of infection with Giardia spp. included keeping weaned calves in pens with sand floors and calf age. Keeping pre-weaned calves in pens with concrete floors and calving in single cow calving areas decreased the risk.


Great cormorants (Phalacrocorax carbo) can detect auditory cues while diving.
In-air hearing in birds has been thoroughly investigated. Sound provides birds with auditory information for species and individual recognition from their complex vocalizations, as well as cues while foraging and for avoiding predators. Some 10% of existing species of birds obtain their food under the water surface. Whether some of these birds make use of acoustic cues while underwater is unknown. An interesting species in this respect is the great cormorant (Phalacrocorax carbo), being one of the most effective marine predators and relying on the aquatic environment for food year round. Here, its underwater hearing abilities were investigated using psychophysics, where the bird learned to detect the presence or absence of a tone while submerged. The greatest sensitivity was found at 2 kHz, with an underwater hearing threshold of 71 dB re 1 μPa rms. The great cormorant is better at hearing underwater than expected, and the hearing thresholds are comparable to seals and toothed whales in the frequency band 1-4 kHz. This opens up the possibility of cormorants and other aquatic birds having special adaptations for underwater hearing and making use of underwater acoustic cues from, e.g., conspecifics, their surroundings, as well as prey and predators.


An investigation of exciton behavior in type-II self-assembled GaSb/GaAs quantum dots.
We report the investigation of exciton dynamics in type-II self-assembled GaSb/GaAs quantum dots. The GaSb/GaAs quantum dots (QDs) were grown using a modified liquid phase epitaxy technique. Statistical size distributions of the uncapped QDs were investigated experimentally by field-emission scanning electron microscopy (SEM) and atomic force microscopy (AFM), and theoretically by an eight-band k · p calculation, which demonstrated a dissolution effect. Furthermore, the low-temperature luminescence spectra of type-II GaSb/GaAs QDs with a thick capping layer exhibit well-resolved emission bands and LO-phonon-assisted transitions in the GaSb wetting layer. However, the luminescence lines quench at temperatures above 250 K, which is attributed to the weak quantum confinement of electrons participating in indirect exciton recombination. It was demonstrated that the room temperature stability of the excitons in type-II GaSb/GaAs QDs could be achieved by growing thin a capping layer, which provides strong quantum confinement in the conduction band and enhances the electron-hole Coulomb interaction, stabilizing the excitons.


Schwann cell involvement in the neurological lesion of the dystonic mutant mouse. A nerve grafting study.
Schwann cell function in the dystonic mutant mouse was studied by grafting peripheral nerve from normal into affected littermates of a C57/BL (Fa.) dt dystonic mouse colony and vice versa. In a control experiment, only unaffected animals of the colony were used, and nerve isografts were found to be ultrastructurally indistinguishable from normal nerve autografts. In addition, the isografts showed no features of the lymphocytic inflammatory rejection reaction observed in normal nerve allografts, and there was evidence that donor Schwann cells remained viable and were active in all isografts examined. When nerve isografts from affected dystonic mutants were implanted into normal littermate nerves, the normal host axons regenerating through the grafted region acquired degenerative changes characteristic of naturally occurring dystonic peripheral nerve. These changes were not seen in the host axons regenerating either outside the dystonic graft regions, or more distally in the host nerve stumps. When normal nerve isografts were implanted into affected dystonic mutant nerves, the dystonic axons regenerated through the normal graft region and became normally myelinated. It is concluded that an underlying Schwann cell defect may be responsible for the abnormalities of the dystonic mouse peripheral neuropathy.


Evaluation of the anti-herpesvirus drug combinations: virazole plus arabinofuranosylhypoxanthine and virazole plus arabinofuranosyladenine.
Combinations of Virazole plus arabinofuranosylhypoxanthine (ara-Hx) and Virazole plus arabinofuranosyladenine (ara-A) were investigated in KB or BHK cells infected with types 1 or 2 herpes viruses. Combinations of Virazole and ara-Hx exhibited significant synergy as evaluated graphically (isobolograms) or by fractional inhibitory concentration (FIC) indices. Optimal ratios for the combination were 1:1 to 1:10 for Virazole to ara-Hx. At these ratios, FIC indices in the range of 0.5-0.2 were commonly observed. Combinations of Virazole and ara-A were antagonistic when observed in the presence of pentostatin, an adenosine deaminase inhibitor. In the absence of pentostatin, the minimum inhibitory concentration (MIC) of ara-A and degree of synergy with Virazole were variable.


Gout and hyperuricemia.
Hyperuricemia is an elevated uric acid level in blood. Gout is a common systemic metabolic disease characterized by deposition of monosodium urate monohydrate crystals with resultant acute intense inflammation of the involved joint. The clinical spectrum ranges from asymptomatic hyperuricemia to intermittent acute episodes of gouty arthritis to chronic tophaceous gout and chronic gouty arthropathy.


Assessment of biotechnologically relevant characteristics of heterologous hemoglobins in E. coli.
The use of the heterologous bacterial hemoglobin (VHb) from Vitreoscilla to enhance growth and productivity of Escherichia coli under conditions of oxygen limitation has been one of the foremost examples of metabolic engineering. Although VHb has earned its merits during the last two decades by providing enhanced physiological enhancements to organisms from all kingdoms of life, it has been the candidate of choice primarily for historical reasons. Findings made during the last years, however, suggest that hemoglobin and flavohemoglobin proteins from bacterial species other than Vitreoscilla or artificially generated mutant proteins or fusion variants of hemoglobins and flavohemoglobins may be better suited for use in biotechnological processes. This account provides guidelines for the assessment of biotechnologically relevant characteristics conferred by such novel heterologous hemoglobins and flavohemoglobins in E. coli.


Genetic diversity of Asian water buffalo (Bubalus bubalis): microsatellite variation and a comparison with protein-coding loci.
Twenty-one microsatellite loci in 11 populations of Asian water buffalo (eight swamp, three river type) were analysed and, within and among populations, genetic variability was compared with results from 25 polymorphic protein-coding loci. Within-population mean heterozygosity ranged from 0.380-0.615, approximately twice that estimated from the protein-coding loci (0.184-0.346). Only eight significant departures from Hardy-Weinberg equilibrium (involving four loci) were detected; global tests showed significant heterozygote deficiencies for these four loci. Non-amplifying alleles are likely to be segregating in some or all populations for one of these loci, and probably for the other three. There was significant differentiation between the swamp and river types of water buffalo, and among populations within each buffalo type. Estimates of theta (measure of population differentiation) for each locus for the eight swamp populations were all highly significant (mean theta = 0.168 +/- 0.018). Mean theta for protein-coding loci was not significantly different (0.182 +/- 0.041). The variance among protein-coding loci was significantly higher than among microsatellite loci, suggesting balancing selection affecting allele frequencies at some protein-coding loci. Genetic distances show clear separation of the swamp and river types, which were estimated to have diverged at least 10,000-15,000 years ago. The topology of the swamp populations' microsatellite tree is consistent with their geographical distribution and their presumed spread through south-east Asia. By contrast, the tree based on the protein-coding loci distances is quite different, being clearly distorted by a bottleneck effect in one population, and possibly in at least two others. As many domestic livestock breeds are possibly descended from small numbers of founders, microsatellite-based trees are to be preferred in assessing breed genetic relationships.


Bottle-neck type of neural network as a mapping device towards food specifications.
A novel methodology is proposed for food specifications associated with the origin of food. The methodology was tested on honey samples collected within the TRACE EU project. The data were sampled in various regions in Europe and analysed for the trace elements content. The sampling sites were characterized by different geological origins, such as limestone, shale, or magmatic. We have chosen 14 elements, B, Na, Mg, A, K, Ca, Mn, Co, Ni, Cu, Zn, Rb, Sr, and Ba, due to their influence on the separation of samples regarding the geology of the sampling sites. A special architecture of an error back-propagation neural network, so called bottle-neck type of neural network was used to project the data into a 2D plane. The data were fed into the 14-nodes input layer and then transferred through the 2-nodes hidden layer (compared to a bottle-neck) to the 14-nodes output layer. The two hidden nodes representing the two coordinates of the projection plane enable us to map the samples used for training of the bottle-neck network. With the knowledge about the classes of individual samples we determine the clusters in the projection plane and consequently obtain the coordinates of the centroid (gravity point) of a particular cluster. The clusters are characterized with an ellipse shape borders spanning the length of up to 3sigma in each dimension. Since the data were classified as regard to the geology, three main clusters were sought: (i) limestone, (ii) shale/mudstone/clay/loess, and (iii) acid-magmatic origin of honey samples. The novel methodology proposed for food specifications was demonstrated on a reduced set of samples, which shows good clustering of all three classes in the projection plane, and on the third class of the original data set.


Thymic carcinoid.
Carcinoid of the thymus is a rare neoplasm. Differentiation from thymoma is important because they have entirely different prognosis. A patient in whom a 19 x 18 x 12 cm carcinoid tumor of the thymus was surgically removed is presented. The tumor metastasized to peritracheal and internal mammary nodes, and invaded the SVC, pleura, lung, and pericardium. This is apparently the largest reported tumor of its kind. Prior to induction of anesthesia cardiopulmonary bypass and rigid bronchoscopy were readily available. Awake intubation was utilized. Even though long-term prognosis is poor, an aggressive surgical approach and adjuvant radiotherapy may achieve extended survival with excellent quality of life. Central aspects of the disease as well as pivotal therapeutic points are discussed.


Effect of egg yolk concentration on cryopreserving Spanish ibex (Capra pyrenaica) epididymal spermatozoa.
Tris-egg yolk based diluents provide adequate cryoprotection for the sperm of most wild species in which they have been tested. The objective of the current study was to evaluate various Tris-based diluents containing different concentrations of egg yolk, for the fertilizing ability of epididymal spermatozoa of the Spanish ibex (Capra pyrenaica) after freezing and thawing. For this purpose, we used heterologous in vivo fertilization by intrauterine insemination of domestic goats (Capra hircus). In Experiment 1, a Tris-citric acid-glucose (TCG) diluent containing 6% (v/v) egg yolk and a TCG extender containing 20% egg yolk were compared. In Experiment 2, a TCG-6% egg yolk extender was compared with Triladyl-20% egg yolk. Diluted samples were cooled slowly to 5 degrees C over 1 h and equilibrated at that temperature for 2 h. At that point, aliquots of samples were loaded into 0.25 ml straws, and frozen in nitrogen vapor for 10 min. The fertility of spermatozoa frozen in TCG-6% egg yolk was higher (P<0.05) than for those extended with TCG-20% egg yolk, and tended to be higher than for those frozen with Triladyl-20% egg yolk. From the results of this study, the use of Tris-based extenders containing low concentrations of egg yolk (6%) is recommended for cryopreserving Spanish ibex epididymal spermatozoa.


[Cervical necrotizing fasciitis].
Necrotizing fasciitis of the head and neck is a rare infection caused by a mixed bacterial flora with anaerobic predominance. Mortality is due to misdiagnosis which results in late and inadequate treatment. The natural course of this serious infection involves spreading necrosis of the soft tissues of the neck with erosion of major blood vessels. A 33-year-old man and a 66-year-old woman are presented to demonstrate the usual etiological factors of cervical necrotizing fasciitis, mainly dental and pharyngeal infections. Diagnosis is by bacteriological culture and CT-scan; a high degree of clinical suspicion is necessary. Treatment included aggressive surgery, appropriate antibiotic coverage and hyperbaric oxygen, and resulted in successful outcomes in our 2 cases.


Effect of preeclampsia, magnesium sulfate prophylaxis, and maternal weight on labor induction: a retrospective analysis.
Our purposes were to determine the effect of preeclampsia, magnesium sulfate prophylaxis, and maternal weight on labor induction in women with preeclampsia and identify risk factors associated with its failure. Fifty-five preeclamptic women and 176 non-preeclamptic women requiring labor induction over an 18-month period were studied retrospectively. Prostaglandin E(2) (dinoprostone) and oxytocin were used for labor induction. Women with rupture of the membranes, spontaneous contraction resulting in cervical change, or an initial cervical examination showing more than 2 cm dilatation and 50% effacement were excluded. Statistics were analyzed with chi(2) test, Fisher's exact test, Student t test, Mann-Whitney U test, and multiple logistic regression. The women with preeclampsia had a significantly higher rate of failed induction than did those without preeclampsia (p = 0.01). However, the women with preeclampsia had a higher mean maternal weight and an increased use of magnesium sulfate, and labor was induced at earlier gestational age than in those without preeclampsia (p < 0.05 for each). Multiple logistic regression showed that the use of magnesium sulfate, higher maternal weight, and unfavorable cervix, but not preeclampsia, were significantly associated with an increased risk of failed induction after correction for known confounding variables. Although the risk of failed induction is increased in preeclamptic women, preeclampsia is not an independent risk factor for failed induction. The use of magnesium sulfate, higher maternal weight, and unfavorable cervix are independent risk factors for failed induction.


End-user involvement in health technology assessment (HTA) development: a way to increase impact.
A mechanism to increase the influence of Health Technology Assessments (HTAs) on hospital policy decisions was developed. We describe the process and results of an experiment in which a local in-hospital HTA unit was created to provide sound evidence on technology acquisition issues, and to formulate locally appropriate policy recommendations. The Unit consists of a small technical staff that accesses and synthesizes the evidence incorporating local health and economic data, and a Policy Committee that develops policy recommendations based on this evidence. It represents administration, health-care professionals, patients, and representatives of the clinical disciplines affected by each issue. The level of success of the Unit was independently evaluated. To date, 16 reports have been completed, each within 2-4 months. Five recommended unrestricted use, seven recommended rejection, and four recommended very limited use of the technology in question. All have been incorporated into hospital policy. Budget impact is estimated at approximately 3 million dollars of savings per year. This local in-house HTA agency has had a major impact on the adoption of new technology. Probable reasons for success are (i) relevance (selection of topics by administration with on-site production of HTAs allowing them to incorporate local data and reflect local needs), (ii) timeliness, and (iii) formulation of policy reflecting community values by a local representative committee. Because over one third of all health-care costs are incurred in the hospital, diffusion of this model could have a significant effect on the quantity and quality of health-care spending.


Solution structure of human survivin and its binding interface with Smac/Diablo.
NMR studies of the antiapoptotic protein survivin have been used to determine the homodimer interface of the protein in solution and to identify residues of the protein that interact with Smac/Diablo. In solution, survivin(1-120) forms a bow-tie-shaped dimer whose interface is composed of its N-terminal residues as well as residues connecting its BIR domain to the C-terminal alpha helix. The solution structure resolves the controversy regarding the two possible dimer interfaces for survivin observed in X-ray crystal structures. The structural basis for the interaction between survivin and Smac/Diablo was also investigated. When Smac/Diablo or N-terminal Smac/Diablo peptide analogues are added to a solution of survivin, specific residues near alpha4 and beta3 are perturbed. NMR experiments indicate that the peptides bind across the third beta-strand of survivin in a manner similar to the way Smac/Diablo peptides bind to the BIR3 domain of X-linked IAP (XIAP).


Postnatal development of carrier-mediated absorption of a foreign amino acid from the rat lung.
To investigate the postnatal development of the carrier-mediated transport process by which certain amino acids are absorbed from the air space of the lung into the blood-stream, a solution of the 14C-labeled nonmetabolized amino acid cycloleucine was administered into the lungs of anesthetized rats of various ages and the rate of absorption of the compound measured. Carrier transport was barely detectable in animals 3-6 days of age; it increased markedly by th age of 12 days, and it reached nearly mature levels by 18 days of age. The rate of development of this carrier process was considerably slower than that previously reported for the organic anion carrier system of the rat lung.


Phenotyping apolipoprotein E*3-leiden transgenic mice by two-dimensional polyacrylamide gel electrophoresis and mass spectrometric identification.
Apolipoprotein E (ApoE) plays an important role in cholesterol and triglyceride metabolism, being one of the major structural components of chylomicrons and very low density lipoprotein (VLDL) remnants. ApoE functions as a ligand in the receptor-mediated uptake of these remnants from the blood by the liver. A variant form of ApoE, apolipoprotein E*3-Leiden, shows reduced affinity for the low density lipoprotein (LDL) receptor, and results in the dominant expression of type III hyperlipoproteinemia. Two-dimensional electrophoresis (2-DE) has been used to characterise protein expression in serum samples from control and transgenic mice expressing the human ApoE*3-Leiden mutation, fed a cholesterol-rich diet, and transgenic mice fed a normal diet. For the identification of proteins, single silver-stained spots were excised from the 2-DE gels and subjected to in-gel enzymatic digestion. Extracted peptides were analysed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). This proteomic approach has enabled the ApoE*3-Leiden variant to be positioned in a 2-DE separation of serum proteins, and has identified changes in the expression of haptoglobin, indicating that this protein may provide a marker for the potential onset of atherosclerosis.


Artificial photosynthetic systems for production of hydrogen.
The rapid consumption of fossil fuels has caused unacceptable environmental problems such as the greenhouse effect, which may lead to disastrous climatic consequences. Because fossil fuels are the products of long-term photosynthesis, it is highly desirable to develop artificial photosynthetic systems for the production of renewable and clean energy such as hydrogen. This article summarizes recent advances on studies of artificial photosynthetic systems for photocatalytic production of hydrogen with hydrogenases and their functional mimics including hybrids of natural and artificial components. Because it is highly desired to convert gaseous H2 to an easily storable form, recent progress on storage of hydrogen as liquid or solid form has also been described in this article.


[Assay of circulating thyroid stimulator determined by I- efflux].
The thyroid stimulating antibodies (TSAb) have been widely used as a clinical marker for diagnosis of hyperthyroidism due to Graves' disease. Immunoglobulins (IgG) of Graves' patients as well as TSH is known to stimulate cAMP production in FRTL-5 cells, a cell-line derived from normal rat thyroid. On the other hand, it has been shown that TSH-induced I- efflux in these cells is associated with production of inositolphosphate as well as intracellular Ca2+ increase. An attempt was made to determine whether Graves' IgG also can mimic such TSH action as a cause of Graves' disease. Polyethyleneglycol precipitated serum fraction of Graves' patients were prepared. The cells grown in the presence of TSH were incubated for 3 weeks in a Ham's 10 medium containing 1% calf serum, insulin and hydrocortisone for TSH depletion. After preincubation with 125I-iodide for 50 min to label intracellular iodide, the cells were challenged by serum samples for 1 min. The addition of normal pooled serum hardly affected the I- efflux. The Graves' immunoglobulin G fractions stimulated I- efflux dose-dependently. The mean potency of 12 patient's sera relative to the values of the pooled serum as 100% was 217 +/- 56.4%, which was significantly higher (p < 0.001) than that for 8 normal subjects (110 +/- 16.1%). The results obtained herein indicate that IgG of Graves' patients activate both adenylate aclase-cAMP system and a phospholipid-Ca2 system. I- efflux stimulating immunoglobulins (IESI) activity is a useful marker in making a diagnosis or determining a remission of hyperthyroidism due to Graves' disease.


Nitric oxide in cyclosporine A-induced hypertension: role of protein kinase C.
Chronic treatment with cyclosporine A (CsA), an immunosuppressive agent, causes hypertension. The effect of CsA on vascular responses was determined in Sprague-Dawley rats and isolated rat aortic rings. Male rats weighing 250 to 300 g were given either CsA (25 mg/kg/day) in olive oil or vehicle by intraperitoneal injection for 7 days. Cyclosporine A administration produced a 42% increase (P<.001) in mean arterial pressure (MAP), which reached a plateau after 3 days. Conversely, the level of both nitrate/nitrite (NO2/NO3), metabolites of nitric oxide (NO), and 3', 5' cyclic guanosine monophosphate (cGMP), which mediates NO action, decreased by 50% (P<.001) and 35% (P<.001), respectively, in the urine. Thoracic aortic rings from rats treated with CsA, and precontracted with endothelin (10(-9) mol/L), showed a 35% increase (P<.001) in tension, whereas acetylcholine-induced (Ach; 10(-9) mol/L) endothelium-dependent relaxation was inhibited 65% (P<.001) compared with untreated rats. This response was similar to that of aortic rings, denuded of endothelium, from untreated rats in which Ach-induced relaxation was completely abolished (P<.001). Ach-induced formation of both NO2/NO3 and cGMP by both denuded and CsA-treated aortic rings was inhibited 95% (P<.001) and 65% P<.001), respectively, compared with intact aortic rings. The effects of CsA were reversed both in vivo and in vitro by pretreatment with L-arginine (L-Arg; 10 mg/kg/day intraperitoneally), the precursor of NO. There were no changes in MAP and tension in rats treated with L-Arg alone. In addition, in the aorta of rats that were treated intraperitoneally with CsA for 7 days, CsA significantly activated protein kinase C (PKC) translocation and decreased NO2/NO3 production. This suggest that PKC mediates, in part, CsA-induced hypertension. In summary, CsA activates PKC, which inhibits endothelial NO formation, with resulting increases in MAP and tension, and this inhibition can be overcome by L-Arg administration.


Increased ischemic stroke, acute coronary artery disease and mortality in patients with granulomatosis with polyangiitis and microscopic polyangiitis.
The aim of our study was to assess major cardiovascular event incidence, predictors, and mortality in ANCA-associated vasculitis (AAV). We conducted a retrospective cohort study of all GPA or MPA, according to Chapel Hill Consensus Conference classification criteria, diagnosed between 1981 and 2015. Major cardiovascular event was defined as acute coronary artery disease, or ischemic stroke, or peripheral vascular disease requiring a revascularization procedure. We calculated the comparative morbidity/mortality figure (CMF) and we used Cox proportional hazards regression models to assess the risk of coronary artery disease, ischemic stroke associated with AAV, after adjusting for covariates. 125 patients, 99 GPA (79,2%) and 26 MPA (20,8%), were followed 88.4 ± 78.3 months. Ischemic stroke incidence was four times higher than in the general population (CMF 4,65; 95% CI 4,06-5,31). Coronary artery disease incidence was four times higher than in the general population (CMF 4,22; 95% CI 1,52-11,68). Smoking habits and history of coronary artery disease were strongly associated with coronary artery disease occurrence (adjusted HR 8.8; 95% CI 2.12-36.56, and adjusted HR 10.3; 95% CI 1.02-104.5, respectively). ENT flare-up was an independent protective factor for coronary artery disease occurrence. We did not identify factors significantly associated with stroke occurrence. The age-adjusted mortality rate was 22.5 per 1000 person-years. Mortality in AAV was 1.5 times higher than in the general population (CMF 1.56; 95% CI 1.34-1.83). AAV have a significantly increased risk of mortality, ischemic stroke, and coronary artery disease.


Two new species of Pseudapis Kirby, 1900 (Hymenoptera: Halictidae: Nomiinae) from Africa.
Two previously unknown species of the genus Pseudapis Kirby, 1900 are described and illustrated: Pseudapis neumayeri Bossert Pauly, sp. nov. (♂, ♀, Kenya, Tanzania), and P. crassivertex Bossert Pauly, sp. nov. (♂, ♀, Mali, Mauritania, Niger, Senegal). We provide diagnoses for the new species and report all currently available records. Lastly, we present a revised identification key for the African species of the genus.


Linear titration plots with ion-selective electrodes.
A computational method for simultaneous determination of the equivalence volume and the Nernstian slope of an ion-selective electrode is described. Treatment of data from linear titration and standard addition procedures is simplified by the use of equal additions of standard solution. Equivalence volumes and concentrations were determined with errors of 0.5-2% by the proposed method.


[Anatomo-surgical notes on transhiatal access in esophagectomy].
The Authors through an anatomic study on 20 cadavers specify the surgical procedure for transhiatal esophagectomy and describe the anatomical structures involved. The proper manoeuvres and artifices to avoid intraoperative accidents are suggested. Finally, the indications for this peculiar operation are discussed.


Videotape and verbal feedback in behavioral couple therapy: a review.
Reviewed the experimental evidence for the efficacy of videotape and verbal feedback in behavioral couple therapy; it is concluded that research to date does not permit definitive conclusions concerning the efficacy of either procedure. Studies on behavioral differences between happy and distressed couples also were summarized. The evidence indicates that it is, as yet, difficult to ascertain just how the communication behaviors of happy and distressed couples differ.


Perioperative course and quality of life in a prospective randomized multicenter phase III trial, comparing standard lobectomy versus anatomical segmentectomy in patients with non-small cell lung cancer up to 2 cm, stage IA (7th edition of TNM staging system).
For early stage non-small cell lung cancer (NSCLC) retrospective data of functionally compromised patients undergoing segmentectomy showed equal outcomes for perioperative complications and quality of life (QoL) compared with lobectomy patients. However no prospectively randomized data comparing patients eligible for both procedures are available. We conducted a prospective, randomized, multicenter phase III trial and investigated perioperative complications and QoL in patients with NSCLC stage IA (7th edition) undergoing segmentectomy versus lobectomy. The EORTC Questionnaire Core-30 (QLQ C-30) supplemented by thirteen-item lung cancer-specific module (LC13) was assessed before surgery, at discharge, 6 weeks, 3, 6 and 12 months post-surgery. 108 patients with verified or suspected NSCLC up to 2 cm diameter were enrolled, whereby 54 were assigned to lobectomy and 54 to segmentectomy. Due to nodal disease, tumor size and surgical reasons estimated during the operation, eight patients of the segmentectomy group received a lobectomy. In hospital and 90 days mortality was 0% in both groups. Perioperative complications were observed in 6 (11.3%) patients after segmentectomy and in 8 patients (14.8%) after lobectomy (p = 0.563), while the 90-day morbidity were 17% and 25.9% (9 and 14 patients), respectively (p = 0.452). Twelve months after surgery, there was a significant deterioration to the baselines of physical (p < 0.001) and cognitive functioning (p = 0.025), dyspnea (p < 0.001) and fatigue (p = 0.003) in the lobectomy group. Dyspnea showed a faster recovery in the segmentectomy compared to lobectomy group with statistical significance (p = 0.016 after 12 months). In patients with early-stage NSCLC, segmentectomy is associated with a statistically not significant lower perioperative morbidity and appears to provide a superior recovery in QoL compared with lobectomy patients.


Cytomegalovirus infection in steroid-refractory ulcerative colitis: a case-control study.
Cytomegalovirus (CMV) infection is reported to be a cause of steroid-refractory ulcerative colitis (UC), but the strength of this association has not been tested in a case control study. Controlled studies have also not been performed to determine the sensitivity of available immunohistochemical techniques to detect CMV in this setting. The pathology database at Stanford Hospital was searched for UC patients with a diagnosis of "severe colitis" between the years 1992 and 2002 and medical records were reviewed. Forty patients were identified with refractory UC, defined as poor response to highdose systemic steroids for >2 weeks. Another group of 40 patients with severe, but nonrefractory, UC was case-matched for age and year of biopsy. A series of 40 patients who underwent colectomy for reasons other than inflammatory bowel disease with representative sections of "normal" colon were selected as noncolitis controls. CMV inclusions were detected on hematoxylin and eosin (H&E) in 2 of 40 patients with refractory UC, but not in other patients. Immunohistochemistry (IHC) detected CMV in 10 of 40 (25%) patients with refractory UC and 1 of 40 (2.5%) patients with nonrefractory UC (P = 0.007). The CMV-positive cases initially identified on IHC but not on H&E were re-reviewed for viral inclusions on H&E: 3 had rare, but typical, inclusions; 3 had atypical inclusions; and 3 had no inclusions. CMV was not detected by H&E or IHC in 40 noncolitis controls. Of 10 steroid-refractory UC patients with CMV detected, 7 were refractory to cyclosporin or 6-mercaptopurine/azathioprine (70%) and 6 had undergone proctocolectomy (60%) prior to detection of the CMV. Two patients with recognized CMV infection were treated with gancyclovir, improved, and were able to taper off steroids and avoid proctocolectomy. This study provides evidence that unrecognized and therefore untreated CMV infection is significantly associated with steroid-refractory UC. Moreover, IHC is more sensitive than H&E for detection of CMV and should be considered as part of the routine evaluation of steroid-refractory UC patients, before proceeding with other medical or surgical therapy that may be unnecessary once the CMV is treated.


Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation.
The potential role of respiratory viruses in the natural history of community-acquired pneumonia (CAP) in adults has not been well described since the advent of nucleic amplification tests (NATs). From 2004 to 2006, adults with CAP who were admitted to five hospitals were prospectively enrolled in the study, and clinical data, cultures, serology, and nasopharyngeal swabs were obtained. NATs from swabs were tested for influenza, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus 1-4, coronaviruses (OC43, 229E, and NL63), and adenovirus. A total of 193 patients were included; the median age was 71 years, 51% of patients were male, and 47% of patients had severe CAP. Overall, 75 patients (39%) had a pathogen identified. Of these pathogens, 29 were viruses (15%), 38 were bacteria (20%), 8 were mixed (4%), and the rest were "unknown." Influenza (n = 7), hMPV (n = 7), and RSV (n = 5) accounted for most viral infections; other infections included rhinovirus (n = 4), parainfluenza (n = 3), coronavirus (n = 4), and adenovirus (n = 2). Streptococcus pneumoniae was the most common bacterial infection (37%). Compared with bacterial infection, patients with viral infection were older (76 vs 64 years, respectively; p = 0.01), were more likely to have cardiac disease (66% vs 32%, respectively; p = 0.006), and were more frail (eg, 48% with limited ambulation vs 21% of bacterial infections; p = 0.02). There were few clinically meaningful differences in presentation and no differences in outcomes according to the presence or absence of viral infection. Viral infections are common in adults with pneumonia. Easily transmissible viruses such as influenza, hMPV, and RSV were the most common, raising concerns about infection control. Routine testing for respiratory viruses may be warranted for adults who have been hospitalized with pneumonia.


Three-body dissociation dynamics of the low-lying Rydberg states of H3 and D3.
The dynamics of the three-body dissociative charge exchange of fast (12 keV) H+3 and D+3 with Cs have been studied using multiparticle translational spectroscopy. The observed partitioning of product momenta was found to be state-specific and yields insights into the nuclear motion during dissociation for the three lowest-lying 2s 2A'1, 2p 2A''2, and 3p 2E' metastable Rydberg states of H3 and the 2s 2A'1 and 2p 2A''2 states for D3. These results provide direct empirical information on the nonadiabatic couplings that govern the three-body dissociation of the lowest-lying Rydberg states of H3 and D3.


Glyphosate-drift but not herbivory alters the rate of transgene flow from single and stacked trait transgenic canola (Brassica napus) to nontransgenic B. napus and B. rapa.
• Transgenic plants can offer agricultural benefits, but the escape of transgenes is an environmental concern. In this study we tested the hypothesis that glyphosate drift and herbivory selective pressures can change the rate of transgene flow between the crop Brassica napus (canola), and weedy species and contribute to the potential for increased transgene escape risk and persistence outside of cultivation. • We constructed plant communities containing single transgenic B. napus genotypes expressing glyphosate herbicide resistance (CP4 EPSPS), lepidopteran insect resistance (Cry1Ac), or both traits ('stacked'), plus nontransgenic B. napus, Brassica rapa and Brassica nigra. Two different selective pressures, a sublethal glyphosate dose and lepidopteran herbivores (Plutella xylostella), were applied and rates of transgene flow and transgenic seed production were measured. • Selective treatments differed in the degree in which they affected gene flow and production of transgenic hybrid seed. Most notably, glyphosate-drift increased the incidence of transgenic seeds on nontransgenic B. napus by altering flowering phenology and reproductive function. • The findings of this study indicate that transgenic traits may be transmitted to wild populations and may increase in frequency in weedy populations through the direct and indirect effects of selection pressures on gene flow.


Identification of a putative binding site for 5-alkyl-benzothiadiazides in the AMPA receptor dimer interface.
Crystal structures of three different allosteric modulators co-crystallized with the iGluR2 ligand-binding domain are currently available. The modulators, cyclothiazide, aniracetam and CX614, bind at overlapping binding sites in the dimer interface between two iGluR2 subunits. However, pharmacological data indicate that there are one or more additional binding sites for this class of compounds. Based on differences in structure-activity relationship data we show that 5-alkyl-benzothiadiazide (5ABTD) modulators and a series of close analogs of cyclothiazide, despite having a common core structure, do not have the same binding site. In the present work, a new potential binding site for allosteric modulators has been identified in the dimer interface of the iGluR2 ligand-binding domain. By comparing different iGluR2 crystal structures including different co-crystallized agonists, this cavity is shown to be a structurally conserved part of the dimer interface. The cavity is characterized with respect to shape and potential favorable interactions with ligands and docking is used to find a reasonable binding mode for the core structure of the 5ABTDs. The extensive structure-activity data available for this series of compounds are in agreement with the proposed binding mode, supporting the conclusion that the identified cavity most likely is the binding site for the 5ABTDs.


[A fourth possibility treating chronical uremic patients: the satellite dialysis station (author's transl)].
It is possible to reduce the lack of dialysis places by establishing so-called satellite-dialysis-stations. Carrying out the normal dialysis treatment the satellite-station shows certain advantages in comparison to the dialysis center. There are presented the results of 21 patients in a satellite-dialysis-station. On average the systolic blood pressure before dialysis was 132,1 +/- 17,7 mm Hg, the diastolic blood pressure 83,5 +/- 14,9 mm Hg, serum creatinin 9,9 +/- 1,5 mg/100ml, hemoglobin 12,4 +/- 3,2 g/100 ml and the hematocrit 34,4 +/- 5,3%. 16 patients are still working. During the first 12 months of treatment in the satellite-dialysis-station the hematocrit of the patiens was raised on average by 6,4%. Concerning the results of the therapeutic and psychic situation of the patients the satellite-dialysis-station is comparable to the home dialysis treatment.


Description of chewing and food intake over the course of a meal.
While the average frequency of chewing and food intake have been reported before, a detailed description of the pattern of chewing and the cumulative intake of food over the course of a meal have not. In order to achieve this goal, video recording of the maxillary-mandibular region of women eating food from a plate was synchronized with video recording of the plate and computer recording of the weight-loss of the plate. Video recording of chewing correlated strongly with chewing identified by magnetic tracking of jaw displacement in a test with chewing gum at three different frequencies, thus ensuring the validity of video recording of chewing. Weight-loss data were corrected by convolution algorithms, validated against human correction, using sliding window filtering to correct errors with video events as reference points. By use of this method, women ate on average 264 g of food over 114 min, they took an average of 51 mouthfuls during the meal and displayed on average 794 chews with 15 chews per chewing sequence. The number of mouthfuls decreased and the duration of the pauses after each mouthful increased in the middle of the meal and these measures were then restored. The ratio between chewing sequences and subsequent pauses remained stable although the weight of each mouthful decreased by the end of the meal, a measure that is hypothesized to be reflected in a decelerated speed of eating. The method allows this hypothesis to be tested and its implication for clinical intervention to be examined.


Analogues of azepinomycin as inhibitors of guanase.
Synthesis and biochemical screening against guanase of analogues of the naturally occurring guanase inhibitor azepinomycin (2) are reported. Compound 6-amino-5,6,7,8,-tetrahydro-4H-imidazo[4,5-e][1,4]diazepine-5,8-dione (3) was synthesized in six steps commencing with 1-benzyl-5-nitroimidazole-4-carboxylic acid (5). Compound 3 and its synthetic precursor 3-benzyl-6-(N-benzyloxycarbonyl)amino-5,6,7,8-tetrahydro-4H-imidazo[4,5- e] [1,4]diazepine-5,8-dione (12) were screened against rabbit liver guanase. Both were found to be moderate inhibitors of the enzyme with K's in the range of 10(-4) M.


Referred pain elicited by palpation and by needling of myofascial trigger points: a comparison.
To investigate the occurrence of referred pain (ReP) elicited by palpation (Pal-ReP) or by needle injection (Inj-ReP) of myofascial trigger point (MTrP), and to assess the correlated factors, including the pain intensity of an active MTrP and the occurrence of local twitch response (LTR). Correlational study. Ninety-five patients who were treated with MTrP injections. MTrP injections. Pain intensity of MTrP and occurrence of Pal-ReP, Inj-ReP, and LTR. Both Pal-ReP and Inj-ReP were elicited in 53.9% of MTrPs, Inj-ReP, but not Pal-ReP, was elicited in 33.7% of MTrPs. Both Pal-ReP and Inj-ReP were unobtainable in 12.3% of MTrPs. The occurrence of ReP was significantly correlated to the pain intensity of active MTrP and the occurrence of LTR. ReP could be elicited more frequently by needling than by palpation. The frequency of occurrence in ReP mainly depends on pain intensity of an active MTrP.


Non-contrast-enhanced hepatic MR angiography: do two-dimensional parallel imaging and short tau inversion recovery methods shorten acquisition time without image quality deterioration?
To study whether shortening the acquisition time for selective hepatic artery visualization is feasible without image quality deterioration by adopting two-dimensional (2D) parallel imaging (PI) and short tau inversion recovery (STIR) methods. Twenty-four healthy volunteers were enrolled. 3D true steady-state free-precession imaging with a time spatial labeling inversion pulse was conducted using 1D or 2D-PI and fat suppression by chemical shift selective (CHESS) or STIR methods. Three groups of different scan conditions were assigned and compared: group A (1D-PI factor 2 and CHESS), group B (2D-PI factor 2×2 and CHESS), and group C (2D-PI factor 2×2 and STIR). The artery-to-liver contrast was quantified, and the quality of artery visualization and overall image quality were scored. The mean scan time was 9.5±1.0 min (mean±standard deviation), 5.9±0.8 min, and 5.8±0.5 min in groups A, B, and C, respectively, and was significantly shorter in groups B and C than in group A (P<0.01). The artery-to-liver contrast was significantly better in group C than in groups A and B (P<0.01). The scores for artery visualization and overall image quality were worse in group B than in groups A and C. The differences were statistically significant (P<0.05) regarding the arterial branches of segments 4 and 8. Between group A and group C, which had similar scores, there were no statistically significant differences. Shortening the acquisition time for selective hepatic artery visualization was feasible without deterioration of the image quality by the combination of 2D-PI and STIR methods. It will facilitate using non-contrast-enhanced MRA in clinical practice.


Posttraumatic hemicrania continua.
Hemicrania continua is a rare, benign headache disorder characterized by a low-level baseline hemicranial headache with superimposed exacerbations of more severe pain. Exacerbations last from minutes to days and may be associated with ipsilateral autonomic features such as ptosis, miosis, conjunctival injection, lacrimation, or rhinorrhea; when present, these features tend to be less pronounced than those seen with cluster headache. Response to treatment with indomethacin, in doses ranging from 25 to 300 mg per day, has been deemed a sine qua non of diagnosis. To date, in the majority of instances, hemicrania continua appears to have arisen de novo, without any identifiable trigger. We report four patients in whom the onset of hemicrania continua was temporally linked to head trauma.


Induction and superinduction of messenger ribonucleic acid specific for aromatase cytochrome P-450 in cultured human skin fibroblasts.
Aromatase cytochrome P-450 (cytochrome P-450AROM) catalyzes the formation of aromatic C18 estrogenic steroids from C19 androgens. Several studies indicate that cytochrome P-450AROM activity is induced by glucocorticoids such as dexamethasone (DEX) and superinduced by DEX plus cycloheximide (CHX). We have used cultured human skin fibroblasts as a model system to investigate the regulation of aromatase gene expression. Whereas Northern blot analysis of total cellular RNA or poly (A)+ RNA from untreated strains of normal human skin fibroblasts failed to demonstrate any hybridization with a specific human placental cytochrome P-450AROM complementary DNA, analysis of RNA from cells treated with DEX demonstrated hybridization of the cytochrome P-450AROM complementary DNA to two transcripts of about 2.5 and 3.0 kilobases. Incubation of cells with DEX plus CHX resulted in a further increase in levels of cytochrome P-450AROM messenger RNA (mRNA) when compared to cells treated with DEX alone, suggesting that inhibition of protein synthesis superinduces transcription of the cytochrome P-450AROM gene. By contrast, levels of beta-actin mRNA were not affected by treatment with DEX and CHX. Treatment of cells with CHX alone did not produce a change in either aromatase activity or levels of cytochrome P-450AROM mRNA transcripts. These results indicate that aromatase activity is regulated by changes in the concentration of cytochrome P-450AROM mRNA, and imply that control of cytochrome P-450AROM gene expression is at the level of gene transcription. We conclude that the cytochrome P-450AROM gene is regulated by a complex mechanism that includes both positive and negative transcription factors.


[Pathogenesis and therapy of gallbladder perforation].
Findings on admission to hospital and after surgery recorded from 35 patients with gallbladder perforation were compared to findings obtained from 98 patients with cholecystitis, with a view to establishing determining factors in pathogenesis of gallbladder perforation and for the purpose of improving therapeutic strategies. That comparison was part of a retrospective analysis. Biological behaviours regarding perforation were found to be hard to assess, though "early operation" was found to reduce the risk of perforation and post-perforation lethality.


[Jacopo's chest (bad history of a pleural empyema). A case report].
We present a case of pleural empyema, occurred in a healty 7 years boy. He was admitted to our hospital because of a lobare pneumonitis. The patient was administered with a 2 degrees generation Cefalosporine given intramuscularly and with Corticosteroid (1 mg/kg/die). After an initial improvement of his clinical conditions, he got worse so that he underwent a TC scan which showed the presence of a left pleural empyema requiring the insertion of an intercostal tube drainage followed by an intervention of decortication. The boy had some evidence of a staphylococcal etiology such as the evolution in empyema itself, the augmentation of antistafilolisinic title found during the illness, and the typical finding of blebs on chest radiograph. As cultures from both blood and drainage liquid samples remained sterile, we were unable to demonstrate a clear bacterial etiology of the empyema. It remains doubtful if corticosteroid administration could contribute to the severity of the pneumonia evolution.


Optimal patellar alignment with minimally invasive approaches in total knee arthroplasty after a minimum five year follow-up.
Patellofemoral syndrome is still a common complication after total knee arthroplasty (TKA). However, the effects of specific surgical approaches on patellar tracking and alignment remain incompletely understood. In this study, we compared patellar alignment in patients who underwent TKA via three different techniques. A total of 96 patients who completed a minimum follow-up of five years were involved in three groups: 30 patients were treated with the traditional medial parapatellar approach (MPP group), 35 patients were treated with the mini-medial parapatellar approach (MMP group) and 31 were treated with a quadriceps-sparing approach (QS group). Radiographic data for patellar alignment and clinical results were compared. Patellar tilt and patellar displacement at the final follow-up evaluation differed significantly among the three groups [P < 0.01, analysis of variance (ANOVA)]. The MMP and QS groups exhibited more proper patellar alignment than the MPP group. The clinical results did not differ significantly among the groups (P > 0.05, ANOVA). In addition, there were no correlations between postoperative patellar alignment and clinical scores. The results of this study indicate that TKA performed using minimally invasive approaches yields superior patellar alignment compared to the traditional MPP approach.


Analyzing electrical activities of pancreatic β cells using mathematical models.
Bursts of repetitive action potentials are closely related to the regulation of glucose-induced insulin secretion in pancreatic β cells. Mathematical studies with simple β-cell models have established the central principle that the burst-interburst events are generated by the interaction between fast membrane excitation and slow cytosolic components. Recently, a number of detailed models have been developed to simulate more realistic β cell activity based on expanded findings on biophysical characteristics of cellular components. However, their complex structures hinder our intuitive understanding of the underlying mechanisms, and it is becoming more difficult to dissect the role of a specific component out of the complex network. We have recently developed a new detailed model by incorporating most of ion channels and transporters recorded experimentally (the Cha-Noma model), yet the model satisfies the charge conservation law and reversible responses to physiological stimuli. Here, we review the mechanisms underlying bursting activity by applying mathematical analysis tools to representative simple and detailed models. These analyses include time-based simulation, bifurcation analysis and lead potential analysis. In addition, we introduce a new steady-state I-V (ssI-V) curve analysis. We also discuss differences in electrical signals recorded from isolated single cells or from cells maintaining electrical connections within multi-cell preparations. Towards this end, we perform simulations with our detailed pancreatic β-cell model.


Role of DDAH/ADMA pathway in TGF-β1-mediated activation of hepatic stellate cells.
Asymmetric dimethylarginine (ADMA) is catalyzed by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) in humans, and the role for ADMA has been associated with hepatic fibrogenesis. Transforming growth factor‑β (TGF‑β) has been shown to mediate the myofibroblastic transformation of quiescent hepatic stellate cells (HSCs), a pivotal step in liver fibrogenesis. However, the underlying molecular mechanisms are not well understood. Accumulation of ADMA due to low activity of DDAH has been reported to be associated with liver damage and hepatic fibrosis. In this study, the role of the DDAH/ADMA pathway in the TGF‑β1‑induced HSC activation was assessed. Freshly harvested primary HSCs from rat liver were used in this study. It was demonstrated that TGF‑β1 treatment significantly suppressed the DDAH protein expression and activity, and increased levels of ADMA in the culture medium of rat primary HSCs. Notably, the TGF‑β1‑mediated effects on DDAH/ADMA were significantly abrogated by the p38 mitogen activated protein kinase specific inhibitor, SB203580. Furthermore, it was demonstrated that excessive ADMA led to an increase in the number of TGF‑β1‑positive HSCs and induced the expression of α‑smooth muscle actin and collagen type I in rat primary HSCs. In addition, rat primary HSCs exposed to excessive ADMA showed a significant increase in the expressions of α‑SMA and collagen type I. Finally, it was revealed that ADMA treatment promoted the proliferation of rat primary HSCs. In conclusion, the results obtained from the study suggest a potentially novel role for the ADMA/DDAH1 signaling pathway in TGF‑β1‑induced HSC activation, and along with the studies of others, suppression of the ADMA/DDAH1 pathway may be an alterative approach for the treatment of liver fibrosis.


Topical amitriptyline and ketamine for post-herpetic neuralgia and other forms of neuropathic pain.
Neuropathic pain (NP) has several therapeutic options but efficacy is limited and adverse effects occur, such that additional treatment options are needed. A topical formulation containing amitriptyline 4% and ketamine 2% (AmiKet) may provide such an option. This report summarizes both published and unpublished results of clinical trials with AmiKet. In post-herpetic neuralgia (PHN), AmiKet produces a significant analgesia which is comparable to that produced by oral gabapentin. In diabetic painful neuropathy, AmiKet showed a strong trend towards pain reduction. In mixed neuropathic pain, case series reports suggest a favourable response rate, but are limited by trial characteristics. AmiKet is absorbed minimally following topical administration. Over 700 patients have now received topical AmiKet in clinical regimens, and it is well-tolerated with the adverse effects mainly being application site reactions. Both agents are polymodal, and several mechanisms may contribute to the peripheral efficacy of AmiKet. Topical AmiKet has the potential to be a first-line treatment option for PHN, and to be useful in other NP conditions. Furthermore, AmiKet has the potential to be an adjunct to systemic therapies, with the targeting of a peripheral compartment in addition to central sites of action representing a rational drug combination.


Atypical early histories predict lower extraversion in captive chimpanzees.
Although much research has been conducted to understand personality development in humans, there remain substantial gaps in our understanding of these processes, particularly in relation to social influences. As such, investigations into personality development in our closest living relative, the chimpanzee, may provide useful insight. We evaluated the impact of early social exposure (to both humans and conspecifics) on personality development by studying 88 chimpanzees, including former pets and entertainers, living in accredited zoos and sanctuaries. During infancy, subjects varied in the amount of time spent with conspecifics compared with humans. Caregivers familiar with the chimpanzees rated them using a modified version of the Hominoid Personality Questionnaire (HPQ) and the ratings were found to have strong inter-rater reliability. We used the published structure of the HPQ to evaluate our results in relation to differences in early life experience. Chimpanzees who as infants spent less time with conspecifics were rated as lower in Extraversion later in life in comparison with chimpanzees who as infants spent more time with conspecifics. These results suggest that a broad range of social influences should be considered when evaluating the impact of early social environment on later personality expression.


Lower production of IL-17A and increased susceptibility to Mycobacterium bovis in mice coinfected with Strongyloides venezuelensis.
The presence of intestinal helminths can down-regulate the immune response required to control mycobacterial infection. BALB/c mice infected with Mycobacterium bovis following an infection with the intestinal helminth Strongyloides venezuelensis showed reduced interleukin-17A production by lung cells and increased bacterial burden. Also, small granulomas and a high accumulation of cells expressing the inhibitory molecule CTLA-4 were observed in the lung. These data suggest that intestinal helminth infection could have a detrimental effect on the control of tuberculosis (TB) and render coinfected individuals more susceptible to the development of TB.


Simultaneity of responses in a hierarchical visual network.
The pattern of anatomical connections between areas of the primate visual system is organized hierarchically. However, onset latencies in parietal and occipital stations are often simultaneous, and this seems to contradict hierarchical organization in its simplest interpretation, as serial organization. To understand the reasons for this contradiction, we simulated the cortical network for which there is onset data, including the network's hierarchical structure. The network's dynamics reproduced the simultaneous onset latencies reported in several dorsal areas. These results show that a strictly hierarchical visual system is compatible with much more complex dynamics than serial processing, and that hodological and biophysical properties, are more closely related to onset dynamics than is hierarchical organisation.


Assessment of preclinical pharmacokinetics and acute toxicity of pioglitazone and telmisartan combination.
The prevalence of hypertension is very common amongst the diabetic patients and is reported as the major cause of mortality in diabetes. Pioglitazone reported to have an ability to alter the blood cholesterol level and cardioprotective efficiency along with its antidiabetic activity. Telmisartan, through activation of PPAR-γ receptor exerts insulin sensitizing property in addition to its primary cardioprotective efficiency. Theoretically, a combination of pioglitazone and telmisartan may be beneficial to effectively control the high blood glucose level and management of coexisting cardiovascular complication in diabetes. The aim of this research was to experimentally evaluate the pharmacokinetic interaction of pioglitazone and telmisartan when are coadministered in rat. Pioglitazone and telmisartan were administered orally as a single dose individually and in combination to the rats. The plasma samples of the pharmacokinetic study were analyzed using a validated LCMS method. The acute toxicity of the combination with a high dose in rats was also evaluated as a part of the determination of its safety profile. There was no significant change in pharmacokinetic parameters were resulted due to the coadministration of pioglitazone and telmisartan in rat. Absence of major toxicological effect supports the in vivosafety of the combination.


Preliminary data on the involvement of B, C and D hepatitis viruses in the etiopathogenesis of chronic lymphoproliferative syndromes in Romania.
THE AIMS OF THE STUDY: Evaluation of the prevalence of HBV, HCV, HDV infection in patients with chronic lymphoproliferative diseases (CL), identification of the most involved viral genotypes, correlation between viremia dynamics and CL evolution, detection of molecular mechanisms implicated in CL pathogenesis, identification of lymphocytic receptors for viral antigens and biologic markers for early diagnosis of CL. We present preliminary results of the first year of our research grant. This is a prospective, analytic, observational study in patients diagnosed with CL and HBV, HCV, HDV chronic infection. We included the following forms of CL: non-Hodgkin malignant lymphoma (NHL), Hodgkin lymphoma (HL) and chronic lymphocytic leukemia (CLL). We used the following commercial test kits: HCV RNA Real time PCR on a COBAS TaqMan (Roche Diagnostics) analyzer with 28 to 140.000.000 UI/ml detection range for HCV viremia, HBV DNA Real time PCR on a COBAS TaqMan (Roche Diagnostics) analyzer with 6 to 110.000.000 UI/ml detection range for HBV and the Roboscreen-RoboGene AJ kit with 10-10.000.000 replica/ml detection range for HDV. We have included 20 patients with CL and chronic hepatitis infection so far. Median age of the patients was 61 years. The identified CL forms were: B cell NHL (15 cases), T cell NHL (1 case), CLL (3 cases), Hodgkin lymphoma (1 case), equally distributed in aggressive and indolent forms of CL. HCV infection was diagnosed in 10 patients with CL, HBV infection was found in 10 patients with CL, 3 of them having co-infection HBV + HDV. In 4 patients with HBV infection viremia was over 20.000 IU/ml and the pattern of the CL was the aggressive form of the disease. The feature of the co-infection HBV + HDV was the predominance of indolent forms of CL. Among patients with HCV infection, only 3 cases were detected with viremia over 600.000 IU/ml and CL was represented by aggressive forms of the disease. We also have immunohistochemical data available in 19 cases, which seem to confirm the role of hepatitis viruses in lymphoproliferative disease etiopathogenesis. We ascertained an almost equally represented prevalence of HCV and HBV infection in patients with CL. The levels of HBV, HCV and HDV viremia were low in most of the cases. The most frequent form of CL was B cell NHL. We found an equal distribution between indolent and aggressive forms of NHL associated to hepatitis virus infection.


Lower airway obstruction in the PICU.
Lower airway obstruction is one of the most frequent causes of admission to pediatric intensive care unit. A thorough understanding of the pathophysiology underlying the disease will lead to effective management and decreased mortality and morbidity.


Fluorocholine Transport Mediated by the Organic Cation Transporter 2 (OCT2, SLC22A2): Implication for Imaging of Kidney Tumors.
[18F]fluorocholine is the fluorinated analog of [11C]choline and is used in positron emission tomography to monitor tumor metabolic activity. Although important to optimize its use and expand the clinical indications, the molecular determinants of fluorocholine cellular uptake are poorly characterized. In this work, we described the influx kinetics of fluorocholine mediated by the organic cation transporter 2 (OCT2, SLC22A2) and compared with that of choline. Then we characterized the expression pattern of OCT2 in renal cell carcinoma (RCC). In HEK293 cells stably transfected with OCT2 fluorocholine influx, kinetics was biphasic, suggesting two independent binding sites: a high-affinity (Km = 14 ± 8 µM, Vmax = 1.3 ± 0.5 nmol mg-1 min-1) and a low-affinity component (Km = 1.8 ± 0.3 mM, Vmax = 104 ± 4.5 nmol mg-1 min-1). Notably, choline was found to be transported with sigmoidal kinetics typical of homotropic positive cooperativity (h = 1.2, 95% confidence interval 1.1-1.3). OCT2 mRNA expression level was found significantly decreased in primary but not in metastatic RCC. Tissue microarray immunostaining of 216 RCC biopsies confirmed that the OCT2 protein level was consistent with that of the mRNA. The kinetic properties described in this work suggest that OCT2 is likely to play a dominant role in [18F]fluorocholine uptake in vivo. OCT2-altered expression in primary and metastatic cancer cells, as compared with the surrounding tissues, could be exploited in RCC imaging, especially to increase the detection sensitivity for small metastatic lesions, a major clinical challenge during the initial staging of RCC.


Clinical and experimental investigation of a smoothed CT reconstruction algorithm.
The usefulness of a smoothed reconstruction CT algorithm was studied using raw data from the EMI Mark I head scanner. The reconstruction algorithm operated on an off-line computer, independent of the EMI algorithm. This technique greatly reduces image noise and improves the visibility of very low-contrast structures, but at the cost of reduced spatial resolution. Phantom tests with contrasts as low as 0.14% demonstrated the validity of the images. Clinical results showed greatly improved visualization of gray and white matter with no increase in dose. It was necessary to expand the CT density scale so that the range from air to water was divided into 2,000 parts.


[Activity of selected enzymes of the anti-oxidase system in the vitreous body, aqueous humor and lens after subconjunctival ozone in experiments].
The influence of ozone on the activity of enzymes of the antioxydation system in selected structures of the eye were checked. Ozone given topically in weak concentrations acts stimulating, increasing the activity of the enzymes of the antioxydation system, instead in high concentrations causes a significant reduction of activity of the enzymes of the mentioned system.


Comparative evaluation of the hypolipidemic effects of coconut water and lovastatin in rats fed fat-cholesterol enriched diet.
The coconut water presents a series of nutritional and therapeutic properties, being a natural, acid and sterile solution, which contains several biologically active components, l-arginine, ascorbic acid, minerals such as calcium, magnesium and potassium, which have beneficial effects on lipid levels. Recent studies in our laboratory showed that both tender and mature coconut water feeding significantly (P<0.05) reduced hyperlipidemia in cholesterol fed rats [Sandhya, V.G., Rajamohan, T., 2006. Beneficial effects of coconut water feeding on lipid metabolism in cholesterol fed rats. J. Med. Food 9, 400-407]. The current study evaluated the hypolipidemic effect of coconut water (4ml/100g body weight) with a lipid lowering drug, lovastatin (0.1/100g diet) in rats fed fat-cholesterol enriched diet ad libitum for 45 days. Coconut water or lovastatin supplementation lowered the levels of serum total cholesterol, VLDL+LDL cholesterol, triglycerides and increased HDL cholesterol in experimental rats (P<0.05). Coconut water feeding decreased activities of hepatic lipogenic enzymes and increased HMG CoA reductase and lipoprotein lipase activity (P<0.05). Incorporation of radioactive acetate into free and ester cholesterol in the liver were higher in coconut water treated rats. Coconut water supplementation increased hepatic bile acid and fecal bile acids and neutral sterols (P<0.05). Coconut water has lipid lowering effect similar to the drug lovastatin in rats fed fat-cholesterol enriched diet.


Luminance-contrast properties of texture-shape and texture-surround suppression of contour shape.
Studies have revealed that textures suppress the processing of the shapes of contours they surround. One manifestation of texture-surround suppression is the reduction in the magnitude of adaptation-induced contour-shape aftereffects when the adaptor contour is surrounded by a texture. Here we utilize this phenomenon to investigate the nature of the first-order inputs to texture-surround suppression of contour shape by examining its selectivity to luminance polarity and the magnitude of luminance contrast. Stimuli were constructed from sinusoidal-shaped strings of either "bright" or "dark" elongated Gaussians. Observers adapted to pairs of contours, and the aftereffect was measured as the shift in the apparent shape frequency of subsequently presented test contours. We found that the suppression of the contour-shape aftereffect by a surround texture made of similar contours was maximal when the adaptor's center and surround contours were of the same polarity, revealing polarity specificity of the surround-suppression effect. We also measured the effect of varying the relative contrasts of the adaptor's center and surround and found that the reduction in the contour-shape aftereffect was determined by the surround-to-center contrast ratio. Finally, we measured the selectivity to luminance polarity of the texture-shape aftereffect itself and found that it was reduced when the adaptors and tests were of opposite luminance polarity. We conclude that texture-surround suppression of contour-shape as well as texture-shape processing itself depend on "on-off" luminance-polarity channel interactions. These selectivities may constitute an important neural substrate underlying efficient figure-ground segregation and image segmentation.


The effect of calcium on non-heme iron uptake, efflux, and transport in intestinal-like epithelial cells (Caco-2 cells).
It has been suggested that calcium inhibits the absorption of dietary iron by directly affecting enterocytes. However, it is not clear if this effect is due to a decreased uptake of iron or its efflux from enterocytes. We studied the effect of calcium on the uptake, efflux, and net absorption of non-heme iron using the intestinal-like epithelial cell line Caco-2 as an in vitro model. Caco-2 cells were incubated for 60 min in a buffer supplemented with non-heme iron (as sulfate) and calcium to achieve calcium to iron molar ratios ranging from 50:1 to 1,000:1. The uptake, efflux, and net absorption of non-heme iron were calculated by following a radioisotope tracer of (55)Fe that had been added to the buffer. Administration of calcium and iron at molar ratios between 500 and 1,000:1 increased the uptake of non-heme iron and decreased efflux. Calcium did not have an effect on the net absorption of non-heme iron. At typical supplementary doses for calcium and non-heme iron, calcium may not have an effect on the absorption of non-heme iron. The effect of higher calcium to iron molar ratios on the efflux of non-heme iron may be large enough to explain results from human studies.


Recent Development of Palladium-Supported Catalysts for Chemoselective Hydrogenation.
This paper describes practical and selective hydrogenation methodologies using heterogeneous palladium catalysts. Chemoselectivity develops dependent on the catalyst activity based on the characteristic of the supports, derived from structural components, functional groups, and/or morphologies. We especially focus on our recent development of heterogeneous palladium catalysts supported on chelate resin, ceramic, and spherically shaped activated carbon. In addition, the application of flow technology for chemoselective hydrogenation using the palladium catalysts immobilized on molecular sieves 3A and boron nitride is outlined.


Drug delivery of aminolevulinic acid from topical formulations intended for photodynamic therapy.
Topical photodynamic therapy is used for a variety of malignant and pre-malignant skin disorders, including Bowen's Disease and Superficial Basal Cell Carcinoma. A haem precursor, typically 5-aminolevulinic acid (ALA), acting as a prodrug, is absorbed and converted by the haem biosynthetic pathway to photoactive protoprophyrin IX (PpIX), which accumulates preferentially in rapidly dividing cells. Cell destruction occurs when PpIX is activated by an intense light source of appropriate wavelength. Topical delivery of ALA avoids the prolonged photosensitivity reactions associated with systemic administration of photosensitisers but its clinical utility is influenced by the tissue penetration characteristics of the drug, its ease of application and the stability of the active agent in the applied dose. This review, therefore, focuses on drug delivery applications for topical, ALA-based PDT. Issues considered in detail include physical and chemical enhancement strategies for tissue penetration of ALA and subsequent intracellular accumulation of PpIX, together with formulation strategies and drug delivery design solutions appropriate to various clinical applications. The fundamental aspects of drug diffusion in relation to the physicochemical properties of ALA are reviewed and specific consideration is given to the degradation pathways of ALA in formulated systems that, in turn, influence the design of stable topical formulations.


Novel Drivers and Modifiers of MPL-dependent Oncogenic Transformation Identified by Deep Mutational Scanning.
The single transmembrane domain (TMD) of the human thrombopoietin receptor (TpoR/MPL), encoded by exon 10 of the MPL gene, is a hotspot for somatic mutations associated with myeloproliferative neoplasms (MPNs). Approximately 6% and 14% of JAK2 V617F-negative essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients, respectively, have 'canonical' MPL exon 10 driver mutations W515L/K/R/A or S505N, which generate constitutively active receptors and consequent loss of Tpo dependence. Other 'non-canonical' MPL exon 10 mutations have also been identified in patients, both alone and in combination with canonical mutations, but in almost all cases their functional consequences and relevance to disease are unknown. Here we used a deep mutational scanning (DMS) approach to evaluate all possible single-amino-acid substitutions in the human TpoR TMD for their ability to confer cytokine-independent growth in Ba/F3 cells. We identified all currently recognized driver mutations and seven novel mutations that cause constitutive TpoR activation, and a much larger number of second-site mutations that enhance S505N-driven activation. We found examples of both of these categories in published and previously unpublished MPL exon 10 sequencing data from MPN patients, demonstrating that some, if not all of the new mutations reported here represent likely drivers or modifiers of myeloproliferative disease.