Serum zinc levels and goitre epidemiology in Germany.
Zinc is an essential element involved in many basic biochemical reactions. Animal experiments and clinical data support the hypothesis that in the presence of inadequate iodine supply zinc deficiency may be a stimulus for the development of goitre. Within the framework of a study to record goitre prevalence and iodine supply of Germany we determined the serum zinc levels in 5932 clinically healthy persons. The mean value was 13.1 +/- 1.75 mumol/l. There were no differences neither in age, in sex nor in regional distribution. Furthermore there were no correlations between serum zinc level, thyroid volume and urinary iodide excretion. Only 1% of all cases had low zinc levels (< 10 mumol/l). Older people (> 40 years) with lowered serum zinc levels showed significantly larger thyroids. We conclude that there is no relevant undersupply of zinc and therefore the trace element is not involved in the goitre endemy of Germany.


Efferent discharge patterns in the ciliary nerve of rabbits and the pupillary light reflex.
Unitary discharges in the efferent ciliary nerves were studied in cervical sympathectomized rabbits. In all, 279 units were recorded and categorized, except 7 units, into the following 3 types from their responses to photic and other stimuli, i.e. type A (170 units), type B (42 units) and type C (60 units). Type A units were characterized by exhibiting excitatory response to ipsilateral eye illumination and the response was closely related to the luminance level. The type A was further classified into AI (excitation), AII (no change) and AIII (inhibition) on the basis of the response to contralateral illumination. It was inferred that the type A was functionally related to active pupilloconstriction. Type B units were characterized by showing an exclusively inhibitory response to ipsilateral and/or contralateral illumination and the inhibition was luminance-dependent. It was therefore assumed that the type B was concerned with active pupillodilation. Type C units were not responsive to light stimulus, though the type C displayed characteristic reflex response to mechanical or thermal stimulus within the receptive field. The reflexive response, however, was not mediated via the oculomotor nerve. In order to confirm the results of the unit analysis, pupillary light reflex was examined. In particular, the consensual reflex varied depending upon individual rabbits. Namely, one became miotic, another mydriatic and a third remained uninfluenced, which corresponded well with the response pattern of the light-sensitive units.


Applying computational modeling to drug discovery and development.
Computational models of cells, tissues and organisms are necessary for increased understanding of biological systems. In particular, modeling approaches will be crucial for moving biology from a descriptive to a predictive science. Pharmaceutical companies identify molecular interventions that they predict will lead to therapies at the organism level, suggesting that computational biology can play a key role in the pharmaceutical industry. We discuss pharmaceutically-relevant computational modeling approaches currently used as predictive tools. Specific examples demonstrate how companies can employ these computational models to improve the efficiency of transforming targets into therapies.


Stereoselective hydrolysis and penetration of propranolol prodrugs: in vitro evaluation using hairless mouse skin.
Stereoselective hydrolysis of two ester prodrugs of propranolol, isovaleryl propranolol (IV-PL) and cyclopropanoyl propranolol (CP-PL), was studied in Tris-HCl buffer (pH 7.4) containing 0.15 M KCl, skin and liver homogenates, 5% plasma in Tris-HCl buffer, skin cytosol and microsomes, and liver cytosol and microsomes. The hydrolysis rate constants of (R)-isomers of the prodrugs were 1.1-30.3 times greater than those of the respective (S)-isomers in tissue preparations. Skin showed considerable metabolic activity and very high stereoselectivity (R/S ratio: 7.3-30.3). The hydrolyzing capacities of buffer and different tissue preparations per milligram of protein content were in the following increasing order: buffer < skin homogenate < plasma < liver homogenate. The studies with microsomes and cytosol indicated that the esterases, which are responsible for the hydrolysis of prodrugs, were mainly present in the cytosolic and microsomal fractions of skin and liver, respectively. There was a good correlation between the octanol-buffer partition coefficients of propranolol and its prodrugs and the skin partition coefficient. In vitro stereoselective penetration of propranolol and the prodrugs through full-thickness hairless mouse skin was evaluated with flow-through diffusion cells.(ABSTRACT TRUNCATED AT 250 WORDS)


End-to-side nerve coaptation: a qualitative and quantitative assessment in the primate.
There are several reasons why end-to-side nerve coaptation has not been widely adopted clinically. Among these are the putative damage inflicted on the donor nerve and the variable quality of the regeneration in the recipient nerve. So far experiments on end-to-side nerve repair have been short term and mostly carried out on rats. This long-term study of end-to-side nerve repair of ulnar to median and median to ulnar nerve was performed using adult nonhuman primates. Eleven nerve repairs were studied at different time points. Eighteen, 22, 33 and 57 months after surgery a qualitative and quantitative analysis of the donor nerve and regenerating nerve revealed variable levels of percentage axonal regeneration compared with matched controls (1.4%-136%). Morphological evidence of donor nerve damage was identified distal to the coaptation site in four of the 11 cases, and in these cases the best axonal regeneration in the corresponding recipient nerves was observed. This donor nerve damage could neither be demonstrated in terms of a decrease in axon counts distal to the coaptation nor as donor target organ denervation. Recipient target organ regeneration like the axonal regeneration varied, with evidence of motor regeneration in eight out of 11 cases and sensory regeneration, as measured by percentage innervation density compared with matched controls, varied from 12.5% to 49%. Results from the present study demonstrate that the end-to-side coaptation technique in the nonhuman primate does not give predictable results. In general the motor recovery appeared better than the sensory and in those cases where donor nerve damage was observed there was better motor and sensory regeneration overall than in the remaining cases.


The RINGS resource for glycome informatics analysis and data mining on the Web.
In the bioinformatics field, many computer algorithmic and data mining technologies have been developed for gene prediction, protein-protein interaction analysis, sequence analysis, and protein folding predictions, to name a few. This kind of research has branched off from the genomics field, creating the transcriptomics, proteomics, metabolomics, and glycomics research areas in the postgenomic age. In the glycomics field, given the complexity of glycan structures with their branches of monosaccharides in various conformations, new data mining and algorithmic methods have been developed in an attempt to gain a better understanding of glycans. However, these methods have not all been implemented as tools such that the glycobiology community may utilize them in their research. Thus, we have developed RINGS (Resource for INformatics of Glycomes at Soka) as a freely available Web resource for glycobiologists to analyze their data using the latest data mining and algorithmic techniques. It provides a number of tools including a 2D glycan drawing and querying interface called DrawRINGS, a Glycan Pathway Predictor (GPP) tool for dynamically computing the N-glycan biosynthesis pathway from a given glycan structure, and data mining tools Glycan Miner Tool and Profile PSTMM. These tools and other utilities provided by RINGS will be described. The URL for RINGS is http://rings.t.soka.ac.jp/.


Primitive glial compartments in the floor plate of mammalian embryos: distinct progenitors of adult astrocytes and microglia support the notoplate hypothesis.
Immunolocalization of lipocortin 1 (LC1) and S100-beta in the ventral midline of the neural tube of rat embryos demonstrates a distinct substructure that may relate to the roles of the floor plate in development of the ventral commissures. A midline longitudinal raphe of primitive glia (6 to 8 cells wide) expresses LC1 to form the median compartment, whereas contiguous radial glia on both sides of the raphe express S100-beta to form the paramedian bands. These compartments extend the full length of the floor plate and are remarkably uniform in width (30 to 50 microns). In addition to reviewing factors that may relate the floor plate compartments to axon guidance during genesis of the commissures, this report discusses two novel bits of evidence. First, LC1 immunoreactivity characterizes not only floor plate raphe glia, but also adult microglia (both dendritic and activated forms). Several lines of morphological evidence are presented to support the hypothesis that LC1 glia of the floor plate raphe are progenitors of adult microglia. Second, this unexpected microglial pedigree (linking the midline of the embryonic floor plate with glial phagocytes having "mesodermal" characteristics) provides evidence from adult mammals in support of the notoplate hypothesis (that is, the notochord and floor plate arise from common ancestors at the lip of the blastopore). The suggestion that the mammalian notoplate is limited to the LC1 raphe in the midline of the floor plate may be relevant to selection of fetal tissues for transplantation.


Reduction and prediction of N2O emission from an Anoxic/Oxic wastewater treatment plant upon DO control and model simulation.
In order to make a better understanding of the characteristics of N2O emission in A/O wastewater treatment plant, full-scale and pilot-scale experiments were carried out and a back propagation artificial neural network model based on the experimental data was constructed to make a precise prediction of N2O emission. Results showed that, N2O flux from different units followed a descending order: aerated grit tank>oxic zone≫anoxic zone>final clarifier>primary clarifier, but 99.4% of the total emission of N2O (1.60% of N-load) was monitored from the oxic zone due to its big surface area. A proper DO control could reduce N2O emission down to 0.21% of N-load in A/O process, and a two-hidden-layers back propagation model with an optimized structure of 4:3:9:1 could achieve a good simulation of N2O emission, which provided a new method for the prediction of N2O emission during wastewater treatment.


Respiratory muscles in internal medicine.
This review provides evidence that respiratory muscle abnormalities are present in many illnesses of internal medicine and emphasizes that clinicians should look for respiratory muscle weakness in many circumstances, particularly immunological disorders. Controversial results in hormonal diseases, metabolic diseases and abdominal disorders indicate areas for further research.


Urea transport in the kidney.
Urea transport within the kidney is regulated and varies dramatically between different nephron segments. The terminal IMCD displays very high rates of transepithelial urea transport enabling delivery of large amounts of urea into the deepest portions of the inner medulla to maintain a high interstitial osmolality for concentrating the urine maximally. Urea in the terminal IMCD is transported by a specific urea transporter that is stimulated by vasopressin and hyperosmolarity. Although the urea transporter has not been cloned, individuals have been identified who lack the urea transporter. Individuals who lacked the Kidd antigen (a minor blood group antigen) also lacked carrier-mediated urea transport in their erythrocytes (and presumably in their kidneys). These same subjects were unable to concentrate their urine above 800 mOsm following overnight water deprivation. This experiment of nature illustrates the critical importance of the urea transporter to concentrating ability in humans.


Effect of co-administration of cationic macromolecules on the in vivo disposition and in situ renal disposition characteristics of rhIL-11.
The effects of co-administration of cationic proteins on the in vivo disposition characteristics of recombinant human interleukin-11 (rhIL-11) in mice and on the renal disposition in the perfused rat kidney were investigated. Following a bolus intravenous injection of 10 microg/kg (111)In-labeled rhIL-11, along with cationic proteins at high dose (50 mg/kg), the plasma clearance of (111)In-labeled rhIL-11 was significantly decreased mainly due to a reduction in the hepatic clearance of (111)In-labeled rhIL-11. The effect on the renal clearance was relatively small, suggesting that the kidney has a high clearance capacity. The urinary excretion ratio increased by a factor of 2 or 4 with co-administration, suggesting that the cationic character of rhIL-11is involved in tubular re-absorption. An in situ renal disposition study supports these postulations. Thus, the renal and hepatic disposition of rhIL-11 is based on nonspecific cationic interaction. These data suggest that an efficient delivery system for this cytokine would require the reduction of electrostatic interaction of this molecule with these tissues in order to reduce the plasma clearance rate. These findings provide useful information for the construction of an rhIL-11 delivery system.


Metabolic syndrome and peripheral artery disease: Two related conditions.
To ascertain the prevalence of metabolic syndrome (MS) in patients with peripheral artery disease (PAD) at the Martorell primary care (PC) center. To analyze the differences in comorbidities and cardiovascular risk factors between patients with PAD with and without MS. A cross-sectional, descriptive study on patients diagnosed with PAD according to computerized clinical records of the Martorell PC center. Variables collected included age, sex, high blood pressure (HBP), dyslipidemia (DLP), diabetes (DM), smoking, obesity, cardiovascular disease (CVD), erectile dysfunction (ED), renal failure (RF), and oligoalbuminuria. An analysis comparing patients with and without MS was performed. There were 131 patients diagnosed with PAD, 104 (79%) of whom were male. Sixty-three (48.1%) also had MS. Patients with both PAD and MS had, as compared to those with PAD only, a higher prevalence of HBP (87.3 vs. 60.3%, P: 0.001), DLP (77.8 vs. 60.3%, P: 0.03), DM (69.8 vs. 30.9%, P<.001), obesity (25.4 vs. 10.3%, P: 0.03), CVD (42.9 vs. 19.1%); P: 0.004), ED (81.3 vs. 54.3%, P: 0.02), and RF (40.3 vs. 17.9%, P: 0.006). Patients with both PAD and MS had a higher prevalence of HBP, DLP, DM, and obesity. They also had more cardiovascular events and were significantly associated with pathological conditions highly relevant for cardiovascular prognosis such as erectile dysfunction and chronic kidney disease.


Merkel Cell Carcinoma: Updates on Staging and Management.
Merkel cell carcinoma is an aggressive neuroendocrine carcinoma with increasing incidence over the past few decades. The TNM Staging System used for Merkel cell carcinoma was updated by the American Joint Committee on Cancer in 2017. Clinical practice guidelines were updated by the National Comprehensive Cancer Network on August 31, 2018. This article reviews the most recent evidence-based updates on staging and management.


Stimulation of the ATPase activity of rat brain protein kinase C by phospho acceptor substrates of the enzyme.
We recently reported that autophosphorylated rat brain protein kinase C (PKC) catalyzes a Ca2(+)- and phosphatidylserine- (PS-) dependent ATPase reaction. The Ca2(+)- and PS-dependent ATPase and histone kinase reactions of PKC each had a Km app(ATP) of 6 microM. Remarkably, the catalytic fragment of PKC lacked detectable ATPase activity. In this paper, we show that subsaturating concentrations of protein substrates accelerate the ATPase reaction catalyzed by PKC and that protein and peptide substrates of PKC induce ATPase catalysis by the catalytic fragment. At subsaturating concentrations, histone III-S and protamine sulfate each accelerated the ATPase activity of PKC in the presence of Ca2+ and PS by as much as 1.5-fold. At saturating concentrations, the protein substrates were inhibitory. Poly(L-lysine) failed to accelerate the ATPase activity, indicating that the acceleration observed with histone III-S and protamine sulfate was not simply a result of their gross physical properties. Furthermore, histone III-S induced the ATPase activity of the catalytic fragment of PKC, at both subsaturating and saturating histone concentrations. The induction of ATPase activity was also elicited by the peptide substrate Arg-Arg-Lys-Ala-Ser-Gly-Pro-Pro-Val, when the peptide was present at concentrations near its Km app. The induction of the ATPase activity by the nonapeptide provides strong evidence that the binding of phospho acceptor substrates to the active site of PKC can stimulate ATP hydrolysis. Taken together, our results indicate that PKC-catalyzed protein phosphorylation is inefficient, since it is accompanied by Pi production.(ABSTRACT TRUNCATED AT 250 WORDS)


Mixed treatment comparisons using aggregate and individual participant level data.
Mixed treatment comparisons (MTC) extend the traditional pair-wise meta-analytic framework to synthesize information on more than two interventions. Although most MTCs use aggregate data (AD), a proportion of the evidence base might be available at the individual level (IPD). We develop a series of novel Bayesian statistical MTC models to allow for the simultaneous synthesis of IPD and AD, potentially incorporating study and individual level covariates. The effectiveness of different interventions to increase the provision of functioning smoke alarms in households with children was used as a motivating dataset. This included 20 studies (11 AD and 9 IPD), including 11 500 participants. Incorporating the IPD into the network allowed the inclusion of information on subject level covariates, which produced markedly more accurate treatment-covariate interaction estimates than an analysis solely on the AD from all studies. Including evidence at the IPD level in the MTC is desirable when exploring participant level covariates; even when IPD is available only for a fraction of the studies. Such modelling may not only reduce inconsistencies within networks of trials but also assist the estimation of intervention subgroup effects to guide more individualised treatment decisions.


[The newborn infant of a mother with tuberculosis].
TBC is a major infectious emergency in the world. OMS suggest that there are 8 millions of affected every year and 2 millions of deaths. Italy is considered a country with low prevalence, but the increase of the immigration from Africa Asia and Est Europa (country with high risk) imposes attention to the problem. The delivery is a critical moment to investigate people at risk of disease. The infection of the newborn can happen intrauterine or in the expulsive period, but is possible also at home, from somebody affected by an active pulmonary disease. Diagnosis in the newborn is not easy for the aspecificity of clinical signs and for the frequent initial negativeness of Mantoux test. Culture of placenta, gastric aspirate, tracheal secretions, urine would be requested, cerebrospinal fluid if necessary. Neonatal disease needs therapy with isoniazide, rifampicine, pirazinamide and, or ethambutol, or streptomycin. Profilaxis of a newborn from a woman affected by an active form of tuberculosis or living with people affected by an active pulmonary form consists in giving isoniazide until diagnostic tests are negative and in removing the sicks (only with pulmonary disease). New dangerous kinds of pharmacological multiresistent tuberculosis are appeared in the last years in the world and, with the coinfection HIV-TBC and the reorganization of the surveillance system, represents the major obligation for the next years.


Impaired cognitive performance in patients with chronic burnout syndrome.
Chronic burnout refers to a syndrome caused by chronic stress. Clinical observations indicate that chronic burnout is associated with impaired cognitive functioning. However, there have been no systematic studies of the cognitive performance in chronic burnout patients. We have evaluated general cognitive ability, memory, and attention in 67 female patients treated for chronic burnout. The patients and 15 healthy control subjects were tested with standardized tests of verbal and nonverbal cognitive ability (WAIS), verbal (Claeson-Dahl) and nonverbal (Rey complex figures) memory, and visual and auditory attention (IVA). Significant reductions in nonverbal memory and auditory and visual attention were found for the patient group. These results indicate that patients with chronic burnout have specific cognitive impairments, which should be emphasized in the evaluation of symptoms and treatment regimes in this disorder.


Central actions of somatostatin.
Somatostatin (SRIF) was applied microiontophoretically to neurons in the frontal and parietal neocortex, the hippocampus and the striatum of rats anaesthetized with either urethane or chloral hydrate. Qualitatively identical results were obtained under both anaesthetic conditions. In urethane-treated rats SRIF elicited a dose-dependent increase of the firing rate of 74% of the neurons studied in the frontal cortex and of 46% of the neurons studied in the parietal cortex. All cortical cells identified as pyramidal cells were excited. In the hippocampus SRIF provoked excitatory responses in two thirds of all neurons. Six out of the nine cells identified as pyramidal cells were excited by SRIF. In the striatum 80% of all neurons were excited. Following repeated exposure of central neurons to SRIF, the magnitude of the excitatory response gradually diminished, indicating desensitisation. SRIF in concentrations ranging from 10(-8) to 10(-4) M did not interfere with the binding of (3H)-muscimol to GABA receptor sites. The release of GABA from synapses preloaded with (3H-GABA) was not influenced by SRIF in the concentration range from 10(-6) to 10(-4) M. These results indicated that SRIF does not evoke the excitatory responses through attenuation of GABA-mediated inhibition. In conclusion, the findings support the hypothesis that somatostatin may function as a neurotransmitter in the central nervous system.


Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii isolates from a Korean hospital that carry blaOXA-23.
To elucidate the epidemicity of carbapenem-resistant Acinetobacter baumannii (CRAB), we investigated the antimicrobial susceptibility, the genetic basis of antimicrobial resistance, and the ability to form biofilms of 147 CRAB isolates collected between 2013 and 2015 from a Korean hospital based on sequence types (STs). Six different STs were identified: ST191 (n=47) and ST208 (n=36) were clones that had already been identified in the study hospital, whereas ST229 (n=28), ST369 (n=18), ST357 (n=17), and ST552 (n=1) were previously unknown. All the CRAB isolates exhibited an extensively drug-resistance. Twelve isolates, including ST191 and ST208, were resistant to tigecycline, and two were resistant to colistin. All the isolates carried ISAbaI-blaOXA-23 structures. The presence of the armA gene and/or a combination of aminoglycoside-modifying enzyme genes (aacC1, aadA1, aacA4, aphA1, and aphA6) was responsible for high-level resistance to aminoglycosides (minimal inhibitory concentrations≥256mg/L). All the ST229 isolates carried the blaPER-1 gene, whereas all the ST357 and ST369 isolates carried both aacA4 and aadA1. The ST229 isolates exhibited the greatest tendency to form biofilms, whereas the ST369 isolates exhibited significantly less tendency to form biofilms than other isolates. In conclusion, we discovered clonal diversity in the CRAB isolates from the study hospital. The resistant gene profiles and biofilm formation capabilities of the emerging CRAB STs differed from those of the circulating STs. The potential relationship between these genotypic and phenotypic traits and the epidemic capacity of CRAB STs requires further investigation.


Alveolar soft-part sarcoma of the tongue: report of a case and review of the literature.
Alveolar soft part sarcoma (ASPS) accounts for less than 1% of all sarcomas. More frequently encountered within the lower limbs, the authors present a 24-year-old male with ASPS presenting as an asymptomatic swelling of the lateral tongue. At 12 months post wide local excision of the lesion, the patient remains well with no evidence of local or regional recurrence. Histological and immunohistochemical features are diagnostic of ASPS. Whilst rare, head and neck surgeons should be aware of ASPS as a potential cause of slow growing lesions, as early surgical resection is vital in view of the propensity for metastatic spread.


Comparison of two biocides--carbamate and glutaraldehyde--in the control of fouling in pulp and paper industry.
Formation of fouling deposits is a serious problem facing paper mills. Despite the search for alternative methods, chemical biocides still represent the chief countermeasure to control microbial growth and general fouling buid-up in pulp and paper mills. The purpose of this work was to determine the effect of two biocides (carbamate and glutaraldehyde) on both planktonic cells and fouling layers of a paper machine system. A flow system was used for the study of fouling accumulation in an industrial white water circuit. Both biocides proved to be more effective in reducing the microbial loading of the white water circuit than the deposit accumulated on the stainless steel surfaces. Carbamate, in contrast to glutaraldehyde, had the ability of promoting cell agglomeration since the microbial loading decreased much more when the white water, treated with carbamate, was filtered through a filter-linen. The retention of suspended cells in the cellulose fibres acquires major importance since it is obtained by using an already existing physical process (filtration), which strongly enhances the overall microbial reduction obtained with the addition of the carbamate, without increasing the economic costs. These results also suggest that the use of conventional retention agents in pulp and paper processes can be efficient in controlling unwanted microbial effects.


Generation of variation and a modified mean fitness principle: Necessity is the mother of genetic invention.
Generation of variation may be detrimental in well-adapted populations evolving under constant selection. In a constant environment, genetic modifiers that reduce the rate at which variation is generated by processes such as mutation and migration, succeed. However, departures from this reduction principle have been demonstrated. Here we analyze a general model of evolution under constant selection where the rate at which variation is generated depends on the individual. We find that if a modifier allele increases the rate at which individuals of below-average fitness generate variation, then it will increase in frequency and increase the population mean fitness. This principle applies to phenomena such as stress-induced mutagenesis and condition-dependent dispersal, and exemplifies "Necessity is the mother of genetic invention."


Expression of polymorphic B-cell antigens on human kidneys.
We have examined the expression on a panel of 22 human kidneys of polymorphic B-cell determinants recognized by mouse monoclonal antibodies. Monoclonal antibodies from a mouse immunized with an antigenic preparation from a DR4 positive B-cell line reacted preferentially with kidneys from DR4 positive donors (p less than 0.005), and the pattern of reactivity with kidney tissues was similar to that of antibodies to monomorphic determinants of class II. However, these antibodies did not show clear specificity for DR4 on lymphocytes in standard serological analyses. These results provide evidence for the expression of polymorphic class II determinants on human kidneys. Reasons for the differences in the apparent specificities of the monoclonal antibodies when tested on kidney sections and lymphocytes are discussed.


Altered expression of potassium channel subunit mRNA and alpha-dendrotoxin sensitivity of potassium currents in rat dorsal root ganglion neurons after axotomy.
Previous studies have raised the possibility that a decrease in voltage-gated K+ currents may contribute to hyperexcitability of injured dorsal root ganglion (DRG) neurons and the emergence of neuropathic pain. We examined the effects of axotomy on mRNA levels for various Kv1 family subunits and voltage-gated K+ currents in L4-L5 DRG neurons from sham-operated and sciatic nerve-transected rats. RNase protection assay revealed that Kv1.1 and Kv 1.2 mRNAs are highly abundant while Kv1.3, Kv1.4, Kv1.5 and Kv1.6 mRNAs were detected at lower levels in L4-L5 DRGs from sham and intact rats. Axotomy significantly decreased Kv1.1, Kv1.2, Kv1.3 and Kv1.4 mRNA levels by approximately 35%, approximately 60%, approximately 40% and approximately 80%, respectively, but did not significantly change Kv1.5 or Kv1.6 mRNA levels. Patch clamp recordings revealed two types of K+ currents in small-sized L4-L5 DRG neurons: sustained delayed rectifier currents elicited from a -40 mV holding potential and slowly inactivating A-type currents that was additionally activated from a -120 mV holding potential. Axotomy decreased both types of K+ currents by 50-60% in injured DRG neurons. In addition, axotomy increased the alpha-dendrotoxin sensitivity of the delayed rectifier, but not slow A-type K+ currents in injured DRG neurons. These results suggest that Kv1.1 and Kv1.2 subunits are major components of voltage-gated K+ channels in L4-L5 DRG neurons and that the decreased expression of Kv1-family subunits significantly contributes to the reduction and altered kinetics of Kv current in axotomized neurons.


Graphene oxide activation with a constant magnetic field.
The effect of constant magnetic field strength on activation of sensors modified with graphene oxide monolayers was investigated. The use of constant magnetic field resulted in improved electroanalytical properties of the sensors. It was proven that level of GO activation is clearly related to constant magnetic field strength. Moreover, it was demonstrated that observed phenomenon is stable in time.


[Effect of dimephosphon and xidifon on parameters of lipid peroxidation and the antioxidant system in rats subjected to the long-term administration of prednisolone].
Experiments in rats with an osteoporosis model induced by the chronic administration of prednisolone (50 mg/kg, p.o., over 14 days) showed that the drug differently affects the lipid peroxidation (LPO) rate and the antioxidant system activity. Xydiphone (45 mg/kg, p.o.) administered over 14 days exhibited a perooxidant action. Dimephosphon (208 mg/kg, p.o.) administered over the same period of time produced an antioxidant effect as manifested by a growth in the catalase activity, an increase in the content of ceruloplasmin and glutathione, and a decrease in the content of LPO products in the blood serum and liver tissues. The results of combined administration of prednisolone and phosphonates indicate good prospects of the dimephosphon treatment as a means of normalization of the LPO and antioxidant system functioning disturbed by prolonged use of glucocorticoids.


Contact exposure to elemental iron causing chromonychia.
An orange-brown chromonychia developed on the toenails of a woman after a geographic move resulted in exposure to rural well water. Samples of the water and qualitative and quantitative examination of nail clippings confirmed the fact that the source for the discoloration was contact exposure to elemental iron. Installation of water purification equipment resulted in resolution of the nail stain over a six-week period of time.


Progesterone receptor isoforms A and B: temporal and spatial differences in expression during murine mammary gland development.
Progesterone is a potent mitogen in the mammary gland. Based on studies using cells and animals engineered to express progesterone receptor (PR) isoforms A or B, PRA and PRB are believed to have different functions. Using an immunohistochemical approach with antibodies specific for PRA only or PRB only, we show that PRA and PRB expression in mammary epithelial cells is temporally and spatially separated during normal mammary gland development in the BALB/c mouse. In the virgin mammary gland when ductal development is active, the only PR protein isoform expressed was PRA. PRA levels were significantly lower during pregnancy, suggesting a minor role at this stage of development. PRB was abundantly expressed only during pregnancy, during alveologenesis. PRA and PRB colocalization occurred in only a small percentage of cells. During pregnancy there was extensive colocalization of PRB with 5-bromo-2'-deoxyuridine (BrdU) and cyclin D1; 95% of BrdU-positive cells and 83% of cyclin D1-positive cells expressed PRB. No colocalization of PRA with either BrdU or cyclin D1 was observed at pregnancy. In the virgin gland, PRA colocalization with BrdU or cyclin D1 was low; only 27% of BrdU-positive cells and 4% of cyclin D1-positive cells expressed PRA. The implication of these findings is that different actions of progesterone are mediated in PRB positive vs. PRA-positive cells in vivo. The spatial and temporal separation of PR isoform expression in mouse mammary gland provides a unique opportunity to determine the specific functions of PRA vs. PRB in vivo.


Dopexamine increases internal mammary artery blood flow following coronary artery bypass grafting.
Vasoactive agents and inotropes influence conduit-coronary blood flow following coronary artery bypass grafting (CABG). It was hypothesized that dopexamine hydrochloride, a dopamine A-1 (DA-1) and beta(2) agonist would increase conduit-coronary blood flow. A prospective randomized double blind clinical trial was carried out to test this hypothesis. DA-1 receptors have previously been localized to human left ventricle. Twenty-six American Society of Anaesthesiology class 2-3 elective coronary artery bypass graft patients who did not require inotropic support on separation from cardiopulmonary bypass (CPB) were studied. According to a randomized allocation patients received either dopexamine (1 microg/kg per min) or placebo (saline) by intravenous infusion for 15 min. Immediately prior to and at 5,10 and 15 min of infusion, blood flow through the internal mammary and vein grafts (Transit time flow probes, Transonic Ltd.), heart rate, cardiac index, mean arterial pressure and pulmonary haemodynamics were noted. The data were analysed using multivariate analysis of variance. Low-dose dopexamine (1 microg/kg per min) caused a significant increase in mammary graft blood flow compared to placebo at 15 min of infusion (P=0.028, dopexamine group left internal mammary artery (LIMA) flow of 43.3+/-14.2 ml/min, placebo group LIMA flow at 26.1+/-16.3 ml/min). Dopexamine recipients demonstrated a non-significant trend to increased saphenous vein graft flow (P=0.059). Increased heart rate was the only haemodynamic change induced by dopexamine (P=0.004, dopexamine group at 85.2+/-9.6 beats/min and placebo group at 71.1+/-7.6 beats/min after 15 min of infusion). This study demonstrates that administration of dopexamine (1 microg/kg per min) was associated with a significant increase in internal mammary artery graft blood flow with mild increase in heart rate being the only haemodynamic change. Low-dose dopexamine may improve graft flow in the early post CABG period with minimal haemodynamic changes.


Organizational responses to accountability requirements: Do we get what we expect?
In health care, accountability is being championed as a promising approach to meeting the dual imperatives of improving care quality while managing constrained budgets. Few studies focus on public sector organizations' responsiveness to government imperatives for accountability. We applied and adapted a theory of organizational responsiveness to community care agencies operating in Ontario, Canada, asking the question: What is the array of realized organizational responses to government-imposed accountability requirements among community agencies that receive public funds to provide home and community care? A sequential complementary mixed methods approach was used. It gathered data through a survey of 114 home and community care organizations in Ontario and interviews with 20 key informants representing 13 home and community care agencies and four government agencies. It generated findings using a parallel mixed analysis technique. In addition to responses predicted by the theory, we found that organizations engage in active, as well as passive, forms of compliance; we refer to this response as internal modification in which internal policies, practices, and/or procedures are changed to meet accountability requirements. We also found that environmental factors, such as the presence of an association representing organizational interests, can influence bargaining tactics. Our study helps us to better understand the range of likely responses to accountability requirements and is a first step toward encouraging the development of accountability frameworks that favor positive outcomes for organizations and those holding them to account. Tailoring agreements to organizational environments, aligning perceived compliance with behaviors that encourage improved performance, and allowing for flexibility in accountability arrangements are suggested strategies to support beneficial outcomes.


UPMC to develop organ donation program for ED.
Rapid response system includes equipment, administrative supervision, and QI. System approach includes planning ahead and rehearsing responses. It can take several years to develop protocols and pilot a new rapid response program.


Myoglobin: methods and diagnostic uses.
Myoglobin is the oxygen-binding protein characteristic of skeletal and cardiac muscle. With muscle disease or dysfunction, myoglobin may enter the circulation, and after renal clearance, it may also appear in the urine. Therefore, the presence of myoglobinemia and myoglobinuria may serve as indicators of the presence and severity of muscle disease. With newly developed methods of detection, myoglobinemia and myoglobinuria are now recognized as complications of trauma, ischemia, surgery, states of exertion and stress, metabolic abnormalities, inherited enzyme disorders, toxin and drug actions, and inflammatory states. Infarction of the heart muscle also can be detected by myoglobin assay. Persistent myoglobinuric states may be complicated by renal failure and electrolyte imbalance. The diagnosis of myoglobinemia and myoglobinuria can be now confirmed with the use of immunoassay techniques. Although not yet widely available, they offer the possibility of the specificity and sensitivity needed for clinical use.


Bioreversible quaternary N-acyloxymethyl derivatives of the tertiary amines bupivacaine and lidocaine--synthesis, aqueous solubility and stability in buffer, human plasma and simulated intestinal fluid.
Design of water-soluble prodrugs may constitute a means to improve the oral bioavailability of drugs suffering from dissolution rate-limited absorption. The model drug bupivacaine containing a tertiary amine function has been converted into bioreversible quaternary N-acyloxymethyl derivatives. The pH-independent solubility of the N-butanoyloxymethyl derivate exceeded 1000 mg ml-1 corresponding approximately to a 10,000-fold increase in water solubility compared to that of bupivacaine base. The kinetics of hydrolysis of the prodrugs was studied in the pH range 0.1-9.8 (37 degrees C). Decomposition was found to follow first-order kinetics and U-shaped pH-rate profiles were constructed. The observed differences between the hydrolytic lability of the derivatives might most likely be ascribed to steric effects. In most cases, the prodrugs were quantitatively converted into bupivacaine. However, for the hydrolysis of the N-butanoyloxymethyl derivative at neutral to slightly alkaline pH parallel formation of bupivacaine (approximately 80%) and an unknown compound X (approximately 20%) was observed. LC-MS analysis of the latter compound suggests that an aromatic imide structure has been formed from an intramolecular acyl transfer reaction involving a nucleophilic attack of the amide nitrogen atom on the ester carbonyl carbon atom. Whereas the derivatives were poor substrates for plasma enzymes; they were hydrolyzed rapidly to parent bupivacaine in the presence of pancreatic enzymes (simulated intestinal fluid) at 37 degrees C. The data indicate that such prodrugs possess sufficient stability in the acidic environment of the stomach to reach the small intestine in intact form where they can be cleaved efficiently by action of pancreatic enzymes prior to drug absorption. Thus, the N-acyloxymethyl approach might be of potential utility to enhance oral bioavailability of tertiary amines exhibiting pKa values below approximately 6 and intrinsic solubilities in the low microM range.


Sustained attention to the owner is enhanced in dogs trained for animal assisted interventions.
Adaptation in human societies requires dogs to pay attention to socially relevant human beings, in contexts that may greatly vary in social complexity. In turn, such selective attention may depend on the dog's training and involvement in specific activities. Therefore, we recruited untrained pet dogs (N=32), dogs trained for agility (N=32) and for animal assisted interventions (N=32) to investigate differences in attention to the owner in relation to the dogs' training/working experience. Average gaze length and frequency of gaze shifting towards the owner were measured in a 'baseline attention test', where dogs were exposed to the owner walking in and out of the experimental room and in a 'selective attention test', where the owner's movements were mirrored by an unfamiliar figurant. In baseline, gazes to the owner by assistance dogs were longer than gazes by untrained dogs, which were longer than gazes by agility dogs. The latter shifted gaze to the owner more frequently than assistance and untrained dogs. In the selective attention test, assistance dogs showed longer and less frequent gazes towards the owner than untrained dogs, with intermediate values for agility dogs. Correlations were found for gaze length between the baseline and selective attention test for untrained and assistance dogs, but not for agility dogs. Therefore, dogs trained for Animal Assisted Interventions express enhanced sustained attention to their owners, and the lack of similar effects in agility dogs suggests that involvement in specific activities is associated with large differences in the patterns of attention paid by dogs to their handler/owner.


The effect of the Massachusetts healthcare reform on the uninsured rate of the orthopaedic trauma population.
The 2006 Massachusetts Healthcare Reform (MHR) has resulted in health coverage for 98.1% of residents in Massachusetts. The purpose of this study was to evaluate the effect of MHR on the actual rate of uninsured individuals in the orthopaedic trauma population in the largest metropolitan area of Massachusetts. We also sought to measure the change in uncompensated care following the implementation of MHR. We performed a retrospective review of all patients treated by the orthopaedic trauma services at three of the four level-I trauma centers in Boston from 2003 to 2010. The primary study cohort consisted of all uninsured patients, while the remaining patients were considered to have insurance. The study population was divided into two groups to compare the uninsured rate before and after MHR. Patients from 2006 to 2007 were excluded from the analysis to allow for an enrollment period in subsidized health insurance. A total of 16,338 patients with extremity and pelvic fractures and dislocations were treated from 2003 to 2010. There was a significant decrease in the uninsured rate from 23.8% to 14.4% following MHR (p < 0.001). The post-MHR risk of being uninsured is approximately 0.6 times the pre-MHR risk, with a 95% confidence interval of 0.56 to 0.65. There was also a reduction in the proportion of uncompensated care from 16.7% to 11.5% after MHR. There was an estimated 40% reduction in risk of uninsured individuals in the orthopaedic trauma population in the metropolitan Boston area following MHR. Despite a significant improvement, these results reveal a rate of uninsured individuals fivefold greater than currently reported by the state of Massachusetts and the U.S. government.


Role of calcium ionophore A23187-induced activation of IkappaB kinase 2 in mast cells.
Mast cells are known to play a pivotal role in allergic diseases by releasing granules containing histamine and other preformed chemical mediators. Cross-linking of high-affinity receptors for IgE (FcεRI) on mast cells results in rapid increases in intracellular free calcium concentration [Ca(2+)]i and consequent activation of many transcription factors, including NFAT, NF-κB, JNK and CREB. Ca(2+) signaling is essential for many cellular activities such as proliferation, gene expression and degranulation in mast cells. In addition to Ca(2+) signaling, previous reports have shown that IkappaB kinase 2 (IKK2 or IKKβ), a central component of the IKK complex mediating NF-κB activation, also plays a crucial role in FcεRI-mediated degranulation and cytokine production. Moreover, it has been demonstrated that activation of PKCβ, a calcium-dependent PKC isoform, leads to IKK2 activation in many cell types. However, the roles of Ca(2+) signaling and PKCβ in the activation of IKK2 in mast cells remain largely unknown. We investigated the effect of PKC inhibitor Gö6976 on calcium ionophore A23187-induced activation of IKK2 in mast cells. We also examined the role of IKK2 in A23187-induced NF-κB-dependent gene induction, degranulation, proinflammatory cytokine production and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation by using IKK2-deficient (IKK2(-/-)) fetal liver-derived mast cells (FLMCs). A23187 activated IKK2 and NF-κB even in the presence of Gö6976 in mast cells. A23187-induced degranulation, cytokine production and activation of ERK1/2 were diminished in IKK2(-/-) FLMCs compared to those in wild-type FLMCs. Ca(2+)-IKK2 signaling is involved in the degranulation and cytokine production in activated mast cells by a mechanism independent of PKCβ.


Phytol loaded PLGA nanoparticles regulate the expression of Alzheimer's related genes and neuronal apoptosis against amyloid-β induced toxicity in Neuro-2a cells and transgenic Caenorhabditis elegans.
Amyloid β (Aβ) induced neurotoxicity has been postulated to initiate synaptic loss and subsequent neuronal degeneration in Alzheimer's disease (AD). The nanoparticles based drug carrier system is considered as a promising therapeutic strategy to combat this incurable disease. It was also found to inhibit cholinesterase activity and apoptosis mediated cell death in Neuro-2a cells. The in vivo study further revealed that the Phytol and Phytol-PLGA NPs (Poly Lactic-co-Glycolic Acid Nanoparticles) was found to increase the lifespan, chemotaxis behavior and decrease Aβ deposition & ROS (Reactive oxygen species) production in transgenic Caenorhabditis elegans models of AD (CL2006, CL4176). Phytol and Phytol-PLGA NPs treatment downregulated the expression of AD associated genes viz Aβ, ace-1 and hsp-4 and upregulated the gene involved in the longevity to nematodes (dnj-14) and it also reduced the expression of Aβ peptide at the protein level. Our results of in vitro and in vivo studies suggest that Phytol and Phytol-PLGA NPs hold promising neuroprotective efficacy and targets multiple neurotoxic mechanisms involved in the AD progression.


[Systematic characterization of sonomorphological changes in the early stage of rheumatoid arthritis].
The early stage of rheumatoid arthritis (RA) is primarily manifested in the soft tissue of the hand. Although ultrasound (US) is regarded as an important imaging process in diagnostic medicine, precise characterization of sonomorphological changes has not yet been undertaken. 20 patients with RA were examined with US. Two radiologists described semiquantitatively the characteristics of synovial changes in the hand in a consensus-based process and measured the synovial width. Statistical methods were used to determine whether the various synovial changes differed significantly and to identify the most frequent locations of changes. On the basis of the significant differences in morphology and synovial width, it is possible to distinguish between unremarkable findings, pannus tissue and band-like synovitis. Pannus tissue is most frequently found on the finger flexor tendons (FFT), the metacarpophalangeal joints (MCP) and the tendon of M. extensor carpi ulnaris (ECU). Band-like synovitis exhibits an uncharacteristic distribution pattern with a slight propensity to favour these locations. The FFT, MCP joints and ECU tendons are particularly important in systematic US screening of the hand for the purpose of establishing reliable evidence of inflammatory changes. Different stages of RA can be identified on the basis of the characteristic types of synovitis and the number of joints and tendons affected.


Clinicopathological analysis of colorectal cancer liver metastasis and intrahepatic cholangiocarcinoma: are they just apples and oranges?
Intrahepatic cholangiocarcinoma and colorectal cancer liver metastasis are the most primary and secondary adenocarcinoma of the liver, respectively. A large-scale long-term comparative study of these two cohort patient is lacking. A total of 166 colorectal cancer liver metastasis patients and 206 intrahepatic cholangiocarcinoma patients who had undergone curative liver resection were retrospectively analysed. Among 206 intrahepatic cholangiocarcinoma, there were 47 intraductal growth type-intrahepatic cholangiocarcinoma and 159 non-intraductal growth type-intrahepatic cholangiocarcinoma. The demographics, clinicopathological data, immunohistochemical study and survival were analysed. The intrahepatic cholangiocarcinoma patients were more female-predominated, associated with hepatolithiasis, symptomatic, jaundiced, and with larger tumour size compared with those of colorectal cancer liver metastasis. Prognostic factors of intrahepatic cholangiocarcinoma were pathologic staging, histologic pattern and section margin; whereas prognostic factors of colorectal cancer liver metastasis were rectal origin, differentiation, section margin and bilobar distribution. CK7 and CK20 differentiated majority of intrahepatic cholangiocarcinoma from colorectal cancer liver metastasis, while CDX2 and MUC5AC helped to differentiate inconclusive cases. The 1-, 3-, 5- and 10-year survival rates of colorectal cancer liver metastasis were 77%, 31%, 20% and 14%, compared to 53%, 21%, 13% and 7% of intrahepatic cholangiocarcinoma (p=.0001). Furthermore, the survival of colorectal cancer liver metastasis was comparable to staged II intrahepatic cholangiocarcinoma (p=.8866) and intraductal growth type-intrahepatic cholangiocarcinoma (p=.1915). Demographics, precipitating factor, clinical manifestations, and prognostic factors of colorectal cancer liver metastasis and intrahepatic cholangiocarcinoma differed remarkably. High incidence of CDX2 and MUC2 expression in colorectal cancer liver metastasis and intraductal growth type-intrahepatic cholangiocarcinoma might explain their similar cytoarchitecture and survival.


Use of phthaloyl protecting group for the automated synthesis of 3'-[(hydroxypropyl)amino] and 3'-[(hydroxypropyl)triglycyl] oligonucleotide conjugates.
The chemical stability of oligonucleotides (ODNs) containing 3'-propanolamine was investigated. Invariably, all the ODNs synthesized from Fmoc-protected 3-aminopropane-1,2-diol-CPG support gave a mixture of three compounds at the end of automated synthesis as analyzed by denaturing PAGE and HPLC. On the basis of analytical procedures, these compounds were identified to be 3'-[N-acetyl-N-(hydroxypropyl)amino],3'-[(hydroxypropyl)amino], and 3'-hydroxyl ODNs. The instability of the amino protecting group under the synthesis conditions was responsible for this observed heterogeneity. In order to evaluate the stability, a comparative study on the chemical stability of the ODN containing amino-protecting groups such as [(9-fluorenylmethyl)oxy]carbonyl (Fmoc), trifluoroacetyl (TFA), and phthaloyl was undertaken. The results indicate that the phthaloyl group provided the best stability for the synthesis of 3' amine-modified ODNs, and the protecting group is cleaved and deprotected in concentrated ammonium hydroxide:40% aqueous methylamine, 1:1, for 5-10 min, at 56 degrees C. The 3'-hydroxypropyl)triglycyl] ODN conjugates were also synthesized from Fmoc- and phthaloyl-protected (hydroxypropyl)triglycine-CPG supports.


[Prognostic value of Fürhman's grade in renal cell carcinoma. A study of 170 cases].
In order to evaluate the prognostic value of the anatomical stage (pTNM 1992) and of the histological factors (Führman's grade, cellular and architectural types), 170 renal cell carcinoma diagnosed between 1971 and 1991 were reviewed. In univariate analysis, the prognosis was correlated with the anatomical stage and Führman's grade: for the 125 patients without metastasis, grades 1 and 2 had a good prognosis, whereas grades 3 and 4 did poorly. The cellular type was not related to survival. Among architectural types, only the pseudo-sarcomatous type was correlated with prognosis. Multivariate analysis revealed that grade and metastasis at diagnosis were two independent predictors of survival; the grade was prognostically superior to metastasis. Führman's grade is essential in determining prognosis; its statistical value is superior to anatomical stage in multivariate analysis.


Cancer surgery in low-income countries: an unmet need.
To describe the surgical oncology experience at a major regional hospital in Malawi and to identify barriers to improved outcomes. Retrospective review of operating logbooks from a single tertiary referral center. Major tertiary referral center (Kamuzu Central Hospital) in Lilongwe, Malawi, in sub-Saharan Africa. Patients were identified with a suspected diagnosis of cancer from January 1, 2004, through March 7, 2007. Cancer cases were classified according to patient demographic characteristics, disease location, and therapeutic intent. The Malawi data were compared with US data from the Surveillance Epidemiology and End Results database. A malignant diagnosis was suspected in 255 of the 1440 patients undergoing a major resection (17.8%) (mean patient age, 53 years). The most common cancers in males were prostate, esophageal, and gastric. In females, the most common cancers were breast, colon, and esophageal. Many of the procedures were performed with palliative intent. Cancer surgery comprises a significant proportion of the surgical caseload in low-income countries. Patients often present with late-stage, inoperable cancer. The participation of the surgical community is critical for addressing barriers to effective cancer care.


New insights into single-compound and binary adsorption of copper and lead ions on a treated sea mango shell: experimental and theoretical studies.
Herein, adsorption isotherms of Pb(ii) and Cu(ii) ions on treated sea mango fruit in both single-compound and binary systems were experimentally realized at different temperatures in the range of 30-50 °C. Experimental results show that adsorption of Pb(ii) was more as compared to that of Cu(ii) ions; however, for both ions, a significant reduction in the adsorption capacity was observed in the binary system as compared to that in the single-compound systems. Moreover, under all the investigated conditions, adsorption seems to be promoted by an increase in temperature. To understand and interpret the experimental evidences, the Hill and competitive Hill models developed on the basis of the grand canonical ensemble were applied for the analysis of adsorption equilibrium data. These models contain some physicochemical parameters that allow an exhaustive analysis of the dynamics of single-compound and binary adsorptions. Based on the fitting results, in particular, through the evaluation of the number of ions bonded per site (n and ni), it was found that lead and copper ions interacted by inclined and horizontal positions on treated sea mango in single-compound and binary systems, respectively. In addition, based on the same parameters, a significant interaction between ions was retrieved. A study focused on the saturation adsorption capacity in single-compound and binary systems affirmed that the adsorbent was more selective for lead than for copper. The reduction of the adsorbed capacity ratio between the binary and single-compound systems (i.e. Qb/Qs) explained and confirmed that an inhibition effect between copper and lead ions at the same receptor site occurred. Finally, based on the energetic investigations, it was deduced that the adsorption energy represented the dominant factor promoting the greater adsorption of lead than that of copper in both systems.


Optimum sensors for color constancy in scenes illuminated by daylight.
The apparent color of an object within a scene depends on the spectrum of the light illuminating the object. However, recording an object's color independent of the illuminant spectrum is important in many machine vision applications. In this paper the performance of a blackbody-model-based color constancy algorithm that requires four sensors with different spectral responses is investigated under daylight illumination. In this investigation sensor noise was modeled as gaussian noise, and the responses were quantized using different numbers of bits. A projection-based algorithm whose output is invariant to illuminant is investigated to improve the results that are obtained. The performance of both of these algorithms is then improved by optimizing the spectral sensitivities of the four sensors using freely available CIE standard daylight spectra and a set of lightness-normalized Munsell reflectance data. With the optimized sensors the performance of both algorithms is shown to be comparable to the human visual system. However, results obtained with measured daylight spectra show that the standard daylights may not be sufficiently representative of measured daylight for optimization with the standard daylight to lead to a reliable set of optimum sensor characteristics.


Comparison between magnetic resonance imaging and arthroscopy in the diagnosis of patellar cartilage lesions: a prospective study.
A blind and prospective study was conducted to assess the accuracy of magnetic resonance imaging (MRI) for diagnosing patellar cartilage lesions. Thirty-three consecutive patients undergoing knee arthroscopy were examined by MRI prior to surgery. Imaging was performed in the axial plane on a 1.5-Tesla unit with spin-echo and gradient-echo T1 and T2 sequences. The MRI and arthroscopic data were compared using a four-grade classification and a patellar map which divided the patellar surface into four quadrants. The overall sensitivity of MRI was 84.7% and the specificity 97.2%. The same pit-fall led to two MRI false positives. A perfect correlation of grading was obtained in 76.5%. When discordance was found, the tendency with MRI was commonly to underestimate the grade of the lesions. The MRI accuracy was high in this study in spite of a high rate of low-grade lesions which are difficult to assess. Related criteria for cartilage assessment with MRI and arthroscopy are suggested for further studies.


Long-term prognostic significance of urinary sodium concentration in patients with acute heart failure.
Lower urinary sodium concentration (UNa) may reflect impaired renal perfusion, higher neurohormonal activity and diuretic resistance. However, the prognostic impact of UNa in patients with acute heart failure (AHF) has not been fully elucidated. We investigate the association between UNa and clinical outcomes in 669 patients admitted with AHF in our prospective registry. Patients were stratified into tertiles based on UNa in a spot urine sample on admission. Patients with lower UNa were more likely to have a history of prior heart failure admission, β-blockers and diuretics use, and had lower blood pressure and serum sodium level, and higher blood urea nitrogen, estimated glomerular filtration rate, blood glucose and troponin T levels on admission than those with higher UNa. Plasma renin activity, aldosterone, cortisol and dopamine levels were also significantly higher in patients with lower UNa (all p<0.001). Furthermore, patients with lower UNa had significantly less weight loss, lower net fluid loss/furosemide equivalent dose and higher incidence of worsening renal function during hospitalization than those with higher UNa (all p<0.01). During a median follow-up period of 560days, lower UNa was significantly associated with the composite of all-cause death and worsening heart failure (p<0.001). In multivariable Cox-proportional hazards model, UNa remained an independent determinant of long-term adverse events (HR, 1.24, 95% CI, 1.06-1.45, p=0.006). Lower UNa was associated with worse long-term clinical outcomes along with increased neurohormonal activities, impaired response to diuretics and higher incidence of worsening renal function in patients with AHF.


Kojic acid reduces the cytotoxic effects of sulfur mustard on cultures containing human melanoma cells in vitro.
In vivo experiments have shown that melanocytes are more sensitive than keratinocytes to the cytotoxic effects of sulfur mustard when it is applied topically to pig skin.1 It has been hypothesized that this is caused by the uncoupling of the melanogenic pathway by depletion of cellular glutathione, resulting in the uncontrolled production of cytotoxic quinone free-radical species by tyrosinase.2. In the present study, the feasibility of blocking the melanogenic pathway as a means of reducing the cytotoxicity of sulfur mustard was evaluated using kojic acid. Kojic acid is a topically applied depigmenting agent that exerts its effect by acting as a slow-binding, competitive inhibitor of tyrosinase.3 Preincubation of G361 pigmented melanoma cells and mixed cultures of G361 cells and SVK keratinocytes with 2.5 mM kojic acid resulted in significant increases in the viability of these cultures as determined by neutral red (NR) and gentian violet (GV) dye binding assays for up to 48 h following exposure to 50 microM sulfur mustard. The highest levels of protection were seen in the G361 cultures, with a 26.8% increase in culture viability (NR assay) compared with the sulfur-mustard-only controls at 24 h. Preincubation of SVK cells alone with kojic acid resulted in lower increases in viability (2.5% at 24 h by the NR assay). Inhibition of the melanogenic pathway reduces the sensitivity of cultures containing pigment cells to sulfur mustard.


[A comparative study of the sensitivity of bladder washing flow cytometry, voided urine cytology and bladder washing cytology in the detection of bladder carcinoma].
In order to evaluate flow cytometric deoxyribonucleic acid measurement (FCM) of bladder washing in the diagnosis of bladder carcinoma, the sensitivity of voided urine cytology, bladder washing cytology and bladder washing FCM was tested in 76 samples from 56 patients with histologically proven bladder carcinomas. The positive rates were 43.2% and 75.7% in bladder washing cytology and bladder washing FCM, respectively. On the other hand, 36.5% and 57.1% positive rates for once- and three-times-voided urine cytology, respectively, were obtained. Bladder washing cytology and bladder washing FCM were positive in 20% and 70% patients with a histological diagnosis of atypia or dysplasia, respectively. The sensitivity of bladder washing FCM according to the tumor grade was 33.3%, 81.9% and 88.9% for grade-1 (G-1), G-2 and G-3 tumors, respectively. The sensitivity of bladder washing cytology according to the tumor grade was 0, 40.9% and 77.8% for G-1, G-2 and G-3 tumors, respectively. The sensitivity of three-times-voided urine cytology was 25.0%, 55.6% and 83.3% for G-1, G-2 and G-3 bladder tumors, respectively, and it was superior to that of single bladder washing cytology. These results indicate that FCM is more sensitive than voided urine cytology and/or bladder washing cytology in patients with bladder carcinoma. FCM may indicate urothelial neoplasia before it is apparent on urine cytology, especially against a background of inflammation. Therefore, FCM is valuable for case finding in suspect populations or for follow-up cases with diagnosed bladder cancer.


Nuclear factor-κB2/p100 promotes endometrial carcinoma cell survival under hypoxia in a HIF-1α independent manner.
Endometrial carcinoma (EC) is a common female cancer, treated mainly by surgery and adjuvant radiotherapy. Relapse following treatment is associated with increased risk of metastases. Hypoxia, a common microenvironment in solid tumors, correlates with malignant progression, rendering tumors resistant to ionizing therapy. Hence, we assessed here the immunohistochemical expression of hypoxia-inducible factor-1α (HIF-1α) and members of the NF-κB family in 82 primary EC and 10 post-radiation recurrences of EC. Post-radiation recurrences were highly hypoxic, with a higher expression of HIF-1α and also RelA (p65) and p52 when compared with primary EC. We next investigated the effects of hypoxia on EC cell lines. We found that EC cell lines are highly resistant to hypoxia-induced apoptosis. We thus focused on the molecular mechanisms involved in conferring hypoxic cell death resistance. We show that in addition to the classical NF-κB, hypoxia activates the alternative NF-κB pathway. To characterize the upstream kinases involved in the activation of these pathways, we used lentiviral-mediated knockdown and mouse embryonic fibroblasts lacking IKKα and IKKβ kinases. Both IKKα and IKKβ kinases are required for RelA (p65) and p100 accumulation, whereas p52 processing under hypoxia is IKKα dependent. Furthermore, Ishikawa endometrial cell line harboring either RelA (p65) or p52 short-hairpin RNA was sensitive to hypoxia-induced cell death, indicating that, in addition to the known prosurvival role of RelA (p65) under hypoxia, alternative NF-κB pathway also enhances hypoxic survival of EC cells. Interestingly, although HIF-1α controlled classical NF-κB activation pathway and survival under hypoxia through RelA (p65) nuclear accumulation, the alternative pathway was HIF-1α independent. These findings have important clinical implications for the improvement of EC prognosis before radiotherapy.


Chagas disease in Latin American pregnant immigrants: experience in a non-endemic country.
Chagas disease is a systemic chronic parasitic infection by Trypanosoma cruzi endemic in Latin America. Migration of women of childbearing age from Latin America to developed countries may spread the disease to non-endemic areas through vertical transmission. Prospective study of seroprevalence of T. cruzi infection in immigrant Latin American pregnant women during a 5-year period (from 2006 to 2010) in Spain. Seven out of 545 participants were seropositive for T. cruzi [prevalence 1.28%, 95% confidence interval (CI) 0.06-2.56]. Four (57%) were from Bolivia and three (43.%) from Paraguay. The seroprevalence in pregnant women from Bolivia was 10.26% (95% CI 4.06-23.58) and in participants from Paraguay was 6.52% (95% CI 2.24-17.5). No congenital transmission occurred. Seroprevalence of T. cruzi infection in Latin American pregnant women coming from Bolivia and Paraguay is high. Those women should be screened for T. cruzi to control mother-to-child transmission in non-endemic areas.


An efficient method to evaluate experimental factor influence on in vitro binding of aptamers.
Nucleic acid-based aptamers are promising alternative to antibodies, however, their selection process (SELEX) is challenging. A number of simulations and few experiments have been reported offering insights into experimental factors (EFs) that govern the effectiveness of the selection process. Though useful, these previous studied were either lack of experimental confirmation, or considered limited EFs. A more efficient experimental method is highly desired. In this study, we developed a fast method that is capable to quantitatively probe the influence of multiple EFs. Based on the fact that the aptamer enrichment efficiency is highly affected by background binding, the binding ratio between the numbers of specific aptamer binders and nonspecific (unselected library) binders per bead was used to quantitatively evaluate EF effects. Taking thrombin and streptavidin as models, three previously studied EFs (surface coverage, buffer composition, and DNA concentration) and four never-studied ones (surface chemistry, heat treatment, elution methodology and pool purity) were investigated. The EFs greatly affected binding ratio (ranging from 0.03 ± 0.03 to 14.60 ± 2.30). The results were in good agreement with the literature, suggesting the good feasibility of our method. Our study provides guidance for the choice of EFs not only for aptamer selection, but also for binding evaluation of aptamers.


Bone marrow stromal colony formation requires stimulation by haemopoietic cells.
In mouse bone marrow cultures plated at low cell density, stromal colonies formed from colony-forming unit fibroblastic (CFUf) failed to develop unless the cultures were supplemented with irradiated feeder cells. Colony-stimulating activity was produced by irradiated bone marrow and spleen cells and by platelets, was dose dependent, not species specific and was maximal at high serum concentration. The efficiency of CFUf colony formation was 1.7 x 10(-4) for mechanically disaggregated and 14.6 x 10(-4) for trypsinised bone marrow cells. The colonies formed in the presence of feeder cells comprised hundreds of fibroblasts. In the absence of feeder cells, small fibroblast foci and single fibroblasts only were present in cultures. PDGF, IL-3 and EGF did not substitute for the colony-stimulating activity of feeder cells. These results suggest that CFUf colony formation requires growth factor(s) released by platelets and megakaryocytes which remain to be identified.


N-Demethylation reactions catalyzed by chloroperoxidase.
The peroxidase-supported N-demethylations catalyzed by chloroperoxidase, a heme protein isolated from Caldariomyces fumago, have been investigated as models for cytochrome P-450-catalyzed N-dealkylations. The turnover number for the ethyl hydrogen peroxide-supported dealkylation of N,N-dimethylaniline by chloroperoxidase (1476) was much greater than that for cytochrome P-450-catalyzed dealkylations. The dealkylations of N,N-dimethylaniline by chloroperoxidase yielded N-methylaniline and formaldehyde in equimolar amounts with no other products detectable by high pressure liquid chromatography analysis of the reaction mixture. Ethyl hydrogen peroxidase could be replaced by other hydroperoxides, peroxides, or peracids. Chloride ions stimulated the reaction at low pH. The dealkylation reaction exhibited normal Michaelis-Menten saturation kinetics with respect to N,N-dimethylaniline (Km = 0.08 mM) and ethyl hydrogen peroxide (Km = 0.8 mM) at low substrate concentrations. However, substrate inhibition occurred at higher concentrations of N,N-dimethylaniline. The chloroperoxidase-catalyzed demethylations were inhibited by inhibitors of cytochrome P-450 such as azide or n-propyl gallate, but not by metyrapone, SKF-525A, or piperonyl butoxide. Although tiron and DL-epinephrine, trapping agents for the superoxide anion, inhibited the demethylation reactions, superoxide dismutase had no effect. There was no significant inhibition by alpha-phenyl-t-butyl-nitrone or 5,5-dimethyl-pyrroline-N-oxide, which react with free radicals. Diphenylfuran and DL-histidine, which react with singlet oxygen, did not inhibit the reaction. Substitution of D2O for H2O resulted in a marked inhibition with a solvent isotope effect (VH/VD) of 3.6. Chloroperoxidase did not catalyze the demethylation of N,N-dimethylaniline-N-oxide, indicating that the reaction does not proceed via an N-oxide intermediate.


In vitro effects of CpG oligodeoxynucleotides delivered by gelatin nanoparticles on canine peripheral blood mononuclear cells of atopic and healthy dogs - a pilot study.
Cytosine-phosphate-guanine (CpG) oligodeoxynucleotides offer a novel promising immunotherapeutic approach for atopic dermatitis (AD) both in humans and animals. Gelatin nanoparticles (GNP) enhance and prolong CpG-associated immunomodulatory effects and minimize adverse effects both in vitro and in vivo. Information about the effects of this combination in dogs is lacking. The aim of this study was to evaluate immunological effects of CpG coupled to GNP on canine peripheral blood mononuclear cells (PBMCs) in vitro. Eight dogs with AD, diagnosed by standard criteria and with a concurrent immediate hypersensitivity to house dust mites were included. Control samples were taken from eight healthy, age-matched control dogs without history or evidence of cutaneous or systemic illness. Peripheral blood mononuclear cells of healthy and allergic dogs were incubated with CpG-GNP and the uptake of CpG-GNP was demonstrated using confocal laser scanning microscopy. Cell culture supernatant concentrations of interferon gamma (IFN-γ), interleukin (IL)-4, IL-6 and IL-10 were measured by Canine Cytokine Milliplex. No significant changes in IFN-γ and IL-4 were found when comparing PBMCs incubated with CpG and CpG-GNP with the negative controls in atopic and healthy dogs. Interleukin-6 was not detected in any of the groups. However, a statistically significant increase in IL-10 concentration was found after 24 h stimulation with CpG-GNP compared with CpG alone both in atopic and healthy dogs. As IL-10 is considered an immunosuppressive cytokine playing a key role in peripheral tolerance; the reported CpG-GNP formulation could be a new approach in allergy treatment.


Endoscopically stapled diverticulostomy for Zenker's diverticulum: results of a multidisciplinary team approach.
A variety of open and endoscopic surgical approaches for the treatment of Zenker's diverticulum have been described. In recent years, growing evidence has shown that the endoscopic techniques are superior to the open approaches in many aspects. Among the endoscopic techniques, endoscopically stapled diverticulostomy (ESD) appears to have better efficacy and safety than the other endoscopic techniques. This study retrospectively reviewed the medical records of all the patients with Zenker's diverticulum treated surgically by the same team, which involved an ear, nose, and throat surgeon and an endoscopic surgeon. From January 2002 to March 2008, 55 consecutive patients with Zenker's diverticulum underwent 60 ESDs. The mean follow-up time was 32.6 months (range, 1-72 months). The mean operative time was 21.8 min (range, 5-45 min), and the average hospital stay was 2.24 days (range, 1-30 days). The treatment was technically feasible for 51 patients (93%), and initial symptom relief without recurrence was achieved for 46 patients (90.2%) after a single procedure. Five patients with recurrent symptoms underwent a successful revision ESD, with a 100% success rate among the patients for whom the procedure was technically feasible. Only two major postoperative complications (3.64%) occurred: one esophageal perforation and pneumomediastinum and one severe esophageal edema. Both patients had complete resolution of their complications with conservative treatment and no long-term sequela. The findings showed endoscopic stapled diverticulostomy to be both safe and effective. Compared with the historical results of open diverticulectomy and myotomy, the reported procedure has fewer complications and better outcomes and should become the procedure of choice for the treatment of most patients with a diagnosis of Zenker's diverticulum.


Comparison of Two Endovascular Steerable Robotic Catheters for Percutaneous Robot-Assisted Fibroid Embolization.
To compare outcomes of percutaneous robot-assisted uterine fibroid embolization (UFE) using two different endovascular robotic catheters. Twenty-one patients with a symptomatic uterine fibroid were prospectively enrolled in a single-center study to be treated with a percutaneous robot-assisted embolization using the Magellan system. Fourteen patients were treated using a first generation steerable robotic catheter, version 1.0 (group 1), and seven were treated using the new version 1.1 (group 2). Demographic, pathologic, and procedural variables were recorded. Dose Area Product (DAP) and physician equivalent doses were registered for each procedure. Procedural related complications and clinical midterm outcomes were also evaluated. Successful robot-assisted UFE was obtained in eight patients (57.1%) in group 1 and 7 patients (100%) in group 2 (p = 0.01). A successful robot-assisted catheterization of the internal iliac artery anterior branch was performed in all patients of both groups. Median selective target vessel catheterization time was 21.0 ± 12.8 vs 13.4 ± 7 min (p = 0.04) and total fluoroscopy time was 30.3 ± 11.2 vs 19.3 ± 5.9 min, respectively, in group 1 and 2. Mean DAP decreased from 18472.6 ± 15622 to 5469.1 ± 4461.0 cGy·cm2 (p = 0.04). All patients obtained a symptoms relief at 6 months follow-up. Robot-assisted uterine fibroid embolization is safe and effective. New version of steerable robotic catheter allows performing a faster procedure without related adverse events compared to old version.


Cardiac papilloma. A case report with evidence of thrombotic origin.
A pulmonic valve cardiac papilloma was found in a patient with coagulopathy and disturbed right ventricular hemodynamics. Fibrin was demonstrated within the cores of the papillae, lending further support to the thrombotic derivation of these lesions. The tumor's papillary configuration was thought to be the result of molding by the turbulent blood flow at that site.


Isolation of distinct progenitor stem cell populations from dental pulp.
The present study compared the cellular characteristics of progenitor stem cell populations present in adult dental pulp, isolated by different methods utilizing 2 different features of stem cell biology. One population expressing high levels of beta1 integrin was isolated by preferential selection of adherent cells to fibronectin over 20 min. In an alternative approach, cells expressing the embryonic neural crest cell marker, low-affinity nerve growth factor receptor (LANGFR), were selected by magnetic-activated cell sorting. For each method, clonal cell lines were established and expanded in culture. One clone derived via the respective methods was examined for embryonic/progenitor cell markers by immunocytochemistry and RT-PCR. Both clonal populations demonstrated the expression of stro-1 and stained positive for vimentin, demonstrating mesenchymal lineage. Of note, cells selected for LANGFR cells demonstrated the additional expression of CD105 and Notch 2. For both clonal populations, expanded cultures demonstrated the ability to differentiate into osteoblasts, adipocytes and chondrocytes. These results would suggest the potential isolation of 2 progenitor cell populations exhibiting different cellular characteristics in terms of their embryonic nature. The potential for both cell populations to derive from a common origin is discussed.


Influence of HMPA on reducing power and reactivity of SmBr(2).
[reaction: see text] Addition of HMPA to SmBr(2) in THF produces a reactant with an estimated redox potential of -2.63 +/- 0.01 V (vs Ag/AgNO(3)). This powerful reductant is capable of reducing ketimines and alkyl chlorides at room temperature. Although the structure of the reductant has not been established, it is nonetheless a powerful addition to the arsenal of samarium-based reductants currently utilized.


Diverse effects of calcium antagonists on glomerular hemodynamics.
This study examined the direct effects of calcium antagonists on glomerular hemodynamics. Rabbit afferent (Af-) or efferent arterioles (Ef-Arts) were microperfused in vitro at constant pressure. Ef-Arts were perfused from the distal end of Af-Art through the glomerulus. Increasing doses (10(-10) to 10(-7) M) of nifedipine (Nif), nicardipine (Nic) or manidipine (Man) were added into the lumen of Af- or Ef-Arts preconstricted (by about 40%) with norepinephrine. Although Nif and Nic dilated Af-Arts in a dose-dependent manner, they did not cause any dilation in Ef-Arts. In contrast, Man dilated both Af- and Ef-Arts in a dose dependent manner; Man at 10(-7) M dilated Af- and Ef-Arts by 71 +/- 12% (N = 7) and 38 +/- 3% (N = 6), respectively. Although Man's dilator effect on Ef-Art was not affected by inhibiting nitric oxide (NO) synthesis (N = 6), it was markedly attenuated by eliminating the influence of glomerulus (14 +/- 3% by Man at 10(-7) M, N = 5). These results demonstrate that in addition to dilating Af-Art, Man, but not Nif or Nic, dilates Ef-Art through a glomerulus-derived vasodilator(s) other than NO. Such diverse actions should be taken into consideration when calcium antagonists are used in the treatment of patients with cardiovascular and renal diseases.


Curvilinear mandibular distraction results and long-term stability effects in a group of 40 patients.
The mandibular internal curvilinear distractor design produces a curvilinear vector to provide ideal three-dimensional curvilinear movements compared with the limited straight unidirectional predecessor devices. In this manner, it corrects craniofacial deformities as anatomically as possible, allowing simultaneous bidirectional (rotational and translational) mandibular movement and multidirectional distraction. The aim of this study was to quantify the sagittal and vertical mandibular changes achieved through curvilinear distraction and to assess the long-term effect of this generated bone. Forty patients (20 male and 20 female), with ages ranging from 5 to 55 years, who underwent mandibular distraction from December of 1999 to August of 2007 at Lucile Packard Children's Hospital in Stanford, California, were included. Preoperatively, postoperatively, and at follow-up (at least 2 years following distraction), panoramic and lateral cephalometric radiographs were traced by plotting different skeletal landmark points and were then analyzed. All patients tolerated the curvilinear distraction process well through completion. The average of the mandibular body elongation recorded was 8 to 9 mm and 6 to 8 mm in the panoramic and cephalometric radiographs, respectively; whereas the vertical change of the mandibular ramus achieved was 10 to 12 mm and 10 to 11 mm, respectively. The curvilinear distraction effect on the mandible was found to be significantly stable when the long-term follow-up measurements were compared with the postoperative data revealed in the panoramic and lateral cephalometric radiographs for the two dimensions. The internal curvilinear device is an effective tool that achieves a stable mandibular distraction, resulting in the correction of craniofacial deformities.


Familial predisposition to monoclonal gammopathy of unknown significance, Waldenström's macroglobulinemia, and multiple myeloma.
The medical literature contains reports of around 130 families with two or more cases of MM, MGUS, or WM. An Icelandic family with multiple cases of MGUS, WM, and lymphoma was first described in 1978. In vitro testing of peripheral blood lymphocytes revealed increased production of immunoglobulins in response to poke-weed mitogen in 10 out of 35 family members, referred to as hyperresponders (HR). Enhanced B-cell survival after stimulation was associated with prolonged expression of Bcl-2. A population-based cancer registry study of 218 MM patients identified 7 additional families. Nine new cases of monoclonal gammopathy were detected by the screening of 350 family members. Further testing confirmed previously identified HR in the originally described family as well as detecting new cases. Only two HR were found in the recently identified families. The long-term aim is to identify the genetic background(s) and biology predisposing to the emergence of a persistent clone of immunoglobulin-producing cells.


Spousal Religiosity, Religious Bonding, and Pornography Consumption.
Religiosity and pornography use are often closely connected. Relatively few studies, however, have examined how this religion-pornography connection plays out within the context of committed romantic relationships. Moreover, virtually all studies of religion and pornography use conceptualize religiosity as a quality intrinsic to the person that typically reduces pornography viewing. Focusing on married Americans, this study shifted the focus to consider whether the religiosity of one's spouse relates to one's own pornography viewing and under what circumstances. Analyses of the nationally representative Portraits of American Life Study (N = 1026) revealed that spousal religiosity was strongly and negatively related to participants viewing pornography, controlling for participants' own religious or sociodemographic characteristics or sexual satisfaction. This relationship held whether spousal religiosity was measured with participants' evaluations of their spouses' religiosity or spouses' self-reported religiosity. The association between spousal religiosity and pornography use was also moderated by participants' religious service attendance, gender, and age. Considering mechanisms, the association between spousal religiosity and pornography use was mediated by frequent participation in religious bonding activities as a couple, suggesting that spousal religiosity may decrease pornography viewing among married Americans by promoting greater religious intimacy and unity between the couple, consequently decreasing one's interest or opportunities to view pornography.


Cellulosic Cr(salen) complex as an efficient and recyclable catalyst for copolymerization of SO2 with epoxide.
The search for green catalytic processes for the synthesis of useful polymers and incorporating the waste SO2 in highly-selective pathways become extremely important in the coming years. Herein, cellulose was modified by ethylenediamine, and then synthesized Schiff base with 3,5-di-tert-butyl-2-hydroxybenzaldehyde to immobilize chromium chloride and formed a novel heterogeneous cellulosic Cr(salen)-type catalyst for the first time. The cellulosic Cr(salen)-type catalyst shows high efficiency and recyclability in copolymerization of cyclohexene oxide with SO2. The influence factors such as the molar ratio of the catalyst and cyclohexene oxide, reaction temperature, and reaction time were researched in detail to study the optimal conditions. The copolymer product was characterized by FTIR and 1H NMR for confirming the structure. The possible copolymer mechanism is given, and we believed that the novel cellulosic Cr(salen)-type complex will be used as an efficient catalyst in other chemical reactions.


Prevalence of protein-energy malnutrition in a large population of elderly people at home.
The prevalence of protein-energy malnutrition (PEM) was examined in 1206 randomly selected elderly people aged 65 to 80 years living in their own homes. Nutritional assessment was based on weight loss, weight index, triceps skin fold, arm muscle circumference, serum albumin and prealbumin, and delayed cutaneous hypersensitivity (DCH) reaction. The prevalence of PEM was 5 per cent. If people with signs of inflammation were excluded, the prevalence of PEM was 3.5 per cent. When other nutritional indices, used by other authors among hospitalized patients, were applied to our sample prevalence values from 2.6 to 4.1 per cent were obtained. the prevalence was not related to sex or age. DCH increased the sensitivity of the screening method but causes of anergy other than PEM must be taken into account. It is concluded that PEM, in a degree shown to impair the prognosis at hospital, does occur among elderly people at home in an industrialized country.


Incidental MRI detection of BRCA1-related solitary peritoneal carcinoma during breast screening--A case report.
The reported cumulative risk of developing primary peritoneal carcinoma (PPC) one to 20 years after prophylactic bilateral oophorectomy is 3.5% to 4.3%. Virtually all reported cases have been stage III or IV. During MRI screening of the breasts, an incidental mass on the surface of the liver was identified in a 56-year-old BRCA1 mutation carrier who had undergone prophylactic bilateral salpingo-oophorectomy several years previously with no evidence of malignancy. After four cycles of chemotherapy a localized, grade 3 serous papillary adenocarcinoma was resected followed by further chemotherapy and radiation. She remains disease-free 3 years post-treatment. The literature on PPC after prophylactic oophorectomy is reviewed. To the best of our knowledge, this is the first description of an apparently localized case of BRCA related PPC outside the pelvis.


Lack of association between hepatotropic transfusion transmitted virus infection and oral lichen planus in British and Italian populations.
A possible association between oral lichen planus (OLP) and chronic hepatic disease has been found in some populations, although this is probably geographically influenced. In 1997 a new hepatotropic virus, transfusion transmitted virus (TTV), was identified but has not been studied in relation to OLP. The present investigation evaluated the genoprevalence of TTV DNA in the sera of British and Italian patients suffering from OLP using two different sets of primers to identify TTV subgenomic DNA. Study groups comprised 40 adult subjects (21 British, 19 Italian) with OLP. For each country, two control groups, a disease-control group and a healthy-control group, were included. The presence of TTV DNA in the sera of patients and control subjects was assessed using two different polymerase chain reactions (PCR) and DNA sequence analysis. Statistical analysis did not reveal evidence of any association between TTV infection and OLP or country of residence. An association between TTV and OLP is unlikely.


Thermal sensitivity and radiosensitization in V79 cells after BrdUrd or IdUrd incorporation.
Chinese hamster V79 cells were exposed to 10(-5) moles/liter bromodeoxyuridine (BrdUrd) or iododeoxyuridine (IdUrd) for 16 or 29 hr and then tested for thermal sensitivity, radiosensitivity, and sensitivity to the combined treatments of heat and radiation. BrdUrd and IdUrd treatment of cells resulted in enhanced radiosensitivity which increased with exposure time but had little or no effect on thermal sensitivity. For 42.0 degrees C heating, no effect was observed, while for 45.0 degrees C heating, a small decrease in thermal sensitivity occurred for both 16- and 29-hr exposure times, in the combined treatment of heat and radiation, the presence of BrdUrd or IdUrd resulted in about the same thermal enhancement in radiosensitivity. BrdUrd and IdUrd uptake into cellular DNA were measured using high-pressure liquid chromatography and, after a 29-hr exposure to 10(-5) moles/liter of BrdUrd or IdUrd, approximately 40% of the thymidine was substituted.


Blind source separation of electrocardiographic signals using system stability criteria.
This paper presents a method for blind source separation (BSS) of electrocardiographic signals disturbed by noise, using the Lyapunov stability conditions for linear time invariant systems. We used records from the MIT Arrhythmia Database and in-vivo records from cardiac voluntary patients to test our signal extraction method. We quantitatively assessed the performance of our separation procedure. The method presented here compares favorably to other BSS algorithms.


Mass spectrometric investigation of buspirone drug in comparison with thermal analyses and MO-calculations.
The buspirone drug is usually present as hydrochloride form of general formula C(21)H(31)N(5)O(2).HCl, and of molecular weight (MW)=421.96. It is an analgesic anxiolytic drug, which does not cause sedative or depression of central nervous system. In the present work it is investigated using electron impact mass spectral (EI-MS) fragmentation at 70 eV, in comparison with thermal analyses (TA) measurements (TG/DTG and DTA) and molecular orbital calculation (MOC). Semi-empirical MO calculation, PM3 procedure, has been carried out on buspirone both as neutral molecule (in TA) and the corresponding positively charged species (in MS). The calculated MOC parameters include bond length, bond order, particle charge distribution on different atoms and heats of formation. The fragmentation pathways of buspirone in EI-MS lead to the formation of important primary and secondary fragment ions. The mechanism of formation of some important daughter ions can be illuminated from comparing with that obtained using electrospray ESIMS/MS mode mass spectrometer through the accurate mass measurement determination. The losses of the intermediate aliphatic part (CH2)4 due to cleavage of N-C bond from both sides is the primary cleavage in both techniques (MS and TA). The PM3 provides a base for fine distinction among sites of initial bond cleavage and subsequent fragmentation of drug molecule in both TA and MS techniques; consequently the choice of the correct pathway of such fragmentation knowing this structural session of bonds can be used to decide the active sites of this drug responsible for its chemical, biological and medical reactivity.


Perioperative goal directed therapy using automated closed-loop fluid management: the future?
 Although surgery has become much safer, it has also becoming increasingly more complex and perioperative complications continue to impact millions of patients worldwide each year. Perioperative hemodynamic optimization utilizing Goal Directed Therapy (GDT) has attracted considerable interest within the last decade due to its ability to improve postoperative short and long-term outcomes in patients undergoing higher risk surgeries. The concept of GDT in this context can be loosely defined as collecting data from minimally invasive hemodynamic monitors with the intention of using such data (flow-related parameters and/or dynamic parameters of fluid responsiveness) to titrate therapeutic interventions (intravenous fluids and/or inotropic therapy administration) with the ultimate aim of optimizing end organ tissue perfusion. Recently, the increasing amount of evidence supporting the implementation of GDT strategies has been considered so robust as to allow for the creation of national recommendations in the United Kingdom (UK), France, and Europe. These recommendations from such influential scientific societies and the potential clinical and economic benefits of GDT protocols need to also be examined within the current shift from a "pay for service" to a "pay for performance" health care system. This shift is strongly encouraged within emerging systems such as the Perioperative Surgical Home (PSH) paradigm from the United States. As a result, hospitals and clinicians around the world have become increasingly incentivized to implement perioperative hemodynamic optimization using GDT strategies within their departments. Unfortunately, its adoption continues to be quite limited and a lack of standardized criteria for perioperative fluid administrations has resulted in significant clinical variability among practitioners. This current review will provide a brief up-to-date overview of GDT, discuss current clinical practice, analyze why implementation has been limited and finally, describe the newer closed-loop GDT concept along with its potential risks and benefits.


Time Needed to Improve Clinical Parameters By Daily Hemodialysis.
Daily hemodialysis therapy (DHD), 2 hours, 6 times per week, is able to cure complications that persist on standard hemodialysis (SHD), 4 hours, 3 times per week. Cardiovascular manifestations (high blood pressure, left ventricular hypertrophy), nutritional deficient states, and postdialysis asthenia are improved during the first month of DHD therapy and are usually cured at 3 months. Daily hemodialysis may be considered as a rescue therapy. The next step will be to select which patients can return to the classical SHD therapy without recurrence of their complications.