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Phosphorylation of the CARMA1 linker controls NF-kappaB activation. PKC isoforms and CARMA1 play crucial roles in immunoreceptor-dependent NF-kappaB activation. We tested whether PKC-dependent phosphorylation of CARMA1 directly regulates this signaling cascade. B cell antigen receptor (BCR) engagement led to the progressive recruitment of CARMA1 into lipid rafts and to the association of CARMA1 with, and phosphorylation by, PKCbeta. Furthermore, PKCbeta interacted with the serine-rich CARMA1 linker, and both PKCbeta and PKCtheta phosphorylated identical serine residues (S564, S649, and S657) within this linker. Mutation of two of these sites ablated the functional activity of CARMA1. In contrast, deletion of the linker resulted in constitutive, receptor- and PKC-independent NF-kappaB activation. Together, our data support a model whereby CARMA1 phosphorylation controls NF-kappaB activation by triggering a shift from an inactive to an active CARMA1 conformer. This PKC-dependent switch regulates accessibility of the CARD and CC domains and controls assembly and full activation of the membrane-associated IkappaB kinase (IKK) signalosome.

Chemistry of groundwater of Al-Ahsa Oasis eastern region Saudi Arabia and its predictive effects on soil properties. Saudi Arabia is an arid and the largest country in the middle east with a total land area of 2.253 x 10(6) km2. Recent urban and rural expansion has shown manifold increases in water use in various sectors. Water resources are limited and non-renewable coupled with unpredicted scanty rainfall. In order to meet the rising water needs, evaluation of water quality is important for allocation to various uses. A total of 101 well water samples were collected from Al-Ahsa Oasis. Water samples were analyzed for total salt concentration, pH, Ca, Mg, Na, K, HCO3, Cl, SO4, NO3, F and B contents. Soil Salinity Development (SSD), adjusted sodium adsorption ratio (adj.SAR), adjusted sodium adsorption ratio (adj. R(Na)) and Exchangeable Sodium Percentage (ESP) were calculated. The EC of groundwater ranged between 1.23 and 5.05 dS m(-1). Sodium was the most abundant cation followed by Ca, Mg and K in descending order. Chloride was the most abundant anion followed by SO4 and HCO3 in groundwater of Al-Ahsa Oasis. A significant correlation was found between Na and Cl (R2 = 0.936). Thermodynamics calculation revealed that an appreciable amount of Ca and Mg is associated with Cl and SO4 ions. The SAR and ESP values are within the permissible limits according to Ayers and Westcot, 1985. The NO3 concentration is within safe limits for drinking purpose according to WHO (1998) standards. The Saturation Indices (SI) indicated that groundwater is under-saturated (negative SI) with respect to certain minerals (for example: calcite, dolomite, gypsum, anhydrite, halite, pyrite, fluorite and aragonite) and oversaturated (positive SI) with respect to some other minerals (For example: Goethite, Siderite and hematite). The negative saturation index (SI) reveals that most of minerals are in un-saturated state and will dissolve more Ca and Mg into the soil solution after irrigation. A good relationship exists between Cl and other ions (Na, Ca and Mg) as well as between SO4 and Ca and Mg ion of groundwater. The salinity and sodicity hazards of groundwater of Al-Ahsa Oasis were classified as C3S1 and C4S2 i.e., high salinity with medium sodicity problems. The predicted soil salinity suggested application of 15-20% leaching requirements to keep soil salinity within permissible limits. Cultivation of slight to moderate salt and sodium tolerant crops is recommended for optimal agricultural production and efficient water use.

Multiple lineages of the non-LTR retrotransposon Rex1 with varying success in invading fish genomes. Rex1, together with the related BABAR: elements, represents a new family of non-long-terminal-repeat (non-LTR) retrotransposons from fish, which might be related to the CR1 clade of LINE elements. Rex1/BABAR: retrotransposons encode a reverse transcriptase and an apurinic/apyrimidinic endonuclease, which is very frequently removed by incomplete reverse transcription. Different Rex1 elements show a conserved terminal 3' untranslated region followed by oligonucleotide tandem repeats of variable size and sequence. Phylogenetic analysis revealed that Rex1 retrotransposons were frequently active during fish evolution. They formed multiple ancient lineages, which underwent several independent and recent bursts of retrotransposition and invaded fish genomes with varying success (from <5 to 500 copies per haploid genome). At least three of these ancient Rex1 lineages were detected within the genome of poeciliids. One lineage is absent from some poeciliids but underwent successive rounds of retrotransposition in others, thereby increasing its copy number from <10 to about 200. At least three ancient Rex1 lineages were also detected in the genome project fish Fugu rubripes. Rex1 distribution within one of its major lineages is discontinuous: Rex1 was found in all Acanthopterygii (common ancestor in the main teleost lineage approximately 90 MYA) and in both European and Japanese eels (divergence from the main teleost lineage about 180 MYA) but not in trout, pike, carp, and zebrafish (divergence 100-120 MYA). This might either result from frequent loss or rapid divergence of Rex1 elements specifically in some fish lineages or represent one of the very rare examples of horizontal transfer of non-LTR retrotransposons. This analysis highlights the dynamics and complexity of retrotransposon evolution and the variability of the impact of retrotransposons on vertebrate genomes.

DBP formation in hot and cold water across a simulated distribution system: effect of incubation time, heating time, pH, chlorine dose, and incubation temperature. This paper demonstrates that disinfection byproducts (DBP) concentration profiles in heated water were quite different from the DBP concentrations in the cold tap water. Chloroform concentrations in the heated water remained constant or even decreased slightly with increasing distribution system water age. The amount of dichloroacetic acid (DCAA) was much higher in the heated water than in the cold water; however, the maximum levels in heated water with different distribution system water ages did not differ substantially. The levels of trichloroacetic acid (TCAA) in the heated water were similar to the TCAA levels in the tap water, and a slight reduction was observed after the tap water was heated for 24 h. Regardless of water age, significant reductions of nonregulated DBPs were observed after the tap water was heated for 24 h. For tap water with lower water ages, there were significant increases in dichloroacetonitrile (DCAN), chloropicrin (CP), and 1,1-dichloropropane (1,1-DCP) after a short period of heating. Heating of the tap water with low pH led to a more significant increase of chloroform and a more significant short-term increase of DCAN. High pH accelerated the loss of the nonregulated DBPs in the heated water. The results indicated that as the chlorine doses increased, levels of chloroform and DCAA in the heated water increased significantly. However, for TCAA, the thermally induced increase in concentration was only notable for the chlorinated water with very high chlorine dose. Finally, heating may lead to higher DBP concentrations in chlorinated water with lower distribution system temperatures.

Fatigue, Pain, Anxiety and Depression in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy. In the clinical evaluation of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), scant attention is paid to symptoms such as fatigue, pain and anxiety/depression. We aimed at addressing seminal studies that focused on the burden of these symptoms and their impact on quality of life (QoL) in these conditions. Fatigue, pain, and anxiety/depression are increasingly being recognized in patients with GBS and CIDP, although their pathophysiological provenance remains unknown. Fatigue and pain are significant in terms of prevalence and intensity, may be a presenting symptom, and can persist for years after apparent functional recovery, suggesting residual injury. Anxiety/depression has also been examined although studies are limited. Despite their negative impact on QoL, the long-term dynamics of these symptoms in patients with GBS and particularly CIDP receiving therapy in routine clinical practice have not been systematically evaluated. Such observations formed the basis for the ongoing (GAMEDIS) studies evaluating the effect of Gamunex on fatigue and depression in patients with CIDP, of which some preliminary data are presented. Strength and sensory deficits are the main areas of focus in patients with GBS and CIDP, but they do not explain the total reduction in QoL, suggesting the possible role of other complaints. A more comprehensive approach to patient care demands that factors such as pain, fatigue and anxiety/depression receive greater attention. The non-interventional GAMEDIS studies are expected to provide valuable insight into the long-term effectiveness of Gamunex in everyday practice.

A study of occlusion as related to the Frankfort-mandibular plane angle. The relation of the Frankfort-mandibular plane angle (FMA) to naturally occurring occlusion groups was studied in 112 subjects. Occlusion types were categorized into four groups depending on the magnitude of first-molar contact on the working side. Percentage (frequency) of occurrence of occlusion groups were: disclusion, 17.9 per cent; delayed disclusion, 19.6 per cent; progressive disclusion, 8.9 per cent; and group function, 53.6 per cent. The mean FMA for the study sample was 25.68 degrees with a range of 13 to 40 degrees. Mean FMA's for the occlusion groups showed a progressive increase from disclusion (19.6 degrees) to group function (28.9 degrees). A statistical test, extension of the median, indicated a highly significant relation between occlusion groups and the FMA. Considering these results, an FMA determination provides a structure-function basis to consider in selecting a scheme for occlusal reconstruction and should be incorporated in the treatment planning procedure as a major adjunctive diagnostic tool. However, further research, focused upon the many variables that determine a type of occlusion, must precede the formulation of a set of "rules" for selection of occlusion.

Insect nicotinic acetylcholine receptor: conserved neonicotinoid specificity of [(3)H]imidacloprid binding site. The insect nicotinic acetylcholine receptor (nAChR) is a major target for insecticide action. The rapidly expanding use of neonicotinoid insecticides of varied structures makes it increasingly important to define similarities and differences in their action, particularly for the first-generation chloropyridinyl compounds versus the second-generation chlorothiazolyl derivatives. We have shown with Musca domestica that a convenient and relevant determination of the neonicotinoid insecticide target is a binding site assay with [(3)H]imidacloprid ([(3)H]IMI). This study uses membranes from the aphids MYZUS: persicae and Aphis craccivora and from heads of the flies Drosophila melanogaster and Musca domestica to characterize the [(3)H]IMI binding sites relative to their number and possible species variation in structure-activity relationships. With emphasis on commercial neonicotinoids, six potent chloropyridinyl compounds are compared with the corresponding six chlorothiazolyl analogues (syntheses are given for chemicals prepared differently than previously described). The preference for chloropyridinyl versus chlorothiazolyl is not dependent on the insect species examined but instead on other structural features of the molecule. The chlorothiazolyl substituent generally confers higher potency in the clothianidin and desmethylthiamethoxam series and the chloropyridinyl moiety in the imidacloprid, thiacloprid, acetamiprid, and nitenpyram series. Two chlorothiazolyl compounds compete directly with the chloropyridinyl [(3)H]IMI for the same binding sites in Myzus and Drosophila membranes. This study shows conserved neonicotinoid specificity of the [(3)H]IMI binding site in each of the four insect species examined.

Rett syndrome and mitochondrial enzyme deficiencies. The etiology of Rett syndrome is unknown. Structural mitochondrial abnormalities have been described in muscle in patients with Rett syndrome. We report three children with Rett syndrome and normal muscle mitochondrial structure on light and electron microscopy. However, all had abnormalities in mitochondrial respiratory chain enzymes.

Antiviral therapy for HCV-associated cryoglobulinemic glomerulonephritis: case report and review of the literature. We describe the case of a 51-year-old woman with HCV-associated cryoglobulinemic glomerulonephritis (GN). She presented mild deterioration of kidney function, non-nephrotic proteinuria, and active urinary sediment. Kidney biopsy showed features of membranoproliferative changes with some sclerosis. Sustained viral response (SVR) was obtained by 6 months of antiviral therapy (peg-IFN-α2a plus ribavirin). SVR was linked with improvement of kidney function and remission of proteinuria. Clinical and virological remission persists over a 25-month follow-up. This case report emphasizes efficacy and safety of antiviral treatment of HCV-associated glomerulonephritis--preliminary but encouraging results exist. We identified by systematic review of the literature 9 studies (156 unique patients); the pooled estimate of frequency of sustained virological response after IFN-based therapy was 0.49 (95% confidence interval, CI: 0.21, 0.77; p < 0.0005; random effects model). Heterogeneity was found (I(2) = 98.9%, p < 0.0001). Two possible regimens should be considered for the treatment of HCV-associated cryoglobulinemic GN according to the clinical presentation. Immunosuppressive therapy is recommended for HCV-related kidney disease having aggressive course, and recent evidence supports rituximab (RTX) use with a reduced exposure to corticosteroids. We identified six studies (66 unique patients) on RTX therapy for HCV-associated kidney disease; at the end of RTX therapy, the pooled estimate of the mean decrease in proteinuria was 1.4 g/24 h (95% CI: 0.75, 2.05, p < 0.001); The p test for heterogeneity gave a value of 0.94 (I(2) = 0). Several questions related to RTX use remain. HCV-induced GN is uncommon among CKD patients of developed countries, and this clearly hampers prospective controlled clinical trials aimed to evaluate efficacy and safety of antiviral or immunosuppressive therapy in this population.

Structure and antigenicity of the major glycolipid from Taenia solium cysticerci. Lipids were extracted from cysticerci of the human tapeworm Taenia solium isolated from various infected pigs and analysed by two-dimensional thin-layer chromatography. These consisted of both alkali-labile and alkali-stable glycolipids, and phosphorylated non-glycosylated lipids. Because abundant and immunogenic glycolipids of parasites have been implicated in host-parasite interactions, the major lipid, an alkali-stable glycolipid, was purified by chromatography and its structure and antigenicity were determined. The structure of the major glycolipid of T. solium, GSL-I, was elucidated through a combination of chemical degradative methods, gas chromatography/mass spectrometry analyses of the degradative products, matrix-assisted-laser desorption/ionisation time of flight mass spectrometry and nuclear magnetic resonance spectroscopy. This analytical strategy led to the identification of a family of beta-galactosylceramides composed mainly of phytosphinganine (2-hydroxylated sphinganine) N-acylated by C16-C24 fatty acids, with the predominance of 2-hydroxylated homologues. Enzyme-linked immunosorbent assay showed no correlation between the antibody titres directed against GSL-I in the human sera and the infective status; in contrast, a very high specific immunoreactivity and a sensitivity above 50% were observed when GSL-I was tested with cerebrospinal fluids from well characterised infected humans. Thus, although these results do not support the use of GSL-I alone as an antigen for the detection of neurocysticercosis, its use as part of an antigen cocktail for the diagnosis of the disease in cerebrospinal fluids merits further investigations.

Clinical Mycoplasma sp. Infections in Free-living Three-toed Box Turtles ( Terrapene carolina triunguis) in Missouri, USA. Mycoplasma species, which can cause upper respiratory tract disease (URTD), are significant pathogens of birds, mammals, fish, and reptiles. Mycoplasmosis is of high concern for chelonian conservation, with the most well-documented cases in gopher and desert tortoises. Mycoplasma sp. infections have been reported in captive and free-living box turtles ( Terrapene spp.). We documented URTD associated with Mycoplasma sp. in two free-living, three-toed box turtles ( Terrapene carolina triunguis) in Missouri, US. Both turtles were Mycoplasma sp. positive by PCR and had URTD-like clinical signs, including nasal and ocular discharge, palpebral edema, lethargy, and weight loss, during a 6-8-wk period between June and September 2014.

Low-Energy CO2 Release from Metal-Organic Frameworks Triggered by External Stimuli. Groundbreaking research over the past 15 years has established metal-organic frameworks (MOFs) as adsorbents capable of unprecedented gas adsorption capacity. This has encouraged the contemplation of their use in applications such as increasing the storage capacity in natural gas fuel tanks, or the capture of carbon dioxide from coal-fired flue gas streams. However, while the gas adsorption capacity of MOFs is large, not all stored gas can be readily released to realize the efficient regeneration of MOF adsorbents. This leads to an increase in energy requirements, or working capacities significantly lower than the amount of gas adsorbed. This requirement for low energy means to efficiently release more stored gas has motivated the research in our group toward the triggered release of the stored gas from MOFs. Using CO2 as a typical gas adsorbate, we have developed three new methods of releasing stored gas with external stimuli that include light induction swing adsorption, magnetic induction swing adsorption, and their combination, denoted as LISA, MISA and MaLISA, respectively. LISA: Light, being naturally abundant, is particularly interesting for reducing the parasitic energy load on coal-fired power stations for regenerating the CO2 adsorbent. We showed that, by incorporating light-responsive organic linkers, exposure of light to a gas-loaded MOF promoted localized movement in the linkers, expelling around 80% of the adsorbed gas, just from the use of concentrated sunlight. Variation of the light-responsive components such as silver nanoparticles in MOFs allowed the response to be moved from UV to visible wavelengths, improving safety and light penetration depth. MISA: In order to expand this discovery to larger scales, more penetrating forms of radiation were sought. MOFs incorporated with magnetic nanoparticles (Magnetic Framework Composites, MFCs) were developed, and absorb the alternating magnetic fields exceptionally efficiently. The rapid heating of magnetic particles delivers local temperature increases to the otherwise thermally insulating MOF material, and in optimized conditions release all adsorbed gas in a matter of minutes. MaLISA: The triggered release methods of LISA and MISA may be combined in MFCs that also contain light-responsive groups. Both stimuli were employed and cooperative enhancement of gas releasing efficiency were found, minimizing the overall energy requirement even further. Initial calculations of the energy costs for these processes have shown them to have the potential to exceed any other reported method, following optimization. Encouragingly, the efficiency of the process was found to increase at larger scales, prompting further research in this area toward widespread deployment.

Environmental, personal, and behavioral influences on BMI and acculturation of second generation Hmong children. This project investigated influences (environmental, personal, and behavioral) on body mass index (BMI) and acculturation of Hmong children born in the United States (US) using the social cognitive theory as the theoretical framework. Using formative information from 12 child focus groups (n = 68) and a review of the literature, a quantitative survey was developed and administered to Hmong children (n = 300) ≥ 9 ≤ 18 years-old. Heights, weights, and acculturation level were measured. B-US(1) were raised in the US and 9-13 years-old (n = 144) and B-US(2) were raised in the US and 14-18 years-old (n = 156). Approximately 50 % of children were classified as overweight/obese (BMI ≥ 85th percentile). Across age and gender sub-groups, questions from the environmental construct appeared to be the most predictive of variances in BMI percentiles (50-60 %). In contrast, acculturation scores were equally predicted by environmental, behavioral, and personal constructs for age and gender sub-groups. Sum acculturation score was significantly higher for B-US(2) compared to B-US(1), with B-US(2) being more acculturated in language use and thought, overall dietary acculturation, and foods eaten at lunch. The high prevalence of obesity in Hmong children suggests that future studies investigate factors influencing obesity to identify the most effective method to reduce/prevent this problem. In particular, acculturation level of the child should be assessed to determine changed dietary behavior and possible risk for obesity.

MPK3- and MPK6-Mediated ICE1 Phosphorylation Negatively Regulates ICE1 Stability and Freezing Tolerance in Arabidopsis. Low temperatures affect plant growth, development, productivity, and ecological distribution. Expression of the C-repeat-binding factor (CBF) transcription factors is induced by cold stress, which in turn activates downstream cold-responsive (COR) genes that are required for the acquisition of freezing tolerance. Inducer of CBF expression 1 (ICE1) is a master regulator of CBFs, and ICE1 stability is crucial for its function. However, the regulation of ICE1 is not well understood. Here, we report that mitogen-activated protein kinase 3 (MPK3) and MPK6 interact with and phosphorylate ICE1, which reduces its stability and transcriptional activity. Consistently, the mpk3 and mpk6 single mutants and the mpk3 mpk6 double mutants show enhanced freezing tolerance, whereas MPK3/MPK6 activation attenuates freezing tolerance. Phosphor-inactive mutations of ICE1 complement freezing sensitivity in the ice1-2 mutant. These combined results indicate that MPK3/MPK6 phosphorylate and destabilize ICE1, which negatively regulates CBF expression and freezing tolerance in plants.

The effect of brief intermittent stair climbing on glycemic control in people with type 2 diabetes: a pilot study. We examined the effect of brief intermittent stair climbing exercise on glycemic control using continuous glucose monitoring in people with type 2 diabetes (n = 7, 5 men; 2 women; age, 21-70 years). The protocol involved three 60-s bouts of vigorously ascending and slowly descending a flight of stairs. Mean 24-h blood glucose was unchanged after an acute session (p = 0.43) and following 18 sessions over 6 weeks (p = 0.13). The protocol was well tolerated by participants but seemingly insufficient to alter glycemic control.

Evaluation of the efficacy of sexual intercourse in expulsion of distal ureteric stones. To evaluate the efficacy of sexual intercourse in expulsion of distal ureteric stones. The study included 56 patients with distal ureteric or intramural stone. The stones size ranged from 5 to 10 mm and were detected by US, plain X-ray film, and non-enhanced CT. The patients were divided randomly into group A included 28 patients who were advised to do sexual intercourse 3-4 times/week with administration of symptomatic treatment, and group B included 28 patients receiving symptomatic treatment only (control group) and were instructed not to do sexual intercourse or masturbation during the study. Follow-up (4 weeks) was done by plain X-ray, US, and urine analysis every week and by asking the patients about stone passage, time of expulsion, number of colicky attacks, and analgesic injections. Group A patients mean age was 36.5 ± 10.7 years and group B 37.3 ± 12.5 years. Stone expulsion rate, in the first 2 weeks for group A, was 82% (23/28), while in group B 53% (16/28), (P = 0.006). At the fourth week, expulsion rate for group A reached to 89%, but in group B 71.4%. The mean expulsion time was shorter in group A (11.9 ± 4.4 days) than group B (16.2 ± 6.7 days). The number of colicky attacks and analgesics for group A was less than group B. Practicing sexual intercourse for 3-4 times/week for married male patients with distal ureteric stone (5-10 mm) increases the expulsion rate and decreases the frequency of renal colic and the needs for analgesic.

Maternal thyroid-blocking immunoglobulins in congenital hypothyroidism. We evaluated 24 mothers whose babies had congenital hypothyroidism (CH) for the presence of immunoglobulins (Igs) that inhibited [125I]bovine TSH binding and blocked TSH-induced growth and function of FRTL-5 cells. Results were compared with those from 2 mothers with known primary myxedema (atrophic thyroiditis) whose babies had transient CH and with normal controls. Only 1 prospectively evaluated CH mother had potent TSH binding inhibitory, growth inhibitory, and function inhibitory IgGs. Further study of this discordant mother's serum indicated that she was hypothyroid, probably due to atrophic thyroiditis. Both mothers with known primary myxedema had blocking IgGs. The thyroid growth-blocking activity was verified by cell count, could be absorbed by and eluted from Staphylococcal protein-A, indicating that it was an IgG, and was not an anti-TSH idiotype. Half-maximal inhibition was similar in the three different assays for thyroid-blocking activity, suggesting that TSH binding inhibitory, growth inhibitory, and function inhibitory IgGs in some patients with primary myxedema may be the same antibody population. There was no correlation with the titer of antimicrosomal antibodies. These data suggest that maternal thyroid-blocking IgGs interacting with the TSH receptor do not play a role in most cases of sporadic CH. Determination of TSH binding inhibitory IgGs, but not antimicrosomal antibodies, is a sensitive screening test for the presence of TSH receptor-blocking antibodies.

Bone marrow micrometastases do not impact disease-free and overall survival in early stage sentinel lymph node-negative breast cancer patients. The presence of lymph node metastases is the most important prognostic factor in early stage breast cancer. Whether bone marrow micrometastases (BMM) impact the prognosis in sentinel lymph node (SLN)-negative breast cancer patients remains a matter of debate. Therefore, the objective of this study was to assess the impact of BMM on 5-year disease-free and overall survival among those patients. We analyzed 410 patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, cN0) who were prospectively enrolled into the Swiss Multicenter Sentinel Lymph Node Study in Breast Cancer between January 2000 and December 2003. All patients underwent bone marrow aspiration followed by SLN biopsy. All SLN were stained with hematoxylin and eosin and immunohistochemistry (Lu-5, CK-22). Cancer cells in the bone marrow were identified after staining with monoclonal antibodies A45-B/B3 against CK-8, -18, and -19. Negative SLN were found in 67.6% (277 of 410) of the enrolled patients. Of those, BMM status was negative in 75.8% (210 of 277) and positive in 24.2% (67 of 277) patients. Median follow-up was 61 (range 11-96) months. Five-year disease-free survival was 93.6% (95% confidence interval [CI] 89.1-96.0) in BMM-negative and 92.2% (95% CI 82.5-96.2) in BMM-positive patients (p = 0.50). Five-year overall survival was 92.7% (95% CI 87.9-95.8) for the BMM-negative and 92.5% (95% CI 83.4-96.2) for the BMM-positive group (p = 0.85). This is one of the first prospective studies to examine 5-year disease-free and overall survivals in SLN-negative patients in correlation to their BMM status. Although BMM are identified in one of four SLN-negative patients, they do not impact disease-free and overall survival.

Inhibitory effect of dehydroepiandrosterone on brain monoamine oxidase activity: in vivo and in vitro studies. To evaluate the acute effect of dehydroepiandrosterone (DHEA) on monoamine oxidase (MAO) activity in the corpus striatum (CS) and the nucleus accumbens (NAc) in vivo and in vitro. Male Wistar rats received an i.p. injection of DHEA (30, 60 and 120mg/kg) and MAO activity was assayed by formation of 4-hydroxyquinoline 2h later. For in vitro studies, DHEA (100nM-1mM) was added to brain tissue homogenates to assay MAO activity. DHEA significantly reduced (-24%) total MAO activity in the NAc (F=8.5, p<0.001), but not in the CS, at 120mg/kg dose. No significant difference was observed when MAO A and MAO B activities were independently analyzed. When assayed in vitro, total MAO, MAO A and MAO B activities were reduced by DHEA to 55.7, 28.2 and 54.4% in the NAc and to 71.9, 44.2 and 61.2% in the CS, respectively (IC(50) 4.7-56.1microM). An inhibitory effect of DHEA on MAO activity may be involved in the antidepressant and neuroprotective effects of the steroid. Since MAO inhibition reduces neurodegeneration in clinical trials for Parkinson's disease, our results suggest that DHEA may be useful to treat depression and to prevent neuronal death in this disorder.

The perceived direction of textured gratings and their motion aftereffects. The stimuli in these experiments are square-wave luminance gratings with an array of small random dots covering the high-luminance regions. Owing to the texture, the direction of these gratings, when seen through a circular aperture, is disambiguated because the visual system is provided with an unambiguous motion energy. Thus, the direction of textured gratings can be varied independently of grating orientation. When subjects are required to judge the direction of textured gratings moving obliquely relative to their orientation, they can do so accurately (experiment 1). This is of interest because most studies of one-dimensional motion perception have involved (textureless) luminance-defined since-wave or square-wave gratings, and the perceived direction of these gratings is constrained by the aperture problem to be orthogonal to their orientation. Thus, direction and orientation have often been confounded. Interestingly, when subjects are required to judge the direction of an obliquely moving textured grating during a period of adaptation and then the direction of the motion aftereffect (MAE) immediately following adaptation (experiments 2 and 3), these directions are not directly opposite each other. MAE directions were always more orthogonal to the orientation of the adapting grating than the corresponding direction judgments during adaptation (by as much as 25 degrees). These results are not readily explained by conventional MAE models and possible accounts are considered.

The effect of electroacupuncture on opioid-like medication consumption by chronic pain patients: a pilot randomized controlled clinical trial. Opioid-like medications (OLM) are commonly used by patients with various types of chronic pain, but their long-term benefit is questionable. Electroacupuncture (EA) has been previously shown beneficial in reducing post-operative acute OLM consumption. In this pilot randomized controlled trial, the effect of EA on OLM usage and associated side effects in chronic pain patients was evaluated. After a two-week baseline assessment, participants using OLM for their non-malignant chronic pain were randomly assigned to receive either real EA (REA, n=17) or sham EA (SEA, n=18) treatment twice weekly for 6 weeks before entering a 12-week follow-up. Pain, OLM consumption and their side effects were recorded daily. Participants also completed the McGill Pain Questionnaire (MPQ), SF-36 and Beck Depression Inventory (BDI) at baseline, and at the 5th, 8th, 12th, 16th and 20th week. Nine participants withdrew during the treatment period with another three during the follow-up period. Intention to treat analysis was applied. At the end of treatment period, reductions of OLM consumption in REA and SEA were 39% and 25%, respectively (p=0.056), but this effect did not last more than 8 weeks after treatment. There was no difference between the two groups with respect to reduction of side effects and pain and the improvement of depression and quality of life. In conclusion, REA demonstrates promising short-term reduction of OLM for participants with chronic non-malignant pain, but such effect needs to be confirmed by trials with adequate sample sizes.

Unilateral benign multinodular versus solitary goiter: Long-term contralateral reoperation rates after lobectomy. Few long-term studies define the appropriate extent of surgery and recurrence rates for unilateral multinodular goiter. We compared the rate and time to reoperation in patients with multinodular goiter who underwent lobectomy to that of patients with benign solitary nodule. Retrospective study of a prospective database of all patients who underwent lobectomy for multinodular goiter or solitary nodule from 1991 to 2017. We analyzed reoperation rates and time to reoperation. Reoperation was defined as the need for completion thyroidectomy determined the following citeria: nodule greater than 3 cm, multiple nodules, nodule growth or suspicion for malignancy by ultrasound or fine-needle aspiration biopsy, or compressive symptoms. Included in the study were 2,675 lobectomies; 852 (31.85%) for multinodular goiter. In total, 394 patients (14.7%) underwent reoperation: 261 (30.6%) with a previous multinodular goiter and 133 (7.29%) with solitary nodule (P < .0001). A total of 80% of the patients with multinodular goiter and 67.66% with solitary nodule recurred as multinodular goiter; 3.5% of all recurrences were carcinomas. The mean time to reoperation was 14.8 years, without difference between groups (P = .5765). Patients without reoperation were younger (47 ± 15 vs 54 ± 13 years of age, P < .0001) and more likely to be male (P < .0001). Lobectomy for unilateral multinodular goiter is the procedure of choice given the length of time to reoperation. Patients and surgeons should be aware of the need for long-term surveillance.

Enhanced reactivity for hydrogen reactions at Pt nanoislands on Au(111). We report high exchange current densities exceeding 1 A cm(-2) at Pt nanostructures on Au(111) for hydrogen-related reactions. Such activity is found at Pt nanoparticles with a coverage of less than 10 % of a monolayer on Au(111) and on single Pt particles deposited on Au(111). Potential pulse technique as well as micropolarization curves with overpotentials of +/-10 mV were used in the case of extended nanostructured surfaces to determine the activity. Single Pt particles were investigated in an in situ electrochemical scanning tunneling microscope setup using the STM tip as local sensor. The reactivity obtained on Pt nanostructured Au(111) towards hydrogen reactions were subsidized by single particle reactivity measurements. The specific activity of platinum is enhanced by more than a factor of 1000 as compared to a Pt(111) single crystal. Aspects that may explain this enhancement such as an involvement of the substrate, highly reactive defect sites and enhanced mass transport are discussed.

What can public health do to address inequities in infectious disease? The recognition of the importance of social conditions informed early public health responses to infectious disease epidemics. By influencing exposure, vulnerability, and access to health services, social determinants of health (SDOH) continue to cause inequalities in infectious disease distribution. Such preventable and unjust inequalities are considered to be inequities. A number of challenges and barriers exist to more widespread public health action that addresses SDOH and inequities, including a lack of clarity on what public health should or could do. The National Collaborating Centre for Determinants of Health (NCCDH) has identified four primary roles for public health action on SDOH and inequities. This paper describes these roles and includes examples of their application to infectious diseases. The critical contribution that organizations make in providing the leadership and support for programs and staff to pursue action on SDOH and inequities is also highlighted. While the challenge is large and complex, approaches such as the NCCDH roles for public health action provide a menu of options to facilitate the analysis and action to address SDOH and inequities in infectious diseases.

Open partial nephrectomy for the treatment of renal cell carcinoma. Open partial nephrectomy, or nephron-sparing surgery (NSS), is now considered the standard of care for the treatment of small renal tumors. The oncologic efficacy and safety of NSS for the treatment of stage-T1a renal tumors has been repeatedly demonstrated to be equivalent to radical nephrectomy. NSS initially was reserved for patients with solitary kidneys, impaired renal function, hereditary tumor syndromes, bilateral renal tumors, and those with significant comorbidities predisposing to future renal failure. The indications have expanded recently to allow elective partial nephrectomy in the setting of a normal contralateral kidney. Furthermore, recent data demonstrate that partial nephrectomy for larger tumors (T1b), which have been historically treated with radical nephrectomy, is a viable option when surgical margins can safely be achieved. In the era of minimally invasive techniques, laparoscopic NSS is technically feasible, yet long-term studies are still needed to assess oncologic efficacy. New NSS ablative technologies, such as cryoablation and radiofrequency ablation, are on the horizon. In this article, we discuss the role of open NSS and surgical technique in the contemporary management of renal tumors.

Human skin absorption and metabolism of the contact allergens, cinnamic aldehyde, and cinnamic alcohol. trans-Cinnamaldehyde and trans-cinnamic alcohol have been commonly reported to cause allergic contact dermatitis (ACD) in humans. Cinnamaldehyde is a more potent skin sensitizer than cinnamic alcohol. It has been hypothesized that cinnamic alcohol is a "prohapten" that requires metabolic activation, presumably by oxidoreductase enzymes such as alcohol dehydrogenase (ADH) or cytochrome P450 2E1 (CYP2E1), to the protein-reactive cinnamaldehyde (a hapten). In this study, the in vitro percutaneous absorption and metabolism of cinnamaldehyde and cinnamic alcohol (78 micromol dose) has been examined using freshly excised, metabolically viable, full-thickness breast and abdomen skin from six female donors. Penetration rates and total cumulative recoveries of cinnamic compounds that were present in receptor fluid, extracted from within the skin, evaporated from the skin surface, or remained unabsorbed on the skin surface after 24 h were quantified by reversed-phase high-performance liquid chromatography. Biotransformation of cinnamaldehyde to both cinnamic alcohol and cinnamic acid was observed. Topically applied cinnamic alcohol was converted to cinnamaldehyde (found on the skin surface only) and cinnamic acid. To establish whether these biotransformations were enzymatic, experiments were performed in the absence and presence of varying concentrations (80-320 micromol) of the ADH/CYP2E1 inhibitors pyrazole or 4-methylpyrazole. The observation that pyrazole significantly reduced (p < 0.05) the total penetration of cinnamic metabolites into receptor fluid, following either cinnamaldehyde or cinnamic alcohol treatment, but did not significantly affect parent chemical penetration, suggests that we are measuring cutaneous metabolic products of ADH activity. The skin absorption and metabolism of cinnamaldehyde and cinnamic alcohol will play an important role in the manifestation of ACD following topical exposure to these compounds.

Regulatory T cells: Friends or foe in human Mycobacterium leprae infection? Regulatory T cells (Tregs) are known to control immune responses by suppressing the antigen-presenting and effector T cells. Some mechanisms adopted by Tregs in combating Mycobacterium infections have been proposed. Nevertheless, in M. leprae infection, also known as leprosy or Hansen's disease, the role of Tregs has not been completely elucidated. Using multicolor flow cytometry, we evaluated the expression of different cell surface and intracellular molecules present in Tregs from peripheral blood samples of leprosy patients. Before initiating treatment, thirteen new cases of leprosy were grouped according to the Ridley-Jopling classification in to the paucibacilary (PB) or multibacilary (MB) group. Fifteen non-infected individuals (NI) were included as control subjects. Tregs were higher in the MB group than in the NI group. Tregs also co-expressed high amounts of PD1 and PDL-1, indicating that these cells could induce apoptosis of effector cells and simultaneously prevent their own apoptosis. Our data showed that compared to the NI group, Tregs from the PB group expressed higher levels of CD95L, which may be associated with other apoptotic pathways that may decrease Tregs in these patients. Correlation analysis reinforced that PD1 and CD95L are efficient apoptosis' pathway that decreased levels of Tregs in the NI and PB groups. We also observed significant differences in cytokine expression of Tregs from the PB and MB groups. Compared to the NI group, Tregs from the MB group showed higher IL-17 expression; however, compared to the PB group, the expression of IL-10 in Tregs from the MB group was lower, suggesting inefficient control of inflammation. Therefore, we concluded that different pathways were involved in Treg-induced suppression of leprosy. Moreover, Treg-mediated regulation of inflammation via IL-10 and IL-17 expression in leprosy patients was inefficient. Thus, we propose that during M. leprae infection, Tregs may impair the immune responses elicited against this bacillus, favor bacterial replication, and aid in persistence of a disseminated multibacillary disease.

Spontaneous Substitutions at Phosphorus Trihalides in Imidazolium Halide Ionic Liquids: Grotthuss Diffusion of Anions? PX3 compounds (X=Cl, Br, I) in imidazolium halide ionic liquids combine with the anion Z (Z=Cl, Br, I) of the solvent to form [PX3 Z]- complex anions. These anions have a sawhorse shape in which the lone pair of the phosphorus atom fills the third equatorial position of the pseudotrigonal bipyramid. Theoretical results show that this association remains incomplete due to strong hydrogen bonding with the cations of the ionic liquid, which competes with the phosphorus trihalide for interaction with the Z- anion. Temperature-dependent 31 P NMR experiments indicated that the P-Z binding is weaker at higher temperature. Both theory and experiment evidence dynamic exchange of the halide anions at the phosphorus atom, together with continuous switching of the ligands at the phosphorus atom between equatorial and axial positions. Detailed knowledge of the mechanism of the spontaneous exchange of halogen atoms at phosphorus trihalides suggests a way to design novel, highly conducting ionic-liquid mixtures.

Quality comparison of retorted Samgyetang made from white semi-broilers, commercial broilers, Korean native chickens, and old laying hens. The aim of this study was to compare the quality characteristics of retorted Samgyetang (Korean ginseng chicken soup) made from white semi-broilers (WSB; Ross × Hyline white, 3 weeks old), commercial broilers (CB; Ross, 4 weeks old), Korean native chickens (KNC; Hanhyup-3-ho, 12 weeks old) and old laying hens (OLH; Hyline white, 72 weeks old) and to explore the possibility of using the carcasses of KNCs and OLHs as raw material for product diversification. Raw and cooked meat quality, fatty acid composition and consumer acceptance were analyzed. Among the chicken breeds, OLH and KNC showed a higher shear force value than WSB and CB due to high insoluble collagen contents. However, the meat of KNC was more tender than that of OLH. The meat of OLH was characterized by the lowest moisture content and highest crude fat content. The meat of KNC was characterized by a higher proportion of saturated fatty acids, α-linolenic acid and arachidonic acid than that of OLH. The meat of OLH showed the highest content of unsaturated fatty acid, particularly linoleic acid, in its thigh meat. Electronic nose readings revealed that the meat aroma pattern was clearly different across breeds. OLH had the lowest overall acceptance score, while no differences were found in flavor, texture, juiciness and appearance among WSB, CB and KNC. KNC shows the possibility to be used as raw material for Samgyetang, while additional preprocessing methods, such as tenderization and fat removal, are required for the utilization of OLH as raw material for retorted Samgyetang.

Laparoscopic treatment of benign adnexial cysts. The results of laparoscopic adnexial cyst excision operations performed within the last 2.5 years in our clinic are reported. Thirty-three adnexial masses thought to be benign after gynaecological examination and ultrasonographic findings were treated. Laparoscopy was done in 32 cases but laparotomy had to be performed in one case of stage IV endometriosis. The mean duration of the operations was 72.78 +/- 34.09 minutes and no major complication occurred. Pathologic examinations of the specimens were reported as benign in all cases. According to these results, laparoscopy should be the preferred method in the treatment of benign adnexial cysts.

DRGs and hospital social work: when policy guides practice. Since the early 1980s cost containment policies have changed the practice of hospital social work. Diagnosis Related Groups (DRGs), a cost containment mechanism, have increased the caseloads of hospital social workers, and placed a greater emphasis on discharge planning. In this article DRGs are described, and their function is discussed from a social work perspective. The literature surrounding DRGs and the role of the hospital social worker is addressed. Recommendations are made for social workers to evaluate the policies affecting their practice. It is proposed that if social workers understand policies, their origins, and how policies affect practice, then they can have greater influence as advocates and policy makers.

[Absorption, distribution, metabolism, excretion and toxicity of biologics and its application in pharmacokinetic modeling]. Recently, more and more attentions of drug development are placed to macromolecules, such as monoclonal antibodies, proteins, etc. It has become one of the most promising areas in drug research and development in 21st Century. In terms of the structure and the ADMET (absorption, distribution, metabolism, excretion and toxicity), macromolecules is different from small molecule drugs, which lead to a distinct modeling strategy. The characterization of biologics ADMET processes and its application in the PK model selection of macromolecules are reviewed in this paper.

Prostaglandin effect on the physical properties of gastric mucus glycoprotein and its susceptibility to pepsin. The effect of 16,16-dimethyl prostaglandin E2 (DMPGE2) on gastric mucus glycoprotein viscosity, permeability to hydrogen ion and degradation by pepsin was investigated. Preincubation with DMPGE2 produced a marked enhancement in the glycoprotein viscosity. The increase was concentration dependent and at 2.6 X 10(-5)M DMPGE2 reached a value of 178%. Permeability measurements revealed that 2.6 X 10(-7)M DMPGE2 increased the retardation ability of the glycoprotein to hydrogen ion by 10%, while 22% increase was obtained with 2.6 X 10(-4)M DMPGE2. The results of peptic activity assay showed that DMPGE2 had no inhibitory effect on the rate of glycoprotein proteolysis, and actually a small stimulatory influence was consistently observed. The results suggest that prostaglandins beneficially affect the physical properties of mucus glycoprotein which are considered to be essential for the protective function of gastric mucus.

Modulation of the stress-induced synthesis of stress proteins by a phorbol ester and okadaic acid. The expression of alphaB crystallin, hsp27, and hsp70 in C6 cells increased when they were exposed to arsenite (50 microM for 1 h) or heat (42 degrees C for 30 min), as detected by specific immunoassays, Western blot analysis, and Northern blot analysis. When cells were exposed to arsenite in the presence of 0.1 microM phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, or 0.2 microM okadaic acid, an inhibitor of phosphoserine/phosphothreonine protein phosphatases, expression of alphaB crystallin was markedly enhanced. The induction of hsp27 and hosp70 expression was also stimulated to a considerable extent in the same cells. The stimulatory effect of PMA was further enhanced in the presence of okadaic acid, but it was strongly inhibited in the presence of 0.5 microM staurosporine, an inhibitor of protein kinase C. PMA and okadaic acid also stimulated the response to heat stress of the expression of alphaB crystallin, but they barely stimulated the response to heat stress of hsp27. The extent of stimulation of the arsenite-induced responses by PMA and okadaic acid was greater when the concentration of arsenite (i.e. the magnitude of the stress) was relatively low (25-50 microM). The arsenite-induced release of arachidonic acid from cells was also stimulated in the presence of PMA and/or akadaic acid, and the stimulatory effects of PMA and okadaic acid on the arsenite-induced accumulation of alphaB crystallin and hsp27 were strongly suppressed by quinacrine, an inhibitor of phospholipase A2. These results suggest that the stimulatory effects of PMA and okadaicacid on the stress responses are cuased, in part, by the increased metabolic activity of the arachidonic acid cascade, as a consequence of the activation of phospholipase A.

Outpatient falls prevention program outcome: an increase, a plateau, and a decrease in incident reports. We implemented an outpatient falls guideline in 2008 in the department of radiology. Here, we describe our multiyear experience. This was a retrospective study conducted between April 2006 and September 2013 to investigate outpatient falls. The span of the study was divided into eight periods. The incident reporting system was searched for the falls and the fall-related variables. A total of 327 falls occurred during 5,080,512 radiology examinations (rate, 0.64/10,000 total examinations). The highest rate was in period 6 (0.83/10,000 examinations). The average for periods 1 and 2 is 0.39/10,000 examinations (37 falls/945,427 examinations), and the average for periods 3-6 is 0.77/10,000 examinations (204 falls/2,656,805 examinations). The average rate for periods 7 and 8 is 0.58/10,000 examinations (86 falls/1,478,280 examinations). There was a statistically significant increase in the total number of falls reported between period 2 and period 3 (p = 0.02). There was a statistically significant decrease in outpatient falls between period 6 and period 7 (p = 0.01). The number of falls among patients 60 years old or older was 177 falls/2,180,093 examinations (rate, 0.81/10,000 examinations), and that among patients younger than 60 years was 150 falls/2,900,419 examinations (rate, 0.52/10,000 examinations), with a statistically significant difference (p = 0.007). Although the rate of falls was higher among female patients, there was no statistically significant difference between the sexes (p = 0.18). The outcome of the outpatient falls guideline was characterized by an increase, a plateau, and a decrease in incident reports. The initial increase may be due to the Hawthorne effect. The plateau may represent the value closest to the true incidence. The decrease may represent the effect of the program.

Wild-type enzyme as a reporter of inhibitor binding by catalytically impaired mutant enzymes. A method for the determination of inhibition constants for catalytically-debilitated mutant enzymes is described. The inhibitor is partitioned between the mutant and wild-type enzymes. Catalytic rates of the wild-type enzyme are used as the signal of inhibitor binding to the mutant enzyme. The method is validated with scytalone dehydratase, the Y50F mutant, and a potent inhibitor. The K(i) value for Y50F determined by this method is 0.49 +/- 0.10 nM. The K(i) value determined using the Y50F catalytic report for inhibitor binding in the absence of wild-type enzyme is 0.20 +/- 0.030 nM. The wild-type enzyme binds the inhibitor ten-fold less tightly, thus indicating that the hydrogen-bonding interaction between the Y50 hydroxyl group and the inhibitor (suggested by X-ray crystallography) is weak. The method is most useful when the catalytic activity of the wild-type enzyme is the most sensitive report of inhibitor binding and the mutant enzyme is greatly crippled in catalytic activity.

Adsorption of phenol, p-chlorophenol and p-nitrophenol onto functional chitosan. Functional chitosan, chemically modified by salicylaldehyde (CS-SA), beta-cyclodextrin (CS-CD), and a cross-linked beta-cyclodextrin polymer (EPI-CD) were prepared as adsorbents to remove phenol, p-nitrophenol and p-chlorophenol from aqueous solution. Langmuir and Freundlich models were applied to describe the adsorption isotherm of phenols, and adsorption parameters were evaluated. Functional chitosan displayed outstanding adsorption ability for phenols. To our surprise, CS-CD exhibited specific adsorption ability for p-chlorophenol. The possible adsorption interaction was discussed. Effects of pH and KCl on the adsorption suggested that the adsorption of phenols was predominated by hydrogen bonding, hydrophobic interaction and pi-pi interaction not electrostatic interaction. Effect of temperature indicated that the low temperature was favorable for the adsorption of phenols. Separation of phenols and adsorbent regeneration were carried out by simple washing with ethanol and filtrating.

Applications of monoclonal antibodies in the diagnosis and treatment of primary brain tumors. The development of monoclonal antibodies has resulted in marked expansion in understanding the central nervous system (CNS). This has been especially true in the study of human neuroectodermal tumors where monoclonal antibodies have been used as physiological probes to define and characterize human neuroectodermal tumor-associated antigens. Utilizing monoclonal antibodies, neuroectodermal tumor-associated antigens have been described in four broad categories; biochemically defined markers, shared nervous system-lymphoid cell markers, shared neuroectodermal-oncofetal markers, and putative restricted tumor markers. Preliminary data have demonstrated the ability to localize animal and human tumors in vitro, ex vivo, and in vivo. Early application of monoclonal antibody technology to neuroimmunology and neuro-oncology has resulted in a new awareness of the complex relationships that exist within the CNS. Their specificity and reproducibility may provide the means to qualitatively and quantitatively define the phenotypic heterogeneity of human neuroectodermal tumors. Potentially, monoclonal antibodies, alone or as carriers of radionuclides, drugs, or toxins, may allow successful diagnosis and treatment of human neuroectodermal tumors.

Workplace bullying among Nurses in South Taiwan. This study was to investigate bullying among hospital nurses and its correlates. Chinese people were unlikely to express their opinions or pursue individual rights. Workplace bullying took place more easily among the educated people within Chinese culture. However, studies related to workplace bullying among hospital nurses in Taiwan were still limited. A cross-sectional design. Two hundred and eighty-five nurses who worked in the regional teaching hospital in south Taiwan were recruited. The significant predictors of workplace bullying were identified by using linear regression analysis. The mean of overall bullying was 1·47, showing that the frequency of the nurses having experienced workplace bullying was between 'never' and 'now and then'. The most frequent bullying item was 'being yelled at or being the target of anger', followed by 'being the objects of untruthful criticism' and 'having views ignored'. Hospital nurses working in the Emergency room would gain 10·888 points more in the overall bullying scale compared with those who worked in operation rooms or haemodialysis rooms. They were more likely to be bullied. Hospital nurses with one year increase in nursing experience were 0·207 points less likely to be bullied. Reducing workplace bullying among hospital nurses was an essential method to provide quality assurance to health care. Nurse managers should build up zero tolerance policy to decrease nurses' exposure to workplace bullying. Training programmes related to bullying prevention are suggested to avoid workplace bullying. The contents of the educational training programmes or workshops should incorporate the characteristics and consequences of the workplace bullying, and the strategies to deal with bullying.

[Selection and properties of totally phage-resistant mutant Pseudomonas putida PpG1]. The efficiency of using bacteria in open systems to degrade different anthropogenic toxic pollutants can depend strongly on the interaction between these bacteria and natural bacteriophages. The possibility of selecting bacterial Pseudomonas putida mutants resistant to all bacteriophages of this species known so far was tested (in our work, these mutants were designated totally phage-resistant mutants). In a model experiment, changes in the composition of a population upon prolonged growth of bacteria in the presence of one of the virulent phages were examined. On the basis of the results obtained, it is postulated that: (1) Mutants differing in resistance to various phages accumulate in a population; relative numbers of different mutants can undergo alterations over the course of time; mutants selected in the presence of a given virulent phage do not often manifest complete resistance to this phage. (2) It is possible to isolate totally phage-resistant mutants of P. putida PpG1. These mutants carry up to three different mutations simultaneously; however, these mutants regain sensitivity to many phages upon pseudoreversion occurrence.

[The use of activated clotting time (ACT) to optimize heparinization during coronary angioplasty. The nursing personnel of the Hemodynamics Laboratory]. Suboptimal anticoagulation during coronary angioplasty is reported to be a major risk factor for occlusive complications. To define an appropriate timing for activated clotting time (ACT) tests in order to optimize anticoagulation with heparin during coronary angioplasty. In 50 consecutive procedures of elective angioplasty ACT was measured at baseline, at 30, 60 and 120 min after heparin 10,000 U iv. In a subgroup of 25 patients (SG1) no additional heparin was given until the ACT test at 60 min. In a second subgroup of 25 patients (SG2) heparin 5,000 U was administered 30-45 min after the initial bolus if the ACT at 30 min was < 300 sec. ACT values were analyzed, and the correlation with the biological variables of patients was tested. In 20 patients out of 50 (40%) ACT values at 30 min were < 275 min. Heparin response was correlated with the body surface area but nor with age, neither with baseline ACT. Values at 60 min showed an adequate anticoagulation in only 6 patients (24%) in SG1 vs 21 (84%) in SG2. There were not complications. ACT testing 30 min after heparin 10,000 U during coronary angioplasty identifies most patients requiring early supplemental heparin. This yields an adequate anticoagulation at 60 min in most patients.

High-resolution melt analysis without DNA extraction affords rapid genotype resolution and species identification. Extracting and sequencing DNA from specimens can impose major time and monetary costs to studies requiring genotyping, or identification to species, of large numbers of individuals. As such, so-called direct PCR methods have been developed enabling significant savings at the DNA extraction step. Similarly, real-time quantitative PCR techniques (qPCR) offer very cost-effective alternatives to sequencing. High-resolution melt analysis (HRM) is a qPCR method that incorporates an intercalating dye into a double-stranded PCR amplicon. The dye fluoresces brightly, but only when it is bound. Thus, after PCR, raising the temperature of the amplicon while measuring the fluorescence of the reaction results in the generation of a sequence-specific melt curve, allowing discrimination of genotypes. Methods combining HRM (or other qPCR methods) and direct PCR have not previously been reported, most likely due to concerns that any tissue in the reaction tube would interfere with detection of the fluorescent signal. Here, we couple direct PCR with HRM and, by way of three examples, demonstrate a very quick and cost-effective method for genotyping large numbers of specimens, using Rotor-Gene HRM instruments (QIAGEN). In contrast to the heated-block design of most qPCR/HRM instruments, the Rotor-Gene's centrifugal rotor and air-based temperature-regulation system facilitate our method by depositing tissues away from the pathway of the machine's fluorescence detection optics.

Multipurpose central venous access in the immunocompromised pediatric patient. During a 21-month period, 50 consecutive pediatric oncology patients undergoing bone marrow transplantation and/or cytoreductive chemotherapy had 61 silastic central venous catheters placed to facilitate their therapy. All catheters were used for medications, routine blood sampling, and transfusions, with 45% also used for hyperalimentation and 57% used for bone marrow transplantation. Catheters were utilized during both inpatient and outpatient therapy periods. Total catheter days numbered 8455, an average of 139 days per catheter. Forty-seven catheters (77%) were removed electively or were in place at time of patient death. Seven were removed for mechanical complications (1/1409 catheter days). Four additional episodes of presumed catheter sepsis were managed with antibiotics and did not require catheter removal (40% of septic episodes). One catheter is still in place after 585 days. Complication rates were not influenced by this multiple use protocol. With standardized catheter care and surveillance, multipurpose, long-term central venous access can be safely utilized in the immunosuppressed pediatric patient.

Stepfather families and the emotional well-being of adolescents. Although approximately one-third of all children born in the United States are expected to spend some time living in a married or cohabiting stepfamily, our understanding of the implications of stepfamilies for the well-being of youth remains incomplete. Using data from the National Longitudinal Study of Adolescent Health, this research investigates adolescent depressive symptomatology and suicide ideation in stepfather families, paying careful attention to variation in pathways of stepfamily formation. I test multiple theoretical explanations for the effects of family structure on adolescent emotional well-being, including perspectives emphasizing economic deprivation, socialization and social control, stress and instability, and community connections. I also explore the possibility that observed associations between family structure and youth well-being might be spuriously produced by the preexisting selective characteristics of stepfamilies. The results of this research point to a complex relationship between stepfamily formation and adolescent emotional well-being, suggesting both positive and negative effects.

[Hardening correction model of energy spectrum for continuous spectrum X-ray ICT]. In the case of a polychromatic source in X-ray ICT, the variation of attenuation coefficient with energy leads to low energy radiation being absorbed preferentially. In other words, the higher the energy, the more lower the attenuation coefficient. With the transmission thickness augmenting, it is easier for X-ray to transmit the matter. The phenomenon is energy spectrum hardening. Thus, hardening correction has to be done. In the present paper, not only energy spectrum hardening is analyzed by experiment and theory and the relation is stated between attenuation coefficient and transmission thickness, but also the new theory method and the precise accurate theory model for hardening correction of energy spectrum are proposed.

Change in atypical maternal behavior predicts change in attachment disorganization from 12 to 24 months in a high-risk sample. This longitudinal study examined links between disorganization and atypical maternal behavior at 12 and 24 months in 71 adolescent mother-child dyads. Organized attachment and maternal not disrupted behavior were more stable than disorganization and disrupted behavior, respectively. At both ages, disorganization and maternal disrupted behavior were significantly correlated. Change in atypical maternal behavior predicted change in disorganization across time. The results provide substantial support for extant theories linking anomalous maternal behavior to the development of disorganized attachment. The Interesting-but-Scary paradigm, introduced in this study, promises to be a useful tool for assessing attachment and maternal behavior in toddlerhood.

[The myocardial contractile function and central hemodynamics of patients with insulin-dependent diabetes mellitus during treatment]. The results of echocardiographic investigation of 48 patients with type I diabetes mellitus (DM) were compared: 48 patients received routine therapy including diabetic management, insulin and vitamin therapy, 32 received this type of therapy plus a complex consisting of inosine, benphothiamine and pyridoxal phosphate. A considerable decrease in myocardial contractility and hemodynamic disorder were revealed against a background of DM decompensation in both groups of patients. Clinical improvement resulting from the use of the above complex showed good correlation with a positive course of echocardiographic values of myocardial contractility and pumping function. Elimination of myocardial insufficiency was accompanied by an increase in the stroke volume, ejection fraction, the rate of circulatory shortening of myocardial fibers, left ventricular mass, and a decrease in end diastolic and systolic volumes. The second type of therapy was well tolerated by the patients and made it possible to considerably lessen myocardial insufficiency and reduce a period of treatment in hospital as compared to routine therapy.

An Appraisal of the Carlisle-Stouffer-Fisher Method for Assessing Study Data Integrity and Fraud. Data fabrication and scientific misconduct have been recently uncovered in the anesthesia literature, partly via the work of John Carlisle. In a recent article in Anaesthesia, Carlisle analyzed 5087 randomized clinical trials from anesthesia and general medicine journals from 2000 to 2015. He concluded that in about 6% of studies, data comparing randomized groups on baseline variables, before the given intervention, were either too similar or dissimilar compared to that expected by usual sampling variability under the null hypothesis. Carlisle used the Stouffer-Fisher method of combining P values in Table 1 (the conventional table reporting baseline patient characteristics) for each study, then calculated trial P values and assessed whether they followed a uniform distribution across studies. Extreme P values targeted studies as likely to contain data fabrication or errors. In this Statistical Grand Rounds article, we explain Carlisle's methods, highlight perceived limitations of the proposed approach, and offer recommendations. Our main findings are (1) independence was assumed between variables in a study, which is often false and would lead to "false positive" findings; (2) an "unusual" result from a trial cannot easily be concluded to represent fraud; (3) utilized cutoff values for determining extreme P values were arbitrary; (4) trials were analyzed as if simple randomization was used, introducing bias; (5) not all P values can be accurately generated from summary statistics in a Table 1, sometimes giving incorrect conclusions; (6) small numbers of P values to assess outlier status within studies is not reliable; (7) utilized method to assess deviations from expected distributions may stack the deck; (8) P values across trials assumed to be independent; (9) P value variability not accounted for; and (10) more detailed methods needed to understand exactly what was done. It is not yet known to what extent these concerns affect the accuracy of Carlisle's results. We recommend that Carlisle's methods be improved before widespread use (applying them to every manuscript submitted for publication). Furthermore, lack of data integrity and fraud should ideally be assessed using multiple simultaneous statistical methods to yield more confident results. More sophisticated methods are needed for nonrandomized trials, randomized trial data reported beyond Table 1, and combating growing fraudster sophistication. We encourage all authors to more carefully scrutinize their own reporting. Finally, we believe that reporting of suspected data fraud and integrity issues should be done more discretely and directly by the involved journal to protect honest authors from the stigma of being associated with potential fraud.

Adequacy of chest compressions performed by medical housestaff. Chest compressions (CCs) are a critical part of cardiopulmonary resuscitation. We studied the presence and duration of adequate CCs performed by medical housestaff, and correlated our findings with gender and body mass index. Fifty-eight first-postgraduate-year medical housestaff performed CCs on a computerized patient simulator equipped with a calibrated CC measurement device. Following initial testing, subjects were trained to perform adequate CCs. Subjects were retested 2 weeks later. Presence and duration of adequate CCs were measured during a 120-second endurance test. Before training, 14/28 (50%) of the male housestaff performed adequate CCs and 0/30 (0%) of the female housestaff performed adequate CCs. After training, 25/28 (89%) of the male housestaff and 16/30 (53%) of the female housestaff performed adequate CCs. Body mass index and height were not related to adequacy of CCs. After training, 7/28 (25%) of the male subjects and 1/30 (3%) of the female subjects were able to maintain adequate CCs for 120 seconds. Training housestaff on a patient simulator is an effective means of improving the adequacy of CCs. Despite training, a significant number of women were unable to perform adequate CCs compared with men; body mass index and height were not determining factors. Very few housestaff were able to sustain 120 seconds of adequate CCs, despite training.

The latissimus dorsi flap. An overview. In the recent past, the latissimus dorsi musculocutaneous flap has added a significant tool to the armamentarium of the reconstructive surgeon. The history of its clinical use is reviewed with emphasis on embryological, anatomical and hemodynamic aspects.

Co-immobilization and interaction of heparin and plasmin on collageno-elastic tubes. Heparin and plasmin were co-immobilized on collageno-elastic tubes (CETs) in order to develop a thromboresistant and fibrinolytic vascular prosthesis. The mutual interaction between heparin and plasmin both in the soluble and in the immobilized state was studied. The immobilization condition rendering maximum co-immobilized heparin and plasmin activity was identified to require heparin immobilization followed by plasmin immobilization. Soluble heparin exerts a positive synergistic effect on soluble plasmin. Immobilized heparin enhances plasmin loading on the CET as compared to the heparin-free graft. Heparin, in both the soluble or immobilized state, significantly decreases the Michaelis-Menten (M-M) parameter Km for immobilized plasmin over heparin-free immobilized plasmin. Furthermore, the M-M parameter Vmax for the immobilized plasmin in the presence of heparin decreases over heparin-free immobilized plasmin. These results suggest a decrease in the kinetic constant k3 for heparin-modified immobilized plasmin over the heparin-free form. Co-immobilized heparin-plasmin collagenous grafts represent a unique advance in the development of fibrinolytically active prostheses.

Factors Associated With Stability of Health Nursing Services for Children With Medical Complexity. The objectives of our study are to: (1) identify the factors associated with lack of stable home healthcare nursing services for children with medical complexity, and (2) describe the implications of unstable home healthcare nursing for children, caregivers, nurses, and home healthcare agencies. We collected qualitative data in 20 semistructured in-depth interviews (15 English, 5 Spanish) with 26 primary caregivers of children with medical complexity, and 4 focus groups of 18 home healthcare nurses inquiring about their experiences about home healthcare nursing services for children with medical complexity. During an iterative analysis process, we identified recurrent themes related to stability of home healthcare nursing. Lack of stability in home healthcare nursing was common. These include: (1) not finding nurses to cover shifts, (2) nurse turnover, (3) nurses calling out frequently, and (4) nurses being fired by caregivers. Reasons for lack of stability of home healthcare nursing services were multifactorial and included: nurse-level, child-level, caregiver-level, residence-level, agency-level, and system-level factors. Lack of stable home healthcare nursing affected the well-being of children with medical complexity, and contributed to substantial caregiver burden. There were negative implications of unstable home healthcare services for nurses and home healthcare agencies as well. Lack of stable home healthcare nursing services is a major problem in the home care of children with medical complexity. Although some of the factors for unstable home healthcare nursing services are not modifiable, there are others that are potentially modifiable. Ensuring stable home healthcare nursing services will likely improve care of children and reduce caregiver burden.

Increased protein carbonyl groups in the serum of patients affected by thalassemia major. High oxidative stress status is known to be one of the most important factors determining cell injury in thalassemic patients and causing other serious medical complications, including a continuous proinflammatory status. The quantification of protein carbonyl groups in peripheral blood is widely used to measure the extent of oxidative modification. Thus, we measured serum concentrations of protein carbonyl groups in 30 patients affected by thalassemia major and in 15 healthy subjects. Strongly higher levels of protein carbonyl groups were measured in the blood from thalassemic patients than in that from healthy controls. Our findings evidence that thalassemic patients suffer from protein oxidative stress; the possibility of a role for carbonyl stress in the progression and severity of the disease needs further investigation.

The survival of cytochalasin-induced multinucleation following irradiation of Chinese hamster ovary cells. Chinese hamster ovary cells were cultured for up to 280 hr in medium containing 1.75 mcg/ml cytochalasin B. The distribution of the number of nuclei per cell in unirradiated cultures on the 6th day was unimodal with some cells containing 27 or more nuclei. The DNA content distribution was in contrast polymodal with the means of the two terminal major peaks occurring at approximately 40 and 80 units of DNA content (antimodes at 29 and 58 units), where 1 unit is the content of untreated G1 cells. Irradiation (gamma, 137-Cs) at doses up to 10 Gy caused an exponential reduction in the proportion of plated cells able to reach high nucleus- or DNA-contents. The reduction due to 5 Gy was stable at least up to 280 hr in culture. The accumulation of total DNA in the culture was well-fitted by a Gompertz function, with little further increase after 230 hr when the average DNA content per cell reached about 90 units.

Controlled delivery of carvedilol nanosuspension from osmotic pump capsule: in vitro and in vivo evaluation. This study intended to develop a novel controlled delivery osmotic pump capsule of carvedilol nanosuspension. The capsule is assembled using a semi-permeable capsule shell with contents including nanosuspension drying powder, mannitol and Plasdone S-630. The physical characteristics of semi-permeable capsule walls were compared among different coating solutions under different temperature. The composition of the coating solution and drying temperature appeared to be important for the formation of the shells. Carvedilol nanosuspension was prepared by precipitation-ultrasonication technique and was further lyophilized. Response surface methodology was used to investigate the influence of factors on the responses. The optimized formulation displayed complete drug delivery and zero-order release rate. The TEM and particle size analysis indicated that the morphology of the resultant nanoparticle in the capsule was spherical shaped with a mean size of 252±19 nm. The in vivo test in beagle dogs demonstrated that the relative bioavailability of the novel system was 203.5% in comparison to that of the marketed preparation. The capsule successfully controlled the release of carvedilol and the fluctuation of plasma concentration was minimized. The system is a promising strategy to improve the oral bioavailability for poorly soluble drugs and preparing it into elementary osmotic pump conveniently.

Non-invasive assessment of coronary flow and coronary flow reserve by transthoracic Doppler echocardiography: a magic tool for the real world. Transthoracic Doppler echocardiography, introduced in the echo-lab in recent last years, to measure coronary flow and coronary flow reserve, is a very attractive tool, totally non-invasive, and easily available at bedside. This review summarizes the actual possibilities of this tool, its multiple potential clinical applications and diagnostic insights, and its arising prognosis value, in coronary artery disease as in various settings affecting the coronary microcirculation.

The role of modularity in primary total hip arthroplasty. A combined series of 795 primary SROM (DePuy, Warsaw, Ind) stems have been reviewed. The mean follow-up is 11 years; 2 (0.25%) were revised for aseptic stem loosening. Two (0.25%) cases of osteolysis distal to the sleeve occurred, 1 of which was revised. The low incidence of distal osteolysis and aseptic loosening justifies the continued use of this stem in primary total hip arthroplasties.

Transcriptional control of the human biliary glycoprotein gene, a CEA gene family member down-regulated in colorectal carcinomas. Biliary glycoprotein (BGP) isoantigens are derived by alternative splicing from a single gene and are the human homologs of rat C-CAM and the mouse Bgp species. These glycoproteins represent a family of cell-adhesion molecules. The mouse Bgp isoforms also act as receptors for the hepatitis viral capsid-protein. BGP is a member of the carcinoembryonic antigen (CEA) gene family, which belongs to the immunoglobulin supergene family, yet it displays restricted expression patterns and unique functions. Since the loss or reduced expression of BGP is associated with human colorectal carcinomas, the elements in its upstream regulatory region were analyzed. A cluster of transcriptional initiation sites and the minimal promoter, located within 150 bp upstream of the major transcriptional start site, were active in human colon carcinoma and hepatoma cells. Unlike the CEA gene, BGP gene transcription was not modulated by a silencer region; repetitive elements in the BGP upstream region were not involved in activation or repression. Footprinting experiments identified two cis-acting elements and mobility-shift assays demonstrated that these elements bound several transcription factors, among them, USF, HNF-4 and an AP-2-like factor. In cotransfection experiments, both the USF and HNF-4 transcription factors transactivate the BGP gene promoter and compete for the same regulatory element. The Sp1 transcription factor, shown to be involved in CEA gene transcriptional regulation, does not bind to the BGP gene promoter. We, therefore, propose that the relative distributions and interactions of these transcription factors mediate distinct transcriptional regulation of the BGP gene in colon and liver; this regulation could be distorted during the oncogenic process.

Light sheet microscopy and SrAl2 O4 nanoparticles codoped with Eu2+ /Dy3+ ions for cancer cell tagging. Light sheet optical microscopy on strontium aluminate nanoparticles (SrAl2 O4 NPs)1 codoped with Eu2+ and Dy3+ was used for cancer cell tagging and tracking. The nanoparticles were synthesized by urea-assisted combustion with optimized percentage values of the 2 codoping rare-earth ions for cell viability and for lower cytotoxic effects. The optical properties of these materials showed an excitation wide range of wavelengths (λexc = 254-460 nm), a broad emission band (λem = 475-575 nm) with the maximum centered wavelength at 525 nm and a half lifetime within the seconds regime. The feasibility to measure the nanoparticle luminescence under the selective plane illumination configuration was studied by immersing the nanoparticles in 1% Agarose. The potential applicability of the synthesized nanophosphors for cancer cell tagging was demonstrated by using in vitro experiments with human breast adenocarcinoma MCF-7 cells. A single MCF-7 cell observed by the use of light sheet microscopy with UV excitation. The cell has been bio-labeled with FA-SrAl2 04 : Eu2+ , Dy3+ NPs and 4',6-diamidino-2-phenylindole, dihydrochloride for nucleus identification.

The 6-PACK programme to decrease falls and fall-related injuries in acute hospitals: protocol for an economic evaluation alongside a cluster randomised controlled trial. Falls are a common hospital occurrence complicating the care of patients. From an economic perspective, the impact of in-hospital falls and related injuries is substantial. However, few studies have examined the economic implications of falls prevention interventions in an acute care setting. The 6-PACK programme is a targeted nurse delivered falls prevention programme designed specifically for acute hospital wards. It includes a risk assessment tool and six simple strategies that nurses apply to patients classified as high-risk by the tool. To examine the incremental cost-effectiveness of the 6-PACK programme for the prevention of falls and fall-related injuries, compared with usual care practice, from an acute hospital perspective. The 6-PACK project is a multicentre cluster randomised controlled trial (RCT) that includes 24 acute medical and surgical wards from six hospitals in Australia to investigate the efficacy of the 6-PACK programme. This economic evaluation will be conducted alongside the 6-PACK cluster RCT. Outcome and hospitalisation cost data will be prospectively collected on approximately 16,000 patients admitted to the participating wards during the 12-month trial period. The results of the economic evaluation will be expressed as 'cost or saving per fall prevented' and 'cost or saving per fall-related injury prevented' calculated from differences in mean costs and effects in the intervention and control groups, to generate an incremental cost-effectiveness ratio (ICER). This economic evaluation will provide an opportunity to explore the cost-effectiveness of a targeted nurse delivered falls prevention programme for reducing in-hospital falls and fall-related injuries. This protocol provides a detailed statement of a planned economic evaluation conducted alongside a cluster RCT to investigate the efficacy of the 6-PACK programme to prevent falls and fall-related injuries. The protocol for the cluster RCT is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12611000332921).

Cell culture contamination. Microbial contamination is a major issue in cell culture, but there are a range of procedures which can be adopted to prevent or eliminate contamination. Contamination may arise from the operator and the laboratory environment, from other cells used in the laboratory, and from reagents. Some infections may present a risk to laboratory workers: containment and aseptic technique are the key defence against such risks. Remedial management of suspected infection may simply mean discarding a single potentially infected culture. However, if a more widespread problem is identified, then all contaminated cultures and associated unused media that have been opened during this period should be discarded, equipment should be inspected and cleaned, cell culture operations reviewed, and isolation from other laboratories instituted until the problem is solved. Attention to training of staff, laboratory layout, appropriate use of quarantine for new cultures or cell lines, cleaning and maintenance, and quality control are important factors in preventing contamination in cell culture laboratories.

Lactose, oligosaccharide and monosaccharide content of milk from mothers delivering preterm newborns over the first month of lactation. Monosaccharide, lactose and oligosaccharide content of milk from mothers delivering prematurely (PT milk) was studied to evaluate whether changes occur during lactation, as observed in milk from mothers delivering at term (T milk). To study a homogeneous population, women having the most common phenotype (secretory both Lewis and A, B, or H phenotype) were selected. Milk samples from 26 mothers who delivered between the 27th and 35th week of gestation were collected at the 4th, 10th, and 30th post-partum days. Monosaccharides, lactose and oligosaccharides were measured by high-pressure liquid chromatography. Lactose concentration increased significantly (p < 0.05) from 52.81 +/- 8.2 g/L on day 4 to 69.24 +/- 9.36 g/L on day 30. During the same period of time oligosaccharide content decreased significantly (p < 0.05) from 25.61 +/- 5.19 g/L to 15.83 +/- 6.05 g/L. Monosaccharides did not show statistically significant variations. Our results indicate that PT milk contains in addition to lactose, a substantial amount of oligosaccharides and a lower percentage of monosaccharides. Compared to T milk, in the colostral phase PT milk presents significantly lower lactose concentration (p < 0.0001); on the contrary its oligosaccharide content is significantly higher (p < 0.0001). The physiological role of human milk carbohydrates in view of the peculiar needs of the preterm newborn is also discussed.

Tetraquark mesons in large-N quantum chromodynamics. It is argued that exotic mesons consisting of two quarks and two antiquarks are not ruled out in quantum chromodynamics with a large number N of colors, as generally thought. Tetraquarks of one class are typically long-lived, with decay rates proportional to 1/N.

Measurements of 129I in human and bovine thyroids in Europe--transfer of 129I into the food chain. Bovine thyroid glands from different countries in Europe and human thyroid glands from Lower Saxony (Federal Republic of Germany) show isotopic 129I/127I ratios of 2.1 X 10(-9) to 8.2 X 10(-8) for cattle and 2.1 X 10(-9) to 8 X 10(-8) in humans. These values give information about the concentration of fallout 129I in Europe since most of these glands were collected in areas without nuclear facilities. Some of the human thyroids were collected after the Chernobyl accident between May 1986 and February 1988. Results obtained from human thyroids taken in some locations of Lower Saxony show no significant increase of the 129I during this time. Higher concentrations of 129I were only found in cattle grazing in the vicinity of a reprocessing plant in Mol, Belgium. Samples of soil, vegetation, milk, and water from this area contained higher than normal concentrations of 129I. The long-term transfer of radioiodine from the soil to the plant and the translocation within the soil were studied using a soil monolith with a 129I-contaminated surface. During the 4 y of the experiment, the transfer factor plant/soil decreased from 0.3 to 2.2 X 10(-3). Soil samples taken in 5-cm steps to a depth of 30 cm then at 40 and 50 cm depths showed that the transport of radioiodine to lower layers proceeds very slowly. The top 5-cm layer contained about 80% of the total radioactivity 52 mo after contamination. In an in-vivo study with a dairy cow, the transfer of radioiodine from feed to milk to cow meat and to pig thyroid gland was followed for 53 d using 129I-labeled pasture grass contaminated via roots. A part of the milk obtained from the cow was fed to a pig as a substitute for humans. The mean value of the transfer factor milk/feed was 2.4 X 10(-3) d kg-1. The values of the transfer factor cow meat/feed obtained for different muscle cuts and organs (excluding thyroid) ranged between 3.0 X 10(-4) (kidney) and 5.4 X 10(-2) d kg-1 f.w. The transfer factors pig thyroid/milk (as pig feed) and pig thyroid/cow feed exhibited values of 1.2 and 8.7 X 10(-3) d kg-1 f.w., respectively.

Increasing PAs' awareness and understanding of self-help groups. An educational model. A model for inclusion of information about self-help groups into a PA training program is provided based on the results of a study of 26 PA students enrolled in a patient-counseling class. Interactions with self-help groups yield more positive beliefs and greater intentions to collaborate with self-help groups than training programs that do not address self-help groups. The experiential component is also useful for increasing understanding of appropriate roles for professionals interacting with self-help groups.

The role of p53 in the cellular toxicity by active trans-platinum complexes containing isopropylamine and hydroxymethylpyridine. Despite some initial research that reported a lack of activity of trans geometry, complexes with general formula trans-[PtCl2(L)(L')] exhibit an important cytotoxic activity in cisplatin-sensitive and resistant cell lines. Based on the proposed mechanism of action for the trans-platinum compounds, they might form DNA adducts initiating a DNA-damage response and ultimately ending in the activation of the p53 protein. In the present work, we have studied the biochemical properties of the trans-[PtCl2(isopropylamine)(L)] complexes (where L is 3- or 4-(hydroxymethyl)-pyridine) against several cell lines and the relationship between cytotoxicity and the protein p53. Both complexes showed different antitumoral properties depending on the presence or absence of protein p53 in isogenic colon carcinoma HCT116 cell lines. Cell cycle studies with the complexes in these cell lines were performed to investigate their antitumoral activity. Apoptosis was observed to be launched from G1 or G2/M accumulations. Confocal microscopy showed the different behaviour of isogenic tumoral cell lines treated with the trans-platinum complexes. Our data suggest that small differences in the carrier ligands could play an important role in the overall biological effects. The body of the research regarding structure-activity relationships such as the different position of groups in the carrier ligands will provide new rational basis for the design of new platinum antitumor drugs.

Dosimetry of small fields for Therac 20 electron beams. The Therac 20 medical linear accelerator produces electron beams of 6, 9, 13, 17, and 20 MeV. We measured depth dose, isodose curves, and output factors for small electron fields using an ionization chamber, film, and thermoluminescent dosimeters. Tables and graphs were generated from these measurements for accurate treatment planning of various blocked and open fields.

Determination of trace elements (Cu, Zn, Mn, Pb) and magnesium by atomical absorption in patients receiving total parenteral nutrition. We measured the serum levels of four trace elements (Cu, Zn, Mn, Pb) and Mg in surgical patients receiving total parenteral nutrition (TPN). The clinical implications and the results are discussed. Two groups of patients were studied: the first group (n = 40) was our study group and the second (n = 40) was the control group. Four measurements of each trace element (TE) in blood serum were carried out: one before initiating TPN, one 24 h after, one 3 d later, and the last one immediately after discontinuing TPN. Each measurement was repeated twice. The Perkin-Elmer atomic absorption spectrophotometer (model 2380) with furnace graphite HGA-300 was used to measure the TE levels and an acetylene flame was used to measure the Mg levels. Levels of all the TEs, except Pb, were lower before the administration of TPN compared with the control group (P < 0.05). The levels of TEs during and immediately after TPN were generally lower in comparison with the initial measurement before the administration of TPN. The results of this study suggest that it may be necessary to 1) add Cu, Zn, Mn, and Mg to the parenteral nutritional solution and 2) follow the fluctuations in serum levels during the administration of TPN.

Early diagnosis of invasive candidiasis with mannan antigenemia and antimannan antibodies. Late treatment of invasive candidiasis (IC) results in severe complications and high mortality. New tools are needed for early diagnosis. We conducted a retrospective study to assess the diagnostic utility of mannan antigenemia (Mn) and antimannan antibodies (anti-Mn) in neutropenic cancer patients at high risk for candidiasis. Twenty-eight patients with IC (based on European Organization for Research and Treatment of Cancer and Mycoses Study Group definitions) and 25 controls were studied. Mn and anti-Mn were positive (> or = 0.25 ng/mL and > or = 5 AU/mL, respectively) in 25/28 (89%) patients with candidiasis and in 4/25 (16%) controls: sensitivity, 89%; specificity, 84%; positive predictive value, 86%; negative predictive value, 88%. In patients with hepatosplenic lesions, assessing Mn/anti-Mn shortened the median time of diagnosis of candidiasis when compared with imaging (9 versus 25 days after fever onset as first sign of infection; P < 0.001). Candidiasis was diagnosed before neutrophil recovery in 78% and 11% of cases with Mn/anti-Mn and radiology, respectively (P < 0.001). Mn and anti-Mn may be useful for early noninvasive diagnosis of IC.

Outcome of emergency percutaneous coronary intervention for acute ST-elevation myocardial infarction complicated by cardiac arrest. The poor prognosis of primary percutaneous coronary intervention (PCI) in patients resuscitated from cardiac arrest complicating acute ST-segment elevation myocardial infarction (STEMI) may at least partly be explained by the common presence of cardiogenic shock. This study examined the impact of emergency primary PCI on outcome in patients with STEMI not complicated by cardiogenic shock who were resuscitated from cardiac arrest. The study group included 948 consecutive patients without cardiogenic shock who underwent emergency primary PCI from 2001 to 2006 for STEMI. Twenty-one of them were resuscitated from cardiac arrest before the intervention. Data on background, clinical characteristics, and outcome were prospectively collected. There were no differences between the resuscitated and nonresuscitated patients in age, sex, infarct location, or left ventricular function. The total one-month mortality rate was higher in the resuscitated patients (14.3 vs. 3.4%, P=0.033), but noncardiac mortality accounted for the entire difference (14.3 vs. 1.2%, P=0.001), whereas cardiac mortality was similarly low in the two groups (0 vs. 2.0%, P=NS). Predictors of poor outcome in the resuscitated patients were older age (r=0.47, P=0.032), unwitnessed sudden death (r=0.44, P=0.04), longer interval between onset of cardiac arrest and arrival of a mobile unit (r=0.67, P=0.001) or to spontaneous circulation (r=0.65, P=0.001), low glomerular filtration rate (r=-0.50, P=0.02), and the initial thrombolysis in myocardial infarction grade of flow (r=-0.51, P=0.017). Emergency PCI for STEMI not associated with cardiogenic shock exerts a similar effect on cardiac mortality in patients who were resuscitated from cardiac arrest and in those without this complication. The higher all-cause mortality rate among resuscitated patients is explained by noncardiac complications.

Impact of heterogeneous perisomatic IPSC populations on pyramidal cell firing rates. Previous computational modeling studies suggested a set of rules underlying the modulation of principal cell firing rates by heterogeneity in the synaptic parameters (peak amplitude and decay kinetics) of populations of GABAergic inputs. Here we performed dynamic clamp experiments in CA1 hippocampal pyramidal cells to test these ideas in biological neurons. In agreement with the simulation studies, the effects of increasing the event-to-event variance in a population of perisomatically injected inhibitory postsynaptic current (IPSC) peak conductances caused either an increase, decrease, or no change in the firing rates of CA1 pyramidal cells depending on the mean around which the scatter was introduced, the degree of the scatter, the depolarization that the pyramidal cell received, and the IPSC reversal potential. In contrast to CA1 pyramidal cells, both model and biological CA3 pyramidal cells responded with bursts of action potentials to sudden, step-wise alterations in input heterogeneity. In addition, injections of 40-Hz IPSC conductances together with -modulated depolarizing current inputs to CA1 pyramidal cells demonstrated that the principles underlying the modulation of pyramidal cell excitability by heterogeneous IPSC populations also apply during membrane potential oscillations. Taken together, these experimental results and the computational modeling data show the existence of simple rules governing the interactions of heterogeneous interneuronal inputs and principal cells.

Upper Extremity Immobilization and Driving: Limitations and Liability. Orthopaedic injuries of the upper extremity remain common, often requiring prolonged immobilization after surgical or nonsurgical management. Upper extremity immobilization often has a profound effect on a patient's daily life, including one's ability to safely operate a motor vehicle. Current literature on the safety of driving while immobilized is varied, although above-elbow immobilization of the upper extremity is generally thought to present a particular hazard to safe driving. Unfortunately, as common as this situation is, currently little to no guidance exists for patients, physicians, or lawmakers with regard to deciding whether a patient is safe to return to driving with upper extremity immobilization. Similar discord exists with the issue of patient and physician liability in such cases. In this review, we seek to present both historical precedent and a contemporary update of this complex, though a frequently encountered situation.

Anxiety sensitivity as a specific and unique marker of anxious symptoms in youth psychiatric inpatients. We addressed several questions regarding the relation of anxiety sensitivity to anxious symptoms among 47 youth psychiatric inpatients (18 boys, 29 girls), ages 9-17 (M = 14.23, SD = 1.89). Participants completed measures of anxiety sensitivity, anxious and depressive symptoms, trait anxiety, and positive and negative affect; chart diagnoses were available. Consistent with hypotheses, we found that (a) anxiety sensitivity was associated with anxious symptoms, even controlling for trait anxiety and depressive symptoms; and (b) anxiety sensitivity displayed symptom specificity to anxious versus depressive symptoms (i.e., was associated with anxiety controlling for depression but not with depression controlling for anxiety). Furthermore, regarding factors of anxiety sensitivity, we obtained mixed support for our prediction that phrenophobia would be associated with both depression and anxiety, whereas fear of physical arousal would be associated with anxiety but not depression. Implications for the construct validity of anxiety sensitivity were discussed.

[Problem-based learning (POL) in environmental medicine]. "Environmental medicine" is a new sub-discipline in the spectrum of medical specialization in Germany. The Berlin Academy of Occupational Medicine and Health Protection, now a branch of the Berlin Chamber of Physicians, developed a 200-lesson curriculum for physicians who want to specialize in this field. Coincidentally during the initial courses, the attendants were already highly qualified ("Facharzt"-level) and experts in various occupational fields, and hence the composition of the classes was highly heterogeneous on the levels of practical experience as well as theoretical knowledge. The Academy therefore decided to change the teaching method to Problem-Oriented Learning (POL). This required training tutors for small learning groups, supervision for these tutors and supplying adequate teaching materials and a stimulating environment for the student. The "Arbeitsgruppe Reformstudiengang Medizin" (Medicine Curriculum Reform Project) at the Berlin Humboldt University as well as the Dutch Rijksuniversiteit Limburg in Maastricht helped in the process of conceptualization. Participants worked in groups of up to 8 persons under non-directive tutors. A new "case" was presented every day, and the students developed individual learning goals according to the Seven Steps-method, which were then researched individually and with the help of outside experts. The findings were reported back and discussed in the group. Initially there was irritation, but after two or three days participants got used to not being lectured. Instead of being passive recipients of expert knowledge they felt that the POL method of learning enhanced their competence to act independently.

Changes in working time arrangements over time as a consequence of work-family conflict. Existing longitudinal studies on the relationship between working time arrangements (WTA) and work-family conflict have mainly focused on the normal causal relationship, that is, the impact of WTA on work-family conflict over time. So far, however, the reversed relationship, that is, the effect of work-family conflict on adjustments in WTA over time, has hardly been studied. Because work-family conflict is highly prevalent in the working population, further insight in this reverse relationship is invaluable to gain insight into secondary selection processes. The aim of this study is to investigate whether work-family conflict is prospectively related to adjustments in work schedules, working hours, and overtime work, and to explore sex differences and different time lags in this relation. Data of the prospective Maastricht Cohort Study were used. To study the effect of work-family conflict on a change from shift- to day work over 32 months of follow-up, male three-shift (n = 727), five-shift (n = 932), and irregular-shift (n = 451) workers were selected. To study effects of work-family conflict on reduction of working hours over 12 and 24 months of follow-up, respectively, only day workers (males and females) were selected, capturing 5809 full-time workers (> or =36 h/wk) and 1387 part-time workers (<36 h/wk) at baseline. To examine effects of work-family conflict on refraining from overtime work over 12 months of follow-up, only day workers reporting frequent overtime work at baseline were selected (3145 full-time and 492 part-time workers). Cox regression analyses were performed with adjustments for age, educational level, and presence of a long-term illness. Work-family conflict was associated with a significantly increased risk of changing from shift- to day work over 32 months of follow-up in three-shift workers (relative risk [RR] = 1.77, 95% confidence interval [CI] 1.19-2.63) but not in five-shift workers (RR = 1.32, 95% CI 0.78-2.24) and irregular-shift workers (RR = 0.81, 95% CI 0.50-1.31). Within day workers, work-family conflict among full-time workers was associated with a significantly increased risk of reducing working hours during 1 yr of follow-up in women (RR = 2.80, 95% CI 1.42-5.54) but not men (RR = 1.34, 95% CI 0.81-2.22). In part-time workers, work-family conflict was associated with a significantly increased risk of reducing working hours during 1 yr of follow-up both in women (RR = 1.99, 95% CI 1.04-3.82) and men (RR = 4.03, 95% CI 1.28-12.68). Whereas the effects of work-family conflict on a reduction of working hours somewhat decreased among female full-time workers after 2 yr of follow-up (RR = 2.13, 95% CI 1.24-3.66), among male full-time workers the effects increased and reached statistical significance (RR = 1.53, 95% CI 1.05-2.21). Work-family conflict was not significantly associated with refraining from overtime work over 1 yr of follow-up. This study shows that work-family conflict has important consequences in terms of adjustments in work schedules and working hours over time, with considerable sex differences. The study thereby clearly illustrates secondary selection processes both in shift- and day workers, with significant implications for labor force participation, emphasizing the need for prevention of work-family conflict.

Appropriate chicken sample size for identifying the composition of broiler intestinal microbiota affected by dietary antibiotics, using the polymerase chain reaction-denaturing gradient gel electrophoresis technique. The bacterial microbiota in the broiler gastrointestinal tract are crucial for chicken health and growth. Their composition can vary among individual birds. To evaluate the composition of chicken microbiota in response to environmental disruption accurately, 4 different pools made up of 2, 5, 10, and 15 individuals were used to determine how many individuals in each pool were required to assess the degree of variation when using the PCR-denaturing gradient gel electrophoresis (DGGE) profiling technique. The correlation coefficients among 3 replicates within each pool group indicated that the optimal sample size for comparing PCR-DGGE bacterial profiles and downstream applications (such as identifying treatment effects) was 5 birds per pool for cecal microbiota. Subsequently, digesta from 5 birds was pooled to investigate the effects on the microbiota composition of the 2 most commonly used dietary antibiotics (virginiamycin and bacitracin methylene disalicylate) at 2 different doses by using PCR-DGGE, DNA sequencing, and quantitative PCR techniques. Thirteen DGGE DNA bands were identified, representing bacterial groups that had been affected by the antibiotics. Nine of them were validated. The effect of dietary antibiotics on the microbiota composition appeared to be dose and age dependent. These findings provide a working model for elucidating the mechanisms of antibiotic effects on the chicken intestinal microbiota and for developing alternatives to dietary antibiotics.

The gloves should have been off before recording a procedure. I was surprised to see a photograph (analysis April 4) showing a nurse with gloved hands using a ballpoint pen.

Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems. One of the milestones in tissue engineering has been the development of 3D scaffolds that guide cells to form functional tissue. Recently, mouldless manufacturing techniques, known as solid free-form fabrication (SFF), or rapid prototyping, have been successfully used to fabricate complex scaffolds. Similarly, to achieve simultaneous addition of cells during the scaffold fabrication, novel robotic assembly and automated 3D cell encapsulation techniques are being developed. As a result of these technologies, tissue-engineered constructs can be prepared that contain a controlled spatial distribution of cells and growth factors, as well as engineered gradients of scaffold materials with a predicted microstructure. Here, we review the application, advancement and future directions of SFF techniques in the design and creation of scaffolds for use in clinically driven tissue engineering.

Pupillary responses and blink reflex in myotonic dystrophy. We have studied pupillary responses to parasympathetic and sympathomimetic agents, pupillary cycle time and the electrophysiology of the blink reflex in 18 patients with myotonic dystrophy. The response of the iris to dilute pilocarpine and phenylephrine did not indicate pharmacologic supersensitivity. Pupillary cycle time was prolonged in nine of the 18 patients. Ipsilateral R1 blink reflex latencies were normal in all cases, and bilateral R2 were normal in 16 of the 18 patients. These results do not support either autonomic or brainstem dysfunction in the majority of patients with myotonic dystrophy. In 50% of the patients the results are compatible with smooth muscle involvement of the iris.

In vivo dual intra- and extracellular recordings suggest bidirectional coupling between CA1 pyramidal neurons. Spikelets, small spikelike membrane potential deflections, are prominent in the activity of hippocampal pyramidal neurons in vivo. The origin of spikelets is still a source of much controversy. Somatically recorded spikelets have been postulated to originate from dendritic spikes, ectopic spikes, or spikes in an electrically coupled neuron. To differentiate between the different proposed mechanisms we used a dual recording approach in which we simultaneously recorded the intracellular activity of one CA1 pyramidal neuron and the extracellular activity in its vicinity, thus monitoring extracellularly the activity of both the intracellularly recorded cell as well as other units in its surroundings. Spikelets were observed in a quarter of our recordings (n = 36). In eight of these nine recordings a second extracellular unit fired in correlation with spikelet occurrences. This observation is consistent with the idea that the spikelets reflect action potentials of electrically coupled nearby neurons. The extracellular spikes of these secondary units preceded the onset of spikelets. While the intracellular spikelet amplitude was voltage dependent, the simultaneously recorded extracellular unit remained unchanged. Spikelets often triggered action potentials in neurons, resulting in a characteristic 1- to 2-ms delay between spikelet onset and firing. Here we show that this relationship is bidirectional, with spikes being triggered by and also triggering spikelets. Secondary units, coupled to pyramidal neurons, showed discharge patterns similar to the recorded pyramidal neuron. These findings suggest that spikelets reflect spikes in an electrically coupled neighboring neuron, most likely of pyramidal cell type. Such coupling might contribute to the synchronization of pyramidal neurons with millisecond precision.

RNAi-mediated knockdown of target genes: a promising strategy for pancreatic cancer research. Pancreatic cancer is one of the most aggressive malignancies with a very poor prognosis, partially due to its very low accessibility to resection and resistance to chemoradiotherapy. As such, it is reasonable to find more effective, specific therapies and the related therapeutic targets. The identification of certain genes contributing to the tumorigenesis and poor prognosis provides the specific targets for efficient silencing by RNA interference (RNAi). As a powerful tool to suppress gene expression in mammalian cells, RNAi can be directed against pancreatic cancer through various pathways, including the inhibition of overexpressed oncogenes, suppression of tumor growth, metastasis and enhancement of apoptosis. In combination with chemoradiotherapy agents, RNAi can also attenuate the chemoradiation resistance of pancreatic cancer. In addition, RNAi has been used to define the 'loss of function' of endogenous genes in pancreatic cancer. This review provides a brief introduction to recent developments of RNAi applications in pancreatic cancer studies and suggestions for further exploration. It substantially demonstrates that RNAi holds a promising therapeutic potential as a future treatment for pancreatic cancer.

Left ventricular remodeling and function in adult aortic stenosis. The aim of this study was to analyze the left ventricular (LV) geometric changes occurring in chronic pressure overload due to valvular aortic stenosis (AS). Fifty-six adult patients (30 women, 26 men, mean age seventy-two +/- nine years, range forty-five to eighty-five years) with isolated AS (mean valve area by Doppler = 0.6 +/- 0.2 cm2) underwent a complete Doppler echocardiographic examination. According to the value of relative wall thickness (RWT = 2 x posterior wall thickness/LV end-diastolic diameter) and LV mass index (LVMI) in normal subjects (RWT < or = 0.44, LVMI < or = 125 gr/m2) AS patients were subdivided into four groups: Normal: no patients; Concentric Remodeling RWT > 0.44, LVMI < or = 125 gr/m2): 4 patients (7%); Concentric Hypertrophy (RWT > 0.44, LVMI > 125 gr/m2): 39 patients (70%); and Eccentric Hypertrophy (RWT < or = 0.44, LVMI > 125 gr/m2): 13 patients [23%]. Eccentric hypertrophy patients had, as compared with those with concentric hypertrophy, a larger left ventricle (61 +/- 6.5 mm vs 47.6 +/- 6 mm, P < or = 0.001), a smaller mean wall thickness (11.3 +/- 1.2 vs 14.7 +/- 1.7 mm, P < 0.001) and reduced LV fractional shortening (FS% = 22.9 +/- 11 vs 42.6 +/- 8.7%, P < 0.001). Furthermore, most patients (11/13) of the former group had heart failure due to LV systolic dysfunction, while only 16 of 39 patients of the latter group had heart failure and all but 2 had normal LV systolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Self-assembled monolayer based impedimetric platform for food borne mycotoxin detection. A self-assembled monolayer (SAM) of 11-amino-1-undecanethiol (AUT) has been fabricated onto a gold (Au) substrate to co-immobilize anti-ochratoxin-A antibodies (AO-IgGs) and bovine serum albumin (BSA) to detect food borne mycotoxin [i.e., ochratoxin-A (OTA)]. AUT/Au electrode, AO-IgGs/AUT/Au immunoelectrode and BSA/IgGs/AUT/Au immunoelectrode have been characterized using scanning electron microscopy (SEM) and electrochemical studies such as cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Electrochemical studies reveal that the AUT-SAM with NH2 groups provide favorable conditions to immobilize AO-IgGs with better orientation, resulting in enhanced electron transport to obtain improved sensing characteristics. The EIS response studies of the BSA/AO-IgGs/AUT/Au immunoelectrode obtained as a function of OTA concentration reveal that the value of the charge transfer resistance (RCT) increases with increased OTA concentration. The BSA/AO-IgGs/AUT/Au immunoelectrode exhibits linearity over 0.5-6.0 ng/dl, detection limit of 0.08 ng/dl using 3σb/m criteria, response time of 30 s and sensitivity of ∼36.83 Ω/ng dl(-1) cm(-2) with a regression coefficient of 0.999. Attempts have been made to monitor the change in RCT of BSA/AO-IgGs/AUT/Au immunoelectrode on addition of coffee samples.

Unraveling the influences of soft-tissue flipper development on skeletal variation using an extinct taxon. Adaptation to an aquatic habitat results in dramatic changes in tetrapod limb morphology as limbs take on the roles of propulsion and steering and lose their weight-bearing function. Changes include enclosure of the limb in a soft-tissue flipper and proportional lengthening of the distal limb, often accomplished through the addition of skeletal elements (hyperphalangy). The flipper structure itself and changes to the developmental architecture permitting hyperphalangy are hypothesized to increase observed limb variation, based on a cetacean model. These hypotheses are examined in the ichthyosaurs Stenopterygius and Mixosaurus. Hyperphalangy combined with high levels of variation in phalangeal counts were observed in both genera. The amount of variation was not proportional to the number of phalanges in a digit, but was related to functional digit length. In addition, qualitative variants were catalogued in both genera. Polyphalangy, phalangeal fusion, and additional ossifications in the zeugopodial row were not observed in Mixosaurus, but were common in Stenopterygius, even though both genera exhibited a similar degree of hyperphalangy. These results suggest that while the flipper structure and processes resulting in hyperphalangy may increase observed variation in phalangeal counts, these factors are unlikely to be causing high levels of qualitative variation in ichthyosaurs. Patterns of variation in ichthyosaur limbs, and thus variability, are unique to species but can change over evolutionary time.

[Cytological research on localizing argentophilic proteins in one-cell mouse embryos]. Localization of argentophilic proteins on mouse one-cell embryos has been studied under light and electron microscope using the silver staining that reveals transcriptionally active nucleolus-organizing chromosome regions (NORs). Although argentophilic proteins are observed in NORs of metaphase chromosomes only after the second cleavage division, they can be detected in nuclear apparatus of one-cell embryos, that is at the stage when ribosomal genes are not yet transcribed. Argentophilic proteins are visualized on the surface of decondensing chromatin of the spermatozoon head and on maternal telophase chromosomes immediately after the fertilization. They migrate into pronuclei and are accumulated in pronucleoli. During mitosis argentophilic proteins bind to chromosomes and move to cytoplasm. The importance of argentophilic proteins at the initial stages of mammalian embryogenesis is discussed.

Enchondroma protuberans masquerading as osteochondroma. Two cases of enchondroma protuberans are presented. The term enchondroma protuberans is designed to indicate a previously unrecognized and probably rare entity occurring in a long bone in an exaggeratedly eccentric fashion and, radiographically, remarkably resembling an osteochondroma. However, the morphologic differences between these two lesions are quite obvious and are easily demonstrable. Two young male patients, 10 and 15 years of age, had essentially similar lesions that developed, coincidentally, in the upper end of the left humerus. Improper radiographic interpretation of the lesions in both cases resulted in unnecessary second operations.

Role of insulin and serum on thyrotropin regulation of thyroid transcription factor-1 and pax-8 genes expression in FRTL-5 thyroid cells. Thyrotropin (TSH), via its cyclic adenosine monophosphate (cAMP) signal, decreases thyrotropin receptor (TSHR) gene expression in FRTL-5 thyroid cells, whereas it increases expression of the thyroglobulin (Tg) gene. Despite the opposite effects of TSH on TSHR and Tg expression, both genes are positively controlled by thyroid transcription factor-1 (TTF-1) and evidence has accumulated that TSH can decrease TTF-1 mRNA levels. In this report, we further characterize the action of TSH on TTF-1 in order to understand its different activities on the TSHR and Tg genes better. The effect of TSH on the TSHR requires the presence of insulin and serum and we show here that also both factors are necessary for the TSH effect to decrease TTF-1 mRNA levels. The decrease is paralleled by a downregulation of TTF-1 protein levels as well as by a decrease in TTF-1/DNA complex when the TTF-1 site of the TSHR promoter was used as probe. Again, the decrease requires insulin and serum. The TSH downregulation of TTF-1 mRNA levels is due to a decrease in its transcription rate. Using a luciferase-linked chimera construct spanning 5.18 kb of the TTF-1 5'-flanking region, we show that TSH decreases TTF-1 promoter activity and that this effect depends on insulin and serum. These data contrast with the action of TSH on Tg and Pax-8 gene expression. TSH increases Pax-8 mRNA levels and the increase is evident whether insulin and serum are present or not. Moreover, this increase is paralleled by an increase in Pax-8 protein binding to an oligonucleotide derived from the C site of the Tg promoter, which can bind both TTF-1 and Pax-8. The present data thus show that TTF-1 gene expression is interdependently regulated by TSH and serum growth factors including insulin. They also show this interdependent-regulation is not duplicated in the case of Pax-8. We suggest that these differences may contribute to the distinct ability of TSH to regulate TSHR versus Tg gene expression in FRLT-5 thyroid cells.

Packaging of medicines for paediatric use: Prescrire's constructive proposals. In May 2011, the European Medicines Agency (EMA) released for public consultation a draft guideline on the pharmaceutical development of medicines for paediatric use. Prescrire made 20 constructive proposals. Background information can be found at english.prescrire.org.

[Stress of the elderly (author's transl)]. Author examines the suicide-motives of elderly people in connection with stress and describes the Hedri-Mallisons disease, which has a very high suicide-rate.

[The role of Fos protein in modulation of dental pain in central nerve system]. The aims of this study were to reveal the relationship between Fos protein expression, the transcription of preproenkephalin (PENK) mRNA, and the change of enkephalin (ENK) level initiated by experimental dental pain, and to understand the central modulation mechanism of dental pain. The techniques of Immunohistochemistry in situ hybridization and radioimmunoassay were applied respectively to detect the expression of Fos, the transcription of PENK mRNA, and the change of ENK level in the experimental nucleus of the spinal tract of the trigeminal nerve, caudal part (sp5c) of rats. It was found that Fos protein expression was in a time-dependent manner. Fos appeared half hour after the pain stimulation, and its peak occurred two hours after the pain stimulation, but disappeared slowly four hours later. The transcription of PENK mRNA was seen two hours after the pain stimulation, its peak appeared four hours later and it disappeared eight hours later. The level of ENK increased significantly (P < 0.01) in the caudal part of the spinal tract of the trigeminal nerve four hours after pain stimulation. Fos protein may take a part in the central modulation of dental pain by initiating PENK mRNA transcription which led to the increment of ENK.

Influences on tocopherol biosynthesis in the cyanobacterium Synechocystis sp. PCC 6803. To elucidate influences on the tocopherol biosynthesis in cyanobacteria, wild type and mutant cells of a putative methyltransferase in tocopherol and plastoquinone biosynthesis of Synechocystis sp. PCC 6803 were grown under different conditions. The vitamin E content of cells grown under different light regimes, photomixotrophic or photoautotrophic conditions and varying carbon dioxide supplies were compared by HPLC measurements. The tocopherol levels in wild type cells increased under higher light conditions and low carbon dioxide supply. Photomixotrophic growth led to lower vitamin E amounts in the cells compared to those grown photoautotrophically. We were able to segregate a homozygous deltasll0418 mutant under photoautotrophic conditions. In contrast to former suggestions in the literature the deletion of this gene is not lethal under photomixotrophic conditions and the influence on tocopherol and plastoquinone amounts is diminutive. The methyltransferase encoded by the gene sll0418 is not essential either for tocopherol or plastoquinone synthesis.

Amide activation: an emerging tool for chemoselective synthesis. It is textbook knowledge that carboxamides benefit from increased stabilisation of the electrophilic carbonyl carbon when compared to other carbonyl and carboxyl derivatives. This results in a considerably reduced reactivity towards nucleophiles. Accordingly, a perception has been developed of amides as significantly less useful functional handles than their ester and acid chloride counterparts. However, a significant body of research on the selective activation of amides to achieve powerful transformations under mild conditions has emerged over the past decades. This review article aims at placing electrophilic amide activation in both a historical context and in that of natural product synthesis, highlighting the synthetic applications and the potential of this approach.

[Experimental studies on pancreatic islet xenotransplantation--effect of irradiation on xenografts survival]. The purpose of the present study was to assess the effect of Total Body Irradiation (TBI) and Total Lymphoid Irradiation (TLI) on pancreatic islet xenografts survival. Wistar rats rendered diabetic by intravenous injection of streptozotocin were used as recipients. Golden hamsters were used as islet donors. Pancreatic islets were isolated by the collagenase digestion method. Twelve hundred islet were transplanted into the portal vein of diabetic rats. In untreated controls, the mean graft survival time was 2.9 +/- 0.6 days (n = 7). In TBI of 400 rad treated group, three out of 9 recipients accepted islet xenografts for more than 80 days. TLI of 1200 rad also significantly prolonged graft survival period (30.3 +/- 11.7 days, n = 7, p less than 0.01). Rat anti-hamster lymphocytotoxic antibody titers began to rise on the second day after islets xenografting in untreated and TLI of 400 rad treated recipients. While, elevation of cytotoxic antibody titers was completely suppressed in spite of occurrence of the rejection in TLI of 800 and 1200 rad treated recipients. This may indicate that xenograft rejection in TLI of 800 and 1200rad treated recipients was mediated by cellular immunity rather than humoral immunity.

La Cura, An Open Source Cure for Cancer. When I was diagnosed with brain cancer, I opened up my medical records to the Web, asking for help. The response was incredible: a global source of crowd-generated information about how to cure my own cancer. This work explores the many issues involved in handling such a peculiar form of information (including privacy, preserving the complexity of the human being, the reliability of responses, and more) and the outcomes of the overall process. "[Critique] does not aim to make possible metaphysics which becomes, in the end, science; its aim is to look as more as possible beyond and beside at the infinite work of freedom." -M. Foucault, "What is Illuminism" "Maybe today the most important objective is not to understand what we are, but to refuse it. We must imagine and build what we could be, to drop that political double bind which is constituted by the simultaneous individualization and totalitarianization of the structures of modern powers. The conclusion might be that the political, ethical, social and philosophical issue today is not to liberate individuals from the State and its institutions, but to free ourselves from the State and from the individualization which is bound to the State. We must promote new ways for subjectivity through the refusal of that kind of individuality which has been imposed to us for so many centuries." -M. Foucault, "Why Study Power: The Question of the Subject" (1).

Yeast ubiquinol: cytochrome c oxidoreductase is still active after inactivation of the gene encoding the 17-kDa subunit VI. The single nuclear gene encoding the 17-kDa subunit VI of yeast ubiquinol: cytochrome c oxidoreductase has been inactivated by one-step gene disruption. Disruption was verified by Southern blot analysis of nuclear DNA and immunoblotting. Cells lacking the 17-kDa protein are still capable of growth on glycerol and they contain all other subunits of complex III at wild-type levels, implying that the 17-kDa subunit is not essential for either assembly of complex III, or its function. In vitro, electron transport activity of complex III of mutant cells is about 40% of the wild-type complex, but for the total respiratory chain no significant differences in activity was measured between mutant and wild type. The energy-transducing capacity of the complex is not reduced in the absence of the 17-kDa protein. In a relatively high proportion of the transformants, disruption of the 17-kDa gene was accompanied by the appearance of a second mutation causing a petite phenotype. In these cells which lack cytochrome b, the presence of the 17-kDa protein (after complementation) results in stabilization of cytochrome c1.

Strategies for dissecting genetic-environmental interactions in neurodegenerative disorders. Complex genetic and environmental interactions contribute to abnormal aging and neurodegenerative disorders. We present information from a series of 1136 consecutive patients presenting with cognitive disorders and show possible significant contribution of toxic environmental and occupational exposures to pathological aging (21% of patients) and interactions of these exposures with common polymorphisms that affect cell injury and inflammation. Such exposures may lower age of onset to same degree as APOE4/4. Common polymorphisms in apolipoprotein E (APOE), hemochromatosis gene (Hfe) and alpha-1-antitrypsin (AAT) are present in up to 40+% of patients and may partially account for differences in clinical syndrome, age of onset and rate of progression. Strategies for the study of these disorders must also consider the role and treatment of common co-morbid illnesses such as alcohol use, nutritional deficiencies, sleep disorders, and pre-existing affective disorder. APOE, Hfe, and AAT genes are expressed in liver tissue and in macrophages and are involved in the host innate immune response to stress, inflammation and infections. Hfe and AAT are involved in iron metabolism and their polymorphisms may contribute to hepatosteatosis and altered homeostasis of lipids (role of APOE), iron, and trace minerals. Some of these responses may be adaptive. Hfe and AAT modulate the apparent effects of toxic exposures on age of onset and progression rate. C282Y polymorphism paradoxically reverses APOE4/4 effect on age of onset. S and Z AAT polymorphisms may attenuate earlier age of onset in persons with toxic or environmental exposure. AAT S or Z polymorphisms are present in 25% of persons with anxiety disorder and 42% of persons with bipolar disorder compared to 10% of control group without pre-existing affective disorder. Common genetic polymorphisms that affect the response to inflammation and cell injury provide a beginning strategy for dissecting neurodegenerative disorders. The effects of APOE, Hfe, and AAT on glucose, lipid, iron and trace mineral homeostasis may affect normal development and aging of the nervous system in addition to their effects on outcome of toxic environmental and occupational exposures and susceptibility and outcome of neurodegenerative illnesses.

The CCL5/CCR5 axis promotes interleukin-6 production in human synovial fibroblasts. CCL5 (RANTES) was originally identified as a product of activated T cells and plays a crucial role in the inflammatory response. This study was undertaken to investigate the intracellular signaling pathways involved in CCL5-induced interleukin-6 (IL-6) production in human synovial fibroblasts. CCL5-mediated IL-6 expression was assessed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The mechanisms of action of CCL5 in different signaling pathways were studied using Western blotting. Knockdown of CCR5 and protein kinase Cδ (PKCδ) protein was achieved by transfection of small interfering RNA (siRNA). Chromatin immunoprecipitation assays were used to study in vivo binding of c-Jun to the IL-6 promoter. Transient transfection was used to examine IL-6 and activator protein 1 (AP-1) activity. Osteoarthritis synovial fibroblasts (OASFs) showed significant expression of CCL5 and CCR5, and expression was higher than that in normal synovial fibroblasts. Stimulation of OASFs with CCL5 induced concentration- and time-dependent increases in IL-6 production. CCL5-mediated IL-6 production was attenuated by CCR5 monoclonal antibody, CCR5 inhibitor (Met-RANTES), and CCR5 siRNA. Pretreatment with a PKCδ inhibitor (rottlerin), a c-Src inhibitor (PP2), or an AP-1 inhibitor (tanshinone IIA) also blocked the potentiating action of CCL5. Treatment of OASFs with CCL5 increased the accumulation of phosphorylated c-Jun in the nucleus, AP-1 luciferase activity, and c-Jun binding to the AP-1 element on the IL-6 promoter. CCL5-mediated AP-1 luciferase activity and c-Jun binding to the AP-1 element were inhibited by Met-RANTES, rottlerin, and PP2. The present results suggest that the interaction between CCL5 and CCR5 increases IL-6 production in human synovial fibroblasts via the PKCδ/c-Src/c-Jun and AP-1 signaling pathways.

Neuronal nicotinic alpha-bungarotoxin receptors. Recent evidence has indicated that the nicotinic acetylcholine receptor and the nicotinic alpha-bungarotoxin (alpha-BGT) site may be distinct in neuronal tissues. With regard to function, the former receptor appears to be involved in mediating synaptic events; however, the role of the nicotinic alpha-BGT site in nervous tissue is currently not known. Since the binding of alpha-BGT exhibits such high affinity and selectivity for a specific receptor, this may implicate an involvement of the toxin binding site in some aspect of neuronal activity with the receptor possibly mediating functions other than nicotinic cholinergic transmission. A further hypothesis to explain the nature of the toxin binding site may be that the natural ligand for the alpha-BGT site is one other than acetylcholine, with acetylcholine acting as a modulator of the site. Current studies in our laboratory are exploring these possibilities by determining whether specific peptides and/or polypeptides can interact at the nicotinic alpha-BGT site in nervous tissue. Studies using both in vivo and in vitro approaches suggest that thymopoietin may serve a role as a modulator of the nicotinic alpha-BGT site in neuronal tissues.

Solid-papillary carcinoma of the breast: clinicopathological study of 20 cases. The purpose of the present paper was to evaluate the clinicopathological and biological features of 20 Japanese patients with solid-papillary carcinoma of the breast (SPC) or SPC associated with invasive breast cancer. All the patients were Japanese women, including two sisters. The mean age was 66.0 years. The incidence of SPC among all the breast cancers treated at two institutions was 1.1% and 1.7%, respectively. The mean disease-free interval was 4 years 11 months. Axillary lymph node metastasis or tumor recurrence did not occur in any of the cases. Fifteen cases of SPC contained invasive cancers that ranged from <5% to 60% of the entire tumor area. Histological types of invasive cancers were mucinous carcinoma in five cases and neuroendocrine cell carcinoma in 10 cases. These results indicate that SPC is a potential precursor lesion for neuroendocrine carcinoma as well as mucinous carcinoma. When all the cases were classified and analyzed according to both the 2002 tumor node metastasis (TNM) classification system and the Nottingham histological grade, SPC patients, even those with invasive cancers, seemed to have longer disease-free survival compared to patients with the other invasive breast cancers of matching grade and stage. Clinicopathologically, SPC could be regarded as a separate type of ductal carcinoma in situ.

[Overlap syndrome between Autoimmune Hepatitis and Primary Biliary Cirrhosis: report of a case]. We present a case of an elderly female, without past medical history of alcohol, medication or hepatotoxic substances intake, with negative serology studies for viral hepatitis, who had evidence of chronic liver disease (Score B in the Child-Turcotte-Pugh scoring system). The patient presents mixed clinical, serologic, immunologic and histologic features of Autoimmune Hepatitis and Primary Biliary Cirrhosis. We postulate this is a variant or overlap syndrome.