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Rotating goblet and talking profiles: does a rotating goblet increase the figural dominance of profiles in Rubin's type of figure-ground reversal patterns? We present a novel three-dimensional (3-D) version of Rubin's classical bistable goblet-profiles figure. An actual goblet sculpture was produced and rotated on a turntable in front of a white background. As the goblet rotates about its central axis, small circular asymmetries around the lips and chin region give a clear impression of two white profiles talking to each other. Although the profiles actually correspond to empty space or white background, they are more likely to be perceived as 'figure' than the 3-D goblet itself. Four experiments that presented the actual goblet (experiment 1) or two-dimensional (2-D) movies of it (experiments 2-4) were designed to verify these observations. We measured perceptual dominance of profiles as 'figure' and rate of reversal as a function of three factors: motion (static vs rotating), orientation (upright vs inverted), and configuration (face-to-face vs back-to-back). Results for the rotating goblet showed a statistically reliable preference for perceiving the talking profiles as 'figure'. Deforming the profiles by manipulating the vertex angle of the mouth region produced an inverted U-shaped curve with the peak representing the stimulus condition in which the profiles perception was most remarkable. We discussed a number of 3-D and 2-D figure-ground factors that might apply to this rather complex stimulus situation.

The Gcn5 bromodomain co-ordinates nucleosome remodelling. The access of transcription factors to eukaryotic promoters often requires modification of their chromatin structure, which is accomplished by the action of two general classes of multiprotein complexes. One class contains histone acetyltransferases (HATs), such as Gcn5 in the SAGA complex, which acetylate nucleosomal histones. The second class contains ATPases, such as Swi2 in the Swi/Snf complex, which provide the energy for nucleosome remodelling. In several promoters these two complexes cooperate but their functional linkage is unknown. A protein module that is present in all nuclear HATs, the bromodomain, could provide such a link. The recently reported in vitro binding of a HAT bromodomain with acetylated lysines within H3 and H4 amino-terminal peptides indicates that this interaction may constitute a targeting step for events that follow histone acetylation. Here we use a suitable promoter to show that bromodomain residues essential for acetyl-lysine binding are not required in vivo for Gcn5-mediated histone acetylation but are fundamental for the subsequent Swi2-dependent nucleosome remodelling and consequent transcriptional activation. We show that the Gcn5 bromodomain stabilizes the Swi/Snf complex on this promoter.

Global proteomic analysis of protein acetylation affecting metabolic regulation in Daphnia pulex. Daphnia (Daphnia pulex) is a small planktonic crustacean and a key constituent of aquatic ecosystems. It is generally used as a model organism to study environmental toxic problems. In the past decade, genomic and proteomic datasets of Daphnia have been developed. The proteomic dataset allows for the investigation of toxicological effects in the context of "Daphnia proteomics," resulting in greater insights for toxicological research. To exploit Daphnia for ecotoxicological research, information on the post-translational modification (PTM) of proteins is necessary, as this is a critical regulator of biological processes. Acetylation of lysine (Kac) is a reversible and highly regulated PTM that is associated with diverse biological functions. However, a comprehensive description of Kac in Daphnia is not yet available. To understand the cellular distribution of lysine acetylation in Daphnia, we identified 98 acetylation sites in 65 proteins by immunoprecipitation using an anti-acetyllysine antibody and a liquid chromatography system supported by mass spectroscopy. We identified 28 acetylated sites related to metabolic proteins and six acetylated enzymes associated with the TCA cycle in Daphnia. From GO and KEGG enrichment analyses, we showed that Kac in D. pulex is highly enriched in proteins associated with metabolic processes. Our data provide the first global analysis of Kac in D. pulex and is an important resource for the functional analysis of Kac in this organism.

Direct ADCC lysis of O,Rh-positive (R1R2) erythrocytes by lymphocytes of individuals sensitized against antigen D. Non-T-cells from individuals sensitized against antigen D were found to lyze O,Rh-positive erythrocytes. The lytic effect was abolished by incubation of the effector cells at 37 degrees C for 30 min, and was reconstituted by addition of anti-D antibodies. These results suggested that sensitized donors have lymphocytes armed with specific antibodies in vivo.

Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation, and airway hyperresponsiveness in mice. We have used a mouse model of allergen-induced airway hyperresponsiveness to demonstrate that immunostimulatory DNA sequences (ISS) containing a CpG DNA motif significantly inhibit airway eosinophilia and reduce responsiveness to inhaled methacholine. ISS not only inhibited eosinophilia of the airway (by 93%) and lung parenchyma (91%), but also significantly inhibited blood eosinophilia (86%), suggesting that ISS was exerting a significant effect on the bone marrow production of eosinophils. The inhibition of the bone marrow production of eosinophils by 58% was associated with a significant inhibition of T cell-derived cytokine generation (IL-5, granulocyte-macrophage CSF, and IL-3). ISS exerted this inhibitory effect on T cell cytokine production indirectly by stimulating monocytes/macrophages and NK cells to generate IL-12 and IFNs. The onset of the ISS effect on reducing the number of tissue eosinophils was both immediate (within 1 day of administration) and sustained (lasted 6 days), and was not due to ISS directly inducing eosinophil apoptosis. ISS was effective in inhibiting eosinophilic airway inflammation when administered either systemically (i.p.), or mucosally (i.e., intranasally or intratracheally). Interestingly, a single dose of ISS inhibited airway eosinophilia as effectively as daily injections of corticosteroids for 7 days. Moreover, while both ISS and corticosteroids inhibited IL-5 generation, only ISS was able to induce allergen-specific IFN-gamma production and redirect the immune system toward a Th1 response. Thus, systemic or mucosal administration of ISS before allergen exposure could provide a novel form of active immunotherapy in allergic diseases.

The use of CVD diamond burs for ultraconservative cavity preparations: a report of two cases. During the past decades, scientific developments in cutting instruments have changed the conventional techniques used to remove caries lesions. Ultrasound emerged as an alternative for caries removal since the 1950s. However, the conventional technology for diamond powder aggregation with nickel metallic binders could not withstand ultrasonic power. Around 5 years ago, an alternative approach using chemical vapor deposition (CVD) resulted in synthetic diamond technology. CVD diamond burs are obtained with high adherence of the diamond as a unique stone on the metallic surface with excellent abrading performance. This technology allows for diamond deposition with coalescent granulation in different formats of substrates. When connected to an ultrasonic handpiece, CVD diamond burs become an option for cavity preparation, maximizing preservation of tooth structure. Potential advantages such as reduced noise, minimal damage to the gingival tissue, extended bur durability, improved proximal cavity access, reduced risk of hitting the adjacent tooth resulting from the high inclination angles, and minimal patient's risk of metal contamination. These innovative instruments also potentially eliminate some problems regarding decreased cutting efficiency of conventional diamond burs. This clinical report presents the benefits of using CVD diamond burs coupled with an ultrasonic handpiece in the treatment of incipient caries. CVD diamond burs coupled with an ultrasonic device offer a promising alternative for removal of carious lesions when ultraconservative cavity preparations are required. Additionally, this system provides a less-painful technique for caries removal, with minimal noise.

Effects of fentanyl versus sufentanil in equianesthetic doses on middle cerebral artery blood flow velocity. Sufentanil has been reported to increase cerebral blood flow in comparison with fentanyl. However, because of the use of animal models, supraclinical doses and/or background anesthetic agents, the clinical applicability of these studies remains difficult to assess. Therefore, transcranial Doppler ultrasonography was used to determine the cerebral hemodynamic effects of equianesthetic doses of fentanyl and sufentanil on middle cerebral artery (MCA) blood flow velocity in patients without intracranial pathologic conditions. Twenty-four unpremedicated American Society of Anesthesiologists physical status 1 and 2 patients undergoing elective nonintracranial neurosurgery were assigned randomly to receive equipotent blinded infusions of either sufentanil (15 micrograms/min) or fentanyl (150 micrograms/min) for anesthetic induction during spontaneous ventilation of 100% oxygen. Normocapnia, as measured by infrared capnography, was maintained by manually assisting ventilation, as necessary. The cerebral opioid effect was quantified using the spectral edge frequency parameter. The infusion was continued until either 1) spectral edge frequency decreased below 10 Hz or 2) 150 micrograms of sufentanil or 1,500 micrograms of fentanyl was infused, whichever occurred first. On average, the patients received 1.7 +/- 0.55 micrograms/kg or 16 +/- 4 micrograms/kg of sufentanil or fentanyl, respectively. The right MCA mean, peak systolic, and peak diastolic velocities and pulsatility index were measured continuously by transcranial Doppler ultrasonography. The mean arterial pressure decreased slightly in both groups, but only in the fentanyl group were the changes significant. The MCA velocity increased by approximately 25% in both groups. However, the relative changes in MCA velocity were not different between groups. The pulsatility indexes were unchanged in both groups. These data suggest that, at clinically relevant doses in the absence of other drugs, cerebral blood flow velocity is increased by both fentanyl and sufentanil. Furthermore, there appears to be no significant differences in the cerebral hemodynamic profiles of the two drugs, as assessed by transcranial Doppler ultrasonography.

Magneto-optic modulator for high bandwidth cavity length stabilization. We propose a novel magneto-optical approach for the repetition frequency stabilization of optical frequency combs. We developed a Yb:fiber mode-locked laser with a fiber-based magneto-optic modulator used to stabilize one of the longitudinal modes to an optical reference with sub-hundred mrad residual phase noise. This modulator does not induce mechanical resonances and as such has the potential to achieve much broader feedback bandwidths than conventional modulators used for cavity length stabilization.

Human neutrophil degranulation responses to nucleotides. Nucleotides have polymorphonuclear neutrophil (PMN)-stimulating actions resembling those of 5-hydroxyicosatetraenoate and its oxo analog, 5-oxoETE. Their effects on degranulation, however, are disputed even though this response may underlie their in vivo toxicity and is well-suited for comparing their mechanism of action with e.g., 5-oxoETE. We measured the direct, synergistic, and cross-desensitizing actions of nine nucleotides and six other stimuli in degranulating unprimed and tumor necrosis factor (TNF)-alpha-primed human PMN. Nucleotides weakly degranulated unprimed PMN but caused far larger responses in TNF-alpha-primed cells. Their actions, while differing from those of N-formyl-MET-LEU-PHE, platelet-activating factor, leukotriene B4, ionomycin, or dioctanoylglycerol, resembled those of 5-oxoETE. Nucleotides also enhanced PMN degranulation responses to the latter stimuli, particularly 5-oxoETE. Nucleotide degranulating and enhancing potencies were: UTP > or = ATP > or = ATP gamma S > ITP > ADP > 2-MeSATP, nonphosphohydrolyzable analogs lacked activity, and adenosine and AMP blocked PMN degranulation. Finally, nucleotides desensitized degranulation responses to each other but not to 5-oxoETE or other agonists, and 5-oxoETE desensitized to itself but not to nucleotides. Nucleotides have intrinsic and synergistic degranulating actions that under appropriate conditions (i.e., in concert with TNF-alpha or 5-oxoETE) are exceedingly prominent. Recognition systems mediating their effects differ from those for various stimuli including 5-oxoETE. These systems likely involve a common "nucleotide" receptor, but studies do not exclude possibilities that other purinergic receptors contribute to their actions.

A study of macrophages, macrophage-related cells, and endothelial adhesion molecules in recurrent aphthous ulcers in HIV-positive patients. The purpose of this immunohistochemical study was to investigate the presence and distribution of macrophages (CD11c+ and CD68+) and macrophage-related dendritic cells (factor XIIIa+ and CD36+) in early and late aphthous ulcers associated with HIV infection. To substantiate a mechanism by which these cells may move from the vascular compartment to tissue spaces, we also investigated expression of ELAM (endothelial leukocyte adhesion molecule), ICAM-1 (intercellular adhesion molecule), and CD18 (leukocyte function antigen). Numerous CD11c+ and CD68+ macrophages were seen in early lesions, though larger numbers of CD68+ cells were present in older lesions. No significant increases in factor XIIIa+ dendrocytes were seen in either early or late lesions, though dendrocytes appeared enlarged. CD36+ cells and CD18+ leukocytes were more numerous in early than in late aphthous ulcers. ELAM and ICAM expression was most intense on endothelial cells in early aphthous ulcers, with staining intensity fading toward the lesion periphery. Control specimens showed weaker ELAM and ICAM staining than did the ulcer specimens. Keratinocytes did not express ICAM. By virtue of their numbers, macrophages and macrophage subtypes appear to have a significant role in both the early and late stages of this disease. Although factor XIIIa-expressing dendrocytes may not have been more numerous in the ulcers, they appeared to be "activated" because of their prominence in the lesions and their occasional co-expression of CD68 antigen (KP1+). They may have a minor role in antigen processing, phagocytosis, and fibroplasia. ELAM and ICAM expression by endothelial cells provides a mechanism by which macrophages and other leukocytes can be recruited to the site of the lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary colonic epithelial cell culture of the rabbit producing prostaglandins. We have established primary colonic epithelial cell culture from adult rabbits and examined effects of anti-inflammatory drugs on prostaglandin (PG) E2 production. Colonic epithelium of adult rabbits was scraped and minced into small pieces. They were incubated for isolation in Hanks' balanced salt solution with 0.35% collagenase and Earle's solution with 1 mM EDTA. Isolated cells were cultured in Coon's modified Ham's F-12 medium with 10% fetal bovine serum and antibiotics on collagen coated cell wells. The medium was refed twice a week. The production of PGs was assessed by high pressure liquid chromatography (HPLC). PGE2 and PGF2 alpha were measured by radioimmunoassay. Within 24 hours after inoculation, the cell clumps attached to the surface of the wells and cells began to spread out and grow. Monolayer cultures became confluent in 4 days. Phase contrast microscopy showed that these cells consisted of a homogeneous population of epithelial cells with large oval nuclei, polyhedral shape, and organized sheet-like growth pattern. HPLC profile showed synthesis of 6-keto-PGF1 alpha, thromboxane B2, PGF2 alpha, PGE2, and PGD2 by cultured cells. Quantitatively, 117 +/- 7 ng/mg-protein/hour PGE2 and 7.4 +/- 0.7 ng/mg-protein/hour PGF2 alpha were produced. While hydrocortisone (10(-4) - 10(-2) M) did not show a significant effect on PGE2 production, indomethacin (10(-8) - 10(-6) M), and 5-aminosalicylic acid (2X10(-4)-5X10(-3) M) inhibited PGE2 production. We have established relatively convenient procedure for primary culture of colonic epithelial cells from adult rabbits. Different actions of anti-inflammatory drugs on PGE2 synthesis suggest that these cultured cells might be a good tool for the various cellular functional studies of normal colonic epithelial cells.

Leisure-Time Daily Walking and Blood Pressure Among Chinese Older Adults: Evidence From the China Health and Retirement Longitudinal Study (CHARLS). This descriptive, cross-sectional study aimed to describe the characteristics of participants who engaged in leisure-time daily walking (LTDW) and examine the relationship between LTDW and blood pressure (BP) in Chinese older adults in general, and specifically among Chinese older adults with hypertension. Participants included 780 adults who were 65 and older from the China Health and Retirement Longitudinal Study (CHARLS). Participants self-reported their LTDW time, and BP was measured three times using an Omron HEM-7200 Monitor. Multiple linear regression models and ordinal logistical models were used to examine the characteristics of daily walkers and associations between LTDW time with systolic BP (SBP) and diastolic BP (DBP). Older adults of younger age (ß = -0.02, p = 0.012) and higher education (ß = 0.52, p = 0.018) were more likely to engage in LTDW, whereas being married was associated with less LTDW (ß = -0.24, p = 0.025). In addition, 2 to 4 hours of LTDW time was associated with lower DBP (ß = -4.13, p = 0.002). For hypertensive older adults, 30 minutes to 2 hours of LTDW time was related to lower DBP (ß = -4.42, p = 0.024). LTDW may have varying benefits on BP. Clinical recommendations should be based on patient characteristics and chronic conditions. [Res Gerontol Nurs. 2019; 12(5): 248-258.].

Fungi outcompete bacteria under increased uranium concentration in culture media. As a key part of water management at the Ranger Uranium Mine (Northern Territory, Australia), stockpile (ore and waste) runoff water was applied to natural woodland on the mine lease in accordance with regulatory requirements. Consequently, the soil in these Land Application Areas (LAAs) presents a range of uranium concentrations. Soil samples were collected from LAAs with different concentrations of uranium and extracts were plated onto LB media containing no (0 ppm), low (3 ppm), medium (250 ppm), high (600 ppm) and very high (1500 ppm) uranium concentrations. These concentrations were similar to the range of measured uranium concentrations in the LAAs soils. Bacteria grew on all plates except for the very high uranium concentrations, where only fungi were recovered. Identifications based on bacterial 16S rRNA sequence analysis showed that the dominant cultivable bacteria belonged to the genus Bacillus. Members of the genera Paenibacillus, Lysinibacillus, Klebsiella, Microbacterium and Chryseobacterium were also isolated from the LAAs soil samples. Fungi were identified by sequence analysis of the intergenic spacer region, and members of the genera Aspergillus, Cryptococcus, Penicillium and Curvularia were dominant on plates with very high uranium concentrations. Members of the Paecilomyces and Alternaria were also present but in lower numbers. These findings indicate that fungi can tolerate very high concentrations of uranium and are more resistant than bacteria. Bacteria and fungi isolated at the Ranger LAAs from soils with high concentrations of uranium may have uranium binding capability and hence the potential for uranium bioremediation.

Recruitment of unmyelinated C-fibers mediates the bladder-inhibitory effects of tibial nerve stimulation in a continuous-fill anesthetized rat model. Although percutaneous tibial nerve stimulation is considered a clinically effective therapy for treating overactive bladder, the mechanism by which overactive bladder symptoms are suppressed remains unclear. The goal of the present study was to better understand the role of specific neural inputs (i.e., fiber types) on the bladder-inhibitory effects of tibial nerve stimulation (TNS). In 24 urethane-anesthetized rats, a continuous suprapubic saline infusion model was used to achieve repeated filling and emptying of the bladder. A total of 4 TNS trials (pulse frequency: 5 Hz) were applied in randomized order, where each trial used different amplitude settings: 1) no stimulation (control), 2) Aβ-fiber activation, 3) Aδ-fiber activation, and 4) C-fiber activation. Each stimulation trial was 30 min in duration, with an intertrial washout period of 60-90 min. Our findings showed that TNS evoked statistically significant changes in bladder function (e.g., bladder capacity, residual volume, voiding efficiency, and basal pressure) only at stimulation amplitudes that electrically recruited unmyelinated C-fibers. In a subset of experiments, TNS also resulted in transient episodes of overflow incontinence. It is noted that changes in bladder function occurred only during the poststimulation period. The bladder-inhibitory effects of TNS in a continuous bladder filling model suggests that electrical recruitment of unmyelinated C-fibers has important functional significance. The implications of these findings in percutaneous tibial nerve stimulation therapy should be further investigated.

Stages of change in clinical nutrition practice. For years, nutritionists have developed education materials that attempted to change dietary behaviors. However, most of these programs were effective only in increasing knowledge and did not produce long-term behavior change. Research indicates that nutrition interventions will be more effective if based on a theoretical model. The stages of change theory attempts to explain behavior change as a series of levels of readiness to changes. The stages range from precontemplation, where an individual does not recognize the need for change, to the maintenance of long-term behavior change. Use of this theory in nutrition education has been found to be most effective if education methods are stage specific and address the individual needs of clients. Unfortunately, little research has been done using this theory in traditional clinical nutrition practice, but implementation may be easy for the nutritionist and may help to increase compliance with dietary recommendations in individuals with chronic disease. The first step in using the stages of change theory is to determine the behavior that is going to be changed. With this information, the clinician can then determine the patient's stage of readiness to change a variety of dietary habits. Through the identification of an individual's stage, education methods can be tailored to meet the needs of the patient, helping to promote life-long dietary change.

[Relationships between biochemical qualities of paddy rice and climate conditions in the Anning River Valley]. Based on the experimental data of paddy rice planted geographically periodically without control in the Anning River Valley of Sichuan Province, this paper quantitatively analyzed the effects of meteorological conditions from 40 days before heading to ripeness on the biochemical qualities of paddy rice, and developed a model about the integrated relationships between biochemical qualities of paddy rice and mean temperature, daily range of temperature and daylight hours, which would be of significance both for the instruction of paddy distribution in the Anning River Valley and for improving rice qualities via adjusting planting time. The results showed that climate conditions had a great effect on the biochemical qualities of paddy rice, which was different in ways and in critical periods. The period when the correlation between some ingredients of rice and climate conditions was most significant was before or after, or from before to after full heading, which widened the existing knowledge about the period which was important for paddy rice qualities forming. Applying this finding in the Anning River Valley during 2002-2003, the accumulated high-grade paddy farming area stood at 73,000 hm2, 30,000 hm2 more than that in 2001, and brought 0.2 billion yuan increment to the peasants, promoting the development of high-grade paddy greatly.

DNA demethylation mediated by down-regulated TETs in the testes of rare minnow Gobiocypris rarus under bisphenol A exposure. Inevitable BPA exposure resulted in disturbance of DNA methylation status and our published study suspected that BPA has the potentiality to disturb DNA demethylation and GSH production in Gobiocypris rarus testes. To confirm this conjecture, several experiments were carried out in the present study. Adult male G. rarus was exposed to 1, 15 and 225 μg L-1 (nominal concentration) BPA for two weeks. The levels of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), glutathione (GSH), and enzyme levels for DNA methylation and GSH synthesis in the testes were detected. Meanwhile, the contents of substrates for GSH synthesis were measured. Furthermore, the transcriptional changes of the studied genes were examined. Results indicated that 1-225 μg L-1 BPA caused decrease of testicular ten-eleven translocation proteins (TETs) with more obvious effects at low concentrations. Moreover, all concentrations of BPA resulted in decrease of 5hmC levels while only 225 μg L-1 BPA resulted in significant increase of 5mC. In addition, all treatments resulted in significant decrease of GSH and the replenishment of GSH might be mainly accomplished by circular synthesis. These results indicated that BPA exposure inhibited TETs-mediated DNA demethylation and the declined DNA demethylation mediated by TETs may result in DNA hypermethylation at 225 μg L-1 BPA. In addition, the changes of DNA methylation status were irrelevant with GSH levels.

Dissociations among tasks involving inhibition: a single-case study. Recent theories of working memory have emphasized the role of inhibition in suppressing irrelevant information. Moreover, psychometric studies have reported that several inhibition tasks with very diverse requirements load on a single inhibition factor. A patient with left inferior frontal damage, Patient M.L., previously reported to have a semantic short-term memory deficit (R. C. Martin & He, 2004), showed evidence of difficulty with inhibition on short-term memory tasks. We investigated whether he would show evidence of inhibition difficulty on two verbal tasks (a Stroop task and a recent-negatives task) and two nonverbal tasks (a nonverbal spatial Stroop task and an antisaccade task). M.L. was impaired on both verbal tasks but performed normally on the nonverbal tasks. M.L.'s data also represent a dissociation between Stroop and antisaccade performance, two tasks that load on a single factor in factor-analytic studies. The implications of these data for theories of inhibition and executive function are discussed.

"Wetting enhancer" pullulan coating for antifog packaging applications. A new antifog coating made of pullulan is described in this work. The antifog properties are discussed in terms of wettability, surface chemistry/morphology, and by quantitative assessment of the optical properties (haze and transparency) before and after fog formation. The work also presents the results of antifog tests simulating the typical storage conditions of fresh foods. In these tests, the antifog efficiency of the pullulan coating was compared with that of two commercial antifog films, whereas an untreated low-density polyethylene (LDPE) film was used as a reference. The obtained results revealed that the pullulan coating behaved as a "wetting enhancer", mainly due to the low water contact angle (∼24°), which in turn can be ascribed to the inherent hydrophilic nature of this polysaccharide, as also suggested by the X-ray photoelectron spectroscopy experiments. Unlike the case of untreated LDPE and commercial antifog samples, no discrete water formations (i.e., droplets or stains) were observed on the antifog pullulan coating on refrigeration during testing. Rather, an invisible, continuous and thin layer of water occurred on the biopolymer surface, which was the reason for the unaltered haze and increased transparency, with the layer of water possibly behaving as an antireflection layer. As confirmed by atomic force microscopy analysis, the even deposition of the coating on the plastic substrate compared to the patchy surfacing of the antifog additives in the commercial films is another important factor dictating the best performance of the antifog pullulan coating.

[Iron, copper, manganese and zinc metabolism in athletes under high physical pressures]. Following the 50-kilometer ski race qualified athletes showed a significant decrease in the iron plasma content and formed elements of the blood. Concurrently the copper blood content also tended to decrease. The zink content had an opposite line of changes. The reduced zink blood content was associated with the augmented zink concentration in plasma. High physical exertion apart from the diet which was not balanced in trace elements produced the increased excretion of iron, copper, manganese and zink from the body of skiers with feces and partly with urine. Retention of trace elements supplied with the diet and their decreased excretion with feces were seen during rest after high physical exertion. There was also a partial making for trace element losses. The results suggest that the diet of athletes be enriched with trace elements, especially with iron in the course of rehabilitation after intensive training and competitions.

Apoptosis in factor-dependent haematopoietic cells is linked to calcium-sensitive mitochondrial rearrangements and cytoskeletal modulation. Apoptosis in murine haematopoietic interleukin (IL)3-dependent cell lines is induced within 6-8 h by IL-3 withdrawal. Direct introduction of cytochrome c by electroporation induces apoptosis within 2 h and was inhibited by caspase inhibitors, such as Z-VADfmk and Z-Dfmk. We report here that apoptosis induced by IL-3 withdrawal was refractory to these inhibitors but was accompanied by striking redistribution of mitochondria, which aggregated into an area associated with centrioles without loss of Deltapsim. Both mitochondrial redistribution and apoptosis were inhibited by the calcium ionophore, ionomycin. Nocodozole, an inhibitor of microtubule assembly, also induced apoptosis, which was unaffected by caspase inhibitors. Although nocodozole did not alter mitochondrial distribution, it significantly reduced Deltapsim, and both reduction of Deltapsim and apoptosis were inhibited by ionomycin. Oligomycin, which inhibits the mitochondrial FoF1 ATPase, similarly induced apoptosis, which was unaffected by caspase inhibitors but was inhibited by ionomycin. Further, oligomycin stimulated the novel formation and release of surface membrane-derived vesicles containing mitochondria with intact Deltapsim; ionomycin also inhibited their production. In all these conditions, Bcl-2 protected cells from apoptosis. Our studies show that apoptosis induced by three very different agents shares insensitivity to caspase inhibitors, suppression by ionomycin and effects on mitochondria, which all appear to be linked to cytoskeletal/microtubule activity. They suggest that microtubules and the cytoskeleton play an important role in apoptosis through mechanisms affecting mitochondria but which are independent of cytochrome c release.

Cross-cultural adaptation and validation of the Japanese version of the Toronto Extremity Salvage Score (TESS) for patients with malignant musculoskeletal tumors in the upper extremities. The Toronto Extremity Salvage Score (TESS) is a widely used disease-specific patient-completed questionnaire for the assessment of physical function in patients with musculoskeletal tumors; however, there had not been the validated Japanese version of the TESS. The aim of this study was to validate the Japanese version of the TESS in patients with musculoskeletal tumors in the upper extremity. After developing a Japanese version of the TESS, the questionnaire was administered to 53 patients to examine its reliability and validity in comparison with the Musculoskeletal Tumor Society (MSTS) scoring system and Short Form-36 (SF-36). Test-retest reliability with intraclass correlation coefficient (0.93) and internal consistency with Cronbach's alpha (0.90) were excellent. Factor analysis showed that the construct structure consisted of 3-item clusters, and the Akaike Information Criterion network also demonstrated that the items could be divided into 3 domains according to their content. The TESS strongly correlated with the MSTS rating scale (r = 0.750; P < 0.001) and the SF-36 physical functioning scale (r = 0.684; P < 0.001). However, as expected, the TESS had low correlations with the SF-36 mental health and role-emotional subscales and the MSTS scoring system manual dexterity domain. Our study suggests that the TESS is a reliable and valid instrument to measure patient-reported physical functioning in patients with upper extremity sarcoma.

Dendritic cell specific targeting of MyD88 signalling pathways in vivo. Dendritic cells (DCs) are key regulators of both innate and adaptive immunity. During infection, DCs recognise pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs) including the Toll-like receptor (TLR) family. TLRs mainly signal via the adaptor protein MyD88. This signalling pathway is required for immune protection during many infections, which are lethal in the absence of MyD88. However, the cell type specific importance of this pathway during both innate and adaptive immune responses against pathogens in vivo remains ill-defined. We discuss recent findings from conditional KO or gain-of-function mouse models targeting TLR/MyD88 signalling pathways in DCs and other myeloid cells during infection. While the general assumption that MyD88-dependent recognition by DCs is essential for inducing protective immunity holds true in some instances, the results surprisingly indicate a much more complex context-dependent requirement for this pathway in DCs and other myeloid or lymphoid cell-types in vivo. Furthermore, we highlight the advantages of Cre-mediated DC targeting approaches and their possible limitations. We also present future perspectives on the development of new genetic mouse models to target distinct DC subsets in vivo. Such models will serve to understand the functional heterogeneity of DCs in vivo.

Long-term surveillance by duplex scanning of nonrevised infragenicular graft stenosis. To define the prognosis of nonrevised graft stenosis, we studied 68 infragenicular bypass grafts in patients entered into our duplex surveillance program between 1986 and 1987. Patients were grouped according to the grade of stenosis as follows: grade I = < 50% stenosis, grade II = 50% to 75% stenosis, and grade III = 75% to 99% stenosis. Time until maximum stenosis was stratified into three intervals (< 3 months, between 3 and 12 months, and > 12 months). Cumulative patency rates from the time of maximum stenosis to failure were calculated using Kaplan-Meier analysis. Fifty-three grafts (78%) developed stenoses: 10 with grade I, 25 with grade II, and 18 with grade III stenosis. Eighty-nine percent of the 18 graft occlusions occurred within 2 years. Two grafts occluded after 2 years without any severe stenosis or preceding clinical signs. During follow-up 15 nonrevised stenosed grafts (four with grade I, five with grade II, and six with grade III stenosis) remained patent longer than 2 years with a mean follow-up of 72 months. Statistical analysis for graft failure determined that grade II to III stenoses led to graft occlusion significantly earlier than grade 0 to I stenoses (p = 0.017). If graft failures resulting from revision were separated from the analysis, the time interval from operation to maximum stenosis (within 1 year) remained marginally significant for predicting occlusion, whereas no correlation was found between the grade of maximum stenosis and occlusion. Thus the prognosis for graft stenosis depends on the grade of stenosis and on the time interval from operation to stenosis. Therefore duplex surveillance seems to be most important within the first 24 months only, but is of little use in predicting impending graft failure beyond 2 years in asymptomatic patients.

Observation of B0 -->D0K0 and B0 -->D0K*0 decays. We report on a search for B(0)-->D(*0)K(*0) decays based on 85 x 10(6) BB events collected with the Belle detector at KEKB. The B(0)-->D0K(0) and B(0)-->D0K(*0) decays have been observed for the first time with the branching fractions B(B(0)-->D0K(0))=(5.0(+1.3)(-1.2)+/-0.6)x10(-5) and B(B(0)-->D0K(*0))=(4.8(+1.1)(-1.0)+/-0.5)x10(-5). No significant signal has been found for the B(0)-->D(*0)K*0) and B(0)-->D(*0)K(*0) decay modes, and upper limits at 90% C.L. are presented.

The method of public morality versus the method of principlism. Two years ago in two articles in a thematic issue of this journal the three of us engaged in a critique of principlism. In a subsequent issue, B. Andrew Lustig defended aspects of principlism we had criticized and argued against our own account of morality. Our reply to Lustig's critique is also in two parts, corresponding with his own. Our first part shows how Lustig's criticisms are seriously misdirected. Our second and philosophically more important part picks up on Lustig's challenge to us to show that our account of mortality is more adequate than principlism. In particular we show that recognition of mortality as public and systematic enables us to provide a far better description of morality than does principlism. This explains why we adopt the label "Dartmouth Descriptivism."

Acetylcoenzyme A and the control of the synthesis of acetylcholine in the brain. Experimental work concerning the relation between the availability of acetylcoenzyme A and the synthesis of acetylcholine in the brain is reviewed and discussed from the viewpoint of the "mass action" ("reaction equilibrium") hypothesis of the control of acetylcholine synthesis.

The prevalence and number of Salmonella in sausages and their destruction by frying, grilling or barbecuing. To determine the prevalence and number of Salmonella and Campylobacter in sausages and to evaluate their destruction during cooking. One hundred and sixty-two packs of uncooked economy or catering sausages, comprising 53 packs of frozen and 109 of chilled sausages, were purchased in Devon between March and July 2000. All were tested for the presence of Salmonella and 51 packs of chilled sausages were also examined for the presence of Campylobacter spp. To investigate the heat tolerance of Salmonella enterica serovar Typhimurium DT104 in sausage-meat, chilled, handmade and frozen sausages were inoculated with approx. 1.5 x 10(4) bacterial cells per sausage (approximately 300 cfu g(-1)) and then cooked by frying, grilling or barbecuing. The levels of creatinine kinase, lactate dehydrogenase and alkaline phosphatase in uncooked and cooked sausages were measured to evaluate their potential as indicators of adequate cooking and, therefore, pathogen elimination. Salmonella were detected in 7.5% of frozen and 9.1% of the chilled sausages (8.6% overall) but Campylobacter spp. were not isolated. After cooking, a visual assessment suggested that all of the sausages were thoroughly cooked. Despite this, barbecuing and frying sometimes allowed Salmonella cells to survive and the temperature profiles during cooking indicated that the lethal range was sometimes not reached. The enzyme levels tested were not reliable indicators of the inactivation of bacterial pathogens because Salmonella were sometimes isolated from sausages with low values of all three enzymes. Salmonella spp. are present in a significant proportion of sausages and are not always killed during the cooking process. These findings have clear implications for public health.

[Successful management of a patient with rhabdomyolysis and marked elevation of serum creatine kinase level]. We experienced successful management of a patient with severe rhabdomyolysis by conservative treatment. A 41-year-old man developed Stanford-A-type acute aortic dissection and underwent an emergent replacement of the aortic root and arch. After the weaning from cardiopulmonary bypass, his left femoral artery was found non-pulsatile, probably due to extension of the aortic dissection, and femoro-femoral artery bypass surgery was added. Estimated ischemia time of the lower extremities was 7 hours. On admission to the intensive care unit (ICU), his left lower extremity showed signs of reperfusion injury accompanied with marked elevation of serum creatine kinase (12,397 IU x l(-1)) and myoglobin (19,980 ng x ml(-1)), and impaired oxygenation (a ratio of PaO2 to FIO2, 130 mmHg). We performed (1) moderately aggressive infusion treatment, (2) maintenance of hyperdynamic states using catecholamine, (3) diuresis therapy using atrial natriuretic peptide and furosemide, and (4) lung protective strategy. Although serum creatinine increased to 2.0 mg x dl(-1) on postoperative day (POD) 1, diuresis was maintained and the level of creatinine returned to normal on POD 6. He was extubated on POD 6 and discharged on POD 7. The early start of these combined therapies seems to have prevented acute renal failure without blood purification.

Systemic opioids enhance the spread of sensory analgesia produced by intrathecal lidocaine. The effect of different doses of fentanyl and nalbuphine on the spread of spinal analgesia produced by lidocaine was studied in 68 patients undergoing transurethral resection of the prostate (TURP) under spinal anesthesia. Patients were randomly assigned to six groups: fentanyl A, B, or C (FA, FB, FC) or nalbuphine A, B, or C (NA, NB, NC), which received intravenous (i.v.) 50, 100, or 150 micrograms of fentanyl or 10, 15, or 20 mg of nalbuphine, respectively, 20 min after spinal anesthesia with lidocaine. We tested the level of spinal analgesia with pinprick sensation 20 min after spinal anesthesia and 10 min after the opioid administration, when 0.4 mg of naloxone was administered i.v. The levels of sensory analgesia were reassessed 10 min after naloxone. Ten minutes after fentanyl or nalbuphine, the level of analgesia increased (1.8 +/- 1.7, 3.1 +/- 1.2, and 4.1 +/- 1.5 cm, in the FA, FB, and FC groups and 1.9 +/- 0.9, 2.6 +/- 1.4, and 3.7 +/- 2.2 cm in the NA, NB, and NC groups, respectively). The increases in the level of analgesia differed significantly between the fentanyl groups (F = 8.0939; df = 2.35; P < 0.001), the increase produced by 150 micrograms being significantly higher than produced by 50 micrograms of fentanyl (limits of confidence -4.236809 and -0.4431909; P < 0.01). Naloxone reversed the effect of fentanyl and 10 min after its administration the fentanyl groups did not differ with regard to the level of spinal analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Nodular prurigo associated with Hodgkin's disease. We report a case of prurigo nodularis of Hyde as the presenting sign of Hodgkin's disease in a 22-year-old girl. Though pruritus is a common symptom of Hodgkin's disease, prurigo nodularis has rarely been reported as a Hodgkin's symptom.

Mutual interactions between repeated flurothyl convulsions and electrical kindling. The interactions between repeated flurothyl seizures and electrical kindling induced from the neocortex or the amygdala were investigated. Three consecutive flurothyl-induced convulsions enhanced the rate of development of subsequent electrical kindling from the neocortex. Similarly multiple (more than 15) generalized kindled seizures, induced from either the neocortex or the amygdala, reduced the latency of onset of flurothyl seizures with repeated exposures producing a 'kindling-like' effect for flurothyl. These results indicate that eventually seizures will beget seizures independently of the site of origination of the seizures.

Three-dimensional nonequilibrium Potts systems with magnetic friction. We study the nonequilibrium steady states that emerge when two interacting three-dimensional Potts blocks slide on each other. As at equilibrium the Potts model exhibits different types of phase transitions for different numbers q of spin states, we consider the following three cases: q=2 (i.e., the Ising case), q=3, and q=9, which at equilibrium yield, respectively, a second-order phase transition, a weak first-order transition, and a strong first-order transition. In our study we focus on the anisotropic character of the steady states that result from the relative motion and discuss the change in finite-size signatures when changing the number q of spin states.

Comparison of a TaqMan real-time polymerase chain reaction assay with a loop-mediated isothermal amplification assay for detection of Gallid herpesvirus 1. A TaqMan real-time polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) assay were developed to detect Gallid herpesvirus 1 (GaHV-1, formerly Infectious laryngotracheitis virus). The standard curve of real-time PCR was established, and the sensitivity reached 10 copies/μl. In the current study, the conversion between viral titer and GaHV-1 genomic copy number was constructed. Six primers for LAMP assay amplified target gene at 65°C within 45 min, and the detection limit was 60 copies/μl. The 6 primers were highly specific, sensitive, and reproducible for detection of GaHV-1. Although the sensitivity of LAMP was lower than that of real-time PCR, LAMP was faster, less expensive, and did not require a thermocycler. The LAMP assay would be a viable alternative assay in diagnostic laboratories that do not employ real-time PCR technology.

Genetic diversity in porcine Oesophagostomum dentatum and O. quadrispinulatum and their delineation by isoenzyme analysis. The genetic diversity in eight strains of Oesophagostomum dentatum and O. quadrispinulatum was investigated by the electrophoresis study of ten enzyme systems. The loci Idh-2, Fbp, Sdh, and Pgm were found to be diagnostic between the species examined. Both the proportion of fixed allelic differences (26.3%) and the genetic distance coefficient (D = 0.54) are well above the range for differentiation of valid species. Isoenzyme patterns of susceptible and resistant lines of O. dentatum showed at polymorphic loci a reduced genetic heterogeneity in the latter group. No qualitative difference in terms of the presence/absence of alleles was observed among susceptible and resistant isolates with the enzymes studied. The detection of one possible hybrid indicates that introgression in O. dentatum and O. quadrispinuatum may occur.

Advancing Hospice and Palliative Care Social Work Leadership in Interprofessional Education and Practice. The importance of interprofessional collaboration in achieving high quality outcomes, improving patient quality of life, and decreasing costs has been growing significantly in health care. Palliative care has been viewed as an exemplary model of interprofessional care delivery, yet best practices in both interprofessional education (IPE) and interprofessional practice (IPP) in the field are still developing. So, too, is the leadership of hospice and palliative care social workers within IPE and IPP. Generating evidence regarding best practices that can prepare social work professionals for collaborative practice is essential. Lessons learned from practice experiences of social workers working in hospice and palliative care can inform educational efforts of all professionals. The emergence of interprofessional education and competencies is a development that is relevant to social work practice in this field. Opportunities for hospice and palliative social workers to demonstrate leadership in IPE and IPP are presented in this article.

Differential relationship between the carbon chain length of jet fuel aliphatic hydrocarbons and their ability to induce cytotoxicity vs. interleukin-8 release in human epidermal keratinocytes. Jet fuels are complex mixtures of hydrocarbons known to cause dermal toxicity and to increase the release of proinflammatory cytokines by human epidermal keratinocytes (HEK). However, the dermatotoxic effects of individual hydrocarbons remain unclear. Since aliphatic hydrocarbons make up more than 80% of the hydrocarbons formulated in jet fuels, the objective of this study was to assess acute cytotoxicity and IL-8 release induced by individual aliphatic hydrocarbons without a vehicle. Ten aliphatic hydrocarbons with carbon (C) chain lengths ranging from 6 to 16 were dosed neat on HEK grown on 96-well plates. Acute exposure (1, 5, and 15 min) to aliphatic hydrocarbons significantly increased HEK mortality such that the increase in cytotoxicity corresponded with the decrease in carbon chain length. Extended exposure time did not increase cytotoxicity significantly until 15 min of exposure by short-chain hydrocarbons (C < or = 11). There were differences between the aliphatic hydrocarbons with respect to their effects on IL-8 release. IL-8 concentration was increased significantly by 3- to 10-fold, with the highest increase found after exposure to hydrocarbons in the C9-C13 range. These studies indicated that individual aliphatic hydrocarbons are toxic to HEK cells and are capable of inducing proinflammatory cytokines. Higher cytotoxicity by shorter-chain aliphatic hydrocarbons did not correlate to increased ability to stimulate IL-8 release, which peaked at mid-chain lengths, suggesting a different structure-activity relationship for these two toxicological endpoints in keratinocyte cell cultures.

A study of sexual variation in Indian femur. Assessment of sex from femoral dimensions have been tried before in several populations. Studies conducted so far have demonstrated that populations differ from one another in size and proportion. Therefore, the discriminant formulae developed for determining sex for one population group cannot be applied on another. As to date no detailed study of femur on the subject has been reported from India, an attempt has been made in the present study to examine the sexual dimorphism in femur of Indian origin using 124 femora from central India. Eleven standard dimensions were measured on the bones. The data were analysed using discriminant function procedures and the results of different measurements are reported independently and in various combinations. Maximum head diameter alone could correctly assign sex to 92.5% of males and 95.5% of females. Evaluation of the discriminating ability of the variables selected in stepwise analysis are then conducted using cross validation procedure. To understand the population variation, the discriminant formula derived from Thai, Chinese, South African white, American black and white were applied on the present sample. The comparison indicated that Indians have very different dimension from South African whites and American whites. Their dimensions are more closer to Thais and Chinese but in no way identical to them.

Prognosis of patients with diabetes mellitus after endarterectomy of the femoral artery. The perioperative prognosis of 81 diabetic patients after endarterectomy of the femoral artery was analyzed by a computer program and compared to the prognosis of a control group of 83 nondiabetic patients. The percentage of female patients in the group with diabetes mellitus was 22% in comparison with 8% of the control group. Most of the diabetic patients in clinical degree II/III were approximately 10 years younger at the time of operation than the patients of the control group. Cardiac complications occurred in 16% of the diabetic patients and in 1% of the nondiabetic patients. The hospital mortality in the group with diabetes mellitus was 14%, significantly higher than the 6% mortality among patients of the control group (x2 = 4.26). Clinical evaluation of the patients in both groups showed that the patency rate of the reconstructed vessels was 80%.

Drug-specific T cells in an HIV-positive patient with nevirapine-induced hepatitis. Nevirapine is associated with idiosyncratic reactions such as skin rash, hepatitis and hypersensitivity syndrome, which have the hallmarks of being immune mediated. However, there is little laboratory evidence to support an immune pathogenesis. A HIV-positive individual who developed hepatitis within 6 weeks of starting nevirapine, in the absence of any cutaneous manifestations, is described. Other causes of hepatitis were excluded, and the patients liver function normalized on withdrawal of nevirapine. Lymphocytes from the patient, and six individuals with HIV who were on nevirapine without adverse effects, were exposed to nevirapine and its metabolites, and lymphocyte proliferation assessed by 3H-thymidine incorporation on day 5. The T cells taken from the nevirapine-hypersensitive patient proliferated in the presence of nevirapine with a stimulation index of greater than 2. There was no proliferation with nevirapine metabolites. T cells taken from HIV-positive control individuals showed no proliferation with either nevirapine or its metabolites. The results from our patient suggest that T cells may be involved in the pathogenesis of nevirapine-induced hepatitis. Larger numbers of patients need to be studied to fully evaluate the role of T cells in nevirapine-induced hepatitis and nevirapine hypersensitivity syndrome.

Experimental confirmation of transformation pathways between inverse double diamond and gyroid cubic phases. A macroscopically oriented double diamond inverse bicontinuous cubic phase (QII(D)) of the lipid glycerol monooleate is reversibly converted into a gyroid phase (QII(G)). The initial QII(D) phase is prepared in the form of a film coating the inside of a capillary, deposited under flow, which produces a sample uniaxially oriented with a ⟨110⟩ axis parallel to the symmetry axis of the sample. A transformation is induced by replacing the water within the capillary tube with a solution of poly(ethylene glycol), which draws water out of the QII(D) sample by osmotic stress. This converts the QII(D) phase into a QII(G) phase with two coexisting orientations, with the ⟨100⟩ and ⟨111⟩ axes parallel to the symmetry axis, as demonstrated by small-angle X-ray scattering. The process can then be reversed, to recover the initial orientation of QII(D) phase. The epitaxial relation between the two oriented mesophases is consistent with topology-preserving geometric pathways that have previously been hypothesized for the transformation. Furthermore, this has implications for the production of macroscopically oriented QII(G) phases, in particular with applications as nanomaterial templates.

Absence of specific IgE antibodies in allergic contact sensitivity to formaldehyde. Immunologic reactions are customarily divided into two broad categories, cell-mediated and antibody-mediated. An interplay between these two pathogenetic principles is indicated by reactions such as cutaneous basophil hypersensitivity, late-phase reaction, and cutaneous lesions indistinguishable from regular allergic contact dermatitis lesions after sensitization with IgE antibodies against certain haptens. In the present study, 23 patients with a history of a positive epicutaneous test to formaldehyde participated. On retest, 15 showed a positive reaction. Eight patients were Phadiatop positive, indicating an atopic diathesis, and eight had a history of or ongoing atopic dermatitis. On RAST test, only two, nonatopic patients had specific IgE antibodies to formaldehyde. In the cellular infiltrates of biopsies from epicutaneous test sites, cells reactive with monoclonal antibodies against IgE were found in positive and negative formalin tests, both in atopics and nonatopics, as well as in control biopsies from nonlesional skin. Double immunofluorescence staining experiments showed that IgE occurred on Langerhans' cells. The proportion of IgE-positive cells correlated to the level of serum IgE, but not to atopy. These cells were also found both in the epidermis and in the dermis in nonatopic patients. ICAM-1 occurred on keratinocytes in all patient groups. This study does not support the hypothesis that specific IgE antibodies are active in the pathogenesis of contact sensitivity to formaldehyde either in atopic or in nonatopic patients.

Small cause, large effect: Structural characterization of cutinases from Thermobifida cellulosilytica. We have investigated the structures of two native cutinases from Thermobifida cellulosilytica, namely Thc_Cut1 and Thc_Cut2 as well as of two variants, Thc_Cut2_DM (Thc_Cut2_ Arg29Asn_Ala30Val) and Thc_Cut2_TM (Thc_Cut2_Arg19Ser_Arg29Asn_Ala30Val). The four enzymes showed different activities towards the aliphatic polyester poly(lactic acid) (PLLA). The crystal structures of the four enzymes were successfully solved and in combination with Small Angle X-Ray Scattering (SAXS) the structural features responsible for the selectivity difference were elucidated. Analysis of the crystal structures did not indicate significant conformational differences among the different cutinases. However, the distinctive SAXS scattering data collected from the enzymes in solution indicated a remarkable surface charge difference. The difference in the electrostatic and hydrophobic surface properties could explain potential alternative binding modes of the four cutinases on PLLA explaining their distinct activities. Biotechnol. Bioeng. 2017;114: 2481-2488. © 2017 Wiley Periodicals, Inc.

Diversity-Oriented Approach Toward the Syntheses of Amaryllidaceae Alkaloids via a Common Chiral Synthon. Functionalized hydroindole (1), a common chiral synthon, for versatile transformations to synthesize a broad range of Amaryllidaceae alkaloids (AAs) including (-)-crinine, (-)-crinane, (-)-amabiline, (+)-mesembrine, (-)-maritidine, (-)-oxomaritidine, and (+)-mesembrane is reported. Scaffold 1 is found as a prime structural motif in a wide variety of the AAs and is a novel synthon toward designing a divergent route for the synthesis of these natural products. This is established in a few steps, starting from a chiral aza-bicyclo-heptene sulfone scaffold (2) via conjugate addition and concomitant stereoselective ring opening with allylmagnesium bromide, a key step that generates a crucial quaternary stereocenter, fixing the stereochemistry of the rest of the molecule at an early stage. One carbon truncation followed by intramolecular reductive amination led to the desired core 1 in a multigram scale.

Prolonged maturation and enhanced transduction of dendritic cells migrated from human skin explants after in situ delivery of CD40-targeted adenoviral vectors. Therapeutic tumor vaccination with viral vectors or naked DNA, carrying the genetic code for tumor-associated Ags, critically depends on the in vivo transduction of dendritic cells (DC). Transfection of predominantly nonprofessional APC and only small numbers of DC may hamper proper T cell activation. Aim of this study was, therefore, the targeted, selective, and enhanced in situ transduction of DC. A human skin explant model was used to explore targeted transduction of cutaneous DC after intradermal injection of a bispecific Ab conjugate to link adenoviral (Ad) vectors directly to CD40 on the DC surface. A significantly enhanced transduction efficiency and selectivity, and an increased activation state of migrating DC were thus achieved. Moreover, DC transduced by CD40-targeted Ad maintained their Ag-specific CTL-stimulatory ability for up to 1 wk after the start of migration, in contrast to DC transduced by untargeted Ad, which had lost this capacity by that time. Because DC targeting in vivo might obviate the need for the in vitro culture of autologous DC for adoptive transfer, CD40-targeted Ad vectors constitute a promising new vaccine modality for tumor immunotherapy.

Hospital case volume is associated with mortality in patients hospitalized with subarachnoid hemorrhage. Prior studies have suggested that hospital case volume may be associated with improved outcomes after subarachnoid hemorrhage (SAH), but contemporary national data are limited. To assess the association between hospital case volume for SAH and in-hospital mortality. Using the Get With The Guidelines-Stroke registry, we analyzed patients with a discharge diagnosis of SAH between April 2003 and March 2012. We assessed the association of annual SAH case volume with in-hospital mortality by using multivariable logistic regression adjusting for relevant patient, hospital, and geographic characteristics. Among 31,973 patients with SAH from 685 hospitals, the median annual case volume per hospital was 8.5 (25th-75th percentile, 6.7-12.9) patients. Mean in-hospital mortality was 25.7%, but was lower with increasing annual SAH volume: 29.5% in quartile 1 (range, 4-6.6), 27.0% in quartile 2 (range, 6.7-8.5), 24.1% in quartile 3 (range, 8.5-12.7), and 22.1% in quartile 4 (range, 12.9-94.5). Adjusting for patient and hospital characteristics, hospital SAH volume was independently associated with in-hospital mortality (adjusted odds ratio 0.79 for quartile 4 vs 1, 95% confidence interval, 0.67-0.92). The quartile of SAH volume also was associated with length of stay but not with discharge home or independent ambulatory status. In a large nationwide registry, we observed that patients treated at hospitals with higher volumes of SAH patients have lower in-hospital mortality, independent of patient and hospital characteristics. Our data suggest that experienced centers may provide more optimized care for SAH patients.

Kainic acid-mediated upregulation of matrix metalloproteinase-9 promotes retinal degeneration. Excitotoxicity has been proposed to play a pivotal role in retinal damage, but the mechanisms that underlie retinal damage are not clearly understood. In this study, the role of matrix metalloproteinases in excitotoxin-mediated retinal damage was investigated. KA, CNQX (6-cyano-7-nitroquinoxaline-2,3,-dione), NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline), MK801, or PBS was injected into the vitreous of CD-1 mice. MMP expression in the retina was analyzed by zymography, Western blot, and immunohistochemistry. Retinal ganglion cells (RGCs) were retrogradely labeled with aminostilbamidine methanesulfonate (Molecular Probes, Eugene, OR), and loss of fluorescently labeled RGCs in retinal flatmounts was quantified. Apoptotic cell death was assessed by TUNEL staining. Astrocyte activation was determined by immunohistochemistry, and laminin decrease was determined by immunohistochemistry and Western blot analysis. Intravitreal injection of KA caused time- and dose-related MMP-9 upregulation in the retina. Increased MMP-9 activity and protein levels were associated with activation of astrocytes. Astrocyte-associated MMP-9 correlated with a decrease in laminin immunoreactivity in the ganglion cell layer and significant loss of retinal ganglion cells. KA-mediated upregulation of MMP-9 activity was associated with apoptosis of cells in the ganglion cell layer as early as 6 hours after injection, followed by apoptosis in cells in the inner nuclear layer by day 1. Intravitreal injection of the non-NMDA receptor antagonists, CNQX and NBQX decreased KA-induced MMP-9 activity and protein levels in the retina and attenuated retinal degeneration, whereas the NMDA receptor antagonist MK801 failed to offer protection. Further, a synthetic MMP inhibitor GM6001 decreased KA-mediated MMP-9 activity and offered significant protection against ganglion cell loss in the retina. These results indicate that KA-mediated upregulation of MMP-9 activity promotes retinal degeneration and suggest that inhibition of KA-mediated MMP activity may offer protection against excitotoxin-induced retinal damage.

Biotechnology of health-promoting bacteria. Over the last decade, there has been an increasing scientific and public interest in bacteria that may positively contribute to human gut health and well-being. This interest is reflected by the ever-increasing number of developed functional food products containing health-promoting bacteria and reaching the market place as well as by the growing revenue and profits of notably bacterial supplements worldwide. Traditionally, the origin of probiotic-marketed bacteria was limited to a rather small number of bacterial species that mostly belong to lactic acid bacteria and bifidobacteria. Intensifying research efforts on the human gut microbiome offered novel insights into the role of human gut microbiota in health and disease, while also providing a deep and increasingly comprehensive understanding of the bacterial communities present in this complex ecosystem and their interactions with the gut-liver-brain axis. This resulted in rational and systematic approaches to select novel health-promoting bacteria or to engineer existing bacteria with enhanced probiotic properties. In parallel, the field of gut microbiomics developed into a fertile framework for the identification, isolation and characterization of a phylogenetically diverse array of health-promoting bacterial species, also called next-generation therapeutic bacteria. The present review will address these developments with specific attention for the selection and improvement of a selected number of health-promoting bacterial species and strains that are extensively studied or hold promise for future food or pharma product development.

Predictive performance of a gentamicin population pharmacokinetic model in two western populations of critically ill patients. External validation of population pharmacokinetic (PK) models is warranted before they can be clinically applied to aid in antibiotic dose selection. The primary objective of this study was to assess the predictive performance of a gentamicin population PK model in intensive care unit (ICU) patients in two independent western populations of critically ill patients. Data were collected from the ICU where the model was developed (Academic Medical Centre, Amsterdam [AMC]) and from the Centre Hospitalier Universitaire de Nîmes (CHU Nîmes). Primary endpoints were bias and accuracy. The model was regarded as valid if bias was not significantly different from 0 and accuracy was equal to or less than 2.5 mg/L. Non-linear mixed-effects modelling (NONMEM) was used for data analysis. The AMC validation dataset consisted of 192 samples from 66 ICU patients and the CHU Nîmes dataset of 230 gentamicin samples from 50 ICU patients. The structural model predicted the gentamicin plasma concentrations in the AMC population with a non-significant bias (0.35, 95%CI: -0.11-0.81) and a sufficient accuracy of 2.5 mg/L (95%CI: 2.3-2.8). The gentamicin plasma concentrations were overpredicted in the CHU Nîmes population with a significant bias of 4.8 mg/L (95%CI: 4.00-5.62) and an accuracy of 5.5 mg/L (95%CI: 4.7-6.2). The model is valid for use in the AMC ICU population but not in the CHU Nîmes ICU population. This illustrates that caution is needed when using a population PK model in an external population.

Magnetic field-induced dissipation-free state in superconducting nanostructures. A superconductor in a magnetic field acquires a finite electrical resistance caused by vortex motion. A quest to immobilize vortices and recover zero resistance at high fields made intense studies of vortex pinning one of the mainstreams of superconducting research. Yet, the decades of efforts resulted in a realization that even promising nanostructures, utilizing vortex matching, cannot withstand high vortex density at large magnetic fields. Here, we report a giant reentrance of vortex pinning induced by increasing magnetic field in a W-based nanowire and a TiN-perforated film densely populated with vortices. We find an extended range of zero resistance with vortex motion arrested by self-induced collective traps. The latter emerge due to order parameter suppression by vortices confined in narrow constrictions by surface superconductivity. Our findings show that geometric restrictions can radically change magnetic properties of superconductors and reverse detrimental effects of magnetic field.

Absorbed in the task: Personality measures predict engagement during task performance as tracked by error negativity and asymmetrical frontal activity. We hypothesized that interactions between traits and context predict task engagement, as measured by the amplitude of the error-related negativity (ERN), performance, and relative frontal activity asymmetry (RFA). In Study 1, we found that drive for reward, absorption, and constraint independently predicted self-reported persistence. We hypothesized that, during a prolonged monotonous task, absorption would predict initial ERN amplitudes, constraint would delay declines in ERN amplitudes and deterioration of performance, and drive for reward would predict left RFA when a reward could be obtained. Study 2, employing EEG recordings, confirmed our predictions. The results showed that most traits that have in previous research been related to ERN amplitudes have a relationship with the motivational trait persistence in common. In addition, trait-context combinations that are likely associated with increased engagement predict larger ERN amplitudes and RFA. Together, these results support the hypothesis that engagement may be a common underlying factor predicting ERN amplitude.

Profile of People Who Inject Drugs in Tehran, Iran. The marked shift in the patterns of drug use in Iran, from opium smoking to injecting drug use, has led to serious health-related outcomes. This study was designed to explore characteristics of people who inject drugs (PWID) in Tehran, Iran. Nine hundred and four PWID were recruited from treatment and harm reduction facilities, as well as drug user hangouts in public areas in Tehran. Participants were interviewed using the Persian version of the World Health Organization Drug Injecting Study Phase II questionnaire. The median age at the time of the first illegal drug use, at the time of the first injection and current age was 20, 24 and 32, respectively. In more than 80% of the cases, the first drug used was opium. The transition from the first drug use to the first drug injection occurred after an average of 6.6 and 2.7 years for those who had started drug use with opium and heroin, respectively. Two-thirds of the participants shared injecting equipment within the last 6 months. Difficulty in obtaining sterile needles and thehigh cost of syringes were reported as the major reasons for needle/syringe sharing. Approximately 80% of community-recruited PWID reported difficulties in using treatment or harm reduction services. Self-detoxification and forced detoxification were the most common types of drug abuse treatment in alifetime. Despite a dramatic shift in drug policy in Iran during the past few years, wider coverage of harm reduction services, improvement of the quality of services, and education about such services are still necessary.

Polyphasic study of microbial communities of two Spanish farmhouse goats' milk cheeses from Sierra de Aracena. The microbial communities present in 2 different types of farmhouse goats' milk cheese from the Aracena mountains (southwest Spain), Quesailla Arochena (hard cheese) and Torta Arochena (soft cheese), have been studied using both culture-dependent and culture-independent techniques. All bacterial isolates were clustered by using randomly amplified polymorphic DNA (RAPD) and identified by 16S rRNA gene sequencing, species-specific PCR and multiplex PCR. Thus a total of 26 different species were identified, the majority belonging to the lactic-acid bacteria (LAB), mainly represented by Lactococcus lactis and Lactobacillus species such as Lactobacillus plantarum and Lactobacillus paracasei, together with a significant proportion of enterococci. Amongst the non-lactic-acid bacteria (NLAB), which represented 37% of the isolates in Torta Arochena, enterobacteria were the most important, Hafnia alvei and Serratia liquefaciens being the predominant species in Quesailla Arochena and Torta Arochena respectively. Moreover, RAPD analysis of the isolates revealed that most of the genotypes were specific to one of the cheeses, although a few genotypes common to both cheeses were found. The culture-independent study carried out by temporal-temperature-gradient gel electrophoresis (TTGE) with 2 target genes, rRNA 16S and rpoB, revealed less species diversity but L. lactis and Lb. plantarum were also predominant. Nevertheless, TTGE carried out using RNAr 16S also detected some organisms that had not been isolated by the culture-dependent method, such as Leuconostoc lactis and Mycoplasma agalactie in Quesailla Arochena. Although TTGE of the rpoB gene revealed less species diversity, it did lead to the detection of previously non-isolated species, such as Ln. lactis in Quesailla Arochena. Apart from this, the fingerprinting of Lactobacillus populations by length-heterogeneity PCR showed the predominance of the Lb. plantarum group, followed by Lactobacillus curvatus and, in smaller quantities, Lb. paracasei in Torta Arochena. From our results we may conclude that both types of methods complement each other and offer a more complete vision of the microbial diversity of these ecosystems.

Quantification of process measures in laparoscopic suturing. Process measures describing the generation of movement are useful for evaluation and performance feedback purposes. This study aimed to identify process measures that differ between novice and advanced laparoscopists while completing a suturing skill. A group of junior and a group of senior residents and fellows in surgery (n = 6) placed 10 laparoscopic sutures in a synthetic model. Process measures were quantified using an opto-electric motion/force sensor assembly that recorded: instrument rotation, applied forces, time, and time delays between force application and instrument rotation. Advanced trainees showed increased instrument rotation, higher peak applied force, and faster performance compared to novices (alll p < .01). However, over trials, only novices showed adaptations for instrument rotation and total time (interactions at p < .01) with no adaptation for the force application. The difference between the moments of force application and instrument rotation was not sensitive to participant training. Movement process measures can enhance our understanding of early adaptation processes and how such factors might be used as feedback to facilitate skill acquisition.

Terminal deletion of the long arm of chromosome 2 in a premature infant with karyotype: 46,XY,del(2)(q37). We present a premature newborn boy with multiple congenital anomalies, including craniofacial anomalies, syndactyly, cardiac defects, and a horseshoe kidney associated with terminal deletion of 2q. The infant's karyotype was 46,XY,del(2)(q37). Clinical, cytogenetic, and autopsy findings are presented in this report. Clinical manifestations in this infant are compared with those four other known patients with terminal deletion of chromosome 2.

The relationship between color discrimination and visual acuity in senile macular degeneration. The course of ocular disease can be monitored by the assessment and measurement of a number of visual functions. In the clinical situation, visual acuity and color discrimination are obvious and simple functions to assess. The relationship between color vision and visual acuity in eye disease has generally been discussed only in qualitative terms. This paper examines the correlation between visual acuity and color discrimination for a number of subjects exhibiting varying degrees of severity of senile macular degeneration.

Possible involvement of transglutaminase in endocytosis and antigen presentation. Experiments were carried out to determine as to whether or not internalization of antigen is necessary for subsequent antigen presentation by accessory cells using monoamines which are known as transglutaminase (TGase) inhibitors. It was found that endocytosis for immune complexes via Fc receptors such as sheep erythrocytes coated with IgG class antibody (EA) was different from receptor-independent endocytosis for soluble protein such as horse radish peroxidase (HRP) in the sensitivity to monoamines; methylamine inhibited the receptor-dependent endocytosis of immune complexes at a concentration of over 20 mM and the receptor-independent endocytosis of HRP at 2 mM, while dansylcadaverine (DC) inhibited both at a concentration of 100 microM. It was noteworthy that antigen-specific T cell proliferation to splenic adherent cells pulsed with DNP9.6-ovalbumin (DNP9.6-OVA) was blocked strongly by DC as well, but weakly by methylamine. These results suggest the possibility that antigen presentation requires internalization of antigen by a mechanism such as receptor-dependent endocytosis for the subsequent reexpression of antigen on membranes. Furthermore, it was confirmed that TGase activity is high in peritoneal exudate and spleen adherent cells, both of which have accessory cell activities for lymphocytes, suggesting the possibility that TGase might be involved intimately in receptor-dependent endocytosis and subsequent antigen presentation.

Quantitative flow ratio virtual stenting and post stenting correlations to post stenting fractional flow reserve measurements from the DOCTORS (Does Optical Coherence Tomography Optimize Results of Stenting) study population. We sought to evaluate the correlations of pre-PCI QFR analysis with virtual PCI called residual QFR and post-PCI QFR compared to post-PCI FFR. Quantitative flow ratio (QFR) is a computation of fractional flow reserve (FFR) based on angiography without use of a pressure wire. The ability to evaluate post-PCI FFR using pre-PCI QFR analysis with a virtual PCI and the correlation between post-PCI QFR compared to post-PCI FFR remains unknown. From the DOCTORS (Does Optical Coherence Tomography Optimize Results of Stenting) study population, we blindly analyzed residual QFR and post-PCI QFR from angiographies and compared them to post-PCI FFR. Ninety-three post-PCI QFR measurements and 84 pre-PCI residual QFR measurements were compared to post-PCI FFR measurements. No significant difference were observed between mean post-PCI FFR value (0.92 ± 0.05) compared to mean residual (0.93 ± 0.05) QFR and between mean post-PCI FFR value compared to mean post-PCI QFR values were (0.93 ± 0.05) (p > .05 for both). The correlation coefficient of residual QFR with post-PCI FFR was 0.68 (95% CI: 0.53-0.78) and the correlation coefficient of post-PCI-QFR with post-PCI FFR was 0.79 (95% CI: 0.70-0.86). Residual QFR corresponding to pre-PCI QFR analysis with virtual PCI, and post-PCI QFR analysis, correlated well with post-PCI FFR. Further studies are needed to prospectively validate a QFR-guided PCI strategy.

Myocardial perfusion reserve quantified by cardiac magnetic resonance imaging is associated with late gadolinium enhancement in hypertrophic cardiomyopathy. Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) imaging has demonstrated the capability of stratifying hypertrophic cardiomyopathy (HCM). Stress perfusion test of CMR can quantify myocardial perfusion reserve (MPR), but its clinical role is not determined. The purpose of this study was to investigate the relationship between MPR and LGE in patients with HCM. A total of 61 consecutive cases underwent complete evaluation with electrocardiography and CMR [cine imaging, coronary MR angiography (MRA), and stress perfusion testing with LGE]. HCM cases were diagnosed by the Japanese conventional guideline prior to this CMR study. Mild LVH was defined as more than 13 mm in maximum LV wall thickness at end diastole on the cine imaging of the CMR. MPR was calculated as the ratio of stress/rest myocardial blood flow using an intensity curve on the stress perfusion test. Cases with ischemic heart disease were excluded from the study based on clinical history and coronary MRA. There were 37 HCM and 24 mild LVH cases (average age: 60.5 ± 10.9 vs. 64.8 ± 10.8; male: 62.2 vs. 75.0%, respectively, non-significant). MPR in HCM was lower than in LVH (1.5 ± 0.5 vs. 2.2 ± 0.9, p < 0.001) and normal subjects (2.4 ± 0.9, p < 0.001). MPR in HCM with LGE (N = 34) was lower than in HCM without LGE (N = 3) (1.4 ± 0.5 vs. 2.1 ± 0.2, p = 0.014). Multiple regression analysis verified that LGE was the strongest predictor of MPR among multiple clinical parameters, including LVH, LV dysfunction (ejection fraction < 50%), and the presence of negative T wave (p < 0.001). MPR was impaired in HCM with LGE compared with HCM without LGE. The clinical role of MPR on CMR needs to be clarified by further research.

How dentists account for social responsibility: economic imperatives and professional obligations. This study explores how dentists explain the concept of social responsibility and its relationship to issues affecting access to oral health care by vulnerable segments of the population. Analysis of open-ended interviews with thirty-four dentists, including dental educators, and administrators and officials of dental public health programs in Canada and the United States revealed that four main themes-economics, professionalism, individual choice, and politics-influenced the respondents' sense of social responsibility in dentistry. There was a belief that social responsibility in dentistry is dominated by economic imperatives that impact negatively on the policies and practices directing access to care. Yet, despite the highly critical stance on dentistry as a business, there was practical recognition of the economic realities of dental practice. Nevertheless, those who focused on social responsibility as a professional obligation highlighted the privileges of self-governance along with the accompanying duty to serve the welfare of everyone and not just those who are socioeconomically advantaged.

Heralding two-photon and four-photon path entanglement on a chip. Generating quantum entanglement is not only an important scientific endeavor, but will be essential to realizing quantum-enhanced technologies, in particular, quantum-enhanced measurements with precision beyond classical limits. We investigate the heralded generation of multiphoton entanglement for quantum metrology using a reconfigurable integrated waveguide device in which projective measurement of auxiliary photons heralds the generation of path-entangled states. We use four and six-photon inputs, to analyze the heralding process of two- and four-photon NOON states-a superposition of N photons in two paths, capable of enabling phase supersensitive measurements at the Heisenberg limit. Realistic devices will include imperfections; as part of the heralded state preparation, we demonstrate phase superresolution within our chip with a state that is more robust to photon loss.

Literature review of outcome parameters used in studies of Geriatric Fracture Centers. A variety of multidisciplinary treatment models have been described to improve outcome after osteoporotic hip fractures. There is a tendency toward better outcomes after implementation of the most sophisticated model with a shared leadership for orthopedic surgeons and geriatricians; the Geriatric Fracture Center. The purpose of this review is to evaluate the use of outcome parameters in published literature on the Geriatric Fracture Center evaluation studies. A literature search was performed using Medline and the Cochrane Library to identify Geriatric Fracture Center evaluation studies. The outcome parameters used in the included studies were evaluated. A total of 16 outcome parameters were used in 11 studies to evaluate patient outcome in 8 different Geriatric Fracture Centers. Two of these outcome parameters are patient-reported outcome measures and 14 outcome parameters were objective measures. In-hospital mortality, length of stay, time to surgery, place of residence and complication rate are the most frequently used outcome parameters. The patient-reported outcomes included activities of daily living and mobility scores. There is a need for generally agreed upon outcome measures to facilitate comparison of different care models.

Impact of asepsis technique on implant success. A review. Asepsis is described as a state free from microorganisms. In medicine, an aseptic environment is necessary and expected to avoid the spread of infection through contact between persons, sprays and splashes, inhalation, and sharps. Most dental procedures are performed in a "clean "environment with the common use of personal protective equipment (PPE) such as disposable gloves, masks and protective eyewear with disinfection of surfaces and sterilization of instruments. For surgical procedure such as the insertion of endosseous implants, the recommendations are not clear. The use of antimicrobials and antibiotics before and after the procedure remains a controversial issue The purpose of this literature review is to evaluate the current evidence as to what is generally expected and widely accepted in the use of aseptic techniques for the surgical placement of endosseous implants, and the impact on implant survival and overall success.

Vesicular Langerhans cell histiocytosis--an uncommon variant. A case of the congenital self-healing reticulohistiocytosis variant of Langerhans cell histiocytosis is described. The child was born with a widespread blistering eruption, which rapidly resolved leaving papules and erosions. These ultimately healed leaving anetoderma. Congenital self-healing reticulohistiocytosis should be considered in the differential diagnosis of blistering eruptions present at birth.

Dysautonomia and ventricular dysfunction in the indeterminate form of Chagas disease. The associations between autonomic function and biventricular function in patients with the indeterminate form of Chagas disease remains to be elucidated. In 42 asymptomatic patients and 19 healthy volunteers, the autonomic function was assessed by time domain indices of heart rate variability (HRV), analyzed for 24 h; the right ventricular function was assessed by fraction area change, right ventricle shortening, and systolic excursion of the tricuspid valve; and the left ventricular function was assessed by ejection fraction and transmitral flow velocities. Data were expressed as mean+/-SD or medians (including the lower quartile and upper quartile). Groups were compared by Student's t or Mann-Whitney U test. Autonomic and ventricular function were correlated by Pearson's or Spearman's correlation coefficient. The level of significance was 5%. Right and left ventricular systolic function indexes were comparable between groups. Transmitral flow velocities were decreased in the Chagas disease group (p<0.05). The patients presented impaired HRV as indicated by the values of SDNN-day (80 (64-99) ms vs. 98 (78-127) ms; p=0.045), SDNNI-24 h (54 (43-71) vs. 65 (54-105) ms; p=0.027), SDNNI-day (49 (42-64) vs. 67 (48-76) ms; p=0.045), pNN50-day (2.2 (0.7-5)% vs. 10 (3-11)%; p=0.033); and pNN50-24 h (3 (1-7)% vs. 12 (8-19)%; p=0.013). There were no correlations between the left ventricular diastolic indices and autonomic dysfunctional indices (p>0.05). Patients with the indeterminate form of Chagas disease have both dysautonomia and left ventricular diastolic dysfunction. However, the right ventricular function is preserved. Importantly, ventricular diastolic dysfunction and dysautonomia are independent phenomena.

Effects of organism preparation in metallothionein and metal analysis in marine invertebrates for biomonitoring marine pollution. Metallothionein (MT) is established as a potentially useful biomarker for monitoring aquatic pollution. This paper addresses widespread inconsistencies in storage conditions, tissue type selection and pre-treatment of samples before MT and metal analysis in biomarker studies. This variation hampers comparability and so the widespread implementation of this monitoring approach. Actively sampled Mytilus edulis in Southampton Water, UK were exposed to different storage temperatures, a variety of tissue types were analysed, and various pre-treatments of transportation on ice, transportation in seawater, depuration, and rapid dissection in the field were examined. Storage temperatures of -20 °C were found to be adequate for periods of at least ten weeks, as MT was not reduced by protein degradation compared with samples kept at -80 °C. Whole tissue and digestive gland concentrations of MT and metals were significantly positively correlated and directly relatable. MT in the digestive gland appeared to be more responsive to metals than in whole tissue, where it may be diluted, masking MT responses. However, longer study periods may suffer the effects of mass changes to the digestive gland, which alters MT concentration, and it may therefore be advisable to measure whole tissue. Depuration and transportation in seawater reduced both MT and metal concentrations in the digestive gland, and few correlations between MT and metals were identified for these treatments. It is therefore recommended that: i) samples are transported to the laboratory on ice and dissected as soon as possible thereafter, ii) depuration should not be used when examining MT response to metal exposure until further research clarifying its utility is reported, iii) either whole tissue or the digestive gland can be used to measure MT, though whole tissue may be preferable on long-term studies, and iv) organisms can be stored at -20 °C before analysis for up to ten weeks. These practices can be applied to future biomonitoring studies and will improve the comparability and repeatability of using MT as a biomarker.

Extent and determinants of cost of road traffic injuries in an Indian city. Studies aimed at estimating losses that are incurred as a result of road traffic injuries (RTIs), especially at the family level, are very limited. To ascertain the direct and productivity costs of road traffic injuries and their determinants. This study was a cross-sectional survey of all the road traffic crashes recorded by traffic police during 2004 in Chandigarh, a modern planned city of north India. All road traffic crashes recorded by the traffic police during the year 1st January to 31st December 2004 were included in the study. The houses of all the victims were visited. The direct costs included the immediate medical costs (i.e., emergency and hospital care, follow-up care, medicines and appliances, doctor bills, etc.), and nonmedical costs (transportation, property damage cost, etc.). Work productivity and activity questionnaire (WPAI-SHP), the health and labor questionnaire (HLQ) and Human Capital Method were used for estimating the productivity costs. Percentage, mean, standard deviation of the outcome parameters were calculated. Of the 121 crash victims listed, 95 agreed to participate in the study. The net direct costs incurred were Rs. 8,55,644 ($19,991). The vehicle repair costs constituted more than half of such cost. Surgery, which was conducted in 28 cases, constituted 14.5% of the direct costs. The total productivity cost incurred was Rs. 8,06,24,530 ($1,883,750). Costs incurred due to premature mortality constituted over 99% of these productivity losses suffered by society. Lost wages due to the crash constituted less than 1% [Rs. 1,40,230 ($3276)] of the total productivity loss. Road traffic injuries are a significant financial drag on the society. The productivity costs far outweigh the direct costs. Premature mortality, vehicle damage and medical costs constituted the major share of the cost of RTIs.

Recurrence of stroke caused by nocturnal hypoxia-induced blood pressure surge in a young adult male with severe obstructive sleep apnea syndrome. Obstructive sleep apnea syndrome (OSAS) causes resistant hypertension and a hypopnea-related nocturnal blood pressure (BP) surge. This could lead to an increase of not only the nocturnal BP level but also nocturnal BP variability, both of which increase an individual's cardiovascular risk. We recently developed a trigger sleep BP monitoring method that initiates BP measurement when an individual's oxygen desaturation falls below a variable threshold, and we demonstrated that it can detect a BP surge during apnea episodes. We here report the case of a 36-year-old man with severe OSAS who experienced the recurrence of stroke due to nocturnal hypoxia and a nocturnal BP surge measured by this trigger sleep BP monitoring device. A nocturnal BP surge during sleep in OSAS patients could be a strong trigger of cardiovascular events.

Evaluation of disability and handicap following injury. Disability and handicap outcome measures are fundamental components of trauma system evaluation. These outcomes are described for survivors of major trauma, attended by the HEMS, London system. Together with measures of injury severity, three functional instruments (Functional Independence Measure (FIM), Glasgow Outcome Scale (GOS) and return to pre-injury work status (RTW)) were used to measure outcome in 201 trauma patients. By 12 months post injury 84.1% of cases were independent in Motor FIM, 88.1% in Cognitive FIM, 79.1% had good outcomes in GOS (grades 4 and 5) and 69.2% had returned to work. The functional measures showed a statistically significant relationship with minor and major and trauma (ISS < 16 and > or = 16): FIM (motor p < 0.002; cognitive p < 0.0003), GOS (p < 0.002) and RTW (p < 0.002). Division according to severity of principal injury confirmed the greatest disability and handicap resulted from the severest injuries (AIS 4-5): 68.9% achieved independence in Motor FIM, 73% in Cognitive FIM and only 40% returned to work. When grouped according to body region of principal injury, neurological injury, particularly severe injury (AIS 4-5) to head and spinal cord regions showed the poorest outcomes. FIM, GOS and RTW are recommended as standard indicators of disability and handicap for trauma registries and outcome studies.

Gene therapy for diabetes mellitus in rats by intramuscular injection of lentivirus containing insulin gene. We assessed therapeutic potential of intramuscular insulin gene delivery in a diabetic murine model. The human proinsulin gene cDNA engineered with concensus furin cleavage sequences was inserted into an advanced lentiviral vector that contained CMV early promoter. After injection of concentrated lentiviral vector (3.5 microg p24 Gag antigen) carrying the insulin gene into the thigh muscle, treated rats demonstrated an increase in body weight, increased survivability, attenuated the hyperglycemic response as well as prevented the formation of ketoacidosis. For these reasons, the intraparenchymal injection of lentiviral vectors into the skeletal muscle to ectopically produce insulin may be an easy and therapeutic treatment modality for type 1 diabetes mellitus.

Impact of all-day physical activity on ventilatory perfusion coupling in patients undergoing cardiac resynchronization therapy. There is still little information about the cardiorespiratory effects of cardiac resynchronization therapy (CRT) in patients undergoing all-day physical activity. This study aimed to assess the effects of CRT on ventilatory perfusion coupling during submaximal exercise. Metabolic and hemodynamic parameters were obtained during treadmill exercise testing as well as during rest for each single-right (RV), -left (LV) and biventricular (BiV) pacing mode as well as during intrinsic conduction (VVI 30) in 37 patients. Only responders to CRT (>10% increase in cardiac output (CO) during BiV pacing; n = 27) were included into the evaluation. LV and BiV pacing increased systolic (144 +/- 25 and 142 +/- 28 vs. 118 +/- 29 mm Hg, p < 0.05) and mean blood pressure (108 +/- 19 and 109 +/- 19 vs. 94 +/- 25 mm Hg, p < 0.05) as well as CO (7.0 +/- 0.6 and 7.2 +/- 0.8 vs. 6.0 +/- 0.6 l/min, p < 0.05 and p < 0.01) during exercise as compared to VVI 30. Simultaneously, LV and BiV pacing decreased dead space ventilation (18 +/- 3 and 17 +/- 3 vs. 20 +/- 4, p < 0.01) and the ventilatory equivalent for oxygen (31 +/- 4 and 31 +/- 5 vs. 36 +/- 6; p < 0.05) compared to intrinsic conduction. The improvement in ventilatory efficacy during CRT, which is demonstrated by the decrease in the ventilatory equivalent for oxygen, results from an increase in CO and thus from a reduction in the ventilatory perfusion mismatch.

Detecting panic disorder in emergency department chest pain patients: a validated model to improve recognition. To develop and validate a detection model to improve the probability of recognizing panic disorder in patients consulting the emergency department for chest pain. Through logistic regression analysis, demographic, self-report psychological, and pain variables were explored as factors predictive of the presence of panic disorder in 180 consecutive patients consulting an emergency department with a chief complaint of chest pain. The detection model was then prospectively validated on a sample of 212 patients recruited following the same procedure. Panic-agoraphobia (Agoraphobia Cognitions Questionnaire, Mobility Inventory for Agoraphobia), chest pain quality (Short Form McGill Pain Questionnaire), pain loci, and gender variables were the best predictors of the presence of panic disorder. These variables correctly classified 84% of chest pain subjects in panic and non-panic disorder categories. Model properties: sensitivity 59%; specificity 93%; positive predictive power 75%; negative predictive power 87% at a panic disorder sample prevalence of 26%. The model correctly classified 73% of subjects in the validation phase. The scales in this model take approximately ten minutes to complete and score. It may improve upon current physician recognition of panic disorder in patients consulting for chest pain.

Vienna focus for Austrian ambitions. The Austrian Academy of Sciences has taken the bold step of closing a successful institute in Salzburg and opening two new ones in Vienna with the aim of creating an internationally attractive critical mass of biological research activity in the capital. Graham Tebb reports.

[Joint Infections Due to Streptococcus agalactiae in Non Immunocompromised Adults: Presentation of Two Cases]. Streptococcus agalactiae (S agalactiae) is a germ habitually associated with infections in neonates and women during the pregnancy and the immediate puerperiumum. S. agalactiae has also been related with bacteriemias, endocarditis and bone, joint, skin and soft tissues infections in adults with concomitant diseases and even in immunocompetent patients. In the last years more than 70 cases of septic arthritis in adults due to this germ have been communicated. We present two cases of axial and peripheral joint infection due to S. agalactiae, comparing finds, treatment and evolution with the cases published until April, 2008.

Changes in right ventricular function in neonates with hypoplastic left heart syndrome before and after the hybrid procedure. Decreased right ventricular function via deformation analysis has been noted in patients with hypoplastic left heart syndrome (HLHS) after the Norwood procedure. No data exist in HLHS patients undergoing the hybrid procedure. The goal of this study was to evaluate right ventricular functional changes in HLHS patients undergoing the hybrid procedure under steady-state conditions. Echocardiograms were prospectively obtained on patients with HLHS before and after the hybrid procedure. Fractional area change, tricuspid inflow velocities, tissue Doppler imaging (TDI), and deformation analysis were performed. Paired Wilcoxon's signed rank or Student's t-test was used for analysis. P < 0.05 was considered significant. Twenty HLHS patients were studied (10 males:10 females). Median age at the pre-hybrid echocardiogram was 3 (1-16) days, age at hybrid procedure was 5 (3-17) days, and age at post-hybrid echocardiogram was 10 (6-34). There were significant decreases in systolic function as measured by TDI and deformation analysis. There was no significant change in right ventricular fractional area change. Diastolic function was also noted to significantly decrease after the hybrid procedure. Systolic and diastolic functions decreased after the hybrid procedure despite the fact that patients avoided cardiopulmonary bypass. These results are comparable with previous reports in HLHS patients undergoing the Norwood procedure. Further studies are needed to determine if these echocardiographic changes have prognostic significance.

Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes. Mature adipocytes originate from fibroblast-like precursor cells, preadipocytes, which differentiate to obtain the characteristics of adipocytes. Our aim was to investigate how differentiation of human preadipocytes affects the distribution of insulin receptors (IR) and IGF-I receptors (IGF-IR) and other cell characteristics. Preadipocytes were differentiated using indomethacine, dexamethasone, isobutyl-methylxantine (IBMX) and high concentration of insulin. Gene expression was quantified by real-time RT-PCR in preadipocytes (PA), differentiated preadipocytes (dPA) and mature adipocytes (mAD). The amount of expressed receptor protein was analyzed using receptor specific ELISAs and Western blot. We also studied DNA synthesis with radiolabeled thymidine incorporation and glucose accumulation with radiolabeled glucose. Differentiation of PA increased gene expression of IR but not IGF-IR. GLUT4, growth hormone receptor (GHR) and adiponectin appeared or increased. In PA and dPA only IR-A was expressed whereas also IR-B was detected in mAD. By Western blot and ELISA, IR and IGF-IR were detected in PA, dPA and mAD. During differentiation the ratio of IR to IGF-IR increased severalfold. In PA both the IR and the IGF-IR was phosphorylated by their own ligand at 1 nM and in dPA the activation of both receptors was stimulated by IGF-I, but not insulin, at 1 nM. Accumulation of glucose in PA was increased by insulin at 10nM and by IGF-I at 1 nM and 10nM. DNA synthesis was increased by insulin and IGF-I at 10nM. In conclusion, both IR and IGF-IR are present in human preadipocytes and adipocytes. Differentiation is characterized by an increased IR/IGF-IR ratio.

Evolution of coauthorship networks: worldwide scientific production on leishmaniasis. Collaboration is one of the defining features of contemporary scientific research, and it is particularly important with regard to neglected diseases that primarily affect developing countries. The present study has identified publications on leishmaniasis in the Medline database from 1945 to 2010, analyzing them according to bibliometric indicators and statistics from social network analysis. Examining aspects such as scientific production, diachronic evolution, and collaboration and configuration of the research groups in the field, we have considered the different types of Leishmania studied and the institutional affiliation and nationality of the authors. Seven-hundred and thirty-five authors participate in 154 prominent research clusters or groups. Although the most predominant and consolidated collaborations are characterized by members from the same country studying the same type of Leishmania, there are also notable links between authors from different countries or who study different clinical strains of the disease. Brazil took the lead in this research, with numerous Brazilian researchers heading different clusters in the center of the collaboration network. Investigators from the USA, India, and European countries, such as France, Spain, the United Kingdom, and Italy, also stand out within the network. Research should be fostered in countries such as Bangladesh, Nepal, Sudan, and Ethiopia, where there is a high prevalence of different forms of the disease but limited research development with reference authors integrated into the collaboration networks.

Immunobiology of the gastrointestinal tract. The interplay between the gut and immune abnormality appears to be a logical extension of the thesis that secretory IgA is the major immunologic line of defense between the outside environment and the host. Thus immunologic deficiency, particularly of IgA and combined T- and B-lymphocyte abnormalites, profoundly influences gut integrity. Conversely, gut pathology is bound to interfere with immunologic function, so that both humoral and cellular immunity may be impaired. Finally, hypersensitivity phenomena in the gut, resulting in immune injury, may cause gastrointestinal disturbances. As better diagnostic tools have become available, more direct evidence of hypersensitivity immune injury has been described.

Heightened cocaine and food self-administration in female rats with neonatal isolation experience. Previously, we demonstrated that the early life stress of neonatal isolation facilitates acquisition of cocaine and food self-administration in adult female rats. We now test whether it enhances responding for these reinforcers after operant performance is established. Adult female rats were derived from litters that were either subjected to neonatal isolation (1 h/day isolation; postnatal days 2-9) or were nonhandled and assigned to one of two experiments. In Experiment 1, female rats well trained to self-administer cocaine were tested under a fixed-ratio 3 (FR3) schedule with several cocaine doses (0.0625-1.0 mg/kg/infusion) and under a progressive-ratio (PR) schedule (0, 0.5, and 1.0 mg/kg/infusion cocaine). In Experiment 2, female rats well trained to respond for food reinforcers under an FR15 schedule were tested under two PR schedules. Results show that neonatal isolation enhanced responding for cocaine under both schedules of reinforcement and increased responding for food under a PR schedule of reinforcement. These data extend our previous acquisition study in female rats to show that neonatal isolation enhances responding under maintenance conditions. These enduring behavioral changes may relate to the ability of neonatal isolation to increase striatal dopamine responses to psychostimulants, effects we showed previously in infant and juvenile rats. Neuropsychopharmacology (2006) 31, 70-76. doi:10.1038/sj.npp.1300779; published online 1 June 2005.

Late effects of radiation therapy in the treatment of Hodgkin's disease. In the last two decades, a considerable amount of clinical and experimental animal data has been accumulated regarding the tolerance of the major normal tissues and organs traversed by the radiation beams in treating Hodgkin's disease. Typically, the tolerance of several tissues and organs must be considered in designing the very large radiation portals such as the mantle. Today, sophisticated machinery such as computerized tomography scanners, simulators, computers, and linear accelerators are available to improve the radiation planning and treatment of Hodgkin's disease. In this paper, we discuss the late effects of radiation therapy to the lung, heart, thyroid, kidney, gastrointestinal tract, and the gonads of adults with Hodgkin's disease. Emphasis is placed on our recommendations for modifications of radiation technique to improve the complication-free cure rate.

Stem cell, biomaterials and growth factors therapy for hepatocellular carcinoma. Hepatocellular carcinoma is an antecedent of liver illnesses, including viral hepatitis, alcohol abuse, or metabolic disease. Transforming growth factor-Beta (TGF-b) plays an important role in creating a favorable microenvironment for tumor cell growth via two major mechanisms: an intrinsic activity as an autocrine growth factor and an extrinsic activity by inducing microenvironment changes. Recently stem cell therapy as also been a promising and potential treatment for liver cancer and in addition signaling pathways like GF/GFR systems, SDF-1α/CXC4 ligand receptor interaction and PI3K/Akt signaling, and cytokines has been identified to regulate cell fate decisions, and can be utilized to positively influence cell therapy outcomes. Thus stem cell-based therapy, together with signaling pathways can become a practical option in regenerative processes for replacing dead hepatocytes cells. Targeted drug delivery systems (TDDS) via biomaterials are presently been explored for cancer therapeutics especially liver cancer as it allows the enhancement of drug concentration in the liver and decrease the dosage and side effects. This review is intended to give a comprehensive summary of available liver cancer therapy using stem cells, growth factor and biomaterials.

Testing prototype products in the operating room. Historically, the discussion of which products to use in a hospital has centered around disposable versus reusable products; however, new technology has produced a line of products that are not only disposable but degradable. Perioperative staff members at Redmond Regional Medical Center, Rome, Ga, participated in the testing, evaluation, and use of these prototype products during their development.

Loss of spinal glycinergic neurons is not necessary for development of neuropathic pain in transgenic mice expressing enhanced green fluorescent protein in glycinergic neurons. It has been proposed that alterations in spinal inhibitory neurotransmission are critically involved in the pathophysiology of neuropathic pain. The mechanisms by which a relief from inhibitory tone contributes to pathological pain are not fully understood. Hitherto it is still under debate whether there is a loss of inhibitory neurons in the spinal cord in neuropathic pain. The aim of the present study was to evaluate whether a specific loss of glycinergic neurons is necessary to develop hyperalgesia and allodynia in the chronic constriction injury (CCI) model of neuropathic pain. The experiments were performed in bacterial artificial chromosome (BAC) transgenic mice which specifically express enhanced green fluorescent protein under the control of the promotor of the glycine transporter 2 gene, which is a reliable marker for glycinergic neurons. Thus, possible technical inconsistencies due to immunoreactivity in fixed tissues could be ruled out. Twelve days after CCI, in neuropathic animals and in sham-operated and naive animals, lumbar and thoracic segments were analyzed using the physical disector method. Although all animals that had undergone CCI showed pathological nociceptive behavior, stereology revealed no significant difference in glycinergic neurons-neither between the different groups nor between the ipsilateral and contralateral side of the thoracic and lumbar spinal segments. Our findings suggest that a loss of glycinergic neurons is not necessary for the development of pathological nociceptive behavior in the chronic constriction injury model of neuropathic pain in mice. A different mechanism may account for the decrease in inhibitory transmission in neuropathic pain.

Fatal complications of bariatric surgery. Bariatric surgery is an increasingly used method to treat morbid obesity. The mortality rate among patients undergoing bariatric operations is generally quoted as between 0.05-2.0%. Our focus was not on mortality rates but rather on the reasons patients die following the procedures. In New York City, deaths that are due to predictable complications of appropriate therapy are certified as therapeutic complications. We retrospectively reviewed all deaths investigated by the Office of the Chief Medical Examiner in New York City between 1997 and 2005 in which bariatric surgery had been performed. We report the fatal complications, the interval between surgery and death, the type of procedure, and coexisting morbidities. Autopsies were performed on 95% of these fatalities. There were 97 deaths due to therapeutic complications of the operations. The interval between the initial surgery and death ranged from several hours to years. The most common complication was an anastomotic leak with subsequent infection. A high percentage of deaths occurred after discharge (40%) and/or >30 days after surgery (37%). There were 8 deaths from complications of bariatric surgery that occurred >1 year after surgery. Studies that report the mortality rate during hospitalization or within 30 days of surgery, underestimate the actual incidence. Bariatric surgery carries both short- and long-term risks.

Relationship Between Diet, Tinnitus, and Hearing Difficulties. Diet may affect susceptibility of the inner ear to noise and age-related effects that lead to tinnitus and hearing loss. This study used complementary single nutrient and dietary pattern analysis based on statistical grouping of usual dietary intake in a cross-sectional analysis of tinnitus and hearing difficulties in a large population study sample. The research was conducted using the UK Biobank resource. Tinnitus was based on report of ringing or buzzing in one or both ears that lasts more than five minutes at a time and is currently experienced at least some of the time. Identification of a hearing problem was based on self-reported difficulties with hearing. Usual dietary intake and dietary patterns (involving statistical grouping of intake to account for how foods are combined in real-life diets) were estimated based on between two and five administrations of the Oxford Web-Q 24-hour dietary recall questionnaire over the course of a year for 34,576 UK adult participants aged 40 to 69. In a multivariate model, higher intake of vitamin B12 was associated with reduced odds of tinnitus, while higher intakes of calcium, iron, and fat were associated with increased odds (B12, odds ratio [OR] 0.85, 95% confidence interval [CI] 0.75 to 0.97; Calcium, OR 1.20, 95% CI 1.08 to 1.34; Iron, OR 1.20, 95% CI 1.05 to 1.37; Fat, OR 1.33, 95% CI 1.09 to 1.62, respectively, for quintile 5 versus quintile 1). A dietary pattern characterised by high protein intake was associated with reduced odds of tinnitus (OR 0.90, 95% CI 0.82 to 0.99 for quintile 5 versus quintile 1). Higher vitamin D intake was associated with reduced odds of hearing difficulties (OR 0.90, 95% CI 0.81 to 1.00 for quintile 5 versus quintile 1), as were dietary patterns high in fruit and vegetables and meat and low in fat (Prudent diet: OR 0.89, 95% CI 0.83 to 0.96; High protein: OR 0.88, 95% CI 0.82 to 0.95; High fat: OR 1.16, 95% CI 1.08 to 1.24, respectively, for quintile 5 versus quintile 1). There were associations between both single nutrients and dietary patterns with tinnitus and hearing difficulties. Although the size of the associations was small, universal exposure for dietary factors indicates that there may be a substantial impact of diet on levels of tinnitus and hearing difficulties in the population. This study showed that dietary factors might be important for hearing health.

Acute renal failure and metformin-associated lactic acidosis following colonoscopy. Two patients with type 2 DM developed acute kidney injury and lactic acidosis following colonoscopy despite withholding metformin. We recommend that DM patients on metformin also withhold ACEI, ARB until their dehydration is reversed after colonoscopy. This should reduce the risk of acute renal failure (ARF) and of lactic acidosis.

BET 2: Striking the right balance: anticoagulation and isolated distal deep vein thrombosis. A short-cut review was carried out to establish whether treatment of isolated distal deep vein thrombosis with therapeutic anticoagulation can reduce adverse clinical outcomes. A meta-analysis from 2011 and 11 subsequent directly relevant papers were found using the reported search strategy. Of these, 7 in total presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. It is concluded that patients diagnosed with isolated distal deep vein thrombosis should be individually risk assessed and treated according to their risk of thrombotic complication, bleeding with anticoagulation and personal preference.

Identification of early developing axon projections from spinal interneurons in the chick embryo with a neuron specific beta-tubulin antibody: evidence for a new 'pioneer' pathway in the spinal cord. The early development of interneurons in the chick embryo spinal cord was studied using a monoclonal antibody against a neuron-specific beta-tubulin isoform. Early developing interneurons were divided into two cell groups on the basis of their location and the pattern of growth of their axons. One group is composed of cells that establish a primitive longitudinal pathway (PL-cells), whereas the other group contains cells constituting a circumferential pathway (C-cells). The onset of axonal development in both cell groups occurs at stage (st.) 15 (embryonic day, (E), 2) in the branchial segments, which is prior to axonogenesis of motoneurons. PL-cells develop in the region between the floor plate and the motoneuron nucleus. Their axons are the first neuronal processes ('pioneer axons') to arrive in the ventrolateral marginal zone and they project both rostrally and caudally to establish a primitive longitudinal association pathway at the ventrolateral surface of the neural tube. This pathway is formed before axons of C-cells arrive in the ventrolateral region. The first C-cells are initially located in the most dorsal portion of the neural tube, whereas later appearing C-cells are also located in both intermediate and ventral regions of the neural tube. The axons of C-cells project ventrally, without fasciculating, along the lateral border of the neural tube. Some of their axons enter the ipsilateral ventrolateral longitudinal pathway at st. 17. We often observed apparent contacts and interactions between preexisting axons of PL-cells and newly arriving axons of C-cells. The axons of commissural C-cells first enter the floor plate at st. 17 and cross the midline at st. 18. Axons of C cells begin to join the contralateral ventrolateral longitudinal pathway at st. 18+ to st. 19. In the floor plate region, contacts between growth cones and axons were often observed. However, axons in the floor plate at these stages were not fasciculated. These observations establish the timing and pattern of growth of axons from two specific populations of early developing interneurons in the chick spinal cord. Additionally, we have identified an early and apparently previously undescribed 'pioneer' pathway that constitutes the first longitudinal pathway in the chick spinal cord.

Consequences of simulated car driving at constant high speed on the sensorimotor control of leg muscles and the braking response. Due to the increase in time spent seated in cars, there is a risk of fatigue of the leg muscles which adjust the force exerted on the accelerator pedal. Any change in their sensorimotor control could lengthen the response to emergency braking. Fourteen healthy male subjects (mean age: 42 ± 4 years) were explored. Before and after a 1-h driving trial at 120 km h-1 , we measured the braking response, the maximal leg extension and foot inversion forces, the tonic vibratory response (TVR) in gastrocnemius medialis (GM) and tibialis anterior (TA) muscles to explore the myotatic reflex, and the Hoffmann reflex (H-reflex). During driving, surface electromyograms (EMGs) of GM and TA were recorded and the ratio between high (H) and low (L) EMG energies allowed to evaluate the recruitment of high- and low-frequency motor unit discharges. During driving, the H/L ratio decreased in TA, whereas modest and often no significant H/L changes occurred in GM muscle. After driving, the maximal foot inversion force decreased (-19%), while the leg extension force did not vary. Reduced TVR amplitude (-29%) was measured in TA, but no H-reflex changes were noted. The braking reaction time was not modified after the driving trial. Driving at constant elevated speed reduced the myotatic reflex and the recruitment of motor units in TA muscle. The corresponding changes were rarely present in the GM muscle that plays a key role in the braking response, and this could explain the absence of a reduced braking reaction time.

Role of probucol in inhibiting intimal hyperplasia after coronary stent implantation: a randomized study. Oxygen-free radicals can stimulate smooth muscle cell proliferation and may therefore be involved in the genesis of in-stent restenosis. Thus, treatment with probucol, a potent antioxidant agent that has been shown to reduce restenosis after balloon angioplasty, may be an effective strategy to prevent intimal hyperplasia after stenting. In a prospective double-blind study, 59 patients submitted to coronary stent implantation were randomly assigned to treatment with either probucol (1 g/d) or placebo, starting two weeks before the procedure and continued for 6 months. The primary end point was the intimal hyperplasia volume at 6 months measured by intravascular ultrasound (IVUS) imaging. Of the 59 randomized patients, 54 underwent successful stent implantation, completed the follow-up period, and underwent repeat angiography, 6.1 +/- 1.1 months after the procedure. Volumetric IVUS analysis revealed similar intimal hyperplasia volumes (403 +/- 26.7 mm3 for probucol vs 44.8 +/- 28.3 mm3 for placebo) and percent volume obstruction of the lumen (30.4% +/- 14.5% for probucol versus 30.7% +/- 17.2% for placebo) in both groups. In addition, quantitative coronary angiography showed no differences in late loss (1.0 +/- 0.8 mm vs 1.1 +/- 0.8 mm), loss index (0.5 +/- 0.4 for both groups), or angiographic restenosis rates (19.4% vs 18.5%) between the probucol and placebo groups, despite the observation of significant changes in the lipid profile and in the plasma antioxidant defenses in patients receiving probucol. Treatment with the antioxidant probucol failed to reduce neointimal formation after coronary stent implantation as assessed by IVUS volumetric analysis.

The role of charge and proton transfer in fragmentation of hydrogen-bonded nanosystems: the breakup of ammonia clusters upon single photon multi-ionization. The charge and proton dynamics in hydrogen-bonded networks are investigated using ammonia as a model system. The fragmentation dynamics of medium-sized clusters (1-2 nm) upon single photon multi-ionization is studied, by analyzing the momenta of small ionic fragments. The observed fragmentation pattern of the doubly- and triply-charged clusters reveals a spatial anisotropy of emission between fragments (back-to-back). Protonated fragments exhibit a distinct kinematic correlation, indicating a delay between ionization and fragmentation (fission). The different kinematics observed for channels containing protonated and unprotonated species provides possible insights into the prime mechanisms of charge and proton transfer, as well as proton hopping, in such a nanoscale system.

Primary midline peritoneal access with optical trocar is safe and effective in morbidly obese patients. The bladed optical access trocar is widely used and provides convenient, safe peritoneal entry. However, it has only been approved for use after insufflation. We used this device as our primary method of entry before insufflation in bariatric surgery and provide an overview of our cumulative experience. In addition, we provide a comprehensive analysis of the published data with respect to optical access as both primary and secondary methods of peritoneal access. From July 30, 2001 to April 4, 2008, laparoscopic access for all bariatric surgery at a single center was achieved using the 5-12-mm optical bladed trocar without previous insufflation for 2207 cases, including 1692 laparoscopic gastric bypass procedures and 515 laparoscopic adjustable gastric band placements. Four vascular injuries occurred (.18%) in our series. Three required conversion to laparotomy and vascular repair, and one was managed laparoscopically. All injuries occurred with off-midline placement. No mortalities occurred secondary to the use of the optical trocar. The present report is as the greatest volume series detailing the safe and effective use of the bladed optical trocar without previous insufflation as the primary method of peritoneal access in the morbidly obese. The insertion of this device in the midline appears to be a safe method of entry.

Prevalence of serotype and multidrug-resistance of Streptococcus pneumoniae respiratory tract isolates in 265 adults and 36 children in Korea, 2002-2005. In total, 301 isolates of Streptococcus pneumoniae collected from patients with respiratory tract infections admitted at primary clinics during 2002-2005 were tested for multidrug-resistance (MDR) phenotypes and their serotypes in Korea. The predominant serotypes were 19F, 19A, 23F, 11A, 3, 6A, and 6B, accounting for 67.8% of all isolates. Their serotype coverage by 23-valent polysaccharide vaccine and 7-valent conjugation vaccine was 73.1% and 39.2%, respectively. For the application of Clinical and Laboratory Standards Institute's new breakpoint for penicillin, the resistance rate of penicillin was 27.9% (but the penicillin resistance was 80.4% based on the previous breakpoint for penicillin of Clinical and Laboratory Standards Institute). Actually, the full resistance rate was only 4.0% (minimum inhibitory concentration >or=8 mg/L). Resistances to erythromycin, clindamycin, and tetracycline were very high (82.9%, 79.4%, and 71.7%, respectively). Especially, 56.1% of all the isolates were MDR, defined as resistant to three or more of the following agents: penicillin, erythromycin, clindamycin, cefotaxime, tetracycline, and levofloxacin. MDR strains were relatively associated with serotypes 19F, 19A, 23F, and 11A, accounting for 58.0% of the isolates. Their serotype coverage by 23-valent polysaccharide vaccine and 7-valent conjugation vaccine was 79.5% and 45.9%, respectively. Levofloxacin, as a representative fluoroquinolone, was active against 88.2% of all MDR isolates. Of particular concern was the high prevalence of MDR pneumococci in non-PCV7 serotypes with an MDR serotype 19A, 11A, 3, and 6A being mostly responsible. It would be prudent to consider more efficient protective strategies for people at high risk for pneumococcal diseases in regions with a high prevalence of MDR pneumococci.

[Polymethylene derivatives of nucleic bases with omega-functional groups: VII. Cytotoxicity in the series of N-(2-oxocyclohexyl)-omega-oxoalkyl substituted purines and pyrimidines]. New polymethylene derivatives of nucleic bases with a beta-diketo function in the omega-position were obtained by alkylation of uracil, thymine, cytosine, hypoxanthine, adenine, and N(2)-isobutyryl guanine with 2-omega-chloroal-kanoyl)cyclohexanones. The physical and chemical characteristics of the compounds synthesized and their effect on the K562 and HCT116 tumor cell lines were studied.

Oral anticoagulants and status of antidotes for the reversal of bleeding risk. Anticoagulants have been used in clinical practice for more than 50 years. Their indications expand, as more people are diagnosed each year with atrial fibrillation and venous thromboembolism. Vitamin K antagonists have been the most popular choice due to their effectiveness and their ability to reverse bleeding using a known antidote; oral and intravenous vitamin K have long been known to reverse the effects of warfarin. With new classes of anticoagulants making their way onto the market, such as factor Xa inhibitors (rivaroxaban, apixaban) and direct thrombin inhibitors (dabigatran), the need for new reversal agents is paramount. Patients tend to be more receptive to these medications because they do not require routine blood monitoring, can be used at fixed doses, and do not have major drug or food interactions. Antidotes for these medications have shown promise in animal models and are currently in clinical trials.

Quantitative determination of hexylresorcinol in commercial antiseptic solution by high-pressure liquid chromatography. High-pressure liquid chromatography was used with a 5-micron silica gel column to quantitate hexylresorcinol in a commercial antiseptic solution following extraction with methylene chloride. This method shows linearity to at least 0.025% hexylresorcinol. A mobile phase consisting of 63% heptane, 34% chloroform, and 5% methanol was used with a UV detector (254 nm) and a flow of 3 ml/min. No interfering substances were observed.

Spectroscopic study of a DNA brush synthesized in situ by surface initiated enzymatic polymerization. We used a combination of synchrotron-based X-ray photoelectron spectroscopy (XPS) and angle-resolved near-edge X-ray absorption fine structure (NEXAFS) spectroscopy to study the chemical integrity, purity, and possible internal alignment of single-strand (ss) adenine deoxynucleotide (poly(A)) DNA brushes. The brushes were synthesized by surface-initiated enzymatic polymerization (SIEP) on a 25-mer of adenine self-assembled monolayer (SAM) on gold (A25-SH), wherein the terminal 3'-OH of the A25-SH serve as the initiation sites for SIEP of poly(A). XPS and NEXAFS spectra of poly(A) brushes were found to be almost identical to those of A25-SH initiator, with no unambiguous traces of contamination. Apart from the well-defined chemical integrity and contamination-free character, the brushes were found to have a high degree of orientational order, with an upright orientation of individual strands, despite their large thickness up to ~55 nm, that corresponds to a chain length of at least several hundred nucleotides for individual ssDNA molecules. The orientational order exhibited by these poly(A) DNA brushes, mediated presumably by base stacking, was found to be independent of the brush thickness as long as the packing density was high enough. The well-defined character and orientational ordering of the ssDNA brushes make them a potentially promising system for different applications.

[Studies on leakage of pancreatic juice following distal pancreatectomy from the standpoint of transition of amylase and trypsin values in exudate]. Selective drainage method of remnant pancreatic stump (RPS) using latex rubber was devised, and I have obtained a good clinical result for the prevention of postoperative bleeding due to the leakage of pancreatic juice after distal pancreatectomy. In this study, amylase (Am:IU/L) and trypsin (Tr:ng/ml) values in exudate were measured to clarify the actual leakage of pancreatic juice. Thirty-three patients with gastric cancer who underwent total gastrectomy with distal pancreatectomy were chosen for this study; 21 cases of selective drainage (group A) and 12 cases of non-selective drainage (group B). The results are noted below. 1) Both Am and Tr values of group A in the exudate from remnant pancreatic stump were statistically higher than those of group B (p < 0.01). Mean values of group A and group B on the first post-operative day were 25.6 x 10(4) versus 2.6 x 10(4)IU/L (Am value) and 324.4 x 10(4) versus 12.2 x 10(4)ng/ml (Tr value), respectively. 2) The mean values rapidly decreased and bottomed on the sixth postoperative day. 3) Not only total drainage amount of Am (sigma Am: sum of Am value x exudate volume from each drain) but also sigma Tr in group B were markedly less than in group A (p < 0.01). It means that more than 40% of pancreatic juice remained in the abdomen without drainage in group B. In conclusion, effective and active drainage of remnant pancreatic stump for the initial three days at least is important to prevent complications and our selective drainage is one of the excellent methods.

[Comparative stability assessment of laccases from the basidiomycetes Coriolus hirsutus and Coriolus zonatus in the presence of effectors]. Stability characteristics of the laccases of the basidiomycetes Coriolus hirsutus and Coriolus zonatus were measured comparatively at temperatures 25 and 40 degrees C in the presence of various effectors (proteins, salts, polyalcohols, polyacids, and polyelectrolytes). Stabilization effects of cations on the laccases from C. hirsutus and C. zonatus decreased in the descending series Cu2+ > Mg2+ > Ca2+ and Ca2+ > Mg2+ > Mn2+, respectively. Tween 20 caused insignificant stabilization of the two enzymes. The C. zonatus laccase was also insignificantly stabilized as a result of treatment with bovine serum albumin. The enzymatic activity of the laccase preparations from C. hirsutus and C. zonatus was conserved virtually completely after vacuum drying (84 and 93%, respectively). The most effective stabilizer of the C. hirsutus laccase was found to be dextran (17 kD). Dry preparations treated with this agent conserved up to 95% of the enzymatic activity. The most effective stabilizer of the C. zonatus was polyacrylic acid (102% of the initial activity).

The role S-nitrosylation in manganese-induced autophagy dysregulation in SH-SY5Y cells. Overexposure to manganese (Mn) has been known to induce nitrosative stress. The dysregulation of autophagy has implicated in nitric oxide (NO) bioactivity alterations. However, the mechanism of Mn-induced autophagic dysregulation is unclear. The protein of Bcl-2 was considered as a key role that could participate to the autophagy signaling regulation. To further explore whether S-nitrosylation of Bcl-2 involved in Mn-induced autophagy dysregulation, we treated human neuroblastoma (SH-SY5Y) cells with Mn and pretreated cells with 1400 W, a selective iNOS inhibitor. After cells were treated with 400 μM Mn for 24 h, there were significant increases in production of NO, inducible NO synthase (iNOS) activity, the mRNA and protein expressions of iNOS. Interestingly, autophagy was activated after cells were treated with Mn for 0-12 h; while the degradation process of autophagy-lysosome pathway was blocked after cells were treated with Mn for 24 h. Moreover, S-nitrosylated JNK and Bcl-2 also increased and phospho-JNK and phospho-Bcl-2 reduced in Mn-treated cells. Then, the affinity between Bcl-2 and Beclin-1 increased significantly in Mn-treated cells. We used the 1400 W to neutralize Mn-induced nitrosative stress. The results showed that S-nitrosylated JNK and Bcl-2 reduced while their phosphorylation were recovered to some extent. The findings revealed that NO-mediated S-nitrosylation of Bcl-2 directly affected the interaction between Beclin-1 and Bcl-2 leading to autophagy inhibition.