Role of T Cell-To-Dendritic Cell Chemoattraction in T Cell Priming Initiation in the Lymph Node: An Agent-Based Modeling Study.
The adaptive immune response is initiated in lymph nodes by contact between antigen-bearing dendritic cells (DCs) and antigen-specific T cells. A selected number of naïve T cells that recognize a specific antigen may proliferate into expanded clones, differentiate, and acquire an effector phenotype. Despite growing experimental knowledge, certain mechanistic aspects of T cell behavior in lymph nodes remain poorly understood. Computational modeling approaches may help in addressing such gaps. Here we introduce an agent-based model describing T cell movements and their interactions with DCs, leading to activation and expansion of cognate T cell clones, in a two-dimensional representation of the lymph node paracortex. The primary objective was to test the putative role of T cell chemotaxis toward DCs, and quantitatively assess the impact of chemotaxis with respect to T cell priming efficacy. Firstly, we evaluated whether chemotaxis of naïve T cells toward a nearest DC may accelerate the scanning process, by quantifying, through simulations, the number of unique T cell-DC contact events. We demonstrate that, in the presence of naïve T cell-to-DC chemoattraction, a higher total number of contacts occurs, as compared to a T cell random walk scenario. However, the forming swarm of naïve T cells, as these cells get attracted to the neighborhood of a DC, may then physically restrict access of additional T cells to the DC, leading to an actual decrease in the cumulative number of unique contacts between naïve T cells and DCs. Secondly, we investigated the potential role of chemotaxis in maintaining cognate T cell clone expansion. The time course of cognate T cells number in the system was used as a quantitative characteristic of the expansion. Model-based simulations indicate that inclusion of chemotaxis, which is selective for already activated (but not naïve) antigen-specific T cells, may strongly accelerate the time of immune response occurrence, which subsequently increases the overall amplitude of the T cell clone expansion process.


Pseudomyxoma peritonei.
Pseudomyxoma peritonei is a rare, slowly progressive disease that produces extensive mucus accumulation within the abdomen and pelvis. It is managed by cytoreductive surgery involving hyperthermic intraoperative intraperitoneal chemotherapy.


Required reconsideration of "do-not-resuscitate" orders in the operating room and certain other treatment settings.
It is time to change the assumption that DNR orders apply in every treatment setting in the hospital. It is appropriate to mandate not only that these orders be reconsidered on the basis of time, but also on the basis of setting. When patients enter treatment settings in which discrete, time-limited therapies that can precipitate cardiac arrest are offered, they or their surrogates should reconsider the question of resuscitation with their current and primary physicians. While this will make patient transition from one hospital setting to another more complicated, it will allow patients to receive treatment directed toward their individual needs, immediate treatment objectives, and long-term treatment goals. It will also assure health care professionals that they will not be required to withhold treatment essential for meeting patients' treatment objectives in these settings.


Lactic acid production with lactate dehydrogenase using the visible light sensitization of zinc porphyrin.
Lactic acid production with L-lactate dehydrogenase from Pig heart (LDH) and reduced methyl viologen produced by the visible light photosensitization of zinc tetrakis(4-methylpyridyl)porphyrin (ZnTMPyP) was investigated. When the sample solution containing triethanolamine as an electron-donating reagent, ZnTMPyP, methyl viologen as an electron carrier, pyruvic acid and LDH in potassium phosphate buffer (pH 7) was irradiated, lactic acid production was observed. After 240 min irradiation, the amount of lactic acid production and the yield of pyruvic acid to lactic acid were estimated to be 0.17 mmol dm(-3) and 17.0%, respectively.


Kinetics and intermediates of marginal band reformation: evidence for peripheral determinants of microtubule organization.
The microtubules of the mature erythrocyte of the chicken are confined to a band at the periphery. Whole-mount electron microscopy after extraction reveals that the number of microtubules in each cell is almost the same. All the microtubules can be depolymerized by incubation in the cold, and the marginal band can be quantitatively and qualitatively reformed by return to 39 degrees C. These properties allow the reformation of the marginal band to be treated as an in vivo microtubule assembly reaction. The kinetics of this reaction and the intermediates detected during reformation suggest a mechanism of microtubule organization that is distinct from that observed in other cell types. Apparently only one or two growing microtubule ends are available for assembly--assembly is only detected at the cell periphery, even at early times--and there is no evidence of the participation of a microtubule-organizing center.


The effects of switching from oral to LAI antipsychotic treatment on subjective experience of schizophrenic and schizoaffective patients: Preliminary results.
To present real-world preliminary evidence on the specific effects of switching from oral to long-acting injectable (LAI) antipsychotic treatment on patient's subjective experience and quality of life (QoL) in a sample of clinically stable psychotic subjects. Twenty-six clinically stable adult schizophrenic and schizoaffective outpatients were recruited. All patients were under a stabilized therapy with a single oral second-generation antipsychotic and were switched to the equivalent maintenance regimen with the long-acting formulation of the same antipsychotic. Two subgroups of patients were created on the basis of the presence/absence of a complete clinical remission at enrollment. Anthropometric (body mass index), psychometric (Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale, and Positive And Negative Syndrome Scale), and patient's reported outcome (Subjective Well-Being Under Neuroleptics scale short form, Drug Attitude Inventory short version, and Short Form-36 health survey) data were collected at enrollment (T0) and after 6 months from the treatment switch (T1). Significant improvements in psychometric indexes, and patients' subjective experience of treatment and attitudes toward drug (reflecting in an enrichment of patients' health-related QoL) were found both in initial remitters and non-remitters. Our preliminary results suggest that the switch from oral to LAI antipsychotic treatment may help to address the subjective core of an optimal and satisfying recovery of psychotic patients. Size and duration of this study need to be expanded in order to produce more solid and generalizable results.


Discovery, Structure-Activity Relationship, and Binding Mode of an Imidazo[1,2-a]pyridine Series of Autotaxin Inhibitors.
Autotaxin (ATX) is a secreted enzyme playing a major role in the production of lysophosphatidic acid (LPA) in blood through hydrolysis of lysophosphatidyl choline (LPC). The ATX-LPA signaling axis arouses a high interest in the drug discovery industry as it has been implicated in several diseases including cancer, fibrotic diseases, and inflammation, among others. An imidazo[1,2-a]pyridine series of ATX inhibitors was identified out of a high-throughput screening (HTS). A cocrystal structure with one of these compounds and ATX revealed a novel binding mode with occupancy of the hydrophobic pocket and channel of ATX but no interaction with zinc ions of the catalytic site. Exploration of the structure-activity relationship led to compounds displaying high activity in biochemical and plasma assays, exemplified by compound 40. Compound 40 was also able to decrease the plasma LPA levels upon oral administration to rats.


Chikungunya virus infection with severe neurologic manifestations: report of four fatal cases.
Here, we present four patients with confirmed Chikungunya virus infection showing atypical neurologic manifestations and death. This case series includes patients ranging in age from five to 92 years, with or without comorbidities. This report is important, as very few cases in the literature reporting death due to atypical Chikungunya virus infection are available.


Temporal and depolarization-induced changes in the absolute amounts of mRNAs encoding metabotropic glutamate receptors in cerebellar granule neurons in vitro.
Cerebellar granule neurons in primary culture express metabotropic glutamate receptors (mGluRs) coupled to the stimulation of phosphoinositide hydrolysis and to the inhibition of cyclic AMP (cAMP) formation. To evaluate which mGluR mRNAs are expressed in granule neurons under different depolarizing conditions, we measured the absolute amounts of selected receptor mRNAs in neurons cultured for 3-13 days in the presence of either 10 or 25 mM KCl. mGluR-specific primer pairs and internal standards, corresponding to unique regions of mGluR1a, mGluR2, mGluR3, mGluR4, and mGluR5, were constructed and used in a competitive PCR-derived assay to quantify the corresponding mRNA levels. For phosphoinositide-coupled receptors, the absolute content of mGluR1a mRNA was three to 10 times higher than the content of mGluR5 mRNA. The expression of mGluR5 mRNA increased up to 9 days in vitro and was much higher in 10 mM than in 25 mM KCl. For the cAMP-coupled receptors, there was a large amount of mGluR4 mRNA and a much smaller content of the mGluR3 and mGluR2 mRNAs. Maintaining the granule neurons in vitro in 10 mM KCl increased the absolute amount of mRNAs encoding mGluR2 and mGluR4 at 9 and 13 days in vitro. In contrast, the content of the mGluR3 mRNA was consistently higher in neurons cultured in 25 mM KCl. These data are consistent with the possibility that in primary cultures of cerebellar neurons, phosphoinositide responses may be predominantly mediated by mGluR1a, rather than mGluR5, and that cAMP inhibition involves preferentially mGluR4 and mGluR3.


Vibrational anharmonicity effects in electronic tunneling through molecular bridges.
Effects of anharmonic bridge vibrations on electronic tunneling in donor-bridge-acceptor complexes are studied using a model of anharmonic bridge vibration coupled nonlinearly to an electronic degree of freedom. An anharmonicity parameter is introduced, enabling to reproduce the standard harmonic model with linear coupling as a limiting case. The frequency of electronic tunneling oscillations between the donor and acceptor sites is shown to be sensitive to the nuclear anharmonicity, where stretching and compression modes have an opposite effect on the electronic frequency. This phenomenon, that cannot be accounted for within the harmonic approximation, is analyzed and explained.


[Degree of familiarity with carcinoma in situ of the testis. A study of a representative selection of established urologists].
By a telephone poll conducted among 143 selected representative urologists in private practice throughout the west German Länder. Via a search for carcinoma in situ of the testicles (CIS, or testicular intra-epithelial neoplasia, TIN), active early detection of testicular germ cell tumors is now possible. Among 143 urologists questioned, 62 claimed to be familiar with testicular CIS. However, only 52% were able correctly to answer one question as to its significance, and only 33% could correctly answer a question on the diagnosis of CIS. Only 28% of all those questioned were able to answer correctly 2 questions about CIS. Knowledge about CIS proved to be inversely correlated with the interval in years since obtaining a licence to practice as a specialist. The poll reveals that, at the present time, too few urologists are familiar with carcinoma in situ of the testicles, and the possibilities of active early detection of testicular tumors.


Lysobacter silvestris sp. nov., isolated from alpine forest soil, and reclassification of Luteimonas tolerans as Lysobacter tolerans comb. nov.
A Gram-stain-negative, rod-shaped, motile, catalase-positive and cytochrome c oxidase-positive bacterial strain, designated AM20-91T, was isolated from alpine forest soil. Phylogenetic analysis based on 16S rRNA gene sequencing showed that strain AM20-91T was related to the genus Lysobacter and had highest 16S rRNA gene sequence similarities to the type strains of Lysobacter novalis THG-PC7T (97.8 %), Luteimonas tolerans UM1T (97.7 %) and Lysobacter ximonensis XM415T (97.0 %). The strain contained ubiquinone 8 as the predominant respiratory quinone; its polar lipid profile contained phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and two unidentified aminophospholipids. The major cellular fatty acids (>10 %) were iso-C15 : 0, iso-C11 : 0 3-OH and iso-C11 : 0. The DNA G+C content was 63.35 % (draft genome sequence). The combined results of phylogenetic, phenotypic, DNA-DNA relatedness and chemotaxonomic analyses demonstrated that strain AM20-91T represents a novel species of the genus Lysobacter, for which the name Lysobacter silvestris sp. nov. is proposed. The type strain is AM20-91T (=DSM 104734T=LMG 30011). In this study, it is also proposed that Luteimonas tolerans be reclassified as member of the genus Lysobacter.


Metalloporphyrins as biomimetic models for cytochrome p-450 in the oxidation of atrazine.
The aim of this work was to evaluate whether metalloporphyrin models could mimic the action of cytochrome P-450 in the oxidation of atrazine, a herbicide. The commercially available second-generation metalloporphyrins 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin metal(III) chloride [M(TDCPP)Cl] and 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin metal(III) chloride [M(TFPP)Cl] (metal = Fe or Mn) and the oxidants iodosylbenzene and metachloroperbenzoic acid were employed in this study. Results showed that the metalloporphyrins used here can oxidize atrazine. Yields as high as 32% were obtained for the Mn(TFPP)Cl/PhIO system, which shows that these catalysts can mimic both the in vivo and the in vitro action of cytochrome P-450, with formation of the metabolites DEA and DIA. The formation of five other unknown products was also detected, but only one of them could be identified, since the other four were present in very low concentrations. The compound COA, identified by mass spectrometry, was the main product in most of the oxidation reactions.


Orthotopic ileal W-shaped neobladder: functional results and oncological outcome.
There still exists an ongoing debate regarding the optimal method of ureterointestinal reimplantation in continent urinary diversion. The main objectives of the present study was to analyze the long-term functional results and the oncological outcome after the construction of orthotopic ileal neobladders, based on the antireflux serous-lined extramural tunnel technique. A total of 32 bladder cancer patients (30 males and 2 females, mean age 588 years), who underwent between 1/9/1996 and 1/9/2006 extended pelvic lymphadenectomy and radical cystectomy, followed by the construction of orthotopic W-shaped ileal neobladder, entered the study. All ureters were reimplanted via serous-lined extramural tunnels for reflux prevention. Adjuvant systemic chemotherapy with gemcitabine plus cisplatin was applied in 17 cases. All patients were evaluable for follow up (mean follow up - 53.938 months). Evaluation included clinical, radiographic and urodynamical studies to determine functional and oncological outcomes. None of the patients died in the hospital. Various early and late complications occurred in 18.8% and 21.9% of the patients, respectively. The overall incidence of day- and nighttime continence was 93.8% and 78.1%. Stenosis at the anastomotic site occurred in 2 uretero-ileal anastomoses (3.2%), while none of the patients showed evidence of pouchoureteral reflux. Renal function was stabilized or improved in 96.8% of the reimplanted renal units. Eight oncological failures were observed during follow-up: 1 local tumor recurrence and 7 metastatic tumor spreads. The overall and disease-specific patient survival was 72% and 81%, resp. The serous-lined extramural tunnel technique provides an effective and safe ureteroileal anastomosis, achieving nonobstructed unidirectional flow of urine. The results are durable and sustained with time. Therefore, this technique should be recommended whenever a construction of a continent intestinal urinary reservoir is considered.


Patients with distant metastases from renal cell carcinoma can be accurately identified: external validation of a new nomogram.
To identify clinical variables that can accurately predict the presence of distant metastases in patients with renal cell carcinoma (RCC). Age, symptom classification, tumour size and the prevalence of distant metastases at diagnosis before nephrectomy were available for 5376 patients with pathologically confirmed RCC. The data of 2660 (49.5%) patients from 11 centres were used to develop a multivariable logistic regression model-based nomogram predicting the individual probability of distant metastases. The remaining data from 2716 (50.5%) patients from three institutions were used for external validation. In the development cohort, 269/2660 (10.1%) had distant metastases, vs 285/2716 (10.5%) in the external validation cohort. Symptom classification and tumour size were independent predictors of distant metastases in the development cohort; age was not an independent predictor. A nomogram based on symptom classification and tumour size was 85.2% accurate in predicting the individual probability of distant metastases in the external validation cohort. Although distant metastases might be easily identifiable in some patients, their diagnosis might be a challenge in others. The current nomogram provides a simple, user-friendly and, most importantly, an accurate tool aimed at predicting the probability of distant metastases in patients with RCC.


Ghrelin plasma levels, gastric ghrelin cell density and bone mineral density in women with rheumatoid arthritis.
Generalized bone loss can be considered an extra-articular manifestation of rheumatoid arthritis (RA) that may lead to the occurrence of fractures, resulting in decreased quality of life and increased healthcare costs. The peptide ghrelin has demonstrated to positively affect osteoblasts in vitro and has anti-inflammatory actions, but the studies that correlate ghrelin plasma levels and RA have contradictory results. We aimed to evaluate the correlation between total ghrelin plasma levels, density of ghrelin-immunoreactive cells in the gastric mucosa, and bone mineral density (BMD) in twenty adult women with established RA with 6 months or more of symptoms (mean age of 52.70±11.40 years). Patients with RA presented higher ghrelin-immunoreactive cells density in gastric mucosa (P=0.008) compared with healthy females. There was a positive relationship between femoral neck BMD and gastric ghrelin cell density (P=0.007). However, these same patients presented a negative correlation between plasma ghrelin levels and total femoral BMD (P=0.03). The present results indicate that ghrelin may be involved in bone metabolism of patients with RA. However, the higher density of ghrelin-producing cells in the gastric mucosa of these patients does not seem to induce a corresponding elevation in the plasma levels of this peptide.


Low-density lipoprotein promotes lymphatic metastasis of esophageal squamous cell carcinoma and is an adverse prognostic factor.
The purpose of the current study was to investigate the prognostic role of preoperative serum lipid levels in patients with esophageal squamous cell carcinoma (ESCC) and to preliminarily explore the mechanism of serum lipids in this disease. Preoperative lipids, including total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels, were assessed in 242 patients with ESCC. To eliminate the influence of nutritional status, all patients had previously undergone esophagectomy. Univariate and multivariate Cox regression analyses were performed to identify predictors of overall survival (OS). Associations between significant lipid targets and clinical features were then analyzed and the results were validated using TE-1 and ECa109 esophageal cancer cell lines. The cell proliferation was evaluated with a Cell Counting Kit-8 (CCK8) assay and the cell cycle was assessed with propidium iodide staining and flow cytometry. Univariate analysis revealed that HDL (P=0.048), LDL (P=0.020), Pathological T-staging status (pT status) (P=0.001), Pathological N-staging status (pN status) (P=0.001) and histological differentiation (P=0.002) were significantly associated with OS. Based on multivariate analysis, LDL [hazard ratio (HR)=2.164, P=0.005], pT status (HR=1.714, P=0.001), pN status (HR=1.966, P=0.001) and histological differentiation (HR=4.083, P=0.002) were risk factors in patients with ESCC. A high LDL level (>3.12 mmol/l) was associated with sex (P=0.001), tumor location (P=0.004) and a higher susceptibility to lymphatic metastasis (P=0.007). A CCK8 assay demonstrated that LDL promoted TE-1 and ECa109 cell proliferation, and flow cytometry analysis revealed that treatment with LDL at an appropriate concentration resulted in an accumulation of cells in G2 phase and decreased the number of cells in G1 phase. In summary, the current study identified that preoperative LDL serum level serves an important role in predicting ESCC outcome as LDL promotes lymphatic metastasis. Furthermore, a preliminary mechanism for this association has been validated in vitro.


Conditional control in visual selection.
Attention and eye movements provide a window into the selective processing of visual information. Evidence suggests that selection is influenced by various factors and is not always under the strategic control of the observer. The aims of this tutorial review are to give a brief introduction to eye movements and attention and to outline the conditions that help determine control. Evidence suggests that the ability to establish control depends on the complexity of the display as well as the point in time at which selection occurs. Stimulus-driven selection is more probable in simple displays than in complex natural scenes, but it critically depends on the timing of the response: Salience determines selection only when responses are triggered quickly following display presentation, and plays no role in longer-latency responses. The time course of selection is also important for the relationship between attention and eye movements. Specifically, attention and eye movements appear to act independently when oculomotor selection is quick, whereas attentional processes are able to influence oculomotor control when saccades are triggered only later in time. This relationship may also be modulated by whether the eye movement is controlled in a voluntary or an involuntary manner. To conclude, we present evidence that shows that visual control is limited in flexibility and that the mechanisms of selection are constrained by context and time. The outcome of visual selection changes with the situational context, and knowing the constraints of control is necessary to understanding when and how visual selection is truly controlled by the observer.


Nicotine improves ethanol-induced impairment of memory: possible involvement of nitric oxide in the dorsal hippocampus of mice.
In the present study, the possible involvement of nitric oxide (NO) systems in the dorsal hippocampus in nicotine's effect on ethanol-induced amnesia and ethanol state-dependent memory was investigated. Adult male mice were cannulated in the CA1 regions of the dorsal hippocampus and trained on a passive avoidance learning task for memory assessment. We found that pre-training intraperitoneal (i.p.) administration of ethanol (1 g/kg) decreased inhibitory avoidance memory when tested 24 h later. The response induced by pre-training ethanol was significantly reversed by pre-test administration of the drug. Similar to ethanol, pre-test administration of nicotine (0.4 and 0.8 μg/mouse, intra-CA1) alone and nicotine (0.2, 0.4 and 0.8 μg/mouse) plus an ineffective dose of ethanol also significantly reversed the amnesia induced by ethanol. Ethanol amnesia was also prevented by pre-test administration of L-arginine (1.2 μg/mouse, intra-CA1), a NO precursor. Interestingly, an ineffective dose of nicotine (0.2 μg/mouse) in combination with a low dose of L-arginine (0.8 μg/mouse) synergistically improved memory performance impaired by ethanol given before training. In contrast, pre-test intra-CA1 microinjection of L-NAME (NG-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS) inhibitor (0.4 and 0.8 μg/mouse), which reduced memory retrieval in inhibitory avoidance task by itself, in combination with an effective dose of nicotine (0.4 μg/mouse) prevented the improving effect of nicotine on memory impaired by pre-training ethanol. Moreover, intra-CA1 microinjection of L-NAME reversed the L-arginine-induced potentiation of the nicotine response. The results suggest the importance of NO system(s) in the CA1 regions of the dorsal hippocampus for improving the effect of nicotine on the ethanol-induced amnesia.


High expression of heat shock protein 60 in follicular cells of Hashimoto's thyroiditis.
Heat shock protein 60 expression in the thyrocytes of Hashimoto's thyroiditis and Graves' disease was studied immunohistochemically. Thyrocytes of Hashimoto's thyroiditis showed high expression of heat shock protein 60 not only in tall eosinophilic-cells but also in low and flattened cells, although the former was stained with moderate to strong staining intensity and the latter weakly to moderately. Follicular cells around lymphoid cell follicles were stained more intensely, whereas cells apart from lymphoid cell follicles were stained weakly to moderately. In Graves' disease, only follicular cells around lymphoid cell follicles were stained with varying intensities. Since the pattern in all positive staining was granular, it was thought that heat shock protein 60 overexpressed in thyrocytes located on mitochondria. To investigate the immunological role of overexpression of self heat shock protein 60 in the thyrocytes of Hashimoto's thyroiditis, gamma delta TCR+ T-cells in the tissue and the IgG class of anti-self heat shock protein 60 antibodies were studied. gamma delta TCR+ T-cells were detected among lymphoid cells scattered in interfollicular connective tissue. No difference in antibody level was seen among subjects with Hashimoto's thyroiditis, Graves' disease and normal subjects. Self heat shock protein 60 overexpression in the thyrocytes of Hashimoto's thyroiditis may play a disease-modifying role, although it does not influence the anti-self heat shock protein 60 antibody level.


Using success stories to share knowledge and lessons learned in health promotion.
Compelling success stories, rich with details about real-life events and people, are a tool that health agencies can use to convey how their health promotion programs work, why they are successful, what lessons they have learned, and how others can launch similar programs. Success stories describe project accomplishments that are not easily captured by quantitative evaluation methods, such as surveys. Although success stories have not been widely used in public health, the North Carolina Department of Health and Human Services developed a series of stories, the Community Change Chronicles, to highlight environmental and policy changes that promote cardiovascular health. In 2003, the Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) program used the Community Change Chronicles as a model to develop success stories about WISEWOMAN projects. WISEWOMAN Works: A Collection of Success Stories from Program Inception Through 2002 includes 12 stories and offers advice on how to create and use success stories in public health. This paper reviews the rationale for developing the stories, presents one success story as an example, and describes the process used to gather information, write the stories, and produce a resource for others interested in developing success stories. We also discuss how the WISEWOMAN success stories are being used to promote women's health and cardiovascular health. As the WISEWOMAN experience suggests, healthcare providers and organizations can use success stories to gain support for successful activities, inform the public about program benefits, complement other quantitative and qualitative evaluation methods, and publicly acknowledge the contributions of staff and organizational partners.


Total synthesis of gambierol.
[structure: see text] The first total synthesis of gambierol, a marine polycyclic ether toxin, has been achieved. The synthesis features the Pd(PPh3)4/CuCl/LiCl-promoted Stille coupling for the stereoselective construction of the sensitive triene side chain that includes a conjugated (Z,Z)-diene moiety.


Measurement of IgG blocking antibodies by interference in the radioallergosorbent test.
We previously found that sera of patients immunized with ragweed pollen extract contained a factor that interfered with the binding of IgE antibodies to solid-phase allergens in the radioallergosorbent test (RAST). We now describe an assay, RAST interference, to measure this factor, and we present evidence that the factor is IgG blocking antibody. Sera from immunized allergic patients were heated at 56 degrees C for 4 hr to destroy heat-labile Fc determinants on IgE and were tested for their ability to prevent binding of additional IgE antibody to solid-phase allergens in the RAST. Eight of 10 sera from allergic immunized patients gave RAST interference dose-response curves that did not differ from the arbitrary standard. The factor causing interference showed specificity for the immunizing antigen, was heat-stable, eluted from Sephadex G-200 in the 7S peak, was present only in sera of immunized patients, and rose after initiation of immunization. These results indicated that RAST interference can be used to measure IgG blocking antibodies with the same reagents employed for the measurement of IgE antibodies, provided the antiserum to IgE is specific for the heat-labile FC determinants on IgE.


New monodentate amidine superbasic ligands with a single configuration in fac-[Re(CO)3(5,5'- or 6,6'-Me2bipyridine)(amidine)]BF4 complexes.
Treatment of two precursors, fac-[Re(CO)(3)(L)(CH(3)CN)]BF(4) [L = 5,5'-dimethyl-2,2'-bipyridine (5,5'-Me(2)bipy) (1) and 6,6'-dimethyl-2,2'-bipyridine (6,6'-Me(2)bipy) (2)], with five C(2)-symmetrical saturated heterocyclic amines yielded 10 new amidine complexes, fac-[Re(CO)(3)(L)(HNC(CH(3))N(CH(2)CH(2))(2)Y)]BF(4) [Y = CH(2), (CH(2))(2), (CH(2))(3), NH, or O]. All 10 complexes possess the novel feature of having only one isomer (amidine E configuration), as established by crystallographic and (1)H NMR spectroscopic methods. We are confident that NMR signals of the other possible isomer (amidine Z configuration) would have been detected, if it were present. Isomers are readily detected in closely related amidine complexes because the double-bond character of the amidine C-N3 bond (N3 is bound to Re) leads to slow E to Z isomer interchange. The new fac-[Re(CO)(3)(L)(HNC(CH(3))N(CH(2)CH(2))(2)Y)]BF(4) complexes have C-N3 bonds with essentially identical double-bond character. However, the reason that the Z isomer is so unstable as to be undetectable in the new complexes is undoubtedly because of unfavorable clashes between the equatorial ligands and the bulky N(CH(2)CH(2))(2)Y ring moiety of the axial amidine ligand. The amidine formation reactions in acetonitrile (25 °C) proceeded more easily with 2 than with 1, indicating that the distortion in 6,6'-Me(2)bipy resulting from the proximity of the methyl substituents to the inner coordination sphere enhanced the reactivity of the coordinated CH(3)CN. Reaction times for 1 and 2 exhibited a similar dependence on the basicity and ring size of the heterocyclic amine reactants. Moreover, when the product of the reaction of 1 with piperidine, fac-[Re(CO)(3)(5,5'-Me(2)bipy)(HNC(CH(3))N(CH(2)CH(2))(2)CH(2))]BF(4), was challenged in acetonitrile-d(3) or CDCl(3) with a 5-fold excess of the strong 4-dimethylaminopyridine ligand, there was no evidence for replacement of the amidine ligand after two months, thus establishing that the piperidinylamidine ligand is a robust ligand. This chemistry offers promise as a suitable means for preparing isomerically pure conjugated fac-[(99m)Tc(CO)(3)L](n±) imaging agents, including conjugates with known bioactive heterocyclic amines.


Promotion of in vivo degradability, vascularization and osteogenesis of calcium sulfate-based bone cements containing nanoporous lithium doping magnesium silicate.
Nanoporous lithium doping magnesium silicate (nl-MS) was introduced into calcium sulfate hemihydrate to prepare calcium sulfate composite (nl-MSC) bone cements. The introduction of nl-MS improved the in vitro degradability of nl-MSC cements, which could neutralize acidic degradable products of calcium sulfate and prevented the pH from dropping. The cements were implanted into the bone defects of femur bone of rabbits, and the results of histological and immunohistochemical analysis revealed that massive new bone tissue formed in the defects while the cements were degradable, indicating that the osteogenesis and degradability of the nl-MSC cements were much better than the control calcium sulfate dihydrate (CSD) cements. Furthermore, the positive expression of vascular endothelial growth factor and collagen type I for nl-MSC cements was higher than CSD, indicating that addition of nl-MS into the cements enhanced vascularization and osteogenic differentiation. The results suggested that the nl-MSC cements with good biocompatibility and degradability could promote vascularization and osteogenesis, and had great potential to treat bone defects.


Uncommon findings in Tc-99m macroaggregated albumin venography in distal inferior vena cava obstruction.
In inferior vena cava obstruction, collateral pathways allow the retrograde flow of venous blood from the lower part of the body. Unanticipated findings of Tc-99m macroaggregated albumin (MAA) venography in 3 cases with deep vein thrombosis of the legs and infrarenal inferior vena cava obstruction are presented. Apart from extensive collateral networks in the legs and the abdomen, the visualization of the liver indicates a shunt of the systemic venous blood flow through the paraumbilical vein to the portal vein. The visualization of lumbar and thoracic vertebrae is attributed to venous flow through a dilated vertebral plexus, resulting in trapping of tracer in the neighboring bone marrow.


Life decisions of Taiwanese women who care for a sibling with cerebral palsy.
We used a phenomenological method to examine how the caregiving experiences of Taiwanese women who care for a sibling with cerebral palsy (CP) influence their life decisions. In-depth qualitative interviews were conducted with six adult women, each of whom self-identified as being the sister most involved in caring for a sibling with CP. Themes emerging from caregivers' experiences were caring through interpretation, caring through protection, and caring through sacrifice. These ways of caring created unique considerations and tensions that appeared to have a profound effect on the women's major life decisions.


CpeF is the bilin lyase that ligates the doubly linked phycoerythrobilin on β-phycoerythrin in the cyanobacterium Fremyella diplosiphon.
Phycoerythrin (PE) is a green light-absorbing protein present in the light-harvesting complex of cyanobacteria and red algae. The spectral characteristics of PE are due to its prosthetic groups, or phycoerythrobilins (PEBs), that are covalently attached to the protein chain by specific bilin lyases. Only two PE lyases have been identified and characterized so far, and the other bilin lyases are unknown. Here, using in silico analyses, markerless deletion, biochemical assays with purified and recombinant proteins, and site-directed mutagenesis, we examined the role of a putative lyase-encoding gene, cpeF, in the cyanobacterium Fremyella diplosiphon. Analyzing the phenotype of the cpeF deletion, we found that cpeF is required for proper PE biogenesis, specifically for ligation of the doubly linked PEB to Cys-48/Cys-59 residues of the CpeB subunit of PE. We also show that in a heterologous host, CpeF can attach PEB to Cys-48/Cys-59 of CpeB, but only in the presence of the chaperone-like protein CpeZ. Additionally, we report that CpeF likely ligates the A ring of PEB to Cys-48 prior to the attachment of the D ring to Cys-59. We conclude that CpeF is the bilin lyase responsible for attachment of the doubly ligated PEB to Cys-48/Cys-59 of CpeB and together with other specific bilin lyases contributes to the post-translational modification and assembly of PE into mature light-harvesting complexes.


Melatonin protects against pro-oxidant enzymes and reduces lipid peroxidation in distinct membranes induced by the hydroxyl and ascorbyl radicals and by peroxynitrite.
We have investigated the action of melatonin against lipid peroxidation in membranes including brain homogenates (BH), brain and liver microsomes (MIC), and phosphatidylcholine (PC) liposomes, as well as its effect on the activity of pro-oxidant enzymes such as constitutive neuronal nitric oxide synthase (cnNOS), xanthine oxidase (XO) and myeloperoxidase (MPO). The liposomes were reconstituted by a dialysis method, lipid peroxidation was monitored using the thiobarbituric reactive substances (TBARS) method and enzyme activities were measured spectrophotometrically. The ascorbyl and hydroxyl free radicals were generated by the reaction of ascorbic acid + FeSO4 and H2O2 + FeCl2, respectively, and peroxynitrite using a mixture of NaNO2 in an alkaline medium. Melatonin protected against lipid peroxidation induced by distinct reactive oxygen species (ROS) in all membranes tested although with different potency, in the following order BH < MIC < PC. The K0.5 for enzyme inhibition by melatonin was determined for nNOS (2.0 +/- 0.1 mm), for XO (0.8 +/- 0.1 mm) and for MPO (0.063 +/- 0.003 mm), the latter one with high affinity. Melatonin showed a weak effect as a nitrogen monoxide (NO) scavenger in the presence of sodium nitroprusside (NO donor) and low reactivity with 1,1-diphenyl-2-picryl hydrazyl (DPPH). These results demonstrate the antioxidant action of melatonin, principally that related to the activity of pro-oxidant enzymes such as XO and MPO.


[Tumor endoprosthesis in malignant bone tumors].
In the Department of Orthopedics at the University of Vienna, tumor endoprostheses have been implanted after resections of tumors of the upper extremities since 1974 and of the knee joint since 1976. For replacement of the humerus after tumor resection, a system of modular tumor endoprostheses was developed very early. Initially, it was ceramic and later on made of titanium alloys, which were also implanted in combination with custom-made prostheses with cementless stem-plate fixation in 57 patients until February 1990. In 43 of these patients (75.4%) adequate resection (2 radical and 41 wide) had been performed. Of 49 patients with a follow-up period of at least 24 months, 36 patients had a mean disease-free survival time of 106.1 months. Between 1976 and 1981, 16 custom-made endoprostheses were used after tumor resection of the knee joint. Since 1982 we have used a modular system of tumor endoprostheses suitable for replacement of the proximal and distal femur, proximal tibia, total femur and total knee joint. Of 75 patients who had been operated on up to February 1990, 67 patients (89.3%) had undergone adequate resection (2 radical and 65 wide). Out of 32 of these patients, 24 (75%) exhibited a disease-free survival time of at least 24 months (mean 48.2 months). Out of 213 patients with resection/reconstruction (160 endoprostheses), 77.8% had a survival time of at least 24 months, a results which is considerably better than in 146 patients with amputation in which case the respective value was 69.4%.(ABSTRACT TRUNCATED AT 250 WORDS)


Survival after high-dose intraperitoneal infusion of glycine solution in the mouse.
We used an animal model to study whether glycine prompts death after absorption of irrigating fluid by the extravascular route. Mice were divided into groups of 10 and given an intraperitoneal infusion of 200, 225, 250, 275 or 300 ml/kg of glycine 1.1%, 1.5% or 2.2%. With all infused volumes, the chance of survival was better after infusion of glycine 1.1% and glycine 1.5% than after glycine 2.2%. The overall death rates were 10%, 16% and 46%, respectively. Logistic regression analysis showed that the outcome was significantly and independently affected by both the glycine concentration and the infused volume. We conclude that the glycine concentration of an irrigating fluid deposited in the peritoneal cavity is important to the chance of survival. The poorest chance is obtained with glycine 2.2%.


Plasma 2-hydroxyglutarate and hexanoylcarnitine levels are potential biomarkers for skeletal muscle toxicity in male Fischer 344 rats.
To identify new candidate biomarkers for skeletal muscle toxicity, an unbiased metabolomic analysis was performed in rats treated with two distinct myotoxicants, cerivastatin (CER) and tetramethyl-p-phenylenediamine (TMPD). Skeletal muscle toxicity was induced in male Fischer 344 rats by administering CER or TMPD and monitored using established endpoints, such as increased plasma creatine kinase (CK) activity and histopathology, and a metabolomic analysis of skeletal muscle and plasma samples. Plasma CK levels in CER-treated rats were markedly elevated at Day 11; however, those in TMPD-treated rats showed a statistically significant decrease at 24 hr after dosing. Light microscopy revealed that vacuolated or necrotic fibers were evident in all CER-treated rats on Day 11, and slightly vacuolated fibers were observed in TMPD-treated rats at 6 and 24 hr after dosing. Metabolomic analysis of the rectus femoris indicated increases in 2-hydroxyglutarate (2HG) in CER-treated rats and hexanoylcarnitine in CER- and TMPD-treated rats. There were also increases in plasma 2HG in CER-treated rats on Days 8 and 11 and in TMPD-treated rats at 24 hr after dosing and increases in plasma hexanoylcarnitine in CER-treated rats on Day 11 and in TMPD-treated rats at 6 and 24 hr after dosing. These experiments demonstrated the potential of plasma 2HG and hexanoylcarnitine as specific and easily detectable biomarkers for skeletal muscle toxicity in rats and demonstrated the value of metabolomics for biomarker detection and identification in toxicological studies.


Effect of S-PRG Eluate on Biofilm Formation and Enzyme Activity of Oral Bacteria.
Recently, the antibacterial activity of a composite resin containing prereacted glass ionomer (S-PRG) filler was revealed. We examined the effect of an S-PRG eluate on various biologic activities of Streptococcus mutans and Porphyromonas gingivalis. Adherence ability of S. mutans was evaluated by microtiter plate assay; protease and gelatinase activities of P. gingivalis were examined by synthetic substrate hydrolysis and gelatin film spot assay, respectively. Coaggregation of P. gingivalis with Fusobacterium nucleatum was also examined. S-PRG eluate was found to suppress streptococcal adherence. S-PRG eluate inhibited the protease and gelatinase activities of P. gingivalis and the coaggregation between P. gingivalis and F. nucleatum. These results indicate that S-PRG eluate suppresses streptococcal adherence and inhibits the protease and coaggregation activities of P. gingivalis. These findings may prompt research into novel strategies for preventing caries and periodontitis.


Experimental investigation of silicon photomultipliers as compact light readout systems for gamma-ray spectroscopy applications in fusion plasmas.
A matrix of Silicon Photo Multipliers has been developed for light readout from a large area 1 in. × 1 in. LaBr3 crystal. The system has been characterized in the laboratory and its performance compared to that of a conventional photo multiplier tube. A pulse duration of 100 ns was achieved, which opens up to spectroscopy applications at high counting rates. The energy resolution measured using radioactive sources extrapolates to 3%-4% in the energy range Eγ = 3-5 MeV, enabling gamma-ray spectroscopy measurements at good energy resolution. The results reported here are of relevance in view of the development of compact gamma-ray detectors with spectroscopy capabilities, such as an enhanced gamma-ray camera for high power fusion plasmas, where the use of photomultiplier is impeded by space limitation and sensitivity to magnetic fields.


Single step purification of locust adipokinetic hormones I and II by reversed-phase high-performance liquid chromatography, and amino-acid composition of the hormone II.
Locust adipokinetic hormones I (AKH I) and II (AKH II) are separated by reversed-phase high-performance liquid chromatography using a mu-Bondapak phenyl column with a trifluoroacetic acid/acetonitrile gradient. The eluant was monitored at 210 nm and the hyperlipaemic activity was detected using a bioassay. The amino-acid composition of AKH II was determined after acid hydrolysis with HCl or methane-sulfonic acid. It contained the following amino-acid residues in almost equimolar amounts: Asp, Ser, Glu, Gly, Ala, Leu, Phe and Trp.


Dihydrogen catalysis of the reversible formation and cleavage of C-H and N-H bonds of aminopyridinate ligands bound to (η(5) -C5 Me5 )Ir(III.).
This study focuses on a series of cationic complexes of iridium that contain aminopyridinate (Ap) ligands bound to an (η(5) -C5 Me5 )Ir(III) fragment. The new complexes have the chemical composition [Ir(Ap)(η(5) -C5 Me5 )](+) , exist in the form of two isomers (1(+) and 2(+) ) and were isolated as salts of the BArF (-) anion (BArF =B[3,5-(CF3 )2 C6 H3 ]4 ). Four Ap ligands that differ in the nature of their bulky aryl substituents at the amido nitrogen atom and pyridinic ring were employed. In the presence of H2 , the electrophilicity of the Ir(III) centre of these complexes allows for a reversible prototropic rearrangement that changes the nature and coordination mode of the aminopyridinate ligand between the well-known κ(2) -N,N'-bidentate binding in 1(+) and the unprecedented κ-N,η(3) -pseudo-allyl-coordination mode in isomers 2(+) through activation of a benzylic C-H bond and formal proton transfer to the amido nitrogen atom. Experimental and computational studies evidence that the overall rearrangement, which entails reversible formation and cleavage of H-H, C-H and N-H bonds, is catalysed by dihydrogen under homogeneous conditions.


Protective effect of phlorotannin components phloroglucinol and eckol on radiation-induced intestinal injury in mice.
Components of phlorotannin, which were extracted from Ecklonia species, have been reported to have in vitro radioprotective and antioxidative effects. The radioprotective effects of two of the components of phlorotannin, phloroglucinol and eckol, in intestinal stem cells were examined by evaluating their effects on jejunal crypt survival and apoptosis in gamma-irradiated mice. Pretreating the mice (i.p. 20 mg/kg of body weight at 12 and 36 h before irradiation) prior to irradiation with either phloroglucinol or eckol significantly improved the survival of the jejunal crypt (p < 0.001 and p < 0.01 vs irradiation controls at 3.5 days after 8 Gy irradiation, respectively). The administration of phloroglucinol and eckol prior to irradiation protected the intestinal crypts from radiation-induced apoptosis (p < 0.05 vs irradiation controls at 12 h after 1 Gy irradiation). Although the mechanism for this inhibitory effect remains unknown, these results showed that phloroglucinol and eckol might be useful radioprotectors that can defend intestinal stem cells against the oxidative damage caused by gamma-irradiation.


Abstraction and simulation of EV battery systems-resilience engineering by biological transformation.
While the demand for electric vehicles (EVs) is continuously growing, safety issues still remain, specifically related to fire hazards. This research aims to improve the resilience of battery systems in EVs by transferring concepts found in biology to a bioinspired battery system. Due to the complexity of modern battery systems, the biological concepts cannot be applied directly. A simplified simulation battery system for EVs is modelled, which contains the essential battery components necessary to understand both, software and battery dynamics. This is used as a baseline model to study the effects of typical heat-related disturbances. Subsequently, this simulation model is modified to demonstrate the transfer of biological concepts underlying specifically the hypersensitization and vasospasm mechanisms related to wound healing, and to test the effects of disturbances and alterations comparable to damages caused by vehicle accidents. As a battery system's mass and volume should not be increased by additional hardware, the biological concepts target the interaction within, and the composition of, the system, while leaving single components relatively unchanged. It is found that small bioinspired alterations to the battery system can have significant impacts on their vulnerability to common hazards.


Broad-Specificity Immunoassay for Simultaneous Detection of Ochratoxins A, B, and C in Millet and Maize.
Ochratoxins A, B, and C (OTA, OTB, and OTC) can be found in cereals and feeds; the simultaneous detection of these ochratoxins holds a great need in food safety. In this study, four antibodies raised from two ochrotoxin haptens and two coating antigens were compared, and then a sensitive and broad-specificity enzyme-linked immunosorbent assay (ELISA) was established for the simultaneous determination of three ochratoxins, where the detection limits were 0.005, 0.001, and 0.001 ng/mL for OTA, OTB, and OTC, respectively, and recoveries of three ochratoxins were between 84.3% and 111.7%. This developed method had been successfully applied to detect ochratoxins in both millet and maize. Molecular modeling revealed that the broad-specificity was related with the chlorine electronegativity on OTA and OTC and the potential of the acetyl ester group on OTC. The proposed ELISA can be used for simultaneous detection of three ochratoxins.


Real-time cell analysis for monitoring cholera toxin-induced human intestinal epithelial cell response.
The pathogenic mechanism of Vibrio cholerae manifests as diarrhea and causes life-threatening dehydration. Here, we observe the human intestinal epithelial cells (HIEC) response to Cholera toxin (CT) by a real-time cell analysis (RTCA) platform, and disclose the difference from CT-induced cytotoxicity and others in HIEC. An HIEC cell of 1.0 × 10(5) cells/mL was characterized as the suitable concentration for each well. For experimentation, the assay requires an inoculation of CT dissolved in Dulbecco's phosphate-buffered saline with 0.1 % gelatin for a period of 18-25 h. The dimensionless impedance cell index curve presented characteristic dose- and time-dependent drop responses at the first stage, and the CT-induced cytotoxicity was the most remarkable following exposure for 18-25 h (P = 0.0002). Following the obvious cytotoxic reaction, the CI curve gradually increased over time until the original CI value, indicating that self-recovery occurred. The CT-induced CI curve for HIEC was different from that induced by other toxins, including diphtheria and Clostridium difficile toxin. Collectively, these results suggest that the CT-induced cytotoxicity in HIEC was absolutely different from that induced by C. difficile and other toxins because of the different pathogeneses that were correlated with the specific CI curve generated by the RTCA system. In summary, our data show that the assay described here is a convenient and rapid high-throughput tool for real-time monitoring of host cellular responses to CT on the basis of the characteristic CI curve.


How relevant are vascular endothelial growth factor and intercellular adhesion molecule in the systemic capillary leak syndrome of psoriasis?
Psoriasis is a chronic disease, characterized by erythematous scaly lesions, presented in eight different forms: plaques, guttate, pustular, erythrodermic, inverse, nail and scalp psoriasis, and psoriatic arthritis. Its development depends on genetic factors, external stimulus and immune response alteration.1 Proinflammatory cytokines such as TNF-alpha, IL-12 and 23 may also be involved. In the worst cases, systemic complications linked to endothelial alterations may occur. A literature review was conducted for a better understanding of what roles VEGF (vascular endothelial growth factor) and ICAM-1 (intercellular adhesion molecule) have, among other cytokines, in systemic capillary leak syndrome, involved in erythrodermic and pustular psoriasis, the most unstable forms of the disease.


Analysis of optically anisotropic properties of biological tissues under stretching based on differential Mueller matrix formalism.
The optical properties of biological tissues under stretching are investigated using a full-field ellipsometry technique based on a differential Mueller matrix formalism. Traditional photoelastic-based formalism for extracting the linear birefringence (LB) properties of stretched anisotropic optical samples ignores the effects of the other optical properties of the sample. By contrast, in the formalism proposed in this study, the LB, linear dichroism (LD), circular birefringence (CB), circular dichroism (CD), and depolarization (Dep) properties are fully decoupled. Simulations are performed to evaluate the performance of the two formalisms in extracting the LB properties of optically anisotropic samples with different degrees of Dep, CB, LD, and CD. The practical feasibility of the proposed all-parameter decoupled formalism is then demonstrated using chicken breast muscle tissue. In general, the results show that both formalisms provide a reliable LB measurement performance for healthy chicken breast tissue under stretching. However, while the LB-only formalism has good robustness toward scattering, its measurement performance is seriously degraded for samples with high CB. Thus, of the two formalisms, the proposed all-parameter decoupled formalism provides a more effective approach for examining the anisotropic properties of biological tissues under stretching.


Effects of cadmium and nisoldipine on the delayed rectifier potassium current in guinea pig ventricular myocytes.
Block of the slow inward calcium current (Isi) during assessment of the delayed rectifier potassium current (IK) of cardiac ventricular myocytes is commonly achieved by use of either inorganic compounds such as cadmium or dihydropyridine derivatives such as nisoldipine. Effects of these two Isi blockers on IK characteristics of guinea pig ventricular myocytes were compared in this study. Currents were measured in the whole cell configuration of the patch-clamp technique and IK tail amplitudes were measured at -40 mV after depolarizations to various test potentials (voltage steps, -20 to +50 mV) for either 250 (IK250), 450 (IK450) or 5000 (IK5000) msec. Activating and tail currents measured in the presence of cadmium were of greater amplitudes when voltage steps were more positive than 0 mV but were of smaller amplitudes at Vtest < or = 0 mV compared to currents measured in the presence of nisoldipine or Tyrode solution. In the presence of the rapid component of the delayed rectifier E-4031, a blocker of cadmium increased IKs amplitude during high voltage tests and caused a positive shift in the voltage dependence of IKs activation at low depolarizing potentials. In contrast, no effect on IK was observed when nisoldipine was added to Tyrode solution. In conclusion, results obtained in this study suggest that cadmium depresses and/or shifts the activation curve of the rapid component and increases and positively shifts the slow component of IK in guinea pig ventricular myocytes. These observations lead us to propose that nisoldipine may be a better tool to inhibit long lasting inward calcium current during assessment of IK.


Effects of Plyometric Training on Soft and Hard Surfaces for Improving Running Economy.
The present study investigated the effects of plyometric jump training on hard and soft surfaces on running economy (RE), maximal oxygen uptake (VO2max), running performance and the rate of force development in orienteers. Nineteen orienteers (11 women and 8 men, body mass 61.1 ± 7.3 kg, age 21 ± 5.8 yrs) were randomly stratified based on sex, age, VO2max and RE to plyometric jumping training (8 sessions over 4 weeks) on either a hard or a soft surface. RE, VO2max and running performance were assessed on a treadmill and outdoor on- and off-trail loops. Moreover, ground reaction forces and force development were assessed during a one leg drop-jump test. The training intervention led to an overall 2-7% improvement in treadmill and off-trail RE, independent of the jumping surface and running velocity assessed. These improvements were not explained by force development during drop jump tests, which remained unchanged following the intervention. The changes in time-trial performance were associated with changes in RE. Plyometric training improved RE with no difference between the hard or the soft training surface and improved RE was also independent of the running speed assessed. Furthermore, improved running performance was associated with changes in RE after the intervention.


The use of phage display in neurobiology.
Phage display has been extensively used to study protein-protein interactions, receptor- and antibody-binding sites, and immune responses, to modify protein properties, and to select antibodies against a wide range of different antigens. In the format most often used, a polypeptide is displayed on the surface of a filamentous phage by genetic fusion to one of the coat proteins, creating a chimeric coat protein, and coupling phenotype (the protein) to genotype (the gene within). As the gene encoding the chimeric coat protein is packaged within the phage, selection of the phage on the basis of the binding properties of the polypeptide displayed on the surface simultaneously results in the isolation of the gene encoding the polypeptide. This unit describes the background to the technique, and illustrates how it has been applied to a number of different problems, each of which has its neurobiological counterparts. Although this overview concentrates on the use of filamentous phage, which is the most popular platform, other systems are also described.


Multifocal Primary Uveal Melanoma: Clinical and Molecular Characteristics.
We report two patients who developed a second distinct choroidal melanoma in the same eye following successful regression of their first choroidal melanoma after iodine-125 plaque brachytherapy. Neither patient demonstrated ocular melanocytosis, local tumor recurrence, or vitreous seeding. One patient had the second tumor arising from a previously documented choroidal nevus, and after undergoing enucleation, there was no detectable connection between the tumors on histopathologic examination. Germline BAP1 mutation was absent in both cases. Multifocal primary uveal melanoma is a rare entity in which the second tumor may occur either de novo or from a malignant transformation of a choroidal nevus. Known risk factors include ocular melanocytosis or germline BAP1 mutation. Additional underlying mechanisms have yet to be elucidated.


Health-related quality of life after 5-12 years of continent ileal urostomy (Kock reservoir) in children and adolescents.
To assess quality of life after continent ileal reservoir diversion in children and adolescents. Nine boys and 9 girls (10.8-18 years old at surgery) were operated with a Kock reservoir and followed for 5-12 years. They participated in an interview using a questionnaire based on the Swedish self-esteem inventory, "I think I am". The questionnaire consisted of 76 questions that covered medical, physical, psychological, social, body image and sexual aspects. Six of 18 patients had some difficulties on catheterization. Five complained of pain or bleeding during evacuation. Two patients had slight urinary leakage between evacuations and 6 had mucus secretion. Ten patients had diarrhea with different frequencies. Physical activities were not hampered by the operation in any patient. Instead, activities such as full day outside home, friend at home overnight, using all types of clothes, and participation in camps were increased in 8, 6, 5 and 5 patients, respectively. All patients but 2 had an excellent relation with friends and family members. More than half of patients had excellent positive self-esteem and body image and the rest had very good self-esteem. However, some patients were concerned about how they looked and felt that life was unfair to them. The patients were satisfied with their operation. They were physically active and declared a positive perspective regarding self-esteem and body image. The medical problems related to the operation did not have any negative influence on the self-esteem or body image. The choice of the operation can only be determined on the basis of an attentive dialogue between surgeon, child and parents.


A Review of Systematic Reviews Targeting the Prevention and Treatment of Overweight and Obesity in Adolescent Populations.
Adolescent obesity is a powerful predictor of morbidity and mortality, yet amenable to modifiable behaviors. To accurately summarize the effects of behavioral interventions on changes in adolescent body mass index and/or weight status, we assessed existing systematic reviews for reporting transparency and methodological quality. Five databases were searched through September 2017 to identify relevant systematic reviews. Reviews were evaluated for reporting transparency and methodological quality using PRISMA Reporting Checklist and Assessment of Multiple Systematic Reviews Instrument. Evidence was synthesized across high-quality reviews. Four of twelve systematic reviews were of high methodological quality. All four focused on the treatment of overweight/obesity in adolescent populations, representing 97 international studies. Findings indicate intervention compared with no intervention/wait list showed larger effects for improving BMI/BMI z-scores. Small improvements (averaging a 3.7-kg decrease) in weight/weight percentile were observed following a supervised exercise plus dietary and/or behavior support intervention. Health-related quality of life may improve following interventions, but overall attention to associated psychological variables (depression, self-esteem/perception) is limited. Adherence to objective checklists and protocols for rigorous conduct and reporting of systematic reviews is warranted. Consensus evidence is urgently needed to define and report behavior change interventions related to obesity prevention and treatment.


Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130.
Gp130 is a shared cell-surface signaling receptor for at least ten different hematopoietic cytokines, but the basis of its degenerate recognition properties is unknown. We have determined the crystal structure of human leukemia inhibitory factor (LIF) bound to the cytokine binding region (CHR) of gp130 at 2.5 A resolution. Strikingly, we find that the shared binding site on gp130 has an entirely rigid core, while the LIF binding interface diverges sharply in structure and chemistry from that of other gp130 ligands. Dissection of the LIF-gp130 interface, along with comparative studies of other gp130 cytokines, reveal that gp130 has evolved a "thermodynamic plasticity" that is relatively insensitive to ligand structure, to enable crossreactivity. These observations reveal a novel and alternative mechanism for degenerate recognition from that of structural plasticity.


Placental specific mRNA in the maternal circulation are globally dysregulated in pregnancies complicated by fetal growth restriction.
Fetal growth restriction (FGR) is a leading cause of perinatal mortality, yet no reliable screening test exists. Placental specific mRNA in the maternal circulation may reflect changes in the placental transcriptome in FGR and could be a novel biomarker for FGR. The aim of the study was to identify placental specific RNA detectable in the maternal circulation and examine whether they are differentially expressed in severe preterm FGR. In silico screening was used to identify placental specific RNAs. Their expression in cases of severe FGR vs controls was examined in both maternal blood and placenta by microarray, RT-PCR, and in situ hybridization. Via in silico analysis, we identified 137 genes very highly expressed in the placenta relative to other tissues. Using microarray, we found that they were detectable in the maternal blood and were globally dysregulated with preterm FGR; 75 genes (55%) had a ≥1.5-fold differential expression compared to controls. Eight genes (ERVWE-1, PSG1, PLAC4, TAC3, PLAC3, CRH, CSH1, and KISS1) were validated by RT-PCR to be significantly increased in both maternal blood and placenta in a larger cohort of severe FGR compared to controls. In situ hybridization confirmed PAPPA2 and ERVWE-1 localized to the syncytiotrophoblast. There is global differential expression of placental specific mRNA in the maternal blood in pregnancies complicated by severe preterm FGR. Placental specific mRNA in maternal blood may represent a new class of biomarkers for preterm FGR.


The Relationship between Locomotive Syndrome and Depression in Young Chinese College Students.
This study investigates the relationship between locomotive syndrome (LS) and mental disorder (depression) in young Chinese college students. Our study population (n = 165; mean age of 19.82 ±1.90 years) comprises college student residents at Tsinghua University in Beijing, China. Three screening methods were used to evaluate LS: 25-question Geriatric Locomotive Function Scale (GLFS-25), a two-step test, and a stand-up test. Depression was screened by the Chinese version of the Zung Self-Rating Depression Scale (ZSDS). The prevalence of LS and depression was 20.1% and 30.9%, respectively. The LS group had lower grip strength and higher ZSDS scores than the non-LS group. Young Chinese college students have a relatively high prevalence of LS, and LS and GLFS-25 scores were significantly related to depression. The present results suggest that management strategies for LS should consider depressive symptoms among young adults.


Anti-proliferative activity of interferon-alpha on human squamous carcinoma of tongue cell lines.
We evaluated the anti-tumour activity of human recombinant interferon-alpha (IFN-alpha) on two human squamous carcinoma of tongue cell lines (T2/CUHK and PWH-S1). The in vitro cytotoxicity was monitored by MTT assay. Continuous exposure to IFN-alpha alone at 500 IU/ml for 48 h produced inhibitory growth of 30% and 7% on T2/CUHK and PWH-S1 cell lines respectively. The ID50 of T2/CUHK cells was approximately 2500 IU/ml. PWH-S1 cells were resistant to treatment with interferon-alpha as 500 IU/ml IFN-alpha gave only 10% growth inhibition on PWH-S1 cells. IFN-alpha increased the anti-neoplastic activity of cisplatin and 5-FU against T2/CUHK cells, but the effect was less evident in PWH-S1 cells. Our findings support the further evaluation of IFN-alpha as a potent anti-proliferative cytokine therapy that may act synergistically with conventional chemotherapeutic agents for the treatment of squamous carcinoma of head and neck.


Treatment of opioid-induced constipation: focus on the peripheral μ-opioid receptor antagonist methylnaltrexone.
Most prescribed opioids exert their analgesic effects via activation of central μ-opioid receptors. However, μ-opioid receptors are also located in the gastrointestinal (GI) tract, and activation of these receptors by opioids can lead to GI-related adverse effects, in particular opioid-induced constipation (OIC). OIC has been associated with increased use of healthcare resources, increased healthcare costs, and decreased quality of life for patients. Nonpharmacologic (e.g., increased fiber uptake) and pharmacologic agents (e.g., laxatives) may be considered for the treatment and prevention of OIC. However, many interventions, such as laxatives alone, are generally insufficient to reverse OIC because they do not target the underlying cause of OIC, opioid activation of μ-opioid receptors in the GI tract. Therefore, there has been keen interest in antagonism of the μ-opioid receptor in the periphery to inhibit the effects of opioids in the GI tract. In this review, currently available pharmacologic therapies for the treatment and prevention of OIC are summarized briefly, with a primary focus on the administration of the peripheral μ-opioid receptor antagonist methylnaltrexone bromide in patients with OIC and advanced illness who are receiving palliative care. Also, clinical trial data of methylnaltrexone treatment in patients with OIC and other pain conditions (i.e., chronic noncancer pain and pain after orthopedic surgery) are reviewed. Data support that methylnaltrexone is efficacious for the treatment of OIC and has a favorable tolerability profile.


Combined thioflavin T-Congo red fluorescence assay for amyloid fibril detection.
Fluorescence represents one of the most powerful tools for the detection and structural characterization of the pathogenic protein aggregates, amyloid fibrils. The traditional approaches to the identification and quantification of amyloid fibrils are based on monitoring the fluorescence changes of the benzothiazole dye thioflavin T (ThT) and absorbance changes of the azo dye Congo red (CR). In routine screening it is usually sufficient to perform only the ThT and CR assays, but both of them, when used separately, could give false results. Moreover, fibrillization kinetics can be measured only by ThT fluorescence, while the characteristic absorption spectra and birefringence of CR represent more rigid criteria for the presence of amyloid fibrils. Therefore, it seemed reasonable to use both these dyes simultaneously, combining the advantages of each technique. To this end, we undertook a detailed analysis of the fluorescence spectral behavior of these unique amyloid tracers upon their binding to amyloid fibrils from lysozyme, insulin and an N-terminal fragment of apolipoprotein A-I with Iowa mutation. The fluorescence measurements revealed several criteria for distinguishing between fibrillar and monomeric protein states: (i) a common drastic increase in ThT fluorescence intensity; (ii) a sharp decrease in ThT fluorescence upon addition of CR; (iii) an appearance of the maximum at 535-540 nm in the CR excitation spectra; (iv) increase in CR fluorescence intensity at 610 nm. Based on these findings we designed a novel combined ThT-CR fluorescence assay for amyloid identification. Such an approach not only strengthens the reliability of the ThT assay, but also provides new opportunities for structural characterization of amyloid fibrils.


Electrophoretic and immunoelectrophoretic analysis of pig epidermal plasma membrane glycoproteins.
he glycoprotein components of a plasma membrane-enriched fraction from pig epidermis were isolated by deoxycholate extraction and affinity chromatography on concanavalin A (ConA)-Sepharose 4B. Reduction with 5% 2-mercaptoethanol, electrophoresis on 10% polyacrylamide slab gels, and periodic acid-Schiff (PAS) staining resolved the major glycoproteins into at least 5 components of Mr 180K, 150K, 130K, 100K and 85K. Neuraminidase removed essentially all the sialic acid whether or not the glycoproteins were solubilized with detergents. Neuraminidase treatment increased the electrophoretic mobility of most components on one-dimension polyacrylamide gels, indicating their sialoglycoprotein nature. An antiserum was raised in rabbits against isolated epidermal plasma membrane glycoproteins. Isolated immunoglobulins were used in crossed immunoelectrophoretic analysis of the glycoproteins and produced 5 major immunoprecipitates. The glycoprotein nature of the immunoprecipitates was shown by their susceptibility to neuraminidase. Crossed immunoelectrophoresis was used to examine the lectin binding specificity of isolated epidermal plasma membrane glycoproteins. The immunoprecipitation patterns were affected strongly by Ricinus communis agglutinin (RCA), moderately by wheatgerm agglutinin (WGA), and weakly by soybean agglutinin (SBA). Peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), and Ulex europaeus agglutinin (UEA) had little effect on the immunoprecipitation patterns, indicating little interaction between epidermal plasma membrane glycoprotein and these lectins. Other glycoproteins and/or glycolipids must therefore be responsible for the binding of these lectins by epidermal cells.


Prenatal findings in a monozygotic twin pregnancy with Costello syndrome.
This report describes the prenatal findings in monozygotic twins with Costello syndrome. At 16 weeks one twin had 9 mm of nuchal oedema: coarctation of the aorta was diagnosed after birth. At 22(5/7) weeks relative macrocephaly, mild pyelectasia and moderate polyhydramnios were noted in both twins. In the following 4 weeks the polyhydramnios increased significantly without visualisation of filling of the stomach. Between 27(5/7) and 30(2/7) weeks a total of 9 l amniotic fluid was drained and at 30(4/7) weeks prelabor premature rupture of membranes (PPROM) occurred followed by premature labor and delivery. The neonatal period was complicated by growth retardation, deglutition problems, hypotonia, cardiac and respiratory problems. Both twins died on Day 57 because of respiratory insufficiency.


Draft Genome Sequence of Desulfuromonas acetexigens Strain 2873, a Novel Anode-Respiring Bacterium.
Here, we report the draft genome sequence of Desulfuromonas acetexigens strain 2873, which was originally isolated from digester sludge from a sewage treatment plant in Germany. This bacterium is capable of anode respiration with high electrochemical activity in microbial electrochemical systems. The draft genome contains 3,376 predicted protein-coding genes and putative multiheme c-type cytochromes.


Anisakis antigens detected in fish muscle infested with Anisakis simplex L3.
Anisakis simplex is a fish parasite that is a public health risk to those consuming raw or poorly cooked marine fish and cephalopods because of the possibility of becoming infested with live larvae. In humans, penetration of the larvae into the gastrointestinal track can cause acute and chronic symptoms and allergic anisakiasis. Excretion and secretion products released by the larvae are thought to play a role in migration through the tissues and induce an immunoglobulin E-mediated immune response. The aim of this preliminary study was to detect parasite antigens and allergens in fish tissues surrounding the migrating larvae. Hake and anchovy fillets were artificially parasitized with Anisakis larvae and stored in chilled conditions for 5 days. Larvae were evaluated for fluorescence, fish muscle tissue was examined with transmission electron microscopy, and immunohistochemical reactions of two rabbit polyclonal antisera against a parasite crude extract and the allergen Ani s 4 were recorded. Larvae immediately migrated into the fish muscle, and no emission of bluish fluorescence was observed. Fish muscle areas in contact with the parasite showed disruptions in the structure and inclusion of granules within sarcomeres. Both parasite antigens and the Ani s 4 allergen were located in areas close to the larvae and where sarcomere structure was preserved. These findings indicate that parasite antigens and allergens are dispersed into the muscle and might cause allergic symptoms such as dyspnea, vomiting, diarrhea, urticaria, angioedema, or anaphylaxis in some individuals sensitive to A. simplex.


Cadmium Concentration in Grains of Durum Wheat (Triticum turgidum L. subsp. durum).
Heavy metal excess in soil represents a critical problem for crop productivity. Among these pollutants, cadmium (Cd) is one of the most dangerous in terms of food-chain contamination. Two durum wheat near-isogenic lines (NILs) and 12 commercial varieties (cultivars Arcangelo, Aureo, Aziziah, Cappelli, Cirillo, Creso, Iride, Maestrale, Parsifal, Russello, Strongfield, and Svevo) of durum wheat were exposed to a nontoxic level of Cd to evaluate its concentration in grains, roots, and shoots, as well as effects on biomass production. Cultivar Iride showed the most interesting behavior because it stored large amounts of Cd in the roots, preventing its translocation to grains. On the contrary, Cirillo and Svevo genotypes were characterized by a high Cd concentration in the grains. Furthermore, a molecular characterization employing the ScOPC20 marker associated with the Cd uptake locus has shown the absence of the expected fragment in the Iride variety and in other varieties characterized by low Cd concentration, as well as the presence of it in high Cd-accumulating cultivars.


Sox genes and cancer.
Sox genes encode transcription factors belonging to the HMG (High Mobility Group) superfamily. They are conserved across species and involved in a number of developmental processes. In vitro studies have shown at least one Sox gene to be capable of inducing oncogenic transformation of fibroblast cells. In addition, overexpression and/or amplification of Sox genes are associated with a large number of tumour types in vivo. We review here the available evidence linking Sox gene expression and cancer, and show that this link is supported by extensive EST database analysis. This work provides a basis for further studies aimed at investigating the possible role of Sox genes in the oncogenic process.


Effects of Virgin Olive Oil on Bone Health in Ovariectomized Rats.
Osteoporosis is a pressing concern facing public health, thus making research into the effects of nutrients on bone health particularly important. Evidence from preclinical studies using animal models and a limited number of studies in human suggests that olive oil (OO) is a protective agent for bone. The aim of this work is to study the effects of virgin olive oil (VOO) consumption by ovariectomized rats on bone health. A total of 48 6-month-old female Wistar rats weighing 320 ± 10 g (mean ± SD) were divided into the following groups: SHAM (n = 12), simulated intervention; OVX (n = 12), ovariectomized; OVX + 100 (n = 12), ovariectomized and treated with VOO (100 µL/day by oral gavage); and OVX + 200 (n = 12) ovariectomized and treated with VOO (200 µL/day by oral gavage), all over 3 months. Femoral (F) and lumbar (L) bone mineral density (FBMD and LBMD), microtomographic parameters, fractal dimension D2D and D3D, and biomechanical properties were studied. After 3 months of VOO treatment, although FBMD and LBMD were not affected, bone quality was improved, as the elasticity of bone and fractal dimension (complexity of bone) were more similar to healthy bone. Our results support the findings of previous research suggesting that dietary intake of olive oil may exert beneficial effect on some bone characteristics.


A dose error evaluation study for 4D dose calculations.
Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms.The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms.The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm; 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex programming structure. The study discloses disadvantages for the bETM and for the DIM. DIM yielded insufficient results for large voxel sizes, while bETM is prone to errors for small voxel sizes.


Modeling the radiolysis of supercritical water by fast neutrons: density dependence of the yields of primary species at 400°c.
A reliable understanding of radiolysis processes in supercritical water (SCW)-cooled reactors is crucial to developing chemistry control strategies that minimize the corrosion and degradation of materials. However, directly measuring the chemistry in reactor cores is difficult due to the extreme conditions of high temperature and pressure and mixed neutron and gamma-radiation fields, which are incompatible with normal chemical instrumentation. Thus, chemical models and computer simulations are an important route of investigation for predicting the detailed radiation chemistry of the coolant in a SCW reactor and the consequences for materials. Surprisingly, information on the fast neutron radiolysis of water at high temperatures is limited, and even more so for fast neutron irradiation of SCW. In this work, Monte Carlo simulations were used to predict the G values for the primary species e(-)aq, H(•), H2, (•)OH and H2O2 formed from the radiolysis of pure, deaerated SCW (H2O) by 2 MeV monoenergetic neutrons at 400°C as a function of water density in the range of ∼0.15-0.6 g/cm(3). The 2 MeV neutron was taken as representative of a fast neutron flux in a reactor. For light water, the moderation of these neutrons after knock-on collisions with water molecules generated mostly recoil protons of 1.264, 0.465, 0.171 and 0.063 MeV. Neglecting oxygen ion recoils and assuming that the most significant contribution to the radiolysis came from these first four recoil protons, the fast neutron yields were estimated as the sum of the G values for these protons after appropriate weightings were applied according to their energy. Calculated yields were compared with available experimental data and with data obtained for low-LET radiation. Most interestingly, the reaction of H(•) atoms with water was found to play a critical role in the formation yields of H2 and (•)OH at 400°C. Recent work has underscored the potential importance of this reaction above 200°C, but its rate constant is still controversial.


Ultrastructural localization of acid phosphatase in normal and X-irradiated epidermis.
Acid phosphatase activity has been studied in normal and X-irradiated rat epidermis. A remarkable reaction increment was found in irradiated epithelium at the granular layer keeping the same pattern of distribution observed in the normal tissue. No reactive lysosomes or keratinosomes were observed in the cytochemical sections, while many keratinosomes but no lysosomes appeared in the electron microscopic preparations of irradiated animals. Irradiated epithelium is discussed as a suitable model to analyze the role of acid phosphatase in the keratinization mechanisms.


Development of a finite element head model for the study of impact head injury.
This study is aimed at developing a high quality, validated finite element (FE) human head model for traumatic brain injuries (TBI) prediction and prevention during vehicle collisions. The geometry of the FE model was based on computed tomography (CT) and magnetic resonance imaging (MRI) scans of a volunteer close to the anthropometry of a 50th percentile male. The material and structural properties were selected based on a synthesis of current knowledge of the constitutive models for each tissue. The cerebrospinal fluid (CSF) was simulated explicitly as a hydrostatic fluid by using a surface-based fluid modeling method. The model was validated in the loading condition observed in frontal impact vehicle collision. These validations include the intracranial pressure (ICP), brain motion, impact force and intracranial acceleration response, maximum von Mises stress in the brain, and maximum principal stress in the skull. Overall results obtained in the validation indicated improved biofidelity relative to previous FE models, and the change in the maximum von Mises in the brain is mainly caused by the improvement of the CSF simulation. The model may be used for improving the current injury criteria of the brain and anthropometric test devices.


Thirdhand tobacco smoke: procedures to evaluate cytotoxicity in cell cultures.
The risks associated to tobacco smoking are not ceased with smoke extinction. Many toxic compounds remain in the environment after the cigarette is extinguished and accumulated in the air or on surfaces. However, little is known about the risks of this exposure. The aim of this study was to evaluate procedures to collect thirdhand smoke (THS) and prepare the samples to perform three in vitro toxicity tests. Cellulose papers and cotton wipes were used to impregnate with nicotine solution and smoke cigarette in a chamber or in smoker's home. Samples were immersed in methanol or Dulbecco's modified Eagle's medium (DMEM) to expose Hep-2 cells. MTT, neutral red uptake (NRU) and trypan blue assays were performed. The concentration of nicotine in DMEM extract of THS in paper and cotton was similar to those in methanol extract (p > 0.05). Alterations in the mitochondrial and lysosomal functions were found in both paper and cotton samples; however, the cytotoxic effect was not always observed. There was a decrease of 21-31% in MTT assay and 38-56% in NRU assay (p < 0.003). There was a dose-response relationship between the amount of cigarettes and lysosomal viability; the correlation was higher for cotton samples (r = -0.843, p < 0.001). As a dose-response relationship was found only in NRU assay, this test may be a more suitable choice rather than the MTT assay. Paper and wipe sampling can be reliable markers of tobacco smoke contamination. Moreover, these materials, if properly prepared, can be used as substrate providers to perform cellular assays.


Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden: a genetically informed register study.
Emerging evidence suggests increased risk of several physical health conditions in people with ADHD. Only a few physical conditions have been thoroughly studied in relation to ADHD, and there is little knowledge on associations in older adults in particular. We aimed to investigate the phenotypic and aetiological associations between ADHD and a wide range of physical health conditions across adulthood. We did a register study in Sweden and identified full-sibling and maternal half-sibling pairs born between Jan 1, 1932, and Dec 31, 1995, through the Population and Multi-Generation Registers. We excluded individuals who died or emigrated before Jan 1, 2005, and included full-siblings who were not twins and did not have half-siblings. ICD diagnoses were obtained from the National Patient Register. We extracted ICD diagnoses for physical conditions, when participants were aged 18 years or older, from inpatient (recorded 1973-2013) and outpatient (recorded 2001-13) services. Diagnoses were regarded as lifetime presence or absence. Logistic regression models were used to estimate the associations between ADHD (exposure) and 35 physical conditions (outcomes) in individuals and across sibling pairs. Quantitative genetic modelling was used to estimate the extent to which genetic and environmental factors accounted for the associations with ADHD. 4 789 799 individuals were identified (2 449 146 [51%] men and 2 340 653 [49%] women), who formed 4 288 451 unique sibling pairs (3 819 207 full-sibling pairs and 469 244 maternal half-sibling pairs) and 1 841 303 family clusters (siblings, parents, cousins, spouses). The mean age at end of follow-up was 47 years (range 18-81; mean birth year 1966); ethnicity data were not available. Adults with ADHD had increased risk for most physical conditions (34 [97%] of 35) compared with adults without ADHD; the strongest associations were with nervous system disorders (eg, sleep disorders, epilepsy, dementia; odds ratios [ORs] 1·50-4·62) and respiratory diseases (eg, asthma, chronic obstructive pulmonary disease; ORs 2·42-3·24). Sex-stratified analyses showed similar patterns of results in men and women. Stronger cross-disorder associations were found between full-siblings than between half-siblings for nervous system, respiratory, musculoskeletal, and metabolic diseases (p<0·007). Quantitative genetic modelling showed that these associations were largely explained by shared genetic factors (60-69% of correlations), except for associations with nervous system disorders, which were mainly explained by non-shared environmental factors. This mapping of aetiological sources of cross-disorder overlap can guide future research aiming to identify specific mechanisms contributing to risk of physical conditions in people with ADHD, which could ultimately inform preventive and lifestyle intervention efforts. Our findings highlight the importance of assessing the presence of physical conditions in patients with ADHD. Swedish Research Council; Swedish Brain Foundation; Swedish Research Council for Health, Working Life, and Welfare; Stockholm County Council; StratNeuro; EU Horizon 2020 research and innovation programme; National Institute of Mental Health.


Effect of Cellulose-Based Bioplastics on Current LDPE Recycling.
The increased use of bioplastics in the market has led to their presence in municipal solid waste streams alongside traditional fossil-based polymers, particularly low-density polyethylene (LDPE), which bioplastics often end up mixed with. This study aimed to assess the impact of cellulose acetate plasticized with triacetin (CAT) on the mechanical recycling of LDPE. LDPE-CAT blends with varying CAT content (0%, 1%, 5%, 7.5%, and 10% by weight) were prepared by melt extrusion and analyzed using scanning electron microscopy, Fourier-transform infrared spectroscopy, thermal analysis (thermogravimetric and differential scanning calorimetry), dynamic rheological measurements, and tensile tests. The results indicate that the presence of CAT does not significantly affect the chemical, thermal, and rheological properties of LDPE, and the addition of CAT at different levels does not promote LDPE degradation under typical processing conditions. However, the addition of CAT negatively impacts the processability and mechanical behavior of LDPE, resulting in the reduced quality of the recycled material. Thus, the presence of cellulose-based bioplastics in LDPE recycling streams should be avoided, and a specific sorting stream for bioplastics should be established.


Effects of large-volume paracentesis on pulmonary function in patients with tense cirrhotic ascites.
Large-volume paracentesis is an accepted therapeutic modality for the treatment of tense ascites in patients with cirrhosis. Whereas the effects of large-volume paracentesis on the cardiovascular system have been studied in great detail, the effects of tense ascites and large-volume paracentesis on the respiratory system have undergone only limited evaluation. Most patients report symptomatic improvement in breathing after large-volume paracentesis. The aim of our study was to prospectively evaluate the effects of large-volume paracentesis on the pulmonary function of patients with tense ascites. Nine patients with alcoholic cirrhosis and tense ascites underwent large-volume paracentesis (mean, 3,500 ml of ascites removed) followed by intravenous albumin infusion (10 gm/L ascites removed). Pulmonary function tests were performed just before and 2 hr after large-volume paracentesis. The functional residual capacity increased from 2.46 +/- 0.92 to 2.99 +/- 0.97 L (p = 0.01) and total lung capacity from 5.08 +/- 1.18 to 5.72 +/- 1.32 L (p = 0.03). The forced vital capacity, expiratory reserve volume and residual volume also increased but were not statistically significant (p = 0.07 for all). We noted no significant improvement in forced expiratory volume in 1 sec, forced expiratory effort 25% to 75%, vital capacity or diffusion capacity. There was marked symptomatic improvement in all patients. We conclude that large-volume paracentesis improves measured lung volumes within hours in patients with tense ascites.


Hypertension therapy: current and future strategies.
Arterial hypertension is one of the three major cardiovascular risk factors and the most common chronic disorder to cause death. The treatment of hypertension, especially moderate and severe cases, produces a marked reduction in cerebrovascular and coronary mortality and morbidity. Several trials, however, have shown that there is no benefit to be gained from treating mild hypertension (diastolic blood pressure 90-104 mmHg) because the unwanted side-effects of antihypertensive drugs outweigh their potential advantages. For this reason, it is important to continue pharmacological research to find new antihypertensive drugs and to develop further classical agents, such as the beta-blockers, which reduce ventricular hypertrophy and prevent coronary mortality in secondary prevention regimes.


Progesterone profiles of fat-tailed tuj ewes following tactile and visual separation of rams at the beginning of the breeding season.
The aim of this study was to determine the level and duration of progesterone secretion during the sequential oestrous cycles in fat-tailed Tuj ewes following tactile and visual separation of rams during the breeding season. For these purposes, rams were separated from the main flock for 50 days starting from the beginning of the breeding season and 21 ewes were randomly selected for the current experiment. In order to assess luteal activity and the length of oestrous cycles, the ewes were blood-sampled thrice or twice weekly for the measurement of progesterone in plasma. The data showed that 3 +/- 0.2 oestrous cycles were observed in this time window, and the first oestrous cycle observed was shorter (P < 0.05) than the following cycles (mean +/- SEM, 14.6 +/- 0.82, 16.5 +/- 0.48 and 17.0 +/- 0.54 days, respectively, for cycles 1, 2 and 3). Progesterone production was significantly lower in the first oestrous cycle compared with the second and third cycles on days 9, 12 and 14 of the cycles. The follicular periods of ewes showed four accumulations (maximum values using a 3-day moving average technique) throughout the study and the percentages of ewes at each accumulation (peak day +/- 1 day) were 50, 35, 65 and 80% for the first, second, third and fourth accumulations, respectively (P < 0.05). It was concluded that progesterone production was lower and the oestrous cycles were shorter during the first oestrous cycle and that tactile and visual separation of rams at the beginning of the breeding season might enhance the synchronizing effect towards the end of the breeding season in the fat-tailed Tuj ewes.


Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes.
Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1. In three families a homozygous 15.9 kb deletion including complete PROP1 was discovered. Breakpoints map within highly homologous AluY sequences. Haplotype analysis revealed a shared haplotype of 350 kb among PROP1 deletion carriers. For the first time we were able to assign the boundaries of a previously reported PROP1 deletion. This gross deletion shows strong evidence to originate from a common ancestor in patients with Kurdish descent. No CNVs within LHX3, LHX4, HESX1, GH1 and GHRHR were found. Our data prove multiplex ligation-dependent probe amplification to be a valuable tool for the detection of CNVs as cause of pituitary insufficiencies and should be considered as an analytical method particularly in Kurdish patients.


Absence of angiogenesis-inhibitory activity in aqueous humor of diabetic rabbits.
We studied inhibitory activity of angiogenesis in the eye to explore the formation of new blood vessels in diabetic microvascular diseases. When we examined the effects of extracts from various ocular tissues of nondiabetic rabbits on the proliferation of bovine aortic endothelial cells, potent inhibitory activity was found in lens and aqueous humor. Aqueous humor inhibited both angiogenesis on chorioallantoic membrane in vivo and promotion of endothelial cell growth in vitro, which were induced by retinal extracts. However, in diabetic rabbits, aqueous humor lost the ability to inhibit the growth of endothelial cells. The loss of activity became evident 1 mo after the alloxan injection and lasted while the animals were hyperglycemic. In addition, diabetic aqueous humor failed to suppress retinal extract-induced angiogenesis promotion and endothelial cell growth. The absence of the inhibitory activity of angiogenesis in diabetic aqueous humor might be involved in promotion of neovascularization in diabetic ocular disease.