Determination of saikosaponin derivatives in Radix bupleuri and in pharmaceuticals of the chinese multiherb remedy xiaochaihu-tang using liquid chromatographic tandem mass spectrometry.
Saikosaponins are bioactive oleanane saponins derived from the Chinese medicinal herb Radix bupleuri ("chaihu" in Chinese). An LC-MS/MS-based method has been developed for characterization and quantification of 15 saikosaponin derivatives (saikosaponin a, saikosaponin b(1), saikosaponin g, saikogenin A, saikogenin H, saikosaponin c, saikosaponin h, saikosaponin i, prosaikogenin C(2), prosaikogenin B(2), saikogenin C, saikogenin B, saikosaponin d, saikosaponin b(2), and saikogenin D) in one chromatographic run. Optimization of the ionization process was performed with electrospray and atmospheric pressure chemical ionization techniques in both positive and negative ion modes. Negative ion ESI was adopted for generation of the precursor deprotonated molecules to achieve the best ionization sensitivity for the analytes. In addition, the most abundant fragment ion was chosen for each analyte to give the best CID sensitivity. Because some of the saponin derivatives are isomeric, complete resolution for the whole analytes was achieved both chromatographically and mass spectroscopically. Furthermore, optimal internal standard was successfully discovered for determination of the analytes by making use of a combinatorial chemistry approach. Good linearity over the range approximately 1.65 or 4.98 to 1200 ng/mL for the analytes was observed. The intraday accuracy and precision at nominal low, intermediate, and high concentration varied between 0.8 and 11.8% and between 80 and 116%, respectively, whereas those for interday assay were between 1.1 and 15.5% and between 86 and 119%, respectively. The lower limits of quantitation for the test compounds were approximately 16.5 to 49.4 pg on-column. The new method offered higher sensitivity and greater specificity than previously reported LC methods. After the validation, the applicability of the method for determination of these chemicals present in a variety of crude chaihu roots and in different brands of the Chinese multiherb remedy Xiaochaihu-tang (or Shosaiko-to) extract granules has been demonstrated. The sensitivity and specificity of the technique will be the basis of a method for the accurate quantification of the saikosaponin derivatives in biomatrixes.


Evidence for a new resonance and search for the Y(4140) in the gammagamma-->phiJ/psi process.
The process gammagamma-->phiJ/psi is measured using a data sample of 825 fb{-1} collected with the Belle detector. A narrow peak of 8.8{-3.2}{+4.2} events, with a significance of 3.2 standard deviations including systematic uncertainty, is observed. The mass and natural width of the structure [named X(4350)] are measured to be [4350.6{-5.1}{+4.6}(stat)+/-0.7(syst)] MeV/c{2} and [13{-9}{+18}(stat)+/-4(syst)] MeV, respectively. The product of its two-photon decay width and branching fraction to phiJ/psi is [6.7{-2.4}{+3.2}(stat)+/-1.1(syst)] eV for J{P}=0{+}, or [1.5{-0.6}{+0.7}(stat)+/-0.3(syst)] eV for J{P}=2{+}. No signal for the Y(4140)-->phiJ/psi structure reported by the CDF Collaboration in B-->K{+}phiJ/psi decays is observed, and limits of Gamma_{gammagamma}(Y(4140))B(Y(4140)-->phiJ/psi)<41 eV for J{P}=0;{+} or <6.0 eV for J{P}=2{+} are determined at the 90% C.L. This disfavors the scenario in which the Y(4140) is a D{s}{*+}D{s}{*-} molecule.


Peptide-induced asymmetric distribution of charged lipids in a vesicle bilayer revealed by small-angle neutron scattering.
Cellular membranes are complex mixtures of lipids, proteins, and other small molecules that provide functional, dynamic barriers between the cell and its environment, as well as between environments within the cell. The lipid composition of the membrane is highly specific and controlled in terms of both content and lipid localization. The membrane structure results from the complex interplay between the wide varieties of molecules present. Here, small-angle neutron scattering and selective deuterium labeling were used to probe the impact of the membrane-active peptides melittin and alamethicin on the structure of lipid bilayers composed of a mixture of the lipids dimyristoyl phosphatidylglycerol (DMPG) and chain-perdeuterated dimyristoyl phosphatidylcholine (DMPC). We found that both peptides enriched the outer leaflet of the bilayer with the negatively charged DMPG, creating an asymmetric distribution of lipids. The level of enrichment is peptide concentration-dependent and is stronger for melittin than it is for alamethicin. The enrichment between the inner and outer bilayer leaflets occurs at very low peptide concentrations and increases with peptide concentration, including when the peptide adopts a membrane-spanning, pore-forming state. The results suggest that these membrane-active peptides may have a secondary stressful effect on target cells at low concentrations that results from a disruption of the lipid distribution between the inner and outer leaflets of the bilayer that is independent of the formation of transmembrane pores.


[MRI-TRUS targeted biopsy combined with large-section prostate pathology for accurate diagnosis of prostate cancer].
To investigate the application value of MRI-transrectal ultrasound (TRUS) targeted biopsy combined with large-section prostate pathology in the diagnosis of prostate cancer (PCa). Totally, 310 patients with suspected PCa underwent MRI-TRUS targeted biopsy combined with large-section prostate pathology (the observation group, n = 183) or standard 12-core TRUS biopsy (the control group, n = 127) in our hospital from January 2018 to December 2020. We compared the findings of biopsies and the detection rate of PCa between the two groups of patients. There were no statistically significant differences between the observation and control groups in the detection rates of PCa (35.52% vs 27.56%, P > 0.05), clinically significant PCa (30.60% vs 23.62%, P > 0.05) and clinically insignificant PCa (4.92% vs 3.94%, P > 0.05). The rate of positive punctures and the length of cancer tissue in the positive puncture were 27.50% and (4.68 ± 1.24) mm in the observation group, significantly higher than 22.38% and (3.70 ± 1.11) mm in the control (P < 0.05). The number of targeted punctures per case was markedly lower than that of system combined with targeted punctures (3 [1-5] vs 15 [13-17], P < 0.05). No statistically significant differences were observed between the targeted biopsy and system combined with targeted biopsy in the detection rates of PCa, clinically significant PCa and clinically insignificant PCa, the rate of positive punctures, or the length of cancer tissue in the positive puncture (P > 0.05). As the MRI features of PCa, the rates of T2WI low signal, irregular shape, blurred edge of lesions and DWI high signal were 63.08%, 76.92%, 83.08% and 84.62%, respectively, significantly higher than those of the benign lesions (P < 0.05), while the apparent diffusion coefficient (ADC) value of PCa was remarkably lower ([0.81 ± 0.15] ×10-3mm2/s) than that of the benign lesions (P < 0.05). MRI-TRUS targeted biopsy combined with large-section prostate pathology has a high application value in the diagnosis of PCa, which can reduce the number of punctures and differentiate benign from malignant prostatic lesions in MRI images.


A Five-Level, 1-MHz, Class-D Ultrasonic Driver for Guided-Wave Transducer Arrays.
This paper presents the design, characterization, and testing of an ultrasonic transducer driver capable of arbitrary waveform generation with a bandwidth of up to 1 MHz and an output range of ±96 V. The architecture is derived from bridged class-D switching amplifiers and has a five-level power stage. The proposed device was implemented with eight synchronized channels and an all-digital control circuitry to transmit guided-wave ultrasound signals using custom piezoelectric multi-element array transducers, allowing programmable mode selectivity.


Elevated levels of decidual insulin-like growth factor binding protein-1 in cervical fluid in early and mid-pregnancy are associated with an increased risk of spontaneous preterm delivery.
To study whether elevated levels of decidual insulin-like growth factor binding protein-1 (IGFBP-1) in the cervical fluid of unselected asymptomatic women in early or mid-pregnancy are associated with spontaneous preterm delivery (PTD). Prospective population-based cohort study. Maternity Clinics, University Central Hospital, Helsinki, Finland. A total of 5180 unselected pregnant women. Cervical swab samples were collected during the first and second trimester ultrasound screening. The concentration of IGFBP-1 was measured by immunoenzymometric assay, which detects the decidual phosphoisoforms of IGFBP-1 (phIGFBP-1). Concentrations of 10 micrograms/l or more were considered to be elevated. Spontaneous PTD. Results In the first trimester, 24.5% of women, and in the mid-second trimester, 20.2% of women, had an elevated cervical fluid phIGFBP-1 level. The rates of spontaneous PTD before 32 and before 37 weeks of gestation were higher in women with an elevated cervical fluid phIGFBP-1 level, compared with women who had cervical phIGFBP-1 of <10 micrograms/l (1.1% versus 0.3% and 5.7% versus 3.2%, respectively). An elevated phIGFBP-1 level in the first trimester was an independent predictor for PTD before 32 and before 37 weeks of gestation, with odds ratios of 3.0 (95% CI 1.3-7.0) and 1.6 (95% CI 1.2-2.3), respectively. Cervical phIGFBP-1 levels of 10 micrograms/l or more in the first trimester predicted PTD before 32 and before 37 weeks of gestation, with sensitivities of 53.8% and 37.0%, respectively. The negative predictive values were 99.7% and 96.8%. Elevated cervical fluid phIGFBP-1 levels in the first trimester were associated with an increased risk of spontaneous PTD.


Low-cost appropriate technologies for body composition assessment: a field researcher's view.
The field setting, as distinct from the clinical and laboratory settings, relates to the study of populations and subpopulations. It can involve either free-living or institutionalized individuals. The concept of 'body composition' goes beyond the traditional assumptions of screening anthropometrics, although it includes many of the same measures. The principal practical considerations for the selection of measurement techniques are ethics and cost. The quantitative considerations are the precision and accuracy of the measures. The biological considerations relate to the interpretation of the measure in terms of underlying body constituents; do the values mean what we hope them to mean?


Mechanism of the DL-alpha-aminoadipic acid inhibitory effect on form-deprived myopia in guinea pig.
To investigate the effect of intravitreal injection of DL-alpha-aminoadipic acid (DL-α-AAA) on ocular refractive state and retinal dopamine, transforming growth factor-β2 (TGFβ2), vasoactive intestinal polypeptide (VIP) in guinea pig form-deprived myopia. Four-week-old pigmented guinea pigs were randomly assigned to 4 groups: normal control, deprivation, deprivation plus DL-α-AAA, deprivation plus saline. Form deprivation was induced with the self-made translucent eye shields, and lasted for 14 days. 8µg DL-α-AAA was injected into the vitreous chamber of deprived eyes. The corneal radius of curvature, refraction and axial length were measured. Retinal dopamine content was evaluated by the high-performance liquid chromatography with electrochemical detection, and TGFβ2 and VIP protein were detected by Western blotting. Fourteen days of eye occlusion caused the axial length to elongate and become myopic in the form-deprived eyes, with the decrease of retinal dopamine and the increase of TGFβ2 and vasoactive intestinal polypeptide (VIP) protein. Intravitreal injection of DL-α-AAA could inhibit the myopic shift from (-3.65±1.06)D to (-1.48±0.63)D, P<0.01 due to goggles occluding and cause the decrease of retinal TGFβ2 protein in the deprived eyes. However, intravitreal injection of DL-α-AAA had no significant effect on retinal dopamine and VIP protein in deprived eyes. Retinal TGFβ2 protein correlated highly with the ocular refraction (y=-3.34+0.31/x, F=74.75, P<0.001) and axial length (y=8.39-0.02/x, F=48.32, P<0.001) in different treatment groups. Intravitreal injection of DL-α-AAA is effectively able to suppress the development of form deprivation myopia, which may be associated with retinal TGFβ2 protein in guinea pigs.


An Extremely Rare Condition: Unilateral and Isolated Temporalis Muscle Hypertrophy.
Unilateral and isolated temporalis muscle hypertrophy is an extremely rare condition causing cosmetic problems and pain in the temporal region. Up to date, 8 isolated and unilateral cases were reported in the English literature. In this article, the authors report 2 new cases of unilateral isolated temporal muscle hypertrophy.


The archaeal lipidome in estuarine sediment dominated by members of the Miscellaneous Crenarchaeotal Group.
The anoxic sediments of the White Oak River estuary comprise a distinctive sulfate-methane transition zone (SMTZ) and natural enrichment of the archaea affiliated with the Miscellaneous Crenarchaeotal Group (MCG). Archaeal biphytanes were generally depleted in (13) C, with δ(13) C values being less than -35‰, indicative of production by active sedimentary archaeal populations. Multivariate analysis of the downcore distributions of 63 lipid biomarkers identified three major groups of lipids that were enriched in the surface, SMTZ or subsurface depths. Intact polar lipids with phosphatidylglycerol headgroups and glycerol dibiphytanyl glycerol tetraethers containing one, two or three cyclopentane rings were enriched at the base of the SMTZ and likely represent the accumulated product of a small but active ANME-1 community. The recently identified butanetriol dibiphytanyl glycerol tetraethers (BDGT), which increased relatively to other lipids with depth, were correlated with the relative abundance of MCG in archaeal 16S rRNA clone libraries, and were (13) C depleted throughout the depth profile, suggesting BDGT lipids as putative biomarkers of an MCG community that may either be autotrophic or feeding on (13) C-depleted organic substrates transported by porewater.


Calcium and cardioplegic protection of the ischemic immature heart: impact of hypoxemia from birth.
Because many infants who require cardiac operation have cyanotic heart disease, we determined whether the existing calcium content of St. Thomas' II solution (1.2 mmol/L) is optimal to protect the immature rabbit heart hypoxemic from birth during subsequent ischemia. Modified hypothermic St. Thomas' II solutions (calcium content, 0 to 2.4 mmol/L) were compared with hypothermic Krebs bicarbonate buffer in protecting chronically hypoxemic (PaO2 = 34 +/- 11 mmHg, SaO2 = 63% +/- 3%) versus normoxemic (PaO2 = 76 +/- 11 mmHg, SaO2 = 92% +/- 3%) immature hearts (7 to 12 days old) during ischemia. Hearts (n = 6 per group) underwent aerobic 'working' perfusion with Krebs bicarbonate buffer and cardiac function was measured. The hearts were then arrested with a 3 minute infusion of either cold (14 degrees C) Krebs buffer (1.8 mmol calcium/L) as hypothermia alone or modified St. Thomas' II solution before 6 hours of hypothermic (14 degrees C) global ischemia. Hearts were reperfused and postischemic enzyme leakage and recovery of function were measured. A bell-shaped dose-response profile was observed for recovery of postischemic aortic flow but not for postischemic creatine kinase leakage, with improved protection occurring at lower calcium concentrations. Optimal myocardial protection occurred at a calcium content of 0.4 mmol/L, which was significantly better than with hypothermia alone or standard St. Thomas' II solution. We conclude that the existing calcium concentration of St. Thomas' II solution is responsible, in part, for its inadequate protection of immature myocardium hypoxemic from birth during ischemia.


Relating formulation variables to in vitro dissolution using an artificial neural network.
The purpose of this paper was to investigate the effect of several experimental variables on the ability of a neural network to predict in vitro dissolution rate as a function of product formulation changes. Neural network software was trained with sets of hypothetical and experimental data consisting of 4-15 formulations with known in vitro drug dissolution profiles and the ability of the trained model to recognize patterns was validated against similar formations not used to train the neural network. The effect of selected variables, e.g., number of hidden-layer nodes and iterations, as well as the use of replicate or mean data on the accuracy of the predictions was investigated. The importance of optimizing the number of hidden-layer nodes and iterations was demonstrated. The prediction error increased for validation data sets that were outside the range of the training data set. Accurate predictions were obtained with as few as four formulations in the training set, provided the formulations were carefully chosen, and the number of formulation variables were small. Also, limiting the validation set to one formulation was not sufficient to validate the neural network model. Increasing the size of the training set, or replication of the input and output data, also provided more accurate predictions. The neural network accurately predicted in vitro drug release provided the neural network variables were optimized, and the training and validation data sets were appropriately selected.


Salivary CA130 with and without unilateral autonomic parotid denervation of rats fed different diets.
Tumor markers such as CA130 can be determined in human whole saliva. Saliva represents an attractive body fluid for longitudinal studies. CA130 was determined in parotid saliva from 8 rats fed different diets, with or without autonomic denervation. CA130 could be determined in parotid saliva of rats, irrespective of diet and/or autonomic denervation. Whether the numerical decrease in CA130 observed after autonomic denervation is statistically significant requires further work. Since salivary CA130 has been shown to decrease following treatment with anti-cancer drugs in humans, the ability to determine this tumor marker in rat saliva opens new opportunities for optimizing cancer chronotherapy in the experimental laboratory.


Trends in Pain Prevalence among Adults Aged 50 and Older across Europe, 2004 to 2015.
Objectives: We examine recent trends in pain prevalence among adults aged 50+ across Europe. Methods: Data for 15 countries from the Survey of Health, Ageing, and Retirement in Europe are examined for two periods: 2004-2011 and 2013-2015. Trends are shown descriptively, using a multilevel modeling strategy controlling for covariates, and modeled on a country-specific basis. Results: Population-level pain prevalence ranges from about 30% to about 60% depending on the country and year. Pain is more prevalent in women and generally increases with age. There is an increase in prevalence over time, net of age, and other predictors. Prevalence increased with an annual average of 2.2% between 2004 and 2011 and 5.8% between 2013 and 2015, in fully adjusted models. Discussion: Trends in pain prevalence have implications for disability, healthcare utilization, productivity, and population health. These findings are not optimistic but align with other population-wide studies, suggesting a global trend of rising pain prevalence.


Examining the impact of active clearance of chest drainage catheters on postoperative atrial fibrillation.
Postoperative atrial fibrillation (POAF) is one of the most frequent complications encountered after heart surgery, and significantly increases complications and mortality. An obstructed chest tube, leaving unevacuated blood around the heart and lungs, can lead to atrial inflammation, which can trigger POAF. The aim of this study was to assess the effectiveness of chest drainage incorporating an active tube clearance (ATC) system in reducing the rate of POAF. This retrospective analysis based on 300 consecutive patients undergoing heart surgery compared 142 patients allocated to an ATC drainage protocol with 158 controls managed with standard chest drainage. Using a 1:1 propensity score match, 214 patients were included in paired analysis (107 in each group). The primary endpoint was POAF. Unmatched patients managed with ATC chest drainage protocol had a reduction of 34% in their POAF rate compared with those managed with standard drains (23% vs 35%, P = .01). In the matched cohort, ATC was associated with a reduction of 31% in the rate of POAF (24% vs 35%, P = .09) and a trend toward shorter postoperative length of stay (5.0 [4.0; 7.0] vs 6.0 [5.0; 8.0], P = .08). In multivariable analysis, chest drainage with ATC showed a protective effect on POAF with odds ratio of 0.5 (95% confidence interval, 0.1-0.9; P = .02). The use of an ATC chest drainage protocol may be associated with reduced POAF. Our results suggest that efforts to maintain chest tube patency could be useful to reduce the incidence of POAF.


Celastrol Alleviates Autoimmune Hepatitis Through the PI3K/AKT Signaling Pathway Based on Network Pharmacology and Experiments.
Objective: This work aims to explore the potential targets and underlying therapeutic mechanisms of celastrol in autoimmune hepatitis (AIH) through network pharmacology and experiments on Laboratory Animals. Methods: A drug-target interaction network was constructed to predict the possible targets of celastrol and their potential relationship with the drug; docking studies were also performed for validation. This study used both acute and chronic rodent models of autoimmune hepatitis. Gross appearance of liver and spleen were obtained from murine models, hematoxylin-eosin staining and Sirius red staining were performed to examine hepatic inflammation and fibrosis respectively. By combining molecular docking and enrichment analysis results, the most prominent signaling pathway was selected and further confirmed by Western blot in AIH models administered with celastrol. Results: In total, 82 common targets of celastrol and AIH were obtained from databases, identified by network pharmacology, and adequately enriched. Among them, PIK3R1, SRC, MAPK1, AKT1, and HRAS were selected as the top 5 closely related targets to celastrol. They all performed effectively in molecular docking, with AKT1 and PIK3R1 exhibiting more-prominent binding energy. Subsequently, celastrol administration significantly ameliorated hepatitis and liver fibrosis by reducing AKT1 and PI3K phosphorylation in both acute liver injury and chronic models of autoimmune hepatitis. Conclusion: In summary, celastrol significantly attenuates autoimmune hepatitis by suppressing the PI3K/AKT signaling pathway, confirmed by validated animal models. These findings may help identify the mechanism involved in the anti-inflammatory action of celastrol in autoimmune hepatitis and provide ideas for future comprehensive studies.


[Neutrality, bisexuality and androgyny of the psychoanalyst].
Proceeding from the fact that Western thought is based on Greek philosophy, the author pinpoints a feature specific to psychoanalysis. Unlike other sciences, which are grounded in the central (and latently homosexual) relation of rhetoric and dialogue between teacher and pupil, psychoanalytic dialogue centers around a heterosexual (male/female) relationship. Prototypic for this is the confrontation of the psychoanalyst with the "complex burden of female love". The fascination of philosophy lies in similarity, that of psychoanalysis in difference. The gender question, and more specifically the sex of the analyst, has been given little attention in connection with the transference/countertransference paradigm. With a discussion of the concepts of neutrality (Freud), bisexuality (Freud, Jung) and with reference to literary sources on androgyny (V. Woolf, Balzac, Le Guin) Molfino undertakes the attempt to take the gender discussion in psychoanalytic theory and practice a stage further.


Cross-resistance to strobilurin fungicides in mitochondrial and nuclear mutants of Saccharomyces cerevisiae.
In yeast the resistance to kresoxim-methyl and azoxystrobin, like the resistance to strobilurin A (mucidin) is under the control of both mitochondrial cob gene and the PDR network of nuclear genes involved in multidrug resistance. The mucidin-resistant mucl (G137R) and muc2 (L275S) mutants of Saccharomyces cerevisiae containing point mutations in mtDNA were found to be cross-resistant to kresoxim-methyl and azoxystrobin. Cross-resistance to all three strobilurin fungicides was also observed in yeast transformants containing gain-of-function mutations in the nuclear PDR3 gene. On the other hand, nuclear mutants containing disrupted chromosomal copies of the PDR1 and PDR3 genes or the PDR5 gene alone were hypersensitive to kresoxim-methyl, azoxystrobin and strobilurin A. The frequencies of spontaneous mutants selected for resistance either to kresoxim-methyl, azoxystrobin or strobilurin A were similar and resulted from mutations both in mitochondrial and nuclear genes. The results indicate that resistance to strobilurin fungicides, differing in chemical structure and specific activity, can be caused by the same molecular mechanism involving changes in the structure of apocytochrome b and/or increased efflux of strobilurins from fungal cells.


One goal: Health for all; Post-COVID public health initiatives.
WHO's theme on its 75th year, "Health for All", is both appropriate and meaningful on account of the unfinished agenda of primary health care (PHC), the Sustainable Development Goals, and the aftermath of the COVID-19 pandemic. The Kerala experience of the pandemic amply demonstrated that the application of these PHC principles helped to address diverse aspects of physical, mental, and social dimensions. The need for 'internalization' of One Health principles and operational strategies cannot be over-emphasized.


Optoelectronic optimization of graded-bandgap thin-film AlGaAs solar cells. Part II: optimal antireflection front-surface texturing.
In Part I [Appl. Opt.59, 1018 (2020)APOPAI0003-693510.1364/AO.381246], we used a coupled optoelectronic model to optimize a thin-film AlGaAs solar cell with a graded-bandgap photon-absorbing layer and a periodically corrugated Ag backreflector combined with localized ohmic Pd-Ge-Au backcontacts, because both strategies help to improve the performance of AlGaAs solar cells. However, the results in Part I were affected by a normalization error, which came to light when we replaced the hybridizable discontinuous Galerkin scheme for electrical computation by the faster finite-difference scheme. Therefore, we re-optimized the solar cells containing an n-AlGaAs photon-absorbing layer with either a (i) homogeneous, (ii) linearly graded, or (iii) nonlinearly graded bandgap. Another way to improve the power conversion efficiency is by using a surface antireflection texturing on the wavelength scale, so we also optimized four different types of 1D periodic surface texturing: (i) rectangular, (ii) convex hemi-elliptical, (iii) triangular, and (iv) concave hemi-elliptical. Our new results show that the optimal nonlinear bandgap grading enhances the efficiency by as much as 3.31% when the n-AlGaAs layer is 400 nm thick and 1.14% when that layer is 2000 nm thick. A hundredfold concentration of sunlight can enhance the efficiency by a factor of 11.6%. Periodic texturing of the front surface on the scale of 0.5-2 free-space wavelengths provides a small relative enhancement in efficiency over the AlGaAs solar cells with a planar front surface; however, the enhancement is lower when the n-AlGaAs layer is thicker.


Detection and prognostic value of cytokeratin positive tumor cells in bone marrow of patients with renal cell carcinoma.
Several investigations indicate the prognostic value of disseminated cytokeratin positive tumor cells in bone marrow of patients with carcinoma of different origin. In this study we evaluated the prognostic significance of epithelial cells in bone marrow of patients with renal cell carcinoma (RCC). Aspiration of bone marrow was performed preoperatively in 335 patients with RCC between 1990 and 1998. A total of 287 patients fulfilled all study inclusion (eg M0 R0 tumor stage) and exclusion (eg second malignancy during followup) criteria for the final analysis. Cytospin preparations were made after density gradient centrifugation of bone marrow samples and incubated with monoclonal antibodies directed against cytokeratin 18 (CK2) and pan-cytokeratin. Staining was performed using the alkaline phosphatase-anti-alkaline phosphatase method and 256 samples were evaluated. RESULTS In 25% (63 of 256) of the patients cytokeratin positive (CK+) cells were detected in bone marrow. Tumor progression (defined as tumor associated death, local recurrence or new metastases) was present in 12% (31 of 256) during the followup period (median 40 months), and 14% (9 of 63) with CK+ cells and 11% (22 of 193) with negative bone marrow status exhibited tumor progression. Survival analysis (log-rank test) showed no significant difference between the CK+ and cytokeratin negative group. The detection of CK+ cells was not an independent prognostic parameter in multivariate analysis (Cox regression model). These results indicate that the immunocytochemical detection of disseminated cytokeratin positive tumor cells in the bone marrow of patients with RCC has no prognostic significance.


Determination of salbutamol in pharmaceuticals by capillary electrophoresis.
A capillary electrophoresis (CE) method for the separation and determination of salbutamol (SAL) in commercial pharmaceuticals was developed. Several parameters affecting the separations were studied including type and concentration of the carrier ion, counter ion, and the pH of the buffer. A hydrodynamically closed CE separation mode employing a 300 mum I.D. capillary, dynamically coated by polymeric buffer additive, provided good performance parameters (precision, accuracy, sensitivity). The obtained results suggest that the proposed method is suitable for routine assay of SAL in pharmaceutical preparations and can be used as an alternative to the conventional open CE mode for this application.


The dynamic expression of extracellular matrix in the bovine endometrium at implantation.
Remodeling of uterine endometrial extracellular matrix (ECM) is pivotal to successful implantation and placentation, and has been well described in the rodents and humans. However, bovine endometrial ECM remodeling is still vaguely defined, especially at the time of implantation. Therefore, this study investigated the distribution of four ECMs namely, types I and IV collagen, laminin and fibronectin, from days 0 to 30 of gestation in bovine endometrium by immunofluorescence microscopy. A change in the distribution pattern of ECMs was evident by day 14 of gestation as features at this stage were clearly different from those of day 14 of the estrous cycle. The immunoreactivity of type I collagen, fibronectin and laminin decreased from day 14 of gestation and was obscured by day 24 of gestation. The type I collagen fibers formed were of thinner consistency than those of the estrous cycle and showed a coarser meshwork within the epithelium sites during the implantation period. In addition, the type IV collagen and laminin immunoreactivities of epithelial basement membrane also remarkably declined at exactly the same time. By day 30 of gestation, the four ECMs had regenerated with the formation of the placentome. In conclusion, this study reveals that remodeling of ECM is essential for the successful establishment of pregnancy in the bovine.


Galectin-3 activates the NADPH-oxidase in exudated but not peripheral blood neutrophils.
Galectin-3, a lactose-binding mammalian lectin that is secreted from activated macrophages, basophils, and mast cells, was investigated with respect to its ability to activate the human neutrophil NADPH-oxidase. The galectin-3-induced activity was determined with in vivo exudated cells (obtained from a skin chamber) and compared with that of peripheral blood neutrophils. Galectin-3 was found to be a potent activator of the NADPH-oxidase only in exudated neutrophils and the binding of galectin-3 to the surface of these cells was increased compared with peripheral blood cells. Different in vitro priming protocols resulting in degranulation were used to mimic the exudation process in terms of increasing the receptor exposure on the cell surface. Galectin-3 could induce an oxidative response similar to that in exudated cells only after a significant amount of the intracellular organelles had been mobilized. This increase in oxidative response was paralleled by an increased binding of galectin-3 to the surface of the cells. The major conclusion of the study is that galectin-3 is a potent stimulus of the neutrophil respiratory burst, provided that the cells have first experienced an extravasation process. The results also imply that the neutrophil response to galectin-3 could be mediated through receptors mobilized from intracellular granules, and we report the presence of galectin-3-binding proteins in such organelles.


Evolution of gene sequence in response to chromosomal location.
Evolutionary forces acting on the repetitive DNA of heterochromatin are not constrained by the same considerations that apply to protein-coding genes. Consequently, such sequences are subject to rapid evolutionary change. By examining the Troponin C gene family of Drosophila melanogaster, which has euchromatic and heterochromatic members, we find that protein-coding genes also evolve in response to their chromosomal location. The heterochromatic members of the family show a reduced CG content and increased variation in DNA sequence. We show that the CG reduction applies broadly to the protein-coding sequences of genes located at the heterochromatin:euchromatin interface, with a very strong correlation between CG content and the distance from centric heterochromatin. We also observe a similar trend in the transition from telomeric heterochromatin to euchromatin. We propose that the methylation of DNA is one of the forces driving this sequence evolution.


Dual processing approach to sedentary behavior and physical activity in the workplace.
Regular physical activity is an important health promoting behavior. Yet, many adults live sedentary lifestyles, especially during their workday. The current study applies an extended theory of planned behavior model, incorporating affective attitudes and instrumental attitudes, along with habit, to predict limiting sedentary behavior and physical activity within an office environment. Theory of planned behavior constructs and habit were assessed with an online survey on a sample of 180 full-time office workers, with self-reported behavior assessed 1 week later (Mage = 25.97, SDage = 10.24; 44 males, 134 females, and 2 nonbinary). Model fit was indicated by BRMSEA (M = 0.057, SD = 0.023), B γ^ (M = 0.984, SD = 0.010) and BCFI (M = 0.959, SD = 0.026), accounting for 46.1% of variance in intention, 21.6% of variance in sedentary behavior, and 17.4% of variance in physical activity behavior. A Bayesian structural equation model revealed direct effects of instrumental attitudes and perceived behavioral control on intention to limit sedentary behavior, direct effects of intention and perceived behavioral control on limiting sedentary behavior, and direct effects of perceived behavioral control and habit on engaging in physical activity. The current study indicates intentions to be active in the office are primarily driven by beliefs about the benefits of activity and individuals' perceived level of control, rather than normative or affective beliefs. As behavior was predicted by both intention and habit, findings also indicate office-based activity is likely not always a consciously driven decision. These findings may have implications for improving activity levels in this highly sedentary population.


Atomic Layer Deposition of V1-xMoxO2 Thin Films, Largely Enhanced Luminous Transmittance, Solar Modulation.
V1-xMoxO2 thin films were fabricated by nanolamination of VO2/MoO3 alternating layers using atomic layer deposition (ALD) process, in which tetrakis-dimethyl-amino vanadium(IV) [V(NMe2)4] and molybdenum hexacarbonyl(VI) [Mo(CO)6] were used as vanadium and molybdenum precursors, respectively. The dopant content of V1-xMoxO2 films was controlled by adjusting MoO3 cycle percentage (PMo) in ALD pulse sequence, which varied from 2 to 10%. Effects of PMo on V1-xMoxO2 crystal structure, morphology, semiconductor-to-metal transition properties, and optical transmittance were studied. A linear reduction of phase transition temperature (Tc) by approximately -11 °C/cycle % Mo was observed for V1-xMoxO2 films within PMo ≤ 5%. Notably, dramatic enhanced luminous transmittance (Tlum = 63.8%) and solar modulation (ΔTsol = 23.5%) were observed for V1-xMoxO2 film with PMo = 7%.


A framework for comparing structural and functional measures of glaucomatous damage.
While it is often said that structural damage due to glaucoma precedes functional damage, it is not always clear what this statement means. This review has two purposes: first, to show that a simple linear relationship describes the data relating a particular functional test (standard automated perimetry (SAP)) to a particular structural test (optical coherence tomography (OCT)); and, second, to propose a general framework for relating structural and functional damage, and for evaluating if one precedes the other. The specific functional and structural tests employed are described in Section 2. To compare SAP sensitivity loss to loss of the retinal nerve fiber layer (RNFL) requires a map that relates local field regions to local regions of the optic disc as described in Section 3. When RNFL thickness in the superior and inferior arcuate sectors of the disc are plotted against SAP sensitivity loss (dB units) in the corresponding arcuate regions of the visual field, RNFL thickness becomes asymptotic for sensitivity losses greater than about 10dB. These data are well described by a simple linear model presented in Section 4. The model assumes that the RNFL thickness measured with OCT has two components. One component is the axons of the retinal ganglion cells and the other, the residual, is everything else (e.g. glial cells, blood vessels). The axon portion is assumed to decrease in a linear fashion with losses in SAP sensitivity (in linear units); the residual portion is assumed to remain constant. Based upon severe SAP losses in anterior ischemic optic neuropathy (AION), the residual RNFL thickness in the arcuate regions is, on average, about one-third of the premorbid (normal) thickness of that region. The model also predicts that, to a first approximation, SAP sensitivity in control subjects does not depend upon RNFL thickness. The data (Section 6) are, in general, consistent with this prediction showing a very weak correlation between RNFL thickness and SAP sensitivity. In Section 7, the model is used to estimate the proportion of patients showing statistical abnormalities (worse than the 5th percentile) on the OCT RNFL test before they show abnormalities on the 24-2 SAP field test. Ignoring measurement error, the patients with a relatively thick RNFL, when healthy, will be more likely to show significant SAP sensitivity loss before statistically significant OCT RNFL loss, while the reverse will be true for those who start with an average or a relatively thin RNFL when healthy. Thus, it is important to understand the implications of the wide variation in RNFL thickness among control subjects. Section 8 describes two of the factors contributing to this variation, variations in the position of blood vessels and variations in the mapping of field regions to disc sectors. Finally, in Sections 7 and 9, the findings are related to the general debate in the literature about the relationship between structural and functional glaucomatous damage and a framework is proposed for understanding what is meant by the question, 'Does structural damage precede functional damage in glaucoma?' An emphasis is placed upon the need to distinguish between "statistical" and "relational" meanings of this question.


Mechanism of infertility in male guinea pigs immunized with sperm PH-20.
PH-20, a testis-specific protein first expressed in haploid germ cells, is present on the posterior head plasma membrane and inner acrosomal membrane of mature guinea pig sperm. PH-20 is bifunctional, having a hyaluronidase activity that allows sperm to penetrate the cumulus layer and a separate activity required for binding of acrosome-reacted sperm to the zona pellucida. The immunization of male guinea pigs with PH-20 reproducibly results in infertility with a duration of 6-12 mo or longer. In this study, we analyzed the immunopathology in the reproductive tract of PH-20-immunized males to probe the mechanism(s) responsible for the induced infertility and found two separate effects. Remarkably, in almost all infertile, PH-20-immunized males, the caudae epididymides were empty (contained no sperm) or contained only abnormal sperm. The complete loss of normal sperm in the epididymis apparently results in infertility. A second effect was the induction of experimental autoimmune orchitis (EAO), representing the first report of EAO induced by a purified testis/sperm molecule of known functions. PH-20-induced EAO differed from EAO induced by crude testis antigens in two respects: 1) an absence of epididymitis with abscess and granuloma and 2) the presence of antibody on germ cells within seminiferous tubules and inside the cauda epididymidis. The former suggests that crude testis antigens other than PH-20 are responsible for epididymitis, and the latter suggests a possible role of antibody in EAO pathogenesis and infertility induction. Return to fertility, after 6-12 mo, was accompanied by regression of EAO and reappearance of spermatozoa in the caudae epididymides.


Residual neuromuscular blockade in critical care.
Neuromuscular blockade is a pharmacological adjunct for anesthesia and for surgical interventions. Neuromuscular blockers can facilitate ease of instrumentation and reduce complications associated with intubation. An undesirable sequela of these agents is residual neuromuscular blockade. Residual neuromuscular blockade is linked to aspiration, diminished response to hypoxia, and obstruction of the upper airway that may occur soon after extubation. If an operation is particularly complex or requires a long anesthesia time, residual neuromuscular blockade can contribute to longer stays in the intensive care unit and more hours of mechanical ventilation. Given the risks of this medication class, it is essential to have an understanding of the mechanism of action of, assessment of, and factors affecting blockade and to be able to identify factors that affect pharmacokinetics.


Quantitative regulation of histone variant H2A.Z during cell cycle by ubiquitin proteasome system and SUMO-targeted ubiquitin ligases.
Quantitative control of histones and histone variants during cell cycle is relevant to their epigenetic functions. We found that the level of yeast histone variant H2A.Z in the G2/M-phase is actively kept low by the ubiquitin proteasome system and SUMO-targeted ubiquitin ligases. Overexpression of H2A.Z induced defects in mitotic progression, suggesting functional importance of this quantitative control.


Local Perceptions, Cultural Beliefs, Practices and Changing Perspectives of Handling Infant Feces: A Case Study in a Rural Geita District, North-Western Tanzania.
We report on the management of infant feces in a rural village in Geita region, Tanzania. Findings discussed here emerged incidentally from a qualitative study aimed at investigating vulnerability and resilience to health challenges in rural settings. Data was gathered through semi-structured focus group discussions (FDGs) with women (n = 4; 32 participants), men (n = 2; 16 participants), and community leaders (n = 1; 8 participants). All FDGs were audio recorded, transcribed verbatim and thematically analyzed using Atlas.ti. Respondents reported feces of a child under the age of six months were considered pure compared to those of older children. Infant feces were seen as transitioning to harmful at the point when the child began to eat solid food, resulting in their stool visually changing in appearance. Caregivers reportedly used soft implements to handle infant feces due to the belief that tools with hard surfaces would physically harm the child. Infant feces were disposed in environments around the house due to the belief that disposal in latrines would prevent developmental milestones and result in other perceived negative health outcomes for the child. Changing views expressed by participants suggest a window of opportunity to implement evidence-based and culturally relevant interventions to encourage the safe disposal of infant feces.


Fermi surface evolution and Luttinger theorem in Na(x)CoO2: a systematic photoemission study.
We report a systematic angle-resolved photoemission study on Na(x)CoO2 for a wide range of Na concentrations (0.3 < or = x < or = 0.72). In all the metallic samples at different x, we observed (i) only a single holelike Fermi surface centered around gamma and (ii) its area changes with x according to the Luttinger theorem. We also observed a surface state that exhibits a larger Fermi surface area. The e'(g) band and the associated small Fermi surface pockets near the K points predicted by band calculations are found to sink below the Fermi energy in a manner almost independent of the doping and temperature.


Discharge planning with older adults: toward a negotiated model of decision making.
Occupational therapists are frequently involved in discharge accommodation decision making with older adults. The literature regarding this process is reviewed. The ways in which risk avoidance and autonomy promotion philosophies influence decisions are examined and a new approach is proposed. One approach is based on risk avoidance, where decisional control rests with professionals, but the client is left out of the process. Another is that of autonomy promotion, in which decisional control rests with the client. When risks are high, this can result in ethical dilemmas. The importance of the environment, its relationship to occupational performance, and differing interpretations of client-centred processes are important considerations. In response to the inadequacy of models grounded in risk avoidance or autonomy promotion, occupational therapists are challenged to move toward a balanced approach to decision making with older people, grounded in partnership, shared power, and negotiation.


CDK2 activation in mouse epidermis induces keratinocyte proliferation but does not affect skin tumor development.
It has been widely assumed that elevated CDK2 kinase activity plays a contributory role in tumorigenesis. We have previously shown that mice overexpressing CDK4 under control of the keratin 5 promoter (K5CDK4 mice) develop epidermal hyperplasia and increased susceptibility to squamous cell carcinomas. In this model, CDK4 overexpression results in increased CDK2 activity associated with the noncatalytic function of CDK4, sequestration of p21(Cip1) and p27(Kip1). Furthermore, we have shown that ablation of Cdk2 reduces Ras-Cdk4 tumorigenesis, suggesting that increased CDK2 activity plays an important role in Ras-mediated tumorigenesis. To investigate this hypothesis, we generated two transgenic mouse models of elevated CDK2 kinase activity, K5Cdk2 and K5Cdk4(D158N) mice. The D158N mutation blocks CDK4 kinase activity without interfering with its binding capability. CDK2 activation via overexpression of CDK4(D158N), but not of CDK2, resulted in epidermal hyperplasia. We observed elevated levels of p21(Cip1) in K5Cdk2, but not in K5Cdk4(D158N), epidermis, suggesting that CDK2 overexpression elicits a p21(Cip1) response to maintain keratinocyte homeostasis. Surprisingly, we found that neither CDK2 overexpression nor the indirect activation of CDK2 enhanced skin tumor development. Thus, although the indirect activation of CDK2 is sufficient to induce keratinocyte hyperproliferation, activation of CDK2 alone does not induce malignant progression in Ras-mediated tumorigenesis.


Laboratory diagnosis of common viral infections of the central nervous system by using a single multiplex PCR screening assay.
A multiplex PCR assay that detects the four commonest causes of viral meningitis and encephalitis in the United Kingdom (herpes simplex virus [HSV] type 1 [HSV-1], HSV type 2 [HSV-2], varicella-zoster virus [VZV], and enteroviruses) was developed, and its sensitivity was compared with those of similar assays described previously for this application. Compared to the previous assays, this single multiplex PCR assay had higher molecular sensitivities for the detection for each of the viruses and improved utility for routine use in a diagnostic laboratory. The assay was used to test a series of 1,683 consecutive cerebrospinal fluid (CSF) samples between June 1997 and March 1998 inclusively. Viral nucleic acid was detected in 138 (8.2%) of the CSF samples, including enteroviruses in 51 samples, HSV-2 in 33 samples, VZV in 28 samples, and HSV-1 in 25 samples. Compared to the accepted relative incidence of viral etiologies, aseptic meningitis due to HSV-2 infection was high, and in adult female patients with symptoms of aseptic meningitis, HSV-2 was the virus most commonly detected in the CSF.


Replacing mechanical protection with colorful faces-twice: parallel evolution of the non-operculate marine worm-snail genera Thylacodes (Guettard, 1770) and Cayo n. gen. (Gastropoda: Vermetidae).
Vermetid worm-snails are sessile and irregularly coiled marine mollusks common in warmer nearshore and coral reef environments that are subject to high predation pressures by fish. Often cryptic, some have evolved sturdy shells or long columellar muscles allowing quick withdrawal into better protected parts of the shell tube, and most have variously developed opercula that protect and seal the shell aperture trapdoor-like. Members of Thylacodes (previously: Serpulorbis) lack such opercular protection. Its species often show polychromatic head-foot coloration, and some have aposematic coloration likely directed at fish predators. A new polychromatic species, Thylacodes bermudensis n. sp., is described from Bermuda and compared morphologically and by DNA barcode markers to the likewise polychromatic western Atlantic species T. decussatus (Gmelin, 1791). Operculum loss, previously assumed to be an autapomorphy of Thylacodes, is shown to have occurred convergently in a second clade of the family, for which a new genus Cayo n. gen. and four new western Atlantic species are introduced: C. margarita n. sp. (type species; with type locality in the Florida Keys), C. galbinus n. sp., C. refulgens n. sp., and C. brunneimaculatus n. sp. (the last three with type locality in the Belizean reef) (all new taxa authored by Bieler, Collins, Golding & Rawlings). Cayo n. gen. differs from Thylacodes in morphology (e.g., a protoconch that is wider than tall), behavior (including deep shell entrenchment into the substratum), reproductive biology (fewer egg capsules and eggs per female; an obliquely attached egg capsule stalk), and in some species, a luminous, "neon-like", head-foot coloration. Comparative investigation of the eusperm and parasperm ultrastructure also revealed differences, with a laterally flattened eusperm acrosome observed in two species of Cayo n. gen. and a spiral keel on the eusperm nucleus in one, the latter feature currently unique within the family. A molecular phylogenetic analysis based on mitochondrial and nuclear rRNA gene sequences (12SrRNA, trnV, 16SrRNA, 28SrRNA) strongly supports the independent evolution of the two non-operculate lineages of vermetids. Thylacodes forms a sister grouping to a clade comprising Petaloconchus, Eualetes, and Cupolaconcha, whereas Cayo n. gen is strongly allied with the small-operculate species Vermetus triquetrus and V. bieleri. COI barcode markers provide support for the species-level status of the new taxa. Aspects of predator avoidance/deterrence are discussed for these non-operculate vermetids, which appear to involve warning coloration, aggressive behavior when approached by fish, and deployment of mucous feeding nets that have been shown, for one vermetid in a prior study, to contain bioactive metabolites avoided by fish. As such, non-operculate vermetids show characteristics similar to nudibranch slugs for which the evolution of warning coloration and chemical defenses has been explored previously.


Linking Pathogen Virulence, Host Immunity and The Microbiota at the Intestinal Barrier.
The mechanisms that allow enteric pathogens to colonize the intestine and host immunity as well as the indigenous microbiota to inhibit pathogen colonization remain poorly understood. Our laboratory is using Citrobacter rodentium, a mouse pathogen that models human infections by enteropathogenic E. coli, to understand the mechanisms that regulate the colonization and clearance of the pathogen in the gut. These studies have revealed how the pathogen colonizes and replicates successfully early during infection and how host immunity and the indigenous microbiota cooperate to eradicate the pathogen in the later stage of the infection. The impairment of the immune system to control the barrier function of the intestine leads to pathogen invasion and the induction of a second layer of host protective immunity to limit the systemic spread of the pathogen.(Presented at the 1931st Meeting, January 17, 2017).


Metabolic topography of the hemiparkinsonism-hemiatrophy syndrome.
We estimated regional and global metabolic rates for glucose using 18F-fluorodeoxyglucose (FDG) and PET in six patients with hemiparkinsonism-hemiatrophy syndrome (HPHA; mean age, 41.0 +/- 12.4 years). We used 18F-fluorodopa (FDOPA) and PET in two patients to quantify presynaptic nigrostriatal dopaminergic function. We compared measures of brain glucose metabolism and striatal FDOPA uptake with those calculated for 10 age-matched normal volunteers (mean age, 35.1 +/- 8.0 years) and 10 patients with typical unilateral Parkinson's disease (unilat-PD; mean age, 58.2 +/- 13.8 years). All six HPHA patients demonstrated significant metabolic reductions (> 3 SD) in the contralateral basal ganglia or frontal cortex as compared with normal control values. Mean normalized glucose metabolism was reduced in the contralateral caudate and lentiform nuclei (p < 0.005) as compared with that in unilat-PD and normal controls. In both patients studied with FDOPA, contralateral striatal uptake was significantly reduced (> 3 SD) as compared with normal control values. These results suggest that the clinical manifestations of HPHA arise through a combination of pre- and postsynaptic nigrostriatal dopaminergic dysfunction. FDG and PET may be useful in differentiating this disorder from typical unilat-PD.


Effect of epirubicin on 3H-thymidine labelling index in cultured L-strain cells.
The effect of epirubicin (EPI) on 3H-thymidine labelling index (3H-TdR LI) of L-strain cells in culture was investigated. EPI concentrations of 0.001 microg/ml, 0.01 microg/ml and 0.1 microg/ml were applied to the cells for 4, 8, 16 and 32 hours. Following the treatment with EPI, labelling process in 3H-TdR medium continued for 0, 2, 4, 8, 16, 20, 22, 25 and 30 hours. The results showed that EPI diminished labelling index of L-strain cells depends on time and applied concentrations. When compared to control this decrease was found statistically significant (p<0.001) in each group.


[Stress as a cardiovascular risk factor].
Stress is a reaction of the organism to a stressor with various negative health consequences including the development of arteriosclerosis. Stress may cause myocardial ischemia, rhythm disturbances, platelet stimulation, increased blood viscosity through hemoconcentration as well as endothelial dysfunction and coronary vasoconstriction in the presence of arteriosclerosis of the coronary arteries. Psychosocial risk factors may also lead to the development and to clinical consequences of arteriosclerosis. The five most important psychosocial risk factors are: depression, anxiety, personality factors, social isolation and chronic life stress. Various components are responsible for the fact that life events or certain psychosocial factors can lead to a stress reaction. Psychosocial risk factors have direct pathophysiologic effects but also influence life style and behavior Various stress management intervention programs have proven to be effective. Psychosocial intervention in conjunction with cardiac rehabilitation programs has shown to reduce cardiovascular morbidity and mortality.


Tissue-specific effects of saposin A and saposin B on glycosphingolipid degradation in mutant mice.
Individual saposin A (A-/-) and saposin B (B-/-)-deficient mice show unique phenotypes caused by insufficient degradation of myelin-related glycosphingolipids (GSLs): galactosylceramide and galactosylsphingosine and sulfatide, respectively. To gain insight into the interrelated functions of saposins A and B, combined saposin AB-deficient mice (AB-/-) were created by knock-in point mutations into the saposins A and B domains on the prosaposin locus. Saposin A and B proteins were undetectable in AB-/- mice, whereas prosaposin, saposin C and saposin D were expressed near wild-type (WT) levels. AB-/- mice developed neuromotor deterioration at >61 days and exhibited abnormal locomotor activity and enhanced tremor. AB-/- mice (~96 days) lived longer than A-/- mice (~85 days), but shorter than B-/- mice (~644 days). Storage materials were observed in Schwann cells and neuronal processes by electron microscopy. Accumulation of p62 and increased levels of LC3-II were detected in the brainstem suggesting altered autophagy. GSL analyses by (liquid chromatography) LC/MS identified substantial increases in lactosylceramide in AB-/- mouse livers. Sulfatide accumulated, but galactosylceramide remained at WT levels, in the AB-/- mouse brains and kidneys. Brain galactosylsphingosine in AB-/- mice was ~68% of that in A-/- mice. These findings indicate that combined saposins A and B deficiencies attenuated GalCer-β-galactosylceramidase and GM1-β-galactosidase functions in the degradation of lactosylceramide preferentially in the liver. Blocking sulfatide degradation from the saposin B deficiency diminished galactosylceramide accumulation in the brain and kidney and galctosylsphingosine in the brain. These analyses of AB-/- mice continue to delineate the tissue differential interactions of saposins in GSL metabolism.


[Possible role of GLI3 gene in the pathogenesis of idiopathic congenital talipes equinovarus].
To investigate the relationship between GLI3 gene and pathogenesis of idiopathic congenital talipes equinovarus (ICTEV). Potential mutations in the coding region of GLI3 were detected among 84 patients with ICTEV by denaturing gradient electrophoresis. Expression of GLI3 in the ICTEV patients' disease tissues was assessed by reverse transcription PCR. Following generation of rat model for ICTEV, mRNA and protein levels of GLI3 were evaluated by real-time PCR and immunohistochemistry and Western blotting. No mutation was found in exons 1 - 8 and 13 of GLI3 gene among the 84 ICTEV patients. No expression of GLI3 gene was detected in the flexor hallucis longus of ICTEV patients or normal controls. Expression of Gli3, in terms of both mRNA and protein, was stronger in the hindlimb of ICTEV rat embryos compared with normal controls. Mutation in the coding region of GLI3 may not be responsible for the occurrence of ICTEV. However, there may still be connection between abnormal expression of the gene and pathogenesis of ICTEV.


[Molecular analysis of peroxisomal disorders].
Peroxisome biogenesis disorders (PBD) include Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD). They are classified into ten complementation groups. Five pathogenic genes have been identified using different model systems of peroxisome deficient mutants. PAF-1 and 2 were identified from CHO mutants and were responsible genes for PBD group F and C. Human PEX 5, 12 and 1, responsible genes for group 2, 3 and 1, respectively, were cloned by homology search between yeast PEX genes and human genes on the cDNA data base. Adrenoleukodystrophy (ALD), the most frequent peroxisomal disorder, shows phenotypic heterogeneity. Its responsible gene was cloned by positional cloning. It encodes a 75 kDa peroxisomal membrane protein (ALDP) that is a member of the ATP-binding cassette transporter family. There are about 120 different mutations including missense, nonsense and splice mutations, as well as insertions and deletions of a few base pairs. There is no correlation between the clinical phenotype and the ALDP gene mutation. Recently, animal models have been produced by targeted mutation of the PBD and ALD genes. The mouse model should facilitate researches on PBD and ALD, especially those on regulatory factors of their phenotypic heterogeneity and on new therapeutic approaches.


Unrecognized Fibrinogen A α-Chain Amyloidosis: Results From Targeted Genetic Testing.
Fibrinogen A α-chain (AFib) amyloidosis results from autosomal-dominant mutations in the gene encoding AFib (FGA). Patients with this disorder typically present with proteinuria. Isolated cases of AFib amyloidosis, carrying the FGA p.Glu545Val variant, were identified in the district of Braga, in northwest Portugal. This observation led us to hypothesize that this disorder might be an unrecognized cause of kidney disease in that region and prompted us to carry out targeted genetic testing for the p.Glu545Val variant in the local hemodialysis population and family members of identified cases. Case series. 3 groups of participants: (1) kidney biopsy registry, n=4; (2) hemodialysis facility, n=122 of 267 patients; and (3) genetically at-risk individuals; n=69 of 167 family members. Kidney disease, kidney disease progression, and survival. The p.Glu545Val variant was identified in all 4 patients of the biopsy registry, 12 of 122 (9.8%) hemodialysis patients tested, and 34 of 69 (49%) relatives tested. These 50 cases belonged to 13 unrelated families with kidney disease or amyloidosis identified in 61% of probands. 35 individuals presented with hypertension at a mean of 51.0±10.4 years. Of these, 30 developed kidney disease at a mean of 56.7±12.0 years, and 21 initiated dialysis therapy at a mean of 61.4±11.3 years. Heart, liver, spleen, colon, and ileum were involved along the progression of the disease. Kidney disease was formerly attributed to hypertension in 25% of patients with AFib amyloidosis undergoing hemodialysis. Retrospective data collection for patients with amyloidosis previously diagnosed. AFib amyloidosis appears to be an under-recognized disorder in Braga, Portugal, where we found a high frequency of the FGA p.Glu545Val variant. Due to the nonspecific nature of its major clinical features, the diagnosis of AFib amyloidosis should have a high index of suspicion, particularly in populations in which hypertension is prevalent.


Transcellular biosynthesis contributes to the production of leukotrienes during inflammatory responses in vivo.
Leukotrienes are lipid mediators that evoke primarily proinflammatory responses by activating receptors present on virtually all cells. The production of leukotrienes is tightly regulated, and expression of 5-lipoxygenase, the enzyme required for the first step in leukotriene synthesis, is generally restricted to leukocytes. Arachidonic acid released from the cell membrane of activated leukocytes is rapidly converted to LTA(4) by 5-lipoxygenase. LTA(4) is further metabolized to either LTC(4) or LTB(4) by the enzyme LTC(4) synthase or LTA(4) hydrolase, respectively. Unlike 5-lipoxygenase, these enzymes are expressed in most tissues. This observation previously has led to the suggestion that LTA(4) produced by leukocytes may, in some cases, be delivered to other cell types before being converted into LTC(4) or LTB(4). While in vitro studies indicate that this process, termed transcellular biosynthesis, can lead to the production of leukotrienes, it has not been possible to determine the significance of this pathway in vivo. Using a series of bone marrow chimeras generated from 5-lipoxygenase- and LTA(4) hydrolase-deficient mice, we show here that transcellular biosynthesis contributes to the production of leukotrienes in vivo and that leukotrienes produced by this pathway are sufficient to contribute significantly to the physiological changes that characterize an ongoing inflammatory response.


Cytokines induce deoxyribonucleic acid strand breaks and apoptosis in human pancreatic islet cells.
We have previously observed that a 6-day exposure of human pancreatic islets to a combination of cytokines (interleukin-1beta 50 U/ml + tumour necrosis factor-alpha 1000 U/ml + interferon-gamma 1000 U/ml) severely impairs beta-cell functions. In the present study, we examined whether this condition affects DNA integrity and viability of human islet cells. Cells were studied after 3, 6, and 9 days of cytokine treatment by both single cell gel electrophoresis (the "comet assay," a sensitive method for detection of DNA strand breaks) and by a cytotoxicity assay using the DNA binding dyes Hoechst 33342 and propidium iodide as indices for the number of viable, necrotic, and apoptotic cells. Cytokine treatment for 6 and 9 days resulted in a 50% increase in comet length (P < 0.01 vs. controls), indicating DNA strand breaks, as well as in a significant increase in the number of apoptotic cells (P < 0.02 vs. controls), but not in the number of necrotic cells. The arginine analogs N(G)-nitro-L-arginine and N(G)-monomethyl-L-arginine prevented nitric oxide formation by the cytokines but did not interfere with cytokine-induced DNA strand breaks and apoptosis. The present data suggest that prolonged (6-9 days) exposure of human pancreatic islets to a mixture of cytokines induces DNA strand breaks and cell death by apoptosis. These deleterious effects of cytokines appear to be independent of nitric oxide generation.


Geometry Optimization for Miniaturized Thermoelectric Generators.
Thermoelectric materials capable of converting heat into electrical energy are used in sustainable electric generators, whose efficiency has been normally increased with incorporation of new materials with high figure of merit (ZT) values. Because the performance of these thermoelectric generators (TEGs) also depends on device geometry, in this study we employ the finite element method to determine optimized geometries for highly efficient miniaturized TEGs. We investigated devices with similar fill factors but with different thermoelectric leg geometries (filled and hollow). Our results show that devices with legs of hollow geometry are more efficient than those with filled geometry for the same length and cross-sectional area of thermoelectric legs. This behavior was observed for thermoelectric leg lengths smaller than 0.1 mm, where the leg shape causes a significant difference in temperature distribution along the device. It was found that for reaching highly efficient miniaturized TEGs, one has to consider the leg geometry in addition to the thermal conductivity.


GENETIC STRUCTURE OF COEXISTING SEXUAL AND CLONAL SUBPOPULATIONS IN A FRESHWATER SNAIL (POTAMOPYRGUS ANTIPODARUM).
We examined clonal diversity and the distribution of both clonal and sexual genotypes in a single population of freshwater snails (Potamopyrgus antipodarum) in which diploid sexual individuals and triploid parthenogens coexist. A genetic analysis of individuals from three habitat zones in Lake Alexandrina, New Zealand revealed extremely high clonal diversity: 165 genotypes among 605 clonal individuals. The frequency of triploid clonal individuals increased with increasing depth in the lake, and most of the individual clones were habitat specific, suggesting that differences among habitats are important in structuring the clonal subpopulation. There were also high levels of clonal diversity within habitats, suggesting frequent origins of habitat-specific clones. In contrast, diploid sexual individuals were proportionately more common in the shallow regions of the lake (where infection by trematode larvae is highest), and there was no significant spatial structure in the sexual subpopulation. We suggest that habitat specialization by clones, as well as parasite-mediated selection against common clones, are important factors affecting the structure of this mixed population of sexual and clonal snails.


Fluctuations of Hyperglycemia and Insulin Sensitivity Are Linked to Menstrual Cycle Phases in Women With T1D.
Factors influencing glycemic variability in type 1 diabetes (T1D) may play a significant role in the refinement of closed loop insulin administration. Phase of menstrual cycle is one such factor that has been inadequately investigated. We propose that unique individual patterns can be constructed and used as parameters of closed loop systems. Women with T1D on continuous subcutaneous insulin infusion and continuous glucose monitoring were studied for 3 consecutive menstrual cycles. Ovulation prediction kits and labs were used to confirm phase of menstrual cycle. Glycemic risks were assessed using the low- and high blood glucose indices (LBGI and HBGI). Insulin sensitivity (SI) was estimated using a Kalman filtering method from meal and insulin data. Overall change significance for glycemic risks was assessed by repeated measures ANOVA, with specific phases emphasized using contrasts. Ovulation was confirmed in 33/36 cycles studied in 12 subjects (age = 33.1 ± 7.0 years, BMI = 25.7 ± 2.9 kg/m(2), A1c = 6.8 ± 0.7%). Risk for hyperglycemia changed significantly during the cycle (P = .023), with HBGI increasing until early luteal phase and returning to initial levels thereafter. LBGI was steady in the follicular phase, decreasing thereafter but not significantly. SI was depressed during the luteal phase when compared to the early follicular phase (P ≤ .05). Total daily insulin, carbohydrates, or calories did not show any significant fluctuations. Women with T1D have glycemic variability changes that are specific to the individual and are linked to phase of cycle. An increased risk of hyperglycemia was observed during periovulation and early luteal phases compared to the early follicular phase; these changes appear to be associated with decreased insulin sensitivity during the luteal phase.


Activation of caspase pathways during iron chelator-mediated apoptosis.
Iron chelators have traditionally been used in the treatment of iron overload. Recently, chelators have also been explored for their ability to limit oxidant damage in cardiovascular, neurologic, and inflammatory disease as well as to serve as anti-cancer agents. To determine the mechanism of cell death induced by iron chelators, we assessed the time course and pathways of caspase activation during apoptosis induced by iron chelators. We report that the chelator tachpyridine sequentially activates caspases 9, 3, and 8. These caspases were also activated by the structurally unrelated chelators dipyridyl and desferrioxamine. The critical role of caspase activation in cell death was supported by microinjection experiments demonstrating that p35, a broad spectrum caspase inhibitor, protected HeLa cells from chelator-induced cell death. Apoptosis mediated by tachpyridine was not prevented by blocking the CD95 death receptor pathway with a Fas-associated death domain protein (FADD) dominant-negative mutant. In contrast, chelator-mediated cell death was blocked in cells microinjected with Bcl-XL and completely inhibited in cells microinjected with a dominant-negative caspase 9 expression vector. Caspase activation was not observed in cells treated with N-methyl tachpyridine, an N-alkylated derivative of tachpyridine which lacks an ability to react with iron. These results suggest that activation of a mitochondrial caspase pathway is an important mechanism by which iron chelators induce cell death.


Exploring structural complexity in the discovery and self-assembly of a family of nanoscale chalcoxides from {Se8Mo36} to {Se26Mo68}.
Herein, we show the controlled generation of multi-component libraries based on the [MoS2O2]2+/MoVIO42-/SeIVO32-/C4O42- system leading to the formation of a whole new family of nanosized molecular chalcoxides, {Se8Mo36} 1, {Se8Mo40} 2, {Se8Mo56} 3, {Se20Mo56} 4 and {Se26Mo68} 5, of the general formula {(MoO2S2)a(OH)b(SeIVO3)c(C4O4)d(MoO7)e}n-, where a, b, c, d, e, n = [16, 20, 8, 6, 2, 20] for 1, [18, 24, 8, 6, 2, 20] for 2, [24, 32, 8, 8, 4, 24] for 3, [28, 32, 20, 8, 0, 32] for 4 and [34, 36, 26, 8, 0, 36] for 5. The coordination modulation effect offered by the SeIVO32- and the C4O42- anions lead to the generation of new building blocks, [(MoO2S2)3(OH)6(C4O4) (MoO7)]4-, and the discovery of a new family of clusters of increasing nuclearity and complexity.


Disrupted tenogenesis in masseter as a potential cause of micrognathia.
Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of mandibular bone have contributed to micrognathia, but concerned little on factors other than osteogenesis. In the current study, we found that ectopic activation of Fgf8 by Osr2-cre in the presumptive mesenchyme for masseter tendon in mice led to micrognathia, masseter regression, and the disrupted patterning and differentiation of masseter tendon. Since Myf5-cre;Rosa26R-Fgf8 mice exhibited the normal masseter and mandibular bone, the possibility that the micrognathia and masseter regression resulted directly from the over-expressed Fgf8 was excluded. Further investigation disclosed that a series of chondrogenic markers were ectopically activated in the developing Osr2-cre;Rosa26R-Fgf8 masseter tendon, while the mechanical sensing in the masseter and mandibular bone was obviously reduced. Thus, it suggested that the micrognathia in Osr2-cre;Rosa26R-Fgf8 mice resulted secondarily from the reduced mechanical force transmitted to mandibular bone. Consistently, when tenogenic or myogenic components were deleted from the developing mandibles, both the micrognathia and masseter degeneration took place with the decreased mechanical sensing in mandibular bone, which verified that the loss of mechanical force transmitted by masseter tendon could result in micrognathia. Furthermore, it appeared that the micrognathia resulting from the disrupted tenogenesis was attributed to the impaired osteogenic specification, instead of the differentiation in the periosteal progenitors. Our findings disclose a novel mechanism for mandibular morphogenesis, and shed light on the prevention and treatment for micrognathia.


[Design concepts and preliminary performances of stationary-sampling whole-body high-resolution positron emission tomography: HEADTOME IV].
Design concepts and preliminary performances of a stationary sampling high-resolution whole-body positron emission tomograph, HEADTOME IV, were reported. The system comprises four layers of detector ring which consists of 768 BGO crystals with 3 mm width, 96 photomultiplier tubes arrayed on 825 mm circle. A sufficiently fine sampling-interval allows data sampling without scan motion along the transaxial plane. But an axial motion (Z-motion) is installed to interlace between adjacent planes. Preliminary performance characteristics were an in-plane resolution of 4.5 mm in full width at half maximum (FWHM), an axial resolution of 9.5 mm in FWHM, sensitivities of 14 and 24 kcps/(microCi/ml) for direct and cross planes, respectively, with 20 cm diam. cylindrical flood phantom. A large scale cache memory prepared for each plane allows a realtime correction for the deadtime and the radionuclide decay, and a realtime calculation of the rate constants using the weighted integral method.


The Analysis of Polyploid Genetic Data.
Though polyploidy is an important aspect of the evolutionary genetics of both plants and animals, the development of population genetic theory of polyploids has seriously lagged behind that of diploids. This is unfortunate since the analysis of polyploid genetic data-and the interpretation of the results-requires even more scrutiny than with diploid data. This is because of several polyploidy-specific complications in segregation and genotyping such as tetrasomy, double reduction, and missing dosage information. Here, we review the theoretical and statistical aspects of the population genetics of polyploids. We discuss several widely used types of inferences, including genetic diversity, Hardy-Weinberg equilibrium, population differentiation, genetic distance, and detecting population structure. For each, we point out how the statistical approach, expected result, and interpretation differ between different ploidy levels. We also discuss for each type of inference what biases may arise from the polyploid-specific complications and how these biases can be overcome. From our overview, it is clear that the statistical toolbox that is available for the analysis of genetic data is flexible and still expanding. Modern sequencing techniques will soon be able to overcome some of the current limitations to the analysis of polyploid data, though the techniques are lagging behind those available for diploids. Furthermore, the availability of more data may aggravate the biases that can arise, and increase the risk of false inferences. Therefore, simulations such as we used throughout this review are an important tool to verify the results of analyses of polyploid genetic data.


Exercise-mediated IL-6 signaling occurs independent of inflammation and is amplified by training in mouse adipose tissue.
The purpose of this investigation was to determine whether exercise-induced increases in adipose tissue interleukin 6 (IL-6) signaling occurred as part of a larger proinflammatory response to exercise and whether the induction of IL-6 signaling with acute exercise was altered in trained mice in parallel with changes in the IL-6 receptor complex. Sedentary and trained C57BL/6J mice were challenged with an acute bout of exercise. Adipose tissue and plasma were collected immediately and 4 h afterward and analyzed for changes in indices of IL-6 signaling, circulating IL-6, markers of adipose tissue inflammation, and expression/content of IL-6 receptor and glycoprotein 130 (gp130). In untrained mice, IL-6 mRNA increased immediately after exercise, and increases in indices of IL-6 signaling were increased 4 h after exercise in epididymal, but not inguinal adipose tissue. This occurred independent of increases in plasma IL-6 and alterations in markers of inflammation. When compared with untrained mice, in trained mice, acute exercise induced the expression of gp130 and IL-6 receptor alpha (IL-6Rα), and training increased the protein content of these. Acute exercise induced the expression, and training increased the protein content, of glycoprotein 130 and IL-6Rα and was associated with a more rapid increase in markers of IL-6 signaling in epididymal adipose tissue from trained compared with untrained mice. The ability of exogenous IL-6 to increase phosphorylation of STAT3 was similar between groups. Our findings demonstrate that acute exercise increases IL-6 signaling in a depot-dependent manner, likely through an autocrine/paracrine mechanism. This response is initiated more rapidly after exercise in trained mice, potentially as a result of increases in IL-6Rα and gp130.


Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks.
Methylxanthines are a group of phytochemicals derived from the purine base xanthine and obtained from plant secondary metabolism. They are unobtrusively included in daily diet in common products as coffee, tea, energetic drinks, or chocolate. Caffeine is by far the most studied methylxanthine either in animal or epidemiologic studies. Theophylline and theobromine are other relevant methylxanthines also commonly available in the aforementioned sources. There are many disseminated myths about methylxanthines but there is increased scientific knowledge to discuss all the controversy and promise shown by these intriguing phytochemicals. In fact, many beneficial physiologic outcomes have been suggested for methylxanthines in areas as important and diverse as neurodegenerative and respiratory diseases, diabetes or cancer. However, there have always been toxicity concerns with methylxanthine (over)consumption and pharmacologic applications. Herein, we explore the structure-bioactivity relationships to bring light those enumerated effects. The potential shown by methylxanthines in such a wide range of conditions should substantiate many other scientific endeavors that may highlight their adequacy as adjuvant therapy agents and may contribute to the advent of functional foods. Newly designed targeted molecules based on methylxanthine structure may originate more specific and effective outcomes.


Congenital internal jugular vein aneurysm in an infant: A rare entity.
A 1-month old baby boy presented with a mass at the root of the neck. On investigation, a saccular aneurysm arising from the internal jugular vein was diagnosed. The aneurysm was excised after ligating the patent internal jugular vein above and below the origin of the aneurysm. Histopathology confirmed the diagnosis of a vascular malformation. Vascular malformation of the internal jugular vein, presenting as neck mass, is extremely rare with no case described in neonates. We present one such interesting case.


[Biomechanical studies on various methods of osteosynthesis on a photoelastic model of the mandible].
Biomechanical studies on a model of the mandible served to verify the stability of a fracture treated with the techniques of pressure-plate osteosynthesis, traction-bandage osteosynthesis and percutaneous compression osteosynthesis, respectively. Stress distribution in the model were determined photoelastically. In this way, it has been possible to obtain informations about stresses caused by different loads (biting-off, stress on the left or right lateral region). Of the methods of osteosynthesis under investigation, plate osteosynthesis yielded the most stable union of the fragments. Satisfactory values were also achieved by means of traction-bandage osteosynthesis and percutaneous compression osteosynthesis. Consequently, these methods may be regarded as function-stable. Conclusions as to the optimal location of the osteosynthesis material can be drawn from an exact analysis of the stress curves. Maximum stress on the mandible, especially in the anterior region, should be avoided for a least 3 weeks.


Role of CPEB3 protein in learning and memory: new insights from synaptic plasticity.
The cytoplasmic polyadenylation element-binding (CPEB) protein family have demonstrated a crucial role for establishing synaptic plasticity and memory in model organisms. In this review, we outline evidence for CPEB3 as a crucial regulator of learning and memory, citing evidence from behavioral, electrophysiological and morphological studies. Subsequently, the regulatory role of CPEB3 is addressed in the context of the plasticity-related proteins, including AMPA and NMDA receptor subunits, actin, and the synaptic scaffolding protein PSD95. Finally, we delve into some of the more well-studied molecular mechanisms that guide the functionality of this dynamic regulator both during synaptic stimulation and in its basal state, including a variety of upstream regulators, post-translational modifications, and important structural domains that confer the unique properties of CPEB3. Collectively, this review offers a comprehensive view of the regulatory layers that allow a pathway for CPEB3's maintenance of translational control that guides the necessary protein changes required for the establishment and maintenance of lasting synaptic plasticity and ultimately, long term learning and memory.


Comparison of reactions to skin grafts in green frogs: Rana lessonae cam., R. esculenta L. and R. ridibunda pall.
Adult, field-collected green frogs, Rana lessonae and R. ridibunda, and their interspecific hybrid R. esculenta were tested with skin grafts at 22 +/- 2 degrees C. Two types of reactions to grafts were observed. 1) Median survival time (MST) was about 25 days, which was observed in R. lessonae hosts in response to allogeneic stimuli and to skin grafts from R. esculenta, and R. esculenta hybrids given grafts from the parental species. 2) MST was equal to or longer than 30 days, which was observed in the case of grafts among R. esculenta, and in R. ridibunda hosts given grafts from R. esculenta and R. lessonae. It seems that a high histocompatibility allele polymorphism occurs in R. lessonae even within one population, whereas lower polymorphism and/or reduced immunological reactivity occurs in R. ridibunda.


Outcome following therapeutic abortion.
Psychological outcome of abortion was studied in 102 patients, measuring multiple variables over four time intervals. Five measured affects--anxiety, depression, anger, guilt, and shame-were significantly lower six months after the preabortion period. The following variables describe subgroups of patients with significant variations in patterns of responses as indicated by changes in affects: marital status, personality diagnosis, character of object relations, past psychopathologic factors, relationship to husband or lover, relationship to mother, ambivalence about abortion, religion, and previous parity. A complex multivariate model, based on conflict and conflict resolution, is appropriate to conceptualize, the unwanted pregnancy and abortion experience. Data suggest that women most vulnerable to conflict are those who are single and nulliparous, those with previous history of serious emotional problems, conflictual relationships to lovers, past negative relationships to mother, strong ambivalence toward abortion, or negative religious or cultural attitudes about abortion.


Transient overexpression of gamma interferon promotes Aspergillus clearance in invasive pulmonary aspergillosis.
Cytokines are critical molecules necessary for normal lung pathogen host defences. Gamma interferon (IFN-gamma) and T1-phenotype immune responses are important components of host defence against Aspergillus. Therefore, we hypothesized that transient overexpression of IFN-gamma within the lung could augment host immunity against Aspergillus. Here it was showed that intranasal administration of 5 x 10(7) colony-forming units (CFU) of Aspergillus fumigatus (Af ) induced the expression of IFN-gamma. Mice were intranasally (i.n) administrated with 5 x 10(8) PFU of a recombinant adenovirus vector containing the murine IFN-gamma cDNA (AdmIFN-gamma), and challenged 24 h later with Af. We observed that i.n. administration of AdmIFN-gamma resulted in about a fourfold increase in levels of IFN-gamma and IL-12 within the lung, about a 75% reduction in lung fungal contents at day 2 and a more than threefold higher survival rate in the AdmIFN-gamma-treated group compared to the controls (P < 0.01). This protection effect was not found when AdmIFN-gamma was i.p. administrated. Alveolar macrophages and lung leucocytes isolated from i.n. AdmIFN-gamma-treated animals displayed enhanced killing of intracellular Aspergillus organisms ex vivo. These results demonstrate that transient overexpression of IFN-gamma could augment host defence against Aspergillus.


[An abnormal hyoid in a panoramic radiograph].
With ossification of the stylohyoid ligament a diverse spectrum of complaints are possible. A conclusive explanation for the appearance of this ossification has so far not been found. Since treatment is not, in principle, necessary, a policy of observation is often preferred. If complaints persist, physiotherapy, anti-inflammatory medication or surgical treatment can be considered.


Properties of C-terminal truncated derivatives of the activator, StrR, of the streptomycin biosynthesis in Streptomyces griseus.
The StrR protein is a DNA-binding protein activating the transcription of streptomycin biosynthesis of Streptomyces griseus N2-3-11 and Streptomyces glaucescens. A putative helix-turn-helix motif located between amino acid positions 207 and 227 of the StrR protein was identified as a prerequisite for its DNA-binding properties. Although, C-terminal truncated StrR proteins were able to interact with StrR-binding sites, they failed to activate transcription from the StrR-dependent promotor strB1p. Therefore, the C-terminal domain of StrR seemed to be necessary for its function as transcriptional activator.


Thematic minireview series on circular proteins.
Circular proteins have now been discovered in all kingdoms of life and are characterized by their exceptional stability and the diversity of their biological activities, primarily in the realm of host defense functions. This thematic minireview series provides an overview of the distribution, evolution, activities, and biological synthesis of circular proteins. It also reviews approaches that biological chemists are taking to develop synthetic methods for making circular proteins in the laboratory. These approaches include solid-phase peptide synthesis based on an adaption of native chemical ligation technology and recombinant DNA approaches that are amenable to the in-cell production of cyclic peptide libraries. The thioester-mediated native chemical ligation approach mimics, to some extent, elements of the natural biosynthetic reaction, which, for disulfide-rich cyclic peptides, appears to involve asparaginyl endopeptidase-mediated processing from larger precursor proteins.


Hysteroscopy in the infertile woman.
In summary, hysteroscopy is a useful diagnostic method in the evaluation of the uterine cavity. Hysteroscopy can localize the uterine lesions and determine their extent with more accuracy than the hysterosalpingogram. However, the meaning of some small lesions and their relation to infertility remains to be determined. Hysterosalpingography should be the first step in the evaluation of the uterine cavity and the tuboperitoneal factor in an infertile woman. Hysteroscopy should be combined with laparoscopy when any lesion is suspected on the hysterogram or when no other cause of infertility has been found. The diagnosis of uterine lesions can be followed by surgical treatment under laparoscopic guidance.


[Prevalence of psychiatric disorders in elderly inpatients of medical and surgical departments].
The aim of the present survey was to study the psychiatric prevalence among elderly patients of medical and surgical wards in Austria. 244 inpatients, 60 years and above, were investigated by research psychiatrists using the Clinical Interview Schedule. The prevalence was found to be 38.7% in medical departments, and 33.0% in surgical departments. According to DSM-III-R criteria, dementia (20.9%) and minor depression (7.0%) were the most frequent psychiatric categories, followed by substance abuse disorders (4.5%). Among those suffering from psychiatric disorders, 68.5% received psychotropics. Only a quarter of these drugs were prescribed by consulting psychiatrists, while about three quarters were ordered by ward physicians. These facts underline the importance of an intensive cooperation between specialists for somatic medicine and psychiatrists.


"Pure" hepatoid tumors of the pancreas harboring CTNNB1 somatic mutations: a new entity among solid pseudopapillary neoplasms.
Hepatoid tumors (HTs) represent a rare group of neoplasms that are histologically similar to hepatocellular carcinoma but arise outside the liver. The current World Health Organization classification recognizes the hepatoid morphology of pancreatic tumors only as a possible variant of pancreatic ductal adenocarcinoma (PDAC). Here, we describe two cases of "pure" HT of the pancreas showing common features and characterized by indolent biological behavior. These tumors were roundish nodules with pushing borders, hyaline globules, and pure hepatoid histology; they were diffusely positive for β-catenin and LEF1 on immunohistochemistry. At next-generation sequencing, both neoplasms harbored only one pathogenic somatic mutation that affected the CTNNB1 gene at exon 3 and showed a loss of heterozygosity on chromosomes 18 and 21. By integrating macroscopic and microscopic features, along with their molecular profiles, we advocate that such tumors represent a distinct entity from PDAC and should be considered a new variant of solid pseudopapillary neoplasms. The recognition of this new neoplastic category may have immediate implications not only for tumor taxonomy but also for clinical practice.


12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced increase in depressed white blood cell counts in patients treated with cytotoxic cancer chemotherapeutic drugs.
Fifty-two patients with solid tumors had depressed white blood cell and neutrophil counts because of prior treatment with cytotoxic cancer chemotherapeutic drugs. These patients were given one or more i.v. infusions of 0.125-0.25 mg of 12-O-tetradecanoylphorbol-13-acetate (TPA), and this treatment increased the low white blood cell and neutrophil counts toward the normal range. The average white blood cell and neutrophil counts were 2.55 x 10(9)/liter and 1.76 x 10(9)/liter, respectively, before treatment with TPA. After one or more i.v. infusions of TPA, the white blood cell and neutrophil counts increased to peak values of 5. 92 x 10(9)/liter and 4.76 x 10(9)/liter, respectively, within a few days. Most patients had increased levels of white blood cells and neutrophils by 24 hr after a single i.v. infusion of 0.25 mg TPA. Elevated levels were observed for at least 3 days. This study demonstrates that treatment with parenteral TPA is feasible with useful biological activity. Only mild and reversible side effects were observed.


Synthesis of Mesoporous TiO2-B Nanobelts with Highly Crystalized Walls toward Efficient H2 Evolution.
Mesoporous TiO2 is attracting increasing interest due to properties suiting a broad range of photocatalytic applications. Here we report the facile synthesis of mesoporous crystalline TiO2-B nanobelts possessing a surface area as high as 80.9 m2 g-1 and uniformly-sized pores of 6-8 nm. Firstly, P25 powders are dissolved in NaOH solution under hydrothermal conditions, forming sodium titanate (Na2Ti3O7) intermediate precursor phase. Then, H2Ti3O7 is successfully obtained by ion exchange through acid washing from Na2Ti3O7 via an alkaline hydrothermal treatment. After calcination at 450 °C, the H2Ti3O7 is converted to a TiO2-B phase. At 600 °C, another anatase phase coexists with TiO2-B, which completely converts into anatase when annealed at 750 °C. Mesoporous TiO2-B nanobelts obtained after annealing at 450 °C are uniform with up to a few micrometers in length, 50-120 nm in width, and 5-15 nm in thickness. The resulting mesoporous TiO2-B nanobelts exhibit efficient H2 evolution capability, which is almost three times that of anatase TiO2 nanobelts.


Spontaneous recovery of effects of contrast adaptation without awareness.
Prolonged exposure to a high contrast stimulus reduces the neural sensitivity to subsequent similar patterns. Recent work has disclosed that contrast adaptation is controlled by multiple mechanisms operating over differing timescales. Adaptation to high contrast for a relatively longer period can be rapidly eliminated by adaptation to a lower contrast (or meanfield in the present study). Such rapid deadaptation presumably causes a short-term mechanism to signal for a sensitivity increase, canceling ongoing signals from long-term mechanisms. Once deadaptation ends, the short-term mechanism rapidly returns to baseline, and the slowly decaying effects in the long-term mechanisms reemerge, allowing the perceptual aftereffects to recover during continued testing. Although this spontaneous recovery effect is considered strong evidence supporting the multiple mechanisms theory, it remains controversial whether the effect is mainly driven by visual memory established during the initial longer-term adaptation period. To resolve this debate, we used a modified Continuous Flash Suppression (CFS) and visual crowding paradigms to render the adapting stimuli invisible, but still observed the spontaneous recovery phenomenon. These results exclude the possibility that spontaneous recovery found in the previous work was merely the consequence of explicit visual memory. Our findings also demonstrate that contrast adaptation, even at the unconscious processing levels, is controlled by multiple mechanisms.


Mutagenic, antimutagenic, antioxidant, anti-lipoxygenase and antimicrobial activities of Scandix pecten-veneris L.
Scandix pecten-veneris L. or Shepherd's-needle is a weed species used in some countries for medicinal purposes. In this study S. pecten-veneris leaves were shade dried, powdered and extracted with methanol. The purpose of this study was to assay the in vitro mutagenic, antimutagenic, antioxidant, antilipoxygenase and antimicrobial activities of S. pecten-veneris leaf extract. The methanolic extract indicated no mutagenicity when tested with Salmonella typhimurium strains TA98 and TA100. Antimutagenic activity was reported with inhibition of mutagenicity in a concentration dependent fashion. The methanolic extract demonstrated antioxidant activity in the DPPH radical-scavenging test (IC50 = 4.57 mg/mL), comparable to ascorbic acid and BHT. Moreover, the extract presented a remarkable and potent inhibition against soybean lipoxygenase (IC50 = 641.57 µg/mL). The methanolic extract was examined for its antimicrobial powers against four different bacteria with MIC values >100. Our results introduced this plant as a useful factor for the treatment of cancer, inflammatory and infectious diseases.