Mutation of CpGs in the murine stem cell virus retroviral vector long terminal repeat represses silencing in embryonic stem cells.
Although DNA methylation and transcriptional repression are generally associated, a causal role for DNA methylation in silencing of retroviral vectors has not been established. The newer generation murine stem cell virus retroviral vector (MSCV) lacks many of the repressive cis-acting DNA sequences identified in Moloney murine leukemia virus but remains sensitive to transcriptional silencing in various cell types. To determine the contribution of cytosine methylation to MSCV silencing, we mutated CpG dinucleotides located in the MSCV long terminal repeat (LTR) that are clustered in the U3 region and directly spanning the transcription start site in the R region. Effects of the CpG mutations on MSCV silencing were assessed in murine embryonic stem cells. An analysis of numerous clonal proviral integrants showed that mutation of CpGs in both clusters eliminated proviral integrants that were completely silenced. Variegated expression was shown to represent a substantial component of intraclonal silencing and was independent of the presence of CpGs in the LTR. Treatment of transduced cells with 5-azadeoxycytidine delayed establishment of the silenced state but had only a modest effect on expression of some proviral integrants at late times post-transduction. These results are direct evidence for a causal contribution of DNA methylation in the LTR to MSCV silencing and define the promoter region CpGs as a repressive element in embryonic stem cells. Furthermore, distinct mechanisms are suggested for establishment and maintenance of the silenced proviral state.


Grandparents in law: investigating the institutionalization of extended family roles.
Previous research on grandparents has focused on the individual and familial level and has characterized grandparent roles as ambiguous and contingent. Emphasizing instead structural phenomena, this theoretical paper argues that grandmother and grandfather roles are being institutionalized through state and federal legislation. This phenomenon provides an opportunity to investigate the process of institutionalization as it happens. Grandparenthood is evaluated as a potential site for institutionalization and law as a source of institutionalization is discussed. Preliminary evidence of the legal institutionalization of grandparenthood is presented and implications and directions for further research are suggested.


Effects of Morphine on Serum Reproductive Hormone Levels and the Expression of Genes Involved in Fertility-related Pathways in Male Rats.
The effects of morphine on serum reproductive hormone levels and markers involved in fertility-related pathways were evaluated. A total of 30 male Wistar rats were divided into three groups (n = 10) and intraperitoneally administered the following substances for 20 days: two single daily doses of morphine (10 mg/kg; morphine group), saline (healthy saline), and intact group. After confirming the morphine dependence of the experimental groups, all the animals were sacrificed and their total testis tissue was extracted and stored at -80 °C until use. Male reproductive parameters (blood serum of testosterone, luteinizing hormone, and follicle-stimulating hormone) and using Q-PCR and western blot, we evaluated mRNA and protein expression of CREM, TBP, CREB1, HDAC1, and FOS involved in fertility-related pathways were analyzed and compared in the testis samples. The luteinizing hormone and testosterone levels were significantly lower in the morphine-administered group than in the saline and intact groups (P < 0.05). Moreover, the expressions of all five target genes were downregulated in the morphine group (P < 0.05). The protein expression of all five target proteins was downregulated in the morphine group (P < 0.05). We concluded that morphine could decrease the reproductive parameters in male rats.


Ultra-Light Clay Intervention Improves Responsiveness and Initiates the Communication of Children With ASD.
The barriers to responsiveness and the initiation of communication are the two key problems encountered by children with autism spectrum disorders (ASD). Prior interventions based on behavioral reinforcement have had an obvious effect on responsive communication but a weak effect on the initiation of communication. Based on psychological development theory, we designed ultra-light clay interventions involving hands-on production or multi-interaction around key concepts and themes, teaching children about basic concepts, relationships, and logic, making abstract knowledge concrete and experience. Two studies (Study 1: N = 3, one-to-one intervention; Study 2: N = 8, one-to-two intervention) showed that ultra-light clay intervention improved both the initiation of and response to communication among children with ASD, but that such improvements show a peer-generalization effect in initiation communication, not in responsive communication. These findings provide a set of ultra-light clay interventions for communication in children with ASD and suggest a relationship between endogenous interventions and the initiation of communication.


Optimizing co-combustion synergy of soil remediation biomass and pulverized coal toward energetic and gas-to-ash pollution controls.
The co-combustion synergy of post-phytoremediation biomass may be optimized to cultivate a variety of benefits from reducing dependence on fossil fuels to stabilizing heavy metals in a small quantity of ash. This study characterized the thermo-kinetic parameters, gas-to-ash products, and energetically and environmentally optimal conditions for the co-combustions of aboveground (PG-A) and belowground (PG-B) biomass of Pfaffia glomerata (PG) with pulverized coal (PC). The mono-combustions of PG-A and PG-B involved the decompositions of cellulose and hemicellulose in the range of 162-400 °C and of lignin in the range of 400-600 °C. PG improved the combustion performance of PC, with the blends of 30 % PG-A and 70 % (PAC37) and 10 % PG-B and 90 % PC (PBC19) exhibiting the strongest synergy. Both PG-A and PG-B interacted with PC in the range of 160-440 °C, while PC positively affected PG in the range of 440-600 °C. PC decreased the apparent activation energy (Eα) of PG, with PBC19 having the lowest Eα value (107.85 kJ/mol). The reaction order models (Fn) best elucidated the co-combustion mechanisms of the main stages. Adding >50 % PC reduced the alkali metal content of PG, prevented the slagging and fouling depositions, and mitigated the Cd and Zn leaching toxicity. The functional groups, volatiles, and N- and S-containing gases fell with PAC37 and PBC19, while CO2 emission rose. Energetically and environmentally multiple objectives for the operational conditions were optimized via artificial neural networks. Our study presents controls over the co-circularity and co-combustion of the soil remediation plant and coal.


Impact of Delayed Appropriate Antibiotic Therapy on Patient Outcomes by Antibiotic Resistance Status From Serious Gram-negative Bacterial Infections.
To examine the clinical and economic burdens associated with delayed receipt of appropriate therapy among patients with Gram-negative bacteria (GNB) infections, stratified by antibiotic resistance status. Retrospective analysis using the Premier Hospital Database. Adult admissions (July 2011-September 2014) with evidence of complicated urinary tract infection, complicated intra-abdominal infection, hospital-associated pneumonia, or bloodstream infection, length of stay (LOS) ≥1 days and a positive GNB culture from a site consistent with infection type (culture draw date = index date) were identified and stratified by antibiotic susceptibility to index pathogens. Delayed appropriate therapy was defined as no receipt of antibiotic(s) with relevant microbiological activity on or within 2 days of index date. Inverse probability weighting and multivariate regression analyses were used to estimate the association between delayed appropriate therapy and outcomes. Generalized linear models were used to evaluate postindex duration of antibiotic therapy, LOS and total in-hospital costs. Logistic models were used to evaluate discharge destination and in-hospital mortality/discharge to hospice. A total of 56,357 patients with GNB infections were identified (resistant, n = 6,055; susceptible, n = 50,302). Delayed appropriate therapy was received by 2,800 (46.2%) patients with resistant and 16,585 (33.0%) patients with susceptible infections. Using multivariate analysis, delayed appropriate therapy was associated with worse outcomes including ∼70% increase in LOS, ∼65% increase in total in-hospital costs and ∼20% increase in the risk of in-hospital mortality/discharge to hospice, regardless of susceptibility status. Our results suggest that outcomes in patients with GNB infections, regardless of resistance status, significantly improve if timely appropriate therapy can be provided.


Modeling and simulation of a beam emission spectroscopy diagnostic for the ITER prototype neutral beam injector.
A test facility for the development of the neutral beam injection system for ITER is under construction at Consorzio RFX. It will host two experiments: SPIDER, a 100 keV H(-)/D(-) ion RF source, and MITICA, a prototype of the full performance ITER injector (1 MV, 17 MW beam). A set of diagnostics will monitor the operation and allow to optimize the performance of the two prototypes. In particular, beam emission spectroscopy will measure the uniformity and the divergence of the fast particles beam exiting the ion source and travelling through the beam line components. This type of measurement is based on the collection of the Hα/Dα emission resulting from the interaction of the energetic particles with the background gas. A numerical model has been developed to simulate the spectrum of the collected emissions in order to design this diagnostic and to study its performance. The paper describes the model at the base of the simulations and presents the modeled Hα spectra in the case of MITICA experiment.


Functional intratumoral lymphatics in patient-derived xenograft models of squamous cell carcinoma of the uterine cervix: implications for lymph node metastasis.
Studies of cell line-derived human tumor xenografts have suggested that the lymphatics seen in immunohistochemical preparations from non-peripheral regions of tumors are nonfunctional. In this investigation, lymphangiogenesis, hemangiogenesis, and lymph node metastasis were studied in patient-derived xenograft (PDX) models of carcinoma of the uterine cervix. Lymph vessel density (LVD) and blood vessel density (BVD) were measured in immunohistochemical preparations. The expression of angiogenesis-related genes was investigated by quantitative PCR. Lymphatic functionality was assessed with the ferritin assay, and tumor interstitial fluid pressure (IFP) was measured with a Millar catheter. The PDX models mirrored the angiogenesis and aggressiveness of the donor patients' tumors, and two highly aggressive models developed functional lymphatics within the tumor mass. Tumors with functional intratumoral lymphatics showed low IFP, high LVD, high BVD, high expression of a large number of angiogenesis-related genes, and high incidence of lymph node metastases. LVD correlated with BVD, and lymph node metastasis was associated with high LVD and high BVD. Nine angiogenesis-related genes associated with the development of functional intratumoral lymhatics were identified. High expression of these genes, high LVD, and high BVD may be important biomarkers for poor outcome in cervix carcinoma.


Directed evolution to improve the catalytic efficiency of urate oxidase from Bacillus subtilis.
Urate oxidase is a key enzyme in purine metabolism and catalyzes the oxidation of uric acid to allantoin. It is used to treat hyperuricemia and gout, and also in a diagnostic kit. In this study, error-prone polymerase chain reaction and staggered extension process was used to generate a mutant urate oxidase with improved enzyme activity from Bacillus subtilis. After several rounds of mutagenesis and screening, two mutants 6E9 and 8E279 were obtained which exhibited 2.99 and 3.43 times higher catalytic efficiency, respectively. They also exhibited lower optimal reaction temperature and higher thermo-stability. D44V, Q268R and K285Q were identified as the three most beneficial amino acid substitutions introduced by site-directed mutagenesis. D44V/Q268R, which was obtained through random combination of the three mutants, displayed the highest catalytic activity. The Km, kcat/Km and enzyme activity of D44V/Q268R increased by 68%, 83% and 129% respectively, compared with that of wild-type urate oxidase. Structural modeling indicated that mutations far from the active site can have significant effects on activity. For many of them, the underlying mechanisms are still difficult to explain from the static structural model. We also compared the effects of the same set of single point mutations on the wild type and on the final mutant. The results indicate strong effects of epistasis, which may imply that the mutations affect catalysis through influences on protein dynamics besides equilibrium structures.


Symmetry-protected hidden order and magnetic neutron Bragg diffraction by URu2Si2.
We investigate how the order parameter of a continuous phase transition can be protected from view by symmetry in a magnetic crystal. The symmetry in question forbids atomic displacements and formation of magnetic dipoles, rendering the order parameter invisible in standard x-ray and magnetic neutron Bragg diffraction. Analysis of the allowed magnetic space-groups reveals exact properties of the hidden order parameter. We demonstrate that Bragg spots forbidden by the chemical structure can unveil magnetic hidden order. The method is applied to URu2Si2, which has been thoroughly investigated in the past few decades using all manner of experimental techniques. Starting from the established chemical structure of URu2Si2, we have performed a critical analysis of available data for magnetic neutron Bragg diffraction.


Recent clinical studies of new pharmacologic agents and their efficacy in the treatment of incontinence.
Two agents for the control of overactive bladder-tolterodine (TOL) and extended-release oxybutynin (Oxy-XL)-have been evaluated in a number of studies for their efficacy in urge incontinence. Studies have demonstrated that TOL achieved a 20% reduction in the frequency of voiding and a 45% reduction in urge incontinent episodes. Efficacy was comparable between TOL and immediate-release oxybutinin (Oxy-IR), the standard anticholinergic comparator. There is a delay of some weeks in achieving relief with TOL, but thereafter there is a continued decrease in the total number of both micturitions and incontinent episodes in 24 hours. Trials demonstrated that there were no safety concerns at all with TOL. In particular, there was a lower incidence of dry mouth with TOL than with Oxy-IR. Dose-ranging studies established that TOL produced the lowest incidence of side effects while maintaining efficacy. In a long-term, community-use study of Oxy-XL, there was a very low incidence of central nervous system side effects, including mental acuity and memory. Among elderly nursing home patients, Oxy-XL achieved a 90% reduction in weekly urge incontinence episodes and an 86% decrease in pad use. Oxy-XL was shown to cause a significantly lower reduction in salivary output than Oxy-IR and TOL. In a recent head-to-head comparison study, there were significant differences found between Oxy-XL and TOL. Other studies have shown that the administration of Oxy-XL results in a significantly lower production of the metabolites responsible for anticholinergic side effect, particularly dry mouth, than with the standard release form, owing largely to the elimination of a first-pass effect. A long-acting form of TOL resulted in a 53% reduction in incontinent episodes. Both these anticholinergic agents have been shown to have excellent efficacy and tolerability. But the future of OAB therapy lies in targeting other mechanisms responsible for incontinence.


Microcoil embolization for treatment of a right coronary arteriovenous fistula.
A patient initially presented with anginal symptoms and a positive stress thallium test. An arteriovenous malformation in the right coronary artery causing a suspected coronary "steal syndrome" was subsequently discovered. This was treated with a microcoil embolization technique in lieu of the traditional surgical approach and this technique is described in detail. The patient had successful clinical, nuclear, and angiographic outcomes.


Bioinspired Cilia Sensors with Graphene Sensing Elements Fabricated Using 3D Printing and Casting.
Sensor designs found in nature are optimal due to their evolution over millions of years, making them well-suited for sensing applications. However, replicating these complex, three-dimensional (3D), biomimetic designs in artificial and flexible sensors using conventional techniques such as lithography is challenging. In this paper, we introduce a new processing paradigm for the simplified fabrication of flexible sensors featuring complex and bioinspired structures. The proposed fabrication workflow entailed 3D-printing a metallic mold with complex and intricate 3D features such as a micropillar and a microchannel, casting polydimethylsiloxane (PDMS) inside the mold to obtain the desired structure, and drop-casting piezoresistive graphene nanoplatelets into the predesigned microchannel to form a flexible strain gauge. The graphene-on-PDMS strain gauge showed a high gauge factor of 37 as measured via cyclical tension-compression tests. The processing workflow was used to fabricate a flow sensor inspired by hair-like 'cilia' sensors found in nature, which comprised a cilia-inspired pillar and a cantilever with a microchannel that housed the graphene strain gauge. The sensor showed good sensitivity against both tactile and water flow stimuli, with detection thresholds as low as 12 µm in the former and 58 mm/s in the latter, demonstrating the feasibility of our method in developing flexible flow sensors.


Polyphosphate as a donor of high-energy phosphate for the synthesis of ADP and ATP.
Here, we studied the potential role of inorganic polyphosphate (polyP) as an energy source for ADP and ATP formation in the extracellular space. In SaOS-2 cells, we show that matrix vesicles are released into the extracellular space after incubation with polyP. These vesicles contain both alkaline phosphatase (ALP) and adenylate kinase (AK) activities (mediated by ALPL and AK1 enzymes). Both enzymes translocate to the cell membrane in response to polyP. To distinguish the process(es) of AMP and ADP formation during ALP hydrolysis from the ATP generated via the AK reaction, inhibition studies with the AK inhibitor A(5')P5(5')A were performed. We found that ADP formation in the extracellular space occurs after enzymatic ATP synthesis. After exposure to polyP, a significant increase of the ADP level was observed, which is likely to be been catalyzed by ALP. This increase is not due to an intensified ATP release via exocytosis. The ATP level in the extracellular space of SaOS-2 cells is strongly increased in response to polyP, very likely mediated by the AK. We propose that the ALP and AK enzymes are involved in the extracellular ADP and ATP synthesis.


Colostomy irrigation: results of 25 cases with particular reference to quality of life.
The aim of this study was to document our results with colostomy irrigation with particular emphasis on the possible contribution of irrigation on quality of life. Colostomy irrigation is a useful method of achieving faecal continence in selected conditions, and may improve quality of life. When successful, irrigation offers a regular, predictable elimination pattern and only a small covering is needed for security between irrigations. The digestive disease quality of life questionnaire-15 (DDQ-15) and Short Form-36 were used to analyse quality of life before and 12 months after stomatherapy in a series of 25 irrigating patients with permanent end colostomies. During the same time period, 10 similar patients with left-end colostomies who also received counselling but did not consent to colostomy irrigation were also analysed for comparison. Colostomy irrigation was found to be effective for achieving faecal continence in selected patients with end colostomies with no complications or significant side-effects, The digestive disease quality of life questionnaire-15 score improved significantly in both groups after stomatherapy (P < 0.0001 and P = 0.009 in the irrigating and non-irrigating groups respectively). The poststomatherapy digestive disease quality of life questionnaire-15 score of the irrigating group was also significantly higher than that of the non-irrigating group (P = 0.039). Although none of the poststomatherapy item scales of Short Form-36 differed significantly between the two groups, stomatherapy with CI resulted in significant improvements in role limitation due to physical problems, social functioning, role limitation due to emotional problems, general mental health, vitality and bodily pain (P < 0.05 for all comparisons). On the contrary, the non-irrigating patient group showed significant improvements only in social functioning and general mental health. Our findings suggest that colostomy irrigation can be a useful method of achieving faecal continence in selected conditions, it is safe, and it may help improve many aspects of quality of life. Colostomy irrigation is free from complications and significant side-effects, and it may serve as a useful adjunct to conventional stomatherapy. Therefore, the enterostomal therapy nurse should assess the appropriateness of routine irrigation as a method of stoma management for patients with left-end colostomy.


Evaluation of breastfeeding behaviors and complementary feeding practices of Turkish and Syrian refugee mothers.
Objectives: The purpose of this study was to compare breastfeeding and related factors (age, level of education, age at first pregnancy, etc.), and complementary feeding practices between Syrian refugee and native Turkish mothers. Material and methods: This descriptive-comparative study examined the nutritional characteristics of infants aged 9 to 60 months whose mothers were Turkish or Syrian refugees who attended Kızıltepe State Hospital between January 2022 and July 2022. Results: 204 mothers (126 Turkish and 78 Syrian) who had a child aged 9-60 months were included. The average age of the mothers was 27.60 ± 5.17 years for Turkish citizens and 28.91 ± 5.62 for Syrian refugees, without significant difference between the two groups (p: 0.091). Postpartum breastfeeding was 91.3% and breastfeeding duration was 12 (0-24) months in Turkish citizens; in Syrian refugees, breastfeeding was 84.6% and average breastfeeding time was 9 (0- 24) months (respectively, breast milk intake p: 0.144, uptake time p: 0.161; no statistical difference). Breastfeeding training was received by 23.8% of Turkish citizens and 5.1% of Syrian refugees; there was a significant difference between the two groups (p: 0.001). Conclusion: In refugee groups, infant and maternal nutrition practices are disrupted. Working in conjunction with local and international organizations and state agencies that give help to refugee groups, the appropriate interventions, initiatives, supports, and awareness-raising activities would strive to improve practices in mother and baby nutrition and narrow gaps.


Nurses as health planners.
Nursing leaders have the knowledge and responsibility to serve on the boards of health planning agencies. This article provides suggestions and strategies for developing your role as an active and articulate member of a health systems agency.


Involvement of the autonomic nervous system in the in vivo memory to glucose of pancreatic beta cell in rats.
The fact that the potentiating effect of prolonged hyperglycemia on the subsequent insulin secretion is observed in vivo but not in vitro suggests the involvement of extrapancreatic factors in the in vivo memory of pancreatic beta cells to glucose. We have investigated the possible role of the autonomic nervous system. Rats were made hyperglycemic by a 48-h infusion with glucose (HG rats). At the end of glucose infusion as well as 6 h postinfusion, both parasympathetic and sympathetic nerve activities were profoundly altered: parasympathetic and sympathetic activities, assessed by the firing rate either of the thoracic vagus nerve or the superior cervical ganglion, were dramatically increased and decreased, respectively. Moreover, 6 h after the end of glucose infusion, insulin secretion in response to a glucose load was dramatically increased in HG rats compared to controls. To determine whether these changes could be responsible for the increased sensitivity of the beta cell to glucose, insulin release in response to glucose was measured in HG and control rats, either under subdiaphragmatic vagotomy or after administration of the alpha 2A-adrenergic agonist oxymetazoline. Both treatments partially abolished the hyperresponsiveness of the beta cell to glucose in HG rats. Therefore chronic hyperglycemia brings about changes in the activity of the autonomic nervous system, which in turn are responsible, at least in part, for the generation of enhanced beta cell responsiveness to glucose in vivo.


Factors Associated with Recent HIV Testing among Men Who Have Sex with Men in Philadelphia: a Cross-Sectional Analysis of the National Behavioral Surveillance System Survey.
The main objective of this study was to determine the demographic, geographic and socioeconomic characteristics of men who have sex with men (MSM) in Philadelphia that were associated with having a recent HIV test. We used data from the National HIV Behavioral Surveillance System (NHBS) surveys from 2011 and 2014 among MSM in Philadelphia, with the outcome of interest of having received an HIV test in the past twelve months. Of 1043 HIV-negative MSM, 70.2% had an HIV test. Multivariable analysis showed that seeing a medical provider (aOR: 1.73; p = .0039) or having heard of PrEP (aOR: 2.24; p < .0001) was associated with recent HIV testing. Those participants forty-five years of age or older (aOR 0.40, p = .0001) and those with Medicaid had lower rates of HIV testing (aOR 0.48, p = .002). Although over 80% of participants had seen a medical provider in the past year, only 50% had been offered an HIV test by a provider. Optimizing HIV testing through the expansion and increased awareness of PrEP, especially among older MSM, is critical. Further research is needed to delineate barriers that prevent MSM from utilizing medical providers for HIV testing and for those with Medicaid from receiving HIV testing.


Presence of "rheumatoid neoantigen-like material" in urine of patients with RA, demonstrated by use of leukocyte adherence inhibition assay.
Peripheral blood leukocytes (PBL) from patients with rheumatoid arthritis (RA) when used in the leukocyte adherence inhibition (LAI) assay were capable of distinguishing antigenic differences between rheumatoid and osteoarthritic synovial membrane extracts. The positive LAI response of RA patients was negated by preincubating the cells with sera or urine proteins obtained from LAI nonreactive RA patients. This study suggests that LAI nonreactive RA subjects have in their serum a material cross reactive with rheumatoid synovium which we have called "rheumatoid neoantigen-like material" which is excreted in their urine, and is capable of being recognized by PBL of reactive, LAI positive RA patients.


Protein-induced geometric constraints and charge transfer in bacteriochlorophyll-histidine complexes in LH2.
Bacteriochlorophyll-histidine complexes are ubiquitous in nature and are essential structural motifs supporting the conversion of solar energy into chemically useful compounds in a wide range of photosynthesis processes. A systematic density functional theory study of the NMR chemical shifts for histidine and for bacteriochlorophyll-a-histidine complexes in the light-harvesting complex II (LH2) is performed using the BLYP functional in combination with the 6-311++G(d,p) basis set. The computed chemical shift patterns are consistent with available experimental data for positive and neutral(tau) (N(tau) protonated) crystalline histidines. The results for the bacteriochlorophyll-a-histidine complexes in LH2 provide evidence that the protein environment is stabilizing the histidine close to the Mg ion, thereby inducing a large charge transfer of approximately 0.5 electronic equivalent. Due to this protein-induced geometric constraint, the Mg-coordinated histidine in LH2 appears to be in a frustrated state very different from the formal neutral(pi) (N(pi) protonated) form. This finding could be important for the understanding of basic functional mechanisms involved in tuning the electronic properties and exciton coupling in LH2.


A Variable Importance-Based Differential Evolution for Large-Scale Multiobjective Optimization.
Large-scale multiobjective optimization problems (LMOPs) bring significant challenges for traditional evolutionary operators, as their search capability cannot efficiently handle the huge decision space. Some newly designed search methods for LMOPs usually classify all variables into different groups and then optimize the variables in the same group with the same manner, which can speed up the population's convergence. Following this research direction, this article suggests a differential evolution (DE) algorithm that favors searching the variables with higher importance to the solving of LMOPs. The importance of each variable to the target LMOP is quantized and then all variables are categorized into different groups based on their importance. The variable groups with higher importance are allocated with more computational resources using DE. In this way, the proposed method can efficiently generate offspring in a low-dimensional search subspace formed by more important variables, which can significantly speed up the convergence. During the evolutionary process, this search subspace for DE will be expanded gradually, which can strike a good balance between exploration and exploitation in tackling LMOPs. Finally, the experiments validate that our proposed algorithm can perform better than several state-of-the-art evolutionary algorithms for solving various benchmark LMOPs.


Circadian rhythmicity in AVP secretion and GABAergic synaptic transmission in the rat suprachiasmatic nucleus.
A variety of physiological and behavioral functions exhibit circadian changes and these circadian rhythms are driven by oscillatory expression of clock genes in the suprachiasmatic nuclei (SCN). It is still unknown how this molecular clockwork is controlled by extracellular neurohormones and neurotransmitters and which membrane receptors undergo circadian modulation. Circadian rhythm can be measured as a secretion of arginine vasopressin (AVP) in organotypic SCN culture for several weeks. Melatonin applied directly to the SCN late in the day induces a phase advance, when applied late at night or at the beginning of the day melatonin causes a phase delay. The time window for phase advance corresponds with the highest level of melatonin receptors in the SCN but the mechanism of melatonin-induced phase delay is unknown. The principal neurotransmitter on SCN synapses is gamma-aminobutyric acid (GABA), which acts at postsynaptic GABA(A) receptors. Spontaneous release of GABA from presynaptic nerve terminals, recorded as miniature inhibitory postsynaptic currents in the presence of TTX, does not change, but zinc sensitivity of exogenous GABA-induced currents varies during the day and night, possibly due to changes in subunit composition of GABA(A) receptors. We conclude that there is daily variation in the postsynaptic, but not presynaptic, function in the SCN.


Abundant expression of AMACR in many distinct tumour types.
Alpha-methylacyl-CoA racemase (AMACR), a mitochondrial and peroxisomal enzyme, is a valuable tool to confirm the diagnosis of prostate cancer, especially if combined with basal cell markers. To extend this diagnostic utility to other neoplasias, we comprehensively surveyed AMACR expression in human tumours. We performed immunohistochemical analyses on tissue microarrays of AMACR expression in over 125 different human tumour types and 80 normal tissues. Microarray analysis revealed that tumours with prominent AMACR expression included adenocarcinomas of the prostate (72%), hepatocellular carcinomas (77%), papillary renal cell carcinomas (70%), and colorectal adenocarcinomas (71%). AMACR expression was equally frequent in colorectal adenomas and carcinomas. No significant difference in AMACR expression between untreated and hormone-refractory prostate cancers was observed. In the thyroid, AMACR expression was found in 42% of the follicular carcinomas but in only 16% of follicular adenomas. However, a more detailed analysis on a thyroid tissue microarray did not confirm a significant difference of AMACR expression in follicular adenoma and carcinomas. Taken together, the results indicate that AMACR is expressed in a wide variety of adenocarcinomas, and its diagnostic utility is restricted to specific areas.


Permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by degeneration of the lateral wall of the cochlea.
Mitochondrial dysfunction in the cochlea is thought to be an important cause of sensorineural hearing loss. Recently, we have established a novel rat model with acute hearing impairment caused by exposure to the mitochondrial toxin 3-nitropropionic acid (3-NP) to analyze the mechanism of cochlear mitochondrial dysfunction. Both permanent and temporary threshold shifts were observed in this model depending on the amount of 3-NP used to induce hearing impairment. In this study, we demonstrate cochlear morphological changes in the permanent threshold shift model. Marked degeneration was detected in type 2 fibrocytes in the spiral prominence, type 4 fibrocytes in the spiral ligament, marginal cells and intermediate cells in the stria vascularis 3 h after 3-NP administration; these changes were progressive for at least 14 days. Less prominent degeneration was detected in type 1 and type 3 fibrocytes in the spiral ligament. These results indicate that permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by cellular degeneration in the lateral wall of the cochlea, and suggest that therapy of cochlear hearing loss due to acute energy failure may be achieved through protection and regeneration of the cochlear lateral wall.


Patient considerations in ocular hypertension: role of bimatoprost ophthalmic solution.
Glaucoma is a leading cause of irreversible blindness worldwide. The reduction of intraocular pressure has been well established as an effective treatment to prevent both the development and the progression of all forms of glaucoma. Bimatoprost 0.03% ophthalmic solution, introduced in 2001, is a synthetic prostamide with the unique mechanism of improving both uveoscleral and trabecular outflow. Comparative studies with other pharmacotherapies have shown favorable results for bimatoprost as a potent ocular hypotensive agent that is generally well tolerated. Common side effects include conjunctival hyperemia, eyelash growth, iris pigmentation and periorbital changes. Hyperemia rates were reduced following the introduction of bimatoprost 0.01%. Bimatoprost should be used with caution in those with higher risk of developing ocular inflammation and macular edema. However, the perceived risk of bimatoprost in these patient populations is likely greater than the actual risk observed in practice. Bimatoprost is currently in the center of several clinical trials including its use for dermatologic applications and sustained-release therapies for the treatment of ocular hypertension and glaucoma.


CHRONIC MIGRAINE. CASE REPORT.
We report a case of a 40-year-old male who had the clinical signs of chronic migraine. The diagnosis of chronic migraine is based on International Headache Society diagnostic criteria. The patient was bothered by unilateral and localized pain in the frontotemporal and ocular area, which lasts 4-72 hours, sensitivity to light and sound. Headache has pulsating quality, moderate or severe pain intensity. Attacks of headache bothered about 15-20 days a month. According to the standard MR scanning protocol, single areas of increased MR signal were detected in the mode Т2, Flair, which do not limit diffusion and do not cause a change in the MR signal in the SWI mode. The foci are located subcortically in the white matter of the frontal lobes of the brain, corresponding to foci of gliosis of the white matter of the frontal lobes. The patient received antiepileptic drugs, β-Blockers, triptans, antidepressants.The patient is recommended to inject botulinum toxin.


[Radiotherapy and chemotherapy in the treatment of oesophageal carcinoma].
Surgery, chemotherapy and radiotherapy are the three major arms of treatment for cancer of the oesophagus, and combined modality therapy is required to treat advanced disease. Exclusive chemoradiotherapy is a feasible option for locoregionally advanced disease in responder patients. Elective surgery as a palliative procedure should not be regarded as a standard option in patients with metastatic or non-resectable oesophageal cancer. Surgery appears more and more as an adjuvant therapy in the curative treatment of oesophageal cancer, especially for advanced tumours.


Optical transfer functions derived from solar adaptive optics system data.
Adaptive optics (AO) systems installed at large ground-based telescopes partially correct Earth's atmosphere, making post facto image reconstruction techniques necessary to produce diffraction-limited observations. To achieve accurate photometry in the reconstructed images, some post facto techniques require knowledge of transfer functions that describe the optical system. I present a new, fast method for the estimation of the long-exposure and speckle transfer functions from data gathered by a solar AO system simultaneously with the observations. The results of the presented method are tested with extensive analytical models, demonstrating that the estimation is robust for situations where the AO system is performing with Strehl ratios larger than 45%. Application to observations of solar granulation produces reconstructed images that are photometrically in agreement with earlier results.


Particles for multiplexed analysis in solution: detection and identification of striped metallic particles using optical microscopy.
In this report, we present data demonstrating that cylindrical metallic particles, with various submicrometer striping patterns, may be readily distinguished in an optical microscope. Accurate particle identification is discussed relative to synthesis reproducibility and the limitations of optical microscopes. Results from a library of these particles, of which over 100 different striping patterns have been produced, are presented. For these particles, made with Au and Ag stripes, more than 70 patterns may be identified with greater than 90% accuracy. The ability to chemically modify the surface of these particles, making them useful for bioanalytical measurements, is also demonstrated. Finally, we discuss improvements in our manufacturing and identification processes that will lead to both larger numbers of striping patterns and improved identification accuracy.


Bleeding risk and complications associated with percutaneous ultrasound-guided liver biopsy in cats.
Liver biopsy is necessary for a diagnosis of liver disease; however, post-biopsy bleeding is a concern. The aim of this study was to describe the extent of bleeding and the occurrence of complications after percutaneous ultrasound-guided liver biopsy (PUGLB) in cats. The medical records of 30 cats that had a PUGLB were retrospectively reviewed. Using human guidelines, bleeding was classified as minor or major when the absolute change in packed cell volume (ΔPCV) was <0 and >-6% or ≤-6%, respectively. Complications were defined as physiologic compromise necessitating an intervention, or death. The relationship between ΔPCV and the occurrence of complications and the signalment, initial PCV, coagulation parameters, serum liver enzymes and bilirubin, number of biopsies, histological diagnosis, ultrasound findings, radiologist experience, concurrent procedures and vitamin K administration were assessed using Fisher's exact test, ANOVA and Pearson's correlation coefficient, with a P value <0.05 considered significant. All cats had a decrease in PCV after biopsy. The mean ΔPCV was -6.9% ± 4.1%. Minor and major bleeding occurred in 13/30 (43.3%) and 17/30 (56.7%) cats, respectively, and non-lethal bleeding complications occurred in 5/30 (16.7%). Cats with complications had a lower pre-biopsy PCV ( P <0.003). Major bleeding was more likely with a diagnosis of hepatic lipidosis ( P = 0.03). There was no correlation between ΔPCV or complications and signalment, coagulation parameters, serum parameters, number of biopsies, ultrasound findings, radiologist experience, concurrent procedures and vitamin K administration. PUGLB is a relatively safe procedure in cats, although many cats have a subclinical decrease in PCV. As conventional coagulation tests did not predict complications or the magnitude of ΔPCV, there is a need for more sensitive indicators of bleeding risk in cats undergoing PUGLB.


Dissolution enhancement of an insoluble drug by physical mixture with a superdisintegrant: optimization with a simplex lattice design.
The aim of the present work was to optimize a tablet formulation containing a physical mixture of a practically insoluble drug (prednisone) with a superdisintegrant (croscarmellose sodium) and two filler-binders characterized by differing water solubility (dicalcium phosphate dihydrate and anhydrous beta-lactose). Crushing strength, disintegration, and dissolution were measured for 10 formulations distributed over a factor space according to a simplex lattice design for a special cubic model. Multiple linear regression analysis was used to assess the best fit for each variable. The model predicted that increasing the amount of disintegrant to a critical amount (50%) would result in reduced disintegration time for dicalcium phosphate/beta-lactose ratios > 0.3, no changes in disintegration time for ratios < 0.3, and for all ratios an improvement in dissolution at 10 min. Crushing strength values of dicalcium phosphate increased with increasing disintegration concentration but not for beta-lactose tablets. The physical mixture of a practically insoluble drug with a superdisintegrant was confirmed as a valid approach to the improvement of dissolution, even in presence of other components. The solubility of the filler-binders influenced the minimum amount of disintegrant needed; when a soluble diluent was used, the amount of disintegrant required was reduced.


Palate morphology after unilateral and bilateral cleft lip and palate closure.
The aim of the present study was to compare the morphology of the hard palate of patients with uni- and bilateral cleft lip and palate after palatoplasty using vomer and palatal pedicled flaps with the palatal morphology of non-cleft individuals. Eighty patients were enrolled into this retrospective study: 40 patients with cleft lip and palate (30 unilateral, 10 bilateral) and 40 non-cleft patients with class I occlusion, who served as controls. Analysis of the development of the maxillary arch and evaluation of palatal morphology were accomplished from reformatted CT scans from plaster casts of the maxilla at the age of 4, 10 and 15 years (cleft patients) and 10 years (controls). Width and symmetry of the maxillary arch and morphology of the hard palate were assessed in the canine and molar region and compared both among the cleft groups and the controls. Maxillary arch width as assessed from plaster casts did not differ significantly between uni- and bilateral cleft patients and was not significantly different from controls at the age of 10. Deviation from symmetry was present in both types of cleft and significant in unilateral clefts when compared to bilateral clefts and non-cleft patients. Palatal morphology did not differ significantly between uni- and bilateral clefts until the age of 15, but was significantly different from control patients in the molar area at the age of 10 presumably due to the medial shift of soft tissue flaps used for palatoplasty. It is concluded that palatoplasty significantly alters hard palate morphology particularly in the posterior area. The relevance of this alteration for speech and articulation remains to be explored.


Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice.
Clinical trials have indicated that preclinical results obtained with human tumor xenografts in mouse models may overstate the potential of adenovirus (Ad)-mediated oncolytic therapies. We have previously demonstrated that the replication of human Ads depends on cyclin E dysregulation or overexpression in cancer cells. ED-1 cell derived from mouse lung adenocarcinomas triggered by transgenic overexpression of human cyclin E may be applied to investigate the antitumor efficacy of oncolytic Ads. Ad-cycE was used to target cyclin E overexpression in ED-1 cells and repress tumor growth in a syngeneic mouse model for investigation of oncolytic virotherapies. Murine ED-1 cells were permissive for human Ad replication and Ad-cycE repressed ED-1 tumor growth in immunocompetent FVB mice. ED-1 cells destroyed by oncolytic Ads in tumors were encircled in capsule-like structures, while cells outside the capsules were not infected and survived the treatment. Ad-cycE can target cyclin E overexpression in cancer cells and repress tumor growth in syngeneic mouse models. The capsule structures formed after Ad intratumoral injection may prevent viral particles from spreading to the entire tumor.


Corticosteroids therapy in the management of infantile cutaneous hemangiomas.
To determine the effectiveness of systemic and intra-lesional corticosteroids, in the management of infantile cutaneous hemangiomas and to compare the results with untreated lesions. Randomized controlled trial. Surgical Unit B of National Institute of Child Health, Karachi, from January 2001 to January 2003. A total of 75 cases with cutaneous hemangiomas were included in the study. Three groups of 25 patients each were made by allocating first patient to control group, every second patient to oral steroid group and every third patient to intra-lesional steroid group. In control group, patients were managed conservatively with repeated hospital visits in order to note down changes occurring in the lesion. In oral steroid group, tablet prednisolone was given at a dose of 2mg/kg/day on alternate days. The dose was gradually tapered over a period of 8 weeks. In intra-lesional steroid group, injection triamcinolone was given at a dose of 1 to 5 mg/kg, with a maximum dose of 30mg. Six injections of triamcinolone in monthly intervals were given. Outcome measures noted were the change in size before and after treatment, duration of proliferative phase, change in morphology and complications. In the control group,76% lesions showed little or no change, 5.8% had less than 50% reduction and 20% lesions showed actual increase in size. In oral steroid group, 32% lesions showed greater than 50% reduction in size, 44% lesions had less than 50% reduction and 24% lesions had little or no change. In intra-lesional steroid group, 44% lesions showed greater than 50% reduction in size, 32% lesions showed less than 50% reduction and 24% lesions had little or no change. Morphology change in terms of color change, surface bosselation and soft consistency was found in 88% lesions of oral steroid group, 92% in intra-lesional steroid group and 16% in observation group. Complication rate was 16% in observation group, 20% in oral steroid group and 24% in intra-lesional steroid group. Hemangiomas when left untreated behave in an unpredictable manner. Low dose steroids whether given orally or intra-lesionally, showed remarkable reduction in size with minimal side effects.


Sudden fetal death with placental mesenchymal dysplasia complicated by placenta previa.
Placental mesenchymal dysplasia (PMD) is a rare placental abnormality that is closely related to severe pregnancy complications. A 27-year-old woman with fetal growth restriction and placenta previa was referred to a university hospital at 22 gestational weeks (GW). She was suspected of having a twin pregnancy with a complete or partial hydatidiform mole and coexisting normal live fetus, because two separate placentas, an enlarged one with multiple cystic lesions and a normal one, were shown on ultrasound examinations. At 27 GW, she experienced a sudden intrauterine fetal death (IUFD) after bleeding due to placenta previa, despite confirmation of fetal well-being at 2 h before bleeding. After delivery, histopathological examination confirmed the diagnosis of PMD. This is the first documented case of a woman with PMD and placenta previa who had a sudden IUFD after bleeding. Patients with both PMD and placenta previa should be considered at extremely high risk for IUFD.


Committee evolution in a medical center.
Development of the Nursing Research Committee in the Mary Hitchcock Memorial Hospital, Hanover, New Hampshire, is described. Six problems were identified, and ways in which the committee solved the problems are discussed.


[Effects of naoxintong capsule on the inflammation and prognosis in borderline lesion coronary heart disease patients].
To study the effects of Naoxintong Capsule (NC) on the inflammation and long-term prognosis in the borderline lesion coronary heart disease patients. A total of 240 coronary heart disease patients with angina symptoms and accompanied with borderline lesion coronary heart disease (with the diameter stenosis in critical 50% -70%) by means of coronary angiography or multislice computed tomography coronary angiography were recruited. These patients were randomly assigned to the conventional treatment group (including nitrate, beta blockers, anti-platelet, anticoagulation, angiotensin converting enzyme inhibitors, and so on) and the NC treatment group (treated the same way as those for the conventional treatment group and NC). All patients were treated for 12 months. The occurrence of cardiovascular events was observed after treatment. The inflammatory factors in serum [interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and high sensitive C reaction protein (hs-CRP)], matrix metalloproteinases-9 (MMP-9), blood lipids and blood sugar, liver and kidney functions were measured before and after treatment. After 12 months of treatment, the incidence of angina pectoris patients (6.67% vs 15.83%, P < 0.05) and hospitalization due to acute coronary syndrome (ACS) attacks (4.17% vs 10.83%) was significantly lower in the NC treatment group than in the conventional treatment group. There was no statistical difference in the serum levels of IL-6, TNF-alpha, hs-CRP, and MMP-9 between the two groups before treatment (P > 0.05). After 12 months of treatment, serum levels of IL-6, TNF-alpha, hs-CRP, and MMP-9 were significantly lower when compared with before treatment in the same group (P < 0.05). Besides, the serum levels of IL-6, TNF-alpha, hs-CRP, and MMP-9 were significantly lower in the NC group than in the conventional treatment group (P < 0.05). By means of Logistic regression analysis we found that the post-treatment MMP-9 level and IL-6 level were independent risk factors influencing the recurrence of angina pectoris. NC could alleviate the inflammation. Long-term administration of NC could reduce the recurrence of angina pectoris and decrease the incidence of ACS attack in borderline lesion coronary heart disease patients. The post-treatment MMP-9 level and IL-6 level were independent risk factors influencing the recurrence of angina pectoris.


Evaluation of non-surgical therapy on glutathione levels in chronic periodontitis.
To compare the levels of glutathione (GSH), both oxidized and reduced forms in patients with and without chronic periodontitis in gingival crevicular fluid (GCF). Twenty GCF samples from maxillary quadrants were collected using capillary micropipettes from the chronic periodontitis patients (test group) at baseline before treatment, at 1-month, 3 months, and 6 months after scaling and root planing and samples from 20 patients without chronic periodontitis (control group) from maxillary quadrants were also collected. GSH, oxidized glutathione (GSSG) levels and GSH: GSSG ratios were determined using the spectrophotometric method. Results were concluded for the test over control groups using paired Student's t-test. Lower concentrations of GSH (P < 0.001) and GSSG (P < 0.001) were detected in GCF in patients with chronic periodontitis (test group) than patients without chronic periodontitis (control group) at baseline. Treatment had a significant effect in improving the GSH and reducing GSSG levels postscaling and root planing at 1-month and 3 months but not significant effect at 6 months. Scaling and root planing increased the GSH: GSSG ratio (P < 0.001) in the test group as compared to the control group (P < 0.001). The concentrations of GSH within GCF are reduced in chronic periodontitis patients. Scaling and root planing (nonsurgical therapy) restores GSH concentration in GCF post 1-month and 3 months along with redox balance (GSH: GSSG ratio), but at 6 months the balance is not maintained. Adjunctive use of micronutritional supplements to boost antioxidant concentration in tissues by preserving GSH or by elevating its level at the inflamed sites is recommended, as nonsurgical periodontal therapy alone is not able to maintain redox balance for longer duration.


Effects of exposure to sublethal propiconazole on the antioxidant defense system and Na+-K+-ATPase activity in brain of rainbow trout, Oncorhynchus mykiss.
Propiconazole (PCZ), a triazole fungicide, is widely present in the aquatic environment, but little is known regarding its chronic toxicity in the fish brain. This study assessed the effects of long-term exposure to PCZ on the antioxidant defense system and Na(+)-K(+)-ATPase activity of rainbow trout brain. Fish were exposed to sublethal concentrations of PCZ (0.2, 50, and 500 microg/l) for 7, 20, and 30 days, respectively. Oxidative stress indices (reactive oxygen species, lipid peroxidation, and carbonyl protein) and antioxidant parameters (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and reduced glutathione) were measured, as well as Na(+)-K(+)-ATPase activity. Adaptive responses to PCZ-induced stress were observed at 7 days. With prolonged exposure, significantly higher levels of oxidative indices were indicative of oxidative stress, as also were the significant inhibition of antioxidant enzyme activity and reduced glutathione content. Na(+)-K(+)-ATPase activity was significantly inhibited after prolonged exposure. Chemometrics of all parameters by principal component analysis, enabled the separation of sampled individuals into four groups with 93.39% of total accumulated variance. A low level of oxidative stress can induce the adaptive responses of the antioxidant defense system, while prolonged exposure to PCZ may lead to serious oxidative damage in fish brain. We suggest that selected biochemical markers in fish brain could be used as potential biomarkers for monitoring residual fungicides present in the aquatic environments.


[The influence of vitamin C and e or beta-carotene on peroxidative processes in persons with myocardial ischemia].
An increasing body of evidence suggests that beside hypercholesterolemia peroxidative processes and natural antioxidant defence system play important role in the development of atherosclerosis. Our earlier investigation showed the increased intensity of the peroxidative processes in the course of the acute myocardial infarction and unsatisfactory tocopherol, ascorbic acid and retinol status. The purpose of the present study was the evaluation of the effect of antioxidant vitamins supplementation by the period of 21 days on the peroxidative processes in patients after heart attack or after "bypass" admitted to the cardiological rehabilitation centre. Daily oral supplementation with vitamin C, E and beta-carotene decreased significantly plasma lipid peroxide concentration (TBARS). The highest drop in TBARS activity was found in the group after bypass. No significant effect of vitamin supplementation was observed on antioxidant enzymes activity.


Revision, extension, and evaluation of a binaural speech intelligibility model.
This study presents revision, extension, and evaluation of a binaural speech intelligibility model (Beutelmann, R., and Brand, T. (2006). J. Acoust. Soc. Am. 120, 331-342) that yields accurate predictions of speech reception thresholds (SRTs) in the presence of a stationary noise source at arbitrary azimuths and in different rooms. The modified model is based on an analytical expression of binaural unmasking for arbitrary input signals and is computationally more efficient, while maintaining the prediction quality of the original model. An extension for nonstationary interferers was realized by applying the model to short time frames of the input signals and averaging over the predicted SRT results. Binaural SRTs from 8 normal-hearing and 12 hearing-impaired subjects, incorporating all combinations of four rooms, three source setups, and three noise types were measured and compared to the model's predictions. Depending on the noise type, the parametric correlation coefficients between observed and predicted SRTs were 0.80-0.93 for normal-hearing subjects and 0.59-0.80 for hearing-impaired subjects. The mean absolute prediction error was 3 dB for the mean normal-hearing data and 4 dB for the individual hearing-impaired data. 70% of the variance of the SRTs of hearing-impaired subjects could be explained by the model, which is based only on the audiogram.


Association of hydrochlorothiazide treatment compared with alternative diuretics with overall and skin cancer risk: a propensity-matched cohort study.
Hydrochlorothiazide (HCT) has been suggested to induce photosensitivity, thereby increasing the incidence of skin cancers. After a pharmacovigilance alert, HCT was frequently withdrawn or substituted by other diuretics. The aim of this study was to compare the association of exposure to HCT with cancer risk versus alternative diuretics. A retrospective cohort study was conducted based on data from the AOK PLUS, a large German statutory health insurance fund. Patients with HCT treatment were propensity score matching to patients using non-HCT diuretics. Incidence of cancer of any kind and, specifically, skin cancer was assessed in both groups. Time-to-incident cancer diagnosis was evaluated and compared between the groups. A total of 199 708 patients were included in the final analysis ( n = 76 855 in the HCT group; n = 122 853 in the non-HCT-diuretics group). After propensity score matching, 122 554 patients remained in the sample ( n = 61 277 for both groups, of which >96% had hypertension, mean age 73 years, 61% female). HCT treatment was associated with a lower incidence of cancer of any kind compared with non-HCT diuretics (incidence rate ratio per 100 patient years 0.84 95% confidence interval: 0.82-0.87). HCT treatment was associated with a small albeit significantly higher incidence rate ratio of skin cancer (1.15 95% confidence interval: 1.06-1.24) with significant variances over time. Although numerically higher, the difference accounts to only 0.05 more skin cancer diagnoses in 100 patient-years. HCT treatment compared with alternative diuretics was associated with a lower all-cancer risk and a numerically small increased skin cancer risk in a large German population. Risk-benefit evaluation should be executed in patients with increased skin cancer risk and treatment with HCT. Furthermore, advice for skin protection is warranted in all patients taking thiazide or thiazide-like diuretics.


Construction of a Biological Age Score to Predict Tooth Loss over 10 Years.
The aim of the present study was to construct a biological age score reflecting one's physiologic capability and aging condition with respect to tooth loss over 10 y. From the follow-up to the population-based Study of Health in Pomerania (i.e., SHIP-2), 2,049 participants were studied for their baseline biomarker measures 10 y before (i.e., in SHIP-0). Metabolic and periodontal data were regressed onto chronological age to construct a score designated as "biological age." For either sex separately, the impact of this individualized score was used to predict tooth loss in the follow-up cohort in comparison with each participant's chronological age. Outcome data after 10 y with respect to tooth loss, periodontitis, obesity, and inflammation were shown to be better for biologically younger subjects than as expected by their chronological age, whereas for the older subjects, data were worse. Especially for tooth loss, a striking increase was observed in subjects whose biological age at baseline appeared to be higher than their chronological age. Biological age produced significantly better tooth loss predictions than chronological age (P < 0.001). Areas under receiver operating characteristic curves for tooth loss of ≥3 teeth in men during follow-up were 0.811 and 0.745 for biological and chronological age, respectively. For women, these figures were 0.788 and 0.724. For total tooth loss, areas under the curve were 0.890 and 0.749 in men and 0.872 and 0.752 in women. Biological age combines various measures into a single score and allows identifying individuals at increased risk of tooth loss.


Point-of-Care Ultrasound Diagnosis of Deep Space Hand Infection.
Point-of-care ultrasound is emerging as an important imaging modality for characterizing soft-tissue infections and provides advantages over physical examination and magnetic resonance imaging (MRI). A 30-year-old man presented to the emergency department with extensive left upper extremity cellulitis. Magnetic resonance imaging of the left arm was preliminarily interpreted as soft-tissue swelling without evidence of deep-space infection. Point-of-care ultrasound revealed pockets of fluid with sonographic fluctuance tracking along the tendon sheath that were concerning for deep abscesses. Based on the ultrasound findings, the patient was taken emergently to the operating room, where multiple left hand and wrist loculated deep-space abscesses were decompressed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case report highlights the significant advantages and easy-to-learn findings present in point-of-care ultrasound of musculoskeletal infections.


Molecular mechanisms of paraquat-induced acute lung injury: a current review.
Paraquat is an organic heterocyclic herbicide that is widely used in agriculture, especially in Asian countries. The prevalence of paraquat poisonings has increased dramatically in the past two decades in China. Nearly all paraquat poisonings resulted from intentional or accidental oral administration leading to acute lung injury and, ultimately, acute respiratory distress syndrome. The mortality rate has been reported to be greater than 90%. However, the exact toxic mechanism remains unclear. Herein, we reviewed and summarized the most recent publications related to the molecular mechanisms of paraquat-induced acute lung injury.


Protein aggregation and autophagy dysfunction: new lessons from mucopolysaccharidoses.
Mucopolysaccharidoses (MPS) are inherited metabolic diseases with strong neurological involvement. MPSs are caused by defects in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs), which consequently accumulate into the lysosomes as primary storage. Macroautophagy/autophagy impairment is well known to drive neurodegeneration in MPSs, however, mechanisms underlying such dysfunction are still poorly understood. Recently, by studying a mouse model for MPS-III (Sanfilippo syndrome) we have shown that the progressive aggregation of amyloid proteins in neuronal cell bodies occurs downstream of the GAG storage and, in turn, impairs the autophagy pathway by affecting lysosomal-dependent autophagosome clearance.


Analysis of the origin of atypical scanning laser polarimetry patterns by polarization-sensitive optical coherence tomography.
To analyze the physical origin of atypical scanning laser polarimetry (SLP) patterns. To compare polarization-sensitive optical coherence tomography (PS-OCT) scans to SLP images. To present a method to obtain pseudo-SLP images by PS-OCT that are free of atypical artifacts. Forty-one eyes of healthy subjects, subjects with suspected glaucoma, and patients with glaucoma were imaged by SLP (GDx VCC) and a prototype spectral domain PS-OCT system. The PS-OCT system acquires three-dimensional (3D) datasets of intensity, retardation, and optic axis orientation simultaneously within 3 seconds. B-scans of intensity and retardation and en face maps of retinal nerve fiber layer (RNFL) retardation were derived from the 3D PS-OCT datasets. Results were compared with those obtained by SLP. Twenty-two eyes showed atypical retardation patterns, and 19 eyes showed normal patterns. From the 22 atypical eyes, 15 showed atypical patterns in both imaging modalities, five were atypical only in SLP images, and two were atypical only in PS-OCT images. In most (15 of 22) atypical cases, an increased penetration of the probing beam into the birefringent sclera was identified as the source of atypical patterns. In such cases, the artifacts could be eliminated in PS-OCT images by depth segmentation and exclusion of scleral signals. PS-OCT provides deeper insight into the contribution of different fundus layers to SLP images. Increased light penetration into the sclera can distort SLP retardation patterns of the RNFL.


YMAP: a pipeline for visualization of copy number variation and loss of heterozygosity in eukaryotic pathogens.
The design of effective antimicrobial therapies for serious eukaryotic pathogens requires a clear understanding of their highly variable genomes. To facilitate analysis of copy number variations, single nucleotide polymorphisms and loss of heterozygosity events in these pathogens, we developed a pipeline for analyzing diverse genome-scale datasets from microarray, deep sequencing, and restriction site associated DNA sequence experiments for clinical and laboratory strains of Candida albicans, the most prevalent human fungal pathogen. The YMAP pipeline (http://lovelace.cs.umn.edu/Ymap/) automatically illustrates genome-wide information in a single intuitive figure and is readily modified for the analysis of other pathogens with small genomes.


The role of myoglobin in retarding oxygen depletion in skeletal muscle.
Myoglobin retards the development of anoxia in a poorly perfused region of skeletal muscle by facilitating diffusion into this region from adjacent normally perfused regions and by releasing bound oxygen directly into the tissue. We examine these phenomena by analyzing a mathematical model of time-dependent myoglobin-facilitated oxygen transport. The governing equations are solved using similarity transformations and multiple-scale techniques. We find that when perfusion of a region is suddenly decreased, oxygen depletion is significantly retarded by direct release of myoglobin-bound oxygen into the tissue and that myoglobin-facilitated diffusion of oxygen from adjacent regions becomes significant at very low oxygen concentration.


Development and assessment of specialized liaison librarian services: clinical vs. basic science in a veterinary medicine setting.
In 1998, the University of Florida Health Science Center Libraries (HSCL) developed and implemented a Liaison Librarian Program, dedicated to providing customized, subject-specific services to the faculty, students, clinicians, researchers, staff, and administrators of the six Health Science Center Colleges (Dentistry, Health Professions, Medicine, Nursing, Pharmacy, and Veterinary Medicine). Subject- and role-specific (clinical vs. basic sciences) liaisons were assigned. This paper describes the HSCL liaison program, exemplified by the liaisons' work with the College of Veterinary Medicine. Preliminary program evaluation, a pilot project developed to discern the needs of the veterinary medicine clientele and facilitate awareness of liaison services, and subsequent re-evaluation of patron awareness and satisfaction are also discussed.


Improved recovery of repeat intoxicated drivers using fingernails and blood spots to monitor alcohol and other substance abuse.
This study reports the results of a pilot program in Kenosha County that used a combination of direct biomarkers extracted from blood spots and nails to monitor repeat intoxicated drivers for their use of alcohol and drugs with a detection window spanning from 3 weeks to several months. The objectives were to test whether the direct biomarkers phosphatidylethanol (PEth), ethylglucuronide (EtG), and 5 drug metabolites would (1) help assessors obtain a more objective evaluation of repeat offenders during the assessment interview, (2) allow for timely identification of relapses and improve classification of drivers into risk categories, and (3) predict recidivism by identifying offenders most likely to obtain a subsequent operating while intoxicated (OWI) offense within 4 years of enrollment in the program. All (N = 261) repeat offenders were tested using PEth obtained from blood spots and EtG obtained from fingernails; 159 participants were also tested for a 5 drugs of abuse nail panel. Drivers were tested immediately after the assessment interview (baseline) and at 3, 6, 9, and 12 months after baseline. Based on biomarker results and self-reports of abstinence, offenders were classified into different risk categories and required to follow specific testing timelines based on the program's decision tree. The baseline analysis shows that 60% of drivers tested positive for alcohol biomarkers (EtG, PEth, or both) at the assessment interview, with lower detection rates (0-11%) for the 5 drug metabolites. The comparison of biomarkers results to self-reports of abstinence identified 28% of all offenders as high risk and assigned them to more frequent testing and more intense monitoring. The longitudinal analysis shows that 56% (completers) of participants completed the program successfully and the remaining 44% (noncompliant) terminated prematurely. Two thirds (68%) of the completers were able to reduce or control their drinking and one third relapsed at least one time during their mandated monitoring periods. After a brief intervention by the assessors, 79% of relapsers tested negative for biomarkers in their repeat tests. The rearrest analysis showed that offenders classified in the noncompliant and relapsers groups were 7 times more likely to receive a new OWI 4 years after enrollment compared to drivers classified as abstainers or controllers. Refractory drivers were monitored the longest and reported no subsequent rearrests. These findings demonstrate the benefits of more individualized interventions with repeat OWI offenders and calls for further development of multimodal approaches in traffic medicine including those that use direct alcohol biomarkers as evidence-based practices to reduce recidivism.


Prevalence of neoplasia in 10 New England populations of the soft-shell clam (Mya arenaria).
Neoplasia was a prevalent disease of the soft-shell clam and was found in widely geographically distinct sites in New England. Two types of neoplasms were recognized. Most were of hematopoietic origin, except in clams from Maine, which also had gonadal neoplasms. Both types were apparently malignant neoplasms, based on their characteristic anaplastic appearance, invasiveness, metastasis, mitotic activity, associated tissue necrosis, and mortality. Diagnosis of neoplasia in the living mollusk was achieved rapidly and accurately by cytologic examination of circulating blood. The etiology of the neoplasms was not identified. In general, nonneoplastic lesions, such as epithelial hyperplasia and accumulations of a orange-brown bodies, were more common in clams from polluted areas.


Stable Liquid Jets Bouncing off Soft Gels.
A liquid jet can stably bounce off a sufficiently soft gel by following the contour of the dimple created upon impact. This new phenomenon is insensitive to the wetting properties of the gels and was observed for different liquids over a wide range of surface tensions, γ=24-72 mN/m. In contrast, other jet rebound phenomena are typically sensitive to γ: only a high γ jet rebounds off a hard solid (e.g. superhydrophobic surface) and only a low γ jet bounces off a liquid bath. This is because an air layer must be stabilized between the two interfaces. For a soft gel, no air layer is necessary and the jet rebound remains stable even when there is direct liquid-gel contact.


Macrolichen Communities Depend on Phorophyte in Conguillío National Park, Chile.
The community composition of epiphytic macrolichens from two tree species (Araucaria araucana and Nothofagus antarctica) was conducted in temperate forests in the Conguillío National Park, Chile. The composition of lichen biota is influenced by phorophyte species, bark pH, and microclimatic conditions. A total of 31 species of macrolichens were found on A. araucana and N. antarctica. Most of the species showed phorophyte preference, with nine being exclusive to A. araucana and 10 to N. antarctica. The detrended correspondence analysis (DCA) indicated the formation of three communities: one representing macrolichens growing on N. antarctica and two others growing chiefly on A. araucana, either with north or south exposure. More work is needed to study the lichen biota of the forests of the Chilean Andes, which are under multiple threats, including clearing and climate change. In order to counteract such risks to native forests and to the biodiversity of the associated epiphytic lichens, conservation plans should be established that consider the factors that influence the composition of the lichen community.


Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo.
Little effort has been made to study the protein-encoding genes isolated from traditional Chinese medicine (TCM) drugs, and the delivery of these genes into malignant cells through recombinant adeno-associated virus (rAAV) vectors has not been attempted. We synthesized the cDNAs of five known cytotoxic proteins isolated from TCM drugs and the FLAG epitope-tagged cDNAs were subcloned into a rAAV plasmid vector. The protein expression was confirmed by Western blot assay. Various cancer cell lines were transfected with the above plasmids and cell growth was monitored both in vitro and in vivo. The best cytotoxic gene was further packaged into rAAV vectors, under the control of a liver cancer-specific promoter. The liver tumor growth was then monitored following intratumor administration of the rAAV vectors. The expression plasmids, encoding individual potential cytotoxic genes tagged with FLAG epitope, were successfully generated and sequenced. Among these genes, trichosanthin (TCS) gene yielded the most promising results for the inhibition of cancer cell growth in vitro. The over-expressed TCS functioned as a type I ribosome-inactivating protein, followed by inducing apoptosis that is associated with the Bcl-PARP signaling pathway. Furthermore, intratumor injection of rAAV vectors containing the TCS gene significantly inhibited the growth of human hepatocellular carcinoma tumors in a murine xenograft model. Our studies suggest that the use of TCM cytotoxic genes is a useful therapeutic strategy for treating human cancers in general, and liver tumors in particular.


A presynaptic role for protein kinase C in hippocampal mossy fiber synaptic transmission.
It has been suggested that the maintenance of long-term potentiation (LTP) in the hippocampal mossy fiber (MF) synapse involves a presynaptic mechanism that does not require the activation of protein kinase C (PKC), since this enzyme appears to be absent in the MF presynaptic terminals. In the present study the authors evaluated this proposal by directly comparing the metabolic properties of hippocampal MF synaptosomes and a conventional P2B synaptosomal preparation prepared from the same hippocampal tissue. Protein kinase C-dependent histone phosphotranferase activity was found to be comparable in MF and P2B synaptosomes. Western blot analysis was performed using antisera prepared against four of the PKC isoforms, and the results demonstrate that the alpha, beta, and gamma PKC isoforms are present in relatively equivalent amounts in these two subcellular fractions. However, the cytosolic fraction derived from the hippocampal MF synaptosomes appeared to contain a greater amount of the PKC-epsilon isoform when compared to the P2B synaptosomal preparation. Four distinct endogenous substrates present in the MF synaptosomes are shown to be phosphorylated in response to PKC activation. A functional role for PKC in the hippocampal MF nerve endings seems to be indicated by the finding that 4 beta-phorbol 12,13-dibutyrate (PDBu) and 4 beta-phorbol 12,13-diacetate produce a dose-dependent potentiation of the K(+)-evoked release of endogenous glutamate and dynorphin B, while the inactive 4-alpha-phorbol was without effect. The PDBu-induced enhancement of transmitter release was blocked by the PKC inhibitor, staurosporine. In addition, PDBu significantly facilitated the rise in cytosolic free calcium that immediately followed depolarization of the MF synaptosomal membrane. It is concluded that hippocampal MF presynaptic terminals possess a variety of PKC isoforms and that their activation may have an important facilitory influence on MF synaptic transmission and plasticity.


Two new species of Pseudoniphargus (Amphipoda: Pseudoniphargidae) from southern Spain.
Two new species of subterranean water amphipod crustaceans of the genus Pseudoniphargus (Pseudoniphargidae) are described from gypsum caves of Andalusia, southern Spain. Both species share the extreme elongation of the male third uropod, a striking feature frequently reported in the genus and that seems to have arisen independently in several lineages. These findings raise the number of species of Pseudoniphargus known from the area to 17.


A novel synthetic peptide microarray assay detects Chlamydia species-specific antibodies in animal and human sera.
Serological analysis of Chlamydia (C.) spp. infections is still mainly based on micro-immunofluorescence and ELISA. To overcome the limitations of conventional serology, we have designed a novel microarray carrying 52 synthetic peptides representing B-cell epitopes from immunodominant proteins of all 11 chlamydial species. The new assay has been validated using monospecific mouse hyperimmune sera. Subsequently, serum samples from cattle, sheep and humans with a known history of chlamydial infection were examined. For instance, the specific humoral response of sheep to treatment with a C. abortus vaccine has been visualized against a background of C. pecorum carriership. In samples from humans, dual infection with C. trachomatis and C. pneumoniae could be demonstrated. The experiments revealed that the peptide microarray assay was capable of simultaneously identifying specific antibodies to each Chlamydia spp. The actual assay represents an open platform test that can be complemented through future advances in Chlamydia proteome research. The concept of the highly parallel multi-antigen microarray proven in this study has the potential to enhance our understanding of antibody responses by defining not only a single quantitative response, but also the pattern of this response. The added value of using peptide antigens will consist in unprecedented serodiagnostic specificity.


Freezing of gait: Promising avenues for future treatment.
Freezing of gait is a devastating symptom of Parkinson's disease and other forms of parkinsonism. It poses a major burden on both patients and their families, as freezing often leads to falls, fall-related injuries and a loss of independence. Treating freezing of gait is difficult for a variety of reasons: it has a paroxysmal and unpredictable nature; a multifaceted pathophysiology, with an interplay between motor elements (disturbed stepping mechanisms) and non-motor elements (cognitive decline, anxiety); and a complex (and likely heterogeneous) underlying neural substrate, involving multiple failing neural networks. In recent years, advances in translational neuroscience have offered new insights into the pathophysiology underlying freezing. Furthermore, the mechanisms behind the effectiveness of available treatments (or lack thereof) are better understood. Driven by these concepts, researchers and clinicians have begun to improve currently available treatment options, and develop new and better treatment methods. Here, we evaluate the range of pharmacological (i.e. closed-looped approaches), surgical (i.e. multi-target and adaptive deep brain and spinal cord stimulation) and behavioural (i.e. biofeedback and cueing on demand) treatment options that are under development, and propose novel avenues that are likely to play a crucial role in the clinical management of freezing of gait in the near future. The outcomes of this review suggest that the successful future management of freezing of gait will require individualized treatments that can be implemented in an on-demand manner in response to imminent freezing. With this review we hope to guide much-needed advances in treating this devastating symptom of Parkinson's disease.


e antigen and anti-e in the serum of asymptomatic carrier mothers as indicators of positive and negative transmission of hepatitis B virus to their infants.
Testing of serum samples of 23 pregnant women who were asymptomatic carriers of hepatitis B surface antigen for e antigen and antibody to e with an immunodiffusion technic identified 10 mothers with e antigen and seven with e antibody. Their babies were tested for hepatitis B surface antigen in serum at intervals for more than 12 months. In all 10 babies born to e-antigen-positive mothers hepatitis B surface antigen developed and persisted through the observation period, and all 10 elder siblings of these newborn babies were found to be asymptomatic carriers. In remarkable contrast, all seven babies born to mothers positive for antibody to e escaped antigenemia, and none of their three elder siblings carried surface antigen. On the basis of these results, e antigen may be used as an indicator of transmission, and antibody to e as that of absence of transmission of hepatitis B virus from carrier mothers to children.


Accurate and continuous ultrasonography evaluation of small diameter vascular prostheses in vivo.
There is a large clinical requirement for novel vascular grafts; however, the development of novel vascular grafts has not been extremely successful to date. The most successful method for the continuous evaluation of vascular grafts in vivo remains unclear. Therefore, an optimal successive, non-invasive imaging modality is necessary for the study of vascular transplantation. In the present study, a common rabbit model of carotid artery defect was utilized. The patency and hemodynamic characteristics of implanted grafts was examined following surgery by color Doppler ultrasound in three modes, including B-mode, color flow map and pulse-Doppler examination. The results revealed that ultrasound had sufficient spatial resolution to generate clear images of the carotid artery of rabbits with or without the implanted grafts. Color Doppler ultrasound may be applied to evaluate and differentiate the patent, stenosis and occlusion of carotid arteries in rabbits with different vascular grafts implanted. Furthermore, color Doppler ultrasound is an optimal imaging modality for continuous evaluation in vivo. It is also possible for some quantitative analyses to be performed, including measuring the diameter of vascular lumens and the flow velocity of the region of interest. The present study suggests vascular ultrasound as the optimum choice for continuous surveillance of vascular prostheses in vivo, which may provide valuable information about the grafts in order to greatly shorten the experimental period.


Comparison between colorectal low- and high-grade mucinous adenocarcinoma with MUC1 and MUC5AC.
To explore useful prognostic factors for mucinous adenocarcinoma (MAC) in the colon and rectum. MAC was divided into low- and high-grade types based on the degree of structural differentiation; low-grade MAC arisen from well to moderately differentiated adenocarcinoma and papillary carcinoma, and high-grade MAC from poorly differentiated adenocarcinoma and signet ring cell carcinoma. Immunohistochemically, the expression of 2 types of MUC1 (MUC1/DF and MUC1/CORE), MUC2, 2 types of MUC5AC (MUC5AC/CHL2 and HGM), MUC6, CDX2, and CD10 was examined in 16 cases of MAC consisting of 6 low- and 10 high-grade types. MUC1/DF3 was expressed in 3 of 6 low-grade MAC (50%) and 10 of 10 high-grade MAC (100%). MUC1/CORE was expressed in 1 of 6 low-grade MAC (16.7%) and 7 of 10 high-grade MAC (70%). MUC2 was expressed in all MAC regardless of the grade. MUC5AC was expressed in 6 of 6 low-grade MAC (100%) and 4 of 10 high-grade MAC (40%). HGM was expressed in 5 of 6 low-grade MAC (83.3%) and 6 of 10 high-grade MAC (60%). Expression of MUC6 and CD10 was undetected in all MAC regardless of the grade. CDX2 was expressed in 5 of 6 low-grade MAC (83.3%) and 7 of 10 high-grade MAC (70%). Taken together, MUC1/DF3 was expressed significantly more frequently in high-grade MAC than in low-grade, and MUC5AC/CHL2 was expressed significantly more frequently in low-grade MAC than in high-grade. It is proposed that MUC1/DF3 and MUC5AC/CHL2 immunostaining is useful to discriminate high-grade MAC from low-grade MAC.


Online coupling of a catalytic continuous microflow reactor to mass spectrometry.
Flow cell reactors used for catalyst development and applications are upcoming due to their small environmental and economic footprint. Online microflow reactor coupling with mass spectrometry (MS) opens new possibilities for monitoring catalyst performance and identifying reaction products in real time. This is demonstrated for the metabolic relevant dealkylation of lidocaine on catalytic gold micro-particles using regular liquid chromatography modules. Yields of up to 90% norlidocaine were realized under mild continuous flow conditions for up to 10 h (pH 7, 30 °C and 20 μL/min). Dissolved oxygen was shown to be a rate-limiting factor, since an inline oxygen generator allowed to increase the reactor capacity by one order of magnitude. Monitoring product time-response curve slopes after starting and ending a substrate feed, provided insights into the adsorption/desorption and conversion kinetics at the catalyst surface indicating the presence of strong adsorption sites that do not contribute substantially to substrate conversion.


Warmth and contingency and their relationship to maternal attitudes toward parenting.
In this study, the authors addressed the question of whether maternal parenting behaviors in terms of sensitivity, warmth, and contingency with respect to small infants were equally represented in attitudes toward parenting. Sixty mothers from central Germany with middle-class socioeconomic backgrounds were videotaped with their 1st born 3-month-old infant in a free-play and a caregiving episode in their home. The different maternal parenting components were behaviorally analyzed. Maternal attitudes toward parenting were assessed with self-report measures. The results showed that behavioral sensitivity was significantly associated with attitudes related to contingency, whereas behavioral warmth and contingency were not associated with maternal attitudes. The authors interpreted differential associations as a reflection of intuitive and explicit parenting strategies, with only sensitivity being explicitly represented.


Surface modification of poly(tetramethylene adipate-co-terephthalate) membrane via layer-by-layer assembly of chitosan and dextran sulfate polyelectrolyte multiplayer.
The improvement of hydrophilicity and hemocompatibility of poly(tetramethylene adipate-co-terephthalate) (PTAT) membrane was developed via polyelectrolyte multilayers (PEMs) immobilization. The polysaccharide PEMs included chitosan (CS, as a positive-charged and antibacterial agent) and dextran sulfate (DS, as a negative-charged and anti-adhesive agent) were successfully prepared using the aminolyzed PTAT membrane in a layer-by-layer (LBL) self-assembly manner. The obtained results showed that the contact angle of as-modified PTAT membranes reached to the steady value after four bilayers of coating, hence suggesting that the full coverage was achieved. It could be found that the PTAT-PEMs membranes with DS as the outmost layer could resist the platelet adhesion and human plasma fibrinogen (HPF) adsorption, thereby prolonging effectively the blood coagulation times. According to L929 fibroblast cell growth inhibition index, the as-prepared PTAT membranes exhibited non-cytotoxic. Overall results demonstrated that such an easy, valid and shape-independent processing should be potential for surface modification of PTAT membrane in the application of hemodialysis devices.


A role of Pygopus as an anti-repressor in facilitating Wnt-dependent transcription.
Wnt/beta-catenin signaling controls animal development and tissue homeostasis, and is also an important cancer pathway. Pygopus (Pygo) is a conserved nuclear Wnt signaling component that is essential for Wingless-induced transcription throughout Drosophila development. It associates with Armadillo/beta-catenin and T cell factor (TCF) through the Legless/BCL9 adaptor, but its molecular function in TCF-mediated transcription is unknown. Here, we use a groucho-null allele to show that Groucho represses Wingless target genes during Drosophila development. Interestingly, groucho pygo double-mutants revealed that Pygo is not obligatory for transcriptional and phenotypic Wingless signaling outputs if the interaction between Groucho and Drosophila TCF is compromised genetically. Pygo function is also non-essential for Wingless outputs in the absence of other transcriptional antagonists of Wingless signaling. This indicates an anti-repressor function of Pygo: we propose that Pygo predisposes Drosophila TCF target genes for rapid Wingless-induced transcription, or that it protects them against premature shut-down.


Does spinal fusion to T2, T3, or T4 affects sagittal alignment of the cervical spine in Lenke 1 AIS patients: A retrospective study.
The aim of this stusy was to investigate whether spinal fusion to T2, T3, or T4 affects sagittal alignment of the cervical spine in Lenke 1 adolescent idiopathic scoliosis (AIS) patients.A retrospective study comprised of 64 Lenke 1 AIS patients was performed to assess the radiographic and clinical outcome. According to the upper instrumented vertebrae (UIV) (T2, T3, or T4), the patients were divided into 3 groups. Comparison analyses were performed among these 3 groups of patients as between pre-op, immediate post-op, and final follow-up, as well as between these groups.Between groups, comparison analyses did not detect a statistical difference in cervical lordosis (CL) preoperatively (P = .501), immediately after surgery (P = .795), and at follow-up (P = .510). Immediately after surgery, CL increased significantly in all groups (T2, P = .004, T3, P < .001 and T4, P = .002 respectively). Compared with immediate postoperatively, CL at final follow-up increased in T2 group (P = .037), and T4 group (P = .010). Furthermore, CL at follow-up was significantly correlated with the following parameters: preoperative (coronal plane balance [r = .349, P = .004], pelvic tilt [r = 0.347, P = .004), pelvic incidence [r = 0.261, P = .031], and CL [r = 0.471, P < .001]) immediately postoperative (CL [r = 0.946, P < .001], T1-slope [r = -0.646, P < .001], and thoracic kyphosis [TK] [r = -0.353, P = .003]), and at follow-up (TK [r = -0.342, P = .004], and T1-slope [r = -0.821, P < .001]). However, there was no significant correlation between a selection of UIV and CL at follow-up (r = 0.031, P = .802). Moreover, Scoliosis Research Society (SRS-22) scores between groups were similar preoperatively (P = .242), immediately after surgery (P = .828), and at follow-up (P = .219).In Lenke 1 AIS patients, the selection of UIV mainly affects the coronal plane, especially shoulder balance. Fusion to T2, T3, or T4 did not affect the alignment of the cervical spine, and the SRS-22 score. Level IV.


[Evaluation of gastric sensitivity and accommodation by simultaneous determination of intra-gastric pressure in liquid load test].
To extensively evaluate the method of simultaneous determination of intra-gastric pressure (IGP) in liquid load test (LLT) in healthy subjects (HS) and patients with functional dyspepsia (FD). Forty HS and 67 FD patients (Rome III criteria) were recruited. All subjects were surveyed with regards to demographic characteristics, features of FD symptom spectrum and psychological status (Zung anxiety and depression scale). And the test of simultaneous determination of IGP in LLT was conducted. Finally all the data were collected and analyzed. HS group: no statistical difference was found in IGP divided by gender, age and body mass index (P > 0.05). The coefficient of variation of IGP at 15.3% was less than that of maximal intake volume (MIV). Twice repeated studies showed quite similar results and the linear interclass correlation coefficient of IGP was 0.806 (P = 0.002). As to the range of normal value from HS, the proportion of gastric hypersensitivity accounted for 35.0% and impaired accommodation for 25.0%. FD group: no statistical difference was found in IGP and MIV divided by gender, age and FD symptom subtype (P > 0.05). FD patients with abnormal psychological status had a lower IGP (4.2 +/- 1.2 mm Hg vs 4.8 +/- 1.1 mm Hg, P = 0.042) and MIV (450 +/- 138 ml vs 526 +/- 121 ml, P = 0.034) than those with normal status. IGP was not related to epigastric pain, epigastric burning, postprandial fullness or early satiation (F = 1.635, P = 0.190). Early satiation was significantly related to MIV (F = 4.682, P = 0.031; correlation coefficient was -6.8, P = 0.033). No statistical difference was found in gastric compliance among HS, all FD patients, patients with hypersensitivity or impaired accommodation (P > 0.05). The test had an excellent safety and tolerability. The method of simultaneous determination of IGP in LLT can differentiate gastric hypersensitivity from impaired accommodation. And it has an excellent feasibility, safety and reliability.


Silicon PAM-4 optical modulator driven by two binary electrical signals with different peak-to-peak voltages.
We demonstrate a silicon PAM-4 optical modulator, which is based on a symmetric Mach-Zehnder interferometer. Two uncorrelated binary electrical signals with different peak-to-peak voltages are applied to the phase shifters of the silicon optical modulator. Accordingly, two different phase shifts are generated in the two arms. After the permutation, there are totally four phase differences between the two arms and the output optical power has four levels. The device can work at 32 Gbaud in the wavelength range from 1525 to 1565 nm, which is promising for the next-generation high-speed silicon optical link.


Overexpression of ORC subunits and increased ORC-chromatin association in transformed mammalian cells.
The origin recognition complex (ORC) is a conserved heterohexamer required for the formation of pre-replication (pre-RC) complexes at origins of DNA replication. Many studies of ORC subunits have been carried out in transformed human cell lines but the properties of ORC in primary cells have not been addressed. Here, we compare the expression levels and chromatin-association of ORC subunits in HeLa cells to the primary human cell line, WI38, and a virally transformed derivative of WI38, VA13. ORC subunits 2 and 4 were highly overexpressed in both HeLa and VA13, whereas ORC1 levels were elevated in VA13 but considerably higher in HeLa cells. Cellular extraction revealed that the proportion of ORC2 and ORC4 subunits bound to chromatin was similar in all three cell lines throughout the cell-cycle. In contrast, very little ORC1 was associated with chromatin after extraction of primary WI38 cells, whereas the majority of overexpressed ORC1 in both HeLa and VA13 co-fractionated with chromatin throughout the cell-cycle. Although none of the cell lines displayed significant changes in the levels or chromatin-association of ORC during the cell-cycle, the chromatin-associated fraction of ORC1 displayed an increase in apparent molecular weight during S-phase. Similar experiments comparing immortalized CHO cells to an isogenic virally transformed derivative revealed no changes in levels of ORC subunits but an increase in the proportion of all three ORC subunits associated with chromatin. These results demonstrate a complex influence of cellular immortalization and transformation properties on the expression and regulation of ORC subunits. These results extend the potential link between cancer and deregulation of pre-RC proteins, and underscore the importance of considering the transformation status of cell lines when working with these proteins.