A novel family of calmodulin-binding transcription activators in multicellular organisms.
Screening of cDNA expression libraries derived from plants exposed to stress, with 35S-labeled recombinant calmodulin as a probe, revealed a new family of proteins containing a transcription activation domain and two types of DNA-binding domains designated the CG-1 domain and the transcription factor immunoglobulin domain, ankyrin repeats, and a varying number of IQ calmodulin-binding motifs. Based on domain organization and amino acid sequence comparisons, similar proteins, with the same domain organization, were identified in the genomes of other multicellular organisms including human, Drosophila, and Caenorhabditis, whereas none were found in the complete genomes of single cell eukaryotes and prokaryotes. This family of proteins was designated calmodulin-binding transcription activators (CAMTAs). Arabidopsis thaliana contains six CAMTA genes (AtCAMTA1-AtCAMTA6). The transcription activation domain of AtCAMTA1 was mapped by testing a series of protein fusions with the DNA-binding domain of the bacterial LexA transcription factor and two reporter genes fused to LexA recognition sequences in yeast cells. Two human proteins designated HsCAMTA1 and HsCAMTA2 were also shown to activate transcription in yeast using the same reporter system. Subcellular fractionation of Arabidopsis tissues revealed the presence of CAMTAs predominantly in the nucleus. Calmodulin binding assays identified a region of 25 amino acids capable of binding calmodulin with high affinity (K(d) = 1.2 nm) in the presence of calcium. We suggest that CAMTAs comprise a conserved family of transcription factors in a wide range of multicellular eukaryotes, which possibly respond to calcium signaling by direct binding of calmodulin.


Non-covalent double bond sensors for gas-phase infrared spectroscopy of unsaturated fatty acids.
The position and configuration of carbon-carbon double bonds in unsaturated fatty acids is crucial for their biological functions and influences health and disease. However, double bond isomers are not routinely distinguished by classical mass spectrometry workflows. Instead, they require sophisticated analytical approaches usually based on chemical derivatization and/or instrument modification. In this work, a novel strategy to investigate fatty acid double bond isomers (18:1) without prior chemical treatment or modification of the ion source was implemented by non-covalent adduct formation in the gas phase. Fatty acid adducts with sodium, pyridinium, trimethylammonium, dimethylammonium, and ammonium cations were characterized by a combination of cryogenic gas-phase infrared spectroscopy, ion mobility-mass spectrometry, and computational modeling. The results reveal subtle differences between double bond isomers and confirm three-dimensional geometries constrained by non-covalent ion-molecule interactions. Overall, this study on fatty acid adducts in the gas phase explores new avenues for the distinction of lipid double bond isomers and paves the way for further investigations of coordinating cations to increase resolution.


Skeletal muscle morphology and capillarization of renal failure patients receiving different dialysis therapies.
The morphology of gastrocnemius muscles was examined in RFPs (renal failure patients) being treated using HD (haemodialysis) and CAPD (continuous ambulatory peritoneal dialysis). RFPs (n=24) volunteered to participate in the present study. Twelve RFPs (five women and seven men; mean age, 55 years) were undergoing CAPD treatment and 12 RFPs (two women and ten men; mean age, 62 years) were undergoing HD treatment. Muscle biopsies from gastrocnemius muscles were found not to differ (P>0.05) in fibre type distribution, MyHC (myosin heavy chain) expression or fibre CSA (cross-sectional area) between the two groups. There were, however, significant differences (P<0.05) in CC/F (capillary contact/fibre), C/F (capillary to fibre ratio) and cytochrome c oxidase activity. The HD group had 33% more CC/F, with a 19% higher C/F and 33% greater cytochrome c activity in glycolytic fibres (II) than the CAPD group. There were no apparent differences in age, gender, co-morbidity, self-reported physical activity or physical functioning between the two groups, which could account for the difference in muscle capillarity between the groups. The HD patients were, however, administered heparin as a routine part of the dialysis therapy. The possibility is discussed that heparin in combination with mild anaemia and acidosis may have augmented angiogenesis in the HD patients.


Protein S-Bacillithiolation Functions in Thiol Protection and Redox Regulation of the Glyceraldehyde-3-Phosphate Dehydrogenase Gap in Staphylococcus aureus Under Hypochlorite Stress.
Bacillithiol (BSH) is the major low-molecular-weight thiol of the human pathogen Staphylococcus aureus. In this study, we used OxICAT and Voronoi redox treemaps to quantify hypochlorite-sensitive protein thiols in S. aureus USA300 and analyzed the role of BSH in protein S-bacillithiolation. The OxICAT analyses enabled the quantification of 228 Cys residues in the redox proteome of S. aureus USA300. Hypochlorite stress resulted in >10% increased oxidation of 58 Cys residues (25.4%) in the thiol redox proteome. Among the highly oxidized sodium hypochlorite (NaOCl)-sensitive proteins are five S-bacillithiolated proteins (Gap, AldA, GuaB, RpmJ, and PpaC). The glyceraldehyde-3-phosphate (G3P) dehydrogenase Gap represents the most abundant S-bacillithiolated protein contributing 4% to the total Cys proteome. The active site Cys151 of Gap was very sensitive to overoxidation and irreversible inactivation by hydrogen peroxide (H2O2) or NaOCl in vitro. Treatment with H2O2 or NaOCl in the presence of BSH resulted in reversible Gap inactivation due to S-bacillithiolation, which could be regenerated by the bacilliredoxin Brx (SAUSA300_1321) in vitro. Molecular docking was used to model the S-bacillithiolated Gap active site, suggesting that formation of the BSH mixed disulfide does not require major structural changes. Conclusion and Innovation: Using OxICAT analyses, we identified 58 novel NaOCl-sensitive proteins in the pathogen S. aureus that could play protective roles against the host immune defense and include the glycolytic Gap as major target for S-bacillithiolation. S-bacillithiolation of Gap did not require structural changes, but efficiently functions in redox regulation and protection of the active site against irreversible overoxidation in S. aureus. Antioxid. Redox Signal. 28, 410-430.


An epidemiologic examination on the prevalence of the periodontal diseases and oral pigmentation in Yusho patients in 2002.
An epidemiologic examination was carried out to reveal the prevalence of the periodontal diseases and oral pigmentation in patients with Yusho. The results obtained were as follows. 1) 95 patients out of 110 patients, who were examined periodontal pocket depth using Ramfjord' methods, had at least one tooth with periodontal pocket deeper than 3 mm. Similarly, 276 teeth out of a total 495 examined teeth showed periodontal pockets with more than 3 mm depth. However, the ratio of the teeth with periodontal pockets deeper than 4 mm to total examined teeth in each age fell to less than 25%. 2) Oral pigmentation was observed in 75 patients out of 121 patients with Yusho. In this examination, gingival pigmentation was most predominant among oral pigmentation. It is of particular interest that severe pigmentation tended to be observed at a much higher frequency in younger patients with Yusho. Taken these findings into consideration, it was suggested that PCBs and related compounds might play an important role in the development of both periodontal diseases and oral pigmentation.


Induced pluripotent stem cells as a model for accelerated patient- and disease-specific drug discovery.
Human induced pluripotent stem (iPS) cells hold great promise for therapy of a number of degenerative diseases such as ischemic heart failure, Parkinson's disease, Alzheimer's disease, diabetes mellitus, sickle cell anemia and Huntington disease. They also have the potential to accelerate drug discovery in 3 ways. The first involves the delineation of chemical components for efficient reprogramming of patient's blood cells or cells from biopsies, obviating the need for cellular delivery of reprogramming exogenous transgenes, thereby converting hope into reality for patients suffering from degenerative diseases. Patients worldwide stand to benefit from the clinical applicability of iPS cell-based cell replacement therapy for a number of degenerative diseases. The second is the potential for discovering novel drugs in a high throughput manner using patient-specific iPS cell-derived somatic cells possessing the etiology of the specific disease. The third is their suitability for toxicological testing of drugs and environmental factors. This review focuses on these potential applications of iPS cells with special emphasis on recent updates of iPS cell research contributing to the accelerated drug discovery.


Neurosurgical Treatments for Patients with Chronic, Treatment-Refractory Depression: A Retrospective, Consecutive, Case Series Comparison of Anterior Capsulotomy, Anterior Cingulotomy and Vagus Nerve Stimulation.
The evidence base to guide therapeutic choices for patients with chronic and treatment-refractory depression (TRD) remains weak. There is limited comparative information available to guide the choice of intervention for patients with the most severe and disabling forms of illness. The aim of this work was to describe the 12-month clinical outcomes of patients with chronic TRD treated with anterior capsulotomy (ACAPS; n = 5), anterior cingulotomy (ACING; n = 5) or vagus nerve stimulation (VNS; n = 5). We performed a retrospective, consecutive, case series comparison. With clinical response defined as a ≥50% reduction from the baseline MADRS score, response rates were 40% for ACAPS, 60% for ACING and 20% for VNS. Adverse effects from all three procedures were relatively mild, consistent with previous reports and, in most cases, transient. Adverse effects from VNS were related to active stimulation, and were modifiable and diminished in severity over time. There were no deaths. Although based on a small sample, our data represent a unique comparison of ACAPS, ACING and VNS for chronic TRD. The three cohorts were broadly equivalent in terms of baseline clinical characteristics, indices of chronicity, illness severity and estimates of previous failed treatments. ACING and ACAPS, but not VNS, were associated with favourable response rates at 12 months.


Trends in pelvic lymphadenectomy at the time of radical cystectomy: 1988 to 2004.
Studies suggest that patients who undergo thorough lymphadenectomy for bladder cancer benefit from improved survival. We evaluated the incidence of and trends in lymphadenectomy in conjunction with radical cystectomy for bladder cancer. Using the Surveillance, Epidemiology and End Results registry we identified 8,072 eligible patients with bladder cancer who underwent radical cystectomy with or without lymphadenectomy from 1988 to 2004. After stratification by age group, race, stage, grade and year of diagnosis we performed logistic and linear regression to correlate variables to the mean number of lymph nodes sampled and the likelihood of undergoing lymphadenectomy (classified as 1 or more, 5 or more and 10 or more nodes removed). In the final cohort 1,660 patients (21%) did not have any lymph nodes sampled at radical cystectomy. This number decreased from 37% in 1988 to 16% in 2004. During this period the mean number of lymph nodes removed increased by 2.6 nodes over all definitions of lymphadenectomy and the percentage of patients undergoing any form of lymph node dissection increased by an average of 19%. Year of diagnosis was most strongly predictive of the likelihood of undergoing lymphadenectomy and most correlative with the mean number of nodes sampled. Over time there has been improvement in terms of the performance of lymphadenectomy and node counts obtained during radical cystectomy. If these trends continue the incidence and quality of lymphadenectomy should continue to increase, ultimately to the benefit of the patients being treated.


Honoring eight senior distinguished plant biologists from India.
We summarize here research contributions of eight stalwarts in photosynthesis research from India. These distinguished scientists (Shree Kumar Apte, Basanti Biswal, Udaya C. Biswal, Agepati S. Raghavendra, Attipalli Ramachandra Reddy, Prafullachandra Vishnu (Raj) Sane, Baishnab Charan Tripathy, and Dinesh C. Uprety) were honored on November 2, 2017, at the School of Life Sciences, University of Hyderabad. We include here two group photographs of this special event, which was organized by the Department of Plant Sciences, during the 8th International Conference on Photosynthesis and Hydrogen Energy Research for Sustainability-2017 ( https://prs.science/wp-content/uploads/2017/10/Photosynthesis-Research-for-Sustainability-2017.pdf , also available at: http://www.life.illinois.edu/govindjee/world-historical.html ). The main conference had honored three international scientists: William Cramer (Purdue University. West Lafayette, Indiana, USA), Govindjee (University of Illinois at Urbana-Champaign, Illinois, USA, one of the authors here); and Agepati S. Raghavendra (University of Hyderabad, India, one of those honored here as well); see papers in this Special Issue, edited by Suleyman Allakhverdiev, one of the authors here.


Data for positive selection test and co-evolutionary analysis on mammalian cereblon.
Cereblon (CRBN) is a substrate recognition subunit of the CRL4 E3 ubiquitin ligase complex, directly binding to specific substrates for poly-ubiquitination followed by proteasome-dependent degradation of proteins. Cellular CRBN is responsible for energy metabolism, ion-channel activation, and cellular stress response through binding to proteins related to the respective pathways. As CRBN binds to various proteins, the selective pressure at the interacting surface is expected to result in functional divergence. Here, we present two mammalian CRBN datasets of molecular evolutionary analyses. (1) The multiple sequence alignment data shows that positive selection occurred, determined with a dN/dS calculation. (2) Data on co-evolutionary analysis between vertebrate CRBN and related proteins are represented by calculating the correlation coefficient based on the comparison of phylogenetic trees. Co-evolutionary analysis shows the similarity of evolutionary traits of two proteins. Further molecular, functional interpretation of these analyses is explained in 'Positive selection of Cereblon modified function including its E3 Ubiquitin Ligase activity and binding efficiency with AMPK' (W. Onodera, T. Asahi, N. Sawamura, Positive selection of cereblon modified function including its E3 ubiquitin ligase activity and binding efficiency with AMPK. Mol Phylogenet Evol. (2019) 135:78-85. [1]).


Teaching alternatives to the standard inferior alveolar nerve block in dental education: outcomes in clinical practice.
Surveys were sent to Harvard School of Dental Medicine students and graduates from the classes of 2000 through 2006 to determine their current primary means of achieving mandibular anesthesia. Orthodontists and orthodontic residents were excluded. All subjects received clinical training in the conventional inferior alveolar nerve block and two alternative techniques (the Akinosi mandibular block and the Gow-Gates mandibular block) during their predoctoral dental education. This study tests the hypothesis that students and graduates who received training in the conventional inferior alveolar nerve block, the Akinosi mandibular block, and the Gow-Gates mandibular block will report more frequent current utilization of alternatives to the conventional inferior alveolar nerve block than clinicians trained in the conventional technique only. At the 95 percent confidence level, we estimated that between 3.7 percent and 16.1 percent (mean=8.5 percent) of clinicians trained in using the Gow-Gates technique use this injection technique primarily, and between 35.4 percent and 56.3 percent (mean=47.5 percent) of those trained in the Gow-Gates method never use this technique. At the same confidence level, between 0.0 percent and 3.8 percent (mean=0.0 percent) of clinicians trained in using the Akinosi technique use this injection clinical technique primarily, and between 62.2 percent and 81.1 percent (mean=72.3 percent) of those trained in the Akinosi method never use this technique. No control group that was completely untrained in the Gow-Gates or Akinosi techniques was available for comparison. However, we presume that zero percent of clinicians who have not been trained in a given technique will use the technique in clinical practice. The confidence interval for the Gow-Gates method excludes this value, while the confidence interval for the Akinosi technique includes zero percent. We conclude that, in the study population, formal clinical training in the Gow-Gates and Akinosi injection techniques lead to a small but significant increase in current primary utilization of the Gow-Gates technique. No significant increase in current primary utilization of the Akinosi technique was found.


Induction of transplantation tolerance through regulatory cells: from mice to men.
Organ transplantation results in the activation of both innate and adaptive immune responses to the foreign antigens. While these responses can be limited with the use of systemic immunosuppressants, the induction of regulatory cell populations may be a novel strategy for the maintenance of specific immunological unresponsiveness that can reduce the severity of the detrimental side effects of current therapies. Our group has extensively researched different regulatory T-cell induction protocols for use as cellular therapy in transplantation. In this review, we address the cellular and molecular mechanisms behind regulatory T-cell suppression and their stability following induction protocols. We further discuss the use of different hematopoietically derived regulatory cell populations, including regulatory B cells, regulatory macrophages, tolerogenic dendritic cells, and myeloid-derived suppressor cells, for the induction of transplantation tolerance in light of new clinical trials developing therapies with some of these populations.


The burden of preserved ejection fraction heart failure in a real-world Swedish patient population.
To evaluate resource use and associated costs in patients with a diagnosis of heart failure with preserved ejection fraction (HF-PEF) in Sweden. This retrospective study identified real-world patients with an ICD-10 diagnosis code for heart failure (I50) for the period between July 1, 2005 and December 31, 2006 from electronic medical records of primary care centers in Uppsala County Council, and in the Swedish patient registry data. Patients were categorized as having HF-PEF (left ventricle ejection fraction [LVEF] > 50%) during the index period. The study assessed medication utilization, outpatient visits, hospitalizations, and associated healthcare costs, as well as the incidence rates and time to all-cause and heart failure mortality following the index period. The study included 137 HF-PEF patients with a mean age of 77.1 (SD = 9.1) years. Over 50% of HF-PEF patients were female and hypertensive. Nearly all patients received ≥ 1 medication post-index. Patients had an average of 1.5 heart failure related hospitalizations per follow-up year. The average annual per patient cost for the management of a HF-PEF patient was found in Sweden to be Swedish Krona (SEK) 108,246 (EURO [EUR] 11,344). Hospitalizations contributed to more than 80% of the total cost. All-cause mortality over the 18-month study period was 25.5%, and more than 50% of these deaths occurred within 1 year of index. Due to the limitations of registry data, it is not possible to confirm the HF diagnosis, and therefore the accuracy of registry records must be assumed. Other factors such as short follow-up time, the study-mandated LVEF assessment, and a lack of drug duration data may also have an impact on the study results. All-cause mortality was high in the HF-PEF population, with more than half of patients dying within 1 year of study follow-up. Study results also indicate that 60% of HF-PEF patients have ≥ 1 hospitalization during follow-up. Hospitalizations, especially heart failure related admissions, represent a substantial proportion of the total healthcare burden of patients with HF-PEF in Sweden.


Estimated glomerular filtration rate is associated with major bleeding complications but not thromboembolic events, in anticoagulated patients taking warfarin.
Decreased glomerular filtration rate is an established risk factor for bleeding but there are limited data on its association with bleeding risk in well-controlled anticoagulated patients taking warfarin. The aim was to investigate the relationship between glomerular filtration rate, major bleeding and thromboembolic complications in patients with tight anticoagulation control. A cohort study of patients from a Swedish quality register for anticoagulation, including all the registered patients that received anticoagulation during 2008 in the anticoagulation center of Skåne University Hospital, Malmö. Key outcome measures were major bleeding and arterial or venous thrombosis during 2008. A total of 3536 patients (2875 treatment years) were included. Total rates of 2.6 (2.0-3.2) bleeding events and 1.8 (1.3-2.3) thrombotic events per 100 treatment years were recorded (75 bleeding and 51 thromboembolic events). Data on estimated glomerular filtration rate were available in 3349 patients. Mean time in therapeutic range (international normalized ratio 2.0-3.0) was 74.5% (n=2894). Major bleeding events were significantly related to age and percentage of time with international normalized ratio >3.0 (P<0.001). Glomerular filtration rate levels <30 ml/min/1.73 m(2) were particularly associated with high risk of bleeding, especially in elderly patients. No correlation between glomerular filtration rate and thromboembolic events was seen. With good anticoagulation control as measured by time in therapeutic range, patients had a relatively low risk for major bleeding if their renal function is normal. Despite good anticoagulation control, severely impaired kidney function is associated with a very high yearly risk of major bleeding events.


Individual and combined effects of DNA methylation and copy number alterations on miRNA expression in breast tumors.
The global effect of copy number and epigenetic alterations on miRNA expression in cancer is poorly understood. In the present study, we integrate genome-wide DNA methylation, copy number and miRNA expression and identify genetic mechanisms underlying miRNA dysregulation in breast cancer. We identify 70 miRNAs whose expression was associated with alterations in copy number or methylation, or both. Among these, five miRNA families are represented. Interestingly, the members of these families are encoded on different chromosomes and are complementarily altered by gain or hypomethylation across the patients. In an independent breast cancer cohort of 123 patients, 41 of the 70 miRNAs were confirmed with respect to aberration pattern and association to expression. In vitro functional experiments were performed in breast cancer cell lines with miRNA mimics to evaluate the phenotype of the replicated miRNAs. let-7e-3p, which in tumors is found associated with hypermethylation, is shown to induce apoptosis and reduce cell viability, and low let-7e-3p expression is associated with poorer prognosis. The overexpression of three other miRNAs associated with copy number gain, miR-21-3p, miR-148b-3p and miR-151a-5p, increases proliferation of breast cancer cell lines. In addition, miR-151a-5p enhances the levels of phosphorylated AKT protein. Our data provide novel evidence of the mechanisms behind miRNA dysregulation in breast cancer. The study contributes to the understanding of how methylation and copy number alterations influence miRNA expression, emphasizing miRNA functionality through redundant encoding, and suggests novel miRNAs important in breast cancer.


Combined beam forming and cross correlation of broadband signals from a multidimensional array using coherent optics.
A coherent optical system design is proposed for simultaneously heterodyning, correlating, and beam forming on a large number of input channels. Techniques are described with application to two- as well as one-dimensional arrays. To accommodate the former, one direction in the optical aperture must serve both as a time and space dimension. The particular technique proposed resolves the apparent ambiguity. The method uses the phase of the correlation amplitude, after heterodyning, to effect the beam forming operation. Although the full theoretical correlation processing gain against background noise is not realized, very substantial gains and fine time and angle resolutions can be achieved. Because of its inherent physical simplicity, particularly as contrasted with electronic methods of similar capacity, the coherent optical correlator-beam former has significant advantages for many applications.


Ga and Ce ion-doped phosphate glass fibres with antibacterial properties and their composite for wound healing applications.
Novel gallium/cerium-doped phosphate glass fibres (PGF) were successfully manufactured by the melt-quenching and melt-spinning process. The amorphous character of the materials produced was confirmed using X-ray powder diffraction (XRD), and the elemental composition was investigated with X-ray fluorescence confirming the presence of 2 mol% of Ga2O3 or CeO2. Fourier Transform Infrared Spectroscopy (FTIR) confirmed the presence of Q1 and Q2 structural phosphate species. Mechanical properties of the PGFs revealed tensile strength values of 428 ± 94 MPa and 379 ± 80 MPa, with elastic modulus values of 45 ± 4 GPa and 54 ± 9 GPa for Ce-PGF (diameter 25 μm) and Ga-PGF (diameter 18 μm), respectively. The influence of both dopants on the glass degradation properties was evaluated by tests in deionised water, which revealed a decreased dissolution rate for gallium-doped PGF in comparison to cerium-doped PGF. Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) measurements were used to explore ion release in cell culture medium, while ICP-mass spectrometry (ICP-MS) was used to measure ion release in deionised water. These techniques showed controlled release of therapeutic and antibacterial ions from the PGF. Antibacterial properties of Ce-PGF and Ga-PGF, based on turbidity measurements, were confirmed against Gram-positive bacteria. Moreover, Ce-doped phosphate glass fibres did not disturb the proliferation of human epidermal keratinocyte (HaCaT) cells or the mobility of mice embryonic fibroblasts (MEF). Applying an in vitro scratch assay showed full wound closure after 24 h of indirect incubation with Ga-PGF. Due to their superior processability as compared with Ga-PGFs, a fully degradable mesh based on Ce-PGF was designed and found to achieve high water uptake (up to 800%), suggesting its suitability for wound healing applications.


[Efficacy and tolerance of PDE-5 in the treatment of erectile dysfunction in schizophrenic patients: A literature review].
Sexual dysfunction is an important public health problem in men and is associated with reduced quality of life. It is more common in patients with schizophrenia. It is well-established that antipsychotic drugs cause sexual dysfunction with consequences on the quality of life of patients, adherence to treatment, and public health costs. Phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are indicated for the management of erectile dysfunction. However, there is little information on such treatment in schizophrenic patients. This literature review aimed to summarize the current data on the efficacy and tolerability of PDE-5 inhibitors in the erectile dysfunction in schizophrenic patients. PubMed, PsycInfo and Cochrane databases were searched for studies published until August 2014. Only 6 studies met the inclusion criteria. Three were randomized, double-blind, cross-over, placebo-controlled trials and three were open studies. Various scales were used to measure erectile and orgasmic function, desire, satisfaction during intercourse, overall satisfaction, quality of life and intensity of schizophrenic symptoms. In the 3 randomized studies (one with sildenafil 25-50 mg, one with lodenafil carbonate 80 mg/j and the last one with tadalafil 10 mg), the rate of participants who completed the trial was high (around 95 %). All three included patients with schizophrenia or schizophrenia spectrum disorders. Patients reported significant improvement on sexual dysfunction. However, no statistical difference was reported between lodenafil and placebo, on different scales, suggesting a very important placebo effect in patients with schizophrenia. All three found a good tolerance of PDE-5 inhibitors. Side effects were rare and were mainly nasal congestion, headaches, nausea and dizziness. There were no major side effects or drug interactions. Considering the 3 open studies, 2 involved sildenafil and one tadalafil. All concluded in improved erectile and orgasmic function, desire, satisfaction during intercourse, overall satisfaction, and even the quality of life when it was studied. However, very few patients were included. Little data are available on the use of PDE5 inhibitors in schizophrenic patients. The 6 studies included few patients which reduces the power and the scope of their conclusions. There is also an important bias due to the use of self-questionnaires. The methodologies of the studies differ in many aspects which limits the comparability. Inclusion and exclusion criteria, drugs used and scales varied among the studies. However, the management of erectile disorder seems to be a consistent target in an integrative approach for the overall well-being of schizophrenic patients. PDE-5 inhibitors appear to be safe and could improve erectile function in schizophrenic patients. In total, the current data suggest efficiency and good tolerance of the use of PDE-5 inhibitors in schizophrenic patients with erectile dysfunction. However, further studies focusing on PDE-5 inhibitors are needed to more deeply assess their efficacy and safety in patients with schizophrenia.


Adhesion molecule expression on epithelial cells infected with respiratory syncytial virus.
Respiratory epithelium is both a target and an effector of airway inflammation. Adhesion molecules on epithelium play an important role in a variety of airway diseases. Respiratory syncytial virus (RSV) is the most important pathogen for airway diseases in infants. The expression of adhesion molecules on epithelium in RSV infection, however, is unclear. The expression of selected adhesion molecules and major histocompatibility complex (MHC) class I and II antigens on a human alveolar type II epithelial cell line (A549) infected with RSV was investigated by means of flow cytometry and immunocytochemistry. The results showed that intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were expressed on A549 cells at a low level. E-cadherin and MHC class I antigen were constitutively expressed on the cells. RSV infection of A549 cells significantly upregulated the expression of ICAM-1, VCAM-1 and MHC class I and II antigens on these cells. RSV infection also altered the expression of E-cadherin on A549 cells. Immunostaining showed that E-cadherin was mainly upregulated around or in RSV-induced giant cells. These data suggest that respiratory syncytial virus infection of respiratory epithelial cells enhances the expression of adhesion molecules and major histocompatibility complex antigens. These changes may play an important role in the pathophysiology of respiratory syncytial virus disease.


Susceptibility to Laurel Wilt and Disease Incidence in Two Rare Plant Species, Pondberry and Pondspice.
Laurel wilt, caused by Raffaelea lauricola, has been responsible for extensive losses of redbay (Persea borbonia) in South Carolina and Georgia since 2003. Symptoms of the disease have been noted in other species of the Lauraceae such as the federally endangered pondberry (Lindera melissifolia) and the threatened pondspice (Litsea aestivalis). Pondberry and pondspice seedlings were inoculated with R. lauricola from redbay, and both species proved highly susceptible to laurel wilt. Field assessments found substantial mortality of pondberry and pondspice, but in many cases the losses were not attributable to laurel wilt. R. lauricola was isolated from only 4 of 29 symptomatic pondberry plants at one site, but the fungus was not recovered from three plants at another site. R. lauricola was isolated from one of two symptomatic pondspice plants at one site, and from five of 11 plants at another site, but not from any plant at a third site. Insect bore holes, similar to those produced by Xyleborus glabratus (the vector of laurel wilt), were found in some pondberry and pondspice stems, but adults were not found. Damage caused by Xylosandrus compactus was found in pondberry stems, but this ambrosia beetle does not appear to be a vector of R. lauricola. Xyleborinus saxeseni adults were found in a dying pondspice with laurel wilt, and R. lauricola was recovered from two of three adults. Isolates of R. lauricola from pondberry, pondspice, and X. saxeseni had rDNA sequences that were identical to previously characterized isolates, and inoculation tests confirmed that they were pathogenic to redbay. Because pondberry and pondspice tend to be shrubby plants with small stem diameters, these species may not be frequently attacked by X. glabratus unless in close proximity to larger diameter redbay.


German short forms of the Oral Health Impact Profile.
We report the development and psychometric evaluation of short forms of the Oral Health Impact Profile German version (OHIP-G) - an instrument to assess oral health-related quality of life (OHRQoL). A five-item short form was developed using best subset regression in 2050 subjects from a national survey. Two 14-item versions were derived from English-language short forms and a 21-item version from previous factor analytic work. A second sample from the general population (n = 163) and a sample of clinical patients with temporomandibular disorders (TMD; n = 175) were used to investigate validity and internal consistency. Test-retest reliability was evaluated in 30 prosthodontic patients before treatment. Responsiveness was assessed in 67 patients treated for their TMD pain. Associations between short form summary scores and self-report of oral health and four oral disorders in the general population and in TMD patients were interpreted as support for convergent/groups validity. The instruments' responsiveness (effect measures of 0.55-0.98), test-retest reliability (intraclass correlation coefficients: 0.72-0.87), and internal consistency (Cronbach's alpha: 0.65-0.92) were sufficient. Sufficient discriminative and evaluative psychometric properties of short forms of the OHIP-G make the instruments suitable to assess OHRQoL in cross-sectional as well as longitudinal studies.


Arbuscular mycorrhizal fungi: effects on plant terpenoid accumulation.
Arbuscular mycorrhizal fungi (AMF) are a diverse group of soil-dwelling fungi that form symbiotic associations with land plants. AMF-plant associations promote the accumulation of plant terpenoids beneficial to human health, although how AMF mediate terpenoid accumulation is not fully understood. A critical assessment and discussion of the literature relating to mechanisms by which AMF influence plant terpenoid accumulation, and whether this symbiosis can be harnessed in horticultural ecosystems was performed. Modification of plant morphology, phosphorus availability and gene transcription involved with terpenoid biosynthetic pathways were identified as key mechanisms associated with terpenoid accumulation in AMF-colonised plants. In order to exploit AMF-plant symbioses in horticultural ecosystems it is important to consider the specificity of the AMF-plant association, the predominant factor affecting terpenoid accumulation, as well as the end use application of the harvested plant material. Future research should focus on resolving the relationship between ecologically matched AMF genotypes and terpenoid accumulation in plants to establish if these associations are effective in promoting mechanisms favourable for plant terpenoid accumulation.


Susceptibility of differentiating muscle cells of the fetal mouse in culture to coxsackievirus A13.
The interaction of coxsackievirus A13 with differentiating muscle cells, cultured from tissues of the fetal mouse, was studied. Cultures infected at that stage of myogenic differentiation characterized by the rapid formation of multinucleated myotubes produced maximum virus titers of over 10(7) plaque-forming units. Virus-induced cytopathic effect was characterized by a marked diminution in the number of multinucleated cells. The susceptibility of these cultures decreased appreciably when infection was initiated after the majority of the myotubes had formed. The demonstration of newly synthesized A13 virus antigen by immunofluorescence provided direct evidence that A13 virus replication occurred both in myoblasts and myotubes. The synthesis of A13 virus was markedly depressed in muscle cultures in which the formation of multinucleated cells was inhibited by BUDR or by fusion-inhibiting media. After reversal of this inhibition, the cultures acquired the increased susceptibility to A13 virus characteristic of cells undergoing myogenic differentiation. In contrast to the results obtained with coxsackievirus A13, the primary fetal mouse muscle cultures were resistant to poliovirus T1. It is suggested that changes in the surfaces of developing muscle cells may coincide with the formation and disappearance of specific virus receptors and thereby regulate the cell susceptibility to coxsackievirus A13.


Identification of (2R,3R)-2-(3,4-dihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxy benzoate as multiple inhibitors of SARS-CoV-2 targets; a systematic molecular modelling approach.
Coronavirus disease of 2019 (COVID-19) is a zoonotic disease caused by a new severe acute respiratory syndrome (SARS-CoV-2) which has quickly resulted in a pandemic. Recent anti-COVID-19 drug discoveries are leaning towards repurposing phytochemicals which have been previously reported for SARS and MERS-CoV outbreaks. However, they have been either virtually screened or tested so far against mono targets and the potent derivatives of virtually sorted lead molecules remain elusive. We aimed to identify the phytochemicals having potentials to inhibit SARS CoV-2 infection via multiple targets. The selected 132 phytochemicals were virtually screened using a structure based in silico technique against main protease (Mpro) which is a potential target of SARS CoV-2. Six compounds were selected based on the LibDock scores and further subjected to induced fit docking using the CDOCKER module of DS. Two compounds namely cinnamtannin-B and gallocatechin gallate were identified as top HITS against main protease (Mpro). Based on the Lipinski rule of five (L-ROF) and synthetic feasibility, gallocatechin gallate was taken for our further studies. Six analogues of gallocatechin gallate were screened against the next important targets such as RNA-dependent RNA polymerase (RdRp), angiotensin converting enzyme-2 (ACE2), transmembrane protease serine -2 (TMPRSS2) and interleukin-6 (IL-6) along with main protease (Mpro). Our molecular docking results reveal that a gallocatechin analogue (GC-2) namely (2R,3R)-2-(3,4-dihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxy benzoate has shown potential to inhibit multiple targets of SARS CoV-2. Further, the molecular dynamics study was carried out to ascertain the stability of the GC-2 and RdRp complex.


Modeling the effects of transforming growth factor-beta on extracellular matrix alignment in dermal wound repair.
We present a novel mathematical model for collagen deposition and alignment during dermal wound healing, focusing on the regulatory effects of transforming growth factor-beta (TGFbeta.) Our work extends a previously developed model which considers the interactions between fibroblasts and an extracellular matrix composed of collagen and a fibrin based blood clot, by allowing fibroblasts to orient the collagen matrix, and produce and degrade the extracellular matrix, while the matrix directs the fibroblasts and control their speed. Here we extend the model by allowing a time varying concentration of TGFbeta to alter the properties of the fibroblasts. Thus we are able to simulate experiments which alter the TGFbeta profile. Within this model framework we find that most of the known effects of TGFbeta, i.e., changes in cell motility, cell proliferation and collagen production, are of minor importance to matrix alignment and cannot explain the anti-scarring properties of TGFbeta. However, we find that by changing fibroblast reorientation rates, consistent with experimental evidence, the alignment of the regenerated tissue can be significantly altered. These data provide an explanation for the experimentally observed influence of TGFbeta on scarring.


Metachronous Pancreatic Metastasis from Rectal Cancer that Masqueraded as a Primary Pancreatic Cancer: A Rare and Difficult-to-Diagnose Metastatic Tumor in the Pancreas.
BACKGROUND Pancreatic metastasis from colorectal cancer is rare and can masquerade as primary pancreatic cancer. CASE REPORT A 70-year-old male was diagnosed with advanced rectal cancer with multiple liver metastases. After neoadjuvant chemotherapy, he underwent radical surgery for the primary tumor and hepatectomy for multiple liver metastases. Adjuvant chemotherapies and additional surgeries were subsequently required for recurrences in the liver, lung, and lymph nodes. A diffuse hypovascular nodule in the pancreatic head and a solitary liver metastasis were detected 2.5 years after the initial surgery and he accordingly underwent further chemotherapy. However, the pancreatic tumor progressed, invading the pancreatic duct and biliary tract. Obstructive jaundice finally prompted discontinuation of chemotherapy and he underwent biliary drainage. His diffuse and hypovascular tumor was clinically and radiographically diagnosed as a primary pancreatic cancer. Pancreatic resection for the pancreatic tumor and hepatectomy for the liver metastasis were performed 4.2 years after the initial surgery, achieving radiographic and surgical curative resection. Pathological examination of the surgical specimen resulted in a definitive diagnosis of metachronous pancreatic metastasis from his primary rectal cancer. Despite further chemotherapy, his general condition worsened; however, he remains alive 5.4 years after the initial surgery, with best supportive care. CONCLUSIONS Pancreatic metastasis originating from rectal cancer can masquerade as primary pancreatic cancer clinically and radiologically. Multimodality treatment is mandatory for metastatic colorectal cancer. Aggressive surgeries for pancreatic metastasis should be considered if curative resection appears possible radiographically and/or intraoperatively.


Pre-analytical factors affecting the establishment of a single tube assay for multiparameter liquid biopsy detection in melanoma patients.
The combination of liquid biomarkers from a single blood tube can provide more comprehensive information on tumor development and progression in cancer patients compared to single analysis. Here, we evaluated whether a combined analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and circulating cell-free microRNA (miRNA) in total plasma and extracellular vesicles (EV) from the same blood sample is feasible and how the results are influenced by the choice of different blood tubes. Peripheral blood from 20 stage IV melanoma patients and five healthy donors (HD) was collected in EDTA, Streck, and Transfix tubes. Peripheral blood mononuclear cell fraction was used for CTC analysis, whereas plasma and EV fractions were used for ctDNA mutation and miRNA analysis. Mutations in cell-free circulating DNA were detected in 67% of patients, with no significant difference between the tubes. CTC was detected in only EDTA blood and only in 15% of patients. miRNA NGS (next-generation sequencing) results were highly influenced by the collection tubes and could only be performed from EDTA and Streck tubes due to hemolysis in Transfix tubes. No overlap of significantly differentially expressed miRNA (patients versus HD) could be found between the tubes in total plasma, whereas eight miRNA were commonly differentially regulated in the EV fraction. In summary, high-quality CTCs, ctDNA, and miRNA data from a single blood tube can be obtained. However, the choice of blood collection tubes is a critical pre-analytical variable.


Population genetics of translational robustness.
Recent work has shown that expression level is the main predictor of a gene's evolutionary rate and that more highly expressed genes evolve slower. A possible explanation for this observation is selection for proteins that fold properly despite mistranslation, in short selection for translational robustness. Translational robustness leads to the somewhat paradoxical prediction that highly expressed genes are extremely tolerant to missense substitutions but nevertheless evolve very slowly. Here, we study a simple theoretical model of translational robustness that allows us to gain analytic insight into how this paradoxical behavior arises.


Multiple distinct small RNAs originate from the same microRNA precursors.
MicroRNAs (miRNAs), which originate from precursor transcripts with stem-loop structures, are essential gene expression regulators in eukaryotes. We report 19 miRNA precursors in Arabidopsis that can yield multiple distinct miRNA-like RNAs in addition to miRNAs and miRNA*s. These miRNA precursor-derived miRNA-like RNAs are often arranged in phase and form duplexes with an approximately two-nucleotide 3'-end overhang. Their production depends on the same biogenesis pathway as their sibling miRNAs and does not require RNA-dependent RNA polymerases or RNA polymerase IV. These miRNA-like RNAs are methylated, and many of them are associated with Argonaute proteins. Some of the miRNA-like RNAs are differentially expressed in response to bacterial challenges, and some are more abundant than the cognate miRNAs. Computational and expression analyses demonstrate that some of these miRNA-like RNAs are potentially functional and they target protein-coding genes for silencing. The function of some of these miRNA-like RNAs was further supported by their target cleavage products from the published small RNA degradome data. Our systematic examination of public small-RNA deep sequencing data from four additional plant species (Oryza sativa, Physcomitrella patens, Medicago truncatula and Populus trichocarpa) and four animals (Homo sapiens, Mus musculus, Caenorhabditis elegans and Drosophila) shows that such miRNA-like RNAs exist broadly in eukaryotes. We demonstrate that multiple miRNAs could derive from miRNA precursors by sequential processing of Dicer or Dicer-like proteins. Our results suggest that the pool of miRNAs is larger than was previously recognized, and miRNA-mediated gene regulation may be broader and more complex than previously thought.


Service evaluation comparing Acute Care at Home for older people service and conventional service within an acute hospital care of elderly ward.
This study evaluated the impact of a consultant-led Acute Care at Home service in comparison with conventional hospital admission to a care of elderly ward. Globally, there has been an increased demand for healthcare services caused by population growth and a rise in chronic conditions and an ageing population. Acute Care at Home services offer acute, hospital-level care in a person's own home. Five services have been commissioned across Northern Ireland since 2014 with limited research investigating their feasibility and effectiveness. Quantitative design, using service evaluation methodology. A 1-year retrospective chart review was undertaken exploring admission demographics and post-discharge clinical outcomes of patients admitted to a Northern Ireland, Care of the Elderly ward (n = 191) and a consultant-led Acute Care at Home Service (n = 314) between April 2018-March 2019. Data were analysed using descriptive and inferential data analysis methods including frequencies, independent t tests and chi-square analysis. Outcome measurements included length of stay, 30-day, 3- and 6-month readmission and mortality rates, functional ability and residence on discharge. STROBE checklist was used in reporting this study. Acute Care at Home services are associated with higher readmission and mortality rates at 30 days, 3 and 6 months. Fewer patients die while under Acute Care at Home care. Patients admitted to the Acute Care at Home services experience a reduced length of stay and decreased escalation in domiciliary care packages and are less likely to require subacute rehabilitation on discharge. There is no difference in gender, age and early warnings score between the two cohorts. The Acute Care at Home service is a viable alternative to hospital for older patients. It prevents functional decline and the need for domiciliary care or nursing home placement. It is likely that the Acute Care at Home service has higher mortality and readmissions rates due to treating a higher proportion of dependent, frail older adults. Acute Care at Home services continue to evolve worldwide. This service evaluation has confirmed that Acute Care at Home services are safe and cost-effective alternatives to traditional older people hospital services. Such services offer patient choice, reduce length of stay and costs and prevent functional decline of older adults. This study accentuates the need to expand Acute Care at Home provision and capacity throughout Northern Ireland.


The prevalence of, and factors associated with, paying for sex among men resident in Britain: findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).
Men who pay for sex (MPS) are considered a bridging population for sexually transmitted infections (STI). However, the extent, characteristics and role of MPS in transmission is poorly understood. We investigate these questions using data from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). We performed complex survey analyses of data from 6293 men aged 16-74 years resident in Britain who completed Natsal-3, a probability sample survey undertaken during 2010-2012, using computer-assisted personal interviewing and computer-assisted self-interview. 11.0% (95% CI10.1% to 11.9%) of all men reported ever paying for sex. Among MPS, 18.4% (95% CI 18.2% to 18.7%) of their lifetime sexual partners were paid. 3.6% (95% CI 3.1% to 4.2%) of men had paid for sex in the past 5 years. Partners of MPS constitute 14.7% of all reported partners and MPS report 15.6% of all reported STI diagnoses in the past 5 years. Paying for sex in the past 5 years was strongly associated with reporting larger numbers of sexual partners (adjusted OR, AOR for 5+ partners, past 5 years, 31.50, 95% CI 18.69 to 53.09). After adjusting for partner numbers, paying for sex remained strongly associated with reporting new foreign partners outside the UK (AOR 7.96; 95% CI 4.97 to 12.73) and STI diagnosis/es (AOR 2.34; 95% CI 1.44 to 3.81), all in the past 5 years. Among men ever paying for sex, 62.6% (95% CI 58.3% to 66.8%) reported paying for sex outside the UK, most often in Europe and Asia. MPS in Britain remain at greater risk of STI acquisition and onward transmission than men who do not. They report high numbers of partners, but the minority are paid partners. They are an important core group in STI transmission.


Effects of lifestyle intervention on neck, shoulder, elbow and wrist symptoms.
The objective of this study was to determine whether lifestyle intervention to control hypertension can affect neck, shoulder, elbow, and wrist symptoms. In a randomized controlled trial, 731 employees from 45 worksites were assigned for 12 months to lifestyle intervention in a rehabilitation center or to usual care provided by occupational or primary health care services. The participants had a systolic blood pressure of 140-179 mm Hg or a diastolic blood pressure of 90-109 mm Hg, or antihypertensive drug treatment. In addition to the cardiovascular risk factors, the occurrences of neck, shoulder, elbow, and wrist symptoms and disability during the previous 12 months were recorded before the intervention and 1 year later. The reported disability due to neck pain during the previous 12 months fell significantly more (-7%) in the intervention group than in the group in usual care (-2%). The perceived shoulder pain during the previous 7 days also decreased significantly more in the intervention group than in the control group among the women (net change 16%) and among the participants who were more highly physically active (net change 10%). Weight, body mass index, and waist and hip circumferences decreased, and physical activity increased, substantially more in the intervention group. The changes in elbow or wrist pain and related disability did not differ significantly between the intervention and control groups. Lifestyle intervention to control hypertension has a favorable impact on perceived disability due to neck pain.


Nuclear translocation of 3'-phosphoinositide-dependent protein kinase 1 (PDK-1): a potential regulatory mechanism for PDK-1 function.
3'-Phosphoinositide-dependent protein kinase 1 (PDK-1) phosphorylates and activates members of the AGC protein kinase family and plays an important role in the regulation of cell survival, differentiation, and proliferation. However, how PDK-1 is regulated in cells remains elusive. In this study, we demonstrated that PDK-1 can shuttle between the cytoplasm and nucleus. Treatment of cells with leptomycin B, a nuclear export inhibitor, results in a nuclear accumulation of PDK-1. PDK-1 nuclear localization is increased by insulin, and this process is inhibited by pretreatment of cells with phosphatidylinositol 3-kinase (PI3-kinase) inhibitors. Consistent with the idea that PDK-1 nuclear translocation is regulated by the PI3-kinase signaling pathway, PDK-1 nuclear localization is increased in cells deficient of PTEN (phosphatase and tensin homologue deleted on chromosome 10). Deletion mapping and mutagenesis studies unveiled that presence of a functional nuclear export signal (NES) in mouse PDK-1 located at amino acid residues 382 to 391. Overexpression of constitutively nuclear PDK-1, which retained autophosphorylation at Ser-244 in the activation loop in cells and its kinase activity in vitro, led to increased phosphorylation of the predominantly nuclear PDK-1 substrate p70 S6KbetaI. However, the ability of constitutively nuclear PDK-1 to induce anchorage-independent growth and to protect against UV-induced apoptosis is greatly diminished compared with the wild-type enzyme. Taken together, these findings suggest that nuclear translocation may be a mechanism to sequestrate PDK-1 from activation of the cytosolic signaling pathways and that this process may play an important role in regulating PDK-1-mediated cell signaling and function.


Microsurgical resection of extensive craniopharyngiomas using a frontolateral approach: operative technique and outcome.
An extensive craniopharyngioma is a tumor that extends into multiple compartments (subarachnoid spaces) and attains a size larger than 4 cm. A wide spectrum of approaches and strategies has been used for resection of such craniopharyngiomas. In this report the authors focused on the feasibility and efficacy of microsurgical resection of extensive craniopharyngiomas using a frontolateral approach. A retrospective analysis was performed on 16 patients with extensive craniopharyngiomas who underwent operations using a frontolateral approach at one institution. The preoperative and postoperative clinical and radiological data, as well as the operative videos, were reviewed. The main focus of the review was the extent of radical tumor removal, early postoperative outcome, and approach-related complications. Gross-total resection of craniopharyngioma was achieved in 14 (87.5%) of 16 cases. Early after surgery (within 3 months), 1 patient showed improvement in hormonal status, while in the remaining 15 patients it worsened. No major neurological morbidity was observed. Two patients experienced temporary psychotic disorders. Visual function improved in 6 patients and remained unchanged in 9. One patient experienced a new bitemporal hemianopsia. Three patients with features of short-term memory disturbances at presentation did show improvement after surgery. There were no deaths or significant approach-related morbidity in this patient series. Only 1 patient required revision surgery for a CSF leak. The safe and simple frontolateral approach provides adequate access even to extensive craniopharyngiomas and enables their complete removal with a reasonable morbidity and approach-related complication rate.


Asian venous thromboembolism guidelines: prevention of venous thromboembolism.
Venous thromboembolism (VTE) prophylaxis is under-utilized in Asia because of the misconception that its incidence is lower in Asians as compared to the Caucasians. The available data on VTE in Asia is limited due to the lack of well-designed multicenter randomized controlled trials as well as non-standardized research designs, making data comparison difficult. Emerging data indicates that the VTE incidence is not low in Asia, and is comparable to that reported in the Western literature in some instances. There is also a trend towards increasing incidence of VTE, as demonstrated by a number of hospital-based studies in Asia. This could be attributed to lifestyle changes, ageing population, increasing awareness of VTE and wider availability of Duplex ultrasound. The risk of VTE in hospitalized patients remain the same in Asians and Caucasians, even though there may be factors that are inherent to patients in Asia that influence the slight variation in incidence. The utilization rate of VTE prophylaxis remains suboptimal in Asia. The Asian Venous Thrombosis Forum (AVTF) comprises participants from various countries such as China, Hong Kong, India, Indonesia, Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand and experts from Australia and Europe. The forum evaluated the available data on VTE from the Asian region and formulated guidelines tailored to meet the needs of the region. We recommend that serious considerations are given to VTE prophylaxis especially in the at-risk group and a formal hospital policy be established to facilitate the implementation. On admission to the hospital, we recommend assessing the patients for both VTE and bleeding risk. We recommend mechanical prophylaxis for patients at increased risk of bleeding and utilizing it as an adjunctive measure in combination with pharmacological prophylaxis in patients with high risk of VTE. For patients undergoing general or gynecological surgery and with moderate risk for VTE, we recommend prophylaxis with one of the following: low dose unfractionated heparin (LDUH), low molecular weight heparin (LMWH), fondaparinux or intermittent pneumatic compression (IPC). For the same group of patients at high risk of VTE, we recommend pharmacological or combination of pharmacological and mechanical prophylaxis. For patients undergoing major orthopedic surgeries like total hip replacement, total knee replacement and proximal hip fracture surgery, we recommend using one of the following: LMWH, fondaparinux, rivaroxaban, apixaban, edoxaban, dabigatran, warfarin or aspirin with IPC. For patients admitted to the hospital with acute medical illness and has moderate risk of VTE, we recommend prophylaxis with LDUH, LMWH or Fondaparinux. For the same group at high risk of VTE, we recommend combination of pharmacological and mechanical prophylaxis.


Tracking capsule activation and crack healing in a microcapsule-based self-healing polymer.
Structural polymeric materials incorporating a microencapsulated liquid healing agent demonstrate the ability to autonomously heal cracks. Understanding how an advancing crack interacts with the microcapsules is critical to optimizing performance through tailoring the size, distribution and density of these capsules. For the first time, time-lapse synchrotron X-ray phase contrast computed tomography (CT) has been used to observe in three-dimensions (3D) the dynamic process of crack growth, microcapsule rupture and progressive release of solvent into a crack as it propagates and widens, providing unique insights into the activation and repair process. In this epoxy self-healing material, 150 µm diameter microcapsules within 400 µm of the crack plane are found to rupture and contribute to the healing process, their discharge quantified as a function of crack propagation and distance from the crack plane. Significantly, continued release of solvent takes place to repair the crack as it grows and progressively widens.


Hyperbolic Positioning with Antenna Arrays and Multi-Channel Pseudolite for Indoor Localization.
A hyperbolic positioning method with antenna arrays consisting of proximately-located antennas and a multi-channel pseudolite is proposed in order to overcome the problems of indoor positioning with conventional pseudolites (ground-based GPS transmitters). A two-dimensional positioning experiment using actual devices is conducted. The experimental result shows that the positioning accuracy varies centimeter- to meter-level according to the geometric relation between the pseudolite antennas and the receiver. It also shows that the bias error of the carrier-phase difference observables is more serious than their random error. Based on the size of the bias error of carrier-phase difference that is inverse-calculated from the experimental result, three-dimensional positioning performance is evaluated by computer simulation. In addition, in the three-dimensional positioning scenario, an initial value convergence analysis of the non-linear least squares is conducted. Its result shows that initial values that can converge to a right position exist at least under the proposed antenna setup. The simulated values and evaluation methods introduced in this work can be applied to various antenna setups; therefore, by using them, positioning performance can be predicted in advance of installing an actual system.


Bubble-Induced Endothelial Microparticles Promote Endothelial Dysfunction.
Decompression sickness is a systemic pathophysiological process caused by bubbles and endothelial microparticles (EMPs) are established markers reflecting competency of endothelial function and vascular biology. Here, we investigated the effects of bubble-induced EMPs on endothelial cells in vitro and vivo. Rat pulmonary microvascular endothelial cells (PMVECs) were isolated and stimulated by bubbles and bubble-induced EMPs were collected and incubated with normal PMVECs in vitro. Cell viability and apoptosis were detected using Cell Counting Kit-8 assay and Annexin V FITC/PI double staining, respectively. Cell permeability and pro-inflammatory cytokines were determined by electric cell substrate impedance sensing and enzyme-linked immunosorbent assay, respectively. Intracellular nitric oxide and reactive oxygen species production were analyzed microscopically. In vivo study, bubble-induced EMPs were intravenously injected to the rats and soluble thrombomodulin, intercellular adhesion molecule 1, and vascullar adhesion molecule 1 were involved in evaluating endothelial dysfunction. In our study, bubble stimulus resulted in a significant increase of EMPs release by 3 fold. Bubble-induced EMPs significantly decreased cell viability and increased cell apoptosis. Moreover, bubble-induced EMPs induced abnormal increase of cell permeability and over-expression of pro-inflammatory cytokines. Intracellular ROS production increased while NO production decreased. These negative effects caused by bubble-induced EMPs were remarkably suppressed when EMPs pretreated with surfactant FSN-100. Finally, intravenous injection of bubble-induced EMPs caused elevations of soluble thrombomodulin and pro-inflammatory cytokines in the circulation. Altogether, our results demonstrated that bubble-induced EMPs can mediate endothelial dysfunction in vitro and vivo, which can be attenuated by EMPs abatement strategy. These data expanded our horizon of the detrimental effects of bubble-induced EMPs, which may be of great concern in DCS.


Clinical correlates of in vitro Plasmodium falciparum cytoadherence.
To determine whether isolates of Plasmodium falciparum have intrinsically different cytoadherent properties and whether these differences contribute to the clinical severity of human falciparum malaria, we studied the cytoadherence to C32 melanoma cells in vitro of 59 parasite isolates from patients with naturally acquired infections in Thailand. Parasitized erythrocytes adhere to these melanoma cells principally via the glycoprotein CD36, which is also expressed on most vascular endothelium. In vitro cytoadherence was significantly greater for isolates from patients with biochemical evidence of severe malaria. The cytoadherent properties of P. falciparum parasites may thus be a virulence factor in human falciparum malaria. However, there was no correlation between the degree of in vitro cytoadherence and cerebral symptoms, which suggests that other receptors and/or host factors may be important in the adherence of malaria parasites to cerebral vascular endothelium. The cytokines tumor necrosis factor, interleukin-1, and gamma interferon, which have been implicated in the pathogenesis of cerebral malaria and are known to promote intercellular adhesion in other systems, did not enhance the cytoadherence of P. falciparum isolates to C32 melanoma cells.


New methods for diagnosis and treatment of vestibular diseases.
Dizziness and vertigo are common complaints, with a lifetime prevalence of over 30%. This review provides a brief summary of the recent diagnostic and therapeutic advances in the field of neuro-otology. A special focus is placed on the clinical usefulness of vestibular tests. While these have markedly improved over the years, treatment options for vestibular disorders still remain limited. Available therapies for selected vestibular diseases are discussed.


Type A behavior and elevated physiological and neuroendocrine responses to cognitive tasks.
Qualitatively distinct patterns of cardiovascular and neuroendocrine responses were observed in male college students during mental work and during sensory intake task performance. During mental work, Type A (coronary-prone) subjects showed greater muscle vasodilatation and more enhanced secretion of norepinephrine, epinephrine, and cortisol than Type B subjects. During sensory intake, Type A hyperresponsivity was found for testosterone and, among those subjects with a positive family history of hypertension, for cortisol. As a demonstration of combined cardiovascular, sympathetic nervous system, and neuroendocrine hyperresponsivity to specific cognitive tasks in Type A subjects, this study breaks ground in the search for mechanisms mediating the increased coronary disease risk among Type A persons.


Cyanobacterial neurotoxin BMAA in ALS and Alzheimer's disease.
The aim of this study was to screen for and quantify the neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) in a cohort of autopsy specimens taken from Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and non-neurological controls. BMAA is produced by cyanobacteria found in a variety of freshwater, marine, and terrestrial habitats. The possibility of geographically broad human exposure to BMAA had been suggested by the discovery of BMAA in brain tissues of Chamorro patients with ALS/Parkinsonism dementia complex from Guam and more recently in AD patients from North America. These observations warranted an independent study of possible BMAA exposures outside of the Guam ecosystem. Postmortem brain specimens were taken from neuropathologically confirmed cases of 13 ALS, 12 AD, 8 HD patients, and 12 age-matched non-neurological controls. BMAA was quantified using a validated fluorescent HPLC method previously used to detect BMAA in patients from Guam. Tandem mass spectrometric (MS) analysis was carried out to confirm the identification of BMAA in neurological specimens. We detected and quantified BMAA in neuroproteins from postmortem brain tissue of patients from the United States who died with sporadic AD and ALS but not HD. Incidental detections observed in two out of the 24 regions were analyzed from the controls. The concentrations of BMAA were below what had been reported previously in Chamarro ALS/ Parkinsonism dementia complex patients, but demonstrated a twofold range across disease and regional brain area comparisons. The presence of BMAA in these patients was confirmed by triple quadrupole liquid chromatography/mass spectrometry/mass spectrometry. The occurrence of BMAA in North American ALS and AD patients suggests the possibility of a gene/environment interaction, with BMAA triggering neurodegeneration in vulnerable individuals.


Passive Membrane Permeability in Cyclic Peptomer Scaffolds Is Robust to Extensive Variation in Side Chain Functionality and Backbone Geometry.
Synthetic and natural cyclic peptides provide a testing ground for studying membrane permeability in nontraditional drug scaffolds. Cyclic peptomers, which incorporate peptide and N-alkylglycine (peptoid) residues, combine the stereochemical and geometric complexity of peptides with the functional group diversity accessible to peptoids. We synthesized cyclic peptomer libraries by split-pool techniques, separately permuting side chain and backbone geometry, and analyzed their membrane permeabilities using the parallel artificial membrane permeability assay. Nearly half of the side chain permutations had permeability coefficients (Papp) > 1 × 10-6 cm/s. Some backbone geometries enhanced permeability due to their ability to form more stable intramolecular hydrogen bond networks compared with other scaffolds. These observations suggest that hexameric cyclic peptomers can have good passive permeability even in the context of extensive side chain and backbone variation, and that high permeability can generally be achieved within a relatively wide lipophilicity range.


Smokers with active Crohn's disease have a clinically relevant dysbiosis of the gastrointestinal microbiota.
Patients with Crohn's disease (CD) have an intestinal dysbiosis with components of the microbiota exerting differential immune effects. Smoking is associated with an increased incidence of CD, more frequent relapse, and greater burden of surgery. This study aimed to investigate the association between smoking and the intestinal microbiota in patients with active CD. Patients with active CD (n = 103) and healthy controls (n = 66) were recruited and demographic and clinical data recorded including current smoking behavior. Fecal samples were collected and analyzed by fluorescent in situ hybridization using probes targeting 16S rRNA of bacteria previously shown to be altered in active CD (bifidobacteria, bacteroides, Clostridium coccoides-Eubacterium rectale, Escherichia coli, and Faecalibacterium prausnitzii). In total, 29/101 (29%) patients with CD and 8/58 (14%) controls were current smokers (P = 0.032). Following multivariate analysis, smoking was found to have a significant and independent effect on the microbiota of patients with CD, with higher Bacteroides-Prevotella in smokers (38.4%) compared with nonsmokers (28.1%) (F((1,93)) = 12.6, P = 0.001). Healthy controls who smoked also had higher Bacteroides-Prevotella (34.8%) than nonsmokers (24.1%) (F((1,55)) = 4.5, P = 0.038). In the pooled multivariate analysis, patients with CD had higher bifidobacteria (F((1,156)) = 30.5, P < 0.001), higher Bacteroides-Prevotella (F((1,156)) = 6.5, P = 0.012), and lower F. prausnitzii (F((1,156)) = 3.8, P = 0.052) compared with healthy controls. Smokers have luminal microbiota that consist of significantly higher bacteroides. Investigation of whether this is one mechanism through which the negative effects of smoking on CD are mediated is warranted.


Altered rate of fibronectin matrix assembly by deletion of the first type III repeats.
The assembly of fibronectin (FN) into a fibrillar matrix is a complex stepwise process that involves binding to integrin receptors as well as interactions between FN molecules. To follow the progression of matrix formation and determine the stages during which specific domains function, we have developed cell lines that lack an endogenous FN matrix but will form fibrils when provided with exogenous FN. Recombinant FNs (recFN) containing deletions of either the RGD cell-binding sequence (RGD-) or the first type III repeats (FN delta III1-7) including the III1 FN binding site were generated with the baculovirus insect cell expression system. After addition to cells, recFN matrix assembly was monitored by indirect immunofluorescence and by insolubility in the detergent deoxycholate (DOC). In the absence of any native FN, FN delta III1-7 was assembled into fibrils and was converted into DOC-insoluble matrix. This process could be inhibited by the amino-terminal 70 kD fragment of FN, showing that FN delta III1-7 follows an assembly pathway similar to FN. The progression of FN delta III1-7 assembly differed from native FN in that the recFN became DOC-insoluble more quickly. In contrast, RGD- recFNs were not formed into fibrils except when added in combination with native FN. These results show that the RGD sequence is essential for the initiation step but fibrils can form independently of the III1-7 modules. The altered rate of FN delta III1-7 assembly suggests that one function of the missing repeats might be to modulate an early stage of matrix formation.


Effects of burn wound excision on bacterial colonization and invasion.
Rates of survival after thermal injury have improved in the past two decades, and rates of wound infections and sepsis have decreased during the same period. Early excision has been advocated as one of the major factors, but its safety and efficacy and the exact timing of burn excision are still under debate. It was hypothesized that acute burn wound excision (in the first 24 hours after burning) would be superior to conservative treatment and delayed excision in preventing bacterial colonization and invasion. Twenty consecutive patients with thermal injuries were studied. Twelve patients underwent acute burn wound excision, and eight patients underwent conservative treatment and delayed excision. The second group of patients received topical treatments in another facility and underwent delayed excision after transfer to our service, on postburn day 6. Quantitative bacteriological assessments of the excised wound and biopsy samples of the wound bed, obtained before autografting and/or homografting, were performed. The effects of time on bacterial counts, differences between superficial and deep biopsy samples, and the effects of early versus late debridement were studied. Patients admitted early exhibited bacterial counts of less than 10 bacteria per gram of tissue. Patients in this group did not experience infection or graft loss. Patients admitted late exhibited counts of more than 10 bacteria (p = 0.001, compared with early admission). Three patients in the late excision group experienced infection and graft loss (p < 0.05, compared with the early excision group). Burn wound excision significantly decreased bacterial colonization for all patients (p < 0.001). Greater bacterial colonization and higher rates of infection were correlated with topical treatment and late excision (p < 0.001). It is concluded that burn wound excision significantly reduces bacterial colonization. Patients who undergo topical treatment and delayed burn wound excision exhibit greater bacterial colonization and increased rates of infection. Acute burn wound excision should be considered for all full-thickness burns.


Strain-specified characteristics of mouse synthetic prions.
Synthetic prions were produced in our laboratory by using recombinant mouse prion protein (MoPrP) composed of residues 89-230. The first mouse synthetic prion strain (MoSP1) was inoculated into transgenic (Tg) 9949 mice expressing N-terminally truncated MoPrP(Delta23-88) and WT FVB mice expressing full-length MoPrP. On first and second passage in Tg9949 mice, MoSP1 prions caused disease in 516 +/- 27 and 258 +/- 25 days, respectively; numerous, large vacuoles were found in the brainstem and gray matter of the cerebellum. MoSP1 prions passaged in Tg9949 mice were inoculated into FVB mice; on first and second passage, the FVB mice exhibited incubation times of 154 +/- 4 and 130 +/- 3 days, respectively. In FVB mice, vacuolation was less intense but more widely distributed, with numerous lesions in the hippocampus and cerebellar white matter. This constellation of widespread neuropatho-logic changes was similar to that found in FVB mice inoculated with Rocky Mountain Laboratory (RML) prions, a strain derived from a sheep with scrapie. Conformational stability studies showed that the half-maximal GdnHCl (Gdn1/2) concentration for denaturation of MoSP1 prions passaged in Tg9949 mice was approximately 4.2 M; passage in FVB mice reduced the Gdn1/2 value to approximately 1.7 M. RML prions passaged in either Tg9949 or FVB mice exhibited Gdn1/2 values of approximately 1.8 M. The incubation times, neuropathological lesion profiles, and Gdn1/2 values indicate that MoSP1 prions differ from RML and many other prion strains derived from sheep with scrapie and cattle with bovine spongiform encephalopathy.


Induction of sulfamethazine acetylation by hydrocortisone in the rabbit.
Daily intravenous administration of hydrocortisone (HC) to rabbits resulted in a marked time-dependent increase in the metabolic clearance of sulfamethazine (SMZ). Kinetic analysis of the plasma concentration-time profiles for SMZ indicated that HC treatment significantly increased the rate of acetylation of SMZ without altering the renal clearances or volumes of distribution for either parent drug or the N-acetyl metabolite N-acetylsulfamethazine (NASMZ). Total body clearance of NASMZ was also unaltered. Doses of HC ranging from 25 to 150 mg/kg were equally effective in enhancing the in vivo acetylation rate of SMZ. Moreover, the induction of SMZ acetylation was reversible when treatment with the steroid was terminated. The in vitro rate of SMZ acetylation was measured in the cytosol of various organs from controls and rabbits treated with HC for 10 days. HC did not alter the Michaelis-Menten parameters for N-acetyltransferase (NAT) activity in kidney, lung, or gut. Similarly, the Km for SMZ acetylation in liver cytosol was not affected by the steroid. However, the Vmax estimates of hepatic NAT activity were significantly increased after HC treatment. At 0.5 mM SMZ and variable [acetyl-CoA], Vmax increased 3-fold from 82 +/- 20 to 244 +/- 43 mumol/min/organ, while at 0.5 mM acetyl-CoA and variable [SMZ], Vmax increased 2.8-fold from 75 +/- 19 to 208 +/- 41 mumol/min/organ. This increase was primarily due to a 69% increase in liver weight since Vmax expressed per mg of cytosolic protein was similar in both groups. The endogenous acetyl CoA concentrations were significantly increased by HC in liver and lung, but not in gut and kidney.(ABSTRACT TRUNCATED AT 250 WORDS)


Dehydration affects brain structure and function in healthy adolescents.
It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing.


Remodeling of the Epithelial-Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging.
Early neoplastic features in oral epithelial dysplasia are first evident at the basal epithelium positioned at the epithelial-connective tissue interface (ECTI), separating the basal epithelium from the underlying lamina propria. The ECTI undergoes significant deformation in early neoplasia due to focal epithelial expansion and proteolytic remodeling of the lamina propria, but few studies have examined these changes. In the present study, we quantitated alterations in ECTI topography in dysplasia using in vivo volumetric multiphoton autofluorescence microscopy and second harmonic generation microscopy. The label-free method allows direct noninvasive visualization of the ECTI surface without perturbing the epithelium. An image-based parameter, "ECTI contour," is described that indicates deformation of the ECTI surface. ECTI contour was higher in dysplasia than control or inflamed specimens, indicating transition from flat to a deformed surface. Cellular parameters of nuclear area, nuclear density, coefficient of variation in nuclear area in the basal epithelium and collagen density in areas adjacent to ECTI were measured. ECTI contour differentiated dysplasia from control/benign mucosa with higher sensitivity and specificity than basal nuclear density or basal nuclear area, comparable with coefficient of variation in nuclear area and collagen density. The presented method offers a unique opportunity to study ECTI in intact mucosa with simultaneous assessment of cellular and extracellular matrix features, expanding opportunities for studies of early neoplastic events near this critical interface and potentially leading to development of new approaches for detecting neoplasia in vivo Cancer Res; 76(16); 4637-47. ©2016 AACR.


Identification of key mechanisms controlling gene expression in Leishmania infected macrophages using genome-wide promoter analysis.
The present study describes the in silico prediction of the regulatory network of Leishmania infected human macrophages. The construction of the gene regulatory network requires the identification of Transcription Factor Binding Sites (TFBSs) in the regulatory regions (promoters, enhancers) of genes that are regulated upon Leishmania infection. The promoters of human, mouse, rat, dog and chimpanzee genes were first identified in the whole genomes using available experimental data on full length cDNA sequences or deep CAGE tag data (DBTSS, FANTOM3, FANTOM4), mRNA models (ENSEMBL), or using hand annotated data (EPD, TRANSFAC). A phylogenetic footprinting analysis and a MATCH analysis of the promoter sequences were then performed to predict TFBS. Then, an SQL database that integrates all results of promoter analysis as well as other genome annotation information obtained from ENSEMBL, TRANSFAC, TRED (Transcription Regulatory Element Database), ORegAnno and the ENCODE project, was established. Finally publicly available expression data from human Leishmania infected macrophages were analyzed using the genome-wide information on predicted TFBS with the computer system ExPlain™. The gene regulatory network was constructed and activated signal transduction pathways were revealed. The Irak1 pathway was identified as a key pathway regulating gene expression changes in Leishmania infected macrophages.


Reflective writing: the student nurse's perspective on reflective writing and poetry writing.
Reflective writing is a mandatory part of nurse education but how students develop their skills and use reflection as part of their experiential learning remains relatively unknown. Understanding reflective writing in all forms from the perspective of a student nurse is therefore important. To explore the use of reflective writing and the use of poetry in pre-registered nursing students. A qualitative design was employed to explore reflective writing in pre-registered nursing students. A small university in Scotland. BSc (Hons) Adult and Mental Health Pre-registration Student Nurses. Two focus groups were conducted with 10 student nurses during March 2012. Data was analysed thematically using the framework of McCarthy (1999). Students found the process of reflective writing daunting but valued it over time. Current educational methods, such as assessing reflective accounts, often lead to the 'narrative' being watered down and the student feeling judged. Despite this, reflection made students feel responsible for their own learning and research on the topic. Some students felt the use of models of reflection constricting, whilst poetry freed up their expression allowing them to demonstrate the compassion for their patient under their care. Poetry writing gives students the opportunity for freedom of expression, personal satisfaction and a closer connection with their patients, which the more formal approach to reflective writing did not offer. There is a need for students to have a safe and supportive forum in which to express and have their experiences acknowledged without the fear of being judged.


Hepatitis C care cascade among persons born 1945-1965: 3 medical centers.
Effective screening, diagnosis, and treatment are needed to reduce chronic hepatitis C virus (HCV) infection-associated morbidity and mortality. In order to successfully increase HCV treatment, it is necessary to identify and understand gaps in linkage of antibody-positive patients with newly identified HCV to subsequent HCV RNA testing, clinical evaluation, and treatment. To estimate attainment of HCV care cascade steps among antibody-positive patients with newly identified HCV, we conducted chart reviews of patients with a new positive HCV antibody test at 3 academic medical centers participating in the Birth-Cohort Evaluation to Advance Screening and Testing of Hepatitis C (BEST-C) study. We tracked receipt of RNA testing, clinical evaluation, treatment initiation, and treatment completion among individuals born between 1945 and 1965 who were newly diagnosed as HCV antibody-positive between December 2012 and October 2015 at 3 BEST-C centers, predominantly from the participating medical centers' primary care practices and emergency departments. Of the 130 HCV-seropositive individuals identified, 118 (91%) had an RNA or genotype test, 75 (58%) were RNA-positive, 73 (56%) were linked to care, 22 (17% overall; 29% among RNA-positive) started treatment, and 21 (16%; 28% among RNA-positive) completed treatment. This analysis showed that although linkage to care was largely successful in the target birth cohort, the largest gap in the HCV care cascade was seen in initiating treatment. Greater emphasis on linking patients to clinical evaluation and treatment is necessary in order to achieve the public health benefits promised by birth-cohort testing.


New approach to improve the accuracy of 3-D shape measurement of moving object using phase shifting profilometry.
When phase shifting profilometry (PSP) is employed for 3-D shape measurement, the object must be kept static during the projection and acquisition of the multiple fringe patterns. Errors will occur when the object moves and if the projection and capture of fringe patterns are not fast enough. In this paper, a new approach is proposed to tackle the problem, consisting of two steps. Firstly, the rotation matrix and translation vector describing the movement of the object are estimated using a set of marks placing on the surface of the object. Then the expressions of the fringe patterns under the influence of 2-D object movement are derived, which are employed to determine the correct phase map, leading to accurate measurement of the profile. Simulations and experiments are presented to verify the effectiveness of the proposed algorithm.


Disturbance of soliton pulse propagation from higher-order dispersive waveguides.
Optical soliton pulses offer many applications within optical communication systems, but by definition a soliton is only subjected to second-order anomalous group-velocity-dispersion; an understanding of higher-order dispersion is necessary for practical implementation of soliton pulses. A numerical model of a waveguide was developed using the nonlinear Schrödinger equation, with parameters set to ensure the input pulse energy would be equal to the fundamental soliton energy. Higher-order group-velocity-dispersion was gradually increased, for various temporal widths and waveguide dispersions. A minimum pulse duration of 100 fs was determined to be necessary for fundamental soliton pulse propagation in practical photonic crystal waveguides.


Structural insight into the DNA polymerase beta deoxyribose phosphate lyase mechanism.
A large number of biochemical and genetic studies have demonstrated the involvement of DNA polymerase beta (Pol beta) in mammalian base excision repair (BER). Pol beta participates in BER sub-pathways by contributing gap filling DNA synthesis and lyase removal of the 5'-deoxyribose phosphate (dRP) group from the cleaved abasic site. To better understand the mechanism of the dRP lyase reaction at an atomic level, we determined a crystal structure of Pol beta complexed with 5'-phosphorylated abasic sugar analogs in nicked DNA. This DNA ligand represents a potential BER intermediate. The crystal structure reveals that the dRP group is bound in a non-catalytic binding site. The catalytic nucleophile in the dRP lyase reaction, Lys72, and all other potential secondary nucleophiles, are too far away to participate in nucleophilic attack on the C1' of the sugar. An approximate model of the dRP group in the expected catalytic binding site suggests that a rotation of 120 degrees about the dRP 3'-phosphate is required to position the epsilon-amino Lys72 close to the dRP C1'. This model also suggests that several other side chains are in position to facilitate the beta-elimination reaction. From results of mutational analysis of key residues in the dRP lyase active site, it appears that the substrate dRP can be stabilized in the observed non-catalytic binding conformation, hindering dRP lyase activity.


Comparative antioxidant activity of tocotrienols and other natural lipid-soluble antioxidants in a homogeneous system, and in rat and human lipoproteins.
The antioxidant activity of tocotrienols toward peroxyl radicals was compared with that of other natural lipid-soluble antioxidants in three different systems by measuring the temporal disappearance of antioxidants and the formation of lipid hydroperoxides. In homogeneous solution, the initial rates of consumption of the various antioxidants, assessed by competition experiments between pairs of antioxidants for radicals, decreased in the order: ubiquinol-10 approximately ubiquinol-9 > alpha-tocopherol approximately alpha-tocotrienol > beta-carotene approximately lycopene > gamma-tocopherol approximately gamma-tocotrienol. Following in vitro incubation of human plasma with alpha-tocotrienol, this form of vitamin E was present in all classes of lipoproteins isolated from the supplemented plasma. Dietary supplementation of rats and humans with a tocotrienol-rich preparation resulted in a dose-dependent appearance of alpha- and gamma-tocotrienols in plasma and all circulating lipoproteins, respectively. Exposure of such enriched rat plasma to aqueous peroxyl radicals resulted in simultaneous consumption of the alpha- and then gamma-isomers of vitamin E. The sequence of radical-induced consumption of antioxidants in freshly isolated, in vitro and in vivo tocotrienol-enriched low density lipoprotein (LDL) was again ubiquinol-10 > alpha-tocotrienol approximately alpha-tocopherol > carotenoids > gamma-tocopherol approximately gamma-tocotrienol. Under conditions where radicals were generated at constant rates, the rate of lipid hydroperoxide formation in LDL was not constant. It proceeded in at least three stages separated by the phase of ubiquinol-10 consumption and, subsequently, that of alpha-tocopherol/alpha-tocotrienol. Our results show that dietary tocotrienols become incorporated into circulating human lipoproteins where they react with peroxyl radicals as efficiently as the corresponding tocopherol isomers.


Mutations in the Drosophila hook gene inhibit endocytosis of the boss transmembrane ligand into multivesicular bodies.
Transmembrane ligands can be internalized across cell boundaries into receptor-expressing cells. In the developing Drosophila eye imaginal disc, the bride of sevenless transmembrane protein (boss) is expressed on the surface of R8 cells. After internalization into neighboring R7 cells, the boss protein accumulates in multivesicular bodies. In a search for genes that affect this cell-type-specific pattern of boss endocytosis, we found that mutations in the hook gene inhibit the accumulation of boss in multivesicular bodies of R7 cells. In addition, hook flies exhibit pleiotropic phenotypes including abnormal bristle morphology and eye degeneration. The wild-type-pattern of boss endocytosis was restored in hook mutants by a genomic rescue fragment containing the hook gene or by a hook cDNA expressed in R7 cells under control of a sevenless (sev) enhancer. The hook gene encodes a novel cytoplasmic protein of 679 amino acids with a central coiled-coil domain of some 200 amino acids. Truncated, epitope-tagged hook proteins coimmunoprecipitated the full-length protein, indicating dimerization mediated by the coiled-coil domain. The hook protein localizes to vesicular structures that are part of the endocytic compartment. The requirement of the hook protein in R7 cells for the accumulation of boss protein in multivesicular bodies, and the localization of the hook protein to endocytic vesicles indicate that the hook gene encodes a novel component of the endocytic compartment that plays an important role in the endocytosis of transmembrane ligands or their transport to multivesicular bodies.


The effects of lower-extremity functional electric stimulation on the orthostatic responses of people with tetraplegia.
To determine whether application of functional electric stimulation (FES) to lower-limb muscles during postural tilting improves orthostatic tolerance in people with tetraplegia. A crossover design. A rehabilitation hospital. Sixteen acute and chronic subjects with tetraplegia (15 men, 1 woman) with complete motor function loss at the C3-7 levels were recruited. Time since injury ranged from 2 to 324 months (mean, 118.9+/-104.2 mo). Subjects were tested on a progressive head-up tilting maneuver with and without the application of FES at 0 degrees , 15 degrees , 30 degrees , 45 degrees , 60 degrees , 75 degrees , and 90 degrees continuously for up to 1 hour. FES was administered to 4 muscle groups including the quadriceps, hamstrings, tibialis anterior, and gastrocnemius muscles bilaterally at an intensity that provided a strong, visible, and palpable contraction. This was to produce a muscle pumping mechanism during the tilting maneuver. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, perceived presyncope score, and the overall duration of orthostatic tolerance, that is, the time that subjects could tolerate the tilting maneuver without developing severe hypotension or other intolerance symptoms. When the tilt angle was increased, the subjects' SBP and DBP tended to decrease, whereas the heart rate tended to increase in both testing conditions. Adding FES to tilting significantly attenuated the drop in SBP by 3.7+/-1.1 mmHg (P = .005), the drop in DBP by 2.3+/-0.9 mmHg (P = .018), and the increase in heart rate by 1.0+/-0.5 beats/min (P = .039) for every 15 degrees increment in the angle of the tilt. FES increased the overall mean standing time by 14.3+/-3.9 min (P = .003). An FES-induced leg muscle contraction is an effective adjunct treatment to delay orthostatic hypotension caused by tilting; it allows people with tetraplegia to stand up more frequently and for longer durations.