Matrix Metalloproteinase 9 Point-of-Care Immunoassay Result Predicts Response to Topical Cyclosporine Treatment in Dry Eye Disease.
We evaluate a matrix metalloproteinase-9 (MMP-9) point-of-care immunoassay (InflammaDry) as a prognostic tool for topical cyclosporine treatment. A total of 20 healthy subjects and 40 patients meeting >3 dry eye disease (DED) criteria (ocular surface disease index [OSDI] score ≥ 12, tear film breakup time [TBUT] ≤10 seconds, Schirmer I test result ≤10 mm/5 minutes, corneal staining ≥1) were included. DED patients were treated with topical cyclosporine ophthalmic emulsion 0.05% twice daily for 1 month. The InflammaDry test was used to grade MMP-9 levels in the tear film. Treatment response was monitored using the OSDI score, TBUT, and Schirmer, corneal staining, and InflammaDry tests. Of the eyes, 18 (22.5%) were negative, 29 (36.3%) trace-positive, 16 (20.0%) weak-positive, 11 (13.8%) positive, and six (7.5%) strong-positive for MMP-9 at baseline. MMP-9 levels correlated with OSDI (P = 0.049), TBUT (P = 0.001), corneal staining (P = 0.002), and Schirmer test (P = 0.027) results. MMP-9-positive patients displayed decreased post-treatment MMP-9 levels (P = 0.001) and corneal staining score (P < 0.001), improved OSDI score (P < 0.001), and increased TBUT (P < 0.001) and Schirmer (P = 0.009) test values. Semiquantitative MMP-9 grading correlated well with DED symptoms and signs, and could be used to predict patient status and monitor treatment response. MMP-9-positive patients responded more favorably to topical cyclosporine than did MMP-9-negative patients. Thus, the InflammaDry test may inform decisions regarding initiating topical cyclosporine treatment. Semiquantitative MMP-9 could be used to predict patient status and monitor treatment response.


The functional anatomy of the MMN: a DCM study of the roving paradigm.
Using dynamic causal modelling (DCM), we have presented provisional evidence to suggest: (i) the mismatch negativity (MMN) is generated by self-organised interactions within a hierarchy of cortical sources [Garrido, M.I., Kilner, J.M., Kiebel, S.J., Stephan, K.E., Friston, K.J., 2007. Dynamic causal modelling of evoked potentials: a reproducibility study. NeuroImage 36, 571-580] and (ii) the MMN rests on plastic change in both extrinsic (between-source) and intrinsic (within source) connections (Garrido et al., under review). In this work we re-visit these two key issues in the context of the roving paradigm. Critically, this paradigm allows us to discount any differential response to differences in the stimuli per se, because the standards and oddballs are physically identical. We were able to confirm both the hierarchical nature of the MMN generation and the conjoint role of changes in extrinsic and intrinsic connections. These findings are consistent with a predictive coding account of repetition-suppression and the MMN, which gracefully accommodates two important mechanistic perspectives; the model-adjustment hypothesis [Winkler, I., Karmos, G., Näätänen, R., 1996. Adaptive modelling of the unattended acoustic environment reflected in the mismatch negativity event-related potential. Brain Res. 742, 239-252; Näätänen, R., Winkler, I., 1999. The concept of auditory stimulus representation in cognitive neuroscience. Psychol Bull 125, 826-859; Sussman, E., Winkler, I., 2001. Dynamic sensory updating in the auditory system. Brain Res. Cogn Brain Res. 12, 431-439] and the adaptation hypothesis [May, P., Tiitinen, H., Ilmoniemi, R.J., Nyman, G., Taylor, J.G., Näätänen, R., 1999. Frequency change detection in human auditory cortex. J. Comput. Neurosci. 6, 99-120; Jääskeläinen, I.P., Ahveninen, J., Bonmassar, G., Dale, A.M., Ilmoniemi, R.J., Levänen, S., Lin, F.H., May, P., Melcher, J., Stufflebeam, S., Tiitinen, H., Belliveau, J.W., 2004. Human posterior auditory cortex gates novel sounds to consciousness. Proc. Natl. Acad. Sci. U. S. A. 101, 6809-6814].


Exploring the solid-phase synthesis of 3,4-disubstituted beta-lactams: scope and limitations.
This work describes a comprehensive study on the solid-phase synthesis of 3,4-disubstituted beta-lactams. In situ generated ketenes react with immobilized aldimines under mild conditions to generate libraries of beta-lactams in good to very good overall isolated yields. Different commercially available solid supports were studied, with the cost-effective Wang resin proving to be the most effective. The utility of the protocol was also demonstrated by the highly efficient asymmetric versions when homochiral ketenes or homochiral aldimines were used. A practical technique for the preparation of manual solid-phase parallel libraries of biologically interesting beta-lactam compounds, using Mukaiyama's salt as dehydrating agent, is also presented. Reactions were easily monitored by FT-IR and gel-phase 13C NMR using conventional equipment.


[Extracorporeal treatments for some autoimmune eye diseases].
Fifty-three patients with eye diseases caused by autoimmune disorders received complex treatment involving extracorporeal techniques, such as hemosorption, plasmapheresis, and double cascade plasma filtration in combination with pulse therapy. Clinical, laboratory, morphometric, and biochemical studies show the efficacy of hemosorption in relieving acute manifestations of an inflammatory process and the stabilizing action of these methods on ocular epithelial tissue, immunological activity, and systemic manifestations of the underlying disease.


Role of echocardiography in the diagnosis and management of infective endocarditis.
Infective endocarditis is one of the most common causes of serious infection and carries a high risk of morbidity and mortality. It represents the fourth leading cause of life-threatening infections after urosepsis, pneumonia, and intra-abdominal sepsis. There is still a continuous rise in the incidence of infective endocarditis, with a rate of about 20,000 new cases in the United States alone. This rise in incidence of infective endocarditis is mainly caused by increasing numbers of intravenous drug abusers, patients with artificial valves and elderly patients. In this paper, we will briefly review the crucial role of echocardiography in the diagnosis and management of infective endocarditis.


Improving management of asthma: closing the loop or progressing along the audit spiral?
To assess whether the management of asthma has improved from three consecutive surveys. Retrospective case note survey of acute asthma admissions in 1983 and 1989; case notes selected from 1985-6 survey of prospectively identified patients to include only patients with a final discharge code of asthma. A large city teaching hospital. Patients--101 patients with acute asthma as the primary diagnosis in 1983; 85 in 1985-6; and 133 in 1989, 14 of whom were subsequently transferred elsewhere. Conformity with a checklist of important aspects of the process of asthma management including initial assessment, treatment, supervision, and discharge and review arrangements. All patient groups were similar in age, smoking habit, and stay in hospital and, as an objective guide to severity of asthma, had similar initial pulse rates. Major improvements occurred in management: by 1989, 119(90%) patients were treated with oral corticosteroids (69(68%), 67(79%) in 1983, 1985-6 respectively) and 109(82%) with oxygen (62(61%), 51(60%)) (both p < 0.001). 114(86%) had regular recording of peak flow measurements (53(52%), 54(64%); p < 0.001), and 103/119(86%) were discharged taking oral corticosteroids (66(65%), 63(74%); p < 0.01). Significantly fewer patients, however, had their regular inhaled corticosteroid treatment increased on discharge (38/119(32%) v 53(52%), 39(46%); p < 0.01), but more were receiving high dose inhaled treatment on admission. The management of asthma improved significantly, and the normal practice of doctors has changed in an area of practice with longstanding problems.


Pertussis and Influenza Vaccination Among Insured Pregnant Women — Wisconsin, 2013-2014.
On February 22, 2013, the Advisory Committee on Immunization Practices (ACIP) revised recommendations for vaccination of pregnant women to recommend tetanus-diphtheria-acellular pertussis vaccine (Tdap) during every pregnancy, optimally at 27-36 weeks of gestation, to prevent pertussis among their newborns. Since 2004, influenza vaccination has been recommended for pregnant women in any trimester to prevent influenza and associated complications for mother and newborn. To evaluate vaccination of pregnant women in Wisconsin after the 2013 Tdap recommendation, health insurance claims data for approximately 49% of Wisconsin births were analyzed. The percentage of women who received Tdap during pregnancy increased from 13.8% of women delivering during January 2013 (63.1% of whom received Tdap 2-13 weeks before delivery) to 51.0% of women delivering during March 2014 (90.9% of whom received Tdap 2-13 weeks before delivery). Among women delivering during November 2013-March 2014, 49.4% had received influenza vaccine during pregnancy. After the 2013 recommendation, Tdap vaccination among pregnant women increased but plateaued at rates similar to influenza vaccination rates. Prenatal care providers should implement, evaluate, and improve Tdap and influenza vaccination programs, and strongly recommend that pregnant patients receive these vaccines to prevent severe illness and complications among mothers and infants.


Distribution and environmental determinants of darkling beetles assemblages (Coleoptera: Tenebrionidae) in Península Valdés (Argentinean Patagonia).
Arid lands provide several products and services to humankind, but human activities affect this environment, increasing the extinction risk of the native species. Thus, to successfully conserve the biodiversity of these ecosystems, it is necessary to identify which environmental factors influence the spatial distribution of the organisms that offer these benefits. Darkling beetles play a relevant role on the functioning of deserts. Although these insects are among the most abundant and diverse in these environments, there is no agreement on the relative importance that different environmental factors have as determinants of their spatial distribution. In this work, we assessed the role of climate, vegetation, and soil variables as factors that determine distribution patterns of darkling beetles within the Natural Protected Area Península Valdés (Northeastern Patagonia). Five groups of environmental units were identified, each one with an exclusive tenebrionid species assemblage and different species diversity. The most influential environmental variables were temperature, precipitations, and soil texture. Results suggest that the magnitude of several ecosystem processes may vary among the groups of environmental units. We recommend prioritizing the conservation of the five groups of environmental units and incorporating the darkling beetles-environment relationship in future conservation strategies for arid Patagonia.


Analyzing the research landscape: Mapping frontiers and hot spots in anti-cancer research using bibliometric analysis and research network pharmacology.
Introduction: Network pharmacology has emerged as a forefront and hotspot in anti-cancer. Traditional anti-cancer drugs are limited by the paradigm of "one cancer, one target, one drug," making it difficult to address the challenges of recurrence and drug resistance. However, the main advantage of network pharmacology lies in its approach from the perspective of molecular network relationships, employing a "one arrow, multiple targets" strategy, which provides a novel pathway for developing anti-cancer drugs. This study employed a bibliometric analysis method to examine network pharmacology's application and research progress in cancer treatment from January 2008 to May 2023. This research will contribute to revealing its forefront and hotspots, offering new insights and methodologies for future investigations. Methods: We conducted a literature search on network pharmacology research in anti-cancer (NPART) from January 2008 to May 2023, utilizing scientific databases such as Web of Science Core Collection (WoSCC) and PubMed to retrieve relevant research articles and reviews. Additionally, we employed visualization tools such as Citespace, SCImago Graphica, and VOSviewer to perform bibliometric analysis. Results: This study encompassed 3,018 articles, with 2,210 articles from WoSCC and 808 from PubMed. Firstly, an analysis of the annual national publication trends and citation counts indicated that China and the United States are the primary contributing countries in this field. Secondly, the recent keyword analysis revealed emerging research hotspots in "tumor microenvironment," "anti-cancer drugs," and "traditional Chinese medicine (TCM). " Furthermore, the literature clustering analysis demonstrated that "calycosin," "molecular mechanism," "molecular docking," and "anti-cancer agents" were widely recognized research hotspots and forefront areas in 2023, garnering significant attention and citations in this field. Ultimately, we analyzed the application of NPART and the challenges. Conclusion: This study represents the first comprehensive analysis paper based on bibliometric methods, aiming to investigate the forefront hotspots of network pharmacology in anti-cancer research. The findings of this study will facilitate researchers in swiftly comprehending the current research trends and forefront hotspots in the domain of network pharmacology in cancer research.


Vasoactive intestinal peptide downregulates proinflammatory TLRs while upregulating anti-inflammatory TLRs in the infected cornea.
TLRs recognize microbial pathogens and trigger an immune response, but their regulation by neuropeptides, such as vasoactive intestinal peptide (VIP), during Pseudomonas aeruginosa corneal infection remains unexplored. Therefore, C57BL/6 (B6) mice were injected i.p. with VIP, and mRNA, protein, and immunostaining assays were performed. After VIP treatment, PCR array and real-time RT-PCR demonstrated that proinflammatory TLRs (conserved helix-loop-helix ubiquitous kinase, IRAK1, TLR1, TLR4, TLR6, TLR8, TLR9, and TNFR-associated factor 6) were downregulated, whereas anti-inflammatory TLRs (single Ig IL-1-related receptor [SIGIRR] and ST2) were upregulated. ELISA showed that VIP modestly downregulated phosphorylated inhibitor of NF-κB kinase subunit α but upregulated ST2 ~2-fold. SIGIRR was also upregulated, whereas TLR4 immunostaining was reduced in cornea; all confirmed the mRNA data. To determine whether VIP effects were cAMP dependent, mice were injected with small interfering RNA for type 7 adenylate cyclase (AC7), with or without VIP treatment. After silencing AC7, changes in mRNA levels of TLR1, TNFR-associated factor 6, and ST2 were seen and unchanged with addition of VIP, indicating that their regulation was cAMP dependent. In contrast, changes were seen in mRNA levels of conserved helix-loop-helix ubiquitous kinase, IRAK1, 2, TLR4, 9 and SIGIRR following AC7 silencing alone; these were modified by VIP addition, indicating their cAMP independence. In vitro studies assessed the effects of VIP on TLR regulation in macrophages and Langerhans cells. VIP downregulated mRNA expression of proinflammatory TLRs while upregulating anti-inflammatory TLRs in both cell types. Collectively, the data provide evidence that VIP downregulates proinflammatory TLRs and upregulates anti-inflammatory TLRs and that this regulation is both cAMP dependent and independent and involves immune cell types found in the infected cornea.


Mouse ovarian granulosa cells produce urokinase-type plasminogen activator, whereas the corresponding rat cells produce tissue-type plasminogen activator.
It is well established that rat ovarian granulosa cells produce tissue plasminogen activator (tPA). The synthesis and secretion of the enzyme are induced by gonadotropins, and correlate well with the time of follicular rupture in vivo. We have found that in contrast, mouse granulosa cells produce a different form of plasminogen activator, the urokinase-type (uPA). As with tPA synthesis in the rat, uPA production by mouse granulosa cells is induced by gonadotropins, dibutyryl cAMP, and prostaglandin E2. However, dexamethasone, a drug which has no effect on tPA synthesis in rat cells inhibits uPA synthesis in the mouse. Results of these determinations made in cell culture were corroborated by examining follicular fluid, which is secreted in vivo predominantly by granulosa cells, from stimulated rat and mouse ovarian follicles. Rat follicular fluid contained only tPA, and mouse follicular fluid only uPA, indicating that in vivo, granulosa cells from the two species are secreting different enzymes. The difference in the type of plasminogen activator produced by the rat and mouse granulosa cells was confirmed at the messenger RNA level. After hormone stimulation, only tPA mRNA was present in rat cells, whereas only uPA mRNA was found in mouse cells. Furthermore, the regulation of uPA levels in mouse cells occurs via transient modulation of steady-state levels of mRNA, a pattern similar to that seen with tPA in rat cells.


Evaluation of the spatial and temporal distribution of and risk factors for Bluetongue serotype 1 epidemics in sheep Extremadura (Spain), 2007-2011.
Extremadura has been one of the regions in Spain most severely affected by Bluetongue (BT) epidemics. The first incursion of BTV, which was successfully eradicated one year later, occurred in 2004, involving the BTV-serotype 4. However, a second incursion occurred in September 2007, this time involving serotype 1. Since then, the implementation of intensive vaccination programs have significantly reduced BTV-1 occurrence, but the disease has not been completely eradicated yet. This study aimed to provide, for the first time, a complete description of the spatial and temporal patterns of BTV-1 occurrence in sheep in Extremadura from 2007 to 2011 and to identify the risk factors that contributed to the seasonal occurrence of BTV-1 in this region. The results showed that risk factors contributing to BTV-1 occurrence in sheep changed between 2007 and 2011. Initially, when the population was still immunologically naïve, the main risk factors for BTV-1 occurrence were extensive management practices, large sheep farms and Culicoides abundance on farms. However, after the implementation of vaccination, other factors became more relevant for BTV-1 occurrence, mostly related to BTV reservoirs, such as the proximity of cattle farms or the introduction of cattle into farms. The Talaverana sheep breed also seemed to be associated with a significantly higher risk of BTV-1 occurrence, although it may be due to confounding factors, such as the geographical concentration of where this breed is kept and/or management practises used for this breed. The results of this study suggest that preventive and control strategies, including vaccination and active surveillance strategies, should be primarily focused on cattle farms kept in close vicinity to sheep flocks as well as in high-risk sheep farms (i.e. farms with a large farm size keeping both cattle and sheep and with a high number of animal introductions). Methods and results presented here may be used to guide decisions for the annual update of the control and eradication program in Spain.


Polyunsaturated fatty acids potentiate cytotoxicity of cisplatin in A549 cells.
In normal and tumor cells, polyunsaturated fatty acids (PUFAs) act as intracellular second messengers, which play a role in signaling, proliferation and cell death. PUFAs have selective tumoricidal action and may alter sensitivity of tumor cells to cisplatin (CDDP), a commonly used anticancer agent. The aim of this study was to evaluate the influence of arachidonic acid (AA, 20:4 n-6), eicosapentaenoic acid (EPA, 20:5 n-3), docosahexaenoic acid (DHA, 22:6 n-3) and CDDP on autophagy and apoptosis in A549 human lung adenocarcinoma cells. Viability of A549 cells treated with CDDP and PUFAs was measured using the XTT tetrazolium salt based assay. Caspase-3/7 activity was estimated using ApoTox-Glo kit (Promega). Autophagic vac- uoles were detected by Cyto-ID Autophagy Detection Kit (Enzo). The results were compared to control cultures maintained in the absence of CDDP and PUFAs. PUFAs, in particular EPA and DHA, added to the cultivation medium, increased the antitumor activity of CDDP in A549 cells in a concentration dependent manner. In case of AA this effect was observed at the highest of the concentrations tested only (100 μM). Both, EPA and DHA, but not AA, significantly increased the amount of autophagic vacuoles and induced caspase-3/7 activity. The obtained results suggest that the antiproliferative effect of CDDP in A549 cells can be enhanced by AA and in particular by EPA and DHA through their influence on autophagic and apoptotic cell death. It is likely that BPA and DHA incorporated to the tumor cells may improve outcomes in lung cancer patients.


Dietary ω-6/ω-3 Polyunsaturated Fatty Acid Ratios Affect the Homeostasis of Th/Treg Cells in Mice With Dextran Sulfate Sodium-Induced Colitis.
This study evaluated the effect of different dietary ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratios on modulating helper T (Th) and regulatory T (Treg) lymphocytes in mice with dextran sulfate sodium (DSS)-induced colitis. There were 3 control and 3 colitis groups. Mice were fed for 24 days with diets with soybean oil (S), a mixture of soybean oil and low fish oil content (LF), or high fish oil content (HF). The ratio of ω-6/ω-3 PUFA in the LF diet was 4:1, and that in the HF diet was 2:1. The control groups drank distilled water while colitis groups were provided 2% DSS in drinking water during days 15-19. All mice drank distilled water from days 20-24 for recovery and were sacrificed on day 25. Colitis resulted in higher blood Th1, Th2, and Th17 and lower Treg percentages. Also, plasma haptoglobin and proinflammatory chemokines were elevated in colon lavage fluid. Colitic groups with fish oil had lower inflammatory mediators in the plasma and colon lavage fluid. Furthermore, the percentages of blood Th1, Th2, and Th17 cells were lower, whereas Treg cell percentages were higher than those in the soybean oil group. The colitis group with an ω-6/ω-3 PUFA ratio of 2:1 had more pronounced effects than the group with a ratio of 4:1. Diets with an ω-6/ω-3 PUFA ratio of 2:1 or 4:1 regulate the Th/Treg balance and attenuate inflammatory mediator production in colitis. Compared with the ω-6/ω-3 PUFA ratio of 4:1, the ratio of 2:1 was more effective in reducing inflammatory reactions in DSS-induced colitis.


Modeling a microbial community and biodiversity assay with OBO Foundry ontologies: the interoperability gains of a modular approach.
The advent of affordable sequencing technology provides for a new generation of explorers who probe the world's microbial diversity. Projects such as Tara Oceans, Moorea Biocode Project and Gut Microbiome rely on sequencing technologies to probe community diversity. Either targeted gene surveys (also known as community surveys) or complete metagenomes are evaluated. The former, being the less costly of the two methods, relies on the identification of specific genomic regions, which can be used as a proxy to estimate genetic distance between related species in a Phylum. For instance, 16 S ribosomal RNA gene surveys are used to probe bacterial communities while internal transcribed spacer surveys, for example, can be used for probing fungal communities. With the explosion of projects and frenzy to explore new domains of life, scientists in the field have issued guidelines to report minimal information (following a checklist), ensuring that information is contextualized in a meaningful way. Yet the semantics of a checklist are not explicit. We demonstrate here how a tabular template can be used to collect information on microbial diversity using an explicit representation in the Resource Description Framework that is consistent with community agreed-upon knowledge representation patterns found in the Ontology for Biomedical Investigations.


Influence of selected cyclodextrins in sorption-desorption of chlorpyrifos, chlorothalonil, diazinon, and their main degradation products on different soils.
Cyclodextrins (CDs) can improve the apparent solubility and bioavailability of a variety of organic compounds through the formation of inclusion complexes; accordingly, they are suitable for application in innovative remediation technologies of contaminated soils. However, the different interactions in the tertiary system CD/contaminant/soil matrix can affect the bioavailability of the inclusion complex through the possible sorption of CD and CD complex in the soil matrix, as well as with the potential of the sorbed CD to form the complex, concurrent with the desorption processes. This work focuses in changes produced by three different CDs in soil sorption-desorption processes of chlorpyrifos (CPF), diazinon (DZN), and chlorothalonil (CTL), and their major degradation products, 3,5,6-trichloro-2-pyridinol (TCP), 2-isopropyl-6-methyl-4-pyrimidinol, and hydroxy-chlorothalonil (OH-CTL). Cyclodextrins used were β-cyclodextrin (β-CD), methyl-β-cyclodextrin (Mβ-CD), and 2-hydroxypropyl-β-cyclodextrin (HPβ-CD). The studied soils belong to the orders Andisol, Ultisol, and Mollisol with different organic matter contents, mineral composition, and pH. The apparent sorption constants were significantly lower for the three pesticides in the presence of all CDs. The highest displacement of sorption equilibria was produced by the influence of Mβ-CD, with the most pronounced effect for CPF, a pesticide strongly sorbed on soils. The same was obtained for TCP and OH-CTL, highlighting the need to assess the risk of generating higher levels of groundwater contamination with polar metabolites if degradation rates are not controlled. The highest desorption efficiency was obtained for the systems CPF-β-CD, DZN-Mβ-CD, and CTL-Mβ-CD. Since the degree of adsorption of the complex is relevant to obtain an increase in the bioavailability of the contaminant, a distribution coefficient for the complexed pesticide in all CD-soil-pesticide system was estimated by using the apparent sorption coefficients, the stability constant for each CD-pesticide complex, and the distribution coefficients of free pesticide.


Patient Profiles in Dutch Forensic Psychiatry Based on Risk Factors, Pathology, and Offense.
Forensic psychiatry embodies a highly heterogeneous population differing widely in terms of diagnoses, crimes committed, and risk factors. All of these are vitally important for treatment indications and should be accounted for in research. However, there is limited empirical knowledge of patient profiles. This study constructed patient profiles on the basis of the three domains mentioned above. Participants were found guilty of having committed crimes due to psychiatric disorders and were admitted to Forensic Psychiatric Center (FPC) 2landen or FPC De Kijvelanden in the Netherlands. Retrospective data were retrieved from patient files. Diagnoses were assessed according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria and risk factors according to the Historical Clinical Future-30 (HKT-30) instrument. Latent class analysis was conducted to define typologies; external variables were included for validation. Four different classes or "patient risk profiles," with varying psychopathologies, risk factors, and crimes, were identified. Results were consistent with previous studies, and external validation with the Psychopathy Checklist-Revised (PCL-R) two-factor model and the four facets of the PCL-R agreed with results found. Results display specific risk factors for specific psychopathology/offense combinations.


Detection of human papillomavirus infection in oral squamous cell carcinoma: a cohort study of Japanese patients.
Recent evidence suggests that human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is a separate HNSCC subgroup with distinct epidemiology, histopathological characteristics, therapeutic response to chemotherapy and radiation, and clinical outcome. This study aimed to investigate the role of HPV infection in oral squamous cell carcinoma (OSCC) and the correlation between HPV infection, tumor suppressor protein p16 expression, and clinicopathological features in Japanese patients. In total, 174 OSCC specimens were examined for p16 levels by immunohistochemistry, and p16-positive OSCCs were analyzed for HPV DNA by in situ hybridization (ISH) and HPV genotypes by real-time PCR. The results were evaluated for the association with clinicopathological characteristics of OSCC patients. Twenty-four OSCC samples were found positive for p16 expression; all of them were well-differentiated tumors. P16 immunoreactivity was significantly associated with the invasion depth and tended to correlate with sex, site in the oral cavity, stromal reaction, TNM stage, and survival. HPV DNA was detected in 13 of 24 (54%) p16-positive OSCC by real-time PCR; HPV 16, 18, and other high-risk genotypes were the most prevalent. However, ISH failed to detect HPV DNA in p16-positive OSCCs. P16 immunoreactivity and HPV genotyping by real-time PCR may be useful markers of HPV infection in OSCC. However, although HPV-related OSCC showed good outcomes, HPV infection may have a minor role in oral oncogenesis in Japanese patients.


Antibiotics for trachoma.
Trachoma is the world's leading cause of preventable blindness. In 1997 the World Health Organization launched an initiative on trachoma control based on the 'SAFE' strategy (surgery, antibiotics, facial cleanliness and environmental improvement). To assess the evidence supporting the antibiotic arm of the SAFE strategy by assessing the effects of antibiotics on both active trachoma (primary objective) and on Chlamydia trachomatis infection of the conjunctiva (secondary objective). We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to February 2005), and EMBASE (1980 to February 2005). We used the Science Citation Index to look for articles that cited the included studies. We searched the reference lists of identified articles and we contacted authors and experts for details of further relevant studies. We included only randomised trials that satisfied either of two criteria: (a) trials in which topical or oral administration of an antibiotic was compared to placebo or no treatment in people with trachoma, (b) trials in which a topical antibiotic was compared with an oral antibiotic in people with trachoma. A subdivision of particular interest was of trials in which topical tetracycline/chlortetracycline was compared with oral azithromycin, as these are the two World Health Organization recommended treatments. Two authors independently assessed trial quality and extracted data. We contacted investigators for missing data. We found 15 studies that randomised a total of 8678 participants. For both outcomes (active trachoma and laboratory evidence of infection) the results of the chi squared tests suggested that there was significant statistical heterogeneity among the trials. There was also marked clinical heterogeneity. No summary statistics were calculated and we therefore present a narrative summary of the results. For the comparisons of oral or topical antibiotic against placebo/no treatment, the data are consistent with there being no effect of antibiotics but are suggestive of a lowering of the point prevalence of relative risk of both active disease and laboratory evidence of infection at three and 12 months after treatment. For the comparison of oral against topical antibiotics the results suggest that oral treatment is neither more nor less effective than topical treatment. There is some evidence that antibiotics reduce active trachoma but results are not consistent and cannot be pooled.


[Relationship between status of physical and mental function and quality of life among the elderly people admitted from long-term care insurance].
This study was performed to determine the levels of quality of life (QOL) according to the grade of long-term care service for the elderly people who were admitted from long-term care insurance, and to reveal its association with the physical and mental functioning such as the Activity of Daily Living (ADL), the Instrumental Activity of Daily Living (IADL), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Mini-Mental State Examination-Korean version (MMSE-K). The interviews were performed during the period from March 1 to May 31, 2009, for 958 elderly people in urban and rural areas. The questionnaire items included various indices such as the ADL, IADL, CES-D, and MMSE-K, as independent variables and the index of QOL, as the dependent ones. For statistical analysis, t-tests were used for the mean scores of QOL according to gender and the grade of long-term care services, and Spearman's correlation was used for each variable. The effects of physical and mental functioning for QOL were assessed by covariance structure analysis. The statistical significance was set at p<0.05. The mean scores of QOL among all the subjects was 55.4 ± 15.62 (Grade I: 49.7 ± 14.17, Grade II: 56.8 ± 14.62, Grade III: 59.4 ± 16.36), and it was lower according to the higher grade of long-term care insurance. In terms of the correlation matrix of the QOL and the physical and mental function factors, the QOL showed positive correlation with the ADL, IADL and MMSE-K, while it had negative correlation with depression. On the analysis of covariance, mental functioning (depression and the MMSE-K) had a greater influence on the level of QOL than the physical functioning (ADL and IADL). The level of the QOL in the elderly people who were admitted from long-term care insurance was lower according to higher the grade of long-term care insurance. Also, the mental functioning (depression and MMSE-K) was more influential on the level of the QOL than the physical functioning (ADL and IADL).


Adhesion of Staphylococcus epidermidis and Staphylococcus saprophyticus to a hydrophobic biomaterial.
The relative surface charge and hydrophobicity of 16 strains of Staphylococcus epidermidis showed large variations. For this species no relationship between the two surface parameters was found. A highly negative surface charge was observed in all seven encapsulated strains (one S. epidermidis and six Staphylococcus saprophyticus strains). The adhesion of the staphylococci to fluorinated polyethylene-propylene films was not related to the relative surface charge and the hydrophobicity of the bacteria. On films pre-exposed to human plasma, the bacterial adhesion was substantially reduced. Mechanisms involved in the adhesion of coagulase-negative staphylococci to this biomaterial are discussed.


Cellular, ultrastructural and molecular analyses of epidermal cell development in the planarian Schmidtea mediterranea.
The epidermis is essential for animal survival, providing both a protective barrier and cellular sensor to external environments. The generally conserved embryonic origin of the epidermis, but the broad morphological and functional diversity of this organ across animals is puzzling. We define the transcriptional regulators underlying epidermal lineage differentiation in the planarian Schmidtea mediterranea, an invertebrate organism that, unlike fruitflies and nematodes, continuously replaces its epidermal cells. We find that Smed-p53, Sox and Pax transcription factors are essential regulators of epidermal homeostasis, and act cooperatively to regulate genes associated with early epidermal precursor cell differentiation, including a tandemly arrayed novel gene family (prog) of secreted proteins. Additionally, we report on the discovery of distinct and previously undescribed secreted organelles whose production is dependent on the transcriptional activity of soxP-3, and which we term Hyman vesicles.


Nonelectrical poling in ferroelectric polythioureas.
A new poling method utilizing the cooperativity and strong hydrogen bonding force of thiourea groups is proposed in ferroelectric polythioureas [poly(octamethylene thiourea) and poly(nonamethyleno thiourea)]. The method, which is named "surface energy poling," takes advantage of the surface energy difference of the polar amorphous material to form remanent polarization. A polythiourea film sandwiched between a metal with higher surface energy and polytetrafluoroethylenes with lower surface energy was heated up to T/sub c/ [1.15/spl times/T/sub g/ (glass transition temperature)] and cooled slowly to room temperature. The resulting film showed a pyroelectric constant of 10 /spl mu//m/sup 2/K, giving evidence of remanent polarization. This method is similar to the orientation process in liquid crystal devices.


Characterization of Pseudomonas aeruginosa enoyl-acyl carrier protein reductase (FabI): a target for the antimicrobial triclosan and its role in acylated homoserine lactone synthesis.
The Pseudomonas aeruginosa fabI structural gene, encoding enoyl-acyl carrier protein (ACP) reductase, was cloned and sequenced. Nucleotide sequence analysis revealed that fabI is probably the last gene in a transcriptional unit that includes a gene encoding an ATP-binding protein of an ABC transporter of unknown function. The FabI protein was similar in size and primary sequence to other bacterial enoyl-ACP reductases, and it contained signature motifs for the FAD-dependent pyridine nucleotide reductase and glucose/ribitol dehydrogenase families, respectively. The chromosomal fabI gene was disrupted, and the resulting mutant was viable but possessed only 62% of the total enoyl-ACP reductase activity found in wild-type cell extracts. The fabI-encoded enoyl-ACP reductase activity was NADH dependent and inhibited by triclosan; the residual activity in the fabI mutant was also NADH dependent but not inhibited by triclosan. An polyhistidine-tagged FabI protein was purified and characterized. Purified FabI (i) could use NADH but not NADPH as a cofactor; (ii) used both crotonyl-coenzyme A and crotonyl-ACP as substrates, although it was sixfold more active with crotonyl-ACP; and (iii) was efficiently inhibited by low concentrations of triclosan. A FabI Gly95-to-Val active-site amino acid substitution was generated by site-directed mutagenesis, and the mutant protein was purified. The mutant FabI protein retained normal enoyl-ACP reductase activity but was highly triclosan resistant. When coupled to FabI, purified P. aeruginosa N-butyryl-L-homoserine lactone (C4-HSL) synthase, RhlI, could synthesize C4-HSL from crotonyl-ACP and S-adenosylmethionine. This reaction was NADH dependent and inhibited by triclosan. The levels of C4-HSL and N-(3-oxo)-dodecanoyl-L-homoserine lactones were reduced 50% in a fabI mutant, corroborating the role of FabI in acylated homoserine lactone synthesis in vivo.


A MORTALITY STUDY OF PRIMARY TUMOURS OF BONE IN CANADA.
A five-year study was undertaken to determine the incidence of primary bone cancer in Canada in order to assess the effects of subsequent increases in background radiation, should such occur. Eight hundred and twenty-seven cases were investigated, and the annual incidence rate was estimated to be 6.3 per million population. Osteosarcoma was the most common type of tumour, accounting for more than half of all confirmed cases. Over 60% of the tumours occurred in males.


The secretion of tropoelastin by chick-embryo artery cells.
Chymotryptic fingerprint analyses of tropoelastin a and tropoelastin b demonstrated a very close relationship between these two polypeptides synthesized in a cell-free system under the direction of chick-embryo polyribosomal mRNA. A similar study on tropoelastin polypeptides extracted in their hydroxylated and under-hydroxylated forms from artery cells incubated with [3H]valine in the absence and presence of alpha alpha'-bipyridine or 3,4-dehydroproline confirmed this close relationship and suggested that tropoelastins a and b are likely to be the products of a single gene. Pulse-chase experiments in which the synthesis and secretion of tropoelastin by artery cells were monitored demonstrated that, after a pulse with [3H]proline, the polypeptides rapidly appeared in the medium and the half-time of tropoelastin secretion was approx. 30 min. Further pulse-chase studies, in which [3H]tropoelastin contents of subcellular fractions were determined, showed that rough and smooth microsomal fractions contained maximal amounts of tropoelastin at different times. The quantity of tropoelastin in the smooth-microsomal fraction was always only a small proportion of that in the rough-microsomal fraction, suggesting rapid translocation of the polypeptides to the plasma membrane. Incubation of the cells with 0.1 mM-colchicine did not markedly alter the rate of secretion or the distribution of tropoelastin between the subcellular fractions, whereas when 1 microM-monensin was included in the incubations the polypeptides were retained in the rough microsomal fraction. The results are consistent with the proposal that tropoelastin may follow a pathway of secretion from rough endoplasmic reticulum to the plasma membrane via secretory vesicles.


Angiotensin antagonism in patients with heart failure: ACE inhibitors, angiotensin receptor antagonists or both?
Chronic heart failure (CHF) is a major cause of morbidity and mortality in western society. It is now widely accepted that the renin-angiotensin-aldosterone system (RAAS) and, in particular, angiotensin II (A-II) play a key role in the pathophysiology of CHF. Large-scale clinical trials have demonstrated that inhibitors of angiotensin-converting enzyme (ACE), the principal enzyme responsible for A-II production, improve symptoms and survival in patients with CHF. This enzyme is also responsible for the breakdown of the vasodilator hormone bradykinin. Administration of ACE inhibitors is associated with increased plasma bradykinin levels and this is thought to contribute to the vascular changes associated with ACE inhibitor therapy. However, RAAS inhibition with ACE inhibitors remains incomplete because ACE inhibitors do not block the non-ACE-mediated conversion of angiotensin I to A-II. Angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) antagonize the action of A-II at the A-II type 1 (AT(1)) receptor, whilst allowing the potentially beneficial actions of A-II mediated via the A-II type 2 (AT(2)) receptor. Evidence that the clinical benefit demonstrated with ACE inhibitors in patients with CHF may extend to ARBs has only emerged recently. Combination therapy with both an ACE inhibitor and an ARB has a number of potential advantages and has been investigated in several large-scale clinical trials recently. In patients with CHF, first-line therapy should include an ACE inhibitor and a beta-adrenoceptor antagonist. The addition of an ARB provides symptomatic relief but has not been shown to improve survival. Where an ACE inhibitor is not tolerated, treatment with an ARB would seem an appropriate alternative. There is insufficient data to support the routine use of ARBs as first-line therapy in the management of CHF.


Immunodissection and culture of rabbit cortical collecting tubule cells.
A mouse monoclonal antibody designated IgG3(rct-30) has been prepared that reacts specifically with an antigen on the surface of all cells comprising the cortical and medullary rabbit renal collecting tubule including the arcades. Plastic culture dishes coated with IgG3(rct-30) were used to isolate collecting tubule cells from collagenase dispersions of rabbit renal cortical cells by immunoadsorption. Typically, 10(6) rabbit cortical collecting tubule (RCCT) cells were obtained from 5 g of renal cortex (2 kidneys). Initial purity was greater than 96% based on immunocytofluorescent staining with three different anti-collecting tubule antibodies. Between 20 and 30% of the RCCT cells were reactive with peanut lectin suggesting that RCCT cells are a mixture of principal and intercalated cells. Approximately 10(7) RCCT cells were obtained after 4 to 5 days in primary culture. Moreover, RCCT cells continued to proliferate after passaging with a doubling time of approximately 32 h. RCCT cells passaged once and then cultured 4-5 days were found 1) to synthesize cAMP in response to arginine vasopressin (AVP), prostaglandin E2 (PGE2), isoproterenol, and parathyroid hormone, but not calcitonin, prostaglandin D2, or prostaglandin I, and 2) to release PGE2 in response to bradykinin but not arginine vasopressin or isoproterenol. Our results indicate that cultured RCCT cells retain many of the hormonal, histochemical, and morphological properties expected for a mixture of principal and intercalated rabbit cortical collecting tubule epithelia. RCCT cells should prove useful both for studying hormonal interactions in the cortical collecting tubule and as a starting population for isolating intercalated collecting tubule epithelia.


A treatment for dysprosody in childhood apraxia of speech.
Dysprosody is considered a core feature of childhood apraxia of speech (CAS), especially impaired production of lexical stress. Few studies have tested the effects of intervention for dysprosody. This Phase II study with 3 children investigated the efficacy of a treatment targeting improved control of relative syllable durations in 3-syllable nonwords representing strong-weak (SW) and weak-strong (WS) stress patterns (e.g., BAtigu or baTIgu). Treatment sessions were structured along the principles of motor learning (PML) approach. Three children, age 7 to 10 years, with mild to moderate CAS and normal language development participated in an intensive 3-week treatment. Within-participant designs with multiple baselines across participants and behaviors were used to examine acquisition, generalization, and maintenance of skill. All children improved in their ability to control relative duration of syllables in SW and WS nonwords. Improvement was also noted in control of loudness and pitch contrasts. Treatment effects generalized to untreated nonword stimuli, but minimal change was seen in production of real words. Findings support the efficacy of this approach for improving production of lexical stress contrasts. Structuring the intervention according to the PML approach likely stimulated strong maintenance and generalization effects.


Fitting E(max) models to clinical trial dose-response data.
We consider fitting Emax models to the primary endpoint for a parallel group dose–response clinical trial. Such models can be difficult to fit using Maximum Likelihood if the data give little information about the maximum possible response. Consequently, we consider alternative models that can be derived as limiting cases, which can usually be fitted. Furthermore we propose two model selection procedures for choosing between the different models. These model selection procedures are compared with two model selection procedures which have previously been used. In a simulation study we find that the model selection procedure that performs best depends on the underlying true situation. One of the new model selection procedures gives what may be regarded as the most robust of the procedures.


[Postcoital test--a useful aid for the family physician].
Gynaecologists still debate the usefulness of the postcoital test. However, in general practice the duration of infertility may be shorter than in infertility outpatient clinic patients. In a primary care subfertility population (mean duration of infertility 20.7 months) it was shown that an abnormal postcoital test is associated with triple reduction in live birth prognosis. The guideline 'Subfertility' of the Dutch College of General Practitioners recommends primary investigations by the general practitioners to start when spontaneous pregnancy has not occurred after one year. Postcoital testing by the general practitioner appears to be useful.


Phagocytes transmit Chlamydia pneumoniae from the lungs to the vasculature.
Chlamydia pneumoniae, a major cause of community-acquired pneumonia, primarily infects the respiratory tract. Chronic infection of nonrespiratory sites, such as the vascular wall, the brain or blood monocytes, requires evasion from the lungs and spreading via the bloodstream. The cell types involved in dissemination are insufficiently characterised. In this study, New Zealand White rabbits were infected intratracheally with C. pneumoniae, and lung manifestation and systemic dissemination were monitored by polymerase chain reaction and immunohistochemistry. Infection of the lungs was characterised by an early phase dominated by granulocytes and a late phase dominated by alveolar macrophages (AM). Granulocytes, AM and alveolar epithelial cells acted as host cells for chlamydiae, which remained detectable for up to 8 weeks. AM transported the pathogen to the peribronchiolar lymphatic tissue, and subsequently C. pneumoniae entered the spleen and the aorta via dissemination by peripheral blood monocytes. In conclusion, Chlamydia pneumoniae-infected alveolar macrophages transmigrate through the mucosal barrier, and give the pathogen access to the lymphatic system and the systemic circulation. Infected peripheral blood monocytes are the vector system within the bloodstream and transmit the infection to the vascular wall. This is the first description of granulocytes acting as a reservoir for Chlamydia pneumoniae early in infection.


The 2,2-Dimethyl-2-(ortho-nitrophenyl)acetyl (DMNPA) Group: A Novel Protecting Group in Carbohydrate Chemistry.
The 2,2-dimethyl-2-(ortho-nitrophenyl)acetyl (DMNPA) group was introduced to synthetic carbohydrate chemistry as a protecting group (PG) for the first time. Benefiting from a unique chemical structure and novel deprotection conditions, the DMNPA group can be cleaved rapidly and mutually orthogonal to other PGs. Orchestrated application of the DMNPA group with other PGs led to the highly efficient synthesis of the glycan of thornasterside A.


Scientists' views about attribution of global warming.
Results are presented from a survey held among 1868 scientists studying various aspects of climate change, including physical climate, climate impacts, and mitigation. The survey was unique in its size, broadness and level of detail. Consistent with other research, we found that, as the level of expertise in climate science grew, so too did the level of agreement on anthropogenic causation. 90% of respondents with more than 10 climate-related peer-reviewed publications (about half of all respondents), explicitly agreed with anthropogenic greenhouse gases (GHGs) being the dominant driver of recent global warming. The respondents' quantitative estimate of the GHG contribution appeared to strongly depend on their judgment or knowledge of the cooling effect of aerosols. The phrasing of the IPCC attribution statement in its fourth assessment report (AR4)-providing a lower limit for the isolated GHG contribution-may have led to an underestimation of the GHG influence on recent warming. The phrasing was improved in AR5. We also report on the respondents' views on other factors contributing to global warming; of these Land Use and Land Cover Change (LULCC) was considered the most important. Respondents who characterized human influence on climate as insignificant, reported having had the most frequent media coverage regarding their views on climate change.


Associative memory advantage in grapheme-color synesthetes compared to older, but not young adults.
People with grapheme-color synesthesia perceive enriched experiences of colors in response to graphemes (letters, digits). In this study, we examined whether these synesthetes show a generic associative memory advantage for stimuli that do not elicit a synesthetic color. We used a novel between group design (14 young synesthetes, 14 young, and 14 older adults) with a self-paced visual associative learning paradigm and subsequent retrieval (immediate and delayed). Non-synesthesia inducing, achromatic fractal pair-associates were manipulated in visual similarity (high and low) and corresponded to high and low memory load conditions. The main finding was a learning and retrieval advantage of synesthetes relative to older, but not to younger, adults. Furthermore, the significance testing was supported with effect size measures and power calculations. Differences between synesthetes and older adults were found during dissimilar pair (high memory load) learning and retrieval at immediate and delayed stages. Moreover, we found a medium size difference between synesthetes and young adults for similar pair (low memory load) learning. Differences between young and older adults were also observed during associative learning and retrieval, but were of medium effect size coupled with low power. The results show a subtle associative memory advantage in synesthetes for non-synesthesia inducing stimuli, which can be detected against older adults. They also indicate that perceptual mechanisms (enhanced in synesthesia, declining as part of the aging process) can translate into a generic associative memory advantage, and may contribute to associative deficits accompanying healthy aging.


Dynamic image data compression in spatial and temporal domains: theory and algorithm.
Advanced medical imaging requires storage of large quantities of digitized clinical data. These data must be stored in such a way that their retrieval does not impair the clinician's ability to make a diagnosis. In this paper, we propose the theory and algorithm for near (or diagnostically) lossless dynamic image data compression. Taking advantage of domain-specific knowledge related to medical imaging, the medical practice and the dynamic imaging modality, a compression ratio greater than 80:1 is achieved. The high compression ratios are achieved by the proposed compression algorithm through three stages: 1) addressing temporal redundancies in the data through application of image optimal sampling, 2) addressing spatial redundancies in the data through cluster analysis, and 3) efficient coding of image data using standard still-image compression techniques. To illustrate the practicality of the proposed compression algorithm, a simulated positron emission tomography (PET) study using the fluoro-deoxy-glucose (FDG) tracer is presented. Realistic dynamic image data are generated by "virtual scanning" of a simulated brain phantom as a real PET scanner. These data are processed using the conventional [8] and proposed algorithms as well as the techniques for storage and analysis. The resulting parametric images obtained from the conventional and proposed approaches are subsequently compared to evaluate the proposed compression algorithm. As a result of this study, storage space for dynamic image data is able to be reduced by more than 95%, without loss in diagnostic quality. Therefore, the proposed theory and algorithm are expected to be very useful in medical image database management and telecommunication.


A long-term study of policosanol in the treatment of intermittent claudication.
Policosanol is a cholesterol-lowering drug with concomitant antiplatelet effects. This study was undertaken to investigate the long-term effects of policosanol administered to patients with moderately severe intermittent claudication. The study consisted of a 6-week single-blind, placebo-controlled run in phase, followed by a 2-year double-blind, randomized treatment step. Fifty-six patients who met study entry criteria were randomized to receive placebo or policosanol 10 mg twice daily. Walking distances on a treadmill (constant speed 3.2 km/h, slope 10 degrees, temperature 25 degrees C) were assessed before and after 6, 12, 18, and 24 months of treatment. Both groups were similar at randomization. After 6 months of therapy, policosanol significantly increased (p < 0.01) the initial claudication distance from 125.9 +/- 8.7 m to 201.1 +/- 24.8 m and the absolute claudication distance from 219.5 +/- 14.1 m to 380.7 +/- 50.2 m. Both variables remained unchanged in the placebo group (p < 0.01). These effects did not wear off but improved after long-term therapy, so that final values were 333.5 +/- 28.6 m (initial claudication distance) and 648.9 +/- 54.1 m (absolute claudication distance); both significantly greater (p < 0.0001) than those obtained in the placebo group, which showed values of 137.9 +/- 21.8 m (initial claudication distance) and 237.7 +/- 28.1 m (absolute claudication distance), respectively. At study completion, 21 policosanol and 5 placebo patients attained increases in claudication distance values > 50% (p < 0.001). Policosanol, but not placebo, significantly increased the ankle/arm pressure index. In addition, from month 6 up to study completion, the frequency of patients reporting improvement of lower limb symptoms was greater in the policosanol group than in the placebo group. The treatment was tolerated well. There were 16 withdrawals (12 placebo, 4 policosanol) from the study. Eight patients in the placebo group experienced a total of 10 serious adverse events, 8 of which were vascular events, compared with none in the policosanol group (p < 0.01). In addition, 3 patients in the policosanol group and 3 patients in the placebo group reported mild adverse events during the study. The present results demonstrate the long-term usefulness of policosanol therapy to treat patients with intermittent claudication.


Electrocatalytic hydrogenation and deoxygenation of glucose on solid metal electrodes.
This Full Paper addresses the electrocatalytic hydrogenation of glucose to sorbitol or 2-deoxysorbitol on solid metal electrodes in neutral media. Combining voltammetry and online product analysis with high-performance liquid chromatography (HPLC), provides both qualitative and quantitative information regarding the reaction products as a function of potential. Three groups of catalysts clearly show affinities toward: (1) hydrogen formation [on early transition metals (Ti, V, Cr, Mn, Zr, Nb, Mo, Hf, Ta, We, and Re) and platinum group metals (Ru, Rh, Ir, and Pt)], (2) sorbitol formation [on late transition metals (Fe, Co, Ni, Cu, Pd, Au, and Ag) and Al (sp metal)], and (3) sorbitol and 2-deoxysorbitol formation [on post-transition metals (In, Sn, Sb, Pb, and Bi), as well as Zn and Cd (d metals)]. Ni shows the lowest overpotential for the onset of sorbitol formation (-0.25 V) whereas Pb generates sorbitol with the highest yield (<0.7 mM cm(-2) ). Different from a smooth Pt electrode, a large-surface-area Pt/C electrode hydrogenates glucose to sorbitol from -0.21 V with relatively low current. This emphasizes the importance of the active sites and the surface area of the catalyst. The mechanism to form 2-deoxysorbitol from glucose and/or fructose is discussed according to the observed reaction products. The yield and selectivity of hydrogenated products are highly sensitive to the chemical nature and state of the catalyst surface.


Can Community Health Workers Report Accurately on Births and Deaths? Results of Field Assessments in Ethiopia, Malawi and Mali.
Most low-income countries lack complete and accurate vital registration systems. As a result, measures of under-five mortality rates rely mostly on household surveys. In collaboration with partners in Ethiopia, Ghana, Malawi, and Mali, we assessed the completeness and accuracy of reporting of births and deaths by community-based health workers, and the accuracy of annualized under-five mortality rate estimates derived from these data. Here we report on results from Ethiopia, Malawi and Mali. In all three countries, community health workers (CHWs) were trained, equipped and supported to report pregnancies, births and deaths within defined geographic areas over a period of at least fifteen months. In-country institutions collected these data every month. At each study site, we administered a full birth history (FBH) or full pregnancy history (FPH), to women of reproductive age via a census of households in Mali and via household surveys in Ethiopia and Malawi. Using these FBHs/FPHs as a validation data source, we assessed the completeness of the counts of births and deaths and the accuracy of under-five, infant, and neonatal mortality rates from the community-based method against the retrospective FBH/FPH for rolling twelve-month periods. For each method we calculated total cost, average annual cost per 1,000 population, and average cost per vital event reported. On average, CHWs submitted monthly vital event reports for over 95 percent of catchment areas in Ethiopia and Malawi, and for 100 percent of catchment areas in Mali. The completeness of vital events reporting by CHWs varied: we estimated that 30%-90% of annualized expected births (i.e. the number of births estimated using a FPH) were documented by CHWs and 22%-91% of annualized expected under-five deaths were documented by CHWs. Resulting annualized under-five mortality rates based on the CHW vital events reporting were, on average, under-estimated by 28% in Ethiopia, 32% in Malawi, and 9% in Mali relative to comparable FPHs. Costs per vital event reported ranged from $21 in Malawi to $149 in Mali. Our findings in Mali suggest that CHWs can collect complete and high-quality vital events data useful for monitoring annual changes in under-five mortality rates. Both the supervision of CHWs in Mali and the rigor of the associated field-based data quality checks were of a high standard, and the size of the pilot area in Mali was small (comprising of approximately 53,205 residents in 4,200 households). Hence, there are remaining questions about whether this level of vital events reporting completeness and data quality could be maintained if the approach was implemented at scale. Our experience in Malawi and Ethiopia suggests that, in some settings, establishing and maintaining the completeness and quality of vital events reporting by CHWs over time is challenging. In this sense, our evaluation in Mali falls closer to that of an efficacy study, whereas our evaluations in Ethiopia and Malawi are more akin to an effectiveness study. Our overall findings suggest that no one-size-fits-all approach will be successful in guaranteeing complete and accurate reporting of vital events by CHWs.


Novel target genes responsive to apoptotic activity by Ocimum gratissimum in human osteosarcoma cells.
Osteosarcoma (OS) is a type of bone cancer. Eighty percent of this tumor will metastasize to the lungs or liver, and as a result, patients generally need chemotherapy to improve survival possibility. Recently, antitumor activity has been reported in Ocimum gratissimum aqueous extract (OGE), which has been the focus of recent extensive studies on therapeutic strategies due to its antioxidant properties. We performed pharmacogenomics analyses for the effect of OGE on human osteosarcoma U2-OS and HOS cell growth. Cell viability, Western blot and flow cytometry analysis were performed before performing pharmacogenomics analyses for the effect of OGE on human osteosarcoma U2-OS and HOS cell growth, including cDNA microarray and RT-PCR assays. Cell viability assays revealed that OGE significantly and dose-dependently decreased the viability of U2-OS and HOS cells. Increases in cell shrinkage, Sub-G1 fragments and the activation of caspase 3 indicated that OGE induced cell apoptosis in U2-OS and HOS cells. There was no change in human osteoblast hFOS cells. cDNA microarray assay demonstrated that the expression of cell cycle regulators, apoptosis-related factors and cell proliferation markers were all modified by OGE treatment. RT-PCR analysis also confirmed the down-regulation of SKA2 and BUB1B, and the up-regulation of PPP1R15A, SQSTM1, HSPA1B, and DDIT4 by OGE treatment. The finding of anticancer activity in OGE and the identification of some potential target genes raise the expectation that OGE may become a useful therapeutic drug for human OS.


Self-assembly in Nafion membranes upon hydration: water mobility and adsorption isotherms.
By means of dissipative particle dynamics (DPD) and Monte Carlo (MC) simulations, we explored geometrical, transport, and sorption properties of hydrated Nafion-type polyelectrolyte membranes. Composed of a perfluorinated backbone with sulfonate side chains, Nafion self-assembles upon hydration and segregates into interpenetrating hydrophilic and hydrophobic subphases. This segregated morphology determines the transport properties of Nafion membranes that are widely used as compartment separators in fuel cells and other electrochemical devices, as well as permselective diffusion barriers in protective fabrics. We introduced a coarse-grained model of Nafion, which accounts explicitly for polymer rigidity and electrostatic interactions between anionic side chains and hydrated metal cations. In a series of DPD simulations with increasing content of water, a classical percolation transition from a system of isolated water clusters to a 3D network of hydrophilic channels was observed. The hydrophilic subphase connectivity and water diffusion were studied by constructing digitized replicas of self-assembled morphologies and performing random walk simulations. A non-monotonic dependence of the tracer diffusivity on the water content was found. This unexpected behavior was explained by the formation of large and mostly isolated water domains detected at high water content and high equivalent polymer weight. Using MC simulations, we calculated the chemical potential of water in the hydrated polymer and constructed the water sorption isotherms, which extended to the oversaturated conditions. We determined that the maximum diffusivity and the onset of formation of large water domains corresponded to the saturation conditions at 100% humidity. The oversaturated membrane morphologies generated in the canonical ensemble DPD simulations correspond to the metastable and unstable states of Nafion membrane that are not realized in the experiments.


Visual factors in the child's gait: effects on locomotor skills.
This kinematic study investigated the effects of visual factors on the angular oscillations of the head and trunk during various locomotor tasks in 3- to 8-yr.-old children and adults. The oscillations of the head under normal vision were limited and changed little across ages. Oscillations of both head and trunk about the roll axis were the most sensitive to difficulty in maintaining lateral equilibrium. On narrow supports, the lateral oscillations of the trunk increased between the ages of 3 and 6 years, with a maximum amplitude at the latter age and then decreased up to adulthood, suggesting a transition phase around the age of 6 years. Visual restriction had little effect on the control of angular oscillations of the head in children or adults. On a narrow support in darkness, adults increased oscillations of the trunk but reduced oscillations of the head. It can be concluded that, regardless of the age, control of locomotor equilibrium aims at limiting the angular oscillations of the head. Vision seems to contribute little to stabilization of the head.


Secretion of trophic gut peptides is not different in bolus- and continuously fed piglets.
In neonates, bolus feeding is associated with greater rates of intestinal growth than is continuous feeding. We tested whether the concentrations and secretion rates of trophic gut peptides are higher in bolus-fed than in continuously fed piglets. Five 21-d-old piglets were surgically implanted with gastric, arterial and portal catheters and a portal blood flow probe. At postnatal d 30 and 31, pigs received an equal amount of primed continuous or bolus feeding of a cow's milk formula in a randomized, crossover design. During a 6-h period, portal blood flow and arterial and portal concentrations of glucagon-like peptide-2 (GLP-2), peptide YY (PYY) and gastric inhibitory polypeptide (GIP) were measured. All hormone levels were significantly increased within 1 h of the start of the experiment, independent of the feeding modality. There were no differences between bolus and continuous feeding in either the arterial concentrations or secretion rates of GLP-2, PYY and GIP. In both treatment groups, the increases in the plasma concentrations of GLP-2 and GIP after feeding were substantially greater than those for PYY. We conclude that the production or circulating concentrations of GLP-2, PYY and GIP are not significantly different in bolus- and primed continuously fed piglets.


Histoid leprosy: the impact of the entity on the postglobal leprosy elimination era.
A fresh focus on histoid leprosy is the primary objective of this article, especially in the context of the postglobal leprosy elimination era. The emergence of the entity following dapsone monotherapy is well recognized, in addition to de novo cases. Irregular and inadequate therapies, coupled with resistance to dapsone and/or mutant organisms, are responsible. It was considered to be worthwhile to take stock of the condition through its history, nomenclature, epidemiology, clinical characteristics, diagnosis, and differential diagnosis. The bacteriologic and histopathologic features and immunologic profile are also described.


Lytic lesions: looking lethal but leaving room for a simple cure? A case of Veillonella spinal osteomyelitis.
Introduction. Diagnosing clinically significant infection caused by Veillonella species can be a challenge. Veillonella species are usually found in polymicrobial processes and are often regarded as a contaminant. Additionally, they are slow to grow in culture and this can lead to a delay in diagnosis or a missed diagnosis. Veillonella species rarely cause serious infections, but have been found to cause bacteraemia and osteomyelitis. Case presentation. A 67-year-old man with a history of treated prostate cancer presented with 2 weeks of progressive lower back pain and weakness. He had no signs or symptoms of active infection. He was found to have multiple lytic lesions in his lumbar spine that were initially suspected to be secondary to metastatic cancer. However, tissue and blood cultures were ultimately consistent with infection by Veillonella species. Conclusion. This case report highlights the fact that uncommon illnesses can often present like common disease processes. Because of the radiological appearance of the patient's lesions and his lack of infectious symptoms, a diagnosis of metastatic cancer was initially thought to be likely. Relying on the pathology and culture data, and waiting on the initiation of antimicrobials until the diagnosis was accurately established, were important factors in diagnosing and treating this infection. Veillonella species can be true pathogens when found in isolation and associated with bacteraemia. Additionally, they can cause an indolent infection that can lead to osteomyelitis. Failure to accurately diagnose this infection in a timely manner would have led to ongoing debility and diagnostic uncertainty for this patient.


On-orbit characterization of the VIIRS solar diffuser and attenuation screens for NOAA-20 using yaw measurements.
The follow-up visible infrared imaging radiometer suite (VIIRS) housed in the NOAA-20 satellite and the first of four in the NOAA Joint Polar Satellite System satellite series, was launched on 18 November 2017. The on-orbit satellite yaw maneuver operation was carried out on 25-26 January 2018 over 15 scheduled orbits to obtain responses of the reflective solar bands (RSBs) and the solar diffuser stability monitor (SDSM) over a specified angular range. This paper presents a comprehensive analysis of the yaw measurements that characterizes the three required input functions for the standard on-orbit RSB calibration pipeline. The characterization functions of the product of the bidirectional reflectance factors (BRFs) of the solar diffuser (SD) with the vignetting function (VF) of the SD screen (SDS), dubbed the BRF-VF-products (BVPs), are derived for the two required outgoing directions from the SD, one set for the RSB BVPs from the SD to the rotation telescope assembly that directs light to the RSBs, and another set for the SDSM BVPs for the outgoing direction from the SD to the SDSM. The VFs for the attenuation screen placed in front of the Sun-view port, the Sun-view screen (SVS), are analyzed as a set of standalone functions to characterize the direct solar illumination reaching the SDSM through the SVS, but the complexity of their non-smooth two-dimensional dependence requires an additional direct treatment in the derivation of the degradation of the SD, the H-factors. The results for the RSB BVPs, SDSM BVPs, and the SVS VFs are presented and discussed, and further applied to derive the early-mission performance of H-factors and the RSB calibration coefficients, or F-factors. The overall results of the H-factors and F-factors showing smooth trends with negligible residuals indicate that the derived BVP functions and the SVS VFs have been accurately characterized or treated, and are ready for use for the standard on-orbit RSB calibration of NOAA-20 VIIRS.


Harnessing "A Billion Years of Experimentation": The Ongoing Exploration and Exploitation of CRISPR-Cas Immune Systems.
The famed physicist-turned-biologist, Max Delbrück, once remarked that, for physicists, "the field of bacterial viruses is a fine playground for serious children who ask ambitious questions." Early discoveries in that playground helped establish molecular genetics, and half a century later, biologists delving into the same field have ushered in the era of precision genome engineering. The focus has of course shifted-from bacterial viruses and their mechanisms of infection to the bacterial hosts and their mechanisms of immunity-but it is the very same evolutionary arms race that continues to awe and inspire researchers worldwide. In this review, we explore the remarkable diversity of CRISPR-Cas adaptive immune systems, describe the molecular components that mediate nucleic acid targeting, and outline the use of these RNA-guided machines for biotechnology applications. CRISPR-Cas research has yielded far more than just Cas9-based genome-editing tools, and the wide-reaching, innovative impacts of this fascinating biological playground are sure to be felt for years to come.


Polygonum cuspidatum and its active components inhibit replication of the influenza virus through toll-like receptor 9-induced interferon beta expression.
Influenza virus infection is a global public health issue. The effectiveness of antiviral therapies for influenza has been limited by the emergence of drug-resistant viral strains. Therefore, there is an urgent need to identify novel antiviral therapies. Here we tested the effects of 300 traditional Chinese medicines on the replication of various influenza virus strains in a lung cell line, A549, using an influenza-specific luciferase reporter assay. Of the traditional medicines tested, Polygonum cuspidatum (PC) and its active components, resveratrol and emodin, were found to attenuate influenza viral replication in A549 cells. Furthermore, they preferentially inhibited the replication of influenza A virus, including clinical strains isolated in 2009 and 2011 in Taiwan and the laboratory strain A/WSN/33 (H1N1). In addition to inhibiting the expression of hemagglutinin and neuraminidase, PC, emodin, and resveratrol also increased the expression of interferon beta (IFN-β) through Toll-like receptor 9 (TLR9). Moreover, the anti-viral activity of IFN-β or resveratrol was reduced when the A549 cells were treated with neutralizing anti-IFN-β antibodies or a TLR9 inhibitor, suggesting that IFN-β likely acts synergistically with resveratrol to inhibit H1N1 replication. This potential antiviral mechanism, involving direct inhibition of virus replication and simultaneous activation of the host immune response, has not been previously described for a single antiviral molecule. In conclusion, our data support the use of PC, resveratrol or emodin for inhibiting influenza virus replication directly and via TLR-9-induced IFN-β production.


Study of the cells proliferating in parent versus F hybrid mixed lymphocyte culture.
Caryotypic analysis of the cells dividing in mouse parent-hybrid MLC showed an F1 hybrid cell proliferation, which varied depending upon the source of lymphoid cells used: strong in spleen MLC (sometimes equal to that of the parental cells), less marked in lymph node cell MLC, and most often absent in MLC between cortisone-resistant (CR) thymocytes. MLC between parental spleen cells and F1 CR thymocytes showed, however, that in certain conditions of culture F thymocytes can also proliferate. Using parental or F1 spleen cells lacking T lymphocytes, it was found that F1 cell proliferation is entirely dependent upon the presence of parental T cells, but does not require the presence of T lymphocytes among the F1 cells. Immunofluorescence analysis of the blasts observed in one-way MLC showed that about 70% of the parental blasts were T blasts, and 25%B blasts (containing a high proportion of plasmablasts); among the F1 blasts, there was also the same percentage of B blasts and plasmablasts, but many of the T blasts bore only small amounts of T-cell antigen (MTLA), and there was also about 20%of unstained blasts, possibly T blasts bearing MTLA in amounts undetectable by immunofluorescence. The possibility is discussed that the F1 responding T cells belong to a subpopulation performing a suppressive function; MLC lacking F1 T cells showed increased [3H] thymidine incorporation. The proliferation and differentiation of parental and F1 B cells may result mainly from an unspecific, "polyclonal" triggering.


Head-to-head comparison of three vaccination strategies based on DNA and raw insect-derived recombinant proteins against Leishmania.
Parasitic diseases plague billions of people among the poorest, killing millions annually, and causing additional millions of disability-adjusted life years lost. Leishmaniases affect more than 12 million people, with over 350 million people at risk. There is an urgent need for efficacious and cheap vaccines and treatments against visceral leishmaniasis (VL), its most severe form. Several vaccination strategies have been proposed but to date no head-to-head comparison was undertaken to assess which is the best in a clinical model of the disease. We simultaneously assayed three vaccination strategies against VL in the hamster model, using KMPII, TRYP, LACK, and PAPLE22 vaccine candidate antigens. Four groups of hamsters were immunized using the following approaches: 1) raw extracts of baculovirus-infected Trichoplusia ni larvae expressing individually one of the four recombinant proteins (PROT); 2) naked pVAX1 plasmids carrying the four genes individually (DNA); 3) a heterologous prime-boost (HPB) strategy involving DNA followed by PROT (DNA-PROT); and 4) a Control including empty pVAX1 plasmid followed by raw extract of wild-type baculovirus-infected T. ni larvae. Hamsters were challenged with L. infantum promastigotes and maintained for 20 weeks. While PROT vaccine was not protective, DNA vaccination achieved protection in spleen. Only DNA-PROT vaccination induced significant NO production by macrophages, accompanied by a significant parasitological protection in spleen and blood. Thus, the DNA-PROT strategy elicits strong immune responses and high parasitological protection in the clinical model of VL, better than its corresponding naked DNA or protein versions. Furthermore, we show that naked DNA coupled with raw recombinant proteins produced in insect larvae biofactories -the cheapest way of producing DNA-PROT vaccines- is a practical and cost-effective way for potential "off the shelf" supplying vaccines at very low prices for the protection against leishmaniases, and possibly against other parasitic diseases affecting the poorest of the poor.


The cDNA and genomic DNA organization of a novel toxin SHT-I from spider Ornithoctonus huwena.
In present study the full-length cDNA of a novel toxin from the venom gland of spider Ornithoctonus huwena, named as SHT-I, has been cloned using the strategy of rapid amplification of cDNA ends, and then the whole genomic sequence of SHT-I (Selenocosmia huwena toxin-I) was determined using sequence-specific primers synthesized based on the acquired 3' and 5' ends of SHT-I cDNA sequence. It is unexpectedly found that intron was lacking in the genomic sequence of SHT-I. The result might evoke an interesting question whether the gene code of inhibitor cystine-knot peptides from spider venom is distinct from that of those known toxic peptides of scorpion and cone snail.


Semaglutide 2.4 Mg for the Management of Overweight and Obesity: Systematic Literature Review and Meta-Analysis.
Semaglutide has demonstrated safe and effective weight loss for overweight and obesity, including participants with concomitant type 2 diabetes mellitus (T2DM), in randomized placebo-controlled trials (RCTs). We conducted a systematic literature review (SLR) and network meta-analyses (NMA) to compare weekly semaglutide 2.4 mg with pharmacological comparators for weight management in overweight or obesity. The SLR was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. NMAs were performed to compare weight change for semaglutide 2.4 mg with comparators using data identified in the SLR. The populations of interest were total population, normal glucose tolerance, non-T2DM, pre-diabetes, and T2DM. Included outcomes were weight change from baseline (CFB, %) at 52 weeks and proportion of participants losing ≥5% baseline fasting body weight at 12 weeks (at full therapeutic dose). The SLR identified 108 RCTs examining non-surgical interventions, of which 41 were considered for inclusion in the NMAs. In all populations, semaglutide 2.4 mg was associated with a greater percentage weight CFB with 52 weeks of treatment versus all available comparators. In all populations, semaglutide was associated with a higher likelihood of participants losing ≥5% of baseline fasting body weight at 12 weeks versus all available comparators. In NMA, semaglutide 2.4 mg demonstrated effective weight loss (≥5%) in the total population and all subpopulations of glucose tolerance versus active comparators. Semaglutide is an effective treatment that may address unmet need in the management of overweight and obesity.


Sexual selection and the evolution of costly female preferences: spatial effects.
Models of Fisher's runaway process show that if there is a cost to female preference, no preference or male trait exaggeration will evolve. Surprisingly, this is true no matter how small the cost, which reveals that these models of Fisher's process are structurally unstable (Bulmer 1989). Here a model of Fisher's runaway process is presented to demonstrate that costly female preference evolves very easily when space is explicitly included in the model. The only requirement is that the optimal male phenotype changes across the species' range. The model shows that the spatial average of the female preference and male trait reach an evolutionary equilibrium that is identical to those of nonspatial models, but that the preference and male trait can deviate greatly from these averages at any point in space. For example, if random mating results in the lowest cost to females, then at equilibrium the spatial average preference will be zero. Nevertheless, there will be some locations at which females prefer males with larger ornaments and others where they prefer males with smaller ornaments. Results also show that the structural instability of nonspatial models of Fisher's process is less of a problem in spatial models. In particular, many of the main qualitative features of cost-free spatial models of Fisher's process remain valid even when there are small costs of female preference. Finally, the model shows that abrupt changes in the optimal male phenotype across space can result in an amplification of this pattern when preference has a small cost, but it can also result in a pattern similar to reproductive character displacement. Which of these occurs depends on the magnitude of the cost of female preference. This suggests that some patterns of reproductive character displacement in nature might be explained simply by sexual selection rather than by hybrid dysgenesis and reinforcement.


Automated calibration of multi-camera-projector structured light systems for volumetric high-speed 3D surface reconstructions.
It is challenging to calibrate multiple camera-projector pairs for multi-view 3D surface reconstruction based on structured light. Here, we present a new automated calibration method for high-speed multi-camera-projector systems. The method uses printed and projected dot patterns on a planar calibration target, which is moved by hand in the calibration volume. Calibration is enabled by automated image processing and bundle-adjusted parameter optimization. We determined the performance of our method by 3D reconstructing a sphere. The accuracy is -0.03 ± 0.09 % as a percentage of the diameter of the calibration volume. Applications include quality control, autonomous systems, engineering measurements, and motion capture, such as the preliminary 3D reconstruction of a bird in flight we present here.


Hormones and the hippocampus.
Hippocampal lesions produce memory deficits, but the exact function of the hippocampus remains obscure. Evidence is presented that its role in memory may be ancillary to physiological regulation. Molecular studies demonstrate that the hippocampus is a primary target for ligands that reflect body physiology, including ion balance and blood pressure, immunity, pain, reproductive status, satiety and stress. Hippocampal receptors are functional, probably accessible to their ligands, and mediate physiological and cognitive changes. This argues that an early role of the hippocampus may have been in sensing soluble molecules (termed here 'enteroception') in blood and cerebrospinal fluid, perhaps reflecting a common evolutionary origin with the olfactory system ('exteroception'). Functionally, hippocampal enteroception may reflect feedback control; evidence is reviewed that the hippocampus modulates body physiology, including the activity of the hypothalamus-pituitary-adrenal axis, blood pressure, immunity, and reproductive function. It is suggested that the hippocampus operates, in parallel with the amygdala, to modulate body physiology in response to cognitive stimuli. Hippocampal outputs are predominantly inhibitory on downstream neuroendocrine activity; increased synaptic efficacy in the hippocampus (e.g. long-term potentiation) could facilitate throughput inhibition. This may have implications for the role of the hippocampus and long-term potentiation in memory.


An ancient bottleneck in the Lost Pines of central Texas.
The retreating edge hypothesis for species responding to climate change predicts severe bottlenecks and eventual extinction. The disjunct Lost Pines population at the westernmost edge of the widespread Pinus taeda range is well suited for testing this prediction. The occurrence of one or more genetic bottlenecks in the Lost Pines population was tested using 34 nuclear microsatellite markers and a control sample from the larger, more continuous east Texas P. taeda forests. The Lost Pines population has undergone drastic contractions in effective population size between 3000 and 30 000 years bp. These results were supported by: (i) detection of transient heterozygosity excess, (ii) a mode-shift indicator of allele frequencies, and (iii) a ratio of allele number to allele size range. No bottleneck was detected for the east Texas control using any of the three methods. The distribution of allele frequencies was skewed for the Lost Pines population compared to the control, indicating a loss of rare alleles. However, allelic diversity was similar between the Lost Pines population and its east Texas control; the mean allele number per locus was 5.29 and 5.38, respectively. It is proposed that the Lost Pines population was the western refugium for P. taeda during Pleistocene glaciation and that East Texas P. taeda forests descended from the bottlenecked Lost Pines population.


Complex cell prototype representation for face recognition.
In this paper we propose a new face recognition system based on a biologically inspired filtering method. Our work differs from previous proposals in: 1) the multistage filtering method employed; 2) the pyramid structure used, and most importantly; 3) the prototype construction scheme to determine the models stored in memory. The method is much simpler than previous proposals and relatively inexpensive computationally, while attaining error rates as low as 5%, very close to the best reported results.


TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus.
The interferon (IFN) system is a major effector of the innate immunity that allows time for the subsequent establishment of an adaptive immune response against a wide-range of pathogens. Their diverse biological actions are thought to be mediated by the products of specific but usually overlapping sets of cellular genes induced in the target cells. Ubiquitin ligase members of the tripartite motif (TRIM) protein family have emerged as IFN-induced proteins involved in both innate and adaptive immunity. In this report, we provide evidence that TRIM22 is a functional E3 ubiquitin ligase that is also ubiquitinated itself. We demonstrate that TRIM22 expression leads to a viral protection of HeLa cells against encephalomyocarditis virus infections. This effect is dependent upon its E3 ubiquitinating activity, since no antiviral effect was observed in cells expressing a TRIM22-deletion mutant defective in ubiquitinating activity. Consistent with this, TRIM22 interacts with the viral 3C protease (3C(PRO)) and mediates its ubiquitination. Altogether, our findings demonstrate that TRIM22 E3 ubiquitin ligase activity represents a new antiviral pathway induced by IFN against picornaviruses.


Healthy Lifestyle Behavior, Goal Setting, and Personality among Older Adults: A Synthesis of Literature Reviews and Interviews.
Despite the well-known health benefits of adopting a healthy lifestyle, older adults' self-determination, goals, and motivation, as well as other personality factors, are known to influence their healthy lifestyle behaviors, yet these interactions have rarely been discussed. The literature that investigated and discussed the interaction of personality, goals, and healthy lifestyle behaviors among older adults was reviewed. In addition, interview responses from older adults regarding their experiences in participating in a real-life physical activity intervention and its relationship with their personality traits and goal setting were synthesized using content analysis. The current review highlights the relationship between healthy living practices, goal setting, and personalities, and it is backed up and expanded upon by interviews with participants. People with different personality types are likely to have diverse views on HLBs. Individuals who are more conscientiousness or extraverted are more likely to adopt HLBs than those who are not. It is suggested that a meta-analysis should be conducted on the relationship between personality, goal setting, and physical exercise or other specific HLBs. In addition, future research should focus on various types of HLB therapies that take into account personality and goal setting.


Allergy and Tourette's syndrome.
Four patients with Tourette's syndrome who presented in an allergist's office are described. The diagnostic criteria, presentation of Tourette's syndrome, and current therapy are discussed. All four patients had increased serum IgE levels and positive skin tests. Symptoms of Tourette patients may mimic allergy or present combined with allergic illness.


An evidence-based approach for estimating present and future damages from child sexual abuse.
This article illustrates the use of evidence-based practice to develop conclusions for a forensic report. The authors present a case vignette in which an early adolescent boy was sexually abused by an employee of a private school, and a lawsuit ensued. They explain how to utilize relevant research regarding the prognosis of victims of sexual abuse to address the forensic issues of psychological injury and future damages. It is notable that the two authors, who have at times testified on opposite sides of similar cases, were able to agree on conclusions that were based on relevant published research.


Physical and chemical characterization of purified ovalbumin messenger RNA.
Preparative agarose gel electrophoresis under denaturing conditions has been successfully employed to purify large quantities of ovalbumin mRNA from hen oviducts. The mRNA thus prepared is physically homogeneous based on its migration as a single component on electrophoresis in both analytical acid-urea agarose gels and formamide-containing, neutral polyacrylaminde gels; it also sediments as a single peak in sucrose gradients containing 70% formamide. The mRNA is chemically free of ribosomal RNA contamination since its oligonucleotide fingerprint map after complete T1 ribonuclease digestion contains no detectable specific large oligonucleotide markers of ribosomal RNAs. It is also not contaminated by other biologically active messenger RNAs because, when it is added to the cell-free wheat germ translation system, the only protein product synthesized is ovalbumin as analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and specific immunoprecipitation. Ovalbumin mRNA has a nucleotide composition of 32.3% A, 21.0% G, 25.7% U, and 20.7% C [(A+U)/(G+C) equal 1.41]. The mRNA contains a heterogeneous poly(A) tract ranging from 20 to 140 residues with a number average chain length of 62 adenylate residues. The molecular weight of the sodium salt of the purified mRNA is approximately 650,000 +/- 63,000, corresponding to a chain length of 1890 +/- 180 nucleotides, as determined by electron microscopy under completely denaturing conditions. This value is in close agreement with the values obtained from: (a) sucrose gradient centrifugation in the presence of 70% formamide; (b) evaluation of poly(A) content in the mRNA and the number average chain length of its poly(A) tract; and (c) sedimentation velocity studies in the presence of 3% formaldehyde. When 125I-labeled ovalbumin mRNA is allowed to hybridize with a large excess of chick DNA, the observed kinetics of hybridization reveal no appreciable reaction between the mRNA and the repeated sequences of the chick DNA, although the mRNA appears to be approximately 600 nucleotides longer than necessary to code for ovalbumin. It thus appears that the entire ovalbumin mRNA is primarily transcribed from a unique sequence in the chick genome.


Clinical course of vesicoureteral reflux in patients with hypospadias.
The prevalence of vesicoureteral reflux (VUR) in hypospadic patients is reportedly higher than in healthy children. We investigated the prevalence and the clinical course of VUR in hypospadic patients. We carried out intraoperative cystography to detect VUR in 338 patients who underwent hypospadias repair. Age, severity of hypospadias and the presence of VUR were investigated. A dimercaptosuccinic acid renal scan and follow-up voiding cystourethrography (VCUG) were carried out if VUR was detected. VUR was detected in 41 patients (12.1%). Of 156 patients who were younger than 1 year-of-age, 34 (21.8%) were found to have VUR. The prevalence of VUR was significantly higher in patients younger than 1year (P<0.001), but was not associated with hypospadias type (P=0.212). The reflux grades were I, II and III in 6, 52 and 1 renal units, respectively. Renal scarring was shown in one of 36 patients. Follow-up VCUG was carried out in 30 patients at a mean of 14.28±3.89months, and reflux resolved in 27 and improved from grade II to grade I in three patients. Although its prevalence is higher in hypospadic children than in healthy children, it is not necessary to screen for VUR in hypospadic patients, because it is likely to be low-grade and to resolve in most cases.


Systematic refinement of a health information technology time and motion workflow instrument for inpatient nursing care using a standardized interface terminology.
Time and motion (T&M) studies provide an objective method to measure the expenditure of time by clinicians. While some instruments for T&M studies have been designed to evaluate health information technology (HIT), these instruments have not been designed for nursing workflow. We took an existing open source HIT T&M study application designed to evaluate physicians in the ambulatory setting and rationally adapted it through empiric observations to record nursing activities in the inpatient setting and linked this instrument to an existing interface terminology, the Omaha System. Nursing activities involved several dimensions and could include multiple activities occurring simultaneously, requiring significant instrument redesign. 94% of the activities from the study instrument mapped adequately to the Omaha System. T&M study instruments require customization in design optimize them for different environments, such as inpatient nursing, to enable optimal data collection. Interface terminologies show promise as a framework for recording and analyzing T&M study data.