Miracle-dz/UniFAR-FTUs huggingface dataset:
Verteporfin photodynamic therapy and anti-angiogenic drugs: potential for combination therapy in exudative age-related macular degeneration

ABSTRACT Objective: To discuss the rationale for combining anti-angiogenic treatment with verteporfin (Visudyne*) photodynamic therapy in the management of choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) and evaluate available evidence for the therapeutic benefits of such approaches. Scope: The Medline and EMBASE databases were searched in October 2006 to retrieve relevant articles. Additional articles were obtained from the reference lists of retrieved articles, as well as from recent scientific meetings and company websites. Findings: Treatments for CNV due to AMD can be directed at either the vascular component of CNV (the new vessels that proliferate and leak blood and fluid) or the angiogenic component that leads to the development of the condition. Verteporfin targets the vascular component, whereas anti-angiogenic agents (such as pegaptanib and ranibizumab) target key mediators of the angiogenic cascade. The different mechanisms of action of these approaches offer the potential for additive or synergistic effects with combination therapy. In addition, anti-angiogenic agents might counteract upregulation of angiogenic factors (including VEGF) that occur after verteporfin photodynamic therapy. Results from preclinical and clinical studies of the combination of ranibizumab or pegaptanib with verteporfin warrant continued investigation. Conclusions: The use of anti-angiogenic agents in combination with verteporfin may have the potential to improve visual outcomes and reduce the number of treatments in eyes with CNV due to AMD, and requires further evaluation in randomized, controlled clinical trials.
Indium Tin Oxide Modified by Au and Vanadium Pentoxide as an Efficient Anode for Organic Light-Emitting Devices

Au/Vanadium pentoxide (V<sub>2</sub>O<sub>5</sub>) films on indium tin oxide (ITO) as composite anodes for hole injection in organic light-emitting devices (OLEDs) have been investigated. The device with ITO/Au(6 nm)/V<sub>2</sub>O<sub>5</sub> (6 nm) anode shows improved current density-voltage characteristics as compared with the device with ITO/Au as anode. Hole injection is significantly reduced when Au was added on ITO as an anode. However, while a thin V<sub>2</sub>O<sub>5</sub> film is deposited on a Au anode, the barrier height is substantially reduced. The hole injection is facilitated, and the driving voltage of the device decreased by 10 V. In addition, the maximum current efficiency for the ITO/Au/V<sub>2</sub>O<sub>5</sub> OLED is ~3.5 cd/A, which is higher than that of the ITO/Au anode device (~1.1 cd/A) and ITO/V<sub>2</sub>O<sub>5</sub> OLED of ~2.8 cd/A.
Structure-Based Design and Engineering of a Nontoxic Recombinant Pokeweed Antiviral Protein with Potent Anti-Human Immunodeficiency Virus Activity

ABSTRACT A molecular model of pokeweed antiviral protein (PAP)-RNA interactions was used to rationally engineer FLP-102(151AA152) and FLP-105(191AA192) as nontoxic PAPs with potent anti-human immunodeficiency virus (anti-HIV) activities. FLP-102 and FLP-105 have been produced in Escherichia coli and tested both in vitro and in vivo. These proteins depurinate HIV type 1 (HIV-1) RNA much better than rRNA and are more potent anti-HIV agents than native PAP or recombinant wild-type PAP. They are substantially less toxic than native PAP in BALB/c mice and exhibit potent in vivo activities against genotypically and phenotypically nucleoside reverse transcriptase inhibitor-resistant HIV-1 in a surrogate human peripheral blood lymphocyte (Hu-PBL) SCID mouse model of human AIDS. Rationally engineered nontoxic recombinant PAPs such as FLP-102 and FLP-105 may provide the basis for effective salvage therapies for patients harboring highly drug-resistant strains of HIV-1. The documented in vitro potencies of FLP-102 and FLP-105, their in vivo antiretroviral activities in the HIV-infected Hu-PBL SCID mouse model, and their favorable toxicity profiles in BALB/c mice warrant the further development of these promising new biotherapeutic agents.
Dual Nature of the Infectious Prion Protein Revealed by High Pressure*

Crude brain homogenates of terminally diseased hamsters infected with the 263K strain of scrapie (PrPSc) and purified prion fibrils were heated or pressurized at 800 megapascals and 60 °C for 2 h in different buffers and in water. Prion proteins (PrP) were analyzed for their proteinase K resistance in immunoblots and for their infectivity in hamster bioassays. A notable decrease in the proteinase K resistance of unpurified prion proteins, probably because of pressure-induced changes in the protein conformation of native PrPSc or the N-truncated PrP-(27–30), could be demonstrated when pressurized at initially neutral conditions in several buffers and in water but not in a slightly acidic pH. A subsequent 6–7 log10 reduction of infectious units/g in phosphate-buffered saline buffer, pH 7.4, was found. The proteinase K-resistant core was also not detectable after purification of prions extracted from pressurized samples, confirming pressure effects at the level of the secondary structure of prion proteins. However, opposite results were found after pressurizing purified prions, arguing for the existence of pressure-sensitive β-structures (PrPScΔPsen) and extremely pressure-resistant β-structures (PrPScΔPres). Remarkably, after the first centrifugation step at 540,000 × g during isolation, prions remained proteinase K-resistant when pressurized in all tested buffers and in water. It is known that purified fibrils retain infectivity, but the isolated protein (full and N-truncated) behaved differently from native PrPSc under pressure, suggesting a kind of semicrystalline polymer structure.
The Use of Haloperidol in Agitated Critically Ill Children

Sedation, analgesia, and muscle relaxants are often used to control agitation and facilitate mechanical ventilation in children with acute hypoxic respiratory failure. In most children, adequate sedation can be achieved with a combination of parenteral benzodiazepines and opioids. However, long-term continuous infusions of opioids and benzodiazepines often result in physiologic tolerance and the need for dose escalation in order to maintain an appropriate level of sedation. Occasionally, mechanically ventilated children remain anxious, agitated, or combative despite escalating doses of opioids and benzodiazepines. In some children, additional doses of these agents seem to exacerbate agitation and combative-
Anti‐α4 integrin antibody induces apoptosis in murine thymocytes and staphylococcal enterotoxin B‐activated lymph node T cells

We have shown that an antibody (9C10) to the α4 integrin induces apoptosis in murine immature CD4+ CD8+ thymocytes and in activated (but not resting) mature lymph node T cells. In both cases, apoptosis is blocked by the highly selective protein kinase C (PKC) inhibitor Ro31.8425, suggesting that 9C10 induces signalling through the α4 integrin resulting in PKC activation leading to apoptosis. Overall, our results indicate the potential role of the α4 integrin‐mediated interactions in apoptosis induction during T‐cell development and following mature T‐cell activation.
Epidemiology of Bruxism in Adults : A Systematic Review of the Literature

Correspondence to: Dr Daniele Manfredini Via Ingolstadt 3 54033 Marina di Carrara (MS) Italy Email: daniele.manfredini@tin.it Aims: To perform a systematic review of the literature dealing with the prevalence of bruxism in adult populations. Methods: A systematic search of the medical literature was performed to identify all peer-reviewed English-language papers dealing with the prevalence assessment of either awake or sleep bruxism at the general population level by the adoption of questionnaires, clinical assessments, and polysomnographic (PSG) or electromyographic (EMG) recordings. Quality assessment of the reviewed papers was performed according to the Methodological evaluation of Observational REsearch (MORE) checklist, which enables the identification of flaws in the external and internal validity. Cut-off criteria for an acceptable external validity were established to select studies for the discussion of prevalence data. For each included study, the sample features, diagnostic strategy, and prevalence of bruxism in relation to age, sex, and circadian rhythm, if available, were recorded. Results: Thirtyfive publications were included in the review. Several methodological problems limited the external validity of findings in most studies, and prevalence data extraction was performed only on seven papers. Of those, only one paper had a flawless external validity, whilst internal validity was low in all the selected papers due to their selfreported bruxism diagnosis alone, mainly based on only one or two questionnaire items. No epidemiologic data were available from studies adopting other diagnostic strategies (eg, PSG, EMG). Generically identified “bruxism” was assessed in two studies reporting an 8% to 31.4% prevalence, awake bruxism was investigated in two studies describing a 22.1% to 31% prevalence, and prevalence of sleep bruxism was found to be more consistent across the three studies investigating the report of “frequent” bruxism (12.8% ± 3.1%). Bruxism activities were found to be unrelated to sex, and a decrease with age was described in elderly people. Conclusion: The present systematic review described variable prevalence data for bruxism activities. Findings must be interpreted with caution due to the poor methodological quality of the reviewed literature and to potential diagnostic bias related with having to rely on an individual’s self-report of bruxism. J OrOfac Pain 2013;27:99–110. doi: 10.11607/jop.921
rRNA Promoter Activity in the Fast-Growing Bacterium Vibrio natriegens

ABSTRACT The bacterium Vibrio natriegens can double with a generation time of less than 10 min (R. G. Eagon, J. Bacteriol. 83:736-737, 1962), a growth rate that requires an extremely high rate of protein synthesis. We show here that V. natriegens' high potential for protein synthesis results from an increase in ribosome numbers with increasing growth rate, as has been found for other bacteria. We show that V. natriegens contains a large number of rRNA operons, and its rRNA promoters are extremely strong. The V. natriegens rRNA core promoters are at least as active in vitro as Escherichia coli rRNA core promoters with either E. coli RNA polymerase (RNAP) or V. natriegens RNAP, and they are activated by UP elements, as in E. coli. In addition, the E. coli transcription factor Fis activated V. natriegens rrn P1 promoters in vitro. We conclude that the high capacity for ribosome synthesis in V. natriegens results from a high capacity for rRNA transcription, and the high capacity for rRNA transcription results, at least in part, from the same factors that contribute most to high rates of rRNA transcription in E. coli, i.e., high gene dose and strong activation by UP elements and Fis.
Characterization of buccal microvascular response in patients with septic shock

Background and objective Microcirculatory alterations are thought to be responsible for much of the morbidity and mortality from sepsis. The aim of the present study was to characterize the buccal microvascular response in patients with septic shock using combined laser Doppler flowmetry/visual light spectroscopy measurements. Methods Microvascular measurements were performed daily on the buccal mucosa in 21 consecutive ICU patients within 24 h of the onset of septic shock, in 20 healthy volunteers, and in eight ICU patients after uncomplicated elective surgery (ICU controls). Results In ICU controls, buccal mucosal flow was higher in the superficial (231.7 ± 69.5 vs. 134 ± 105.3 arbitrary unit, P = 0.03) and lower in the deep (235.3 ± 30.8 vs. 376.2 ± 107.3 arbitrary unit, P = 0.001) channel compared with healthy volunteers; microvascular oxygen haemoglobin saturations (μHbO2) were similar in the two groups. Microvascular flow within 24 h of onset of shock was similar in patients with septic shock and healthy individuals; however, μHbO2 was lower in the deep channel (78.3 ± 10.3 vs. 91.1 ± 4.5%, P < 0.001). Superficial buccal mucosal μHbO2 within 24 h of onset of septic shock was lower in nonsurvivors than in survivors. Superficial buccal mucosal flow increased during the 2nd day of septic shock in survivors and decreased thereafter; μHbO2 decreased steadily. Conclusion Buccal laser Doppler flowmetry/visual light spectroscopy may be useful for tracing microvascular alterations in critically ill patients. The surgical stress response was associated with alterations in local flow with preserved μHbO2. However, in patients with septic shock, μHbO2 was reduced in the deep channel, probably muscular tissue, with no changes in microvascular flow.
Terfezia disappears from the American truffle mycota as two new genera and Mattirolomyces species emerge

Reexamination and molecular phylogenetic analyses of American Terfezia species and Mattirolomyces tiffanyae revealed that their generic assignments were wrong. Therefore we here propose these combinations: Mattirolomyces spinosus comb. nov. (≡ Terfezia spinosa), Stouffera longii gen. & comb. nov. (≡ Terfezia longii) and Temperantia tiffanyae gen. & comb. nov. (≡ Mattirolomyces tiffanyae). In addition we describe a new species, Mattirolomyces mexicanus spec. nov. All species belong to the Pezizaceae. Based on these results Terfezia is not known from North America, Mattirolomyces is represented by two species and two new monotypic genera are present.
Dense gas in IRAS 20343+4129: an ultracompact H ii region caught in the act of creating a cavity

The intermediate- to high-mass star-forming region IRAS 20343+4129 is an excellent laboratory to study the influence of high- and intermediate-mass young stellar objects on nearby starless dense cores, and investigate for possible implications in the clustered star formation process. We present 3 mm observations of continuum and rotational transitions of several molecular species (C_(2)H, c-C_(3)H_(2), N_(2)H+, NH_(2)D) obtained with the Combined Array for Research in Millimetre-wave Astronomy, as well as 1.3 cm continuum and NH_3 observations carried out with the Very Large Array, to reveal the properties of the dense gas. We confirm undoubtedly previous claims of an expanding cavity created by an ultracompact H ii region associated with a young B2 zero-age main sequence (ZAMS) star. The dense gas surrounding the cavity is distributed in a filament that seems squeezed in between the cavity and a collimated outflow associated with an intermediate-mass protostar. We have identified 5 mm continuum condensations in the filament. All of them show column densities consistent with potentially being the birthplace of intermediate- to high-mass objects. These cores appear different from those observed in low-mass clustered environments in several observational aspects (kinematics, temperature, chemical gradients), indicating a strong influence of the most massive and evolved members of the protocluster. We suggest a possible scenario in which the B2 ZAMS star driving the cavity has compressed the surrounding gas, perturbed its properties and induced the star formation in its immediate surroundings.
Significant association of BDNF haplotypes in European‐American male smokers but not in European‐American female or African‐American smokers

Brain‐derived neurotrophic factor (BDNF) influences dopamine and serotonin neurotransmission in the brain, both of which are involved in the reward system of addiction. The BDNF gene is located in a genomic region on chromosome 11p where we and others have found ‘significant’ linkage to nicotine dependence (ND). We tested the potential role of variants within BDNF in vulnerability to ND, which was assessed by Smoking Quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerström Test for ND (FTND). Six single nucleotide polymorphisms (SNPs) in BDNF were analyzed in an extensively phenotyped cohort of 602 nuclear families with smokers and non‐smokers of African‐American (AA) or European‐American (EA) ancestry. Individual SNP analysis revealed that two SNPs in the pooled male and three SNPs in the EA male samples were significantly associated with at least one adjusted ND measure. However, none of these associations remained significant after correction for multiple testing. Haplotype analysis of rs6484320‐rs988748‐rs2030324‐rs7934165 revealed that a major T–C–T–G haplotype was significantly associated, even after Bonferroni correction, with the three ND measures in the pooled and EA male samples (maximum Z = 3.00, P = 0.002 and maximum Z = 3.13, P = 0.0009 for SQ, respectively). No significant association of a major haplotype with ND was found in the AA or EA female smokers. The significant association of BDNF variants with ND implies that this gene plays a role in the etiology of ND in EAs and that its involvement is gender specific. BDNF may warrant further investigation in ND. © 2005 Wiley‐Liss, Inc.
In vitro susceptibility of Candida albicans to four disinfectants and their combinations.

AIM The aim of this study was to evaluate the susceptibility of seven strains of Candida albicans to four disinfectants: iodine potassium iodide, chlorhexidine acetate, sodium hypochlorite and calcium hydroxide. In addition, all possible pairs of the disinfectants were tested in order to compare the effect of the combination and its components. METHODOLOGY Filter paper discs were immersed in standardized yeast suspensions and then transferred to disinfectant solutions of different concentrations and incubated at 37 degrees C for 30 s, 5 min, 1 h and 24 h. After incubation the filter paper discs were transferred to vials with PBS and glass beads that were then vigorously shaken for dispersal of the yeast cells. PBS with resuspended yeasts was serially diluted 10-fold. Droplets of 25 microL from each dilution were inoculated on TSB agar plates and incubated in air at 37 degrees C for 24 h. The number of colony-forming units was then calculated from appropriate dilutions. RESULTS C. albicans cells were highly resistant to calcium hydroxide. Sodium hypochlorite (5% and 0.5%) and iodine (2%) potassium iodide (4%) killed all yeast cells within 30 s, whilst chlorhexidine acetate (0.5%) showed complete killing after 5 min. Combinations of disinfectants were equally or less effective than the more effective component. All C. albicans strains tested showed similar susceptibility to the medicaments tested. CONCLUSIONS This study indicates that sodium hypochlorite, iodine potassium iodide and chlorhexidine acetate are more effective than calcium hydroxide against C. albicans in vitro. However, combining calcium hydroxide with sodium hypochlorite or chlorhexidine may provide a wide-spectrum antimicrobial preparation with a long-lasting effect.
Using population viability analysis, genomics, and habitat suitability to forecast future population patterns of Little Owl Athene noctua across Europe

Abstract The agricultural scene has changed over the past decades, resulting in a declining population trend in many species. It is therefore important to determine the factors that the individual species depend on in order to understand their decline. The landscape changes have also resulted in habitat fragmentation, turning once continuous populations into metapopulations. It is thus increasingly important to estimate both the number of individuals it takes to create a genetically viable population and the population trend. Here, population viability analysis and habitat suitability modeling were used to estimate population viability and future prospects across Europe of the Little Owl Athene noctua, a widespread species associated with agricultural landscapes. The results show a high risk of population declines over the coming 100 years, especially toward the north of Europe, whereas populations toward the southeastern part of Europe have a greater probability of persistence. In order to be considered genetically viable, individual populations must count 1,000–30,000 individuals. As Little Owl populations of several countries count <30,000, and many isolated populations in northern Europe count <1,000 individuals, management actions resulting in exchange of individuals between populations or even countries are probably necessary to prevent losing <1% genetic diversity over a 100‐year period. At a continental scale, a habitat suitability analysis suggested Little Owl to be affected positively by increasing temperatures and urban areas, whereas an increased tree cover, an increasing annual rainfall, grassland, and sparsely vegetated areas affect the presence of the owl negatively. However, the low predictive power of the habitat suitability model suggests that habitat suitability might be better explained at a smaller scale.
The fine structure of the absorptive epithelial cells of the developing small intestine of the rat.

Early descriptions of the development of the mucous membranes of the mammalian small intestine, such as those of Hilton (1902) in the rat, and Johnson (1910) in the human, were largely concerned with the histogenesis of the organ, and cytological development received little attention. On the other hand recent investigations using modern techniques have been confined to relatively circumscribed cytological problems, ignoring the more general aspects. Thus ribosomes and polysomes in developing rat intestine have been studied by Behnke (1963 a, b); Overton & Shoup (1964) have observed the autogeny of the brush border in the chick; and Moog (1961) has examined the cells histochemically. The only accounts of general differentiation have been those of Bonneville (1963) and of van Lennep (1964). This survey aims to give a general description of the development of the jejunal absorptive epithelial cells in the rat, from the 13th day of pregnancy until birth.
Effect of luteinizing hormone antiserum on progesterone and 20 -dihydroprogesterone secretion in the pregnant rat.

The effect of a single injection of luteinizing hormone (LH) antiserum on ovarian progesterone and 20\g=a\-dihydroprogesteronein day-8 and day-15 pregnant rats was studied. Within 24 h of an injection of LH antiserum, progesterone secretion was reduced by 80% in day-8 and by 25 % in day-15 pregnant rats. The 20\g=a\-dihydroprogesteronelevels after antiserum treatment were markedly increased in rats which were 8 days pregnant but reduced in rats which were 15 days pregnant. The free cholesterol content of the ovary did not change after antiserum injection but the cholesteryl ester content markedly increased. It is thus apparent that neutralization of endogenous LH resulted in a significant reduction in the progesterone secretion of the corpus luteum of the pregnant rat. The significance of these results is discussed.