Miracle-dz/UniFAR-FTUs huggingface dataset:
Eradication of mucoid Pseudomonas aeruginosa with fluid liposome-encapsulated tobramycin in an animal model of chronic pulmonary infection

Despite controversies associated with forms and value of antibiotic therapy for cystic fibrosis patients, antibiotherapy remains a cornerstone in the management of those patients. Locally administered liposome-encapsulated antibiotics may offer advantages over free antibiotics, including sustained concentration of the antibiotic, minimal systemic absorption, reduced toxicity, and increased efficacy. We evaluated the efficacy of free and encapsulated tobramycin in fluid and rigid liposomal formulations administered to rats chronically infected with Pseudomonas aeruginosa. Chronic infection in lungs was established by intratracheal administration of 10(5) CFU of a mucoid variant of P. aeruginosa PA 508 prepared in agar beads. Antibiotic treatments were given intratracheally at time intervals of 16 h. After the last treatment, lung bacterial counts were determined and tobramycin levels in the lungs and kidneys were evaluated by high-performance liquid chromatographic analysis and microbiological assay. Two independent experiments showed that animals treated with encapsulated tobramycin in fluid liposomes had a number of CFU less than the minimal CFU number required to be statistically acceptable compared with > or = 10(6) CFU per pair of lungs for animals treated with encapsulated tobramycin in rigid liposomes, free antibiotic, or liposomes without tobramycin. Tobramycin measured in the lungs at 16 h after the last treatment following the administration of encapsulated antibiotic was still active, and its concentration was > or = 27 micrograms/mg of tissue. Low levels of tobramycin were detected in the kidneys (0.59 to 0.87 micrograms/mg of tissue) after the administration of encapsulated antibiotic, while 5.31 micrograms/mg of tissue was detected in the kidneys following the administration of free antibiotic. These results suggest that the local administration of fluid liposomes with encapsulated tobramycin could greatly improve the management of chronic pulmonary infection in cystic fibrosis patients.
Class 1 Integrons Potentially Predating the Association with Tn402-Like Transposition Genes Are Present in a Sediment Microbial Community

ABSTRACT Integrons are genetic elements that contribute to lateral gene transfer in bacteria as a consequence of possessing a site-specific recombination system. This system facilitates the spread of genes when they are part of mobile cassettes. Most integrons are contained within chromosomes and are confined to specific bacterial lineages. However, this is not the case for class 1 integrons, which were the first to be identified and are one of the single biggest contributors to multidrug-resistant nosocomial infections, carrying resistance to many antibiotics in diverse pathogens on a global scale. The rapid spread of class 1 integrons in the last 60 years is partly a result of their association with a specific suite of transposition functions, which has facilitated their recruitment by plasmids and other transposons. The widespread use of antibiotics has acted as a positive selection pressure for bacteria, especially pathogens, which harbor class 1 integrons and their associated antibiotic resistance genes. Here, we have isolated bacteria from soil and sediment in the absence of antibiotic selection. Class 1 integrons were recovered from four different bacterial species not known to be human pathogens or commensals. All four integrons lacked the transposition genes previously considered to be a characteristic of this class. At least two of these integrons were located on a chromosome, and none of them possessed antibiotic resistance genes. We conclude that novel class 1 integrons are present in a sediment environment in various bacteria of the β-proteobacterial class. These data suggest that the dispersal of this class may have begun before the “antibiotic era. ”
In Vivo Monitoring of Angiogenesis Inhibitory Treatment Effects by Dynamic Contrast-Enhanced Computed Tomography in a Xenograft Tumor Model

Rationale and Objectives:To evaluate the potential of dynamic CT enhanced by iohexol or a novel macromolecular contrast agent, PEG12000-Gen4-triiodo, to monitor microvascular changes in tumors treated with the angiogenesis inhibitor bevacizumab. Materials and Methods:Ten female nude rats with MDA-MB 435 xenograft tumors were treated with 1 mg intraperitoneal bevacizumab when tumors reached 1 cm diameter and, for 4 rats, treated again 7 days later. Just before and 24 hours after the first injection of anti-VEGF antibody, the tumors were imaged by dynamic CT scans enhanced with PEG12000-Gen4-triiodo (n = 3 rats) or iohexol (n = 3 rats). The other 4 rats underwent dynamic CT scans enhanced with PEG12000-Gen4-triiodo just before and 24 hours after the second injection of anti-VEGF antibody. Microvascular leakiness (KPS) was calculated for the tumors using a 2-compartment tissue model. Results:PEG12000-Gen4-triiodo-enhanced CT scans showed progressive reductions in KPS from day 1 to 2 to 9 (from 2.55 to 1.27 to 0.69 &mgr;L min−1 cm−3, respectively, P < 0.005 for each comparison of day 1–2 and day 2–9). No significant difference was seen in the KPS estimates derived from iohexol-enhanced CT scans obtained before or after treatment (276 vs. 223.8 &mgr;L min−1 cm−3, respectively, P = 0.54). The microvascular leak (KPS) was significantly larger for iohexol than for PEG12000-Gen4-triiodo-enhanced CT, P < 0.05. Conclusion:Dynamic macromolecular contrast-enhanced CT can be used to monitor serial decreases in tumor microvessel leakiness induced by repeated doses of an angiogenesis inhibitor drug.
Mental health and the built environment: cross-sectional survey of individual and contextual risk factors for depression.

BACKGROUND Little is known about the effects of the physical environment on individual health. AIMS The present study tested the hypothesis that the prevalence of depression is associated with independently rated measures of the built environment, after adjusting for individuals' socio-economic status and the internal characteristics of their dwellings. METHOD Cross-sectional survey of 1887 individuals aged 16 years and over in two electoral wards in north London. Depression was ascertained using the Center for Epidemiologic Studies Depression scale (CES-D). The built environment was rated independently, using a validated measure. RESULTS After adjusting for socio-economic status, floor of residence and structural housing problems, statistically significant associations were found between the prevalence of depression and living in housing areas characterised by properties with predominantly deck access (odds ratio=1.28, 95% CI 1.03-1.58; P=0.02) and of recent (post-1969) construction (odds ratio=1.43, 95% CI 1.06-1.91; P=0.02). CONCLUSIONS The prevalence of depression was associated with independently rated features of the built environment, independent of individuals' socio-economic status and internal characteristics of dwellings.
Comparison of fluoride uptake into tooth enamel from two fluoride varnishes containing different calcium phosphate sources.

OBJECTIVE The objective of this in vitro study was to compare two 5% sodium fluoride varnishes, each containing different sources of calcium and phosphate, for their ability to deliver fluoride into treated sound tooth enamel and adjacent, but untreated demineralized enamel. METHODS Six sets of 12 bovine enamel cores were mounted in plexiglass rods and the exposed surfaces were polished. Synthetic lesions were formed in the surface of three sets by soaking in thickened, pH 5.0, 1M lactic acid, 50% saturated with calcium hydroxyapatite. A fluoride varnish containing tri-calcium phosphate (TCP) was applied to one set of sound enamel cores, and a second, delivering amorphous calcium phosphate (ACP), was applied to another. A third set of sound enamel cores was water-treated. Each treated sound core was paired with an untreated lesioned core, and the pairs were soaked in artificial saliva for 24 hours at 37 degrees C. The treated cores, but not their lesioned counterparts, were initially soaked in 1.0 N KOH saturated with calcium phosphate for 18 hours. Each core was separately etched with 1.0 N perchloric acid for exactly 15 seconds, and fluoride measured by an ion-sensitive electrode after neutralizing with NaOH and buffering in TISAB II. The amount of calcium extracted was also determined by atomic absorption spectrophotometry as a measure of etch depth. RESULTS Fluoride uptake average was 1677 +/- 193 ppm, 455 + 38 ppm, and 44 +/- 5 ppm for the sound enamel cores treated with ACP varnish, TCP varnish, and water treatment, respectively. Fluoride uptake into the demineralized enamel averaged 5567 +/- 460 ppm, 2126 +/-126 ppm, and 49 -/+ 4 ppm for demineralized enamel paired with the sound cores treated with ACP varnish, TCP varnish, and water, respectively. The differences between the ACP varnish, the TCP varnish, and the water treatments were statistically significant (p < 0.05). CONCLUSION The ACP varnish formulation delivers statistically significantly more fluoride to both intact and demineralized enamel than the formulation containing TCP.
Dual translational initiation sites control function of the lambda S gene.

Lysis gene S of phage lambda has a 107 codon reading frame beginning with the codons Met1‐Lys2‐Met3. Genetic data have suggested that translational initiation occurs at both Met1 and Met3, generating two polypeptides, S107 and S105 respectively. We have proposed a model in which the proper scheduling of lysis depends on the partition of translational initiations between the two start codons. Here, using in vitro methods, we show that two stem‐loop structures, one immediately upstream of the reading frame and a second approximately 10 codons within the gene, control the partitioning event. Utilizing primer‐extension inhibition or ‘toeprinting’, we show that the two S start codons are served by two adjacent Shine‐Dalgarno sequences. Moreover, the timing of lysis supported by the wild‐type and a number of mutant alleles in vivo can be correlated with the ratio of ternary complex formation over Met1 and Met3 in vitro. Thus the regulation of the S gene is unique in that the products of two adjacent in‐frame initiation events have opposing function.
Integrins and Other Cell Adhesion Molecules in Endometrium and Endometriosis

Endometriosis is a disease that affects about 5% of women of reproductive age, but is found much more frequently in those with pelvic pain and/or infertility. In affected individuals, shed endometrium is thought to attach and spread within the pelvis through specific cell adhesion receptors. To understand why some women develop endometriosis while others do not, researchers have begun to examine these receptors and their extracellular matrix ligands. Cell adhesion molecules fall into 4 major groups including cadherins, selectins, members of the immunoglobulin superfamily, and integrins. Based on our current understanding, each may potentially play a role in the development or progression of this disease. In addition, the use of integrins as markers of the normal endometrial phenotype may be useful for the diagnosis of endometriosis and may identify women with defects in endometrial function leading to infertility or recurrent pregnancy loss. As more information becomes available, it may be possible to develop better treatments for endometriosis based on these concepts and to identify those women at risk for development of this common yet serious disorder.
Sexual harassment in work organizations: A view from the 21st century.

http://dx.doi. org/10.1037/0000060-012 APA Handbook of the Psychology of Women: Vol. 2. Perspectives on Women’s Private and Public Lives, C. B. Travis and J. W. White (Editors-in-Chief) Copyright © 2018 by the American Psychological Association. All rights reserved. The explosion of interest and research in sexual harassment, much of it dating to the 1990s and early 2000s, continues to demonstrate that its parameters are broader and more pervasive than originally thought. Women and girls are harassed not only in their workplaces and universities (Fitzgerald et al., 1988; Rospenda, Richman, & Shannon, 2009), but also by strangers in public (Davidson, Butchko, Robbins, Sherd, & Gervais, 2016), by landlords in their homes and apartments (Reed, Collinsworth, & Fitzgerald, 2005; Tester, 2008), by teachers and peers in high schools (Hill & Kearl, 2011), and even in middle schools (Davis v. Monroe County Board of Education, 1999; Espelage, Hong, Rinehart, & Doshi, 2016). Nurses are harassed by physicians (Williams, 1996) and female physicians by patients (Phillips & Schneider, 1993), service workers by customers (Gettman & Gelfand, 2007), hotel maids by guests (Kensbock, Bailey, Jennings, & Patiar, 2015), and female inmates by correctional officers (Bell et al., 1999). Harassment reaches down into middle schools, where it blends into more general bullying, and up the age scale into nursing homes (Levine, 2003), where it is characterized as “elder abuse,” thus obscuring its often sexual nature. Technology continues to provide new methods and venues for harassment (e.g., cell phones, video games, the Internet, untraceable message services; Barak, 2005), whereas the pervasive sexualization of youth culture, concomitant change in gendered sexual norms, and even the emergence of sexualized forms of nonsex work1 have rendered the models, as well as mores, of the last decade increasingly irrelevant. It is with some regret that we limit our present review to the classic issue of sexual harassment in work organizations. The reasons for this choice are many; as always, practicality and issues of space loom large; equally important, however, is the fact that the sheer heterogeneity and complexity that have emerged across the last three decades humbles any attempt at comprehensive summary, much less “grand theory. ” Such a project, though desirable and possibly ripe, is far too ambitious to be attempted here (see Chapter 9, this volume).
Histological and biomechanical changes in a mouse model of venous thrombus remodeling.

BACKGROUND Deep vein thrombosis and the risk of pulmonary embolism are significant causes of morbidity and mortality. Much remains unclear, however, about the mechanisms by which a venous thrombus initiates, progresses, or resolves. In particular, there is a pressing need to characterize the evolving mechanical properties of a venous thrombus for its mechanical integrity is fundamental to many disease sequelae. OBJECTIVE The primary goal of the present study was to initiate a correlation between evolving histological changes and biomechanical properties of venous thrombus. METHODS We employed an inferior vena cava ligation model in mice to obtain cylindrical samples of thrombus that were well suited for mechanical testing and that could be explanted at multiple times following surgery. Using uniaxial micro-mechanical testing, we collected stress-stretch data that were then fit with a microstructurally-inspired material model before submitting the samples to immunohistological examination. RESULTS We found that venous thrombus underwent a radially inward directed replacement of fibrin with collagen between 2 weeks and 4 weeks of development, which was accompanied by the infiltration of inflammatory and mesenchymal cells. These histological changes correlated with a marked increase in material stiffness. CONCLUSIONS We demonstrated that 2 to 4 week old venous thrombus undergoes drastic remodeling from a fibrin-dominated mesh to a collagen-dominated microstructure and that these changes are accompanied by dramatic changes in biomechanical behavior.
Work area measurements as predictors of personal exposure to endotoxin and cotton dust in the cotton textile industry.

OBJECTIVES To determine if work area measurements of endotoxin and/or cotton dust obtained from the vertical elutriator (VE) can be used to predict levels of personal endotoxin exposure as measured by the Institute of Occupational Medicine (IOM) inhalable dust sampler in the cotton textile industry. METHODS Fifty-six work area cotton dust samples were collected from 14 areas and 82 personal cotton dust samples were collected from 41 workers in three textile mills (Mills A, B and C) in Shanghai, China. Cotton dust concentrations were determined gravimetrically from sample filters, of which endotoxin concentrations were determined using a kinetic chromogenic modification of the limulus amoebocyte lysate assay. Linear regression models were used to determine the association between log IOM personal endotoxin concentration and log VE area endotoxin concentration. RESULTS Median cotton dust and endotoxin concentrations measured from VE area samples in the three mills were 0.36 mg m(-3) and 1280.76 endotoxin units per cubic meter (EU m(-3)), respectively, compared to 1.74 mg m(-3) and 2226.83 EU m(-3) from IOM personal samples. Excluding samples from weaving processes, we observed linear associations between VE area measures of endotoxin and IOM personal endotoxin concentrations; VE area concentration of endotoxin explained 83 and 89% of the total variation in IOM personal endotoxin concentration for Mills A and B, respectively (Mill A: R2 = 0.83, P < 0.0001; Mill B: R2 = 0.89, P < 0.0001). Although area measures of cotton dust was also a significant predictor of person endotoxin, the model explained less of the variance in personal endotoxin measurements. CONCLUSIONS Specific to the conditions of the textile mills investigated in this study, work area measurements of endotoxin, but not cotton dust, may be reasonable proxies for personal levels, at least for rank-ordering exposures.
Use of procalcitonin for the prediction and treatment of acute bacterial infection in children

Purpose of review Procalcitonin (PCT) is increasingly utilized to determine the presence of infection or to guide antibiotic therapy. This review will highlight the diagnostic and prognostic utility of serum PCT in children. Recent findings Recent studies endorse the use of serum PCT to detect invasive infection, to differentiate sepsis from noninfectious systemic inflammatory response syndrome, and to guide antibiotic therapy. Typical values for maximal sensitivity and specificity are less than 0.5 ng/ml for noninfectious inflammation and greater than 2.0 ng/ml for bacterial sepsis. PCT appears to be a reliable indicator of infection. PCT has performed better than C-reactive protein in some settings, though pediatric comparative data are lacking. PCT may aid in diagnosing infection in challenging patient populations such as those with sickle cell disease, congenital heart defects, neutropenia, and indwelling central venous catheters. Antibiotic therapy tailored to serial PCT measurements may shorten the antibiotic exposure without increasing treatment failure. Summary PCT is a reliable serum marker for determining the presence or absence of invasive bacterial infection and response to antibiotic therapy. Tailoring antibiotics to PCT levels may reduce the duration of therapy without increasing treatment failure, but more research is needed in children.
The chromatin environment shapes DNA replication origin organization and defines origin classes

To unveil the still-elusive nature of metazoan replication origins, we identified them genome-wide and at unprecedented high-resolution in mouse ES cells. This allowed initiation sites (IS) and initiation zones (IZ) to be differentiated. We then characterized their genetic signatures and organization and integrated these data with 43 chromatin marks and factors. Our results reveal that replication origins can be grouped into three main classes with distinct organization, chromatin environment, and sequence motifs. Class 1 contains relatively isolated, low-efficiency origins that are poor in epigenetic marks and are enriched in an asymmetric AC repeat at the initiation site. Late origins are mainly found in this class. Class 2 origins are particularly rich in enhancer elements. Class 3 origins are the most efficient and are associated with open chromatin and polycomb protein-enriched regions. The presence of Origin G-rich Repeated elements (OGRE) potentially forming G-quadruplexes (G4) was confirmed at most origins. These coincide with nucleosome-depleted regions located upstream of the initiation sites, which are associated with a labile nucleosome containing H3K64ac. These data demonstrate that specific chromatin landscapes and combinations of specific signatures regulate origin localization. They explain the frequently observed links between DNA replication and transcription. They also emphasize the plasticity of metazoan replication origins and suggest that in multicellular eukaryotes, the combination of distinct genetic features and chromatin configurations act in synergy to define and adapt the origin profile.
Indigenous Knowledge in Governance of REDD+ for Climate Change Mitigation in Tanzania: Opportunities and Challenges

Abstract Reducing Emissions from Deforestation and Forest Degradation (REDD) governance is a climate change mitigation measure with opportunities and challenges. A case is made for development of a hybrid environmental ethics in Tanzania, based on indigenous knowledge and other knowledge systems. There is impressive progress made in the establishment of structures at the national and district levels with build-up of a complex system that presents considerable challenges as well as opportunities. There is an opportunity to involve indigenous communities, increase financial streams and improve on existing systems. Improvements to the REDD+ framework should be robust in addressing the diverse emerging issues and the wide range of stakeholders and interest groups and must be put within the broader context of Tanzania’s priorities of livelihood improvement and poverty alleviation. Proper mapping of indigenous communities, research and capacity building programmes should be undertaken.
Isolation frequency and growth properties of HIV‐variants: Multiple simultaneous variants in a patient demonstrated by molecular cloning

The biological properties and efficiency of isolation of different HIV (LAV/HTLV III, ARV, and AAV) subtypes were evaluated by recovering and growing HIV on fresh peripheral human lymphocytes. Cultures for virus isolaton were performed from more than 180 German AIDS, ARC, LAS, and virus‐exposed asymptomatic patients. The virus isolation rate depended on the state of health of the patients being close to 80% in AIDS patients, 3040% in ARC/LAS patients, and lower in asymptomatic HIV seropositive patients.
Emotional Problems of Displaced Children

IT IS A WELL-KNOWN fact today that all emigres have difficulties in readjustment when they reach a new country. We have all seen that emigrants suffer at first from low spirits, that they all have a typical kind of anxiety, usually the fear of starvation, even if they are living in comfortable circumstances and there is no reality basis for their depression and fears. In the article "Homesickness and the Mother's Breast," 1 I have demonstrated that the loss of the mother country is very often experienced as an oral loss, that the loss of the homeland is experienced as identical with the trauma of weaning. One might expect that displaced children and adolescents coming to this country after the trying experiences of concentration camps and Nazi persecution would present fewer problems when they are finally settled in a secure and stabilized environment. From consultation with social agencies, however, it became obvious to me that the displaced children had certain problems that were still present at a time when the difficulties of readjustment to a new coun-