Elevated Levels of circRUNX1 in Colorectal Cancer Promote Cell Growth and Metastasis via miR-145-5p/IGF1 Signalling.
Emerging evidence suggests that circular RNAs (circRNAs) are vital regulators in a range of cancers. "miRNA sponge" is the most reported role played by circRNAs in many tumors. The insulin-like growth factor (IGF) 1 pathway plays a key role in the development and progression of many cancers, including colorectal cancer (CRC). The aim of the study is to establish the potential clinical value and driving molecular mechanisms of circRNAs in CRC. Real-time quantitative RT-PCR (qRT-PCR) was performed to measure the circRUNX1 expression in 52 tissue samples from CRC patients. We verified the tumor promotor role of circRUNX1 in cell-based in vitro and in vivo assays. Human growth factor array was used to identify circRUNX1-regulated signaling pathways. We then used a double luciferase reporter assay and RNA fluorescence in situ hybridization to identify the downstream miR-145-5p of circRUNX1. Furthermore, we performed Western blotting and biological function assays to demonstrate if the circRUNX1/miR-145-5p/IGF1 axis is responsible for the proliferation of CRC cells and promotes CRC development. By performing qRT-PCR from CRC tissues and paired adjacent normal mucosa tissues, we identified that circRUNX1 expression was significantly upregulated in CRC tissues and positively related with lymph node metastasis, distant metastasis and advanced tumor-node-metastasis tumor stage in patients. Functionally, circRUNX1 knockdown inhibited cell proliferation and migration and promoted apoptosis, whereas its overexpression exerted opposite effects. In vivo, circRUNX1 promoted tumor growth and metastasis. Mechanically, circRUNX1 shared miRNA response elements with IGF1. circRUNX1 competitively bound to miR-145-5p and prevented miR-145-5p from decreasing the expression of IGF1, which facilitated tumor growth. Our studies verified that circRUNX1 functions as a tumor promotor in CRC cells by targeting the miR-145-5p/IGF1 signaling pathway and may have potential use as a prognostic indicator and therapeutic target in CRC patients.


[Cerebral damage due to hypoglycaemia in otherwise healthy breast-fed term infants].
Two healthy breast-fed term infants were admitted to the neonatal unit with symptomatic hypoglycaemia and seizures. In both patients, risk factors (i.e. hypothermia) and symptoms ofhypoglycaemia went unrecognised until apnoea or seizures developed. Both patients required antiepileptic medication for neonatal seizures. One patient had isolated restricted growth in head circumference in the first year of life. Follow-up at II years showed cognitive impairment and epilepsy. The other patient had normal head circumference and mild global delay in neurological development at the age of 36 months. Severe symptomatic hypoglycaemia in healthy breast-fed term infants may cause severe brain damage. Early recognition of risk factors such as hypothermia lasting more than 3 hours is essential to preventing hypoglycaemia. The presence of risk factors warrants additional bottle-feeding to maintain sufficient intake until breastfeeding is adequately established. Any uncertainty regarding the symptoms of hypoglycaemia should be investigated promptly.


Insulin receptor binding from mid-term and full-term placentas of patients with gestational diabetes mellitus and normal pregnant women.
Insulin receptor binding was examined in the microvillous membranes of mid-term (20-22 weeks of gestation, MT) and full-term (FT) placentas from patients with gestational diabetes mellitus (GDM) and in normal pregnant control (N). Mid-term placentas were obtained from patients who have had spontaneous abortion. The maximum per cent specific binding (%SB) in MT placenta for GDM was significantly lower (4.8%) compared with the FT placenta (22%, p < 0.001), while in the N group the maximum per cent specific binding for MT placenta was 14.1% compared with 26% for the FT placenta (p < 0.001). Binding data from FT placenta of well-controlled GDM patients were similar with the FT placenta from N group (22% SB for GDM VS 26% SB for N). Even as there were similarities in the binding characteristics of FT placentas from both groups the placental membrane protein content in the GDM group was lower by 50% compared with the N control (2.5 +/- 0.11 VS 4.8 +/- 0.15 mg protein/g placenta respectively, p < 0.001) suggesting that in the GDM group achieving a tight glycemic control could improve receptor affinities. Data from the competitive binding assay of GDM patients showed that the insulin necessary to achieve 50% inhibition (ID50) was significantly lower in MT compared with the FT placenta (0.9 x 10(-9) M VS 3.8 x 10(-9) M, p < 0.001) but in the N placenta there was no alteration in the ID50 of MT and FT placentas (3.1 x 10(-9) M VS 4 x 10(-9) M, p < 0.01, respectively). The present study demonstrated that in GDM the placental insulin receptor binding was significantly lower in spontaneously aborted placenta compared with placentas collected at full-term. Furthermore, these data suggest that the objective to achieve a tight glycemic control in GDM patients could optimize insulin receptor function similar to that of a normal pregnancy. Thus a full term placenta from GDM patients under a well managed glycemic control throughout the entire duration of pregnancy would result in an optimum insulin receptor function.


An Alexandrium Spp. Cyst Record from Sequim Bay, Washington State, USA, and its Relation to Past Climate Variability(1).
Since the 1970s, Puget Sound, Washington State, USA, has experienced an increase in detections of paralytic shellfish toxins (PSTs) in shellfish due to blooms of the harmful dinoflagellate Alexandrium. Natural patterns of climate variability, such as the Pacific Decadal Oscillation (PDO), and changes in local environmental factors, such as sea surface temperature (SST) and air temperature, have been linked to the observed increase in PSTs. However, the lack of observations of PSTs in shellfish prior to the 1950s has inhibited statistical assessments of longer-term trends in climate and environmental conditions on Alexandrium blooms. After a bloom, Alexandrium cells can enter a dormant cyst stage, which settles on the seafloor and then becomes entrained into the sedimentary record. In this study, we created a record of Alexandrium spp. cysts from a sediment core obtained from Sequim Bay, Puget Sound. Cyst abundances ranged from 0 to 400 cysts · cm(-3) and were detected down-core to a depth of 100 cm, indicating that Alexandrium has been present in Sequim Bay since at least the late 1800s. The cyst record allowed us to statistically examine relationships with available environmental parameters over the past century. Local air temperature and sea surface temperature were positively and significantly correlated with cyst abundances from the late 1800s to 2005; no significant relationship was found between PDO and cyst abundances. This finding suggests that local environmental variations more strongly influence Alexandrium population dynamics in Puget Sound when compared to large-scale changes.


Functional levels of alpha 2-macroglobulin in plasma in relation to emphysema.
In most studies, concentrations of alpha 2-macroglobulin are determined by immunological techniques. In this study, the amidolytic activity of porcine pancreatic elastase complexed with alpha 2-macroglobulin was measured using an elastase-specific substrate, succinyl-trialanyl-p-nitroanilide. The activities of plasmas from 47 emphysema cases were compared with 39 normal subjects. The age ranges of both groups were from 50 to 84 years. The mean activity of bound elastase in emphysema cases was 2.48 +/- 0.03 kU/l of plasma. The mean for normal subjects was 1.48 +/- 0.11 kU/l of plasma. The difference was very significant (2P less than 0.001). All except 2 of the emphysema cases had smoked. The same results were obtained when only people who had smoked for 25 years or more were included in the analysis. All the plasma samples of people included in the study were assayed by an immunological method for absolute level (in g/l) of alpha 1-proteinase inhibitor. The levels of alpha 1-proteinase inhibitor for all the persons studied fell within the normal range for MM-phenotypes (2 to 4 g/l).


Charting the protein complexome in yeast by mass spectrometry.
It has become evident over the past few years that many complex cellular processes, including control of the cell cycle and ubiquitin-dependent proteolysis, are carried out by sophisticated multisubunit protein machines that are dynamic in abundance, post-translational modification state, and composition. To understand better the nature of the macromolecular assemblages that carry out the cell cycle and ubiquitin-dependent proteolysis, we have used mass spectrometry extensively over the past few years to characterize both the composition of various protein complexes and the modification states of their subunits. In this article we review some of our recent efforts, and describe a promising new approach for using mass spectrometry to dissect protein interaction networks.


High throughput nanoparticle tracking analysis for monitoring outer membrane vesicle production.
Outer membrane vesicles (OMVs) are spherical membrane nanoparticles released by Gram-negative bacteria. OMVs can be quantified in complex matrices by nanoparticle tracking analysis (NTA). NTA can be performed in static mode or with continuous sample flow that results in analysis of more particles in a smaller time-frame. Flow measurements must be performed manually despite the availability of a sample changer on the NanoSight system. Here we present a method for automated measurements in flow mode. OMV quantification in flow mode results in lower variance in particle quantification (coefficient of variation (CV) of 6%, CV static measurements of 14%). Sizing of OMVs was expected to be less favorable in flow mode due to the increased movement of the particles. However, we observed a CV of 3% in flow mode and a CV of 8% in static measurements. Flow rates of up to 5 µL/min displayed correct size and particle measurements, however, particle concentration was slightly lower than in static measurements. The automated method was used to assess OMV release of batch cultures of Neisseria meningitidis. The bacteria released more OMVs in stationary growth phase, while the size of the vesicles remained constant throughout the culture. Taken together, this study shows that automated measurements in flow mode can be established with advanced scripting to reduce the workload for the user.


Infiltrating the Curriculum: Integrating Medical History with Existing Surgical Pathology Tutorials.
This article was migrated. The article was marked as recommended. Objective: To assess medical students' perspective on medical history embedded into a pre-existing learning module. Design, Setting, and Participants: This study was performed in 2018 at the University of Tasmania; participants were medical students in year three of the Bachelor of Medicine Bachelor of Surgery course. This was a cross-sectional study which used a mixed-method survey before and after a lecture series to assess medical students' perspectives on history of medicine. Intervention: Historical perspectives were incorporated into existing surgical pathology tutorials. Main outcome measures: Students completed a survey on medical history before and after the lecture series. The survey used both qualitative and quantitative measures to assess students' perception of the utility of medical history and how it was taught in this project. Results: In the initialquestionnaire, students indicated they believed medical history would help make them better doctors and enhance their learning of pathology. In the final questionnaire, students agreed that learning medical history was important in becoming a doctor. Students enjoyed the content and found the integration of history and pathology beneficial to learning. Conclusion: This study demonstrates one method by which to increase medial history teaching without major alterations to an existing medical curriculum.


O-methyl sugars in lipopolysaccharides of Rhodospirillaceae. Identification of 3-O-methyl-D-mannose in Rhodopseudomonas viridis and of 4-O-methyl-D-xylose and 3-O-methyl-6-deoxy-D-talose in Rhodopseudomonas palustris respectively.
1. This paper deals with the identification of three O-methyl sugars in lipopolysaccharides isolated from strains of the Gram-negative photosynthetic family Rhodospirillaceae. In addition to the previously described 3-O-methyl-l-xylose, a second O-methyl sugar was encountered in the lipopolysaccharide of Rhodopseudomonas viridis F, namely 3-O-methyl-d-mannose. The lipopolysaccharides of two strains of Rhodopseudomonas palustris (strain 1e5 and 8/1) contain two O-methylsugars, 4-O-methyl-d-xylose and 3-O-methyl-6-deoxy-d-talose (d-acovenose). 4-O-Methyl-d-xylose, but not 3-O-methyl-6-deoxy-d-talose, could be identified in the lipopolysaccharides of the strains K/1 and 2/2 of the same species. 2. The O-methyl sugars described in this communication were isolated by paper chromatography and identified by g.l.c., paper chromatography, high-voltage electrophoresis and mass spectrometry. Besides the genuine sugars, their alditol acetates and their demethylated (parental) forms were investigated. Optical rotation measurements and, in one case, enzymic reactions were used to establish the optical configuration of the sugars under investigation.


2,2',3,3',6,6'-hexachlorobiphenyl hydroxylation by active site mutants of cytochrome P450 2B1 and 2B11.
The structural basis of species differences in cytochrome P450 2B-mediated hydroxylation of 2,2',3,3',6,6'-hexachlorobiphenyl (236HCB) was evaluated by using 14 site-directed mutants of cytochrome P450 2B1 and three point mutants of 2B11 expressed in Escherichia coli. To facilitate metabolite identification, seven possible products, including three hydroxylated and four dihydroxylated hexachlorobiphenyls, were synthesized by direct functionalization of precursors and Ullmann and crossed Ullmann reactions. HPLC and GC/MS analysis and comparison with authentic standards revealed that 2B1, 2B11, and all their mutants produced 4, 5-dihydroxy-236HCB and 5-hydroxy-236HCB, while 2B11 L363V and 2B1 I114V mutants also catalyzed hydroxylation at the 4-position. The amount of products formed by 2B1 mutants I114V, F206L, L209A, T302S, V363A, V363L, V367A, I477A, I477L, G478S, I480A, and I480L was smaller than that of the wild type. I477V exhibited unaltered 236HCB metabolism, and I480V produced twice as much dihydroxy product as the wild type. For 2B11, substitution of Val-114 or Asp-290 with Ile decreased the product yields. Replacement of Leu-363 with Val dramatically altered the profile of 236HCB metabolites. In addition to an increase in the overall level of hydroxylation, the mutant mainly catalyzed hydroxylation at the 4-position. Incubation of P450 2B1 with 5-hydroxy-236HCB produced 4,5-dihydroxy-236HCB, which indicates that 4,5-dihydroxy-236HCB may be formed by a direct hydroxylation of 5-hydroxy-236HCB. The findings from this study demonstrate the importance of residues 114, 206, 209, 302, 363, 367, 477, 478, and 480 in 2B1 and 114, 290, and 363 in 2B11 for 236HCB metabolism.


Curve-fitting overlapped bands: quantification and improvement of curve-fitting robustness in the presence of errors in the model and in the data.
Estimation of the band parameters of overlapped bands often relies on curve-fitting. It has been demonstrated that curve-fitting provides the maximum likelihood estimation of band parameters under a series of assumptions. One of these assumptions is that the curve-fitting model is correct and any error in the data is random. Under real conditions, we have to acknowledge the unavoidable presence of errors in the model and systematic errors in the data. Here, we derive an expression for the estimation of how these errors affect the quality of the parameters obtained from curve-fitting. In addition, we derive theoretical expressions to quantify the extent to which different methods can improve the curve-fitting robustness to these errors. The methods considered are: (i) deterministic and (ii) probabilistic constraints in the band parameters, (iii) curve-fitting band-narrowed data, and (iv) building a more accurate model. The theoretical expressions obtained are tested in the curve-fitting of a synthetic noisy spectrum with either baseline or band shape errors, and in the curve-fitting of the experimental infrared amide I band of the membrane protein bacteriorhodopsin.


Paenibacillus chinjuensis sp. nov., a novel exopolysaccharide-producing bacterium.
A novel exopolysaccharide-producing bacterium (WN9T) was isolated from Chinju, Korea, and was identified as a member of the genus Paenibacillus on the basis of phenotypic characteristics and phylogenetic inference based on 16S rDNA sequence. This organism is a facultatively anaerobic, endospore-forming rod. The diamino acid found in the peptidoglycan is meso-diaminopimelic acid. The predominant menaquinone is MK-7. The major cellular fatty acid is anteiso-C15:0. The G+C content is 53 mol%. The phylogenetic tree shows that strain WN9T falls within the radiation of a cluster comprising the Paenibacillus species. The levels of 16S rDNA similarity between strain WN9T and the type strains of validly described Paenibacillus species are 92.1-95.8%. Strain WN9T is clearly distinguishable from some phylogenetically related Paenibacillus species on the basis of DNA-DNA relatedness data and phenotypic characters. Therefore, on the basis of these data, a novel species of the genus Paenibacillus, Paenibacillus chinjuensis sp. nov., is proposed. The type strain is strain WN9T (= KCTC 8951PT = JCM 10939T).


Nrt1 and Tna1-independent export of NAD+ precursor vitamins promotes NAD+ homeostasis and allows engineering of vitamin production.
NAD(+) is both a co-enzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD(+) consuming enzymes. NAD(+) biosynthesis is required for two different regimens that extend lifespan in yeast. NAD(+) is synthesized from tryptophan and the three vitamin precursors of NAD(+): nicotinic acid, nicotinamide and nicotinamide riboside. Supplementation of yeast cells with NAD(+) precursors increases intracellular NAD(+) levels and extends replicative lifespan. Here we show that both nicotinamide riboside and nicotinic acid are not only vitamins but are also exported metabolites. We found that the deletion of the nicotinamide riboside transporter, Nrt1, leads to increased export of nicotinamide riboside. This discovery was exploited to engineer a strain to produce high levels of extracellular nicotinamide riboside, which was recovered in purified form. We further demonstrate that extracellular nicotinamide is readily converted to extracellular nicotinic acid in a manner that requires intracellular nicotinamidase activity. Like nicotinamide riboside, export of nicotinic acid is elevated by the deletion of the nicotinic acid transporter, Tna1. The data indicate that NAD(+) metabolism has a critical extracellular element in the yeast system and suggest that cells regulate intracellular NAD(+) metabolism by balancing import and export of NAD(+) precursor vitamins.


First-Principles Computational Screening of Perovskite Hydrides for Hydrogen Release.
This study investigates perovskite hydrides (ABH3) comprising alkali metals of A, where A is Li, Na, K, Rb, or Cs, and alkaline-earth metals of B, where B is Be, Mg, Ca, Sr, or Ba, to screen the highest potential hydrides for hydrogen release. Herein, we investigated the most favorable dehydrogenation pathway for each ABH3 system and found that NaCaH3 was the most attractive ABH3 system. Analysis was performed to determine the influence of the alkali dopants (at the A-site) and alkaline-earth dopants (at the B-site) on hydrogen release from NaCaH3. For this analysis, we calculated the reaction enthalpies of a NaCaH3 system for hydrogen release with different dopants and pathways. Cs was the best dopant for improving hydrogen release with the lowest reaction enthalpy. However, no clear effect from B-site doping on the dehydrogenation was found.


Ab Initio Simulations of Poorly and Well Equilibrated (CH3CN)n- Cluster Anions: Assigning Experimental Photoelectron Peaks to Surface-Bound Electrons and Solvated Monomer and Dimer Anions.
Excess electrons in liquid acetonitrile are of particular interest because they exist in two different forms in equilibrium: they can be present as traditional solvated electrons in a cavity, and they can form some type of solvated molecular anion. Studies of small acetonitrile cluster anions in the gas phase show two isomers with distinct vertical detachment energies, and it is tempting to presume that the two gas-phase cluster anion isomers are precursors of the two excess electron species present in bulk solution. In this paper, we perform DFT-based ab initio molecular dynamics simulations of acetonitrile cluster anions to understand the electronic species that are present and why they have different binding energies. Using a long-range-corrected density functional that was optimally tuned to describe acetonitrile cluster anion structures, we have theoretically explored the chemistry of (CH3CN)n- cluster anions with sizes n = 5, 7, and 10. Because the temperature of the experimental cluster anions is not known, we performed two sets of simulations that investigated how the way in which the cluster anions are prepared affects the excess electron binding motif: one set of simulations simply attached excess electrons to neutral (CH3CN)n clusters, providing little opportunity for the clusters to relax in the presence of the excess electron, while the other set allowed the cluster anions to thermally equilibrate near room temperature. We find that both sets of simulations show three distinct electron binding motifs: electrons can attach to the surface of the cluster (dipole-bound) or be present either as solvated monomer anions, CH3CN-, or as solvated molecular dimer anions, (CH3CN)2-. All three species have higher binding energies at larger cluster sizes. Thermal equilibration strongly favors the formation of the valence-bound molecular anions relative to surface-bound excess electrons, and the dimer anion becomes more stable than the monomer anion and surface-bound species as the cluster size increases. The calculated photoelectron spectra from our simulations in which there was poor thermal equilibration are in good agreement with experiment, suggesting assignment of the two experimental cluster anion isomers as the surface-bound electron and the solvated molecular dimer anion. The simulations also suggest that the shoulder seen experimentally on the low-energy isomer's detachment peak is not part of a vibronic progression but instead results from molecular monomer anions. Nowhere in the size range that we explore do we see evidence for a nonvalence, cavity-bound interior-solvated electron, indicating that this species is likely only accessible at larger sizes with good thermal equilibration.


Socioeconomic status and alcohol use disorders across the lifespan: A co-relative control study.
Alcohol use disorders (AUD) is well known to aggregate in families and is associated with socioeconomic status (SES). The objective was to study the effect of education, income and neighborhood SES in adulthood on AUD, and to explore whether the potential associations were confounded by shared familial factors, by using a co-relative control design. Data on AUD was drawn from the Swedish inpatient and outpatient care registers; prescription drug register; and crime data. Through national population registers we collected information on income, education and neighborhood SES at age 25, 30, 35 and 40 years in all individuals born in Sweden between 1950 and 1980. Each sex-specific stratum consisted of approximately 750,000-1,200,000 individuals, who were followed for AUD for a mean follow-up time ranging between 10 and 15 years until the end of 2013. Cox proportional hazards models were used to investigate the risk of AUD as a function of income, education and neighborhood SES in the general population and in pairs of first cousins and full siblings within the same sex, who differed in their exposure to the SES measure. Higher educational level, higher income and higher neighborhood SES were all associated with a reduced risk for AUD for both males and females in all ages. The potentially protective effect remained but was attenuated when comparing pairs of first cousins and full siblings. High educational level and income in adulthood, as well as high neighborhood socioeconomic status, may represent protective factors against alcohol use disorders, even when shared familial factors, e.g. childhood socioeconomic status and genetic factors, have been taken into account.


Crystallization and characterization of a fragment of pseudouridine synthase RluC from Escherichia coli.
RluC from E. coli is the enzyme responsible for catalyzing the isomerization of uridines 955, 2504 and 2580 in 23S rRNA to pseudouridine. Histidine-tagged RluC was cloned, overexpressed and purified by nickel-affinity chromatography. A proteolytically derived fragment of the enzyme consisting of residues 89-319 has been shown to retain catalytic activity. Crystals of this fragment, grown by precipitation with sodium acetate at pH 8.0, belong to space group P321, with unit-cell dimensions a = b = 97.1, c = 86.3 A and have two molecules in the crystallographic asymmetric unit. The flash-frozen crystals diffract X-rays to at least 2.3 A resolution and appear suitable for crystal structure determination.


Differences in Infant Diet Quality Index by Race and Ethnicity Predict Differences in Later Diet Quality.
Racial and ethnic disparities in infant-feeding practices may negatively influence diet quality and health. This study investigated the racial, ethnic, and language (English or Spanish) differences in infant diet quality, later diet quality, and weight status at 2-5 y, and whether these differences were explained through infant diet quality among participants in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Using the WIC Infant and Toddler Feeding Practices Study-2 (unweighted n = 2663; weighted n = 362,712), relationships between the Infant Dietary Quality Index (IDQI; range 0-1) and Healthy Eating Index-2020 (HEI-2020; range 0-100) and BMI z-score (BMIz) at 2-5 y were analyzed by race, ethnicity, and language preference [Hispanic Spanish-speaking, Hispanic English-speaking, non-Hispanic (NH) White, and NH Black participants]. Statistical interaction between IDQI and each group was evaluated in multivariable models. The mediation of each group through the IDQI was assessed using causal mediation methods. Differences in IDQI [mean (standard deviation)] were observed between Hispanic Spanish-speaking participants [0.41 (0.10)], Hispanic English-speaking participants [0.37 (0.10)], NH White participants [0.36 (0.10)], and NH Black participants [0.35 (0.09)], P < 0.001. Differences in HEI-2020 occurred at 2-5 y, with the Hispanic Spanish-speaking participants having consistently higher HEI-2020 scores. Differences in BMIz were observed at 5 y, with higher scores among Hispanic Spanish-speaking participants. Interaction between race, ethnicity, and IDQI was observed for all outcomes except for BMIz at 3 y. Through mediation, IDQI explained 13%-20% of the difference in HEI-2020 scores between Hispanic Spanish-speaking and NH White participants at 2-5 y. IDQI explained 22%-25% of the difference in HEI-2020 scores between the Hispanic Spanish-speaking and NH Black participants at 4 y and 5 y. Higher infant diet quality scores observed in Hispanic Spanish-speaking participants explain some of the racial and ethnic differences observed in later diet quality, suggesting that improving infant diet quality may help reduce diet disparities during early childhood.


A spectacular new leaf-tailed gecko (Carphodactylidae: Saltuarius) from the Melville Range, north-east Australia.
Leaf-tailed geckos are a distinctive group of carphodactyline geckos of rainforests and rocky habitats of eastern Australia. Three genera are recognized: Phyllurus (9 species), Saltuarius (6 species) and Orraya (1 species). Leaf-tailed geckos have been the subject of much survey and taxonomic work because they are large, impressive geckos and generally have highly localized distributions. The six species comprising Saltuarius are distributed in rock outcrops and rainforests along the ranges from northern New South Wales to the Wet Tropics region of north-east Queensland. Here we report the discovery of a new Saltuarius species at Cape Melville, a rainforest outlier on Cape York Peninsula in north-east Queensland. The new species is assigned to Saltuarius based on morphological and genetic data. Saltuarius eximius sp. nov. is highly distinct from all congeners in many aspects of morphology. It has a very long slender form, with relatively longer limbs, lon- ger body, narrower body and narrower neck than all congeners. It also has a highly distinct head that is relatively smaller than that of all other Saltuarius, with very large eyes that are grey rather than patterned. The tail is large but with a relatively short attenuated tip. Saltuarius eximius sp. nov. appears to be highly localized to upland rainforest associated with boulder habitat in the Cape Melville Range. The unusual elongate form and large eyes of S. eximius sp. nov. likely reflect adaptation to deep boulder habitat. Two other new vertebrate species (a skink and a frog) were discovered in the rainforest and boulder-fields of Cape Melville during recent surveys, bringing the number of vertebrates known to be endemic to the Cape Melville Range to six (three frogs, two skinks and one gecko).


Focal, transient mechanical narrowing of a pipeline embolization device following treatment of an internal carotid artery aneurysm.
Flow diversion is a promising technique for cerebral aneurysm treatment but presents new and sometimes unique challenges. Transient reversible narrowing due to device reconfiguration of the pipeline embolization device (PED) has not been previously described. Here we describe a patient with dolichoectasia of the distal right internal carotid artery with an associated saccular sidewall aneurysm who developed asymptomatic circumferential narrowing of the proximal aspect of the PED in the first month following deployment. The patient was followed conservatively and demonstrated partial resolution of device narrowing on 6 month follow-up imaging.


Comments on EuroFlow standard operating procedures for instrument setup and compensation for BD FACS Canto II, Navios and BD FACS Lyric instruments.
This commentary discusses particularities of application of the EuroFlow standardization of flow cytometric analyses on three different flow cytometers. The EuroFlow consortium developed a fully standardized approach for flow cytometric immunophenotyping of hematological malignancies and primary immunodeficiencies. Standardized instrument setup is an essential part of EuroFlow standardization. Initially, the EuroFlow Consortium developed and optimized a step-by-step standard operating procedure (SOP) to setup 8-color BD FACSCanto II flow cytometer (Canto), with the later inclusion of Navios (Beckman Coulter) and BD FACSLyric (Lyric). Those SOPs were developed to enable standardized and fully comparable fluorescence measurements in the three flow cytometers. In Canto and Navios, mean fluorescence intensity (MFI) of a reference peak of Rainbow beads calibration particles is used to set up photomultiplier (PMT) voltages for each detector channel in individual instruments to reach the same MFI across distinct instruments. In turn, a new feature of Lyric instruments allows to share collection of attributes that are used to place the positive population at the same position among instruments in the form of assays, as one of its components integrated in the Cytometer Setup and Tracking (CS&T) module. The EuroFlow Lyric assays thus allow for standardized acquisition of 8-color EuroFlow panels on Lyric without the need to setup the PMT voltages on the individual instruments manually. In summary, the standardized instrument setup developed by EuroFlow enables cross-platform inter- and intra-laboratory standardization of flow cytometric measurements. This commentary provides a perspective on the modifications of the standardized EuroFlow instrument setup of Canto, Navios and Lyric instruments that are described in detail in individual instrument-specfic SOPs available at the EuroFlow website.


Stimulation of interleukin 1 and 3 production by retinoic acid in vitro.
Retinoic acid and other retinoids stimulate or inhibit a number of immune responses, but their mechanism of action on immune cells is not fully understood. However, retinoids have been shown to inhibit interferon production, so they could act by influencing the production of lymphokines. Hence we have studied the effect of retinoic acid on the production of interleukins (ILs) 1 and 3 in vitro. Models for the production of ILs were the murine macrophage cell line P388D1 and human peripheral blood mononuclear cells for IL 1 and the murine WEHI-3 cell line for IL 3. Retinoic acid stimulated IL 1 release by P388D1 cells in a dose-related fashion, starting at 10(-9) M and maximally at 10(-8)-10(-6) M. With peripheral blood mononuclear cells a maximal stimulation of IL 1 release was observed with 10(-7) M-retinoic acid. IL 3 release by WEHI-3 cells was also stimulated by retinoic acid in a dose-related fashion. The maximal response was obtained with 10(-8) M-retinoic acid. These results show that retinoic acid, in physiological concentrations, exerts selective effects on interleukin production in vitro, and this stimulation of IL 1 and IL 3 release may explain some of the immunostimulatory effects of retinoids in vivo. Moreover, since IL 1 is known to influence connective tissues and bone, an increase in IL 1 might also explain some of the changes observed in these tissues in vitamin A poisoning and with high-dose retinoid therapy.


Deprivation indicators as predictors of life events 1981-1992 based on the UK ONS Longitudinal Study.
To investigate the association between the level of social deprivation in electoral wards and various life events. Life events include mortality, self reported long term illness, and for women: still-birth, underweight birth, birth while a teenager, and sole registered birth. Associations with area deprivation are tested before and after allowing for levels of personal deprivation. Prospective census follow up using the Office for National Statistics Longitudinal Study. England and Wales. A random sample of more than 300,000 people enumerated at the 1981 census, and aged 10 to 64 in 1981. Some analyses are necessarily restricted to certain age/sex groups. Several outcomes in the decade 1981-1992 are investigated: risk of premature death (before age 70, all cause), risk of long term limiting illness in 1991, and risk of inauspicious fertility outcomes in women. Without adjusting for personal circumstances all outcomes, except risk of stillbirth, show a clear, significant, and approximately linear association with social deprivation of ward of residence in 1981. Associations are much stronger for outcomes where a greater "social" component can be constructed (teenage birth, sole registered birth) than for outcomes that are probably more physiologically determined (mortality, stillbirth, low birth weight). When adjustment is made for personal disadvantage the simple associations with local area deprivation are all attenuated, especially for those living in the more deprived areas. A variety of adverse or "inauspicious" life events show association with residence in more deprived areas. These are particularly strong for teenage birth and sole registered birth, but are also stronger for long term illness than mortality. These associations seem to be largely because residence in more deprived areas is associated with personal disadvantage, which is more damaging to life chances than area of residence. For some outcomes there is evidence that the personally disadvantaged fare less well if living in relatively advantaged areas, than if living in more homogenously deprived areas.


Identifying clinical improvement in consolidation single-arm phase 2 trials in patients with ovarian cancer in second or greater clinical remission.
Estimates of progression-free survival (PFS) from single-arm phase 2 consolidation/maintenance trials for recurrent ovarian cancer are usually interpreted in the context of historical controls. We illustrate how the duration of second-line therapy (SLT), the time on the investigational therapy (IT), and patient enrollment plan can affect efficacy measures from maintenance trials and might result in underpowered studies. Efficacy data from 3 published single-arm consolidation therapies in second remission in ovarian cancer were used for illustration. The studies were designed to show an increase in estimated median PFS from 9 to 13.5 months. We partitioned PFS as the sum of the duration of SLT, treatment-free interval, and duration of IT. We calculated the statistical power when IT is given concurrently with SLT or after SLT by varying the start of IT. We compared the sample sizes required when PFS includes the time on SLT versus PFS that starts after SLT at initiation of IT. Required sample sizes varied with duration of SLT. If IT starts with initiation of SLT, only 34 patients are needed to provide 80% power to detect a 33% hazard reduction. In contrast, 104 patients are required for a single-arm study for 80% power, if IT begins 7.5 months after SLT initiation. Designs of nonrandomized consolidation trials that aim to prolong PFS must consider the effect of the duration of SLT on the end point definition and on required sample size. If IT is given concurrently with SLT, and after SLT, then SLT duration must be restricted per protocol eligibility, so that a comparison with historical data from other single-arm phase 2 studies is unbiased. If IT is given after SLT, the duration of SLT should be taken into account in the design stage because it will affect statistical power and sample size.


Association between human immunodeficiency virus serostatus and the prevalence of atrial fibrillation.
Atrial fibrillation (AF) leads to increased risk for stroke. Human immunodeficiency virus (HIV) is associated with cardiovascular disease (CVD), although it is unclear if HIV is associated with AF. The purpose of this study was to evaluate the association between HIV serostatus and the prevalence of AF in the Multicenter AIDS Cohort Study.A cross sectional study was conducted among 1674 HIV-infected (HIV+) and uninfected (HIV-) men who completed resting 12-lead electrocardiograms, and/or ambulatory electrocardiogram monitoring. Multivariable logistic regression was used to evaluate the association between AF, defined as the presence of either AF or atrial flutter, and HIV+ serostatus. Associations were adjusted for demographic variables, and then also for CVD risk factors.HIV+ men were younger than HIV- men (median 55.5 vs 61.7 years, P < .001) and were more frequently African-American (30.5% vs 17.8%, P < .001). Most HIV+ men (81%) had undetectable viral load. The age and race adjusted prevalence of AF was 3.0% in HIV+ and 3.3% in HIV- men. There was only 1 case of AF among African-American men. There were no associations between AF and HIV serostatus after adjusting for demographic factors (odds ratio 0.76; 95% CI 0.37 to -1.58; P = .47) or after further adjustment for CVD risk factors (odds ratio 0.84; 95% CI 0.39 to -1.81; P = .66).We found no association between HIV and AF in this cohort in which viral replication among the HIV+ men is generally suppressed. The overall prevalence of AF was low and was rare in African-American men.


High prevalence of self-reported injuries and illnesses in talented female athletes.
A thorough knowledge of the epidemiology and severity of injuries and illness in youth female elite sports is lacking due to the methodological challenges involved in recording them. In this study, the prevalence and incidence of injuries and illness are assessed among youth female elite athletes. Instead of solely focusing on time-loss injuries, our study included all substantial and non-substantial health problems (ie, injuries, mental problems and illnesses). Sixty young elite Dutch female athletes (age: 16.6 years (SD: 2.3), weight: 58.3 kg (SD: 15.1), height: 154.1 cm (SD: 44.2)) participating in soccer (n=23), basketball (n=22) and gymnastic (n=15) talent development programmes were prospectively followed during one season (September 2014 to April 2015). To collect health problem data, all athletes completed the Oslo Sports Trauma Research Center Questionnaire on Health Problems every other week. Main outcome measures were average prevalence of injury and incidence density of injury. At any given time, 47.9% of the athletes reported an injury (95% CI 43.6% to 52.6%) and 9.1% reported an illness (95% CI 5.1 to 19.0). The average injury incidence density was 8.6 per 1000 hours of athlete exposure. The average number of self-reported injuries per athlete per season was significantly higher in soccer athletes (4.3±2.7) than in basketball athletes (2.6±2.0) (p=0.03) and not significantly higher than in the gymnastic squad. The knee and the ankle were two of the most common injury locations for all squads. Knee injuries in basketball and soccer and heel injuries in the gymnastic squad had the highest impact on sports participation. High prevalence of self-reported injuries among talented female athletes suggests that future efforts towards their prevention are warranted.


Transmission line method for the simulation of fiber Bragg gratings.
A new method for the analysis and design of fiber Bragg gratings (FBGs) based on the theory of transmission lines has been developed and verified both theoretically and experimentally. The method is an extension of the coupled-mode theory and utilizes the equivalent transmission lines in order to simulate any type of grating, with an easy and direct implementation. The method provides the ability to analyze the optical devices without using full wave approaches, while also facilitating the incorporation of core materials with a complex or non-linear refractive index, non-uniform distributions of the grating's refractive index, and tilted and phase-shifted gratings. The approach also allows the design of the grating for a given reflection spectra. Numerical results of the method's application on a randomly varied inscription of the refractive index of a FBG have also been simulated and discussed. Using this method, the characteristics of an erbium-doped (ED)-FBG have been simulated and the predictions verified experimentally.


Significance of alterations in plasma lipid profile levels in breast cancer.
The relationship between lipids and breast cancer is obscure. Until now, conflicting results have been reported on the association between lipids and risk of breast cancer in women. Therefore, the major aim of this study is to examine the role of alterations in lipid profile in breast cancer. Plasma lipids (ie, total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], very-low-density lipoprotein [VLDL], and triglycerides [TG]) were analyzed from 70 controls, 30 patients with benign breast disease (BBD), 125 untreated breast cancer patients, and 93 posttreatment follow-up samples. Samples were analyzed using highly sensitive and specific spectrophotometric methods. Plasma TC, LDL, VLDL, and TG were significantly lower (p = .042, p = .003, p = .024, p = .014, respectively) in patients with BBD compared with controls. Plasma TC and HDL were significantly lower (p = .026, p = .0001, respectively), and VLDL and TG were significantly higher (p = .009, p = .05) in breast cancer patients as compared with controls. Plasma VLDL and TG were significantly higher in breast cancer patients as compared with patients with BBD. The receiver-operating characteristic curve showed that plasma TC, LDL, VLDL, and TG levels could significantly discriminate (p = .001, p = .005, p = .005, p = .005, respectively) between controls and patients with BBD. Plasma levels of TC, HDL, VLDL, and TG could significantly distinguish (p = .01, p = .002, p = .001, p = .002, respectively) between controls and breast cancer patients. Plasma levels of VLDL and TG could significantly discriminate (p = .000, p = .000, respectively) between patients with BBD and breast cancer patients. Odds ratio analysis revealed that higher levels of TC and HDL were significantly associated with a reduction in breast cancer risk (p = .01 and p = .0001, respectively), whereas higher levels of VLDL and TG were significantly associated with increased breast cancer risk (p = .001 and p = .002, respectively). Plasma VLDL and TG levels were significantly lower in complete responders as compared with pretreatment levels (p = .000, p = .000, respectively), and plasma TC and LDL levels were significantly lower in nonresponders as compared with pretreatment levels (p = .015, p = .009, respectively). The alterations in lipid profile levels showed a significant correlation with breast cancer risk, disease status, and treatment outcome.


Perioperative Management in Hepatic Resections: Comparative Effectiveness of Neuraxial Anesthesia and Disparity of Care Patterns.
Complication rates after hepatic resection can be affected by management decisions of the hospital care team and/or disparities in care. This is true in many other surgical populations, but little study has been done regarding patients undergoing hepatectomy. Data from the claims-based national Premier Perspective database were used for 2006 to 2014. The analytical sample consisted of adults undergoing partial hepatectomy and total hepatic lobectomy with anesthesia care consisting of general anesthesia (GA) only or neuraxial and GA (n = 9442). The key independent variable was type of anesthesia that was categorized as GA versus GA + neuraxial. The outcomes examined were clinical complications and health care resource utilization. Unadjusted bivariate and adjusted multivariate analyses were conducted to examine the effects of the different types of anesthesia on clinical complications and health care resource utilization after controlling for patient- and hospital-level characteristics. Approximately 9% of patients were provided with GA + neuraxial anesthesia during hepatic resection. In multivariate analyses, no association was observed between types of anesthesia and clinical complications and/or health care utilization (eg, admission to intensive care unit). However, patients who received blood transfusions were significantly more likely to have complications and intensive care unit stays. In addition, certain disparities of care, including having surgery in a rural hospital, were associated with poorer outcomes. Neuraxial anesthesia utilization was not associated with improvement in clinical outcome or cost among patients undergoing hepatic resections when compared to patients receiving GA alone. Future research may focus on prospective data sources with more clinical information on such patients and examine the effects of GA + neuraxial anesthesia on various complications and health care resource utilization.


[Utilization of magneto-biological effects in neurosurgery].
After referring to the application of magnetoes used until now for fixation of ferromagnetic substancies in aneurysms, the new results obtained with externally exployed magnetic fields are discussed. Target site is calculated according to stereotactic principles. In the magnetic field the circulating blood is influenced in such a manner, that in the anode region clotting will occure, wherease in the region of cathode the clotting will be inhibited. After developing the appropiate equipment, these conditions were studied on the basis of experimentally produced aneurysms in thyroid arteries of animals as well as in 30 ptients. It is assumed, that magnetic fields increase the immunoresistance of the organism and also exert a direct influence on the growth of tumourcells.


Relations between diabetic retinopathy and cardiovascular neuropathy--a cross-sectional study in IDDM and NIDDM patients.
The pathogenetic process of diabetic retinopathy and the role of different systemic risk factors in IDDM and NIDDM is not completely understood. The aim of the present cross-sectional clinical study was (1) to compare the prevalence of systemic risk factors for diabetic retinopathy in IDDM and NIDDM patients, (2) to determine relations between these risk factors and the degree of retinopathy and (3) to evaluate the relationship between retinopathy and neuropathy. The study included 1,218 IDDM and 784 NIDDM patients attending our hospital during 1994. The mean diabetes duration was 15.4 and 13.2 years, respectively. IDDM patients with proliferative retinopathy were characterized by higher mean age of 46.4 +/- 1.08 vs. 21.8 +/- 0.42 years and longer diabetes duration of 30.0 +/- 0.79 vs. 7.7 +/- 0.26 years. Among the NIDDM patients, those ones with proliferative retinopathy had the lowest mean age of 40.5 +/- 1.42 vs. 49.7 +/- 0.61 years (p < 0.01) at diabetes manifestation. There was no statistical difference between mean HbA1c concentrations in relation to retinopathy stages. Albumin excretion was increased in both IDDM and NIDDM patients with proliferative retinopathy (p < 0.01) along with increased BMI of IDDM and increased insulin requirement of NIDDM patients (p < 0.01). Multiple regression analysis showed that proliferative retinopathy with the inclusion of non-proliferative retinopathy of IDDM and NIDDM patients was significantly correlated with diabetes duration, albumin excretion, somatic and autonomic neuropathy (p < 0.01). In NIDDM patients proliferative retinopathy with the inclusion of non-proliferative retinopathy was correlated with the age at diabetes manifestation and with cholesterol levels (p < 0.05). In IDDM and NIDDM patients proliferative retinopathy was found to be correlated with somatic and autonomic neuropathy, albumin excretion (p < 0.01) and hypertension (p < 0.05). The importance of the significant correlation of autonomic neuropathy both with background and proliferative retinopathy in IDDM and NIDDM patients needs to be prospectively investigated.


Cholangiocarcinomas express Fas ligand and disable the Fas receptor.
Cholangiocarcinoma is a highly-malignant adenocarcinoma originating from cholangiocytes. Current concepts support escape from immune surveillance using aberrant expression of Fas ligand (FasL) and dysregulation of receptor (FasR) signaling as a potential mechanism for tumor progression. Our aims were to determine if altered expression of FasR and FasL or changes in expression of FLICE inhibitor (I-FLICE) allow cholangiocarcinoma cells to escape immune surveillance. Human cholangiocarcinoma cell lines were evaluated for the functional expression of FasR and FasL by (1) quantitating apoptosis after incubation of cells with agonistic antibodies and (2) an in vitro cell death assay involving coculture of cholangiocarcinoma cells with Fas-sensitive thymocytes. I-FLICE antisense treatment was performed by stable transfection with complementary DNA (cDNA) for I-FLICE in the reverse orientation. We found that normal cholangiocytes in vivo express FasL. Human cholangiocarcinoma cell lines express both FasL and FasR and I-FLICE. FasL expressed by cholangiocarcinomas in vitro induced lymphocyte cell death (70% after 24 hours). Despite the expression of FasR, exposure of the cells to agonistic antibodies (500 ng/mL) induced only minimal apoptosis in the Jurkat cells. Antisense treatment of cholangiocarcinomas in vitro with I-FLICE reduced protein expression of I-FLICE by 90% to 95% and increased Fas-mediated apoptosis 2-fold. We concluded that cholangiocarcinomas escape immune surveillance either by disabling FasR signaling through the expression of I-FLICE and/or increased FasL expression to induce apoptosis of invading T cells. Reduction of I-FLICE expression in cholangiocarcinoma cells restored Fas-mediated apoptosis. Therapeutic maneuvers to inhibit expression of I-FLICE may aid in the treatment of cholangiocarcinoma.


An Isochroman Analog of CD3254 and Allyl-, Isochroman-Analogs of NEt-TMN Prove to Be More Potent Retinoid-X-Receptor (RXR) Selective Agonists Than Bexarotene.
Bexarotene is an FDA-approved drug for the treatment of cutaneous T-cell lymphoma (CTCL); however, its use provokes or disrupts other retinoid-X-receptor (RXR)-dependent nuclear receptor pathways and thereby incites side effects including hypothyroidism and raised triglycerides. Two novel bexarotene analogs, as well as three unique CD3254 analogs and thirteen novel NEt-TMN analogs, were synthesized and characterized for their ability to induce RXR agonism in comparison to bexarotene (1). Several analogs in all three groups possessed an isochroman ring substitution for the bexarotene aliphatic group. Analogs were modeled for RXR binding affinity, and EC50 as well as IC50 values were established for all analogs in a KMT2A-MLLT3 leukemia cell line. All analogs were assessed for liver-X-receptor (LXR) activity in an LXRE system to gauge the potential for the compounds to provoke raised triglycerides by increasing LXR activity, as well as to drive LXRE-mediated transcription of brain ApoE expression as a marker for potential therapeutic use in neurodegenerative disorders. Preliminary results suggest these compounds display a broad spectrum of off-target activities. However, many of the novel compounds were observed to be more potent than 1. While some RXR agonists cross-signal the retinoic acid receptor (RAR), many of the rexinoids in this work displayed reduced RAR activity. The isochroman group did not appear to substantially reduce RXR activity on its own. The results of this study reveal that modifying potent, selective rexinoids like bexarotene, CD3254, and NEt-TMN can provide rexinoids with increased RXR selectivity, decreased potential for cross-signaling, and improved anti-proliferative characteristics in leukemia models compared to 1.


Trust Information and Privacy Policies - Enablers for pHealth and Ubiquitous Health.
pHealth occurs in uncontrolled and unsecure environment where predefined organizational trust does not exist. To be accepted by users, pHealth requires a privacy model where privacy is a personal property, i.e., a person can perform own will and define policies which regulate how personal health information (PHI) is used. Privacy and trust are interconnected concepts. Therefore, before beginning to use pHealth services, the person needs practical and reliable information that enables her or him to determine the trustworthiness level of services. To avoid the use of blind trust, organizations, researchers, policymakers, and standardization organizations have proposed the use of dynamic context-aware policies for privacy management in pHealth. To make meaningful privacy decision, a person should understand the impact of selected policy rules on the processing of PHI in different situations. In this paper, the use of computational trust information for defining privacy polies and reducing their number is proposed. A trust value and understandable trust attributes enable a person to tailor privacy policies requested for trustworthy use of pHealth services. Trust attributes proposed are derived from privacy concerns existing in open ubiquitous environment. These attributes also force pHealth services providers to publish information needed for trust calculation and in this way to support openness and transparency.


Epilepsy in dogs five years of age and older: 99 cases (2006-2011).
To classify the etiology of epilepsy and evaluate use of abnormal neurologic examination findings to predict secondary epilepsy in dogs ≥ 5 years of age. Retrospective case series. 99 dogs with epilepsy. Medical records were reviewed to identify client-owned dogs evaluated for seizures at ≥ 5 years of age with a diagnosis of primary or secondary epilepsy. Dogs were stratified by age; prevalence of primary and secondary epilepsy and the proportion of dogs with secondary epilepsy that had a diagnosis of neoplasia (on the basis of MRI findings) versus other disease were evaluated. Sensitivity and specificity of abnormal neurologic findings to detect secondary epilepsy were determined. 7 of 30 (23%) dogs 5 to 7 years of age, 13 of 29 (45%) dogs 8 to 10 years of age, 13 of 33 (39%) dogs 11 to 13 years of age, and 2 of 7 dogs ≥ 14 years of age had primary epilepsy. Prevalence of primary vs secondary epilepsy did not differ among age groups. The proportion of dogs with neoplasia at 5 to 7 years of age was lower than that of dogs in other age groups. Abnormal neurologic examination results had 74% sensitivity and 62% specificity to predict secondary epilepsy. A substantial proportion of dogs ≥ 5 years of age had primary epilepsy. Results indicated that lack of abnormalities on neurologic examination does not exclude the possibility of intracranial lesions, and MRI with CSF analysis (when applicable) should be recommended for all dogs with onset of seizures at ≥ 5 years of age.


Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report.
The etiology of primary cutaneous anaplastic large-cell CD30+ lymphoma is largely unknown, and although an infectious involvement has been suspected, the implication of infectious agents in its pathogenesis is still unclear. We report the case of a HIV-negative patient referred to our hospital with a rapidly enlarging skin tumor on her upper eyelid. Surgical excision was performed and histological analysis evidenced a primary cutaneous anaplastic large-cell lymphoma. Due to the ocular localization and to the prominent angiogenic component of the lesion, molecular analyses for the detection of Chlamydophila pneumoniae and HHV8 were performed, revealing the presence of an infection by both pathogens in surgical biopsy and in peripheral blood mononuclear cells. These findings suggest for the first time a possible association of C. pneumoniae and/or HHV8 infection, or both together, with primary cutaneous anaplastic large-cell lymphoma in non-immunocompromised and HIV-negative subjects. This potential pathogenic association, if confirmed, could provide potential indications for future therapy.


A systematic review of longitudinal population-based studies on the predictors of smoking cessation in adolescent and young adult smokers.
To describe the determinants of self-initiated smoking cessation of duration of at least 6 months as identified in longitudinal population-based studies of adolescent and young adult smokers. A systematic search of the PubMed and EMBASE databases using smoking, tobacco, cessation, quit and stop as keywords was performed. Limits included articles related to humans, in English, published between January 1984 and August 2010, and study population aged 10-29 years. A total of 4502 titles and 871 abstracts were reviewed independently by 2 and 3 reviewers, respectively. Nine articles were retained for data abstraction. Data on study location, timeframe, duration of follow-up, number of data collection points, sample size, age/grade of participants, number of quitters, smoking status at baseline, definition of cessation, covariates and analytic method were abstracted from each article. The number of studies that reported a statistically significant association between each determinant investigated and cessation were tabulated, from among all studies that assessed the determinant. Despite heterogeneity in methods across studies, five factors robustly predicted quitting across studies in which the factor was investigated: not having friends who smoke, not having intentions to smoke in the future, resisting peer pressure to smoke, being older at first use of cigarette and having negative beliefs about smoking. The literature on longitudinal predictors of cessation in adolescent and young adult smokers is not well developed. Cessation interventions for this population will remain less than optimally effective until there is a solid evidence base on which to develop interventions.


Binary Solutions of Hyaluronan and Lactose-Modified Chitosan: The Influence of Experimental Variables in Assembling Complex Coacervates.
A miscibility study between oppositely charged polyelectrolytes, namely hyaluronic acid and a lactose-modified chitosan, is here reported. Experimental variables such as polymers' weight ratios, pH values, ionic strengths and hyaluronic acid molecular weights were considered. Transmittance analyses demonstrated the mutual solubility of the two biopolymers at a neutral pH. The onset of the liquid-liquid phase separation due to electrostatic interactions between the two polymers was detected at pH 4.5, and it was found to be affected by the overall ionic strength, the modality of mixing and the polymers' weight ratio. Thorough Dynamic Light Scattering (DLS) measurements were performed to check the quality of the formed coacervates by investigating their dimensions, homogeneity and surface charge. The whole DLS results highlighted the influence of the hyaluronic acid molecular weight in affecting coacervates' dispersity and size.


Non-invasively improving the Schottky barriers of metal-MoS2 interfaces: effects of atomic vacancies in a BN buffer layer.
Using first-principles calculations within density functional theory, vacancies in the BN buffer layer have been predicted to improve the Schottky barrier of the metal-MoS2 interface without deteriorating the intrinsic properties of the MoS2 layer. Here, the effects of concentrations, sizes and types of vacancies on the contact properties of metal/BN-MoS2 sandwich interfaces are comparatively studied. The results show that vacancies in the BN buffer layer not only don't deteriorate the charge scatterings and electronic properties of the MoS2 layer at the metal/BN-MoS2 interface, but also improve the charge density and contact resistance between the metal surface and the BN layer. Although these vacancies have a negligible influence on the Fermi level pinning effect of the metal/BN-MoS2 interface, both N-vacancies and B-vacancies significantly change the position of the Fermi level of the metal/BN-MoS2 interface and then tune the Schottky barriers. Moreover, the Schottky barriers of metal/BN-MoS2 interfaces can decrease at first with the increasing concentrations and sizes of vacancies. When the concentration of vacancies increases to 4%, the Schottky barriers of metal/BN-MoS2 interfaces can reduce to the minimum value. The lowest n-type and p-type Schottky barriers of Au/BN-MoS2 and Pt/BN-MoS2 interfaces can reduce to -0.16 and 0.28 eV, respectively. However, the Schottky barriers are deteriorated when the sizes and concentrations of vacancies continue to increase because vacancies with large sizes and concentrations obviously change the interfacial structures of metal/BN-MoS2 interfaces and disarrange the directions of interface dipoles. The predictions in this work provide a non-invasive method to achieve high performance metal-MoS2 interfaces with low Schottky barriers.


Metabolic and haemodynamic effects of alpha 2-adrenoceptor stimulation and antagonism in man.
Six healthy volunteers received a 60 min infusion of guanfacine (alpha 2-agonist) on two occasions, preceded by either idazoxan (alpha 2-antagonist) or vehicle. Idazoxan elevated blood pressure by 8/7 mmHg, but there was no change on either day during guanfacine infusion. Guanfacine reduced plasma noradrenaline by approximately 30%, and this was not antagonized by idazoxan. By contrast, the 30-fold increase in plasma growth hormone caused by guanfacine was almost completely blocked by idazoxan. Guanfacine caused a two- to three-fold increase in plasma glucagon and a similar reduction in plasma insulin. Only the latter was antagonized by idazoxan. No consistent changes in plasma ACTH were observed after either idazoxan or guanfacine. Idazoxan itself elevated plasma noradrenaline up to twice baseline values, but did not affect the other metabolic measurements. alpha 2-Adrenoceptor stimulation plays a minor role in control of hormone release but has a greater physiological role in regulating release of the neurotransmitter, noradrenaline.


The personal meaning of romantic relationships for young people with psychosis.
Romantic relationships are of particular importance to young people, and play a key role in the transition from adolescence to adulthood. Psychosis typically develops during late adolescence or early adulthood, a crucial period for gaining romantic experience. The significance of these relationships for young people with psychosis has never been explored. Eight participants were interviewed about their experiences and perceptions of romantic relationships using a semi-structured interview. The research was conducted using Interpretative Phenomenological Analysis (IPA). Five overarching themes emerged, suggesting that participants experienced conflict regarding romantic relationships, as they considered such relationships incompatible with psychosis, whilst they also associated them with normality and recovery. Relationships were perceived to be "risky", and participants were concerned with strategies for reducing these risks. Respondents typically perceived themselves to have a relative lack of experience and resources, making it more difficult for them to engage in romantic relationships. As romantic relationships are associated with a range of personal and social benefits, young people who have experienced psychosis may benefit from services supporting them in negotiating stigma and facilitating their involvement in romantic relationships.


Chemical and photonic interactions in vitro and in vivo between fluorescent tracer and nanoparticle-based scavenger for enhanced molecular imaging.
We hereby present a concept of scavenging excess imaging agent prior to a diagnostic imaging session, consequently allowing for enhanced contrast of signals originating from the tissue area of interest to the signals originating from systemic imaging agent residues. In our study, a prospective silica core-shell nanoparticle-based scavenger was designed and explored for its feasibility to scavenge a specific imaging agent (tracer) in the bloodstream. The developed tracer-scavenger system was first investigated under in vitro conditions to ensure proper binding between tracer and scavenger is taking place, as confirmed by Förster/fluorescence resonance energy transfer studies. In vivo, two-photon imaging was utilized to directly study the interaction of the scavenger particles and the tracer molecules in the vasculature of mice. To our knowledge, a methodological solution for in vivo differentiation between signals, originating from tissue and blood, has not been presented elsewhere.


Chronic diffuse interstitial fibrosis of the lung in uranium miners.
Many uranium miners have been disabled by and died of pulmonary fibrosis that was not recognized as an occupational disease. A review of animal studies, complications from whole body irradiation, pulmonary function, and mortality studies of uranium miners led us to suspect radiation-induced chronic diffuse interstitial fibrosis in miners who had inhaled excessive radon progeny. A selected group of uranium miners (22) with severe respiratory disease (but no rounded nodules in chest films) were studied. Lung tissue from five disclosed severe diffuse interstitial fibrosis, with "honeycomb lung" in all. Some also had small anthrasilicotic nodules and birefringent crystals. Although quartz crystals probably contributed, we concluded that the predominant injurious agent in these cases was alpha particles from radon progeny. This disease, after a long latent period, usually results in pulmonary hypertension, shortness of breath, and death by cardiopulmonary failure.


Phycobilisome-Deficient Strains of Synechocystis sp. PCC 6803 Have Reduced Size and Require Carbon-Limiting Conditions to Exhibit Enhanced Productivity.
Reducing excessive light harvesting in photosynthetic organisms may increase biomass yields by limiting photoinhibition and increasing light penetration in dense cultures. The cyanobacterium Synechocystis sp. PCC 6803 harvests light via the phycobilisome, which consists of an allophycocyanin core and six radiating rods, each with three phycocyanin (PC) discs. Via targeted gene disruption and alterations to the promoter region, three mutants with two (pcpcT→C) and one (ΔCpcC1C2:pcpcT→C) PC discs per rod or lacking PC (olive) were generated. Photoinhibition and chlorophyll levels decreased upon phycobilisome reduction, although greater penetration of white light was observed only in the PC-deficient mutant. In all strains cultured at high cell densities, most light was absorbed by the first 2 cm of the culture. Photosynthesis and respiration rates were also reduced in the ΔCpcC1C2:pcpcT→C and olive mutants. Cell size was smaller in the pcpcT→C and olive strains. Growth and biomass accumulation were similar between the wild-type and pcpcT→C under a variety of conditions. Growth and biomass accumulation of the olive mutant were poorer in carbon-saturated cultures but improved in carbon-limited cultures at higher light intensities, as they did in the ΔCpcC1C2:pcpcT→C mutant. This study shows that one PC disc per rod is sufficient for maximal light harvesting and biomass accumulation, except under conditions of high light and carbon limitation, and two or more are sufficient for maximal oxygen evolution. To our knowledge, this study is the first to measure light penetration in bulk cultures of cyanobacteria and offers important insights into photobioreactor design.


Human blood genomics: distinct profiles for gender, age and neurofibromatosis type 1.
Application of gene expression profiling to human diseases will be limited by availability of tissue samples. It was postulated that germline genetic defects affect blood cells to produce unique expression patterns. This hypothesis was addressed by using a test neurological disease-neurofibromatosis type 1 (NF1), an autosomal dominant genetic disease caused by mutations of the NF1 gene at chromosome 17q11.2. Oligonucleotide arrays were used to survey the blood gene expression pattern of 12 NF1 patients compared to 96 controls. A group of genes related to tissue remodeling, bone development and tumor suppression were down-regulated in NF1 blood samples. In addition, there were blood genomic patterns for gender and age: Y chromosome genes showing higher expression in males, indicating a gene-dosage effect; and genes related to lymphocyte functions showing higher expression in children. The results suggest that genetic mutations can be manifested at the transcriptional level in peripheral blood cells and blood gene expression profiling may be useful for studying phenotypic differences of human genetic diseases and possibly providing diagnostic and prognostic markers.


Substantial improvement in compliance with universal precautions in an emergency department following institution of policy.
Seven months following the introduction of an institutional policy mandating compliance with universal precautions (UPs), we observed 127 health care workers performing 1421 interventions on 155 critically ill and injured patients in an emergency department setting in July 1989. Results were compared with a similar study undertaken exactly 1 year previously when UPs were considered as guidelines only. Overall adherence to UPs improved from 44.0% to 72.7% from 1 year to the next. Adherence to UPs improved from 19.5% to 55.7% during interventions on patients with profuse bleeding and from 16.7% to 54.5% during performance of major procedures. Compliance improved from 47.9% to 81.0% for emergency department-based health care workers (residents, attending physicians, nurses, x-ray film technicians). Prehospital care providers, a group not accountable to the institution, remained particularly noncompliant with only 13% adherence. We conclude that mandating UPs as policy with a monitoring component is effective in ensuring a reasonable level of adherence. However, given current barrier technology, achieving appropriate levels of compliance during unscheduled visits by patients requiring immediate attention and rapid intervention remains a challenge.


[Antioxidant impact on specific antiviral activity of human recombinant interferon alpha-2b with respect to Herpes simplex in cell culture].
In vitro synergistic antiviral effect of interferon alpha-2b in combination with unithiol (an antioxidant) on diverse variants of Herpes simplex, including the clinical acyclovir-resistant isolates, was demonstrated. Unithiol showed immediate antiherpes activity in the cell culture. However, its activity was lower than that of ascorbic acid, another highly active antioxidant. It was also observed that the specific antiherpes activity of interferon alpha-2b in the presence of unithiol increased several times. The data could be useful in the clinical practice, since the drugs combinations or complex formulations provide higher efficacy of the herpetic infection therapy with the use of the same concentrations of the available agents.


Treatment of smoke inhalation by hyperbaric oxygen.
Five patients with smoke inhalation from house fires presented to the hospital in a comatose state. Carboxyhemoglobin levels were elevated in all five patients, mean=32% +/- 6. Arterial blood gases revealed the following means: pH 7.16 +/- 0.06; PCO2 35 mm HG +/- 10.5; HCO3 12.6 mEq/L +/- 0.07; base excess -16 mEq/L +/- 1.58; PO2 353 mm Hg +/- 149; O2 saturation 66% +/- 5.5. The patients were presumed to have both cyanide and carbon monoxide intoxication and were treated with the cyanide antidote kit and hyperbaric oxygen (HBO). Four of five patients awoke within 15 minutes of reaching maximum pressure and remained neurologically intact thereafter. The fifth patient died one week later. Cyanide blood levels drawn prior to treatment revealed a mean of 1.62 microgram/mL +/- 1.44. The highest cyanide level was 3.9 microgram/mL (the death) and the lowest 0.35 microgram/mL. We conclude that smoke inhalation can result in acute cyanide poisoning and that hyperbaric oxygen is a useful adjunct in the treatment of smoke inhalation.


Pain coping skills training for African Americans with osteoarthritis (STAART): study protocol of a randomized controlled trial.
African Americans bear a disproportionate burden of osteoarthritis (OA), with higher prevalence rates, more severe pain, and more functional limitations. One key barrier to addressing these disparities has been limited engagement of African Americans in the development and evaluation of behavioral interventions for management of OA. Pain Coping Skills Training (CST) is a cognitive-behavioral intervention with shown efficacy to improve OA-related pain and other outcomes. Emerging data indicate pain CST may be a promising intervention for reducing racial disparities in OA symptom severity. However, there are important gaps in this research, including incorporation of stakeholder perspectives (e.g. cultural appropriateness, strategies for implementation into clinical practice) and testing pain CST specifically among African Americans with OA. This study will evaluate the effectiveness of a culturally enhanced pain CST program among African Americans with OA. This is a randomized controlled trial among 248 participants with symptomatic hip or knee OA, with equal allocation to a pain CST group and a wait list (WL) control group. The pain CST program incorporated feedback from patients and other stakeholders and involves 11 weekly telephone-based sessions. Outcomes are assessed at baseline, 12 weeks (primary time point), and 36 weeks (to assess maintenance of treatment effects). The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index, and secondary outcomes include self-efficacy, pain coping, pain interference, quality of life, depressive symptoms, and global assessment of change. Linear mixed models will be used to compare the pain CST group to the WL control group and explore whether participant characteristics are associated with differential improvement in the pain CST program. This research is in compliance with the Helsinki Declaration and was approved by the Institutional Review Boards of the University of North Carolina at Chapel Hill, Durham Veterans Affairs Medical Center, East Carolina University, and Duke University Health System. This culturally enhanced pain CST program could have a substantial impact on outcomes for African Americans with OA and may be a key strategy in the reduction of racial health disparities. ClinicalTrials.gov, NCT02560922 , registered 9/22/2015.


Application of active contours for photochromic tracer flow extraction.
This paper addresses the implementation of image processing and computer vision techniques to automate tracer flow extraction in images obtained by the photochromic dye technique. This task is important in modeled arterial blood flow studies. Currently, it is performed via manual application of B-spline curve fitting. However, this is a tedious and error-prone procedure and its results are nonreproducible. In the proposed approach, active contours, snakes, are employed in a new curve-fitting method for tracer flow extraction in photochromic images. An algorithm implementing snakes is introduced to automate extraction. Utilizing correlation matching, the algorithm quickly locates and localizes all flow traces in the images. The feasibility of the method for tracer flow extraction is demonstrated. Moreover, results regarding the automation algorithm are presented showing its accuracy and effectiveness. The proposed approach for tracer flow extraction has potential for real-system application.


Incorporation of fucose and glucosamine into cell bound and medium released macromolecules.
(1) Determinations were carried out on the incorporation of fucose-6-(3H) and glucosamine-6-(3H) into trichloracetic acid insoluble macromolecules which remained bound to the cells or were released into the medium of chick embryo muscle cell cultures. The radioactivity determined in the medium was corrected for unspecific binding of label to components of the medium. (2) During an incorporation period of six hours the incorporation per microgram DNA with fucose as label into cell bound macromolecules is about twice as high as the incorporation into macromolecules released into medium. With glucosamine about twice as much is incorporated into medium released into the cell bound macromolecules. (3) The incorporation per microgram DNA increased during a culture period of three days but the increase ceases at different times during this culture period when determined with fucose or glucosamine or for cell bound and medium released material. (4) An increase in cell density increases the incorporation per DNA of fucose and to a much slighter extent that of glucosamine. Reduction of cell density by addition of cytosine arabinoside to the medium does not increase the incorporation per microgram DNA. (5) The effect of changes of fibroblast/myoblast ratios on the incorporation of fucose and glucosamine were examined. No significant effect was observed for a ratio of 10-30% fibroblasts when control cultures or cultures after cell sedimentation were maintained in complete medium. Marked changes were observed after culture in medium without protein components. Under these conditions an increase in the fibroblast/myoblast ratios were observed as well as an increase in the incorporation of label into medium released and a decrease into cell bound macromolecules.


Selfish, promiscuous and sometimes useful: how mobile genetic elements drive horizontal gene transfer in microbial populations.
Horizontal gene transfer (HGT) drives microbial adaptation but is often under the control of mobile genetic elements (MGEs) whose interests are not necessarily aligned with those of their hosts. In general, transfer is costly to the donor cell while potentially beneficial to the recipients. The diversity and plasticity of cell-MGEs interactions, and those among MGEs, result in complex evolutionary processes where the source, or even the existence of selection for maintaining a function in the genome, is often unclear. For example, MGE-driven HGT depends on cell envelope structures and defense systems, but many of these are transferred by MGEs themselves. MGEs can spur periods of intense gene transfer by increasing their own rates of horizontal transmission upon communicating, eavesdropping, or sensing the environment and the host physiology. This may result in high-frequency transfer of host genes unrelated to the MGE. Here, we review how MGEs drive HGT and how their transfer mechanisms, selective pressures and genomic traits affect gene flow, and therefore adaptation, in microbial populations. The encoding of many adaptive niche-defining microbial traits in MGEs means that intragenomic conflicts and alliances between cells and their MGEs are key to microbial functional diversification. This article is part of a discussion meeting issue 'Genomic population structures of microbial pathogens'.


Ex vivo two-photon imaging of whole-mount skeletal muscles to visualize stem cell behavior.
Quiescent skeletal muscle stem cells (MuSCs) are morphologically and functionally heterogeneous and exhibit different lengths of cellular extensions, which we call protrusions. Here, we present a protocol for ex vivo two-photon imaging of MuSCs in their native environment. We describe steps for muscle dissection, fixation, embedding, imaging, and analysis of datasets. This protocol allows the examination of MuSC morphology and protrusions at the single-cell level as well as stem cell numbers. For complete details on the use and execution of this protocol, please refer to Ma et al. (2022).1.


Considerations about sample-size sensitivity of a family of edited nearest-neighbor rules.
The edited nearest neighbor classification rules constitute a valid alternative to k-NN rules and other nonparametric classifiers. Experimental results with synthetic and real data from various domains and from different researchers and practitioners suggest that some editing algorithms (especially, the optimal ones) are very sensitive to the total number of prototypes considered. This paper investigates the possibility of modifying optimal editing to cope with a broader range of practical situations. Most previously introduced editing algorithms are presented in a unified form and their different properties (acid not just their asymptotic behavior) are intuitively analyzed. The results show the relative limits in the applicability of different editing algorithms.


A Framework for Predicting X-Nuclei Transmitter Gain Using 1H Signal.
Commercial human MR scanners are optimised for proton imaging, containing sophisticated prescan algorithms with setting parameters such as RF transmit gain and power. These are not optimal for X-nuclear application and are challenging to apply to hyperpolarised experiments, where the non-renewable magnetisation signal changes during the experiment. We hypothesised that, despite the complex and inherently nonlinear electrodynamic physics underlying coil loading and spatial variation, simple linear regression would be sufficient to accurately predict X-nuclear transmit gain based on concomitantly acquired data from the proton body coil. We collected data across 156 scan visits at two sites as part of ongoing studies investigating sodium, hyperpolarised carbon, and hyperpolarised xenon. We demonstrate that simple linear regression is able to accurately predict sodium, carbon, or xenon transmit gain as a function of position and proton gain, with variation that is less than the intrasubject variability. In conclusion, sites running multinuclear studies may be able to remove the time-consuming need to separately acquire X-nuclear reference power calibration, inferring it from the proton instead.


Oncogenesis by retroviruses: old and new paradigms.
Retroviruses are associated with a variety of diseases including an array of malignancies, immunodeficiencies and neurological disorders. In particular, studies of oncogenic retroviruses established fundamental principles of modern molecular cancer biology. Studies of avian Rous sarcoma virus (RSV) led to the discovery of the viral oncogene src, and this was followed by the discovery of other viral oncogenes in retroviruses of mammals including rodents, cats, monkeys and so forth. Studies of the viral oncogenes in turn led to the discovery of cellular proto-oncogenes in the host genome; cellular oncogenes have been shown to be activated in a variety of human cancers, including those with no viral involvement. Oncogenic animal retroviruses can be divided into two groups based on their mechanisms of tumourigenesis, acute transforming retroviruses and nonacute retroviruses. Acute transforming retroviruses are typically replication defective and they induce tumours rapidly due to expression of their viral oncogenes. Nonacute retroviruses are replication competent and they induce tumours with longer latencies, by activating cellular proto-oncogenes in the tumour cells; this results from insertion of proviral DNA in the vicinity of the activated proto-oncogene. More recently, human T-cell leukaemia virus type I (HTLV-I) was discovered as an etiological agent of human cancer (adult T-cell leukaemia [ATL]); this virus also encodes regulatory genes some of which are important for its oncogenic potential. Most recently, the retroviral structural protein Envelope (Env) has been shown to be directly involved in oncogenic transformation for certain retroviruses. Env-induced transformation is a new paradigm for retroviral oncogenesis. In this review, we will summarise research on retrovirus oncogenic transformation over the past 100 years since the first published report of an oncogenic virus with particular attention to Env-induced transformation.


A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa.
CsrA/RsmA homologs are an extensive family of ribonucleic acid (RNA)-binding proteins that function as global post-transcriptional regulators controlling important cellular processes such as secondary metabolism, motility, biofilm formation and the production and secretion of virulence factors in diverse bacterial species. While direct messenger RNA binding by CsrA/RsmA has been studied in detail for some genes, it is anticipated that there are numerous additional, as yet undiscovered, direct targets that mediate its global regulation. To assist in the discovery of these targets, we propose a sequence-based approach to predict genes directly regulated by these regulators. In this work, we develop a computer code (CSRA_TARGET) implementing this approach, which leads to predictions for several novel targets in Escherichia coli and Pseudomonas aeruginosa. The predicted targets in other bacteria, specifically Salmonella enterica serovar Typhimurium, Pectobacterium carotovorum and Legionella pneumophila, also include global regulators that control virulence in these pathogens, unraveling intricate indirect regulatory roles for CsrA/RsmA. We have experimentally validated four predicted RsmA targets in P. aeruginosa. The sequence-based approach developed in this work can thus lead to several testable predictions for direct targets of CsrA homologs, thereby complementing and accelerating efforts to unravel global regulation by this important family of proteins.


Influences of mechanical barrier permeability on guided bone augmentation in the rat calvarium.
We used radiological and histological analyses to evaluate the effects of mechanical barrier permeability in a rat model of calvarial guided bone augmentation (GBA). The calvaria of 20 rats were exposed, and one of four types of plastic caps (an occlusive cylindrical plastic cap; a plastic cap with no top; a plastic cap with three holes; and a plastic cap with four holes) was randomly placed on both sides. Newly generated bone in the plastic caps was evaluated with micro-computed tomography (micro-CT) and histological analysis. Micro-CT volumetric analysis and decalcified hematoxylin and eosin-stained sections showed that GBA barrier permeability was inversely associated with the quantity of augmented bone obtained. Masson's trichrome staining showed that collagen in newly generated bony tissue was more mature in plastic caps with three holes than in those with more-permeable or more-occlusive barriers. Bone augmentation was inhibited in specimens exhibiting invasion of soft tissue through penetrating holes, and barrier permeability was associated with the quantity of augmented bone developed. In conclusion, moderate barrier permeability is optimal for development of mature augmented bone.


First-line treatment with cephalosporins in spontaneous bacterial peritonitis provides poor antibiotic coverage.
Spontaneous bacterial peritonitis is a common infection in cirrhosis, associated with a high mortality. Third-generation cephalosporins are recommended as first-line treatment. The aim was to evaluate the epidemiology of microbiological ascitic fluid findings and antimicrobial resistance in Denmark. All patients with cirrhosis and a positive ascitic fluid culture, at three university hospitals in the Copenhagen area during a 7-year period, were retrospectively evaluated. Patients with apparent secondary peritonitis were excluded from the study. One hundred and forty cases with 187 microbiological isolates were identified. The findings were: Gram-positive cocci, n = 86 (45.9%); Enterobacteriaceae, n = 59 (31.7%), with Escherichia coli identified in 31 cases; anaerobes, n = 14 (7.5%); yeast, n = 12 (6.4%); and cutaneous flora, n = 15 (8.0%). One case of Listeria monocytogenes was identified (0.5%). Overall antibiotic coverage was 57% for cephalosporins, 73% for piperacillin-tazobactam, and 72% for meropenem. Mortality rates in patients with isolates susceptible or resistant to the initial antibiotic treatment at 30 days follow-up were 35% and 55%, respectively (p = 0.017, Log-rank test). Almost half of the isolates were Gram-positive cocci, and as the overall antibiotic coverage with a cephalosporin was only 57%, and survival significantly dependent on whether the microbial etiology was susceptible to initial antibiotic treatment or not, a change of standard empiric antibiotic regime should be considered. Piperacillin-tazobactam could be a favorable choice.


Treatment of infection with the use of carbon dioxide laser: a 10-year experience.
Despite technical advances in the surgical treatment of infected wounds, this surgery remains a serious problem as it represents more than 27% of infection complications. In the majority of these operations, the wounds are left open and patients undergo long treatments of antibiotics. When the carbon dioxide laser technique was introduced in our country in 1984, it was tested using quantitative bacteriology: it was shown that when used on infected wounds, it reduced the bacterial population of these lesions to low levels with low tissue injury. At our center, between August 1984 and 1994, 539 patients with infected wounds were treated using a carbon dioxide laser. Out of 495 patients (91.84%) 1 patient was cured, 37 patients (6.86%) required more than one operation to be cured, and in 7 patients (1.30%) the treatment failed.


Heparin-induced thrombocytopenia in children: 12 new cases and review of the literature.
Immune-mediated heparin-induced thrombocytopenia (HIT) is a rare but severe adverse effect of heparin therapy. Only few data are available on clinical presentation, diagnosis and management of HIT in children. Records of all patients sent to our laboratory between 1995 and November 2003 were reviewed. To identify literature reports a Medline search was performed, the reference lists of those publications were screened and the abstracts of meetings on thrombosis and hemostasis between 2000 and 2003 were assessed. We identified 12 new HIT patients between 13 months and 18 years of age from our laboratory and 71 reports on HIT in children in the literature. For the assessment of frequency of HIT all studies enrolling > 100 patients were analyzed. HIT is rare in children. In pediatric patients, there seem to be two risk groups: newborns and infants under 4 years of age undergoing cardiac surgery (incidence approximately 1-2%), and teenagers treated with heparin for thrombosis. For confirmation of HIT in children, antigen assays are most important. There are conflicting data on the optimal cut-off, with one randomized, double-blind trial indicating that the cut-off established in adults is appropriate. There are no systematic studies on alternative anticoagulants in children affected by HIT. Most data are available for lepirudin and danaparoid. Substitution of unfractionated heparin by low-molecular-weight heparins for regular anticoagulation may reduce the incidence of HIT.


Liver Resection for Intrahepatic Cholangiocarcinoma-Single-Center Experience with 286 Patients Undergoing Surgical Exploration over a Thirteen Year Period.
Intrahepatic cholangiocarcinoma (iCCA) accounts for about 10% of primary liver cancer. Surgery is the only potentially curative treatment. We report on our current series of 229 consecutive hepatic resections for iCCA, which is one of the largest Western single-center series published so far. Between January 2008 to December 2020, a total of 286 patients underwent 307 surgical explorations for intended liver resection of iCCA at our department. Data were analyzed with regard to (1) preoperative treatment of tumor, (2) operative details, (3) perioperative morbidity and mortality, (4) histopathology, (5) outcome measured by tumor recurrence, treatment of recurrence and survival and (6) prognostic factors for overall and disease-free survival. the resectability rate was 74.6% (229/307). In total, 202 primary liver resections, 21 repeated, 5 re-repeated, and 1 re-re-repeated liver resections were performed. In primary liver resections there were 77% (155/202) major hepatectomies. In 39/202 (20%) of patients additional hepatic wedge resections and in 87/202 (43%) patients additional 119 other surgical procedures were performed next to hepatectomy. Surgical radicality in first liver resections was 166 R0-, 33 R1- and 1 R2-resection. Following the first liver resection, the calculated 1-, 3- and 5-year-survival is 80%, 39%, and 22% with a median survival of 25.8 months. Until the completion of data acquisition, tumors recurred in 123/202 (60.9%) patients after a median of 7.5 months (range 1-87.2 months) after resection. A multivariate cox regression revealed tumor size (p < 0.001), T stage (p < 0.001) and N stage (p = 0.003) as independent predictors for overall survival. N stage (p = 0.040), preoperative therapy (p = 0.005), T stage (p = 0.004), tumor size (p = 0.002) and M stage (p = 0.001) were independent predictors for recurrence-free survival. For complete surgical removal, often extended liver resection in combination with complex vascular or biliary reconstruction is required. However, despite aggressive surgery, tumor recurrence is frequent and long-term oncological results are poor. This indicated that surgery alone is unlikely to make great strides in improving prognosis of patients with iCCA, instead clearly suggesting that liver resection should be incorporated in multimodal treatment concepts.


Recent outbreaks of lymphocytic choriomeningitis in the United States of America.
Lymphocytic choriomeningitis (LCM) has been rarely reported in the American literature since 1960. It is interesting that each of the 3 epidemics reported since then has been associated with exposure to hamsters. In 1973, 48 cases of LCM spanning the years 1971-1973 occurred at the University of Rochester Medical School associated with hamsters implanted with tumour tissues. These tissues were found to be LCM-positive, as in an earlier outbreak in 1965 at the National Institutes of Health. A nationwide outbreak of LCM occurred in late 1973 and early 1974 totalling at least 181 cases in 12 states; all were associated with pet hamsters from a single breeder in Birmingham, Alabama. He was an employee of a biological products firm whose tumour tissues were found positive for LCM and were also incriminated in the 1973 Rochester outbreak. The last outbreak occurred in a graduate school laboratory in New York State involving 7 individuals working with hamster tumours from the same Birmingham biological firm. The nationwide epidemic ended in middle April 1974 following removal of incriminated hamsters from pet shops throughout the country and voluntary cessation of distribution of hamsters from the incriminated breeder. The biological firm notified all laboratories of the possible contamination of tumours and has voluntarily stopped distribution of known positive tumours.


Fibromyxoma of the trachea. A review of benign tracheal tumors.
A 59-year-old woman presented with asthmatic symptoms. A fibromyxoma obstructing her trachea was surgically removed. Benign tracheal tumors are rare lesions usually misdiagnosed as asthma. Histologically, the majority are soft-tissue-type tumors of mesenchymal origin. They are more frequently located in the lower third of the trachea with the exception of benign mixed tumor and granular cell myoblastoma that arise more frequently in the upper third. Though endoscopic removal of some tumors has been successful, complete cure without recurrence is better accomplished by segmental tracheal resection with end-to-end anastomosis.