Longitudinal Effects of Cigarette Smoking and Smoking Cessation on Aortic Wave Reflections, Pulse Wave Velocity, and Carotid Artery Distensibility.

Background We evaluated the effects of smoking and smoking cessation on aortic wave reflections (augmentation index), aortic pulse wave velocity, and carotid artery distensibility and stiffness (distensibility coefficient, Young's elastic modulus). Methods and Results Current smokers underwent carotid, radial, and femoral artery tonometry and carotid ultrasound at baseline and 3 years after a quit attempt. Baseline associations of smoking heaviness markers (exhaled carbon monoxide and cigarettes smoked/d) and effects of smoking cessation at year 3 on changes in arterial measures were assessed using multivariable linear regression models. The 1417 smokers (54% female) were mean (SD) 49.3 (11.6) years old and smoked 17.2 (8.3) cigarettes/d (exhaled carbon monoxide 14.7 [8.2] parts per million). Arterial measures were associated more strongly with age, blood pressure (BP), and waist circumference than with smoking heaviness markers. Augmentation index was associated independently with carbon monoxide (P=0.004). Pulse wave velocity, distensibility coefficient, and Young's elastic modulus had small, inconsistent associations with smoking heaviness markers. At year 3, augmentation index improved with smoking cessation (P=0.006) despite more weight gain (2.54 vs 0.36 kg, P<0.001) and insulin resistance (P=0.001) among abstainers, but distensibility coefficient decreased (P=0.004). Changes in arterial measures were related more strongly to changes in BP than smoking cessation. Conclusions Arterial wave reflection and stiffness measures were associated more strongly with age, BP, and waist circumference than smoking heaviness. Smoking cessation was associated with weight gain and increased insulin resistance. Changes in arterial measures were predicted by changes in BP, highlighting the need to address weight gain and BP changes during a quit attempt.

Health assessments and screening tools for adults experiencing homelessness: a systematic review.

BACKGROUND: Homelessness is increasing globally. It results in poorer physical and mental health than age matched people living in permanent housing. Better information on the health needs of people experiencing homelessness is needed to inform effective resourcing, planning and service delivery by government and care organisations. The aim of this review was to identify assessment tools that are valid, reliable and appropriate to measure the health status of people who are homeless. METHODS: Data sources: A systematic literature search was conducted in PubMed (and Medline), PsychInfo, Scopus, CINAHL and ERIC from database inception until September 2018. Key words used were homeless, homelessness, homeless persons, vagrancy, health status, health, health issues, health assessment and health screening. The protocol was registered with PROSPERO. The National Health and Medical Research Council of Australia (NHMRC) hierarchy of evidence was applied; methodological quality of included articles was assessed using the McMaster critical appraisal tools and psychometric properties of the tools were appraised using the International Centre for Allied Health Evidence Ready Reckoner. RESULTS: Diverse tools and measures (N = 71) were administered within, and across the reviewed studies (N = 37), with the main focus being on general health, oral health and nutrition. Eleven assessment tools in 13 studies had evidence of appropriate psychometric testing for the target population in domains of quality of life and health status, injury, substance use, mental health, psychological and cognitive function. Methodological quality of articles and tools were assessed as moderate to good. No validated tools were identified to assess oral health, chronic conditions, anthropometry, demography, nutrition, continence, functional decline and frailty, or vision and hearing. However, assessments of physical constructs (such as oral health, anthropometry, vision and hearing) could be applied to homeless people on a presumption of validity, because the constructs would be measured with clinical indicators in the same manner as people living in permanent dwellings. CONCLUSIONS: This review highlighted the need to develop consistent and comprehensive health assessment tools validated with, and tailored for, adults experiencing homelessness.

Stable Ischemic Heart Disease in Women.

PURPOSE OF THE REVIEW: Paradoxically, although women have a lower burden of coronary atherosclerosis, they experience more symptoms, more frequent hospitalizations, and a worse prognosis compared to men. This is in part due to biological variations in pathophysiology between the two sexes, and in part related to inadequate understanding of these differences, subconscious referral bias, and suboptimal application of existing women-specific guidelines. We sought to review the contemporary literature and provide an update on risk assessment, diagnosis, and management of IHD in women. RECENT FINDINGS: IHD in women is often secondary to diffuse non-obstructive atherosclerosis, coronary spasm, inflammation, and endothelial and microvascular dysfunction, and less commonly due to the male pattern of flow-limiting epicardial stenosis. Both IHD patterns likely represent sex-specific manifestations of the same disease process. Additionally, there is a differential expression of risk factors and symptoms between men and women. Application of male-pattern IHD risk factors and presentation to women contributes to under-recognition, under-testing, and under-treatment of IHD in women compared to men. Traditional diagnostic evaluation has focused on detection of epicardial disease, amenable to revascularization. Our improved understanding of sex-specific pathophysiology of IHD has enabled us to also develop tools for detection of microvascular disease. Advances in stress MRI, flow quantification on stress PET, and provocative invasive angiography have filled this void and offer important diagnostic and prognostic information. Despite our improved understanding of sex-specific differences in presentation, risk factors, pathophysiology, diagnostic testing, and management strategies of IHD, women with IHD continue to experience worse outcomes than men. This disparity underscores the need for improved research and understanding of biological sex differences, elimination of subconscious gender bias in referral patterns, and improved application of existing research into clinical practice.

Situ: Identifying and Explaining Suspicious Behavior in Networks.

Despite the best efforts of cyber security analysts, networked computing assets are routinely compromised, resulting in the loss of intellectual property, the disclosure of state secrets, and major financial damages. Anomaly detection methods are beneficial for detecting new types of attacks and abnormal network activity, but such algorithms can be difficult to understand and trust. Network operators and cyber analysts need fast and scalable tools to help identify suspicious behavior that bypasses automated security systems, but operators do not want another automated tool with algorithms they do not trust. Experts need tools to augment their own domain expertise and to provide a contextual understanding of suspicious behavior to help them make decisions. In this paper we present Situ, a visual analytics system for discovering suspicious behavior in streaming network data. Situ provides a scalable solution that combines anomaly detection with information visualization. The system's visualizations enable operators to identify and investigate the most anomalous events and IP addresses, and the tool provides context to help operators understand why they are anomalous. Finally, operators need tools that can be integrated into their workflow and with their existing tools. This paper describes the Situ platform and its deployment in an operational network setting. We discuss how operators are currently using the tool in a large organization's security operations center and present the results of expert reviews with professionals.

Clickable Microgel Scaffolds as Platforms for 3D Cell Encapsulation.

While microporous scaffolds are increasingly used for regenerative medicine and tissue repair applications, the most common techniques to fabricate these scaffolds use templating or top-down fabrication approaches. Cytocompatible bottom-up assembly methods afford the opportunity to assemble microporous systems in the presence of cells and create complex polymer-cell composite systems in situ. Here, microgel building blocks with clickable surface groups are synthesized for the bottom-up fabrication of porous cell-laden scaffolds. The facile nature of assembly allows for human mesenchymal stem cells to be incorporated throughout the porous scaffold. Particles are designed with mean diameters of ≈10 and 100 µm, and assembled to create varied microenvironments. The resulting pore sizes and their distribution significantly alter cell morphology and cytoskeletal formation. This microgel-based system provides numerous tunable properties that can be used to control multiple aspects of cellular growth and development, as well as providing the ability to recapitulate various biological interfaces.

Laser interferometric method for measuring linear polymerization shrinkage in light cured dental restoratives.

OBJECTIVE: A novel laser interferometric method for monitoring linear polymerization shrinkage in dental restoratives is demonstrated. METHODS: The experimental apparatus consists of a low power Helium-Neon laser, a home-built Michelson interferometer, amplified photodiode detectors, and a computer data acquisition system. The feasibility of using interferometry to measure linear shrinkage was evaluated by measuring the percent linear contraction in five commercially available light cured restorative systems. RESULTS: Five-min interferometric curing profiles were collected for each restorative using a 400 mW/cm2 curing light irradiance. The 'interferograms' were converted into percent linear contraction profiles that revealed the relative kinetics of material shrinkage. The overall percent linear contraction after 5 min compares favorably with literature data for the five commercial restoratives studied here. SIGNIFICANCE: Interferometry offers several advantages over conventional methods of measuring polymerization contraction. These advantages include the inherent sensitivity and accuracy offered by interferometric measurements; the instrument does not need to be calibrated since the wavelength of the laser light source provides an accurate length standard. Also, the ability to collect data at high acquisition rates allows for the real-time characterization of unusually fast photopolymerization reactions. The low cost and relative ease of use associated with the apparatus are also advantageous.

Bogorol A produced in culture by a marine Bacillus sp. reveals a novel template for cationic peptide antibiotics.

[figure: see text] Bogorol A (1), a novel peptide antibiotic active against MRSA and VRE, has been isolated from cultures of a marine Bacillus sp. collected in Papua New Guinea. The structure of bogorol A was elucidated by a combination of spectroscopic analyses and chemical degradation. Bogorol A illustrates a new structural template for "cationic peptide antibiotics".

Transcription initiation-defective forms of sigma(54) that differ in ability To function with a heteroduplex DNA template.

Transcription by sigma(54)-RNA polymerase holoenzyme requires an activator that catalyzes isomerization of the closed promoter complex to an open complex. We examined mutant forms of Salmonella enterica serovar Typhimurium sigma(54) that were defective in transcription initiation but retained core RNA polymerase- and promoter-binding activities. Four of the mutant proteins allowed activator-independent transcription from a heteroduplex DNA template. One of these mutant proteins, L124P V148A, had substitutions in a sequence that had not been shown previously to participate in the prevention of activator-independent transcription. The remaining mutants did not allow efficient activator-independent transcription from the heteroduplex DNA template and had substitutions within a conserved 20-amino-acid segment (Leu-179 to Leu-199), suggesting a role for this sequence in transcription initiation.

Cell-based screen for antimitotic agents and identification of analogues of rhizoxin, eleutherobin, and paclitaxel in natural extracts.

We describe a cell-based assay for antimitotic compounds that is suitable for drug discovery and for quantitative determination of antimitotic activity. In the assay, cells arrested in mitosis as a result of exposure to antimitotic agents in pure form or in crude natural extracts are detected by ELISA using the monoclonal antibody TG-3. The assay was used to screen >24,000 extracts of marine microorganisms and invertebrates and terrestrial plants and to guide the purification of active compounds from 5 of 119 positive extracts. A new rhizoxin analogue was found in a Pseudomonas species, six new eleutherobin analogues were identified from the octocoral Erythropodium caribaeorum, and two paclitaxel analogues were found in the stem bark of the tree Ilex macrophylla. The assay was also used for quantitative comparison of the antimitotic activity of different analogues. It revealed the importance of the C-11 to C-13 segment of the diterpene core of eleutherobin for its antimitotic activity. The identification of antimitotic compounds in very low abundance and their high (0.5%) occurrence in natural extracts indicates that drug discovery efforts using this cell-based assay may lead to the identification of structurally novel antimitotic agents.

Determination of taurine in plasma by capillary zone electrophoresis following derivatisation with fluorescamine.

A novel capillary zone electrophoresis method is described for the determination of taurine in plasma. The method is rapidly executed and is highly selective for taurine as separation is based on the difference in ionisation of this amino acid from that of other amino acids. Following addition of homotaurine as internal standard, plasma proteins were precipitated with acetonitrile and the supernatant was derivatised with fluorescamine in the presence of a borate buffer. Capillary electrophoresis (CE) separations were carried out in reverse polarity mode at 27.5 kV on a Beckman P/ACE MDQ CE instrument, equipped with a diode array detector (DAD) set at 266 nm. The sample tray was cooled to 5 degrees C and separations were carried out at 20 degrees C. The fused-silica capillary was 50.2 cm in length (40.2 cm to detector) with an internal diameter of 75 microm. A capillary conditioning solution was applied daily in order to suppress the residual electroosmotic flow (EOF). The method, which was validated using feline plasma as the blank matrix, was shown to be linear and reproducible over the concentration range 2.5-100 microg/mL. The coefficients of variation (CVs) of replicate analyses were less than 4.5% at 1 microg/mL taurine in feline plasma and less than 3% for 2.5 microg/mL in human plasma. Recovery was estimated at 99.2% with a CV of 4.85%. It has been demonstrated that quantitation in aqueous solution yields similar results to those obtained by interpolation on a plasma calibration curve provided that subtraction for the taurine peak in unspiked plasma is carried out and that a suitable internal standard is employed.

The amino terminus of Salmonella enterica serovar Typhimurium sigma(54) is required for interactions with an enhancer-binding protein and binding to fork junction DNA.

Transcription initiation by the sigma(54)-RNA polymerase holoenzyme requires an enhancer-binding protein that is thought to contact sigma(54) to activate transcription. To identify potential enhancer-binding protein contact sites in sigma(54), we compared the abilities of wild-type and truncated forms of Salmonella enterica serovar Typhimurium sigma(54) to interact with the enhancer-binding protein DctD in a chemical cross-linking assay. Removal of two regions in the amino-terminal portion of sigma(54), residues 57 to 105 and residues 144 to 179, prevented cross-linking, but removal of either region alone did not. In addition, deletion of 56 amino-terminal residues of sigma(54) (region I) reduced the affinity of the protein for a fork junction DNA probe.

Comparison of molecular methods for typing Vibrio parahaemolyticus.

An outbreak of Vibrio parahaemolyticus gastroenteritis on Canada's west coast in 1997 emphasized the need to develop molecular methods for differentiation and typing of these organisms. Isolates were analyzed by enterobacterial repetitive intergenic consensus sequence (ERIC) PCR, detection of restriction fragment length polymorphisms (RFLP) in rRNA genes (ribotyping), pulsed-field gel electrophoresis (PFGE), and RFLP analysis of the genetic locus encoding the polar flagellum (Fla locus RFLP analysis). ERIC PCR and ribotyping were the most informative typing methods, especially when used together, while Fla locus RFLP analysis was the least discriminatory. PFGE exhibited good discrimination but suffered from a high incidence of DNA degradation. ERIC PCR and ribotyping will be useful for the evaluation of genetic and epidemiological relationships among V. parahaemolyticus strains.

Mutant forms of Salmonella typhimurium sigma54 defective in transcription initiation but not promoter binding activity.

Transcription initiation with sigma54-RNA polymerase holoenzyme (sigma54-holoenzyme) has absolute requirements for an activator protein and ATP hydrolysis. sigma54's binding to core RNA polymerase and promoter DNA has been well studied, but little is known about its role in the subsequent steps of transcription initiation. Following random mutagenesis, we isolated eight mutant forms of Salmonella typhimurium sigma54 that were deficient in transcription initiation but still directed sigma54-holoenzyme to the promoter to form a closed complex. Four of these mutant proteins had amino acid substitutions in region I, which had been shown previously to be required for sigma54-holoenzyme to respond to the activator. From the remaining mutants, we identified four residues in region III which when altered affect the function of sigma54 at some point after closed-complex formation. These results suggest that in addition to its role in core and DNA binding, region III participates in one or more steps of transcription initiation that follow closed-complex formation.

Multinational outbreak of Salmonella enterica serotype Newport infections due to contaminated alfalfa sprouts.

CONTEXT: In December 1995, reported Salmonella enterica serotype Newport (SN) infections increased sharply in Oregon and British Columbia but not elsewhere in North America. Similar unexplained increases had been noted in 6 other states in the fall of 1995. OBJECTIVE: To determine the source of the outbreak(s). DESIGN: Case-control studies, environmental investigations, bacterial subtyping, and surveillance information review. SETTINGS: Oregon and British Columbia communities (winter 1995-1996) and Georgia, Oklahoma, Pennsylvania, Vermont, Virginia, and West Virginia (fall 1995). PARTICIPANTS: Oregon and British Columbia residents with culture-confirmed SN infections and onset from December 1, 1995, through February 29, 1996, and healthy community controls. MAIN OUTCOME MEASURES: Odds ratio (OR) of illness associated with exposures; distribution patterns and culture of alfalfa seeds and sprouts; subtyping of SN isolates. RESULTS: We identified 133 cases in Oregon and British Columbia; 124 (93%) occurred in patients older than 18 years; 87 (65%) were female. Case patients were more likely than community control subjects to report having eaten alfalfa sprouts in the 5 days preceding illness (41% [17/41] vs 4% [3/75]; OR, 17.0; 95% confidence interval, 4.3-96.0). Case isolates shared a distinctive pulsed-field gel electrophoresis (PFGE) pattern. The SN was grown from seeds and alfalfa sprouts. The distribution of 1 seed lot to multiple growers corresponded to the distribution of cases. Distribution of a second seed lot from the same European wholesaler corresponded to the location of the fall outbreak, which was characterized by a similar demographic profile. The PFGE pattern of fall outbreak isolates and confiscated sprouts and seeds was indistinguishable from the Oregon and British Columbia outbreak and differed from background isolates. CONCLUSIONS: The SN-contaminated alfalfa seeds were distributed to multiple growers across North America in 1995 and resulted in a protracted international outbreak scattered over many months. Current sprouting methods are inadequate to protect consumers from such events. Alfalfa sprouts may be an elusive but important vehicle for salmonellosis and other enteric infections.

Loloatins A-D, cyclic decapeptide antibiotics produced in culture by a tropical marine bacterium.

Loloatins A (1) to D (4), a family of new cyclic decapeptide antibiotics, have been isolated from laboratory cultures of a tropical marine bacterium recovered from the Great Barrier Reef in Papua New Guinea. The structures of loloatins A-D were elucidated via a combination of spectroscopic analyses and chemical degradation. Loloatins A-D exhibit in vitro antimicrobial activity against methicillin-resistant Staphyloccoccus aureus, vancomycin-resistant enterococci, and drug-resistant Streptococcus pneumoniae.

Inexpensive, in-situ monitoring of borohydride concentrations.

Non-destructive, in-situ detection of 10(-3) to 10(-4) M borohydride ions in aqueous alkaline solutions containing borates can be easily and rapidly accomplished by simply measuring open circuit potentials of selected metals (relative to a suitable reference) immersed in these solutions.

High-throughput assay for G2 checkpoint inhibitors and identification of the structurally novel compound isogranulatimide.

Treatment of cancer cells lacking p53 function with G2 checkpoint inhibitors sensitizes them to the toxic effects of DNA damage and has been proposed as a strategy for cancer therapy. However, few inhibitors are known, and they have been found serendipitously. We report the development of a G2 checkpoint inhibition assay that is suitable for high-throughput screening and its application to a screen of 1300 natural extracts. We present the isolation of a new G2 checkpoint inhibitor, the structurally novel compound isogranulatimide. In combination with gamma-irradiation, isogranulatimide selectively kills MCF-7 cells lacking p53 function.

Determination of aspirin and salicylic acid in transdermal perfusates.

A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of aspirin and salicylic acid in transdermal perfusates. The compounds were separated on a C8 Nucleosil column (5 microm, 250x4.6 mm) using a mobile phase containing a mixture of water-acetonitrile-orthophosphoric acid (650:350:2, v/v/v) and a flow-rate of 1 ml/min. The transdermal samples were in phosphate-buffered saline (PBS) and could be injected directly onto the HPLC system. The method was reproducible with inter-day R.S.D. values of no greater than 3.46 and 2.60% for aspirin and salicylic acid, respectively. The method was linear over the concentration range 0.2-5.0 microg/ml and had a limit of detection of 0.05 microg/ml for both compounds. For certain samples, it was necessary to ensure that no transmembrane leakage of the aspirin prodrugs had occurred. In these cases, a gradient was introduced by increasing the acetonitrile content of the mobile phase after the salicylic acid had eluted. The method has been applied to the determination of aspirin and salicylic acid in PBS following in vitro application of the compounds to mouse skin samples.

Determination of aspirin and salicylic acid in human plasma by column-switching liquid chromatography using on-line solid-phase extraction.

A column-switching liquid chromatographic method is described for the simultaneous determination of aspirin and salicylic acid in human plasma. Blood samples are taken into chilled tubes containing a fluoride anticoagulant, and the plasma is isolated by centrifugation. Following a simple acidification step, a 200 microL aliquot of the sample is injected directly onto the HPLC system. The C-18 extraction column is washed with acidified water for 2 min, after which time the compounds are removed by back-flushing directly onto the analytical column (C-8 Nucleosil, 5 microns, 250 mm x 4.6 mm). The flow rate through both columns is 1 mL/min, and the analytes are quantified by measurement of their UV absorbance at 225 nm. The mobile phase is a mixture of water-methanol-acetonitrile-orthophosphoric acid (650:200:150:1 v/v/v/v). The method is linear in the concentration ranges 0.10-5.00 micrograms/mL for aspirin and 0.25-15.00 micrograms/mL for salicylic acid. Both compounds have a limit of quantitation of 0.10 microgram/mL and a limit of detection of 0.04 microgram/mL. Extensive stability tests have been carried out, and validation studies reveal the method to be reproducible and repeatable. Excellent recoveries from plasma obviate the need for an internal standard. The procedure is easier to execute and requires less sample handling than methods currently described in the literature. It has been successfully applied to the investigation of the levels of aspirin and salicylic acid in a healthy, nonfasting volunteer following a 600 mg oral dose of aspirin.