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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Alcohol policy endorsements have changed over time, probably interacting with the implementation and effectiveness of alcohol policy measures. The Standardized European Alcohol Survey (SEAS) evaluated public opinion toward alcohol policies in 20 European locations (19 countries and one subnational region) in 2015 and 2016 (n = 32,641; 18–64 years). On the basis of the SEAS report, we investigated regional differences and individual characteristics related to categories of alcohol policy endorsement. Latent class analysis was used to replicate cluster structure from the SEAS report and to examine individual probabilities of endorsement. Hierarchical quasi-binomial regression models were run to analyze the relative importance of variables of interest (supranational region, gender, age, educational achievement, and drinking status) on class endorsement probability, with random intercepts for each location. The highest support for alcohol control policies was recorded in Northern countries, which was in contrast to the Eastern countries, where the lowest support for control policies was found. Across all locations, positive attitudes toward control policies were associated with the female gender, older age, and abstaining from alcohol. Our findings underline the need to communicate alcohol-related harm and the implications of alcohol control policies to the public in order to increase awareness and support for such policies in the long run.

© 2019, © 2019 Informa UK Limited, trading as Taylor  &  Francis Group. Introduction: Due to the polymorphic clinical presentations and manifestations of systemic lupus erythematosus (SLE), biomarkers with enough diagnostic and prognostic value are of paramount importance. Recently, anti-double stranded DNA (anti-dsDNA) auto-antibodies have been proposed to monitor the response to different therapies. It has also been suggested that they should be employed as entry markers in trial studies. However, their clinical use remains still debated and, sometimes, controversial, due to conflicting findings reported. Areas covered: Through an extensive literature review, we evaluated changes in anti-dsDNA auto-antibodies levels before and after the administration of the treatment (either biological or non-biological). Expert opinion: Anti-dsDNA auto-antibodies related findings are still difficult to compare mainly because of the different detecting methods employed, even though in most studies included in this review a consistent decreasing pattern after the treatment seems to emerge. Hence, if properly standardized, anti-dsDNA auto-antibody profile may be a reliable biomarker to monitor the effectiveness of biologics as well as of non-biological drugs, especially if grouped in composite outcomes scores, such as the ‘Lupus Multivariable Outcome Score’ (LUMOS) or measured with other biomarkers, such as anti-nucleosome auto-antibodies. We recommend the assessment of anti-dsDNA auto-antibodies levels in both daily practice and research settings.

© 2019 Elsevier Ltd We did a global review to synthesise data on the prevalence, harms, and interventions for stimulant use, focusing specifically on the use of cocaine and amphetamines. Modelling estimated the effect of cocaine and amphetamine use on mortality, suicidality, and blood borne virus incidence. The estimated global prevalence of cocaine use was 0·4% and amphetamine use was 0·7%, with dependence affecting 16% of people who used cocaine and 11% of those who used amphetamine. Stimulant use was associated with elevated mortality, increased incidence of HIV and hepatitis C infection, poor mental health (suicidality, psychosis, depression, and violence), and increased risk of cardiovascular events. No effective pharmacotherapies are available that reduce stimulant use, and the available psychosocial interventions (except for contingency management) had a weak overall effect. Generic approaches can address mental health and blood borne virus infection risk if better tailored to mitigate the harms associated with stimulant use. Substantial and sustained investment is needed to develop more effective interventions to reduce stimulant use.

BACKGROUND/AIMS: Small intestinal bacterial overgrowth (SIBO) and hemodynamic changes are common in cirrhosis. We wanted to examine our hypothesis whether SIBO leads to hemodynamic changes in cirrhosis. MATERIALS AND METHODS: A total of 50 patients with cirrhosis and 15 healthy controls were enrolled in a pilot prospective study. All participants underwent the lactulose hydrogen breath test for SIBO and echocardiography with a simultaneous assessment of blood pressure and heart rate. Cardiac output and systemic vascular resistance were calculated. RESULTS: Study participants with SIBO had a lower systolic blood pressure and systemic vascular resistance compared to those without SIBO and to healthy controls (110.2±12.3 mmHg vs. 126.2±21.0 mmHg and 121.2±9.8 mmHg; p=0.005 and p=0.011, respectively; 1312±352 dyn•s•cm-5 vs. 1704±424 dyn•s•cm-5 and 1648±272 dyn•s•cm-5; p=0.001 and p=0.006, respectively), but a higher cardiac output (5.38±1.41 l/min vs. 4.52±1.03 l/min and 4.40±0.68 l/min; p=0.034 and p=0.041, respectively) and C-reactive protein (10.5[1.2-16.5] mg/l vs. 2.8[0.6-9.1] mg/l; p=0.028; no comparison with healthy controls). There were no significant differences between patients without SIBO and healthy controls with regard to systolic blood pressure (p=0.554), systemic vascular resistance (p=0.874), and cardiac output (p=0.795). SIBO was associated with vasodilation and hyperdynamic circulation in decompensated cirrhosis (p=0.002; p=0.012), but not in compensated cirrhosis (p=1.000; p=0.474). CONCLUSIONS: SIBO is associated with hyperdynamic circulation and other hemodynamic changes in cirrhosis and may be a principal factor causing these through systemic inflammation.

© 2019, Springer Nature B.V. Objectives: Various techniques can be used for endoscopic enucleation of the prostate (EEP): removal of all nodes as a single unit (en bloc) or a step-by-step removal of adenomatous nodes (two- and three-lobe techniques). The objective of this study was to perform a comparative analysis of en bloc and two-lobe techniques for holmium laser enucleation of the prostate (HoLEP) and thulium fiber laser enucleation of the prostate (ThuFLEP). Methods: Retrospective assessment included patients with bladder outlet obstruction (IPSS > 20, Qmax < 10) secondary to BPH treated from January 2013 to December 2018. All the patients were assessed prior to surgery, as well as at 1, 3 and 6 months after surgery. Results: The data of 1115 patients who underwent HoLEP or ThuFLEP were analyzed. Two techniques were used: en bloc (406 patients) and two-lobe (709 patients). Mean prostate volumes were comparable between groups. Mean surgery times (68.8 ± 30.6 min vs 67.4 ± 30.1 min; p = 0.604) and enucleation rates (1.9 ± 0.74 g/min vs 1.9 ± 0.69 g/min; p = 0.217) were also comparable. Morcellation rate was lower in en bloc patients with prostate > 150 cc (2.8 ± 1.1 g/min vs 3.7 ± 2.3 g/min; p < 0.001). At 6 months, no differences in functional outcomes (IPSS, PVR, Qmax and QoL) were found. Conclusions: Outcomes and complication rates of en bloc and two-lobe EEP techniques were comparable. En bloc technique was found to have less favorable outcomes in morcellation rate for prostates > 150 cc. The choice of the technique should depend on surgeon’s preferences.

© 2019 Elsevier Ltd What was the impact of one-way radio messages aimed at hostages kidnapped by the FARC and held captive in the Colombian jungle? Messages were read out every Saturday night (reception in the Colombian jungle is best between 01:00am and 04:00am) for 22 years. Here, radio animated emotional registers of lived experience as one-way radio messages intensified novel forms of imagination for both speaker, hearer and the ‘community’ of other hearers, in this case thousands of hostages dotted around the jungle. This article examines the linguistic instrumentality of the radio voice. By analysing the Voces del Secuestro messages, it is shown how a phenomenological listening of the radio voice gave hope in times of anguish.

© 2019 Wiley Periodicals, Inc. Background: Despite advances in treatment, the recurrence rates for laryngeal cancer range from 16% to 40%. Methods: Patients with recurrent laryngeal cancer treated at Memorial Sloan Kettering (MSK) from 1999 to 2016 were reviewed. Survival outcomes were analyzed. Results: Of 241 patients, 88% were male; the median age was 67 years; 71% had primary glottic tumors. At initial treatment, 72% of patients were seen with early stage disease; primary treatment was radiation (68%), chemoradiation (29%), and surgery (3%). The most common salvage surgery was total laryngectomy (74%). Forty-seven percentage were upstaged at salvage surgery. The 2- and 5-year disease-specific survival (DSS) was 74% and 57%, respectively. Patients with cT4 disease treated with nonsurgical primary management had a 0% 5-year DSS. Independent predictors of DSS were tumor location, perineural invasion, margin, and stage. Conclusions: Salvage surgery results in acceptable oncologic outcomes. Stage, disease site, perineural invasion, and margins are associated with inferior DSS.

© 2019 Wiley Periodicals, Inc. Background: The management of patients with incidentally discovered metastatic thyroid cancer in cervical lymph nodes in neck dissection specimens for other pathologies is unclear. Methods: Retrospective review of neck dissection specimens for nonthyroid malignancy during a 30-year period was undertaken to identify incidental metastatic papillary thyroid cancer (PTC). Results: Twenty-six patients had an incidental finding of PTC in lymph node(s) in neck dissection specimens. Subsequent ultrasound of the thyroid showed nodules in 20 patients. Eleven (42%) underwent total thyroidectomy, 1 (4%) had a lobectomy, and 14 (54%) were kept under active surveillance only. At a median follow-up of 48 months (range 10-189 months), all patients who had undergone surgery and those under surveillance were free of PTC recurrence. Conclusion: Evaluation for detection of a primary thyroid tumor is essential in all patients with incidentally discovered metastatic PTC. Decision regarding surgery or surveillance is dependent on clinical and radiological tumor features and patient factors.

© 2019 Elsevier B.V. S-Methyl methanethiosulfonate (MMTS) is used in experimental biochemistry for alkylating thiol groups of protein cysteines. Its applications include mainly trapping of natural thiol-disulfide states of redox-sensitive proteins and proteins which have undergone S-nitrosylation. The reagent can also be employed as an inhibitor of enzymatic activity, since nucleophilic cysteine thiolates are commonly present at active sites of various enzymes. The advantage of using MMTS for this purpose is the reversibility of the formation of methylthio mixed disulfides, compared to irreversible alkylation using conventional agents. Additional benefits include good accessibility of MMTS to buried protein cysteines due to its small size and the simplicity of the protection and deprotection procedures. In this study we report examples of MMTS application in experiments involving oxidoreductase (glyceraldehyde-3-phosphate dehydrogenase, GAPDH), redox-regulated protein (recoverin) and cysteine protease (triticain-α). We demonstrate that on the one hand MMTS can modify functional cysteines in the thiol enzyme GAPDH, thereby preventing thiol oxidation and reversibly inhibiting the enzyme, while on the other hand it can protect the redox-sensitive thiol group of recoverin from oxidation and such modification produces no impact on the activity of the protein. Furthermore, using the example of the papain-like enzyme triticain-α, we report a novel application of MMTS as a protector of the primary structure of active cysteine protease during long-term purification and refolding procedures. Based on the data, we propose new lines of MMTS employment in research, pharmaceuticals and biotechnology for reversible switching off of undesirable activity and antioxidant protection of proteins with functional thiol groups.

© 2019 Elsevier Ltd Introduction: Contemporary research papers have highlighted the issue of lesion-aphasia discordance in reference to the classic ‘associationist’ model provided by Wernicke-Lichtheim. The objective of the present study is to explore frequency, pattern and evolution of lesion-discordant aphasia following first ever acute stroke in Bengali-speaking subjects. Methods: Bengali version of Western Aphasia Battery, a validated scale, was used for language assessment in our study subjects. Lesion localization was done by using Magnetic resonance imaging (MRI) (3T) for ischemic stroke (if not contraindicated) and computed tomography (CT) for hemorrhagic stroke. Among 515 screened cases of first-ever acute stroke, 208 presented aphasia. Language assessment was done between 7 and 14 days in all study subjects and was repeated between 90 and 100 days in patients available for follow-up. Ischemic stroke cases with contraindication for MRI underwent CT imaging. Discordance between lesion and aphasic phenotype was determined only for right-handed subjects with cortical involvement (isolated or in combination with sub-cortical white matter) in the left hemisphere. Appropriate statistical tests were used to analyze the collected data. Results: Lesion-aphasia discordance was found in 20 out of 134 patients with aphasia who were dextral and had cortical involvement in the left hemisphere (14.92%). The pattern of discordance observed were- posterior lesion with Broca's aphasia (4; 20%); posterior lesion with global aphasia (8; 40%); anterior lesion with global aphasia (4; 20%), and posterior lesion with mixed transcortical aphasia (4; 20%). On univariate analysis, the factors significantly associated with lesion-aphasia discordance were hemorrhagic stroke (p = 0.000); posterior perisylvian location (p = 0.002), and higher education (p = 0.048). After adjusting for all other variables, hemorrhagic stroke was found to have strong association with lesion-aphasia discordance (p = 0.001, OR = 11.764, 95% CI, 2.83–50.0). Discordant cases were more likely to recover or change to a milder type compared to concordant cases (p = 0.007, OR = 11.393, 95% CI, 1.960–66.231), after adjusting for all other variables including initial severity of aphasia (p = 0.006, OR = 8.388, 95% CI, 1.816–38.749). Conclusion: Lesion-aphasia discordance following acute stroke is not uncommon among Bengali-speaking subjects. In the discordant group, preponderance towards non-fluent aphasia was observed. Discordance occurred more frequently after hemorrhagic stroke. Subjects with lesion-discordant aphasia presented better recovery during early post-stroke phase.

© The Author(s) 2019. Responses of five rotary blood pumps, namely HeartAssist 5, HeartMate II, HeartWare, Sputnik 1, and Sputnik 2, were extensively assessed in six test cases using a mathematical model of the cardiovascular system. Data for the rotary pumps were derived from pressure–flow curves reported in the literature. The test cases were chosen to attempt to cover most common clinical conditions, such as partial or full support or transitions between different levels of ventricular support. The investigated parameters are collected in a table and presented in figures, such as pressure–volume loops, H-Q curves, pump flow, and aortic pressure waveforms. HeartAssist, Sputnik 1, and Sputnik 2 pumps provide comparable level of aortic pressure, pump flow pulsatility PI(QP), and aortic pressure pulsatility PI(AoP) due to the similarity of pressure–flow characteristic curves of these pumps. HeartMate II provides a minimal backflow among other investigated rotary blood pumps due to the maximum pressure head at zero flow. HeartWare provides minimal pulsation of flow, which is confirmed by a flow range from −2 to 7 L/min in case 1. At the same time, the greatest degree of unloading was demonstrated by the HeartWare due to the flatness of the pressure–flow curve shape. The conclusions were made based on the obtained results, including the influence of pressure–flow curve shape on the pump performance and occurrences of adverse events, such as backflow or suction. For example, the increase of the pressure head at zero flow decreases the likelihood of backflow through the pump, and with it, increasing the flow under minimal pressure head increases the likelihood of suction.

© 2019 John Wiley  &  Sons Australia, Ltd. AIM: The aim of this research was to evaluate the possibility of identifying the sex of 1 subject through visual assessment of a frontal photograph of dentition, and to investigate if some morphological characteristics are related to sex determination. METHODS: 5 expert dentists, 5 non-expert dentists and 5 laypeople were made to watch 100 intraoral photographs for 5 seconds each and to establish their sex. The responses of the participants and the baseline characteristics of photographed dentitions were analyzed. RESULTS: The proportion of right answers was 56.0% ± 8.2% in the group of expert dentists, 65.0% ± 6.0% in the group of non-expert dentists and 58.6% ± 4.5% in the group of non-expert people. The round shape of maxillary central incisors was related to the female gender (P = .006). The male condition was correlated with poor oral hygiene for 4 observers. Female sex perception was correlated with round morphology of upper central incisors for 3 observers. CONCLUSION: No difference in the ability to determine the sex was registered among groups, suggesting that sex perception is not strongly influenced by the characteristics of dentition.

© 2019 by the authors. Controlled fabrication of 45 nm width nanowire using simulated emission depletion (STED) direct laser writing with a rod-shape effective focus spot is presented. In conventional STED direct laser writing, normally a donut-shaped depletion focus is used, and the minimum linewidth is restricted to 55 nm. In this work, we push this limit to sub-50 nm dimension with a rod-shape effective focus spot, which is the combination of a Gaussian excitation focus and twin-oval depletion focus. Effects of photoinitiator type, excitation laser power, and depletion laser power on the width of the nanowire are explored, respectively. Single nanowire with 45 nm width is obtained, which is λ/18 of excitation wavelength and the minimum linewidth in pentaerythritol triacrylate (PETA) photoresist. Our result accelerates the progress of achievable linewidth reduction in STED direct laser writing.

The arterial pulse wave (PW) is a rich source of information on cardiovascular (CV) health. It is widely measured by both consumer and clinical devices. However, the physical determinants of the PW are not yet fully understood, and the development of PW analysis algorithms is limited by a lack of PW data sets containing reference CV measurements. Our aim was to create a database of PWs simulated by a computer to span a range of CV conditions, representative of a sample of healthy adults. The typical CV properties of 25-75 yr olds were identified through a literature review. These were used as inputs to a computational model to simulate PWs for subjects of each age decade. Pressure, flow velocity, luminal area, and photoplethysmographic PWs were simulated at common measurement sites, and PW indexes were extracted. The database, containing PWs from 4,374 virtual subjects, was verified by comparing the simulated PWs and derived indexes with corresponding in vivo data. Good agreement was observed, with well-reproduced age-related changes in hemodynamic parameters and PW morphology. The utility of the database was demonstrated through case studies providing novel hemodynamic insights, in silico assessment of PW algorithms, and pilot data to inform the design of clinical PW algorithm assessments. In conclusion, the publicly available PW database is a valuable resource for understanding CV determinants of PWs and for the development and preclinical assessment of PW analysis algorithms. It is particularly useful because the exact CV properties that generated each PW are known.NEW & NOTEWORTHY First, a comprehensive literature review of changes in cardiovascular properties with age was performed. Second, an approach for simulating pulse waves (PWs) at different ages was designed and verified against in vivo data. Third, a PW database was created, and its utility was illustrated through three case studies investigating the determinants of PW indexes. Fourth, the database and tools for creating the database, analyzing PWs, and replicating the case studies are freely available.

© 2019 Elsevier B.V. A new sample extraction protocol was developed for pharmacokinetic studies of dabigatran with high-performance liquid chromatography separation - electrospray ionization time-of-flight mass spectrometry analysis. After protein precipitation with acetonitrile, free dabigatran and its metabolites are separated into water phase by water-dichloromethane liquid-liquid extraction to purify the sample from proteins and endogenous lipophilic compounds. Chromatographic separation was achieved on an Agilent Zorbax SB-CN column (150 × 4.6 mm, 5 µm)) using 0.1% aqueous solution of formic acid and acetonitrile (80:20) as the mobile phase. Agilent Zorbax SB-CN column was selected to improve sample resolution and to avoided early elution of dabigatran previously seen when using a C18 column. The extended calibration curve was constructed from 5 to 1000 ng/L while precision and accuracy were assessed at four levels across the linear dynamic ranges. Within-run precision was <5.6% and the between-run precision was <3.9%. The method accuracy ranged from 89.8% to 104.4%. The developed method was successfully applied to 30 patient samples to evaluate antithrombotic efficacy and anticoagulant activity of dabigatran following knee endoprosthesis surgery.

© 2019 American Chemical Society. Various agents, including drugs as well as nonmolecular stimuli, induce alterations in the physicochemical properties of proteins in cell lysates, living cells, and organisms. These alterations can be probed by applying a stability- and solubility-modifying factor, such as elevated temperature, to a varying degree. As a second dimension of variation, drug concentration or agent intensity/concentration can be used. Compared to standard approaches where curves are fitted to protein solubility data acquired at different temperatures and drug concentrations, Proteome Integral Solubility Alteration (PISA) assay increases the analysis throughput by 1 to 2 orders of magnitude for an unlimited number of factor variation points in such a scheme. The consumption of the compound and biological material decreases in PISA by the same factor. We envision widespread use of the PISA approach in chemical biology and drug development.

Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics. Many peptide ligands of nicotinic acetylcholine receptors (nAChRs) contain a large number of positively charged amino acid residues, a striking example being conotoxins RgIA and GeXIVA from marine mollusk venom, with an arginine content of >30%. To determine whether peptides built exclusively from arginine residues will interact with different nAChR subtypes or with their structural homologs such as the acetylcholine-binding protein and ligand-binding domain of the nAChR α9 subunit, we synthesized a series of R3, R6, R8, and R16 oligoarginines and investigated their activity by competition with radioiodinated α-bungarotoxin, two-electrode voltage-clamp electrophysiology, and calcium imaging. R6 and longer peptides inhibited muscle-type nAChRs, α7 nAChRs, and α3β2 nAChRs in the micromolar range. The most efficient inhibition of ion currents was detected for muscle nAChR by R16 (IC50 = 157 nM) and for the α9α10 subtype by R8 and R16 (IC50 = 44 and 120 nM, respectively). Since the R8 affinity for other tested nAChRs was 100-fold lower, R8 appears to be a selective antagonist of α9α10 nAChR. For R8, the electrophysiological and competition experiments indicated the existence of two distinct binding sites on α9α10 nAChR. Since modified oligoarginines and other cationic molecules are widely used as cell-penetrating peptides, we studied several cationic polymers and demonstrated their nAChR inhibitory activity. SIGNIFICANT STATEMENT: By using radioligand analysis, electrophysiology, and calcium imaging, we found that oligoarginine peptides are a new group of inhibitors for muscle nicotinic acetylcholine receptors (nAChRs) and some neuronal nAChRs, the most active being those with 16 and 8 Arg residues. Such compounds and other cationic polymers are cell-penetrating tools for drug delivery, and we also demonstrated the inhibition of nAChRs for several of the latter. Possible positive and negative consequences of such an action should be taken into account.

© 2019 The Authors Introduction: Abdominal abscesses are one of the frequent and dangerous postoperative complication. They occur as a result of failure of seams esophagojejunal anastomosis after gastrectomy (17%), perforation of gastric and duodenal ulcers (26.8%), splenectomy (25.4%), failure of biliodigestive anastomoses (23.8%), inadequate drainage of the subphrenic space (22.2%), acute pancreatitis (14%). Left-sided subphrenic abscesses are the most common of them. Case presentation: We present a patient with the left-sided subphrenic abscess, formed as a result of insolvency of the esophagojejunal anastomosis after gastrectomy and splenectomy, which underwent percutaneous drainage under the control of ultrasound and X-ray. Sanitation of the abscess cavity and the introduction of fibrin glue into it made it possible to close the fistula and heal the patient. Discussion: The described case shows that the rehabilitation of the abscess and the injection of fibrin glue into it, made it possible to avoid surgery, eliminate the abscess and close the connection with the esophagojejunal anastomosis in a short time. Conclusion: Percutaneous drainage under the control of ultrasound made it possible to avoid surgery and heal the patient with the left-sided subphrenic abscess in a short time. Fistula treatment with fibrin glue is not only effective, but is also less risky than surgery.