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Opioid overdose and Opioid Use Disorder (OUD) statistics underscore an urgent need to significantly expand access to evidence-based OUD treatment. Office Based Opioid Treatment (OBOT) has proven effective for treating OUD. However, limited access to these treatments persists. Recognizing the need for significant investment in clinical, behavioral, and translational research, the Indiana State Department of Health and Indiana University embarked on a research initiative supported by the “Responding to the Addictions Crisis” Grand Challenge Program. This brief presents recommendations based on existing research and our own analyses of medical claims data in Indiana, where opioid misuse is high and treatment access is limited. The recommendations cover target providers, intervention focus, priority regions, and delivery methods.

The authors analyses the issues inherent in implementation of a multi-sensory mobile application which uses a map as an interface for an edutainment-style city guide for tourists. Two models – the triad of tourist experiences (3E), i.e. education, entertainment, and excitement, and the hierarchy of needs of Abraham Maslow – were used as the basis for identifying what conditions should be met by such an application to encourage its use by both local residents and tourists, in equal measure. It was decided that only open source software would be used to achieve the goal of the application.

Definitions in learners’ dictionaries are usually written within a limited defining vocabulary (DV), that is, a set of lexical units specified prior to defining. Some researchers claim that this approach to vocabulary control may lead to definitions being syntactically complex, convoluted, and wordy. This paper aims to examine whether the introduction of a limited DV in OALD5 made its definitions more difficult to read for learners as compared to the definitions in OALD4, which were written with no explicit restrictions on the definition vocabulary. The study examines a selection of construction patterns that are potentially difficult for less advanced learners, using quantitative and qualitative methods. The examination shows that the introduction of the limited DV had no effect on most parameters studied. However, it led to significant increases in the length of definitions and the number of nominal constructions with a postmodifying past participle (e.g., performance given, spice ground, phrase used).

Research background: This paper attempts to introduce the concept of Polish housing policy and define its course.

Backward induction (BI) was one of the earliest methods developed for solving finite sequential games with perfect information. It proved to be especially useful in the context of Tom Schelling’s ideas of credible versus incredible threats. BI can be also extended to solve complex games that include an infinite number of actions or an infinite number of periods. However, some more complex empirical or experimental predictions remain dramatically at odds with theoretical predictions obtained by BI. The primary example of such a troublesome game is Centipede. The problems appear in other long games with sufficiently complex structure. BI also shares the problems of subgame perfect equilibrium and fails to eliminate certain unreasonable Nash equilibria.

The main aim is to present recent developments in applications of symbolic computing in probabilistic and stochastic analysis, and this is done using the example of the well-known MAPLE system. The key theoretical methods discussed are (i) analytical derivations, (ii) the classical Monte-Carlo simulation approach, (iii) the stochastic perturbation technique, as well as (iv) some semi-analytical approaches. It is demonstrated in particular how to engage the basic symbolic tools implemented in any system to derive the basic equations for the stochastic perturbation technique and how to make an efficient implementation of the semi-analytical methods using an automatic differentiation and integration provided by the computer algebra program itself. The second important illustration is probabilistic extension of the finite element and finite difference methods coded in MAPLE, showing how to solve boundary value problems with random parameters in the environment of symbolic computing. The response function method belongs to the third group, where interference of classical deterministic software with the non-linear fitting numerical techniques available in various symbolic environments is displayed. We recover in this context the probabilistic structural response in engineering systems and show how to solve partial differential equations including Gaussian randomness in their coefficients.

This paper reports on the computational modelling of static extension tests of the round steel bar. The main objective was to apply the generalised stochastic perturbation technique implemented as the Stochastic Finite Element Method to carry out the numerical simulation of its elasto-plastic behaviour. This approach was based on: the general order Taylor expansion of all input random variables and the resulting state functions of their average means, as well as on the Least Squares Method employed to determine analytical functions of in-between design parameters and the given structural responses. Tvergaard coefficients were assumed as the uncorrelated Gaussian random variables to check the effect of material porosity uncertainty on the statistical scattering of its deformations and stresses. The computational implementation employed the FEM system ABAQUS and computer algebra system MAPLE, including polynomial and non-polynomial local response functions of the displacements, plastic strains and reduced stresses. Moreover, 4-node axisymmetric, continuum, reduced-integration FEM elements (CAX4R) were used in the conducted analyses. The basic probabilistic characteristics of the structural response (expectations, coefficients of variation, skewness and kurtosis) were determined throughout the entire deformation process as the functions of input uncertainty level. The obtained results were finally contrasted with the classical Monte-Carlo Simulation scheme and the semi-analytical technique for input coefficient of variation of porous plasticity coefficients not larger than 0.20.

Cognitive assessment in neurological diseases represents a relevant topic due to its diagnostic significance in detecting disease, but also in assessing progress of the treatment. Computer-based tests provide objective and accurate cognitive skills and capacity measures. The Ruff Figural Fluency Test (RFFT) provides information about non-verbal capacity for initiation, planning, and divergent reasoning. The traditional paper form of the test was transformed into a computer application and examined. The RFFT was applied in an experiment performed among 70 male students to assess their cognitive performance in the laboratory environment. Each student was examined in three sequential series. Besides the students’ performances measured by using in app keylogging, the eye-tracking data obtained by non-invasive video-based oculography were gathered, from which several features were extracted. Eye-tracking features combined with performance measures (a total number of designs and/or error ratio) were applied in machine learning classification. Various classification algorithms were applied, and their accuracy, specificity, sensitivity and performance were compared.

The principal goal of this work is to investigate an application of the stochastic perturbation technique of the 10th order in coupled thermo-elasto-plastic analysis of tension of the steel elastic bar exposed to fire with thermally dependent material characteristics. An ambient temperature, calculated from the fire curve after ISO 834-1, equivalent to the fire exposure of the steel structure is treated here as the input Gaussian random variable. It is uniquely defined by the constant mean value at outer surfaces of this element, where material parameters of the steel as Young modulus, yield strength, heat conductivity, capacity and thermal elongation are considered all as highly temperature-dependent. Computational implementation known as the Stochastic Finite Element Method is carried out with the use of the FEM system ABAQUS and computer algebra system MAPLE. It uses both polynomial and non-polynomial local response functions of stresses and displacements. The basic probabilistic characteristics of time-dependent structural response are determined (expectations, coefficients of variation, skewness and kurtosis) and verified with classical Monte-Carlo simulation scheme and semi-analytical technique for input coefficient of variation not larger than 0.20. Finally, probabilistic convergence of all three methods versus increasing input uncertainty level is investigated.

Abstract Background Progressive left ventricular (LV) diastolic dysfunction due to hypertension (HTN) alters left atrial (LA) contractile function in a predictable manner. While increased LA size is a marker of LV diastolic dysfunction and has been shown to be predictive of adverse cardiovascular outcomes, the prognostic significance of altered LA contractile function is unknown. Methods A consecutive group of patients with chronic hypertension but without significant valvular disease or prior MI underwent clinically-indicated CMR for assessment of left ventricular (LV) function, myocardial ischemia, or viability. Calculation of LA volumes used in determining LA emptying functions was performed using the biplane area-length method. Results Two-hundred and ten patients were included in this study. During a median follow-up of 19 months, 48 patients experienced major adverse cardiac events (MACE), including 24 deaths. Decreased LA contractile function (LAEFContractile) demonstrated strong unadjusted associations with patient mortality, non-fatal events, and all MACE. For every 10% reduction of LAEFContractile, unadjusted hazards to MACE, all-cause mortality, and non-fatal events increased by 1.8, 1.5, and 1.4-folds, respectively. In addition, preservation of the proportional contribution from LA contraction to total diastolic filling (Contractile/Total ratio) was strongly associated with lower MACE and patient mortality. By multivariable analyses, LAEFContractile was the strongest predictor in each of the best overall models of MACE, all-cause mortality, and non-fatal events. Even after adjustment for age, gender, left atrial volume, and LVEF, LAEFContractile maintained strong independent associations with MACE (p < 0.0004), all-cause mortality (p < 0.0004), and non-fatal events (p < 0.0004). Conclusions In hypertensive patients at risk for left ventricular diastolic dysfunction, a decreased contribution of LA contractile function to ventricular filling during diastole is strongly predictive of adverse cardiac events and death.

Schools of medicine are increasingly focusing on efforts beyond the immediate needs of individual patients and addressing the needs of whole populations. This study examined the characteristics of population health departments and related programs within, and affiliated with, schools of medicine and how these programs address the schools' educational, clinical care, research, and service missions. Structured reviews of school of medicine websites were used to identify population health departments and related programs. An on-line survey was distributed to a subset of these programs to capture details on their activities and organizational characteristics. The authors convened leaders of population health programs to elaborate on core themes. Of 154 school of medicine websites reviewed, 37 (24%) had affiliated population health programs, including 28 (18%) with distinct departments of population health. Departments reported a variety of teaching activities related to undergraduate medical education, graduate degree programs, and certificate programs addressing a variety of population health domains including public health, health administration, epidemiology, biostatistics, informatics, and research methods. Research was a core activity for most departments with significant support coming from federal funding, with many playing major roles in clinical and translational research institutes and cancer centers. Most departments had research, data sharing, and other collaborations with affiliated health systems. All departments engaged in community service activities, including activities supporting the response to the COVID-19 pandemic. Population health programs are playing an increasingly important role in the teaching, clinical care, research, and community service missions in schools of medicine and academic medical centers.

An optimization experiment with different acid concentrations was carried out to assess the use of acid to minimum sustainable limits for the extraction of microfossils from indurated limestones. Two different limestone formations of Jurassic and Miocene ages were tested. Different concentrations of acid ranging from 50 to 100% and processing times varying from 2 to 10 h were tested for optimal recoveries. The acid residue recoveries show a similar trend for both formations. The weight percentage of residue with particle size >1 mm decreased as the acid concentration increased, especially in the 50-80% acid concentration range. On the other hand, the weight percentage of the smallest size particles > 0.063 mm increased as acid concentration increased. This means that the higher concentrations of acid dissolve more of the unnecessary large particles while the foraminifera, which comprise the sand fraction size, are left in the residue. Although higher acid concentrations with longer reaction times yielded better recoveries than with less reaction time, we recommended a 60% concentration of acetic acid and a reaction time of 10 h for optimal recovery of micropaleontological samples in Saudi Arabian carbonate rocks. By lowering the recommended concentration, the consumption of acid is reduced without compromising the recovery of microfossils.•Acetic acid leaching method is applied on two different age limestone samples to extract foraminifera.•Different concentrations of acetic acid are tried and tested, and consensus is made on an optimum concentration of 60% for a submersion time of 10 h.•The sample recoveries are optimal while using this concentration for a time of 10 h., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

There is increasing imperative to train residents in population health. The Accreditation Council for Graduate Medical Education (ACGME) enhanced its mission with revised Common Program Requirements (CPRs), which were fully implemented on July 1, 2020. The revised CPRs state ACGME's mission: "The development of physicians in GME focused on excellence in delivery of safe, equitable, affordable, quality care; and the health of the populations they serve." The new CPRs clearly articulate the need for graduate medical education (GME) trainees to develop and understand population health concepts during their GME experience, including social determinants of health and community impact. However, currently there is no standardized and widely available curriculum for GME to implement these revised CPRs. This paper proposes a curriculum in population health management for GME, which was developed in 1 institution, using a blend of didactic and experiential learning.

Background: Central-line bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) negatively impact clinical outcomes and hospital reimbursement. In this report, 4 year trends involving 11 hospitals in New York City were examined., Methods: Data from the National Healthcare Safety Network (NHSN) were extracted for 11 acute-care hospitals belonging to the NYC Health + Hospital system from 2016 through 2019. Trends in device infections per 1,000 patient days, device utilization ratios, and standardized infection ratios (SIRs) were examined for the 11 hospitals and for the entire system., Results: Over the 4-year period, there were progressive declines in central-line days, infections per 1,000 central-line days, and device utilization ratios for the system. The average annual SIRs for the system also declined: 1.40 in 2016, 1.09 in 2017, 1.04 in 2018, and 0.82 in 2019. Case-mix indices correlated with SIRs for CLABSIs. Level 1 trauma centers had higher SIRs and a disproportionately greater number of CLABSIs in patients located in NHSN-defined surgical intensive care units. Similar trends with CAUTIs were noted, with progressive declines in catheter days, infections per 1,000 patient days, device utilization ratios, and SIRs (1.42 in 2016, 0.93 in 2017, 1.18 in 2018, and 0.78 in 2019) over the 4-year period., Conclusions: Across an 11-hospital system, continuing efforts to reduce device utilization and infection rates resulted in declining SIRs for CLABSIs and CAUTIs. Hospitals with higher case-mix indices, and particularly level 1 trauma centers, had significantly higher central-line infection rates and SIRs.

In this study, we investigated the relationship between environmental parameters (water and sediment) and benthic foraminiferal assemblages found in nearshore siliciclastic sediment in the Arabian Gulf. Nearshore marine water and sediment samples were collected from a beach on the Gulf of Bahrain located south of Al Khobar, Saudi Arabia. The water samples were analyzed for biochemical oxygen demand (BOD 5 ) and other chemical analyses. The sediment samples were tested for sediment oxygen demand (SOD) and heavy metal analysis. Results showed the BOD 5 levels were below the detection limit (<1 ppm), while the mean SOD value was 0.97 ± 0.08 g/m 2 ·day. The water and sediments were unpolluted and free of eutrophic enrichment, while the sediment was anoxic. The two most common genera in the benthic foraminiferal assemblage, Ammonia and Elphidium , are typical of shallow water sandy substrates. This is the first reported comparison between SOD and benthic foraminiferal assemblages., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: The release of pro-inflammatory cytokines, resulting in cytokine storm syndrome, contributes to the morbidity and mortality associated with COVID-19 disease. This study aimed to compare the effects of intravenous (IV) and subcutaneous (SC) tocilizumab, an IL-6 receptor antagonist, on respiratory parameters and clinical outcome in patients with COVID 19., Methods: We performed a retrospective cohort study of hospitalized patients with COVID-19 treated with either IV or SC tocilizumab from March 26, 2020, to May 18, 2020. Respiratory parameters seven days after receiving tocilizumab therapy were compared to baseline measurements. All patients were assessed until discharged from the hospital., Results: Tocilizumab was administered to 125 patients: 65 received IV, and 60 received SC therapy. At day seven, 52% of the IV group patients demonstrated improvement in respiratory parameters, compared to 28% in the SC group (P = 0.01). Mortality rates at days seven and 28 were 15% and 37%, respectively, in the IV group and 17% and 50%, respectively, in the SC group (PNS). The in-hospital mortality rate was 38% for the IV group versus 57% for the SC group (P = 0.04). More than 90% of patients in each group received corticosteroids; however, significantly more patients received convalescent plasma in the IV group., Conclusions: At the doses used in this study, IV tocilizumab is preferred over SC therapy to treat cytokine storm syndrome due to COVID-19., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This dataset supports the paper entitled "A baseline investigation of benthic foraminifera in relation to marine sediments parameters in western parts of the Arabian Gulf". Duplicate sediment samples (sets A and B) were collected from 30 stations in an area covering approximately 25000 km 2 in the offshore northern Arabian Gulf, using a van Veen grab (0.1 m 2 area) and the top 1 cm was analysed for living benthic foraminifera. A set of samples was devoted to foraminiferal analysis while the other, set B, for sediment analyses. In situ hydrographical parameters such as temperature, salinity, pH, turbidity and DO were measured at surface waters. The top 1 cm was subsampled for foraminiferal analyses from the grab and preserved using 70% ethanol with Rose-Bengal stain. Potentially Toxic Elements (PTE) levels in sediment and grain size distributions were analysed. The dataset is expected to provide a baseline for PTE levels in sediment, benthic foraminiferal communities, and identify endemic species adapted to extremes of temperature and saline conditions typical of the Gulf. It can also be used by environmental managers, micropaleotologists, students in environmental/geology/marine science as reference background conditions based on sediment toxicity and benthic community information in revising environmental guidelines in the region. Data from this study suggest that PTEs are within the range of background values, and the sediments support highly diversified and stable benthic foraminiferal communities adapted to the unique environmental conditions in the Gulf. To date, this dataset documents the highest number of living benthic foraminifera species reported from the Gulf, and the most diverse living community compared to all previous studies. It also provides evidence for the full recovery of areas impacted during the 1991 Gulf oil spill which is evident by the diverse and flourishing assemblages of living benthic foraminifera documented., (© 2019 The Authors.)

Sphingopyxis inhabit diverse environmental niches, including marine, freshwater, oceans, soil and anthropogenic sites. The genus includes 20 phylogenetically distinct, valid species, but only a few with a sequenced genome. In this work, we analyzed the nearly complete genome of the newly described species, Sphingopyxis lindanitolerans , and compared it to the other available Sphingopyxis genomes. The genome included 4.3 Mbp in total and consists of a circular chromosome, and two putative plasmids. Among the identified set of lin genes responsible for γ-hexachlorocyclohexane pesticide degradation, we discovered a gene coding for a new isoform of the LinA protein. The significant potential of this species in the remediation of contaminated soil is also correlated with the fact that its genome encodes a higher number of enzymes potentially involved in aromatic compound degradation than for most other S p hingopyxis strains. Additional analysis of 44 Sphingopyxis representatives provides insights into the pangenome of Sphingopyxis and revealed a core of 734 protein clusters and between four and 1667 unique proteins per genome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

This baseline paper discusses the distribution and abundance of living benthic foraminifera in relation to Potentially Toxic Elements (PTEs) such as As, Al, Fe Cd, Co, Cr, Cu, V, Ni, Hg, Pb, and Zn in marine sediments collected from 30 stations in the offshore Arabian Gulf to define baseline environmental conditions for the implementation of future biomonitoring programs. A total of 271 living benthic foraminiferal species were identified belonging to 66 genera, 37 families and 6 orders. Data from this work suggest that PTEs are within the range of background values, and the sediments support highly diversified and stable benthic foraminiferal communities adapted to the unique environmental conditions in the Gulf. Thus, the effect of anthropogenic activities is deemed negligible. This study is expected to provide a baseline dataset for PTE levels in sediment, benthic foraminiferal communities, and identify endemic species adapted to extremes of temperature and saline conditions typical of the Gulf., (Copyright © 2019. Published by Elsevier Ltd.)

Attached epilithic foraminifera constitute an important but overlooked component of the benthic foraminiferal assemblage in the Pleistocene sediment of the central Arctic Ocean. We report 12 types of epilithic foraminifera that have colonised lithic and biogenic grains found in glacial sediments, including representatives of the genera Rhizammina, Hemisphaerammina, Ammopemphix, Diffusilina, Subreophax, Placopsilina, Placopsilinella, Hormosinelloides and Tholosina, accompanied by mat-like and ribbon-like forms of uncertain taxonomic affinity. The attached agglutinated forms appear to be colonisers, adapted to extremely oligotrophic conditions., Competing Interests: The authors declare there are no competing interests.

An aerobic, Gram-stain-negative, rod-shaped, non-motile, mesophilic soil bacterium, strain WS5A3p T , was isolated from a pesticide burial site in north-west Poland. The strain grew at 12-37 °C, at pH 8-9 and with 0-2 % (w/v) NaCl. The main fatty acids detected in WS5A3p T were summed feature 3, summed feature 8 and C16 : 0. The major respiratory quinone was Q-10 and major polar lipids were phosphatidylethanolamine, sphingoglycolipid and phosphatidylglycerol. The G+C content of the genome was 65.1 mol%. Phylogenetic pairwise distance analysis of the 16S rRNA gene placed this strain within the genus Sphingopyxis, with the highest similarity to Sphingopyxis witflariensis W-50 T (98.8 %), Sphingopyxis bauzanensis BZ30 T and Sphingopyxis ginsengisoli Gsoil 250 T (98.3 %) and Sphingopyxis granuli NBRC 100800 T (98.09 %). Genomic similarity analyses using ANIb and dDDH algorithms indicated levels of similarity of 81.44, 80.84 and 81.16 % between WS5A3p T and S. witflariensis, S. bauzanensisand S. granuli, respectively for average nucleotide identity and 25.90, 25.00 and 26.10 % for digital DNA-DNA hybridization. Based on the phylogenetic and phenotypic data, strain WS5A3p T should be considered as a representative of a novel Sphingopyxis species. The name Sphingopyxis lindanitolerans sp. nov. is proposed with the type strain WS5A3p T (=DSM 106274 T =PCM 2932 T ).

Pseudomonas are known from their flexible degradation capabilities and their engagement in xenobiotic biotransformation and bioremediation in habitats like soil, active sludge, plant surfaces, and freshwater or marine environments. Here we present taxonomic characterization of three efficient sodium dodecyl sulfate degrading strains: AP3&#95;10, AP3&#95;20 and AP3&#95;22 T belonging to the genus Pseudomonas, recently isolated from peaty soil used in a biological wastewater treatment plant. Sequence analyses of 16S rRNA and housekeeping genes: gyrB, rpoD and rpoB showed that the three closely related isolates classify within the Pseudomonas jessenii subgroup. ANIb or dDDH genomic comparisons of AP3&#95;22 T (type strain DSM 105098 T =PCM 2904 T ) supported by biochemical tests showed that the isolates differ significantly from their closest relatives. The combined genotypic, phenotypic and chemotaxonomic data strongly support the classification of the three strains: AP3&#95;10, AP3&#95;20 and AP3&#95;22 T as a novel species of Pseudomonas, for which we propose the name Pseudomonas laurylsulfatovorans sp. nov. with AP3&#95;22 T as the type strain., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Microorganisms classified in to the Pseudomonas genus are a ubiquitous bacteria inhabiting variety of environmental niches and have been isolated from soil, sediment, water and different parts of higher organisms (plants and animals). Members of this genus are known for their metabolic versatility and are able to utilize different chemical compounds as a source of carbon, nitrogen or phosphorus, which makes them an interesting microorganism for bioremediation or bio-transformation. Moreover, Pseudomonas sp. has been described as a microorganism that can easily adapt to new environmental conditions due to its resistance to the presence of high concentrations of heavy metals or chemical pollution. Here we present the isolation and analysis of Pseudomonas silesiensis sp. nov. strain A3 T isolated from peaty soil used in a biological wastewater treatment plant exploited by a pesticide packaging company. Phylogenetic MLSA analysis of 4 housekeeping genes (16S rRNA, gyrB, rpoD and rpoB), complete genome sequence comparison (ANIb, Tetranucleotide identity, digital DDH), FAME analysis, and other biochemical tests indicate the A3 T strain (type strain PCM 2856 T =DSM 103370 T ) differs significantly from the closest relative species and therefore represents a new species within the Pseudomonas genus. Moreover, bioinformatic analysis of the complete sequenced genome showed that it consists of 6,823,539bp with a 59.58mol% G+C content and does not contain any additional plasmids. Genome annotation predicted the presence of 6066 genes, of which 5875 are coding proteins and 96 are RNA genes., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Due to their particular properties, detergents are widely used in household cleaning products, cosmetics, pharmaceuticals, and in agriculture as adjuvants tailoring the features of pesticides or other crop protection agents. The continuously growing use of these various products means that water soluble detergents have become one of the most problematic groups of pollutants for the aquatic and terrestrial environments. Thus it is important to identify bacteria having the ability to survive in the presence of large quantities of detergent and efficiently decompose it to non-surface active compounds. In this study, we used peaty soil sampled from a surface flow constructed wetland in a wastewater treatment plant to isolate bacteria that degrade sodium dodecyl sulfate (SDS). We identified and initially characterized 36 Pseudomonas spp. strains that varied significantly in their ability to use SDS as their sole carbon source. Five isolates having the closest taxonomic relationship to the Pseudomonas jessenii subgroup appeared to be the most efficient SDS degraders, decomposing from 80 to 100% of the SDS present in an initial concentration 1 g/L in less than 24 h. These isolates exhibited significant differences in degree of SDS degradation, their resistance to high detergent concentration (ranging from 2.5 g/L up to 10 g/L or higher), and in chemotaxis toward SDS on a plate test. Mass spectrometry revealed several SDS degradation products, 1-dodecanol being dominant; however, traces of dodecanal, 2-dodecanol, and 3-dodecanol were also observed, but no dodecanoic acid. Native polyacrylamide gel electrophoresis zymography revealed that all of the selected isolates possessed alkylsulfatase-like activity. Three isolates, AP3&#95;10, AP3&#95;20, and AP3&#95;22, showed a single band on native PAGE zymography, that could be the result of alkylsulfatase activity, whereas for isolates AP3&#95;16 and AP3&#95;19 two bands were observed. Moreover, the AP3&#95;22 strain exhibited a band in presence of both glucose and SDS, whereas in other isolates, the band was visible solely in presence of detergent in the culture medium. This suggests that these microorganisms isolated from peaty soil exhibit exceptional capabilities to survive in, and break down SDS, and they should be considered as a valuable source of biotechnological tools for future bioremediation and industrial applications.

Here, we report the draft genome sequence of Pseudomonas umsongensis type strain DSM 16611. The assembly consists of 14 contigs containing 6,701,403 bp with a GC content of 59.73%., (Copyright © 2017 Furmanczyk et al.)

We present the draft genome sequence of Pseudomonas jessenii type strain DSM 17150. The assembly consists of 13 contigs, contains 6,537,206 bp, and has a GC content of 59.7%., (Copyright © 2017 Furmanczyk et al.)

We present here the draft genome sequence of Sphingopyxis bauzanensis DSM 22271. The assembly contains 4,258,005 bp in 28 scaffolds and has a GC content of 63.3%. A series of specific genes involved in the catabolism or transport of aromatic compounds was identified., (Copyright © 2017 Kaminski et al.)

Here, we present the draft genome sequence of Sphingopyxis witflariensis strain DSM 14551. The assembly consists of 38 contigs and contains 4,306,761 bp, with a GC content of 63.3%., (Copyright © 2017 Kaminski et al.)

Current treatment regimens for non-tuberculous mycobacteria (NTM) and tuberculosis (TB) generally require long duration of therapy with multiple drugs, some of which are broad spectrum antibiotics. Despite some advances in antimicrobial compounds, there remains a need in therapy for antibiotics with specific mycobacterial targets. It has been shown that MmpL3 is an essential transporter required for the translocation of mycolic acids to the mycobacterial cell envelope. Here, we synthesized a series of indole-2-carboxamides that inhibit MmpL3 and have potent pan-activity against mycobacterial species. The compounds were tested against several fast and slow-growing Mycobacterium species, including M. abscessus, M. massiliense, M. bolletii, M. chelonae, M. tuberculosis, M. avium, M. xenopi and M. smegmatis. The target of these indole-based compounds makes them selective for mycobacteria, while showing no clinically relevant bactericidal activity against S. aureus or P. aeruginosa. These compounds were tested against THP-1, a human-cell line, and showed minimal in vitro cytotoxicity and good selectivity indices. The data shown and discussed suggest that lead indole-2-carboxamides are strong contenders for further preclinical testing as NTM therapeutics., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To demonstrate the robustness of the Featherstone pH cycling model when tested in three independent laboratories and to evaluate the use of "non-inferiority" testing at those laboratories., Methods: The fundamental principles for the Featherstone laboratory pH cycling model to be an appropriate alternative to animal testing is that it must demonstrate equivalent accuracy to the "Gold Standard" (rat caries model) by: (1) providing a meaningful representation of the caries process; (2) demonstrating a proportionate response to fluoride dose (or concentration); (3) being able to show that clinically proven formulations perform similarly relative to the controls; and (4) differentiating products that have attenuated fluoride activity., Results: This cross-validation study confirmed the ability of the three independent laboratories to discriminate between various concentrations of fluoride-containing dentifrice formulations, demonstrated that clinically proven formulas perform as expected and identified an attenuated fluoride formulation (NaF/CaCO3 dentifrice - 1100 ppm NaF) as inferior compared to the 1100 ppm F (NaF/silica) positive control.

Purpose: As a requirement of the Food & Drug Administration's final monograph on "Anticaries drug products for over-the-counter human use", the toothpaste industry has been conducting animal caries tests on every fluoride-containing toothpaste introduced into the U.S. market since 1996. The practice of testing in animals, although required by law, is in stark conflict with the corporate policy of many U.S. and global toothpaste manufacturers, in which, if possible, alternatives to animal testing are utilized. A provision does exist within the regulation which allows the use of an alternative method to demonstrate efficacy. However, to take advantage of this provision, a petition must be submitted to the FDA and in this petition data demonstrating the alternative provides results of "equivalent accuracy" must be included. After many years of research, model development and model comparisons, we have identified one particular laboratory model that demonstrated excellent correlation with the currently accepted animal caries models. This model, known as the Featherstone pH cycling model, is discussed in this paper., Methods: The Featherstone pH cycling model has been shown to produce results of equivalent accuracy to the animal caries model by: (1) demonstrating a clinically relevant fluoride dose response similar to that shown in the animal caries model (including 1100 ppm F, 250 ppm F and placebo); (2) demonstrating similar results to the animal caries model for clinically proven dentifrice formulations relative to positive and negative controls; (3) demonstrating discriminating ability in strong agreement with the animal caries model for differentiating between a dentifrice formulation with attenuated fluoride activity and a USP standard; and (4) providing a clinically relevant representation of the caries process, as demonstrated by orthodontic banding studies. In addition, the model sufficiently addresses both salivary and abrasive/anticalculus agent interference concerns., Results: For more than 50 years, fluoride has been the first defense in the fight against dental caries. The clinical effectiveness of fluoride is well accepted and documented extensively in the literature. The mechanism through which fluoride provides its benefit is very straightforward and well understood. The proposed laboratory model effectively simulates the effect of the caries process and has been shown to demonstrate equivalent accuracy to animal caries. This indicates that there are strong scientific grounds for the use of this model as an alternative to the animal caries test. Based on the strength of the data and the correlations noted between the two models, we recommend that the scientific community and the toothpaste industry broadly accept the Featherstone laboratory pH cycling model as an appropriate alternative to animal testing, particularly for ionic fluoride based dentifrices.

Background: The long-term prognostic significance of early (<48 hours) ventricular fibrillation (VF) or sustained ventricular tachycardia (VT) in patients with an acute myocardial infarction remains controversial. Emerging data suggest that some of the benefit of renin-angiotensin-aldosterone system (RAAS) antagonism may be derived from a reduction in the incidence of these arrhythmias in the setting of acute myocardial infarction., Methods: We assessed the relationship between early VF/VT (defined as within 48 hours after admission) and mortality in 16,588 patients from global use of strategies to open coronary arteries (GUSTO) V trial. Furthermore, we examined the relationship between baseline use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), early VF/VT, and mortality., Results: Early VF or VT occurred in 732 (4.4%) patients. Compared to patients without VF/VT, those experiencing early VF or VT had a significant increase in 30-day mortality (22% vs 5%, P < .001). Baseline use of an ACEI/ARB was associated with a decreased incidence of early VF/VT (odds ratio 0.65, 0.47-0.89, P = .008). A lower 30-day mortality was seen in patients with early VF/VT on baseline ACEI/ARB compared with patients with early VF/VT not receiving an ACEI/ARB at baseline (17.7% vs 24.2%, respectively, P = .04). The association between baseline RAAS antagonism and mortality persisted after adjustment for multiple confounders., Conclusions: In patients presenting with acute myocardial infarction, early VF/VT identifies those at increased risk for 30-day mortality. Baseline use of RAAS antagonists is associated with a reduced incidence of malignant arrhythmias. Identifying how this association impacts short-term mortality in this patient population requires further prospective evaluation.

The use of biocide in oral care products is important for controlling microbial pathogens. However, the use of biofilm tests that investigate repeated exposure to biocide, to mimic in situ treatment, has rarely been reported in the literature. The present study describes the application of a biofilm-based efficacy protocol, for testing the effect of repeated exposure to antimicrobials on biofilm, in an attempt to mimic oral care regimens. The activity of different treatment regimens, including repeated exposure to amine oxide (AO; C(10)-C(16)-alkyldimethyl N-oxides; 1.1% v/v), was conducted against 16-h Streptococcus mutans biofilms grown on hydroxyapatite disks. Single exposure to AO alone produced a 3 log(10) reduction in microbial count, but when combined with mechanical removal, a 5 log(10) reduction in microbial count was observed. Treatments incorporating repeated exposure to AO reduced the microbial count below the level of detection, even when exposure to AO was interspersed with recovery periods. The presence of organic load produced an additional 2 log(10) reduction in the microbial count. This study showed that the application of a biofilm-based efficacy protocol to mimic oral care regimens allowed the reproducible testing of repeated antimicrobial exposures against bacterial biofilm. In addition, AO was confirmed to be an excellent biocide for eliminating S. mutans biofilms and could therefore be beneficial in oral care formulations.

Aims: To assess the potential bactericidal activity of amine oxide (C10-C16-alkyldimethyl N-oxides) against Streptococcus mutans grown as planktonic suspension and as biofilm on hydroxyapatite discs, and its ability to control acidification of the media., Methods: Amine oxide bacteriostasis was investigated using the Bioscreen C Microbiological Growth Analyser, while a standard suspension test was used to determine its bactericidal efficacy. In addition, the lethal activity of amine oxide was studied against sedimentation biofilms of S. mutans on hydroxyapatite (HA) discs and resuspended biofilms. Several parameters were considered such as the surfactant concentration, pH, the starting inoculum and the maturity of the biofilm., Results: Amine oxide was bacteriostatic against planktonic S. mutans at a low concentration (0.006% v/v) and highly bactericidal against S. mutans in suspension or in a mature biofilm on hydroxyapatite, although the concentration required to achieve the latter effect was four times higher. The activity of amine oxide against biofilms depended upon its concentration and the age of the biofilm. In addition, amine oxide pre-treatment of the HA discs did not affect the growth of the biofilm. Finally, amine oxide did not prevent the acidification of the medium, although lower pHs had a potentiating effect on amine oxide activity., Conclusion: Amine oxide showed high potential for controlling early biofilms caused by periodontal bacteria. Further investigations should be carried out, particularly on the potential toxicity of amine oxide and its efficacy in complex formulations for oral care products.

A series of non-amide-linked 6-substituted-2-naphthamidine urokinase plasminogen activator (uPA) inhibitors are described. These compounds possess excellent binding activities and selectivities with significantly improved pharmacokinetic profiles versus previously described amide-linked inhibitors.

Protein adducts of the lipid peroxidation product trans-4-hydroxy-2-nonenal (HNE) are features of oxidative damage in neuronal cell bodies in Alzheimer's disease but are also seen in axons of normal as well as diseased individuals. In this study, focusing on the axons of the mouse sciatic nerve, we found that HNE adducts characterize axons of mice from birth to senility. Immunoblots of axonal proteins showed that HNE adducts are only detected in neurofilament heavy subunit (NFH) and, to a lesser extent, neurofilament medium subunit (NFM), both lysine-rich proteins, consistent with the adducts being limited to lysine residues. In vitro, HNE treatment of permeabilized sciatic nerve showed the same specificity, i.e. NFH and NFM are the only proteins that reacted with HNE, providing they are phosphorylated. Quantitative immunoblot analysis of two strains of mice ages 1-33 months showed that the levels of HNE adducts on NFH are consistent throughout life. Additionally, mice transgenic for human superoxide dismutase-1 with G85R mutation show no difference in HNE adduction to NFH compared with controls. Taken together, these studies indicate that HNE adduction to NFH is physiological, and its constancy from birth to senility as well as its dependence on phosphorylation argues that NFH and NFM modification may play a role in protecting the membrane-rich axon from toxic aldehydes resulting from oxidative damage.

Thirty ovariectomized sows were used in an experiment designed to determine whether the ability of the porcine uterus to release prostaglandin (PG) F(2alpha) in response to oxytocin is regulated by progesterone (P(4)) and estradiol (E(2)). Sows were assigned to one of four treatment groups: 1) no steroids (ovariectomized controls; n = 8), 2) E(2) (n = 8), 3) P(4) (n = 7), or 4) E(2) + P(4) (n = 7). P(4) and E(2) were administered so as to mimic the normal temporal changes that occur in these hormones during the estrous cycle. A group of intact sows (n = 9) was included for comparison. All sows received an injection of oxytocin (30 IU, i.v.) on Days 12, 15, and 18 postestrus. Jugular venous blood samples were collected from 60 min before through 120 min after injection of oxytocin for quantification of 13,14-dihydro-15-keto-PGF(2alpha) (PGFM). Preinjection baseline concentrations of PGFM, the magnitude of the PGFM response above baseline, and area under the PGFM response curve (AUC) were calculated for each sow on each day and compared among treatment groups by ANOVA. Among the ovariectomized sows receiving steroid replacement, baseline concentrations of PGFM were low on Day 12 postestrus in all four groups. On Days 15 and 18, baseline concentrations remained low in the two groups that did not receive P(4) but increased in those that did. Both the magnitude of the response to oxytocin and AUC were small on Day 12 postestrus in all 4 groups. By Day 15, the magnitude of the response and AUC increased in the group that received both P(4) and E(2) but remained low in the other three groups. By Day 18, responses to oxytocin were greater in both groups that received P(4) than in those that did not. Baseline concentrations were similar in intact sows and in those that received both P(4) and E(2) on all three days examined. The magnitude of the response and the AUC were greater in the ovariectomized sows receiving P(4) and E(2) replacement than in the intact control sows on Days 15 and 18 postestrus. From these results, we conclude that P(4) and E(2) interact to control the time when the uterus begins to secrete PGF(2alpha) in response to oxytocin and the amount of PGF(2alpha) secreted.

Expression of the gene encoding cytochrome P450 17alpha-hydroxylase, CYP17, is necessary for adrenal and gonadal steroidogenesis in most species. However, some animals, such as the pig, express CYP17 in the trophectoderm of the preattachment blastocyst, an event associated with estrogen synthesis and the establishment of pregnancy. How trophoblastic expression of CYP17 is regulated in the porcine blastocyst remains unknown and forms the basis of the following studies. The porcine CYP17 gene, including the complete coding and several kilobases of 5'-flanking regions, was cloned and sequenced. Blastocysts were examined by Northern analysis to verify the level of CYP17 transcript, and tissue-specific expression in the trophectoderm was confirmed by in situ hybridization. Primer extension, S1 nuclease protection, and 5'-rapid amplification of cDNA ends confirmed a common proximal transcription start site in adrenals and gonads (-48 bp) but identified a unique distal start site used in porcine trophectoderm (-182 bp). Additionally, reporter analysis of the CYP17 regulatory region demonstrated that constructs (-27 to -718 bp) were unresponsive to forskolin when expressed in porcine trophoblast cells, suggesting that trophoblast may not be able to respond to cAMP induction of this gene. The identification of this distal, previously undescribed, transcriptional start site suggests that unique mechanisms control the expression of CYP17 in porcine trophectoderm and possibly other genes important in implantation and early placental development.