bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic profiles of the active metamizole metabolites in healthy horses
Authors: Giorgi M. , Aupanun S. , Lee H.‐K. , Poapolathep A. , Rychshanova R. , Vullo C. , Faillace V. , Laus F. 
Published: August 2016

Metamizole (MT) is an analgesic and antipyretic drug labelled for use in humans, horses, cattle, swine and dogs. MT is rapidly hydrolysed to the active primary metabolite 4‐methylaminoantipyrine (MAA). MAA is formed in much larger amounts compared with other minor metabolites. Among the other secondary metabolites, 4‐aminoantipyrine (AA) is also relatively active. The aim of this research was to evaluate the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.) and intramuscular (i.m.) routes in healthy horses. Six horses were randomly allocated to two equally sized treatment groups according to a 2 × 2 crossover study design. Blood was collected at predetermined times within 24 h, and plasma was analysed by a validated HPLC‐UV method. No behavioural changes or alterations in health parameters were observed in the i.v. or i.m. groups of animals during or after (up to 7 days) drug administration. Plasma concentrations of MAA after i.v. and i.m. administrations of MT were detectable from 5 min to 10 h in all the horses. Plasma concentrations of AA were detectable in the same range of time, but in smaller amounts. Maximum concentration (Cmax), time to maximum concentration (Tmax) and AUMC0‐last of MAA were statistically different between the i.v. and i.m. groups. The AUCIM/AUCIV ratio of MAA was 1.06. In contrast, AUC0‐last of AA was statistically different between the groups (P < 0.05) with an AUCIM/AUCIV ratio of 0.54. This study suggested that the differences in the MAA and AA plasma concentrations found after i.m. and i.v. administrations of MT might have minor consequences on the pharmacodynamics of the drug.
Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of danofloxacin in ruminant and preruminant calves
Authors: Mzyk D. A. , Baynes R. E. , Messenger K. M. , Martinez M. , Smith G. W. 
Published: August 2016

The objective of this study was to compare active drug concentrations in the plasma vs. different effector compartments including interstitial fluid (ISF) and pulmonary epithelial lining fluid (PELF) of healthy preruminating (3‐week‐old) and ruminating (6‐month‐old) calves. Eight calves in each age group were given a single subcutaneous (s.c.) dose (8 mg/kg) of danofloxacin. Plasma, ISF, and bronchoalveolar lavage (BAL) fluid were collected over 96 h and analyzed by high‐pressure liquid chromatography. PELF concentrations were calculated by a urea dilution assay of the BAL fluids. Plasma protein binding was measured using a microcentrifugation system. For most preruminant and ruminant calves, the concentration–time profile of the central compartment was best described by a two‐compartment open body model. For some calves, a third compartment was also observed. The time to maximum concentration in the plasma was longer in preruminating calves (3.1 h) vs. ruminating calves (1.4 h). Clearance (CL/F) was 385.15 and 535.11 mL/h/kg in preruminant and ruminant calves, respectively. Ruminant calves maintained higher ISF/plasma concentration ratios throughout the study period compared to that observed in preruminant calves. Potential reasons for age‐related differences in plasma concentration–time profiles and partitioning of the drug to lungs and ISF as a function of age are explored.
Evaluation of the ability of Acinetobacter baumannii to form biofilms on six different biomedical relevant surfaces
Authors: Greene C. , Wu J. , Rickard A.H. , Xi C. 
Published: August 2016

Abstract
The human opportunistic pathogen, Acinetobacter baumannii, has the propensity to form biofilms and frequently cause medical device-related infections in hospitals. However, the physio-chemical properties of medical surfaces, in addition to bacterial surface properties, will affect colonization and biofilm development. The objective of this study was to compare the ability of A. baumannii to form biofilms on six different materials common to the hospital environment: glass, porcelain, stainless steel, rubber, polycarbonate plastic and polypropylene plastic. Biofilms were developed on material coupons in a CDC biofilm reactor. Biofilms were visualized and quantified using fluorescent staining and imaged using confocal laser scanning microscopy (CLSM) and by direct viable cell counts. Image analysis of CLSM stacks indicated that the mean biomass values for biofilms grown on glass, rubber, porcelain, polypropylene, stainless steel and polycarbonate were 0·04, 0·26, 0·62, 1·00, 2·08 and 2·70 μm3/μm2 respectively. Polycarbonate developed statistically more biofilm mass than glass, rubber, porcelain and polypropylene. Viable cell counts data were in agreement with the CLSM-derived data. In conclusion, polycarbonate was the most accommodating surface for A. baumannii ATCC 17978 to form biofilms while glass was least favourable. Alternatives to polycarbonate for use in medical and dental devices may need to be considered.

Significance and Impact of the Study
In the hospital environment, Acinetobacter baumannii is one of the most persistent and difficult to control opportunistic pathogens. The persistence of A. baumannii is due, in part, to its ability to colonize surfaces and form biofilms. This study demonstrates that A. baumannii can form biofilms on a variety of different surfaces and develops substantial biofilms on polycarbonate – a thermoplastic material that is often used in the construction of medical devices. The findings highlight the need to further study the in vitro compatibility of medical materials that could be colonized by A. baumannii and allow it to persist in hospital settings.
Spatiotemporal relationship between adult census size and genetic population size across a wide population size gradient
Authors: Bernos Thaїs A. , Fraser Dylan J. 
Published: August 2016

AbstractAdult census population size (N) and effective number of breeders (Nb) are highly relevant for designing effective conservation strategies. Both parameters are often challenging to quantify, however, making it of interest to determine whether one parameter can be generalized from the other. Yet, the spatiotemporal relationship between N and Nb has not been well characterized empirically in many taxa. We analysed this relationship for 5–7 consecutive years in twelve brook trout populations varying greatly in N (49‐10032) and Nb (3‐567) and identified major environmental variables affecting the two parameters. N or habitat size alone explained 47–57% of the variance in Nb, and Nb was strongly correlated with effective population size. The ratio Nb/N ranged from 0.01 to 0.45 and increased at small N or following an annual decrease in N, suggesting density‐dependent constraints on Nb. We found no evidence for a consistent, directional difference between variability in Nb and/or Nb/N among small and large populations; however, small populations had more varying temporal variability in Nb/N ratios than large populations. Finally, Nb and Nb/N were 2.5‐ and 2.3‐fold more variable among populations than temporally within populations. Our results demonstrate a clear linkage between demographic and evolutionary parameters, suggesting that Nb could be used to approximate N (or vice versa) in natural populations. Nevertheless, using one variable to infer the other to monitor trends within populations is less recommended, perhaps even less so in small populations given their less predictable Nb vs. N dynamics.
Lanthanum carbonate: safety data after 10 years
Authors: Hutchison Alastair J , Wilson Rosamund J , Garafola Svetlana , Copley John Brian 
Published: August 2016

AbstractDespite 10 years of post‐marketing safety monitoring of the phosphate binder lanthanum carbonate, concerns about aluminium‐like accumulation and toxicity persist. Here, we present a concise overview of the safety profile of lanthanum carbonate and interim results from a 5‐year observational database study (SPD405‐404; ClinicalTrials.gov identifier: NCT00567723). The pharmacokinetic paradigms of lanthanum and aluminium are different in that lanthanum is minimally absorbed and eliminated via the hepatobiliary pathway, whereas aluminium shows appreciable absorption and is eliminated by the kidneys. Randomised prospective studies of paired bone biopsies revealed no evidence of accumulation or toxicity in patients treated with lanthanum carbonate. Patients treated with lanthanum carbonate for up to 6 years showed no clinically relevant changes in liver enzyme or bilirubin levels. Lanthanum does not cross the intact blood–brain barrier. The most common adverse effects are mild/moderate nausea, diarrhoea and flatulence. An interim Kaplan–Meier analysis of SPD405‐404 data from the United States Renal Data System revealed that the median 5‐year survival was 51.6 months (95% CI: 49.1, 54.2) in patients who received lanthanum carbonate (test group), 48.9 months (95% CI: 47.3, 50.5) in patients treated with other phosphate binders (concomitant therapy control group) and 40.3 months (95% CI: 38.9, 41.5) in patients before the availability of lanthanum carbonate (historical control group). Bone fracture rates were 5.9%, 6.7% and 6.4%, respectively. After more than 850 000 person‐years of worldwide patient exposure, there is no evidence that lanthanum carbonate is associated with adverse safety outcomes in patients with end‐stage renal disease.
Transcriptome response ofLolium arundinaceumto its fungal endophyteEpichloë coenophiala
Authors: Dinkins Randy D. , Nagabhyru Padmaja , Graham Michelle A. , Boykin Deborah , Schardl Christopher L. 
Published: August 2016

SummaryTall fescue (Lolium arundinaceum) is one of the primary forage and turf grasses in temperate regions of the world. A number of favourable characteristics of tall fescue are enhanced by its seed‐transmissible fungal symbiont (endophyte)Epichloë coenophiala.Our approach was to assemble the tall fescue transcriptome, then identify differentially expressed genes (DEGs) for endophyte‐symbiotic (E+) vs endophyte‐free (E−) clones in leaf blades, pseudostems, crowns and roots.RNA‐seq reads were used to construct a tall fescue reference transcriptome and compare gene expression profiles.Over all tissues examined, 478DEGs were identified between the E+ and E− clones for at least one tissue (more than two‐fold;P < 0.0001, 238 E+ > E− and 240 E− > E+), although no genes were differentially expressed in all four tissues. Gene ontology (GO) terms,GO:0010200 (response to chitin),GO:0002679 (respiratory burst during defence response) andGO:0035556 (intracellular signal transduction) were significantly overrepresented among 25 E− > E+DEGs in leaf blade, and a number of otherDEGs were associated with defence and abiotic response.In particular, endophyte effects on variousWRKYtranscription factors may have implications for symbiotic stability, endophyte distribution in the plant, or defence against pathogens.
The efficacy of intra‐alveolar 0.2% chlorhexidine gel on alveolar osteitis: a meta‐analysis
Authors: Zhou J , Hu B , Liu Y , Yang Z , Song J 
Published: August 2016

ObjectivesThe objective of this meta‐analysis was to assess the effect of 0.2% chlorhexidine gel in preventing alveolar osteitis following mandibular third molar extraction(s).MethodsPubMed, Cochrane Library, Embase, Web of Science, Science Direct and the references of identified articles were searched for relevant studies that met our eligibility criteria. Treatment effects were combined by meta‐analysis using RevMan 5.3 and Stata 12.0 software.ResultsWe included 11 trials in this meta‐analysis. Compared to the control, 0.2% chlorhexidine gel reduced the risk of alveolar osteitis by 62% (RR = 0.38, 95% CI = 0.28–0.53, P < 0.00001) following mandibular third molar extraction(s). The subgroup analysis results indicated that 0.2% chlorhexidine gel reduced the risk of alveolar osteitis after mandibular third molar extraction(s) by 75% (RR = 0.25, 95% CI = 0.11–0.58) and 56% (RR = 0.44, 95% CI = 0.30–0.63) compared to no treatment and placebo, respectively. However, the occurrence of alveolar osteitis following mandibular third molar extraction(s) was not significantly different between 0.2% chlorhexidine gel and 0.12% chlorhexidine mouthwash (RR = 0.24, 95% CI = 0.06–1.00).ConclusionThe results showed that 0.2% chlorhexidine gel was effective in preventing alveolar osteitis after lower third molar extraction(s).
Obtaining consensus regarding international transplantation continues to be difficult for pediatric centers in the United States
Authors: Lorts Angela , Ryan Thomas D. , Matheny Antommaria Armand H. , Lake Michael , Bucuvalas John 
Published: August 2016

AbstractOrgan transplant is life‐saving and any given organ may be valuable to a multitude of potential recipients. An allocation system must be used to reconcile the difference between supply and demand, and this system must take into account the impact that accepting international patients may have on the local system. The principles for allocation must be clear, equitable, provide utility and must be monitored so as to maintain public trust. The impact of the system on metrics deemed to be critical must be measured. Finally, strategies must take into account the local culture, size of the region to be supported, the number and experience of transplant centers, and the resources of the healthcare delivery system. Our focus is on the United States, recognizing that strategies and challenges may vary across countries.
Characteristics of Telephone Crisis Hotline Callers with Suicidal Ideation in Japan
Authors: Ohtaki Yuh , Oi Yuichi , Doki Shotaro , Kaneko Hidetoshi , Usami Kazuya , Sasahara Shinichiro , Matsuzaki Ichiyo 
Published: August 2016

Hotline callers do not always have suicidal ideation and previous studies have noted that the rate of such callers is limited. Crisis hotline counselors must be able to identify high‐risk callers in order to provide appropriate support. This study investigated the characteristics of Japanese crisis hotline callers in 2012 (N = 541,694) and is the first to analyze crisis hotline data for all parts of Japan over 1 year. About 14% of the callers had suicidal ideation and 6% had a history of attempted suicide. The odds ratio for suicidal ideation among those with a history of attempted suicide was 15.5. The suicidal ideation rate was much smaller compared to previous studies in other countries. There is a psychological barrier that must be broken for high‐risk people to use support hotlines. In addition, attempted suicide is a strong exclusive predisposing factor for death due to suicide; therefore, counselors should pay careful attention to callers with a history of attempted suicide. The characteristics of Japanese crisis hotline callers and the features of suicidal ideation revealed in the present study are expected to be useful in developing telephone crisis hotline strategies.
Nonsuicidal Self‐Injury in Adolescents: Characterization of the Disorder and the Issue of Distress and Impairment
Authors: Zetterqvist Maria 
Published: August 2016

Nonsuicidal self‐injury disorder (NSSID) is a condition in need of further study to assess the validity of the potential diagnosis and its suggested criteria. This study examined the NSSID diagnosis and investigated the distress/impairment criterion by comparing community adolescents who met all criteria for NSSID (n = 186) to adolescents with five or more nonsuicidal self‐injury (NSSI) episodes (n = 314), and to a group of adolescents who met all criteria but negated that their NSSI caused them any distress or impairment, thus failing to meet criterion E (n = 29). The NSSID group delimited from the ≥ 5 NSSI group by reporting significantly more frequent and severe self‐injurious thoughts and behaviors, as well as having more experiences of negative life events and higher levels of trauma symptoms. There were also some differences between the NSSID group and adolescents without distress/impairment, which together contribute valuable information on the potential NSSID diagnosis, as well as the discussion of criterion E.
Describing and Measuring the Pathway to Suicide Attempts: A Preliminary Study
Authors: Millner Alexander J. , Lee Michael D. , Nock Matthew K. 
Published: August 2016

To die by suicide, one must think about suicide, make a plan, and then carry it out. Prior research has examined the presence and predictors of these outcomes; however, virtually no studies have characterized how these steps unfold along the pathway to suicide. A novel instrument was administered to 30 recent suicide attempters. Results revealed that although the median onset for suicidal ideation occurs 1 to 5 years prior to attempting, the median for 6 of the 10 steps measured was within 6 hours of attempting. Overall, 86.5% of proximal planning steps took place within 1 week of attempting and 66.6% occurred within 12 hours.
Optimal cue combination and landmark‐stability learning in the head direction system
Authors: Jeffery Kate J. , Page Hector J. I. , Stringer Simon M. 
Published: August 2016

AbstractMaintaining a sense of direction requires combining information from static environmental landmarks with dynamic information about self‐motion. This is accomplished by the head direction system, whose neurons – head direction cells – encode specific head directions. When the brain integrates information in sensory domains, this process is almost always ‘optimal’ – that is, inputs are weighted according to their reliability. Evidence suggests cue combination by head direction cells may also be optimal. The simplicity of the head direction signal, together with the detailed knowledge we have about the anatomy and physiology of the underlying circuit, therefore makes this system a tractable model with which to discover how optimal cue combination occurs at a neural level. In the head direction system, cue interactions are thought to occur on an attractor network of interacting head direction neurons, but attractor dynamics predict a winner‐take‐all decision between cues, rather than optimal combination. However, optimal cue combination in an attractor could be achieved via plasticity in the feedforward connections from external sensory cues (i.e. the landmarks) onto the ring attractor. Short‐term plasticity would allow rapid re‐weighting that adjusts the final state of the network in accordance with cue reliability (reflected in the connection strengths), while longer term plasticity would allow long‐term learning about this reliability. Although these principles were derived to model the head direction system, they could potentially serve to explain optimal cue combination in other sensory systems more generally.
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A Physiologically Based Pharmacokinetic Model of Isoniazid and Its Application in Individualizing Tuberculosis Chemotherapy
Authors: Cordes Henrik , Thiel Christoph , Aschmann Hélène E. , Baier Vanessa , Blank Lars M. , Kuepfer Lars 
Published: August 2016

ABSTRACT

Due to its high early bactericidal activity, isoniazid (INH) plays an essential role in tuberculosis treatment. Genetic polymorphisms of
N
-acetyltransferase type 2 (NAT2) cause a trimodal distribution of INH pharmacokinetics in slow, intermediate, and fast acetylators. The success of INH-based chemotherapy is associated with acetylator and patient health status. Still, a standard dose recommended by the FDA is administered regardless of acetylator type or immune status, even though adverse effects occur in 5 to 33% of all patients. Slow acetylators have a higher risk of development of drug-induced toxicity, while fast acetylators and immune-deficient patients face lower treatment success rates. To mechanistically assess the trade-off between toxicity and efficacy, we developed a physiologically based pharmacokinetic (PBPK) model describing the NAT2-dependent pharmacokinetics of INH and its metabolites. We combined the PBPK model with a pharmacodynamic (PD) model of antimycobacterial drug effects in the lungs. The resulting PBPK/PD model allowed the simultaneous simulation of treatment efficacies at the site of infection and exposure to toxic metabolites in off-target organs. Subsequently, we evaluated various INH dosing regimens in NAT2-specific immunocompetent and immune-deficient virtual populations. Our results suggest the need for acetylator-specific dose adjustments for optimal treatment outcomes. A reduced dose for slow acetylators substantially lowers the exposure to toxic metabolites and thereby the risk of adverse events, while it maintains sufficient treatment efficacies. Vice versa, intermediate and fast acetylators benefit from increased INH doses and a switch to a twice-daily administration schedule. Our analysis outlines how PBPK/PD modeling may be used to design and individualize treatment regimens.
Characterization of
In Vitro
Resistance Development to the Novel Echinocandin CD101 in Candida Species
Authors: Locke Jeffrey B. , Almaguer Amanda L. , Zuill Douglas E. , Bartizal Ken 
Published: August 2016

ABSTRACT

CD101 is a novel echinocandin with a long half-life undergoing clinical development for treatment of candidemia/invasive candidiasis and vulvovaginal candidiasis. The potential for and mechanisms underlying the development of resistance to CD101 in
Candida
species were investigated by using spontaneous resistance and serial passage selection methodologies. Four
Candida
spp. (
C. albicans
,
C. glabrata
,
C. parapsilosis
, and
C. krusei
) were chosen for resistance characterization with CD101, anidulafungin, and caspofungin. The frequency of spontaneous, single-step mutations conferring reduced susceptibility to CD101 at 1× the agar growth inhibition concentration was low across all species, with median frequencies ranging from 1.35 × 10
−8
to 3.86 × 10
−9
, similar to ranges generated for anidulafungin and caspofungin. Serial passage of
Candida
spp. on agar plates containing drug gradients demonstrated a low potential for resistance development, with passage 20 CD101-selected strains possessing increases in MICs equivalent to or lower than those for the majority of strains generated under selection with anidulafungin and caspofungin. A total of 12
fks
“hot spot” mutations were identified, typically in strains with the highest MIC shifts. Cross-resistance was broadly observed among the 3 echinocandins evaluated, with no CD101-selected mutants (with or without
fks
hot spot mutations) exhibiting reduced susceptibility to CD101 but not also to anidulafungin and/or caspofungin. Consistent with currently approved echinocandins, CD101 demonstrates a low potential for resistance development, which could be further enhanced
in vivo
by the high maximum concentration of drug in serum (
C
max
)/area under the concentration-time curve (AUC) plasma drug exposure achieved with once-weekly dosing of CD101.