bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics, Pharmacodynamics, and Tolerability of Single-Dose Oral LCB01-0371, a Novel Oxazolidinone with Broad-Spectrum Activity, in Healthy Volunteers
Authors: Cho Yong-Soon , Lim Hyeong-Seok , Lee Shi-Hyang , Cho Young Lag , Nam Hee-sook , Bae Kyun-Seop
Published: April 2018

LCB01-0371 is a novel oxazolidinone with broad-spectrum activity against Gram-positive pathogens in bothin vitrostudies and animal infection models. The objectives of this study were to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamics following single ascending doses. Single oral doses of 600 mg linezolid, a placebo, or LCB01-0371 of between 50 mg and 3,200 mg were tested in 69 healthy male subjects. Blood and urine were sampled, LCB01-0371 concentrations were measured, and the serum inhibitory and bactericidal titers of LCB01-0371 and linezolid were determined. LCB01-0371 was well tolerated up to 2,400 mg. The most common drug-related clinical and laboratory adverse events were nausea with or without vomiting, decreased neutrophil counts, and increased total bilirubin levels. The frequency of adverse events and drug-related adverse events was similar among the treatment groups. The systemic exposure was approximately dose proportional over the range of 50 mg to 800 mg, which includes the anticipated clinical dose. The mean clearance, renal clearance, and volume of distribution were significantly decreased at higher doses (above 800 mg). LCB01-0371 exhibited early bacteriostatic activity against all tested strains except forStreptococcus pneumoniaestrains, and the potency of LCB01-0371 at 800 mg was similar to that of linezolid at the therapeutic dose (600 mg). However, LCB01-0371 had less bactericidal activity than linezolid. Taken together, LCB01-0371 was well tolerated, exhibited approximate dose proportionality within the anticipated clinically relevant dose range, and showed bacteriostatic and bactericidal activity comparable to that of linezolid. These results support the further clinical development of LCB01-0371. (This study has been registered at ClinicalTrials.gov under registration no. NCT01554995.)
Complete Genome Sequence of Methylomonas denitrificans Strain FJG1, an Obligate Aerobic Methanotroph That Can Couple Methane Oxidation with Denitrification
Authors: Orata Fabini D. , Kits K. Dimitri , Stein Lisa Y.
Published: April 2018

Methylomonas denitrificans
strain FJG1 is a member of the gammaproteobacterial methanotrophs. The sequenced genome of FJG1 reveals the presence of genes that encode methane, methanol, formaldehyde, and formate oxidation. It also contains genes that encode enzymes for nitrate reduction to nitrous oxide, consistent with the ability of FJG1 to couple denitrification with methane oxidation.
Complete Genome Sequence of the Freshwater Bacterium Beggiatoa leptomitoformis Strain D-401
Authors: Fomenkov Alexey , Sun Zhiyi , Vincze Tamas , Dubinina Galina , Orlova Maria , Tarlachkov Sergey V. , Anton Brian P. , Grabovich Margarita Y. , Roberts Richard J.
Published: April 2018

Here, we report the complete closed genome sequence and methylome analysis of
Beggiatoa leptomitoformis
strain D-401 (DSM 14945, UNIQEMU 779), which is quite different from the previously described
Beggiatoa leptomitoformis
neotype strain D-402
T
(DSM 14946, UNIQEM U 779) with regard to morphology and lithotrophic growth in the presence of thiosulfate.
Draft Genome Sequence of the Interspecies Hybrid Saccharomyces pastorianus Strain HA2560, Isolated from a Municipal Wastewater Treatment Plant
Authors: Tafer Hakim , Sterflinger Katja , Lopandic Ksenija
Published: April 2018

Saccharomyces pastorianus
is an industrially relevant yeast frequently isolated from brewing environments. Here, we report the draft genome sequence of the
S. pastorianus
HA2560 strain isolated from a municipal wastewater treatment plant.
Taxon Disappearance from Microbiome Analysis Reinforces the Value of Mock Communities as a Standard in Every Sequencing Run
Authors: Yeh Yi-Chun , Needham David M. , Sieradzki Ella T. , Fuhrman Jed A.
Published: April 2018

Despite the routine use of standards and blanks in virtually all chemical or physical assays and most biological studies (a kind of “control”), microbiome analysis has traditionally lacked such standards. Here we show that unexpected problems of unknown origin can occur in such sequencing runs and yield completely incorrect results that would not necessarily be detected without the use of standards. Assuming that the microbiome sequencing analysis works properly every time risks serious errors that can be detected by the use of mock communities.
Nonpareil 3: Fast Estimation of Metagenomic Coverage and Sequence Diversity
Authors: Rodriguez-R Luis M. , Gunturu Santosh , Tiedje James M. , Cole James R. , Konstantinidis Konstantinos T.
Published: April 2018

Estimation of the coverage provided by a metagenomic data set, i.e., what fraction of the microbial community was sampled by DNA sequencing, represents an essential first step of every culture-independent genomic study that aims to robustly assess the sequence diversity present in a sample. However, estimation of coverage remains elusive because of several technical limitations associated with high computational requirements and limiting statistical approaches to quantify diversity. Here we described Nonpareil 3, a new bioinformatics algorithm that circumvents several of these limitations and thus can facilitate culture-independent studies in clinical or environmental settings, independent of the sequencing platform employed. In addition, we present a new metric of sequence diversity based on rarefied coverage and demonstrate its use in communities from diverse ecosystems.
Inferring the Minimal Genome of
Mesoplasma florum
by Comparative Genomics and Transposon Mutagenesis
Authors: Baby Vincent , Lachance Jean-Christophe , Gagnon Jules , Lucier Jean-François , Matteau Dominick , Knight Tom , Rodrigue Sébastien
Published: April 2018

The last years have witnessed the development of whole-genome cloning and transplantation methods and the complete synthesis of entire chromosomes. Recently, the first minimal cell,
Mycoplasma mycoides
JCVI-syn3.0, was created. Despite these milestone achievements, several questions remain to be answered. For example, is the composition of minimal genomes virtually identical in phylogenetically related species? On the basis of comparative genomics and transposon mutagenesis, we investigated this question by using an alternative model,
Mesoplasma florum
, that is also amenable to genome reduction efforts. Our results suggest that the creation of additional minimal genomes could help reveal different gene compositions and strategies that can support life, even within closely related species.
The relationship between intimate partner violence reported at the first antenatal booking visit and obstetric and perinatal outcomes in an ethnically diverse group of Australian pregnant women: a population-based study over 10 years
Authors: Dahlen Hannah Grace , Munoz Ana Maria , Schmied Virginia , Thornton Charlene
Published: April 2018

Objectives

Intimate partner violence (IPV) is a global health issue affecting mainly women and is known to escalate during pregnancy and impact negatively on obstetric and perinatal outcomes. The aim of this study is to determine the incidence of IPV in a pregnant multicultural population and to determine the relationship between IPV reported at booking interview and maternal and perinatal outcomes.

Design

This is a retrospective population-based data study. We analysed routinely collected data (2006–2016) from the ObstetriX system on a cohort of pregnant women.

Setting and participants

33 542 women giving birth in a major health facility in Western Sydney.

Primary outcomes

Incidence of IPV, association with IPV and other psychosocial variables and maternal and perinatal outcomes.

Result

4.3% of pregnant women reported a history of IPV when asked during the routine psychosocial assessment. Fifty-four per cent were not born in Australia, and this had increased significantly over the decade. Women born in New Zealand (7.2%) and Sudan (9.1%) were most likely to report IPV at the antenatal booking visit, with women from China and India least likely to report IPV. Women who reported IPV were more likely to report additional psychosocial concerns including Edinburgh Postnatal Depression Scale scores>13 (7.6%), thoughts of self-harm (2.4%), childhood abuse (23.6%), and a history of anxiety and depression (34.2%). Women who reported IPV were more likely to be Australian born, smoke and be multiparous and to have been admitted for threatened preterm labour (Adjusted Odds Ratio (AOR) 1.8, 95% CI 1.28 to 2.39).

Conclusions

A report of IPV at the first antenatal booking visit is associated with a higher level of reporting on all psychosocial risks, higher antenatal admissions, especially for threatened preterm labour. More research is needed regarding the effectiveness of current IPV screening for women from other countries.
The incidence of injury in elite camogie, an in-season prospective study
Authors: Buckley Catherine Susan , Blake Catherine
Published: April 2018

Background

Camogie is a stickhandling, high-velocity, multidirectional field sport for females which is native to Ireland, but is also played internationally.

Aim

To establish the incidence, nature and severity of injuries in elite camogie players.

Methods

A prospective, observational cohort study was carried out during the Provincial Championships and extending into the All-Ireland Championship until a participating team was eliminated (11 weeks). A purposive sample of 62 players from 3 of the total 11 senior intercounty teams participated to generate geographical representation. Injury data were recorded and classified by team physiotherapists using a time loss definition, consistent with consensus statements. A concurrent measure of exposure to matches and training was recorded.

Results

Twenty-one incidents of injury were recorded with 14 players injured. Injury incidence rate was 26.4 (95% CI 13.44 to 47.16) per 1000 match hours and 4.2 (95% CI 2.12 to 7.46) per 1000 training hours. There were 11 contact and 10 non-contact injuries. The lower limb accounted for 71.4% (n=15), the upper limb 9.5% (n=2) and the trunk and head 19.1% (n=4) of injuries. The main tissues injured were both muscle and ligament, representing 57.2% (n=6 each). The mean duration time loss from sport per injury was 12.14 days.

Conclusion

These results provide data on the incidence, nature and severity of camogie injuries using definitions that reflect international consensus statements. Further study of injury incidence over a full season or multiple seasons is recommended.
Effects of preoperative and postoperative resistance exercise interventions on recovery of physical function in patients undergoing abdominal surgery for cancer: a systematic review of randomised controlled trials
Authors: Stephensen David , Hashem Ferhana , Corbett Kevin , Bates Amanda , George Michelle , Hobbs Ralph Peter , Hopkins Malcolm , Hutchins Irena , Lowery David Peter , Pellatt-Higgins Tracy , Stavropoulou Charitini , Swaine Ian , Tomlinson Lee , Woodward Hazel , Ali Haythem
Published: April 2018

Objective

To systematically review the effects of preoperative and postoperative resistance exercise training on the recovery of physical function in patients undergoing abdominal surgery for cancer.

Data sources

A systematic review of English articles using Medline, Physiotherapy Evidence Database, CINAHL and the Cochrane Library electronic databases was undertaken.

Eligibility criteria for selecting studies

Studies were included if they used a randomised, quasi-randomised or controlled trial study design and compared the effects of a muscle-strengthening exercise intervention (±other therapy) with a comparative non-exercise group; involved adult participants (≥18 years) who had elected to undergo abdominal surgery for cancer; and used muscle strength, physical function, self-reported functional ability, range of motion and/or a performance-based test as an outcome measure.

Results

Following screening of titles and abstracts of the 588 publications retrieved from the initial search, 24 studies met the inclusion criteria and were accessed for review of the full-text version of the article, and 2 eligible studies met the inclusion criteria and were included in the review. One exercise programme was undertaken preoperatively and the other postoperatively, until discharge from hospital. The exercise interventions of the included studies were performed for five and eight sessions, respectively. There were no differences between groups in either study.

Conclusion

The only two studies designed to determine whether preoperative or postoperative resistance muscle-strengthening exercise programmes improved or negatively affected physical function outcomes in patients undergoing abdominal surgery for cancer provide inconclusive results.
Individual participant data analysis of two trials on aldosterone blockade in myocardial infarction
Authors: Beygui Farzin , Van Belle Eric , Ecollan Patrick , Machecourt Jacques , Hamm Christian W , Lopez De Sa Estaeban , Flather Marcus , Verheugt Freek W A , Vicaut Eric , Zannad Faiez , Pitt Bertram , Montalescot Gilles
Published: April 2018

Background

Two recent randomised trials studied the benefit of mineralocorticoid receptor antagonists (MRAs) in ST-segment elevation myocardial infarction (STEMI) irrespective or in absence of heart failure. The studies were both undersized to assess hard clinical endpoints. A pooled analysis was preplanned by the steering committees.

Methods

We conducted a prespecified meta-analysis of patient-level data of patients with STEMI recruited in two multicentre superiority trials, randomised within 72 hours after symptom onset. Patients were allocated (1:1) to two MRA regimens: (1) an intravenous bolus of potassium canrenoate (200 mg) followed by oral spironolactone (25 mg once daily) versus standard therapy or (2) oral eplerenone (25–50 mg) versus placebo. The primary and key secondary outcomes, all-cause death and the composite of all-cause death or resuscitated sudden death, respectively, were assessed in the intention-to-treat population using a Cox model stratified on the study identifier.

Results

Patients were randomly assigned to receive (n=1118) or not the MRA regimen (n=1123). After a median follow-up time of 188 days, the primary and secondary outcomes occurred in 5 (0.4%) and 17 (1.5%) patients (adjusted HR (adjHR) 0.31, 95% CI 0.11 to 0.86, p=0.03) and 6 (0.5%) and 22 (2%) patients (adjHR 0.26, 95% CI 0.10 to 0.65, p=0.004) in the MRA and control groups, respectively. There were also trends towards lower rates of cardiovascular death (p=0.06) and ventricular fibrillation (p=0.08) in the MRA group.

Conclusion

Our analysis suggests that compared with standard therapy, MRA regimens are associated with a reduction of death and death or resuscitated sudden death in STEMI.
Disruption of protein function by pathogenic mutations: common and uncommon mechanisms
Authors: Taipale Mikko
Published: April 2018

Mutations in protein-coding regions underlie almost all Mendelian disorders, drive tumorigenesis, and contribute to susceptibility to common diseases. Despite the great diversity of diseases that are caused by coding mutations, the cellular processes that affect, and are affected by, pathogenic variants at the molecular level are fundamentally conserved. Experimental and computational approaches have revealed that a substantial fraction of disease mutations are not simple loss-of-function alleles. Rather, these pathogenic variants disrupt protein function in more subtle ways by tuning protein folding pathways, altering subcellular trafficking, interrupting signaling cascades, and rewiring highly connected interaction networks. Focusing mainly on Mendelian disorders, this review discusses the common mechanisms by which deleterious mutations disrupt protein function and how these disruptions can be exploited in the development of novel therapies.
Comparison of two depth-averaged numerical models for debris flow runout estimation
Authors: Vagnon Federico , Pirulli Marina , Yague Angel , Pastor Manuel
Published: April 2018

This paper analyses an important aspect of the continuum numerical modelling of rapid landslides as debris flows: “By using the same rheological parameter values, are the results obtained with codes that implement the same constitutive equations, but a different numerical solver, equal?” To answer this question, the two numerical codes RASH3D and GeoFlow_SPH are used here to back-analyse the debris flow event that occurred in the Nora stream (northwestern Italian Alps) in October 2000. Comparison of results evidenced that the RASH3D best-fit rheological values for the Nora event back-analysis overestimated both the final depositional heights and the simulated flow velocities if used in GeoFlow_SPH. To obtain thickness values comparable with those measured in situ, it was necessary to re-calibrate GeoFlow_SPH rheological parameter values. This way, with the exception of a larger lateral spreading of the sliding mass given by RASH3D, both thickness and velocity values were similar for the two numerical codes.
Macleaya cordata extracts suppressed the increase of a part of antibiotic resistance genes in fecal microorganism of weaned pigs
Authors: Li Y. , Li H. , Chu Q. , Xu F. , Liang T. , Zhou B.
Published: April 2018

This study was designed to evaluate the effects of Macleaya cordata extracts (Chinese herbal medicine extracts) and antibiotics combination with chlortetracycline (CTC) on the antibiotic resistance genes in fecal microorganism. Compared with the group without antibiotics, the relative abundances of all six tetracycline resistance genes were increased after 75 mg kg−1 CTC supplementation. Interestingly, M. cordata extracts in feed suppressed the increase of a part of tetracycline resistance genes in fecal microorganism of weaned pigs.
Clebsch–Gordan coefficients of discrete groups in subgroup bases
Authors: Chen Gaoli
Published: April 2018

We express each Clebsch–Gordan (CG) coefficient of a discrete group as a product of a CG coefficient of its subgroup and a factor, which we call an embedding factor. With an appropriate definition, such factors are fixed up to phase ambiguities. Particularly, they are invariant under basis transformations of irreducible representations of both the group and its subgroup. We then impose on the embedding factors constraints, which relate them to their counterparts under complex conjugate and therefore restrict the phases of embedding factors. In some cases, the phase ambiguities are reduced to sign ambiguities. We describe the procedure of obtaining embedding factors and then calculate CG coefficients of the group [Formula: see text] in terms of embedding factors of its subgroups [Formula: see text] and [Formula: see text].
A conservation law, entropy principle and quantization of fractal dimensions in hadron interactions
Authors: Zborovský I.
Published: April 2018

Fractal self-similarity of hadron interactions demonstrated by the [Formula: see text]-scaling of inclusive spectra is studied. The scaling regularity reflects fractal structure of the colliding hadrons (or nuclei) and takes into account general features of fragmentation processes expressed by fractal dimensions. The self-similarity variable [Formula: see text] is a function of the momentum fractions [Formula: see text] and [Formula: see text] of the colliding objects carried by the interacting hadron constituents and depends on the momentum fractions [Formula: see text] and [Formula: see text] of the scattered and recoil constituents carried by the inclusive particle and its recoil counterpart, respectively. Based on entropy principle, new properties of the [Formula: see text]-scaling concept are found. They are conservation of fractal cumulativity in hadron interactions and quantization of fractal dimensions characterizing hadron structure and fragmentation processes at a constituent level.
Can You See What I See? Quality-of-Experience Measurements of Mobile Live Video Broadcasting
Authors: Siekkinen Matti , kämäräinen Teemu , Favario Leonardo , Masala Enrico
Published: April 2018

Broadcasting live video directly from mobile devices is rapidly gaining popularity with applications like Periscope and Facebook Live. The quality of experience (QoE) provided by these services comprises many factors, such as quality of transmitted video, video playback stalling, end-to-end latency, and impact on battery life, and they are not yet well understood. In this article, we examine mainly the Periscope service through a comprehensive measurement study and compare it in some aspects to Facebook Live. We shed light on the usage of Periscope through analysis of crawled data and then investigate the aforementioned QoE factors through statistical analyses as well as controlled small-scale measurements using a couple of different smartphones and both versions, Android and iOS, of the two applications. We report a number of findings including the discrepancy in latency between the two most commonly used protocols, RTMP and HLS, surprising surges in bandwidth demand caused by the Periscope app’s chat feature, substantial variations in video quality, poor adaptation of video bitrate to available upstream bandwidth at the video broadcaster side, and significant power consumption caused by the applications.
Science, policy, and service
Authors: Martonosi Margaret
Published: April 2018

Some thoughts on the way forward.
Functional features of the “finger” domain of the DEG/ENaC channels MEC-4 and UNC-8
Authors: Matthewman Cristina , Johnson Christina K. , Miller David M. , Bianchi Laura
Published: April 2018

UNC-8 and MEC-4 are two members of the degenerin/epithelial Na+ channel (DEG/ENaC) family of voltage-independent Na+ channels that share a high degree of sequence homology and functional similarity. For example, both can be hyperactivated by genetic mutations [UNC-8(d) and MEC-4(d)] that induce neuronal death by necrosis. Both depend in vivo on chaperone protein MEC-6 for function, as demonstrated by the finding that neuronal death induced by hyperactive UNC-8 and MEC-4 channels is prevented by null mutations in mec-6. UNC-8 and MEC-4 differ functionally in three major ways: 1) MEC-4 is calcium permeable, whereas UNC-8 is not; 2) UNC-8, but not MEC-4, is blocked by extracellular calcium and magnesium in the micromolar range; and 3) MEC-6 increases the number of MEC-4 channels at the cell surface in oocytes but does not have this effect on UNC-8. We previously reported that Ca2+permeability of MEC-4 is conferred by the second transmembrane domain. We show here that the extracellular “finger” domain of UNC-8 is sufficient to mediate inhibition by divalent cations and that regulation by MEC-6 also depends on this region. Thus, our work confirms that the finger domain houses residues involved in gating of this channel class and shows for the first time that the finger domain also mediates regulation by chaperone protein MEC-6. Given that the finger domain is the most divergent region across the DEG/ENaC family, we speculate that it influences channel trafficking and function in a unique manner depending on the channel subunit.
Maximum heart rate does not limit cardiac output at rest or during exercise in the American alligator (Alligator mississippiensis)
Authors: Joyce William , Elsey Ruth M. , Wang Tobias , Crossley Dane A.
Published: April 2018

In most vertebrates, increases in cardiac output result from increases in heart rate (fH) with little or no change in stroke volume (Vs), and maximum cardiac output (Q̇) is typically attained at or close to maximum fH. We therefore tested the hypothesis that increasing maximum fHmay increase maximum Q̇. To this end, we investigated the effects of elevating fHwith right atrial pacing on Q̇ in the American alligator ( Alligator mississippiensis) at rest and while swimming. During normal swimming, Q̇ increased entirely by virtue of a tachycardia (29 ± 1 to 40 ± 3 beats/min), whereas Vsremained stable. In both resting and swimming alligators, increasing fHwith right atrial pacing resulted in a parallel decline in Vsthat resulted in an unchanged cardiac output. In swimming animals, this reciprocal relationship extended to supraphysiological fH(up to ~72 beats/min), which suggests that maximum fHdoes not limit maximum cardiac output and that fHchanges are secondary to the peripheral factors (for example vascular capacitance) that determine venous return at rest and during exercise.
Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation
Authors: Kumaravelu Karthik , Oza Chintan S. , Behrend Christina E. , Grill Warren M.
Published: April 2018

Parkinson’s disease is associated with altered neural activity in the motor cortex. Chronic high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in suppressing parkinsonian motor symptoms and modulates cortical activity. However, the anatomical pathways responsible for STN DBS-mediated cortical modulation remain unclear. Cortical evoked potentials (cEP) generated by STN DBS reflect the response of cortex to subcortical stimulation, and the goal of this study was to determine the neural origin of STN DBS-generated cEP using a two-step approach. First, we recorded cEP over ipsilateral primary motor cortex during different frequencies of STN DBS in awake healthy and unilateral 6-OHDA-lesioned parkinsonian rats. Second, we used a detailed, biophysically based model of the thalamocortical network to deconstruct the neural origin of the recorded cEP. The in vivo cEP included short (R1)-, intermediate (R2)-, and long-latency (R3) responses. Model-based cortical responses to simulated STN DBS matched remarkably well the in vivo responses. The short-latency response was generated by antidromic activation of layer 5 pyramidal neurons, whereas recurrent activation of layer 5 pyramidal neurons via excitatory axon collaterals reproduced the intermediate-latency response. The long-latency response was generated by polysynaptic activation of layer 2/3 pyramidal neurons via the cortico-thalamic-cortical pathway. Antidromic activation of the hyperdirect pathway and subsequent intracortical and cortico-thalamo-cortical synaptic interactions were sufficient to generate cortical potential evoked by STN DBS, and orthodromic activation through basal ganglia-thalamus-cortex pathways was not required. These results demonstrate the utility of cEP to determine the neural elements activated by STN DBS that might modulate cortical activity and contribute to the suppression of parkinsonian symptoms.

NEW & NOTEWORTHY Subthalamic nucleus (STN) deep brain stimulation (DBS) is increasingly used to treat Parkinson’s disease (PD). Cortical potentials evoked by STN DBS in patients with PD exhibit consistent short-latency (1–3 ms), intermediate-latency (5–15 ms), and long-latency (18–25 ms) responses. The short-latency response occurs as a result of antidromic activation of the hyperdirect pathway comprising corticosubthalamic axons. However, the neural origins of intermediate- and long-latency responses remain elusive, and the dominant view is that these are produced through the orthodromic pathway (basal ganglia-thalamus-cortex). By combining in vivo electrophysiology with computational modeling, we demonstrate that antidromic activation of the cortico-thalamic-cortical pathway is sufficient to generate the intermediate- and long-latency cortical responses to STN DBS.
Efectividad de las intervenciones psicológicas basadas en el Modelo Transteórico (MTT) del Cambio para el control metabólico de pacientes diabéticos.
Authors: Pacheco Lopez Manuela , Rodriguez R Laura , Caneo Robles Constanza
Published: April 2018

Objetivo: Evaluar el rol de las intervenciones basadas en el Modelo Transteórico (MTT) para mejorar el autocuidado de pacientes con diabetes mellitus tipo 1 ó tipo 2 (DM1, DM2).Metodología: Se realizó una búsqueda (mayo 2017), en las bases de datos Pubmed, Academic Search Complete y PsycInfo, utilizando términos en inglés relacionados con Glucose Metabolic Disorder, Motivational Interviewing y Randomized Control Trial. Criterios de inclusión: pacientes diabéticos, mayores de 18 años, estudios realizados en atención primaria y cuyo resultado primario fuere el control glicémico. La selección de estudios fue realizada de forma independiente por MP y LR, resolviendo discrepancias con CC. Los resultados son presentados en base al protocolo PRISMA. Resultados: Se identificaron 455 estudios, en base a título y resumen se seleccionaron 68, de los cuales 8 cumplían con los criterios de inclusión. Los participantes presentaban entre 53 y 64 años de edad. No se encontraron estudios con población con DM1. No se encontraron resultados significativos para el control metabólico. Sin embargo, cuatro de los estudios demostraron que el MTT fue efectivo para aumentar la actividad física y dos reportaron mejorar la adherencia al tratamiento farmacológico y mitigar las barreras percibidas para la toma de medicamentos. Conclusiones: Intervenciones psicológicas basadas en el MTT para el cambio de estilo de vida de los pacientes con DM2, favorecen el autocuidado de la enfermedad a través de la adherencia al tratamiento farmacológico y actividad física. No existe evidencia que sugiera que estas intervenciones impacten directamente en el control metabólico.
ASTX660, a Novel Non-peptidomimetic Antagonist of cIAP1/2 and XIAP, Potently Induces TNFα-Dependent Apoptosis in Cancer Cell Lines and Inhibits Tumor Growth
Authors: Ward George A. , Lewis Edward J. , Ahn Jong Sook , Johnson Christopher N. , Lyons John F. , Martins Vanessa , Munck Joanne M. , Rich Sharna J. , Smyth Tomoko , Thompson Neil T. , Williams Pamela A. , Wilsher Nicola E. , Wallis Nicola G. , Chessari Gianni
Published: April 2018

Because of their roles in the evasion of apoptosis, inhibitor of apoptosis proteins (IAP) are considered attractive targets for anticancer therapy. Antagonists of these proteins have the potential to switch prosurvival signaling pathways in cancer cells toward cell death. Various SMAC-peptidomimetics with inherent cIAP selectivity have been tested clinically and demonstrated minimal single-agent efficacy. ASTX660 is a potent, non-peptidomimetic antagonist of cIAP1/2 and XIAP, discovered using fragment-based drug design. The antagonism of XIAP and cIAP1 by ASTX660 was demonstrated on purified proteins, cells, and in vivo in xenograft models. The compound binds to the isolated BIR3 domains of both XIAP and cIAP1 with nanomolar potencies. In cells and xenograft tissue, direct antagonism of XIAP was demonstrated by measuring its displacement from caspase-9 or SMAC. Compound-induced proteasomal degradation of cIAP1 and 2, resulting in downstream effects of NIK stabilization and activation of noncanonical NF-κB signaling, demonstrated cIAP1/2 antagonism. Treatment with ASTX660 led to TNFα-dependent induction of apoptosis in various cancer cell lines in vitro, whereas dosing in mice bearing breast and melanoma tumor xenografts inhibited tumor growth. ASTX660 is currently being tested in a phase I–II clinical trial (NCT02503423), and we propose that its antagonism of cIAP1/2 and XIAP may offer improved efficacy over first-generation antagonists that are more cIAP1/2 selective. Mol Cancer Ther; 17(7); 1381–91. ©2018 AACR.
Is Sclerostin Level Associated with Cardiovascular Diseases in Hemodialysis Patients?
Authors: Kundakci Gelir Gokce , Sengul Sule , Nergizoglu Gokhan , Ertürk Sehsuvar , Duman Neval , Kutlay Sim
Published: April 2018

Background/Aims: The objective of this study is to evaluate the relation between sclerostin, arterial stiffness, and cardiovascular events (CVE) in hemodialysis patients (HD). Methods: Sclerostin level and carotid-femoral pulse wave velocity (PWV) in 97 HD patients and sclerostin level in 40 controls were measured. Results: Sclerostin level was significantly higher in patients than in controls. Sclerostin associated positively with age, male gender, cardiovascular disease, statin use, BMI, and PWV while negatively with alkaline phosphatase, parathormone (PTH), Kt/V, cinacalcet and vitamin D use in univariable correlation analyses. Sclerostin associated positively with male gender and statin use but negatively with PTH in multivariate regression analyses. During observation, 30 fatal or nonfatal CVEs were observed. While univariate correlation analysis showed a positive association between PWV and sclerostin, there was no relation between the two in multivariate regression analysis. Conclusion: Further studies are needed to understand the role of sclerostin in predicting PWV changes in HD patients.
Draft Genome Sequence of Bacillus cereus CITVM-11.1, a Strain Exhibiting Interesting Antifungal Activities
Authors: Caballero Javier , Peralta Cecilia , Molla Antonella , Del Valle Eleodoro E. , Caballero Primitivo , Berry Colin , Felipe Verónica , Yaryura Pablo , Palma Leopoldo
Published: April 2018

Bacillus cereus is a gram-positive, spore-forming bacterium possessing an important and historical record as a human-pathogenic bacterium. However, several strains of this species exhibit interesting potential to be used as plant growth-promoting rhizobacteria. Here, we report the draft genome sequence of B. cereus strain CITVM-11.1, which consists of 37 contig sequences, accounting for 5,746,486 bp (with a GC content of 34.8%) and 5,752 predicted protein-coding sequences. Several of them could potentially be involved in plant-bacterium interactions and may contribute to the strong antagonistic activity shown by this strain against the charcoal root rot fungus, Macrophomina phaseolina. This genomic sequence also showed a number of genes that may confer this strain resistance against several polluting heavy metals and for the bioconversion of mycotoxins.
Remote Monitoring of Automated Peritoneal Dialysis Improves Personalization of Dialytic Prescription and Patient’s Independence
Authors: Milan Manani Sabrina , Crepaldi Carlo , Giuliani Anna , Virzì Grazia Maria , Garzotto Francesco , Riello Caterina , de Cal Massimo , Rosner Mitchell H. , Ronco Claudio
Published: April 2018

Background: Remote monitoring (RM) supports a healthcare model that enhances patients’ self-management. We evaluated the utility of RM in patients undergoing automated peritoneal dialysis (APD). Methods: We observed 37 ­RM-APD patients, 16 incidents, and 21 prevalents switched from traditional APD (T-APD). We observed the number of changes for APD prescription, the frequency of visits, and PD adequacy parameters during 1 year of RM utilization in APD. Results: The APD prescriptions were modified more frequently in RM-APD vs. T-APD in incident (p = 0.002) and prevalent patients (p = 0.045). Visits were significant less in ­RM-APD than in T-APD for incident patient (p = 0.008). No significant difference was found between prevalent populations. PD adequacy was similar in both groups. Conclusions: Our results demonstrate that RM allows an efficient use of healthcare resources, helping to improve personalization of APD prescription and to intervene early with “trouble shooting”, thereby reducing the frequency of in-person visits for emergency problems.
Amyloidoma of Stomach: A Case Report
Authors: Savant Deepika , Adler Michael , Kahn Leonard , Cocker Rubina
Published: April 2018

Objective: Amyloidomas are tumor-like deposits of amyloid. Amyloidoma of the gastrointestinal tract is rare. To the best of our knowledge, this is the first instance of diagnosis of an amyloidoma in the gastrointestinal tract by fine needle aspiration (FNA). Study Design: We report a case of a 64-year-old male with a history of ulcerative colitis and primary sclerosing cholangitis who was incidentally found to have a mass in the stomach wall. Results: Initially thought to be gastrointestinal stromal tumor, FNA demonstrated the lesion to be amyloidoma with a prominent giant cell reaction. This was further confirmed by mass spectrometry. This is the only case report of diagnosis of a gastric amyloidoma by FNA. Conclusion: The presence of a florid giant cell reaction in the absence of ulceration or an inflammatory or neoplastic lesion should alert the pathologist to the possibility of an amyloidoma. This is the only case report of diagnosis of a gastric amyloidoma by FNA.
Low Expression of LncRNA Cancer Susceptibility Candidate 2 and its Clinical Significance in Cancer Tissues
Authors: Zhu Zheng-ming , Liu Fang-teng , Chen Xuan
Published: April 2018

Background/Aims: Long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is downregulated in various cancers and involved in both tumorigenesis and progression. The aim of this study was to assess the prognostic value of lncRNA CASC2 in cancer patients. Methods: We searched the Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and the Wanfang database to identify studies evaluating the prognostic value of lncRNA CASC2 in cancer patients. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects/random-effects models. Results: A total of eight studies were included. The combined results showed that lncRNA CASC2 was significantly associated with decreased overall survival (OS) (HR = 0.37, 95% CI, 0.27–0.46, P < 0.001). Subgroup analyses further indicated that low expression of lncRNA CASC2 predicted decreased OS in cancer patients. Additionally, low CASC2 expression levels in cancer tissues appeared to be correlated with advanced clinical staging (OR = 3.32, 95% CI, 2.29–4.80, P < 0.001). Conclusions: Low CASC2 expression appears to be predictive of poor OS and advanced tumor stage in multiple cancers. CASC2 expression may serve as unfavorable prognostic factor for clinical outcomes in cancer patients.
ДОСЛІДЖЕННЯ АСОРТИМЕНТУ ЛІКАРСЬКИХ ЗАСОБІВ ДЛЯ МІСЦЕВОГО ЗАСТОСУВАННЯ В СТОМАТОЛОГІЇ
Authors: Kozyr G. R. , Vasenda М. M. , Mits I. R. , Kozyr R. L.
Published: April 2018

Мета роботи. Вивчити асортимент лікарських засобів для місцевого застосування у стоматології, які представлені на фармацевтичному ринку України та доступні споживачам шляхом порівняння асортименту за останні 5 років.Матеріали і методи. Асортимент лікарських засобів і динаміку його зміни впродовж 5 років вивчали за допомогою доступних електронних ресурсів та аналітичних систем.Результати й обговорення. Встановлено країни, які експортують на український фармацевтичний ринок лікарські засоби досліджуваної групи. Визначено основних вітчизняних виробників досліджуваного асортименту лікарських засобів. При сегментації ринку препаратів за лікарськими формами встановлено, що іноземні виробники постачають на ринок гелі та розчини, тоді як вітчизняні фірми віддають перевагу лікарській рослинній сировині.Висновки. Проведені дослідження дають підстави стверджувати, що розробка лікарських препаратів у формі гелю є перспективною та необхідною.
ВИВЧЕННЯ ГОСТРОЇ ТОКСИЧНОСТІ ПРЕПАРАТУ АРГОЦИД ПРИ ВНУТРІШНЬООЧЕРЕВИННОМУ ВВЕДЕННІ
Authors: Polova Zh. M. , Seredinskaya N. M.
Published: April 2018

Мета роботи. Вивчення гострої токсичності ветеринарного препарату Аргоцид, розчин для інтрацистернального введення, при внутрішньоочеревинному введенні статевозрілим білим щурам.Матеріали і методи. Об'єктом дослідження були серії препарату Аргоцид, який містить цитрат срібла, D- пантенол та L- аргінін, призначений для лікування субклінічного маститу великої рогатої худоби. Дослідження гострої токсичності тест-зразків препарату Аргоцид проводили у дослідах на білих нелінійних статевозрілих щурах обох статей, віповідно до вимог, що висувають до потенційних ліків. Випробування проведені при внутрішньочеревному введенні препарату в різних дозах – від 2,0 до 6,3 мл / кг. Статистична обробка даних була виконана з використанням t-критерію Стьюдента. Для статистичної обробки даних використано програму MS Excel.Результати й обговорення. У результаті дослідження гострої токсичності препарату Аргоцид встановлено, що інтегральні показники життєдіяльності тварин – маса та температура тіла не зазнавали суттєвих індивідуальних змін вподовж 14 діб спостереження після одноразового внутрішньоочеревинного введення. При досліджені дози препарату у діапазоні від 1,58 мл/кг маси тіла тварини до 5,0 мл/кг визначено, що жодного випадку загибелі тварин не зареєстровано за внутрішньоочеревинного введення препарату у будь-якій дозі. При застосуванні препарату у дозах 2,5 мл/кг та вище у тварин проявилися клінічні ознаки інтоксикації відразу після введення препарату, що може бути пов’язано з подразненням очеревини. Через 3 доби після внутрішньоочеревинного застосування Аргоциду жодних клінічних ознак інтоксикації не спостерігали.Висновки. Аналіз отриманих даних дозволяє віднести препарат Аргоцид, розчин для інтрацистернального введення за ступенем небезпеки до відносно нешкідливих препаратів (VI клас) оскільки середня летальна доза перевищує 3,0 мл/кг маси тіла тварини за внутрішньоочеревинного введення.
ГУМКИ ЖУВАЛЬНІ ЛІКУВАЛЬНІ: ПРИЗНАЧЕННЯ, ТЕХНОЛОГІЯ І АНАЛІЗ
Authors: Koval V. M. , Denys A. I. , Hroshovyi T. A. , Vronska L. V.
Published: April 2018

Мета роботи. Аналіз і систематизація даних літератури щодо призначення і класифікації гумок жувальних лікувальних, їх технології, методів дослідження і показників якості.Матеріали і методи. У роботі використано методи інформаційного пошуку, аналізу даних літератури щодо лікарської форми – гумка жувальна лікувальна.Результати й обговорення. Гумка жувальна лікувальна є зручною системою доставки лікарського засобу і може забезпечувати високу комплаєнтність пацієнта. Для виготовлення гумки жувальної лікувальної використовують метод плавлення; метод замороження, подрібнення і таблетування; метод прямого пресування. Фармакопейними показниками якості гумок є опис, ідентифікація, середня маса, однорідність маси, однорідність вмісту, розчинення, мікробіологічна чистота, кількісне визначення. У процесі розробки складу і технології гумок набір фармако-технологічних показників і методик випробувань суттєво відрізняється від фармакопейних і включає визначення численних органолептичних властивостей, вивчення текстури інструментальними методами.Висновок. Гумка жувальна лікувальна – це мобільна система доставки ліків, яка містить один або кілька активних інгредієнтів, що вивільняються шляхом жування. Розглянуто методи та особливості технології, фармако-технологічні показники і показники якості гумок жувальних лікувальних. Дана лікарська форма має переваги порівняно з традиційними системами доставки ліків, характеризується високим комплаєнсом. Серед трьох відомих методів отримання гумок, за рахунок появи готових основ промислового виробництва, все більшого застосування набуває метод прямого пресування.
Brain Ischemia Induces Diversified Neuroantigen-Specific T-Cell Responses That Exacerbate Brain Injury
Authors: Jin Wei-Na , Gonzales Rayna , Feng Yan , Wood Kristofer , Chai Zhi , Dong Jing-Fei , La Cava Antonio , Shi Fu-Dong , Liu Qiang
Published: April 2018

Background and Purpose—

Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in the periphery or central nervous system in several neurological diseases. However, whether autoimmune responses emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that brain ischemia facilitates the genesis of autoimmunity and aggravates ischemic brain injury.

Methods—

Using a mouse strain that harbors a transgenic T-cell receptor to a central nervous system antigen, MOG
35-55
(myelin oligodendrocyte glycoprotein) epitope (2D2), we determined the anatomic location and involvement of antigen-presenting cells in the development of T-cell reactivity after brain ischemia and how T-cell reactivity impacts stroke outcome. Transient middle cerebral artery occlusion and photothrombotic stroke models were used in this study. We also quantified the presence and status of T cells from brain slices of ischemic patients.

Results—

By coupling transfer of labeled MOG
35-55
-specific (2D2) T cells with tetramer tracking, we show an expansion in reactivity of 2D2 T cells to MOG
91-108
and MOG
103-125
in transient middle cerebral artery occlusion and photothrombotic stroke models. This reactivity and T-cell activation first occur locally in the brain after ischemia. Also, microglia act as antigen-presenting cells that effectively present MOG antigens, and depletion of microglia ablates expansion of 2D2 reactive T cells. Notably, the adoptive transfer of neuroantigen-experienced 2D2 T cells exacerbates Th1/Th17 responses and brain injury. Finally, T-cell activation and MOG-specific T cells are present in the brain of patients with ischemic stroke.

Conclusions—

Our findings suggest that brain ischemia activates and diversifies T-cell responses locally, which exacerbates ischemic brain injury.
Distribution of Lacunar Infarcts in Asians With Intracerebral Hemorrhage
Authors: Tsai Hsin-Hsi , Pasi Marco , Tsai Li-Kai , Chen Ya-Fang , Lee Bo-Ching , Tang Sung-Chun , Fotiadis Panagiotis , Huang Chen-Yu , Yen Ruoh-Fang , Gurol M. Edip , Jeng Jiann-Shing
Published: April 2018

Background and Purpose—

We evaluated whether lacunes in centrum semiovale (lobar lacunes) were associated with cerebral amyloid angiopathy (CAA) markers in an Asian intracerebral hemorrhage (ICH) population.

Methods—

One hundred ten patients with primary ICH were classified as CAA-ICH (n=24; mean age, 70.9±13.9) or hypertensive ICH (n=86; mean age, 59.3±13.0) according to the presence of strictly lobar (per modified Boston criteria) or strictly deep bleeds (both ICH and cerebral microbleeds), respectively. Lacunes were evaluated in the supratentorial area and classified as lobar or classical deep based on the location. A subgroup of 36 patients also underwent Pittsburgh Compound B positron emission tomography to measure cerebral amyloid deposition and global standardized uptake value ratio were calculated.

Results—

Lobar lacunes were more frequent in CAA-ICH than hypertensive ICH (29.2 versus 11.6%;
P
=0.036). In multivariable models, lobar lacunes were associated with lobar cerebral microbleed (odds ratio, 6.8; 95% confidence interval, 1.6–29.9;
P
=0.011) after adjustment for age, sex, hypertension, and white matter hyperintensity. In 15 CAA-ICH and 21 hypertensive ICH patients with Pittsburgh Compound B positron emission tomography, correlation analyses between lobar lacune counts and global standardized uptake value ratio showed positive association (ρ=0.40;
P
=0.02) and remained significant after adjustment for age (
r
=0.34;
P
=0.04).

Conclusions—

Our findings expand on recent work showing that lobar lacunes are more frequent in CAA-ICH than hypertensive ICH. Their independent association with lobar cerebral microbleeds and brain amyloid deposition suggests a relationship with CAA even in an Asian cohort with overall higher hypertensive load.