The ideal anticoagulant should prevent ischemic complications without increasing the risk of bleeding. Controlled anticoagulation is possible with the REG1 system, an RNA aptamer pair comprising the ...direct factor IXa inhibitor RB006 and its active control agent RB007.
This phase 2a study included a roll-in group (n=2) treated with REG1 plus glycoprotein IIb/IIIa inhibitors followed by 2 groups randomized 5:1 to REG1 or unfractionated heparin. In group 1 (n=12), RB006 was partially reversed with RB007 after percutaneous coronary intervention and fully reversed 4 hours later. In group 2 (n=12), RB006 was fully reversed with RB007 immediately after percutaneous coronary intervention. Femoral sheaths were removed after complete reversal. Patients were pretreated with aspirin and clopidogrel. End points included major bleeding within 48 hours; composite of death, myocardial infarction, or urgent target vessel revascularization within 14 days; and pharmacodynamic measures. All cases were successful, with final Thrombolysis in Myocardial Infarction grade 3 flow and no angiographic thrombotic complications. There were 2 ischemic end points in the REG1 group and 1 in the unfractionated heparin group, with 1 major bleed in the unfractionated heparin group. Median activated clotting time values rose from 151 to 236 seconds after RB006. Administration of the partial RB007 dose reversed anticoagulation to an intermediate activated clotting time value of 186 seconds. Complete reversal with RB007 returned the median activated clotting time value to 144 seconds. Both reversal strategies enabled scheduled femoral sheath removal.
This study demonstrates the clinical translation of a novel platform of anticoagulation targeting factor IXa and its active reversal to percutaneous coronary intervention and provides the basis for further investigation.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00715455.
Moisture-Induced Swelling of Coal Fry, Robyn; Day, Stuart; Sakurovs, Richard
International journal of coal preparation and utilization,
12/9/2009, Letnik:
29, Številka:
6
Journal Article
Recenzirano
The gas-induced swelling behavior of coal is important when considering CO
2
sequestration into coal seams or enhanced coalbed methane applications, but coals may also swell in the presence of ...moisture, or shrink on drying. In this paper we examine the moisture-swelling properties of coals from Australia and elsewhere. Results on the moisture uptake and corresponding swelling measurements are presented for 15 coals of various ranks (sub-bituminous and bituminous) at 22°C and atmospheric pressure. Measurements were made by exposing sample blocks of coal (nominally 30 × 10 × 10 mm) to relative humidities ranging from 0% to 97%. A selection of coals was also fully saturated in water.
Moisture uptake at 97% relative humidity (RH) ranged from about 2.5% to more than 16% db. Maximum linear strain associated with the moisture sorption (measured at 97% RH) varied from about 0.2% to 1.3%, with lower rank coals showing the most swelling. In all cases, swelling was greater in the direction perpendicular to the bedding plane. These results correspond to volumetric swelling of about 0.5% to around 5%. Although exhibiting significant expansion, all of the samples returned to their original dimensions upon drying.
Volumetric moisture sorption and the amount of swelling induced were found to be strongly correlated by a single linear expression that held for all of the coals examined. It was further found that the volume of the water adsorbed was linearly related to the pore space within the coal, however, at 97% relative humidity, only about 60% of the available pore space is occupied by water. Exposure to liquid water allowed the pores to completely fill; although for the lowest rank coals, the volume of water absorbed appeared to be slightly more than the corresponding pore volume. Despite the additional water uptake, immersion in water did not produce further swelling beyond that induced at 97% relative humidity.
In eukaryotic cells, the peak of protein phosphorylation occurs during mitosis, switching the activities of a significant proportion of proteins and orchestrating a wholesale reorganization of cell ...shape and internal architecture. Most mitotic protein phosphorylation events are catalysed by a small subset of serine/threonine protein kinases. These include members of the Cdk (cyclin-dependent kinase), Plk (Polo-like kinase), Aurora, Nek (NimA-related kinase) and Bub families, as well as Haspin, Greatwall and Mps1/TTK. There has been steady progress in resolving the structural mechanisms that regulate the catalytic activities of these mitotic kinases. From structural and biochemical perspectives, kinase activation appears not as a binary process (from inactive to active), but as a series of states that exhibit varying degrees of activity. In its lowest activity state, a mitotic kinase may exhibit diverse autoinhibited or inactive conformations. Kinase activation proceeds via phosphorylation and/or association with a binding partner. These remodel the structure into an active conformation that is common to almost all protein kinases. However, all mitotic kinases of known structure have divergent features, many of which are key to understanding their specific regulatory mechanisms. Finally, mitotic kinases are an important class of drug target, and their structural characterization has facilitated the rational design of chemical inhibitors.
Record keeping within research animal care facilities is a key part of the guidelines set forth by national regulatory bodies and mandated by federal laws. Research facilities must maintain records ...of animal health issues, procedures and usage. Facilities are also required to maintain records regarding regular husbandry such as general animal checks, feeding and watering. The level of record keeping has the potential to generate excessive amounts of paper which must be retained in a fashion as to be accessible. In addition it is preferable not to retain within administrative areas any paper records which may have been in contact with animal rooms. Here, we present a flexible, simple and inexpensive process for the generation and storage of electronic animal husbandry records using smartphone technology over a WiFi or cellular network.
Summary The purpose of this investigation was to determine if a single set of strenuous squat exercise would result in an acute oxidative stress, as demonstrated previously by a single sprint. ...Thirteen resistance trained men performed one set of 15 repetitions of barbell squats using 70% of one repetition maximum and a 30 s maximal cycle sprint on two different occasions. The total work performed was calculated for each exercise bout. Heart rate, perceived exertion, blood lactate, protein carbonyls, 8-hydroxydeoxyguanosine, and malondialdehyde were measured before and within 1 min following exercise. No differences were noted between the squat and sprint tests for total work, heart rate or perceived exertion. An exercise test by time interaction was evident for blood lactate with values greater following sprinting compared to squatting ( P = 0.0005). Postexercise protein carbonyls were not different between exercise tests but were elevated above rest ( P = 0.04) by 111% and 74% following sprinting and squatting, respectively, while 8-hydroxydeoxyguanosine and malondialdehyde were relatively unaffected by either exercise test. These data indicate that a single bout of strenuous squatting and sprinting performed by resistance trained men results in elevated protein carbonyls, while having little impact on 8-hydroxydeoxyguanosine or malondialdehyde during the immediate postexercise period.
Association between sleep nocturnal breathing disorders and acute aortic syndrome (AAS) has been described but mid-term data are scarce.
We assessed the prognostic value of sleep apnea parameters and ...their relationship with aortic morphology after the onset of a type B AAS.
Between January 2010 and January 2018, sleep apnea screening in post type B AAS was prospectively performed. The association of sleep apnea parameters with aortic morphology and aortic expansion during follow-up was studied.
Over the 8-year-study period, 103 patients were included, with a mean age of 57.8 ± 12.1 years old. Median follow-up was 25.0 months (11.0-51.0). Thirty-two patients (31%) required aortic stenting during the acute phase. In patients treated by aortic stenting, the descending thoracic aortic diameter was positively associated with a higher percentage of nocturnal time of saturation ≤ 90% after adjustment (p = 0.016). During follow-up, the nocturnal time of saturation ≤ 90% in patients treated by medical therapy was the only parameter associated with significant aortic expansion rate (r = 0.26, p = 0.04). Thirty-eight patients started and sustained nocturnal ventilation during follow-up. The association between aortic expansion rate and nocturnal time of saturation ≤ 90% did not persist during follow-up after adjustment on nocturnal ventilation initiation (r = 0.25, p = 0.056).
Nocturnal hypoxemia parameters are positively associated with the max onset aortic diameter and significant aortic growth after type B AAS. Nocturnal ventilation seems to mitigate aortic expansion during follow-up.
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Novel (non-fluoroquinolone) inhibitors of bacterial type II topoisomerases (NBTIs) are an emerging class of antibacterial agents. We report an optimized series of ...cyclobutylaryl-substituted NBTIs. Compound 14 demonstrated excellent activity both in vitro (S. aureus MIC90=0.125μg/mL) and in vivo (systemic and tissue infections). Enhanced inhibition of Topoisomerase IV correlated with improved activity in S. aureus strains with mutations conferring resistance to NBTIs. Compound 14 also displayed an improved hERG IC50 of 85.9μM and a favorable profile in the anesthetized guinea pig model.
In 2009, a novel influenza virus (2009 pandemic influenza A (H1N1) virus (pH1N1)) caused significant disease in the United States. Most states, including Florida, experienced a large fall wave of ...disease from September through November, after which disease activity decreased substantially. We determined the prevalence of antibodies due to the pH1N1 virus in Florida after influenza activity had peaked and estimated the proportion of the population infected with pH1N1 virus during the pandemic.
During November-December 2009, we collected leftover serum from a blood bank, a pediatric children's hospital and a pediatric outpatient clinic in Tampa Bay Florida. Serum was tested for pH1N1 virus antibodies using the hemagglutination-inhibition (HI) assay. HI titers ≥40 were considered seropositive. We adjusted seroprevalence results to account for previously established HI assay specificity and sensitivity and employed a simple statistical model to estimate the proportion of seropositivity due to pH1N1 virus infection and vaccination.
During the study time period, the overall seroprevalence in Tampa Bay, Florida was 25%, increasing to 30% after adjusting for HI assay sensitivity and specificity. We estimated that 5.9% of the population had vaccine-induced seropositivity while 25% had seropositivity secondary to pH1N1 virus infection. The highest cumulative incidence of pH1N1 virus infection was among children aged 5-17 years (53%) and young adults aged 18-24 years (47%), while adults aged ≥50 years had the lowest cumulative incidence (11-13%) of pH1N1 virus infection.
After the peak of the fall wave of the pandemic, an estimated one quarter of the Tampa Bay population had been infected with the pH1N1 virus. Consistent with epidemiologic trends observed during the pandemic, the highest burdens of disease were among school-aged children and young adults.
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