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In situself-ion irradiations (150 keV W+) have been carried out on W and W–5Re at 500 °C, with doses ranging from 1016to 1018W+m−2(∼1.0 dpa). Early damage formation (1016W+m−2) was observed in both materials. Black–white contrast experiments and image simulations using the TEMACI software suggested that vacancy loops were formed within individual cascades, and thus, the loop nucleation mechanism is likely to be ‘cascade collapse’. Dynamic observations showed the nucleation and growth of interstitial loops at higher doses, and that elastic loop interactions may involve changes in loop Burgers vector. Elastic interactions may also promote loop reactions such as absorption or coalescence or loop string formation. Loops in both W and W–5Re remained stable after annealing at 500 °C. One-dimensional hopping of loops (b = 1/2 ⟨111>) was only seen in W. At the final dose (1018W+m−2), a slightly denser damage microstructure was seen in W–5Re. Both materials had about 3–4 × 1015loops m−2. Detailed post-irradiation analyses were carried out for loops of size ⩾ 4 nm. Bothb = 1/2 ⟨111⟩ (∼75%) andb = ⟨100> (∼25%) loops were present. Inside–outside contrast experiments were performed under safe orientations to determine the nature of loops. The interstitial-to-vacancy loop ratio turned out close to unity for 1/2 ⟨111⟩ loops in W, and for both 1/2 ⟨111⟩ and ⟨100⟩ loops in W–5Re. However, interstitial loops were dominant for ⟨100⟩ loops in W. Re seemed to restrict loop mobility, leading to a smaller average loop size and a higher number density in the W-Re alloy. [ABSTRACT FROM AUTHOR]

Edgar Marin,1–3 Maria Isabel Briceño,2 Catherina Caballero-George11Unit of Pharmacology, Center of Biodiversity and Drug Discovery, Institute of Scientific Research and High Technology Services, 2Nano Dispersions Technology, Panama, Republic of Panama; 3Department of Biotechnology, Archaria Nagarjuna University, Guntur, IndiaAbstract: Use of biodegradable polymers for biomedical applications has increased in recent decades due to their biocompatibility, biodegradability, flexibility, and minimal side effects. Applications of these materials include creation of skin, blood vessels, cartilage scaffolds, and nanosystems for drug delivery. These biodegradable polymeric nanoparticles enhance properties such as bioavailability and stability, and provide controlled release of bioactive compounds. This review evaluates the classification, synthesis, degradation mechanisms, and biological applications of the biodegradable polymers currently being studied as drug delivery carriers. In addition, the use of nanosystems to solve current drug delivery problems are reviewed.Keywords: biodegradable polymers, nanoparticles, drug delivery, cellular uptake, biomedical applications

The sustainability has to go through social, political, economic, technological and educational challenges that would take any program beyond a specific action to achieve it. The aim of this study was to examine the sustainability perception of the participants during the activities conducted by Área Educada, a metropolitan program of Valle de Aburrá, Antioquia Colombia. It managed to hit 180,000 citizens and made inquiries about the perception of 260 students and 100 teachers. Here is shown two examples of how to work sustainability into the classroom with teachers and students. We conclude that the stakeholders in our strategies recognize that sustainability is related to environmental elements and economic development. However, the human aspect is highly favored by the students compared with teachers.

Aims: Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) are at increased risk of atherothrombotic events. Ticagrelor reduces ischaemic events compared to clopidogrel, with the greatest risk reduction in patients with both DM and CKD. How CKD status affects the pharmacodynamic (PD) and pharmacokinetic (PK) profiles of different ticagrelor maintenance dose regimens in patients with DM is unknown., Methods and Results: In this randomized, crossover study, patients with DM on treatment with dual antiplatelet therapy (aspirin and clopidogrel) were stratified according to CKD status and randomized to ticagrelor 90 or 60 mg bid. PK/PD assessments were performed at baseline, after 7-10 days of ticagrelor (peak and trough), and after 7-10 days of alternative ticagrelor regimen (peak and trough). PK assessments included plasma concentrations of ticagrelor and its major metabolite. PD assessments included vasodilator-stimulated phosphoprotein (VASP)-platelet reactivity index (PRI), VerifyNow P2Y12, and light transmittance aggregometry (LTA). A total of 92 patients with DM (CKD, n = 44; non-CKD, n = 48) were randomized. Levels of platelet reactivity were lower with the 90 mg compared with the 60 mg ticagrelor dose, which was statistically significant in non-CKD but not in CKD patients for most PD measures. There were no significant differences in the primary endpoint (trough levels of VASP-PRI following ticagrelor 90 mg dosing) between cohorts (31 ± 20 vs. 25 ± 14; P = 0.105). VerifyNow and LTA provided similar findings. PK assessments tracked PD profiles showing increased plasma concentrations of ticagrelor and its major metabolite in CKD compared to non-CKD patients., Conclusion: In patients with DM, although ticagrelor maintenance dose regimens (60 and 90 mg) yield potent P2Y12 inhibition, levels of platelet reactivity tended to be higher and subject to broader variability in non-CKD compared with CKD patients., Clinical Trial Registration: http://www.clinicaltrials.gov Unique Identifier: NCT02539160., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Small pore zeolites have shown great potential in a number of catalytic reactions. While Mo-containing medium pore zeolites have been widely studied for methane dehydroaromatisation (MDA), the use of small pore supports has drawn limited attention due to the fast deactivation of the catalyst. This work investigates the structure of the small pore Mo/H-SSZ-13 during catalyst preparation and reaction by operando X-ray absorption spectroscopy (XAS), in situ synchrotron powder diffraction (SPD), and electron microscopy; then, the results are compared with the medium pore Mo/H-ZSM-5. While SPD suggests that during catalyst preparation, part of the MoO x anchors inside the pores, Mo dispersion and subsequent ion exchange was less effective in the small pore catalyst, resulting in the formation of mesopores and Al 2 (M O O 4 ) 3 particles. Unlike Mo/H-ZSM-5, part of the Mo species in Mo/H-SSZ-13 undergoes full reduction to Mo 0 during MDA, whereas characterisation of the spent catalyst indicates that differences also exist in the nature of the formed carbon deposits. Hence, the different Mo speciation and the low performance on small pore zeolites can be attributed to mesopores formation during calcination and the ineffective ion exchange into well dispersed Mo-oxo sites. The results open the scope for the optimisation of synthetic routes to explore the potential of small pore topologies.

Background Vorapaxar as an adjunct to dual antiplatelet therapy (DAPT) reduces thrombotic events in patients with prior myocardial infarction at the expense of increased bleeding. Withdrawal of aspirin has emerged as a bleeding reduction strategy. The pharmacodynamic effects of vorapaxar with potent P2Y 12 inhibitors as well as the impact of dropping aspirin is unexplored and represented the aim of the VORA-PRATIC (Vorapaxar Therapy in Patients With Prior Myocardial Infarction Treated With Newer Generation P2Y 12 Receptor Inhibitors Prasugrel and Ticagrelor) study. Methods and Results Post-myocardial infarction patients (n=130) on standard DAPT (aspirin+prasugrel or ticagrelor) were randomized to 1 of 3 arms: (1) triple therapy: aspirin+prasugrel/ticagrelor+vorapaxar; (2) dual therapy (drop aspirin): prasugrel/ticagrelor+vorapaxar; (3) DAPT: aspirin+prasugrel/ticagrelor. Pharmacodynamic assessments were performed at 3 time points (baseline and 7 and 30 days). Vorapaxar reduced CAT (collagen-ADP-TRAP)-induced platelet aggregation, a marker of platelet-mediated global thrombogenicity (triple therapy versus DAPT at 30 days: mean difference=-27; 95% CI,-35 to -19; P <0.001; primary end point). This effect was attenuated but still significant in the absence of aspirin (dual therapy versus DAPT at 30 days: mean difference=-15; 95% CI,-23 to -7; P <0.001; between-group comparisons, P <0.05). Vorapaxar abolished TRAP-induced aggregation ( P <0.001), without affecting thrombin generation and clot strength. There were no differences in markers of P2Y 12 reactivity. Markers sensitive to aspirin-induced effects increased ( P <0.001) in the dual-therapy arm. Conclusions In post-myocardial infarction patients treated with potent P2Y 12 inhibitors, vorapaxar reduces platelet-driven global thrombogenicity, an effect that persisted, albeit attenuated, in the absence of aspirin and without affecting markers of P2Y 12 reactivity or clot kinetics. The clinical implications of these PD observations warrant future investigation. Registration URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT02545933.

The feasibility of rapid genetic testing in patients undergoing percutaneous coronary intervention (PCI) and the comparison of the pharmacodynamic effects of prasugrel versus ticagrelor among carriers of cytochrome P450 2C19 loss-of-function alleles treated with PCI has been poorly explored. Rapid genetic testing using the Spartan assay was shown to be feasible and provides results in a timely fashion in a real-world setting of patients undergoing coronary angiography (n = 781). Among patients (n = 223, 28.5%), carriers of at least 1 loss-of-function allele treated with PCI (n = 65), prasugrel, and ticagrelor achieve similar levels of platelet inhibition. (A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients Undergoing PCI With CYP2C19 Loss-of-function [NCT02065479])., (© 2020 The Authors.)

In patients requiring dual antiplatelet therapy (DAPT) who also have an indication to be treated with oral anticoagulant (OAC) drugs, aspirin withdrawal reduces the risk of bleeding. There is limited data on the pharmacodynamic effects associated with adding a nonvitamin K antagonist OAC on a background of aspirin and a P2Y 12 inhibitor as well as dropping aspirin. Seventy-five patients on DAPT (aspirin plus clopidogrel) were randomized to DAPT plus high-dose edoxaban (60 mg once daily, Group A), DAPT plus low-dose edoxaban (30 mg once daily, Group B), or DAPT only (Group C) for 10 ± 2 days (Phase I). Afterwards, Groups A and B interrupted aspirin and maintained clopidogrel plus edoxaban for 10 ± 2 days, while patients in Group C maintained DAPT (Phase II). Platelet aggregation and clot kinetics were assessed at baseline, end of Phase I, and end of Phase II using thrombelastography (TEG), light transmittance aggregometry (LTA), VerifyNow P2Y 12 , and serum thromboxane-B 2 . The primary endpoint was the comparison of maximum amplitude (MA) measured by TEG, a measure of clot strength, between patients on DAPT plus high-dose edoxaban and patients on DAPT only. Edoxaban prolonged in a dose-dependent manner speed of thrombin generation (TEG R; Group A: 7.7 [6.8-8.7] vs. Group B: 7.4 [6.4-8.5] vs. Group C: 6.3 [5.7-7.0]; p  = 0.05) but did not affect other markers of clot kinetics, including TEG MA (Group A: 63 [61-64] vs. Group B: 65 [63-67] vs. Group C: 64 [63-65]; p  = 0.10). After aspirin discontinuation, platelet reactivity assessed by LTA using thrombin receptor activating peptide as agonist increased to a greater extent with low-dose edoxaban. Stopping aspirin did not affect markers of P2Y 12 reactivity and had no or marginal effects on clot kinetics, but increased markers sensitive to cyclooxygenase-1 blockade., Competing Interests: F.F. declares that he has received consulting fees or honoraria from AstraZeneca and Sanofi.F.R. declares that she has received consulting fees or honoraria from Chiesi. D.J.A. declares that he has received consulting fees or honoraria from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company and has received payments for participation in review activities from CeloNova and St Jude Medical. He also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, and Renal Guard Solutions. The rest of the authors have nothing to disclose., (Georg Thieme Verlag KG Stuttgart · New York.)

Vorapaxar reduces thrombotic cardiovascular events at the expense of increased bleeding. However, the differential pharmacodynamic (PD) effects of vorapaxar according to diabetes mellitus (DM) status are unknown. Moreover, although withdrawal of aspirin has emerged as a bleeding reduction strategy, the PD effects of stopping aspirin in patients treated with vorapaxar also are unknown. In this prospective PD investigation, vorapaxar was associated with reduced platelet-mediated thrombogenicity without affecting clot kinetics irrespective of DM status. However, platelet-mediated thrombogenicity increased after aspirin withdrawal, particularly among patients with DM. (Optimizing anti-Platelet Therapy In diabetes MellitUS-5 Study [OPTIMUS-5]; NCT02548650)., (© 2019 The Authors.)

Background: The platelet inhibitory effects induced by oral P2Y 12 receptor antagonists are delayed in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (P-PCI). In turn, this leads to a gap in platelet inhibition, exposing patients to an increased risk of early thrombotic complications and underscoring the need to define strategies associated with more effective platelet inhibition in the peri-primary percutaneous coronary intervention period. Cangrelor is an intravenous P2Y 12 inhibitor with prompt and potent antiplatelet effects. However, to date, there are limited data on the effects of cangrelor used in combination with ticagrelor in patients undergoing primary percutaneous coronary intervention. Moreover, questions have emerged on the potential for drug-drug interactions during the transition from cangrelor to oral P2Y 12 inhibitors., Methods: This was a prospective, randomized, double-blind, placebo-controlled pharmacodynamic study conducted in patients undergoing primary percutaneous coronary intervention (n=50) who were randomized to treatment with either cangrelor or matching placebo (bolus followed by 2-hour infusion). All patients received ticagrelor 180-mg loading dose administered as crushed tablets at the time of cangrelor/placebo bolus administration. Pharmacodynamic analyses were performed at 8 time points. Pharmacodynamic effects were measured as P2Y 12 reaction units by VerifyNow and platelet reactivity index by vasodilator-stimulated phosphoprotein., Results: Compared with placebo, cangrelor was associated with reduced P2Y 12 reaction units as early as 5 minutes after bolus, which persisted during the entire duration of drug infusion, including at 30 minutes (63 [32-93] versus 214 [183-245]; mean difference, 152 [95% CI, 108-195]; P<0·001; primary end point). Parallel findings were shown with platelet reactivity index. Accordingly, high on-treatment platelet reactivity rates were reduced with cangrelor. After discontinuation of cangrelor/placebo infusion, there were no differences in levels of platelet reactivity between groups, ruling out a drug-drug interaction when cangrelor and ticagrelor are concomitantly administered., Conclusions: In patients undergoing primary percutaneous coronary intervention, cangrelor is an effective strategy to bridge the gap in platelet inhibition associated with the use of oral P2Y 12 inhibition induced by ticagrelor. Ticagrelor can be administered as a crushed formulation concomitantly with cangrelor without any apparent drug-drug interaction. The clinical implications of these pharmacodynamic findings warrant investigation in an adequately powered clinical trial., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03247738.

Background: Switching between different classes of P2Y 12 inhibitors, including de-escalation from ticagrelor to clopidogrel, commonly occurs in clinical practice. However, the pharmacodynamic profiles of this strategy have been poorly explored., Methods: This was a prospective, randomized, open-label study conducted in patients on maintenance dosing (MD) of aspirin (81 mg/d) and clopidogrel (75 mg/d). After a 7-day run-in with ticagrelor (180 mg loading dose [LD] followed by 90 mg twice daily MD), patients (n=80) were randomized into 1 of 4 groups: group A, clopidogrel 600 mg LD 24 hours after the last MD of ticagrelor (C-600 mg-24h); group B, clopidogrel 600 mg LD 12 hours after the last MD of ticagrelor (C-600 mg-12h); group C, clopidogrel 75 mg/d MD 24 hours after the last MD of ticagrelor (C-75 mg-24h); and group D, ticagrelor 90 mg twice daily MD (T-90 mg twice daily). MD of the randomized treatment was maintained for 10±3 days. Pharmacodynamic assessments were performed at baseline, after run-in, and at 2, 24, 48, and 72 hours and 10 days with P2Y 12 reaction units by VerifyNow; platelet reactivity index was assessed by vasodilator-stimulated phosphoprotein; and maximal platelet aggregation was determined by light transmittance aggregometry., Results: T-90 mg twice daily led to lower platelet reactivity than any clopidogrel regimen using all assays at all time points. P2Y 12 reaction unit levels were similar between the C-600 mg-24h (group A) and the C-75 mg-24h (group C) ( P =0.29), including at 48 hours (primary end point; least mean difference, -6.9; 95% confidence interval, -38.1 to 24.3; P =0.66). P2Y 12 reaction unit levels were lower with C-600 mg-12h (group B) than with C-75 mg-24h (group C; P =0.024). Maximal platelet aggregation over time was lower with both C-600 mg-24h (group A; P =0.041) and C-600 mg-12h (group B; P =0.028) compared with C-75 mg-24h (group C). Platelet reactivity index profiles paralleled those observed with P2Y 12 reaction units. There were no pharmacodynamic differences for all tests between C-600 mg-24h (group A) and C-600 mg-12h (group B). In group C (C-75 mg-24h), platelet reactivity increased compared with baseline as early as 24 hours, reaching statistical significance at 48 and 72 hours and up to 10 days. These pharmacodynamic findings were delayed and blunted in magnitude with the administration of an LD, regardless of the timing of administration., Conclusions: De-escalation from ticagrelor to clopidogrel therapy is associated with an increase in platelet reactivity. The use of an LD before the initiation of an MD regimen of clopidogrel mitigates these observations, although this is not affected by the timing of its administration after ticagrelor discontinuation., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02287909., (© 2018 American Heart Association, Inc.)

Objectives: To determine the most common clinical conditions associated with older adults visiting Urgent care centers (UCCs) and the potential need for further resource use., Design: Cross-sectional retrospective study., Setting: Nonprofit academic medical center with campuses and multiple satellite offices in Ohio and Florida., Participants: Individuals aged 55 and older who visited UCCs between August 2014 and March 2015 (N = 9,445; average age 63.1 ± 10.1, 64% female). Of those, 2,445 had at least one encounter within the same healthcare system within 30 days after the index visit and were included in our final analysis., Measurements: 30-day ED visits and hospitalizations., Results: Of the 2,445 patients, 578 (23.6%) visited the emergency department (ED) or were hospitalized, 974 (39.8%) returned to the UCC, and 895 (63.4%) visited their primary care physician's office. A significantly higher proportion (38.4%, n = 68/177) of individuals aged 85 and older visited the ED or were hospitalized within 30 days (P < .010) than of those younger than 65 (20.0%, n = 273/1,367). Diabetes mellitus (odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.40-2.15, P < .001), coronary artery disease or cerebrovascular disease (OR = 2.45 CI 1.95-3.09, P < .001), chronic obstructive pulmonary disorder or asthma (OR = 1.57, 95% CI = 1.23-2.01, P < .001), polypharmacy (OR = 1.45, 95% CI = 1.18-1.78, P = .004), and cognitive impairment (OR = 2.74, 95% CI = 1.74-4.31, P < .010) were associated with higher rates of ED visits or hospitalizations within 30 days of the UCC visit., Conclusion: Older adults (especially those aged ≥85) and those with conditions such as polypharmacy and dementia are at higher risk of being hospitalized or visit the ED after seeking care at UCCs than younger adults and those without these conditions., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

In situ straining experiments conducted in a transmission electron microscope have been performed to reveal how dislocations interact with and annihilate isolated stacking-fault tetrahedra, common defect clusters in irradiated face-centered cubic metals. Comparison of the experimental results with the predictions from molecular dynamics computer simulations shows some similarities and some striking differences. The comparison suggests challenges for the simulations and demonstrates how, despite the disparity in operational parameters, the simulations can be used to interpret experimental results., ((c) 2009 Wiley-Liss, Inc.)

Immunoprophylaxis using intravenous (IV) hepatitis B immune globulin (HBIG) decreases the recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). However, IV HBIG is expensive, has significant side effects, and is inconvenient to administer. An alternative approach for prophylaxis using intramuscular (IM) HBIG and oral lamivudine was prospectively evaluated in this study. Ten consecutive patients with cirrhosis with HBV infection who underwent OLT were included in this study. Nine of 10 patients received lamivudine, 150 mg/d, for an average duration of 8.6 months before OLT. Two of 10 patients with detectable HBV DNA at the time of OLT received 10,000 U (45 mL) of IV HBIG daily for 7 consecutive days, followed by 5 mL of IM HBIG weekly for the next 3 weeks, then every 3 weeks. The other 8 patients were HBV DNA negative at OLT and received one dose of IV HBIG (45 mL) during surgery, followed by 5 mL of IM HBIG weekly for 4 weeks, then every 3 weeks. All patients received lamivudine, 150 mg/d, after OLT. During a mean follow-up of 15.6 months, 9 of 10 patients achieved a protective hepatitis B surface antibody (HBsAb) titer greater than 200 IU/L and had no evidence of HBV recurrence. One patient failed to develop an adequate HBsAb titer and developed histological and virological evidence of recurrence. One patient died unrelated to HBV recurrence. Our preliminary data suggest that this combination prophylaxis with IM HBIG and lamivudine is effective and potentially cost saving.

This report details the clinical experience of 150 patients with rhabdomyosarcomas treated by one group of surgeons. Of the 150 patients, 103 suffered from pleomorphic rhabdomyosarcomas, 40 patients had embryonal rhabdomyosarcomas, and 7 had alveolar cell type of rhabdomyosarcoma. The males suffered almost twice as much as the females from this form of cancer (96 males to 54 females). The fifth decade had the highest incidence of all rhabdomyosarcomas. The younger patients generally suffered from embryonal rhabdomyosarcomas and the older ones from pleomorphic rhabdomyosarcomas, although age was no barrier to the occurrence of embryonal rhabdomyosarcomas in some of the older patients and pleomorphic rhabdomyosarcomas in some of the younger patients. Caucasians were almost exclusively afflicted by this form of cancer (93% of this series). The lower extremity was the most frequent site of the lesion, occurring in 50.7% of the 150 cases. The upper extremity was the second most frequently involved site (28%), and the trunk was the least involved site (21.3%). Of the 150 patients studied, 40 were considered indeterminate. Thirteen patients are alive and free of cancer, but were treated less than 5 years ago; 12 patients reported for consultation only. There were 13 who were free of sarcomas at periods in excess of 2 years but were lost to follow-up. Two patients in this series died before the 5-year period, and autopsy revealed the death to be due to causes other than the rhabdomyosarcoma. Of the 110 determinate patients, 75 (68%) died as a result of the cancer. The 5-year survival rate equals 32%. The fact of the 30% 5-year survival after treatment for recurrences should help dismiss the pessimism which prevails once a recurrence is noted subsequent to major therapy. Age per se had no great effect on prognosis. The poorest results occurred in the 11-20 age range, with a 5-year survival of 15%. This value reflects on increased incidence of embryonal rhabdomyosarcomas which tend to be more malignant and metastasize earlier than do the pleomorphic type. The effect of location upon survival revealed that of 76 patients with involvement of the lower extremity, 34% survived 5 years or longer, and those with sarcomas of the trunk had the poorest survival (26%). The fact that the trunk, by virtue of its anatomy, limits the degree of surgery that can be perfomred, probably helps to explain this difference. The role of radiation therapy and chemotherapy awaits elucidation. Reports of combined surgery, radiation therapy, and chemotherapy are encouraging.

The liver extended a minimum of 5 cm inferior to the right costal margin in 51% of the 504 patients studied. In 53% of these patients, experienced, mature physicians declared that the liver was not palpable on physical examination. In 3% of the cases, a mass was palpated which was believed to be liver by the examining physician but was found to be extrahepatic upon scanning and laparotomy. The unreliability of physical examination in determining whether or not the liver extends inferior to the costal margin in many instances is demonstrated.