Aspirin Dosing for the Prevention and Treatment of Ischemic Stroke: An Indication-Specific Review of the Literature

OBJECTIVE: To evaluate the efficacy of aspirin for the treatment and prevention of ischemic stroke and identify the minimum dose proven to be effective for each indication. DATA SOURCES: PubMed and MEDLINE searches (January 2009–January 2010) were performed to identify primary literature, using search terms including aspirin, stroke prevention, acute ischemic stroke, acetylsalicylic acid, atrial fibrillation, myocardial infarction, and carotid endarterectomy. Additionally, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles published in English were evaluated and relevant primary literature evaluating the efficacy of aspirin in the prevention of stroke was included in this review. DATA SYNTHESIS: Antiplatelet therapy is the benchmark for the prevention of ischemic stroke. Aspirin has been proven to prevent ischemic stroke in a variety of settings. Despite the frequency at which aspirin continues to be prescribed in patients at risk of ischemic stroke, there remains confusion in clinical practice as to what minimum dose is required in various at-risk patients. A thorough review of the primary literature suggests that low-dose (50–81 mg daily) aspirin is insufficient for some indications. Acute ischemic stroke treatment requires 160–325 mg, while atrial fibrillation and carotid arterial disease require daily doses of 325 and 81–325 mg, respectively. CONCLUSIONS: Available evidence suggests that aspirin dosing must be individualized according to indication. Recommendations provided by national guidelines at times recommend lower doses of aspirin than have been proven effective. Higher doses are indicated for stroke prevention in atrial fibrillation (325mg) and acute ischemic stroke patients (160–325 mg). Aspirin has not yet been proven effective for primary prevention of strokes in men, and a minimum dose for these patients cannot be determined from the available data

Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites

Protozoan infections are a serious global health problem1, 2. Natural killer (NK) cells and cytolytic T lymphocytes (CTLs) eliminate pathogen-infected cells by releasing cytolytic granule contents—granzyme (Gzm) proteases and the pore-forming perforin (PFN)—into the infected cell3. However, these cytotoxic molecules do not kill intracellular parasites. CD8+ CTLs protect against parasite infections in mice primarily by secreting interferon (IFN)-γ4, 5, 6, 7, 8, 9, 10. However, human, but not rodent, cytotoxic granules contain the antimicrobial peptide granulysin (GNLY), which selectively destroys cholesterol-poor microbial membranes11, 12, 13, 14, and GNLY, PFN and Gzms rapidly kill intracellular bacteria15. Here we show that GNLY delivers Gzms into three protozoan parasites (Trypanosoma cruzi, Toxoplasma gondii and Leishmania major), in which the Gzms generate superoxide and inactivate oxidative defense enzymes to kill the parasite. PFN delivers GNLY and Gzms into infected cells, and GNLY then delivers Gzms to the intracellular parasites. Killer cell–mediated parasite death, which we term 'microbe-programmed cell death' or 'microptosis', is caspase independent but resembles mammalian apoptosis, causing mitochondrial swelling, transmembrane potential dissipation, membrane blebbing, phosphatidylserine exposure, DNA damage and chromatin condensation. GNLY-transgenic mice are protected against infection by T. cruzi and T. gondii, and survive infections that are lethal to wild-type mice. Thus, GNLY-, PFN- and Gzm-mediated elimination of intracellular protozoan parasites is an unappreciated immune defense mechanism

Thermodynamic properties of binary HCP solution phases from special quasirandom structures

Three different special quasirandom structures (SQS) of the substitutional hcp $A_{1-x}B_x$ binary random solutions ($x=0.25$, 0.5, and 0.75) are presented. These structures are able to mimic the most important pair and multi-site correlation functions corresponding to perfectly random hcp solutions at those compositions. Due to the relatively small size of the generated structures, they can be used to calculate the properties of random hcp alloys via first-principles methods. The structures are relaxed in order to find their lowest energy configurations at each composition. In some cases, it was found that full relaxation resulted in complete loss of their parental symmetry as hcp so geometry optimizations in which no local relaxations are allowed were also performed. In general, the first-principles results for the seven binary systems (Cd-Mg, Mg-Zr, Al-Mg, Mo-Ru, Hf-Ti, Hf-Zr, and Ti-Zr) show good agreement with both formation enthalpy and lattice parameters measurements from experiments. It is concluded that the SQS's presented in this work can be widely used to study the behavior of random hcp solutions.Comment: 15 pages, 8 figure

Relationship between casting modulus and grain size in cast A356 aluminium alloys

Microstructure of Al-Si alloy castings depends most generally on melt preparation and on the cooling rate imposed by the thermal modulus of the component. In the case of Al-Si alloys, emphasis is put during melt preparation on refinement of pro-eutectic (Al) grains and on modification of the Al-Si eutectic. Thermal analysis has been used since long to check melt preparation before casting, i.e. by analysis of the cooling curve during solidification of a sample cast in an instrumented cup. The conclusions drawn from such analysis are however valid for the particular cooling conditions of the cups. It thus appeared of interest to investigate how these conclusions could extrapolate to predict microstructure in complicated cast parts showing local changes in the solidification conditions. For that purpose, thermal analysis cups and instrumented sand and die castings with different thermal moduli and thus cooling rates have been made, and the whole set of cooling curves thus recorded has been analysed. A statistical analysis of the characteristic features of the cooling curves related to grain refinement in sand and die castings allowed determining the most significant parameters and expressing the cube of grain size as a polynomial of these parameters. After introduction of a further parameter quantifying melt refining an excellent correlation, with a R2 factor of 0.99 was obtained

Assessment techniques, database design and software facilities for thermodynamics and diffusion

The purpose of this article is to give a set of recommendations to producers of assessed thermodynamic data, who may be involved in either the critical evaluation of limited chemical systems or the creation and dissemination of larger thermodynamic databases. Also, it is hoped that reviewers and editors of scientific publications in this field will find some of the information useful. Good practice in the assessment process is essential, particularly as datasets from many different sources may be combined together into a single database. With this in mind, we highlight some problems that can arise during the assessment process and we propose a quality assurance procedure. It is worth mentioning at this point, that the provision of reliable assessed thermodynamic data relies heavily on the availability of high quality experimental information. The different software packages for thermodynamics and diffusion are described here only briefly

The Effect of Regional Analgesia on Vascular Tone in Hip Arthroplasty Patients

Background: While it is assumed that neuraxial analgesia and pain management may beneficially influence perioperative hemodynamics, few studies provided data quantifying such effects and none have assessed the potential contribution of the addition of a nerve block. Questions/purposes: This clinical trial compared the visual analog scale (VAS) scores and measurement of arterial tone using augmentation index of patients who received combined spinal-epidural (CSE) only to patients who received both CSE and lumbar plexus block. Methods: After obtaining written consent, 92 patients undergoing total hip arthroplasty were randomized to receive either CSE or CSE with lumbar plexus block (LPB). Perioperative pain and arterial tone were measured using VAS scores and augmentation index (AI) respectively, at baseline and at various times postoperatively. Results: After the exclusion of 2 patients, 44 patients received CSE alone and 46 patients received CSE and LPB. Patient demographics and perioperative characteristics were similar in both groups. AI continuously decreased after placement of a CSE with or without LBP, beyond full resolution of neuraxial and peripheral blockade. Although the LPB group demonstrated a statistically significant reduction of VAS pain scores in the postanesthesia care unit (PACU; P \u3c 0.05), overall, the addition of a LPB did not significantly reduce the AI when compared to the control group. Conclusion: The addition of a LPB provided better pain control in the PACU but did not reduce the AI, compared to the control group. We conclude that the addition of a LPB may have limited ability to affect arterial tone in the presence of a continuous infusion of epidural analgesics. In summary, the addition of a LPB in patients undergoing total hip arthroplasty is clinically effective and provided better pain control, especially in the immediate postoperative period. The continuous decrease on the AI in both groups beyond the full resolution of the neuroaxial and LPB will require further studies

Microscopic View on Short-Range Wetting at the Free Surface of the Binary Metallic Liquid Gallium-Bismuth: An X-ray Reflectivity and Square Gradient Theory Study

We present an x-ray reflectivity study of wetting at the free surface of the binary liquid metal gallium-bismuth (Ga-Bi) in the region where the bulk phase separates into Bi-rich and Ga-rich liquid phases. The measurements reveal the evolution of the microscopic structure of wetting films of the Bi-rich, low-surface-tension phase along different paths in the bulk phase diagram. A balance between the surface potential preferring the Bi-rich phase and the gravitational potential which favors the Ga-rich phase at the surface pins the interface of the two demixed liquid metallic phases close to the free surface. This enables us to resolve it on an Angstrom level and to apply a mean-field, square gradient model extended by thermally activated capillary waves as dominant thermal fluctuations. The sole free parameter of the gradient model, i.e. the so-called influence parameter, $\kappa$, is determined from our measurements. Relying on a calculation of the liquid/liquid interfacial tension that makes it possible to distinguish between intrinsic and capillary wave contributions to the interfacial structure we estimate that fluctuations affect the observed short-range, complete wetting phenomena only marginally. A critical wetting transition that should be sensitive to thermal fluctuations seems to be absent in this binary metallic alloy.Comment: RevTex4, twocolumn, 15 pages, 10 figure

What Is Gender Dysphoria? A Critical Systematic Narrative Review

In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, the American Psychiatric Association has changed the diagnosis of gender identity disorder to gender dysphoria (GD). In this critical narrative review we ask: What is gender dysphoria? We report on some of the inconsistencies in the articles that foreground distress while obfuscating the fact that not all trans and intersex people suffer stress or impaired functioning, and the inappropriate referencing to intersex people in the diagnostic criterion, claims about the GD diagnosis contributing to the depathologization of and reducing stigma surrounding trans people, the conceptualizations of “gender dysphoric” research subjects, and finally we question the etiological approaches using GD as a conceptual framework. We further suggest that there are a number of methodological issues that need to be resolved to be able to claim that the GD diagnosis can be validated. To shed light on these paradoxes and methodological issues in the DSM-5, we report on the content validity of GD by reviewing research articles postdiagnostic inception. These findings will contribute to the debate about the validity of GD as a diagnosis for the 21st century for those people who need to live a different gender to that assigned at birth

Best practice model for outpatient psychiatric pharmacy practice, part 2: Confirmation of the attribute statements

Introduction: The American Association of Psychiatric Pharmacists (AAPP) used multiple modalities to develop and refine 28 attribute statements to describe a best practice model for outpatient psychiatric pharmacists. Before addressing implementation, assessment, and field testing, it was necessary to finalize and confirm the statements and their supporting narratives among stakeholders. The objective of this project was to confirm the attribute statements and supporting justifications for a best practice model for outpatient psychiatric pharmacists providing direct patient care. Methods: The 4 phases that resulted in the 28 attribute statements and supporting narratives have been described and published elsewhere. As part of phase 5, the confirmation survey was distributed to pharmacists and resident members of AAPP in November 2021 for 3 weeks. Results: The survey respondents (n = 74; 6.1%) were licensed pharmacists for an average of 15.6 years (SD = 12.0) and had been practicing as psychiatric pharmacists for an average of 11.3 years (SD = 10.4). Slightly more than half (54.2%) of the respondents reported practicing in the outpatient setting and three-fourths (74.3%) were Board Certified Psychiatric Pharmacists. For each of the 28 statements, more than 90% of respondents either agreed or agreed with minimal reservations. Discussion: Given the high degree of agreement on the proposed practice model statements, they will be used as the basis for the outpatient psychiatric pharmacist best practice model. Next steps in developing this model include establishing implementation guidance, determining appropriate metrics for evaluation of these statements in practice, and establishing appropriate field-testing methods

Best practice model for outpatient psychiatric pharmacy practice, part 1: Development of initial attribute statements

Introduction: A 2019 survey identified significant variability of practice characteristics among outpatient psychiatric pharmacists (OPPs). No published model establishes which attributes constitute best practice for OPPs. By developing a consensus for best practice model attributes, OPPs can work toward consistent, effective patient care. This project aimed to develop attribute statements for a best practice model for OPPs providing direct patient care. Methods: Board Certified Psychiatric Pharmacists and American Association of Psychiatric Pharmacists (AAPP) members were questioned using a 5-phase (P1-P5) survey and summit approach. The phases were: P1, broad ideation survey; P2, 10-person summit to develop draft statements; P3, survey of the draft statements for acceptance; P4, summit to resolve review feedback; and P5, survey of AAPP membership to confirm the finalized statements. Results: P1 survey results generated a list of 143 possible attributes that informed the P2 summit, which were refined to 28 statements. P3 survey results confirmed at least 70% agreement with each statement. The P4 summit evaluated all P3 survey results and made significant modifications to 4 statements. Informal feedback was sought with other stakeholders, and supporting narratives and references were developed to provide clarity regarding the intent of each statement. Finalized statements and supporting narratives were confirmed in the P5 survey. Discussion: The 28 attribute statements were developed over 18 months by gathering input and consensus through multiple modalities, including 3 surveys, 2 summit meetings, and numerous informal feedback requests. The agreement on the attribute statements was consistently high across all phases. The final attribute statements are presented elsewhere in this issue