Characteristics of a Diverse Cohort of Stroke Patients with SARS-CoV-2 and Outcome by Sex.

BACKGROUND AND PURPOSE: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with stroke. The role of sex on stroke outcome has not been investigated. To objective of this paper is to describe the characteristics of a diverse cohort of acute stroke patients with COVID-19 disease and determine the role of sex on outcome. METHODS: This is a retrospective study of patients with acute stroke and SARS-CoV-2 infection admitted between March 15 to May 15, 2020 to one of the six participating comprehensive stroke centers. Baseline characteristics, stroke subtype, workup, treatment and outcome are presented as total number and percentage or median and interquartile range. Outcome at discharge was determined by the modified Rankin Scale Score (mRS). Variables and outcomes were compared for males and females using univariate and multivariate analysis. RESULTS: The study included 83 patients, 47% of which were Black, 28% Hispanics/Latinos, and 16% whites. Median age was 64 years. Approximately 89% had at least one preexisting vascular risk factor (VRF). The most common complications were respiratory failure (59%) and septic shock (34%). Compared with females, a higher proportion of males experienced severe SARS-CoV-2 symptoms requiring ICU hospitalization (73% vs. 49%; p = 0.04). When divided by stroke subtype, there were 77% ischemic, 19% intracerebral hemorrhage and 3% subarachnoid hemorrhage. The most common ischemic stroke etiologies were cryptogenic (39%) and cardioembolic (27%). Compared with females, males had higher mortality (38% vs. 13%; p = 0.02) and were less likely to be discharged home (12% vs. 33%; p = 0.04). After adjustment for age, race/ethnicity, and number of VRFs, mRS was higher in males than in females (OR = 1.47, 95% CI = 1.03-2.09). CONCLUSION: In this cohort of SARS-CoV-2 stroke patients, most had clinical evidence of coronavirus infection on admission and preexisting VRFs. Severe in-hospital complications and worse outcomes after ischemic strokes were higher in males, than females.

Pharmacogenomics-Based Point-of-Care Clinical Decision Support Significantly Alters Drug Prescribing.

Changes in behavior are necessary to apply genomic discoveries to practice. We prospectively studied medication changes made by providers representing eight different medicine specialty clinics whose patients had submitted to preemptive pharmacogenomic genotyping. An institutional clinical decision support (CDS) system provided pharmacogenomic results using traffic light alerts: green = genomically favorable, yellow = genomic caution, red = high risk. The influence of pharmacogenomic alerts on prescribing behaviors was the primary endpoint. In all, 2,279 outpatient encounters were analyzed. Independent of other potential prescribing mediators, medications with high pharmacogenomic risk were changed significantly more often than prescription drugs lacking pharmacogenomic information (odds ratio (OR) = 26.2 (9.0-75.3), P < 0.0001). Medications with cautionary pharmacogenomic information were also changed more frequently (OR = 2.4 (1.7-3.5), P < 0.0001). No pharmacogenomically high-risk medications were prescribed during the entire study when physicians consulted the CDS tool. Pharmacogenomic information improved prescribing in patterns aimed at reducing patient risk, demonstrating that enhanced prescription decision-making is achievable through clinical integration of genomic medicine.

Patient Perceptions of Care as Influenced by a Large Institutional Pharmacogenomic Implementation Program.

Despite growing clinical use of genomic information, patient perceptions of genomic-based care are poorly understood. We prospectively studied patient-physician pairs who participated in an institutional pharmacogenomic implementation program. Trust/privacy/empathy/medical decision-making (MDM)/personalized care dimensions were assessed through patient surveys after clinic visits at which physicians had access to preemptive pharmacogenomic results (Likert scale, 1 = minimum/5 = maximum; mean [SD]). From 2012-2015, 1,261 surveys were issued to 507 patients, with 792 (62.8%) returned. Privacy, empathy, MDM, and personalized care scores were significantly higher after visits when physicians considered pharmacogenomic results. Importantly, personalized care scores were significantly higher after physicians used pharmacogenomic information to guide medication changes (4.0 [1.4] vs. 3.0 [1.6]; P < 0.001) compared with prescribing visits without genomic guidance. Multivariable modeling controlling for clinical factors confirmed personalized care scores were more favorable after visits with genomic-influenced prescribing (odds ratio [OR] = 3.26; 95% confidence interval [CI] = (1.31-8.14); P < 0.05). Physicians seem to individualize care when utilizing pharmacogenomic results and this decision-making augmentation is perceived positively by patients.

Criteria and indicators of sustainable forest management.

Sustainable development is a term reflecting human, societal, and environmental values and in order to determine progress toward this goal; it is necessary to identify and define these values, and for governments or other institutions to establish the means to assess progress. Canada is directly involved in national and international processes to assess the sustainability of forest management processes using Criteria and Indicators. These consist of a group of broad core values (Criteria) and are supported by an number of measures (Indicators) to assess status or progress toward the realization of these values. Measuring and monitoring indicators is necessary to demonstrate progress toward sustainable development nationally and internationally. The criteria that have been identified include the traditional concepts of timber values, and include economics, environmental, social values, and national infrastructures. Each criterion is supported by a number of indicators to track progress. Countries in the international process also collaborate on defining terms, methods of reporting, and improving and enhancing indicators. C&I facilitate international reporting and provide a framework for international agreements while reflecting national differences in characteristics and descriptions of forests. The reporting process has stimulated the emergence of forest management issues that will influence forest science and forest ecosystem management in the future. For Canada, these include the development of a national system of forest ecosystem inventory, and ecological classification, the interpretation of the range of historic variation, and the adequacy and applicability of data sources.

The moving of St Vincent's: a tale in two cities.

In Australia, demographic changes have seen the population of large cities move away from the inner city. This, combined with changes in healthcare delivery and the ageing of many tertiary teaching hospitals, has led governments to attempt to close, relocate or redefine the role of some institutions. Tracing the media coverage of two such events--the attempts to move St Vincent's hospitals in Sydney and Melbourne--provides some interesting insights into the challenges of resource allocation facing policymakers within the healthcare sector. Both hospitals were long-established, much-loved fixtures on inner-city sites with powerful connections to government and business. In Sydney, where the attempt was part of a larger plan to reallocate resources to the western suburbs, the announcement was met with 10 days of intense media coverage and scrutiny by lobby groups and the general public. By contrast, in Melbourne, no such announcement was made and the low-key reporting of support and opposition to the move occurred over two months. Both attempts failed. No matter how the debate is handled, radical changes involving long-established hospitals, powerful provider groups and loyal communities are very difficult to accomplish.

A selenopyrylium photosensitizer for photodynamic therapy related in structure to the antitumor agent AA1 with potent in vivo activity and no long-term skin photosensitization.

Cationic chalcogenopyrylium dyes 5 were synthesized in six steps from p-aminophenylacetylene (9), have absorption maxima in methanol of 623, 654, and 680 nm for thio-, seleno-, and telluropyrylium dyes, respectively, and generate singlet oxygen with quantum yields [Phi((1)O(2))] of 0.013, 0.029, and 0.030, respectively. Selenopyrylium dye 5-Se was phototoxic to cultured murine Colo-26 and Molt-4 cells. Initial acute toxicity studies in vivo demonstrate that, at 29 mg (62 micromol)/kg, no toxicity was observed with 5-Se in animals followed for 90 days under normal vivarium conditions. In animals given 10 mg/kg of 5-Se via intravenous injection, 2-8 nmol of 5-Se/g of tumor was found at 3, 6, and 24 h postinjection. Animals bearing R3230AC rat mammary adenocarcinomas were treated with 10 mg/kg of 5-Se via tail-vein injection and with 720 J cm(-2) of 570-750-nm light from a filtered tungsten lamp at 200 mW cm(-2) (24 h postinjection of 5-Se). Treated animals gave a tumor-doubling time of 9 +/- 4 days, which is a 300% increase in tumor-doubling time relative to the 3 +/- 2 days for untreated dark controls. Mechanistically, the mitochondria appear to be a target. In cultured R3230AC rat mammary adenocarcinoma cells treated with 0.1 and 1.0 microM 5-Se and light, mitochondrial cytochrome c oxidase activity was inhibited relative to cytochrome c oxidase activity in untreated cells. Irradiation of isolated mitochondrial suspensions treated with 10 microM dye 5-Se inhibited cytochrome c oxidase activity. The degree of enzyme inhibition was abated in a reduced oxygen environment. Superoxide dismutase, at a final concentration of 30 U, did not alter the photosensitized inhibition of mitochondrial cytochrome c oxidase by dye 5-Se. The data suggest that singlet oxygen may play a major role in the photosensitized inhibition of mitochondrial cytochrome c oxidase.

Alginate-poly-L-lysine microcapsule biocompatibility: a novel RT-PCR method for cytokine gene expression analysis in pericapsular infiltrates.

Transplantation of microencapsulated islets of Langerhans is impaired by a pericapsular host reaction that eventually induces graft failure. We are studying the role of cytokines in the pathogenesis of this reaction, using the model of alginate-polylysine microcapsule implantation in rat epididymal fat pads. The objectives were: (1) to develop a method to measure, by semiquantitative PCR, TGF-beta1 gene expression in fat pad pericapsular infiltrates, and (2) to use this method to evaluate TGF-beta1 gene expression 14 days after microcapsule implantation. TGF-beta1 mRNA level was significantly higher in pericapsular infiltrate cells than in nonimplanted tissue cells and saline-injected tissue cells (p < 0.0001 and p < 0.01, respectively). There was no significant difference between the TGF-beta1 mRNA levels of the two types of controls (p = 0.0945). These results suggest that TGF-beta1 plays a role in the pathogenesis of the pericapsular reaction. The method developed can be used to study the role of other fibrogenic cytokines potentially involved. This will shed light on the mechanisms underlying the pericapsular reaction and will serve as a basis for the development of strategies to control this reaction.

The osmoregulatory pathway represses mating pathway activity in Saccharomyces cerevisiae: isolation of a FUS3 mutant that is insensitive to the repression mechanism.

Mitogen-activated protein (MAP) kinase cascades are conserved signal transduction pathways that are required for eukaryotic cells to respond to a variety of stimuli. Multiple MAP kinase pathways can function within a single cell type; therefore, mechanisms that insulate one MAP kinase pathway from adventitious activations by parallel pathways may exist. We have studied interactions between the mating pheromone response and the osmoregulatory (high-osmolarity glycerol response [HOG]) pathways in Saccharomyces cerevisiae which utilize the MAP kinases Fus3p and Hog1p, respectively. Inactivating mutations in HOG pathway kinases cause an increase in the phosphotyrosine content of Fus3p, greater expression of pheromone-responsive genes, and increased sensitivity to growth arrest by pheromone. Therefore, the HOG pathway represses mating pathway activity. In a HOG1+ strain, Fus3p phosphotyrosine increases modestly and transiently following an increase in the extracellular osmolarity; however, it increases to a greater extent and for a sustained duration in a hog1-delta strain. Thus, the HOG-mediated repression of mating pathway activity may insulate the mating pathway from activation by osmotic stress. A FUS3 allele whose gene product is resistant to the HOG-mediated repression of its phosphotyrosine content has been isolated. This mutant encodes an amino acid substitution in the highly conserved DPXDEP motif in subdomain XI. Other investigators have shown that the corresponding amino acid is also mutated in a gain-of-function allele of the MAP kinase encoded by the rolled locus in Drosophila melanogaster. These data suggest that the DPXDEP motif plays a role in the negative regulation of MAP kinases.

SMK1, a developmentally regulated MAP kinase, is required for spore wall assembly in Saccharomyces cerevisiae.

Mitogen-activated protein (MAP) kinases comprise a family of conserved, eukaryotic enzymes that mediate responses to a wide variety of extracellular stimuli. In yeast, different signal transduction pathways utilize distinct MAP kinase family members. We have identified a new yeast MAP kinase gene (named SMK1) that is required for the completion of sporulation. Molecular and cytologic markers indicate that meiotic development proceeds normally in homozygous smk1-delta 1 diploids through meiosis II. However, light and electron microscopy show that smk1 asci are defective in organizing spore wall assembly. Consistent with a defect in spore wall assembly, smk1-delta 1 mutant asci display enhanced sensitivities to enzymatic digestion, heat shock, and exposure to ether. SMK1 mRNA, which is not detectable in vegetative cells, is derepressed at least 200-fold just prior to prospore enclosure. We propose that the SMK1 MAP kinase participates in a developmentally regulated signal transduction pathway that coordinates cytodifferentiation events with the transcriptional program.

A cost-effectiveness analysis of alternative strategies for the prevention of heart disease.

The identification of risk factors, such as a raised cholesterol level, hypertension, cigarette smoking, and obesity, permits the prediction of the possible development of ischaemic heart disease and has led to attempts at its prevention through modification of these factors. A high risk of developing ischaemic heart disease is also associated with age, specific socioeconomic groups, a family history of ischaemic heart disease, and preexisting evidence of the disease. Preventive strategies have either sought to reduce the average levels of risk in the general population or to identify by population screening individuals or groups who are at particular risk and to reduce their level of risk. Differing methods of risk-factor identification and modification are appropriate for each of the high-risk groups. For a number of strategies that are directed at either the whole population or high-risk groups we have estimated the costs of identification and risk-factor modification and the probable benefits of undertaking such a strategy. A strategy which educates the whole population by way of the media costs considerably less than does any strategy that involves the identification of individuals at high risk. At a medium cost estimate, with a reduction in risk of only 1%, such an approach costs approximately $8000 per case that is prevented; when risk reduction approaches 3% it actually results in a saving of health-care expenditure within five years. The costs of the other strategies vary between $12,000 and $26,000 per case that is prevented in a five-year period.

Current practice in health promotion.

Progress in health promotion and preventive programme planning is limited by a lack of data on the development of current activities. A cross sectional survey of hospitals, community health centres, and other health agencies in New South Wales was therefore undertaken to determine the nature and extent of health promotion programmes being conducted in the period July to December 1983. A subsample of 1198 preventive programmes in child and family health was identified, making up 26% of all programmes operating in this period. Results indicate that three major types of programme are being conducted in child health. These are in the areas of (1) parent education and support, (2) school health education, including drug and alcohol education and personal development, and (3) child safety and first aid. Although the nature of these programmes generally corresponds with current thinking on what priorities in health promotion should be, results also indicate that evaluation of these programmes is limited. Most programmes assess only what participants think of the programme rather than assessing changes in knowledge, attitude, behaviour, or health status. Improvements in evaluation practice are required if preventive intervention programmes are to undertake seriously the task of altering the pattern of diseases and problems in childhood and adolescence.

Adult respiratory medical emergencies.

Respiratory emergencies are a challenge, both to the patient's life and to the nurse who must deal with the emergency. Regardless of the initiating event, the patient must be assessed and treatment instituted rapidly. Clearing of the airway and breathing are the first two considerations for action in the emergency department's protocol, and in many cases it will be the sole responsibility of the nurse to facilitate these essential functions.

X-ray structure of [Ru3 O2 (NH3)14]6+, cation of the cytological reagent Ruthenium Red.

The X-ray crystal structure of [Ru3 O2 (NH3)14] (S2 O3)3 . 4H2 O, the thiosulphate salt of Ruthenium Red, has been determined. The cation contains an essentially linear N-Ru-O-Ru-O-Ru-N backbone formed from three ruthenium coordination octahedra, giving an effectively cylindrical shape to the ion. Resonance Raman spectra are consistent with retention of this structure in solution.